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[Coping with leprosy in the Dutch West Indies in the 19th century; opposing but meaningful views from Suriname].
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Leprosy was highly prevalent among African slaves in the Dutch West Indian colony of Suriname. Largely based on observations in Suriname, Dutch physicians described the aetiology of leprosy in terms of'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed ('seed and soil'). This explanatory model with multiple options for prevention and treatment left room for different developmental trajectories to control the spread of the disease in the various tropical colonies of the Dutch empire. In Suriname there was a growing worry in the 19th century regarding the spread of leprosy, threatening the health of slaves, settlers and colonial administrators. And this could be harmful to an already weakening plantation economy. This concern prompted the local administration to develop a rigorous policy of strict isolation of leprosy sufferers. This, in turn, intersected with a changing insight in Europe - including the Netherlands - that leprosy was non-contagious. However,'in splendid isolation' in the economically and politically marginal colony Suriname, Dutch physicians like Charles Landre and his son, Charles Louis Drognat Landré, could afford to ignore the European non-contagious approach and continue to support the strict isolation policies. Moreover, they developed a dissident radical explanation of leprosy as a disease caused only by contagion. In the absence of a receptive Dutch audience Drognat Landré published his contagion theory in French and so succeeded in inspiring the Norwegian Hansen, who subsequently discovered the culpable micro-organism. At the same time colonial administrators and physicians in the economically and politically important Dutch colonies in the East Indies adhered to the prevailing European concept and changed policies: the system of isolation was abolished. Given the rather different trajectories of leprosy health policies in the Dutch East and West Indies we point out the importance of a comparative approach.
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Some studies indirectly link the pandemic to the Anthropocene. However, this brief essay identifies the Anthropocene as a Western-bred phenomenon, which has evolved from Europe's colonial past. Pandemics are not new to settler colonialism, for instance. In this broader framework, the Covid-19 pandemic comes at a time when the West is confronting a new challenge to its global influence, i.e. the climate emergency resulting from a long history of colonial experiments, successes and failures.
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[Coping with leprosy in the Dutch West Indies in the 19th century; opposing but meaningful views from Suriname].
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Leprosy was highly prevalent among African slaves in the Dutch West Indian colony of Suriname. Largely based on observations in Suriname, Dutch physicians described the aetiology of leprosy in terms of'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed ('seed and soil'). This explanatory model with multiple options for prevention and treatment left room for different developmental trajectories to control the spread of the disease in the various tropical colonies of the Dutch empire. In Suriname there was a growing worry in the 19th century regarding the spread of leprosy, threatening the health of slaves, settlers and colonial administrators. And this could be harmful to an already weakening plantation economy. This concern prompted the local administration to develop a rigorous policy of strict isolation of leprosy sufferers. This, in turn, intersected with a changing insight in Europe - including the Netherlands - that leprosy was non-contagious. However,'in splendid isolation' in the economically and politically marginal colony Suriname, Dutch physicians like Charles Landre and his son, Charles Louis Drognat Landré, could afford to ignore the European non-contagious approach and continue to support the strict isolation policies. Moreover, they developed a dissident radical explanation of leprosy as a disease caused only by contagion. In the absence of a receptive Dutch audience Drognat Landré published his contagion theory in French and so succeeded in inspiring the Norwegian Hansen, who subsequently discovered the culpable micro-organism. At the same time colonial administrators and physicians in the economically and politically important Dutch colonies in the East Indies adhered to the prevailing European concept and changed policies: the system of isolation was abolished. Given the rather different trajectories of leprosy health policies in the Dutch East and West Indies we point out the importance of a comparative approach.
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Despite facing manifold social and educational barriers, British asylum nurses across the long nineteenth century articulated distinctive professional identities as a means of leveraging their position in the medical hierarchy. This article draws upon a corpus of previously unattributed contributions to the Asylum News (1897-1919) - one of the first journals produced for the edification of asylum workers - to illustrate the diversity of medical personae developed and disseminated by these employees in the Edwardian era. Through scientific and creative works, nurses engaged with the pressing social and medical debates of the day, in the process exposing a heterogeneous intellectual culture. Moreover, as their writings attest, for some ambitious nurses these pretensions to intellectual authority prompted claims for medical autonomy, driving agitation on the hospital wards. The article thus strengthens claims for the 'cultural agency' of asylum workers and offers new insights into the cultural antecedents of professionalisation and trade unionism.
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[Coping with leprosy in the Dutch West Indies in the 19th century; opposing but meaningful views from Suriname].
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Leprosy was highly prevalent among African slaves in the Dutch West Indian colony of Suriname. Largely based on observations in Suriname, Dutch physicians described the aetiology of leprosy in terms of'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed ('seed and soil'). This explanatory model with multiple options for prevention and treatment left room for different developmental trajectories to control the spread of the disease in the various tropical colonies of the Dutch empire. In Suriname there was a growing worry in the 19th century regarding the spread of leprosy, threatening the health of slaves, settlers and colonial administrators. And this could be harmful to an already weakening plantation economy. This concern prompted the local administration to develop a rigorous policy of strict isolation of leprosy sufferers. This, in turn, intersected with a changing insight in Europe - including the Netherlands - that leprosy was non-contagious. However,'in splendid isolation' in the economically and politically marginal colony Suriname, Dutch physicians like Charles Landre and his son, Charles Louis Drognat Landré, could afford to ignore the European non-contagious approach and continue to support the strict isolation policies. Moreover, they developed a dissident radical explanation of leprosy as a disease caused only by contagion. In the absence of a receptive Dutch audience Drognat Landré published his contagion theory in French and so succeeded in inspiring the Norwegian Hansen, who subsequently discovered the culpable micro-organism. At the same time colonial administrators and physicians in the economically and politically important Dutch colonies in the East Indies adhered to the prevailing European concept and changed policies: the system of isolation was abolished. Given the rather different trajectories of leprosy health policies in the Dutch East and West Indies we point out the importance of a comparative approach.
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Death is a constant feature of lives lived at the borders for migrants trying to reach Europe without the necessary authorizations from nation-states. At the border between Melilla and Morocco, many stories are told about near death experiences during attempts to cross both land and maritime borders, as well as about abandoned bodies. Other common narratives focus on the living dead, on the missing presumed dead, on unidentified bodies, and on the living who continue to be haunted by the disappeared. Drawing on ethnographic material, this paper examines the ways in which migrants' journeys and subjectivities are shaped by death on the migrant trail to Europe.
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[Coping with leprosy in the Dutch West Indies in the 19th century; opposing but meaningful views from Suriname].
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Leprosy was highly prevalent among African slaves in the Dutch West Indian colony of Suriname. Largely based on observations in Suriname, Dutch physicians described the aetiology of leprosy in terms of'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed ('seed and soil'). This explanatory model with multiple options for prevention and treatment left room for different developmental trajectories to control the spread of the disease in the various tropical colonies of the Dutch empire. In Suriname there was a growing worry in the 19th century regarding the spread of leprosy, threatening the health of slaves, settlers and colonial administrators. And this could be harmful to an already weakening plantation economy. This concern prompted the local administration to develop a rigorous policy of strict isolation of leprosy sufferers. This, in turn, intersected with a changing insight in Europe - including the Netherlands - that leprosy was non-contagious. However,'in splendid isolation' in the economically and politically marginal colony Suriname, Dutch physicians like Charles Landre and his son, Charles Louis Drognat Landré, could afford to ignore the European non-contagious approach and continue to support the strict isolation policies. Moreover, they developed a dissident radical explanation of leprosy as a disease caused only by contagion. In the absence of a receptive Dutch audience Drognat Landré published his contagion theory in French and so succeeded in inspiring the Norwegian Hansen, who subsequently discovered the culpable micro-organism. At the same time colonial administrators and physicians in the economically and politically important Dutch colonies in the East Indies adhered to the prevailing European concept and changed policies: the system of isolation was abolished. Given the rather different trajectories of leprosy health policies in the Dutch East and West Indies we point out the importance of a comparative approach.
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This paper considers the way the outbreak of coronavirus and the subsequent lockdown has egregiously impeded the Hindu death ceremonies and mourning rituals in India. It makes a comparative analysis of how Hindu death rituals get renegotiated, modified and reinterpreted across two vastly different regions of India, both of which have their local customs. Whilst death rituals in India are contingent on the deceased's caste, community, class, gender and age, the impediment to the major death rituals creates a central conundrum for all mourners. It results from the substitution of 'sacred' ritual guidelines with new 'profane' ones for the 'disposal' of deceased COVID-19 patients. Departure from many significant pre-liminal rites, specific transition rites, and post-liminal rites has eschatological, ritual and cultural ramifications. The inability to grieve in unison during a Shraddh ceremony denies mourners any scope to quell distressing feelings about mortality which serves as a source of consolation.
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Dosing considerations for inhaled biologics.
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The number of biologics in the therapeutic development pipeline is increasing including those delivered though inhalation (Morales, 2017; Fathe, 2016). Biologics comprise a broad variety of complex macromolecules with unique physicochemical characteristics. These distinctive characteristics control their pharmacological mechanisms of action, stability, and ultimately affect their processing, formulation, and delivery requirements. This review systematically covers crucial aspects of biologic powders formulations and dry powder inhalers which need to be taken into consideration to establish the drug loading and the payload to be delivered to reach the desired clinical dose.
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Generic drugs are approved on the basis of pharmaceutical equivalence and bioequivalence. Some drug products have unique structural or functional attributes, necessitating modified approaches to bioequivalence determinations.
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Dosing considerations for inhaled biologics.
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The number of biologics in the therapeutic development pipeline is increasing including those delivered though inhalation (Morales, 2017; Fathe, 2016). Biologics comprise a broad variety of complex macromolecules with unique physicochemical characteristics. These distinctive characteristics control their pharmacological mechanisms of action, stability, and ultimately affect their processing, formulation, and delivery requirements. This review systematically covers crucial aspects of biologic powders formulations and dry powder inhalers which need to be taken into consideration to establish the drug loading and the payload to be delivered to reach the desired clinical dose.
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The preclinical safety studies required to support the development of inhaled drugs are generally the same as for other routes of administration. Repeat-dose toxicology studies should be conducted by inhalation to ensure the characterization of both the local (i.e., respiratory) and systemic toxicity, although some studies (e.g., reproductive) can be performed by utilizing alternative routes, when it is paramount to maximize systemic exposure. Respiratory tract changes in preclinical species can include irritancy of the larynx and nasal cavity, particularly in rodents. Such changes are not necessarily predictive of a risk to humans because of the exquisite sensitivity of the rodent larynx and the lack of exposure to the nasal cavity after oro-inhalation of drugs in the clinical setting. The design of poorly soluble molecules to limit systemic exposure places greater emphasis on the elimination of drugs from the lungs by macrophages. Consequently, an increase in macrophage numbers is often noted, and in the absence of any other changes, this is generally considered to be a nonadverse, physiological response to an inhaled particulate. Other changes in the lung, which can include an inflammatory response and/or epithelial hyperplasia, resulting from irritancy or particulate overload, are a safety concern and are not monitorable in humans. For such changes, safety margins can be calculated in terms of the drug deposited per unit weight of lung. These factors should be taken into account when designing preclinical studies or programs for inhaled drugs.
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Dosing considerations for inhaled biologics.
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The number of biologics in the therapeutic development pipeline is increasing including those delivered though inhalation (Morales, 2017; Fathe, 2016). Biologics comprise a broad variety of complex macromolecules with unique physicochemical characteristics. These distinctive characteristics control their pharmacological mechanisms of action, stability, and ultimately affect their processing, formulation, and delivery requirements. This review systematically covers crucial aspects of biologic powders formulations and dry powder inhalers which need to be taken into consideration to establish the drug loading and the payload to be delivered to reach the desired clinical dose.
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Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases. However, unwanted adverse reactions--including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity--pose a challenge to the development of new (and safer) immunomodulatory biologics. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use. We also outline how these approaches can inform the development of safer immunomodulatory biologics.
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Dosing considerations for inhaled biologics.
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The number of biologics in the therapeutic development pipeline is increasing including those delivered though inhalation (Morales, 2017; Fathe, 2016). Biologics comprise a broad variety of complex macromolecules with unique physicochemical characteristics. These distinctive characteristics control their pharmacological mechanisms of action, stability, and ultimately affect their processing, formulation, and delivery requirements. This review systematically covers crucial aspects of biologic powders formulations and dry powder inhalers which need to be taken into consideration to establish the drug loading and the payload to be delivered to reach the desired clinical dose.
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Drugs must be properly formulated for administration to patients, regardless of age. Pediatric patients provide some additional challenges to the formulator in terms of compliance and therapeutic efficacy. Due to the lack of sufficient drug products for the pediatric population, the pharmaceutical industry and compounding pharmacies must develop and provide appropriate medications designed for children.
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Dosing considerations for inhaled biologics.
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The number of biologics in the therapeutic development pipeline is increasing including those delivered though inhalation (Morales, 2017; Fathe, 2016). Biologics comprise a broad variety of complex macromolecules with unique physicochemical characteristics. These distinctive characteristics control their pharmacological mechanisms of action, stability, and ultimately affect their processing, formulation, and delivery requirements. This review systematically covers crucial aspects of biologic powders formulations and dry powder inhalers which need to be taken into consideration to establish the drug loading and the payload to be delivered to reach the desired clinical dose.
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In 2003, Crommelin et al. published an article titled: "Shifting paradigms: biopharmaceuticals versus low molecular weight drugs" (https://doi.org/10.1016/S0378-5173(03)00376-4). In the present commentary, 16 years later, we discuss pharmaceutically relevant aspects of the evolution of biologics since then. First, we discuss the increasing repertoire of biologics, in particular, the rapidly growing monoclonal antibody family and the advent of advanced therapy medicinal products. Next, we discuss trends in formulation and characterization as well as summarize our current insights into immunogenicity of biologics. We spend a separate section on new product(ion) paradigms for biologics, such as cell-free production systems, production of advanced therapy medicinal products, and downscaled production approaches. Furthermore, we share our views on issues related to reaching the patient, including routes and techniques of administration, alternative development models for affordable biologics, biosimilars, and handling of biologics. In the concluding section, we outline outstanding issues and make some suggestions for resolving those.
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Preventing hypoglycemia with novel technology and flexible therapy.
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Diabetes is increasing at an alarming rate. Treatment-associated hypoglycemia is a major limitation to achieving glycemic control in diabetes. Appropriate use of new technology and flexible treatment regimens, especially in those with defined risk factors, may decrease the frequency of hypoglycemia.
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Hypoglycaemia is common in both type 1 and type 2 diabetes and has both acute and long-term consequences. Therefore, a key to proper glucose-lowering therapy in diabetes is to avoid or prevent hypoglycaemia. Incretin therapy (DPP-4 inhibitors and GLP-1 receptor agonists) offers an advantage in this respect, because it reduces glucose with a low risk of hypoglycaemia, both in monotherapy and in combination with other therapies. The reason for this low risk of hypoglycaemia is the glucose dependency of action of incretin therapy and the sustainment of glucose counter-regulatory hormone responses to hypoglycaemia, in particular the glucagon response. Incretin therapy is also associated with a low risk of hypoglycaemia in patient groups which are especially vulnerable and susceptible for hypoglycaemia, e.g., subjects with renal impairment, elderly subjects and subjects with on-going insulin therapy. This review summarizes how incretin therapy may meet the challenges of hypoglycaemia and suggests that incretin therapy is a therapy of choice to avoid hypoglycaemia, both in the general diabetes population and in subjects with increased risk or vulnerability for hypoglycaemia.
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Preventing hypoglycemia with novel technology and flexible therapy.
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Diabetes is increasing at an alarming rate. Treatment-associated hypoglycemia is a major limitation to achieving glycemic control in diabetes. Appropriate use of new technology and flexible treatment regimens, especially in those with defined risk factors, may decrease the frequency of hypoglycemia.
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Hyperglycemia is common in hospitalized patients with and without prior history of diabetes and is an independent marker of morbidity and mortality in critically and noncritically ill patients. Tight glycemic control using insulin has been shown to reduce cardiac morbidity and mortality in hospitalized patients, but it also results in hypoglycemic episodes, which have been linked to poor outcomes. Thus, alternative treatment options that can normalize blood glucose levels without undue hypoglycemia are being sought. Incretin-based therapies, such as glucagon-like peptide (GLP)-1 receptor agonists (RAs) and dipeptidyl peptidase (DPP)-4 inhibitors, may have this potential.
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Preventing hypoglycemia with novel technology and flexible therapy.
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Diabetes is increasing at an alarming rate. Treatment-associated hypoglycemia is a major limitation to achieving glycemic control in diabetes. Appropriate use of new technology and flexible treatment regimens, especially in those with defined risk factors, may decrease the frequency of hypoglycemia.
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Intensive insulin treatment in type 1 diabetes reduces the incidence and slows the progression of microvascular and macrovascular complications; however, it is associated with an increased risk of hypoglycaemia and weight gain. In this review, we propose dual-hormone treatment with insulin and glucagon as a method for achieving near normalization of blood glucose levels without increasing hypoglycaemia frequency and weight gain. We briefly summarize glucagon pathophysiology in type 1 diabetes as well as the current applications of glucagon for the treatment of hypoglycaemia. Until now, the use of glucagon has been limited by the need for reconstitution immediately before use, because of instability of the available compounds; however, stabile compounds are soon to be launched and will render long-term intensive dual-hormone treatment in type 1 diabetes possible.
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Preventing hypoglycemia with novel technology and flexible therapy.
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Diabetes is increasing at an alarming rate. Treatment-associated hypoglycemia is a major limitation to achieving glycemic control in diabetes. Appropriate use of new technology and flexible treatment regimens, especially in those with defined risk factors, may decrease the frequency of hypoglycemia.
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Drug-induced (insulin/insulin secretagogue) hypoglycaemia is the most common cause of hypoglycaemia particularly in the elderly. It is estimated that hypoglycaemia of any severity occurs annually in 5-20% of patients taking antihyperglycaemic agents. Although these hypoglycaemic episodes are rarely fatal, they can be associated with serious clinical sequelae. The half-life for most sulfonylurea medications is 14-16 h; they can cause severe, prolonged hypoglycaemia. It is important to recognise, prevent and treat hypoglycaemic episodes secondary to the use of antihyperglycaemic agents. Patient education has become focused on minimising hyperglycaemia but emphasis must be placed on minimising even minor subclinical hypoglycaemia because it will contribute to a vicious cycle of hypoglycaemia begetting hypoglycaemia. Ten per cent dextrose is recommended for the reversal of all hypoglycaemic episodes rather than the conventional 50% dextrose. Octreotide can be an option for recurrent and relapsing hypoglycaemia in an acute setting.
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Preventing hypoglycemia with novel technology and flexible therapy.
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Diabetes is increasing at an alarming rate. Treatment-associated hypoglycemia is a major limitation to achieving glycemic control in diabetes. Appropriate use of new technology and flexible treatment regimens, especially in those with defined risk factors, may decrease the frequency of hypoglycemia.
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The management of type 1 diabetes is being advanced by innovations in glucose measurement, development of an artificial pancreas, and in alternate routes of insulin delivery. Emerging technologies will allow insulin to be delivered more effectively. In the future, patients with type 1 diabetes will receive insulin in optimal quantities (because of more information about blood glucose values) at optimal times (because of better integration of blood glucose values with appropriate insulin dosages) by way of optimal routes into the body (because of needle-free routes of administration) in order to achieve optimal blood glucose control. Emerging technologies for improved care of patients with type 1 diabetes include: 1. new methods for monitoring glucose, including noninvasive, minimally invasive, continuous, and alternate site measurement technologies; 2. new methods for integrating glucose values and insulin dosages, known as the artificial pancreas; and 3. new routes of insulin administration, including inhaled, oral, buccal, nasal, and transdermal drug delivery systems. These new technologies will facilitate proper treatment of type 1 diabetes and improve the lives of affected patients.
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[Percutaneous coronary interventions in patients with ischemic heart disease and chronic renal failure].
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Patients with chronic renal failure (CRF) consist of about 10% of all patients with ischemic heart disease (IHD) undergoing percutaneous coronary interventions (PCI). These patients have a higher rate of in-hospital and long-term major adverse cardiac events. Coronary stents improved prognosis in CRF patients, however long-term survival is still poor. Coronary artery bypass graft (CABG) surgery is an alternative modality of treatment, with better long-term prognosis but at the cost of higher in-hospital mortality. CABG surgery probably should be preferred in patients with CRF and multivessel coronary artery disease, left main stenosis or diabetes. The influence of drug-eluting stents on survival in patients with CRF is unknown.
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To evaluate the effects of mutual goal-based continuous care program on the outcomes of patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).
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[Percutaneous coronary interventions in patients with ischemic heart disease and chronic renal failure].
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Patients with chronic renal failure (CRF) consist of about 10% of all patients with ischemic heart disease (IHD) undergoing percutaneous coronary interventions (PCI). These patients have a higher rate of in-hospital and long-term major adverse cardiac events. Coronary stents improved prognosis in CRF patients, however long-term survival is still poor. Coronary artery bypass graft (CABG) surgery is an alternative modality of treatment, with better long-term prognosis but at the cost of higher in-hospital mortality. CABG surgery probably should be preferred in patients with CRF and multivessel coronary artery disease, left main stenosis or diabetes. The influence of drug-eluting stents on survival in patients with CRF is unknown.
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Percutaneous coronary intervention (PCI) is an effective method for the treatment ofcoronary artery disease (CAD) that allows for a short hospital stay and fast recovery. It has been shown that PCI is a predictor of nonattendance at cardiac rehabilitation and correlates with poor adherence to lifestyle changes.
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[Percutaneous coronary interventions in patients with ischemic heart disease and chronic renal failure].
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Patients with chronic renal failure (CRF) consist of about 10% of all patients with ischemic heart disease (IHD) undergoing percutaneous coronary interventions (PCI). These patients have a higher rate of in-hospital and long-term major adverse cardiac events. Coronary stents improved prognosis in CRF patients, however long-term survival is still poor. Coronary artery bypass graft (CABG) surgery is an alternative modality of treatment, with better long-term prognosis but at the cost of higher in-hospital mortality. CABG surgery probably should be preferred in patients with CRF and multivessel coronary artery disease, left main stenosis or diabetes. The influence of drug-eluting stents on survival in patients with CRF is unknown.
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Occasionally, high-risk patients in the post-myocardial infarction (MI) period require surgical intervention for stabilization and/or revascularization. In a meta-analysis involving 3,088 patients with ischemic heart disease, revascularization was associated with nearly an 80% reduction in the risk of death. Coronary artery bypass graft (CABG) surgery is commonly performed in post-MI patients and is associated with more favorable outcomes than medical therapy. However, several factors have to be considered in proper patient selection for CABG, such as the left ventricular ejection fraction (LVEF), severity of heart failure (HF), and myocardial viability. The ongoing Surgical Treatment for Ischemic Heart Failure (STICH) trial will assess the benefits of CABG in patients with both a low LVEF and HF. Unstable post-MI patients who fail revascularization can be managed via mechanical circulatory support devices or pumps. These options significantly improve hemodynamic parameters. In addition, other surgical techniques, such as mitral valve repair, ventricular reconstruction surgery, and atrial fibrillation ablation, are being evaluated in patients with ischemic heart disease.
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[Percutaneous coronary interventions in patients with ischemic heart disease and chronic renal failure].
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Patients with chronic renal failure (CRF) consist of about 10% of all patients with ischemic heart disease (IHD) undergoing percutaneous coronary interventions (PCI). These patients have a higher rate of in-hospital and long-term major adverse cardiac events. Coronary stents improved prognosis in CRF patients, however long-term survival is still poor. Coronary artery bypass graft (CABG) surgery is an alternative modality of treatment, with better long-term prognosis but at the cost of higher in-hospital mortality. CABG surgery probably should be preferred in patients with CRF and multivessel coronary artery disease, left main stenosis or diabetes. The influence of drug-eluting stents on survival in patients with CRF is unknown.
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The risk of intra-stent restenosis has diminished considerably with the advent of endoprostheses which actively release sirolimus or paclitaxel. Patients with chronic renal failure constitute a high cardiovascular risk population, in whom the incidence of coronary heart disease is particularly high, representing one of the principal causes of death. The aim of this study, which included 152 patients, was to quantify the value of active stents for coronary angioplasty in patients with chronic renal failure. Thirty eight patients with chronic renal failure who underwent angioplasty with active stents were matched for age, sex and the presence of diabetes with 3 other groups of patients: one group with active stents but without renal failure, one group with inactive stents and no renal failure, and one group with inactive stents and chronic renal failure. The average follow up was 16 +/- 5 months. The acute stent thrombosis rate (2%) was not elevated in cases of renal failure nor after active stent implantation. Chronic renal failure significantly increased the mortality rate 16 months after angioplasty, whichever type of stent was used: 8 versus 2% deaths in patients with an inactive stent (p = 0.001). In renal failure, the risk of death was lower with an active stent (8 vs 26% with an inactive stent, p<0.05). Similarly, there was a non-significant trend towards a lower risk of death and/or infarction in renal failure after active stents (8 vs 21% with an inactive stent, NS).
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[Percutaneous coronary interventions in patients with ischemic heart disease and chronic renal failure].
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Patients with chronic renal failure (CRF) consist of about 10% of all patients with ischemic heart disease (IHD) undergoing percutaneous coronary interventions (PCI). These patients have a higher rate of in-hospital and long-term major adverse cardiac events. Coronary stents improved prognosis in CRF patients, however long-term survival is still poor. Coronary artery bypass graft (CABG) surgery is an alternative modality of treatment, with better long-term prognosis but at the cost of higher in-hospital mortality. CABG surgery probably should be preferred in patients with CRF and multivessel coronary artery disease, left main stenosis or diabetes. The influence of drug-eluting stents on survival in patients with CRF is unknown.
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Heart failure is a complex clinical syndrome and represents the final path of numerous heart diseases. Coronary artery disease is recognized as the primary risk factor for heart failure development, being the main etiological factor in more than 50% of heart failure patients in North America and Europe. Regardless of overt coronary artery disease, myocardial ischemia is a common finding in failing hearts, likely due to structural or functional coronary circulation alterations. Ischemia is a self-propagating process which irreversibly impairs the cardiac function and negatively impacts prognosis. Thus, a better and thorough understanding of myocardial ischemia pathophysiology in heart failure would likely lead to significantly improved outcomes in these patients. This review aims to describe the mechanisms of myocardial ischemia and coronary artery disease in heart failure, focusing on coronary circulation dysfunctions due to increased parietal stress or non-obstructive coronary disease, and discussing the association and management of coronary artery disease in patients with heart failure.
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Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome.
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Hypoplastic left heart syndrome (HLHS) is associated with significant mortality and morbidity. Fetal head growth abnormalities have been identified in a subset of HLHS fetuses, but it is unclear whether specific patterns of maladaptive growth affect clinical outcomes. We hypothesized that poor fetal head growth is associated with an increased frequency of adverse clinical outcomes.
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Heart-hand syndromes show substantial clinical and genetic heterogeneity. The unusual case of a patient with a heart-hand syndrome consisting of preaxial polydactylia, postaxial syndactylia, parachute mitral valve, mild subaortic stenosis, and double outlet right ventricle is presented and discussed. The importance of distinguishing Holt-Oram syndrome from its phenocopies and other heart-hand syndromes is underlined.
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Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome.
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Hypoplastic left heart syndrome (HLHS) is associated with significant mortality and morbidity. Fetal head growth abnormalities have been identified in a subset of HLHS fetuses, but it is unclear whether specific patterns of maladaptive growth affect clinical outcomes. We hypothesized that poor fetal head growth is associated with an increased frequency of adverse clinical outcomes.
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Herein we present the fatal case of premature baby with coincidence of extreme form of ectopia cordis and hypoplastic left heart structures.
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Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome.
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Hypoplastic left heart syndrome (HLHS) is associated with significant mortality and morbidity. Fetal head growth abnormalities have been identified in a subset of HLHS fetuses, but it is unclear whether specific patterns of maladaptive growth affect clinical outcomes. We hypothesized that poor fetal head growth is associated with an increased frequency of adverse clinical outcomes.
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To delineate prevalence of stroke in the pediatric intensive care unit and to determine risk factors for stroke and association of stroke with mortality in patients with congenital heart disease. Retrospective cohort study. Patients admitted to pediatric intensive care units in the USA participating in the Pediatric Health Information System database from 2016 to 2021. Patients were categorized as those who experienced ischemic or hemorrhagic stroke and those with congenital heart disease. We performed univariate and multivariate logistic regressions to determine risk factors associated with stroke and then developed a predictive model for stroke development in patients with congenital heart disease. Of 426,029 admissions analyzed, 4237 (0.9%) patients experienced stroke and 1197 (1.4%) of 80,927 patients with congenital heart disease developed stroke (odds ratio 1.15, 95% confidence interval 1.06-1.24). Patients with congenital heart disease, younger age, extracorporeal membrane oxygenation, mechanical ventilation, and cardiac arrest were most strongly associated with increased risk of stroke. Stroke increased odds of mortality for patients with congenital heart disease (odds ratio 2.49, 95% confidence interval 2.08-2.98). A risk score greater than 0 was associated with a 33.3% risk of stroke for patients with congenital heart disease (negative predictive value of 99%, sensitivity 69%, specificity 63%). Children with congenital heart disease are at increased risk for developing stroke, which is associated with increased mortality. Early identification of the most vulnerable patients may enable providers to implement preventative measures or rapid treatment strategies to prevent neurologic morbidity.
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Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome.
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Hypoplastic left heart syndrome (HLHS) is associated with significant mortality and morbidity. Fetal head growth abnormalities have been identified in a subset of HLHS fetuses, but it is unclear whether specific patterns of maladaptive growth affect clinical outcomes. We hypothesized that poor fetal head growth is associated with an increased frequency of adverse clinical outcomes.
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The study objectives were to compare the neurodevelopmental outcomes of preschool survivors of the Fontan procedure with those of children with congenital heart disease undergoing biventricular repair and to investigate predictors of neurodevelopmental outcome for those with single ventricle congenital heart disease, including hypoplastic left heart syndrome.
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Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome.
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Hypoplastic left heart syndrome (HLHS) is associated with significant mortality and morbidity. Fetal head growth abnormalities have been identified in a subset of HLHS fetuses, but it is unclear whether specific patterns of maladaptive growth affect clinical outcomes. We hypothesized that poor fetal head growth is associated with an increased frequency of adverse clinical outcomes.
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To determine whether differential exposure to an adverse maternal fetal environment partially explains disparate outcomes in infants with major congenital heart disease (CHD).
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[Electrochemical sensors based on carbon nanotubes and their use in biomedical research].
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Electrochemical sensors based on carbon nanotubes are widely used in biomedical studies. According to design the sensors can be divided into three groups: (i) sensors based on a carbon nanotube array; (ii) sensors manufactured by means of composites containing carbon nanotubes; (iii) sensors, which are electrodes with working surface containing carbon nanotubes. The development directions of sensors of the first and the second group, and also sensors of the third group which are manufactured by abrasive immobilization of carbon nanotubes on an electrode surface and by solvent dispersion and casting immobilization of carbon nanotubes on an electrode surface by means of N,N-dimethylformamide, surfactants, and Nafion are analyzed. The general information on manufacturing techniques of these sensors is given. The opportunities of these sensors for biomedical researches are demonstrated.
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The unique physical, chemical and mechanical properties of carbon nanotubes make them attractive for a variety of biomedical applications. Carbon nanotubes have been used to modify conventional biomedical materials to enhance mechanical properties, biocompatibility, or to impart other functionalities. New multifunctional composite materials using carbon nanotubes have been developed by combining them with inorganic, polymeric or biological materials. The biomedical applications for which novel carbon nanotube composites have been investigated include antimicrobial coatings, neural implants, tissue engineering scaffolds and electrochemical biosensors. In this paper, research on development and application of carbon nanotube composites for biomedical applications has been reviewed.
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[Electrochemical sensors based on carbon nanotubes and their use in biomedical research].
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Electrochemical sensors based on carbon nanotubes are widely used in biomedical studies. According to design the sensors can be divided into three groups: (i) sensors based on a carbon nanotube array; (ii) sensors manufactured by means of composites containing carbon nanotubes; (iii) sensors, which are electrodes with working surface containing carbon nanotubes. The development directions of sensors of the first and the second group, and also sensors of the third group which are manufactured by abrasive immobilization of carbon nanotubes on an electrode surface and by solvent dispersion and casting immobilization of carbon nanotubes on an electrode surface by means of N,N-dimethylformamide, surfactants, and Nafion are analyzed. The general information on manufacturing techniques of these sensors is given. The opportunities of these sensors for biomedical researches are demonstrated.
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Carbon nanotubes (CNTs) have unique atomic structure, as well as outstanding thermal, mechanical, and electronic properties, making them extremely attractive materials for several different applications. Many research groups are focusing on biomedical applications of carbon-based nanomaterials, however the application of CNTs to the biomedical field is not developing as fast as in other areas. While CNTs-based products are already being used in textiles, polymer matrices to strengthen materials, sports articles, microelectronics, energy storage, etc., medicinal products and medical devices for in vivo application based on CNTs have not been commercialized yet. However, CNTs for biomedical application, i.e., CNTs conjugated to siRNA for cancer therapy, or CNTs for imaging of colorectal cancer and many other products may enter clinical trials in the next years. Concerns related to the toxicity of CNTs must be overcome in order to have these products commercialized in a near future. This article reviews emerging biomedical applications of CNTs, specifically for therapy. It also deals with challenges associated with possible medical applications of CNTs, such as their not fully understood toxicological profile in the human body.
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[Electrochemical sensors based on carbon nanotubes and their use in biomedical research].
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Electrochemical sensors based on carbon nanotubes are widely used in biomedical studies. According to design the sensors can be divided into three groups: (i) sensors based on a carbon nanotube array; (ii) sensors manufactured by means of composites containing carbon nanotubes; (iii) sensors, which are electrodes with working surface containing carbon nanotubes. The development directions of sensors of the first and the second group, and also sensors of the third group which are manufactured by abrasive immobilization of carbon nanotubes on an electrode surface and by solvent dispersion and casting immobilization of carbon nanotubes on an electrode surface by means of N,N-dimethylformamide, surfactants, and Nafion are analyzed. The general information on manufacturing techniques of these sensors is given. The opportunities of these sensors for biomedical researches are demonstrated.
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Carbon materials (CMs), such as carbon nanotubes (CNTs), carbon nanofibers (CNFs), and carbon microparticles (CMPs) are used as doping materials for electrochemical sensors. The efficiency of these materials (either before or after acidic treatments) while being used as electrocatalysts in electrochemical sensors is discussed for beta-nicotinamide adenine dinucleotide (NADH) detection using cyclic voltammetry (CV). The sensitivity of the electrodes (glassy carbon (GC) and gold (Au)) modified with both treated and untreated materials have been deeply studied. The response efficiencies of the GC and Au electrodes modified with CNF and CMP, using dimethylformamide (DMF) as dispersing agent are significantly different due to the peculiar physical and chemical characteristics of each doping material. Several differences between the electrocatalytic activities of CMs modified electrodes upon NADH oxidation have been observed. The CNF film promotes better the electron transfer of NADH minimizing the oxidation potential at +0.352 V. Moreover higher currents for the NADH oxidation peak have been observed for these electrodes. The shown differences in the electrochemical reactivities of CNF and CMP modified electrodes should be with interest for future applications in biosensors.
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[Electrochemical sensors based on carbon nanotubes and their use in biomedical research].
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Electrochemical sensors based on carbon nanotubes are widely used in biomedical studies. According to design the sensors can be divided into three groups: (i) sensors based on a carbon nanotube array; (ii) sensors manufactured by means of composites containing carbon nanotubes; (iii) sensors, which are electrodes with working surface containing carbon nanotubes. The development directions of sensors of the first and the second group, and also sensors of the third group which are manufactured by abrasive immobilization of carbon nanotubes on an electrode surface and by solvent dispersion and casting immobilization of carbon nanotubes on an electrode surface by means of N,N-dimethylformamide, surfactants, and Nafion are analyzed. The general information on manufacturing techniques of these sensors is given. The opportunities of these sensors for biomedical researches are demonstrated.
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Carbon nanotubes are nano-sized cylindrical chicken wire-like structures made of carbon atoms. Carbon nanotubes have applications in electronics, energy storage, electromagnetic devices, environmental remediation and medicine as well. The biomedical applications of carbon nanotubes can be owed to features like low toxicity, non-immunogenicity, high in vivo stability and rapid cell entry. Carbon nanotubes have a great prospect in the treatment of diseases through diagnostic as well as therapeutic approaches. These nanostructures are interesting carriers for delivery and translocation of therapeutic molecules e.g. proteins, peptides, nucleic acids, drugs, etc. to various organs like the brain, lungs, liver, and pancreas. Commonly used methods to synthesize carbon nanotubes are arc discharge, chemical vapor deposition, pyrolysis, laser ablation etc. These methods have many disadvantages such as operation at high temperature, use of chemical catalysts, prolonged synthesis time and inclusion of toxic metallic particles in the final product requiring additional purification processes. In order to avoid these setbacks, various green chemistry-based synthetic methods have been devised, e.g., those involving interfacial polymerization, supercritical carbon dioxide drying, plant extract assisted synthesis, water- assisted synthesis, etc. This review will provide a thorough outlook of the eco-friendly synthesis of carbon nanotubes reported in the literature and their biomedical applications. Besides, the most commonly used spectroscopic techniques used for the characterization of carbon nanotubes are also discussed.
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[Electrochemical sensors based on carbon nanotubes and their use in biomedical research].
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Electrochemical sensors based on carbon nanotubes are widely used in biomedical studies. According to design the sensors can be divided into three groups: (i) sensors based on a carbon nanotube array; (ii) sensors manufactured by means of composites containing carbon nanotubes; (iii) sensors, which are electrodes with working surface containing carbon nanotubes. The development directions of sensors of the first and the second group, and also sensors of the third group which are manufactured by abrasive immobilization of carbon nanotubes on an electrode surface and by solvent dispersion and casting immobilization of carbon nanotubes on an electrode surface by means of N,N-dimethylformamide, surfactants, and Nafion are analyzed. The general information on manufacturing techniques of these sensors is given. The opportunities of these sensors for biomedical researches are demonstrated.
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Methods of electrochemical analysis of biological objects based on the reaction of electro-oxidation/electro-reduction of molecules are presented. Polymer nanocomposite materials that modify electrodes to increase sensitivity of electrochemical events on the surface of electrodes are described. Examples of applications electrochemical biosensors constructed with nanocomposite material for detection of biological molecules are presented, advantages and drawbacks of different applications are discussed.
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Exploring transmembrane allostery in the MexB: DB08385 variant as a promising inhibitor-like candidate against <i>Pseudomonas aeruginosa</i> antibiotic resistance: a computational study.
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<i>Pseudomonas aeruginosa</i>, a formidable pathogen renowned for its antimicrobial resistance, poses a significant threat to immunocompromised individuals. In this regard, the MexAB-OprM efflux pump acts as a pivotal line of defense by extruding antimicrobials from bacterial cells. The inner membrane homotrimeric protein MexB captures antibiotics and translocates them into the outer membrane OprM channel protein connected through the MexA adaptor protein. Despite extensive efforts, competitive inhibitors targeting the tight (T) protomer of the MexB protein have not received FDA approval for medical use. Over the past few years, allosteric inhibitors have become popular as alternatives to the classical competitive inhibitor-based approach because of their higher specificity, lower dosage, and reduced toxicological effects. Hence, in this study, we unveiled the existence of a transmembrane allosteric binding pocket of MexB inspired by the recent discovery of an important allosteric inhibitor, BDM88855, for the homolog AcrB protein. While repurposing BDM88855 proved ineffective in controlling the MexB loose (L) protomer, our investigation identified a promising alternative: a chlorine-containing variant of DB08385 (2-Cl DB08385 or Variant 1). Molecular dynamics simulations, including binding free energy estimation coupled with heterogeneous dielectric implicit membrane model (implicit-membrane MM/PBSA), interaction entropy (IE) analysis and potential of mean force (PMF) calculation, demonstrated Variant 1's superior binding affinity to the transmembrane pocket, displaying the highest energy barrier in the ligand unbinding process. To elucidate the allosteric crosstalk between the transmembrane and porter domain of MexB, we employed the 'eigenvector centrality' measure in the linear mutual information obtained from the protein correlation network. Notably, this study confirmed the presence of an allosteric transmembrane site in the MexB L protomer. In addition to this, Variant 1 emerged as a potent regulator of allosteric crosstalk, inducing an 'O-L intermediate state' in the MexB L protomer. This induced state might hold the potential to diminish substrate intake into the access pocket, leading to the ineffective efflux of antibiotics.
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Label="OBJECTIVES" NlmCategory="OBJECTIVE">Meropenem is commonly used against Pseudomonas aeruginosa. Traditionally, the time unbound antibiotic concentration exceeds the MIC (fT<sub>></sub><sub>MIC</sub>) is used to select carbapenem regimens. We aimed to characterize the effects of different baseline resistance mechanisms on bacterial killing and resistance emergence; evaluate whether fT<sub>></sub><sub>MIC</sub> can predict these effects; and, develop a novel Quantitative and Systems Pharmacology (QSP) model to describe the effects of baseline resistance mechanisms on the time-course of bacterial response.
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Exploring transmembrane allostery in the MexB: DB08385 variant as a promising inhibitor-like candidate against <i>Pseudomonas aeruginosa</i> antibiotic resistance: a computational study.
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<i>Pseudomonas aeruginosa</i>, a formidable pathogen renowned for its antimicrobial resistance, poses a significant threat to immunocompromised individuals. In this regard, the MexAB-OprM efflux pump acts as a pivotal line of defense by extruding antimicrobials from bacterial cells. The inner membrane homotrimeric protein MexB captures antibiotics and translocates them into the outer membrane OprM channel protein connected through the MexA adaptor protein. Despite extensive efforts, competitive inhibitors targeting the tight (T) protomer of the MexB protein have not received FDA approval for medical use. Over the past few years, allosteric inhibitors have become popular as alternatives to the classical competitive inhibitor-based approach because of their higher specificity, lower dosage, and reduced toxicological effects. Hence, in this study, we unveiled the existence of a transmembrane allosteric binding pocket of MexB inspired by the recent discovery of an important allosteric inhibitor, BDM88855, for the homolog AcrB protein. While repurposing BDM88855 proved ineffective in controlling the MexB loose (L) protomer, our investigation identified a promising alternative: a chlorine-containing variant of DB08385 (2-Cl DB08385 or Variant 1). Molecular dynamics simulations, including binding free energy estimation coupled with heterogeneous dielectric implicit membrane model (implicit-membrane MM/PBSA), interaction entropy (IE) analysis and potential of mean force (PMF) calculation, demonstrated Variant 1's superior binding affinity to the transmembrane pocket, displaying the highest energy barrier in the ligand unbinding process. To elucidate the allosteric crosstalk between the transmembrane and porter domain of MexB, we employed the 'eigenvector centrality' measure in the linear mutual information obtained from the protein correlation network. Notably, this study confirmed the presence of an allosteric transmembrane site in the MexB L protomer. In addition to this, Variant 1 emerged as a potent regulator of allosteric crosstalk, inducing an 'O-L intermediate state' in the MexB L protomer. This induced state might hold the potential to diminish substrate intake into the access pocket, leading to the ineffective efflux of antibiotics.
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In an effort to identify key domains of the Pseudomonas aeruginosa MexAB-OprM drug efflux system involved in component interactions, extragenic suppressors of various inactivating mutations in individual pump constituents were isolated and studied. The multidrug hypersusceptibility of P. aeruginosa expressing MexB with a mutation in a region of the protein implicated in oligomerization (G220S) was suppressed by mutations in the alpha/beta domain of MexA. MexB(G220S) showed a reduced ability to bind MexA in vivo while representative MexA suppressors (V66M and V259F) restored the MexA-MexB interaction. Interestingly, these suppressors also restored resistance in P. aeruginosa expressing OprM proteins with mutations at the proximal (periplasmic) tip of OprM that is predicted to interact with MexB, suggesting that these suppressors generally overcame defects in MexA-MexB and MexB-OprM interaction. The multidrug hypersusceptibility arising from a mutation in the helical hairpin of MexA implicated in OprM interaction (V129M) was suppressed by mutations (T198I and F439I) in the periplasmic alpha-helical barrel of OprM. Again, the MexA mutation compromised an in vivo interaction with OprM that was restored by the T198I and F439I substitutions in OprM, consistent with the hairpin domain mediating MexA binding to this region of OprM. Interestingly, these OprM suppressor mutations restored multidrug resistance in P. aeruginosa expressing MexB(G220S). Finally, the oprM(T198I) suppressor mutation enhanced the yields of all three constituents of a MexA-MexB-OprM(T198I) pump as detected in whole-cell extracts. These data highlight the importance of MexA and interactions with this adapter in promoting MexAB-OprM pump assembly and in stabilizing the pump complex.
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Exploring transmembrane allostery in the MexB: DB08385 variant as a promising inhibitor-like candidate against <i>Pseudomonas aeruginosa</i> antibiotic resistance: a computational study.
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<i>Pseudomonas aeruginosa</i>, a formidable pathogen renowned for its antimicrobial resistance, poses a significant threat to immunocompromised individuals. In this regard, the MexAB-OprM efflux pump acts as a pivotal line of defense by extruding antimicrobials from bacterial cells. The inner membrane homotrimeric protein MexB captures antibiotics and translocates them into the outer membrane OprM channel protein connected through the MexA adaptor protein. Despite extensive efforts, competitive inhibitors targeting the tight (T) protomer of the MexB protein have not received FDA approval for medical use. Over the past few years, allosteric inhibitors have become popular as alternatives to the classical competitive inhibitor-based approach because of their higher specificity, lower dosage, and reduced toxicological effects. Hence, in this study, we unveiled the existence of a transmembrane allosteric binding pocket of MexB inspired by the recent discovery of an important allosteric inhibitor, BDM88855, for the homolog AcrB protein. While repurposing BDM88855 proved ineffective in controlling the MexB loose (L) protomer, our investigation identified a promising alternative: a chlorine-containing variant of DB08385 (2-Cl DB08385 or Variant 1). Molecular dynamics simulations, including binding free energy estimation coupled with heterogeneous dielectric implicit membrane model (implicit-membrane MM/PBSA), interaction entropy (IE) analysis and potential of mean force (PMF) calculation, demonstrated Variant 1's superior binding affinity to the transmembrane pocket, displaying the highest energy barrier in the ligand unbinding process. To elucidate the allosteric crosstalk between the transmembrane and porter domain of MexB, we employed the 'eigenvector centrality' measure in the linear mutual information obtained from the protein correlation network. Notably, this study confirmed the presence of an allosteric transmembrane site in the MexB L protomer. In addition to this, Variant 1 emerged as a potent regulator of allosteric crosstalk, inducing an 'O-L intermediate state' in the MexB L protomer. This induced state might hold the potential to diminish substrate intake into the access pocket, leading to the ineffective efflux of antibiotics.
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Carbapenem resistance in <i>Pseudomonas aeruginosa</i> is primarily due to the acquisition of carbapenemases and is often associated with a diminution of the membrane permeability. The outer membrane protein, OprD, is a well-known route, by which carbapenems, predominantly imipenem, can enter the cell, and its loss has been associated with reduced susceptibility to imipenem. In this study, we investigated the antibiotic susceptibility patterns of isogenic <i>P. aeruginosa</i> mutants containing various acquired β-lactamases, including carbapenemases, in a porin-depleted background. We identified that the deletion of <i>oprF</i> was associated with some recovery of susceptibility to carbapenems.
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Exploring transmembrane allostery in the MexB: DB08385 variant as a promising inhibitor-like candidate against <i>Pseudomonas aeruginosa</i> antibiotic resistance: a computational study.
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<i>Pseudomonas aeruginosa</i>, a formidable pathogen renowned for its antimicrobial resistance, poses a significant threat to immunocompromised individuals. In this regard, the MexAB-OprM efflux pump acts as a pivotal line of defense by extruding antimicrobials from bacterial cells. The inner membrane homotrimeric protein MexB captures antibiotics and translocates them into the outer membrane OprM channel protein connected through the MexA adaptor protein. Despite extensive efforts, competitive inhibitors targeting the tight (T) protomer of the MexB protein have not received FDA approval for medical use. Over the past few years, allosteric inhibitors have become popular as alternatives to the classical competitive inhibitor-based approach because of their higher specificity, lower dosage, and reduced toxicological effects. Hence, in this study, we unveiled the existence of a transmembrane allosteric binding pocket of MexB inspired by the recent discovery of an important allosteric inhibitor, BDM88855, for the homolog AcrB protein. While repurposing BDM88855 proved ineffective in controlling the MexB loose (L) protomer, our investigation identified a promising alternative: a chlorine-containing variant of DB08385 (2-Cl DB08385 or Variant 1). Molecular dynamics simulations, including binding free energy estimation coupled with heterogeneous dielectric implicit membrane model (implicit-membrane MM/PBSA), interaction entropy (IE) analysis and potential of mean force (PMF) calculation, demonstrated Variant 1's superior binding affinity to the transmembrane pocket, displaying the highest energy barrier in the ligand unbinding process. To elucidate the allosteric crosstalk between the transmembrane and porter domain of MexB, we employed the 'eigenvector centrality' measure in the linear mutual information obtained from the protein correlation network. Notably, this study confirmed the presence of an allosteric transmembrane site in the MexB L protomer. In addition to this, Variant 1 emerged as a potent regulator of allosteric crosstalk, inducing an 'O-L intermediate state' in the MexB L protomer. This induced state might hold the potential to diminish substrate intake into the access pocket, leading to the ineffective efflux of antibiotics.
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The ability of antimicrobial resistance developed by bacteria enhanced the complexity of bacterial treatment leading a serious threat to human health. Production of β-lactamase by bacteria that inactivates β-lactam is a generic cause of resistance. One such β-lactamase enzyme is New Delhi Metallo-β-lactamase (NDM) which is recently reported to have clinically more importance and recognized as an antibiotic resistance marker. Mutations in active and passive residues of NDM protein play a fateful role in the substrate and inhibitor specificity. In this study, <i>in silico</i> point mutations of residues near the active site and flexible regions of protein were investigated. Hybrid modelling and molecular dynamics (MD) simulations were carried to build up the mutant models and monitored structural stability. Molecular docking results articulated that mutant proteins had lesser binding affinities with methicillin, oxacillin and doripenem drugs. Further, to scrutinize the structural alterations and rescore the binding energies per-residue basis, MD simulations of wildtype (WT) and mutant (MT) NDM proteins with methicillin, oxacillin and doripenem were performed. Our results demonstrated that mutations in N193A, S217A, G219A and T262A residues led to protein destabilization and amend their binding affinities with methicillin, oxacillin and doripenem. The present study exploited computational approaches which displayed differential binding of drugs with WT and MT NDM proteins that confer resistance to oxacillin and doripenem. The study features the significance of passive residues, thus provides a clue to accelerate the process of designing an ergastic antibiotic against NDM protein. Communicated by Ramaswamy H. Sarma.
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Exploring transmembrane allostery in the MexB: DB08385 variant as a promising inhibitor-like candidate against <i>Pseudomonas aeruginosa</i> antibiotic resistance: a computational study.
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<i>Pseudomonas aeruginosa</i>, a formidable pathogen renowned for its antimicrobial resistance, poses a significant threat to immunocompromised individuals. In this regard, the MexAB-OprM efflux pump acts as a pivotal line of defense by extruding antimicrobials from bacterial cells. The inner membrane homotrimeric protein MexB captures antibiotics and translocates them into the outer membrane OprM channel protein connected through the MexA adaptor protein. Despite extensive efforts, competitive inhibitors targeting the tight (T) protomer of the MexB protein have not received FDA approval for medical use. Over the past few years, allosteric inhibitors have become popular as alternatives to the classical competitive inhibitor-based approach because of their higher specificity, lower dosage, and reduced toxicological effects. Hence, in this study, we unveiled the existence of a transmembrane allosteric binding pocket of MexB inspired by the recent discovery of an important allosteric inhibitor, BDM88855, for the homolog AcrB protein. While repurposing BDM88855 proved ineffective in controlling the MexB loose (L) protomer, our investigation identified a promising alternative: a chlorine-containing variant of DB08385 (2-Cl DB08385 or Variant 1). Molecular dynamics simulations, including binding free energy estimation coupled with heterogeneous dielectric implicit membrane model (implicit-membrane MM/PBSA), interaction entropy (IE) analysis and potential of mean force (PMF) calculation, demonstrated Variant 1's superior binding affinity to the transmembrane pocket, displaying the highest energy barrier in the ligand unbinding process. To elucidate the allosteric crosstalk between the transmembrane and porter domain of MexB, we employed the 'eigenvector centrality' measure in the linear mutual information obtained from the protein correlation network. Notably, this study confirmed the presence of an allosteric transmembrane site in the MexB L protomer. In addition to this, Variant 1 emerged as a potent regulator of allosteric crosstalk, inducing an 'O-L intermediate state' in the MexB L protomer. This induced state might hold the potential to diminish substrate intake into the access pocket, leading to the ineffective efflux of antibiotics.
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The global crisis of antibiotic resistance increases the demand for the novel promising alternative drugs such as antimicrobial peptides (AMPs). Here, the antibiofilm activity of the WLBU2 peptide against Pseudomonas aeruginosa (P. aeruginosa) isolates was investigated in this study.
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Patient Blood Management Program Implementation: Comprehensive Recommendations and Practical Strategies.
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Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems.
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Health education and self-management are among key strategies for managing diabetes and hypertension to reduce morbidity and mortality. Inappropriate self-management support can potentially worsen chronic diseases outcomes if relevant barriers are not identified and self-management solutions are not contextualised. Few studies deliberately solicit suggestions for enhancing self-management from patients and their providers.
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Patient Blood Management Program Implementation: Comprehensive Recommendations and Practical Strategies.
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Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems.
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Clinical guidelines are support tools, aiming to improve quality of the clinical practice. Patient centered care allows best satisfaction rates, with greater health self-management, and potential gains in quality with fewer costs.
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Patient Blood Management Program Implementation: Comprehensive Recommendations and Practical Strategies.
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Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems.
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How to summarize and facilitate the implementation of national and international guidelines in clinical practice? To adress these issues, we present a summary of dyslipidemia management for general practitioners. To achieve these aims, we adopted strategies based on international and national guidelines and focused on clinical applications which implies to choose specific options, such as the use of cardiovascular risk score and specific therapies as first options.
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Patient Blood Management Program Implementation: Comprehensive Recommendations and Practical Strategies.
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Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems.
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Best practices comprise recent, relevant, and helpful nursing practices, methods, interventions, procedures or techniques based on high-quality evidence. Best practices should be implemented to improve individual patients' health outcomes the overall quality of health care, and to strengthen the health system at large. Four facilitators (benefit levers) to effectively roll-out best practices in healthcare organizations were identified: alignment, permeation plans, leadership for change, as well as supporting and reinforcing structures.
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Patient Blood Management Program Implementation: Comprehensive Recommendations and Practical Strategies.
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Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems.
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To identify the barriers and enablers to implementing clinical practice guidelines (CPGs) recommendations in primary care and to provide recommendations that could facilitate the uptake of CPGs recommendations.
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Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar.
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PPAR (peroxisome proliferator-activated receptor) pan agonists play a critical role in treating metabolic diseases, especially the Type-2 diabetes mellitus (T2DM). GlaxoSmithKline's sodelglitazar (GW677954) is one of the potent PPAR pan agonists, which is currently being investigated in Phase II clinical trials for the treatment of T2DM and its complications. The present study was aimed at investigation into the effect of sodelglitazar at the binding pockets of PPARs. The Schrodinger Suite program (2009) was used for the molecular docking, while the GROMACS program used for the molecular dynamics (MD) simulations. The results thus obtained showed that sodelglitazar being docked well in the active site of PPARs. It was revealed by the MD simulations that the structures of the receptors remained quite stable during the simulations and that the important AF-2 helix showed less flexibility after binding with sodelglitazar. Also, it was observed that sodelglitazar could periodically form hydrogen bonds with the AF-2 helix of PPARs to stabilize the AF-2 helix in an active conformation. Our findings have confirmed that GlaxoSmithKline's sodelglitazar can activate the PPARs, which is quite consistent with the previous biological studies.
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To investigate the expression and significance of peroxisome proliferators-activated receptor gamma (PPAR gamma) in human glioma.
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Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar.
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PPAR (peroxisome proliferator-activated receptor) pan agonists play a critical role in treating metabolic diseases, especially the Type-2 diabetes mellitus (T2DM). GlaxoSmithKline's sodelglitazar (GW677954) is one of the potent PPAR pan agonists, which is currently being investigated in Phase II clinical trials for the treatment of T2DM and its complications. The present study was aimed at investigation into the effect of sodelglitazar at the binding pockets of PPARs. The Schrodinger Suite program (2009) was used for the molecular docking, while the GROMACS program used for the molecular dynamics (MD) simulations. The results thus obtained showed that sodelglitazar being docked well in the active site of PPARs. It was revealed by the MD simulations that the structures of the receptors remained quite stable during the simulations and that the important AF-2 helix showed less flexibility after binding with sodelglitazar. Also, it was observed that sodelglitazar could periodically form hydrogen bonds with the AF-2 helix of PPARs to stabilize the AF-2 helix in an active conformation. Our findings have confirmed that GlaxoSmithKline's sodelglitazar can activate the PPARs, which is quite consistent with the previous biological studies.
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The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that contribute to the regulation of lipid, glucose and cholesterol homeostases. They are considered as therapeutic targets for metabolic diseases such as dyslipidemia and type 2 diabetes mellitus. Various PPAR agonists have been developed, but most of them contain a carboxylic acid (CA) or thiazolidinedione (TZD) moiety, which is essential for the activity. However, we recently discovered non-CA/non-TZD class PPARα/δ dual agonists having an acetamide structure. Here, we describe structure-activity relationship (SAR) studies of these novel acetamide-based PPARα/δ dual agonists. The SAR studies revealed that the acetamide functionality and adjacent methyl group contribute greatly to the agonistic activity. Compound (S)-10 was the most potent PPARα/δ dual agonist among the compounds synthesized (PPARα EC<sub>50</sub>=17nM, PPARδ EC<sub>50</sub>=23nM).
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Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar.
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PPAR (peroxisome proliferator-activated receptor) pan agonists play a critical role in treating metabolic diseases, especially the Type-2 diabetes mellitus (T2DM). GlaxoSmithKline's sodelglitazar (GW677954) is one of the potent PPAR pan agonists, which is currently being investigated in Phase II clinical trials for the treatment of T2DM and its complications. The present study was aimed at investigation into the effect of sodelglitazar at the binding pockets of PPARs. The Schrodinger Suite program (2009) was used for the molecular docking, while the GROMACS program used for the molecular dynamics (MD) simulations. The results thus obtained showed that sodelglitazar being docked well in the active site of PPARs. It was revealed by the MD simulations that the structures of the receptors remained quite stable during the simulations and that the important AF-2 helix showed less flexibility after binding with sodelglitazar. Also, it was observed that sodelglitazar could periodically form hydrogen bonds with the AF-2 helix of PPARs to stabilize the AF-2 helix in an active conformation. Our findings have confirmed that GlaxoSmithKline's sodelglitazar can activate the PPARs, which is quite consistent with the previous biological studies.
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PPARs are nuclear receptors with a critical physiological role in lipid and glucose metabolism. As part of our effort to develop new and selective PPAR agonists containing stilbene and its bioisoster phenyldiazene, novel analogs were synthesized starting from tyrosine and evaluated as PPAR agonists. We tested the effects of phenyloxazole replacement of GW409544, a well-known PPARα/γ dual agonist, with stilbene or phenyldiazene moiety, spaced by an ether bridge to tyrosine portion. These structural modifications provided potent and selective PPARγ agonists. Molecular docking studies performed on these new compounds complemented the experimental results and allowed to gain some insights into the nature of binding of the ligands.
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Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar.
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PPAR (peroxisome proliferator-activated receptor) pan agonists play a critical role in treating metabolic diseases, especially the Type-2 diabetes mellitus (T2DM). GlaxoSmithKline's sodelglitazar (GW677954) is one of the potent PPAR pan agonists, which is currently being investigated in Phase II clinical trials for the treatment of T2DM and its complications. The present study was aimed at investigation into the effect of sodelglitazar at the binding pockets of PPARs. The Schrodinger Suite program (2009) was used for the molecular docking, while the GROMACS program used for the molecular dynamics (MD) simulations. The results thus obtained showed that sodelglitazar being docked well in the active site of PPARs. It was revealed by the MD simulations that the structures of the receptors remained quite stable during the simulations and that the important AF-2 helix showed less flexibility after binding with sodelglitazar. Also, it was observed that sodelglitazar could periodically form hydrogen bonds with the AF-2 helix of PPARs to stabilize the AF-2 helix in an active conformation. Our findings have confirmed that GlaxoSmithKline's sodelglitazar can activate the PPARs, which is quite consistent with the previous biological studies.
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The nuclear receptors Peroxisome Proliferator-Activated Receptors (PPAR)α and PPARγ are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively. Evidence is now emerging that the PPARβ/δ isotype is a potential pharmacological target for the treatment of insulin resistance and type 2 diabetes mellitus.
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Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar.
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PPAR (peroxisome proliferator-activated receptor) pan agonists play a critical role in treating metabolic diseases, especially the Type-2 diabetes mellitus (T2DM). GlaxoSmithKline's sodelglitazar (GW677954) is one of the potent PPAR pan agonists, which is currently being investigated in Phase II clinical trials for the treatment of T2DM and its complications. The present study was aimed at investigation into the effect of sodelglitazar at the binding pockets of PPARs. The Schrodinger Suite program (2009) was used for the molecular docking, while the GROMACS program used for the molecular dynamics (MD) simulations. The results thus obtained showed that sodelglitazar being docked well in the active site of PPARs. It was revealed by the MD simulations that the structures of the receptors remained quite stable during the simulations and that the important AF-2 helix showed less flexibility after binding with sodelglitazar. Also, it was observed that sodelglitazar could periodically form hydrogen bonds with the AF-2 helix of PPARs to stabilize the AF-2 helix in an active conformation. Our findings have confirmed that GlaxoSmithKline's sodelglitazar can activate the PPARs, which is quite consistent with the previous biological studies.
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In order to define new PPARbeta/delta ligands, SAR study on the selective PPARbeta/delta activator L-165,041 led to the identification of one key functional group for selective PPARbeta/delta activation. Furthermore, taking advantage of SAR studies done elsewhere on the most selective PPARbeta/delta ligand GW501516, the conception of new ligands showing good affinity for PPARbeta/delta is reported. Finally, synthesis and biological evaluation of pyridine analogues have shown the benefical effect of the pyridine ring on the PPARbeta/delta subtype selectivity.
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Accessing the stapedius muscle via novel surgical retrofacial approach during cochlear implantation surgery: Intraoperative results on feasibility and safety.
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Human stapedius muscle (SM) can be directly and safely accessed via retrofacial approach, opening new approaches to directly measure the electrically evoked stapedius reflex threshold (eSRT). The measurement of the SM activity via direct surgical access represents a potential tool for objective eSRT fitting of cochlear implants (CI), increasing the benefit experienced by the CI users and leading to new perspectives in the development of smart implantable neurostimulators. 3D middle-ear reconstructions created after manual segmentation and related SM accessibility metrics were evaluated before the CI surgery for 16 candidates with assessed stapedius reflex. Retrofacial approach to access the SM was performed after facial recess exposure. In cases of poor exposition of SM, the access was performed anteriorly to the FN via drilling of the pyramidal eminence (PE). The total access rate of the SM via both the retrofacial and anterior approach of the FN was 100%. In 81.2% of cases (13/16), the retrofacial approach allowed to access the SM on previously categorized well exposed (8/8), partially exposed (4/5), and wholly concealed (1/3) SM with respect to FN. Following intraoperative evaluation in the remaining 18.8% (3/16), the SM was accessed anteriorly via drilling of the PE. Exposure of SM with respect to the FN and the sigmoid sinus's prominence was a predictor for the suitable surgical approach. The retrofacial approach offers feasible and reproducible access to the SM belly, opening direct access to electromyographic sensing of the eSRT. Surgical planner tools can quantitatively assist pre-surgical assessment.
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We developed a novel keyhole surgery, named "percutaneous endoscopic ear surgery" (PEES), with the aim of further reducing the invasiveness of otologic surgery. We reported the cases we encountered and retrospectively analyzed the invasiveness of PEES.
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Accessing the stapedius muscle via novel surgical retrofacial approach during cochlear implantation surgery: Intraoperative results on feasibility and safety.
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Human stapedius muscle (SM) can be directly and safely accessed via retrofacial approach, opening new approaches to directly measure the electrically evoked stapedius reflex threshold (eSRT). The measurement of the SM activity via direct surgical access represents a potential tool for objective eSRT fitting of cochlear implants (CI), increasing the benefit experienced by the CI users and leading to new perspectives in the development of smart implantable neurostimulators. 3D middle-ear reconstructions created after manual segmentation and related SM accessibility metrics were evaluated before the CI surgery for 16 candidates with assessed stapedius reflex. Retrofacial approach to access the SM was performed after facial recess exposure. In cases of poor exposition of SM, the access was performed anteriorly to the FN via drilling of the pyramidal eminence (PE). The total access rate of the SM via both the retrofacial and anterior approach of the FN was 100%. In 81.2% of cases (13/16), the retrofacial approach allowed to access the SM on previously categorized well exposed (8/8), partially exposed (4/5), and wholly concealed (1/3) SM with respect to FN. Following intraoperative evaluation in the remaining 18.8% (3/16), the SM was accessed anteriorly via drilling of the PE. Exposure of SM with respect to the FN and the sigmoid sinus's prominence was a predictor for the suitable surgical approach. The retrofacial approach offers feasible and reproducible access to the SM belly, opening direct access to electromyographic sensing of the eSRT. Surgical planner tools can quantitatively assist pre-surgical assessment.
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To analyse the safety and effectiveness of a microsurgical unilateral approach in minimally invasive surgery of extramedullary, intradural spinal tumours.
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Accessing the stapedius muscle via novel surgical retrofacial approach during cochlear implantation surgery: Intraoperative results on feasibility and safety.
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Human stapedius muscle (SM) can be directly and safely accessed via retrofacial approach, opening new approaches to directly measure the electrically evoked stapedius reflex threshold (eSRT). The measurement of the SM activity via direct surgical access represents a potential tool for objective eSRT fitting of cochlear implants (CI), increasing the benefit experienced by the CI users and leading to new perspectives in the development of smart implantable neurostimulators. 3D middle-ear reconstructions created after manual segmentation and related SM accessibility metrics were evaluated before the CI surgery for 16 candidates with assessed stapedius reflex. Retrofacial approach to access the SM was performed after facial recess exposure. In cases of poor exposition of SM, the access was performed anteriorly to the FN via drilling of the pyramidal eminence (PE). The total access rate of the SM via both the retrofacial and anterior approach of the FN was 100%. In 81.2% of cases (13/16), the retrofacial approach allowed to access the SM on previously categorized well exposed (8/8), partially exposed (4/5), and wholly concealed (1/3) SM with respect to FN. Following intraoperative evaluation in the remaining 18.8% (3/16), the SM was accessed anteriorly via drilling of the PE. Exposure of SM with respect to the FN and the sigmoid sinus's prominence was a predictor for the suitable surgical approach. The retrofacial approach offers feasible and reproducible access to the SM belly, opening direct access to electromyographic sensing of the eSRT. Surgical planner tools can quantitatively assist pre-surgical assessment.
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The objective of the present biomechanical and clinical study was to evaluate the consequences of the preservation of stapedius muscle tendon during stapedoplasty. The biomechanical investigations included mathematical simulation with the construction of the model based on the kinematic approach. The comparative clinical study of the results of stapedoplasty carried out between 2001 and 2010 involved 340 patients (77 men and 263 women) at the mean age of 48.18 years. Twenty patients underwent piston stapedoplasty by the method of Shi, 320 ones were treated by stapedoplasty with the preservation of stapedius muscle tendon. The state of speech hearing and the audiometric air-bone gap (ABG) were deduced from the audiograms. The biomechanical study demonstrated a significant increase in the range of the movements of the long crus of the incus, after the removal of the stapedius tendon muscle and the preservation in part of the acoustic reflex in case of tendon preservation. The preservation of the tendon partly dampened excessive sound vibrations. The clinical study revealed the improvement of speech hearing parameters throughout the three-year postoperative follow-up period; it was especially pronounced within the first year after surgery with the preservation of stapedius muscle tendon. The size of ABG at a the frequencies falling in the 0.5-1 kHz and 6-8 kHz ranges after surgery with the preservation of stapedius muscle tendon was smaller than after the removal of the tendon during the three-year follow-up (p<0.005). The difference was especially well-apparent within the first year after stapedoplasty. The difference in this parameter between the interventions with the preservation of stapedius muscle tendon and with its removal was insignificant (p>0.05).
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Accessing the stapedius muscle via novel surgical retrofacial approach during cochlear implantation surgery: Intraoperative results on feasibility and safety.
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Human stapedius muscle (SM) can be directly and safely accessed via retrofacial approach, opening new approaches to directly measure the electrically evoked stapedius reflex threshold (eSRT). The measurement of the SM activity via direct surgical access represents a potential tool for objective eSRT fitting of cochlear implants (CI), increasing the benefit experienced by the CI users and leading to new perspectives in the development of smart implantable neurostimulators. 3D middle-ear reconstructions created after manual segmentation and related SM accessibility metrics were evaluated before the CI surgery for 16 candidates with assessed stapedius reflex. Retrofacial approach to access the SM was performed after facial recess exposure. In cases of poor exposition of SM, the access was performed anteriorly to the FN via drilling of the pyramidal eminence (PE). The total access rate of the SM via both the retrofacial and anterior approach of the FN was 100%. In 81.2% of cases (13/16), the retrofacial approach allowed to access the SM on previously categorized well exposed (8/8), partially exposed (4/5), and wholly concealed (1/3) SM with respect to FN. Following intraoperative evaluation in the remaining 18.8% (3/16), the SM was accessed anteriorly via drilling of the PE. Exposure of SM with respect to the FN and the sigmoid sinus's prominence was a predictor for the suitable surgical approach. The retrofacial approach offers feasible and reproducible access to the SM belly, opening direct access to electromyographic sensing of the eSRT. Surgical planner tools can quantitatively assist pre-surgical assessment.
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This paper explains and illustrates the surgical procedure, step by step, to close a dehiscence of Superior Semicircular Canal using a transmastoid approach. This approach has several advantages over the middle cranial fossa craniotomy. Firstly, the morbidity is substantially lower. Secondly, mastoid cortical bone graft is less likely to get reabsorbed than outer table temporal bone. Therefore, surgical result is bound to be better. Finally, most otologists are more familiar and feel more comfortable with the transmastoid route than with the middle fossa one.
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Accessing the stapedius muscle via novel surgical retrofacial approach during cochlear implantation surgery: Intraoperative results on feasibility and safety.
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Human stapedius muscle (SM) can be directly and safely accessed via retrofacial approach, opening new approaches to directly measure the electrically evoked stapedius reflex threshold (eSRT). The measurement of the SM activity via direct surgical access represents a potential tool for objective eSRT fitting of cochlear implants (CI), increasing the benefit experienced by the CI users and leading to new perspectives in the development of smart implantable neurostimulators. 3D middle-ear reconstructions created after manual segmentation and related SM accessibility metrics were evaluated before the CI surgery for 16 candidates with assessed stapedius reflex. Retrofacial approach to access the SM was performed after facial recess exposure. In cases of poor exposition of SM, the access was performed anteriorly to the FN via drilling of the pyramidal eminence (PE). The total access rate of the SM via both the retrofacial and anterior approach of the FN was 100%. In 81.2% of cases (13/16), the retrofacial approach allowed to access the SM on previously categorized well exposed (8/8), partially exposed (4/5), and wholly concealed (1/3) SM with respect to FN. Following intraoperative evaluation in the remaining 18.8% (3/16), the SM was accessed anteriorly via drilling of the PE. Exposure of SM with respect to the FN and the sigmoid sinus's prominence was a predictor for the suitable surgical approach. The retrofacial approach offers feasible and reproducible access to the SM belly, opening direct access to electromyographic sensing of the eSRT. Surgical planner tools can quantitatively assist pre-surgical assessment.
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Minimally invasive cardiac surgery (MICS) has attracted increasing attention, with institutions increasingly adopting this approach over conventional median sternotomy (MS). This study aimed to describe the outcomes of minimally invasive cardiac surgery in our institution as the only centre with an established MICS programme in Singapore.
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Discrimination of three medicinal materials from the Citrus genus by HPLC fingerprint coupled with two complementary software.
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Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride and Fructus Aurantii come from the fruit of Citrus genus and possess analogous pharmacological activities. Either two or three of them are often present in one preparation. However, there is no standard method to differentiate the three herbal medicines for quality control.
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The composition of traditional Chinese medicine is extremely complex, so it is difficult to ensure quality consistency. We took Compound Danshen Tablets as the object of the study, by using high-performance liquid chromatography to establish multiwavelength fusion fingerprints. Characteristic fingerprints of 30 batches of samples were generated at four wavelengths and evaluated by systematic quantified fingerprint method. An on-line antioxidant determination method was used for the determination of the antioxidant components in Compound Danshen Tablets. The fingerprint analysis of the marker compounds can reflect the content of the marker compounds, which were determined by using the external standard method. This study elucidated that multiwavelength fusion fingerprint profiles and multiple markers compound analysis in conjunction with the assay of antioxidant activity offered a reliable and efficient approach to quantitatively evaluate the quality consistency of the traditional Chinese medicine and herbal preparations.
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Discrimination of three medicinal materials from the Citrus genus by HPLC fingerprint coupled with two complementary software.
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Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride and Fructus Aurantii come from the fruit of Citrus genus and possess analogous pharmacological activities. Either two or three of them are often present in one preparation. However, there is no standard method to differentiate the three herbal medicines for quality control.
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In this study, we aim to determine the chemical constituents of six Chinese medicinal materials from the Citrus genus using high-performance liquid chromatography and high-resolution mass spectrometry. Eight flavonoids and one coumarin were identified and further quantified as marker substances by high-performance liquid chromatography method. The separation was performed on an Agilent TC-C<sub>18</sub> column with 0.1% formic acid and acetonitrile as the mobile phase under gradient elution. The analytical method was fully validated in terms of linearity, sensitivity, intra- and inter-day precision and repeatability, limit of detection, limit of quantitation, and recovery. It was subsequently applied to evaluate the quality of 103 batches of the Chinese medicinal materials from the Citrus genus. In addition, the principal constituent analysis was used to compare the samples of different species from the Citrus genus leading to successful classification of the samples in accordance with their origins. It was found that the contents of nine constituents varied greatly in different ripening stages and varieties of the samples from the Citrus genus. In addition, neoeriocitrin and 5,7-dimethoxycoumarin were determined as two unique constituents of 'Zhiqiao' and 'Foshou', respectively. In conclusion, this study provides a chemical basis for quality control of Chinese medicinal materials from the Citrus genus.
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Discrimination of three medicinal materials from the Citrus genus by HPLC fingerprint coupled with two complementary software.
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Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride and Fructus Aurantii come from the fruit of Citrus genus and possess analogous pharmacological activities. Either two or three of them are often present in one preparation. However, there is no standard method to differentiate the three herbal medicines for quality control.
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The detection of regulated and forbidden herbs in pharmaceutical preparations and nutritional supplements is a growing problem for laboratories charged with the analysis of illegal pharmaceutical preparations and counterfeit medicines. This article presents a feasibility study of the use of chromatographic fingerprints for the detection of plants in pharmaceutical preparations. Fingerprints were developed for three non-regulated common herbal products--Rhamnus purshiana, Passiflora incarnata L. and Crataegus monogyna--and this was done by combining three different types of detection: diode-array detection, evaporative light scattering detection and mass spectrometry. It is shown that these plants could be detected in respective triturations of the dry extracts with lactose and three different herbal matrices as well as in commercial preparations purchased on the open market.
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Discrimination of three medicinal materials from the Citrus genus by HPLC fingerprint coupled with two complementary software.
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Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride and Fructus Aurantii come from the fruit of Citrus genus and possess analogous pharmacological activities. Either two or three of them are often present in one preparation. However, there is no standard method to differentiate the three herbal medicines for quality control.
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This study utilized computer vision to extract color and texture features of Pericarpium Citri Reticulatae (PCR). The ultra-fast gas-phase electronic nose (UF-GC-E-nose) technique successfully identified 98 volatile components, including olefins, alcohols, and esters, which significantly contribute to the flavor profile of PCR. Multivariate statistical Analysis was applied to the appearance traits of PCR, identifying 57 potential marker-trait factors (VIP > 1 and P < 0.05) from the 118 trait factors that can distinguish PCR from different origins. These factors include color, texture, and odor traits. By integrating multivariate statistical Analysis with the BP neural network algorithm, a novel artificial intelligence algorithm was developed and optimized for traceability of PCR origin. This algorithm achieved a 100% discrimination rate in differentiating PCR samples from various origins. This study offers a valuable reference and data support for developing intelligent algorithms that utilize data fusion from multiple intelligent sensory technologies to achieve rapid traceability of food origins.
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Discrimination of three medicinal materials from the Citrus genus by HPLC fingerprint coupled with two complementary software.
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Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride and Fructus Aurantii come from the fruit of Citrus genus and possess analogous pharmacological activities. Either two or three of them are often present in one preparation. However, there is no standard method to differentiate the three herbal medicines for quality control.
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To establish HPLC fingerprint of Prunella vulgaris and provide evidence for quality control and identification of the Chinese crude drug.
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[Age-related changes in the psychophysiological parameters in male teenagers].
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The time course of changes in the time of a simple visuaI motor reaction, force and lability of the nervous system, stability of attention and memory was studied in 2104 urban and rural males aged 18-27 years to develop standard phychophysiological status rating tables. It was shown that the score of the central nervous system should be used to detect some functional impairments of the central nervous system. Positive changes in higher nervous performance were noted, which were more pronounced in young rural males. Rating scales were developed to diagnose the individual characteristics of the central nervous system in young men of call-up age.
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We assessed the significance of psycho physiological markers of accelerated aging of the function of attention using comparative analysis of two occupational groups in order to reveal how the working process affects mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that decrease in the mnestic functions of lorry-drivers takes place 10-15 years earlier compared to the control group. Psycho physiological indices, reflecting the functioning of attention, decreased not only with aging but also with longer driving experience. Our results show that it is necessary to conduct further studies of psycho physiological markers of age-related decrease in short-term memory depending on the activities at work in order to prevent accelerated aging and achieve professional longevity.
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[Age-related changes in the psychophysiological parameters in male teenagers].
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The time course of changes in the time of a simple visuaI motor reaction, force and lability of the nervous system, stability of attention and memory was studied in 2104 urban and rural males aged 18-27 years to develop standard phychophysiological status rating tables. It was shown that the score of the central nervous system should be used to detect some functional impairments of the central nervous system. Positive changes in higher nervous performance were noted, which were more pronounced in young rural males. Rating scales were developed to diagnose the individual characteristics of the central nervous system in young men of call-up age.
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This Mini-Review describes sex differences in 66 quantitative characteristics of the brain and body measured in a community-based sample of 1,024 adolescents 12-18 years of age, members of the Saguenay Youth Study. Using an extensive phenotyping protocol, we have obtained measures in a number of domains, including brain structure, cognition, mental health, substance use, body composition, metabolism, cardiovascular reactivity, and life style. For each measure, we provide estimates of effect size (Cohen's d) and sex-specific correlations with age (Pearson R). In total 59 of the 66 characteristics showed sex differences (at a nominal P < 0.05), with small (32), medium-sized (13), and large (11) effects. Some, but not all, of these sex differences increase during adolescence; this appears to be the case mostly for anatomical and physiological measures. © 2016 Wiley Periodicals, Inc.
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[Age-related changes in the psychophysiological parameters in male teenagers].
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The time course of changes in the time of a simple visuaI motor reaction, force and lability of the nervous system, stability of attention and memory was studied in 2104 urban and rural males aged 18-27 years to develop standard phychophysiological status rating tables. It was shown that the score of the central nervous system should be used to detect some functional impairments of the central nervous system. Positive changes in higher nervous performance were noted, which were more pronounced in young rural males. Rating scales were developed to diagnose the individual characteristics of the central nervous system in young men of call-up age.
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To analyze sex differences in the prevalence of obesity phenotypes and their risk factors among children and adolescents aged 7-18 years in China.
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[Age-related changes in the psychophysiological parameters in male teenagers].
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The time course of changes in the time of a simple visuaI motor reaction, force and lability of the nervous system, stability of attention and memory was studied in 2104 urban and rural males aged 18-27 years to develop standard phychophysiological status rating tables. It was shown that the score of the central nervous system should be used to detect some functional impairments of the central nervous system. Positive changes in higher nervous performance were noted, which were more pronounced in young rural males. Rating scales were developed to diagnose the individual characteristics of the central nervous system in young men of call-up age.
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The aim of this study was to find stabilometric parameters, the values of which correlate with chronological age. The results of the standard stabilometric test with open and closed eyes, which obtained during the examination of 87 people aged from 20 to 70 years, were considered. Basic, vector and frequency indicators of 618 tests (334 with open eyes and 284 with closed eyes) were analyzed. The necessity of using different stabilometric parameters for determining the biological age for male and female is substantiated. The ratio of the average angular speed to the average linear speed of pressure center movement corresponds for men and the average angular speed is suitable for women. The models and regression equations that determine the statistically significant dependence of the parameters on age are revealed. These parameters can be used as markers that represent state of locomotor system in biological-age determination complex methods.
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[Age-related changes in the psychophysiological parameters in male teenagers].
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The time course of changes in the time of a simple visuaI motor reaction, force and lability of the nervous system, stability of attention and memory was studied in 2104 urban and rural males aged 18-27 years to develop standard phychophysiological status rating tables. It was shown that the score of the central nervous system should be used to detect some functional impairments of the central nervous system. Positive changes in higher nervous performance were noted, which were more pronounced in young rural males. Rating scales were developed to diagnose the individual characteristics of the central nervous system in young men of call-up age.
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Subjective symptoms of Internet addiction (IA), such as interpersonal and health-related problems (IH-RP), do not correlate with objective physiological parameters. This study aimed to investigate the cardiovascular reactivity after physical exercise in 15-16-year-old adolescents showing different severities of symptoms of health-related problems due to Internet overuse.
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Sex-specific effects of albumen removal and nest environment manipulation on Barn Swallow nestlings.
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In avian species, maternal provisioning to the eggs is predicted to be more valuable for the offspring under adverse environmental conditions and intense sibling competition. However, studies manipulating both the amount of maternal pre-hatching resources and the harshness of post-hatching environment have seldom been performed to date. In this experimental study of Barn Swallow (Hirundo rustica) nestlings, we tested the consequences of a reduction in the albumen content of the eggs for fitness-related offspring traits, while performing an unbalanced partial cross-fostering soon after hatching, either increasing or decreasing brood size by one nestling. By molecular sexing of the chicks, we additionally tested for sex-specific sensitivity of individual nestlings to experimental treatments and to sex ratio variation in nestmates. We predicted that chicks hatching from albumen-deprived eggs should suffer more than control chicks from the harsher rearing conditions of enlarged broods. However, although albumen removal depressed chick body mass, chicks hatching from control eggs did not fare better than those hatching from eggs with reduced albumen content in enlarged vs. reduced broods. Albumen removal had sex-specific effects on immunity, with males, but not females, hatching from eggs with reduced albumen content showing a lower T-cell-mediated immune response than controls, suggesting that the two sexes were differentially susceptible to resource deprivation during early ontogeny. In addition, both immune response and chick body mass at age 7 days, when maximum growth rate is attained, declined with an increasing proportion of male nestmates. The effect of brood size manipulation on chick body mass at age 12 days, when peak body mass is attained, was also found to depend on brood sex composition, in that an increase in the proportion of male nestmates depressed offspring body mass in reduced broods, while the reverse was true in enlarged broods. On the whole, these findings suggest that sex differences may exist in environmental sensitivity and patterns of resource allocation among different body functions, and that brood size variation and sex composition may affect offspring fitness-related traits.
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In altricial birds, the nestling period is an important part of the breeding phase because the juveniles may spend quite a long time in the nest, with associated high energy costs for the parents. The length of the nestling period can be variable and its duration may be influenced by both biotic and abiotic factors; however, studies of this have mostly been undertaken on passerine birds. We studied individual duration of nestling period of 98 Tengmalm's owl chicks (Aegolius funereus) at 27 nests during five breeding seasons using a camera and chip system and radio-telemetry. We found the nestlings stayed in the nest box for 27 - 38 days from hatching (mean ± SD, 32.4 ± 2.2 days). The individual duration of nestling period was negatively related to wing length, but no formally significant effect was found for body weight, sex, prey availability and/or weather conditions. The fledging sequence of individual nestlings was primarily related to hatching order; no relationship with wing length and/or other factors was found in this case. We suggest the length of wing is the most important measure of body condition and individual quality in Tengmalm's owl young determining the duration of the nestling period. Other differences from passerines (e.g., the lack of effect of weather or prey availability on nestling period) are considered likely to be due to different life-history traits, in particular different food habits and nesting sites and greater risk of nest predation among passerines.
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Sex-specific effects of albumen removal and nest environment manipulation on Barn Swallow nestlings.
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In avian species, maternal provisioning to the eggs is predicted to be more valuable for the offspring under adverse environmental conditions and intense sibling competition. However, studies manipulating both the amount of maternal pre-hatching resources and the harshness of post-hatching environment have seldom been performed to date. In this experimental study of Barn Swallow (Hirundo rustica) nestlings, we tested the consequences of a reduction in the albumen content of the eggs for fitness-related offspring traits, while performing an unbalanced partial cross-fostering soon after hatching, either increasing or decreasing brood size by one nestling. By molecular sexing of the chicks, we additionally tested for sex-specific sensitivity of individual nestlings to experimental treatments and to sex ratio variation in nestmates. We predicted that chicks hatching from albumen-deprived eggs should suffer more than control chicks from the harsher rearing conditions of enlarged broods. However, although albumen removal depressed chick body mass, chicks hatching from control eggs did not fare better than those hatching from eggs with reduced albumen content in enlarged vs. reduced broods. Albumen removal had sex-specific effects on immunity, with males, but not females, hatching from eggs with reduced albumen content showing a lower T-cell-mediated immune response than controls, suggesting that the two sexes were differentially susceptible to resource deprivation during early ontogeny. In addition, both immune response and chick body mass at age 7 days, when maximum growth rate is attained, declined with an increasing proportion of male nestmates. The effect of brood size manipulation on chick body mass at age 12 days, when peak body mass is attained, was also found to depend on brood sex composition, in that an increase in the proportion of male nestmates depressed offspring body mass in reduced broods, while the reverse was true in enlarged broods. On the whole, these findings suggest that sex differences may exist in environmental sensitivity and patterns of resource allocation among different body functions, and that brood size variation and sex composition may affect offspring fitness-related traits.
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Siblings within the same family often differ dramatically in phenotype. Some differences are attributable to initial maternal handicaps (birth or hatching asynchrony, differences in egg or neonate size and hormonal or antioxidant titre); but differences among siblings may also arise from differences in the brood-rearing environment that offspring experience. Here, I use a model system--a long-term study of nestlings in an altricial bird--to study how an initial maternal handicap, hatching asynchrony, regulates the effective social environment of siblings in the same family as measured by offspring survival. The interaction of family size and structure generated wide differences in the effective environments of siblings living in the same physical space (a nest), and reared by the same parents, in the same family structure. Social rank was the key component of the unshared environment of contemporary siblings, and was alone sufficient to generate near-maximal differences in offspring performance. Nestlings sitting side-by-side effectively lived in different worlds.
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Sex-specific effects of albumen removal and nest environment manipulation on Barn Swallow nestlings.
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In avian species, maternal provisioning to the eggs is predicted to be more valuable for the offspring under adverse environmental conditions and intense sibling competition. However, studies manipulating both the amount of maternal pre-hatching resources and the harshness of post-hatching environment have seldom been performed to date. In this experimental study of Barn Swallow (Hirundo rustica) nestlings, we tested the consequences of a reduction in the albumen content of the eggs for fitness-related offspring traits, while performing an unbalanced partial cross-fostering soon after hatching, either increasing or decreasing brood size by one nestling. By molecular sexing of the chicks, we additionally tested for sex-specific sensitivity of individual nestlings to experimental treatments and to sex ratio variation in nestmates. We predicted that chicks hatching from albumen-deprived eggs should suffer more than control chicks from the harsher rearing conditions of enlarged broods. However, although albumen removal depressed chick body mass, chicks hatching from control eggs did not fare better than those hatching from eggs with reduced albumen content in enlarged vs. reduced broods. Albumen removal had sex-specific effects on immunity, with males, but not females, hatching from eggs with reduced albumen content showing a lower T-cell-mediated immune response than controls, suggesting that the two sexes were differentially susceptible to resource deprivation during early ontogeny. In addition, both immune response and chick body mass at age 7 days, when maximum growth rate is attained, declined with an increasing proportion of male nestmates. The effect of brood size manipulation on chick body mass at age 12 days, when peak body mass is attained, was also found to depend on brood sex composition, in that an increase in the proportion of male nestmates depressed offspring body mass in reduced broods, while the reverse was true in enlarged broods. On the whole, these findings suggest that sex differences may exist in environmental sensitivity and patterns of resource allocation among different body functions, and that brood size variation and sex composition may affect offspring fitness-related traits.
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It is widely accepted that recent increases in environmental temperature have had a causal effect on changing life histories; however, much of the evidence for this is derived from long-term observations, whereas inferences of causation require experimentation. Here, we assess effects of increased environmental temperature during incubation on posthatching development, nestling begging and parental care, and reproductive success in two wild, cavity-nesting songbirds, the Carolina wren and prothonotary warbler. We heated experimental nests only during incubation, which increased nest-cavity temperature by ca. 1 °C. This reduced the length of the incubation and nestling periods, and reduced fledging success in prothonotary warblers, while nestling Carolina wrens had similar fledging success but reduced body condition in response to increased temperature. Increased nest-cavity temperature during incubation also reduced posthatching begging by nestlings generally and parental care within Carolina wrens specifically, suggesting potential mechanisms generating these carry-over effects. Offspring body mass and fledging age are often predictive of post-fledging survival and recruitment. Thus, our results suggest that increasing temperatures may affect fitness in wild populations in species-specific ways, and induce life-history changes including the classic trade-off parents face between the size and number of offspring.
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Sex-specific effects of albumen removal and nest environment manipulation on Barn Swallow nestlings.
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In avian species, maternal provisioning to the eggs is predicted to be more valuable for the offspring under adverse environmental conditions and intense sibling competition. However, studies manipulating both the amount of maternal pre-hatching resources and the harshness of post-hatching environment have seldom been performed to date. In this experimental study of Barn Swallow (Hirundo rustica) nestlings, we tested the consequences of a reduction in the albumen content of the eggs for fitness-related offspring traits, while performing an unbalanced partial cross-fostering soon after hatching, either increasing or decreasing brood size by one nestling. By molecular sexing of the chicks, we additionally tested for sex-specific sensitivity of individual nestlings to experimental treatments and to sex ratio variation in nestmates. We predicted that chicks hatching from albumen-deprived eggs should suffer more than control chicks from the harsher rearing conditions of enlarged broods. However, although albumen removal depressed chick body mass, chicks hatching from control eggs did not fare better than those hatching from eggs with reduced albumen content in enlarged vs. reduced broods. Albumen removal had sex-specific effects on immunity, with males, but not females, hatching from eggs with reduced albumen content showing a lower T-cell-mediated immune response than controls, suggesting that the two sexes were differentially susceptible to resource deprivation during early ontogeny. In addition, both immune response and chick body mass at age 7 days, when maximum growth rate is attained, declined with an increasing proportion of male nestmates. The effect of brood size manipulation on chick body mass at age 12 days, when peak body mass is attained, was also found to depend on brood sex composition, in that an increase in the proportion of male nestmates depressed offspring body mass in reduced broods, while the reverse was true in enlarged broods. On the whole, these findings suggest that sex differences may exist in environmental sensitivity and patterns of resource allocation among different body functions, and that brood size variation and sex composition may affect offspring fitness-related traits.
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The composition of polychlorinated biphenyl (PCB) congeners was compared between non-incubated and embryonated eggs of tree swallows (Tachycineta bicolor) and little terns (Sterna albifrons) to determine if measurable changes in PCB congeners occurred during the embryonic period. There was no indication of changes in PCB congener patterns over the incubation period in tree swallows in 1999 and 2000 at a site with very high PCB exposure or a site with more modest PCB exposure. Additionally, congeners known to be either quickly metabolized or conserved based on experimental studies did not generally respond as predicted. Similarly, PCB congener patterns in eggs of little terns from Bottsand, Schleswig-Holstein, Germany, did not differ between non-incubated and embryonated eggs. The results from both species suggest that the stage of incubation is not an important consideration when evaluating PCB congener patterns; comparisons and assessments can be made with eggs collected at all stages of incubation.
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Sex-specific effects of albumen removal and nest environment manipulation on Barn Swallow nestlings.
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In avian species, maternal provisioning to the eggs is predicted to be more valuable for the offspring under adverse environmental conditions and intense sibling competition. However, studies manipulating both the amount of maternal pre-hatching resources and the harshness of post-hatching environment have seldom been performed to date. In this experimental study of Barn Swallow (Hirundo rustica) nestlings, we tested the consequences of a reduction in the albumen content of the eggs for fitness-related offspring traits, while performing an unbalanced partial cross-fostering soon after hatching, either increasing or decreasing brood size by one nestling. By molecular sexing of the chicks, we additionally tested for sex-specific sensitivity of individual nestlings to experimental treatments and to sex ratio variation in nestmates. We predicted that chicks hatching from albumen-deprived eggs should suffer more than control chicks from the harsher rearing conditions of enlarged broods. However, although albumen removal depressed chick body mass, chicks hatching from control eggs did not fare better than those hatching from eggs with reduced albumen content in enlarged vs. reduced broods. Albumen removal had sex-specific effects on immunity, with males, but not females, hatching from eggs with reduced albumen content showing a lower T-cell-mediated immune response than controls, suggesting that the two sexes were differentially susceptible to resource deprivation during early ontogeny. In addition, both immune response and chick body mass at age 7 days, when maximum growth rate is attained, declined with an increasing proportion of male nestmates. The effect of brood size manipulation on chick body mass at age 12 days, when peak body mass is attained, was also found to depend on brood sex composition, in that an increase in the proportion of male nestmates depressed offspring body mass in reduced broods, while the reverse was true in enlarged broods. On the whole, these findings suggest that sex differences may exist in environmental sensitivity and patterns of resource allocation among different body functions, and that brood size variation and sex composition may affect offspring fitness-related traits.
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Studies of acoustic interactions in animal groups, such as chorusing insects, anurans, and birds, have been invaluable in showing how cooperation and competition shape signal structure and use. The begging calls of nestling birds are ideal for such studies, because they function both as a cooperative signals of the brood's needs and as competitive signals for parental allocation within the brood. Nonetheless, studies of acoustic interactions among nestlings are rare. Here we review our work on acoustic interactions in nestling tree swallows (Tachycineta bicolor), especially how calls are used in competition for parental feedings. Nestlings attracted parental attention and responded to acoustic interference mainly by increasing call output. However, nestlings also gave more similar calls when they called together and decreased their call bandwidth when exposed to elevated noise. We suggest that these competitive uses of calls might intensify the cooperative brood signal, affecting both parental provisioning and vocal development. Given their tremendous variation across species, begging calls offer promising opportunities for developmental and comparative studies of acoustic signaling.
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Automatic point correspondence using an artificial immune system optimization technique for medical image registration.
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In this paper, an automatic method for determining pairs of corresponding points between medical images is proposed. The method is based on the implementation of an artificial immune system (AIS). AIS is a relatively novel, population based category of algorithms, inspired by theoretical immunologic models. When used as function optimizers, AIS have the attractive property of locating the global optimum of a function as well as a large number of strong local optimum points. In this work, AIS has been applied both for the extraction of an optimal set of candidate points on the reference image and the definition of their corresponding ones on the second image. The performance of the proposed AIS algorithm is evaluated against the widely used Iterative Closest Point (ICP) algorithm in terms of the accuracy of the obtained correspondences and in terms of the accuracy of the point-based registration by the two correspondence algorithms and the Mutual Information criterion, as an intensity-based registration method. Qualitative and quantitative results involving 92 X-ray dental and 10 retinal image pairs subject to known and unknown transformations are presented. The results indicate a superior performance of the proposed AIS algorithm with respect to the ICP algorithm and the Mutual Information, in terms of both correct correspondence and registration accuracy.
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This document presents a non-rigid registration algorithm for the use of brain magnetic resonance (MR) images comparison. More precisely, we want to compare pre-operative and post-operative MR images in order to assess the deformation due to a surgical removal. The proposed algorithm has been studied in Chesseboeuf et al. ((Non-rigid registration of magnetic resonance imaging of brain. IEEE, 385-390. doi: 10.1109/IPTA.2015.7367172 , 2015), following ideas of Trouvé (An infinite dimensional group approach for physics based models in patterns recognition. Technical Report DMI Ecole Normale Supérieure, Cachan, 1995), in which the author introduces the algorithm within a very general framework. Here we recalled this theory from a practical point of view. The emphasis is on illustrations and description of the numerical procedure. Our version of the algorithm is associated with a particular matching criterion. Then, a section is devoted to the description of this object. In the last section we focus on the construction of a statistical method of evaluation.
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Automatic point correspondence using an artificial immune system optimization technique for medical image registration.
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In this paper, an automatic method for determining pairs of corresponding points between medical images is proposed. The method is based on the implementation of an artificial immune system (AIS). AIS is a relatively novel, population based category of algorithms, inspired by theoretical immunologic models. When used as function optimizers, AIS have the attractive property of locating the global optimum of a function as well as a large number of strong local optimum points. In this work, AIS has been applied both for the extraction of an optimal set of candidate points on the reference image and the definition of their corresponding ones on the second image. The performance of the proposed AIS algorithm is evaluated against the widely used Iterative Closest Point (ICP) algorithm in terms of the accuracy of the obtained correspondences and in terms of the accuracy of the point-based registration by the two correspondence algorithms and the Mutual Information criterion, as an intensity-based registration method. Qualitative and quantitative results involving 92 X-ray dental and 10 retinal image pairs subject to known and unknown transformations are presented. The results indicate a superior performance of the proposed AIS algorithm with respect to the ICP algorithm and the Mutual Information, in terms of both correct correspondence and registration accuracy.
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Optimal transport has emerged as a promising and useful tool for supporting modern image processing applications such as medical imaging and scientific visualization. Indeed, the optimal transport theory enables great flexibility in modeling problems related to image registration, as different optimization resources can be successfully used as well as the choice of suitable matching models to align the images. In this paper, we introduce an automated framework for fundus image registration which unifies optimal transport theory, image processing tools, and graph matching schemes into a functional and concise methodology. Given two ocular fundus images, we construct representative graphs which embed in their structures spatial and topological information from the eye's blood vessels. The graphs produced are then used as input by our optimal transport model in order to establish a correspondence between their sets of nodes. Finally, geometric transformations are performed between the images so as to accomplish the registration task properly. Our formulation relies on the solid mathematical foundation of optimal transport as a constrained optimization problem, being also robust when dealing with outliers created during the matching stage. We demonstrate the accuracy and effectiveness of the present framework throughout a comprehensive set of qualitative and quantitative comparisons against several influential state-of-the-art methods on various fundus image databases.
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Automatic point correspondence using an artificial immune system optimization technique for medical image registration.
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In this paper, an automatic method for determining pairs of corresponding points between medical images is proposed. The method is based on the implementation of an artificial immune system (AIS). AIS is a relatively novel, population based category of algorithms, inspired by theoretical immunologic models. When used as function optimizers, AIS have the attractive property of locating the global optimum of a function as well as a large number of strong local optimum points. In this work, AIS has been applied both for the extraction of an optimal set of candidate points on the reference image and the definition of their corresponding ones on the second image. The performance of the proposed AIS algorithm is evaluated against the widely used Iterative Closest Point (ICP) algorithm in terms of the accuracy of the obtained correspondences and in terms of the accuracy of the point-based registration by the two correspondence algorithms and the Mutual Information criterion, as an intensity-based registration method. Qualitative and quantitative results involving 92 X-ray dental and 10 retinal image pairs subject to known and unknown transformations are presented. The results indicate a superior performance of the proposed AIS algorithm with respect to the ICP algorithm and the Mutual Information, in terms of both correct correspondence and registration accuracy.
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Identification of anatomical landmarks on skeletal tissue reconstructed from CT/MR images is indispensable in patient-specific preoperative planning (tumour referencing, deformity evaluation, resection planning, and implant alignment and anchoring) as well as intra-operative navigation (bone registration and instruments referencing). Interactive localisation of landmarks on patient-specific anatomical models is time-consuming and may lack in repeatability and accuracy. We present a computer graphics-based method for automatic localisation and identification (labelling) of anatomical landmarks on a 3D model of bone reconstructed from CT images of a patient. The model surface is segmented into different landmark regions (peak, ridge, pit and ravine) based on surface curvature. These regions are labelled automatically by an iterative process using a spatial adjacency relationship matrix between the landmarks. The methodology has been implemented in a software program and its results (automatically identified landmarks) are compared with those manually palpated by three experienced orthopaedic surgeons, on three 3D reconstructed bone models. The variability in location of landmarks was found to be in the range of 2.15-5.98 mm by manual method (inter surgeon) and 1.92-4.88 mm by our program. Both methods performed well in identifying sharp features. Overall, the performance of the automated methodology was better or similar to the manual method and its results were reproducible. It is expected to have a variety of applications in surgery planning and intra-operative navigation.
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Automatic point correspondence using an artificial immune system optimization technique for medical image registration.
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In this paper, an automatic method for determining pairs of corresponding points between medical images is proposed. The method is based on the implementation of an artificial immune system (AIS). AIS is a relatively novel, population based category of algorithms, inspired by theoretical immunologic models. When used as function optimizers, AIS have the attractive property of locating the global optimum of a function as well as a large number of strong local optimum points. In this work, AIS has been applied both for the extraction of an optimal set of candidate points on the reference image and the definition of their corresponding ones on the second image. The performance of the proposed AIS algorithm is evaluated against the widely used Iterative Closest Point (ICP) algorithm in terms of the accuracy of the obtained correspondences and in terms of the accuracy of the point-based registration by the two correspondence algorithms and the Mutual Information criterion, as an intensity-based registration method. Qualitative and quantitative results involving 92 X-ray dental and 10 retinal image pairs subject to known and unknown transformations are presented. The results indicate a superior performance of the proposed AIS algorithm with respect to the ICP algorithm and the Mutual Information, in terms of both correct correspondence and registration accuracy.
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A nonrigid B-spline-based point-matching (BPM) method is proposed to match dense surface points. The method solves both the point correspondence and nonrigid transformation without features extraction. The registration method integrates a motion model, which combines a global transformation and a B-spline-based local deformation, into a robust point-matching framework. The point correspondence and deformable transformation are estimated simultaneously by fuzzy correspondence and by a deterministic annealing technique. Prior information about global translation, rotation and scaling is incorporated into the optimization. A local B-spline motion model decreases the degrees of freedom for optimization and thus enables the registration of a larger number of feature points. The performance of the BPM method has been demonstrated and validated using synthesized 2D and 3D data, mouse MRI and micro-CT images. The proposed BPM method can be used to register feature point sets, 2D curves, 3D surfaces and various image data.
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Automatic point correspondence using an artificial immune system optimization technique for medical image registration.
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In this paper, an automatic method for determining pairs of corresponding points between medical images is proposed. The method is based on the implementation of an artificial immune system (AIS). AIS is a relatively novel, population based category of algorithms, inspired by theoretical immunologic models. When used as function optimizers, AIS have the attractive property of locating the global optimum of a function as well as a large number of strong local optimum points. In this work, AIS has been applied both for the extraction of an optimal set of candidate points on the reference image and the definition of their corresponding ones on the second image. The performance of the proposed AIS algorithm is evaluated against the widely used Iterative Closest Point (ICP) algorithm in terms of the accuracy of the obtained correspondences and in terms of the accuracy of the point-based registration by the two correspondence algorithms and the Mutual Information criterion, as an intensity-based registration method. Qualitative and quantitative results involving 92 X-ray dental and 10 retinal image pairs subject to known and unknown transformations are presented. The results indicate a superior performance of the proposed AIS algorithm with respect to the ICP algorithm and the Mutual Information, in terms of both correct correspondence and registration accuracy.
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Image registration is a commonly required task in computer assisted surgical procedures. Existing registration methods in laparoscopic navigation systems suffer from several constraints, such as lack of deformation compensation. The proposed algorithm aims to provide the surgeons with updated navigational information about the deep-seated anatomy, which considers the continuous deformations in the operating environment. We extended an initial rigid registration to a shape-preserving deformable registration pathway by incorporating user interaction and an iterative mesh editing scheme which preserves local details. The proposed deformable registration workflow was tested with phantom and animal trial datasets. A qualitative evaluation based on expert feedback demonstrated satisfactory outcome, and an commensurate execution efficiency was achieved. The improvements offered by the method, couples with its relatively easy implementation, makes it an attractive method for adoption in future pre-clinical and clinical applications of augmented reality assisted surgeries.
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Transfers of patient care between house staff on internal medicine wards: a national survey.
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Transfer of responsibility for patient care between physicians is a key process in the care of hospitalized patients. Systems of transfer management and transfer frequency may affect clinical outcomes.
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Ward rounds play a crucial role in the delivery of patient care in inpatient settings, but involve a complex mix of tasks, skills and challenges for junior doctors to negotiate. This study informs the development of high-quality training by identifying the activities that junior doctors perform, and those associated with stress during real-life ward rounds.
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Transfers of patient care between house staff on internal medicine wards: a national survey.
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Transfer of responsibility for patient care between physicians is a key process in the care of hospitalized patients. Systems of transfer management and transfer frequency may affect clinical outcomes.
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This cross-sectional study assesses the daily percentage of floor and intensive care unit bed available at in-network hospitals for patients with COVID-19 in Tennessee.
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Transfers of patient care between house staff on internal medicine wards: a national survey.
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Transfer of responsibility for patient care between physicians is a key process in the care of hospitalized patients. Systems of transfer management and transfer frequency may affect clinical outcomes.
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There is little evidence for solutions to improve the handoff process between units, particularly from the emergency department (ED) to the inpatient unit. A systematic approach was used to improve the handoff communication process between the ED and the four private physician groups serving Juneau, Alaska, that admit and deliver care to patients of a 73-bed, Level 4 trauma center community hospital.
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Transfers of patient care between house staff on internal medicine wards: a national survey.
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Transfer of responsibility for patient care between physicians is a key process in the care of hospitalized patients. Systems of transfer management and transfer frequency may affect clinical outcomes.
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Staff perceptions of risks associated with patient handoffs were investigated in a survey of nurses in 6 Japanese hospitals. A total of 1462 valid responses were collected from nurses with an overall response rate of 74%. Respondents are moderately satisfied with the transfer of information and responsibility during handoffs. However, the handoff system was identified as immature. Hospital, work setting, and work experience affected nurses' views of handoff quality. Strategies for improving patient handoffs in Japan are proposed.
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Transfers of patient care between house staff on internal medicine wards: a national survey.
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Transfer of responsibility for patient care between physicians is a key process in the care of hospitalized patients. Systems of transfer management and transfer frequency may affect clinical outcomes.
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The transfer of patient care from one health care worker to another involves communication in high-pressure contexts that are often vulnerable to error. This research project captured current practices for handoffs during the critical care stage of surgical recovery in a hospital setting. The objective was to characterize information flow during transfer and identify patterns of communication between nurses and physicians.
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Assessment rates and compliance with assertive follow-up after self-harm: cohort study.
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The objectives of this study were to identify 1) the proportion of self-harm episodes that resulted in assessment by a specialist self-harm team and offers, attendance, and completion of brief therapy and 2) the factors associated with these treatment options. A prospective cohort study of 717 hospital presentations of self-harm was conducted. Rates of assessment, offers and completion of therapy ranged from 50% to 60%. Of those offered therapy, 73% attended one or more sessions. Attendance was associated with depressive psychopathology and existing treatment in primary care. These results may reflect some of the challenges of engaging this patient group. We found that receipt of treatment was determined by patient factors. Future studies might also examine the role of service-related or clinician factors.
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The aim of this study was to examine the effectiveness of assertive case management intervention in preventing suicidal behaviour in self-poisoning patients. We conducted a secondary analysis of data from the ACTION-J study. Participants were self-poisoning patients with clear suicide intent admitted to emergency departments and with a primary psychiatric diagnosis (as per DSM-IV-TR axis 1). Patients were randomly assigned either to assertive case management or enhanced usual care. The primary outcome measure was the incidence of a first recurrent suicide attempt within 6 months. This study is registered at ClinicalTrials.gov (NCT00736918) and UMIN-CTR (C000000444). There were 297 self-poisoning patients in the intervention group and 295 in the control group. The primary outcome was significantly lower in the intervention group than in the control group. The incidence of a first recurrent suicide attempt within 1 and 3 months was also significantly lower in the intervention group, as was the number of overall self-harm episodes over the entire study period. Furthermore, the number of non-suicidal self-harm episodes and suicide attempts was significantly lower in the intervention group. Assertive case management is effective when promptly introduced in a hospital setting as an intervention following a suicide attempt, particularly for self-poisoning patients.
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Assessment rates and compliance with assertive follow-up after self-harm: cohort study.
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The objectives of this study were to identify 1) the proportion of self-harm episodes that resulted in assessment by a specialist self-harm team and offers, attendance, and completion of brief therapy and 2) the factors associated with these treatment options. A prospective cohort study of 717 hospital presentations of self-harm was conducted. Rates of assessment, offers and completion of therapy ranged from 50% to 60%. Of those offered therapy, 73% attended one or more sessions. Attendance was associated with depressive psychopathology and existing treatment in primary care. These results may reflect some of the challenges of engaging this patient group. We found that receipt of treatment was determined by patient factors. Future studies might also examine the role of service-related or clinician factors.
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There is limited evidence about how patients' initial preoperative psychological evaluation outcomes (require follow-up [RFU], no required follow-up [NFU], and place on hold [POH]) and current psychiatric diagnoses associate with postoperative outcomes.
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Assessment rates and compliance with assertive follow-up after self-harm: cohort study.
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The objectives of this study were to identify 1) the proportion of self-harm episodes that resulted in assessment by a specialist self-harm team and offers, attendance, and completion of brief therapy and 2) the factors associated with these treatment options. A prospective cohort study of 717 hospital presentations of self-harm was conducted. Rates of assessment, offers and completion of therapy ranged from 50% to 60%. Of those offered therapy, 73% attended one or more sessions. Attendance was associated with depressive psychopathology and existing treatment in primary care. These results may reflect some of the challenges of engaging this patient group. We found that receipt of treatment was determined by patient factors. Future studies might also examine the role of service-related or clinician factors.
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<i>Survivors Healing from Abuse: Recovery through Exposure</i> (SHARE) is a brief, exposure-based group treatment for incarcerated female survivors of sexual violence. Preliminary evaluations of SHARE showed declines in depression and posttraumatic stress disorder (PTSD) symptoms from pre- to posttreatment. However, prior investigations have not included a longitudinal follow-up period and thus knowledge of whether therapeutic benefits persist following the termination of the group is lacking. Here, we examined data from 57 incarcerated women who completed SHARE and provided follow-up data while still incarcerated (<i>M</i> = 95 days posttreatment). Results from a one-way repeated-measures ANOVA showed significant reductions in PTSD and depression symptoms from pre- to posttreatment (large effect sizes), with symptoms further reduced during the follow-up period. In addition, McNemar tests showed a significant reduction in the proportion of participants at or above the clinical cut-off for probable PTSD and depression from pre- to posttreatment as well as from posttreatment to the follow-up assessment. Together, results suggest that the therapeutic benefits of SHARE persist after treatment is completed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Assessment rates and compliance with assertive follow-up after self-harm: cohort study.
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The objectives of this study were to identify 1) the proportion of self-harm episodes that resulted in assessment by a specialist self-harm team and offers, attendance, and completion of brief therapy and 2) the factors associated with these treatment options. A prospective cohort study of 717 hospital presentations of self-harm was conducted. Rates of assessment, offers and completion of therapy ranged from 50% to 60%. Of those offered therapy, 73% attended one or more sessions. Attendance was associated with depressive psychopathology and existing treatment in primary care. These results may reflect some of the challenges of engaging this patient group. We found that receipt of treatment was determined by patient factors. Future studies might also examine the role of service-related or clinician factors.
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To describe spontaneous preterm birth prevention practices self-reported before and after the dissemination of relevant guidelines, and to identify personal and organisational factors associated with adherence.
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Assessment rates and compliance with assertive follow-up after self-harm: cohort study.
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The objectives of this study were to identify 1) the proportion of self-harm episodes that resulted in assessment by a specialist self-harm team and offers, attendance, and completion of brief therapy and 2) the factors associated with these treatment options. A prospective cohort study of 717 hospital presentations of self-harm was conducted. Rates of assessment, offers and completion of therapy ranged from 50% to 60%. Of those offered therapy, 73% attended one or more sessions. Attendance was associated with depressive psychopathology and existing treatment in primary care. These results may reflect some of the challenges of engaging this patient group. We found that receipt of treatment was determined by patient factors. Future studies might also examine the role of service-related or clinician factors.
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In-depth understanding of factors perceived by young people with congenital heart disease (CHD) to affect continued follow-up care is needed to tailor preventive strategies for discontinuation of follow-up care. To identify facilitating factors, low-prevalence settings in terms of discontinuation should be investigated.
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Comparison of tissue deterioration of ripening banana fruit (Musa spp., AAA group, Cavendish subgroup) under chilling and non-chilling temperatures.
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In fleshy fruits, induced programmed cell death (PCD) has been observed in heat-treated tomato, and in ethylene-treated and low-temperature exposure in immature cucumber. No other fleshy fruit has been evaluated for chilling-injury-induced PCD, especially mature fruit with full ripening capacity. The purpose of this research was to identify and evaluate the presence of PCD processes during the development of low-temperature-induced physiopathy of banana fruit.
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The effect of fish gelatin and chitosan coatings on the physicochemical characteristics of fresh-cut apples (<i>Malus pumila</i> Mill.), stored at 5 °C and 22 °C, was investigated. Chitosan provided an effective control for microbial growth, maintained firmness during 4 days of storage at room temperature (22 °C), and 12 days at refrigerator (5 °C). The results indicated that chitosan coating caused a significant decrease (<i>p</i> < 0.05) in the <i>L</i>* value of cube color of cut apples. Fish gelatin-chitosan coatings mitigated the <i>L</i>* value and decrease in hue angle of the cut apple samples, at cold storage. Experimental results showed that fish gelatin-chitosan and chitosan coatings, can be used to mitigate the formation of vitamin C, due to respiration, microbial growth, and weight loss at cold storage. Fish gelatin-chitosan coating might be a better combination for maintaining appearance and extending shelf-life of cut apples, compared to only chitosan coatings.
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Comparison of tissue deterioration of ripening banana fruit (Musa spp., AAA group, Cavendish subgroup) under chilling and non-chilling temperatures.
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In fleshy fruits, induced programmed cell death (PCD) has been observed in heat-treated tomato, and in ethylene-treated and low-temperature exposure in immature cucumber. No other fleshy fruit has been evaluated for chilling-injury-induced PCD, especially mature fruit with full ripening capacity. The purpose of this research was to identify and evaluate the presence of PCD processes during the development of low-temperature-induced physiopathy of banana fruit.
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Sunburn is a physiological fruit disorder induced by exposure to excessive solar radiation. This disorder leads to significant losses in the yield of marketable fruits by negatively affecting quality parameters such as maturity and external color of the fruits. The purpose of this work was to characterize the physiological and biochemical aspects related to oxidative metabolism in Beurré D'Anjou pear fruit with different sunburn levels. Fruits were collected and classified into three sunburn levels at harvest: no sunburn (S0), mild sunburn (S1), and moderate sunburn (S2). On sunburned area, the maturity indices were measured on the fruit flesh, while external color, photosynthetic and photoprotective pigments, total phenols, electrolyte leakage, lipid peroxidation, antioxidant capacity and antioxidant enzymatic activities were determined on fruit peel. The hue angle and saturation of peel color of pears with different sunburn levels showed significant reduction with increasing damage. These changes in peel color were associated with a reduction in chlorophyll content and variations in carotenoid and anthocyanin levels. Due to metabolic changes resulting from defense and adaptive responses to high solar radiation, sunburned tissues showed significantly increased firmness, soluble solids content, and starch degradation, and lower acidity compared to undamaged fruits. We observed also increased antioxidant capacity in the peel of S1 and S2 fruit, related to higher phenolic contents and increased SOD and APX activities. Consistent with previous reports in apple, our study demonstrates that sunburn affects pear fruit quality traits and maturity state by enhancing oxidative metabolism.
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Comparison of tissue deterioration of ripening banana fruit (Musa spp., AAA group, Cavendish subgroup) under chilling and non-chilling temperatures.
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In fleshy fruits, induced programmed cell death (PCD) has been observed in heat-treated tomato, and in ethylene-treated and low-temperature exposure in immature cucumber. No other fleshy fruit has been evaluated for chilling-injury-induced PCD, especially mature fruit with full ripening capacity. The purpose of this research was to identify and evaluate the presence of PCD processes during the development of low-temperature-induced physiopathy of banana fruit.
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The aim of this study was to determine physical changes in nectarine and distinctive physiological characteristics related to red and green peel under stresses occurring during fruit maturation, information on which is currently not available.
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Comparison of tissue deterioration of ripening banana fruit (Musa spp., AAA group, Cavendish subgroup) under chilling and non-chilling temperatures.
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In fleshy fruits, induced programmed cell death (PCD) has been observed in heat-treated tomato, and in ethylene-treated and low-temperature exposure in immature cucumber. No other fleshy fruit has been evaluated for chilling-injury-induced PCD, especially mature fruit with full ripening capacity. The purpose of this research was to identify and evaluate the presence of PCD processes during the development of low-temperature-induced physiopathy of banana fruit.
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Arabinose is one of the most dynamic cell wall glycosyl residues released during fruit ripening, alpha-L-arabinofuranosidase (alpha-Arab) are major glycosidases that may remove arabinose units from fruit cell wall polysaccharides. To find out whether alpha-Arab plays important roles in banana fruit softening, the enzyme activities in peel and pulp, fruit firmness, respiration rate and ethylene release rate were assayed during banana softening. The results showed that alpha-Arab activities in banana pulp and peel increased slightly at the beginning of storage and reached their maxima when the fruit firmness decreased drastically, alpha-Arab activity increased by more than ten folds in both pulp and peel during ripening and alpha-Arab activities were higher in pulp than in peel. Treatment of banana fruits with ethylene absorbent postponed the time of reaching of its maxima of respiration and ethylene, enhanced the firmness of pup and decreased alpha-Arab activity in the peel and pulp. These results suggest that alpha-Arab induced the decrease of fruit firmness and played an important role in banana fruit softening, and its activity was regulated by ethylene.
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Comparison of tissue deterioration of ripening banana fruit (Musa spp., AAA group, Cavendish subgroup) under chilling and non-chilling temperatures.
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In fleshy fruits, induced programmed cell death (PCD) has been observed in heat-treated tomato, and in ethylene-treated and low-temperature exposure in immature cucumber. No other fleshy fruit has been evaluated for chilling-injury-induced PCD, especially mature fruit with full ripening capacity. The purpose of this research was to identify and evaluate the presence of PCD processes during the development of low-temperature-induced physiopathy of banana fruit.
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Macadamia nuts ('nuts-in-shell') are subjected to many impacts from dropping during postharvest handling, resulting in damage to the raw kernel. The effect of dropping on roasted kernel quality is unknown. Macadamia nuts-in-shell were dropped in various combinations of moisture content, number of drops and receiving surface in three experiments. After dropping, samples from each treatment and undropped controls were dry oven-roasted for 20 min at 130 °C, and kernels were assessed for colour, mottled colour and surface damage.
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Design of the Academic Emergency Department.
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This article introduces a clinical audience to the process of emergency department (ED) design, particularly relating to academic EDs. It explains some of the major terms, processes, and key decisions that clinical staff will experience as participants in the design process. Topics covered include an overview of the planning and design process, issues related to determining needed patient capacity, the impact of patient flow models on design, and a description of several common ED design types and their advantages and disadvantages.
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Apart from operating theaters, intensive care units and diagnostic services, the central emergency department is one of the areas of any hospital with a high workload, which is very susceptible to risk. The following aspects of routine daily work can lead to a great strain on the personnel working in the central emergency department: the need for quick, targeted decisions, especially for patients with life-threatening disorders, a high number of patients with insufficient available resources, dissatisfaction of patients with low treatment priority and longer waiting times and delayed inpatient admissions with long stays. Interruptions in the individual work process during activities are not uncommon but represent additional disruptive factors for employees and can lead to treatment errors. Furthermore, a workload that is permanently perceived as too high leads to psychological and physical disturbances for the team members. Suitable structural, organizational and personnel prerequisites as well as solution strategies for the central emergency department are necessary to avoid corresponding treatment errors and also as a duty of care for employees.
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Design of the Academic Emergency Department.
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This article introduces a clinical audience to the process of emergency department (ED) design, particularly relating to academic EDs. It explains some of the major terms, processes, and key decisions that clinical staff will experience as participants in the design process. Topics covered include an overview of the planning and design process, issues related to determining needed patient capacity, the impact of patient flow models on design, and a description of several common ED design types and their advantages and disadvantages.
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There are nearly 120 million visits to emergency departments each year, one for every three people in the United States. Fifty percent of all hospital admissions come from this group, a marked change from the mid-1990s when the emergency department was a source of only a third of admissions. As the population increases and ages, the growth rate for emergency department visits and the resulting admissions will exceed historical trends creating a surge in demand for inpatient beds.
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Design of the Academic Emergency Department.
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This article introduces a clinical audience to the process of emergency department (ED) design, particularly relating to academic EDs. It explains some of the major terms, processes, and key decisions that clinical staff will experience as participants in the design process. Topics covered include an overview of the planning and design process, issues related to determining needed patient capacity, the impact of patient flow models on design, and a description of several common ED design types and their advantages and disadvantages.
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To assess the nature, severity, and mechanisms of ocular trauma in the emergency room at an academic teaching hospital.
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Design of the Academic Emergency Department.
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This article introduces a clinical audience to the process of emergency department (ED) design, particularly relating to academic EDs. It explains some of the major terms, processes, and key decisions that clinical staff will experience as participants in the design process. Topics covered include an overview of the planning and design process, issues related to determining needed patient capacity, the impact of patient flow models on design, and a description of several common ED design types and their advantages and disadvantages.
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In the context of the introduction of advanced practice nurses in emergency departments (APNs), the Collège de Médecine d'Urgence du Nord-Pas-de-Calais teamed up with the Unité de Formation et de Recherche des Sciences de la Santé et du Sport at the University of Lille to conduct a survey of emergency department management teams, with the aim of gaining a better understanding of their needs. The results revealed a number of obstacles and levers to the implementation of APNs, and led to a better understanding of the patient pathways in these departments. As a result, the content of the university teaching program could be reviewed with a view to meeting the needs expressed in the field.
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Design of the Academic Emergency Department.
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This article introduces a clinical audience to the process of emergency department (ED) design, particularly relating to academic EDs. It explains some of the major terms, processes, and key decisions that clinical staff will experience as participants in the design process. Topics covered include an overview of the planning and design process, issues related to determining needed patient capacity, the impact of patient flow models on design, and a description of several common ED design types and their advantages and disadvantages.
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The emergency medicine clerkship director serves an important role in the education of medical students. The authors sought to update the demographic and academic profile of the emergency medicine clerkship director.
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New Phenolic Dimers from Plant <i>Paeonia suffruticosa</i> and Their Cytotoxicity and NO Production Inhibition.
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The <i>Paeonia suffruticosa</i>, known as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A-E (<b>1</b>-<b>5</b>), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds <b>2</b>, <b>4</b>, and <b>5</b> showed cytotoxicity against three human cancer cell lines, with IC<sub>50</sub> values ranging from 6.7 to 25.1 μM. Compounds <b>1</b> and <b>2</b> showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of <i>P. suffruticosa</i> are reported for the first time in this paper.
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Five new iridoids, patriscabioins M-Q and a new monoterpene, eldanolide acid, together with three known iridoids, were isolated from the 95% aqueous EtOH extract whole plants of <i>Patrinia villosa</i> Juss. The structures were established by a variety of spectroscopic analysis, such as IR, 1 D and 2 D NMR spectra, MS, ECD and X-ray diffraction data. Bioactivity screening revealed the inhibitory effects on nitric oxide (NO) production of them in lipopolysaccharide-activated RAW264.7 cells with Aminoguanidine Hydrochloride as the positive control. Among them, patriscabioin M (1), patriscabioin N (2), patriscabioin P (4), patriscabioin Q (5), 8,9-didehydro-7-hydroxydolichodia (7) were found to markedly reduce LPS-induced NO production in murine macrophage cells with IC<sub>50</sub> values of 18.14, 18.93, 22.00, 13.64, 26.48 μM, respectively.
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New Phenolic Dimers from Plant <i>Paeonia suffruticosa</i> and Their Cytotoxicity and NO Production Inhibition.
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The <i>Paeonia suffruticosa</i>, known as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A-E (<b>1</b>-<b>5</b>), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds <b>2</b>, <b>4</b>, and <b>5</b> showed cytotoxicity against three human cancer cell lines, with IC<sub>50</sub> values ranging from 6.7 to 25.1 μM. Compounds <b>1</b> and <b>2</b> showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of <i>P. suffruticosa</i> are reported for the first time in this paper.
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Two new indole diterpene derivatives, 5<i>S</i>-hydroxy-<i>β</i>-aflatrem (<b>1</b>) and 14<i>R</i>-hydroxy-<i>β</i>-aflatrem (<b>2</b>), along with one known analogue, 14-(<i>N</i>,<i>N</i>-dimethl-<i>L</i>-valyloxy)paspalinine (<b>3</b>), were isolated from the fermentation broth of the fungus <i>Aspergillus</i> sp. PQJ-1 derived from <i>Sphagneticola trilobata</i>. The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses. All the compounds (<b>1</b>-<b>3</b>) were evaluated for their cytotoxicity against A549, Hela, Hep G2, and MCF-7 cell lines. Compounds <b>1</b> and <b>2</b> exhibited selective inhibition against Hela cells. Further studies showed that <b>1</b> significantly induced apoptosis and suppressed migration and invasion in Hela cells. Moreover, <b>1</b> could up-regulate pro-apoptotic genes BAX and Caspase-3 and down-regulate anti-apoptotic genes Bcl-xL and XIXP.
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New Phenolic Dimers from Plant <i>Paeonia suffruticosa</i> and Their Cytotoxicity and NO Production Inhibition.
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The <i>Paeonia suffruticosa</i>, known as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A-E (<b>1</b>-<b>5</b>), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds <b>2</b>, <b>4</b>, and <b>5</b> showed cytotoxicity against three human cancer cell lines, with IC<sub>50</sub> values ranging from 6.7 to 25.1 μM. Compounds <b>1</b> and <b>2</b> showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of <i>P. suffruticosa</i> are reported for the first time in this paper.
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Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC<sub>50</sub> value of 7.28 ± 0.94 μmol·<sup>-1</sup>.
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New Phenolic Dimers from Plant <i>Paeonia suffruticosa</i> and Their Cytotoxicity and NO Production Inhibition.
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The <i>Paeonia suffruticosa</i>, known as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A-E (<b>1</b>-<b>5</b>), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds <b>2</b>, <b>4</b>, and <b>5</b> showed cytotoxicity against three human cancer cell lines, with IC<sub>50</sub> values ranging from 6.7 to 25.1 μM. Compounds <b>1</b> and <b>2</b> showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of <i>P. suffruticosa</i> are reported for the first time in this paper.
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A new compound, 2-hydroxy-4-[3',5'-dihydroxyhexyl]phenyl-<i>β</i>-D-glucopyranoside (<b>1</b>), together with five known compounds (<b>2</b>-<b>6</b>), were isolated from the leaves of <i>Microsorium fortunei</i>. Their structures were determined by spectroscopic techniques, especially 2D NMR and MS data analyses. All of these compounds are phenolic glycosides and were isolated from this plant for the first time. In addition, compound <b>1</b> showed moderate inhibitory activity against α-glucosidase with IC<sub>50</sub> value at 0.111 ± 0.061 mg/mL.
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New Phenolic Dimers from Plant <i>Paeonia suffruticosa</i> and Their Cytotoxicity and NO Production Inhibition.
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The <i>Paeonia suffruticosa</i>, known as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A-E (<b>1</b>-<b>5</b>), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds <b>2</b>, <b>4</b>, and <b>5</b> showed cytotoxicity against three human cancer cell lines, with IC<sub>50</sub> values ranging from 6.7 to 25.1 μM. Compounds <b>1</b> and <b>2</b> showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of <i>P. suffruticosa</i> are reported for the first time in this paper.
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A new homo-aro-cholestane glycoside parispolyside H, along with nine known compounds, were isolated from 75% ethanolic extract of the rhizome of <i>Paris polyphylla</i> var. <i>chinensis</i>. Their chemical structures were elucidated on the basic of analysis of detailed spectroscopic and physicochemical properties. In addition, the isolated compounds (<b>1</b>, <b>6</b>-<b>9</b>) were evaluated for their cytotoxic activity against HepG2 human liver cancer cell lines. Among them, four known compounds (<b>6</b>-<b>9</b>) showed cytotoxicity with IC<sub>50</sub> values ranging from 0.41 to 3.6 μM.
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Platelet factor XI: intracellular localization and mRNA splicing following platelet activation.
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The structure and function of platelet factor XI (FXI) protein and the presence of F11 mRNA in platelets are controversial. Although platelets are anucleated cells they contain spliceosome components and pre-mRNAs. Three platelet proteins have been demonstrated to be spliced upon platelet activation.
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Arterial thrombosis manifesting as heart attack and stroke is the leading cause of death worldwide. Platelets are central mediators of thrombosis that can be activated through multiple activation pathways. Platelet-derived extracellular vesicles (pEVs), also known as platelet-derived microparticles, are granular mixtures of membrane structures produced by platelets in response to various activating stimuli. Initial studies have attracted interest on how platelet agonists influence the composition of the pEV proteome. In the current study, we used physiological platelet agonists of varying potencies which reflect the microenvironments that platelets experience during thrombus formation: adenosine diphosphate, collagen, thrombin as well as a combination of thrombin/collagen to induce platelet activation and pEV generation. Proteomic profiling revealed that pEVs have an agonist-dependent altered proteome in comparison to their cells of origin, activated platelets. Furthermore, we found that various protein classes including those related to coagulation and complement (prothrombin, antithrombin, and plasminogen) and platelet activation (fibrinogen) are attributed to platelet EVs following agonist stimulation. This agonist-dependent altered proteome suggests that protein packaging is an active process that appears to occur without de novo protein synthesis. This study provides new information on the influence of physiological agonist stimuli on the biogenesis and proteome landscape of pEVs.
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Platelet factor XI: intracellular localization and mRNA splicing following platelet activation.
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The structure and function of platelet factor XI (FXI) protein and the presence of F11 mRNA in platelets are controversial. Although platelets are anucleated cells they contain spliceosome components and pre-mRNAs. Three platelet proteins have been demonstrated to be spliced upon platelet activation.
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Because of their ability to become rapidly activated at places of vascular injury, platelets are important players in primary hemostasis as well as in arterial thrombosis. In addition, they are also involved in chronic pathological processes including the atherosclerotic remodeling of the vascular system. Although primary adhesion of platelets to the vessel wall is largely independent of G protein-mediated signaling, the subsequent recruitment of additional platelets into a growing platelet thrombus requires mediators such as ADP, thromboxane A(2), or thrombin, which act through G protein-coupled receptors. Platelet activation via G protein-coupled receptors involves 3 major G protein-mediated signaling pathways that are initiated by the activation of the G proteins G(q), G(13), and G(i). This review summarizes recent progress in understanding the mechanisms underlying platelet activation and thrombus extension via G protein-mediated signaling pathways.
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Platelet factor XI: intracellular localization and mRNA splicing following platelet activation.
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The structure and function of platelet factor XI (FXI) protein and the presence of F11 mRNA in platelets are controversial. Although platelets are anucleated cells they contain spliceosome components and pre-mRNAs. Three platelet proteins have been demonstrated to be spliced upon platelet activation.
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Platelets, in addition to their function in hemostasis, play an important role in wound healing and tumor growth. Because platelets contain angiogenesis stimulators and inhibitors, the mechanisms by which platelets regulate angiogenesis remain unclear. As platelets adhere to activated endothelium, their action can enhance or inhibit local angiogenesis. We therefore suspected a higher organization of angiogenesis regulators in platelets. Using double immunofluorescence and immunoelectron microscopy, we show that pro- and antiangiogenic proteins are separated in distinct subpopulations of alpha-granules in platelets and megakaryocytes. Double immunofluorescence labeling of vascular endothelial growth factor (VEGF) (an angiogenesis stimulator) and endostatin (an angiogenesis inhibitor), or for thrombospondin-1 and basic fibroblast growth factor, confirms the segregation of stimulators and inhibitors into separate and distinct alpha-granules. These observations motivated the hypothesis that distinct populations of alpha-granules could undergo selective release. The treatment of human platelets with a selective PAR4 agonist (AYPGKF-NH(2)) resulted in release of endostatin-containing granules, but not VEGF-containing granules, whereas the selective PAR1 agonist (TFLLR-NH(2)) liberated VEGF, but not endostatin-containing granules. In conclusion, the separate packaging of angiogenesis regulators into pharmacologically and morphologically distinct populations of alpha-granules in megakaryocytes and platelets may provide a mechanism by which platelets can locally stimulate or inhibit angiogenesis.
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Platelet factor XI: intracellular localization and mRNA splicing following platelet activation.
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The structure and function of platelet factor XI (FXI) protein and the presence of F11 mRNA in platelets are controversial. Although platelets are anucleated cells they contain spliceosome components and pre-mRNAs. Three platelet proteins have been demonstrated to be spliced upon platelet activation.
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Polyphosphate (polyP) promotes feedback activation of factor (F) XI by thrombin by serving as a template. The contribution of thrombin's exosites to these interactions is unclear.
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Platelet factor XI: intracellular localization and mRNA splicing following platelet activation.
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The structure and function of platelet factor XI (FXI) protein and the presence of F11 mRNA in platelets are controversial. Although platelets are anucleated cells they contain spliceosome components and pre-mRNAs. Three platelet proteins have been demonstrated to be spliced upon platelet activation.
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Platelets shed microparticles, which support haemostasis via adherence to the damaged vasculature and by promoting blood coagulation. We investigated mechanisms through which storage-induced microparticles might support blood coagulation. Flow cytometry was used to determine microparticle number, cellular origin and surface expression of tissue factor (TF), procoagulant phosphatidylserine (PtdSer) and glycoprotein (GP) Ib-alpha. The influence of microparticles on initiation and propagation of coagulation were examined in activated factor X (factor Xa; FXa) and thrombin generation assays and compared with that of synthetic phospholipids. About 75% of microparticles were platelet derived and their number significantly increased during storage of platelet concentrates. About 10% of the microparticles expressed functionally active TF, as measured in a FXa generation assay. However, TF-driven thrombin generation was only found in plasma in which tissue factor pathway inhibitor (TFPI) was neutralised, suggesting that microparticle-associated TF in platelet concentrates is of minor importance. Furthermore, 60% of all microparticles expressed PtdSer. In comparison with synthetic procoagulant phospholipids, the maximal rate of thrombin formation in TF-activated plasma was 15-fold higher when platelet-free plasma was titrated with microparticles. This difference could be attributed to the ability of microparticles to propagate thrombin generation by thrombin-activated FXI. Collectively, our findings indicate a role of microparticles in supporting haemostasis by enhancement of the propagation phase of blood coagulation.
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Pollution characteristics and ecological risk assessment of 11 unheeded metals in sediments of the Chinese Xiangjiang River.
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With the change in global climate and environment, water scarcity has been of great concern around the word and exacerbated by serious pollution in water resources. Pollutants accumulated in sediments are threatening water safety and ecological security. Different from others focusing on prevalent heavy metals (Cu, Pb, Zn, As, Cd, Cr, Hg, etc.), in this study, some unheeded metal pollutants Tl, Sb, Mo, Sr, Co, V, Ti, Ca, Mg, Be and Li were monitored in sediments of the Xiangjiang River, China. It was found that there was no remarkable vertical variation with depth, but the seasonal characteristics of Tl, Sb, Mo, Be and Li. The enrichment, pollution and potential ecological risk of Tl, Sb and Mo were revealed by the enrichment factor (EF), geoaccumulation index (I<sub>geo</sub>), pollution load index (PLI<sub>site</sub> and PLI<sub>zone</sub>) and potential ecological risk index (RI). It is noticed that the pollution of Tl mainly occurred in summer at midstream and downstream and Mo pollution was much higher than Sb in summer and the reverse in other seasons. Additionally, sediment quality on east side was worse than on west side in Songbai section of the Xiangjiang River. For the first time, the toxic-response factor was figured out as Mo = 18, Tl = 17, Sb = 13, Sr = 6, Co = Be = 1, V = Li = 0, and importantly, the high potential ecological risk of Tl, Sb and Mo needs to be taken seriously for the comprehensive assessment on watershed environmental quality.
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The contents of heavy metals (As, Cd, Cu, Zn, Ni and Pb) in soils from Xiangjiang River Basin, Hunan Province, China, were analyzed by toxicity characteristic leaching procedure (TCLP) and Nemrow method. Results showed that the total contents of As, Cd, Cu, Zn, Ni and Pb were 4.25-549.67, 0.13-76.84, 11.49-281.69, 7.75-7234.81, 5.50-56.65 and 8.60-2084.81 mg x kg(-1), respectively, and the available contents of As, Cd, Cu, Zn, Ni and Pb extracted by TCLP were 0.02-10.97, 0.06-28.41, 0.04-72.29, 0.59-1 152.32, 0.07-10. 65 and 0.17-1 165.58 mg x kg(-1). The contents of available heavy metals extracted by TCLP correlated with total contents of heavy metals. Moreover, the pollution index Nemrow method showed that 72 samples at safety level, alert level, light pollution level, medium pollution level and heavy pollution level ratios were 60.52%, 11.33%, 5.65%, 4.22% and 18.38% separately, illustrating that pollution of heavy metals in soil samples of Xiangjiang River Basin is serious.
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