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TITLE: Production, Isolation, and Characterization of Bioengineered Bacterial Extracellular Membrane Vesicles Derived from Bacteroides thetaiotaomicron and Their Use in Vaccine Development.. ABSTRACT: Bacterial extracellular vesicles (BEVs) possess features that make them well suited for the delivery of therapeutics and vaccines. This chapter describes methods for engineering the commensal human intestinal bacterium Bacteroides thetaiotaomicron (Bt) to produce BEVs carrying vaccine antigens and accompanying methods for isolating and purifying BEVs for mucosal vaccination regimens.
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TITLE: Multiepitope Fusion Antigen: MEFA, an Epitope- and Structure-Based Vaccinology Platform for Multivalent Vaccine Development.. ABSTRACT: Vaccines are regarded as the most cost-effective countermeasure against infectious diseases. One challenge often affecting vaccine development is antigenic diversity or pathogen heterogeneity. Different strains produce immunologically heterogeneous virulence factors, therefore an effective vaccine needs to induce broad-spectrum host immunity to provide cross-protection. Recent advances in genomics and proteomics, particularly computational biology and structural biology, establishes structural vaccinology and highlights the feasibility of developing effective and precision vaccines. Here, we introduce the epitope- and structure-based vaccinology platform multiepitope-fusion-antigen (MEFA), and provide instructions to generate polyvalent MEFA immunogens for vaccine development. Conceptually, MEFA combines epitope vaccinology and structural vaccinology to enable a protein immunogen to present heterogeneous antigenic domains (epitopes) and to induce broadly protective immunity against different virulence factors, strains or diseases. Methodologically, the MEFA platform first identifies a safe, structurally stable and strongly immunogenic backbone protein and immunodominant (ideally neutralizing or protective) epitopes from heterogeneous strains or virulence factors of interest. Then, assisted with protein modeling and molecule dynamic simulation, MEFA integrates heterogeneous epitopes into a backbone protein via epitope substitution for a polyvalent MEFA protein and mimics epitope native antigenicity. Finally, the MEFA protein is examined for broad immunogenicity in animal immunization, and assessed for potential application for multivalent vaccine development in preclinical studies.
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TITLE: Well-being of Polish university students after the first year of the coronavirus pandemic: The role of core self-evaluations, social support and fear of COVID-19.. ABSTRACT: BACKGROUND: The SARS-CoV-2 pandemic represents an unprecedented situation in the most recent history. It has had a number of negative consequences for individuals and for whole societies. Individual effects of the pandemic include not only loss of life and of physical health, but also deteriorated quality of life.OBJECTIVE: This study examines the effect of core self-evaluations (CSE), social support and fear of COVID-19 on the well-being of university students in Poland during the COVID-19 pandemic.METHODS: We conducted an online survey on a nationwide group of 1,000 students of Polish universities. The survey was carried out between 1 and 15 March 2021. The respondents filled out the following set of tools: World Health Organization Quality of Life Scale, Core Self-Evaluations Scale, Multidimensional Scale of Perceived Social Support and The Fear of COVID-19 Scale.RESULTS: The findings showed that core self-evaluations (CSE) were significantly positively associated with well-being in each of the four domains studied: physical health (r = 0.519), psychological (r = 0.763), social relationships (r = 0.465) and environment (r = 0.496). Similarly, social support correlated positively with physical health (r = 0.277), psychological health (r = 0.306), social relationships (r = 0.552) and environment (r = 0.496). Fear of COVID-19 correlated negatively with well-being in the domain of physical health (r = 0.188), in social relationships (r = 0.042) and with regard to the environment (r = 0.071), the correlations were weak. However, the relationship between fear of COVID-19 and well-being in the psychological domain was not confirmed.CONCLUSION: The findings point to the significant role of CSE and the role of social support in the perceived quality of life of young people during the pandemic. They provide valuable data concerning individuals who are particularly vulnerable to the adverse psychological effects at the time of the pandemic. They also prove that research conducted to explore other factors protecting individual well-being in difficult situations, including that of the pandemic, should be continued.
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TITLE: Anger among Chinese migrants amid COVID-19 discrimination: The role of host news coverage, cultural distance, and national identity.. ABSTRACT: As the early COVID-19 outbreak sparked xenophobia against people of Asian and Chinese background, we collected data from Chinese migrants worldwide to test how discrimination at a macro-level was perceived by the Chinese during COVID-19 globally. Specifically, we examined (1) whether/how the Chinese migrants were aware of discrimination against their co-nationals during COVID; (2) if so, whether anger was a predominant reaction of these Chinese towards certain exposure to relevant information; (3) how responses of anger transcend across the group of Chinese migrants. Integrating the ecological approach to media and cultural psychology, as well as the intergroup perspective of social psychology, we conducted a study that explored the impact of traditional media exposure to discrimination on collective anger-a process mediated by national identity among the Chinese migrants. Findings provide some evidence that geographically dispersed mono-cultural groups may share or identify with collective emotions when facing xenophobic threats in a macro context. Further examination of cultural distance (between China and the host country) among the Chinese migrants also revealed a particular interaction between host newspaper coverage and cultural distance on national identity. These findings suggest further research to examine the emotional norms of similar cultures bonded via strong collective identities in times of intergroup threat and the theoretical possibility for diasporic identity processes.
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TITLE: Assessing the impact of non-pharmaceutical interventions (NPI) on the dynamics of COVID-19: A mathematical modelling study of the case of Ethiopia.. ABSTRACT: The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2020 and by November 14, 2020 there were 53.3M confirmed cases and 1.3M reported deaths in the world. In the same period, Ethiopia reported 102K cases and 1.5K deaths. Effective public health preparedness and response to COVID-19 requires timely projections of the time and size of the peak of the outbreak. Currently, Ethiopia under the COVAX facility has begun vaccinating high risk populations but due to vaccine supply shortages and the absence of an effective treatment, the implementation of NPIs (non-pharmaceutical interventions), like hand washing, wearing face coverings or social distancing, still remain the most effective methods of controlling the pandemic as recommended by WHO. This study proposes a modified Susceptible Exposed Infected and Recovered (SEIR) model to predict the number of COVID-19 cases at different stages of the disease under the implementation of NPIs at different adherence levels in both urban and rural settings of Ethiopia. To estimate the number of cases and their peak time, 30 different scenarios were simulated. The results indicated that the peak time of the pandemic is different in urban and rural populations of Ethiopia. In the urban population, under moderate implementation of three NPIs the pandemic will be expected to reach its peak in December, 2020 with 147,972 cases, of which 18,100 are symptomatic and 957 will require admission to an Intensive Care Unit (ICU). Among the implemented NPIs, increasing the coverage of wearing masks by 10% could reduce the number of new cases on average by one-fifth in urban-populations. Varying the coverage of wearing masks in rural populations minimally reduces the number of cases. In conclusion, the models indicate that the projected number of hospital cases during the peak time is higher than the Ethiopian health system capacity. To contain symptomatic and ICU cases within the health system capacity, the government should pay attention to the strict implementation of the existing NPIs or impose additional public health measures.
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TITLE: Sampling site for SARS-CoV-2 RT-PCR-An intrapatient four-site comparison from Tampere, Finland.. ABSTRACT: BACKGROUND: SARS-CoV-2 diagnosis relies on the performance of nasopharyngeal swabs. Alternative sample sites have been assessed but the heterogeneity of the studies have made comparing different sites difficult.OBJECTIVES: Our aim was to compare the performance of four different sampling sites for SARS-CoV-2 samples with nasopharynx being the benchmark.STUDY DESIGN: COVID-19 positive patients were recruited prospectively, and samples were collected and analysed for SARS-CoV-2 with RT-PCR from all four anatomical sites in 43 patients, who provided written informed consent.RESULTS: All anterior nasal and saliva samples were positive, while two oropharyngeal samples were negative. There was no significant difference in the cycle threshold values of nasopharyngeal and anterior nasal samples while saliva and oropharynx had higher cycle threshold values.CONCLUSIONS: Anterior nasal swab performs as good as nasopharynx swab with saliva also finding all the positives but with higher cycle threshold values. Thus, we can conclude that anterior nasal swabs can be used for SARS-CoV-2 detection instead of nasopharyngeal swabs if the situation would require so.
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TITLE: Differential effects of COVID-19 and containment measures on mental health: Evidence from ITA.LI-Italian Lives, the Italian household panel.. ABSTRACT: This study used a subsample of a household panel study in Italy to track changes in mental health before the onset of COVID-19 and into the first lockdown period, from late April to early September 2020. The results of the random-effects regression analyses fitted on a sample of respondents aged 16 years and older (N = 897) proved that there was a substantial and statistically significant short-term deterioration in mental health (from 78,5 to 67,9; â = -10.5, p < .001; Cohen's d -.445), as measured by a composite index derived from the mental component of the 12-item Short-Form Health Survey (SF-12). The findings also showed heterogeneity in the COVID-related effects. On the one hand, evidence has emerged that the pandemic acted as a great leveller of pre-existing differences in mental health across people of different ages: the decrease was most pronounced among those aged 16-34 (from 84,2 to 66,5; â = -17.7, p < .001; Cohen's d -.744); however, the magnitude of change reduced as age increased and turned to be non-significant among individuals aged 70 and over. On the other hand, the COVID-19 emergency widened the mental health gender gap and created new inequalities, based on the age of the youngest child being taken care of within the household.
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TITLE: At home and online during the early months of the COVID-19 pandemic and the relationship to alcohol consumption in a national sample of U.S. adults.. ABSTRACT: INTRODUCTION: The current study aimed to understand the links between social media use and alcohol consumption during the early months of the COVID-19 pandemic.METHOD: Data were from the national Understanding American Study, a probability-based Internet panel weighted to represent the U.S. population. Subjects (N = 5874; 51% female) were adults, 18 years and older, who completed a March survey (wave 1) and a follow-up survey one month later (wave 3). Analyses assessed the relationships of social media use at wave 1 with wave 3 alcohol use frequency, accounting for wave 1 alcohol use frequency and the sociodemographic characteristics of the sample. Two alcohol use change variables were also assessed as outcomes-increased and decreased alcohol use between waves. We considered the effect of work status changes (working/studying from home and job loss) as potential moderators.RESULTS: Twitter and Instagram users and users of multiple social media platforms, but not Facebook users, drank more frequently at wave 3. The results were similar when assessing relationships between social media use and increased alcohol use between waves. For Instagram users, more frequent alcohol use at wave 3 was at least partially attributed to drinking frequency at wave 1. Additionally, working/studying from home at wave 3 and employment (rather than job loss) were associated with greater consumption. The interaction effect between Twitter use and working/studying from home was statistically significant in association with alcohol use frequency at wave 3, as was the interaction effect between using multiple platforms and working/studying from home in association with decreased alcohol use between waves.DISCUSSION: Exposure to content about COVID-19 and increased alcohol consumption during the pandemic may have contributed to more frequent alcohol use for some social media users. The study of public health messaging via social media to change alcohol use behaviors during traumatic events is warranted.
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TITLE: Association of SARS-CoV-2 Infection With Psychological Distress, Psychotropic Prescribing, Fatigue, and Sleep Problems Among UK Primary Care Patients.. ABSTRACT: Importance: Infection with SARS-CoV-2 is associated with fatigue and sleep problems long after the acute phase of COVID-19. In addition, there are concerns of SARS-CoV-2 infection causing psychiatric illness; however, evidence of a direct effect is inconclusive.Objective: To assess risk of risk of incident or repeat psychiatric illness, fatigue, or sleep problems following SARS-CoV-2 infection and to analyze changes according to demographic subgroups.Design, Setting, and Participants: This cohort study assembled matched cohorts using the Clinical Practice Research Datalink Aurum, a UK primary care registry of 11 923 499 individuals aged 16 years or older. Patients were followed-up for up to 10 months, from February 1 to December 9, 2020. Individuals with less than 2 years of historical data or less than 1 week follow-up were excluded. Individuals with positive results on a SARS-CoV-2 test without prior mental illness or with anxiety or depression, psychosis, fatigue, or sleep problems were matched with up to 4 controls based on sex, general practice, and year of birth. Controls were individuals who had negative SARS-CoV-2 test results. Data were analyzed from January to July 2021.Exposure: SARS-CoV-2 infection, determined via polymerase chain reaction testing.Main Outcomes and Measures: Cox proportional hazard models estimated the association between a positive SARS-CoV-2 test result and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue, or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking, and body mass index.Results: Of 11 923 105 eligible individuals (6 011 020 [50.4%] women and 5 912 085 [49.6%] men; median [IQR] age, 44 [30-61] years), 232 780 individuals (2.0%) had positive result on a SARS-CoV-2 test. After applying selection criteria, 86 922 individuals were in the matched cohort without prior mental illness, 19 020 individuals had prior anxiety or depression, 1036 individuals had psychosis, 4152 individuals had fatigue, and 4539 individuals had sleep problems. After adjusting for observed confounders, there was an association between positive SARS-CoV-2 test results and psychiatric morbidity (adjusted hazard ratio [aHR], 1.83; 95% CI, 1.66-2.02), fatigue (aHR, 5.98; 95% CI, 5.33-6.71), and sleep problems (aHR, 3.16; 95% CI, 2.64-3.78). However, there was a similar risk of incident psychiatric morbidity for those with a negative SARS-CoV-2 test results (aHR, 1.71; 95% CI, 1.65-1.77) and a larger increase associated with influenza (aHR, 2.98; 95% CI, 1.55-5.75).Conclusions and Relevance: In this cohort study of individuals registered at an English primary care practice during the pandemic, there was consistent evidence that SARS-CoV-2 infection was associated with increased risk of fatigue and sleep problems. However, the results from the negative control analysis suggest that unobserved confounding may be responsible for at least some of the positive association between COVID-19 and psychiatric morbidity.
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TITLE: Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction: The PARALLAX Randomized Clinical Trial.. ABSTRACT: Importance: There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%).Objective: To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%.Design, Setting, and Participants: A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019).Interventions: Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor.Main Outcomes and Measures: Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks.Results: Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%).Conclusions and Relevance: Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients.Trial Registration: ClinicalTrials.gov Identifier: NCT03066804.
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TITLE: Breast Implants: Common Questions and Answers.. ABSTRACT: Breast implants are used for a wide range of cosmetic and reconstructive purposes. In addition to breast augmentation, implants can be used for postmastectomy breast reconstruction, correction of congenital breast anomalies, breast or chest wall deformities, and male-to-female top surgery. Breast implants may confer significant benefits to patients, but several factors are important to consider preoperatively, including the impact on mammography, future lactation, and potential long-term implant complications (e.g., infection, capsular contracture, rupture, and the need for revision, replacement, or removal). A fundamental understanding of implant monitoring is also paramount to implant use. Patients with silicone breast implants should undergo routine screening for implant rupture with magnetic resonance imaging or ultrasonography completed five to six years postoperatively and then every two to three years thereafter. With the exception of complications, there are no formal recommendations regarding the timing of breast implant removal or exchange. Women with unilateral breast swelling should be evaluated with ultrasonography for an effusion that might indicate breast implant-associated anaplastic large cell lymphoma. There are no specific breast cancer screening recommendations for patients with breast implants, but special mammographic views are indicated to enhance accuracy. Although these discussions are a routine component of consultation and postoperative follow-up for plastic surgeons performing these procedures, family physicians should have a working knowledge of implant indications, characteristics, and complications to better counsel their patients, to ensure appropriate screening, and to coordinate care after surgery.
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TITLE: Medical Clearance for Common Dental Procedures.. ABSTRACT: Medical consultations before dental procedures present opportunities to integrate cross-disciplinary preventive care and improve patient health. This article presents recommendations related to patients with certain medical conditions who are planning to undergo common dental procedures, such as cleanings, extractions, restorations, endodontic procedures, abscess drainage, and mucosal biopsies. Specifically, prophylactic antibiotics are not recommended for preventing prosthetic joint infections or infectious endocarditis except in certain circumstances. Anticoagulation and antiplatelet therapies typically should not be suspended for common dental treatments. Elective dental care should be avoided for six weeks after myocardial infarction or bare-metal stent placement or for six months after drug-eluting stent placement. It is important that any history of antiresorptive or antiangiogenic therapies be communicated to the dentist. Ascites is not an indication for initiating prophylactic antibiotics before dental treatment, and acetaminophen is the analgesic of choice for patients with liver dysfunction or cirrhosis who abstain from alcohol. Nephrotoxic medications should be avoided in patients with chronic kidney disease, and the consultation should include the patient's glomerular filtration rate. Although patients undergoing chemotherapy may receive routine dental care, it should be postponed when possible in those currently undergoing head and neck radiation therapy. A detailed history of head and neck radiation therapy should be provided to the dentist. Multimodal, nonnarcotic analgesia is recommended for managing acute dental pain.
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TITLE: End-Stage Renal Disease: Medical Management.. ABSTRACT: End-stage renal disease (ESRD) is diagnosed when kidney function is no longer adequate for long-term survival without kidney transplantation or dialysis. Primary care clinicians should refer people at risk of ESRD to nephrology to optimize disease management. Kidney transplantation typically yields the best patient outcomes, although most patients are treated with dialysis. The decision to initiate dialysis is best made through shared decision-making. Because most patients with ESRD elect to receive hemodialysis, the preservation of peripheral veins is important for those with stage III to V chronic kidney disease. A palliative approach to ESRD is a reasonable alternative to dialysis, particularly for individuals with limited life expectancy, with severe comorbid conditions, or who wish to avoid medical interventions. For patients with ESRD, vaccination against seasonal influenza, tetanus, hepatitis B, human papillomavirus (through 26 years of age), and Streptococcus pneumoniae is advised. Routine cancer screening for patients not receiving kidney transplantation is discouraged. Controlling blood pressure in patients receiving dialysis improves mortality. Volume control through adequate dialysis and sodium restriction can help optimize hypertension treatment in these patients. Insulin is the preferred treatment for patients with ESRD and diabetes mellitus requiring medication. Patients should be monitored for signs of protein-energy wasting and malnutrition. Clinicians must be aware of the many medical complications associated with ESRD.
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TITLE: Fetal Growth Restriction Before and After Birth.. ABSTRACT: Fetal growth restriction, previously called intrauterine growth restriction, is a condition in which a fetus does not achieve its full growth potential during pregnancy. Early detection and management of fetal growth restriction are essential because it has significant clinical implications in childhood. It is diagnosed by estimated fetal weight or abdominal circumference below the 10th percentile on formal ultrasonography. Early-onset fetal growth restriction is diagnosed before 32 weeks' gestation and has a higher risk of adverse fetal outcomes. There are no evidence-based measures for preventing fetal growth restriction; however, aspirin used for the prevention of preeclampsia in high-risk pregnancies may reduce the likelihood of developing it. Timing of delivery for pregnancies affected by growth restriction must be adjusted based on the risks of premature birth and ongoing gestation, and it is best determined in consultation with maternal-fetal medicine specialists. Neonates affected by fetal growth restriction are at risk of feeding difficulties, glucose instability, temperature instability, and jaundice. As these children age, they are at risk of abnormal growth patterns, as well as later cardiac, metabolic, neurodevelopmental, reproductive, and psychiatric disorders.
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TITLE: Recent-Onset Altered Mental Status: Evaluation and Management.. ABSTRACT: Potential precipitating factors for the recent onset of altered mental status (AMS) include primary central nervous system insults, systemic infections, metabolic disturbances, toxin exposure, medications, chronic systemic diseases, and psychiatric conditions. Delirium is also an important manifestation of AMS, especially in older people who are hospitalized. Clinicians should identify and treat reversible causes of the AMS, some of which require urgent intervention to minimize morbidity and mortality. A history and physical examination guide diagnostic testing. Laboratory testing, chest radiography, and electrocardiography help diagnose infections, metabolic disturbances, toxins, and systemic conditions. Neuroimaging with computed tomography or magnetic resonance imaging should be performed when the initial evaluation does not identify a cause or raises concern for intracranial pathology. Lumbar puncture and electroencephalography are also important diagnostic tests in the evaluation of AMS. Patients at increased risk of AMS benefit from preventive measures. The underlying etiology determines the definitive treatment. When intervention is needed to control patient behaviors that threaten themselves or others, nonpharmacologic interventions are preferred to medications. Physical restraints should rarely be used and only for the shortest time possible. Medications should be used only when nonpharmacologic treatments are ineffective.
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TITLE: What support do young people affected by adverse childhood experiences need?. ABSTRACT: The studyLester S, Khatwa M, Sutcliffe K. Service needs of young people affected by adverse childhood experiences (ACEs): A systematic review of UK qualitative evidence. Child Youth Serv Rev 2020;118:105429.To read the full NIHR Alert, go to https://evidence.nihr.ac.uk/alert/support-needs-of-young-people-affected-by-adverse-childhood-experiences/.
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TITLE: Prevalence of cardiac pathology and relation to mortality in a multiethnic population hospitalised with COVID-19.. ABSTRACT: OBJECTIVE: To determine the prevalence of cardiac abnormalities and their relationship to markers of myocardial injury and mortality in patients admitted to hospital with COVID-19.METHODS: A retrospective and prospective observational study of inpatients referred for transthoracic echocardiography for suspected cardiac pathology due to COVID-19 within a London NHS Trust. Echocardiograms were performed to assess left ventricular (LV), right ventricular (RV) and pulmonary variables along with collection of patient demographics, comorbid conditions, blood biomarkers and outcomes.RESULT: In the predominant non-white (72%) population, RV dysfunction was the primary cardiac abnormality noted in 50% of patients, with RV fractional area change <35% being the most common marker of this RV dysfunction. By comparison, LV systolic dysfunction occurred in 18% of patients. RV dysfunction was associated with LV systolic dysfunction and the presence of a D-shaped LV throughout the cardiac cycle (marker of significant pulmonary artery hypertension). LV systolic dysfunction (p=0.002, HR 3.82, 95% CI 1.624 to 8.982), pulmonary valve acceleration time (p=0.024, HR 0.98, 95% CI 0.964 to 0.997)-marker of increased pulmonary vascular resistance, age (p=0.047, HR 1.027, 95% CI 1.000 to 1.055) and an episode of tachycardia measured from admission to time of echo (p=0.004, HR 6.183, 95% CI 1.772 to 21.575) were independently associated with mortality.CONCLUSIONS: In this predominantly non-white population hospitalised with COVID-19, the most common cardiac pathology was RV dysfunction which is associated with both LV systolic dysfunction and elevated pulmonary artery pressure. The latter two, not RV dysfunction, were associated with mortality.
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TITLE: Nanometer-resolution in situ structure of the SARS-CoV-2 postfusion spike protein.. ABSTRACT: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates membrane fusion to allow entry of the viral genome into host cells. To understand its detailed entry mechanism and develop a specific entry inhibitor, in situ structural information on the SARS-CoV-2 spike protein in different states is urgent. Here, by using cryo-electron tomography, we observed both prefusion and postfusion spikes in â-propiolactone-inactivated SARS-CoV-2 virions and solved the in situ structure of the postfusion spike at nanometer resolution. Compared to previous reports, the six-helix bundle fusion core, the glycosylation sites, and the location of the transmembrane domain were clearly resolved. We observed oligomerization patterns of the spikes on the viral membrane, likely suggesting a mechanism of fusion pore formation.
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TITLE: Impact of tick-borne Anaplasma phagocytophilum infections in calves of moose (Alces alces) in southern Norway.. ABSTRACT: The Gram-negative, obligate intracellular tick-transmitted pathogen Anaplasma phagocytophilum can cause acute febrile diseases in humans and domestic animals. The expansion of the tick Ixodes ricinus (Linnaeus, 1758) in northern Europe due to climate change is of serious concern for animal and human health. The aim of the present study was to investigate the impact of A. phagocytophilum infection in moose Alces alces (Linnaeus) calves by evaluating the carcass weights of infected and non-infected animals and examining animal tissues samples for co-infections with either species of Babesia Starcovici, 1893 or bacteria of the genus Bartonella. The carcasses of 68 free-ranging moose calves were weighed by hunters during the hunting seasons from 2014 to 2017 in two regions in southern Norway and spleen samples were collected. Anaplasma phagocytophilum was detected in moose sampled from locations infected with ticks with a prevalence of 82% (n = 46). The carcass weights of A. phagocytophilum-infected calves (n = 46) and non-infected (n = 22) calves were compared. Although the average weight of infected calves (45.6 kg) was lower than that of non-infected calves (46.5 kg), the difference was not statistically significant. Three different variants of the bacterium 16S rRNA gene were identified. The average weight of animals infected with variant I was 49.9 kg, whereas that of animals infected with variant III was 42.0 kg, but the difference was not statistically significant (p = 0.077). Co-infections of A. phagocytophilum with Bartonella spp. or with Babesia spp. were found in 20 and two calves, respectively. A triple infection was found in two calves. Sequence analysis of the 18S rRNA gene of Babesia-positive samples revealed the presence of Babesia cf. odocoilei (Emerson et Wright, 1970). Strains of Bartonella closely related to Bartonella bovis (Bermond, Boulouis, Heller, Laere, Monteil, Chomel, Sander, Dehio et Piemont, 2002) were identified based on phylogenetic analysis of the gltA and rpoB genes. The loss of body mass in moose calves in the tick-infected site was probably influenced by multiple factors.
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TITLE: An Expert System for COVID-19 Infection Tracking in Lungs Using Image Processing and Deep Learning Techniques.. ABSTRACT: The proposed method introduces algorithms for the preprocessing of normal, COVID-19, and pneumonia X-ray lung images which promote the accuracy of classification when compared with raw (unprocessed) X-ray lung images. Preprocessing of an image improves the quality of an image increasing the intersection over union scores in segmentation of lungs from the X-ray images. The authors have implemented an efficient preprocessing and classification technique for respiratory disease detection. In this proposed method, the histogram of oriented gradients (HOG) algorithm, Haar transform (Haar), and local binary pattern (LBP) algorithm were applied on lung X-ray images to extract the best features and segment the left lung and right lung. The segmentation of lungs from the X-ray can improve the accuracy of results in COVID-19 detection algorithms or any machine/deep learning techniques. The segmented lungs are validated over intersection over union scores to compare the algorithms. The preprocessed X-ray image results in better accuracy in classification for all three classes (normal/COVID-19/pneumonia) than unprocessed raw images. VGGNet, AlexNet, Resnet, and the proposed deep neural network were implemented for the classification of respiratory diseases. Among these architectures, the proposed deep neural network outperformed the other models with better classification accuracy.
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TITLE: Serial Screening for SARS-CoV-2 in Rectal Swabs of Symptomatic COVID-19 Patients.. ABSTRACT: We used serial rectal swabs to investigate the amount and duration of virus secretion through the gastrointestinal tract and assessed the association between fecal shedding and gastrointestinal symptoms and to clarify the clinical usefulness testing rectal swabs. We enrolled ten adult patients hospitalized with symptomatic coronavirus disease 2019 (COVID-19). Respiratory and stool specimens were collected by physicians. The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed using real-time reverse-transcription polymerase chain reaction. All ten patients had respiratory symptoms, six had diarrhea, and seven were positive for SARS-CoV-2 on rectal swabs. The viral loads in the respiratory specimens was higher than those in the rectal specimens, and no rectal specimens were positive after the respiratory specimens became negative. There was no association between gastrointestinal symptoms, pneumonia, severity, and rectal viral load. Rectal swabs may play a role in detecting SARS-CoV-2 in individuals with suspected COVID-19, regardless of gastrointestinal symptoms.
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TITLE: Maternal and Neonatal Outcomes of Critically Ill Pregnant and Puerperal Patients Diagnosed with COVID-19 Disease: Retrospective Comparative Study.. ABSTRACT: BACKGROUND: We assessed maternal and neonatal outcomes of critically ill pregnant and puerperal patients in the clinical course of coronavirus disease 2019 (COVID-19).METHODS: Records of pregnant and puerperal women with polymerase chain reaction positive COVID-19 virus who were admitted to our intensive care unit (ICU) from March 2020 to August 2021 were investigated. Demographic, clinical and laboratory data, pharmacotherapy, and neonatal outcomes were analyzed. These outcomes were compared between patients that were discharged from ICU and patients who died in ICU.RESULTS: Nineteen women were included in this study. Additional oxygen was required in all cases (100%). Eight patients (42%) were intubated and mechanically ventilated. All patients that were mechanically ventilated have died. Increased levels of C-reactive protein (CRP) was seen in all patients (100%). D-dimer values increased in 15 patients (78.9%); interleukin-6 (IL-6) increased in 16 cases (84.2%). Sixteen patients used antiviral drugs. Eleven patients were discharged from the ICU and eight patients have died due to complications of COVID-19 showing an ICU mortality rate of 42.1%. Mean number of hospitalized days in ICU was significantly lower in patients that were discharged (P = 0.037). Seventeen patients underwent cesarean-section (C/S) (89.4%). Mean birth week was significantly lower in patients who died in ICU (P = 0.024). Eleven preterm (57.8%) and eight term deliveries (42.1%) occurred.CONCLUSION: High mortality rate was detected among critically ill pregnant/parturient patients followed in the ICU. Main predictors of mortality were the need of invasive mechanical ventilation and higher number of days hospitalized in ICU. Rate of C/S operations and preterm delivery were high. Pleasingly, the rate of neonatal death was low and no neonatal COVID-19 occurred.
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TITLE: COVID-19 prevalence among healthcare workers in Jakarta and neighbouring areas in Indonesia during early 2020 pandemic.. ABSTRACT: BACKGROUND: The COVID-19 disease has overwhelmed and disrupted healthcare services worldwide, particularly healthcare workers (HCW). HCW are essential workers performing any job in a healthcare setting who are potentially directly or indirectly exposed to infectious materials. Our retrospective cohort study aimed to determine the prevalence of COVID-19 infections among HCW in Jakarta and neighbouring areas during the first three months of the pandemic.METHODS: Nasopharyngeal/oropharyngeal swab specimens from HCW working at private and public hospitals in Jakarta and neighbouring areas were screened for SARS-CoV-2 between March and May 2020. Data on demography, clinical symptoms, contact history, and personal protective equipment (PPE) use were collected using standardised forms.RESULTS: Among 1201 specimens, 7.9% were confirmed positive for SARS-CoV-2 with the majority coming from medical doctors (48.4%) and nurses (44.2%). 64.2% of the positive cases reported to have contact with suspect/confirmed COVID-19 cases, including 32 (52.2%) with patient and 3 (6.6%) with co-worker. The symptomatic HCW had a significantly lower median Ct value as compared to their asymptomatic counterpart (p < .001). Tendency to have a higher prevalence of pneumonia was observed in the age group of 40 - 49 and ?50 years old.CONCLUSION: Our findings highlighted the necessity to implement proper preventive and surveillance strategies for this high-risk population including adherence to strict PPE protocol and appropriate training.Key MessageHealthcare workers (HCW), defined as those handling any job in a healthcare setting, are at the frontline of risk of infection as SARS-CoV-2 is easily transmitted through airborne droplets and direct contact with contaminated surfaces. The aim of our study is to attain a more comprehensive and accurate picture of the impact of COVID-19 on HCW during the earlier phase of the outbreak in Indonesia to develop effective strategies that protect the health and safety of this workforce. Our findings highlighted that COVID-19 infections in HCW were mostly acquired in healthcare settings, with significant consequences of pneumonia and hospitalisation occurring across all age groups.
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TITLE: Suppression of the hypothalamic-pituitary-thyroid axis is associated with the severity of prognosis in hospitalized patients with COVID-19.. ABSTRACT: BACKGROUND: The outbreak of severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. SARS-CoV-2 has been found to cause multiple organ damage; however, little attention has been paid to the damage to the endocrine system caused by this virus, and the subsequent impact on prognosis. This may be the first research on the hypothalamic-pituitary-thyroid (HPT) axis and prognosis in coronavirus disease 2019 (COVID-19).METHODS: In this retrospective observational study, 235 patients were admitted to the hospital with laboratory-confirmed SARS-CoV-2 infection from 22 January to 17 March 2020. Clinical characteristics, laboratory findings, and treatments were obtained from electronic medical records with standard data collection forms and compared among patients with different thyroid function status.RESULTS: Among 235 patients, 17 (7.23%) had subclinical hypothyroidism, 11 (4.68%) severe non-thyroidal illness syndrome (NTIS), and 23 (9.79%) mild to moderate NTIS. Composite endpoint events of each group, including mortality, admission to the ICU, and using IMV were observed. Compared with normal thyroid function, the hazard ratios (HRs) of composite endpoint events for mild to moderate NTIS, severe NTIS, subclinical hypothyroidism were 27.3 (95% confidence interval [CI] 7.07-105.7), 23.1 (95% CI 5.75-92.8), and 4.04 (95% CI 0.69-23.8) respectively. The multivariate-adjusted HRs for acute cardiac injury among patients with NTF, subclinical hypothyroidism, severe NTIS, and mild to moderate NTIS were 1.00, 1.68 (95% CI 0.56-5.05), 4.68 (95% CI 1.76-12.4), and 2.63 (95% CI 1.09-6.36) respectively.CONCLUSIONS: Our study shows that the suppression of the HPT axis could be a common complication in COVID-19 patients and an indicator of the severity of prognosis. Among the three different types of thyroid dysfunction with COVID-19, mild to moderate NTIS and severe NTIS have a higher risk of severe outcomes compared with subclinical hypothyroidism.
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TITLE: Characterization and reverse genetic establishment of cattle derived Akabane virus in China.. ABSTRACT: BACKGROUND: Akabane virus (AKAV) is an important insect-borne virus which is widely distributed throughout the world except the Europe and is considered as a great threat to herbivore health.RESULTS: An AKAV strain defined as TJ2016 was firstly isolated from the bovine sera in China in 2016. Sequence analysis of the S and M segments suggested that the isolated AKAV strain was closely related to the AKAV strains JaGAr39 and JaLAB39, which belonged to AKAV genogroup II. To further study the pathogenic mechanism of AKAV, the full-length cDNA clone of TJ2016 S, M, and L segment was constructed separately into the TVT7R plasmid at the downsteam of T7 promoter and named as TVT7R-S, TVT7R-M, and TVT7R-L, respectively. The above three plasmids were further transfected into the BSR-T7/5 cells simultaneously with a ratio of 1:1:1 to produce the rescued virus AKAV. Compared with the parental wild type AKAV (wtAKAV), the rescued virus (rAKAV) was proved to be with similar cytopathic effects (CPE), plaque sizes and growth kinetics in BHK-21 cells.CONCLUSION: We successfully isolated a AKAV strain TJ2016 from the sera of cattle and established a reverse genetic platform for AKAV genome manipulation. The established reverse genetic system is also a powerful tool for further research on AKAV pathogenesis and even vaccine studies.
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TITLE: Metabolomic diferences between COVID-19 and H1N1 influenza induced ARDS.. ABSTRACT: BACKGROUND: Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by lung inflammation and pulmonary edema. Coronavirus disease 2019 (COVID-19) is associated with ARDS in the more severe cases. This study aimed to compare the specificity of the metabolic alterations induced by COVID-19 or Influenza A pneumonia (IAP) in ARDS.METHODS: Eighteen patients with ARDS due to COVID-19 and twenty patients with ARDS due to IAP, admitted to the intensive care unit. ARDS was defined as in the American-European Consensus Conference. As compared with patients with COVID-19, patients with IAP were younger and received more often noradrenaline to maintain a mean arterial pressure > 65 mm Hg. Serum samples were analyzed by Nuclear Magnetic Resonance Spectroscopy. Multivariate Statistical Analyses were used to identify metabolic differences between groups. Metabolic pathway analysis was performed to identify the most relevant pathways involved in ARDS development.RESULTS: ARDS due to COVID-19 or to IAP induces a different regulation of amino acids metabolism, lipid metabolism, glycolysis, and anaplerotic metabolism. COVID-19 causes a significant energy supply deficit that induces supplementary energy-generating pathways. In contrast, IAP patients suffer more marked inflammatory and oxidative stress responses. The classificatory model discriminated against the cause of pneumonia with a success rate of 100%.CONCLUSIONS: Our findings support the concept that ARDS is associated with a characteristic metabolomic profile that may discriminate patients with ARDS of different etiologies, being a potential biomarker for the diagnosis, prognosis, and management of this condition.
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TITLE: Differential diagnosis of primary immunodeficiency in patients with BCGitis and BCGosis: A single-centre study.. ABSTRACT: BCG infections occur more frequently in patients with underlying primary immunodeficiency disease (PIDD). In this study, we aimed to evaluate the ratio of PIDD in the patients with BCG infections. Patients with BCG infections were analyzed in a tertiary referral centre in the 2015-2020 period. Forty-seven patients with BCGitis/BCGosis were evaluated; thirty-four (72.3%) had BCGitis, and 13 (27.7%) had BCGosis. Common tissue and organs affected are lymph nodes (57.4%), skin and subcutaneous tissue (48.9%), lungs (23.4%) and liver (17%). PIDD was shown in 26 patients (55.3%), including 92.3% of patients with BCGosis and 41.2% of patients with BCGitis. Ten patients had Mendelian susceptibility to Mycobacterial disease (MSMD) (21.2%), six had predominantly antibody deficiency (PAD) (12.7%), five had severe combined immunodeficiency (SCID) (10.6%), three had CGD (6.3%), and two had CID (4.2%). Mortality was reported in two patients (4.2%) with CID (ZAP70 deficiency (n = 1) and PIK3R1 deficiency (n = 1)). Parental consanguinity (84%), axillary lymphadenopathy (65%), mycobacterial lung disease (42%), hepatomegaly (30%) and growth retardation (19%) were significantly high in patients with PIDD diagnosis. Isolated vaccination site infection was also recorded in patients with PIDD (CID (n = 1), SCID (n = 1), PAD (n = 5)). BCG vaccination should be planned with caution for the cases with suspected PIDD. This study indicates that almost all patients (92.3%) with BCGosis and one in every two patients (41.2%) with BCGitis have an underlying PIDD. Parental consanguinity, axillary lymphadenopathy, mycobacterial lung disease, hepatomegaly and growth retardation (19%) are important clinical features in the differential diagnosis of PIDD.
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TITLE: Association of reduced maternal sHLA-G5 isoform levels and elevated TNF-á/IL-4 cytokine ratio with Recurrent Pregnancy Loss: A study on South Indian women.. ABSTRACT: Inflammation is of critical importance in successful implantation during pregnancy. However, the establishment of maternal immune tolerance towards semi-allograft foetus is more exigent and is achieved predominantly by human leukocyte antigen-G (HLA-G) isoforms with a special emphasis on soluble HLA-G5 (sHLA-G5). Constant inflammation and lack of resolution by anti-inflammatory milieu, due to aberrant expression of critical immunoregulatory molecules such as sHLA-G5 and dysfunctional T helper cells 1 and 2 (Th1-Th2) cytokine shift, can lead to adverse pregnancy outcomes including recurrent pregnancy loss (RPL). Serum samples of 270 pregnant women (135 healthy parous and 135 with a history of RPL) were evaluated for the concentrations of sHLA-G5, interleukin-4 (IL-4) and tumour necrosis factor-alpha (TNF-á) using sandwich enzyme-linked immunosorbent assay (ELISA) and found elevated levels of sHLA-G5 and IL-4 in controls and higher TNF-á levels and TNF-á:IL-4 ratio in patients (P < .05). Stratified data analysis based on the time of sample collection, that is the first and second trimesters exhibited higher sHLA-G5 and IL-4 in both first and second trimesters in controls than patients, while they displayed lower levels concerning TNF-á and TNF-á:IL-4 ratio (P < .05). However, within patients and controls in the first or second trimesters, there was a significant variation concerning sHLA-G5 alone. Further, the outcome of pregnancies studied in the present investigation revealed a significant elevation in sHLA-G5 levels among women with successful pregnancies compared with women who experienced pregnancy loss, therefore, concluding the potential application of sHLA-G5 isoform as a marker in assisting improved pregnancy outcomes.
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TITLE: Identifying sincerity of effort by grip strength ratio of three wrist positions in individuals with upper extremity musculoskeletal disorders.. ABSTRACT: OBJECTIVES: To evaluate whether the grip strength ratio of three wrist positions could determine sincerity of effort (SOE), by differentiating between maximal effort (ME) and submaximal effort (SE), in individuals with upper extremity musculoskeletal disorders (MSDs).METHODS: A total of 19 volunteers with unilateral upper extremity MSDs (9 males, 10 females) participated in this study. Participants performed grip strength tests in neutral, full flexion, and full extension wrist positions for both hands. In each wrist position, they exerted grip force with their ME and preferred SE for three times.RESULTS: Significant main effects of type of effort, wrist position (P < .001), and hand (P = .005) were observed. The results also showed significant interactions for type of effort ? wrist position (P < .001) and wrist positions ? hand (P = .001). Moreover, the grip strength ratios of neutral/flexion (N/F) and neutral/extension (N/E) between ME and SE differed significantly (P < .001).CONCLUSION: This study suggests that the N/F and N/E grip strength ratios can discriminate between ME and SE in individuals with upper extremity MSDs. Thus, this test might be applicable to use for identifying SOE in clinical setting.
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TITLE: Editor Profile: Eli Arama.. ABSTRACT: In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Eli Arama is an Associate Professor at the Weizmann Institute of Science in Rehovot, Israel. He has served as an editorial board member of The FEBS Journal since 2018.
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TITLE: Banning Loose Cigarettes and Other Tobacco Products in India: A Policy Analysis.. ABSTRACT: BACKGROUND: Sale of single cigarettes (also known as singles or loosies) is a key driver for early initiation of smoking and is a leading contributor to the smoking epidemic in India. Sale of singles additionally deter implementation of tobacco control strategies of pictorial health warnings including plain packaging and defeat effective taxation and promote illicit trade. We review India's tobacco control policy responses towards banning singles and other products sold as loose tobacco and identify opportunities for future policy intervention especially in the context of the ongoing COVID-19 pandemic.METHODS: Existing national and sub-national policy documents were analyzed for their content since the inception of the tobacco control laws in the country.RESULTS: There are no effective provisions at national level to ban loose tobacco products in India. However, the implementation of multiple legislative and regulatory measures (Acts/circulars/letters/notifications/orders/court judgements) in 16 Indian states and jurisdictions provide sufficient legal framework to substantiate its complete ban pan India. While the majority of state governments have adopted state level measures, Rajasthan had issued specific directive to all the 33 districts banning loose cigarettes and other tobacco products. Himachal Pradesh introduced the most unique and comprehensive legislation, for banning the sale of cigarettes and beedis (Dated November 7, 2016). The most recent notification in the state of Maharashtra (September 24, 2020) is the first to leverage powers using a mix of national and state legislations including the legislation addressing the rapidly emerging challenge of managing COVID-19.CONCLUSION: A robust national policy which supports strong provision to deter tobacco companies, their distribution network and vendors from selling singles or loose tobacco products is urgently needed. Such policy should be backed by cautionary messaging for consumers as well. Eliminating singles and loose tobacco sale will help in blunting tobacco use prevalence besides curbing spread of infectious diseases like COVID-19 pandemic.
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TITLE: Structural stigma and sexual minority men's depression and suicidality: A multilevel examination of mechanisms and mobility across 48 countries.. ABSTRACT: Sexual minority men are at greater risk of depression and suicidality than heterosexuals. Stigma, the most frequently hypothesized risk factor for this disparity, operates across socioecological levels-structural (e.g., laws), interpersonal (e.g., discrimination), and individual (e.g., self-stigma). Although the literature on stigma and mental health has focused on interpersonal and individual forms of stigma, emerging research has shown that structural stigma is also associated with adverse mental health outcomes. However, there is limited data on whether changes in structural stigma, such as when a stigmatized person moves to a lower stigma context, affect mental health, and on the mechanisms underlying this association. To address these questions, we use data from the 2017/18 European Men-who-have-sex-with-men Internet Survey (n = 123,428), which assessed mental health (i.e., Patient Health Questionnaire) and psychosocial mediators (i.e., sexual orientation concealment, internalized homonegativity, and social isolation). We linked these data to an objective indicator of structural stigma related to sexual orientation-including 15 laws and policies as well as aggregated social attitudes-in respondents' countries of origin (N = 178) and receiving countries (N = 48). Among respondents who still live in their country of birth (N = 106,883), structural stigma was related to depression and suicidality via internalized homonegativity and social isolation. Among respondents who moved from higher-to-lower structural stigma countries (n = 11,831), longer exposure to the lower structural stigma environments of their receiving countries was associated with a significantly: 1) lower risk of depression and suicidality; 2) lower odds of concealment, internalized homonegativity, and social isolation; and 3) smaller indirect effect of structural stigma on mental health through these mediators. This study provides additional evidence that stigma is a sociocultural determinant of mental health. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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TITLE: More by stick than by carrot: A reinforcement learning style rooted in the medial frontal cortex in anorexia nervosa.. ABSTRACT: Anorexia nervosa (AN) is characterized by a relentless pursuit of thinness, despite serious implications for health and social relations. In a previous study wielding the power of computational psychiatry, we found alterations in learning from negative feedback and in neural activity in the posterior medial frontal cortex (pMFC) in young acutely underweight AN patients (acAN). Here we ask whether these abnormalities are merely a state-related consequence of the illness or whether they might constitute a trait marker predisposing individuals to AN. To address this question, we employed the same reinforcement learning paradigm during fMRI with 31 female former AN patients after complete weight-recovery (recAN) and 31 age-matched healthy volunteers (15-28 years). Participants performed a decision task that required adaptation to changing reward contingencies. Data were analyzed within a hierarchical Gaussian filter model, which captures interindividual variability in feedback learning and decision-making under uncertainty. Similar to acute patients, individuals recovered from AN appear to emphasize negative over positive feedback when updating expectations regarding changing reward-punishment contingencies (difference in learning rate between punished and rewarded trials was increased in recAN: p = .006, d = .70. This behavioral pattern was mirrored in hyperactivation of the pMFC following negative feedback (FWE p < .001). Because the previously observed alterations in acANs are also evident after recovery and do not correlate with state variables like weight, altered feedback learning might be a trait marker of AN. The neural underpinnings of these alterations may lie in the pMFC. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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TITLE: Functional assessment of restrictive eating: A three-study clinically heterogeneous and transdiagnostic investigation.. ABSTRACT: Restrictive eating is common and associated with negative psychological outcomes across the life span and eating disorder (ED) severity levels. Little is known about functional processes that maintain restriction, especially outside of narrow diagnostic categories (e.g., anorexia nervosa). Here, we extend research on operant four-function models (identifying automatic negative, automatic positive, social negative, and social positive reinforcement functions) that have previously been applied to nonsuicidal self-injury (NSSI), binge eating, and purging to restricting. We assessed restrictive eating functions in three samples: clinically heterogeneous adolescents (Study 1: N = 457), transdiagnostic adults (Study 2: N = 145), and adults with acute or recently weight-restored anorexia nervosa (Study 3: N = 45). Study 1 indicated the four-function model was a good fit for restricting (root mean square error of approximation [RMSEA] = .06, Tucker-Lewis index [TLI] = .88). This factor structure replicated in Study 2 (comparative fit index [CFI] = .97, RMSEA = .07, TLI = .97, standardized root mean square residual [SRMR] = .09). Unlike NSSI, binge eating, and purging, which have been found to primarily serve automatic negative reinforcement functions, all three present studies found automatic positive reinforcement was most highly endorsed (by up to 85% of participants). In Studies 1 and 3, automatic functions were associated with poorer emotion regulation (ps < .05). In Study 1, social functions were associated with less social support (ps < .001). Across studies, automatic functions were associated with greater restriction ps < .05). Functions varied slightly by ED diagnosis. Across ED presentation, severity, and developmental stage, restrictive eating may be largely maintained by automatic positive reinforcement, with some variability across presentations. Continued examination of restrictive eating functions will establish processes that maintain restriction, allowing more precise treatment targeting for these problematic behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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TITLE: Volatility of subliminal haptic feedback alters the feeling of control in schizophrenia.. ABSTRACT: It has been proposed that agency disorders found in schizophrenia rely on aberrant processing of prediction error. Overreactivity to nonpertinent prediction errors may lead to the attribution of one's own actions to an external source. When applied to perception, this could explain hallucinations. However, experiments in motor control or perception have mainly suggested deficient prediction errors. Using a novel approach based on the manipulation of temporal delays, 23 patients with schizophrenia, 18 patients with bipolar disorder, and 22 healthy participants performed a pointing task with a haptic device that provided haptic feedback without or with delays, which were processed consciously (65 ms) or unconsciously (15 ms). The processing of prediction errors was measured via the adaptation of the hand trajectory, that is, the deceleration in anticipation of the surface, and its modulation as a function of recent history (stable or unstable sensory feedback). Agency was evaluated by measuring the participants' feeling of controlling the device. Only patients with schizophrenia reported a decrease in the feeling of control following subliminally delayed haptic feedback and adapted deceleration durations following subliminally delayed haptic feedback. This effect was correlated with positive symptoms. The overreactivity to subliminal delays was present only when delays occurred repeatedly in an unpredictable way, that is, with a volatile distribution. The results suggest that small temporal uncertainties that should be held as negligible, trigger an aberrant overreactivity which could account for hallucinations and alterations of the patients' conscious feeling of control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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TITLE: Self-reported perceptual aberrations in psychosis map to event-related potentials and semantic appraisals of objects.. ABSTRACT: Psychotic disorders have been associated with visual deficits and deviant semantic processing, making it unclear whether object detection abnormalities in psychosis originate from low-level or higher-order visual processes. The current study investigated how high-level visual processing is affected in psychosis by presenting object stimuli with equivalent low-level visual features. Outpatients with affective and nonaffective psychotic disorders, first-degree biological relatives, and psychiatrically unaffected individuals (N = 130) completed the Fragmented Ambiguous Object Task (FAOT) to assess recognition of objects in ambiguous stimuli. During the task, we recorded electroencephalography, quantified event-related potential (ERP) components (P1, N1, negative closure [NCL], N400), and derived four spatiotemporal event-related potential factors using principal components analysis (PCA). In addition to traditional diagnoses, psychosis was characterized using a dimensional measure of individual differences in self-reported sensory experiences (perceptual absorption) calculated from scales that tap the psychotic domain of the hierarchical structure of psychopathology. Rates of detecting objects within fragmented stimuli failed to differ across diagnostic groups or significantly predict perceptual absorption (p = .057). PCA factors that reflected smaller N1 and larger NCL amplitudes were associated with detecting objects. Exploratory analyses revealed that higher perceptual absorption was associated with reductions in the N400 and a late positive PCA factor. Although early and midlatency brain responses modulate during object detection, late brain responses tied to semantic appraisal of objects are related to perceptual aberrations often reported by individuals with severe psychopathology. Dimensional measures of personality appear sensitive to variation in biological systems relevant to psychotic symptomatology and object perception. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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TITLE: Sequencing of SARS-CoV-2 in local transmission cases through Oxford Nanopore MinION platform from Karachi Pakistan.. ABSTRACT: INTRODUCTION: The first case of severe acute respiratory syndrome 2 (SARS-CoV-2) was imported to Pakistan in February 2020, since then 8,260 deaths have been witnessed. The virus has been constantly mutating and local transmission cases from different countries vary due to host dependent viral adaptation. Many distinct clusters of variant SARS-CoV-2 have been defined globally. In this study, the epidemiology of SARS-CoV-2 was studied and locally transmitted SARS-CoV-2 isolates from Karachi were sequenced to compared and identify any possible variants.METHODOLOGY: The real time PCR was performed on nasopharyngeal specimen to confirm SARS-CoV-2 with Orf 1ab and E gene as targets. The virus isolates were sequenced through oxford nanopore technology MinION platform. Isolates from the first and second wave of COVID-19 outbreak in Karachi were compared.RESULTS: The overall positivity rate for PCR was 26.24% with the highest number of positive cases in June. Approximately, 37.45% PCR positive subjects aged between 19-40 years. All the isolates belonged to GH clade and shared missense mutation D614G in spike protein linked to increased transmission rate worldwide. Another spike protein mutation A222V coexisted with D614G in the virus from the second wave of COVID-19.CONCLUSIONS: Based on the present findings it is suggested that the locally transmitted virus from Karachi varies from those reported from other parts of Pakistan. Slight variability was also observed between viruses from the first and second wave. Variability in any potential vaccine target may result in failed trials, therefore information on any local viral variants is always useful for effective vaccine design and/or selection.
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TITLE: COVID-19 pandemic and "survival of the fittest".. ABSTRACT: Occurrence and recurrence of COVID-19 cases have been observed globally. The complex relationship of host-pathogen and the environment plays a vital role in understanding the widespread recurrence of the SARS-CoV-2 among humans. Though the pathobiology of the disease is not completely understood, it is well established that COVID-19 poses a greater threat to individuals with co-morbidities and a weakened immune system. The article deals with the notion of innate immunity, natural selection, and the survival of the fittest during the COVID-19 outbreak. The article also attempts to introduce the concept of "lifestyle and cultural immunity" that needs to be addressed and incorporated at an early stage of childhood to boost up the human immune system. The communication further discusses the role of vaccination and micro-organisms pre-existing in the environment which are required to enhance the immunity of an individual.
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TITLE: COVID-19 vaccine demand, hesitancy, and nationalism: a case of protection motivation behavior in Bangladesh.. ABSTRACT: INTRODUCTION: Immunization, as a process of fighting against the COVID-19, has gained important research appeal, but very limited endeavor has been paid for vaccine behavioral studies in underdeveloped and developing countries. This study explores the vaccine demand, hesitancy, and nationalism as well as vaccine acceptance and domestic vaccine preference among young adults in Bangladesh.METHODOLOGY: This quantitative study followed the snowball sampling technique and collected responses from 1,018 individuals from various social media platforms. The analysis covered both descriptive and inferential statistics including chi-square, F-statistic, and logistic regression.RESULTS: The findings of the fully-adjusted regression model suggest that the individuals who had more vaccine demand were 3.29 times (95% confidence interval = 2.39-4.54; p < 0.001) higher to accept vaccine compared to those who had no vaccine demand. Conversely, vaccine hesitancy was negatively associated with vaccine acceptance. Here, the odds ratio was found 0.70 (95% confidence interval = 0.62-0.80; p < 0.001), which means that those who had higher vaccine hesitancy were about 30% less likely to accept vaccines than those who had no hesitancy. In addition, the persons who had vaccine nationalism were 1.75 times (95% confidence interval = 1.62-1.88; p < 0.001) more prone to prefer domestic vaccine.CONCLUSIONS: This study suggests that policymakers may take initiatives for making people aware and knowledgeable about the severity and vulnerability to specific health threats. In this concern, perception and efficacy-increasing programs may take part in increasing protection motivation behaviors like vaccine acceptance and (domestic) vaccine preference.
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TITLE: Association between obesity and diabetes prevalence and COVID-19 mortality in Mexico: an ecological study.. ABSTRACT: INTRODUCTION: Mortality rates associated with COVID-19 vary widely between countries and, within countries, between regions. These differences might be explained by population susceptibility, environmental factors, transmission dynamics, containment strategies, and diagnostic approaches. We aimed to analyze if obesity and diabetes prevalence are associated with higher COVID-19 mortality rates in Mexico.METHODOLOGY: We analyzed the mortality rate for each of the 2,457 municipalities in Mexico, one of the countries with highest COVID-19 mortality rate, during the first seven months of the pandemic to identify factors associated with higher mortality, including demographic, health-related characteristics (prevalence of obesity, diabetes, and hypertension in adults older than 20 years old), and altitude.RESULTS: During the first seven months of the COVID-19 pandemic there were 85,666 deaths reported in Mexico, with a cumulative mortality rate of 67 per 100,000 population. The mean mortality rate for the 2,457 municipalities in Mexico was 33.9 per 100,000 population. At a municipal level, the prevalence of diabetes and obesity, as well as high human development index, and location at < 500 or > 2000 above sea level were associated with higher mortality rate.CONCLUSIONS: Elevated obesity and diabetes prevalence explain, in part, high COVID-19 mortality rates registered in certain municipalities in Mexico. These results suggest that a regionalized approach should be considered to successfully limit the impact of SARS-CoV-2.
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TITLE: Spontaneous pneumothorax, with or without pulmonary cysts, in patients with COVID-19 pneumonia.. ABSTRACT: INTRODUCTION: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects mainly the lungs causing pneumonia and complications like acute respiratory distress syndrome. Pneumothorax is a rare manifestation of the disease. This report is a description of a series of patients with COVID-19 and spontaneous pneumothorax, some of them with associated pulmonary cysts.METHODOLOGY: Cases were collected retrospectively. We included clinical data from medical records and described radiologic findings. Patients that developed pneumothorax during mechanical ventilation were excluded.RESULTS: Ten cases were included in this report, nine of them were male. The median age of our series was 62 years (IQR = 57-68). The median days since the onset of symptoms until the development of pneumothorax was 27 (IQR = 17-31), most cases developed after the second week of the diagnosis of pneumonia. Two cases required invasive mechanical ventilation, but pneumothorax occurred after ventilator weaning. Three cases showed subpleural pulmonary cysts.CONCLUSIONS: Cysts and pneumothorax are rare manifestations of SARS-CoV-2 pneumonia with mechanisms not completely understood. This report highlights the role of CT scan in diagnosis of COVID-19 complications.
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TITLE: Investigation of Viral Load Cycle Threshold Values in Patients with SARS-CoV-2 Associated Pneumonia with Real-Time PCR Method.. ABSTRACT: INTRODUCTION: In this study, we aimed investigate the relationship of SARS-CoV-2 viral load cycle threshold (Ct) values with pneumonia.METHODOLOGY: A total of 158 patients in whom SARS-CoV-2 was confirmed in upper respiratory tract (URT) samples with molecular method and who had computed tomography (CT) of the chest, between April 2020 and June 2020 were included in this retrospective cross-sectional study.RESULTS: Mean age of 158 PCR positive patients was 45.22 ± 17.89 and 60.8% of them were male. Pneumonia was detected in 40.5% of the patients on their chest CT. A weak but significant correlation was found between SARS-CoV-2 Ct value detected with PCR in analysis of oropharyngeal/ nasopharyngeal (OP/NP) samples and chest CT score (Pearson's r: 0.197, p = 0.01). No correlation was found between the first detected viral load Ct value and age, gender and mortality. There was no significant correlation between chest CT score and mortality. While the areas remaining under ROC curve for Ct value in analysis of OP/NP samples in prediction of chest CT score ? 1, ? 5 and ? 10 were 0.564, 0.640 and 0.703 respectively.CONCLUSIONS: We found that the amount of SARS-CoV-2 viral load (inverse relationship with Ct) detected in OP/NP samples of patients with COVID-19 pneumonia did not reflect the increasing severity of pulmonary lesions on chest CT. Although primary target of SARS-CoV-2 is all epithelial cells of the respiratory tract we believe studies comparing viral loads in lower respiratory tract samples are needed to determine the severity of pulmonary disease.
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TITLE: Focusing on Asthma and Chronic Obstructive Pulmonary Disease with COVID-19.. ABSTRACT: INTRODUCTION: We aimed to evaluate clinical and laboratory findings of hospitalized asthma and chronic obstructive pulmonary disease (COPD) patients with COVID-19 and demonstrate that they have different symptoms and/or laboratory results and outcomes than COVID-19 patients with comorbidity (CoV-com) and without comorbidity (CoV-alone).METHODOLOGY: The data of the demographic, clinical, laboratory findings of hospitalized CoV-alone, asthma, COPD patients with COVID-19 (CoV-asthma, CoV-COPD, respectively), and CoV-com were analyzed.RESULTS: Out of 1082 patients hospitalized for COVID-19, 585 (54.1%) had CoV-alone, 40 (3.7%) had CoV-asthma, 46 (4.3%) had CoV-COPD and 411 (38%) had CoV-com. Cough, shortness of breath, fever and weakness were the most common four symptoms seen in all COVID-19 patients. Shortness of breath, myalgia, headache symptoms were more common in CoV-asthma than the other groups (p < 0.001, p < 0.01, p < 0.05 respectively). Sputum was more common in CoV-COPD than other groups (p < 0.01). COPD group most frequently had increased values, different from the other groups with CRP>5ng/mL in 91.3%, D-dimer > 0.05mg/dL in 89.1%, troponin > 0.014micg/L in %63.9, INR>1.15 in 52.2%, CK-MB>25U/L in 48.5%, PT>14s in 40.9% of patients (p < 0.05, p < 0.001, p < 0.001, p < 0.001, p < 0.05, p < 0.001, respectively). NT-ProBNP was found to have the highest AUC value and the best differentiating parameter for CoV-asthma from CoV-alone. Typical CT findings were present in 44.4% of CoV-alone, 57.5% of CoV-asthma, 28.3% of CoV-COPD and 38.9% of CoV-com groups. CoV-COPD and CoV-com patients died more frequently than other groups (17.8%, 18.5%).CONCLUSIONS: CoV-asthma and CoV-COPD patients might have different symptoms and laboratory parameters than other COVID-19 patients which can guide the physicians.
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TITLE: Human leukocyte antigen-C and killer immunoglobulin-like receptors in reproductive medicine.. ABSTRACT: Proper communication between natural killer cells and the human leukocyte antigens of the embryonic trophoblast at the maternal-fetal interface during pregnancy is essential for successful reproduction. However, specific combinations of embryonic human leukocyte antigen-C with killer immunoglobulin-like receptors on decidual natural killer cells (the immunological code of pregnancy) can be associated with obstetric morbidity and pregnancy loss. This article presents an updated review of the mechanisms underlying the interaction between embryonic human leukocyte antigen-C and maternal killer immunoglobulin-like receptors and their relevance to the physiology and pathophysiology of human reproduction.
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TITLE: Evaluation of a bioaerosol sampler for indoor environmental surveillance of Severe Acute Respiratory Syndrome Coronavirus 2.. ABSTRACT: The worldwide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has ubiquitously impacted many aspects of life. As vaccines continue to be manufactured and administered, limiting the spread of SARS-CoV-2 will rely more heavily on the early identification of contagious individuals occupying reopened and increasingly populated indoor environments. In this study, we investigated the utility of an impaction-based bioaerosol sampling system with multiple nucleic acid collection media. Heat-inactivated SARS-CoV-2 was utilized to perform bench-scale, short-range aerosol, and room-scale aerosol experiments. Through bench-scale experiments, AerosolSense Capture Media (ACM) and nylon flocked swabs were identified as the highest utility media. In room-scale aerosol experiments, consistent detection of aerosol SARS-CoV-2 was achieved at an estimated aerosol concentration equal to or greater than 0.089 genome copies per liter of room air (gc/L) when air was sampled for eight hours or more at less than one air change per hour (ACH). Shorter sampling periods (75 minutes) yielded consistent detection at ~31.8 gc/L of room air and intermittent detection down to ~0.318 gc/L at (at both 1 and 6 ACH). These results support further exploration in real-world testing scenarios and suggest the utility of indoor aerosol surveillance as an effective risk mitigation strategy in occupied buildings.
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TITLE: Immunoinformatics mapping of potential epitopes in SARS-CoV-2 structural proteins.. ABSTRACT: All approved coronavirus disease 2019 (COVID-19) vaccines in current use are safe, effective, and reduce the risk of severe illness. Although data on the immunological presentation of patients with COVID-19 is limited, increasing experimental evidence supports the significant contribution of B and T cells towards the resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the availability of several COVID-19 vaccines with high efficacy, more effective vaccines are still needed to protect against the new variants of SARS-CoV-2. Employing a comprehensive immunoinformatic prediction algorithm and leveraging the genetic closeness with SARS-CoV, we have predicted potential immune epitopes in the structural proteins of SARS-CoV-2. The S and N proteins of SARS-CoV-2 and SARS-CoVs are main targets of antibody detection and have motivated us to design four multi-epitope vaccines which were based on our predicted B- and T-cell epitopes of SARS-CoV-2 structural proteins. The cardinal epitopes selected for the vaccine constructs are predicted to possess antigenic, non-allergenic, and cytokine-inducing properties. Additionally, some of the predicted epitopes have been experimentally validated in published papers. Furthermore, we used the C-ImmSim server to predict effective immune responses induced by the epitope-based vaccines. Taken together, the immune epitopes predicted in this study provide a platform for future experimental validations which may facilitate the development of effective vaccine candidates and epitope-based serological diagnostic assays.
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TITLE: Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19.. ABSTRACT: Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.
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TITLE: Internal and external drivers for compliance with the COVID-19 preventive measures in Slovenia: The view from general deterrence and protection motivation.. ABSTRACT: The emergence of a pandemic is usually accompanied by different measures-economic, social, preventive, and (self)protective. In the case of the COVID-19, several preventive measures were formally enforced by state authorities in the majority of countries worldwide. Thus, during the COVID-19 pandemic, the intertwining of formal and informal social control could be observed. Hence, in this study a cross-sectional design was chosen to explore the issue in Slovenia. To the best of our knowledge, this research is the first in the current literature to empirically test the general deterrence theory in pandemic circumstances (as external factors predicting individuals' compliance with the COVID-19 preventive measures). The results suggest an important role of informal punishment, with perceived informal severity being the only statistically significant factor from the general deterrence theory. In contrast to external factors, internal factors play a significantly greater role in promoting people's self-protective behavior in pandemic circumstances. During the unknown, the uncertain and delicate situations with which people have no previous experience, both personal beliefs about the effectiveness of measures and perceived self-efficacy are more important than fear of formal sanctions.
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TITLE: COVID-19 outcomes in hospitalized puerperal, pregnant, and neither pregnant nor puerperal women.. ABSTRACT: OBJECTIVE: To compare hospitalized reproductive age women with COVID-19 who were pregnant, puerperal, or neither one nor the other in terms of demographic and clinical characteristics and disease progression using Brazilian epidemiological data.METHODS: A retrospective analysis of the records of the Information System of the Epidemiological Surveillance of Influenza of the Health Ministry of Brazil was performed. It included the data of female patients aged 10 to 49 years hospitalized because of severe COVID-19 disease (RT-PCR+ for SARS-CoV-2), from February 17, 2020 to January 02, 2021. They were separated into 3 groups: pregnant, puerperal, and neither pregnant nor puerperal. General comparisons and then adjustments for confounding variables (propensity score matching [PSM]) were made, using demographic and clinical characteristics, disease progression (admission to the intensive care unit [ICU] and invasive or noninvasive ventilatory support), and outcome (cure or death). Deaths were analyzed in each group according to comorbidities, invasive or noninvasive ventilatory support, and admission to the ICU.RESULTS: As many as 40,640 reproductive age women hospitalized for COVID-19 were identified: 3,372 were pregnant, 794 were puerperal, and 36,474 were neither pregnant nor puerperal. Groups were significantly different in terms of demographic data and comorbidities (p<0.0001). Pregnant and puerperal women were less likely to be symptomatic than the women who were neither one nor the other (72.1%, 69.7% and 88.8%, respectively). Pregnant women, however, had a higher frequency of anosmia, and ageusia than the others. After PSM, puerperal women had a worse prognosis than pregnant women with respect to admission to the ICU, invasive ventilatory support, and death, with OR (95% CI) 1.97 (1.55 - 2.50), 2.71 (1.78 - 4.13), and 2.51 (1.79 - 3.52), respectively.CONCLUSION: Puerperal women were at a higher risk for serious outcomes (need for the ICU, need for invasive and noninvasive ventilatory support, and death) than pregnant women.
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TITLE: Can vaccination roll-out be more equitable if population risk is taken into account?. ABSTRACT: BACKGROUND: COVID-19 vaccination in many countries, including England, has been prioritised primarily by age. However, people of the same age can have very different health statuses. Frailty is a commonly used metric of health and has been found to be more strongly associated with mortality than age among COVID-19 inpatients.METHODS: We compared the number of first vaccine doses administered across the 135 NHS Clinical Commissioning Groups (CCGs) of England to both the over 50 population and the estimated frail population in each area. Area-based frailty estimates were generated using the English Longitudinal Survey of Ageing (ELSA), a national survey of older people. We also compared the number of doses to the number of people with other risk factors associated with COVID-19: atrial fibrillation, chronic kidney disease, diabetes, learning disabilities, obesity and smoking status.RESULTS: We estimate that after 79 days of the vaccine program, across all Clinical Commissioning Group areas, the number of people who received a first vaccine per frail person ranged from 4.4 (95% CI 4.0-4.8) and 20.1 (95% CI 18.3-21.9). The prevalences of other risk factors were also poorly associated with the prevalence of vaccination across England.CONCLUSIONS: Vaccination with age-based priority created area-based inequities in the number of doses administered relative to the number of people who are frail or have other risk factors associated with COVID-19. As frailty has previously been found to be more strongly associated with mortality than age for COVID-19 inpatients, an age-based priority system may increase the risk of mortality in some areas during the vaccine roll-out period. Authorities planning COVID-19 vaccination programmes should consider the disadvantages of an age-based priority system.
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TITLE: COVID-19 vaccination perceptions and intentions of maternity care consumers and providers in Australia.. ABSTRACT: INTRODUCTION: Vaccination against COVID-19 is a key global public health strategy. Health professionals including midwives and doctors support and influence vaccination uptake by childbearing women. There is currently no evidence regarding the COVID-19 vaccination perceptions and intentions of those who receive or provide maternity care in Australia. The aim of this study was to address this gap in knowledge and explore the perceptions and intentions regarding COVID-19 vaccination from consumers and providers of maternity care in Australia.METHODS: A national cross-sectional online study conducted in early 2021 in Australia, a country that has had a very low number of COVID-19 cases and deaths. Recruitment was undertaken through parenting and health professional social media sites and professional college distribution lists. A total of 853 completed responses, from women (n = 326), maternity care providers including doctors (n = 58), midwives (n = 391) and midwifery students (n = 78).FINDINGS: Personal intention to be vaccinated ranged from 48-89% with doctors most likely and women least likely. Doctors and midwifery students were significantly more likely to recommend the vaccine to pregnant women in their care than midwives (p<0.001). Fewer doctors (2%) felt that women should wait until breastfeeding had concluded before being vaccinated compared with 24% of midwives and 21% of midwifery students (p<0.001). More than half of the midwives (53%) had concerns about the COVID-19 vaccine for the women in their care compared with 35% of doctors and 46% of midwifery students. Despite national guidelines recommending vaccination of breastfeeding women, 54% of practitioners were unlikely to recommend vaccination for this group.CONCLUSION: This is the first study to explore the perceptions and intentions regarding COVID-19 vaccination from the perspective of those who receive and provide maternity care in Australia. Findings have utility to support targeted public health messaging for these and other cohorts.
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TITLE: A qualitative assessment of factors affecting nursing home caregiving staff experiences during the COVID-19 pandemic.. ABSTRACT: BACKGROUND: A large portion of COVID-19 cases and deaths in the United States have occurred in nursing homes; however, current literature including the frontline perspective of staff working in nursing homes is limited. The objective of this qualitative assessment was to better understand what individual and facility level factors may have contributed to the impact of COVID-19 on Certified Nursing Assistants (CNAs) and Environmental Services (EVS) staff working in nursing homes.METHODS: Based on a simple random sample from the National Healthcare Safety Network (NHSN), 7,520 facilities were emailed invitations requesting one CNA and/or one EVS staff member for participation in a voluntary focus group over Zoom. Facility characteristics were obtained via NHSN and publicly available sources; participant demographics were collected via SurveyMonkey during registration and polling during focus groups. Qualitative information was coded using NVIVO and Excel.RESULTS: Throughout April 2021, 23 focus groups including 110 participants from 84 facilities were conducted homogenous by participant role. Staffing problems were a recurring theme reported. Participants often cited the toll the pandemic took on their emotional well-being, describing increased stress, responsibilities, and time needed to complete their jobs. The lack of consistent and systematic guidance resulting in frequently changing infection prevention protocols was also reported across focus groups.CONCLUSIONS: Addressing concerns of low wages and lack of financial incentives may have the potential to attract and retain employees to help alleviate nursing home staff shortages. Additionally, access to mental health resources could help nursing home staff cope with the emotional burden of the COVID-19 pandemic. These frontline staff members provided invaluable insight and should be included in improvement efforts to support nursing homes recovering from the impact of COVID-19 as well as future pandemic planning.
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TITLE: Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants.. ABSTRACT: Importance: Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)-specifically fluoxetine hydrochloride and fluvoxamine maleate-with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size.Objective: To investigate the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs).Design, Setting, and Participants: This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers across the US.Exposures: Selective serotonin reuptake inhibitors and specifically (1) fluoxetine, (2) fluoxetine or fluvoxamine, and (3) other SSRIs (ie, not fluoxetine or fluvoxamine).Main Outcomes and Measures: Death.Results: A total of 3401 adult patients with COVID-19 prescribed SSRIs (2033 women [59.8%]; mean [SD] age, 63.8 [18.1] years) were identified, with 470 receiving fluoxetine only (280 women [59.6%]; mean [SD] age, 58.5 [18.1] years), 481 receiving fluoxetine or fluvoxamine (285 women [59.3%]; mean [SD] age, 58.7 [18.0] years), and 2898 receiving other SSRIs (1733 women [59.8%]; mean [SD] age, 64.7 [18.0] years) within a defined time frame. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06).Conclusions and Relevance: These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.
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TITLE: Seroprevalence of Unidentified SARS-CoV-2 Infection in Hong Kong During 3 Pandemic Waves.. ABSTRACT: Importance: Seroprevalence studies inform the extent of infection and assist evaluation of mitigation strategies for the COVID-19 pandemic.Objective: To estimate the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong.Design, Setting, and Participants: A prospective cross-sectional study was conducted in Hong Kong after each major wave of the COVID-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). Adults (age ?18 years) who had not been diagnosed with COVID-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and COVID-19 testing history were collected.Main Outcomes and Measures: The main outcome was prevalence of SARS-CoV-2 infection. SARS-CoV-2 IgG antibodies were detected by an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor binding domain of spike protein.Results: The study enrolled 4198 participants (2539 [60%] female; median age, 50 years [IQR, 25 years]), including 903 (22%), 1046 (25%), and 2249 (53%) during April 21 to July 7, 2020; during September 29 to November 23, 2020; and during January 15 to April 18, 2021, respectively. The numbers of participants aged 18 to 39 years, 40 to 59 years, and 60 years or older were 1328 (32%), 1645 (39%), and 1225 (29%), respectively. Among the participants, 2444 (58%) stayed in Hong Kong since November 2019 and 2094 (50%) had negative SARS-CoV-2 RNA test results. Only 170 (4%) reported ever having contact with individuals with confirmed cases, and 5% had been isolated or quarantined. Most (2803 [67%]) did not recall any illnesses, whereas 737 (18%), 212 (5%), and 385 (9%) had experienced respiratory symptoms, gastrointestinal symptoms, or both, respectively, before testing. Six participants were confirmed to be positive for anti-SARS-CoV-2 IgG; the adjusted prevalence of unidentified infection was 0.15% (95% CI, 0.06%-0.32%). Extrapolating these findings to the whole population, there were fewer than 1.9 unidentified infections for every recorded confirmed case. The overall prevalence of SARS-CoV-2 infection in Hong Kong before the roll out of vaccination was less than 0.45%.Conclusions and Relevance: In this cross-sectional study of participants from the general public in Hong Kong, the prevalence of unidentified SARS-CoV-2 infection was low after 3 major waves of the pandemic, suggesting the success of the pandemic mitigation by stringent isolation and quarantine policies even without complete city lockdown. More than 99.5% of the general population of Hong Kong remain naive to SARS-CoV-2, highlighting the urgent need to achieve high vaccine coverage.
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TITLE: Assessment of Excess Mortality and Household Income in Rural Bangladesh During the COVID-19 Pandemic in 2020.. ABSTRACT: Importance: A slow or incomplete civil registry makes it impossible to determine excess mortality due to COVID-19 and difficult to inform policy.Objective: To quantify the association of the COVID-19 pandemic with excess mortality and household income in rural Bangladesh in 2020.Design, Setting, and Participants: This repeated survey study is based on an in-person census followed by 2 rounds of telephone calls. Data were collected from a sample of 135 villages within a densely populated 350-km2 rural area of Bangladesh. Household data were obtained first in person and subsequently over the telephone. For the analysis, mortality data were stratified by month, age, sex, and household education. Mortality rates were modeled by bayesian multilevel regression, and the strata were aggregated to the population by poststratification. Data analysis was performed from February to April 2021.Exposures: Date and cause of any changes in household composition, as well as changes in income and food availability.Main Outcomes and Measures: Mortality rates were compared for 2019 and 2020, both without adjustment and after adjustment for nonresponse and differences in demographic variables between surveys. Income and food availability reported for January, May, and November 2020 were also compared.Results: Enumerators collected data from an initial 16 054 households in January 2020; 14 551 households (91%) responded when contacted again by telephone in May 2020, and 11 933 households (74%)responded when reached again over the telephone in November 2020, for a total of 58 806 individuals (29 726 female participants [50.5%]; mean [SD] age, 26.4 [19.8] years). A total of 276 deaths were reported between February and the end of October 2020 for the subset of the population that could be contacted twice over the telephone, slightly below the 289 deaths reported for the same population over the same period in 2019. After adjustment for survey nonresponse and poststratification, 2020 mortality changed by -8% (95% CI, -21% to 7%) compared with an annualized mortality of 6.1 deaths per 1000 individuals in 2019. However, in May 2020, salaried primary income earners reported a 40% decrease in monthly income (from 17 485 to 10 835 Bangladeshi Taka), and self-employed earners reported a 60% decrease in monthly income (23 083 to 8521 Bangladeshi Taka), with only a small recovery observed by November 2020.Conclusions and Relevance: In this study of households in rural Bangladesh, all-cause mortality was lower in 2020 compared with 2019. Restrictions imposed by the government may have limited the scale of the COVID-19 pandemic in rural areas, although economic data suggest that these restrictions need to be accompanied by expanded welfare programs.
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TITLE: High YAP and TEAD4 immunolabelings are associated with poor prognosis in patients with gallbladder cancer.. ABSTRACT: Yes-associated protein (YAP) and TEA domain-containing sequence-specific transcription factors 4 (TEAD4) are essential components of the Hippo pathway. Abnormal regulation of the Hippo pathway contributes to the progression and metastasis of many cancer types. However, their clinicopathologic and prognostic significances have not been studied in gallbladder cancers. Here, we systematically evaluated the YAP and TEAD4 immunolabelings and their association with clinicopathologic characteristics and survival outcomes using 212 specimens of surgically resected gallbladder cancers. High YAP and TEAD4 immunolabelings were identified in 70 (33%) cases and were associated with infiltrative growth pattern, poor differentiation, perineural invasion, and advanced pT classification and AJCC stage. High YAP immunolabeling was significantly associated with high TEAD4 immunolabeling (p < 0.001). High immunolabeling levels of YAP or TEAD4 alone and the combined YAPhigh TEAD4high group were significantly associated with poor survival in both univariate (p < 0.001) and multivariate analyses (HR = 2.358; 95% CI, 1.369-4.061; p = 0.002). Therefore, the YAP and TEAD4 immunolabelings are associated with aggressive behavior of gallbladder cancers and may be useful as a prognostic indicator in patients with surgically resected gallbladder cancer.
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TITLE: Restless Leg Syndrome and Sleep Disorders in Patients with Rheumatoid Arthritis and Its Relation with Anemia Parameters.. ABSTRACT: OBJECTIVES: We aimed to investigate the prevalence of restless legs syndrome (RLS) and sleep disorders in patients with rheumatoid arthritis (RA), and the association of iron deficiency with them.MATERIALS AND METHODS: The study included 72 patients with RA (59 females, 13 males), and 50 healthy control subjects (57 females, 15 males). Assessments were made using the International RLS Rating Scale, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, Fatigue Severity Scale (FSS), Beck anxiety and depression index and the SF-36 quality of life scores.RESULTS: We found that the frequency of RLS in RA patients was 29.1% and 13.8% in healthy control (p = 0.021). RA patients had 44.4% iron deficiency and 5.5% anemia of chronic disease. We found that 52.3% of patients with iron deficiency had RLS. There was an independent relationship between present of RLS and FSS (Beta [â] = 0.317, p = 0.005) and total iron binding capacity (TIBC) (â = 0.244, p = 0.031). There was an independent relationship between RLS severity score and PSQI (â = 0.264, p = 0.025) and social functionality (â = 0.302, p = 0.009).CONCLUSION: The prevalence of iron deficiency is high in RA in the developing countries. Analysis obtained in patients with RA is suggestive of an association between iron deficiency and increased frequency of RLS. The presence of RLS in patients with RA negatively affects sleep quality, psychiatric status, and quality of life of patients with RA. TIBC value may be a predictive marker for early detection of RLS in patients with RA.
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TITLE: A Comparison of the Neuroprotective and Reactivating Efficacy of a Novel Bispyridinium Oxime K870 with Commonly Used Pralidoxime and the Oxime HI-6 in Tabun-Poisoned Rats.. ABSTRACT: AIM: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats.METHODS: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method.RESULTS: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage.CONCLUSION: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.
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TITLE: Gene Expression of Antioxidant Enzymes in the Resected Intestine in Crohn's Disease.. ABSTRACT: INTRODUCTION: The inflammatory process in Crohn's disease (CD) is closely associated with the formation of reactive oxygen species. Antioxidant enzymes can play an important role in the outcome of CD and may influence postoperative recurrence in these patients. The aim of our study was to evaluate gene expression of intracellular antioxidant enzymes in surgically resected intestinal specimens of patients with CD, both in macroscopically normal and in inflamed tissue.METHODS: A total of 28 patients referred for elective bowel resection were enrolled in the study. Full-thickness small intestinal specimens were investigated. Gene expression of antioxidant enzymes - superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GSR) - was evaluated both in macroscopically normal and inflamed samples.RESULTS: There were significantly lower levels of SOD1 mRNA (p = 0.007) and GSR mRNA (p = 0.027) in inflamed tissue compared to macroscopically normal areas. No significant differences were found between affected and non-affected intestinal segments in mRNA for SOD2, SOD3 and GPX.CONCLUSIONS: Our pilot data clearly showed that the gene expression of major antioxidant enzymes is not a uniform mechanism in the pathogenesis of Crohn's disease. Topically decreased gene expression of SOD1 and GSR might facilitate the segmental tissue injury caused by reactive oxygen species.
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TITLE: Obesity in Children with Leptin Receptor Gene Polymorphisms.. ABSTRACT: INTRODUCTION: The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes.MATERIAL AND METHODS: 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald's sequential analysis, Spearman's correlation analysis, analysis of nominal data and multiple discriminant analysis.RESULTS: 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald's analysis allowed us to identify 6 important predictors of MUO (? ? 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ? 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ?4 (RR = 3.8, PC = +5.8).CONCLUSION: Children with the genotype rs3790435 gene LEPR had signs of MUO more often.
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TITLE: Laparoscopic Right Hemicolectomy for Appendiceal Mucocele.. ABSTRACT: Appendiceal mucocele is a rare disease with an incidence of 0.07-0.63% of all appendectomies and was first described in 1842 by Carl von Rokitansky. It is defined as an abnormal intraluminal accumulation of mucin. The clinical picture of AM can vary from asymptomatic mass in the right lower quadrant to symptoms of acute appendicitis. In some cases, AM can be found accidentally on CT performed due to other reasons or during surgery. Diagnosis consists mainly of imaging methods such as ultrasound, CT, and MRI with the finding of encapsulated cystic mass with calcifications. The main goal of surgical treatment is to remove an intact mucocele and prevent spillage of mucin into the peritoneal cavity. We present a case of large mucocele treated with laparoscopic right hemicolectomy.
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TITLE: Guillan-Barr? Syndrome after First Vaccination Dose against COVID-19: Case Report.. ABSTRACT: A number of neurological complications have been reported after the administration of flu vaccine, including Guillain-Barr? syndrome (GBS), especially after vaccination against swine flu. Only facial nerve neuropathy has thus far been reported after vaccination against COVID-19. More recently, there was a case of an elderly woman with GBS. In our report, we describe a case of a 42-year-old, previously almost healthy male who developed sensory symptoms 14 days after the first dose of Pfizer vaccine. One week later, the patient developed right facial nerve palsy and lower limb weakness and was no longer able to walk. Albuminocytological dissociation was detected in the cerebrospinal fluid, and there were inflammatory radicular changes in MRI scans of the lumbosacral spine. EMG indicated significant demyelinating polyradiculoneuritis and no antibodies against gangliosides were demonstrated. A 5-day course of immunoglobulins at a dose of 2 g/kg lead to a significant improvement and the patient was soon able to walk. In conclusion, we report a case of Guillan-Barr? syndrome after COVID-19 vaccine in a young patient with a rapid diagnosis and prompt administration of immunoglobulins.
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TITLE: Oral Ibandronate Therapy in Three Patients with Osteogenesis Imperfecta.. ABSTRACT: INTRODUCTION: Treatment with orally administered ibandronate is an effective way to increase bone mineral density (BMD) and reduce fracture rate in post-menopausal women and in men with osteoporosis. There are only very few reports concerning ibandronate therapy in children and adolescents, and in patients with osteogenesis imperfecta (OI), as bisphosphonates are not registered for therapeutic use in pediatrics.CASE REPORT: We present three patients with OI, where once-monthly oral ibandronate increased spinal BMD after two and four years, respectively, of therapy without any occurrence of new fractures and no adverse reactions. Somatic growth was not affected by the ibandronate treatment.CONCLUSION: Once-monthly oral ibandronate increased BMD and most probably improved bone quality in young patients with OI.
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TITLE: Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone.. ABSTRACT: Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non-COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.
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TITLE: Key points of technical review for the registration of SARS-CoV-2 nucleic acid tests in China.. ABSTRACT: In response to the outbreak of COVID-19, in accordance with the principles of 'unified command, early involvement, prompt review and scientific approval' as well as the requirements of ensuring product safety, effectiveness and controllable quality, the Center for Medical Device Evaluation (CMDE) has issued Key Points of Technical Review for the Registration of SARS-CoV-2 Nucleic Acid Tests (Key Points) to provide the requirements of tests. Because of the sustainability of the pandemic, more efforts and attempts are needed for SARS-CoV-2 detection and control. This article interprets the Key Points issued by the CMDE and provides certain refinements to wider audiences.
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TITLE: The Dynamic Immunological Parameter Landscape in Coronavirus Disease 2019 Patients With Different Outcomes.. ABSTRACT: Objectives: The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported.Methods: Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset.Results: This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+ T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+ T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+ and CD8+ T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+ proinflammatory monocytes and HLA-DR-CD14+ monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ?10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+ monocytes, and IL-6) but a decrease of host immunity markers.Conclusions: This study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.
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TITLE: Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19.. ABSTRACT: Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. Flow cytometry and next-generation sequencing were done on peripheral blood cells and urokinase-type plasminogen activator receptor (suPAR), and cytokines were measured from and mass spectrometry-based proteomics was done on plasma samples from an Indian cohort of COVID-19 patients. Publicly available single-cell RNA sequencing data were analyzed for validation of primary data. Statistical analyses were performed to validate risk stratification. We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcomes, in terms of both survival benefit (hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus, we identified suPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.
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TITLE: Divergent COVID-19 Disease Trajectories Predicted by a DAMP-Centered Immune Network Model.. ABSTRACT: COVID-19 presentations range from mild to moderate through severe disease but also manifest with persistent illness or viral recrudescence. We hypothesized that the spectrum of COVID-19 disease manifestations was a consequence of SARS-CoV-2-mediated delay in the pathogen-associated molecular pattern (PAMP) response, including dampened type I interferon signaling, thereby shifting the balance of the immune response to be dominated by damage-associated molecular pattern (DAMP) signaling. To test the hypothesis, we constructed a parsimonious mechanistic mathematical model. After calibration of the model for initial viral load and then by varying a few key parameters, we show that the core model generates four distinct viral load, immune response and associated disease trajectories termed "patient archetypes", whose temporal dynamics are reflected in clinical data from hospitalized COVID-19 patients. The model also accounts for responses to corticosteroid therapy and predicts that vaccine-induced neutralizing antibodies and cellular memory will be protective, including from severe COVID-19 disease. This generalizable modeling framework could be used to analyze protective and pathogenic immune responses to diverse viral infections.
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TITLE: Genome-Wide Profiling Reveals Alternative Polyadenylation of Innate Immune-Related mRNA in Patients With COVID-19.. ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has caused many deaths worldwide. To date, the mechanism of viral immune escape remains unclear, which is a great obstacle to developing effective clinical treatment. RNA processing mechanisms, including alternative polyadenylation (APA) and alternative splicing (AS), are crucial in the regulation of most human genes in many types of infectious diseases. Because the role of APA and AS in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown, we performed de novo identification of dynamic APA sites using a public dataset of human peripheral blood mononuclear cell (PBMC) RNA-Seq data in COVID-19 patients. We found that genes with APA were enriched in innate immunity -related gene ontology categories such as neutrophil activation, regulation of the MAPK cascade and cytokine production, response to interferon-gamma and the innate immune response. We also reported genome-wide AS events and enriched viral transcription-related categories upon SARS-CoV-2 infection. Interestingly, we found that APA events may give better predictions than AS in COVID-19 patients, suggesting that APA could act as a potential therapeutic target and novel biomarker in those patients. Our study is the first to annotate genes with APA and AS in COVID-19 patients and highlights the roles of APA variation in SARS-CoV-2 infection.
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TITLE: Mathematical Modelling of COVID-19 Transmission in Kenya: A Model with Reinfection Transmission Mechanism.. ABSTRACT: In this study we propose a Coronavirus Disease 2019 (COVID-19) mathematical model that stratifies infectious subpopulations into: infectious asymptomatic individuals, symptomatic infectious individuals who manifest mild symptoms and symptomatic individuals with severe symptoms. In light of the recent revelation that reinfection by COVID-19 is possible, the proposed model attempt to investigate how reinfection with COVID-19 will alter the future dynamics of the recent unfolding pandemic. Fitting the mathematical model on the Kenya COVID-19 dataset, model parameter values were obtained and used to conduct numerical simulations. Numerical results suggest that reinfection of recovered individuals who have lost their protective immunity will create a large pool of asymptomatic infectious individuals which will ultimately increase symptomatic individuals with mild symptoms and symptomatic individuals with severe symptoms (critically ill) needing urgent medical attention. The model suggests that reinfection with COVID-19 will lead to an increase in cumulative reported deaths. Comparison of the impact of non pharmaceutical interventions on curbing COVID19 proliferation suggests that wearing face masks profoundly reduce COVID-19 prevalence than maintaining social/physical distance. Further, numerical findings reveal that increasing detection rate of asymptomatic cases via contact tracing, testing and isolating them can drastically reduce COVID-19 surge, in particular individuals who are critically ill and require admission into intensive care.
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TITLE: Impacts of morally distressing experiences on the mental health of Canadian health care workers during the COVID-19 pandemic.. ABSTRACT: Background: Research is urgently needed to understand health care workers' (HCWs') experiences of moral-ethical dilemmas encountered throughout the COVID-19 pandemic, and their associations with organizational perceptions and personal well-being. This research is important to prevent long-term moral and psychological distress and to ensure that workers can optimally provide health services.Objective: Evaluate associations between workplace experiences during COVID-19, moral distress, and the psychological well-being of Canadian HCWs.Method: A total of 1362 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in an online survey. Participants completed measures reflecting moral distress, perceptions of organizational response to the pandemic, burnout, and symptoms of psychological disorders, including depression, anxiety, and posttraumatic stress disorder (PTSD).Results: Structural equation modelling showed that when organizational predictors were considered together, resource adequacy, positive work life impact, and ethical work environment negatively predicted severity of moral distress, whereas COVID-19 risk perception positively predicted severity of moral distress. Moral distress also significantly and positively predicted symptoms of depression, anxiety, PTSD, and burnout.Conclusions: Our findings highlight an urgent need for HCW organizations to implement strategies designed to prevent long-term moral and psychological distress within the workplace. Ensuring availability of adequate resources, reducing HCW risk of contracting COVID-19, providing organizational support regarding individual priorities, and upholding ethical considerations are crucial to reducing severity of moral distress in HCWs.
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TITLE: A longitudinal study of mental health before and during the COVID-19 pandemic in Syrian refugees.. ABSTRACT: Background: The COVID-19 pandemic has resulted in increased anxiety and depression around the world. Refugees may be particularly vulnerable to the mental health effects of the pandemic because of their higher rates of mental health disorders, trauma histories, and daily stressors.Objectives: This study used data from a controlled trial of a brief behavioural intervention for psychological distress in Syrian refugees living in Azraq Camp in Jordan to examine the psychological effects of the pandemic on refugee mental health.Method: A total of 410 participants were randomized to either the intervention or control arms of the trial and were assessed at baseline and 3-month follow-up. Half the sample (199; 48.5%) completed their 3-month follow-up assessment after the pandemic restrictions began in Jordan and 211 (51.5%) completed the assessment prior to the pandemic. Refugees were independently assessed for symptoms of PTSD, anxiety, and depression at baseline and follow-up, and pandemic-related worries were assessed at follow-up for those who completed their assessment during the pandemic.Results: The most commonly reported worries were economic difficulties (82.4%), shortage of essential supplies (71.3%), and infecting others (59.7%) or themselves (51.9%). Refugees who were assessed during the pandemic had less severe PTSD symptoms than those assessed prior to the pandemic. Significant predictors of pandemic-related worries were lower levels of depression prior to the pandemic and greater anxiety during the pandemic.Conclusion: These findings highlight the specific needs of refugees during the pandemic and suggest that pre-existing mental health issues may not necessarily be the key risk factors for who will experience major mental health issues or worries during the pandemic.
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TITLE: Functional Activity of the Complement System in Hospitalized COVID-19 Patients: A Prospective Cohort Study.. ABSTRACT: Aims: Although the exact factors promoting disease progression in COVID-19 are not fully elucidated, unregulated activation of the complement system (CS) seems to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by SARS-CoV-2. In particular, the lectin pathway (LP) has been implicated in previous autopsy studies. The primary purpose of our study is to investigate the role of the CS in hospitalized COVID-19 patients with varying degrees of disease severity.Methods: In a single-center prospective observational study, 154 hospitalized patients with PCR-confirmed SARS-CoV-2 infection were included. Serum samples on admission to the COVID-19 ward were collected for analysis of CS pathway activities and concentrations of LP proteins [mannose-binding lectin (MBL) and ficolin-3 (FCN-3)] & C1 esterase inhibitor (C1IHN). The primary outcome was mechanical ventilation or in-hospital death.Results: The patients were predominately male and had multiple comorbidities. ICU admission was required in 16% of the patients and death (3%) or mechanical ventilation occurred in 23 patients (15%). There was no significant difference in LP activity, MBL and FCN-3 concentrations according to different peak disease severities. The median alternative pathway (AP) activity was significantly lower (65%, IQR 50-94) in patients with death/invasive ventilation compared to patients without (87%, IQR 68-102, p=0.026). An optimal threshold of <65.5% for AP activity was derived from a ROC curve resulting in increased odds for death or mechanical ventilation (OR 4,93; 95% CI 1.70-14.33, p=0.003) even after adjustment for confounding factors. Classical pathway (CP) activity was slightly lower in patients with more severe disease (median 101% for death/mechanical ventilation vs 109%, p=0.014). C1INH concentration correlated positively with length of stay, inflammatory markers and disease severity on admission but not during follow-up.Conclusion: Our results point to an overactivated AP in critically ill COVID-19 patients in vivo leading to complement consumption and consequently to a significantly reduced AP activity in vitro. The LP does not seem to play a role in the progression to severe COVID-19. Apart from its acute phase reaction the significance of C1INH in COVID-19 requires further studies.
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TITLE: Clinical Features and Temporal Lung Radiographic Changes in 25 Patients Recovering from COVID-19 Pneumonia: A Retrospective Case-Control Study.. ABSTRACT: BACKGROUND Little is known of the changes in lung radiographic characteristics over time in patients recovering from COVID-19. This study analyzed the clinical features and temporal lung radiographic changes in patients with moderate and severe COVID-19 pneumonia who did not require invasive mechanical ventilation during the acute and convalescent periods. MATERIAL AND METHODS The data of 25 patients with COVID-19 pneumonia from January 29, 2020, to November 24, 2020, who did not require invasive mechanical ventilation and who were followed up were retrospectively collected. The 25 patients were divided into severe and moderate groups. Clinical characteristics and computed tomography (CT) manifestations were compared. A total of 121 consecutive thin-slice CT scans were collected at 4 weeks, 2 months, and 5 months after admission to evaluate lung abnormalities in the patients. The CT score was used to assess disease severity. RESULTS The severe group had a lower rate of nucleic acid conversion within 10 days of admission and higher D-dimer, creatine kinase, and lactate dehydrogenase values. In the severe group, hospital stay was longer and hospitalization costs were higher. The average CT score of the severe group peaked in the second week, while the moderate group peaked in the first week and then decreased over time. There were no statistically significant differences in the average CT score between the 2 groups at the 5-month follow-up. CONCLUSIONS The pulmonary lesions of patients recovering from COVID-19 and who do not require invasive mechanical ventilation were gradually absorbed and resolved over time.
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TITLE: Analysis of transcriptomic data sets supports the role of IL-6 in NETosis and immunothrombosis in severe COVID-19.. ABSTRACT: BACKGROUND: There is an urgent need to understand the key events driving pathogenesis of severe COVID-19 disease, so that precise treatment can be instituted. In this respect NETosis is gaining increased attention in the scientific community, as an important pathological process contributing to mortality. We sought to test if indeed there exists robust evidence of NETosis in multiple transcriptomic data sets from human subjects with severe COVID-19 disease. Gene set enrichment analysis was performed to test for up-regulation of gene set functional in NETosis in the blood of patients with COVID-19 illness.RESULTS: Blood gene expression functional in NETosis increased with severity of illness, showed negative correlation with blood oxygen saturation, and was validated in the lung of COVID-19 non-survivors. Temporal expression of IL-6 was compared between severe and moderate illness with COVID-19. Unsupervised clustering was performed to reveal co-expression of IL-6 with complement genes. In severe COVID-19 illness, there is transcriptional evidence of activation of NETosis, complement and coagulation cascade, and negative correlation between NETosis and respiratory function (oxygen saturation). An early spike in IL-6 is observed in severe COVID-19 illness that is correlated with complement activation.CONCLUSIONS: Based on the transcriptional dynamics of IL-6 expression and its downstream effect on complement activation, we constructed a model that links early spike in IL-6 level with persistent and self-perpetuating complement activation, NETosis, immunothrombosis and respiratory dysfunction. Our model supports the early initiation of anti-IL6 therapy in severe COVID-19 disease before the life-threatening complications of the disease can perpetuate themselves autonomously.
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TITLE: In depth analysis of Cyprus-specific mutations of SARS-CoV-2 strains using computational approaches.. ABSTRACT: BACKGROUND: This study aims to characterize SARS-CoV-2 mutations which are primarily prevalent in the Cypriot population. Moreover, using computational approaches, we assess whether these mutations are associated with changes in viral virulence.METHODS: We utilize genetic data from 144 sequences of SARS-CoV-2 strains from the Cypriot population obtained between March 2020 and January 2021, as well as all data available from GISAID. We combine this with countries' regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of Cyprus-specific mutations are obtained by mutation tracking analysis. This entails calculating specific mutation frequencies within the Cypriot population and comparing these with their prevalence world-wide throughout the course of the pandemic. We further make use of linear regression models to extrapolate additional information that may be missed through standard statistical analysis.RESULTS: We report a single mutation found in the ORF1ab gene (nucleotide position 18,440) that appears to be significantly enriched within the Cypriot population. The amino acid change is denoted as S6059F, which maps to the SARS-CoV-2 NSP14 protein. We further analyse this mutation using regression models to investigate possible associations with increased deaths and cases per million. Moreover, protein structure prediction tools show that the mutation infers a conformational change to the protein that significantly alters its structure when compared to the reference protein.CONCLUSIONS: Investigating Cyprus-specific mutations for SARS-CoV-2 can lead to a better understanding of viral pathogenicity. Researching these mutations can generate potential links between viral-specific mutations and the unique genomics of the Cypriot population. This can not only lead to important findings from which to battle the pandemic on a national level, but also provide insights into viral virulence worldwide.
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TITLE: Severe COVID-19 acute respiratory distress syndrome in an adult with single-ventricle physiology: a case report.. ABSTRACT: BACKGROUND: COVID-19 can induce acute respiratory distress syndrome (ARDS). In patients with congenital heart disease, established treatment strategies are often limited due to their unique cardiovascular anatomy and passive pulmonary perfusion.CASE PRESENTATION: We report the first case of an adult with single-ventricle physiology and bidirectional cavopulmonary shunt who suffered from severe COVID-19 ARDS. Treatment strategies were successfully adopted, and pulmonary vascular resistance was reduced, both medically and through prone positioning, leading to a favorable outcome.CONCLUSION: ARDS treatment strategies including ventilatory settings, prone positioning therapy and cannulation techniques for extracorporeal oxygenation must be adopted carefully considering the passive venous return in patients with single-ventricle physiology.
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TITLE: Using genetics to understand the role of kidney function in COVID-19: a mendelian randomization study.. ABSTRACT: BACKGROUND: Kidney dysfunction occurs in severe COVID-19, and is a predictor of COVID-19 mortality. Whether kidney dysfunction causes severe COVID-19, and hence is a target of intervention, or whether it is a symptom, is unclear because conventional observational studies are open to confounding. To obtain unconfounded estimates, we used Mendelian randomization to examine the role of kidney function in severe COVID-19.METHODS: We used genome-wide significant, uncorrelated genetic variants to predict kidney function, in terms of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), and then assessed whether people with genetically instrumented higher eGFR or lower UACR, an indication of better kidney function, had a lower risk of severe COVID-19 (8779 cases, 1,001,875 controls), using the largest available cohorts with extensive genotyping. For comprehensiveness, we also examined their role in COVID-19 hospitalization (24,274 cases, 2,061,529 controls) and all COVID-19 (1,12,612 cases, 2,474,079 controls).RESULTS: Genetically instrumented higher eGFR was associated with lower risk of severe COVID-19 (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.83, 0.98) but not related to COVID-19 hospitalization or infection. Genetically instrumented UACR was not related to COVID-19.CONCLUSIONS: Kidney function appears to be one of the key targets for severe COVID-19 treatment. Use of available medications to improve kidney function, such as antihypertensives, might be beneficial for COVID-19 treatment, with relevance to drug repositioning.
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TITLE: Estimating causal effects of atherogenic lipid-related traits on COVID-19 susceptibility and severity using a two-sample Mendelian randomization approach.. ABSTRACT: BACKGROUND: As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach.METHODS: We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls). We performed two-sample MR analyses using the inverse variance weighted (IVW) method. As sensitivity analyses, the MR-Egger regression, weighted median, and weighted mode methods were conducted as were leave-one-out sensitivity analysis, the MR-PRESSO global test, PhenoScanner searches, and IVW multivariable MR analyses. A P value below 0.0055 with Bonferroni correction was considered statistically significant.RESULTS: This MR study suggested that serum apolipoprotein B or LDL-cholesterol levels were not significantly associated with COVID-19 risk. On the other hand, we inferred that higher serum triglyceride levels were suggestively associated with higher risks of COVID-19 susceptibility (odds ratio [OR] per standard deviation increase in lifelong triglyceride levels, 1.065; 95% confidence interval [CI], 1.001-1.13; P = 0.045) and hospitalization (OR, 1.174; 95% CI, 1.04-1.33; P = 0.012), and were significantly associated with COVID-19 severity (OR, 1.274; 95% CI, 1.08-1.50; P = 0.004). Sensitivity and bidirectional MR analyses suggested that horizontal pleiotropy and reverse causation were unlikely.CONCLUSIONS: Our MR study indicates a causal effect of higher serum triglyceride levels on a greater risk of COVID-19 severity in the European population using the latest and largest GWAS datasets to date. However, as the underlying mechanisms remain unclear and our study might be still biased due to possible horizontal pleiotropy, further studies are warranted to validate our findings and investigate underlying mechanisms.
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TITLE: ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.. ABSTRACT: BACKGROUND: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma.METHODS: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort.RESULTS: Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis.CONCLUSION: We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.
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TITLE: Home-based exercise program for adolescents with juvenile dermatomyositis quarantined during COVID-19 pandemic: a mixed methods study.. ABSTRACT: BACKGROUND: Exercise has been suggested to prevent deterioration of health-related quality of life (HRQL) and overall health in pediatric rheumatologic diseases during the COVID-19 pandemic. Herein we describe the effects of a 12-week, home-based, exercise program on overall health and quality of life among quarantined patients with juvenile dermatomyositis (JDM).METHOD: This prospective, quasi-experimental, mixed methods (qualitative and quantitative) study was conducted between July and December 2020, during the most restricted period of COVID-19 pandemic in Brazil. The home-based exercise program consisted of a 12-week, three-times-a-week, aerobic and strengthening (bodyweight) training program. Qualitative data were systematically evaluated. Strengths and Difficulties Questionnaire (SDQ), Pediatric Quality of Life Inventory (PedsQOL) and Pittsburgh Sleep Quality Index (PSQI) evaluate symptoms of mental health disorder, HRQL, and quality of sleep.FINDINGS: 11 patients (out of 27) met the inclusion criteria (91% female; mean ± SD age: 13.5 ± 3.2 years). Adherence to the intervention was 72.6%. Barriers to exercise involved poor internet connectivity, excessive weekly sessions, and other commitments. Even though not statistically significant, Self-report SDQ subscales Total Difficulties Score, Emotional Problems Score, and PedsQOL School Functioning Score improved after intervention (- 2.4; 95%confidence interval [CI] -5.1; 0.2, p = 0.06; - 1.0; 95%CI -2.2; 0.2, p = 0.09 and; 11.7; 95%CI -2.5; 25.8, p = 0.09, respectively). Remaining SDQ subscales were not altered. Six themes emerged from patients' and parents' comments (qualitative results). Patients engaged in exercise reported other health-related benefits including increased motivation, concentration and strength.INTERPRETATION: A home-based exercise program was associated with qualitative perceptions of improvements in overall health and HRQL by quarantined adolescents with JDM during COVID-19 pandemic. Lessons from this trial may help developing interventions focused on tackling physical inactivity in JDM.
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TITLE: Safety and preliminary efficacy of the Gam-COVID-Vac vaccine and outcomes of SARS-CoV-2 infection in Russian patients with genitourinary malignancies.. ABSTRACT: BACKGROUND: To our knowledge, there is no clinical data pertaining to COVID-19 outcomes and safety of COVID-19 vaccination in Russian patients with genitourinary (GU) malignancies. Aim of our analysis was to describe the characteristics of the COVID-19 infection course as well as preliminary safety and efficacy of Gam-COVID-Vac vaccine in patients with active GU malignancies.METHODS: Patients were retrospectively identified at nine cancer centers in different regions. Patients were included if COVID-19 was diagnosed by a polymerase chain reaction. Data from additional patients with GU cancers who had no positive SARS-CoV-2 RT-PCR test before vaccination and who received two doses of Gam-COVID-Vac (Sputnik V) between 11 February and 31 August 2021 were collected for safety assessment. Anonymized data were collected through an online registry covering demographics, treatments, and outcomes.RESULTS: The Gam-COVID-Vac vaccine was well tolerated; no grade 3-5 toxicities were reported in 112 vaccinated metastatic GU cancer patients. The most common grade 1 adverse events (81%) were injection site reactions (76%), flu-like illness (68%), and asthenia (49%). Five patients experienced grade 2 chills (4.5%) and 3 patients had grade 2 fever (2.7%). With median follow-up of 6.2 months, two COVID-19 cases were confirmed by RT-PCR test in the vaccine group (of 112 participants; 1.8%). Eighty-eight patients with COVID-19 disease were included in the analysis. The average age as of the study enrollment was 66 (range 39-81) and the majority of patients were male with renal cell carcinoma (RCC). Thirty-six patients (41%) had evidence of metastatic disease, of these 22 patients were receiving systemic therapy. More than half of patients required hospitalization. Fifty-four patients (61%) experienced complications. Sixteen patients who developed COVID-19 pneumonia required mechanical ventilator support. Sixteen patients (18%) died in a median of 23.5 days after the date of COVID-19 diagnosis was established. The 3-month survival rate was 82%. Clinical and/or radiographic progression of cancer during COVID-19 infection or the subsequent 3 months was observed in 10 patients (11.4%).CONCLUSION: Patients with GU malignancies are at increased risk of mortality from COVID-19 infection when compared to the general population. Vaccination could be safe in GU cancer patients.TRIAL REGISTRATION: retrospectively registered.
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TITLE: PCR Primer Design for the Rapidly Evolving SARS-CoV-2 Genome.. ABSTRACT: Real-time quantitative PCR is currently the most widely used method for the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identification. Due to the rapid evolution of the SARS-CoV-2 genome, novel mutations on the primer binding sites will cause the failure of PCR. Therefore, in addition to a well-designed primer set, these primers need to be updated and evaluated regularly to ensure that the rapidly evolving genome primers can be amplified. In this protocol, (1) we firstly use assembled genome sequences in the SARS-CoV-2 database to identify and characterize indels and point mutations; (2) design primers skipping the sites of mutations; (3) check the coverage of the primers with the daily update SARS-CoV-2 database; (4) redesign them if novel mutations found in the primer binding sites. Although this protocol takes SARS-CoV-2 as an example, it is suitable for other species that have genomes accumulating mutations over time.
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TITLE: C-reactive protein as an effector molecule in Covid-19 pathogenesis.. ABSTRACT: The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.
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TITLE: Route of infectious bronchitis virus vaccination determines the type and magnitude of immune responses in table egg laying hens.. ABSTRACT: Chicken immune responses to infectious bronchitis virus (IBV) vaccination can depend on route of administration, vaccine strain and bird age. Typically for layer chickens, IBV vaccinations are administered by spray in the hatchery at day-old and boosted at intervals with live vaccines via drinking water (DW). Knowledge of live attenuated IBV vaccine virus kinetics and the immune response in egg-laying hens is exceptionally limited. Here, we demonstrated dissemination of vaccine viruses and differences in hen innate, mucosal, cellular and humoral immune responses following vaccination with Massachusetts or 793B strains, administered by DW or oculonasal (ON) routes. Detection of IBV in the Mass-vaccinated groups was greater during early time-points, however, 793B was detected more frequently at later timepoints. Viral RNA loads in the Harderian gland and turbinate tissues were significantly higher for ON-Mass compared to all other vaccinated groups. Lachrymal fluid IgY levels were significantly greater than the control at 14 days post-vaccination (dpv) for both vaccine serotypes, and IgA mRNA levels were significantly greater in ON-vaccinated groups compared to DW-vaccinated groups, demonstrating robust mucosal immune responses. Cell mediated immune gene transcripts (CD8-á and CD8-â) were up-regulated in turbinate and trachea tissues. For both vaccines, dissemination and vaccine virus clearance was slower when given by DW compared to the ON route. For ON administration, both vaccines induced comparable levels of mucosal immunity. The Mass vaccine induced cellular immunity to similar levels regardless of vaccination method. When given either by ON or DW, 793B vaccination induced significantly higher levels of humoral immunity.
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TITLE: Lessons learned from urgent computing in Europe: Tackling the COVID-19 pandemic.. ABSTRACT: PRACE (Partnership for Advanced Computing in Europe), an international not-for-profit association that brings together the five largest European supercomputing centers and involves 26 European countries, has allocated more than half a billion core hours to computer simulations to fight the COVID-19 pandemic. Alongside experiments, these simulations are a pillar of research to assess the risks of different scenarios and investigate mitigation strategies. While the world deals with the subsequent waves of the pandemic, we present a reflection on the use of urgent supercomputing for global societal challenges and crisis management.
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TITLE: Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology Clinic of University Clinical Hospital Mostar, Bosnia and Herzegovina: A Cross-Sectional Study.. ABSTRACT: BACKGROUND The pandemic of Coronavirus infectious disease 2019 (COVID-19) poses a major public health challenge, and an effective vaccine is the potential mechanism to resolve this specific situation. The present study aimed to evaluate acceptance of COVID-19 vaccination among patients attending the Oncology Clinic of University Clinical Hospital Mostar. MATERIAL AND METHODS This cross-sectional observational study enrolled 364 patients with cancer from the Oncology Clinic of University Clinical Hospital Mostar during February 2021. Data were collected using a questionnaire that captured general information about the participants and their attitudes toward COVID-19 vaccination. RESULTS Of the participants, 41.8% answered "Yes" when asked if they would take the vaccine once it becomes available, 37.6% answered "Not sure", and 20.6% answered "No". For patients in favor of vaccination, the main reasons reported were fear of getting sick (77.6%), the desire to contribute to herd immunity (57.8%), and trusting the recommendations of health professionals (57.2%). The main reasons for the patients' vaccination -refusal/indecision were doubts about the results from clinical trials of COVID-19 vaccines (49.1%), concerns about adverse effects (24.5%), and confusion about the various vaccine options (19.8%). The majority of participants (82.4%) stated that recommendation by their oncologist could influence their decision about vaccination. Of the participants who indicated unwillingness (refusal or indecision) to be vaccinated against COVID-19, 65.3% stated that recommendation by their oncologist could influence their decision about vaccination. CONCLUSIONS The findings from the present study showed most patients had refused or were indecisive regarding immunization with COVID-19 vaccine. Increasing physician awareness of this situation may result in higher rates of vaccination.
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TITLE: Computational redesign of Fab CC12.3 with substantially better predicted binding affinity to SARS-CoV-2 than human ACE2 receptor.. ABSTRACT: SARS-CoV-2 is responsible for COVID-19 pandemic, causing large numbers of cases and deaths. It initiates entry into human cells by binding to the peptidase domain of angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain of S1 subunit of spike protein (SARS-CoV-2-RBD). Employing neutralizing antibodies to prevent binding between SARS-CoV-2-RBD and ACE2 is an effective COVID-19 therapeutic solution. Previous studies found that CC12.3 is a highly potent neutralizing antibody that was isolated from a SARS-CoV-2 infected patient, and its Fab fragment (Fab CC12.3) bound to SARS-CoV-2-RBD with comparable binding affinity to ACE2. To enhance its binding affinity, we employed computational protein design to redesign all CDRs of Fab CC12.3 and molecular dynamics (MD) to validate their predicted binding affinities by the MM-GBSA method. MD results show that the predicted binding affinities of the three best designed Fabs CC12.3 (CC12.3-D02, CC12.3-D05, and CC12.3-D08) are better than those of Fab CC12.3 and ACE2. Additionally, our results suggest that enhanced binding affinities of CC12.3-D02, CC12.3-D05, and CC12.3-D08 are caused by increased SARS-CoV-2-RBD binding interactions of CDRs L1 and L3. This study redesigned neutralizing antibodies with better predicted binding affinities to SARS-CoV-2-RBD than Fab CC12.3 and ACE2. They are promising candidates as neutralizing antibodies against SARS-CoV-2.
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TITLE: Internet memes related to the COVID-19 pandemic as a potential coping mechanism for anxiety.. ABSTRACT: This study examined whether significantly anxious individuals differed from non-anxious individuals in their perceptual ratings of internet memes related to the Covid-19 pandemic, whilst considering the mediating role of emotion regulation. Eighty individuals presenting clinically significant anxiety symptoms (indicating ? 15 on the GAD-7) and 80 non-anxious controls (indicating ? 4) rated the emotional valance, humour, relatability, shareability, and offensiveness of 45 Covid-19 internet memes. A measure of emotion regulation difficulties was also completed. The perception of humour, relatability, and shareability were all greater amongst anxious individuals relative to non-anxious controls. These differences were not mediated by emotion regulation deficits. Internet memes related to the current Covid-19 pandemic may tentatively serve as coping mechanism for individuals experiencing severe symptoms of anxiety.
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TITLE: The first report of iron-rich population of adapted medicinal spinach (Blitum virgatum L.) compared with cultivated spinach (Spinacia oleracea L.).. ABSTRACT: Folk medicine such as herbal and natural products have been used for centuries in every culture throughout the world. The Chenopodiaceae family with more than 1500 species is dispersed worldwide. The Iranian wild spinach (Blitum virgatum L.) is an important traditional medicinal plant used for antiviral diseases such as pneumonia and other respiratory track infections. This plant is a mountainous herb and is growing upper than 3000 m. We performed a mass selection plant breeding program on wild populations of this Iranian wild spinach during 2013-2020. Based on experimental and field characteristics this plant was identified as B. virgatum, |abbaricum|, and related characteristics were prepared with reference to the International Union for the Protection of New Varieties of Plants (UPOV). Mass selection program resulted from an adapted population named as medicinal spinach (MSP) population. To compare the mineral content of the mass-selected population with cultivated spinach (Spinacia oleracea L. |Varamin 88|), both plants were planted in pots and fields under similar conditions. In five leaves stage, plant samples were taken from both leaf and crown sections and used for experimental analysis. Atomic absorption spectroscopy was used to determine the mineral content including iron (Fe), zinc (Z), manganese (Mn), and copper (Cu). Our results showed the selected medicinal spinach population (MSP) with about 509 ppm iron was an important iron-rich population with about 3.5-4 times more than the amount of iron in cultivated spinach in the same conditions. Because iron is an important essential element for blood production, respiration process, energy metabolisms, synthesis of collagen, and some neurotransmitters are needed for proper immune function, so the supply of absorbable adequate iron is very important. The reasons such as the prevalence of the COVID-19 pandemic, which affects the amount of exchangeable oxygen in the lungs and historical local evidences of the use of this plant (MSP) for pneumonia, could open new horizons for focusing on studies related to the use of ancestral human experiences in addition to scientifically modern research.
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TITLE: Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1.. ABSTRACT: The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ÄNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ÄNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ÄNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ÄNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ÄNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.
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TITLE: Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells.. ABSTRACT: To initiate SARS-CoV-2 infection, the Receptor Binding Domain (RBD) on the viral spike protein must first bind to the host receptor ACE2 protein on pulmonary and other ACE2-expressing cells. We hypothesized that cardiac glycoside drugs might block the binding reaction between ACE2 and the Spike (S) protein, and thus block viral penetration into target cells. To test this hypothesis we developed a biochemical assay for ACE2:Spike binding, and tested cardiac glycosides as inhibitors of binding. Here we report that ouabain, digitoxin, and digoxin, as well as sugar-free derivatives digitoxigenin and digoxigenin, are high-affinity competitive inhibitors of ACE2 binding to the Original [D614] S1 and the á/â/ã [D614G] S1 proteins. These drugs also inhibit ACE2 binding to the Original RBD, as well as to RBD proteins containing the â [E484K], Mink [Y453F] and á/â/ã [N501Y] mutations. As hypothesized, we also found that ouabain, digitoxin and digoxin blocked penetration by SARS-CoV-2 Spike-pseudotyped virus into human lung cells, and infectivity by native SARS-CoV-2. These data indicate that cardiac glycosides may block viral penetration into the target cell by first inhibiting ACE2:RBD binding. Clinical concentrations of ouabain and digitoxin are relatively safe for short term use for subjects with normal hearts. It has therefore not escaped our attention that these common cardiac medications could be deployed worldwide as inexpensive repurposed drugs for anti-COVID-19 therapy.
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TITLE: Evaluating Feasibility of Human Tissue Engineered Respiratory Epithelium Construct as a Potential Model for Tracheal Mucosal Reconstruction.. ABSTRACT: The normal function of the airway epithelium is vital for the host's well-being. Conditions that might compromise the structure and functionality of the airway epithelium include congenital tracheal anomalies, infection, trauma and post-intubation injuries. Recently, the onset of COVID-19 and its complications in managing respiratory failure further intensified the need for tracheal tissue replacement. Thus far, plenty of naturally derived, synthetic or allogeneic materials have been studied for their applicability in tracheal tissue replacement. However, a reliable tracheal replacement material is missing. Therefore, this study used a tissue engineering approach for constructing tracheal tissue. Human respiratory epithelial cells (RECs) were isolated from nasal turbinate, and the cells were incorporated into a calcium chloride-polymerized human blood plasma to form a human tissue respiratory epithelial construct (HTREC). The quality of HTREC in vitro, focusing on the cellular proliferation, differentiation and distribution of the RECs, was examined using histological, gene expression and immunocytochemical analysis. Histological analysis showed a homogenous distribution of RECs within the HTREC, with increased proliferation of the residing RECs within 4 days of investigation. Gene expression analysis revealed a significant increase (p < 0.05) in gene expression level of proliferative and respiratory epithelial-specific markers Ki67 and MUC5B, respectively, within 4 days of investigation. Immunohistochemical analysis also confirmed the expression of Ki67 and MUC5AC markers in residing RECs within the HTREC. The findings show that calcium chloride-polymerized human blood plasma is a suitable material, which supports viability, proliferation and mucin secreting phenotype of RECs, and this suggests that HTREC can be a potential candidate for respiratory epithelial tissue reconstruction.
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TITLE: Characterization of the Trans-Epithelial Transport of Green Tea (C. sinensis) Catechin Extracts with In Vitro Inhibitory Effect against the SARS-CoV-2 Papain-like Protease Activity.. ABSTRACT: This work describes an untargeted analytical approach for the screening, identification, and characterization of the trans-epithelial transport of green tea (Camellia sinensis) catechin extracts with in vitro inhibitory effect against the SARS-CoV-2 papain-like protease (PLpro) activity. After specific catechin extraction, a chromatographic separation obtained six fractions were carried out. The fractions were assessed in vitro against the PLpro target. Fraction 5 showed the highest inhibitory activity against the SARS-CoV-2 PLpro (IC50 of 0.125 ìg mL-1). The untargeted characterization revealed that (-)-epicatechin-3-gallate (ECG) was the most abundant compound in the fraction and the primary molecule absorbed by differentiated Caco-2 cells. Results indicated that fraction 5 was approximately 10 times more active than ECG (IC50 value equal to 11.62 ± 0.47 ìg mL-1) to inhibit the PLpro target. Overall, our findings highlight the synergistic effects of the various components of the crude extract compared to isolated ECG.
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TITLE: Early life blood lead levels and asthma diagnosis at age 4-6 years.. ABSTRACT: The USA has a high burden of childhood asthma. Previous studies have observed associations between higher blood lead levels and greater hypersensitivity in children. The objective of the present study was to estimate the association between blood lead concentrations during early childhood and an asthma diagnosis between 48 and 72 months of age amongst a cohort with well-characterized blood lead concentrations. Blood lead concentrations were measured at 6, 12, 18, 24, 36, and 48 months of age in 222 children. The presence of an asthma diagnosis between 48 and 72 months was assessed using a questionnaire which asked parents or guardians whether they had been told by a physician, in the past 12 months, that their child had asthma. Crude and adjusted risk ratios (RR) of an asthma diagnosis were estimated for several parameterizations of blood lead exposure including lifetime average (6 to 48 months) and infancy average (6 to 24 months) concentrations. After adjustment for child sex, birthweight, daycare attendance, maternal race, education, parity, breastfeeding, income, and household smoking, age-specific or composite measures of blood lead were not associated with asthma diagnosis by 72 months of age in this cohort.
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TITLE: Frequency and source of worries in an International sample of pregnant and postpartum women during the Covid-19 pandemic.. ABSTRACT: BACKGROUND: Pregnant and postpartum women face unique challenges and concerns during the COVID-19 pandemic. Thus far, no studies have explored the factors associated with increased levels of worry in this population globally. The current study sought to assess the frequency and sources of worry during the COVID-19 pandemic in an international sample of pregnant and postpartum women.METHODS: We conducted an anonymous, online, cross-sectional survey in 64 countries between May and June 2020. The survey was available in 12 languages and hosted on the Pregistry platform for COVID-19 studies. Participants were sought mainly on social media platforms and online parenting forums. The survey included questions related to demographics, level of worry, support, stress, COVID-19 exposure, frequency of media usage, and mental health indicators.RESULTS: The study included 7561 participants. Eighty-three percent of all participants indicated that they were either 'somewhat' or 'very' worried. Women 13-28 weeks pregnant were significantly more likely to indicate that they were 'very worried' compared to those who were postpartum or at other stages of pregnancy. When compared with women living in Europe, those in Africa, Asia and Pacific, North America and South/Latin America were more likely to have increased levels of worry, as were those who more frequently interacted with social media. Different forms of support and stress also had an impact upon level of worry, while indicators of stress and anxiety were positively associated with worry level.CONCLUSION: Pregnant and postpartum women are vulnerable to the changes in societal norms brought about by the COVID-19 pandemic. Understanding the factors associated with levels of worry within this population will enable society to address potential unmet needs and improve the current and future mental health of parents and children.
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TITLE: Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.. ABSTRACT: BACKGROUND: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies.METHODS: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies.RESULTS: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39).CONCLUSION: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.
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TITLE: Facilitating Perinatal Access to Resources and Support (PeARS): a feasibility study with external pilot of a novel intervention.. ABSTRACT: BACKGROUND: Up to 50% of women in areas of high socio-economic deprivation are at risk of developing depressive symptoms in pregnancy. Feeling well supported, can facilitate good mental health perinatally. A brief, innovative intervention to facilitate access to support and resources was developed and tested. This included one antenatal and one postnatal session, each with three evidence-based components: i) support from a non-professional peer to enable a woman to identify her needs; ii) information about local community services and signposting; and iii) development of a personalised If-Then plan to access that support. The aims were to evaluate the intervention and research methods for feasibility and acceptability for perinatal women, maternity care providers and peers, and provide preliminary effectiveness indications.METHODS: Pregnant women living in an area of high deprivation were recruited from community-based antenatal clinics and randomised to intervention or control condition (a booklet about local resources). Outcome measures included women's use of community services by 34 + weeks gestation and 6 months postnatally; mental health and wellbeing measures, and plan implementation. Interviews and focus groups were conducted with women participants, providers, and peers. Data were analysed using framework analysis. Recruitment and retention of peers and participants, intervention fidelity, and acceptability of outcome measures were recorded.RESULTS: Peer facilitators could be recruited, trained, retained and provide the intervention with fidelity. One hundred twenty six women were recruited and randomised, 85% lived in the 1% most deprived UK areas. Recruitment constituted 39% of those eligible, improving to 54% after midwifery liaison. Sixty five percent were retained at 6 months postnatally. Women welcomed the intervention, and found it helpful to plan access to community services. Providers strongly supported the intervention philosophy and integrated this easily into services. The study was not powered to detect significant group differences but there were positive trends in community service use, particularly postnatally. No differences were evident in mental health and wellbeing.CONCLUSIONS: This intervention was well received and easily integrated into existing services. Women living in highly deprived areas could be recruited, randomised and retained. Measures were acceptable. Peer facilitators were successfully trained and retained. Full effectiveness studies are warranted.
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TITLE: Fermentation quality of herbal tea residue and its application in fattening cattle under heat stress.. ABSTRACT: BACKGROUND: Herbal tea residue (HTR) is generally considered to be the waste of herbal tea beverage production while it still retains rich nutrients and active substances. The main aim of the present study was to investigate the effect of fermentation technology on improving the quality of HTRs, and focus on the fermented HTR-induced alleviation of summer heat stress in fattening cattle.RESULTS: In this study, the waste HTR was fermented and then fed to a total of 45 fattening cattle that were divided into 3 groups (fermented HTR replaced 0, 15, 30% of the forage component of the diet), and the feeding experiment was lasted for 40 days. The physiological indexes, growth performance and fecal microbiota of fattening cattle were evaluated and results showed that fermented HTR could effectively reduce the respiratory rate and rectal temperature of fattening cattle under heat stress, increase the daily feed intake and daily gain, and improve the antioxidant content and blood immune index. In addition, we studied the fecal microbiota composition of 6 fattening cattle in control and 30% HTR substitution groups and found fermented HTR significantly changed the composition of fecal microbiota and increased microbial diversity, and correlation analysis suggested that the bacteria were closely related to fecal SCFA levels of fattening cattle under heat stress.CONCLUSIONS: In this study, fermented HTR replaced 30% of the forage component of the diet that can change the intestine microorganisms, maintain health and alleviate the heat stress of fattening cattle.
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TITLE: Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2.. ABSTRACT: Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (á-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.
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