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Background: Although social isolation is known to limit the spread of a pandemic, the impact of mental health for such measures is yet unknown. In this cross-sectional study, we investigated the impact on mental health among different age groups due to social isolation during the ongoing COVID-19 pandemic in Dhaka, Bangladesh. Methods: : We conducted a carefully designed cross sectional survey on mental health that was disseminated widely by way of email, personal contact and social media to subjects aged between 11 and >70 years. For our analysis we stratified data into three distinct groups: children/young adults (11-40), middle age (40-60) and older adult age (> 60) groups. 3214 respondents answered the survey. Bonferroni corrected Chi-square tests were used to find significant relationships between the demographic groups and mental health related variables. Results: : We observed a high percentage of insomnia (79%) in old age respondants compared to children/young adults (61%) and middle age (66%) groups, suggesting that age is significantly associated (p= 3.8 X 10 -06 ;odds ratio (OR) = 2.34) with insomnia. Respondents who were retired also reported a higher prevalence (73%) of insomnia (p = 2.79 X 10 -8 ) compare to employed individuals. A higher level of mental stress (84%) was observed in middle aged respondents followed by old adult (71%) respondents (p=0.001). Significantly higher rates (p = 5.08 X 10 -27 ;OR = 2.06) of mental stress were detected in people with preexisting comorbidities compared with the healthy group. The old age participants were less familiar with the concept of social isolation and 54% of old age participants had a negative perception towards social isolation compared to children/young adults (12%) and middle-aged (7%) respondents. Conclusion: Our results indicate an association between age and mental stress concomitant on the COVID-19 social isolation policy in Bangladesh. Social isolation increased insomnia and mental stress, particularly in old age and middle age group. Moreover, these older age groups also tended to have a negative perception of the COVID-19 isolation policy. Therefore, providing mental healthcare services and policy related education in developing countries should target these older age groups to ensure maintenance of their mental wellbeing and adherence to safe practice.
Impact of Social Isolation on Mental Health Amid COVID-19 Pandemic: A Nationwide Survey
Protein structures are crucial for understanding their biological activities. Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need to understand the biological behavior of the virus and provide a basis for developing effective therapies. Since the proteome of the virus was determined, some of the protein structures could be determined experimentally, and others were predicted via template-based modeling approaches. However, tertiary structures for several proteins are still not available from experiment nor they could be accurately predicted by template-based modeling because of lack of close homolog structures. Previous efforts to predict structures for these proteins include efforts by DeepMind and the Zhang group via machine learning-based structure prediction methods, i.e. AlphaFold and C-I-TASSER. However, the predicted models vary greatly and have not yet been subjected to refinement. Here, we are reporting new predictions from our in-house structure prediction pipeline. The pipeline takes advantage of inter-residue contact predictions from trRosetta, a machine learning-based method. The predicted models were further improved by applying molecular dynamics simulation-based refinement. We also took the AlphaFold models and refined them by applying the same refinement method. Models based on our structure prediction pipeline and the refined AlphaFold models were analyzed and compared with the C-I-TASSER models. All of our models are available at https://github.com/feiglab/sars-cov-2-proteins.
Modeling of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Proteins by Machine Learning and Physics-Based Refinement
Beyond their immediate effects on mortality, disasters have widespread, indirect impacts on mental and physical well-being by exposing survivors to stress and potential trauma. Identifying the disaster-related stressors that predict health adversity will help officials prepare for the coronavirus disease 2019 (COVID-19) pandemic. Using data from a prospective study of young, low-income mothers who survived Hurricane Katrina, we find that bereavement, fearing for loved ones well-being, and lacking access to medical care and medications predict adverse mental and physical health 1 y postdisaster, and some effects persist 12 y later. Adjusting for preexisting health and socioeconomic conditions attenuates, but does not eliminate, these associations. The findings, while drawn from a demographically unique sample, suggest that, to mitigate the indirect effects of COVID-19, lapses in medical care and medication use must be minimized, and public health resources should be directed to those with preexisting medical conditions, their social networks, and the bereaved.
Lessons from Hurricane Katrina for predicting the indirect health consequences of the COVID-19 pandemic
BACKGROUND & AIMS: Vitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). METHODS: This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding. RESULTS: A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). CONCLUSION: The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.
Vitamin D deficiency in critically ill COVID-19 ARDS patients
The objective of the study based on the analysis and evaluation of key performance indicators of the all-Russian center for disaster medicine "Zaschita" FMBA Rossii (WCMC "Protection" in the Center) and disaster medical Service (QMS), Russian Ministry of health to develop proposals and to identify priority areas for further development and improvement of the system of medical support of the population in emergency situations (es) Materials and methods of research Materials research: normative and methodical documents governing the organization and operation of the all-Russian service for disaster medicine (VSMK), medical aid to victims in emergency and medical evacuation;records of the regional centers of emergency medical care and disaster medicine (SMP RC and IC), the territorial centers of emergency medicine (TSMC) and WCMC "Protection" on the activity of the elimination of the health consequences of emergencies in 2020 etc Research methods: analytical, statistical, direct observation method, logical and information modeling The results of the study and their analysis In 2020, 2108 emergencies with health consequences occurred in the Russian Federation, excluding the COVID-19 pandemic, which is almost 25% less than in 2019 This situation can be explained by a decrease in the intensity of transport operations and the activity of the population during the pan-demic In order to further develop the system of medical support for the population in emergencies, the tasks for 2021 are formulated ? ARCDM Zashchita
Main results of activities of all-Russian centre for disaster medicine Zashchita of federal medical biological agency in 2020 and tasks for 2021
The pandemic caused by Sars-CoV-2 (COVID-19) has been a great concern for public and mental health systems worldwide. The identification of risk groups is essential for the establishment of preventive and therapeutic strategies, as for substance users. During COVID-19 pandemic, there was an increase in the use of psychoactive substances during the lockdown, including cannabis. This commentary reviews relevant findings and discusses scientific evidence on the risks of worse clinical and psychiatric complications due to coronavirus disease COVID-19 in subjects who use cannabis. Although they are not included as a risk group in the health recommendations for that disease, they may have a more vulnerable respiratory system to viral diseases. There are certain similarities between the harmful cardiovascular and respiratory effects of cannabis use and those of smoking. Due to the different modes of smoking, cannabis chemicals are retained in the body for longe and may also contain other toxic substances such as tar, a substance found in tobacco and which has been associated with the development of lung cancer, bronchitis and pulmonary emphysema. Therefore, we discuss if individuals who use cannabis regularly might be more vulnerable to COVID-19 infection. This population deserves more clinical attention worldwide and this manuscript can help clinicians become more aware of cannabis risks during pandemics and develop specific intervention strategies.
Multiple clinical risks for cannabis users during the COVID-19 pandemic
The coronavirus disease of 2019 or COVID-19 was first identified in Hubei Province in China in November of 2019 and quickly spread to become a global pandemic. The virus, SARS-Coronavirus-2 (2-SARS-CoV-2), is particularly virulent in the elderly who can develop symptoms and become mortally ill within days of contracting the virus. The virus is easily transmitted by droplets (e.g., sneezing, coughing) and communal living settings such as personal care homes can be vulnerable to the spread of the virus. Identifying patients early in the disease process is important to providing appropriate medical interventions. To date, most of the medical literature, including Center for Disease Control guidelines, has relied on three necessary symptoms in making the diagnosis of COVID-19: fever, cough and shortness of breath. We present four cases of elderly patients who developed altered mental status as their presenting symptom without associated fever or respiratory symptoms.
Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly
BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed ( 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN- as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.
Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo
PURPOSE: With the rise in COVID-19 cases, the Eye Bank of Canada (Ontario Division), the largest eye bank in Canada, was faced with challenges related to ocular donor suitability which resulted in tissue shortages after the first wave of COVID-19 cases in Ontario, Canada. This article aims to analyze the impact of COVID-19 on ocular tissue donation and transplant surgeries. METHODS: Trends in ocular donations in 2020 and the transplant rates were compared with the data from the previous year, as a benchmark of normal eye bank activity. RESULTS: Ocular donor volumes decreased during the first wave of the COVID-19 pandemic (March-June 2020) by 65% as compared to the same period in 2019. By the end of the year 2020, this had resulted in a total reduction of 29% of ocular donor volumes as compared to 2019. The ocular transplant surgery volumes in the year 2020 decreased by 32% compared to the previous year, mostly secondary to elective surgery shutdown during the first wave. Because of tissue shortages, the Eye Bank of Canada (Ontario Division) had to import 24 corneas from the United States and cancel 7 surgeries in the year 2020. CONCLUSIONS: The decline in ocular tissue donor volumes and transplant surgery was a result of an interplay of causes related to the COVID-19 pandemic. Most importantly, ruling out of COVID-19 carriers, lockdown measures affecting tissue retrieval processes, and shutdown of elective surgery were the 3 major factors accounting for tissue shortages and surgical volume reductions.
The Effect of COVID-19 on Corneal Donor Volumes and Eye Bank Processes: An Analysis From the Eye Bank of Canada (Ontario Division)
BACKGROUND Experimental knowledge about mesh behavior at the esophageal hiatus is rare, but such information is essential in order to find a safe and effective method of mesh reinforcement. This study aimed to investigate the influence of mesh structure on the biological behavior of polypropylene prostheses placed at the hiatus. MATERIALS AND METHODS Twenty-four pigs in three groups of eight underwent implantation of heavyweight small-porous (HW-SP), heavyweight large-porous (HW-LP), or lightweight large-porous (LW-LP) circular polypropylene mesh at the hiatus. Eight weeks later, the meshes were explanted. Macroscopic analysis was performed evaluating mesh deformation, adhesions, and position relative to the hiatal margin. Histological analysis comprised evaluation of foreign body reaction and tissue integration by mononuclear cell count and immunostaining of Ki-67, collagen type I, and collagen type III. RESULTS No mesh-related complications occurred. Mesh shrinkage was observed within all groups and was the lowest for HW-LP, higher for HW-SP, and highest for LW-LP (13.8% versus 19.5% versus 25.5%; P<.001). The adhesion score was highest for HW-SP, lower for HW-LP, and lowest for LW-LP (11.0 versus 8.0 versus 6.0; P<.001). The collagen type I/III ratio was higher for HW-SP compared with HW-LP and LW-LP (3.1 versus 2.2 versus 1.8; P=.014). CONCLUSIONS Heavyweight polypropylene meshes may be advantageous for application at the hiatus. They provide a solid fixation of the esophagogastric junction by adhesions, which may contribute to a reduction of hernia recurrence. In heavyweight meshes, the large-porous structure is associated with superior form stability, and small-porous meshes are superior with regard to solidity of tissue integration, which may prevent mesh migration.
Influence of weight and structure on biological behavior of polypropylene mesh prostheses placed at the esophageal hiatus.
COVID-19 rapidly emerged as a crippling public health crisis in the last few months, which has presented a series health risk. Understanding of the immune response and biomarker analysis is needed to progress toward understanding disease pathology and developing improved treatment options. The goal of this study is to identify pathogenic factors that are linked to disease severity and patient characteristics. Patients with COVID-19 who were hospitalized from March 17 to June 5, 2020 were analyzed for clinical features of disease and soluble plasma cytokines in association with disease severity and sex. Data from COVID-19 patients with acute illness were examined along with an age- and gender-matched control cohort. We identified a group of 16 soluble factors that were found to be increased in COVID-19 patients compared to controls, whereas 2 factors were decreased. In addition to inflammatory cytokines, we found significant increases in factors known to mediate vasculitis and vascular remodeling (PDGF-AA, PDGF-AB-BB, soluble CD40L (sCD40L), FGF, and IP10). Four factors such as platelet-derived growth factors, fibroblast growth factor-2, and IFN-?3-inducible protein 10 were strongly associated with severe disease and ICU admission. Th2-related factors (IL-4 and IL-13) were increased with IL-4 and sCD40L present at increased levels in males compared with females. Our analysis revealed networking clusters of cytokines and growth factors, including previously unknown roles of vascular and stromal remodeling, activation of the innate immunity, as well activation of type 2 immune responses in the immunopathogenesis of COVID-19. These data highlight biomarker associations with disease severity and sex in COVID-19 patients.
Cytokine release syndrome in COVID-19: Innate immune, vascular, and platelet pathogenic factors differ in severity of disease and sex
PURPOSE: Delay of routine medical care during the COVID-19 pandemic may have serious consequences for the health and functioning of older adults. The aim of this study was to investigate whether older adults reported cancellation or avoidance of medical care during the first months of the COVID-19 pandemic, and to explore associations with health and socio-demographic characteristics. METHODS: Cross-sectional data of 880 older adults aged 62 years (mean age 73.4 years, 50.3% female) were used from the COVID-19 questionnaire of the Longitudinal Aging Study Amsterdam, a cohort study among community-dwelling older adults in the Netherlands. Cancellation and avoidance of care were assessed by self-report, and covered questions on cancellation of primary care (general practitioner), cancellation of hospital outpatient care, and postponed help-seeking. Respondent characteristics included age, sex, educational level, loneliness, depression, anxiety, frailty, multimorbidity and information on quarantine. RESULTS: 35% of the sample reported cancellations due to the COVID-19 situation, either initiated by the respondent (12%) or by healthcare professionals (29%). Postponed help-seeking was reported by 8% of the sample. Multimorbidity was associated with healthcare-initiated cancellations (primary care OR = 1.92, 95% CI = 1.09C3.50; hospital OR = 1.86, 95% CI = 1.28C2.74) and respondent-initiated hospital outpatient cancellations (OR = 2.02, 95% CI = 1.04C4.12). Depressive symptoms were associated with postponed help-seeking (OR = 1.15, 95% CI = 1.06C1.24). CONCLUSION: About one third of the study sample reported cancellation or avoidance of medical care during the first months of the pandemic, and this was more common among those with multiple chronic conditions. How this impacts outcomes in the long term should be investigated in future research.
Older adults report cancellation or avoidance of medical care during the COVID-19 pandemic: results from the Longitudinal Aging Study Amsterdam
BACKGROUND This quality improvement (QI) project was performed at a single center to determine the incidence of postoperative complications associated with use of cuffed airway devices. An educational program was then completed that involved training our anesthesia providers about complications related to excessive cuff pressure and how to utilize a quantitative cuff pressure measurement device (manometer). The impact of this educational initiative was assessed by comparing the incidence of postoperative complications associated with the use of airway devices before and after the training period. METHODS After approval by our institution's Institutional Review Board, a pre-intervention (baseline) survey was obtained from 259 adult patients after having undergone surgery with general anesthesia with the use of an endotracheal tube (ETT) or laryngeal mask airway (LMA). Survey responses were used to determine the baseline incidence of sore throat, hoarseness, and dysphagia. Once these results were obtained, education was provided to the anesthesia department members addressing the complications associated with excessive cuff pressures, appropriate cuff pressures based on manufacturer recommendations, and instructions on the use of a quantitative monitor to determine cuff pressure (manometry). Clinical care was then changed by requiring intraoperative cuff pressure monitoring throughout our institution for all surgical patients. After this educational period, 299 patients completed the same survey describing postoperative airway complications. RESULTS The use of manometry reduced the incidence of moderate-to-severe postoperative sore throat in the pre- vs. post-intervention groups (35 patients vs 31 patients, p = 0.045), moderate to severe hoarseness (30 patients vs 13, patients p = 0.0001), and moderate-to-severe dysphagia (13 patients vs 5 patients, p = 0.03). CONCLUSION Caring for patients in the perioperative setting frequently entails placement of an airway device. This procedure is associated with several potential complications, including sore throat, coughing, and vocal cord damage. Our quality improvement initiative has shown that intraoperative management of intra-cuff pressure based on manometry is feasible to implement in clinical practice and can reduce postoperative airway complications.
Detrimental Effects of Filling Laryngotracheal Airways To Excessive Pressure (DEFLATE-P): a quality improvement initiative.
Background In March and April 2020, public health authorities in the United States acted to mitigate transmission of and hospitalizations from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). These actions were not coordinated at the national level, which raises the question of what might have happened if they were. It also creates an opportunity to use spatial and temporal variation to measure their effect with greater accuracy. Methods We combine publicly available data sources on the timing of stay-at-home orders and daily confirmed COVID-19 cases at the county level in the United States (N = 132,048). We then derive from the classic SIR model a two-way fixed-effects model and apply it to the data with controls for unmeasured differences between counties and over time. This enables us to estimate the effect of stay-at-home orders while accounting for local variation in factors like health systems and demographics, and temporal variation in national mitigation actions, access to tests, or exposure to media reports that could influence the course of the disease. Findings Mean county-level daily growth in COVID-19 infections peaked at 17.2% just before stay-at-home orders were issued. Two way fixed-effects regression estimates suggest that orders were associated with a 3.8 percentage point (95% CI 0.7 to 8.6) reduction in the growth rate after one week and an 8.6 percentage point (3.0 to 14.1) reduction after two weeks. By day 22 the reduction (18.2 percentage points, 12.3 to 24.0) had surpassed the growth at the peak, indicating that growth had turned negative and the number of new daily infections was beginning to decline. A hypothetical national stay-at-home order issued on March 13, 2020 when a national emergency was declared might have reduced cumulative county infections by 62.3%, and might have helped to reverse exponential growth in the disease by April 5. Interpretation Although stay-at-home orders impose great costs to society, delayed responses and piecemeal application of these orders generate similar costs without obtaining the full potential benefits suggested by this analysis. The results here suggest that a coordinated nationwide stay-at-home order may have reduced by hundreds of thousands the current number of infections and by thousands the total number of deaths from COVID-19. Future efforts in the United States and elsewhere to control pandemics should coordinate stay-at-home orders at the national level, especially for diseases for which local spread has already occurred and testing availability is delayed. Since stay-at-home orders reduce infection growth rates, early implementation when infection counts are still low would be most beneficial.
The Effect of Stay-at-Home Orders on COVID-19 Infections in the United States
The purpose of the study is to explore how international faculty at Japanese universities view their integration. An exploratory study of semi-structural interviews with 40 full-time international faculty hired in Japanese universities with various backgrounds was conducted. The key findings indicate that international faculty perceived their integration as a beneficial longstanding two-way process of acquiring equality, developing engagement, and forming a feeling of attachment towards Japan. Meanwhile, their actual practices towards their integration appear to be diverse, which can be summarized into three broad categories, namely, preventive, occasional, and promotional. The study suggests a disjunction between international facultys attitudes and their actual practices towards their integration, which is influenced by the overall host environment from a macro perspective, work role from a meso perspective, and personal intention, origin of country, and previous experience in Japan from a micro perspective. Theoretical and practical implications drawn from the key findings are provided to not only better understand the integration of international faculty at Japanese universities, but also to better serve and support them in practice.
How do international faculty at Japanese universities view their integration?
BACKGROUND: Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour\derived and host\derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities. METHODS: Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia\inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well\established mouse models of CCx and in different cohorts of weight\stable and weight\losing cancer patients with different tumour entities. Genetic PLA2G7 knock\down in tumours and pharmacological treatment using the well\studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour\bearing mice. RESULTS: High expression and secretion of PLA2G7 were hallmarks of cachexia\inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock\down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx. CONCLUSIONS: Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre\cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.
Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy
Respiratory RNA viruses are responsible for recurrent acute respiratory illnesses that still represent a major medical need. Previously we developed a large variety of benzimidazole derivatives able to inhibit these viruses. Herein, two series of (thio)semicarbazone- and hydrazone-based benzimidazoles have been explored, by derivatizing 5-acetyl benzimidazoles previously reported by us, thereby evaluating the influence of the modification on the antiviral activity. Compounds 6, 8, 16 and 17, bearing the 5-(thio)semicarbazone and 5-hydrazone functionalities in combination with the 2-benzyl ring on the benzimidazole core structure, acted as dual inhibitors of influenza A virus and human coronavirus. For respiratory syncytial virus (RSV), activity is limited to the 5-thiosemicarbazone (25) and 5-hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. These molecules proved to be the most effective antiviral agents, able to reach the potency profile of the licensed drug ribavirin. The molecular docking analysis explained the SAR of these compounds around their binding mode to the target RSV F protein, revealing the key contacts for further assessment. The herein-investigated benzimidazole-based derivatives may represent valuable hit compounds, deserving subsequent structural improvements towards more efficient antiviral agents for the treatment of pathologies caused by these human respiratory viruses.
Synthesis and Biological Evaluation of Novel (thio)semicarbazone-Based Benzimidazoles as Antiviral Agents against Human Respiratory Viruses
BACKGROUND Strategies to minimize the risk of transmission and acquisition of COVID-19 infection in patients with ESKD receiving in-center hemodialysis have been rapidly implemented across the globe. Despite these interventions, confirmed COVID-19 infection rates have been high in the United Kingdom. Prevalence of asymptomatic disease in an adult hemodialysis population has not been reported. Also, to our knowledge, the development of humoral response to SARS-CoV-2 has not been previously reported in this population. Although serologic testing does not provide information on the infectivity of patients, seroprevalence studies may enable investigation of exposure within dialysis units and hence, assessment of current screening strategies. METHODS To investigate the seroprevalence of SARS-CoV-2 antibodies in a hemodialysis population, we used the Abbott IgG assay with the Architect system to test serum samples from 356 patients receiving in-center hemodialysis for SARS-CoV-2 antibodies. RESULTS Of 356 patients, 121 had been symptomatic when screened before a dialysis session and received an RT-PCR test; 79 (22.2% of the total study population) tested positive for COVID-19. Serologic testing of all 356 patients found 129 (36.2%) who tested positive for SARS-CoV-2 antibodies. Only two patients with PCR-confirmed infection did not seroconvert. Of the 129 patients with SARS-CoV-2 antibodies, 52 (40.3%) had asymptomatic disease or undetected disease by PCR testing alone. CONCLUSIONS We found a high seroprevalence of SARS-CoV-2 antibodies in patients receiving in-center hemodialysis. Serologic evidence of previous infection in asymptomatic or PCR-negative patients suggests that current diagnostic screening strategies may be limited in their ability to detect acute infection.
High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening.
This article explores our experiences on a Wellcome Trust-funded project on women's experiences of 'everyday health' in Britain between the 1960s and the 1990s. We explore issues around researching 'everyday health', including the generation and interpretation of source materials, and the role of empathy and emotion in interactions with different audiences as we share these materials in public engagement activities. We discuss three case studies of engagement activities to draw out potential uses of source materials and the responses of different audiences to these materials, and reflect on what we have learnt since embarking on these public engagement activities. We took into our interactions with different audiences the belief that fully historicised understandings of 'health' enrich individual lives and create new capacities for meaningful action now. The public engagement activities we carried out reinforced this belief, but also caused us to question some of our assumptions. In particular, an activity with trainee healthcare professionals designed to demonstrate how active and empathetic listening can prevent the unintentional infliction of harm in healthcare settings achieved this end-but did so in a way that was itself unintentionally insensitive to the pressures healthcare professionals face. Medical humanities can help to contextualise, nuance and improve healthcare practice-but only through active listening and dialogue across medicine and the humanities. We conclude by considering how these activities, which currently rely on the interpersonal relations of the team with audiences, might be adapted and preserved in digital form beyond the span of the project.
Women's voices, emotion and empathy: engaging different publics with 'everyday' health histories.
Introduction: Outbreaks of infectious diseases trigger an increase in scientific research and output. Early in outbreaks, evidence is scarce, but it accumulates rapidly. We are continuously facing new disease outbreaks, including the new coronavirus (SARS-nCoV-2) in December 2019.The objective of this study was to describe the accumulation of evidence during the 2013-2016 Zika virus (ZIKV) outbreak in the Pacific and the Americas related to aetiological causal questions about congenital abnormalities and Guillain-Barre syndrome. Methods: We hypothesised that the temporal sequence would follow a pre-specified order, according to study design. We assessed 1) how long it takes before findings from a specific study design appear, 2) how publication of preprints could reduce the time to publication and 3) how time to publication evolves over time. Results: We included 346 publications published between March 6, 2014 and January 1, 2019. In the 2013-2016 ZIKV outbreak, case reports, case series and basic research studies were published first. Case-control and cohort studies appeared between 400-700 days after ZIKV was first detected in the region of the study origin. Delay due to the publication process were lowest at the beginning of the outbreak. Only 4.6% of the publications was available as preprints. Discussion: The accumulation of evidence over time in new causal problems generally followed a hierarchy. Preprints reduced the delay to initial publication. Our methods can be applied to new emerging infectious diseases.
Emergence of evidence during disease outbreaks: lessons learnt from the Zika virus outbreak