BACKGROUND: Direct-acting antivirals can cure hepatitis C virus (HCV). Persons with HCV/HIV and living with substance use are disadvantaged in benefiting from advances in HCV treatment. METHODS: In this randomized controlled trial, participants with HCV/HIV were randomized between February 2016 and January 2017 to either care facilitation or control. Twelve-month follow-up assessments were completed in January 2018. Care facilitation group participants received motivation and strengths-based case management addressing retrieval of HCV viral load results, engagement in HCV/HIV care, and medication adherence. Control group participants received referral to HCV evaluation and an offer of assistance in making care appointments. Primary outcome was number of steps achieved along a series of 8 clinical steps (eg, receiving HCV results, initiating treatment, sustained virologic response [SVR]) of the HCV/HIV care continuum over 12 months postrandomization. RESULTS: Three hundred eighty-one individuals were screened and 113 randomized. Median age was 51 years; 58.4% of participants were male and 72.6% were Black/African American. Median HIV-1 viral load was 27 209 copies/mL, with 69% having a detectable viral load. Mean number of steps completed was statistically significantly higher in the intervention group vs controls (2.44 vs 1.68 steps; (2) [1] = 7.36, P = .0067). Men in the intervention group completed a statistically significantly higher number of steps than controls. Eleven participants achieved SVR with no difference by treatment group. CONCLUSIONS: The care facilitation intervention increased progress along the HCV/HIV care continuum, as observed for men and not women. Study findings also highlight continued challenges to achieve individual-patient SVR and population-level HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02641158.

The onset of COVID-19 has escalated healthcare workers psychological distress. Multiple factors, including prolonged exposure to COVID-19 patients, irregular working hours, and workload, have substantially contributed to stress and burnout among healthcare workers. To explore the impact of COVID-19 on healthcare workers, our study compares the job stress, social support, and intention to leave the job among healthcare workers working in a pandemic (H(P)) and a non-pandemic hospital (H(NP)) in Turkey during the pandemic. The cross-sectional, paper-based survey involved 403 healthcare workers including physicians, registered nurses, health technicians, and auxiliary staff across two hospitals from 1 September 2020 to 31 November 2020. The findings indicate a significant impact of Job stress on Intent to leave job among participants in the H(P). We noted that intent to leave and job stress were significantly higher among the H(P) healthcare workers than those working in the H(NP,) respectively. However, workers social support was significantly lower in the H(P). Healthcare workers, during COVID-19, face several hurdles such as job stress, reduced social support, and excessive workload, all of which are potential factors influencing a care providers intent to leave the job.

The aim of this prospective study was to determine prevalence and potential risk factors of feline coronavirus (FCoV) shedding. Four consecutive fecal samples of 179 cats from 37 German breeding catteries were analyzed for FCoV ribonucleic acid (RNA) by real-time reverse transcriptase polymerase chain reaction (RT-qPCR). Prevalence of shedding was calculated using different numbers of fecal samples per cat (1C4) and different sampling intervals (5C28 days). Information on potential risk factors for FCoV shedding was obtained by a questionnaire. Risk factor analysis was performed using a generalized linear mixed model (GLMM). Most cats (137/179, 76.5%, 95% confidence interval (CI) 69.8C82.2) shed FCoV at least at once. None of the tested 37 catteries was free of FCoV. Prevalence calculated including all four (76.5%, 95% CI 69.8C82.2) or the last three (73.7%, 95% CI 66.8C79.7) samples per cat was significantly higher than the prevalence calculated with only the last sample (61.5%, 95% CI 54.2C68.3; p = 0.0029 and 0.0175, respectively). Young age was significantly associated with FCoV shedding while the other factors were not. For identification of FCoV shedders in multi-cat households, at least three fecal samples per cat should be analyzed. Young age is the most important risk factor for FCoV shedding.

BACKGROUND: Rapid and simple serological assays for characterizing antibody responses are important in the current COVID-19 pandemic caused by SARS-CoV-2. Multiplex immunoblot (IB) assays termed COVID-19 IB assays were developed for detecting IgG and IgM antibodies to SARS-CoV-2 virus proteins in COVID-19 patients. METHODS: Recombinant nucleocapsid protein and the S1, S2 and receptor binding domain (RBD) of the spike protein of SARS-CoV-2 were used as target antigens in the COVID-19 IBs. Specificity of the IB assay was established with 231 sera from persons with allergy, unrelated viral infections, autoimmune conditions and suspected tick-borne diseases, and 32 goat antisera to human influenza proteins. IgG and IgM COVID-19 IBs assays were performed on 84 sera obtained at different times after a positive RT-qPCR test from 37 COVID-19 patients with mild symptoms. RESULTS: Criteria for determining overall IgG and IgM antibody positivity using the four SARS-CoV-2 proteins were developed by optimizing specificity and sensitivity in the COVID-19 IgG and IgM IB assays. The estimated sensitivities and specificities of the COVID-19 IgG and IgM IBs for IgG and IgM antibodies individually or for either IgG or IgM antibodies meet the US recommendations for laboratory serological diagnostic tests. The proportion of IgM-positive sera from the COVID-19 patients following an RT-qPCR positive test was maximal at 83% before 10 days and decreased to 0% after 100 days, while the proportions of IgG-positive sera tended to plateau between days 11 and 65 at 78C100% and fall to 44% after 100 days. Detection of either IgG or IgM antibodies was better than IgG or IgM alone for assessing seroconversion in COVID-19. Both IgG and IgM antibodies detected RBD less frequently than S1, S2 and N proteins. CONCLUSIONS: The multiplex COVID-19 IB assays offer many advantages for simultaneously evaluating antibody responses to different SARS-CoV-2 proteins in COVID-19 patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06031-9.

Lethality of Covid-19 during the 2020 pandemic, currently in the exponentially-accelerating phase in most countries, is critically driven by disruption of the alveolo-capillary barrier of the lung, leading to lung edema as a direct consequence of SARS-CoV-2 infection. We argue for inhibition of the TRPV4 calcium-permeable ion channel as a strategy to address this issue, based on the rationale that TRPV4 inhibition is protective in various preclinical models of lung edema, and that TRPV4 hyperactivation potently damages the alveolo-capillary barrier, with lethal outcome. We believe that TRPV4 inhibition has a powerful prospect at protecting this vital barrier in Covid-19 patients, even to rescue a damaged barrier. A clinical trial using a selective TRPV4 inhibitor demonstrated a benign safety profile in healthy volunteers and in patients suffering from cardiogenic lung edema. We argue for expeditious clinical testing of this inhibitor in Covid-19 patients with respiratory malfunction and at risk for lung edema. We note that among the currently pursued therapeutic strategies against Covid-19, none is designed to directly protect the alveolo-capillary barrier. Successful protection of the alveolo-capillary barrier will not only reduce Covid-19 lethality but will pre-empt a catastrophic scenario in healthcare with insufficient capacity to provide ventilator-assisted respiration.

Weather and climate exist on a massive scale: over the last 650,000 years, only seven glacial cycles have occurred. The end of the last ice age 12,000 years ago marked the beginning of modern civilization - since then, an estimated 400 generations have passed. Yet it is only since the 1950s that greenhouse gas concentrations and global surface, atmospheric, and ocean temperatures have climbed to their highest levels in millennia, destabilizing climate systems and causing extreme weather events.

Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat's safety, make it a likely candidate drug to treat COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the COVID-19 infectious disease that spreads via the respiratory route and has reached a drastic level of a global pandemic. Symptoms of COVID-19 may vary from mild (fever, dry cough, shortness of breath) to severe pneumonia-like respiratory symptoms as exacerbation of disease occurs. Unlike SARS-CoV, the SARS-CoV-2 has a higher binding affinity to ACE-2 receptors which signify its higher transmission rate from person to person. Even though ACE-2 is significant in the renin-angiotensin-aldosterone system (RAAS) regulation that exhibits protection to various organs, they play a significant role in COVID-19 disease pathogenesis. Viral interferences with the ACE-2 peptidase activity are found in SARS-CoV-2 infected patients leading to pro-inflammatory responses, hypertension and multi-organ damage. Angiotensin-converting enzyme-2 is constrained to a variety of organ systems but surface ACE-2 receptors on lung epithelia are largely affected, that lead to pathological alterations in lung histology which may progress to respiratory failure. The viral tropism mainly occurs by the attachment to the angiotensin-converting enzymes-2 receptors in the host cell, thus drugs targeting ACE-2 expressions may arise as the future therapeutic strategy to combat COVID-19 infections.The innovative approach of repurposing of drugs has shown temporary effectiveness to the rising pandemic. This article mainly focuses on the prominence of ACE-2 receptors which are expressed during the COVID infections and repurposing strategy of available drug therapies.

The Problems of Genocide points to a displace site of globalism, namely globalised mass murders. The book suggests two parallel stories, namely the unfolding of the theme of mass murders in global politics in the twentieth century and the ways race has become integrated with the phenomenon of modern liberal nations. The question of mass murders as a problem for global governance became acute only when mass murder created a crisis or took place in the context of a crisis. The book presents a detailed historical account of the context in which genocide emerges as a crucial legal concept to account for the large scale killings of populations in our time. Yet, as the book shows, the concept has remained highly problematic owing to the deeply hierarchised notion of mass murders.

The coronavirus disease 2019 (COVID-19) outbreak that began in Wuhan, Hubei Province, China in late 2019 has spread globally within a few months. The Director General of the World Health Organization (WHO) declared the COVID-19 outbreak to be a public health emergency of international concern (PHEIC) after the second meeting of the IHR (2005) Emergency Committee on 30 January 2020. On 12 March 2020, the outbreak of COVID-19 was characterized as a pandemic.

BACKGROUND Severe coronavirus disease 2019 (COVID-19) may lead to the cytokine storm syndrome which may cause acute respiratory failure syndrome and death. Our aim was to investigate the therapeutic effects of infliximab, intravenous gammaglobulin (IVIg) or combination therapy in patients with severe COVID-19 disease admitted to the intensive care unit (ICU). METHODS In this observational research, we studied 104 intubated adult patients with severe COVID-19 infection (based on clinical symptoms, and radiographic or CT scan parameters) who were admitted to the ICU of a multispecialty hospital during March 2020 in Tehran, Iran. All cases received standard treatment regimens as local protocol (Oseltamivir + hydroxychloroquine + lopinavir/ritonavir or sofosbuvir or atazanavir ribavirin). The cases were grouped as controls (n = 43), infliximab (n = 27), IVIg (n = 23) and combination (n = 11). RESULTS There was no significant difference between controls and treatment groups in terms of underlying diseases or the number of underlying diseases. The mean age (SD) of cases was 72.42 (16.06) in the control group, 64.52 (12.965) in IVIg, 63.40 (17.57) in infliximab and 64.00 (11.679) in combination therapy; (P = 0.047, 0.031 and 0.11, respectively). Also, 37% in the infliximab group, 26.1% in IVIg, 45.5% in combination therapy, and 62.8% in the control group expired (all P < 0.05). Hazard ratios were 0.31 in IVIg (95% CI: 0.12-0.76, P = 0.01), 0.30 in infliximab (95% CI: 0.13-0.67, P = 0.004), 0.39 in combination therapy (95% CI: 0.12-1.09, P = 0.071). CONCLUSION According to the findings of this study, it seems that infliximab and IVIg, alone or together, in patients with severe COVID-19 disease can be considered an effective treatment.

Swedens strategy to manage the spread of Covid-19 has not included any form of lockdown, in contrast to the approaches adopted by most other countries Instead, the strategy has been largely based on strong recommendations for society Even though Sweden has not had any form of lockdown, the Covid-19 pandemic has during a relatively short period of time brought changes for society, significantly disrupting everyday life The pandemic poses both challenges and opportunities for sustainable future transport, not least public transport provision, supply and use The purpose of this study is to investigate how changes for society have translated into changes for mobility as an element of everyday life during the early stages of a pandemic This study draws on a map-based online survey (public participatory GIS) which was purposefully designed to allow people to contribute with their experiences in order to capture how the current situation has affected several different facets of peoples everyday life Results suggest that effects on mobility, such as the possibility to telework, affect different groups differently and may exacerbate existing differences in terms of gender, geography and mobility In order to mitigate negative effects, transport policy needs to be tailored in order to take these heterogeneities into account Both spatio-temporal adjustment and modal adjustment were dominant themes for most activities, although the dominance of these themes varied among the activities Our findings give an indication of both the short and long-term impacts on everyday mobility in the Swedish context, for groups of inhabitants in the city of Malm? Through deepening our understanding of the processes at play, we suggest eight possible policy responses that can be carefully tailored, both in the interim and into the future

Owing to the pandemic caused by the coronavirus disease of 2019 (COVID-19), several universities have closed their campuses for preventing the spread of infection. Consequently, the university classes are being held over the Internet, and students attend these classes from their homes. While the COVID-19 pandemic is expected to be prolonged, the online-centric lifestyle has raised concerns about secondary health issues caused by reduced physical activity (PA). However, the actual status of PA among university students has not yet been examined in Japan. Hence, in this study, we collected daily PA data (including the data corresponding to the number of steps taken and the data associated with six types of activities) by employing smartphones and thereby analyzed the changes in the PA of university students. The PA data were collected over a period of ten weeks from 305 first-year university students who were attending a mandatory class of physical education at the university. The obtained results indicate that compared to the average number of steps taken before the COVID-19 pandemic (6474.87 steps), the average number of steps taken after the COVID-19 pandemic (3522.5 steps) has decreased by 45.6%. Furthermore, the decrease in commuting time (7 AM to 10 AM), classroom time, and extracurricular activity time (11 AM to 12 AM) has led to a decrease in PA on weekdays owing to reduced unplanned exercise opportunities and has caused an increase in the duration of being in the stationary state in the course of daily life.

AIMS: This study aims to define the epidemiology of trauma presenting to a single centre providing all orthopaedic trauma care for a population of 900,000 over the first 40 days of the COVID-19 pandemic compared to that presenting over the same period one year earlier. The secondary aim was to compare this with population mobility data obtained from Google. METHODS: A cross-sectional study of consecutive adult (> 13 years) patients with musculoskeletal trauma referred as either in-patients or out-patients over a 40-day period beginning on 5 March 2020, the date of the first reported UK COVID-19 death, was performed. This time period encompassed social distancing measures. This group was compared to a group of patients referred over the same calendar period in 2019 and to publicly available mobility data from Google. RESULTS: Orthopaedic trauma referrals reduced by 42% (1,056 compared to 1,820) during the study period, and by 58% (405 compared to 967) following national lockdown. Outpatient referrals reduced by 44%, and inpatient referrals by 36%, and the number of surgeries performed by 36%. The regional incidence of traumatic injury fell from 5.07 (95% confidence interval (CI) 4.79 to 5.35) to 2.94 (95% CI 2.52 to 3.32) per 100,000 population per day. Significant reductions were seen in injuries related to sports and alcohol consumption. No admissions occurred relating to major trauma (Injury Severity Score > 16) or violence against the person. Changes in population mobility and trauma volume from baseline correlated significantly (Pearsons correlation 0.749, 95% CI 0.58 to 0.85, p < 0.001). However, admissions related to fragility fractures remained unchanged compared to the 2019 baseline. CONCLUSION: The profound changes in social behaviour and mobility during the early stages of the COVID-19 pandemic have directly correlated with a significant decrease in orthopaedic trauma referrals, but fragility fractures remained unaffected and provision for these patients should be maintained. Cite this article: Bone Joint Open 2020;1-6:182C189.

AbstractInzwischen k?nnen wir die zellul?ren Prozesse in lebenden Zellen verfolgen, und zwar mit subzellul?rer Fluoreszenzmikroskopie mit Aufl?sung im Nanometerbereich Ob Ribosomen die richtigen Proteine herstellen oder eine Leseschw?che haben, l?sst sich durch Ribosomenprofiling untersuchen Und: Bisher haben intrinsische Dynamik und Heterogenit?t erschwert, die dreidimensionale Struktur von Multiproteinkomplexen zu bestimmen Kryoelektronenmikroskopie erlaubt es nun, diese schwer greifbaren Maschinerien mit h?chster Aufl?sung abzubilden

Persistent infection is a situation of metastability in which the pathogen and the host coexist. A common outcome for viral infections, persistence is a widespread phenomenon through all kingdoms. With a clear benefit for the virus and/or the host at the population level, persistent infections act as modulators of the ecosystem. The origin of persistence being long time elusive, here we explore the concept of 'endogenization' of viral sequences with concomitant activation of the host immune pathways, as a main way to establish and maintain viral persistent infections. Current concepts on viral persistence mechanisms and biological role are discussed.

For years, the conventional imaging modalities are generally used in dental practice routine. They provide precious information about dentomaxillofacial region; they also have some limitations such as superimpositions, magnifications, distortions, and low-image quality. Because of these limitations, some pathologies, calcifications, and anatomical variations may be missed. Any findings on a radiographic image which are not related to the research areas of interest could be a description of incidental findings. Calcifications are one of these incidental findings. They are asymptomatic and also common in TMJ images. Although most of the calcifications require no treatment, correct identification will reduce further diagnostic assessments. Incidental findings on TMJ images were rare, while examining images for temporomandibular disorders and associated issues, it is important not only to examine the TMJ structures but also to look at the nearby anatomical features to check for evidence of incidental findings pathologies that may have mimicked signs and symptoms of TMJ disorders.

Background: There is increased interest in early intervention and prevention of mental health difficulties during adolescence; thus, we are seeing increased efforts to optimize well-being during this epoch. Positive emotional experiences are a central component of overall well-being. However, research exploring what adolescents perceive to be the cause(s) of their emotional difficulties is lacking. Improving understanding of this issue within non-clinical adolescent groups may provide useful insight into how to develop strategies to support young people as they navigate emotional difficulties. Objectives: The aim of this research was to explore if meaningful categories of perceived cause(s) for emotional distress exist for non-clinical adolescent groups. Methods: The data for this study were drawn from interviews across 6 sites in England conducted as part of the 5-year national evaluation of the HeadStart Learning Programme. The sample comprised of 32 young people aged 11C12 years from the first annual wave of qualitative data collection in 2017. Ideal type analysisa qualitative form of person-centered analysiswas used to construct a typology of adolescents perceived cause(s) for emotional distress. Findings: We identified five distinct categories of perceived cause: (1) perceived lack of control; (2) unfair treatment; (3) others, their actions and judgements as the catalyst; (4) concerns for self and others; and, (5) self as cause. Conclusions: Our findings illustrate that distinct categories for perceived cause of emotional distress exist among adolescents considered to be at risk of developing mental health difficulties, which provides a foundation for future necessary work seeking to investigate the possible link between perceived cause for emotional distress and help-seeking behavior among sub-clinical groups.

This study presents numerical simulations of UVC light propagation through seven different filtered face respirators (FFR) to determine their suitability for UV germicidal inactivation (UVGI). UV propagation was modelled using the FullMonte program for two external light illuminations. The optical properties of the dominant three layers were determined using the inverse adding doubling method. The resulting fluence rate volume histograms and the lowest fluence rate recorded in the modelled volume, sometimes in the nW cm-2, provide feedback on a respirator's suitability for UVGI and the required exposure time for a given light source. While UVGI can present an economical approach to extend an FFR's useable lifetime, it requires careful optimization of the illumination setup and selection of appropriate respirators.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been a major public health importance and its specimen needs to be handled safely due to concerns of potential transmissibility to health care workers. Heat inactivation of the sample before nucleic acid isolation might permit safe testing processes. Hence, it is important to assess the effect of heat inactivation on SARS-CoV-2 RT-PCR detection in resource limited settings. METHODS: An experimental study was conducted at Ethiopian Public Health Institute (EPHI) from September 25 to October 15, 2020. A total of 188 Oro-pharyngeal swabs were collected from COVID-19 suspected cases, referred to EPHI for SARS COV-2 testing. One batch of the sample was inactivated at 56 C heat for 30 min, and the other batch was stored at 4 C for a similar period of time. RNA extraction and detection were done by DAAN Gene kit protocols. Abbott m2000 RT-PCR was used for amplification and detection. Data analysis was done by using SPSS version 23.0; Chi-square and Pearson correlation test for qualitative and semi-quantitative analysis were used. p-value < 0.05 was considered as statistically significant. RESULTS: Out of 188 total samples, 119 (63.3%) were positive and 69 (36.7%) were negative in the non-inactivated group. While, 115 (61.2%) of samples were positive and 73 (38.8) were negative in heat inactivated sample batch. Rate of positivity between groups did not have statistically significant difference (p > 0.05). The mean Cycle threshold (Ct) value difference between the two groups of ORF1a/b gene and N gene was 0.042 (95% CI ? 0.247C0.331; t = 0.28; p = 0.774) and 0.38 (95% CI 0.097C0.682; t = 2.638; p = 0.010) respectively. CONCLUSION: Heat inactivation at 56 C for 30 min did not affect the qualitative rRT-PCR detection of SARS-CoV-2. However, the finding showed that there was statistically significant Ct value increment after heat inactivation compared to untreated samples. Therefore, false-negative results for high Ct value (Ct > 35) samples were found to be the challenge of this protocol. Hence alternative inactivation methods should be investigated and further studies should be considered.