COVID-19 has infected more than 10 million people worldwide and it has become one of the biggest challenges in the modern medical history Wearing of face masks, social distancing, effective hand hygiene and the use of appropriate personal protective equipment are important in flattening the curve of the pandemic The role of the surgeons in this battle against COVID-19 include curbing the spread of the disease, to protect and preserve the surgical workforce and to ensure the continuance of essential surgical services We report our experience in dealing with the COVID-19 outbreak in a tertiary surgical centre in the Penang General Hospital in Northern Malaysia

BACKGROUND Xenotropic murine leukemia virus (MLV)-related virus (XMRV) and other related MLVs have been described with chronic fatigue syndrome and certain types of prostate cancer. In addition, prevalence rates as high as 7% have been reported in blood donors, raising the risk of transfusion-related transmission. Several laboratories have utilized microneutralization assays as a surrogate marker for detection of anti-MLV serologic responses--with up to 25% of prostate cancer patients reported to harbor neutralizing antibody responses. STUDY DESIGN AND METHODS We developed a high-throughput microneutralization assay for research studies on blood donors using retroviral vectors pseudotyped with XMRV-specific envelopes. Infection with these pseudotypes was neutralized by sera from both macaques and mice challenged with XMRV, but not preimmune serum. A total of 354 plasma samples from blood donors in the Reno/Tahoe area were screened for neutralization. RESULTS A total of 6.5% of donor samples gave moderate neutralization of XMRV, but not control pseudotypes. However, further testing by Western blot revealed no evidence of antibodies against MLVs in any of these samples. Furthermore, no evidence of infectious virus or viral nucleic acid was observed. CONCLUSION A microneutralization assay was developed for detection of XMRV and can be applied in a high-throughput format for large-scale studies. Although a proportion of blood donors demonstrated the ability to block XMRV envelope-mediated infection, we found no evidence that this inhibition was mediated by specific antibodies elicited by exposure to XMRV or MLV. It is likely that this moderate neutralization is mediated through another, nonspecific mechanism.

Tuberculosis (TB) remains one of the leading causes of death globally. Although abdominal or peritoneal TB is a recognised site for extrapulmonary TB to manifest, the diagnosis is often delayed due to the non-specific nature of the presenting clinical features. We present the diagnostically challenging case of a 32-year-old patient with recurrent episodes of fever and a non-productive cough that was initially treated as community-acquired pneumonia with oral antibiotics. A computed tomography scan of the thorax was unrevealing, aside from a large volume of ascites within the partially imaged upper abdomen. The patient did not report any abdominal symptoms and the abdominal examination was unremarkable. Subsequently, a transvaginal ultrasound, a contrast-enhanced computed tomography scan of the abdomen and pelvis, and magnetic resonance imaging of the abdomen and pelvis confirmed a large volume of ascites in the absence of any definite aetiology. A peritoneal biopsy was required before the diagnosis of peritoneal TB was eventually confirmed. This case highlights the importance of considering peritoneal TB in patients presenting with treatment-resistant chest symptoms and persistent pyrexia of undetermined aetiology, even in the absence of abdominal signs and symptoms.

Delirium, a form of acute brain dysfunction, is very common in the critically ill adult patient population. Although its pathophysiology is poorly understood, multiple factors associated with delirium have been identified, many of which are coincident with critical illness. To date, no drug or non-drug treatments have been shown to improve outcomes in patients with delirium. Clinical trials have provided a limited understanding of the contributions of multiple triggers and processes of intensive care unit (ICU) acquired delirium, making identification of therapies difficult. Delirium is independently associated with poor long term outcomes, including persistent cognitive impairment. A longer duration of delirium is associated with worse long term cognition after adjustment for age, education, pre-existing cognitive function, severity of illness, and exposure to sedatives. Interestingly, differences in prevalence are seen between ICU survivor populations, with survivors of acute respiratory distress syndrome experiencing higher rates of cognitive impairment at early follow-up compared with mixed ICU survivor populations. Although cognitive performance improves over time for some ICU survivors, impairment is persistent in others. Studies have so far been unable to identify patients at higher risk of long term cognitive impairment; this is an active area of scientific investigation.

The outbreak and rapid spread of SARS-CoV-2 virus has led to a dire global pandemic with millions of people infected and ~ 400,000 deaths thus far. Highly accurate detection of antibodies for COVID-19 is an indispensable part of the effort to combat the pandemic1,2. Here we developed two-plex antibody detection against SARS-CoV-2 spike proteins3 (the S1 subunit and receptor binding domain RBD) in human serum and saliva on a near-infrared nano-plasmonic gold (pGOLD) platform4C8. By testing nearly 600 serum samples, pGOLD COVID-19 assay achieved ~ 99.78 % specificity for detecting both IgG and IgM with 100 % sensitivity in sera collected > 14 days post disease symptom onset, with zero cross-reactivity to other diseases. Two-plex correlation analysis revealed higher binding of serum IgM to RBD than to S1. IgG antibody avidity toward multiple antigens were measured, shedding light on antibody maturation in COVID-19 patients and affording a powerful tool for differentiating recent from remote infections and identifying re-infection by SARS-CoV-2. Just as important, due to high analytical sensitivity, the pGOLD COVID-19 assay detected minute amounts of antibodies in human saliva, offering the first non-invasive detection of SARS-CoV-2 antibodies.

The coronavirus outbreak has introduced many challenges for the health-care delivery system, its workers, and health-care recipients. To overcome the challenges coming up during the coronavirus disease-2019 (COVID-19) pandemic, health-care sector was majorly helped by telehealth, e-health, and technologies involved in consultation, diagnosis, and treatment of patients from a distance. However, it has own benefits and barriers, which are discussed in this review. This review has been conducted through searching five databases including PubMed, ResearchGate, Google Scholar, Cochrane, and ScienceDirect. Inclusion criteria included studies clearly defining any use of telehealth services during COVID-19 pandemic and its effects and barriers, written in English language, published from 2019 to till date, and including studies from different countries. Narrative synthesis was undertaken to summarize and report the findings. Ten studies met the inclusion criteria out of the 97 search results. The articles included in our studies showed a significant increase in the uptake of telehealth services during this COVID-19 pandemic. Countries like the U.S.A showed an 80% decline in-person visits among the Canadian population 41% of them wanted virtual visits compared to in-person visits. The patients have reported high satisfaction with telehealth services according to the related studies although have reported hindrances and potential barriers to it like limited access to Internet availability, devices, lack of awareness about technology, high cost for implementation, and legal framework related to policies that includes privacy and confidentiality. Based on the findings of this review study, telehealth has been found as an effective way of health delivery system in these difficult times, but there are certain factors and issues related to its use which need to be looked upon. This narrative review indicates that the use of telemedicine and telehealth services during this COVID-19 pandemic has a plan of much help, as when compared to the barriers, it may produce to reach a large population at their home without putting the lives of health-care workers and the patients themselves at risk.

TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis.

Reports of the novel and more contagious strains of SARS-CoV-2 originating in different countries have further aggravated the pandemic situation. The recent substitutions in spike protein may be critical for the virus to evade the host's immune system and therapeutics that have already been developed. Thus, this study has employed an immunoinformatics pipeline to target the spike protein of this novel strain to construct an immunogenic epitope (CTL, HTL, and B cell) vaccine against the new variant. Our investigation revealed that 12 different epitopes imparted a critical role in immune response induction. This was validated by an exploration of physiochemical properties and experimental feasibility. In silico and host immune simulation confirmed the expression and induction of both primary and secondary immune factors such as IL, cytokines, and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety.

The global spread of COVID-19 is placing unprecedented demands on healthcare services. In this time of crisis, innovative and adaptive methods of practising will be required across all health professions. In order to maximise the use of current available resources, it is vital that existing services are comprehensively reviewed and full use is made of any unrealised potential among healthcare providers. Community pharmacy is one of a number of health professions that has a key role to play in responding to the current pandemic. As the scope of community pharmacy practice varies considerably across countries, it is important to examine ways in which the profession can assist with the public health response to COVID-19 and maintaining the continuity of healthcare services. This article seeks to highlight roles and activities that community pharmacists can undertake to help in relieving pressure on other areas of the health service, such as general practice. This information could help to inform future decisions about the restructuring of existing health services by governments, public health bodies and policy makers in response to public health crises such as COVID-19.

Drawing on autoregressive vector (VAR) model, this paper analyses supply and demand of automobiles and light commercial vehicles in Brazil from January 2012 to February 2020. Then, it points out how the automotive activity in the country responds to shocks of political proposals or unexpected shocks. The results on the short-term forecast suggest that credit, income, price, and tax influence the business cycles of the industry and returns to a stationary trend over a period of five months. Therefore, the analysis suggests that the automotive activity has a capacity for quick recovery in face of an eventual adverse shock, such as COVID-19 outbreak. This convergence time can be shortened by credit and tax reduction policies, as well as the new automation and electrification technologies in the automotive industry.

OBJECTIVES: To explore in-depth the views on Internet-based psychological therapies and their implementation from the perspective of National Health Service (NHS) commissioners and managers. DESIGN: Qualitative interview study. METHOD: Ten NHS commissioners and managers participated in a semi-structured, co-produced interview. Each transcribed interview was double-coded and thematically analysed using The Framework Method. RESULTS: Interviews generated three main themes. (1) Capacity issues across psychological therapy services create barriers to face-to-face therapies, and Internet-based interventions offer a solution. (2) Despite reservations, there is growing acceptance of Internet-based therapies. Different ways of connecting with patients are required, and Internet-based treatments are accessible and empowering treatment options, with guided self-help (GSH) preferred. Internet-based interventions may however exclude some individuals and be a threat to the therapeutic relationship between patient and practitioner. (3) Successful roll-out of Internet-based interventions would be facilitated by a strong empirical- or practice-based evidence, a national coordinated approach and timely training and supervision. Barriers to the roll-out include digital intervention set-up costs and delays due to NHS inflexibility. CONCLUSIONS: The study highlights factors influencing access to Internet-based therapies, important given the rapid evolution of e-therapies, and particularly timely given increasing use of remote therapies due to COVID-19 restrictions. Interviewees were open to Internet-based approaches, particularly GSH interventions, so long as they do not compromise on therapy quality. Interviewees acknowledged implementation may be challenging, and recommendations were offered. PRACTITIONER POINTS: There is a shift in practice and increasingly positive views from NHS staff around remote psychological therapies and different ways of connecting with patients, particularly since the COVID-19 pandemic. There is a strong preference for Internet-based psychological interventions that are guided and that include built-in outcome measures co-produced with service users. There is a need to raise awareness of the growing evidence base for Internet-based psychological therapies, including research examining therapeutic alliance across Internet-based and face-to-face therapies. Challenges implementing Internet-based psychological therapies include therapist resistance to changing working practices in general, and inflexibility of the NHS, and national, coordinated implementation efforts are encouraged.

The wide spread of coronavirus disease 2019 (COVID-19) has declared a global health emergency. As one of the most important targets for antibody and drug developments, Spike RBD-ACE2 interface has received extensive attention. Here, using molecular dynamics simulations, we explicitly evaluated the binding energetic features of the RBD-ACE2 complex of both SARS-CoV and SARS-CoV-2 to find the key residues. Although the overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, the difference in binding affinity is as large as -16.35 kcal/mol. Energy decomposition analyses identified three binding patches in the SARS-CoV-2 RBD and eleven key residues (Phe486, Tyr505, Asn501, Tyr489, Gln493, Leu455 and etc) which are believed to be the main targets for drug development. The dominating forces are from van der Waals attractions and dehydration of these residues. It is also worth mention that we found seven mutational sites (Lys417, Leu455, Ala475, Gly476, Glu484, Gln498 and Val503) on SARS-CoV-2 which unexpectedly weakened the RBD-ACE2 binding. Very interestingly, the most repulsive residue at the RBD-ACE2 interface (E484), is found to be mutated in the latest UK variant, B1.1.7, cause complete virus neutralization escapes from highly neutralizing COVID-19 convalescent plasma. Our present results indicate that at least from the energetic point of view such E484 mutation may have beneficial effects on ACE2 binding. The present study provides a systematical understanding, from the energetic point of view, of the binding features of SARS-CoV-2 RBD with ACE2 acceptor. We hope that the present findings of three binding patches, key attracting residues and unexpected mutational sites can provide insights to the design of SARS-CoV-2 drugs and identification of cross-active antibodies.

Diffuse alveolar hemorrhage (DAH) is a rare syndrome resulting from the accumulation of intra-alveolar red blood cells originating most often from the alveolar capillaries and, less frequently, from precapillary arterioles or postcapillary venules. The causes of DAH can be divided into infectious and noninfectious. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has not been previously identified in humans, and it is responsible for coronavirus disease-19 (COVID-19) infection. Here, we present a case of DAH that is believed to be a consequence of COVID-19 infection in a female patient with no known past medical history. The patient was found to be positive for perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) and anti-glomerular basement membrane antibodies. The patient was diagnosed with ANCA-associated vasculitis with glomerulonephritis and was treated successfully with methylprednisolone 500 mg intravenous (IV) daily for three days, followed by rituximab 375 mg/m(2) IV once weekly for four weeks. The long-term complications of COVID-19 are not entirely known and are still being investigated. The association between COVID-19 infection and DAH is not fully known. However, the inflammatory process of COVID-19 infection may have a role in vasculitis, leading to DAH.

Megalocytivirus is an important viral pathogen to many farmed fishes, including Japanese flounder (Paralichthys olivaceus). In this study, we examined megalocytivirus-induced RNA responses in the spleen of flounder by high-throughput sequencing and integrative analysis of various RNA-seq data. A total of 1327 microRNAs (miRNAs), including 368 novel miRNAs, were identified, among which, 171 (named DEmiRs) exhibited significantly differential expressions during viral infection in a time-dependent manner. For these DEmiRs, 805 differentially expressed target mRNAs (DETmRs) were predicted, whose expressions not only significantly changed after megalocytivirus infection but were also negatively correlated with their paired DEmiRs. Integrative analysis of immune-related DETmRs and their target DEmiRs identified 12 hub DEmiRs, which, together with their corresponding DETmRs, formed an interaction network containing 84 pairs of DEmiR and DETmR. In addition to DETmRs, 19 DEmiRs were also found to regulate six key immune genes (mRNAs) differentially expressed during megalocytivirus infection, and together they formed a network consisting of 21 interactive miRNA-messenger RNA (mRNA) pairs. Further analysis identified 9434 circular RNAs (circRNAs), 169 of which (named DEcircRs) showed time-specific and significantly altered expressions during megalocytivirus infection. Integrated analysis of the DETmR-DEmiR and DEcircR-DEmiR interactions led to the identification of a group of competing endogenous RNAs (ceRNAs) constituted by interacting triplets of circRNA, miRNA, and mRNA involved in antiviral immunity. Together these results indicate that complicated regulatory networks of different types of non-coding RNAs and coding RNAs are involved in megalocytivirus infection.

The capacity for social media to influence the utilization of re-purposed medicines to manage COVID-19, despite limited availability of safety and efficacy data, is a cause for concern within health care systems. This study sought to ascertain links between social media reports and utilization for three re-purposed medicines: hydroxychloroquine (HCQ), ivermectin and colchicine. A combined retrospective analysis of social media posts for these three re-purposed medicines was undertaken, along with utilization and clinical trials data, in South Africa, between January 2020 and June 2021. In total, 77,257 posts were collected across key social media platforms, of which 6884 were relevant. Ivermectin had the highest number of posts (55%) followed by HCQ (44%). The spike in ivermectin use was closely correlated to social media posts. Similarly, regarding chloroquine (as HCQ is not available in South Africa), social media interest was enhanced by local politicians. Sentiment analysis revealed that posts regarding the effectiveness of these repurposed medicines were positive. This was different for colchicine, which contributed only a small number of mentions (1%). Of concern is that the majority of reporters in social media (85%) were unidentifiable. This study provides evidence of social media as a driver of re-purposed medicines. Healthcare professionals have a key role in providing evidence-based advice especially with unidentifiable posts.

The unprecedented outbreak and continuous spread of the COVID-19 virus starting in December 2019 resulted in a strict lockdown and nationwide long-term home isolation, which has possibly led to increased levels of family violence in China. This commentary aims to explore two issues related to the impacts of the COVID-19 pandemic on family violence in China, with intimate partner violence as its most common form. These two issues are whether the COVID-19 pandemic has indeed had a negative impact on family violence and, if so, what its specific influences upon family violence in China have been. This commentary is largely descriptive and based upon previously published literature and public statistical reports from newspaper, government, and criminal justice sources on family violence during the COVID-19 pandemic in China. Despite the lack of relevant and accurate nationwide statistics on family violence in China, multiple reports seem to suggest that family violence has surged during the COVID-19 pandemic. This increase in family violence may be primarily due to the large-scale lockdown that aggravates family conflicts, economic distress and tension caused by the pandemic among family members, and inadequate support for victims of family violence during the pandemic. Family violence has become an important social issue that needs to be dealt properly and swiftly during the ongoing COVID-19 pandemic. Both governmental and non-governmental organizations (NGOs), as well as agencies and service sectors, need to be aware of the needs of family violence victims and provide appropriate and immediate assistance to the victims during the pandemic. A detailed discussion of the policy implications and suggestions for future research are provided at the end of this commentary.

We use novel and comprehensive monthly data on electronic payments, by municipality and sector, together with cash withdrawals, to study the impact of Covid\19 in Portugal. Our difference\in\differences event study identifies a causal decrease of 17 and 40 percentage points on the year\on\year growth rate of overall purchases in March and April 2020. We document a stronger impact of the crisis in more central and more urban municipalities, due to a combination of the sectorial composition effect of the local economy and the sharper confinement behavioral effect in these locations. We discuss the importance of tourism for the results.

Electroporation has a specific application in the delivery of drugs into the cells. In addition, the challenge is to be able to deliver the drugs effectively. The key to the electroporation-based delivery method is regulated induced transmembrane voltage (ITMV). Recently, with the advent of COVID-19, there has been an increase in clinical trials on the delivery of DNA plasmids by electroporation. As a result, the substantial number of laboratory experiments are not feasible, thereby increasing the dependency on simulation-based research. Simulations of delivery of extracellular material into the cell depend upon molecular transport modeling in an electroporated cell. In this paper, molecular transport through a single nanopore is being studied theoretically. The closed-form expression of molecular transport is used in COMSOL Multiphysics simulation to obtain extracellular concentration variation as a function of time. Sinusoidal pulses with the varying magnitude of electric field (8kV/cm and 10 kV/cm) and time duration were used to understand pulse parameters' effect on molecular transport. The simulation results match the empirical result from the literature hence validate the simulation study. ? 2021 by the authors.

The novel COVID-19 is a worldwide transmitted pandemic and has received global attention. Since there is no effective medication yet, to minimize and control the transmission of the COVID-19, non-pharmaceutical interventions (NPIs) are followed globally. However, for the implementation of needful NPIs through effective management strategies and planning, space-time-based information on the nature, magnitude, pattern of transmission, hotspots, the potential risk factors, vulnerability, and risk level of the pandemic are important. Hence, this study was an attempt to in-depth assess and analyze the COVID-19 outbreak and transmission dynamics through space and time in Bangladesh using 154 day real-time epidemiological data series. District-level data were analyzed for the geospatial analysis and modelling using GIS. Getis-Ord Gi* statistics was applied for the hotspot analysis, and on the other hand, the analytical hierarchy process-based weighted sum method (AHP-WSM) was used for the modelling of vulnerability zoning of COVID-19. In Bangladesh, the status of the pandemic COVID-19 still is in exposure level. Disease transmitted at a high rate (20.37%), and doubling time of the cases were 11 days (latest week of the study period). The fatality rate was comparatively low (1.3%), and the recovery rate was about 57.50%. Geospatial analysis exhibits the disease propagates from the central parts, and Dhaka was the most exposed district followed by Chattogram, Narayanganj, Cumilla, and Bogra. A single strong clustering pattern in the central part, which spread out mainly to the south-eastern part, was identified as a prime hotspot in both the cases and deaths distributions. Additionally, potential linkages between the transmission of disease and the selected factors that gear up the spreading of the disease were identified. The central, eastern, and south-eastern parts were recognized as high vulnerable zone, and conversely, the western, south-western, north-western, and north-eastern parts as medium vulnerable zone. The vulnerable zoning exercise made it possible to identify vulnerable areas with the different magnitude that require urgent intervention through proper management and action plan, and accordingly, comprehensive management strategies were anticipated. Thus, this study will be a useful guide towards understanding the space-time-based investigations and vulnerable area delineation of the COVID-19 and assist to formulate an effective management action plan to reduce and control the disease propagation and impacts. By appropriate adjustment of some factors with local relevance, COVID-19 vulnerability zoning derived here can be applied to other regions, and generally can be used for any other infectious disease. This method was applied at a regional scale, but the availability of larger scale data of the determining factors could be applied in small areas too, and accordingly, management strategies can be formulated.

We have inserted heterologous genetic material into the nonessential gene 4 of the coronavirus mouse hepatitis virus (MHV) in order to test the applicability of targeted RNA recombination for site-directed mutagenesis of the MHV genome upstream of the nucleocapsid (N) gene and to develop further genetic tools for site-directed mutagenesis of structural genes other than N. Initially, a 19-nucleotide tag was inserted into the start of gene 4a of MHV strain A59 with the N gene deletion mutant Alb4 as the recipient virus. In further work, the entire gene for the green fluorescent protein (GFP) was inserted in place of gene 4, creating the currently largest known RNA virus. The expression of GFP was demonstrated by Western blot analysis of infected cell lysates; however, the level of GFP expression was not sufficient to allow detection of fluorescence of viral plaques. Northern blot analysis of transcripts of GFP recombinants showed the expected alteration of the pattern of the nested MHV subgenomic mRNAs. Surprisingly, though, GFP recombinants also produced an RNA species that was the same size as wild-type mRNA4. Analysis of the 5' end of this species revealed that it was actually a collection of mRNAs originating from 10 different genomic fusion sites, none possessing a canonical intergenic sequence. The finding of these aberrant mRNAs suggests that long-range RNA or the ribonucleoprotein structure of the MHV genome can sometimes be the sole determinant of the site of initiation of transcription.