title: The unique architecture of Bunyamwera virus factories around the Golgi complex

text: Viral factories are novel structures built by viruses in infected cells. During their construction organelles are recruited and build a large scaffold for viral replication and morphogenesis. We have studied how a bunyavirus uses the Golgi to build the factory. With the help of confocal and 3D ultrastructural imaging together with molecular mapping in situ and in vitro we have characterized a tubular structure that harbours the viral replication complexes in a globular domain. Numerous ribonucleoproteins were released from purified tubes disrupted in vitro. Actin and myosin I were identified by peptide mass fingerprinting in isolated tubes while actin and the viral NSm non‐structural protein were detected in the tubes' internal proteinaceous scaffold by immunogold labelling. Studies with NSm deletion mutants and drugs affecting actin showed that both NSm and actin are key factors for tube and virus assembly in Golgi. Three‐dimensional reconstructions based on oriented serial sections of infected cells showed that tubes anchor cell organelles to Golgi stacks and make contacts with intracellular viruses. We propose that this new structure, unique among enveloped viruses, assembles in association with the most stable component of Golgi stacks, the actin‐containing matrix scaffold, connecting viral replication and morphogenesis inside viral factories.


title: Human coronavirus alone or in co-infection with rhinovirus C is a risk factor for severe respiratory disease and admission to the pediatric intensive care unit: A one-year study in Southeast Brazil

text: OBJECTIVE: We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. DESIGN: Prospective observational cohort study. SETTING: A tertiary-care university hospital in Brazil. PATIENTS: Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal aspirates were collected from patients from June 1(st), 2008 to May 31(st), 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15–4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23–4.58) was independently associated with PICU admission. CONCLUSIONS: The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.


title: Current and emergent strategies for disinfection of hospital environments

text: A significant number of hospital-acquired infections occur due to inefficient disinfection of hospital surfaces, instruments and rooms. The emergence and wide spread of multiresistant forms of several microorganisms has led to a situation where few compounds are able to inhibit or kill the infectious agents. Several strategies to disinfect both clinical equipment and the environment are available, often involving the use of antimicrobial chemicals. More recently, investigations into gas plasma, antimicrobial surfaces and vapour systems have gained interest as promising alternatives to conventional disinfectants. This review provides updated information on the current and emergent disinfection strategies for clinical environments.


title: Mannose-Binding Lectin Deficiency and Respiratory Tract Infection

text: Mannose-binding lectin (MBL) is an innate immune system pattern recognition protein that kills a wide range of pathogenic microbes through complement activation. A substantial proportion of all human populations studied to date have MBL deficiency due to MBL2 polymorphisms, which potentially increases susceptibility to infectious disease. MBL binds numerous respiratory pathogens but the capsule of Streptococcus pneumoniae abrogates its efficient binding. Clinical studies in humans have shown that MBL deficiency appears to predispose to severe respiratory tract infection. A recent meta-analysis shows that MBL deficiency was associated with death in patients with pneumococcal infection after adjusting for bacteraemia and comorbidities. Human clinical studies have also shown associations between MBL deficiency and various less common respiratory infections. Intracellular infections like tuberculosis may be less common with MBL deficiency because of reduced opsonophagocytosis. Lung secretions contain small amounts of MBL that are potentially sufficient to activate complement, but their measurement is confounded by dilution inherent in collection techniques. Therefore, if this protein does play a role in pulmonary immunity it is presumably through prevention of haematogenous dissemination of respiratory pathogens while adding to mucosal defences. Ficolins are collectins that are structurally and functionally related to MBL and are either present in serum or expressed in tissues including the lung. Limited variation in serum levels of L- and H-ficolin result from the presence of FCN2 and FCN3 polymorphisms. Initial studies on the impact of FCN2 polymorphisms or low L-ficolin levels do not seem to show major associations with respiratory infection. MBL is being developed as a new immunotherapeutic agent for prevention of infection in immunocompromised hosts. The available literature suggests that it may also be of benefit in MBL deficient patients with severe pneumonia. This review concentrates on clinical associations between MBL deficiency and susceptibility to respiratory tract infection.


title: Development and Validation of RT‐PCR Tests for the Detection and S1 Genotyping of Infectious Bronchitis Virus and Other Closely Related Gammacoronaviruses Within Clinical Samples

text: Two tests were developed that allow the detection and genotyping of infectious bronchitis virus (IBV) and other closely related gammacoronaviruses. The first test employs a one‐step, reverse transcription‐polymerase chain reaction (RT‐PCR) assay in which the amplification is monitored in real time using a TaqMan(®) probe. This real‐time RT‐PCR test was used to examine a panel of field samples and its performance compared to virus isolation in embryonated fowls’ eggs. A total of 323 field samples were tested; 176 samples were positive using the real‐time RT‐PCR method, but only three were positive by virus isolation. Sequencing was used to confirm the positive real‐time RT‐PCR results for a subset of samples. The test is suitable for swabs and post‐mortem samples and has been shown to be highly sensitive and specific. The second test, a genotyping method, was developed for identification of the strain of IBV present in field samples based on nucleotide variations within the gene encoding the S1 subunit of the surface spike (S) glycoprotein. This method was developed to provide a tool to inform vaccination decisions and for ongoing surveillance to detect new and emerging strains of IBV within the UK. The performance of the test was evaluated using laboratory isolates of IBV and field samples. Both tests are suitable for use in a high‐throughput diagnostic laboratory.


title: Cell permeabilization by poliovirus 2B viroporin triggers bystander permeabilization in neighbouring cells through a mechanism involving gap junctions

text: Poliovirus 2B protein is a well‐known viroporin implicated in plasma membrane permeabilization to ions and low‐molecular‐weight compounds during infection. Translation in mammalian cells expressing 2B protein is inhibited by hygromycin B (HB) but remains unaffected in mock cells, which are not permeable to the inhibitor. Here we describe a previously unreported bystander effect in which healthy baby hamster kidney (BHK) cells become sensitive to HB when co‐cultured with a low proportion of cells expressing poliovirus 2B. Viroporins E from mouse hepatitis virus, 6K from Sindbis virus and NS4A protein from hepatitis C virus were also able to permeabilize neighbouring cells to different extents. Expression of 2B induced permeabilization of neighbouring cell lines other than BHK. We found that gap junctions are responsible mediating the observed bystander permeabilization. Gap junctional communication was confirmed in 2B‐expressing co‐cultures by fluorescent dye transfer. Moreover, the presence of connexin 43 was confirmed in both mock and 2B‐transfected cells. Finally, inhibition of HB entry to neighbouring cells was observed with 18α‐glycyrrhethinic acid, an inhibitor of gap junctions. Taken together, these findings support a mechanism involving gap junctional intercellular communication in the bystander permeabilization effect observed in healthy cells co‐cultured with poliovirus 2B‐expressing cells.


title: 14 Specific testing of textiles for transportation

text: Abstract The use of textiles in transportation may be associated with the need to combine comfort and functionality. The evolution of each mean of transportation along with the increased awareness about the importance of passengers' safety pushed research and development forward towards a larger use of lightweight, fire-resistant, nontoxic, and durable textiles in transportation. This in turn led to the development of test methods assessing the different aspects of textiles in transportation. This chapter starts with a presentation of the transportation textile market. Then, different aspects of textile testing relevant to the transportation industry are discussed: safety, flammability, hygiene, performance of composite parts, and durability. The chapter ends with considerations regarding future trends for textiles in transportation.


title: Expression of soluble forms of rubella virus glycoproteins in mammalian cells

text: Abstract Rubella virus (RV) virions contain two envelope glycoproteins, E1 and E2. Removal of hydrophobia regions in their carboxyl termini by genetic engineering caused them to be secreted rather than maintained in cell membranes of transfected COS cells. Truncated E2 was secreted in the absence of E1, whereas E1 lacking its transmembrane domain required coexpression of E2 for export from the cell. Secreted E2 was found to contain both O-linked and N-linked complex glycans, whereas secreted E1 retained virus neutralization and hemagglutination epitopes, suggesting the possibility of using soluble RV antigens as subunit vaccines and for serodiagnostic purposes. Stable Chinese hamster ovary cell lines secreting RV E1 were constructed for large scale preparation of recombinant E1.


title: COVID‐19: Recommended sampling sites at different stage of the disease

text: Coronavirus Disease 2019 (COVID‐19) is mainly an acute respiratory infectious disease caused by a novel coronavirus (officially named Severe acute respiratory syndrome coronavirus 2, SARS‐CoV‐2) in December 2019, which is currently a worldwide pandemic, mainly causes the novel coronavirus pneumonia (NCP). At present, it mainly relies on Real‐time RT‐PCR to detect SARS‐CoV‐2 virus nucleic acid collected from the clinical specimens of patients as the standard for diagnosis, discontinuation of quarantine and discharge.(1,2) This article is protected by copyright. All rights reserved.


title: News coverage of the COVID-19 pandemic: Missed opportunities to promote health sustaining behaviors

text: BACKGROUND: Given that individuals may make health decisions based on mass media coverage, and given that such decisions have broad consequences in the case of highly contagious infectious disease, it is imperative that public health practitioners are aware of mass media coverage on emerging health threats such as COVID-19. The purpose of this study was to examine the content of news segments covering COVID-19 posted on-line. METHODS: Using the Google Videos function on a cleared browser, all videos identified from January and February, 2020 were archived by URL for analysis. After applying exclusion criteria, a total of 401 remained, comprising the sample. Content categories derived from trusted sources were applied to assess the content of broadcast news segments pertaining to COVID-19 on Google Videos. RESULTS: The most common topic mentioned across all videos was death and the death rate (43.6%) and many connoted anxieties surrounding the COVID-19 outbreak (37.4%). Critically important information about the prevention of COVID-19 spread received little attention. For example, only 3.0% of videos discussed coughing into or blowing one's nose into a tissue and throwing the tissue away, 6.2% talked about wearing a facemask when caring for the ill, and 8.8% covered disinfecting highly touched objects and surfaces. International videos more often presented captions and English subtitles (with and without narration) (7.8% vs. 0.9%, p = 0.018) and even more frequently discussed death and the death rate associated with COVID-19 (56.9% vs. 41.7%, p = 0.04). CONCLUSION: Coupled with the resultant increase in negative emotion, the majority of video messages missed an opportunity to reframe messages to encourage/promote coping strategies and health sustaining behaviors.


title: Creative Production of ‘COVID‐19 Social Distancing’ Narratives on Social Media

text: This paper offers an insight into the role of young people in shifting risk perception of the current global pandemic, COVID‐19, via social distancing narratives on social media. Young people are creatively and affectively supporting the social distancing initiatives in Brunei Darussalam through the use of social media platforms such as Instagram, Twitter, and Tik Tok. Using qualitative content analysis (QCA) data of social media content by Bruneian youth, this paper reveals the localised and contextualised creative production of five ‘social distancing’ narratives as a response to the national and global concerns in times of a global pandemic: narrative of fear; narrative of responsibility; narrative of annoyance; narrative of fun; and narrative of resistance. This paper reflects on three key socio‐cultural reconfigurations that have broader implications beyond the COVID‐19 crisis: new youth spatialities and social engagements; youth leadership in development; and consideration of social participation and reach in risk communication.


title: A search for new microorganisms in calf pneumonia by the inoculation of gnotobiotic calves

text: In a detailed microbiological and pathological study of eight outbreaks of calf pneumonia, which included the inoculation of respiratory material into 18 gnotobiotic calves, a total of five viruses, four species of mycoplasma and 19 species of bacteria were identified. The only microorganism not previously associated with bovine respiratory disease was a Coronavirus. The experimental disease produced in the majority of the gnotobiotic calves by the intratracheal inoculation of unpassaged respiratory material, closely resembled the natural disease. However statistical analysis of the results could not ascribe the disease seen to a single microorganism or to a particular combination of microorganisms. Assuming therefore that no microorganisms were missed in the study, it was concluded that the microbiological cause of the experimental disease lay amongst the organisms already found and that one or more of three other factors, discussed in the paper, accounted for the experimental disease produced.


title: Application of cognitive Internet of Medical Things for COVID-19 pandemic

text: BACKGROUND AND AIM: In the age of advanced digital technology, smart healthcare based on the Internet of Things (IoT) is gaining importance to deal with the current COVID-19 pandemic. In this paper, the novel application of cognitive radio (CR) based IoT specific for the medical domain referred to as Cognitive Internet of Medical Things (CIoMT) is explored to tackle the global challenge. This concept of CIoT is best suited to this pandemic as every person is to be connected and monitored through a massive network that requires efficient spectrum management. METHODS: An extensive literature survey is conducted in the Google Scholar, Scopus, PubMed, Research Gate, and IEEE Xplore databases using the terms “COVID-19" and “Cognitive IoT” or “Corona virus” and “IoMT”. The latest data and inputs from official websites and reports are used for further investigation and analysis of the application areas. RESULTS: This review encompasses different novel applications of CIoMT for fighting the ongoing COVID-19 health crisis. The CR based dynamic spectrum allocation technique is the solution for accommodating a massive number of devices and a wide number of applications. The CIoMT platform enables real-time tracking, remote health monitoring, rapid diagnosis of the cases, contact tracking, clustering, screening, and surveillance thus, reducing the workload on the medical industry for prevention and control of the infection. The challenges and future research directions are also identified. CONCLUSIONS: CIoMT is a promising technology for rapid diagnosis, dynamic monitoring and tracking, better treatment and control without spreading the virus to others.


title: Viruses and Bioterrorism

text: The use of viral agents for biological warfare has a long history, which predates their recognition and isolation by culture. Advances in viral culture and virus stabilization made during the second half of the twentieth century raised the level of concern by facilitating the large-scale production of viral agents for aerosol dissemination. Furthermore, the nucleic acid of many viruses, including some that are currently not threats, can be manipulated in the laboratory. Thus, the potential for genetic engineering and misuse of biotechnology is a serious threat. An effective defense against viral agents requires a comprehensive approach including restricting access to viral stocks, detecting deliberately induced disease outbreaks, rapid laboratory identification of viral agents in clinical specimens, preventing person-to-person transmission, using reliable decontamination procedures, and developing effective vaccines and antiviral drugs.


title: More on: ‘COVID‐19 coagulopathy in Caucasian patients’

text: We read with interest the report from Fogarty and colleagues about COVID-19 coagulopathy in Caucasian patients. [1] However, we think that some aspects of this report may deserve further attention. The major concern regards the doses of low-molecular weight heparin (LMWH) used for thromboprophylaxis in this study. Indeed, the Authors report on a weight-adjusted dose of enoxaparin higher than that registered in Europe for the prophylaxis of venous thromboembolism (VTE) in hospitalized acutely ill medical patients.


title: COVID-19 as a factor influencing air pollution?

text: • Longer-chain perfluoroalkyl substances strongly inhibited carboxylesterase. • The higher binding affinity caused more severe inhibition. • Inhibition kinetics was studied, and in vitro-in vivo extrapolation was performed.


title: Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins

text: Pathogenic clostridial species secrete potent toxins that induce severe host tissue damage. Paeniclostridium sordellii lethal toxin (TcsL) causes an almost invariably lethal toxic shock syndrome associated with gynecological infections. TcsL is 87% similar to C. difficile TcdB, which enters host cells via Frizzled receptors in colon epithelium. However, P. sordellii infections target vascular endothelium, suggesting that TcsL exploits another receptor. Here, using CRISPR/Cas9 screening, we establish semaphorins SEMA6A and SEMA6B as TcsL receptors. We demonstrate that recombinant SEMA6A can protect mice from TcsL-induced edema. A 3.3 Å cryo-EM structure shows that TcsL binds SEMA6A with the same region that in TcdB binds structurally unrelated Frizzled. Remarkably, 15 mutations in this evolutionarily divergent surface are sufficient to switch binding specificity of TcsL to that of TcdB. Our findings establish semaphorins as physiologically relevant receptors for TcsL and reveal the molecular basis for the difference in tissue targeting and disease pathogenesis between highly related toxins.


title: How the COVID‐19 pandemic changed cellular therapy at Columbia University Irving Medical Center/NewYork‐Presbyterian Hospital

text: New York is at the epicenter of the coronavirus disease 2019 (COVID‐19) pandemic caused by the SARS‐CoV‐2 virus. Columbia University Irving Medical Center/NewYork‐Presbyterian Hospital (CUIMC/NYPH) had to make changes to its cellular therapy operations to ensure patient, donor, and staff safety and well‐being. In this article, we discuss the process changes we instituted for cellular therapy clinical care, collection, processing, and cryopreservation to cope with the rapidly evolving pandemic.


title: Tumor necrosis factor α gene expression and the response to interferon in chronic hepatitis C

text: Tumor necrosis factor α (TNF‐α) is a cytokine with pleiotropic properties that is induced in a variety of pathological situations including viral infections. In this work, we analyzed the expression of TNF‐α gene in patients with chronic hepatitis C. Serum TNF‐α levels were found to be elevated in all chronic hepatitis C patients including those cases presenting sustained biochemical remission of the disease after interferon therapy. Untreated patients with chronic hepatitis C showed increased TNF‐α messenger RNA (mRNA) levels in the liver and mononuclear cells as compared with healthy controls. After completion of treatment with interferon, patients experiencing sustained complete response showed values of TNF‐α mRNA, both in the liver and in peripheral mononuclear cells, within the normal range, significantly lower than patients who did not respond to interferon and than those with complete response who relapsed after interferon withdrawal. Pretreatment values of TNF‐α mRNA were lower in long‐term responders to interferon than in cases who failed to respond to the treatment. Values of TNF‐α mRNA in the liver or in mononuclear cells were higher in specimens with positive hepatitis C virus (HCV) RNA than in those samples where the virus was undetectable. Neither the intensity of the liver damage nor the amount of HCV RNA in serum or in cells showed correlation with the levels of TNF‐α transcripts in peripheral mononuclear cells but it was found that high TNF‐α values were associated with genotype 1b. In conclusion, there is an enhanced expression of TNF‐α in HCV infection. High levels of this cytokine may play a role in the resistance to interferon therapy.


title: Conservation implications of primate trade in China over 18 years based on web news reports of confiscations

text: Primate species have been increasingly threatened by legal and illegal trade in China, mainly for biomedical research or as pets and traditional medicine, yet most reports on trade from China regard international trade. To assess a proxy for amount of national primate trades, we quantified the number of reports of native primate species featuring in unique web news reports from 2000 to 2017, including accuracy of their identification, location where they were confiscated or rescued, and their condition upon rescue. To measure temporal trends across these categories, the time span was divided into three sections: 2000–2005, 2006–2011 and 2012–2017. A total of 735 individuals of 14 species were reported in 372 news reports, mostly rhesus macaques (n = 165, 22.5%, Macaca mulatta) and two species of slow lorises (n = 487, 66.3%, Nycticebus spp.). During the same period, live individuals of rhesus macaques were recorded 206 times (70,949 individuals) in the Convention on International Trade in Endangered Species of Wild Fauna and Flora Trade Database, whereas slow lorises were only recorded four times (nine individuals), indicating that the species originated illegally from China or were illegally imported into China. Due to their rescued locations in residential areas (n = 211, 56.7%), most primates appeared to be housed privately as pets. A higher proportion of ‘market’ rescues during 2006–2011 (χ(2) = 8.485, df = 2, p = 0.014), could be partly attributed to an intensive management on wildlife markets since the outbreak of severe acute respiratory syndrome (SARS) in 2003. More than half (68.3%, 502 individuals) of the primate individuals were unhealthy, injured or dead when rescued. Thus, identification and welfare training and capacity-building should be provided to husbandry and veterinary professionals, as well as education to the public through awareness initiatives. The increase in presence of some species, especially slow lorises, with a declining population in restricted areas, also suggests the urgent need for public awareness about the illegal nature of keeping these taxa as pets.


title: Transference of COVID-19 patient in hospitals – A crucial phase

text: • COVID-19 virus is primarily transmitted between humans through respiratory droplets and contact routes. • Transportation of COVID-19 patient carries very high transmission risk to personals involved. • Worldwide, clinicians are using many measures that can be executed easily to prevent aerosol exposure.


title: Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin–angiotensin system inhibitors

text: In December 2019, COVID-19 outbroke in Wuhan, China. The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension. In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020. All study cases were grouped according to whether they had a history of hypertension. Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs. The mean age of 110 patients was 57.7 years (range, 25–86 years), of which 60 (54.5%) were male patients. The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)]. Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 × 10(9)/L vs 1.26 × 10(9)/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)]. Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)]. In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission. The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19. Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension.


title: Diagnosis and treatment of emergency surgeries in otorhinolaryngology, head and neck surgeryduring the covid-19 outbreak: a single center experience

text: The 2019 Novel Coronavirus (2019-nCoV, SARS-CoV-2) infection has already been assigned as a Class B infectious disease requiring Class A management strategy according to “the Law on the Prevention and Control of Infectious Diseases of the People's Republic of China” and become a global pandemic. The incidence of emergencies in otorhinolaryngology, head and neck surgery such as foreign bodies in the esophagus and the respiratory tract, epistaxis, laryngeal obstruction with dyspnea, and head and neck trauma are relatively high. Emergency surgeries are required as some of these diseases progress rapidly and probably be life-threatening. In this article, we drafted the recommendations for diagnosis and treatment of emergency surgeries in otorhinolaryngology, head and neck surgery in the epidemic area of novel coronavirus pneumonia based on “Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional; 7th Edition Revisions)”and WHO guidelines, combined with the experience of emergency surgeries in the Department of Otorhinolaryngology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, which is at the center outbreak area of the SARS-CoV-2 pneumonia (COVID-19) in China, to improve the success rate of treatment for otorhinolaryngology, head and neck surgeryemergency surgeries and to reduce the SARS-CoV-2 infection rate in the perioperative period.


title: Chapter 4 Current trends of antimicrobials used in food animals and aquaculture

text: Abstract Human population has been increasing rapidly, which ultimately increases human consumption, especially, animal protein requirements. Therefore, demands of animal protein consumption are increasing worldwide at an extraordinary rate. In order to meet the protein demand, intensive animal and aquaculture farming are considered. Like livestock farming (poultry, pigs, sheep, livestock, horses, rabbits, etc.), aquaculture farming (fish, crustaceans, mollusks, etc.) is also becoming the globe's emergent protein production sector. More than 580 aquaculture species are farmed worldwide. Current food animal and aquaculture farming are coupled with standard usage of antimicrobials. The antimicrobial drugs are major solutions for the management of contagious illnesses in food animals and aquaculture. In animal husbandry, antimicrobials are widely utilized for animal therapy, prophylaxis, or as growth promoters. Imprudent usage of these antimicrobials in food animals and aquaculture is a major contributing factor in the spread of antimicrobial resistance. The widespread use of veterinary medicines is considered to signify a frightening population health threat. It not only results in the disclosure and escalation of resistant microbes but also causes other individual, animal, and ecological deterioration. The contribution of resistant microbes from various sources seems to be the major base of resistance in the environment. However, strict policies and regulations for antimicrobial usage in food animals and aquaculture must be made and applied. It is important to prevent their negative effects in humans, food animals, aquaculture, and the environment.


title: Triage and management of the ACHD patient with COVID-19: A single center approach

text: With the recent emergence of SARS-CoV-2 and COVID-19, healthcare facilities and personnel are expected to rapidly triage and care for even the most complex medical conditions. Adults with congenital heart disease (ACHD) represent an often-intimidating group of complex cardiovascular disorders. Given that general internists and general cardiologists will often be asked to evaluate this group during the pandemic, we propose here an abbreviated triage algorithm that will assist in identifying the patient's overarching ACHD phenotype and baseline cardiac status. The strategy outlined allows for rapid triage and groups various anatomic CHD variants into overarching phenotypes, permitting care teams to quickly review key points in the management of moderate to severely complex ACHD patients.


Proposed model for hospital and community pharmacy services during COVID‐19 pandemic in Nigeria


title: Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study

text: BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK’s largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity.


title: Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

text: BACKGROUND: Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. METHODS: Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT), 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS) and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. RESULTS: Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder). CONCLUSION: The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.


Elder Abuse in the time of COVID-19 – Increased Risks for Older Adults and Their Caregivers


title: Point-Of-Care Testing Curriculum and Accreditation for Public Health—Enabling Preparedness, Response, and Higher Standards of Care at Points of Need

text: Objectives: To develop awareness of benefits of point-of-care testing (POCT) education in schools of public health, to identify learning objectives for teaching POCT, to enable public health professionals and emergency responders to perform evidence-based diagnosis and triage effectively and efficiently at points of need, and to better improve future standards of care for public health practice, including in limited-resource settings and crisis situations. Methods: We surveyed all U.S. schools of public health, colleges of public health, and public health schools accredited by the Council on Education in Public Health (CEPH). We included accredited public health programs, so that all states offering public health education were represented. We analyzed survey data, public health books, and board certification guidelines. We used PubMed to identify public health curriculum papers, and assessed 2019 CEPH accreditation requirements. We merged POCT knowledge bases to design a new curriculum for teaching public health students and practitioners the principles and practice of POCT. Results: Public health curricula, certification requirements, and textbooks generally do not include POCT instruction. Only one book, Global Point of Care: Strategies for Disasters, Emergencies, and Public Health Resilience, and one online course on public health preparedness address POCT and public health intervention issues. The topic, POC HIV/HCV ED testing, appeared in one course and POC diagnostics in local clinics, in another. Papers on public health curriculum have not incorporated POCT. No curriculum addresses POCT in isolation units during quarantine, despite evidence that recent Ebola virus disease cases in the U.S. and elsewhere proved unequivocally the need for POCT. The modular learning objectives identified in this paper were customized for public health students. Public health graduates can use boot camps, online credentialing, and self-study to acquire POCT skills. Conclusions: Enhancing accreditation requirements, academic training, board certification, and field experience will generate public health healthcare professionals who will rely upon evidence-based medical decision making at points of care, including during crises when time is of the essence. A POCT-enabled public health workforce can help prevent and stop outbreaks. Public health-based medical professionals urgently need the skills necessary to perform POCT and prepare America and other nations for threats portending significant adverse medical, economic, social, and cultural impact.


title: Amino acids 15–28 in the ectodomain of SARS coronavirus 3a protein induces neutralizing antibodies

text: A synthetic peptide corresponding to amino acids (aa) 15–28 of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein was used to raise polyclonal antibodies in rabbits. This anti-3a N-terminal antibody could detect 3a protein in infected cells, as did an anti-3a C-terminal antibody previously described. The latter targeted the C-terminal cytoplasmic domain of 3a (aa 134–274). The anti-3a N-terminal antibody could detect intracellular 3a as well as 3a expressed on the cell surface. Interestingly, only the anti-3a N-terminal antibody can inhibit SARS-CoV propagation in Vero E6 culture although the binding affinity of the anti-3a N-terminal antibody was lower than the anti-3a C-terminal antibody.


title: Cyclophilin A up-regulates MMP-9 expression and adhesion of monocytes/macrophages via CD147 signalling pathway in rheumatoid arthritis

text: Objectives. To investigate whether cyclophilin A (CypA) can up-regulate the expression of MMP-2 and MMP-9 in monocytes/macrophages and whether CD147 facilitates this regulation in RA. Methods. Peripheral blood monocytes were isolated from RA patients and differentiated into macrophages by M-CSF (15 ng/ml). Under CypA stimulation (200 ng/ml), the protein release and activation of MMPs were detected by gelatin zymography and invasion assay. Human monocyte cell line THP-1 cells were selected for the advanced searching for potential interaction between CypA and CD147 in production of MMPs and cell adhesion to extracellular matrix (ECM). Results. CypA significantly increased production and activation of MMP-9, not MMP-2, in the monocytes/macrophages derived from RA SF. CSA and HAb18G/CD147 antagonistic peptide AP-9 against CD147, respectively, dramatically decreased MMP-2 and MMP-9 expression, both in the absence or presence of CypA. Similar effects of CypA on MMP-9 production and cell invasion were observed in THP-1 cells. CypA-induced nuclear factor κB (NF-κB) activity for MMP-9 transcription were strongly blocked by extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK) inhibitors (U0126 and SP600125, respectively), but not by p38 mitogen-activated protein kinase (MAPK) inhibitors (SB203580). CypA also induced calcium mobilization and increased the adhesion of THP-1 cells to ECM. Conclusions. These findings suggest that in RA, the abundant CypA, by its direct binding to CD147, up-regulates MMP-9 expression and adhesion of monocytes/macrophages to ECM, and the cyclophilin-CD147 interactions might contribute to the destruction of cartilage and bone.


Rhinovirus-induced bronchiolitis: Lack of association between virus genomic load and short-term outcomes


title: Adjusting to life during a pandemic

text: This article will deal with the pandemic and one university's response. I am sure everyone has their own story, but I am from a town in New Jersey that was called the epicenter of the virus in the early stages of its spread.


title: 150 Fever in the Returned Traveler

text: Abstract International travel is associated with a risk of infections not typically seen in high-income settings. Malaria is the most important tropical infection in travelers, but epidemics of dengue, chikungunya, and Zika emphasize that clinicians need to be aware of the rapidly changing distribution of many arboviruses. A detailed travel history and a syndromic approach to the investigation and management of patients is key. Consultation with a specialist is often recommended to ensure that appropriate management and investigations are undertaken in febrile returned travelers.


Impacts of COVID‐19 on U.S. aquaculture, aquaponics, and allied businesses


title: Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice

text: Advanced age is a risk factor of severe acute respiratory syndrome (SARS) in humans. To understand its pathogenesis, we developed an animal model using BALB/c mice and the mouse-passaged Frankfurt 1 isolate of SARS coronavirus (SARS-CoV). We examined the immune responses to SARS-CoV in both young and adult mice. SARS-CoV induced severe respiratory illness in all adult, but not young, mice on day 2 after inoculation with a mortality rate of 30 to 50%. Moribund adult mice showed severe pulmonary edema and diffuse alveolar damage accompanied by virus replication. Adult murine lungs, which had significantly higher interleukin (IL)-4 and lower IL-10 and IL-13 levels before infection than young murine lungs, rapidly produced high levels of proinflammatory chemokines and cytokines known to induce macrophage and neutrophil infiltration and activation (eg, tumor necrosis factor-α). On day 2 after inoculation, young murine lungs produced not only proinflammatory cytokines but also IL-2, interferon-γ, IL-10, and IL-13. Adult mice showed early and acute excessive proinflammatory responses (ie, cytokine storm) in the lungs after SARS-CoV infection, which led to severe pulmonary edema and diffuse alveolar damage. Intravenous injection with anti-tumor necrosis factor-α antibody 3 hours after infection had no effect on SARS-CoV infection. However, intraperitoneal interferon-γ injection protected adult mice from the lethal respiratory illness. The experimental model described here may be useful for elucidating the pathophysiology of SARS and for evaluating therapies to treat SARS-CoV infection.


Coronaviruses: Molecular and Cellular Biology


title: Elicitation Enhanced the Yield of Glycyrrhizin and Antioxidant Activities in Hairy Root Cultures of Glycyrrhiza glabra L.

text: Glycyrrhiza glabra L. has become an endangered medicinal plant due to the unabated extraction of glycyrrhizin. Glycyrrhizin is a triterpenoid saponin that is a root centric secondary metabolite having numerous pharmacological properties, such as anti-inflammatory, immunomodulatory, antiallergic, antiulcer, and is found to be effective even against HIV. Harvesting of the roots for high value glycyrrhizin destroys the whole plant causing existential threat to the plant itself and consequent damage to biodiversity. The present study establishes that hairy root cultures of G. glabra, using an optimized elicitor, can dramatically enhance focused production of glycyrrhizin at a much faster pace year-round without causing destruction of the plant. Hairy root cultures of G. glabra were developed using the Agrobacterium rhizogenes A4 strain. The glycyrrhizin content was enhanced using different biotic and abiotic elicitors, for example, PEG (polyethylene glycol), CdCl(2), cellulase, and mannan at different concentrations and durations. PEG at 1% concentration enhanced the yield of glycyrrhizin up to 5.4-fold after 24 h of exposure, whereas 200 µg mL(−1) cellulase enhanced glycyrrhizin yield to 8.6-fold after 7 days of treatment. Mannan at 10 mg L(−1) concentration enhanced the production of glycyrrhizin up to 7.8-fold after 10 days of stress. Among different antioxidant enzymes, SOD activity was significantly enhanced under drought, cellulase and mannan stress. This identification of elicitors can result in abundant supply of valuable glycyrrhizin to meet broad spectrum demand through commercial production without endangering G. glabra L.


Ventilator management in the age of COVID-19: response to “Logistic and organizational aspects of a dedicated intensive care unit for COVID-19 patients”


title: Comparison of sputum and nasopharyngeal swabs for detection of respiratory viruses

text: Diagnostic tests for respiratory viral infections use traditionally either nasopharyngeal washes or swabs. Sputum is representative of the lower respiratory tract but is used rarely for viral testing. The aim of this study was to compare the detection rates of respiratory viruses from nasopharyngeal swabs and sputum using a multiplex real‐time reverse transcription‐polymerase chain reaction (RT‐PCR). Adults who were admitted or presented to the clinics of Gil Medical Center with acute respiratory symptoms were recruited from 1 November 2012 to 31 March 2013. Paired specimens of nasopharyngeal swabs and sputum were obtained from 154 subjects, and RNA was extracted and tested for 16 different respiratory viruses using the Anyplex II RV16 Detection kit (Seegene, Seoul, Korea). The positive rate was 53% (81/154) for nasopharyngeal swabs and 68% (105/154) for sputum (P < 0.001). One hundred thirty‐four viruses were identified for 107 illnesses. Influenza A virus, RSV A, HRV, coronavirus OC43, and adenovirus were detected more frequently in sputum samples than in nasopharyngeal swabs (P < 0.001). Importantly, 12 of 44 (27%) influenza A infections and 11 of 27 (41%) RSV infections were positive in only sputum samples. The detection rates of respiratory viruses from sputum samples were significantly higher than those from nasopharyngeal swabs in adults using real‐time multiplex RT‐PCR. These findings suggest that sputum would benefit for the detection of respiratory viruses by nucleic acid amplification tests (NAATs) in patients who produce sputum. Further studies are needed to establish standardized RNA extraction methods from sputum samples. J. Med. Virol. 86:2122–2127, 2014. © 2014 Wiley Periodicals, Inc.


title: Expression of a multi-epitope DPT fusion protein in transplastomic tobacco plants retains both antigenicity and immunogenicity of all three components of the functional oligomer

text: Expression of genes in plant chloroplasts provides an opportunity for enhanced production of target proteins. We report the introduction and expression of a fusion DPT protein containing immunoprotective exotoxin epitopes of Corynebacterium diphtheriae, Bordetella pertussis, and Clostridium tetani in tobacco chloroplasts. Using biolistic-mediated transformation, a plant-optimized synthetic DPT gene was successfully transferred to tobacco plastomes. Putative transplastomic T0 plants were identified by PCR, and Southern blot analysis confirmed homoplasmy in T1 progeny. ELISA assays demonstrated that the DPT protein retained antigenicity of the three components of the fusion protein. The highest level of expression in these transplastomic plants reached 0.8% of total soluble protein. To assess whether the functional recombinant protein expressed in tobacco plants would induce specific antibodies in test animals, a mice feeding experiment was conducted. For mice orally immunized with freeze-dried transplastomic leaves, production of IgG and IgA antibodies specific to each toxin were detected in serum and mucosal tissues.


title: Modelling conditional skewness: Heterogeneous beliefs, short sale restrictions and market declines

text: Abstract This paper tests the relationship among heterogeneous beliefs, short sale restrictions and time-varying conditional skewness under different market conditions. The results show that heterogeneous beliefs and short sale restrictions have negative impacts on conditional skewness during periods of market decline but have negative, positive or no impacts during periods of market growth. This evidence reconciles conflicting evidence in recent empirical studies on the relationship among heterogeneous beliefs, short sale restrictions and conditional skewness.


title: Detection of coronavirus in calf faeces with a haemadsorption-elution-haemagglutination assay (HEHA)

text: Abstract A simple and rapid procedure has been developed for the detection of bovine coronaviruses in faecal specimens. The method consists of adsorption of the virus onto mouse erythrocytes at 4°C, removal of unadsorbed material and elution of adsorbed viral material at 37°C. The eluate is then used in a haemagglutination test. Specificity of the reaction is checked by a blocking assay. No non-specific reactions have been observed. The sensitivity of the test appeared to be better than that of the electron microscope, at least when crude faecal extracts are used. By ultracentrifugation of the eluates the sensitivity of the assay can be further improved.


title: Typing and subtyping of influenza viruses and respiratory syncytial viruses by multiplex RT-PCR

text: We developed a series of oligonucleotide primers capable of detecting, typing, and subtyping influenza virus type A (H1 and H3) and type B and respiratory syncytial viruses types A and B. RNAs were isolated from culture fluid or clinical specimens, and cDNA synthesis and PCR were carried out with mixtures of primers specific to each virus. Amplified products were detected by ethidium bromide staining of amplified products after agarose gel electrophoresis. For each virus, five amplified products of different sizes could be distinguished on agarose gels. Multiplex RT-PCR can also be used to detect more than one viral template in the same reaction mixture, allowing identification of multiple strains in the same specimen.


title: Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19

text: The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient–provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.


title: Phylogenetic analysis of SARS-CoV-2 genomes in Turkey

text: COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first 30 SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find 2 of the seventeen subclusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.


title: Liver profile in COVID-19: a meta-analysis

text: BACKGROUND: Few studies have been performed to investigate multiorgan failure occurring with extrapulmonary symptoms like diarrhea, anorexia, and vomiting. There has been no attempt at a systematic review on this major health issue. Hence, in this study, a meta-analysis was undertaken to quantify the overall risk of liver damage in COVID-19 patients and also find the overall variation in risk outcome. MATERIALS AND METHODS: A meta-analysis was carried out on the findings of four published studies that were related to the albumin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels of COVID-19 patients. The pooled mean for each of these three measurements was estimated by using a random-effects model. RESULTS: The pooled means for albumin, AST, and ALT in COVID-19 patients were 38.84 g/L [95% confidence interval (CI): 35.83–41.86], 27.28 IU/L (95% CI: 18.30–36.26), and 24.44 IU/L (95% CI: 15.73–33.15) respectively. There was a high degree of divergence among the studies, with the index of heterogeneity being more than 90%. CONCLUSION: The ALT and albumin pooled means were reported to be within the normal range; however, the pooled mean of the serum AST level was found to be high in COVID-19 patients. The pooled means reported in this study can be useful for working out the degree of liver damage in COVID-19 patients.


title: Consequences of Pathogen Lists: Why Some Diseases May Continue to Plague Us

text: The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular focus on what products we need to have.


title: Characterization of the RNA-binding activity of VP3, a major structural protein of Infectious bursal disease virus

text: Infectious bursal disease virus (IBDV) is the agent of an immune-depressive disease affecting the poultry industry worldwide. Infection of IBDV leads to expression of five mature virus-encoded proteins. Proteolytic processing of the virus-encoded polyprotein generates VP3 which coats the inner surface of the IBDV capsid. In this report, we describe the characterization of the RNA-binding activity of VP3. For these studies, the VP3 coding region was fused to a histidine tag and expressed in insect cells using a recombinant baculovirus. The histidine-tagged VP3 was affinity-purified and used to study its ability to bind RNA molecules using three complementary methods: (i) Northwestern blotting; (ii) binding of VP3 protein-RNA complexes to nitrocellulose membranes; and (iii) electrophoretic mobility shift assays. The results demonstrated that VP3 efficiently bound ssRNA and dsRNA. Under the experimental conditions used in this study, the formation of VP3-RNA complexes did not depend upon the presence of specific RNA sequences. A series of histidine-tagged VP3 deletion mutants spanning the whole VP3 coding region were generated. The use of these mutants revealed that the VP3 RNA-binding domain layed in a highly conserved 69 aa stretch close to the N-terminus of the protein.


title: Studies on the mechanism of general anesthesia

text: Inhaled anesthetics are a chemically diverse collection of hydrophobic molecules that robustly activate TWIK-related K(+) channels (TREK-1) and reversibly induce loss of consciousness. For 100 y, anesthetics were speculated to target cellular membranes, yet no plausible mechanism emerged to explain a membrane effect on ion channels. Here we show that inhaled anesthetics (chloroform and isoflurane) activate TREK-1 through disruption of phospholipase D2 (PLD2) localization to lipid rafts and subsequent production of signaling lipid phosphatidic acid (PA). Catalytically dead PLD2 robustly blocks anesthetic TREK-1 currents in whole-cell patch-clamp recordings. Localization of PLD2 renders the TRAAK channel sensitive, a channel that is otherwise anesthetic insensitive. General anesthetics, such as chloroform, isoflurane, diethyl ether, xenon, and propofol, disrupt lipid rafts and activate PLD2. In the whole brain of flies, anesthesia disrupts rafts and PLD(null) flies resist anesthesia. Our results establish a membrane-mediated target of inhaled anesthesia and suggest PA helps set thresholds of anesthetic sensitivity in vivo.


Pattern of Vascular Disease in Lombardia (Italy) during the first month of the COVID-19 outbreak


title: “Clinical Characteristics, Outcomes and Prognosticators in Adult Patients Hospitalized with COVID-19”

text: BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into three groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years respectively (p=.0001). Of those who received MV and died, 61% were male (p=.01). More than half the patients (n=90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, LDH > 445.6 units/L and BNP > 104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9 respectively for MV (p < .05 for all). Peak BNP > 167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (p= .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, LDH and BNP may serve as early indicators of disease trajectory.


Evidencia viva como respuesta a las controversias en el uso de antimaláricos en COVID-19


title: Outcomes of COVID-19 among Patients on In-Center Hemodialysis: An Experience from the Epicenter in South Korea.

text: Patients with advanced chronic kidney disease (CKD) or who are on hemodialysis (HD) could have increased susceptibility to the 2019 coronavirus disease (COVID-19) given their pre-existing comorbidities, older age, compromised immune system, and regular visits to populated outpatient dialysis centers. This study included 14 consecutive patients on HD or with advanced CKD who initiated HD after being diagnosed with laboratory-confirmed COVID-19 from February to April 2020 in hospitals throughout Daegu, South Korea. The included patients, 42.9% of whom were men, had a mean age of 63.5 years. Four patients had a history of contact with a patient suffering from COVID-19. The most common symptom was cough (50.0%), followed by dyspnea (35.7%). The mean time from symptom onset to diagnosis and admission was 2.6 and 3.5 days, respectively. Patients exhibited lymphopenia and elevated inflammatory markers, including C-reactive protein and ferritin. Chest radiography findings showed pulmonary infiltration in 10 patients. All patients underwent regular HD in a negative pressure room and received antiviral agents. Four patients received mechanical ventilation and continuous renal replacement therapy at a median duration of 14.0 and 8.5 days, respectively. One patient underwent extracorporeal membrane oxygenation for three days. Among the 14 patients included, two died due to acute respiratory distress syndrome, nine were discharged from the hospital, and three remained hospitalized. Despite the high-risk conditions associated with worse outcomes, patients on HD did not exhibit extremely poor overall COVID-19 outcomes perhaps due to early diagnosis, prompt hospitalization, and antiviral therapy.


title: Point of care lung ultrasound is useful when screening for CoVid-19 in Emergency Department patients

text: BACKGROUND: CoVid-19 can be a life-threatening lung disease or a trivial upper respiratory infection depending on whether the alveoli are involved. Emergency department (ED) screening in symptomatic patients with normal vital signs is frequently limited to oro-nasopharyngeal swabs. We tested the null hypothesis that patients being screened for CoVid-19 in the ED with normal vital signs and without hypoxia would have a point-of-care lung ultrasound (LUS) consistent with CoVid-19 less than 2% of the time. METHODS: SUBJECTS: Subjects were identified from ED ultrasound logs. INCLUSION CRITERIA: Age 14 years or older with symptoms prompting ED screening for CoVid-19. EXCLUSION CRITERIA: Known congestive heart failure or other chronic lung condition likely to cause excessive B lines on LUS. INTERVENTION: Structured blinded ultrasound review and chart review ANALYSIS: We used a two-sided exact hypothesis test for binomial random variables. We also measured LUS diagnostic performance using computed tomography as the gold standard. RESULTS: We reviewed 77 charts; 49 met inclusion criteria. Vital signs were normal in 30/49 patients; 10 (33%) of these patients had LUS consistent with CoVid-19. We rejected the null hypothesis (p-value <0.001). The treating physicians’ interpretation of their own point of care lung ultrasounds had a sensitivity of 100% (95% CI 75%, 100%) and specificity of 80% (95% CI 68%, 89%). CONCLUSION: LUS has a meaningful detection rate for CoVid-19 in symptomatic ED patients with normal vital signs. We recommend at least LUS be used in addition to PCR testing when screening symptomatic ED patients for CoVid-19.


title: Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference

text: Abstract The International Society for Influenza and other Respiratory Virus Diseases held its 5th Antiviral Group (isirv-AVG) Conference in Shanghai, China, in conjunction with the Shanghai Public Health Center and Fudan University from 14-16 June 2017. The three-day programme encompassed presentations on some of the clinical features, management, immune responses and virology of respiratory infections, including influenza A(H1N1)pdm09 and A(H7N9) viruses, MERS-CoV, SARS-CoV, adenovirus Type 80, enterovirus D68, metapneumovirus and respiratory syncytial virus (RSV). Updates were presented on several therapeutics currently in clinical trials, including influenza polymerase inhibitors pimodivir/JNJ6362387, S033188, favipiravir, monoclonal antibodies MHAA45449A and VIS410, and host directed strategies for influenza including nitazoxanide, and polymerase ALS-008112 and fusion inhibitors AK0529, GS-5806 for RSV. Updates were also given on the use of the currently licensed neuraminidase inhibitors. Given the location in China, there were also presentations on the use of Traditional Chinese Medicines. Following on from the previous conference, there were ongoing discussions on appropriate endpoints for severe influenza in clinical trials from regulators and clinicians, an issue which remains unresolved. The aim of this conference summary is to provide information for not only conference participants, but a detailed referenced review of the current status of clinical trials, and pre-clinical development of therapeutics and vaccines for influenza and other respiratory diseases for a broader audience.


title: Reducing onward spread of COVID-19 from imported cases: quarantine and ‘stay at home’ measures for travellers and returning residents to Singapore

text: Singapore imposed a 14-day ‘Stay Home Notice’ (SHN) on travellers and returning residents to reduce secondary transmission from imported cases of COVID-19. In this article, we describe the processes and enforcement of SHN, and explore the issues faced by individuals under such quarantine, and the steps taken to address them.


title: Pulmonary ct manifestations of COVID-19: changes within 2 weeks duration from presentation

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest computed tomography (CT) plays an essential role in the evaluation of COVID-19. This retrospective study aims to determine and compare the pulmonary changes in Iraqi patients with COVID-19 disease across the first two weeks after onset of symptoms using computerized tomography (CT) scan. Ninety-six patients with COVID-19 disease were enrolled in this study. Patients were divided into two groups according to the duration of symptoms (the first group has been scanned within the first week of presentation while the second group has been scanned in the second week). RESULTS: The CT findings in the first and second group were as follows: ground glass opacity (GGO) were 94.3% vs. 88.5%, consolidation were 25.7% vs. 34.6%, broncho vascular thickening were 18.6% vs. 7.7%, crazy paving appearance were 15.7% vs. 3.8%, tree-in-bud appearance were 4.3% vs. 10.7%, pulmonary nodules were 5.1% vs. 7.7%, and bronchiectasis were 5.5% vs. 7.7%. Pleural effusion and cavitation were seen only in the first group (2.9% and 1.4% respectively). The distribution of CT changes across the two groups were as follows: bilateral changes were 85.7% vs. 100%; central distribution were 11.4% vs. 11.5%; peripheral distribution were 64.3% vs. 42.3%, and diffuse (central and peripheral) distribution were 24.3% vs. 46.2% while multilobar distribution were 70% vs. 80.8%. CONCLUSION: The type, extent, and distributions of pulmonary manifestations associated with COVID-19 infection are significantly different between the two groups who have been scanned in different stages of the disease.


title: Chinese herbal medicine for coronavirus disease 2019: a systematic review and meta-analysis

text: Currently, coronavirus disease 2019 (COVID-19), which can lead to severe respiratory failure and death, is now a global pandemic with no specific anti-viral drugs or vaccines. However, It is worth noting that traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM), has been widely applied in mainland China since outbreak, bringing new hope for the prevention and control of COVID-19. A comprehensive literature searching was conducted in 7 electronic databases from their inception up to June 21, 2020 to evaluate the efficacy and safety of CHM for COVID-19. Eighteen randomized controlled trials (RCTs) involving 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquoric Root (Gancao, Radix Glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellariae Baicalensis), Pinellia Rhizome (Banxia, Rhizoma Pinelliae Tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae Suspensae), and Bitter Apricot Seed (Kuxingren, Semen Armeniacae Amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction. Our meta-analyses found that comparing CHM group and conventional western medicine group, CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein). Besides, no severe adverse effects was identified by CHM. CHM, especially classical Chinese herbal formulas, could be used as potential candidates for COVID-19 in this battle.


title: Dengue Fever, COVID‐19 (SARS‐CoV‐2), and Antibody‐Dependent Enhancement (ADE): A Perspective

text: SARS‐CoV‐2 pandemic and recurrent dengue epidemics in tropical countries have turned into a global health threat. While both virus‐caused infections may only reveal light symptoms, they can also cause severe diseases. Here, we review the possible antibody‐dependent enhancement (ADE) occurrence, known for dengue infections, when there is a second infection with a different virus strain. Consequently, preexisting antibodies do not neutralize infection, but enhance it, possibly by triggering Fcγ receptor‐mediated virus uptake. No clinical data exist indicating such mechanism for SARS‐CoV‐2, but previous coronavirus infections or infection of SARS‐CoV‐2 convalescent with different SARS‐CoV‐2 strains could promote ADE, as experimentally shown for antibodies against the MERS‐CoV or SARS‐CoV spike S protein. © 2020 International Society for Advancement of Cytometry


title: Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes

text: Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November–April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV.


Reply to letters vide manuscript ID IPEJ-D-20-00072, and IPEJ-D-20-00073 regarding our paper “Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: A scientific statement from the Indian Heart Rhythm Societyˮ


title: Understudied Factors Influencing Fc-Mediated Immune Responses against Viral Infections

text: Antibodies play a crucial role in host defense against viruses, both by preventing infection and by controlling viral replication. Besides their capacity to neutralize viruses, antibodies also exert their antiviral effects by crystallizable fragment (Fc)-mediated effector mechanisms. This involves a bridge between innate and adaptive immune systems, wherein antibodies form immune complexes that drive numerous innate immune effector functions, including antibody-dependent cellular cytotoxicity, antibody-dependent complement-mediated lysis, and antibody-dependent phagocytosis. Here, we review certain mechanisms that modulate these antibody-mediated effector functions against virally infected cells, such as viral glycoprotein shedding, viral glycoprotein internalization, antibody cooperativity, and antibody glycosylation. These mechanisms can either protect viral replication or enhance infected cell clearance. Here we discuss the importance of these understudied factors in modulating Fc-mediated effector functions.


title: Orphan drugs: Unmet societal need for non-profitable privately supplied new products

text: Abstract Due to the severity of rare diseases, the societal need for biopharmaceutical treatments for these diseases is high, despite low numbers of patients. Therefore, we investigated the barriers currently hindering the willingness to develop orphan drugs in the Netherlands. To this end, a robust, small sample, exploratory analysis of Dutch multi-actor development of orphan drugs was performed. Various factors that were expected to stimulate the adoption of orphan drug development were found to be important barriers. Concerted actions of producers, users, and especially regulators are necessary to overcome these barriers, but the prerequisite of a shared problem definition is lacking.


title: Clinical differentiation of anticoagulant and non‐anticoagulant properties of heparin

text: I thank Lindahl and Li for their thoughtful comments on the non‐anticoagulant properties of heparin.(1) Heightened awareness of hypercoagulability has made heparin part and parcel of the COVID‐19 management algorithms. In addition, reports of prophylactic anticoagulation failure have triggered several trials where escalated doses of heparin are compared with standard doses with the aim of preventing thrombotic complications. At this juncture, we do need to consider where do the non‐anticoagulant properties of heparin fit in the COVID‐19 clinical context?


title: Terpenoid and flavonoid spectrum of in vitro cultures of Glycyrrhiza glabra revealed high chemical heterogeneity: platform to understand biosynthesis

text: Simultaneous qualitative and quantitative assessment of eight flavonoids and two terpenoids were performed in fourteen in vitro raised morphogenic cultures of Glycyrrhiza glabra. Our study revealed that the spectrum and production of ten compounds, under investigation, were higher in organized tissue than the undifferentiated mass, however, aerial portions of the in vitro raised plants (leaf and stem) were found to be devoid of therapeutically relevant triterpenoid, glycyrrhizin. A correlation was observed between cell maturation, morphological differentiation and glycyrrhizin accumulation. Mature stolons (4 months) were characterized by the maximum accumulation of glycyrrhizin (8.60 µg/mg) in in vitro plantlets. The cytotoxic effect of the extracts evaluated against a panel of human cancer cell lines (in vitro) indicated that the pancreatic cell line (MIA-PaCa-2) were sensitive to all the fourteen extracts investigated. To the best of our knowledge this is the first comprehensive report relating plant growth regulators to metabolite spectrum and cytotoxic assessment in in vitro raised G. glabra cultures. Overall, our findings demonstrated that the metabolite spectrum of in vitro raised morphogenetic lines, under different stages of maturation, might offer a platform to understand the regulatory aspects of the concerned metabolite pathway and their consequent role in differentiation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11240-015-0910-4) contains supplementary material, which is available to authorized users.


title: Obstetric Management of COVID-19 in Pregnant Women

text: The 2019 novel coronavirus disease (COVID-19), which is caused by the novel beta coronavirus, SARS-CoV-2, is currently prevalent all over the world, causing thousands of deaths with relatively high virulence. Like two other notable beta coronaviruses, severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 can lead to severe contagious respiratory disease. Due to impaired cellular immunity and physiological changes, pregnant women are susceptible to respiratory disease and are more likely to develop severe pneumonia. Given the prevalence of COVID-19, it is speculated that some pregnant women have already been infected. However, limited data are available for the clinical course and management of COVID-19 in pregnancy. Therefore, we conducted this review to identify strategies for the obstetric management of COVID-19. We compared the clinical course and outcomes of COVID-19, SARS, and MERS in pregnancy and discussed several drugs for the treatment of COVID-19 in pregnancy.


title: Resistance is futile

text: A new study of dominant negative functions in cells infected by a positive-strand RNA virus detects an array of locus- and allele-specific effects. Exploiting subunit defects in multi-component complex assemblies provides a new approach to identifying targets for antiviral therapies that may inhibit the emergence of drug-resistant RNA virus populations.


title: Manipulating angiotensin metabolism with angiotensin converting enzyme 2 (ACE2) in heart failure

text: Angiotensin converting enzyme 2 (ACE2), is a monocarboxypeptidase which metabolizes several peptides including the degradation of Ang II, a peptide with vasoconstrictive/proliferative/effects, to generate Ang 1–7, which acting through its receptor Mas exerts vasodilatory/anti-proliferative actions. The classical pathway of the RAS involving the ACE-Ang II-AT1 receptor axis is antagonized by the second arm constituted by the ACE2-Ang 1–7/Mas receptor axis. Loss of ACE2 enhances the adverse pathological remodeling susceptibility to pressure-overload and myocardial infarction. Human recombinant ACE2 is also a negative regulator of Ang II-induced myocardial hypertrophy, fibrosis and diastolic dysfunction and suppresses pressure-overload induced heart failure. Due to its characteristics, the ACE2-Ang 1–7/Mas axis may represent new possibilities for developing novel therapeutic strategies for the treatment of heart failure. Human recombinant ACE2 has been safely administered to healthy human volunteers intravenously resulting in sustained lowering of plasma Ang II levels. In this review, we will summarize the beneficial effects of ACE2 in heart disease and the potential use of human recombinant ACE2 as a novel therapy for heart failure.


title: Off-the-shelf barrier for emergency intubation in the cardiac catheterization laboratory during the coronavirus disease 2019 (COVID-19) pandemic

text: With the spread of SARS-CoV-2, it is expected that cases of acute coronary syndrome in the setting of coronavirus disease 2019 (COVID-19) develop. As expensive and sophisticated protection devices are not widely available, we have been working on a simple, off-the-shelf protection device for endotracheal intubation of potentially infected patients. For this purpose, we used a large transparent plastic bag (such as the sterile protective cover of the lead glass shield) for protection from airborne infections. The cover is moved over the patient's head from cranial to caudal, covering the catheter table including the torso with no need for patient mobilization. The intubation is done conventionally under direct visual control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00392-020-01696-9) contains supplementary material, which is available to authorized users.


title: Lithium Toxicity in Two Coronavirus Disease 2019 (COVID-19) Patients

text: Coronavirus disease 2019 (COVID-19) is a highly contagious disease, which is currently causing a devastating pandemic resulting in more than millions of infected cases worldwide. Emerging evidence reports the impact of several co-morbidities on the clinical features and outcomes of COVID-19. However, the evidence regarding the association of mental health illnesses and psychiatric treatment on the prognoses of COVID-19 is still lacking. Lithium is a commonly prescribed psychiatric medication that is also well known for its highly lethal toxicity. Many factors can fluctuate the level of lithium, such as drug interaction, illness, and infection. Prompt recognition and management of lithium intoxication is required to reduce patients’ morbidity and mortality. Currently, there is no report regarding COVID-19 and lithium toxicity. Herein, we are presenting two patients with COVID-19 who initially presented with signs and symptoms of lithium toxicity. Our cases emphasize the need for special attention in taking care of patients who are taking lithium during the COVID-19 pandemic. In general, we recommend obtaining lithium levels in all patients who have been taking lithium and have the diagnosis of COVID-19.


title: Self-reported needs of patients with Parkinson’s disease during COVID-19 emergency in Italy

text: Because of COVID-19 outbreak, regular clinical services for Parkinson’s disease (PD) patients have been suddenly suspended, causing worries, confusion and unexpected needs in such frail population. Here, we reviewed the messages spontaneously sent by patients to an Italian PD clinic during the first two weeks of COVID-19 lockdown (9–21 March 2020), in order to highlight their main needs and then outline appropriate strategies of care for this critical period. One hundred sixty-two messages were analysed. Forty-six percent queried about clinical services; 28% communicated an acute clinical worsening for which a therapeutic change was done in 52% of cases; 17% (those patients with younger age and milder disease) asked about the relationship between PD and COVID-19; 8% informed about an intercurrent event. Our analysis suggests that PD patients’ needs during COVID-19 emergency include appropriate and complete information, a timely update on changes in clinical services, and the continuity of care, even in a remote mode. By addressing these issues, acute clinical worsening, complications and subsequent therapeutic changes could be prevented. In this perspective, telecommunication systems and virtual medicine should be implemented.


title: Lung function monitoring in the era of respiratory pandemics

text: Oscillometry has been used in adjunct with spirometry in many studies and in clinical practice. Recent events with the spread of a viral respiratory pandemic has caused many clinics to stop using standard spirometry for the fear of aerosol transmission of virus. With recent experiences of our and other groups using oscillometry demonstrating its sensitivity, precision, and ease of use without any forced maneuvers, we suggest that it could be an alternative to spirometry while minimizing exhalation aerosol generation.


title: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2

text: Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process.


title: Antiviral strategies for hepatitis E virus

text: Abstract The hepatitis E virus is a common cause of acute hepatitis. Contrary to hepatitis B and C, hepatitis E is mostly a mild infection, although it has a high mortality in pregnant women and can evolve to chronicity in immunocompromised patients. Ribavirin and pegylated interferon-α are the only available therapies, but both have side effects that are not acceptable for prophylaxis or treatment of mild infections. In addition, these drugs cannot be used for all patient types (e.g. in case of pregnancy, specific organ transplants or co-morbidities) and in resource-poor settings. Hence there is an urgent need for better antiviral treatments that are efficacious and safe, also during pregnancy. In this review, a concise introduction to the virus and disease is provided, followed by a discussion of the available assay systems and potential molecular targets (viral proteins and host factors) for the development of inhibitors of HEV replication. Finally, directions for future research are presented.


title: Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia

text: We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.


title: Erratum to : Guidance for building a dedicated health facility to contain the spread of the 2019 novel coronavirus outbreak (Indian J Med Res) 151, (5), 503

text: In the article entitled "Guidance for building a dedicated health facility to contain the spread of the 2019 novel coronavirus outbreak" published on pages 177-83, Issue 2 & 3, volume 151 in Indian J Med Ressup1/sup, the negative pressure number 1 in Figure 2 is incorrectly mentioned as 3 in the "replica ward" Copyright © 2020, Indian Council of Medical Research All rights reserved


The Missing Pieces of the COVID‐19 Puzzle


title: Coronavirus Disease 2019 With Acute Respiratory Distress Syndrome Mimicking Heart Failure Exacerbation: Time to Rethink

text: A 67-year-old man with a prior heart failure presented with fever, cough and dyspnea for 4 days. Physical examination showed bilateral rales on the lung exam, yet no lower extremity edema. The combination of symptoms, elevated inflammatory markers, normal baseline pro-B-type natriuretic peptide, PaO(2)/FiO(2) < 300 and positive swab suggested coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS) rather than heart failure exacerbation. We discuss the challenges in management of ARDS in COVID-19 patients that may initially mimic as acute exacerbation of heart failure.


title: Investigation of Griffithsin's Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate

text: Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin.


title: Case Report: Right Bundle Brunch Block and QTc Prolongation in a Patient with Novel Coronavirus Disease (COVID-19) Treated with Hydroxychloroquine

text: Novel coronavirus disease (COVID-19) is a highly contagious disease caused by severe adult respiratory syndrome-coronavirus-2 that has resulted in the current global pandemic. Currently, there is no available treatment proven to be effective against COVID-19, but multiple medications, including hydroxychloroquine (HCQ), are used off label. We report the case of a 60-year-old woman without any cardiac history who developed right bundle brunch block and critically prolonged corrected electrocardiographic QT interval (QTc 631 ms) after treatment for 3 days with HCQ, which resolved on discontinuation of the medication. This case highlights a significant and potentially life-threatening complication of HCQ use.


Pediatric genetics: rare is common


title: Chapter 4 Structure and Genotypes of Noroviruses

text: Abstract Human noroviruses are structurally very simple, but how this correlates with their highly infectious nature, environmental stability, and the fact that they survive commonly used food sterilization processes remains elusive. Noroviruses are genetically very diverse, and new genogroups and genotypes are continuously being discovered. Some norovirus genotypes are more commonly found in foodborne outbreaks, suggesting that virological factors may determine virus adsorption characteristics to food surfaces and the efficiency of food-to-person transmission. Noroviruses can be found in a wide range of mammalian species, including pigs and cows that are extensively farmed for human consumption. The zoonotic potential of animal noroviruses via the food chain cannot be ignored.


title: A study on the role of noninvasive ventilation in mild-to-moderate acute respiratory distress syndrome

text: AIM: There is sparse data on the role of noninvasive ventilation (NIV) in acute respiratory distress syndrome (ARDS) from India. Herein, we report our experience with the use of NIV in mild to moderate ARDS. MATERIALS AND METHODS: This was a prospective observational study involving consecutive subjects of ARDS treated with NIV using an oronasal mask. Patients were monitored clinically with serial arterial blood gas analysis. The success of NIV, duration of NIV use, Intensive Care Unit stay, hospital mortality, and improvement in clinical and blood gas parameters were assessed. The success of NIV was defined as prevention of endotracheal intubation. RESULTS: A total of 41 subjects (27 women, mean age: 30.9 years) were included in the study. Tropical infections followed by abdominal sepsis were the most common causes of ARDS. The use of NIV was successful in 18 (44%) subjects, while 23 subjects required intubation. The median time to intubation was 3 h. Overall, 19 (46.3%) deaths were encountered, all in those requiring invasive ventilation. The mean duration of ventilation was significantly higher in the intubated patients (7.1 vs. 2.6 days, P = 0.004). Univariate analysis revealed a lack of improvement in PaO(2)/FiO(2) at 1 h and high baseline Acute Physiology and Chronic Health Evaluation II (APACHE II) as predictors of NIV failure. CONCLUSIONS: Use of NIV in mild to moderate ARDS helped in avoiding intubation in about 44% of the subjects. A baseline APACHE II score of >17 and a PaO(2)/FiO(2) ratio <150 at 1 h predicts NIV failure.


title: Coupling between death spikes and birth troughs. Part 1: Evidence

text: Abstract In the wake of the influenza pandemic of 1889–1890 Jacques Bertillon, a pioneer of medical statistics, noticed that after the massive death spike there was a dip in birth numbers around 9 months later which was significantly larger than that which could be explained by the population change as a result of excess deaths. In addition it can be noticed that this dip was followed by a birth rebound a few months later. However having made this observation, Bertillon did not explore it further. Since that time the phenomenon was not revisited in spite of the fact that in the meanwhile there have been several new cases of massive death spikes. The aim here is to analyze these new cases to get a better understanding of this death–birth coupling phenomenon. The largest death spikes occurred in the wake of more recent influenza pandemics in 1918 and 1920, others were triggered by the 1923 earthquakes in Tokyo and the Twin Tower attack on September 11, 2001. We shall see that the first of these events indeed produced an extra dip in births whereas the 9/11 event did not. This disparity highlights the pivotal role of collateral sufferers. In the last section it is shown how the present coupling leads to predictions; it can explain in a unified way effects which so far have been studied separately, as for instance the impact on birth rates of heat waves. Thus, it appears that behind the apparent randomness of birth rate fluctuations there are in fact hidden explanatory factors.


title: Training Room Management of Medical Conditions: Infectious Diseases

text: Management of infectious diseases in athletes encompasses a wide range of pathogens, clinical presentations, and treatment options. Certain athletic activities and training regimens may predispose athletes to increased risk of contracting infectious diseases, some of which may limit athletic participation and pose the threat of significant morbidity. The sports medicine physician plays an important role as a first line of defense in preventing, recognizing, and appropriately treating infectious diseases in athletes.