title: Models of Eucalypt phenology predict bat population flux

text: Fruit bats (Pteropodidae) have received increased attention after the recent emergence of notable viral pathogens of bat origin. Their vagility hinders data collection on abundance and distribution, which constrains modeling efforts and our understanding of bat ecology, viral dynamics, and spillover. We addressed this knowledge gap with models and data on the occurrence and abundance of nectarivorous fruit bat populations at 3 day roosts in southeast Queensland. We used environmental drivers of nectar production as predictors and explored relationships between bat abundance and virus spillover. Specifically, we developed several novel modeling tools motivated by complexities of fruit bat foraging ecology, including: (1) a dataset of spatial variables comprising Eucalypt‐focused vegetation indices, cumulative precipitation, and temperature anomaly; (2) an algorithm that associated bat population response with spatial covariates in a spatially and temporally relevant way given our current understanding of bat foraging behavior; and (3) a thorough statistical learning approach to finding optimal covariate combinations. We identified covariates that classify fruit bat occupancy at each of our three study roosts with 86–93% accuracy. Negative binomial models explained 43–53% of the variation in observed abundance across roosts. Our models suggest that spatiotemporal heterogeneity in Eucalypt‐based food resources could drive at least 50% of bat population behavior at the landscape scale. We found that 13 spillover events were observed within the foraging range of our study roosts, and they occurred during times when models predicted low population abundance. Our results suggest that, in southeast Queensland, spillover may not be driven by large aggregations of fruit bats attracted by nectar‐based resources, but rather by behavior of smaller resident subpopulations. Our models and data integrated remote sensing and statistical learning to make inferences on bat ecology and disease dynamics. This work provides a foundation for further studies on landscape‐scale population movement and spatiotemporal disease dynamics.


title: Novel Compound Heterozygous DST Variants Causing Hereditary Sensory and Autonomic Neuropathies VI in Twins of a Chinese Family

text: Background: Hereditary sensory and autonomic neuropathies (HSANs) are a rare and severe group of sensory axonal neuropathies. HSANs have been classified into eight groups based on mode of inheritance, clinical features, and the involved genes. HSAN-VI, perhaps the most notable type, is an autosomal recessive disease, which manifests as the severely impaired pain sensitivity, autonomic disturbances, distal myopathy, spontaneous or surgical amputations, and sometimes early death. Mutations in DST have been identified as the cause of HSAN-VI. DST encodes dystonin, a member of the plakin protein family that is involved in cytoskeletal filament networks. Dystonin has seven major isoforms in nerve, muscle, and epithelium. Material and Methods: The present study investigated a Chinese family with HSAN and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatics analysis and prediction of variant pathogenicity. Co-segregation analysis was subsequently conducted. Results: We identified compound heterozygous variants of DST (c.3304G>A, p.V1102I and c.13796G>A, p.R4599H) in two patients. Conclusion: We reported on a Chinese family with HSAN-VI family and detected the disease-causing variants. Our description expands the spectrum of known DST variants and contributes to the clinical diagnosis of HSAN-VI.


title: Severe atypical pneumonia in critically ill patients: a retrospective multicenter study

text: BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients could require intensive care unit (ICU) admission for acute respiratory failure. METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven atypical pneumonia were retrospectively described. Patients with MP were compared to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A total of 104 patients were included, 71 men and 33 women, with a median age of 56 [44–67] years. MP was the causative agent for 76 (73%) patients and CP for 28 (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%] patients). Median number of involved quadrants on chest X-ray was 2 [1–4], with alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra-pulmonary manifestations were present in 34 (33%) patients. Mechanical ventilation was required for 75 (72%) patients and vasopressors for 41 (39%) patients. ICU length of stay was 16.5 [9.5–30.5] days, and 11 (11%) patients died in the ICU. Compared with SP patients, MP patients had more extensive interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6 (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at admission could discriminate MP and SP. MP was more often associated with hemolytic anemia, abdominal manifestations, and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial pneumonia requiring ICU admission, mortality was 11%. The comparison with SP pneumonia identified clinical, laboratory, and radiographic features that may suggest MP or CP pneumonia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-018-0429-z) contains supplementary material, which is available to authorized users.


title: SARS Outbreak, Taiwan, 2003

text: We studied the severe acute respiratory syndrome (SARS) outbreak in Taiwan, using the daily case-reporting data from May 5 to June 4 to learn how it had spread so rapidly. Our results indicate that most SARS-infected persons had symptoms and were admitted before their infections were reclassified as probable cases. This finding could indicate efficient admission, slow reclassification process, or both. The high percentage of nosocomial infections in Taiwan suggests that infection from hospitalized patients with suspected, but not yet classified, cases is a major factor in the spread of disease. Delays in reclassification also contributed to the problem. Because accurate diagnostic testing for SARS is currently lacking, intervention measures aimed at more efficient diagnosis, isolation of suspected SARS patients, and reclassification procedures could greatly reduce the number of infections in future outbreaks.


title: A review of the importance of cryptosporidiosis in farm animals

text: Abstract Cryptosporidium species are coccidian parasites with a large capacity to reproduce and to disseminate. Several species are known to infect farm animals, although the economic importance of cryptosporidiosis is highly host species dependent. This paper reviews the impact of cryptosporidial infections in livestock and poultry. For different farm animals, the Cryptosporidium spp. that occur, as well as their clinical and pathological features, and their interactions with other pathogens, are described. In addition, data concerning the prevalence, the transmission and the epidemiology of the disease are mentioned and a description of the economic losses associated with cryptosporidiosis in each of the hosts is given. Cryptosporidiosis seems to be mainly a problem in neonatal ruminants. Cryptosporidium parvum is considered to be an important agent in the aetiology of the neonatal diarrhoea syndrome of calves, lambs and goat kids, causing considerable direct and indirect economic losses. Avian cryptosporidiosis is an emerging health problem in poultry, associated with respiratory disease in chickens and other Galliformes, and with intestinal disease in turkeys and quails. Because of limited availability of effective drugs, the control of cryptosporidiosis relies mainly on hygienic measures and good management.


title: CXCR2 Signaling Protects Oligodendrocytes and Restricts Demyelination in a Mouse Model of Viral-Induced Demyelination

text: BACKGROUND: The functional role of ELR-positive CXC chemokines during viral – induced demyelination was assessed. Inoculation of the neuroattenuated JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible mice results in an acute encephalomyelitis that evolves into a chronic demyelinating disease, modeling white matter pathology observed in the human demyelinating disease Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: JHMV infection induced the rapid and sustained expression of transcripts specific for the ELR (+) chemokine ligands CXCL1 and CXCL2, as well as their binding receptor CXCR2, which was enriched within the spinal cord during chronic infection. Inhibiting CXCR2 signaling with neutralizing antiserum significantly (p<0.03) delayed clinical recovery. Moreover, CXCR2 neutralization was associated with an increase in the severity of demyelination that was independent of viral recrudescence or modulation of neuroinflammation. Rather, blocking CXCR2 was associated with increased numbers of apoptotic cells primarily within white matter tracts, suggesting that oligodendrocytes were affected. JHMV infection of enriched oligodendrocyte progenitor cell (OPC) cultures revealed that apoptosis was associated with elevated expression of cleaved caspase 3 and muted Bcl-2 expression. Inclusion of CXCL1 within JHMV infected cultures restricted caspase 3 cleavage and increased Bcl-2 expression that was associated with a significant (p<0.001) decrease in apoptosis. CXCR2 deficient oligodendrocytes were refractory to CXCL1 mediated protection from JHMV – induced apoptosis, readily activating caspase 3 and down regulating Bcl-2. CONCLUSION/SIGNIFICANCE: These findings highlight a previously unappreciated role for CXCR2 signaling in protecting oligodendrocyte lineage cells from apoptosis during inflammatory demyelination initiated by viral infection of the CNS.


title: The RNA pseudoknots in foot-and-mouth disease virus are dispensable for genome replication but essential for the production of infectious virus

text: The positive stranded RNA genomes of picornaviruses comprise a single large open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). Foot-and-mouth disease virus (FMDV) has an unusually large 5′ UTR (1.3 kb) containing five structural domains. These include the internal ribosome entry site (IRES), which facilitates initiation of translation, and the cis-acting replication element (cre). Less well characterised structures are a 5′ terminal 360 nucleotide stem-loop, a variable length poly-C-tract of approximately 100-200 nucleotides and a series of two to four tandemly repeated pseudoknots (PKs). We investigated the structures of the PKs by selective 2′ hydroxyl acetylation analysed by primer extension (SHAPE) analysis and determined their contribution to genome replication by mutation and deletion experiments. SHAPE and mutation experiments confirmed the importance of the previously predicted PK structures for their function. Deletion experiments showed that although PKs are not essential for replication, they provide genomes with a competitive advantage. However, although replicons and full-length genomes lacking all PKs were replication competent, no infectious virus was rescued from genomes containing less than one PK copy. This is consistent with our earlier report describing the presence of putative packaging signals in the PK region.


docid: oznelaus

title: Digital prosthetic workflow during COVID‐19 pandemic to limit infection risk in dental practice

text: A novel human coronavirus(SARS‐CoV‐2) causing a severe acute respiratory syndrome, coronavirus disease 2019 (COVID‐19), was reported in Wuhan, China at the end of 2019(Wang, Horby, Hayden, & Gao,2020; Khan, Ali, Siddique, Nabi, 2020).The infectionhas an estimated incubation period of 1‐14 days and its clinical manifestations and symptoms include cough, fever and shortness of breath (Zhuet al., 2020).


title: Why Challenge Trials of SARS‐CoV‐2 Vaccines Could Be Ethical Despite Risk of Severe Adverse Events

text: Human challenge trials to test the efficacy of vaccine candidates against SARS‐CoV‐2, the novel coronavirus behind Covid‐19, could save considerable time and many lives. But they may initially seem unethical because they expose healthy volunteers to a live virus that is killing many people and for which no cure exists. This article argues that this is not the correct test of their ethics. The correct test is comparative. And in the special circumstances of the Covid‐19 pandemic, human challenge trials meet the correct test better than standard efficacy testing would.


A commentary on “World Health Organization declares global emergency: A review of the 2019 novel Coronavirus (COVID-19)”


title: The importance of cellular-scale viral dynamics in bat reservoirs for emerging zoonotic disease

text: Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats’ virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity to promote the establishment of rapidly-propagating persistent infections within-host. Rapidly-replicating viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.


title: Severe Immune Thrombocytopenia Complicated by Intracerebral Haemorrhage Associated with Coronavirus Infection: A Case Report and Literature Review

text: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that causes isolated thrombocytopenia. Many viruses have been identified as triggering the autoimmune process, including HIV, MCV, EBV, parvovirus, rubella and measles. However, ITP in association with coronavirus infection has not previously been reported. We describe the case of a healthy man who presented with severe ITP complicated by intracranial haemorrhage following upper respiratory tract infection. An infection screen revealed coronavirus infection. LEARNING POINTS: Coronavirus can cause severe immune thrombocytopenic purpura (ITP). Intracerebral haemorrhage is an uncommon presentation of ITP. Intravenous immunoglobulin and steroids are very effective treatments for severe ITP.


title: The first six weeks - setting up a UK urgent dental care centre during the COVID-19 pandemic

text: Introduction The COVID-19 pandemic has posed many challenges, including provision of urgent dental care. This paper presents a prospective service evaluation during establishment of urgent dental care in the North East of England over a six-week period. Aim To monitor patient volumes, demographics and outcomes at the North East urgent dental care centre and confirm appropriate care pathways. Main outcome methods Data were collected on key characteristics of patients accessing urgent care from 23 March to 3 May 2020. Analysis was with descriptive statistics. Results There were 1,746 patient triages (1,595 telephone and 151 face-to-face), resulting in 1,322 clinical consultations. The most common diagnoses were symptomatic irreversible pulpitis or apical periodontitis. Sixty-five percent of clinical consultations resulted in extractions and 0.8% in an aerosol generating procedure. Patients travelled 25 km on average to access care; however, this reduced as more urgent care centres were established. The majority of patients were asymptomatic of COVID-19 and, to our knowledge, no staff acquired infection due to occupational exposure. Conclusion The urgent dental care centre effectively managed urgent and emergency dental care, with appropriate patient pathways established over the six-week period. Dental preparedness for future pandemic crises could be improved and informed by this data. Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1038/s41415-020-1708-2 für autorisierte Leser zusätzliche Dateien abrufbar.


title: Rapid identification of human‐infecting viruses

text: Viruses have caused much mortality and morbidity to humans and pose a serious threat to global public health. The virome with the potential of human infection is still far from complete. Novel viruses have been discovered at an unprecedented pace as the rapid development of viral metagenomics. However, there is still a lack of methodology for rapidly identifying novel viruses with the potential of human infection. This study built several machine learning models to discriminate human‐infecting viruses from other viruses based on the frequency of k‐mers in the viral genomic sequences. The k‐nearest neighbor (KNN) model can predict the human‐infecting viruses with an accuracy of over 90%. The performance of this KNN model built on the short contigs (≥1 kb) is comparable to those built on the viral genomes. We used a reported human blood virome to further validate this KNN model with an accuracy of over 80% based on very short raw reads (150 bp). Our work demonstrates a conceptual and generic protocol for the discovery of novel human‐infecting viruses in viral metagenomics studies.


title: Identification of a subdomain of CENP-B that is necessary and sufficient for localization to the human centromere

text: We have combined in vivo and in vitro approaches to investigate the function of CENP-B, a major protein of human centromeric heterochromatin. Expression of epitope-tagged deletion derivatives of CENP-B in HeLa cells revealed that a single domain less than 158 residues from the amino terminus of the protein is sufficient to localize CENP-B to centromeres. Centromere localization was abolished if as few as 28 amino acids were removed from the amino terminus of CENP-B. The centromere localization signal of CENP-B can function in an autonomous fashion, relocating a fused bacterial enzyme to centromeres. The centromere localization domain of CENP-B specifically binds in vitro to a subset of alpha-satellite DNA monomers. These results suggest that the primary mechanism for localization of CENP-B to centromeres involves the recognition of a DNA sequence found at centromeres. Analysis of the distribution of this sequence in alpha- satellite DNA suggests that CENP-B binding may have profound effects on chromatin structure at centromeres.


title: Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China

text: Coronavirus disease 2019 (COVID‐19) is a respiratory disorder caused by the highly contagious SARS‐CoV‐2. The immunopathological characteristics of COVID‐19 patients, either systemic or local, have not been thoroughly studied. In the present study, we analyzed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID‐19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells, and NK cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID‐19. IL‐6, IL‐10, and C‐reactive protein were remarkably up‐regulated in patients with severe COVID‐19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, the elevation of IL‐6, IL‐10, and C‐reactive protein are reliable indicators of severe COVID‐19.


title: Long-Term Stability Monitoring of Printed Proteins on Paper-Based Membranes

text: [Image: see text] Monitoring of long-term stability of proteins on paper-based membranes is important as it is directly related to paper-based sensor fabrication. By using a simple piezo printhead inkjet printer, recombinant proteins and antibodies were printed on paper-based membranes to test their stability and sensitivity under varying lengths of storage and temperature conditions. Our data show that a printed IgG-HRP antibody on simple printing paper maintains >50% functionality up to ∼2 months under 4 and −20 °C storage. Antibodies printed on polyvinylidene difluoride (PVDF) and nitrocellulose showed 5.3 and 9.7% decreases, respectively, in initial signal intensities compared to printing paper. Prostate-specific membrane antigen and tumor necrosis factor alpha recombinant proteins printed on paper-based membranes can be detected by antibodies, and antibody signal intensities can be detected up to 28 days after storage at 4 and −20 °C when printed on PVDF membrane or printing paper. These data suggest that printed proteins on simple printing paper and PVDF membrane can maintain their functionality up to few months when stored at 4 °C or lower and can be potentially applied in paper-based sensor development.


title: Susceptibility to phishing on social network sites: A personality information processing model

text: Today, the traditional approach used to conduct phishing attacks through email and spoofed websites has evolved to include social network sites (SNSs). This is because phishers are able to use similar methods to entice social network users to click on malicious links masquerading as fake news, controversial videos and other opportunities thought to be attractive or beneficial to the victim. SNSs are a phisher's “market” as they offer phishers a wide range of targets and take advantage of opportunities that exploit the behavioural vulnerabilities of their users. As such, it is important to further investigate aspects affecting behaviour when users are presented with phishing. Based on the literature studied, this research presents a theoretical model to address phishing susceptibility on SNSs. Using data collected from 215 respondents, the study examined the mediating role that information processing plays with regard to user susceptibility to social network phishing based on their personality traits, thereby identifying user characteristics that may be more susceptible than others to phishing on SNSs. The results from the structural equation modeling (SEM) analysis revealed that conscientious users were found to have a negative influence on heuristic processing, and are thus less susceptible to phishing on SNSs. The study also confirmed that heuristic processing increases susceptibility to phishing, thus supporting prior studies in this area. This research contributes to the information security discipline as it is one of the first to examine the effect of the relationship between the Big Five personality model and the heuristic-systematic model of information processing.


title: Race for a vaccine

text: With the coronavirus pandemic getting worse, we are turning to new techniques to deliver a vaccine in record time. Can it be done, asks Carrie Arnold


title: Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis

text: Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T-helper lymphocytes (P = 0·029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0·043) were significantly reduced during acute infection. Up-regulated expression both of Fas (P < 0·001) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (P < 0·001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0·03). Plasma levels of soluble Fas ligand (P = 0·028) and caspase-1 (P = 0·037), determined by enzyme-linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin-18, a product of caspase-1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.


Ethics and practical mitigations for ongoing clinical trials during the COVID-19 pandemic


title: Production of CCHF virus-like particle by a baculovirus-insect cell expression system

text: Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is a tick-born virus of the Nairovirus genus within the Bunyaviridae family, which is widespread and causes high fatality. The nucleocapsid of CCHFV is comprised of N proteins that are encoded by the S segment. In this research, the N protein of CCHFV was expressed in insect cells using a recombinant baculovirus. Under an electron microscope, Virus-Like Particles (VLPs) with various size and morphology were observed in cytoplasmic vesicles in the infected cells. Sucrose-gradient purification of the cell lysate indicated that the VLPs were mainly located in the upper fraction after ultracentrifugation, which was confirmed by Western blot analysis and immuno-electron microscopy (IEM).


title: REVISIÓNEcografía en el manejo del paciente crítico con infección por SARS-CoV-2 (COVID-19): aplicaciones clínicas en Medicina Intensiva-una revisión narrativa

text: RESUMEN La infección por SARS-CoV-2 (COVID-19) se caracteriza por producir en las formas graves, un cuadro de insuficiencia respiratoria que puede evolucionar hacia neumonía y síndrome de distrés respiratorio agudo (SDRA), presentar complicaciones como fenómenos trombóticos y disfunción cardiaca, lo que motiva el ingreso en la Unidad de Cuidados Intensivos (UCI). La ecografía, convertida en una herramienta de uso habitual en la UCI, puede ser muy útil durante la pandemia COVID-19 ya que la información obtenida por el clínico puede ser interpretada e integrada en la valoración global durante la exploración del paciente. Este documento describe algunas de sus aplicaciones con el objetivo de proporcionar una guía a los médicos responsables adaptado al paciente crítico con COVID-19. Alguna de sus aplicaciones desde el ingreso en la UCI incluyen confirmar la correcta posición del tubo endotraqueal, facilitar la inserción segura de las vías, e identificar complicaciones y fenómenos trombóticos. Además, la ecografía pleuropulmonar puede ser una alternativa diagnóstica válida que permite evaluar el grado de afectación pulmonar, mediante el análisis de patrones ecográficos específicos, identificación del derrame pleural y del barotrauma. La ecocardiografía proporciona información acerca de la afectación cardíaca, detección del cor pulmonale y estados de shock. ABSTRACT The clinical picture of SARS-CoV-2 infection (COVID-19) is characterized in its more severe form, by an acute respiratory failure which can worsen to pneumonia and acute respiratory distress syndrome (ARDS), and get complicated with thrombotic events and heart dysfunction. Therefore, admission to the Intensive Care Unit (ICU) is common. Ultrasound, which has become an everyday tool in the ICU, can be very useful during COVID-19 pandemic, since it provides the clinician with information which can be interpreted and integrated within a global assessment during the physical examination. A description of some of the potential applications of ultrasound is depicted in this document, in order to supply the physicians taking care of these patients with a adapted guide to the intensive care setting. Some of its applications since ICU admission include verification of the correct position of the endotracheal tube, contribution to safe cannulation of lines, and identification of complications and thrombotic events. Furthermore, pleural and lung ultrasound can be an alternative diagnostic test to assess the degree of involvement of the lung parenchyma by means of the evaluation of specific ultrasound patterns, identification of pleural effusions and barotrauma. Echocardiography provides information of heart involvement, detects cor pulmonale and shock states.


title: SARS-CoV-2 growth, furin-cleavage-site adaptation and neutralization using serum from acutely infected, hospitalized COVID-19 patients

text: SARS-CoV-2, the causative agent of COVID-19, emerged at the end of 2019 and by mid-June 2020, the virus has spread to at least 215 countries, caused more than 8,000,000 confirmed infections and over 450,000 deaths, and overwhelmed healthcare systems worldwide. Like SARS-CoV, which emerged in 2002 and caused a similar disease, SARS-CoV-2 is a betacoronavirus. Both viruses use human angiotensin-converting enzyme 2 (hACE2) as a receptor to enter cells. However, the SARS-CoV-2 spike (S) glycoprotein has a novel insertion that generates a putative furin cleavage signal and this has been postulated to expand the host range. Two low passage (P) strains of SARS-CoV-2 (Wash1: P4 and Munich: P1) were cultured twice in Vero-E6 cells and characterized virologically. Sanger and MinION sequencing demonstrated significant deletions in the furin cleavage signal of Wash1: P6 and minor variants in the Munich: P3 strain. Cleavage of the S glycoprotein in SARS-CoV-2-infected Vero-E6 cell lysates was inefficient even when an intact furin cleavage signal was present. Indirect immunofluorescence demonstrated the S glycoprotein reached the cell surface. Since the S protein is a major antigenic target for the development of neutralizing antibodies we investigated the development of neutralizing antibody titers in serial serum samples obtained from COVID-19 human patients. These were comparable regardless of the presence of an intact or deleted furin cleavage signal. These studies illustrate the need to characterize virus stocks meticulously prior to performing either in vitro or in vivo pathogenesis studies.


title: Incidence of Venous Thromboembolism in Critically Ill Coronavirus Disease 2019 Patients Receiving Prophylactic Anticoagulation

text: OBJECTIVES: One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses. The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation. DESIGN: Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation. SETTING: Tertiary-care center in Indianapolis, IN, United States. PATIENTS: Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 45 patients were included. Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis. Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02). Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). d-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both). Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35). Ultrasound evaluation is recommended if d-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if d-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%). CONCLUSIONS: Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019. There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. d-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.


title: Has there been an increased interest in smoking cessation during the first months of the COVID-19 pandemic? A Google Trends study

text: [Figure: see text]


title: The presence of viral subpopulations in an infectious bronchitis virus vaccine with differing pathogenicity – A preliminary study

text: There are currently four commercially available vaccines in Australia to protect chickens against infectious bronchitis virus (IBV). Predominantly, IBV causes clinical signs associated with respiratory or kidney disease, which subsequently cause an increase in mortality rate. Three of the current vaccines belong to the same subgroup (subgroup 1), however, the VicS vaccine has been reported to cause an increased vaccinal reaction compared to the other subgroup 1 vaccines. Molecular anomalies detected in VicS suggested the presence of two major subspecies, VicS-v and VicS-del, present in the commercial preparation of VicS. The most notable anomaly is the absence of a 40 bp sequence in the 3′UTR of VicS-del. In this investigation, the two subspecies were isolated and shown to grow independently and to similar titres in embryonated chicken eggs. An in vivo investigation involved 5 groups of 20 chickens each and found that VicS-del grew to a significantly lesser extent in the chicken tissues collected than did VicS-v. The group inoculated with an even ratio of the isolated subspecies scored the most severe clinical signs, with the longest duration. These results indicate the potential for a cooperative, instead of an expected competitive, relationship between VicS-v and VicS-del to infect a host, which is reminiscent of RNA viral quasi-species.


title: SARS-CoV2 (COVID-19) Structural/Evolution Dynamicome: Insights into functional evolution and human genomics

text: The SARS-CoV-2 pandemic, starting in 2019, has challenged the speed at which labs perform science, ranging from discoveries of the viral composition to handling health outcomes in humans. The small ~30kb single-stranded RNA genome of Coronaviruses makes them adept at cross species spread and drift, increasing their probability to cause pandemics. However, this small genome also allows for a robust understanding of all proteins coded by the virus. We employed protein modeling, molecular dynamic simulations, evolutionary mapping, and 3D printing to gain a full proteome and dynamicome understanding of SARS-CoV-2. The Viral Integrated Structural Evolution Dynamic Database (VIStEDD) has been established (prokoplab.com/vistedd), opening future discoveries and educational usage. In this paper, we highlight VIStEDD usage for nsp6, Nucleocapsid (N), and Spike (S) surface glycoprotein. For both nsp6 and N we reveal highly conserved surface amino acids that likely drive protein-protein interactions. In characterizing viral S protein, we have developed a quantitative dynamics cross correlation matrix insight into interaction with the ACE2/SLC6A19 dimer complex. From this quantitative matrix, we elucidated 47 potential functional missense variants from population genomic databases within ACE2/SLC6A19/TMPRSS2, warranting genomic enrichment analyses in SARS-CoV-2 patients. Moreover, these variants have ultralow frequency, but can exist as hemizygous in males for ACE2, which falls on the X-chromosome. Two noncoding variants (rs4646118 and rs143185769) found in ~9% of African descent individuals for ACE2 may regulate expression and be related to increased susceptibility of African Americans to SARS-CoV-2. This powerful database of SARS-CoV-2 can aid in research progress in the ongoing pandemic.


title: Conduites addictives: faits cliniques*

text: Résumé Malgré les fréquentes comorbidités psychiatriques, le trouble de l’usage de substance doit être appréhendé comme une pathologie autonome par ses déterminants, sa sémiologie et ses modalités évolutives spontanées ou sous traitement. De multiples produits de synthèse sont désormais accessibles via internet : associé à la créativité des chimistes cela a participé à l'émergence de pratiques inédites allant du chemsex au purple drank. Les conduites addictives résultent d’un ensemble de facteurs individuels (vulnérabilités biologique et psychique) et contextuels (disponibilité et banalisation du toxique dans l’environnement). Les pathologies mentales autres sont des facteurs de vulnérabilité à la pathologie addictive, tout comme les conduites addictives peuvent révéler une pathologie émotionnelle ou psychotique. Le médecin se doit d’entendre l’impuissance du malade face au besoin irrépressible de consommer (craving) et proposer une thérapeutique qui peut être chimique (y compris traitement de substitution) et psychologique. Dans la majorité des cas un accompagnement social s’impose pour corriger les effets désocialisants du trouble de l’usage de substances ou des comportements addictifs. Abstract Despite the frequency of psychiatric comorbidities, substance use disorder must be understood as an autonomous pathology due to its own determinants, semiology and possibilities of evolution, either spontaneous or under treatment. The ease of access to multiple synthetic products via the Internet combined with the creativity of chemists are contributing to the emergence of novel practices ranging from chemsex to purple drank. Addictive behaviours result from a combination of individual factors (biological and psychological vulnerability) and contextual factors (availability and triviality of the toxicant in the environment). Other mental disorders are factors of vulnerability to addictive pathology as well as the addictive behaviours can reveal an emotional or psychotic pathology. The physician needs to hear the patient powerlessness hidden behind the craving and propose a therapy that may be chemical (including substitution treatment) and psychological. Most of the time, social support is necessary to correct the desocializing effects of substance use disorder or addictive behaviours.


title: JAK Inhibition as a New Treatment Strategy for Patients with COVID-19

text: After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1–7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19. Since the combination of MTX and baricitinib leads to outstanding clinical outcomes, the addition of baricitinib to MTX might be a potential strategy.


title: Quantitative Proteomic Identification of Host Factors Involved in the Salmonella typhimurium Infection Cycle

text: Quantitative proteomics, based on stable isotope labeling by amino acids in cell culture (SILAC), can be used to identify host proteins involved in the intracellular interplay with pathogens. This method allows identification of proteins subject to degradation or upregulation in response to intracellular infection. It can also be used to study intracellular dynamics (trafficking) of proteins in response to the infection. Here, we describe the analysis of changes in protein profiles determined in Golgi-enriched fractions isolated from cells that were either mock-infected or infected with Salmonella typhimurium. Using the SILAC approach we were able to identify 105 proteins in Golgi-enriched fractions that were significantly changed in their abundance as a result of Salmonella infection.


Aktuelles medizinrechtliches Schrifttum, Richtlinien und Empfehlungen


title: Trafficking of Plant Plasma Membrane Aquaporins: Multiple Regulation Levels and Complex Sorting Signals

text: Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions.


Letter in response to the article: Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers (Singh et al.)


Protecting the world from infectious disease threats: now or never


title: Lockdown Maths: Part 1: Why We Must Comply

text: The following article is reproduced with permission from The Telegraph, Kolkata (Guest Column, Published on 25 March 2020).


title: Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

text: Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.


title: Viral nephropathy

text: Viral infections can cause many glomerular diseases. The diagnostic criteria for virus-related nephropathy include detailed clinical and laboratory data, and tissue molecular analysis. Several mechanisms are involved in the pathogenesis of virus-related nephropathy, including tropism of the virus in the kidney, induction of abnormal immune complexes, direct cytopathogenic effects, and multiorgan failure. Hepatitis B virus is associated with membranous nephropathy and mesangiocapillary glomerulonephritis in endemic areas. Hepatitis C virus causes various forms of glomerulonephritis, including cryoglobulinemia-mediated glomerulonephritis. Infection with HIV is associated with a collapsing focal segmental glomerulosclerosis, a distinctive disease that affects mainly Africans and African Americans. In the course of HIV infection, other types of immune complex glomerulonephritis can occur, most frequently in whites. Recent reports indicate a role for parvovirus B19 in 'idiopathic' collapsing focal segmental glomerulosclerosis. Both hantaviruses, and coronaviruses associated with severe acute respiratory syndrome, can lead to acute renal failure. Renal biopsy followed by appropriate serological and molecular testing is essential for defining virus-related glomerular lesions and guiding prognostic and therapeutic evaluation.


title: BAG3 down-modulation sensitizes HPV18+ HeLa cells to PEITC-induced apoptosis and restores p53

text: Abstract BAG3 is a multi-functional component of tumor cell pro-survival machinery, and its biological functions have been largely associated to proteasome system. Here, we show that BAG3 down-modulation resulted in reduced cell viability and enhanced PEITC-induced apoptosis largely more extensively in HeLa (HPV18+) rather than in C33A (HPV−) cervical carcinoma cell lines. Moreover, we demonstrate that BAG3 suppression led to a decrease of viral E6 oncoprotein and a concomitant recovery of p53 tumor suppressor, the best recognized target of E6 for proteasome degradation. E6 and p53 expression were modulated at protein level, since their respective mRNAs were unaffected. Taken together our findings reveal a novel role for BAG3 as host protein contributing to HPV18 E6-activated pro-survival strategies, and suggest a possible relevance of its expression levels in drug/radiotherapy-resistance of HPV18-bearing cervical carcinomas.


title: Update on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection, and Guidance for the Public, Clinicians, and Public Health Authorities — January 2015

text: CDC continues to work with the World Health Organization (WHO) and other partners to closely monitor Middle East respiratory syndrome coronavirus (MERS-CoV) infections globally and to better understand the risks to public health. The purpose of this report is to provide a brief update on MERS-CoV epidemiology and to notify health care providers, public health officials, and others to maintain awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula.


title: Clinical and laboratory predictors of in-hospital mortality in patients with COVID-19: a cohort study in Wuhan, China

text: BACKGROUND: This study aimed to develop mortality-prediction models for patients with Coronavirus disease 2019 (COVID-19). METHODS: The training cohort were consecutive patients with COVID-19 in the First People’s Hospital of Jiangxia District in Wuhan from January 7, 2020 to February 11, 2020. We selected baseline clinical and laboratory data through the stepwise Akaike information criterion and ensemble XGBoost model to build mortality-prediction models. We then validated these models by randomly collecting COVID-19 patients in the Infection department of Union Hospital in Wuhan from January 1, 2020, to February 20, 2020. RESULTS: 296 patients with COVID-19 were enrolled in the training cohort, 19 of whom died during hospitalization and 277 were discharged from the hospital. The clinical model developed with age, history of hypertension and coronary heart disease showed AUC of 0.88 (95% CI, 0.80-0.95); threshold, -2.6551; sensitivity, 92.31%; specificity, 77.44% and negative predictive value (NPV), 99.34%. The laboratory model developed with age, high-sensitivity C-reactive protein (hsCRP), peripheral capillary oxygen saturation (SpO2), neutrophil and lymphocyte count, D-dimer, aspartate aminotransferase (AST) and glomerular filtration rate (GFR) had a significantly stronger discriminatory power than the clinical model (p=0.0157), with AUC of 0.98 (95% CI, 0.92-0.99); threshold, -2.998; sensitivity, 100.00%; specificity, 92.82% and NPV, 100.00%. In the subsequent validation cohort (N=44), the AUCs (95% CI) were 0.83 (0.68, 0.93) and 0.88 (0.75, 0.96) for clinical model and laboratory model, respectively. CONCLUSIONS: We developed two predictive models for the in-hospital mortality of patients with COVID-19 in Wuhan and validated in patients from another center.


title: Rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in Chinese macaques

text: Abstract Angiotensin converting enzyme 2 (ACE2) is the receptor that severe acute respiratory syndrome coronavirus (SARS-CoV) utilizes for target cell entry and, therefore, plays an important role in SARS pathogenesis. Since Chinese rhesus (rh) macaques do not usually develop SARS after SARS-CoV infection, it has been suggested that rh-ACE2 probably does not support viral entry efficiently. To determine the role of rh-ACE2 in early lung pathogenesis in vivo, we studied eleven Chinese rhesus monkeys experimentally infected with a pathogenic SARS-CoVPUMC01 strain. Rh-ACE2 genes were amplified from all animals by reverse transcription polymerase chain reaction, and their function was studied in vitro using a pseudovirus entry assay. Many natural non-synonymous (NS) changes were found in rh-ACE2 genes. Compared to human (hu) ACE2, thirty-eight consensus NS changes were found in rh-ACE2. Since these changes do not interact with the receptor binding domain of SARS-CoV, rh-ACE2 in general is as effective as human homolog in supporting viral entry. Rh-ACE2, however, is more polymorphic than hu-ACE2. Additional sporadic NS substitutions in clone Rh11-7 reduced the level of rh-ACE2 protein expression and did not support viral entry effectively. Further mutagenesis analysis showed that a natural mutation Y217N dramatically alters ACE2 expression and entry efficiency. Moreover, introduction of the Y217N mutation into hu-ACE2 caused the down-regulation of expression and reduced viral entry efficiency. These results indicate that the Y217N mutation plays a role in modulating SARS-CoV infection. Our results provide insights for understanding the role of rh-ACE2 in SARS lung pathogenesis in a non-human primate model.


title: Control of cryptosporidiosis in neonatal calves: Use of halofuginone lactate in two different calf rearing systems

text: Abstract To date there is no effective treatment for bovine cryptosporidiosis. This study describes the use of halofuginone lactate in preventing cryptosporidiosis in naturally infected neonatal calves on a dairy farm with a high prevalence of infection. The animals were kept in two different calf rearing systems. A randomized double-blind trial was carried out with 32 naturally infected calves, divided into four groups. The two prophylactic halofuginone lactate treated groups were kept in either individual or group pens. Similarly, the animals receiving the placebo were housed in either individual pens or together in a large pen. A total of ten faecal samples were collected periodically during the 28 days study from each calf and tested for the presence of Cryptosporidium spp. using microscopic and molecular methods. Generalized estimating equations models were used to determine if the effects of the various treatments and/or rearing systems on the presence of diarrhoea and infection were statistically significant. Further analysis (classification trees models) was carried out to explore possible risk factors for cryptosporidiosis and interactions between treatments and rearing systems. Halofuginone lactate was shown to be effective in reducing clinical signs of cryptosporidiosis and environmental contamination. However, the treatment did not delay the onset of diarrhoea and did not reduce the risk of infection amongst calves reared together in a highly contaminated environment. The use of halofuginone lactate in combination with good hygienic measures, such as rearing animals in clean individual pens, was the most effective method to reduce the risk of cryptosporidiosis amongst 7–13 days old calves. It was concluded that the control of the parasite could be achieved by the combination of using effective preventive drugs, such as halofuginone lactate and good animal husbandry procedures.


docid: ikhtwyzy

title: Porcine deltacoronavirus causes diarrhea in various ages of field-infected pigs in China

text: Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes acute diarrhea in suckling piglets. In Henan province of China, three swine farms broke out diarrhea in different ages of pigs during June of 2017, March of 2018 and January of 2019, respectively. PCR method, Taqman real-time RT-PCR method, sequencing, histopathology and immunohistochemistry (IHC) were conducted with the collected samples, and the results showed that PDCoV was detected among the suckling piglets, commercial fattening pigs and sows with diarrhea. PDCoV-infected suckling piglets were characterized with thin and transparent intestinal walls from colon to caecum, spot hemorrhage at mesentery and intestinal bleeding. PDCoV RNA was detected in multiple organs and tissues by Taqman real-time RT-PCR, which had high copies in ileum, inguinal lymph node, rectum and spleen. PDCoV antigen was detected in the basal layer of jejunum and ileum by IHC. In this research, we found that PDCoV could infect various ages of farmed pigs with watery diarrhea and anorexia in different seasons in a year.


docid: clrwsgni

title: Passive immunotherapy of viral infections: ‘super-antibodies’ enter the fray

text: Antibodies have been used for more than 100 years in the therapy of infectious diseases but a new generation of highly potent and/or broadly cross-reactive human monoclonal antibodies (sometimes referred to as ‘super-antibodies’) offers new opportunities for intervention. The isolation of these antibodies, which are often rarely induced in human infections, has primarily been achieved by large-scale screening for suitable donors and new single B cell approaches to human monoclonal antibody generation. Engineering the antibodies to improve half-life and effector functions has further augmented their in vivo activity in some cases. Super-antibodies offer promise for the prophylaxis and therapy of infections with a range of viruses, including those that are highly antigenically variable and those that are newly emerging or have pandemic potential. The next few years will be decisive in the realization of the promise of super-antibodies.


Genotyping SARS-CoV-2 through an interactive web application


title: The Covid-19 crisis as a career shock: Implications for careers and vocational behavior

text: Abstract The covid-19 pandemic is a career shock for many people across the globe. In this article, we reflect on how insights from the literature on career shocks can help us understand the career consequences of the pandemic and offer suggestions for future research in this area. In particular, we offer three “key lessons”. The first lesson is that the implications of Covid-19 reflect the dynamic interplay between individual and contextual factors. Here, we argue that although the pandemic was difficult to predict and control, research shows that certain psychological resources – such as career competencies and resilience – could make this career shock more manageable. The second lesson is that the pandemic may have differential implications over time, as suggested by research that has shown the consequences of career shocks to differ between short-term vs. long-term time horizons, and across life- and career stages. The third lesson is that, even though the pandemic is clearly a negatively valenced shock for most people, further into the future it may allow for more positive outcomes. This lesson builds on research showing how negative career shocks have long-term positive consequences for some people. We hope that these insights will inspire both scholars and practitioners to study and understand the work and career implications of Covid-19 as a career shock, as well as to support people in dealing with its consequences.


title: RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses

text: As the COVID-19 outbreak spreads, there is a growing need for a compilation of conserved RNA genome regions in the SARS-CoV-2 virus along with their structural propensities to guide development of antivirals and diagnostics. Using sequence alignments spanning a range of betacoronaviruses, we rank genomic regions by RNA sequence conservation, identifying 79 regions of length at least 15 nucleotides as exactly conserved over SARS-related complete genome sequences available near the beginning of the COVID-19 outbreak. We then confirm the conservation of the majority of these genome regions across 739 SARS-CoV-2 sequences reported to date from the current COVID-19 outbreak, and we present a curated list of 30 ‘SARS-related-conserved’ regions. We find that known RNA structured elements curated as Rfam families and in prior literature are enriched in these conserved genome regions, and we predict additional conserved, stable secondary structures across the viral genome. We provide 106 ‘SARS-CoV-2-conserved-structured’ regions as potential targets for antivirals that bind to structured RNA. We further provide detailed secondary structure models for the 5’ UTR, frame-shifting element, and 3’ UTR. Last, we predict regions of the SARS-CoV-2 viral genome have low propensity for RNA secondary structure and are conserved within SARS-CoV-2 strains. These 59 ‘SARS-CoV-2-conserved-unstructured’ genomic regions may be most easily targeted in primer-based diagnostic and oligonucleotide-based therapeutic strategies.


title: Updating the diagnostic criteria of COVID-19 “suspected case” and “confirmed case” is necessary

text: On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of “suspected case” and “confirmed case” according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People’s Republic of China.


title: Prion-like Domains in Eukaryotic Viruses

text: Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.


title: A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L

text: Human cathepsin L belongs to the cathepsin family of proteolytic enzymes with primarily an endopeptidase activity. Although its primary functions were originally thought to be only of a housekeeping enzyme that degraded intracellular and endocytosed proteins in lysosome, numerous recent studies suggest that it plays many critical and specific roles in diverse cellular settings. Not surprisingly, the dysregulated function of cathepsin L has manifested itself in several human diseases, making it an attractive target for drug development. Unfortunately, several redundant and isoform-specific functions have recently emerged, adding complexities to the drug discovery process. To address this, a series of chemical biology tools have been developed that helped define cathepsin L biology with exquisite precision in specific cellular contexts. This review elaborates on the recently developed small molecule inhibitors and probes of human cathepsin L, outlining their mechanisms of action, and describing their potential utilities in dissecting unknown function.


Union Promises About Pandemic Safety


title: Radiological Society of North America Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA

text: Routine screening CT for the identification of COVID-19 pneumonia is currently not recommended by most radiology societies. However, the number of CTs performed in persons under investigation (PUI) for COVID-19 has increased. We also anticipate that some patients will have incidentally detected findings that could be attributable to COVID-19 pneumonia, requiring radiologists to decide whether or not to mention COVID-19 specifically as a differential diagnostic possibility. We aim to provide guidance to radiologists in reporting CT findings potentially attributable to COVID-19 pneumonia, including standardized language to reduce reporting variability when addressing the possibility of COVID-19. When typical or indeterminate features of COVID-19 pneumonia are present in endemic areas as an incidental finding, we recommend contacting the referring providers to discuss the likelihood of viral infection. These incidental findings do not necessarily need to be reported as COVID-19 pneumonia. In this setting, using the term “viral pneumonia” can be a reasonable and inclusive alternative. However, if one opts to use the term “COVID-19” in the incidental setting, consider the provided standardized reporting language. In addition, practice patterns may vary, and this document is meant to serve as a guide. Consultation with clinical colleagues at each institution is suggested to establish a consensus reporting approach. The goal of this expert consensus is to help radiologists recognize findings of COVID-19 pneumonia and aid their communication with other healthcare providers, assisting management of patients during this pandemic.


Editorial: Emerging Swine Viruses


title: Inevitable isolation and the change of stress markers in hemodialysis patients during the 2015 MERS-CoV outbreak in Korea

text: During the outbreak of Middle East respiratory syndrome coronavirus(MERS-CoV) in 2015, one hemodialysis patient was infected with MERS-CoV, and the remaining hemodialysis(HD) patients (n = 83) and medical staff (n = 12) had to undergo dialysis treatment in an isolated environment. This study was performed to investigate the effects of stress caused by dialysis treatment under isolation. Plasma samples from the HD patients and medical staff were collected at the time of isolation(M0), the following month(M1), and three months after isolation(M3). Parameters for stress included circulating cell-free genomic DNA(ccf-gDNA), circulating cell-free mitochondria DNA(ccf-mtDNA), and pentraxin-3(PTX-3). Decreased values of Hct, kt/v and ca x p were recovered after the end of two weeks of isolation. The levels of ccf-gDNA and ccf-mtDNA were the highest at M0 and decreased gradually in both HD patients and the medical staff. The normalization of ccf-gDNA and ccf-mtDNA was significantly delayed in HD patients compared with the response in the medical staff. PTX-3 increased only in HD patients and was highest at M0, and it then gradually decreased. Medical isolation and subnormal quality of care during the MERS outbreak caused extreme stress in HD patients. Plasma cell-free DNA and PTX-3 seems to be good indicators of stress and quality of care in HD patients.


title: Patient factors associated with SARS‐CoV‐2 in an admitted emergency department population

text: Background: The SARS‐CoV‐2 (COVID‐19) virus has wide community spread. The aim of this study was to describe patient characteristics and to identify factors associated with COVID‐19 among emergency department patients under investigation for COVID‐19 who were admitted to the hospital. Methods: This was a retrospective observational study from eight emergency departments within a nine‐hospital health system. Patients with COVID‐19 testing around the time of hospital admission were included. The primary outcome measure was COVID‐19 test result. Patient characteristics were described and a multivariable logistic regression model was used to identify factors associated with a positive COVID‐19 test. Results: During the study period from March 1, 2020 to April 8, 2020, 2,182 admitted patients had a test resulted for COVID‐19. Of these patients, 786 (36%) had a positive test result. For COVID positive patients, 63 (8.1%) died during hospitalization. COVID‐19 positive patients had lower pulse oximetry (0.91 [95%CI], [0.88‐0.94]), higher temperatures (1.36 [1.26‐1.47]), and lower leukocyte counts than negative patients (0.78 [0.75‐0.82]). Chronic lung disease (OR 0.68, [0.52‐0.90]) and histories of alcohol (0.64 [0.42‐0.99]) or substance abuse (0.39 [0.25‐0.62]) were less likely to be associated with a positive COVID‐19 result. Conclusion: We observed a high percentage of positive results among an admitted emergency department cohort under investigation for COVID‐19. Patient factors may be useful in early differentiation of patients with COVID‐19 from similarly presenting respiratory illnesses although no single factor will serve this purpose. This article is protected by copyright. All rights reserved


title: Relationship between hospital ward design and healthcare-associated infection rates: a systematic review and meta-analysis

text: BACKGROUND: The influence of the hospital’s infrastructure on healthcare-associated colonization and infection rates has thus far infrequently been examined. In this review we examine whether healthcare facility design is a contributing factor to multifaceted infection control strategies. METHODS: We searched PubMed/MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) from 1990 to December 31(st), 2015, with language restriction to English, Spanish, German and French. RESULTS: We identified three studies investigating accessibility of the location of the antiseptic hand rub dispenser. Each of them showed a significant improvement of hand hygiene compliance or agent consumption with the implementation of accessible dispensers near the patient bed. Nine eligible studies evaluated the impact of single-patient rooms on the acquisition of healthcare-associated colonization and infections in comparison to multi-bedrooms or an open ward design. Six of these studies showed a significant benefit of single-patient bedrooms in reducing the healthcare-associated colonization and infection rate, whereas three studies found that single-patient rooms are neither a protective nor risk factor. In meta-analyses, the overall risk ratio for acquisition of healthcare-associated colonization and infection was 0.55 (95% CI: 0.41 to 0.74), for healthcare-associated colonization 0.52 (95% CI: 0.32 to 0.85) and for bacteremia 0.64 (95% CI: 0.53 to 0.76), all in favor of patient care in single-patient bedrooms. CONCLUSION: Implementation of single-patient rooms and easily accessible hand rub dispensers located near the patient’s bed are beneficial for infection control and are useful parts of a multifaceted strategy for reducing healthcare-associated colonization and infections.


Séance commune de l’Académie nationale de médecine et de l’Académie d’Agriculture de France : « Émergence des maladies infectieuses : causes, détection, prévision »


title: Biosafety in the preparation and processing of cytology specimens with potential coronavirus (COVID‐19) infection: Perspectives from Taiwan

text: This commentary focuses on the cytopathology laboratory, the authors' experiences with coronavirus (COVID‐19) in Taiwan, and current guidelines on COVID‐19 infection prevention and control. The objective of this report is to provide cytopathology professionals a timely, in‐depth, evidence‐based review of biosafety practices for those at risk for coronavirus (COVID‐19) infection.


title: Panglobalism and pandemics: ecological and ethical concerns.

text: A pandemic is a human medical problem but must be understood at multiple levels. Analysis of social and commercial forces is vital, and, more comprehensively, an ecological framework is necessary for an inclusive picture. Ecological health webworked with political and social determinants surrounds issues of human health. In this constellation of both natural and social factors, ethical concerns will arise at these multiple levels, from human health to the conservation and health of wild nature.


title: Hedging jet fuel price risk: The case of U.S. passenger airlines

text: Abstract Jet fuel accounts for a large portion of passenger airlines' operating costs, and airlines' earnings are susceptible to swings in the price of jet fuel. This study uses daily data over the past two decades to determine the minimum variance hedge ratio for airlines wishing to hedge jet fuel price risk with futures, while also establishing the best cross hedging asset. Airlines hedging with futures would create the most effective hedge by using heating oil futures contracts with a 3-month maturity. We also find that beyond the 3-month veil, increased time to maturity makes heating oil less effective as a cross hedge proxy for jet fuel. However, both in-sample analysis and Monte Carlo simulation results with daily data show that none of the 4 cross hedge proxies, including heating oil, can be considered highly effective.


title: Education to Action: Improving Public Perception of Bats

text: Public perception of bats has historically been largely negative with bats often portrayed as carriers of disease. Bats are commonly associated with vampire lore and thus elicit largely fearful reactions despite the fact that they are a vital and valuable part of the ecosystem. Bats provide a variety of essential services from pest control to plant pollination. Despite the benefits of bats to the environment and the economy, bats are suffering at the hands of humans. They are victims of turbines, human encroachment, pesticides, and, most recently, white nose syndrome. Because of their critical importance to the environment, humans should do what they can to help protect bats. We propose that humans will be more likely to do so if their perceptions and attitudes toward bats can be significantly improved. In a preliminary study we found some support for the idea that people can be educated about bats through bat oriented events and exhibits, and that this greater knowledge can inspire humans to act to save bats.


title: Can extreme MHC class I diversity be a feature of a wide geographic range? The example of Seba’s short-tailed bat (Carollia perspicillata)

text: The major histocompatibility complex (MHC) is one of the most diverse genetic regions under pathogen-driven selection because of its central role in antigen binding and immunity. The highest MHC variability, both in terms of the number of individual alleles and gene copies, has so far been found in passerine birds; this is probably attributable to passerine adaptation to both a wide geographic range and a diverse array of habitats. If extraordinary high MHC variation and duplication rates are adaptive features under selection during the evolution of ecologically and taxonomically diverse species, then similarly diverse MHC architectures should be found in bats. Bats are an extremely species-rich mammalian group that is globally widely distributed. Many bat species roost in multitudinous groups and have high contact rates with pathogens, conspecifics, and allospecifics. We have characterized the MHC class I diversity in 116 Panamanian Seba’s short-tailed bats (Carollia perspicillata), a widely distributed, generalist, neotropical species. We have detected a remarkable individual and population-level diversity of MHC class I genes, with between seven and 22 alleles and a unique genotype in each individual. This diversity is comparable with that reported in passerine birds and, in both taxonomic groups, further variability has evolved through length polymorphisms. Our findings support the hypothesis that, for species with a geographically broader range, high MHC class I variability is particularly adaptive. Investigation of the details of the underlying adaptive processes and the role of the high MHC diversity in pathogen resistance are important next steps for a better understanding of the role of bats in viral evolution and as carriers of several deadly zoonotic viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00251-019-01128-7) contains supplementary material, which is available to authorized users.


title: Production of Monospecific Rabbit Antisera Recognizing Nidovirus Proteins

text: The importance of monospecific antisera for the experimental analysis of viral proteins is undisputed. They make it possible to identify and analyze the target protein against a background of a large number of other proteins, either in whole fixed cells or in cell lysates. This chapter describes our experience with the production of such rabbit antisera directed against proteins of coronaviruses and other nidoviruses. The use as antigens of either synthetic peptides (coupled to a carrier protein) or proteins expressed in Escherichia coli is described, and detailed protocols for immunization and preparation of test bleeds are provided. For screening of the immune response following immunization, detailed protocols for three commonly used techniques are described, all of which are based on the use of infected cells or cells expressing the protein of interest, side by side with appropriate controls. The in situ immunodetection of the target in fixed cells by immunofluorescence microscopy is described, as are protocols for techniques that can be applied to cell lysates containing the target protein (Western blotting and immunoprecipitation). The latter techniques are performed in combination with polyacrylamide gel electrophoresis, thus allowing confirmation of the molecular weight of the target that is recognized by the antiserum.


title: The dirigent multigene family in Isatis indigotica: gene discovery and differential transcript abundance

text: BACKGROUND: Isatis indigotica Fort. is one of the most commonly used traditional Chinese medicines. Its antiviral compound is a kind of lignan, which is formed with the action of dirigent proteins (DIR). DIR proteins are members of a large family of proteins which impart stereoselectivity on the phenoxy radical-coupling reaction, yielding optically active lignans from two molecules of E-coniferyl alcohol. They exist in almost every vascular plant. However, the DIR and DIR-like protein gene family in I. indigotica has not been analyzed in detail yet. This study focuses on discovery and analysis of this protein gene family in I. indigotica for the first time. RESULTS: Analysis of transcription profiling database from I. indigotica revealed a family of 19 full-length unique DIR and DIR-like proteins. Sequence analysis found that I. indigotica DIR and DIR-like proteins (IiDIR) were all-beta strand proteins, with a signal peptide at the N-terminus. Phylogenetic analysis of the 19 proteins indicated that the IiDIR genes cluster into three distinct subfamilies, DIR-a, DIR-b/d, and DIR-e, of a larger plant DIR and DIR-like gene family. Gene-specific primers were designed for 19 unique IiDIRs and were used to evaluate patterns of constitutive expression in different organs. It showed that most IiDIR genes were expressed comparatively higher in roots and flowers than stems and leaves. CONCLUSIONS: New DIR and DIR-like proteins were discovered from the transcription profiling database of I. indigotica through bioinformatics methods for the first time. Sequence characteristics and transcript abundance of these new genes were analyzed. This study will provide basic data necessary for further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-388) contains supplementary material, which is available to authorized users.


title: Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia

text: PURPOSE: To review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid’s secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated. RESULTS: All cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC. CONCLUSION: U-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.


docid: zgdfupfm

title: Intestinal microbiome transfer, a novel therapeutic strategy for COVID-19 induced hyperinflammation?: In reply to, ‘COVID-19: Immunology and treatment options’, Felsenstein, Herbert McNamara et al. 2020′


title: Assessment of SARS-CoV-2 Infection Prevalence in Homeless Shelters — Four U.S. Cities, March 27–April 15, 2020

text: In the United States, approximately 1.4 million persons access emergency shelter or transitional housing each year (1). These settings can pose risks for communicable disease spread. In late March and early April 2020, public health teams responded to clusters (two or more cases in the preceding 2 weeks) of coronavirus disease 2019 (COVID-19) in residents and staff members from five homeless shelters in Boston, Massachusetts (one shelter); San Francisco, California (one); and Seattle, Washington (three). The investigations were performed in coordination with academic partners, health care providers, and homeless service providers. Investigations included reverse transcription-polymerase chain reaction testing at commercial and public health laboratories for SARS-CoV-2, the virus that causes COVID-19, over approximately 1-2 weeks for residents and staff members at the five shelters. During the same period, the team in Seattle, Washington, also tested residents and staff members at 12 shelters where a single case in each had been identified. In Atlanta, Georgia, a team proactively tested residents and staff members at two shelters with no known COVID-19 cases in the preceding 2 weeks. In each city, the objective was to test all shelter residents and staff members at each assessed facility, irrespective of symptoms. Persons who tested positive were transported to hospitals or predesignated community isolation areas.


docid: viccvfbl

title: Hospital-Acquired Respiratory Viral Infections: Incidence, Morbidity, and Mortality in Pediatric and Adult Patients

text: BACKGROUND. Hospital-acquired respiratory viral infections can result in morbidity and mortality of hospitalized patients. This study was undertaken to better understand the magnitude of the problem of nosocomial respiratory viral infections in adult and pediatric patients. METHODS. This was a retrospective study at a tertiary care adult and pediatric teaching hospital. Study patients met a priori criteria for definite or possible nosocomial respiratory viral infection. RESULTS. From April 1, 2015 to April 1, 2016, we identified 40 nosocomial respiratory viral infections in 38 patients involving 14 definite and 3 possible cases in our adult hospital and 18 definite and 5 possible cases in our pediatric hospital. The incidence was 5 cases/10 000 admissions and 44 cases/10 000 admissions to our adult and pediatric hospitals, respectively. Only 6.8% of cases were due to influenza. Although 63% of cases occurred during the fall and winter, such infections were identified throughout the year. Five (13%) nosocomial respiratory viral infections occurred in 2 adult and 3 pediatric patients who died during the hospitalization. CONCLUSIONS. Nosocomial respiratory viral infections are an underappreciated cause of morbidity and mortality in hospitalized adult and pediatric patients. The incidence was nearly 10-fold higher in our pediatric hospital. We estimate there are approximately 18 955 pediatric and adult cases of nosocomial respiratory viral infections in US acute care hospitals each year.


La neumología en tiempos del COVID-19


title: Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability. Moreover, these peptides, particularly HKU4-HR2P2 and HKU4-HR2P3, exhibited potent inhibitory activity against MERS-CoV S-mediated cell–cell fusion and viral infection, suggesting that these HKU4 HR2-derived peptides could be candidates for futher development as antiviral agents against MERS-CoV infection.


title: Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?

text: Severe coronavirus disease (COVID-19) is characterized by pulmonary hyper-inflammation and potentially life-threatening “cytokine storms”. Controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral therapies. Endogenous lipid autacoid mediators, referred to as eicosanoids, play a critical role in the induction of inflammation and pro-inflammatory cytokine production. SARS-CoV-2 may trigger a cell death (“debris”)-induced “eicosanoid storm”, including prostaglandins and leukotrienes, which in turn initiates a robust inflammatory response. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving lipid autacoid mediators (SPMs), such as resolvins. Resolvins and other SPMs stimulate macrophage-mediated clearance of debris and counter pro-inflammatory cytokine production, a process called inflammation resolution. SPMs and their lipid precursors exhibit anti-viral activity at nanogram doses in the setting of influenza without being immunosuppressive. SPMs also promote anti-viral B cell antibodies and lymphocyte activity, highlighting their potential use in the treatment of COVID-19. Soluble epoxide hydrolase (sEH) inhibitors stabilize arachidonic acid-derived epoxyeicosatrienoic acids (EETs), which also stimulate inflammation resolution by promoting the production of pro-resolution mediators, activating anti-inflammatory processes, and preventing the cytokine storm. Both resolvins and EETs also attenuate pathological thrombosis and promote clot removal, which is emerging as a key pathology of COVID-19 infection. Thus, both SPMs and sEH inhibitors may promote the resolution of inflammation in COVID-19, thereby reducing acute respiratory distress syndrome (ARDS) and other life-threatening complications associated with robust viral-induced inflammation. While most COVID-19 clinical trials focus on “anti-viral” and “anti-inflammatory” strategies, stimulating inflammation resolution is a novel host-centric therapeutic avenue. Importantly, SPMs and sEH inhibitors are currently in clinical trials for other inflammatory diseases and could be rapidly translated for the management of COVID-19 via debris clearance and inflammatory cytokine suppression. Here, we discuss using pro-resolution mediators as a potential complement to current anti-viral strategies for COVID-19.


title: Clinical and histological characterization of late appearance maculopapular eruptions in association with the coronavirus disease 2019. A case series of seven patients.

text: Since the first report of cutaneous manifestations of the coronavirus disease 2019 (COVID‐19) by Recalcati et al(1), there has been described five clinical patterns including pseudo‐chilblain lesions, vesicular eruptions, urticarial lesions, livedo and necrosis and maculopapular eruptions(2). Several clinical reports have been published recently describing these clinical patterns although there is still a lack of information regarding histopathology of maculopapular eruptions. We designed a retrospective study of patients attended in our department over the course of three weeks. We collected clinical data and pictures, and performed a biopsy when possible.


title: Rhinoviruses

text: This article is an updated version of the previous edition article by Birgit Winther, volume 5, pp. 577–581, © 2008, Elsevier Inc.


title: Preventive cardiology as a dedicated clinical service: The past, the present, and the (Magnificent) future

text: • Ischemic cardiovascular disease continues to be most common cause of death after age 55 everywhere in the world. • As the average person is exposed over life to a variety of artery-damaging insults it is easy to predict that this trend will continue for decades. • We face an unprecedented opportunity to consolidate, strengthen, and broaden the effort to prevent cardiovascular events, both ischemic and non ischemic. • This effort requires professional lifestyle counseling, dietary interventions, use of natural supplements, pharmacotherapy, and efficient cross-referral strategies. • The nascent subspecialty of preventive cardiology must reach uniformity in protocols of care, and must develop a system of training and certification for the next generation of expert providers.


docid: llumyzno

title: ATENCIÓN DOMICILIARIA Y COVID-19. ANTES, DURANTE Y DESPUÉS DEL ESTADO DE ALARMA

text: Abstract In Spain, Home Care as a fundamental tool of Primary Health Care, has had uneven development both before and during the COVID-19 pandemic, although it initially played a relevant role in the control and monitoring of infected people and their families. However, at no time it was used the desirable community perspective and community participation throughout the process as it has been successfully done in other settings. Subsequently, with the closure of health centers, it ceased to be provided in some autonomous communities, when all the attention was transferred to the hospital setting. This exacerbated hospital-centrism, to the detriment of PHC and Home Care, is showing a high contagion in healthcare professionals. The circulation of professionals in the hospitals, where the main focus of infection is concentrated, and from these to their homes is a clear risk factor. In addition, we must not forget that Home Care is of special importance for the care of people with terminal illnesses or very advanced chronic diseases (dementia, COPD ...), although always taking into account recommendations tending to extreme precautions for infection for professionals, family and caregivers. This can be adapted to the pandemic situation by using tools that digital health offers (telephone care, video calls ...). Finally, it would be very interesting that, once the crisis was over, research was carried out that allowed the incorporation of people who have been treated by the health service during the pandemic, through the technique called public participation in research projects.


title: Human Genomics in Asia

text: Abstract In the past decade, Asia has been actively engaged in human genomic studies and has made great contributions to the field. There is an increase in the number of genomics institutes, consortiums, and initiatives across the continent to study the association between genetic variation and disease. Despite these laudable efforts, Asia faces tremendous challenges in terms of funding, regulation, collaboration, and ethical, legal, and social issues related to genomics. These need to be addressed in the near future to promote the development of genomic medicine.


title: Viruses in Faeces

text: KEYWORDS Enteroviruses, Echoviruses, Polioviruses, Hepatitis A virus, Rotavirus, Parvovirus-like viruses, Astroviruses, Caliciviruses, Coronaviruses.


title: The diagnoses and outcomes of emergency patients with an elevated D-dimer over the next 90 days

text: BACKGROUND: it is not known what diagnoses are associated with an elevated D-dimer in unselected patients attending emergency departments (ED), nor their associated outcomes. METHODS: prospective observational study of 1,612 unselected patients attending a Danish ED, with 100% follow up for 90 days after presentation. RESULTS: the 765 (47%) of ED patients with an elevated D-dimer level (i.e. >= 0.5 mg/L) were more likely to be admitted to hospital (p <0.0001), represent (p 0.02), and die within 90 days (i.e. 8.1% of patients, p <0.0001). Only ten patients with a normal D-dimer level (1.2%) died within 90 days: five had chronic obstructive pulmonary disease and infection, and five had cancer (four of whom also had infection). Venous thromboembolism, infection, neoplasia, anaemia, heart failure and unspecified soft tissue disorders were significantly associated with an elevated D-dimer. Of the 72 patients with venous thromboembolism 20 also had infection, 8 had cancer and 4 anaemia. None of the patients with heart failure, stroke or acute myocardial infarction with a normal D-dimer level died within 90 days. CONCLUSION: Nearly half of all patients attending an ED have an elevated D-dimer level and these patients were more likely to be admitted to hospital, and to represent and/or die within 90 days. While elevated D-dimer levels are significantly associated with venous thromboembolism, in this unselected ED patient population they are also associated with infection, cancer, heart failure and anaemia.


title: Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia

text: Summary Background Although the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) has been sequenced and a possible animal reservoir identified, seroprevalence studies and mass screening for detection of subclinical and non-pneumonic infections are still lacking. Methods We cloned and purified the nucleocapsid protein and spike polypeptide of SARS-CoV and examined their immunogenicity with serum from patients with SARS-CoV pneumonia. An ELISA based on recombinant nucleocapsid protein for IgG detection was tested with serum from 149 healthy blood donors who donated 3 years previously and with serum positive for antibodies against SARS-CoV (by indirect immunofluorescence assay) from 106 patients with SARS-CoV pneumonia. The seroprevalence of SARS-CoV was studied with the ELISA in healthy blood donors who donated during the SARS outbreak in Hong Kong, non-pneumonic hospital inpatients, and symptom-free health-care workers. All positive samples were confirmed by two separate western-blot assays (with recombinant nucleocapsid protein and recombinant spike polypeptide). Findings Western-blot analysis showed that the nucleocapsid protein and spike polypeptide of SARS-CoV are highly immunogenic. The specificity of the IgG antibody test (ELISA with positive samples confirmed by the two western-blot assays) was 100%, and the sensitivity was 94·3%. Three of 400 healthy blood donors who donated during the SARS outbreak and one of 131 non-pneumonic paediatric inpatients were positive for IgG antibodies, confirmed by the two western-blot assays (total, 0·48% of our study population). Interpretation Our findings support the existence of subclinical or non-pneumonic SARS-CoV infections. Such infections are more common than SARS-CoV pneumonia in our locality.


title: CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor

text: The power of forward genetics in yeast is the foundation on which the field of autophagy research firmly stands. Complementary work on autophagy in higher eukaryotes has revealed both the deep conservation of this process, as well as novel mechanisms by which autophagy is regulated in the context of development, immunity, and neuronal homeostasis. The recent emergence of new clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-based technologies has begun facilitating efforts to define novel autophagy factors and pathways by forward genetic screening in mammalian cells. Here, we set out to develop an expanded toolkit of autophagy reporters amenable to CRISPR/Cas9 screening. Genome-wide screening of our reporters in mammalian cells recovered virtually all known autophagy-related (ATG) factors as well as previously uncharacterized factors, including vacuolar protein sorting 37 homolog A (VPS37A), transmembrane protein 251 (TMEM251), amyotrophic lateral sclerosis 2 (ALS2), and TMEM41B. To validate this data set, we used quantitative microscopy and biochemical analyses to show that 1 novel hit, TMEM41B, is required for phagophore maturation. TMEM41B is an integral endoplasmic reticulum (ER) membrane protein distantly related to the established autophagy factor vacuole membrane protein 1 (VMP1), and our data show that these two factors play related, albeit not fully overlapping, roles in autophagosome biogenesis. In sum, our work uncovers new ATG factors, reveals a malleable network of autophagy receptor genetic interactions, and provides a valuable resource (http://crispr.deniclab.com) for further mining of novel autophagy mechanisms.


title: Echovirus 30, Jiangsu Province, China

text: An outbreak of aseptic meningitis occurred in the northern area of Jiangsu Province in China from January to July in 2003. A total of 1,681 cases were involved in this outbreak, and 99% of patients were <15 years of age. To identify the etiologic agent, 66 cerebrospinal fluid specimens were tested by cell culture. Eighteen showed an enteroviruslike cytopathic effect on MRC-5 human fetal diploid lung cells. An enterovirus primer-mediated reverse transcriptase–polymerase chain reaction, a standard neutralization assay, and sequencing of the complete capsid-encoding (VP1) gene identified the 18 isolates (FDJS03) as echovirus 30. At least a 10% difference was seen in nucleotide sequences of VP1 between FDJS03 isolates and other global strains of echovirus 30. Phylogenetic analysis based on complete sequences of VP1 was performed to further characterize the FDJS03 isolates. This report is the first to identify a distinct lineage of echovirus 30 as a probable cause of this outbreak.


title: Racial Variations in COVID‐19 Deaths May Be Due to Androgen Receptor Genetic Variants Associated with Prostate Cancer and Androgenetic Alopecia. Are Anti‐Androgens a Potential Treatment for COVID‐19?

text: Racial disparities in COVID‐19 infection rates and disease severity are due to a multifactorial etiology that can include socioeconomic as well as other factors. Nevertheless, genetic factors in different ethnic groups often contribute to disease severity and treatment response. In particular, the frequency of genetic variations in the androgen receptor differs by ethnicity and gender. For example, the increased prevalence of prostate cancer and androgenetic alopecia among African Americans correlates with the frequency of these variants. In this communication, we propose that androgens may be implicated in COVID‐19 disease severity. As such, special attention may need to be given to African Americans infected by the SARS‐CoV‐2 virus. Finally, if a link to genetic variations in the androgen receptor and COVID‐19 disease severity can be established, it would suggest new treatment options.