docid: dvbgbrvo

title: Serological evidence of coronavirus infections in native hamadryas baboons (Papio hamadryas hamadryas) of the Kingdom of Saudi Arabia

text: The hamadryas baboon (Papio hamadryas hamadryas) is the only indigenous species of non-human primates (NHP) found in the Kingdom of Saudi Arabia (KSA). There are no peer-reviewed publications on viral infections of the baboons of KSA. Apart from camels, other animals are likely sources of the novel Middle East Respiratory Syndrome coronavirus (MERSCoV) for humans. We investigated evidence of highly pathogenic coronavirus infections including MERSCoV in a large group of commensal baboons accompanied by feral dogs, on the outskirts of Ta'if city, KSA, in February 2013. Fifty baboons (16 juveniles and 34 adults) were screened for serum antibodies to human coronaviruses (HCoV-043/-NL63/-229) and canine coronaviruses (CCoV-1-3) using direct Enzyme-linked Immunosorbent Assay (ELISA) technique and for MERSCoV antibodies using Serum Neutralization Test (SNT). Of the 50 sampled baboons, 22% (n = 11) were seropositive to HCoVs, 10% (n = 5) were seropositive to CCoVs, while none had detectable MERSCoV antibodies. These findings bear potentially significant implications for public health, canine health and baboon conservation efforts, necessitating follow-up investigations and preventive measures at locations where baboons frequent human habitations, or are regarded as tourist attractions, in KSA.


title: Prevalence of human coronavirus antibody in the population of southern iraq

text: Sera from adults in Southern Iraq were collected during winter and screened by an enzyme–linked immunosorbent assay for the presence of antibodies to the two antigenic groups of human coronaviruses, the 229E and the OC43 groups: 91% of the sera had antibodies to at least one of the groups, whereas 4 and 5% of the sera had antibodies to only the 229E or OC43 groups, respectively. There was significant correlation between the levels of antibody to the 229E and OC43 group coronaviruses in these sera.


title: Molecular evolution and emergence of avian gammacoronaviruses

text: Abstract Coronaviruses, which are single stranded, positive sense RNA viruses, are responsible for a wide variety of existing and emerging diseases in humans and other animals. The gammacoronaviruses primarily infect avian hosts. Within this genus of coronaviruses, the avian coronavirus infectious bronchitis virus (IBV) causes a highly infectious upper-respiratory tract disease in commercial poultry. IBV shows rapid evolution in chickens, frequently producing new antigenic types, which adds to the multiple serotypes of the virus that do not cross protect. Rapid evolution in IBV is facilitated by strong selection, large population sizes and high genetic diversity within hosts, and transmission bottlenecks between hosts. Genetic diversity within a host arises primarily by mutation, which includes substitutions, insertions and deletions. Mutations are caused both by the high error rate, and limited proof reading capability, of the viral RNA-dependent RNA-polymerase, and by recombination. Recombination also generates new haplotype diversity by recombining existing variants. Rapid evolution of avian coronavirus IBV makes this virus extremely difficult to diagnose and control, but also makes it an excellent model system to study viral genetic diversity and the mechanisms behind the emergence of coronaviruses in their natural host.


Next WHO Director-General: hear the angels while fighting the wolves


title: Estudio de contactos en infectados por SARS-CoV-2. El papel fundamental de la Atención Primaria y de la Salud Pública

text: Resumen Con el objetivo de favorecer la rápida identificación de los contactos de pacientes infectados por SARS-CoV-2 y por tanto el control de la pandemia, se revisaron diferentes metodologías y recomendaciones sobre estudio de contactos (EECC) aplicables a la Atención Primaria (AP) y a la Salud Pública (SP): artículos en Pubmed sobre COVID-19 y EECC, definiciones de contacto en documentos oficiales, el sistema clásico de EECC en tuberculosis (TB), informaciones sobre apps para EECC y el papel de las pruebas diagnósticas. Para establecer medidas de prevención y control eficientes, se precisa actuar siempre bajo sospecha clínica, diagnóstico y aislamiento precoz de los casos y de los contactos y su seguimiento. El modelo clásico de EECC en TB es aplicable a esta nueva infección pero acelerando el proceso dada su carácter agudo y su potencial gravedad. Es imprescindible una buena coordinación entre AP y SP y disponer de recursos suficientes. Abstract The aim of this study was to promote the rapid identification of the contacts of patients infected with SARS-CoV-2 and therefore the control of the pandemic. Different methodologies and recommendations on contact tracing for Primary Health Care (PHC) and Public Health Services (PHS), like articles in Pubmed about COVID-19 and contact tracing, official contact definitions, the classic contact tracing model in tuberculosis (TB), information about apps for contact tracing and the role of the diagnostic tests, were reviewed. To establish efficient prevention and control measures, it is always necessary to implement contact tracing based on clinical suspicion, early diagnosis and isolation of cases and contacts and their follow-up. The classic contact tracing model in TB can be applied to this new infection, but accelerating the process given its acute nature and its potential severity. Good coordination between PHC and PHS and having sufficient resources is essential.


Public-health risks of melamine in milk products


title: Conserved microsatellites may contribute to stem-loop structures in 5′, 3′ terminals of Ebolavirus genomes

text: Abstract Microsatellites (SSRs) are ubiquitous in coding and non-coding regions of the Ebolavirus genomes. We synthetically analyzed the microsatellites in whole-genome and terminal regions of 219 Ebolavirus genomes from five species. The Ebolavirus sequences were observed with small intraspecies variations and large interspecific variations, especially in the terminal non-coding regions. Only five conserved microsatellites were detected in the complete genomes, and four of them which well base-paired to help forming conserved stem-loop structures mainly appeared in the terminal non-coding regions. These results suggest that the conserved microsatellites may be evolutionary selected to form conserved secondary structures in 5′, 3′ terminals of Ebolavirus genomes. It may help to understand the biological significance of microsatellites in Ebolavirus and also other virus genomes.


title: H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment

text: PURPOSE: During the 2009 H1N1 influenza A virus pandemic, a minority of patients developed rapidly progressive pneumonia leading to acute lung injury (ALI)—acute respiratory distress syndrome (ARDS). A recent meta-analysis provides support for prolonged corticosteroid treatment in ALI-ARDS. We prospectively evaluated the response to oseltamivir and prolonged corticosteroid treatment in patients with ALI-ARDS and suspected H1N1 influenza. METHODS: From June 24 through 12 July 2009, 13 patients with suspected H1N1 pneumonia and ALI-ARDS were admitted to the intensive care unit (ICU) of a tertiary care hospital. H1N1 influenza was confirmed with real-time reverse transcriptase-polymerase chain reaction assay in eight patients. Oseltamivir and corticosteroid treatment were initiated concomitantly at ICU admission; those with severe ARDS received methylprednisolone (1 mg/kg/day), and others received hydrocortisone (300 mg/day) for a duration of 21 ± 6 days. RESULTS: Patients with and without confirmed H1N1 influenza had similar disease severity at presentation and a comparable response to treatment. By day 7 of treatment, patients experienced a significant improvement in lung injury and multiple organ dysfunction scores (P < 0.001). Twelve patients (92%) improved lung function, were extubated, and discharged alive from the ICU. Hospital length of stay and mortality were 18.7 ± 9.6 days and 15%, respectively. Survivors were discharged home without oxygen supplementation. CONCLUSIONS: In ARDS patients, with and without confirmed H1N1 influenza, prolonged low-to-moderate dose corticosteroid treatment was well tolerated and associated with significant improvement in lung injury and multiple organ dysfunction scores and a low hospital mortality. These findings provide the rationale for developing a randomized trial.


title: Clinical and surgical management of patients with head and neck cancer in a COVID‐19 dedicated center in Italy

text: INTRODUCTION: For the EARs NOSE AND THROAT (ENT) surgeon, there are many challenges that show‐up in the clinical management of a patient affected by a head and neck cancer during COVID‐19 pandemic, especially in the postoperative period. METHODS: During the acute COVID‐19 emergency phase in Italy, we analyzed the management of a patient affected by a head and neck cancer. We reported several clinical data about the hospitalization period, pointing out the difficulties encountered both from clinical and management point of view. RESULTS: During pandemic, we admitted 27 oncological patients at our ENT Department. Delays in surgical procedures, complications of hospitalizations, need for radiological studies, and possible transfer to other hospital ward, due to suspect SARS‐CoV‐2 infection, were registered. CONCLUSIONS: The changes in the whole health care system during the COVID‐19 pandemic have impacted the management of patients with head and neck cancer, generating several clinical challenges for the ENT surgeon.


docid: nvhkhidr

title: Molecular Detection of Porcine Torovirus in Piglets with Diarrhea in Southwest China

text: Porcine torovirus (PToV) was detected from intestinal samples of piglets with diarrhea from 20 farms in southwest China. The total prevalence of PToV was 45% (9 out of 20 farms); it was the first detection of PToV in China, and also the study analyzed the phylogenetic relationships between the Chinese PToV and PToV reference strains as well as other representative toroviruses. Genetic and phylogenetic analysis showed the existence of genetic diversity among geographically separated PToV. Statistical analysis of the PToV positive rate as well as a survey for other enteric pathogens in diarrheic pigs suggests that PToV may play a role as a causative agent of severe diarrhea in piglets.


title: Rab11-FIP1C and Rab14 Direct Plasma Membrane Sorting and Particle Incorporation of the HIV-1 Envelope Glycoprotein Complex

text: The incorporation of the envelope glycoprotein complex (Env) onto the developing particle is a crucial step in the HIV-1 lifecycle. The long cytoplasmic tail (CT) of Env is required for the incorporation of Env onto HIV particles in T cells and macrophages. Here we identify the Rab11a-FIP1C/RCP protein as an essential cofactor for HIV-1 Env incorporation onto particles in relevant human cells. Depletion of FIP1C reduced Env incorporation in a cytoplasmic tail-dependent manner, and was rescued by replenishment of FIP1C. FIP1C was redistributed out of the endosomal recycling complex to the plasma membrane by wild type Env protein but not by CT-truncated Env. Rab14 was required for HIV-1 Env incorporation, and FIP1C mutants incapable of binding Rab14 failed to rescue Env incorporation. Expression of FIP1C and Rab14 led to an enhancement of Env incorporation, indicating that these trafficking factors are normally limiting for CT-dependent Env incorporation onto particles. These findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14.


title: Australian infectious bronchitis viruses: identification of nine subtypes by a neutralisation test

text: The antigenic relationships between 17 Australian infectious bronchitis viruses, including six vaccine viruses, were studied by a neutralisation test using a plaque reduction method in chick embryo kidney cell monolayers. The 17 viruses formed nine distinct subtypes. Antiserum to each subtype had a high titre to viruses of the same subtype and a lower litre to viruses of different subtypes. The heterologous titres of sera varied widely.


title: Rapidly progressive COVID-19 viral pneumonia: a report of two patients with a focus on imaging findings

text: BACKGROUND: The novel coronavirus causes viral pneumonia characterized by lower respiratory tract symptoms and 19severe inflammatory response syndrome. Studies have suggested that the virus has a clinical course with the stepwise progression of clinical signs and symptoms and radiologic alterations. CASE PRESENTATION: In the present case report, we discuss two patients who presented with mild symptoms and CT imaging not suggestive of COVID-19, but subsequently had a rapid deterioration, with severe involvement happening in CT imaging. One of the patients survived the initial deterioration, but the other passed away. CONCLUSION: We suggest that the clinical course of the virus may be rapidly progressive in some patients, and special attention should be paid to patients being treated for the virus outside of the hospital as an outpatient.


Impact of COVID-19 outbreak on acute low back pain


title: The role of pro-resolution lipid mediators in infectious disease

text: Inflammation is an essential host defence against infection, but can be damaging when excessive. Resolution of inflammation is an active process, and the pro-resolution effects of lipoxins, resolvins and protectins have received significant interest. Here, we review emerging data on the role of these lipid mediators in infectious disease. Lipoxins influence host control of Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma cruzi and Plasmodium berghei cerebral malaria in mice. Their effects are protective in toxoplasmosis, T. cruzi infection and cerebral malaria but detrimental in tuberculosis; related to the balance between pathogen-control and excessive immune response. Topical lipoxin abrogates the tissue damage seen in a rabbit model of Porphyromonas gingivalis periodontitis. The increased virulence of H5N1 influenza A virus in mice correlates with reduced expression of SOCS2, required to mediate the effects of lipoxin. Mice unable to synthesize lipoxin suffer increased lung pathology during respiratory syncytial virus infection. Protectin suppresses influenza A virus replication in vitro and increases survival in a mouse model of severe influenza infection. Resolvins were investigated in a number of animal models of systemic bacterial infection, and were found to enhance phagocytic clearance of bacteria, reduce inflammation severity, promote neutrophil apoptosis, modulate neutrophil chemotaxis and importantly, reduce mortality. Interestingly, resolvin also enhances the antibacterial effect of ciprofloxacin and vancomycin. Topical resolvin application reduces the severity of herpes simplex virus ocular infection in mice. If the effects of these mediators translate from pre-clinical studies into successful clinical trials, they represent promising new strategies in managing infectious disease.


title: Antiviral innate immunity and stress granule responses

text: Viral infection triggers the activation of antiviral innate immune responses in mammalian cells. Viral RNA in the cytoplasm activates signaling pathways that result in the production of interferons (IFNs) and IFN-stimulated genes. Some viral infections have been shown to induce cytoplasmic granular aggregates similar to the dynamic ribonucleoprotein aggregates termed stress granules (SGs), suggesting that these viruses may utilize this stress response for their own benefit. By contrast, some viruses actively inhibit SG formation, suggesting an antiviral function for these structures. We review here the relationship between different viral infections and SG formation. We examine the evidence for antiviral functions for SGs and highlight important areas of inquiry towards understanding cellular stress responses to viral infection.


title: Drinking Water Quality and the Geospatial Distribution of Notified Gastro-Intestinal Infections

text: INTRODUCTION: Even brief episodes of fecal contamination of drinking water can lead directly to illness in the consumers. In water-borne outbreaks, the connection between poor microbial water quality and disease can be quickly identified. The impact of non-compliant drinking water samples due to E. coli taken for regular monitoring on the incidence of notified acute gastrointestinal infections has not yet been studied. METHODS: The objective of this study was to analyse the geographical distribution of notified acute gastrointestinal infections (AGI) in Slovenia in 2010, with hotspot identification. The second aim of the study was to correlate the fecal contamination of water supply system on the settlement level with the distribution of notified AGI cases. Spatial analysis using geo-information technology and other methods were used. RESULTS: Hot spots with the highest proportion of notified AGI cases were mainly identified in areas with small supply zones. The risk for getting AGI was drinking water contaminated with E. coli from supply zones with 50–1000 users: RR was 1.25 and significantly greater than one (p-value less than 0.001). CONCLUSION: This study showed the correlation between the frequency of notified AGI cases and non-compliant results in drinking water monitoring.


title: Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections

text: The pathogenesis of severe acute respiratory syndrome (SARS) is poorly understood and cytokine dysregulation has been suggested as one relevant mechanism to be explored. We compared the cytokine profile in Caco2 cells after infection of SARS coronavirus (SARS‐CoV) with other respiratory viruses including respiratory syncytial virus (RSV), influenza A virus (FluAV), and human parainfluenza virus type 2 (hPIV2). Interferon (IFN) system (production and response) was not suppressed by SARS‐CoV infection. Therefore, SARS‐CoV replication was suppressed by pretreatment with IFN. SARS‐CoV and RSV induced high levels of IL‐6 and RANTES compared with FluAV and hPIV2. Induction level of suppressor of cytokine signaling‐3 (SOCS3) by SARS‐CoV was significantly lower than that by RSV in spite of the significant production of IL‐6. Toll‐like receptors 4 and 9, which correlate with the induction of inflammatory response, were upregulated by SARS‐CoV infection. Collectively, overinduction of inflammatory cytokine and dysregulation of cytokine signaling may contribute to the immunopathology associated with “severe” inflammation in SARS. J. Med. Virol. 78:417–424, 2006. © 2006 Wiley‐Liss, Inc.


title: Regulation of p90RSK phosphorylation by SARS-CoV infection in Vero E6 cells

text: The 90 kDa ribosomal S6 kinases (p90RSKs) are a family of broadly expressed serine/threonine kinases with two kinase domains activated by extracellular signal-regulated protein kinase in response to many growth factors. Our recent study demonstrated that severe acute respiratory syndrome (SARS)-coronavirus (CoV) infection of monkey kidney Vero E6 cells induces phosphorylation and dephosphorylation of signaling pathways, resulting in apoptosis. In the present study, we investigated the phosphorylation status of p90RSK, which is a well-known substrate of these signaling pathways, in SARS-CoV-infected cells. Vero E6 mainly expressed p90RSK1 and showed weak expression of p90RSK2. In the absence of viral infection, Ser221 in the N-terminal kinase domain was phosphorylated constitutively, whereas both Thr573 in the C-terminal kinase domain and Ser380 between the two kinase domains were not phosphorylated in confluent cells. Ser380, which has been reported to be involved in autophosphorylation by activation of the C-terminal kinase domain, was phosphorylated in confluent SARS-CoV-infected cells, and this phosphorylation was inhibited by SB203580, which is an inhibitor of p38 mitogen-activated protein kinases (MAPK). Phosphorylation of Thr573 was not upregulated in SARS-CoV-infected cells. Thus, in virus-infected cells, phosphorylation of Thr573 was not necessary to induce phosphorylation of Ser380. On the other hand, Both Thr573 and Ser380 were phosphorylated by treatment with epidermal growth factor (EGF) in the absence of p38 MAPK activation. Ser220 was constitutively phosphorylated despite infection. These results indicated that phosphorylation status of p90RSK by SARS-CoV infection is different from that by stimulation of EGF. This is the first detailed report regarding regulation of p90RSK phosphorylation by virus infection.


title: Water matrices as potential source of SARS-CoV-2 transmission – An overview from environmental perspective

text: Abstract Evidently, the emergence of novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has rapidly blowout across the world. Since, the presence of coronaviruses, including SARS-CoV-2 in the fecal specimens and anal swabs of some infected patients, has raised emerging concern with the likelihood of fecal-based spread must be inspected and clarified. Therefore, herein, an effort has been made to spotlight the current scenarios and possible solutions to better understand the risks associated with the wastewater matrices as a potential source of SARS-CoV-2 transmission in the environment. The information reviewed here constitutes a paramount intellectual basis to sustenance ongoing research to tackle the SARS-CoV-2 issue. Thus, this overview indicates the most accessible frontiers related to the detection, quantification, and possible transmission of SARS-CoV-2 in the environment through water routes. The regulatory authorities and policymakers must assure the society via dissemination of evidence-based guidelines that the water matrices, including groundwater and drinking water resources are safe. Finally, we have identified and enlisted a number of pressing questions concerning the ongoing SARS-CoV-2 transmission or COVID-19 emergence issue that must be carefully answered to put further and deeper insight into SARS-CoV-2/COVID-19 in future studies.


title: Advanced Diagnostic Approaches and Current Management of Proventricular Dilatation Disease

text: Proventricular dilatation disease (PDD) is a fatal inflammatory disease that affects mainly, but not exclusively, psittacine birds (Order: Psittaciformes). PDD has long been suspected to be a viral disease, but its causative agent, a novel Bornavirus, was only identified in 2008.


title: Epidemiology and prevention of influenza in children in Argentina and Brazil

text: A group of influenza experts from Argentina and Brazil got together to discuss the burden of influenza in children, review current vaccine coverage rates in both countries, analyze vaccine effectiveness, and discuss strategies to improve prevention. Active surveillance of respiratory viruses is carried out nationwide in both countries. Years 2014 and 2015 were mild influenza seasons; influenza virus type A/H3N2 prevailed, whereas type B represented less than 30% of isolates. Trivalent inactivated influenza vaccine is included in National Immunization Programs for 1) children 6 months to 2 years old in Argentina; 2) children 6 months to 5 years old in Brazil; and 3) all high-risk individuals. Coverage rates in both countries were about 80% (albeit lower for the second dose). Experts from both countries proposed the following strategies to improve prevention: 1) increase surveillance; 2) assess effectiveness and long-term safety of influenza vaccines; 3) reinforce vaccination programs in order to increase coverage rates; and 4)consider introducing more effective vaccines, such as adjuvanted trivalent vaccines. In Argentina, estimating casefatality rates was also recommended. Other proposed actions included enhancing education of health professionals and the lay community, and better use of communication resources to raise awareness of the burden of influenza and promote vaccine uptake.


title: Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa

text: Abstract Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses.


title: Novel vaccine strategies against emerging viruses

text: One of the main public health concerns of emerging viruses is their potential introduction into and sustained circulation among populations of immunologically naïve, susceptible hosts. The induction of protective immunity through vaccination can be a powerful tool to prevent this concern by conferring protection to the population at risk. Conventional approaches to develop vaccines against emerging pathogens have significant limitations: lack of experimental tools for several emerging viruses of concern, poor immunogenicity, safety issues, or lack of cross-protection against antigenic variants. The unpredictability of the emergence of future virus threats demands the capability to rapidly develop safe, effective vaccines. We describe some recent advances in new vaccine strategies that are being explored as alternatives to classical attenuated and inactivated vaccines, and provide examples of potential novel vaccines for emerging viruses. These approaches might be applied to the control of many other emerging pathogens.


title: The key molecular events during Macrobrachium rosenbergii nodavirus (MrNV) infection and replication in Sf9 insect cells

text: Abstract In this study we demonstrated that Macrobrachium rosenbergii nodavirus (MrNV) was able to internalize and replicate in Sf9 insect cells, with levels of infection altered by substances affecting the caveolin-(CAV) mediated endocytosis pathway. The use of Sf9 cells for efficient MrNV replication and propagation was demonstrated by confocal microscopy and PCR amplification, through which early viral binding and internalization were initially detectable at 30min post-infection; whereas at 72h, the distinguishable sign of late-MrNV infection was observable as the gradual accumulation of a cytopathic effect (CPE) in the cells, ultimately resulting in cellular disruption. Moreover, during the early period of infection, the MrNV signals were highly co-localized with CAV1 signals of the CAV-mediated endocytosis pathway. The use of genistein as an inhibitor of the CAV-mediated endocytosis pathway significantly reduced MrNV and CAV1 co-localization, and also reduced the levels of MrNV infection in Sf9 cells as shown by PCR and ELISA. Moreover, the addition of the pathway agonist okadaic acid not only recovered but also augmented both the levels of MrNV co-localization with CAV1 and of Sf9 infection in the presence of genistein inhibition; therefore demonstrating that MrNV infection in Sf9 cells was associated with the CAV-mediated endocytosis pathway machinery.


title: A potential role for integrins in host cell entry by SARS-CoV-2

text: • Integrin may act as an alternative receptor for SARS-CoV-2 and could be implicated in its transmission and pathology. • The spike protein of SARS-CoV-2 acquired a RGD motif known to bind integrins. This motif is absent from other coronaviruses. • The integrin-binding motif is present at the surface of the spike protein, close to the ACE2 receptor-binding region. • Integrin binding may be a promising therapeutics target, and should be tested experimentally.


title: Risk Factors Associated with Mental Illness in Hospital Discharged Patients Infected with COVID-19 in Wuhan, China

text: The coronavirus disease 2019 (COVID-19) pandemic can have a profound impact on the mental health of patients who survived the illness. However, little is known about the prevalence rate of mental health disorders among hospital discharged COVID-19 patients and its associated factors. A cross-sectional survey of hospital discharged patients was conducted April 11-22, 2020 in Wuhan, China (where the pandemic began). 675 participants completed the survey, including 90 (13.3%) medical staff (physicians and nurses who had been ill). We used Fisher's exact test and multivariable logistic regression methods to explore the risk factors associated with mental health problems (anxiety, depression, and PTSD symptoms associated with COVID-19 hospitalization). Adverse mental health effects of COVID-19 are evident after discharge from the hospital, with sleep difficulties highlighted as a central issue. As we found that perceived discrimination was a central predictor of mental illness, preventing and addressing social stigma associated with COVID-19 may be crucial for improving mental health for recovered patients.


title: Surface-displayed porcine IFN-λ3 in Lactobacillus plantarum inhibits porcine enteric coronavirus infection of porcine intestinal epithelial cells.

text: Interferon (IFN)-λ plays an essential role in mucosal cells which exhibit strong antiviral activity. Lactobacillus plantarum (L. plantarum) has substantial application potential in the food and medical industries because of its probiotic properties. Alphacoronaviruses, especially porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), cause high morbidity and mortality in piglets resulting in economic loss. The co-infection of the two viruses is becoming increasingly frequent. Therefore, it is particularly important to develop a new drug to prevent diarrhea infected with mixed viruses in piglets. In this study, we first constructed an anchored expression vector with CWA (C-terminal cell wall anchor) on L. plantarum. Second, we constructed two recombinant L. plantarum strains that anchored IFN-λ3 via pgsA (N‑terminal transmembrane anchor) and CWA. Third, we demonstrated that both recombinant strains possess strong antiviral effects against coronavirus infection in the intestinal porcine epithelial cell line J2 (IPEC-J2). However, recombinant L. plantarum with the CWA anchor exhibited a more powerful antiviral effect than recombinant L. plantarum with pgsA. Consistent with this finding, Lb.plantarum-pSIP-409-IFN-λ3-CWA enhanced the expression levels of IFN-stimulated genes (ISGs) (ISG15, OASL, and Mx1) in IPEC-J2 cells more than did recombinant Lb.plantarum-pSIP-409-pgsA'-IFN-λ3. Our study verifies that recombinant L. plantarum inhibits PEDV and TGEV infection in IPEC-J2 cells, which may offer great potential for use as a novel oral antiviral agent in therapeutic applications for combating porcine epidemic diarrhea and transmissible gastroenteritis. This study was the first study that recombinant L. plantarum suppresses PEDV and TGEV infection of IPEC-J2 cells.


title: Quantitative proteomic identification of host factors involved in the Salmonella typhimurium infection cycle

text: To identify host factors involved in Salmonella replication, SILAC‐based quantitative proteomics was used to investigate the interactions of Salmonella typhimurium with the secretory pathway in human epithelial cells. Protein profiles of Golgi‐enriched fractions isolated from S. typhimurium‐infected cells were compared with those of mock‐infected cells, revealing significant depletion or enrichment of 105 proteins. Proteins annotated to play a role in membrane traffic were overrepresented among the depleted proteins whereas proteins annotated to the cytoskeleton showed a diverse behavior with some proteins being enriched, others being depleted from the Golgi fraction upon Salmonella infection. To study the functional relevance of identified proteins in the Salmonella infection cycle, small interfering RNA (siRNA) experiments were performed. siRNA‐mediated depletion of a selection of affected proteins identified five host factors involved in Salmonella infection. Depletion of peroxiredoxin‐6 (PRDX6), isoform β‐4c of integrin β‐4 (ITGB4), isoform 1 of protein lap2 (erbin interacting protein; ERBB2IP), stomatin (STOM) or TBC domain containing protein 10b (TBC1D10B) resulted in increased Salmonella replication. Surprisingly, in addition to the effect on Salmonella replication, depletion of STOM or ITGB4 resulted in a dispersal of intracellular Salmonella microcolonies. It can be concluded that by using SILAC‐based quantitative proteomics we were able to identify novel host cell proteins involved in the complex interplay between Salmonella and epithelial cells.


title: Behaviors and perceptions of Japanese tourists affecting diarrheal illness and health care need assessment: A questionnaire study

text: OBJECTIVES: To measure the prevalence rate of, and determine the association between food and drink related behaviors and diarrheal illness among Japanese tourists, and assess their health care needs. METHODS: Eligible Japanese tourists (1,480) aged ≥15 years traveling in Chiangmai Province in the north, Ayutthaya Province in the center, Kanchanaburi Province in the west, Pattaya City in the east, and Krabi Province in the south of Thailand were enrolled in the study. Of these tourists, 1,318 consented to participate in this study and completed questionnaires in Japanese, giving a response rate of 89.1%. RESULTS: Among these Japanese tourists 21.3% had diarrheal illness, and of these tourists, 5.0% had classical travelers’ diarrhea (TD), 11.8% had mild TD, 3.3% had good food and drink related behaviors, and 75.4% had moderate level of perception of diarrhea related to drinking and eating. Multiple logistic regression analysis indicated three significant diarrheal illness predictors: large number of previous visits to Thailand, longer stay in Thailand, and the experience of visiting other countries. Furthermore, 56.9% suggested providing an adequate number of toilets at tourist destinations; 53.9% suggested providing a 24-hour emergency call facility for a public ambulance; and 51.9% suggested providing garbage bins and garbage disposal facilities at tourist destinations. CONCLUSIONS: TD still affects experienced Japanese tourists who visit Thailand. Although the proportions of the good levels of food and drink related behaviors were low, there were indications that Japanese tourists perceived the risk of contracting TD.


title: A Policy to Do Better Next Time: Lessons Learned From the COVID‐19 Pandemic

text: We write at the end of the second week in April, a necessary introduction since anything we say about the Covid-19 pandemic may be relevant only for the next few days. That's about the half-life of perceived wisdom in preventing exposure that may give rise to new cases and in providing medical care to existing cases. At the risk of trying to find lessons for the next pandemic while in the midst of the current one, there is much that we have already learned from this one. Weeks ago, in the early stages of the pandemic, several states and localities were at the same point in the pandemic, but have taken dramatically different paths since then. Why? It is the power of exponentiation in which a couple of days can make a huge difference, a geometric difference in prevalence and outcomes.


title: Virus- and Interferon Alpha-Induced Transcriptomes of Cells from the Microbat Myotis daubentonii

text: Antiviral interferons (IFN-alpha/beta) are possibly responsible for the high tolerance of bats to zoonotic viruses. Previous studies focused on the IFN system of megabats (suborder Yinpterochiroptera). We present statistically robust RNA sequencing (RNA-seq) data on transcriptomes of cells from the “microbat” Myotis daubentonii (suborder Yangochiroptera) responding at 6 and 24 h to either an IFN-inducing virus or treatment with IFN. Our data reveal genes triggered only by virus, either in both humans and Myotis (CCL4, IFNL3, CH25H), or exclusively in Myotis (STEAP4). Myotis cells also express a series of conserved IFN-stimulated genes (ISGs) and an unusually high paralog number of the antiviral ISG BST2 (tetherin) but lack several ISGs that were described for megabats (EMC2, FILIP1, IL17RC, OTOGL, SLC24A1). Also, in contrast to megabats, we detected neither different IFN-alpha subtypes nor an unusually high baseline expression of IFNs. Thus, Yangochiroptera microbats, represented by Myotis, may possess an IFN system with distinctive features.


title: CGAP: a new comprehensive platform for the comparative analysis of chloroplast genomes

text: BACKGROUND: Chloroplast is an essential organelle in plants which contains independent genome. Chloroplast genomes have been widely used for plant phylogenetic inference recently. The number of complete chloroplast genomes increases rapidly with the development of various genome sequencing projects. However, no comprehensive platform or tool has been developed for the comparative and phylogenetic analysis of chloroplast genomes. Thus, we constructed a comprehensive platform for the comparative and phylogenetic analysis of complete chloroplast genomes which was named as chloroplast genome analysis platform (CGAP). RESULTS: CGAP is an interactive web-based platform which was designed for the comparative analysis of complete chloroplast genomes. CGAP integrated genome collection, visualization, content comparison, phylogeny analysis and annotation functions together. CGAP implemented four web servers including creating complete and regional genome maps of high quality, comparing genome features, constructing phylogenetic trees using complete genome sequences, and annotating draft chloroplast genomes submitted by users. CONCLUSIONS: Both CGAP and source code are available at http://www.herbbol.org:8000/chloroplast. CGAP will facilitate the collection, visualization, comparison and annotation of complete chloroplast genomes. Users can customize the comparative and phylogenetic analysis using their own unpublished chloroplast genomes.


title: Lessons from Corporate Influence in the Opioid Epidemic: Toward a Norm of Separation

text: There is overwhelming evidence that the opioid crisis—which has cost hundreds of thousands of lives and trillions of dollars (and counting)—has been created or exacerbated by webs of influence woven by several pharmaceutical companies. These webs involve health professionals, patient advocacy groups, medical professional societies, research universities, teaching hospitals, public health agencies, policymakers, and legislators. Opioid companies built these webs as part of corporate strategies of influence that were designed to expand the opioid market from cancer patients to larger groups of patients with acute or chronic pain, to increase dosage as well as opioid use, to downplay the risks of addiction and abuse, and to characterize physicians’ concerns about the addiction and abuse risks as “opiophobia.” In the face of these pervasive strategies, conflict of interest policies have proven insufficient for addressing corporate influence in medical practice, medical research, and public health policy. Governments, the academy, and civil society need to develop counterstrategies to insulate themselves from corporate influence and to preserve their integrity and public trust. These strategies require a paradigm shift—from partnerships with the private sector, which are ordinarily vehicles for corporate influence, to a norm of separation.


title: On the Regularities of the Polar Profiles of Proteins Related to Ebola Virus Infection and their Functional Domains

text: The number of fatalities and economic losses caused by the Ebola virus infection across the planet culminated in the havoc that occurred between August and November 2014. However, little is known about the molecular protein profile of this devastating virus. This work represents a thorough bioinformatics analysis of the regularities of charge distribution (polar profiles) in two groups of proteins and their functional domains associated with Ebola virus disease: Ebola virus proteins and Human proteins interacting with Ebola virus. Our analysis reveals that a fragment exists in each of these proteins—one named the “functional domain”—with the polar profile similar to the polar profile of the protein that contains it. Each protein is formed by a group of short sub-sequences, where each fragment has a different and distinctive polar profile and where the polar profile between adjacent short sub-sequences changes orderly and gradually to coincide with the polar profile of the whole protein. When using the charge distribution as a metric, it was observed that it effectively discriminates the proteins from their functional domains. As a counterexample, the same test was applied to a set of synthetic proteins built for that purpose, revealing that any of the regularities reported here for the Ebola virus proteins and human proteins interacting with Ebola virus were not present in the synthetic proteins. Our results indicate that the polar profile of each protein studied and its corresponding functional domain are similar. Thus, when building each protein from its functional domai—adding one amino acid at a time and plotting each time its polar profile—it was observed that the resulting graphs can be divided into groups with similar polar profiles.


title: Genetic variability of human coronavirus OC43‐, 229E‐, and NL63‐like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients

text: In the winter–spring seasons 2003–2004 and 2004–2005, 47 (5.7%) patients with acute respiratory infection associated with human coronavirus (hCoV) 229E‐, NL63‐, and OC43‐like strains were identified among 823 (597 immunocompetent and 226 immunocompromised) patients admitted to hospital with acute respiratory syndromes. Viral infections were diagnosed by either immunological (monoclonal antibodies) or molecular (RT‐PCR) methods. Each of two sets of primer pairs developed for detection of all CoVs (panCoV) failed to detect 15 of the 53 (28.3%) hCoV strains identified. On the other hand, all hCoV strains could be detected by using type‐specific primers targeting genes 1ab and N. The HuH‐7 cell line was found to be susceptible to isolation and identification of OC43‐ and 229E‐like strains. Overall, hCoV infection was caused by OC43‐like, 229E‐like, and NL63‐like strains in 25 (53.2%), 10 (21.3%), and 9 (19.1%) patients, respectively. In addition, three patients (6.4%) were infected by untypeable hCoV strains. NL63‐like strains were not found to circulate in 2003–2004, and 229E‐like strains did not circulate in 2004–2005, while OC43‐like strains were detected in both seasons. The monthly distribution reached a peak during January through March. Lower predominated over upper respiratory tract infections in each age group. In addition, hCoV infections interested only immunocompetent infants and young children during the first year of life, while all adults were immunocompromised patients. Coinfections of hCoVs and other respiratory viruses (mostly interesting the first year of life) were observed in 14 of the 47 (29.8%) patients and were associated with severe respiratory syndromes more frequently than hCoV single infections (P = 0.002). In conclusion, the use of multiple primer sets targeting different genes is recommended for diagnosis of all types of hCoV infection. In addition, the detection of still untypeable hCoV strains suggests that the number of hCoVs involved in human pathology might further increase. Finally, hCoVs should be screened routinely for in both infants and immunocompromised patients with acute respiratory infection. J. Med. Virol. 78:938–949, 2006. © 2006 Wiley‐Liss, Inc.


title: Anti-herpetic and anti-dengue activity of abietane ferruginol analogues synthesized from (+)-dehydroabietylamine

text: The abietane-type diterpenoid (+)-ferruginol (1), a bioactive compound isolated from several plants, has attracted much attention as consequence of its pharmacological properties, which includes antibacterial, antifungal, antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and antitumor actions. In this study, we report on the antiviral evaluation of ferruginol (1) and several analogues synthesized from commercial (+)-dehydroabietylamine. Thus, the activity against Human Herpesvirus type 1, Human Herpesvirus type 2 and Dengue Virus type 2, was studied. Two ferruginol analogues showed high antiviral selectivity index and reduced viral plaque-size in post-infection stages against both Herpes and Dengue viruses. A promising lead, compound 8, was ten-fold more potent (EC(50) = 1.4 μM) than the control ribavirin against Dengue Virus type 2. Our findings suggest that the 12-hydroxyabieta-8,11,13-triene skeleton, which is characteristic of the diterpenoid ferruginol (1), is an interesting molecular scaffold for development of novel antivirals. In addition, the cytotoxic and antifungal activities of the synthesized ferruginol analogues have also been investigated. (©)20155 Elsevier Science. All rights reserved.


Which lessons shall we learn from the 2019 novel coronavirus outbreak?


title: A Functional Promoter Polymorphism of IFITM3 Is Associated with Susceptibility to Pediatric Tuberculosis in Han Chinese Population

text: A susceptibility locus for tuberculosis, a re-emerging infectious disease throughout the world, was previously discovered to exist on chromosome 11p15. IFITM3 gene encoding for interferon inducible transmembrane protein 3, is located at 11p15. It acts as an effector molecule for interferon-gamma, which is essential for anti-tuberculosis immune response. In order to investigate the association between susceptibility to TB and genetic polymorphisms of the IFITM3 core promoter, a case-control study including 368 TB patients and 794 healthy controls was performed in Han Chinese children in northern China. The rs3888188 polymorphism showed significant association with susceptibility to TB. The rs3888188 G allele, acting recessively, was more frequent in TB patients (95% confidence interval: 1.08–1.56, Bonferroni P-value: 0.039). We further assessed the effect of rs3888188 polymorphism on IFITM3 transcription in vitro. As based on luciferase promoter assays, the promoter activity of haplotypes with rs3888188 G allele was lower than that of haplotypes with rs3888188 T allele. Moreover, peripheral-blood mononuclear cells carrying rs3888188 GG genotype showed a reduced IFITM3 mRNA level compared to cells carrying TT or GT genotype. In conclusion, rs3888188, a functional promoter polymorphism of IFITM3, was identified to influence the risk for pediatric TB in Han Chinese population.


title: SARS – Unprecedented global response to a newly emerging disease

text: Abstract No Abstract


title: The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable Haemophilus influenzae

text: Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide. It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases. Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea. The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections. Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria. This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations. Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response. Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system. These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.” Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status. In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients.


title: Healthcare workers and H1N1 vaccination: Does having a chronic disease make a difference?

text: Abstract Introduction A novel H1N1 vaccine was manufactured in response to the pandemic in 2009. This study describes the willingness to be vaccinated for H1N1 among healthcare workers (HCWs) in primary healthcare clinics with and without chronic medical conditions, their reasons for refusing vaccination and whether they sought additional information to make an informed decision for the vaccination. Materials and methods An anonymous survey was conducted in November 2009 among all medical, nursing, allied health and operations HCWs in nine primary care clinics in Singapore. Participants were asked if they had any chronic medical conditions associated with influenza-related complications (example: asthma, stroke, heart disease, cancer, diabetes mellitus, renal disease), their perception towards vaccination for H1N1 and against seasonal influenza within the preceding 2 years. Results The initial response rate was 80%, of which 711 (54.7%) of the completed surveys were analysed. Among the 711 respondents, 16.6% reported having at least 1 chronic disease. Asthma (10.8%), hypertension (10.4%) and dyslipidaemia (9.8%) were the main chronic conditions. Only 39.4% of respondents were willing to be vaccinated against H1N1. Males were 2.07 (95% CI 1.19–3.62) times more likely than females to receive the H1N1 vaccination; the 45–54 and 55+ years old were 2.12 (95% CI 1.06–4.24) and 2.44 (95% CI 1.13–5.27) times more willing than those below 25 years old; and those who considered accepting the seasonal influenza vaccine were 7.0 times more likely than those who did not (95%CI 4.48–10.92). The 2 principal barriers were “fear of side effects” and “unsure of vaccine's effectiveness”. Although 78% attended some H1N1-related talks, only 7% of all HCWs felt that they had sufficient information. Most wanted more information about the vaccine's safety profile and contraindications. Conclusion Fewer than 40% of HCWs expressed willingness to receive the H1N1 vaccination, lower than past rates of influenza vaccine. HCWs in primary care clinics who had a chronic condition did not perceive themselves to be at higher risk of developing H1N1-related complications and were not more willing than the rest of the HCWs to accept H1N1 vaccination. Vaccine's side effects and effectiveness were the main concerns. Uptake of H1N1 vaccine may improve with targeted health information covering the vaccine's safety profile.


Rhinovirus in acute otitis media


docid: yyynlrpo

title: Utilisation des bactéries lactiques comme vecteurs vaccinaux

text: Today, sufficient consistent data are available to reinforce the interest of the use of Lactic Acic Bacteria (LAB), particularly lactococci and lactobacilli strains, to develop novel mucosal vaccination strategies. LAB are Gram positive bacteria exploited since the highest Antiquity by humans to produce fermented foods. They are thus good candidates to develop novel oral vectors and constitute attractive alternatives to vaccinal strategies based on attenuated pathogens which could induce healthy risks. Here, we summarized the most recent researches performed on the use of LAB as live vaccine delivery vectors.


Abstract 33. Transmission studies of neurological and psychiatric disease in the marmoset


title: Progression of COVID‐19 From Urban to Rural Areas in the United States: A Spatiotemporal Analysis of Prevalence Rates

text: PURPOSE: There are growing signs that the COVID‐19 virus has started to spread to rural areas and can impact the rural health care system that is already stretched and lacks resources. To aid in the legislative decision process and proper channelizing of resources, we estimated and compared the county‐level change in prevalence rates of COVID‐19 by rural‐urban status over 3 weeks. Additionally, we identified hotspots based on estimated prevalence rates. METHODS: We used crowdsourced data on COVID‐19 and linked them to county‐level demographics, smoking rates, and chronic diseases. We fitted a Bayesian hierarchical spatiotemporal model using the Markov Chain Monte Carlo algorithm in R‐studio. We mapped the estimated prevalence rates using ArcGIS 10.8, and identified hotspots using Gettis‐Ord local statistics. FINDINGS: In the rural counties, the mean prevalence of COVID‐19 increased from 3.6 per 100,000 population to 43.6 per 100,000 within 3 weeks from April 3 to April 22, 2020. In the urban counties, the median prevalence of COVID‐19 increased from 10.1 per 100,000 population to 107.6 per 100,000 within the same period. The COVID‐19 adjusted prevalence rates in rural counties were substantially elevated in counties with higher black populations, smoking rates, and obesity rates. Counties with high rates of people aged 25‐49 years had increased COVID‐19 prevalence rates. CONCLUSIONS: Our findings show a rapid spread of COVID‐19 across urban and rural areas in 21 days. Studies based on quality data are needed to explain further the role of social determinants of health on COVID‐19 prevalence.


title: PC2/CPE-mediated pro-protein processing in tumor cells and its differentiated cells or tissues

text: Abstract Pro-protein convertase-2 (PC2) and carboxypeptidase-E (CPE) proteins are two major members of the pro-protein convertases that involve in the maturation of protein precursor. By using PC2 activity, immunocytochemistry (ICC) and Western blot method, PC2, CPE and preproNPY protein expression levels were compared among mature retina tissue, RGC-5 cells and its differentiated cells, or brain cortex tissue, NS20Y tumor cells and its differentiated cells, or mature breast tissue, breast tumor cell RM1 and breast adenocarcinoma tissue. The experimental results indicated that the differentiated cells or tissues had higher or highest PC2 activity. In the comparative experiments, more PC2 protein expression in the mature tissues and more CPE and preproNPY protein expression in the tumor cells or tumor tissue were observed, but no expression of preproNPY protein was observed in the mature tissues. Compared with NS20Y or RGC-5 undifferentiated cells, its differentiated cells showed less proPC2, more proCPE and more preproNPY protein expressions. The results demonstrated that the mature tissues showed stronger PC2/CPE-mediated pro-protein processing ability than the tumor cells or tissue. The results also showed that the artificial differentiation of RGC-5 or NS20Y cells was different from maturation of its corresponding normal tissue.


title: Chapter 14 Membrane Transport

text: Abstract Carefully controlled solute movement into and out of cells is an essential feature of life. There are many ways solutes are transported across the thin (~40 Å) hydrophobic barrier. Transport is divided into passive diffusion and active transport. A biological membrane is semi-permeable, being permeable to some molecules, most notably water, while being very impermeable to most solutes that require some form of transporter. Passive diffusion (simple and facilitated) only requires the energy inherent in the solute’s electrochemical gradient and results in equilibrium across the membrane. In contrast, active transport requires additional energy (i.e. ATP), and results in a non-equilibrium, net accumulation of the solute. Passive transport can involve simple diffusion or facilitated carriers including ionophores and channels. Active transport comes in many, often complex forms. Examples of active transport include primary active transport (uniport), secondary active transport (cotransport, antiport) and group translocation. Besides the multitude of transport systems, transport can be accomplished by Gap Junctions, receptor-mediated endocytosis, phagocytosis, pinocytosis, exocytosis and apoptotic membrane blebbing.


title: Diagnosing COVID-19: The Disease and Tools for Detection

text: [Image: see text] COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.


title: A prospective study to assess the burden of influenza-related hospitalizations and emergency department visits among children in Bilbao, Spain (2010–2011)

text: Abstract Introduction This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age. Patients and methods Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture. Results A total of 501 children were recruited, of whom 91 were hospitalized. Influenza diagnosis was confirmed in 131 children (26.1%); 120 of 410 (29.3%) treated as outpatients and 11 of 91 (12.1%) hospitalized children. A total of 370 of 501 children (73.9%) had no laboratory test positive for influenza. The proportion of subjects with other respiratory viruses was 145/501 (28.9%) cases and co-infection with the influenza virus plus another respiratory virus was detected in 7/501 (1.4%) cases. Influenza virus types were: A (H1N1 and H3N2) 53.2% (67/126); B (Victoria and Yamagata) 46.0% (58/126); A+B 0.8% (1/126). The median direct medical costs associated with each case of laboratory-confirmed influenza was €177.00 (N =131). No significant differences were observed between the medical costs associated with influenza A and B. Conclusion Almost half of the cases were influenza virus B type. The administration of a vaccine containing influenza A and B types to children below 15 years of age might reduce the overall burden of the illness.


docid: jgwvjkbj

title: Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses

text: Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.


title: Prolonged SARS‐CoV‐2 RNA shedding: Not a rare phenomenon

text: A few studies have reported the long shedding of SARS-CoV-2 RNA. However, the duration of RNA shedding in Wuhan is rarely known and the meaning of the prolonged shedding is still under investigation. Almost 10% patients diagnosed of COVID-19 had a RNA shedding longer than 30 days even if the symptom elimination. The IgM was in a high level in the 9th week after symptom onset in these prolonged-RNA-shedding patients. Further study should be conducted to know the infectivity of the virus and the relationship between RNA shedding and antibody expression. This article is protected by copyright. All rights reserved.


title: SCHOOL Model and New Targeting Strategies

text: Protein-protein interactions play a central role in biological processes and thus are an appealing target for innovative drug design and development. They can be targeted by small molecule inhibitors, peptides and peptidomimetics, which represent an alternative to protein therapeutics that carry many disadvantages. In this chapter, I describe specific protein-protein interactions suggested by a novel model of immune signaling, the Signaling Chain HOmoO Ligomerization (SCHOOL) model, to be critical for cell activation mediated by multichain immune recognition receptors (MIRRs) expressed on different cells of the hematopoietic system. Unraveling a long-standing mystery of MIRR triggering and transmembrane signaling, the SCHOOL model reveals the intrareceptor transmembrane interactions and interreceptor cytoplasmic homointeractions as universal therapeutic targets for a diverse variety of disorders mediated by immune cells. Further, assuming that the general principles underlying MIRR-mediated transmembrane signaling mechanisms are similar, the SCHOOL model can be applied to any particular receptor of the MIRR family. Thus, an important application of the SCHOOL model is that global therapeutic strategies targeting key protein-protein interactions involved in MIRR triggering and transmembrane signal transduction may be used to treat a diverse set of immune-mediated diseases. This assumes that clinical knowledge and therapeutic strategies can be transferred between seemingly disparate disorders, such as T-cell-mediated skin diseases and platelet disorders, or combined to develop novel pharmacological approaches. Intriguingly, the SCHOOL model unravels the molecular mechanisms underlying ability of different human viruses such as human immunodeficiency virus, cytomegalovirus and severe acute respiratory syndrome coronavirus to modulate and/or escape the host immune response. It also demonstrates how the lessons learned from viral pathogenesis can be used practically for rational drug design. Application of this model to platelet collagen receptor signaling has already led to the development of a novel concept of platelet inhibition and the invention of new platelet inhibitors, thus proving the suggested hypothesis and highlighting the importance and broad perspectives of the SCHOOL model in the development of new targeting strategies.


title: A model for the emergence of drug resistance in the presence of asymptomatic infections

text: Abstract An analysis of a mathematical model, which describes the dynamics of an aerially transmitted disease, and the effects of the emergence of drug resistance after the introduction of treatment as an intervention strategy is presented. Under explicit consideration of asymptomatic and symptomatic infective individuals for the basic model without intervention the analysis shows that the dynamics of the epidemic is determined by a basic reproduction number R 0 . A disease-free and an endemic equilibrium exist and are locally asymptotically stable when R 0 < 1 and R 0 > 1 respectively. When treatment is included the system has a basic reproduction number, which is the largest of the two reproduction numbers that characterise the drug-sensitive ( R 1 ) or resistant ( R 2 ) strains of the infectious agent. The system has a disease-free equilibrium, which is stable when both R 1 and R 2 are less than unity. Two endemic equilibria also exist and are associated with treatment and the development of drug resistance. An endemic equilibrium where only the drug-resistant strain persists exists and is stable when R 2 > 1 and R 1 < R 2 . A second endemic equilibrium exists when R 1 > 1 and R 1 > R 2 and both drug-sensitive and drug-resistant strains are present. The analysis of the system provides insights about the conditions under which the infection will persist and whether sensitive and resistant strains will coexist or not.


title: Use of Ceftolozane-Tazobactam in Patient with Severe Medium Chronic Purulent Otitis by XDR Pseudomonas aeruginosa

text: We present a case of a male Italian patient of 66 years with a history of kidney transplantation in treatment with cyclosporine and methylprednisolone. He visited an ENT clinic and was diagnosed as chronic left purulent otitis media. He began at-home antibiotic therapy with poor benefit. On 09/13/18, he was admitted to the hospital “S. Maria ”of Terni for persistence of left ear pain and complete hearing loss. Magnetic resonance imaging (MRI) of the brain showed “in correspondence of the petrous rock and the mastoid…presence of flogistic tissue.” Auricular swabs and later surgical drainage of the purulent material were performed and both were positive for extensively drug-resistant (XDR) Pseudomonas aeruginosa sensitive only to colistin in absence of synergism with rifampin. The patient underwent antibiotic therapy with ceftolozane-tazobactam, a new generation cephalosporin with anti-Pseudomonas activity and a β-lactamase inhibitor, that currently is indicated for the treatment of complicated urinary tract infections and complicated intra-abdominal infections, with complete healing. In literature, it is described a series of 12 patients with severe MDR (multidrug-resistant) Pseudomonas aeruginosa infections (6 pneumonia) who received salvage therapy with ceftolozane-tazobactam after inappropriate empirical and/or suboptimal treatment. This study included a case of a male patient of 45 years, affected by Burkitt lymphoma and severe neutropenia, who presented with otitis and mastoiditis, and isolation of Pseudomonas aeruginosa in surgical drainage of the purulent material of the ear (blood cultures were negative). He underwent antibiotic therapy with ceftolozane–tazobactam at a dosage of 3 g/8 h for 21.3 days. The patient was healed, but a late recurrence was described because of isolation of ceftolozane-tazobactam-resistant Pseudomonas after therapy. The possibility of acquiring resistance to ceftolozane-tazobactam should be considered in patients with previous exposure to beta-lactams and with poor response to these antibiotics.


Why Am I, as a Geriatric Medicine Fellow with Symptoms, Unable to Get Tested for COVID‐19 While Politicians, Oil Executives, and NBA Players Are?


title: Isolation and Identification of Porcine Epidemic Diarrhea Virus and Its Effect on Host Natural Immune Response

text: Porcine epidemic diarrhea (PED) is a highly infectious intestinal disease caused by porcine epidemic diarrhea virus (PEDV). A PEDV strain was isolated from the piglet intestinal tract in Vero cells in Jiangsu Province, designated as the JS-A strain. PEDV was identified as the isolated virus by cytopathology, immunofluorescence assay, western blotting, transmission electron microscopy, and sequence analysis. The full-length genome of the JS-A isolate and the S gene were systematically analyzed, indicating that PEDV JS-A belongs to the G2a subtype, which is closely related to the prevalent PEDV in many countries and different from many current vaccines. Animal regression tests showed that piglets that are orally infected with the virus continue to develop diarrhea with yellowish and unpleasant odors. Further, piglets showed reduced food consumption and weight loss in the challenged group, while there were no abnormalities in the control group. In addition, Toll-like receptors (TLRs), RIG-I, and the downstream medium gene in the intestinal mucosa of newborn pigs infected with PEDV JS-A strain were studied. The neonatal Fc receptor (FcRn) was the only IgG transport receptor and protected IgG from degradation. Therefore, PEDV JS-A infection might inhibit FcRn expression by down-regulating TLRs and downstream signaling molecules. Taken together, isolation of the JS-A variant contributes to evolutionary analysis of the diarrhea virus. Further, the experimental infection model lays a foundation for further research related to vaccine development and the antiviral natural immune response of infected piglets, which helps us to better understand PEDV pathogenesis and immune mechanism.


docid: wlhmcdcn

title: Hot start reverse transcriptase: an approach for improved real-time RT-PCR performance

text: BACKGROUND: Reverse transcriptase is an indispensable enzyme for real-time reverse transcriptase (RT)-PCR, a standard method in molecular diagnostics for detection and quantification of defined RNA molecules. The prevention of non-specific products due to elongation of misprimed oligonucleotides by the enzyme at temperatures beneath the specific annealing temperature is one of the biggest challenges in real-time RT-PCR. In the present study, an aptamer directed against the reverse transcriptase was analyzed for its potential to attain a temperature-dependent reverse transcriptase (“hot start” RT). FINDINGS: The hot start effect was investigated in a one-step real-time RT-PCR assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV). Results with aptamer revealed a reduced RT activity at low temperatures while achieving full activity at the specific annealing temperature of 55 °C. Sensitivity (limit of detection (LoD) 95 %) of the MERS-CoV assay was increased by about two times in the presence of aptamer. CONCLUSIONS: The study demonstrates the potential of aptamer-dependent hot start RT for the improvement of diagnostic real-time RT-PCR assays.


title: Applications of Paper as a support material in biomedical sciences: A Decadal review

text: Abstract: In human history, the paper has long been used as a platform to record and preserve information. However, over the decades, paper has found its application in Biomedical Sciences, too. Both paper-based microfluidic devices (μPADs) and paper-based cultures and scaffolds have shown immense potential to be used as a sensor as well as a supporting material for in vitro tissue engineering. μPADs can be used to perform low-cost and fast biomolecular assays at Point-Of-Care (POC). They are being used to detect various biomarkers like viral proteins, metabolites, oncogenes, and antigens; and conditions like Venous Thromboembolism (VTE). On the other hand, the paper has also been used to develop paper-based 3D cultures and scaffolds to test drugs, and monitor cytotoxic effects in vitro cell microenvironments and also as implantable tissues. In this review, we intend to enumerate the development in the field of μPADs, paper-based cell cultures, and paper-based scaffolds and their plethora of applications over the last decade.


title: Chapter 1 Sialic acid and biology of life: An introduction

text: Abstract Sialic acids are important molecule with high structural diversity. They are known to occur in higher animals such as Echinoderms, Hemichordata, Cephalochorda, and Vertebrata and also in other animals such as Platyhelminthes, Cephalopoda, and Crustaceae. Plants are known to lack sialic acid. But they are reported to occur in viruses, bacteria, protozoa, and fungi. Deaminated neuraminic acid although occurs in vertebrates and bacteria, is reported to occur in abundance in the lower vertebrates. Sialic acids are mostly located in terminal ends of glycoproteins and glycolipids, capsular and tissue polysialic acids, bacterial lipooligosaccharides/polysaccharides, and in different forms that dictate their role in biology. Sialic acid play important roles in human physiology of cell-cell interaction, communication, cell-cell signaling, carbohydrate-protein interactions, cellular aggregation, development processes, immune reactions, reproduction, and in neurobiology and human diseases in enabling the infection process by bacteria and virus, tumor growth and metastasis, microbiome biology, and pathology. It enables molecular mimicry in pathogens that allows them to escape host immune responses. Recently sialic acid has found role in therapeutics. In this chapter we have highlighted the (i) diversity of sialic acid, (ii) their occurrence in the diverse life forms, (iii) sialylation and disease, and (iv) sialic acid and therapeutics.


title: Spezielle ophthalmologische Schutzmaßnahmen in der COVID‑19‑Pandemie

text: BACKGROUND: Healthcare work is a risk factor for coronavirus disease 2019 (COVID-19). OBJECTIVES: To review risk mitigation strategies in ophthalmology during the COVID-19 pandemic. MATERIAL AND METHODS: Risk mitigation strategies to maintain ophthalmology care, to prevent collateral damage from care disruption, and to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are summarized based on the example of a tertiary referral center in Germany. RESULTS: Clinical management strategies included restricted access to buildings, triage systems, telemedicine approaches, strategies for rapid treat and release, and transparent communication strategies. Strategies to protect patients and staff relied on both standard hygiene precautions and the use of personal protective equipment for prevention of droplet infections. Physical barriers supported risk mitigation strategies. CONCLUSION: To maintain ophthalmological care during the COVID-19 pandemic, a coordinated, multifaceted approach using risk mitigation strategies to protect staff, patients, and the public was initiated.


title: Reverse transcription loop-mediated isothermal amplification for the detection of highly pathogenic porcine reproductive and respiratory syndrome virus

text: Abstract A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay targeting the open reading frames 1a of highly pathogenic porcine reproductive and respiratory syndrome virus genome was developed. The 10 reference strains, 1 clinical isolation strain and 122 positive samples were tested. Positive reactions were confirmed for all strains and specimens by reverse transcription loop-mediated isothermal amplification and nested reverse transcription polymerase chain reaction (RT-PCR). The results showed this detection technique is more reliable and convenient for rapid and sensitive diagnosis of highly pathogenic porcine reproductive and respiratory syndrome virus infection.


title: Will First-Responders Show Up for Work During a Pandemic? Lessons From a Smallpox Vaccination Survey of Paramedics

text: Background The presence of H5N1 influenza in Southeast Asia has reawakened fears of a worldwide influenza pandemic of the sort that occurred in 1918. It is estimated that up to 1.9 million people in the United States could die if such an outbreak occurs. It is unlikely that a vaccine for a pandemic strain will be available quickly enough to protect first-responders. Similar concerns existed in 2002 when the United States attempted to vaccinate first-responders against smallpox, a potential biologic weapon. Method We conducted a survey of one group of first-responders, paramedics, to determine if fear of infection would compromise their ability to care for persons potentially infected with smallpox. Results Three hundred paramedics were given the survey, and 95 (32%) responded. More than 80% of paramedics polled would not remain on duty if there were no vaccine and no protective gear. Even if protective gear was available but the vaccine was unavailable, only 39% of respondents would remain on duty. Finally, although 91% of paramedics would remain on duty if they were fully protected, this number falls to 38% if the respondent believed that his or her immediate family was not protected. The results of this survey are relevant to current concerns about an influenza pandemic. Every effort must be made to protect first-responders from pandemic influenza and educate them about it.


title: Early Enhanced Expression of Interferon-Inducible Protein-10 (CXCL-10) and Other Chemokines Predicts Adverse Outcome in Severe Acute Respiratory Syndrome

text: Background: Exaggerated activation of cytokines/chemokines has been proposed as a factor in adverse outcome of severe acute respiratory syndrome (SARS). Previous studies on chemokines have included only small numbers of patients, and the utility of plasma chemokines as prognostic indicators is unclear. Methods: We studied 255 archival plasma samples collected during the first or second week after disease onset. The chemokines interferon-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation normal T cell expressed and secreted (RANTES) were measured by cytometric bead array with a 4-color FACSCalibur flow cytometer. Reverse transcription and real-time quantitative PCR and immunohistochemical staining were performed to analyze the production of IP-10 in lung tissue at autopsy. Conditional logistic regression was used to identify independent predictors for adverse disease outcome. Results: Increases in IP-10, MIG, and IL-8 during the first week after onset of fever were associated with adverse outcome (intensive care unit admission or death) in the univariate analysis. During the second week, only MIG concentration was associated with prognosis. After adjusting for other risk factors, plasma IP-10 concentration at the first week remained as an independent prognostic factor, with an odds ratio for adverse outcome of 1.52 (95% confidence interval, 1.05–2.55) per fold increase in plasma IP-10 concentration above the median. During the second week, chemokines provided little independent prognostic information. IP-10 was increased in lung tissue from patients who died of SARS. Conclusions: Increased plasma IP-10 during the first week of SARS symptoms is an independent predictor of outcome. Chemokine activation may be an early event in SARS, and an exaggerated host response may produce complications.


COVID19 ¿CÓMO AFECTA A LA REALIZACIÓN DE EJERCICIO FÍSICO EN MÉDICOS?


title: Polyadenylation of genomic RNA and initiation of antigenomic RNA in a positive-strand RNA virus are controlled by the same cis-element

text: Genomes and antigenomes of many positive-strand RNA viruses contain 3′-poly(A) and 5′-poly(U) tracts, respectively, serving as mutual templates. Mechanism(s) controlling the length of these homopolymeric stretches are not well understood. Here, we show that in coxsackievirus B3 (CVB3) and three other enteroviruses the poly(A) tract is ∼80–90 and the poly(U) tract is ∼20 nt-long. Mutagenesis analysis indicate that the length of the CVB3 3′-poly(A) is determined by the oriR, a cis-element in the 3′-noncoding region of viral RNA. In contrast, while mutations of the oriR inhibit initiation of (−) RNA synthesis, they do not affect the 5′-poly(U) length. Poly(A)-lacking genomes are able to acquire genetically unstable AU-rich poly(A)-terminated 3′-tails, which may be generated by a mechanism distinct from the cognate viral RNA polyadenylation. The aberrant tails ensure only inefficient replication. The possibility of RNA replication independent of oriR and poly(A) demonstrate that highly debilitated viruses are able to survive by utilizing ‘emergence’, perhaps atavistic, mechanisms.


title: Biological targets for isatin and its analogues: Implications for therapy

text: Isatin and its metabolites are constituents of many natural substances. They are also components of many synthetic compounds exhibiting a wide range of effects, including antiviral activity, antitumor and antiangiogenic activity, antibacterial, antitubercular, antifungal, antiaptotic, anticonvulsant and anxyolytic activities. Isatin itself is an endogenous oxidized indole with a wide spectrum of behavioral and metabolic effects. It has a distinct and discontinuous distribution in the brain, peripheral tissues and body fluids and isatin binding sites are widely distributed also. Its output is increased during stress. Its most potent known in vitro actions are as an antagonist of atrial natriuretic peptide (ANP) function and NO signaling. As we understand more about its function and sites of action we may be able to develop new pharmacological agents to mimic or counteract its activity. We consider here the most promising biological targets for various isatin analogues and/or metabolites, which are employed for the development of various groups of therapeutics. It is also possible that the level of endogenous isatin may influence the in vivo pharmacological activity of compounds possessing the isatin moiety.


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title: AI-Empowered Data Analytics for Coronavirus Epidemic Monitoring and Control

text: Governments and authorities knew little about the virus since the emergency of COVID-19 outbreak. The Chinese government upon the discovery of the early patients in Wuhan, informed WHO on 31 December 2019, as pneumonia of unknown causes. Epidemiologists, data scientists and biostatisticians have been working hand-in-hand for a common mission of trying to characterize and understand the characteristics of the infection as well as the virus itself, which is SARS alike.


title: Pathways and control of connexin oligomerization

text: Connexins form gap junction channels that link neighboring cells into an intercellular communication network. Many cells that express multiple connexins produce heteromeric channels containing at least two connexins, which provides a means to fine tune gap junctional communication. Formation of channels by multiple connexins is controlled at two levels: by inherent structural compatibilities that enable connexins to hetero-oligomerize and by cellular mechanisms that restrict the formation of heteromers by otherwise compatible connexins. Here, I discuss roles for secretory compartments beyond the endoplasmic reticulum in connexin oligomerization and evidence that suggests that membrane microdomains help regulate connexin trafficking and assembly.


COVID-19 Effect on Foot & Ankle Surgery in Shiraz, South of Iran


title: Trend and forecasting of the COVID-19 outbreak in China

text: By using the public data from Jan. 20 to Feb. 11, 2020, we perform data-driven analysis and forecasting on the COVID-19 epidemic in mainland China, especially Hubei province. Our results show that the turning points of the daily infections are predicted to be Feb. 6 and Feb. 1, 2020, for Hubei and China other than Hubei, respectively. The epidemic in China is predicted to end up after Mar. 10, 2020, and the number of the total infections are predicted to be 51600. The data trends reveal that quick and active strategies taken by China to reduce human exposure have already had a good impact on the control of the epidemic.


title: Lobar flexible fiberoptic lung lavage: therapeutic benefit in severe respiratory failure in pulmonary alveolar proteinosis and influenza A H1N1 pneumonia

text: Lobar fiberoptic lung lavage is a well-known procedure used in primary pulmonary alveolar proteinosis (PAP); the use of this procedure has increased in the recent years. This procedure has also been used in other pulmonary diseases such as desquamative interstitial pneumonia with good results. We describe a case of extremely severe respiratory failure due to concurrence of PAP and Influenza A H1N1 virus pneumonia which resolved with the help of this procedure. The patient, a 41-year-old woman, needed less mechanical ventilation after undergoing lobar fiberoptic bronchoscopic lavage. Moreover, a rapid and progressive improvement in the computed tomography of the lungs was observed. Flexibile fiberoptic bronchoscopic lobar lavage is a simple, safe procedure used not only in milder disease, but also in particular severe cases in which the physiological derangement of whole lung lavage would not be tolerated by patient or when extra-corporeal membrane oxygenation is not available.


title: Development and evaluation of a broadly reactive reverse transcription recombinase polymerase amplification assay for rapid detection of murine norovirus

text: BACKGROUND: Murine norovirus (MNV) is recognized as the most prevalent viral pathogen in captive mouse colonies. The rapid detection assay for MNV would be a useful tool for monitoring and preventing MNV infection. A recombinase polymerase amplification (RPA) assay was established in this study to provide a solution for rapid and sensitive detection of MNV. RESULTS: The detection limit of the RT-RPA assay for the detection of MNV was 1 × 10(2) copies of RNA molecules per reaction. The assay was specific since there was no cross-reaction with other common murine viruses. In addition, the broad reactivity of the RT-RPA assay was validated using the synthesized template carrying seven point mutations among several MNV strains. The MNV RT-RPA assay could detect as few as 1 × 10(2) copies of the mutant per reaction, suggesting the assay could be broadly reactive against a large diversity of MNV strains. Forty eight clinical samples including 16 gastric tissue specimens, 16 cecal tissue specimens and 16 fecal specimens were tested for the validation of the new developed RT-RPA assay. The detection results of RT-RPA and RT-qPCR for clinical samples were very similar, except that a gastric tissue sample which was positive by RT-qPCR, with a RNA titer of 27 copies, was negative by RT-RPA. CONCLUSIONS: A broadly reactive RT-RPA assay was successfully established for MNV detection.


title: Virus RNA Persists within the Retina in Coronavirus-Induced Retinopathy

text: Abstract The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase, Day 1 to Day 7, a retinal vasculitis is noted which is associated with the presence of viral proteins and infectious virus. In the late phase, Day 10 to Day 140, a retinal degeneration is associated with the absence of viral proteins, infectious virus, and inflammatory cells. The purpose of this study was to determine if viral RNA persists within the retina during the retinal degenerative phase of the disease. BALB/c mice were inoculated by the intravitreal route with 104.0TCID50/5 μl of virus. The presence of viral RNA was detected byin situhybridization with a viral cDNA probe and viral proteins were identified by immunocytochemical staining. During the acute phase of the infection, viral RNA was found in the retina, RPE, ciliary body epithelium, and the iris epithelium. During the late phase of the infection, viral RNA was almost exclusively found within the retina and RPE and not in the anterior segment of the eye. Within the retina, viral RNA was detected in the ganglion cell layer, the inner retina, the outer retina, and the RPE cell. Immunocytochemical staining identified viral protein within the retina only from Day 1 to Day 8. This ocular disease was also associated with a persistent systemic infection. Both viral RNA and viral proteins were identified within the liver during the first 8 days. However, only viral RNA was detected in the liver from Day 8 to Day 60. These studies demonstrate that MHV established an acute infection (Day 1–8) where infectious virus and viral proteins were identified. This was followed by a persistent infection within the retina and liver where only viral RNA were detected byin situhybridization.


title: Rhabdomyolysis Associated with Parainfluenza Virus

text: Influenza virus is the most frequently reported viral cause of rhabdomyolysis. A 7-year-old child is presented with rhabdomyolysis associated with parainfluenza type 2 virus. Nine cases of rhabdomyolysis associated with parainfluenza virus have been reported. Complications may include electrolyte disturbances, acute renal failure, and compartment syndrome.


title: Recombinational histories of avian infectious bronchitis virus and turkey coronavirus

text: Phylogenetic analysis of complete genomes of the avian coronaviruses avian infectious bronchitis (AIBV) and turkey coronavirus (TCoV) supported the hypothesis that numerous recombination events have occurred between these viruses. Although the two groups of viruses differed markedly in the sequence of the spike protein, the gene (S) encoding this protein showed no evidence of positive selection or of an elevated mutation rate. Rather, the data suggested that recombination events have homogenized the portions of the genome other than the S gene between the two groups of viruses, while continuing to maintain the two distinct, anciently diverged versions of the S gene. The latter hypothesis was supported by a phylogeny of S proteins from representative coronaviruses, in which S proteins of AIBV and TCoV fell in the same clade. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-011-1061-5) contains supplementary material, which is available to authorized users.


title: Efficient amplification and cloning of near full-length hepatitis C virus genome from clinical samples

text: Abstract Long RT-PCR (LRP) amplification of RNA templates is sometimes difficult compared to long PCR of DNA templates. Among RNA templates, hepatitis C virus (HCV) represents an excellent example to challenge the potential of LRP technology due to its extensive secondary structures and its difficulty to be readily cultured in vitro. The only source for viral genome amplification is clinical samples in which HCV is usually present at low titers. We have created a comprehensive optimization protocol that allows robust amplification of a 9.1kb fragment of HCV, followed by efficient cloning into a novel vector. Detailed analyses indicate the lack of potential LRP-mediated recombination and the preservation of viral diversity. Thus, our LRP protocol could be applied for the amplification of other difficult RNA templates and may facilitate RNA virus research such as linked viral mutations and reverse genetics.


title: Tertiary structure prediction of SARS coronavirus helicase

text: Abstract SARS coronavirus, SCV, has been recently responsible of a sudden and widespread infection which caused almost 800 victims. The limited amount of SCV protein structural information is partially responsible of the lack of specific drugs against the virus. Coronavirus helicases are very conserved and peculiar proteins which have been proposed as suitable targets for antiviral drugs, such as bananins, which have been recently shown to inhibit the SCV helicase in vitro. Here, the quaternary structure of SCV helicase has been predicted, which will provide a solid foundation for the rational design of other antiviral helicase inhibitors.


title: Educating Surgeons to Educate Patients about the COVID-19 Pandemic

text: Abstract: The spring of 2020 has been a trying time for the global medical community as it has faced the latest pandemic, COVID-19. This contagious and lethal virus has impacted patients and healthcare workers alike. Elective surgeries have been suspended and the very core of our healthcare system is being strained. The following brief communication reviews pertinent details about the virus, delaying elective surgeries and what patients can do during this time. The goal is to disseminate factual data that surgeons can then use to educate their patients.


title: On Answering the Call to Action for COVID-19: Continuing a Bold Legacy of Health Advocacy

text: The disproportionately high burden of death and disability observed for racial and ethnic minorities under the Coronavirus pandemic necessitates sustained advocacy by the medical and public health communities around critical determinants of population health. Prompting our advocacy should be the understanding that our collective ability to rebound from such crises may ultimately hinge on protecting and equipping our most vulnerable racial-ethnic minority groups and any susceptible individuals within those populations. If proven effective, recent historic firsts by the U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), the Office of Minority Health (OMH) and the Centers for Disease Control and Prevention (CDC) in response to COVID-19 should be championed for permanency within policy, practice and funding. In addition, given the complex history of Black Americans in this country and persistent and substantial Black-white disparities on health and economic measures across the board, some kind of reparations for this group may serve as a logical starting point for further advocacy. Nevertheless, we remain supportive allies of all organizations concerned with communities who suffer the weight of this pandemic and any future world health disasters. Let us as human clinicians and public health professionals capture this moment of challenge and engage in thoughtful unification of effort and commit to measurable progress for as long as the need exists and certainly for the foreseeable future.


title: Role of the Backbenchers of the Renin-Angiotensin System ACE2 and AT2 Receptors in COVID-19: Lessons From SARS

text: The novel coronaviruses causing severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) have been shown to utilize angiotensin-converting enzyme 2 (ACE2) as the receptor for entry into the host cells. The involvement of the renin-angiotensin system (RAS) in the evolution and pathogenesis of lung diseases has been implicated in recent years. The two enzymes of RAS, angiotensin-converting enzyme (ACE) and ACE2, serve a contrasting function. ACE helps in the formation of angiotensin II (AGII) from angiotensin I (AGI), and ACE2 cleaves AGI and AGII into AG (1-9) and AG (1-7) respectively. The ACE-induced AGII has vasoconstrictor and pro-inflammatory properties via AT1R, whereas ACE2 has been shown to protect against lung injury. The less spoken about AGII receptor, angiotensin receptor type 2 (AT2R), has anti-inflammatory and anti-fibrotic effects in lung tissue and may be of significance in light of the lung pathology presentation in COVID-19. A review of articles searched in PubMed and peer-reviewed journals of importance was done using search terms “ACE2,” “AT2,” “SARS,” and COVID-19.” Lung involvement in both SARS and COVID-19 has been very severe and suggestive of severe inflammatory and immune reactions. Animal studies have shown that ACE2 and AT2 receptors counter the pro-inflammatory and other effects mediated by angiotensin II by their vasodilator, anti-inflammatory, anti-fibrotic, and anti-proliferative effects. They have been shown to protect against and revert acute lung injuries. The instrumental role of recombinant ACE2, AT2 receptor agonists, and AT1 receptor blockers may be helpful in the treatment of COVID-19.


title: Acute Renal Failure in Critically Ill COVID-19 Patients With a Focus on the Role of Renal Replacement Therapy: A Review of What We Know So Far

text: Acute renal failure remains a significant concern in all patients with the coronavirus disease 2019 (COVID-19) infection. Management is particularly challenging in critically ill patients requiring intensive care unit (ICU) level of care. Supportive care in the form of accurate volume correction and avoiding nephrotoxic agents are the chief cornerstone of the management of these patients. The pathophysiology of acute renal failure in COVID-19 is multifactorial, with significant contributions from excessive cytokine release. Gaining a better insight into the pathophysiology of renal failure will hopefully help develop more directed treatment options. A considerable number of these patients deteriorate despite adequate supportive care owing to the complexity of the disease and multi-organ involvement. Renal replacement therapy is used for a long time in critically ill septic patients who develop progressive renal failure despite adequate conservative support. Timing and choice of renal replacement therapy in critically ill COVID-19 patients remains an area of future research that may help decrease mortality in this patient population.