title: Paying Participants in COVID-19 Trials

text: Trials are in development and underway to examine potential interventions for treatment and prophylaxis of coronavirus disease 2019 (COVID-19). How should we think about offering payment to participants in these trials? Payment for research participation is ethically contentious even under ideal circumstances. Here, we review 3 functions of research payment—reimbursement, compensation, and incentive—and identify heightened and novel ethical concerns in the context of a global pandemic. We argue that COVID-19 trial participants should usually be offered reimbursement for research-related expenses, and compensation for their time and effort, as for other types of research under usual circumstances. Given increased risk of undue influence against pandemic background conditions, incentive payment should be avoided unless essential to recruitment and retention in important trials whose social value outweighs this risk. Where essential, however, incentives can be ethically permissible, so long as reasonable efforts are made to minimize the possibility of undue influence.


ACEi and ARB with COVID‐19


title: A review of cardiac manifestations and predictors of outcome in patients with COVID – 19

text: Abstract Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196, 000 deaths, with more than 50, 000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.


Abstract 43. Neural cell cultures as a tool in analyzing neurovirulence and persistence of viruses


Endonasal Drilling May Be Employed Safely in the COVID‐19 Era


title: Imaging findings in COVID-19 pneumonia

text: The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan city and was declared a pandemic in March 2020. Although the virus is not restricted to the lung parenchyma, the use of chest imaging in COVID-19 can be especially useful for patients with moderate to severe symptoms or comorbidities. This article aimed to demonstrate the chest imaging findings of COVID-19 on different modalities: chest radiography, computed tomography, and ultrasonography. In addition, it intended to review recommendations on imaging assessment of COVID-19 and to discuss the use of a structured chest computed tomography report. Chest radiography, despite being a low-cost and easily available method, has low sensitivity for screening patients. It can be useful in monitoring hospitalized patients, especially for the evaluation of complications such as pneumothorax and pleural effusion. Chest computed tomography, despite being highly sensitive, has a low specificity, and hence cannot replace the reference diagnostic test (reverse transcription polymerase chain reaction). To facilitate the confection and reduce the variability of radiological reports, some standardizations with structured reports have been proposed. Among the available classifications, it is possible to divide the radiological findings into typical, indeterminate, atypical, and negative findings. The structured report can also contain an estimate of the extent of lung involvement (e.g., more or less than 50% of the lung parenchyma). Pulmonary ultrasonography can also be an auxiliary method, especially for monitoring hospitalized patients in intensive care units, where transfer to a tomography scanner is difficult.


docid: gwdneuin

title: The Application of Artificial Neural Networks and Logistic Regression in the Evaluation of Risk for Dry Eye after Vitrectomy

text: Supervised machine-learning (ML) models were employed to predict the occurrence of dry eye disease (DED) after vitrectomy in this study. The clinical data of 217 patients receiving vitrectomy from April 2017 to July 2018 were used as training dataset; the clinical data of 33 patients receiving vitrectomy from August 2018 to September 2018 were collected as validating dataset. The input features for ML training were selected based on the Delphi method and univariate logistic regression (LR). LR and artificial neural network (ANN) models were trained and subsequently used to predict the occurrence of DED in patients who underwent vitrectomy for the first time during the period. The area under the receiver operating characteristic curve (AUC-ROC) was used to evaluate the predictive accuracy of the ML models. The AUCs with use of the LR and ANN models were 0.741 and 0.786, respectively, suggesting satisfactory performance in predicting the occurrence of DED. When the two models were compared in terms of predictive power, the fitting effect of the ANN model was slightly superior to that of the LR model. In conclusion, both LR and ANN models may be used to accurately predict the occurrence of DED after vitrectomy.


Disinfection tunnels (DT): potentially counterproductive in the context of a prolonged pandemic of COVID-19


title: The non-structural protein Nsp10 of mouse hepatitis virus binds zinc ions and nucleic acids

text: The non-structural protein Nsp10 of coronaviruses is a small cleavage product of the viral replicase polyprotein that has been implicated in RNA synthesis. Nsp10 of mouse hepatitis virus (MHV) displays an apparent molecular mass of 13–16 kDa in reducing SDS–PAGE and analytical gel filtration, while dynamic light scattering suggests the existence of oligomeric forms. Atomic absorption spectroscopy reveals two metal ions per Nsp10 monomer, with a preference for Zn(2+) over Fe(2+/3+) and Co(2+). These are probably bound by two Zn-finger-like motifs. Moreover, MHV Nsp10 interacts with tRNA, single-stranded RNA, double-stranded DNA and, to a lesser extent, single-stranded DNA as shown by gel-shift experiments. The K(d) for tRNA is 2.1 ± 0.2 μM.


title: Evaluation of respiratory protection programs and practices in California hospitals during the 2009–2010 H1N1 influenza pandemic

text: BACKGROUND: Emergence of the novel 2009 influenza A H1N1 virus in California led to an evaluation of hospital respiratory protection programs (RPPs) and practices by the California Department of Public Health during the 2009–2010 influenza season. METHODS: Onsite evaluation of 16 hospitals consisted of interviews with managers and health care workers about RPPs and practices, review of written RPPs, and limited observations of personnel using respirators. Data were analyzed using descriptive statistics. RESULTS: All hospitals had implemented policies requiring the minimum use of N95 filtering facepiece respirators when working with patients with H1N1 virus infection; 95.5% of health care workers (n = 199) reported they would wear at least this level of protection when in close contact with a patient with confirmed or suspected H1N1 virus infection. However, evaluation of written RPPs indicated deficiencies in required areas, most commonly in recordkeeping, designation of a program administrator, program evaluation, employee training, and fit testing procedures. CONCLUSIONS: Health care workers were aware of respiratory protection required when providing care for patients with confirmed or suspected H1N1 virus infection. Hospitals should improve written RPPs, fully implement written procedures, and conduct periodic program evaluation to ensure effectiveness of respirator use for health care worker protection. Increased accessibility of resources tailored for hospital respirator program administrators may be helpful.


title: Liver involvement is not associated with mortality: results from a large cohort of SARS‐CoV‐2 positive patients

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is frequently associated with liver tests abnormalities. AIMS: To describe the evolution of liver involvement during SARS‐CoV‐2 infection and its effect on clinical course and mortality. METHODS: Data of 515 SARS‐CoV‐2 positive patients were collected at baseline and during follow‐up, last evaluation or death. Stratification based on need for hospitalization, severe disease and admission to intensive care unit (ICU) was performed. The association between liver tests abnormalities (baseline and peak values) and ICU admission or death was also explored. RESULTS: Liver tests abnormalities were found in 161 (31.3%) patients. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were increased in 20.4%, 19% and 13.6% of patients, respectively. Baseline liver tests abnormalities were associated with increased risk of ICU admission (OR 2.19 [95%CI 1.24‐3.89], p=0.007) but not with mortality (OR 0.84 [95%CI 0.49‐1.41], p=0.51). Conversely, ALP peak values were correlated with the risk of death (OR 1.007 [95%CI 1.002‐1.01], p=0.005) along with age, multiple comorbidities, acute respiratory distress syndrome (ARDS), ICU admission, and C‐reactive protein. Alterations of liver tests worsened within 15 days after hospitalization; however, in patients with the longest median follow‐up, the prevalence of liver tests alterations decreased over time, returning similar to that of baseline. CONCLUSIONS: In SARS‐CoV‐2 positive patients without pre‐existing severe chronic liver disease, baseline liver tests abnormalities are associated with the risk of ICU admission and tend to normalize over time. ALP peak value seems to be predictive of a worse prognosis.


title: Involvement of a joker mutation in a polymerase-independent lethal mutagenesis escape mechanism

text: Abstract We previously characterized a foot-and-mouth disease virus (FMDV) with three amino acid replacements in its polymerase (3D) that conferred resistance to the mutagenic nucleoside analogue ribavirin. Here we show that passage of this mutant in the presence of high ribavirin concentrations resulted in selection of viruses with the additional replacement I248T in 2C. This 2C substitution alone (even in the absence of replacements in 3D) increased FMDV fitness mainly in the presence of ribavirin, prevented an incorporation bias in favor of A and U associated with ribavirin mutagenesis, and conferred the ATPase activity of 2C decreased sensitivity to ribavirin-triphosphate. Since in previous studies we described that 2C with I248T was selected under different selective pressures, this replacement qualifies as a joker substitution in FMDV evolution. The results have identified a role of 2C in nucleotide incorporation, and have unveiled a new polymerase-independent mechanism of virus escape to lethal mutagenesis.


Covid-19, que fait l'Europe ?


title: Oligomerization is essential for transport of vesicular stomatitis viral glycoprotein to the cell surface

text: Abstract Using ts045, a temperature sensitive strain of Vesicular stomatitis virus, we show that oligomerization of G protein is a prerequisite for its transport from RER to the Golgi apparatus and for its subsequent maturation. While wild-type G forms an oligomer in the RER, ts045 G synthesized at the nonpermissive temperature does not. When the permissive temperature is reinstated, ts045 G forms an oligomer and moves to the Golgi. The state of oligomerization was determined by chemical cross-linking and by the ability of a microinjected monoclonal antibody specific for the carboxy-terminal five amino acids of the cytoplasmic tail of G to cause patching of G in intracellular membranes. We conclude that formation of an oligomer of G protein, probably a trimer, is necessary for G protein maturation.


title: Biological sex impacts COVID-19 outcomes

text: The current novel coronavirus disease 2019 (COVID-19) pandemic is revealing profound differences between men and women in disease outcomes worldwide. In the United States, there has been inconsistent reporting and analyses of male–female differences in COVID-19 cases, hospitalizations, and deaths. We seek to raise awareness about the male-biased severe outcomes from COVID-19, highlighting the mechanistic differences including in the expression and activity of angiotensin-converting enzyme 2 (ACE2) as well as in antiviral immunity. We also highlight how sex differences in comorbidities, which can be associated with both age and race, impact male-biased outcomes from COVID-19.


title: Risk Factors for Mortality among COVID-19 Patients

text: Abstract Aims COVID-19 is a current globalpandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. Methods A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. Results Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. Conclusions Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.


El reto de una UCI en un recinto ferial


CAPACITY-COVID: a European registry to determine the role of cardiovascular disease in the COVID-19 pandemic


title: Survival of surrogate coronaviruses in water

text: Abstract The emergence of a previously unknown coronavirus infection, Severe Acute Respiratory Syndrome (SARS), demonstrated that fecally contaminated liquid droplets are a potential vehicle for the spread of a respiratory virus to large numbers of people. To assess potential risks from this pathway, there is a need for surrogates for SARS coronavirus to provide representative data on viral survival in contaminated water. This study evaluated survival of two surrogate coronaviruses, transmissible gastroenteritis (TGEV) and mouse hepatitis (MHV). These viruses remained infectious in water and sewage for days to weeks. At 25°C, time required for 99% reduction in reagent-grade water was 22 days for TGEV and 17 days for MHV. In pasteurized settled sewage, times for 99% reduction were 9 days for TGEV and 7 days for MHV. At 4°C, there was <1log10 infectivity decrease for both viruses after four weeks. Coronaviruses can remain infectious for long periods in water and pasteurized settled sewage, suggesting contaminated water is a potential vehicle for human exposure if aerosols are generated.


title: The burden of type 2 diabetes: are we doing enough?

text: Summary Increasing levels of obesity, arising from energy-rich diets and sedentary lifestyles, are driving a global pandemic of type 2 diabetes. The prevalence of type 2 diabetes worldwide is set to increase from its present level of 150 million, to 225 million by the end of the decade and to as many as 300 million by 2025. Shocking as they are, these figures represent only clinically diagnosed diabetes, and many more cases of diabetes remain undiagnosed and untreated. In addition, up to one-quarter of western populations have impaired glucose tolerance or the dysmetabolic syndrome, which are considered to represent pre-diabetic states. Type 2 diabetes is appearing increasingly in children and adolescents, and the frequency of diagnosis of paediatric type 2 diabetes is outstripping that of type 1 diabetes in some areas. The long-term complications associated with type 2 diabetes carries a crushing burden of morbidity and mortality, and most type 2 diabetic patients die prematurely from a cardiovascular event. Diabetic patients are more than twice as costly to manage as non-diabetic patients, due mainly to the high costs associated with management of diabetic complications. Indeed, diabetes care already accounts for about 2-7% of the total national health care budgets of western European countries. Controlling the type 2 diabetes epidemic will require changes to the structure of healthcare delivery. Well-resourced interventions will be required, with effective co-ordination between all levels of government, health care agencies, multidisciplinary health care teams, professional organisations, and patient advocacy groups. Above all, intervention is needed today.


title: The Critical Role of Nonhuman Primates in Medical Research

text: The sponsors of this report endorse carefully regulated research with nonhuman primates. This research is essential to learning about the biology, treatment and prevention of diseases and conditions that cause human suffering.


title: Activation of JNK1/2 and p38 MAPK signaling pathways promotes enterovirus 71 infection in immature dendritic cells

text: BACKGROUND: c-Jun NH(2)-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38 MAPK) are important components of cellular signal transduction pathways, which have been reported to be involved in viral replication. However, little is known about JNK1/2 and p38 MAPK signaling pathways in enterovirus 71 (EV71)-infected immature dendritic cells (iDCs). Thus, iDCs were induced from peripheral blood mononuclear cells (PBMC) and performed to explore the expressions and phosphorylation of molecules in the two signaling pathways as well as secretions of inflammatory cytokines and interferons during EV71 replication. RESULTS: We showed that EV71 infection could activate both JNK1/2 and p38 MAPK in iDCs and phosphorylate their downstream transcription factors c-Fos and c-Jun, which further promoted the production of IL-2, IL-6, IL-10, and TNF-α. Moreover, EV71 infection also increased the release of IFN-β and IL-12 p40. Pretreatment of iDCs with SP600125 and SB203580 (20 μM) could severely impair viral replication and its induced phosphorylation of JNK1/2,p38 MAPK, c-Fos and c-Jun. In addition, treatment of EV71-infected iDCs with SP600125 and SB203580 could inhibit secretions of IL-6, IL-10 and TNF-α. CONCLUSION: JNK1/2 and p38 MAPK signaling pathways are beneficial to EV71 infection and positively regulate secretions of inflammatory cytokines in iDCs.


title: Epitope‐based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study

text: Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope‐based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope‐based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell‐mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post‐therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope‐based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments.


title: Coping with the threat of severe acute respiratory syndrome: Role of threat appraisals and coping responses in health behaviors

text: The present study examines the psychological impact of severe acute respiratory syndrome (SARS) by exploring the coping strategies and health behaviors enacted in response to the SARS epidemic. Hierarchical linear regression indicated that the use of wishful thinking in response to the threat of SARS was related to both avoiding public places and avoiding people perceived to be possible carriers of the SARS virus, but was not associated with the use of more adaptive health behaviors, such as using disinfectants and hand washing. Conversely, those who reported engaging in empathic responding in response to the threat of SARS were both less likely to report avoiding people perceived as being at a high risk for SARS and more likely to report engaging in effective health behaviors. Support seeking was not a significant predictor of the health behaviors examined in the present study. Results are discussed in terms of coping with health threats and health promotion.


title: Upper respiratory infections in a rural area with reduced malaria transmission in Senegal: a pathogens community study

text: BACKGROUND: Acute Respiratory Infections (ARI) are common causes of febrile illnesses in many settings in Senegal. These infections are usually managed presumptively due to lack of appropriate diagnostic tools. This situation, can lead to poor management of febrile illness or antibiotic misuse. In addition, there are limited data on the spectrum of pathogens commonly responsible for these ARI. This study was conducted to explore the pathogens community among patients with acute respiratory infection in a rural area in Senegal. METHODS: A cross sectional study was conducted from August to December 2015. Children and adult patients attending Keur Socé health post for signs suggestive of acute respiratory infection were enrolled after providing inform consent. Eligible participants were recruited using a consecutive sampling method. Paired nose and throat swabs were collected for pathogen detection. Samples were processed using a multiplex PCR designed to identify 21 pathogens including both virus and bacteria. RESULTS: Two hundred and fifty patients participated in the study. Samples positivity rate was evaluated at 95.2% (238/250). Streptococcus pneumoniae was the predominant pathogen (74%) and was present in all months and all age-groups, followed by Staphylococcus aureus (28,8%) and rhinovirus (28,4%). Respiratory syncytial virus (RSV) was detected only among children under 5 years old in August and September while coronavirus was present in all age groups, during the months of October and December. CONCLUSION: This pilot study revealed a diversity of pathogens over the time and across all age groups, highlighting the need for further exploration. A pathogen community approach including both virus and bacteria at a larger scale becomes crucial for a better understanding of transmission dynamics at population level in order to help shape ARI control strategies.


title: Epidemic Intelligence Service Officers and Field Epidemiology Training Program in Korea

text: Korea has adopted Epidemic Intelligence Service (EIS) officers through the Field Epidemiology Training Program (FETP) since 1999 for systematic control of emerging and re-emerging infectious diseases. Graduates of medical schools in Korea are selected and serve as public health doctors (PHDs) for their mandatory military service. The duration of service is 3 years and PHDs comprise general practitioners and specialists. Some PHDs are selected as EIS officers with 3 weeks basic FETP training and work for central and provincial public health authorities to conduct epidemiological investigations. The total number of EIS officers is 31 as of 2012. The Korea Centers for Disease Control and Prevention (KCDC) has 12 specialists, whereas specialists and each province has one or two EIS officers to administer local epidemiological investigations in 253 public health centers. The Korean EIS officers have successfully responded and prevented infectious diseases, but there is a unique limitation: the number of PHDs in Korea is decreasing and PHDs are not allowed to stay outside Korea, which makes it difficult to cope with overseas infectious diseases. Furthermore, after 3 years service, they quit and their experiences are not accumulated. KCDC has hired full-time EIS officers since 2012 to overcome this limitation.


title: Surviving the surge: Evaluation of early impact of COVID-19 on inpatient pharmacy services at a community teaching hospital

text: PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has presented novel challenges to healthcare systems; however, an analysis of the impact of the pandemic on inpatient pharmacy services has not yet been conducted. METHODS: Results of an observational assessment of operational and clinical pharmacy services at a community teaching hospital during the first weeks of the COVID-19 pandemic are presented. Service outcomes of the inpatient pharmacy were evaluated from February 1 to April 8, 2020. Outcomes during the weeks preceding the first COVID-19 admission (February 1 to March 11, 2020) and during the pandemic period (March 12 to April 8, 2020) were compared. Evaluated outcomes included daily order verifications, clinical interventions, and usage of relevant medications. An exploratory statistical analysis was conducted using Student’s t test. RESULTS: During the pandemic period, the number of new order verifications decreased from approximately 5,000 orders per day to 3,300 orders per day (P < 0.01), a reduction of 30% during the first 4 weeks of the pandemic compared to the weeks prior. Average daily pharmacokinetic dosing consults were reduced in the pandemic period (from 82 to 67; P < 0.01) compared to the prepandemic period; however, total daily pharmacist interventions did not differ significantly (473 vs 456; P = 0.68). Dispensing of hydroxychloroquine, azithromycin, enoxaparin, and sedative medications increased substantially during the pandemic period (P < 0.01 for all comparisons). CONCLUSION: The operational and clinical requirements of an inpatient pharmacy department shifted considerably during the first weeks of the COVID-19 pandemic. Pharmacy departments must be adaptable in order to continue to provide effective pharmaceutical care during the pandemic.


docid: ozzgzotr

title: Will legal international rhino horn trade save wild rhino populations?

text: Wild vertebrate populations all over the globe are in decline, with poaching being the second-most-important cause. The high poaching rate of rhinoceros may drive these species into extinction within the coming decades. Some stakeholders argue to lift the ban on international rhino horn trade to potentially benefit rhino conservation, as current interventions appear to be insufficient. We reviewed scientific and grey literature to scrutinize the validity of reasoning behind the potential benefit of legal horn trade for wild rhino populations. We identified four mechanisms through which legal trade would impact wild rhino populations, of which only the increased revenue for rhino farmers could potentially benefit rhino conservation. Conversely, the global demand for rhino horn is likely to increase to a level that cannot be met solely by legal supply. Moreover, corruption is omnipresent in countries along the trade routes, which has the potential to negatively affect rhino conservation. Finally, programmes aimed at reducing rhino horn demand will be counteracted through trade legalization by removing the stigma on consuming rhino horn. Combining these insights and comparing them with criteria for sustainable wildlife farming, we conclude that legalizing rhino horn trade will likely negatively impact the remaining wild rhino populations. To preserve rhino species, we suggest to prioritize reducing corruption within rhino horn trade, increasing the rhino population within well-protected 'safe havens' and implementing educational programmes and law enforcement targeted at rhino horn consumers.


title: Pediatric Drug Nitazoxanide: A Potential Choice for Control of Zika

text: Zika virus (ZIKV) infection can be the cause of congenital malformations, including microcephaly in infants and can cause other disorders such as Guillain-Barré syndrome, meningoencephalitis, and myelitis, which can also occur in some infected adults. However, at this time, there is no drug approved to treat ZIKV infection. Drug repurposing is the promptest way to obtain an effective drug during a global public health emergency such as the spread of Zika virus. In this study, we report a US Food and Drug Admistration-approved drug that is safe for pediatric use. Nitazoxanide and its bioactive metabolite, tizoxanide, have anti-ZIKV potential in vitro, and we identified that they exerts antiviral effect possibly by targeting the viral postattachment step.


Getting a handle on RNA virus recombination


docid: smlumvqc

title: Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases

text: This study aimed to identify what information triggered social media users’ responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.


title: The risks of targeting co-inhibitory pathways to modulate pathogen-directed T cell responses

text: The identification of T cell co-inhibition as a central mechanism in the regulation of adaptive immunity during infectious diseases provides new opportunities for immunotherapeutic interventions. However, the fact that T cell activity is frequently downregulated during pathogen-directed responses suggests a pivotal physiological role of co-inhibitory pathways during infectious disease. Reports of exacerbated immunopathology in conditions of impaired co-inhibition foster the view that downregulation of T cell activity is an essential negative feedback mechanism that protects from excessive pathogen-directed immunity. Thus, targeting co-inhibitory pathways can bear detrimental potential through the deregulation of physiological processes. Here, we summarize recent preclinical and clinical interventions that report immune-related adverse events after targeting co-inhibitory pathways.


title: Neumonías comunitarias graves del adulto

text: Las neumonías agudas comunitarias son causa frecuente de hospitalización y mortalidad. El reconocimiento inmediato de las formas graves según criterios simples, clínicos, radiológicos y de laboratorio, es una etapa esencial para un tratamiento rápido en el servicio de reanimación con el fin de controlar los fallos orgánicos. La obtención de muestras apropiadas para realizar estudios microbiológicos precede al tratamiento antibiótico, que se debe instaurar con rapidez después de diagnosticar la neumonía. Pese a las técnicas de identificación, sólo la mitad de las neumonías se documentan adecuadamente. El tratamiento antibiótico, en principio empírico, integra los gérmenes patógenos, tanto extracelulares como intracelulares, que producen neumonías con mayor frecuencia; siempre debe ser activo contra el neumococo, la bacteria implicada más a menudo. La asociación de un betalactámico y un macrólido o una fluoroquinolona es la que mejor responde a este objetivo. En las recomendaciones más comunes, las fluoroquinolonas activas contra los neumococos sustituyen a los fármacos precedentes. En el caso excepcional de los pacientes con factores de riesgo especiales, el tratamiento empírico debe tener en cuenta Pseudomonas aeruginosa. La gravedad de parte de las neumonías comunitarias justifica el que se recurra a tratamientos complementarios. Se debe evaluar de nuevo el tratamiento antibiótico en las 72 horas siguientes a su instauración, a fin de valorar su eficacia, adaptar el tratamiento en caso necesario y simplificarlo. El mantenimiento de antibióticos de amplio espectro expone al paciente a efectos secundarios y contribuye a producir resistencias bacterianas. En cuanto a las neumonías neumocócicas, las fluoroquinolonas activas contra el neumococo podrían representar una alternativa en caso de que el neumococo desarrolle resistencia a los betalactámicos. La mortalidad persistente de las neumonías sigue siendo notable. Esto debe fomentar la mejora del tratamiento inicial y la búsqueda de nuevas opciones terapéuticas.


title: Probability, logic and the cognitive foundations of rational belief

text: Abstract Since Pascal introduced the idea of mathematical probability in the 17th century discussions of uncertainty and “rational” belief have been dogged by philosophical and technical disputes. Furthermore, the last quarter century has seen an explosion of new questions and ideas, stimulated by developments in the computer and cognitive sciences. Competing ideas about probability are often driven by different intuitions about the nature of belief that arise from the needs of different domains (e.g., economics, management theory, engineering, medicine, the life sciences etc). Taking medicine as our focus we develop three lines of argument (historical, practical and cognitive) that suggest that traditional views of probability cannot accommodate all the competing demands and diverse constraints that arise in complex real-world domains. A model of uncertain reasoning based on a form of logical argumentation appears to unify many diverse ideas. The model has precursors in informal discussions of argumentation due to Toulmin, and the notion of logical probability advocated by Keynes, but recent developments in artificial intelligence and cognitive science suggest ways of resolving epistemological and technical issues that they could not address.


title: Crystal structures of the X-domains of a Group-1 and a Group-3 coronavirus reveal that ADP-ribose-binding may not be a conserved property

text: The polyproteins of coronaviruses are cleaved by viral proteases into at least 15 nonstructural proteins (Nsps). Consisting of five domains, Nsp3 is the largest of these (180–210 kDa). Among these domains, the so-called X-domain is believed to act as ADP-ribose-1″-phosphate phosphatase or to bind poly(ADP-ribose). However, here we show that the X-domain of Infectious Bronchitis Virus (strain Beaudette), a Group-3 coronavirus, fails to bind ADP-ribose. This is explained on the basis of the crystal structure of the protein, determined at two different pH values. For comparison, we also describe the crystal structure of the homologous X-domain from Human Coronavirus 229E, a Group-1 coronavirus, which does bind ADP-ribose.


title: ACE2 levels are altered in comorbidities linked to severe outcome in COVID-19

text: Aims: Severity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). We examined if serum levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2, were altered in these high-risk groups. Methods: Associations of serum ACE2 levels to hypertension, T2D, obesity, CHD, smokers and males in a single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75+/-6 years). Results: Smokers, males, and individuals with T2D or obesity have altered serum levels of ACE2 that may influence productive infection of SARS-CoV-2 in these high-risk groups. Conclusion: ACE2 levels are upregulated in some patient groups with comorbidities linked to COVID-19 and as such may have an emerging role as a circulating biomarker for severity of outcome in COVID-19.


title: Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009

text: BACKGROUND: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season. METHODOLOGY/PRINCIPAL FINDINGS: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive. CONCLUSIONS: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.


title: Ten Strategies of Interferon Evasion by Viruses

text: Viruses infecting vertebrate hosts must overcome the interferon (IFN)-mediated antiviral response to replicate and propagate to new hosts. The complex regulation of the IFN response allows viruses to antagonize IFN at multiple levels. However, no single strategy appears to be the golden ticket, and viruses have adopted multiple means to dampen this host defense. This review does not exhaustively cover all mechanisms of viral IFN antagonism. Rather it examines the ten most common strategies that viruses use to subvert the IFN response with examples from publications appearing in the last 10 years of Cell Host & Microbe. The virus-host interactions involved in induction and evasion of IFN represent a fertile area of research due to the significant large number of host and viral products that regulate this response, resulting in an intricate dance between hosts and their pathogens to achieve an optimal balance between virus replication, host disease and survival.


title: Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020

text: BACKGROUND: As of March 31, 2020, the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued. METHODS: Here we estimate the effective reproduction number, R(t), of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts. RESULTS: The local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI 0.3, 1.0) during the first transmission wave by February 14, 2020, while the overall R based on the cluster size distribution as of March 17, 2020, was estimated at 0.6 (95% CI 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test, p < 0.001). CONCLUSION: The trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.


title: Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications

text: Abstract Baculovirus infects insects in nature and is non-pathogenic to humans, but can transduce a broad range of mammalian and avian cells. Thanks to the biosafety, large cloning capacity, low cytotoxicity and non-replication nature in the transduced cells as well as the ease of manipulation and production, baculovirus has gained explosive popularity as a gene delivery vector for a wide variety of applications. This article extensively reviews the recent understandings of the molecular mechanisms pertinent to baculovirus entry and cellular responses, and covers the latest advances in the vector improvements and applications, with special emphasis on antiviral therapy, cancer therapy, regenerative medicine and vaccine.


title: A novel recombinant bacterial vaccine strain expressing dual viral antigens induces multiple immune responses to the Gag and gp120 proteins of HIV-1 in immunized mice

text: Abstract Recombinant Salmonella enterica serovar Typhi can function as a live vector to deliver foreign antigens to the mammalian immune system and induce both mucosal and systemic immunity. In this study, we generated a recombinant Salmonella Typhi strain pilS− pilT−Gag+(pVAX1-gp120) harboring the human immunodeficiency virus (HIV) gag gene integrated into the bacterial chromosome and gp120 gene carried by a plasmid. Mice inoculated with this recombinant bacterium through intranasal route produced high titers of IgG to gp120 in sera and IgA to gp120 in fecal washes. In addition, Gag-specific and gp120-specific cytotoxic T lymphocyte (CTL) responses were observed in sorted spleen lymphocytes of immunized mice. These results demonstrated that this recombinant Salmonella Typhi strain elicits multiple immune responses against both Gag and gp120 antigens of HIV, and thus would be a potential vaccine candidate to the prevention of HIV/AIDS.


title: Integrated travel network model for studying epidemics: Interplay between journeys and epidemic

text: The ease of travelling between cities has contributed much to globalization. Yet, it poses a threat on epidemic outbreaks. It is of great importance for network science and health control to understand the impact of frequent journeys on epidemics. We stress that a new framework of modelling that takes a traveller’s viewpoint is needed. Such integrated travel network (ITN) model should incorporate the diversity among links as dictated by the distances between cities and different speeds of different modes of transportation, diversity among nodes as dictated by the population and the ease of travelling due to infrastructures and economic development of a city, and round-trip journeys to targeted destinations via the paths of shortest travel times typical of human journeys. An example is constructed for 116 cities in China with populations over one million that are connected by high-speed train services and highways. Epidemic spread on the constructed network is studied. It is revealed both numerically and theoretically that the traveling speed and frequency are important factors of epidemic spreading. Depending on the infection rate, increasing the traveling speed would result in either an enhanced or suppressed epidemic, while increasing the traveling frequency enhances the epidemic spreading.


title: Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. MERS-CoV is thought to be transmitted to humans through dromedary camels. The occurrence of the virus was first reported in the Middle East and it subsequently spread to several parts of the world. Since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. Notably, the recent human-to-human ‘superspreading' of MERS-CoV in hospitals in South Korea has raised a major global health concern. The fatality rate in MERS-CoV infection is four times higher compared with that of the closely related severe acute respiratory syndrome coronavirus infection. Currently, no drug has been clinically approved to control MERS-CoV infection. In this study, we highlight the potential drug targets that can be used to develop anti-MERS-CoV therapeutics.


title: 4 Southeast Asia

text: Abstract Southeast Asia exhibits an enormous diversity in types and levels of sophistication of e-government. Singapore has one of the world's best-developed systems. At the other end of this spectrum lie impoverished states such as Laos, Cambodia, and Myanmar, where e-government barely exists. Malaysia and Thailand occupy positions in between. The Philippines is an interesting case where e-government centers largely around text messaging.


title: Bronchiolitis – Rationale for current recommendations for diagnosis and management

text: Abstract Bronchiolitis is a lower respiratory infection caused commonly by RSV in the initial 2 years of life. It is responsible for a large number of hospitalizations. Pulse oximetry plays an important role in monitoring the progression of disease. Supplemental oxygen administration is not recommended at saturation levels above 90%.


title: Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study

text: Background: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear. Methods: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models. Results: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P < 0.05). Cox regression analyses revealed that platelet count was an independent risk factor associated with in-hospital mortality in a dose-dependent manner. An increment of per 50 × 10(9)/L in platelets was associated with a 40% decrease in mortality (hazard ratio: 0.60, 95%CI: 0.43, 0.84). Dynamic changes of platelets were also closely related to death during hospitalization. Conclusions: Baseline platelet levels and changes were associated with subsequent mortality. Monitoring platelets during hospitalization may be important in the prognosis of patients with coronavirus disease in 2019.


title: Comprehensive viral oligonucleotide probe design using conserved protein regions

text: Oligonucleotide microarrays have been applied to microbial surveillance and discovery where highly multiplexed assays are required to address a wide range of genetic targets. Although printing density continues to increase, the design of comprehensive microbial probe sets remains a daunting challenge, particularly in virology where rapid sequence evolution and database expansion confound static solutions. Here, we present a strategy for probe design based on protein sequences that is responsive to the unique problems posed in virus detection and discovery. The method uses the Protein Families database (Pfam) and motif finding algorithms to identify oligonucleotide probes in conserved amino acid regions and untranslated sequences. In silico testing using an experimentally derived thermodynamic model indicated near complete coverage of the viral sequence database.


title: Bacillus anthracis: Balancing innocent research with dual-use potential

text: Abstract Anthrax Euronet, a Coordination Action of the EU 6th Framework Programme, was designed to strengthen networking activities between anthrax research groups in Europe and to harmonise protocols for testing anthrax vaccines and therapeutics. Inevitably, the project also addressed aspects of the current political issues of biosecurity and dual-use research, i.e. research into agents of important diseases of man, livestock or agriculture that could be used as agents of bioterrorism. This review provides a comprehensive overview of the biology of Bacillus anthracis, of the pathogenesis, epidemiology and diagnosis of anthrax, as well as vaccine and therapeutic intervention strategies. The proposed requirement for a code of conduct for working with dual-use agents such as the anthrax bacillus is also discussed.


title: The origin of HIV-1, the AIDS virus

text: Abstract This article proposes a series of experiments to determine if cows and sheep could be used as animal models for HIV-1, the AIDS virus. To justify this effort, a substantial case is presented that HIV-1 is a natural recombinant of Bovine Leukemia Virus (BLV) and Visna Virus. This natural recombinant may have been inadvertently transferred to humans through the Intensified Smallpox Eradication Program conducted in sub-Saharan Africa in the late 1960s and most of the 1970s.


title: Successful treatment of suckling Red Angus calves for bovine respiratory disease is not associated with increased mean pulmonary arterial pressures at weaning

text: The purposes of this study were to determine if the successful treatment of bovine respiratory disease (BRD) in suckling calves was associated with a long-term increase in mean pulmonary arterial pressure (mPAP) and, to screen for associations between blood leukogram variables and mPAP. A cohort of Red Angus calves (n = 74) were followed from birth to weaning at an altitude of 975 m. Calves were weaned at 172 ± 14 d when their mPAP was measured and whole blood collected. Thirty calves that had been treated for BRD (34 to 45 d prior) and 30 calves that had not required treatment for BRD were sampled. Treatment for BRD had no effect on mPAP (P = 0.37). Mean mPAP was 48 ± 8 mm Hg (± SD) with a minimum of 34 mm Hg and a maximum at 69 mm Hg. Weaning weight and sex tended to be associated with mPAP, but they explained just 5% of the variation in mPAP (P = 0.08; Adj. r(2) = 0.05). Fibrinogen (P = 0.008) and absolute lymphocyte count (P = 0.06) were negatively associated with mPAP, whereas absolute monocyte count was positively associated with mPAP (P = 0.01). The findings of this study suggest that pre-weaning treatment for BRD does not increase a calves’ post-weaning risk of congestive right heart failure. Further, components of the immune and acute phase response system may play a role in the development and progression of pulmonary hypertension.


An urgent need to institute COVID-19 testing in patients with IBD experiencing flares


title: An LC-MRM assay for the quantification of metanephrines from dried blood spots for the diagnosis of pheochromocytomas and paragangliomas

text: The quantitation of metanephrine (MN), normetanephrine (NMN), and 3-methoxytyramine (3MT) – referred to as metanephrines -- by LC-MS/MS is the gold-standard for screening for pheochromocytoma and paragangliomas (PPGLs), tumors of the adrenal gland and the peripheral nervous system. An assay for metanephrines from dried blood spots (DBSs) would be of high clinical utility as it simplifies sample collection, enables remote sampling, and could increase compliance with the clinical recommendation for supine sampling. Moreover, DBS sampling facilitates the measurement of blood-derived metanephrines in pediatric patients – where DBSs are well-established – in order to diagnose neuroblastomas. Here, we adapted an established derivatization-based LC-MRM-MS assay for plasma catecholamines, and optimized the sample extraction, LC, and MS parameters to produce a fast, sensitive, and robust method for the measurement of metanephrines from DBSs, including 3-methoxytyramine. The DBS samples were excised, derivatized with phenyl isothiocyanate (PITC) on-spot, extracted, and measured by LC-MRM-MS. To validate assay suitability and performance, we assessed the linearity, precision, accuracy, recovery, and matrix effects of the method, and determined the stability of metanephrines in DBSs under different storage conditions. Assay performance for NMN, MN, and 3MT was sufficient for quantitation from a single DBS within a linear range from 40 – 2000 pg/mL MN and NMN were stable in DBSs for 2 weeks, whereas 3MT was stable for one week regardless of storage temperature. Altogether, this work represents the first quantitative LC-MS/MS method for metanephrines from DBSs and provides a novel opportunity for the diagnosis of PPGLs and neuroblastomas in the future.


title: Severe acute respiratory syndrome coronavirus membrane protein interacts with nucleocapsid protein mostly through their carboxyl termini by electrostatic attraction

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) membrane protein is an abundant virion protein, and its interaction with the nucleocapsid protein is crucial for viral assembly and morphogenesis. Although the interacting region in the nucleocapsid protein was mapped to residues 168–208, the interacting region in the membrane protein and the interaction nature are still unclear. In this work, by using yeast two-hybrid and surface plasmon resonance techniques, the residues 197–221 of the membrane protein and the residues 351–422 of the nucleocapsid protein were determined to be involved in their interaction. Sequence analysis revealed that these two fragments are highly charged at neutral pH, suggesting that their interaction may be of ionic nature. Kinetic assays indicated that the endodomain (aa102–221) of the membrane protein interacts with the nucleocapsid protein with high affinity (K D =0.55±0.04μM), however, this interaction could be weakened greatly by acidification, higher salt concentration (400mM NaCl) and divalent cation (50mM Ca2+), which suggests that electrostatic attraction might play an important role in this interaction. In addition, it is noted that two highly conserved amino acids (L218 and L219) in the membrane protein are not involved in this interaction. Here, we show that electrostatic interactions between the carboxyl termini of SARS-CoV membrane protein and nucleocapsid protein largely mediate the interaction of these two proteins. These results might facilitate therapeutic strategies aiming at the disruption of the association between SARS-CoV membrane and nucleocapsid proteins.


title: Factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises

text: Summary The epidemics of severe acute respiratory syndrome (SARS) in 2003 highlighted both short- and long-range transmission routes, i.e. between infected patients and healthcare workers, and between distant locations. With other infections such as tuberculosis, measles and chickenpox, the concept of aerosol transmission is so well accepted that isolation of such patients is the norm. With current concerns about a possible approaching influenza pandemic, the control of transmission via infectious air has become more important. Therefore, the aim of this review is to describe the factors involved in: (1) the generation of an infectious aerosol, (2) the transmission of infectious droplets or droplet nuclei from this aerosol, and (3) the potential for inhalation of such droplets or droplet nuclei by a susceptible host. On this basis, recommendations are made to improve the control of aerosol-transmitted infections in hospitals as well as in the design and construction of future isolation facilities.


title: Porcine reproductive and respiratory syndrome virus activates the transcription of interferon alpha/beta (IFN-α/β) in monocyte-derived dendritic cells (Mo-DC)

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is known to be a poor inducer of interferon alpha/beta (IFN-α/β), which may contribute to the delayed development of adaptive immunity and the resultant viral persistence. However, the exact mechanism by which PRRSV inhibits the induction of IFN-α/β during infection of its natural host cells remains less well defined. Here, we show that PRRSV efficiently activates the transcription of IFN-α/β in porcine monocyte-derived dendritic cells (Mo-DC) in a time-dependent and transient manner; and this effect is dependent on the activation of phosphatidylinositol 3-kinase (PI3K). Despite the abundant IFN-α transcripts detected in PRRSV-infected Mo-DC, little or no detectable IFN-α is found in the supernatants and cell lysates of PRRSV-infected Mo-DC, suggesting that PRRSV either blocks the translation of IFN-α or inhibits the RNA processing and transport. Furthermore, we observed that PRRSV infection significantly reduced the induction of IFN-α by Poly I:C treatment; and virus replication is essential to the effect since heat-inactivated PRRSV has no effect on IFN-α induction by Poly I:C. Overall, our data provide evidence for the possible role of PI3K in the activation of the transcription of IFN-α/β by PRRSV. We conclude that PRRSV inhibits the induction of IFN-α in Mo-DC by as yet undefined post-transcriptional mechanisms.


title: Cross-reactive antibodies in convalescent SARS patients' sera against the emerging novel human coronavirus EMC (2012) by both immunofluorescent and neutralizing antibody tests

text: Summary Objectives A severe acute respiratory syndrome (SARS)-like disease due to a novel betacoronavirus, human coronavirus EMC (HCoV-EMC), has emerged recently. HCoV-EMC is phylogenetically closely related to Tylonycteris-bat-coronavirus-HKU4 and Pipistrellus-bat-coronavirus-HKU5 in Hong Kong. We conducted a seroprevalence study on archived sera from 94 game-food animal handlers at a wild life market, 28 SARS patients, and 152 healthy blood donors in Southern China to assess the zoonotic potential and evidence for intrusion of HCoV-EMC and related viruses into humans. Methods Anti-HCoV-EMC and anti-SARS-CoV antibodies were detected using screening indirect immunofluorescence (IF) and confirmatory neutralizing antibody tests. Results Two (2.1%) animal handlers had IF antibody titer of ≥1:20 against both HCoV-EMC and SARS-CoV with neutralizing antibody titer of <1:10. No blood donor had antibody against either virus. Surprisingly, 17/28 (60.7%) of SARS patients had significant IF antibody titers with 7/28 (25%) having anti-HCoV-EMC neutralizing antibodies at low titers which significantly correlated with that of HCoV-OC43. Bioinformatics analysis demonstrated a significant B-cell epitope overlapping the heptad repeat-2 region of Spike protein. Virulence of SARS-CoV over other betacoronaviruses may boost cross-reactive neutralizing antibodies against other betacoronaviruses. Conclusions Convalescent SARS sera may contain cross-reactive antibodies against other betacoronaviruses and confound seroprevalence study for HCoV-EMC.


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title: Immunoregulatory functions of immune complexes in vaccine and therapy

text: Clinical and experimental preparations of IgG/soluble antigen complexes, as well as those formed following antibody therapy in vivo, are multifaceted immune regulators. These immune complexes (ICs) have been tested in humans and animal models, mostly in forms of experimental or clinical vaccination, for at least a century. With intensified research on Fcγ receptor‐mediated immune modulation, as well as with immune complex‐directed antigen processing, presentation, and inflammatory responses, there are renewed interests of using ICs in vaccines and immunotherapies. Currently, IC‐based immune therapy has been broadly experimented in HBV and HIV viral infection control and antitumor treatments. However, mechanistic insights of IC‐based treatments are relatively recent subjects of study; strong efforts are needed to establish links to connect laboratory findings with clinical practices. This review covers the history, mechanisms, and in vivo outcomes of this safe and effective therapeutic tool, with a clear aim to bridge laboratory findings with evolving clinical applications.


title: Genetic variation analysis of reemerging porcine epidemic diarrhea virus prevailing in central China from 2010 to 2011

text: Porcine epidemic diarrhea has re-emerged with devastating impact in central China since October 2010. To investigate and analyze the reason of this outbreak, the M and ORF3 genes of 15 porcine epidemic diarrhea viruses (PEDV), which were collected from different areas of central China during October 2010 and December 2011, were amplified by reverse transcriptase polymerase chain reaction, cloned, sequenced, and analyzed. Sequence analyses showed that the nucleotides and amino acids were changed at some sites in the M and ORF3 genes of the 15 PEDV strains compared with those genes of CV777 reference strain. Based on the phylogenetic analyses, PEDVs in central China and reference strains could be separated into three groups: G1, G2, and G3. The 15 PEDV strains belonged to G3 group and showed a close relationship with Korean strains (2007), Thai strains (2007–2008), and partial other Chinese strains (2010–2011), but differed genetically from European strains (Br1/87) and the vaccine strain (CV777 vs) being used in China. Furthermore, all 15 PEDV strains from central China and some other isolates in China from 2003 to 2007 (LJB-03, QH, and LZC) belonged to different group. Therefore, PEDV exhibits rapid variation and genetic evolution, and the currently prevailing PEDV strains in central China are a new genotype.


PPI Or User Involvement: Taking stock from a service user perspective in the twenty first century


Developing Guidelines for COVID-19 Management: A Moving Target. An invited commentary on "Evidence Based Management Guideline for the COVID-19 Pandemic - Review article"


title: Surveillance for enterotoxigenic & enteropathogenic Escherichia coli isolates from animal source foods in Northwest Iran

text: BACKGROUND & OBJECTIVES: Diarrhoeagenic Escherichia coli strains are common agents of diarrhoea particularly in developing countries. Food products of animal origin are considered as common carriers of E. coli. This study was undertaken to identify enterotoxigenic Escherichia coli (ETEC) and enteropathogenic E. coli (EPEC) pathotypes in animal-source foods (ASF). METHODS: A total of 222 ASF samples were investigated. Based on the culture and biochemical tests, 109 E. coli isolates were identified. Duplex-polymerase chain reaction assay was used to detect ETEC and EPEC. The target genes selected for each category were the lt and st for the ETEC, and eae and bfp for the EPEC isolates. RESULTS: The occurrence of E. coli in dairy and meat products was 45 and 52.5 per cent, respectively. Among the E. coli isolates, two ETEC, one typical EPEC and three atypical EPEC were detected in meat samples, whereas only one typical EPEC and one atypical EPEC were detected in dairy samples. INTERPRETATION & CONCLUSIONS: Our results showed presence of ETEC and EPEC strains in ASFs. The milk without pasteurization and traditional dairy products produced in unhygienic conditions are most likely the main sources of E. coli pathotypes and other zoonotic pathogens and thus can be considered a potential hazard to the health of the community.


Value of RVP in clinical settings: intensive care


title: Bacterial communities in commercial aircraft high‐efficiency particulate air (HEPA) filters assessed by PhyloChip analysis

text: Abstract Air travel can rapidly transport infectious diseases globally. To facilitate the design of biosensors for infectious organisms in commercial aircraft, we characterized bacterial diversity in aircraft air. Samples from 61 aircraft high‐efficiency particulate air (HEPA) filters were analyzed with a custom microarray of 16S rRNA gene sequences (PhyloChip), representing bacterial lineages. A total of 606 subfamilies from 41 phyla were detected. The most abundant bacterial subfamilies included bacteria associated with humans, especially skin, gastrointestinal and respiratory tracts, and with water and soil habitats. Operational taxonomic units that contain important human pathogens as well as their close, more benign relatives were detected. When compared to 43 samples of urban outdoor air, aircraft samples differed in composition, with higher relative abundance of Firmicutes and Gammaproteobacteria lineages in aircraft samples, and higher relative abundance of Actinobacteria and Betaproteobacteria lineages in outdoor air samples. In addition, aircraft and outdoor air samples differed in the incidence of taxa containing human pathogens. Overall, these results demonstrate that HEPA filter samples can be used to deeply characterize bacterial diversity in aircraft air and suggest that the presence of close relatives of certain pathogens must be taken into account in probe design for aircraft biosensors. PRACTICAL IMPLICATIONS: A biosensor that could be deployed in commercial aircraft would be required to function at an extremely low false alarm rate, making an understanding of microbial background important. This study reveals a diverse bacterial background present on aircraft, including bacteria closely related to pathogens of public health concern. Furthermore, this aircraft background is different from outdoor air, suggesting different probes may be needed to detect airborne contaminants to achieve minimal false alarm rates. This study also indicates that aircraft HEPA filters could be used with other molecular techniques to further characterize background bacteria and in investigations in the wake of a disease outbreak.


title: A novel screening method for influenza patients using a newly developed non-contact screening system

text: Summary Objectives In places of mass gathering, rapid infection screening prior to definite diagnosis is vital during the epidemic season of a novel influenza. In order to assess the possibility of clinical application of a newly developed non-contact infection screening system, we conducted screening for influenza patients. Materials and methods The system is operated by a screening program via a linear discriminant analysis using non-contact derived variables, i.e., palmar pulse derived from a laser Doppler blood-flow meter, respiration rate determined by a 10-GHz microwave radar, and average facial temperature measured by thermography. The system was tested on 57 seasonal influenza (2008–2009) patients (35.7 °C ≤ body temperature ≤ 38.3 °C, 19–40 years) and 35 normal control subjects (35.5 °C ≤ body temperature ≤ 36.9 °C, 21–35 years) at the Japan Self-defense Forces Central Hospital. Results A significant linear discriminant function (p < 0.001) was determined to distinguish the influenza group from the control group (Mahalanobis D-square = 6.5, classification error rate > 10%). The system had a positive predictive value (PPV) of 93%, which is higher than the PPV value (PPV ≤ 65.4%) reported in the recent summary of studies using only thermography performed mainly in hospitals. Conclusions The proposed system appears promising for application in accurate screening for influenza patients at places of mass gathering.


title: Is virus coinfection a predictor of severity in children with viral respiratory infections?

text: Abstract Molecular assays have resulted in increased detection of viral respiratory infections, including virus coinfection, from children with acute respiratory infections. Yet the clinical severity of virus coinfection compared to single virus infection remains uncertain. We performed a retrospective study of children presenting with acute respiratory infections comparing clinical severity of single respiratory virus infection to virus coinfection, detected on midturbinate swabs by molecular assays. Patient characteristics and measures of clinical severity were abstracted from health records. A total of 472 virus-infected children were included, 391 with a single virus infection and 81 with virus coinfection. Virus status did not affect admission to hospital (odds ratio (OR) = 0.8; 95 % confidence interval (CI) 0.5–1.4; p 0.491) or clinical disease severity among inpatients (OR = 0.8; 95% CI 0.5–1.5; p 0.515) after adjusting for age and underlying comorbidities. However, children infected with rhinovirus/enterovirus (HRV/ENT) alone were more likely to be admitted to the hospital compared to those coinfected with HRV/ENT and at least another virus, although this was not significant in multivariable analyses (OR 0.47; 95% CI 0.22–1.0; p 0.051). In multivariable analyses, children coinfected with respiratory syncytial virus (RSV) and other viruses were significantly more likely to present with radiologically confirmed pneumonia compared to those with an isolated RSV infection (OR 3.16, 95% CI 1.07–9.34, p 0.037). Equivalent clinical severity was observed between children with single virus infection and virus coinfection, although children coinfected with RSV and other viruses presented more frequently with pneumonia than those with single RSV infection. Increased disease severity observed among children with single HRV/ENT infection requires further investigation.


title: Insights from molecular structure predictions of the infectious bronchitis virus S1 spike glycoprotein

text: Abstract Infectious bronchitis virus is an important respiratory pathogen in chickens. The IBV S1 spike is a viral structural protein that is responsible for attachment to host receptors and is a major target for neutralizing antibodies. To date, there is no experimentally determined structure for the IBV S1 spike. In this study, we sought to find a predicted tertiary structure for IBV S1 using I-TASSER, which is an automated homology modeling platform. We found that the predicted structures obtained were robust and consistent with experimental data. For instance, we observed that all four residues (38, 43, 63, and 68) that have been shown to be critical for binding to host tissues, were found at the surface of the predicted structure of Massachusetts (Mass) S1 spike. Together with antigenicity index analysis, we were also able to show that Ma5 vaccine has higher antigenicity indices at residues close to the receptor-binding region than M41 vaccine, thereby providing a possible mechanism on how Ma5 achieves better protection against challenge. Examination of the predicted structure of the Arkansas IBV S1 spike also gave insights on the effect of polymorphisms at position 43 on the surface availability of receptor binding residues. This study showcases advancements in protein structure prediction and contributes useful, inexpensive tools to provide insights into the biology of IBV.


title: Detection of rhinovirus RNA in nasal epithelial cells by in situ hybridization

text: Abstract This paper describes the development and evaluation of in situ hybridization (ISH) for the detection of rhinovirus in cells obtained from nasal washings of volunteers infected with human rhinovirus 14 (HRV-14). Twenty-five (66%) and 27 (71%) of 38 volunteers inoculated with HRV-14 had evidence of infection by virus isolation and ISH, respectively, on at least one of 4 days investigated after virus challenge. In contrast, only 14 of 38 (37%) volunteers had significant antibody rises as detected by the neutralization test. Of the 38 volunteers inoculated with HRV-14, only 13 (34%) had symptoms of colds. Of these, 12 (92%) and 10 (77%) were positive by virus isolation or ISH, respectively, on at least one day. Six (46%) had significant antibody rises by neutralization. Similarly, of the 38 volunteers challenged, 22 (58%) were asymptomatic and of these 10 (45.5%) and 12 (54.5%) were positive by virus isolation and ISH, respectively, on at least one day. Only 8 (36.4%) of these asymptomatic volunteers showed significant antibody rises by neutralization. There were significant associations between the detection of rhinoviruses by ISH and virus isolation on the third day (P<0.025) after virus challenge in the group as a whole and in the symptomatic group. These results show that generally rhinovirus detection by ISH compares well with virus isolation and both tests are clearly more sensitive than the neutralization test in detecting evidence of infection. It is concluded that ISH is an interesting new technique that may play an important role in the study of rhinovirus infection and pathogenesis.


title: Harnessing DNA Synthesis to Develop Rapid Responses to Emerging and Pandemic Pathogens

text: Given the interconnected nature of our world today, emerging pathogens and pandemic outbreaks are an ever-growing threat to the health and economic stability of the global community. This is evident by the recent 2009 Influenza A (H1N1) pandemic, the SARS outbreak, as well as the ever-present threat of global bioterrorism. Fortunately, the biomedical community has been able to rapidly generate sequence data so these pathogens can be readily identified. To date, however, the utilization of this sequence data to rapidly produce relevant experimental results or actionable treatments is lagging in spite of obtained sequence data. Thus, a pathogenic threat that has emerged and/or developed into a pandemic can be rapidly identified; however, translating this identification into a targeted therapeutic or treatment that is rapidly available has not yet materialized. This commentary suggests that the growing technology of DNA synthesis should be fully implemented as a means to rapidly generate in vivo data and possibly actionable therapeutics soon after sequence data becomes available.


title: Snapshot of Viral Infections in Wild Carnivores Reveals Ubiquity of Parvovirus and Susceptibility of Egyptian Mongoose to Feline Panleukopenia Virus

text: The exposure of wild carnivores to viral pathogens, with emphasis on parvovirus (CPV/FPLV), was assessed based on the molecular screening of tissue samples from 128 hunted or accidentally road-killed animals collected in Portugal from 2008 to 2011, including Egyptian mongoose (Herpestes ichneumon, n = 99), red fox (Vulpes vulpes, n = 19), stone marten (Martes foina, n = 3), common genet (Genetta genetta, n = 3) and Eurasian badger (Meles meles, n = 4). A high prevalence of parvovirus DNA (63%) was detected among all surveyed species, particularly in mongooses (58%) and red foxes (79%), along with the presence of CPV/FPLV circulating antibodies that were identified in 90% of a subset of parvovirus-DNA positive samples. Most specimens were extensively autolysed, restricting macro and microscopic investigations for lesion evaluation. Whenever possible to examine, signs of active disease were not present, supporting the hypothesis that the parvovirus vp2 gene fragments detected by real-time PCR possibly correspond to viral DNA reminiscent from previous infections. The molecular characterization of viruses, based on the analysis of the complete or partial sequence of the vp2 gene, allowed typifying three viral strains of mongoose and four red fox’s as feline panleukopenia virus (FPLV) and one stone marten’s as newCPV-2b type. The genetic similarity found between the FPLV viruses from free-ranging and captive wild species originated in Portugal and publicly available comparable sequences, suggests a closer genetic relatedness among FPLV circulating in Portugal. Although the clinical and epidemiological significance of infection could not be established, this study evidences that exposure of sympatric wild carnivores to parvovirus is common and geographically widespread, potentially carrying a risk to susceptible populations at the wildlife-domestic interface and to threatened species, such as the wildcat (Felis silvestris) and the critically endangered Iberian lynx (Lynx pardinus).


title: Epidemiology of Viral Pneumonia

text: The burden of pneumonia, including that due to respiratory viruses, is markedly higher in the very young (<5 years) and older adults (≥50 years). Respiratory viruses substantially contribute to pneumonia in both adults and children, and when systematically tested for, are more commonly detected than bacteria in both adults and children. It is difficult to distinguish between viruses by clinical presentation, and the exact clinical implication of viral detections among patients with pneumonia depends on the pathogen detected; however, there is increasing evidence of their importance in pneumonia.


title: Telemental health comes into its own with social distancing

text: Telepsychiatry, telemental health, telepsychology, teletherapy — whatever you call it, it is now required in the era of the coronavirus/COVID‐19 pandemic. “We should be doing it immediately; the more, the better,” said Robert Caudill, M.D., a member of the American Psychiatric Association's Committee on Telepsychiatry. “It's exploded in the past week, obviously,” he told CABL in a Zoom interview on March 23. But he thinks it should be the norm.


title: Production of second-generation cloned cats by somatic cell nuclear transfer

text: Abstract We successfully produced second-generation cloned cats by somatic cell nuclear transfer (SCNT) using skin cells from a cloned cat. Skin cells from an odd-eyed, all-white male cat (G0 donor cat) were used to generate a cloned cat (G1 cloned cat). At 6 months of age, skin cells from the G1 cloned cat were used for SCNT to produce second-generation cloned cats. We compared the in vitro and in vivo development of SCNT embryos that were derived from the G0 donor and G1 cloned donor cat's skin fibroblasts. The nuclei from the G0 donor and G1 cloned donor cat's skin fibroblasts fused with enucleated oocytes with equal rates of fusion (60.7% vs. 58.8%, respectively) and cleavage (66.3% vs. 63.4%). The 2–4-cell SCNT embryos were then transferred into recipients. One of the five recipients of G0 donor derived NT embryos (20%) delivered one live male cloned kitten, whereas 4 of 15 recipients of the G1 cloned donor cat derived NT embryos (26%) delivered a total of seven male second-generation cloned kittens (four live kittens from one surrogate, plus two stillborn kittens, and one live kitten that died 2d after birth from three other surrogate mothers). The four second-generation cloned kittens from the same surrogate all had a white coat color; three of the four second-generation cloned kittens had two blue eyes, and one of the second-generation cloned kittens had an odd-eye color. Despite low cloning efficiency, cloned cats can be used as donor cats to produce second-generation cloned cats.


Positive Screening for Wuhan Novel Coronavirus Infection at International Airport: What's the Final Diagnosis for Positive Cases


title: The contribution of dry indoor built environment on the spread of Coronavirus: Data from various Indian states

text: Coronavirus spread is more serious in urban metropolitan cities compared to rural areas. It is observed from the data on the infection rate available in the various sources that the cold and dry conditions accelerate the spread of coronavirus. In the present work, the existing theory of respiratory droplet drying is used to propose the mechanism of virus spread under various climates and the indoor environment conditions which plays a greater role in the virus spread. This concept is assessed using four major parameters such as population density, climate severity, the volume of indoor spaces, and air-conditioning usage which affect the infection spread and mortality using the data available for various states of India. Further, it is analysed using the data from various states in India along with the respective climatic conditions. It is found that under some indoor scenarios, the coronaviruses present in the respiratory droplets become active due to size reduction that occurs both in sessile and airborne droplet nuclei causing an increase in the spread. Understanding this mechanism will be very useful to take the necessary steps to reduce the rate of transmission by initiating corrective measures and maintaining the required conditions in the indoor built environment.


Recommended Practices for Prevention of Transmissible Infections in the Perioperative Practice Setting


title: Laboratory Diagnosis of SARS

text: The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription–polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%–40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity.


title: Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein

text: Summary Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct α-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.


title: Pathogen-specific risk factors in acute outbreaks of respiratory disease in calves

text: ABSTRACT Respiratory tract infections (bovine respiratory disease) are a major concern in calf rearing. The objective of this study was to identify pathogen-specific risk factors associated with epidemic respiratory disease in calves. A cross-sectional study was conducted, involving 128 outbreaks (29 dairy, 58 dairy-mixed, and 41 beef) in Belgium (2016–2018). A semiquantitative PCR for 7 respiratory pathogens was done on a pooled nonendoscopic bronchoalveolar lavage sample for each herd. Potential risk factors were collected by questionnaire and derived from the national cattle registration databank. Most outbreaks occurred between October and March, and single and multiple viral infections were detected in 58.6% (75/128) and 13.3% (17/128), respectively. Bovine coronavirus (BCV) was the most frequently isolated virus (38.4%), followed by bovine respiratory syncytial virus (bRSV; 29.4%) and parainfluenzavirus type 3 (PI-3; 8.1%). Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni were detected in 33.3, 41.2, 89.1, and 36.4% of the herds, respectively. Specific risk factors for BCV detection were detection of M. haemolytica [odds ratio (OR) = 2.8 (95% confidence interval = 1.1–7.5)], increasing herd size [OR = 1.3 (1.0–1.8) for each increase with 100 animals] and detection of BCV by antigen ELISA on feces in calves in the last year [OR = 3.6 (1.2–11.1)]. A seasonal effect was shown for bRSV only {more in winter compared with autumn [OR = 10.3 (2.8–37.5)]}. Other factors associated with bRSV were PI-3 detection [OR = 13.4 (2.1–86.0)], prevalence of calves with respiratory disease [OR = 1.02 (1.00–1.04) per 1% increase], and number of days with respiratory signs before sampling [OR = 0.99 (0.98–0.99) per day increase]. Next to its association with BCV, M. haemolytica was more frequently detected in herds with 5 to 10 animals per pen [OR = 8.0 (1.4–46.9)] compared with <5 animals, and in herds with sawdust as bedding [OR = 18.3 (1.8–191.6)]. Also, for H. somni, housing on sawdust was a risk factor [OR = 5.2 (1.2–23.0)]. Purchase of cattle [OR = 2.9 (1.0–8.0)] and housing of recently purchased animals in the same airspace [OR = 5.0 (1.5–16.5)] were risk factors for M. bovis. This study identified pathogen-specific risk factors that might be useful for the development of customized control and prevention and for the design of decision support tools to justify antimicrobial use by predicting the most likely pathogen before sampling results are available.


Novel Middle East respiratory syndrome coronavirus


title: Indirubin, a bisindole alkaloid from Isatis indigotica, reduces H1N1 susceptibility in stressed mice by regulating MAVS signaling

text: Isatis indigotica has a long history in treating virus infection and related symptoms in China. Nevertheless, its antivirus evidence in animal studies is not satisfactory, which might be due to the lack of appropriate animal model. Previously, we had utilized restraint stress to establish mouse H1N1 susceptibility model which was helpful in evaluating the anti-virus effect of medicines targeting host factors, such as type I interferon production. In this study, this model was employed to investigate the effect and mechanism of indirubin, a natural bisindole alkaloid from Isatis indigotica, on influenza A virus susceptibility. In the in vitro study, the stress hormone corticosterone was used to simulate restraint stress. Our results demonstrated that indirubin decreased the susceptibility to influenza virus with lowered mortality and alleviated lung damage in restraint-stressed mice model. Moreover, indirubin promoted the expression of interferon-β and interferon inducible transmembrane 3. In addition, indirubin maintained the morphology and function of mitochondria following influenza A virus infection. Further study revealed that indirubin promoted interferon-β production through promoting mitochondrial antiviral signaling pathway. Our study indicated that indirubin could be a candidate for the therapy of influenza.


title: Genotypic analysis of virulence genes and antimicrobial profile of diarrheagenic Escherichia coli isolated from diseased lambs in Iran

text: The aim of the present study was to determine the analysis of virulence genes and antimicrobial profile of diarrheagenic Escherichia coli isolated from diseased lambs. Two hundred ninety E. coli isolates were recovered from 300 rectal swabs of diarrheic lambs and were confirmed by biochemical tests. The pathotype determination was done according to the presence of genes including f5, f41, LTI, STI, bfp, ipaH, stx (1), stx (2), eae, ehlyA, cnf (1), cnf (2), cdIII, cdIV, and f17 by PCR method. Sixty-six isolates (23.72%) possessed the STI gene and categorized into entrotoxigenic E. coli (ETEC). Nine isolates (3.1%) and five isolates (1.72%) were positive for the cnf1 and cnf2 genes which categorized into necrotoxic E. coli (NTEC). Hundred and seventeen isolates (40.34%) harbored stx (1) and/or stx (2) and classified as Shiga toxin-producing E. coli (STEC). Thirteen isolates (4.48%) were assigned to atypical entropathogenic E. coli (aEPEC) and possessed eae gene. Two isolates (0.68%) were positive for ipaH gene and were assigned to entroinvasive E. coli (EIEC). Statistical analysis showed a specific association between eae gene and STEC pathotype (P < 0.0001). The most prevalent resistance was observed against lincomycin (96.5%) and the lowest resistance was against kanamycine (56.02%), respectively. The high prevalence of STEC and ETEC indicates that diarrheic lambs represent an important reservoir for humans. ETEC may play an important role for frequent occurrence of diarrhea in lambs observed in this region. Due to high antibiotic resistance, appropriate control should be implemented in veterinary medicine to curb the development of novel resistant isolates.


title: Nontraditional Antibiotics—Challenges and Triumphs

text: The pursuit of nontraditional antibiotics is becoming an increasingly important means to tackle seemingly insurmountable challenges faced by contemporary antibiotic researchers as they overcome the shifting landscape of bacterial pathogenesis, particularly for Gram-negative bacteria [...].


157 Coronaviruses, Including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)


title: The demand for inpatient and ICU beds for COVID-19 in the US: lessons from Chinese cities

text: BACKGROUND: Sustained spread of SARS-CoV-2 has happened in major US cities. Capacity needs in Chinese cities could inform the planning of local healthcare resources. METHODS: We described the intensive care unit (ICU) and inpatient bed needs for confirmed COVID-19 patients in two Chinese cities (Wuhan and Guangzhou) from January 10 to February 29, 2020, and compared the timing of disease control measures in relation to the timing of SARS-CoV-2 community spread. We estimated the peak ICU bed needs in US cities if a Wuhan-like outbreak occurs. RESULTS: In Wuhan, strict disease control measures were implemented six weeks after sustained local transmission of SARS-CoV-2. Between January 10 and February 29, COVID-19 patients accounted for an average of 637 ICU patients and 3,454 serious inpatients on each day. During the epidemic peak, 19,425 patients (24.5 per 10,000 adults) were hospitalized, 9,689 (12.2 per 10,000 adults) were considered to be in serious condition, and 2,087 patients (2.6 per 10,000 adults) needed critical care per day. In Guangzhou, strict disease control measures were implemented within one week of case importation. Between January 24 and February 29, COVID-19 accounted for an average of 9 ICU patients and 20 inpatients on each day. During the epidemic peak, 15 patients were in critical condition, and 38 were classified as serious. If a Wuhan-like outbreak were to happen in a US city, the need for healthcare resources may be higher in cities with a higher prevalence of vulnerable populations. CONCLUSION: Even after the lockdown of Wuhan on January 23, the number of seriously ill COVID-19 patients continued to rise, exceeding local hospitalization and ICU capacities for at least a month. Plans are urgently needed to mitigate the effect of COVID-19 outbreaks on the local healthcare system in US cities.


title: Gastroenteritis, Viral

text: Abstract Viral gastroenteritis (VGE) is an acute, self-limiting gastrointestinal infection caused by several viruses which most often trigger nausea, vomiting, abdominal pain and diarrhea. It is one of the most common human illnesses with its greatest impact on the very young and elderly. In the developing world, VGE can be life threatening whereas in most developed countries, it is self-limited and managed with hydration. Most agents of VGE are spread by the fecal oral route or may occur in explosive outbreaks due to food or water contamination. Control of these infections depends upon proper food handling, hand hygiene, clean water and the rotavirus vaccination of infants. This chapter will discuss the common viruses which cause this syndrome.


title: Molecular detection and genetic characterization of kobuviruses and astroviruses in asymptomatic local pigs in East Africa

text: In this study, swine fecal specimens (n = 251) collected from nursing and weaned piglets raised under smallholder production systems were screened for the presence of kobuviruses by RT-PCR. Porcine kobuviruses were detected in 13.1 % (33/251) of the samples. We demonstrated that porcine kobuvirus infections exist in indigenous pigs in Kenya and Uganda and that the prevalence was higher in young piglets than older pigs: nursing piglets (15 %), post-weaning (3-month-old) pigs (17 %), 4-month-old pigs (10 %). Genetic analysis of the partial RNA-dependent RNA polymerase (RdRp) region (690 nt) revealed that kobuviruses circulating in East Africa are diverse, sharing nucleotide sequence identities ranging from 89.7 to 99.1 % and 88 to 92.3 % among them and with known porcine kobuviruses, respectively. The nucleotide sequence identities between our kobuvirus strains and those of human, bovine and canine kobuviruses were 69.4-70.7 %, 73.1-74.4 % and 67-70.7 %, respectively. Additionally, upon sequencing selected samples that showed consistent 720-bp RT-PCR bands while using the same primer set, we detected porcine astroviruses in our samples belonging to type 2 and type 3 mamastroviruses. To our knowledge, this study reports the first detection and molecular analysis of both porcine kobuviruses and astroviruses in an African region. Further studies are required to determine the role of these viruses in gastrointestinal infections of pigs in this region and to determine the genetic diversity of the circulating strains to develop accurate diagnostic tools and implement appropriate control strategies.


Notes on Covid-19 and the contradictions of capital: a call for papers


title: Surface-displayed porcine epidemic diarrhea viral (PEDV) antigens on lactic acid bacteria

text: In this report, for surface display of viral antigen on lactobacilli, we have developed a surface antigen display system using the poly-γ-glutamate synthetase A protein (pgsA) of Bacillus subtilis as an anchoring matrix. Recombinant fusion proteins comprised of pgsA and neucleocapsid protein of PEDV were stably expressed in Lactobacillus casei. Surface location of fusion protein was verified by ELISA, immunofluoresence microscopy. Oral and intranasal inoculations of recombinant L. casei into pregnant sow and mice resulted in high levels of serum immunoglobuline G (IgG) and mucosal IgA, as demonstrated by rnELISA(recombinant N protein ELISA) using recombinant N protein. Absorbance of IgG in pregnant sow sera highly increased duration of the experiment. More importantly, the level of IgA in colostrum were increased significantly higher than that of IgG. The IgG levels of the piglets were increased after suckling colostrum secreted from sows previously inoculated recombinant L. casei. These results indicate that mucosal immunization with recombinant L. casei expressing PEDV N protein (neucleoprotein of PEDV) on its surface elicited high levels of mucosal IgA and circulation IgG immune responses against the antigen N of PEDV.