title: Guidelines for managing lesser prairie‐chicken populations and their habitats

text: Lesser prairie‐chicken (Tympanuchus pallidicinctus) populations have declined by >90% since the 1800s. These declines have concerned both biologists and private conservation groups and led to a petition to list the lesser prairie‐chicken as threatened under the Endangered Species Act. Most of the land in the current range of the lesser prairie‐chicken is privately owned, and declines have been primarily attributed to anthropogenic factors. Conversion of native rangeland to cropland and excessive grazing have been implicated as leading causes in the species' decline. Periodic drought probably has exacerbated these problems. Little research on habitat requirements was conducted prior to 1970. Despite recent advances in the knowledge of lesser prairie‐chicken ecology, no comprehensive guidelines for management of the species have been published. In these guidelines, we provide a synopsis of our current knowledge of lesser prairie‐chicken habitat requirements and suggest management strategies to monitor, maintain, and enhance lesser prairie‐chicken populations.


A World of Changes: The Inheritance of COVID-19


title: COVID19: A Systematic Approach to Early Identification and Healthcare Worker Protection

text: The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms “COVID-19,” “2019-nCoV,” “SARS-CoV-2,” or “Novel Coronavirus Pneumonia.” The main symptoms of COVID-19 are fever (83–98.6%), cough (59.4–82%), and fatigue (38.1–69.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.


title: Pansteatitis and severe hypocalcaemia in a cat

text: A 13-year-old Siamese cat was presented for investigation of lethargy and progressive abdominal enlargement. Serum chemistry revealed severe reduction of total and ionised serum calcium. The omentum appeared hyperechoic with scattered hypoechoic foci on abdominal ultrasound examination. Elevated serum parathormone and low fractional excretion of calcium excluded a parathyroid disorder and renal loss of the electrolyte. During laparotomy the omentum appeared opaque, white and firm. Post-mortem examination revealed that the thoracic and subcutaneous fat was also affected. Histopathology confirmed the diagnosis of pansteatitis with diffuse calcium soaps formation. While, severe hypocalcaemia is occasionally seen in cats, the association with pansteatitis has not been reported previously. In man, a cause-and-effect relationship between calcium soaps and hypocalcaemia is recognised, though the association is rare.


title: Replacement Management in Cattle | Health Management

text: Replacements are the future of the dairy industry. Focusing on improving health management of replacements will yield tremendous returns through decreased losses of animals with the greatest genetic potential on the dairy, decreased costs of medication, improved growth rates, improved feed efficiency and earlier entry into the milking herd. Health management begins before replacements are born with attention to the nutrition of lactating and dry cows, the vaccination of lactating and dry cows, control of length of the dry period and both control of the disease status of the dams and the cleanliness of the calving environment. Adequate consumption of colostrums by newborn calves is very important. Attention must be paid to biosecurity to prevent introduction of diseases into the herd and to digestive disorders such as diarrhea, internal parasites and appropriate vaccination programs for the calves. Health management of replacements is often overlooked because producers do not see the immediate returns for their efforts.


title: Genetic and antigenic characterization of influenza A(H3N2) in Cameroon during the 2014-2016 influenza seasons

text: The first outbreak of influenza A(H3N2) occurred in 1968 and caused the third flu pandemic of the 20(th) century. It has affected multiple countries over time. The best strategy to reduce the burden of influenza is through vaccination whose efficacy varies with respect to the circulating strains. This study was performed to better understand the molecular evolution of influenza A(H3N2) and assess vaccine efficacy in Cameroon. Complete sequences of three gene segments were obtained from 2014 to 2016 influenza seasons in Cameroon. Hemagglutinin (HA), Neuraminidase (NA) and matrix (M) genes of 35 A(H3N2) virus strains were amplified and sequenced. Predicted vaccine efficacy was measured using the P(epitope) model. Phylogenetic analysis of the HA gene showed that all Cameroonian strains had evolved away from the 3C.1-A/Texas/50/2012-like clade. Globally, 2014 virus strains clustered with the 2015–2016 vaccine strain, 3C.3a-A/Switzerland/9715293/2013, whereas 2015 and 2016 virus strains clustered with the 2016–2017 vaccine strain, 3C.2a-A/HongKong/4801/2014. In order to determine the genotypic drug susceptibility to neuraminidase inhibitors and amantadine, the NA and M2 protein coding sequences were analyzed. There was no strain with characteristic mutation for resistance to neuraminidase inhibitors, per contra; all strains possessed the substitution S31N, peculiar of resistance to adamantanes. There was drift in influenza A(H3N2) dominant epitopes B (2014 and 2015) to epitopes A (2016) with a theoretical efficiency in vaccine ranging from low to moderate. The presence of several antigenic site mutations among H3N2 virus strains between 2014–2016 influenza seasons in Cameroon confirms the progressing evolution of circulating H3N2 strains.


title: Evaluation of the Secondary Transmission Pattern and Epidemic Prediction of COVID-19 in the Four Metropolitan Areas of China

text: Understanding the transmission dynamics of COVID-19 is crucial for evaluating its spread pattern, especially in metropolitan areas of China, as its spread could lead to secondary outbreaks. In addition, the experiences gained and lessons learned from China have the potential to provide evidence to support other metropolitan areas and large cities outside China with their emerging cases. We used data reported from January 24, 2020, to February 23, 2020, to fit a model of infection, estimate the likely number of infections in four high-risk metropolitan areas based on the number of cases reported, and increase the understanding of the COVID-19 spread pattern. Considering the effect of the official quarantine regulations and travel restrictions for China, which began January 23~24, 2020, we used the daily travel intensity index from the Baidu Maps app to roughly simulate the level of restrictions and estimate the proportion of the quarantined population. A group of SEIR model statistical parameters were estimated using Markov chain Monte Carlo (MCMC) methods and fitting on the basis of reported data. As a result, we estimated that the basic reproductive number, R(0), was 2.91 in Beijing, 2.78 in Shanghai, 2.02 in Guangzhou, and 1.75 in Shenzhen based on the data from January 24, 2020, to February 23, 2020. In addition, we inferred the prediction results and compared the results of different levels of parameters. For example, in Beijing, the predicted peak number of cases was 467 with a peak time of March 01, 2020; however, if the city were to implement different levels (strict, moderate, or weak) of travel restrictions or regulation measures, the estimation results showed that the transmission dynamics would change and that the peak number of cases would differ by between 54% and 209%. We concluded that public health interventions would reduce the risk of the spread of COVID-19 and that more rigorous control and prevention measures would effectively contain its further spread, and awareness of prevention should be enhanced when businesses and social activities return to normal before the end of the epidemic. Further, the experiences gained and lessons learned from China offer the potential to provide evidence supporting other metropolitan areas and big cities with their emerging cases outside China.


title: Clinical Features and the Treatment of Children with COVID‐19: A Case Series from Wenzhou, China

text: The clinical features and treatment of children with COVID‐19 is unclear and understudied. Here, three children with COVID‐19 infection, ages 2 to 12 years, were prospectively followed from hospital admission to discharge. We provide information and experience with treatment of pediatric cases with confirmed COVID‐19 infection. This article is protected by copyright. All rights reserved.


title: A Pandemic in Times of Global Tourism: Superspreading and Exportation of COVID-19 Cases from a Ski Area in Austria

text: On January 7, 2020, the World Health Organization (WHO) announced a novel coronavirus to be the cause of unclear pneumonia cases in China.….


title: Religious Cliché and Stigma: A Brief Response to Overlooked Barriers in COVID-19 Management

text: For decades, religion has provided explanations and answers to existential questions and queries that can emerge during a pandemic. This characteristic of religion has helped communities in finding answers and meanings to their confusions. During a pandemic, healthcare professionals are often unprepared in answering the patients’ religious beliefs regarding the diseases. Moreover, patients are faced with religious clichés and stigma that results because of religious beliefs and practices. To overcome the religious stigma, a deeper understanding of religious beliefs and values is required so that a perception or practice change can take place. Therefore, the inclusion and collaboration of spiritual leaders with healthcare professionals are needed to ensure a holistic understanding and overcome the stigma that can shape as a barrier for reaching an optimal therapeutic outcome.


title: Covid-19 Testing, Hospital Admission, and Intensive Care Among 2,026,227 United States Veterans Aged 54–75 Years

text: IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States. OBJECTIVE: To determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care. EXPOSURES: Demographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a validated summary measure of physiologic injury (VACS Index). MAIN OUTCOMES AND MEASURES: We evaluated which factors were associated with Covid-19+ among all who tested. Among Covid-19+ we identified factors associated with hospitalization or intensive care. We identified independent associations using multivariable and conditional multivariable logistic regression with multiple imputation of missing values. RESULTS: Among Veterans aged 54–75 years, 585/3,789 (15.4%) tested Covid-19+. In adjusted analysis (C-statistic=0.806) black race was associated with Covid-19+ (OR 4.68, 95% Cl 3.795.78) and the association remained in analyses conditional on site (OR 2.56, 95% Cl 1.89–3.46). In adjusted models, laboratory abnormalities (especially fibrosis-4 score [FIB-4] >3.25 OR 8.73, 95% Cl 4.11–18.56), and VACS Index (per 5-point increase OR 1.62, 95% Cl 1.43–1.84) were strongly associated with hospitalization. Associations were similar for intensive care. Although significant in unadjusted analyses, associations with comorbid conditions and medications were substantially reduced and, in most cases, no longer significant after adjustment. CONCLUSIONS AND RELEVANCE: Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure.


title: Canine and Feline Uveitis

text: The clinical signs of uveitis occur as a result of inflammation within the vascular coat of the eye, which causes breakdown of the blood-aqueous barrier and blood-retinal barrier. Many infectious and noninfectious causes can incite episodes of uveitis. Although a complete diagnostic evaluation is highly recommended to identify any underlying etiologic agent, many cases remain idiopathic in nature. The goals of therapy are preserving vision, minimizing pain, and halting inflammation.


docid: ghimngvf

title: Restaurant diners’ self-protective behavior in response to an epidemic crisis

text: This study is designed to conceptually propose and empirically examine a theoretical model for restaurant diners’ self-protective behavior in response to an epidemic crisis. Based on Weinstein's five-stage PAPM, a prospective model and a classification scheme for five corresponding types of self-protective behavior adopters are proposed in this study. By using ten-year longitudinal survey data provided by a timely research sample which was obtained from a multi-store restaurant's diner club members immediately after the peak period of the SARS outbreak in Taiwan, both theoretical and managerial applicability of the proposed stage-based model are empirically verified in this study. The results show that the type of self-protective behavior respondents adopted is significantly associated with their marital status and risk attitude toward the epidemic. Besides, respondents significantly advance their type of self-protective behavior adoption along successive epidemics from the SARS to avian influenza A(H7N9) in decade.


title: An electrochemical immunosensor for the corona virus associated with the Middle East respiratory syndrome using an array of gold nanoparticle-modified carbon electrodes

text: The Middle East respiratory syndrome corona virus (MERS-CoV) is highly pathogenic. An immunosensor for the determination of MERS-CoV is described here. It is based on a competitive assay carried out on an array of carbon electrodes (DEP) modified with gold nanoparticles. Recombinant spike protein S1 was used as a biomarker for MERS CoV. The electrode array enables multiplexed detection of different CoVs. The biosensor is based on indirect competition between free virus in the sample and immobilized MERS-CoV protein for a fixed concentration of antibody added to the sample. Voltammetric response is detected by monitoring the change in the peak current (typically acquired at a working potential of −0.05 V vs. Ag/AgCl) after addition of different concentrations of antigen against MERS-CoV. Electrochemical measurements using ferrocyanide/ferricyanide as a probe were recorded using square wave voltammetry (SWV). Good linear response between the sensor response and the concentrations from 0.001 to 100 ng.mL(−1) and 0.01 to 10,000 ng.mL(−1) were observed for MERS-CoV and HCoV, respectively. The assay was performed in 20 min with detection limit as low as 0.4 and 1.0 pg.mL(−1) for HCoV and MERS-CoV, respectively. The method is highly selective over non-specific proteins such as Influenza A and B. The method is single-step, sensitive and accurate. It was successfully applied to spiked nasal samples. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00604-019-3345-5) contains supplementary material, which is available to authorized users.


Poverty, Inequality & COVID-19: The Forgotten Vulnerable


Emergency Endoscopy During the SARS-CoV-2 Pandemic in the North of Italy: Experience from St. Orsola University Hospital—Bologna


docid: zgvhaqce

title: Parkinson's Disease and COVID‐19: Perceptions and Implications in Patients and Caregivers


title: Exploring challenges of health system preparedness for communicable diseases in Arbaeen mass gathering: a qualitative study

text: Background: Infectious diseases are common problems in mass gatherings, especially when there is a lack of health system preparedness. Since Iran is one of the most important countries on the walking path of Arbaeen and has a vital role in providing health services to pilgrims, the experiences of health challenges by participants is of key importance. The aim of this study is to explore stakeholders’ experiences on the health system's preparedness and challenges, and to provide suggestions for preventing infectious diseases during the Arbaeen mass gathering. Methods: A qualitative research method was used with a conventional content analysis approach. The number of participants was 17, including 13 executive managers and 4 health policymakers who entered the study among participants. Semi-structured interviews were used to generate the data. Interviews were analyzed by means of content analysis after face-to-face interviews. Results: Data analysis resulted in the extraction of four main themes and 11 sub-themes. Health infrastructure defects in Iraq has three sub-themes (health abandonment in Iraq, the weaknesses in health culture and problems related to the health system); poor control of the causative factors of infectious diseases has three sub-themes (the underlying factors of the prevalence of contagious diseases, health system response to communicable diseases and ignoring the risks of the Arbaeen ceremony); the low perception of risk in pilgrims has three sub-themes (lack of awareness in pilgrims, fatalism in pilgrims and unhygienic belief in pilgrims); and the ineffectiveness of health education has two sub-themes (training shortage in the targeted group and educational content problems) that shows participant’s experiences of the health system's challenges for coping with infectious diseases during the Arbaeen ceremony. Conclusion: Pilgrim-based training, planning and controlling other challenges may change these threats to opportunities and improve the health of participants of the mass gathering of Arbaeen in the region.


title: Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis

text: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a global pandemic by the World Health Organisation and urgent treatment and prevention strategies are needed. Many clinical trials have been initiated with existing medications, but assessments of the expected plasma and lung exposures at the selected doses have not featured in the prioritisation process. Although no antiviral data is currently available for the major phenolic circulating metabolite of nitazoxanide (known as tizoxanide), the parent ester drug has been shown to exhibit in vitro activity against SARS-CoV-2. Nitazoxanide is an anthelmintic drug and its metabolite tizoxanide has been described to have broad antiviral activity against influenza and other coronaviruses. The present study used physiologically-based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported nitazoxanide 90% effective concentration (EC90) against SARS-CoV-2. Methods: A whole-body PBPK model was constructed for oral administration of nitazoxanide and validated against available tizoxanide pharmacokinetic data for healthy individuals receiving single doses between 500 mg SARS-CoV-2 4000 mg with and without food. Additional validation against multiple-dose pharmacokinetic data when given with food was conducted. The validated model was then used to predict alternative doses expected to maintain tizoxanide plasma and lung concentrations over the reported nitazoxanide EC90 in >90% of the simulated population. Optimal design software PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials. Results: The PBPK model was validated with AAFE values between 1.01 SARS-CoV-2 1.58 and a difference less than 2-fold between observed and simulated values for all the reported clinical doses. The model predicted optimal doses of 1200 mg QID, 1600 mg TID, 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food, to provide tizoxanide plasma and lung concentrations over the reported in vitro EC90 of nitazoxanide against SARS-CoV-2. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12h post dose was estimated. Conclusion: The PBPK model predicted that it was possible to achieve plasma and lung tizoxanide concentrations, using proven safe doses of nitazoxanide, that exceed the EC90 for SARS-CoV-2. The PBPK model describing tizoxanide plasma pharmacokinetics after oral administration of nitazoxanide was successfully validated against clinical data. This dose prediction assumes that the tizoxanide metabolite has activity against SARS-CoV-2 similar to that reported for nitazoxanide, as has been reported for other viruses. The model and the reported dosing strategies provide a rational basis for the design (optimising plasma and lung exposures) of future clinical trials of nitazoxanide in the treatment or prevention of SARS-CoV-2 infection.


title: CSFV proliferation is associated with GBF1 and Rab2

text: The Golgi apparatus and its resident proteins are utilized and regulated by viruses to facilitate their proliferation. In this study, we investigated Classical swine fever virus (CSFV) proliferation when the function of the Golgi was disturbed. Golgi function was disturbed using chemical inhibitors, namely, brefeldin A (BFA) and golgicide A (GCA), and RNA interfering targets, such as the Golgi-specific BFA-resistance guanine nucleotide exchange factor 1 (GBF1) and Rab2 GTPases. CSFV proliferation was significantly inhibited during RNA replication and viral particle generation after BFA and GCA treatment. CSFV multiplication dynamics were retarded in cells transfected with GBF1 and Rab2 shRNA. Furthermore, CSFV proliferation was promoted by GBF1 and Rab2 overexpression using a lentiviral system. Hence, Golgi function is important for CSFV multiplication, and GBF1 and Rab2 participate in CSFV proliferation. Further studies must investigate Golgi-resident proteins to elucidate the mechanism underlying CSFV replication.


title: Should breast reconstruction and breast oncoplastic procedures be performed during the coronavirus pandemic?

text: The onset of the COVID-19 pandemic has changed the face of the treatment of breast cancer and breast reconstruction globally. Mastectomy with immediate implant-based breast reconstruction was on the rise due to advances in meshes and implants. However, due to the prioritisation of the critically ill and diversion of the work force, breast cancer treatment has drastically changed. This is an opinion paper written by the authors with experience and importance in the scenario of breast reconstructive surgery. The authors are from different countries with the COVID-19 pandemic in different stages.


docid: rpfecwhg

title: The Independence of Ontario's Public Health Units: Does Governing Structure Matter?

text: Do autonomous health units fulfil their mandate better than ones that are integrated into municipal structures? Many observers of Ontario's public health system seem to think so, but this assumption is based on very little evidence. This paper seeks to help fill this gap by grounding a comparison of the spending growth of two health units with different governing structures in the multilevel governance literature. The study finds that, after an increase in provincial funding, an autonomous health unit, the Middlesex-London Health Unit, behaved more in accordance with provincial expectations than Hamilton Public Health Services, which is integrated into the City of Hamilton. The paper contributes by providing theoretical and empirical explanations for variation among local health units.


title: From empiricism to rational design: a personal perspective of the evolution of vaccine development

text: Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner — and later Pasteur — inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri3694) contains supplementary material, which is available to authorized users.


title: Shifting trends in pathogen dynamics on a changing planet

text: In this perspective we offer views on how microbial activities may change in response to the impact of human activities and an increasing human population. New knowledge is forthcoming in microbiology and immunology on the biology of emerging pathogens. With the exposure of human populations to changing environments, through climate change and human encroachment into previously unpopulated areas, there is likely to be increased incidences of diseases caused by existing, emerging and previously unrecognised pathogens.


title: The 2003 SARS outbreak and its impact on infection control practices

text: Summary Severe Acute Respiratory Syndrome (SARS) emerged recently as a new infectious disease that was transmitted efficiently in the healthcare setting and particularly affected healthcare workers (HCWs), patients and visitors. The efficiency of transmission within healthcare facilities was recognised following significant hospital outbreaks of SARS in Canada, China, Hong Kong, Singapore, Taiwan and Vietnam. The causative agent of SARS was identified as a novel coronavirus, the SARS coronavirus. This was largely spread by direct or indirect contact with large respiratory droplets, although airborne transmission has also been reported. High infection rates among HCWs led initially to the theory that SARS was highly contagious and the concept of ‘super-spreading events’. Such events illustrated that lack of infection control (IC) measures or failure to comply with IC precautions could lead to large-scale hospital outbreaks. SARS was eventually contained by the stringent application of IC measures that limited exposure of HCWs to potentially infectious individuals. As the ‘global village’ becomes smaller and other microbial threats to health emerge, or re-emerge, there is an urgent need to develop a global strategy for infection control in hospitals. This paper provides an overview of the main IC practices employed during the 2003 SARS outbreak, including management measures, dedicated SARS hospitals, personal protective equipment, isolation, handwashing, environmental decontamination, education and training. The psychological and psychosocial impact on HCWs during the outbreak are also discussed. Requirements for IC programmes in the post-SARS period are proposed based on the major lessons learnt from the SARS outbreak.


title: Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19

text: Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin-angiotensin system (RAS) in vitro by inhibiting angiotensin 1 receptor (AT1R) expression. The rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19 by helping reduce the production of the inflammatory cytokines without deleterious effects on the immune system to delay viral clearance. Moreover, PTX can restore the balance of the immune response, reduce damage to the endothelium and alveolar epithelial cells, improve circulation, and prevent microvascular thrombosis. There is further evidence that PTX can improve ventilatory parameters. Therefore, we propose repositioning PTX in the treatment of COVID-19. The main advantage of repositioning PTX is that it is an affordable drug that is already available worldwide with an established safety profile, further offering the possibility of immediately analysing the result of its use and associated success rates. Another advantage is that PTX selectively reduces the concentration of TNF-α mRNA in cells, which, in the case of an acute infectious state such as COVID-19, would seem to offer a more strategic approach.


title: S-allylmercaptocysteine inhibits mucin overexpression and inflammation via MAPKs and PI3K-Akt signaling pathways in acute respiratory distress syndrome

text: Cytokine storm is an important cause of acute respiratory distress syndrome and multiple organ failure. Excessive secretion and accumulation of mucins on the surface of airway cause airway obstruction and exacerbate lung infections. MUC5AC and MUC5B are the main secreted mucins and overexpressed in various inflammatory responses. S-allylmercaptocysteine, a water-soluble organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. The aim of this work was to investigate the therapeutic effects of SAMC on mucin overproduction and inflammation in 16HBE cells and LPS-induced ARDS mice. Results show that SAMC treatment ameliorated inflammatory cell infiltration and lung histopathological changes in the LPS-induced ARDS mice. SAMC also inhibited the expressions of MUC5AC and MUC5B, decreased the production of pro-inflammatory markers (IL-6, TNF-α, CD86 and IL-12) and increased the production of anti-inflammatory markers (IL-10, CD206 and TGF-β). These results confirm that SAMC had potential beneficial effects on suppressed hyperinflammation and mucin overexpression. Furthermore, SAMC exerted the therapeutic effects through the inhibition of phosphorylation of MAPKs and PI3K-Akt signaling pathways in the 16HBE cells and mice. Overall, our results demonstrate the effects of SAMC on the LPS-induced mucin overproduction and inflammation both in the 16HBE cells and mice.


title: Characterization of a Novel Chimeric Swine Enteric Coronavirus from Diseased Pigs in Central Eastern Europe in 2016

text: During a severe outbreak of diarrhoea and vomiting in a pig herd in Central Eastern Europe, faecal samples were tested positive for porcine epidemic diarrhoea virus (PEDV) and negative for transmissible gastroenteritis virus (TGEV) using a commercial RT‐qPCR assay that can detect both of these coronaviruses. However, further analyses, using other TGEV‐ and PEDV‐specific RT‐qPCR assays, provided results inconsistent with infection by either of these viruses. Sequencing of an amplicon (ca. 1.6 kb), generated by an RT‐PCR specific for the PEDV S‐gene, indicated a very close similarity (ca. 99% identity) to recently described chimeric viruses termed swine enteric coronaviruses (SeCoVs). These viruses (with an RNA genome of ca. 28 kb) were first identified in Italy in samples from 2009 but have not been detected there since 2012. A closely related virus was detected in archived samples in Germany from 2012, but has not been detected subsequently. Building on the initial sequence data, further amplicons were generated and over 9 kb of sequence corresponding to the 3′‐terminus of the new SeCoV genome was determined. Sequence comparisons showed that the three known SeCoVs are ≥98% identical across this region and contain the S‐gene and 3a sequences from PEDV within a backbone of TGEV, but the viruses are clearly distinct from each other. It is demonstrated, for the first time, that pigs from within the SeCoV‐infected herd seroconverted against PEDV but tested negative in a TGEV‐specific ELISA that detects antibodies against the S protein. These results indicate that SeCoV is continuing to circulate in Europe and suggest it can cause a disease that is very similar to PED. Specific detection of the chimeric SeCoVs either requires development of a new diagnostic RT‐qPCR assay or the combined use of assays targeting the PEDV S‐gene and another part of the TGEV genome.


Corporate expertise can help nonprofits weather pandemic


title: 108 Preventing activation of the IFN inducible OAS-RNase L pathway by A-kinase anchoring protein 7 (AKAP7)

text: The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is an interferon inducible pathway that blocks virus infections by cleaving viral and cellular single-stranded RNA. Viral dsRNA, produced during infections by both RNA and DNA viruses, activates OAS (a pathogen recognition receptor) resulting in production of 2-5A from ATP, which then activates RNase L leading to RNA cleavage. The factors that determine how cells limit activation of OAS-RNase L pathway to avoid tissue damage are poorly understood. Recently, we reported that the coronavirus, murine hepatitis virus (MHV) strain A59 accessory protein, ns2, blocks the RNase L pathway in macrophages and facilitates the development of hepatitis (Zhao et al., Cell Host & Microbe 11:607–16, 2012). The ns2 protein is a 2H phosphoesterase family member with two conserved His-x-Thr/Ser motifs that eliminates 2-5A, the activator of RNase L, through its 2′,5′-phosphodiesterase activity. Here we will show that cellular A-kinase anchoring protein 7 (AKAP7), another 2H phosphoesterase and homolog of ns2, has a similar enzymatic activity that degrades 2-5A. AKAP7 thus potentially provides the host cell with a mechanism for eliminating excess 2-5A and thus terminating RNase L activation. Accordingly, RNase L-mediated cleavage of rRNA in response to poly (rI):poly (rC) activation of OAS was suppressed by AKAP7 as determined in RNA chip analyses. In addition, cellular levels of active 2-5A were reduced by AKAP7 expression as determined by fluorescence resonance energy transfer assays for RNase L activation. These findings suggest that AKAP7 may be cytoprotective by preventing sustained activation of RNase L.


title: Do Pre-existing Anxiety-Related and Mood Disorders Differentially Impact COVID-19 Stress Responses and Coping?

text: BACKGROUND: People with pre-existing mental health conditions may be more susceptible to stressors associated with COVID-19 relative to the general population; however, no studies have assessed whether susceptibility differs between classes of mental health disorders. We assessed COVID-19-related stress, self-isolation stressors, and coping in those with a primary anxiety-related disorder diagnosis, a primary mood disorder diagnosis, and no mental health disorder. METHODS: Adults from a population-representative sample from the United States and Canada who reported current (past year) anxiety-related (n = 700) or mood disorders (n = 368) were compared to a random sample of respondents who did not report a current mental health diagnosis (n = 500) on COVID-19-related stress and self-isolation stress and coping. RESULTS: The anxiety-related disorders group exhibited higher COVID Stress Scales total scores and higher scores on its fears about danger and contamination, socioeconomic consequences, xenophobia, and traumatic stress symptoms scales than the other groups. The mood disorders group had higher scores on the traumatic stress symptoms and socioeconomic consequences scales than those with no current mental disorder. Those with current anxiety-related or mood disorders were more likely to voluntarily self-isolate and were more likely to report greater self-isolation stressors and distress than those without a mental health disorder. Yet, there were no major differences in perceived effectiveness of coping strategies across groups. CONCLUSION: People with anxiety-related or mood disorders were more negatively affected by COVID-19 compared to those with no mental health disorder; however, adding to psychological burden, those with anxiety-related disorders reported greater fears about danger and contamination, socioeconomic consequences, xenophobia, and traumatic stress symptoms than the other groups. These findings suggest the need for tailoring COVID-19-related mental health interventions to meet the specific needs of people with pre-existing mental health conditions.


title: Nucleic acid amplification tests for detection of respiratory viruses

text: Abstract Nucleic acid amplification tests (NATs) are increasingly being used for diagnosis of respiratory virus infections. The most familiar formats use DNA or RNA target amplification methods for enhanced sensitivity above culture and antigen-based procedures. Although gel and plate-hybridisation methods are still utilised for analysis of amplified products, detection using “real-time” methods which do not require handling of amplified products are favoured in many laboratories. Assays based on nucleic acid amplification and detection can be designed against a broad range of respiratory viruses and have been particularly useful for detection of recently identified viruses such as human metapneumovirus and coronaviruses NL63 and HKU1. However, the wide range of potential pathogens which can cause similar respiratory symptomology and disease makes application of individual diagnostic assays based on detection of DNA and RNA both complex and expensive. One way to resolve this potential problem is to undertake multiplexed nucleic acid amplification reactions with analysis of amplified products by suspension microarray. The Respiratory Virus Panel (RVP) from Luminex Molecular Diagnostics is one example of such an approach which could be made available to diagnostic and public health laboratories for broad spectrum respiratory virus detection.


title: Technoeconomic Modeling of Plant-Based Griffithsin Manufacturing

text: Griffithsin is a marine algal lectin that exhibits broad-spectrum antiviral activity by binding oligomannose glycans on viral envelope glycoproteins, including those found in HIV-1, HSV-2, SARS, HCV and other enveloped viruses. An efficient, scalable and cost-effective manufacturing process for Griffithsin is essential for the adoption of this drug in human antiviral prophylaxis and therapy, particularly in cost-sensitive indications such as topical microbicides for HIV-1 prevention. The production of certain classes of recombinant biologics in plants can offer scalability, cost and environmental impact advantages over traditional biomanufacturing platforms. Previously, we showed the technical viability of producing recombinant Griffithsin in plants. In this study, we conducted a technoeconomic analysis (TEA) of plant-produced Griffithsin manufactured at commercial launch volumes for use in HIV microbicides. Data derived from multiple non-sequential manufacturing batches conducted at pilot scale and existing facility designs were used to build a technoeconomic model using SuperPro Designer(®) modeling software. With an assumed commercial launch volume of 20 kg Griffithsin/year for 6.7 million doses of Griffithsin microbicide at 3 mg/dose, a transient vector expression yield of 0.52 g Griffithsin/kg leaf biomass, recovery efficiency of 70%, and purity of >99%, we calculated a manufacturing cost for the drug substance of $0.32/dose and estimated a bulk product cost of $0.38/dose assuming a 20% net fee for a contract manufacturing organization (CMO). This is the first report modeling the manufacturing economics of Griffithsin. The process analyzed is readily scalable and subject to efficiency improvements and could provide the needed market volumes of the lectin within an acceptable range of costs, even for cost-constrained products such as microbicides. The manufacturing process was also assessed for environmental, health and safety impact and found to have a highly favorable environmental output index with negligible risks to health and safety. The results of this study help validate the plant-based manufacturing platform and should assist in selecting preferred indications for Griffithsin as a novel drug.


docid: qyboryzy

title: The impact of the COVID-19 pandemic on cancer care

text: The COVID-19 pandemic has disrupted the spectrum of cancer care, including delaying diagnoses and treatment and halting clinical trials. In response, healthcare systems are rapidly reorganizing cancer services to ensure that patients continue to receive essential care while minimizing exposure to SARS-CoV-2 infection.


title: Characteristics of 1,573 healthcare workers who underwent nasopharyngeal swab for SARS-CoV-2 in Milano, Lombardy, Italy

text: OBJECTIVES: The management of healthcare workers (HCWs) exposed to confirmed cases of COVID-19 is still a matter of debate. We aimed to assess in this group the attack rate of asymptomatic carriers and the symptoms most frequently associated with the infection. METHODS: Occupational and clinical characteristics of HCWs who performed a nasopharyngeal swab for the detection of SARS-CoV-2 in a University Hospital from February 24, to March 31, 2020, were collected. For those who tested positive and for the asymptomatic positives we checked laboratory and clinical data as of May 22 to calculate the time necessary to become test-negative and to verify whether symptoms developed thereafter. Frequencies of positive tests were compared according to selected variables using multivariable logistic regression models. RESULTS: Positive tests were 139 among 1,573 HCWs (8.8%, 95% confidence interval [CI]: 7.5-10.3), with a marked difference between symptomatic (122/503, 24.2%) and asymptomatic (17/1,070, 1.6%) workers (p<0.001). Physicians were the group with the highest frequency of positive tests (61/582, 10.5%), whereas clerical workers and technicians displayed the lowest frequency (5/137, 3.6%). The likelihood of being positive increased with the number of reported symptoms and the strongest predictors were taste and smell alterations (odds ratio [OR]= 76.9) and fever (OR = 9.12). The median time from first positive test to a negative test was 27 days (95% CI: 24-30). CONCLUSIONS: A relevant number of HCWs can be infected by SARS-CoV-2 without displaying any symptom. Among symptomatic workers, the key symptoms to guide diagnosis are taste and smell alterations and fever. In median, almost four weeks are necessary to achieve negativity of nasopharyngeal swab.


title: Impacto de la COVID-19 en la mortalidad de la comunidad autónoma de Castilla y León

text: ABSTRACT Objective: To estimate the increase in mortality associated with the SARS-CoV-2 coronavirus pandemic in the autonomous community of Castilla y León (Spain). Method: Ecological study based on population and death data for the months of March 2016 to 2020 in Castilla y León. The general and provincial standardized rates, the relative risks of the year 2020 with respect to previous years and the risks adjusted by sex, periods and province, using Poisson regression, were calculated. Trend analysis was performed using joinpoint linear regression. Results: An increase in mortality was observed in March 2020 with respect to previous years, with an increase of 39% for men (relative risk [RR]: 1.39; 95% confidence interval [95%CI]: 1.32-1.47) and 28% for women (RR: 1.28; 95%CI: 1.21-1.35). The model predicts excess mortality of 775 deaths. In the trend analysis there is a significant turning point in 2019 in men, globally and for almost all provinces. The increase in mortality is general, although heterogeneous by sex, age group and province. Conclusions: Although the observed increase in mortality cannot be totally attributed to the disease, it is the best estimate we have of the real impact on deaths directly or indirectly related to it. The number of declared deaths only reaches two thirds of the increase in mortality observed.


title: Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial

text: OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. TRIAL DESIGN: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. PARTICIPANTS: Eligible participants include adults (≥ 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for ≥ 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. INTERVENTION AND COMPARATOR: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 – 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 – 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. MAIN OUTCOMES: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. RANDOMIZATION: Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. BLINDING (MASKING): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. TRIAL STATUS: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


docid: dflkggjt

title: Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency

text: Abstract Background Merkel cell polyomavirus (MCPyV) was discovered recently. It is considered a potential causative agent of Merkel cell carcinoma, a life-threatening skin cancer. Objectives To study the prevalence of MCPyV in a large number of clinical samples of various types. Most of the samples were examined also for the other newly found polyomaviruses KI (KIPyV) and WU (WUPyV). Study design Altogether 1390 samples from immunocompetent or immunocompromised patients, including (i) tonsillar tissues and sera from tonsillectomy patients; (ii) nasopharyngeal aspirates (NPAs) and sera from wheezing children and (iii) nasal swabs, sera and stools from febrile leukemic children were studied for MCPyV. The tonsils, nasal swabs and stools were also studied for KIPyV and WUPyV. Results MCPyV DNA was detected in 14 samples altogether; 8 of 229 (3.5%) tonsillar tissues, 3 of 140 (2.1%) NPAs, 2 of 106 (1.9%) nasal swabs and 1 of 840 (0.1%) sera. WUPyV and KIPyV were detected in 5 (2.2%) and 0 tonsils, 1 (0.9%) and 4 (3.8%) nasal swabs and 0 and 2 (2.7%) fecal samples, respectively. The patients carrying in tonsils MCPyV were of significantly higher age (median 42years) than those carrying WUPyV (4years, p <0.001). Conclusions MCPyV DNA occurs in tonsils more frequently in adults than in children. By contrast, WUPyV DNA is found preferentially in children. MCPyV occurs also in nasal swabs and NPAs, in a frequency similar to that of KIPyV and WUPyV. The tonsil may be an initial site of WUPyV infection and a site of MCPyV persistence.


title: Supplemental flaxseed modulates ovarian functions of weanling gilts via the action of selected fatty acids

text: Abstract The aim of this study was to examine the influence of dietary flaxseed on the endocrine and ovarian functions of weanling gilts challenged with E. coli and Coronavirus infections treated with dietary probiotic cheeses and to understand the possible mechanisms of its effects on ovarian function. Probiotics were used as a natural substitution for antibiotics and 10% dietary flaxseed is an effective prebiotic which supports the action of probiotics and has other beneficial effects on the organism. Probiotics with or without flaxseed were fed to weanling gilts starting 10 days before and lasting up until 14 days after weaning. The ovaries were measured and histologically analysed. The blood samples for the levels of steroid hormones and insulin-like growth factor I (IGF-I) were assessed using immunoassays and the levels of fatty acids were assessed using gas chromatography. All samples were collected on the day of weaning and 14 days after weaning. On the day of weaning, increased levels of linoleic acid and IGF-I was associated with higher body weight. The steroid hormones were not affected by the diet. The conversion of alpha-linolenic acid (ALA) to timodonic (EPA) and cervonic (DHA) acids were lower compared to controls, and together with high levels of myristic, palmitic and palmitoleic acids was associated with the higher proliferation and lower apoptosis in the primordial, primary and secondary follicles; although the inhibition of the cell cycle was observed in relation to the low level of eicosadienoic acid. The high levels of ALA, EPA and DHA and the low levels of myristic, palmitic and palmitoleic acids may have been the effect of flaxseed feeding 14 days post-weaning and may have had a reverse effect on the proliferation and apoptosis of ovarian follicles. These data suggest that flaxseed may suppress the follicle development in weanlings via the stimulation of apoptosis and the inhibition of proliferation via the modulation of the metabolism of selected fatty acids.


title: Chapter 11 Detection of Biomarkers for Different Diseases on Biosensor Surfaces Part II

text: Abstract In this chapter the authors analyze the binding and dissociation kinetics (if applicable) of (1) interferon-gamma as a function of aptamer variants and inclusion of spacer, (2) GST-N protein in PBS and GST-N protein in 10-fold diluted serum to a localized surface plasmon resonance coupled fluorescence biosensor, (3) cytochrome c mutant to a superoxide biosensor, (4) Carbonic Anhydrase-II to an 4-(2-aminoethyl)-benzene sulfonamide ligand on an surface plasmon resonance biosensor surface, (5) glycerol secretion from differentiated (murine 3T3-L1) adipocytes to a microfluidic platform for fluorescence-based assay, and (6) different concentrations of C-reactive protein in solution to a sandwich-type assay using reflectometric interference spectroscopy (label-free detection method).


title: A robust lentiviral pseudotype neutralisation assay for in-field serosurveillance of rabies and lyssaviruses in Africa

text: The inflexibility of existing serological techniques for detection of rabies in surveillance constrains the benefit to be gained from many current control strategies. We analysed 304 serum samples from Tanzanian dogs for the detection of rabies antibodies in a pseudotype assay using lentiviral vectors bearing the CVS-11 envelope glycoprotein. Compared with the widely used gold standard fluorescent antibody virus neutralisation assay, a specificity of 100% and sensitivity of 94.4% with a strong correlation of antibody titres (r = 0.915) were observed with the pseudotype assay. To increase the assay's surveillance specificity in Africa we incorporated the envelope glycoprotein of local viruses, Lagos bat virus, Duvenhage virus or Mokola virus and also cloned the lacZ gene to provide a reporter element. Neutralisation assays using pseudotypes bearing these glycoproteins reveal that they provide a greater sensitivity compared to similar live virus assays and will therefore allow a more accurate determination of the distribution of these highly pathogenic infections and the threat they pose to human health. Importantly, the CVS-11 pseudotypes were highly stable during freeze–thaw cycles and storage at room temperature. These results suggest the proposed pseudotype assay is a suitable option for undertaking lyssavirus serosurveillance in areas most affected by these infections.


title: Potential Application of Whole Body Vibration Exercise for Improving the Clinical Conditions of COVID-19 Infected Individuals: A Narrative Review from the World Association of Vibration Exercise Experts (WAVex) Panel

text: COVID-19 is a highly infectious respiratory disease which leads to several clinical conditions related to the dysfunction of the respiratory system along with other physical and psychological complaints. Severely affected patients are referred to intensive care units (ICUs), limiting their possibilities for physical exercise. Whole body vibration (WBV) exercise is a non-invasive, physical therapy, that has been suggested as part of the procedures involved with pulmonary rehabilitation, even in ICU settings. Therefore, in the current review, the World Association of Vibration Exercise Experts (WAVEX) reviewed the potential of WBV exercise as a useful and safe intervention for the management of infected individuals with COVID-19 by mitigating the inactivity-related declines in physical condition and reducing the time in ICU. Recommendations regarding the reduction of fatigue and the risk of dyspnea, the improvement of the inflammatory and redox status favoring cellular homeostasis and the overall improvement in the quality of life are provided. Finally, practical applications for the use of this paradigm leading to a better prognosis in bed bound and ICU-bound subjects is proposed.


title: Three-dimensional structure of Rubella virus factories

text: Abstract Viral factories are complex structures in the infected cell where viruses compartmentalize their life cycle. Rubella virus (RUBV) assembles factories by recruitment of rough endoplasmic reticulum (RER), mitochondria and Golgi around modified lysosomes known as cytopathic vacuoles or CPVs. These organelles contain active replication complexes that transfer replicated RNA to assembly sites in Golgi membranes. We have studied the structure of RUBV factory in three dimensions by electron tomography and freeze-fracture. CPVs contain stacked membranes, rigid sheets, small vesicles and large vacuoles. These membranes are interconnected and in communication with the endocytic pathway since they incorporate endocytosed BSA-gold. RER and CPVs are coupled through protein bridges and closely apposed membranes. Golgi vesicles attach to the CPVs but no tight contacts with mitochondria were detected. Immunogold labelling confirmed that the mitochondrial protein p32 is an abundant component around and inside CPVs where it could play important roles in factory activities.


title: Antibody Response of Patients with Severe Acute Respiratory Syndrome (SARS) Targets the Viral Nucleocapsid

text: The recent outbreak of severe acute respiratory syndrome (SARS) provided an opportunity to study the antibody response of infected individuals to the causative virus, SARS coronavirus. We examined serum samples obtained from 46 patients with SARS, 40 patients with non-SARS pneumonia, and 38 healthy individuals, by use of Western blotting (WB), enzyme-linked immunoassay (ELISA), and immunofluorescence assay, using both native and bacterially produced antigens of the virus. We found a highly restricted, immunoglobulin G-dominated antibody response in patients with SARS, directed most frequently (89% by ELISA) and predominantly at the nucleocapsid. Almost all of the subjects without SARS had no antinucleocapsid antibodies. The spike protein was the next most frequently targeted, but only 63% of the patients (by ELISA) responded. Other targets of the response identified by use of WB included antigens of 80 and 60 kDa. Several nonstructural proteins cloned were not antigenic, and the culture-derived nucleocapsid appeared to be specifically degraded.


title: Structure of the SARS Coronavirus Nucleocapsid Protein RNA-binding Dimerization Domain Suggests a Mechanism for Helical Packaging of Viral RNA

text: Abstract Coronavirus nucleocapsid proteins are basic proteins that encapsulate viral genomic RNA to form part of the virus structure. The nucleocapsid protein of SARS-CoV is highly antigenic and associated with several host-cell interactions. Our previous studies using nuclear magnetic resonance revealed the domain organization of the SARS-CoV nucleocapsid protein. RNA has been shown to bind to the N-terminal domain (NTD), although recently the C-terminal half of the protein has also been implicated in RNA binding. Here, we report that the C-terminal domain (CTD), spanning residues 248–365 (NP248-365), had stronger nucleic acid-binding activity than the NTD. To determine the molecular basis of this activity, we have also solved the crystal structure of the NP248-365 region. Residues 248–280 form a positively charged groove similar to that found in the infectious bronchitis virus (IBV) nucleocapsid protein. Furthermore, the positively charged surface area is larger in the SARS-CoV construct than in the IBV. Interactions between residues 248–280 and the rest of the molecule also stabilize the formation of an octamer in the asymmetric unit. Packing of the octamers in the crystal forms two parallel, basic helical grooves, which may be oligonucleotide attachment sites, and suggests a mechanism for helical RNA packaging in the virus.


title: The evolution of fetal echocardiography before and during COVID-19

text: The World Health Organization declared the novel coronavirus, or COVID-19, a pandemic in March 2020. Given the severity of COVID-19, appropriate use criteria have been implemented for fetal echocardiography. Screening low risk pregnancies for critical congenital heart disease has typically been a shared responsibility by pediatric cardiologists, obstetricians, and maternal fetal medicine (MFM). Currently, many of the fetal echocardiograms for low risk pregnancies for critical congenital heart disease have been deferred or cancelled with the emphasis on suspected abnormalities by MFMs and obstetricians. In this review, we discuss the literature that has been the basis of screening of low risk pregnancies by pediatric cardiologists. A new approach to more widespread usage of fetal tele-echocardiography may play a large part during COVID-19 and may continue after the pandemic.


title: Coronavirus in the Amazon

text: The global pandemic could soon threaten uncontacted tribes


title: Modeling the Transmission of Middle East Respirator Syndrome Corona Virus in the Republic of Korea

text: The 2015 epidemic of Middle East respiratory syndrome (MERS) in the Republic of Korea has been the largest outbreak outside Middle East. This epidemic had caused 185 laboratory-confirmed cases and 36 deaths in the Republic of Korea until September 2, 2015, which attracted public’s attention. Based on the detailed data of patients released by World Health Organization (WHO) and actual propagation of the epidemic, we construct two dynamical models to simulate the propagation processes from May 20 to June 8 and from June 9 to July 10, 2015, respectively and find that the basic reproduction number R (0) reaches up to 4.422. The numerical analysis shows that the reasons of the outbreak spread quickly are lack of self-protection sense and targeted control measures. Through partial correction analysis, the parameters β (1) and γ have strong correlations with R (0), i.e., the infectivity and proportion of the asymptomatic infected cases have much influence on the spread of disease. By sensitivity analysis, strengthening self-protection ability of susceptible and quickly isolating or monitoring close contacts are effective measures to control the disease.


title: Chapter 9 Cell Culture Growing Cells as Model Systems In Vitro

text: Abstract Cell culture is a very versatile tool in the investigation of basic scientific and translation research questions. The advantage of using cell lines in scientific research is their homogeneity and associated reproducibility in data generated. This chapter introduces the principles behind the setup of a cell culture lab and the guidelines that ensure safety of the lab personnel as well as the cultured cells. It also addresses potential microbiological contaminants and how they can be avoided but also detected early. Since the selection of a particular cell line and specific cell culture conditions depends on the readout of the desired assay, this chapter will present a generalized overview of common mammalian cell culture components and properties that contribute to a suitable cell culture microenvironment. Consequently, this chapter outlines several techniques that are crucial for cell propagation and can be easily adapted to a broad number of cell types and experimental procedures.


title: A web-based daily care training to improve the quality of life of mothers of children with cerebral palsy: A randomized controlled trial

text: BACKGROUND: Mothers of moderately to severely affected children with cerebral palsy (CP) have to spend a long time to take care of their children. This time-consuming responsibility affects their physical and psychosocial health. Therefore, mothers as caregivers are required to receive special training to take care of their children. AIMS: The aim of this study was to evaluate the effectiveness of a developed web-based intervention for daily care training of children with CP on their mothers’ quality of life (QOL), anxiety, depression, stress, and their musculoskeletal pain. METHODS AND PROCEDURES: This study was a single blind randomized controlled trial. 91 mothers of children with CP with Gross Motor Function Classification System (GMFCS) levels III, IѴ, and Ѵ, who aged from 4 to 12 years were assigned to the intervention and control groups using block randomization. Mothers in the control group received their routine face to face occupational therapy intervention and mothers in the intervention group received 12 weeks web-based intervention. QOL, depression, anxiety, stress, and pain were measured before and after the intervention in both groups. OUTCOMES AND RESULTS: The results of analysis of covariance showed that after controlling the mean score of pretest of pain, the mean score of post-tests in the intervention and control groups was significantly different (P < 0.05). The mean scores of physical health and total QOL scores of post-tests in the intervention group were significantly higher than the control group with controlling pretest scores. CONCLUSIONS AND IMPLICATIONS: Designed web-based intervention affects the caregivers’ QOL and pain significantly. This intervention can be used to provide daily care training for mothers of children with CP.


docid: ubferyqe

title: Guidelines on common cold for Traditional Chinese Medicine based on pattern differentiation

text: Abstract Objective To establish the guidelines on common cold treated with Traditional Chinese Medicine (TCM) in terms of pattern identification. Methods The guidelines were formulated by using the basic patterns of common cold in China Pharmacopeia integrated with findings from systematic literature review and the experts' consensus on the issue in question. Results Common cold was divided into four patterns in the guidelines. The medications were recommended respectively: Ganmaoqingre granule for wind-cold exterior syndrome, Yinqiaojiedu granule for wind-heat exterior syndrome, Huoxiang Zhengqi Wan for summer-heat dampness exterior syndrome and Shensu Wan for wind-cold exterior syndrome accompanied with Qi deficiency. Conclusion The guidelines were primarily derived from the practice experience of TCM and the experts' consensus. The process was not strictly evidence-based because of lacking enough clinical studies. Further refinement of the guidelines should be needed as more studies are available.


title: Are antibodies tests accurate? Understanding predictive values and uncertainty of serology tests for the novel coronavirus.

text: Antibodies testing in the coronavirus era is frequently promoted, but the underlying statistics behind their validation has come under more scrutiny in recent weeks. We provide calculations, interpretations, and plots of positive and negative predictive values under a variety of scenarios. Prevalence, sensitivity, and specificity are estimated within ranges of values from researchers and antibodies manufacturers. Illustrative examples are highlighted, and interactive plots are provided in the Supplementary Material. Implications are discussed for society overall and across diverse locations with different levels of disease burden. Specifically, the proportion of positive serology tests that are false can differ drastically from up to 3% to 88% for people from different places with different proportions of infected people in the populations while the false negative rate is typically under 10%.


title: Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Regulates Cell Stress Response and Apoptosis

text: Severe acute respiratory syndrome virus (SARS-CoV) that lacks the envelope (E) gene (rSARS-CoV-ΔE) is attenuated in vivo. To identify factors that contribute to rSARS-CoV-ΔE attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, apoptosis and cell cycle and differentiation were differentially regulated in cells infected with rSARS-CoV with or without the E gene. Administration of E protein in trans reduced the stress response in cells infected with rSARS-CoV-ΔE or with respiratory syncytial virus, or treated with drugs, such as tunicamycin and thapsigargin that elicit cell stress by different mechanisms. In addition, SARS-CoV E protein down-regulated the signaling pathway inositol-requiring enzyme 1 (IRE-1) of the unfolded protein response, but not the PKR-like ER kinase (PERK) or activating transcription factor 6 (ATF-6) pathways, and reduced cell apoptosis. Overall, the activation of the IRE-1 pathway was not able to restore cell homeostasis, and apoptosis was induced probably as a measure to protect the host by limiting virus production and dissemination. The expression of proinflammatory cytokines was reduced in rSARS-CoV-ΔE-infected cells compared to rSARS-CoV-infected cells, suggesting that the increase in stress responses and the reduction of inflammation in the absence of the E gene contributed to the attenuation of rSARS-CoV-ΔE.


The Certificate of Advanced Studies (CAS) course adapted to a pandemic: Restructuring the CAS course at the University of Zürich during the COVID-19 pandemic. Challenges and learnings for future change in the delivery of cardiovascular education


title: Impact of renal function on admission in COVID-19 patients: an analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID 19) Registry

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its international aggressive extension, with a significant morbidity and mortality, the impact of renal function on its prognosis is uncertain. METHODS: Analysis from the international HOPE-Registry (NCT04334291). The objective was to evaluate the association between kidney failure severity on admission with the mortality of patients with SARS-CoV-2 infection. Patients were categorized in 3 groups according to the estimated glomerular filtration rate on admission (eGFR > 60 mL/min/1.73 m(2), eGFR 30–60 mL/min/1.73 m(2) and eGFR < 30 mL/min/1.73 m(2)). RESULTS: 758 patients were included: mean age was 66 ± 18 years, and 58.6% of patient were male. Only 8.5% of patients had a history of chronic kidney disease (CKD); however, 30% of patients had kidney dysfunction upon admission (eGFR < 60 mL/min/1.73 m(2)). These patients received less frequently pharmacological treatment with hydroxychloroquine or antivirals and had a greater number of complications such as sepsis (11.9% vs 26.4% vs 40.8%, p < 0.001) and respiratory failure (35.4% vs 72.2% vs 62.0%, p < 0.001) as well as a higher in-hospital mortality rate (eGFR > 60 vs eGFR 30-60 vs and eGFR < 30, 18.4% vs 56.5% vs 65.5%, p < 0.001). In multivariate analysis: age, hypertension, renal function, 0(2) saturation < 92% and lactate dehydrogenase elevation on admission independently predicted all-cause mortality. CONCLUSIONS: Renal failure on admission in patients with SARS-CoV-2 infection is frequent and is associated with a greater number of complications and in-hospital mortality. Our data comes from a multicenter registry and therefore does not allow to have a precise mortality risk assessment. More studies are needed to confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40620-020-00790-5) contains supplementary material, which is available to authorized users.


title: Diagnostics and Surveillance for Swine Influenza

text: Collective knowledge regarding the occurrence of influenza among swine is incomplete due to inconsistent surveillance of swine populations. In this chapter, we review what surveillance activities exist and some of the practical challenges encountered. Furthermore, to support robust surveillance activities, accurate laboratory assays are needed for the detection of the virus and viral nucleic acids within clinical samples, or for antiviral antibodies in serum samples. The most common influenza diagnostic assays used for swine are explained and their use as surveillance tools evaluated.


title: Psychological crisis intervention for college students during novel coronavirus infection epidemic

text: Abstract At the beginning of the 2020 New year, novel coronavirus infection continues to affect our lives. The anxiety and stress caused by rising epidemic data, the helplessness and fear caused by city closure and isolation, and the boredom and irritability caused by extended holiday grounding all have a great impact on the psychology of students. In this special stress period of "suspension of classes and non-stop learning", teachers actively help and guide students, do a good job of students' psychological support, perform the duties of spiritual mentors, and do a good job of students' psychological care.


title: Ebola Virus Disease Ethics and Emergency Medical Response Policy

text: Caring for patients affected with Ebola virus disease (EVD) while simultaneously preventing EVD transmission represents a central ethical challenge of the EVD epidemic. To address this challenge, we propose a model policy for resuscitation and emergent procedure policy of patients with EVD and set forth ethical principles that lend support to this policy. The policy and principles we propose bear relevance beyond the EVD epidemic, offering guidance for the care of patients with other highly contagious, virulent, and lethal diseases. The policy establishes (1) a limited code status for patients with confirmed or suspected EVD. Limited code status means that a code blue will not be called for patients with confirmed or suspected EVD at any stage of the disease; however, properly protected providers (those already in full protective equipment) may initiate resuscitative efforts if, in their clinical assessment, these efforts are likely to benefit the patient. The policy also requires that (2) resuscitation not be attempted for patients with advanced EVD, as resuscitation would be medically futile; (3) providers caring for or having contact with patients with confirmed or suspected EVD be properly protected and trained; (4) the treating team identify and treat in advance likely causes of cardiac and respiratory arrest to minimize the need for emergency response; (5) patients with EVD and their proxies be involved in care discussions; and (6) care team and provider discretion guide the care of patients with EVD. We discuss ethical issues involving medical futility and the duty to avoid harm and propose a utilitarian-based principle of triage to address resource scarcity in the emergency setting.


title: COVID‐19: Shedding light on racial and health inequities in the USA

text: The sudden and rapid advancement of the novel Coronavirus (COVID-19) pandemic has led to an unanticipated and unprecedented global crisis. Since its emergence in the United States, there is increasing discussion surrounding the impact of the virus among vulnerable populations. Older adults, young children, and persons with chronic medical or mental health conditions, persons with disabilities, pregnant women, immunocompromised persons and those who are institutionalized or homeless are considered most vulnerable to death and lost quality of life (World Health Organization, 2020).


title: Current Status of Infection Prevention and Control Programs for Emergency Medical Personnel in the Republic of Korea

text: OBJECTIVES: Emergency medical personnel (EMPs) are pre-hospital emergency responders who are at risk of exposure to infections and may also serve as a source for the transmission of infections. However, few studies of infection control have specifically addressed EMPs in the Republic of Korea (hereafter Korea). The goal of this study was to assess the current status of infection prevention and control programs (IPCPs) for EMPs in Korea. METHODS: A cross-sectional survey was conducted to quantitatively assess the resources and activities of IPCPs. A total of 907 EMPs in five metropolitan cities completed a structured questionnaire from September 2014 to January 2015. The data were analyzed using descriptive statistics, multi-response analysis, and the chi-square test. RESULTS: The mean age of the participants was 34.8±15.1 years. IPCPs were found to have weaknesses with regard to the following resources: the assignment of infection control personnel (ICP) (79.5%), hand hygiene resources such as waterless antiseptics (79.3%), the use of paper towels (38.9%), personal protective equipment such as face shields (46.9%), and safety containers for sharps and a separated space for the disposal of infectious waste (10.1%). Likewise, the following activities were found to be inadequately incorporated into the workflow of EMPs: education about infection control (77.5%), post-exposure management (35.9%), and the decontamination of items and spaces after use (88.4%). ICP were found to have a significant effect on the resources and activities of IPCPs (p<0.001). The resources and activities of IPCPs were found to be significantly different among the five cities (p<0.001). CONCLUSIONS: IPCPs for EMPs showed some limitations in their resources and activities. IPCPs should be actively supported, and specific IPCP activities for EMPs should be developed.


title: Are tariffs bad for growth? Yes, say five decades of data from 150 countries()

text: The empirical evidence on the growth effects of import tariffs is sparse in the literature, notwithstanding strong views held by the public and politicians. Using an annual panel of macroeconomic data for 151 countries over 1963–2014, we find that tariff increases are associated with an economically and statistically sizeable and persistent decline in output growth. Thus, fears that the ongoing trade war may be costly for the world economy in terms of foregone output growth are justified.


title: General recommendations to the colorectal surgeon during the COVID-19 pandemic

text: Abstract The COVID-19 pandemic has shown our country in an unfavorable light, as Brazil has reported the second highest number of deaths to date. When the social isolation phase is finished, professional activities (including the medical ones) will resume their routines and the specialist must be updated in order to provide effective and safe care. Although many published recommendations are based on low levels of evidence, disclosing them has become necessary, since the coronavirus infection may affect operative outcomes. Overall, it is suggested that physicians adopt preventive measures, starting with the medical appointment, and extending them to the surgical procedure. Furthermore, it is also necessary to provisionally change criteria for operative indications and conducts. Currently, postponing elective surgeries seems to be a universally agreed decision. Moreover, we need to establish the early diagnosis of the viral infection, before or after the surgery. Several safety measures related to minimally-invasive procedures have been reported, disclosing the risks of aerosol dissemination by the pneumoperitoneum and smoke from energy-powered devices. The present article aimed to bring to the colorectal surgeon the current recommendations and general safety measures in order to prevent infection dissemination, to improve surgical planning in terms of timing and specific technical aspects.


Is minimal access surgery possible and safe during the COVID‐19 pandemic?


title: Antigenic relationships of murine coronaviruses: Analysis using monoclonal antibodies to JHM (MHV-4) virus

text: Abstract Monoclonal antibodies were produced to JHMV-DL, a neurotropic member of the mouse hepatitis virus (MHV) or murine coronavirus group. Of 23 antibodies isolated, 10 were specific for the major envelope glycoprotein, gp180/90, 10 for the nucleocapsid protein, pp60, and 3 for the minor envelope glycoprotein, gp25. Eleven different MHV isolates were used in antibody binding assays to study antigenic relationships among the viruses. Each MHV isolate tested had a unique pattern of antibody binding, indicating that each is a distinct strain. Conservation of JHMV-DL antigenic determinants varied among the three proteins, with pp60 showing intermediate conservation, gp180/90 little conservation, and gp25 marked conservation in the different MHV strains. Monoclonal antibodies to pp60 proved most useful in delineating antigenic relationships among MHV strains. These antigenic groups correlated with pathogenic types, indicating that pp60 may be one of the gene products which mediates the distinct disease patterns manifested by different murine coronaviruses.


Improving New Zealand's preparations for the next pandemic


docid: szhzmzys

title: A paucity of co-infecting respiratory viral pathogens in nasopharyngeal specimens from patients infected with H274Y-positive influenza A (H1N1) strains


title: Frequency of viral etiology in symptomatic adult upper respiratory tract infections

text: Abstract Aims To determine the frequency of viral pathogens causing upper respiratory tract infections in non-hospitalized, symptomatic adults in the city of Rio de Janeiro. Methods Respiratory samples (nasal/throat swabs) were collected between August 2010 and November 2012 and real time PCR was used to detect different viral pathogens. Results Viruses were detected in 32.1% (43/134) of samples from 101 patients. Specifically, 9% (12/134) were positive for HBoV, 8.2% (11/134) were positive for HAdV, 5.2% (7/134) were positive for HRV, and 1.5% (2/134) were positive for FLUBV or HMPV, as single infections. HRSV-A, HPIV-3, and HCoV-HKU1 were detected in one (0.75%) sample each. Co-infections were detected in 4.8% (6/134) of the samples. Peaks of viral infections were observed in March, April, May, August, and October. However, positive samples were detected all year round. Only 23.3% (10/43) of the positive samples were collected from patients with febrile illness. Conclusion Results presented in this report suggest that respiratory viral infections are largely under diagnosed in immunocompetent adults. Although the majority of young adult infections are not life-threatening they may impose a significant burden, especially in developing countries since these individuals represent a large fraction of the working force.


title: Current epidemiological status of Middle East respiratory syndrome coronavirus in the world from 1.1.2017 to 17.1.2018: a cross-sectional study

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is considered to be responsible for a new viral epidemic and an emergent threat to global health security. This study describes the current epidemiological status of MERS-CoV in the world. METHODS: Epidemiological analysis was performed on data derived from all MERS-CoV cases recorded in the disease outbreak news on WHO website between 1.1.2017 and 17.1.2018. Demographic and clinical information as well as potential contacts and probable risk factors for mortality were extracted based on laboratory-confirmed MERS-CoV cases. RESULTS: A total of 229 MERS-CoV cases, including 70 deaths (30.5%), were recorded in the disease outbreak news on world health organization website over the study period. Based on available details in this study, the case fatality rate in both genders was 30.5% (70/229) [32.1% (55/171) for males and 25.8% (15/58) for females]. The disease occurrence was higher among men [171 cases (74.7%)] than women [58 cases (25.3%)]. Variables such as comorbidities and exposure to MERS-CoV cases were significantly associated with mortality in people affected with MERS-CoV infections, and adjusted odds ratio estimates were 2.2 (95% CI: 1.16, 7.03) and 2.3 (95% CI: 1.35, 8.20), respectively. All age groups had an equal chance of mortality. CONCLUSIONS: In today’s “global village”, there is probability of MERS-CoV epidemic at any time and in any place without prior notice. Thus, health systems in all countries should implement better triage systems for potentially imported cases of MERS-CoV to prevent large epidemics.


title: Orthomyxoviruses: Structure of Antigens

text: The orthomyxoviruses include influenza viruses, thogotoviruses, and isaviruses. Influenza A viruses circulate in reservoir of wild aquatic birds, occasionally cause human pandemics, undergo antigenic drift and antigentic shift, and have been used as model viruses to understand many fundamental processes including receptor binding, membrane fusion, protein structure, and adaptive immunity. Influenza A and B viruses contain a hemagglutinin (HA) surface glycoprotein, the dominant surface antigen that promotes receptor binding and membrane fusion during viral entry, and a neuraminidase (NA) glycoprotein, a secondary antigen that has receptor-destroying activity necessary for virus release from infected cells. Influenza C viruses contain a single antigen, the hemagglutinin-esterase-fusion (HEF) protein, which possesses receptor binding, membrane fusion, and virus release functions. The HA and HEF proteins are prototypic, trimeric, structural class I viral fusion proteins with a membrane-distal, immunodominant (and highly variable) receptor-binding head domain and a more highly conserved membrane-proximal, metastable, stalk domain that catalyzes membrane fusion. The tetrameric NA protein has a membrane-distal globular head domain with an antiparallel β-propeller topology and a membrane-proximal coiled-coil stalk. For the influenza A and B viruses, the HA protein is the predominant target for naturally acquired and vaccine-induced adaptive immunity. Recent structural studies of broadly reactive monoclonal antibodies bound to the HA protein, along with complementary immunological experiments, suggest ways to generate “universal” influenza vaccines that are effective after antigenic drift and shift.


title: Emerging Viral Infections

text: Unique disorders appear episodically in human populations and cause life-threatening systemic or neurological disease. Historical examples of such disorders include von Economo encephalitis, a disorder of presumed viral etiology; acquired immune deficiency syndrome, caused by the human immunodeficiency virus; and severe acute respiratory syndrome, caused by a member of the coronavirus family. This article describes the factors that contribute to the emergence of infectious diseases and focuses on selected recent examples of emerging viral infections that can affect the nervous system of infants, children, and adolescents.


title: Drosophila as a genetic model for studying pathogenic human viruses

text: Abstract Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area.


title: Molecular epidemiology, evolution and phylogeny of SARS coronavirus

text: Abstract Shortly after its emergence in southern China in 2002/2003, Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) was confirmed to be the cause of SARS. Subsequently, SARS-related CoVs (SARSr-CoVs) were found in palm civets from live animal markets in Guangdong and in various horseshoe bat species, which were believed to be the ultimate reservoir of SARSr-CoV. Till November 2018, 339 SARSr-CoV genomes have been sequenced, including 274 from human, 18 from civets and 47 from bats [mostly from Chinese horseshoe bats (Rhinolophus sinicus), n = 30; and greater horseshoe bats (Rhinolophus ferrumequinum), n = 9]. The human SARS-CoVs and civet SARSr-CoVs were collected in 2003/2004, while bat SARSr-CoVs were continuously isolated in the past 13 years even after the cessation of the SARS epidemic. SARSr-CoVs belong to the subgenus Sarbecovirus (previously lineage B) of genus Betacoronavirus and occupy a unique phylogenetic position. Overall, it is observed that the SARSr-CoV genomes from bats in Yunnan province of China possess the highest nucleotide identity to those from civets. It is evident from both multiple alignment and phylogenetic analyses that some genes of a particular SARSr-CoV from bats may possess higher while other genes possess much lower nucleotide identity to the corresponding genes of SARSr-CoV from human/civets, resulting in the shift of phylogenetic position in different phylogenetic trees. Our current model on the origin of SARS is that the human SARS-CoV that caused the epidemic in 2002/2003 was probably a result of multiple recombination events from a number of SARSr-CoV ancestors in different horseshoe bat species.


New guidance for treating patients with lung cancer and COVID‐19


title: Ebola Holding Units at government hospitals in Sierra Leone: evidence for a flexible and effective model for safe isolation, early treatment initiation, hospital safety and health system functioning

text: The 2014-2015 West African outbreak of Ebola Virus Disease (EVD) claimed the lives of more than 11,000 people and infected over 27,000 across seven countries. Traditional approaches to containing EVD proved inadequate and new approaches for controlling the outbreak were required. The Ministry of Health & Sanitation and King’s Sierra Leone Partnership developed a model for Ebola Holding Units (EHUs) at Government Hospitals in the capital city Freetown. The EHUs isolated screened or referred suspect patients, provided initial clinical care, undertook laboratory testing to confirm EVD status, referred onward positive cases to an Ebola Treatment Centre or negative cases to the general wards, and safely stored corpses pending collection by burial teams. Between 29th May 2014 and 19th January 2015, our five units had isolated approximately 37% (1159) of the 3097 confirmed cases within Western Urban and Rural district. Nosocomial transmission of EVD within the units appears lower than previously documented at other facilities and staff infection rates were also low. We found that EHUs are a flexible and effective model of rapid diagnosis, safe isolation and early initial treatment. We also demonstrated that it is possible for international partners and government facilities to collaborate closely during a humanitarian crisis.


title: MERS-CoV spillover at the camel-human interface

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here, we use existing MERS-CoV sequence data to explore its phylodynamics in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times, we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.


title: MBL-associated serine proteases (MASPs) and infectious diseases

text: Abstract The lectin pathway of the complement system has a pivotal role in the defense against infectious organisms. After binding of mannan-binding lectin (MBL), ficolins or collectin 11 to carbohydrates or acetylated residues on pathogen surfaces, dimers of MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2) activate a proteolytic cascade, which culminates in the formation of the membrane attack complex and pathogen lysis. Alternative splicing of the pre-mRNA encoding MASP-1 results in two other products, MASP-3 and MAp44, which regulate activation of the cascade. A similar mechanism allows the gene encoding MASP-2 to produce the truncated MAp19 protein. Polymorphisms in MASP1 and MASP2 genes are associated with protein serum levels and functional activity. Since the first report of a MASP deficiency in 2003, deficiencies in lectin pathway proteins have been associated with recurrent infections and several polymorphisms were associated with the susceptibility or protection to infectious diseases. In this review, we summarize the findings on the role of MASP polymorphisms and serum levels in bacterial, viral and protozoan infectious diseases.


title: B cell characterization and reactivity analysis in multiple sclerosis

text: Abstract B cells are one of the key players in the pathogenesis of multiple sclerosis (MS). The peripheral B cell distributions are similar in healthy persons and MS patients. In healthy controls, B cells are rarely present in the cerebrospinal fluid (CSF) while in MS patients, a clonally expanded B cell population is detected. This consists of memory B cells, centroblasts and antibody-secreting plasma blasts and plasma cells that are responsible for intrathecal immunoglobulin G production and oligoclonal band formation in more than 90% of MS patients. Unfortunately, the targets of the autoreactive B cells and antibodies remain largely unknown. Various candidate antigens have been identified but often their involvement in the disease process is still unclear. Most studies characterizing these target antigens examined autoantibodies by analyzing sera or CSF of MS patients. An alternative approach is focusing on the clonally expanded B cells. In this way B cells directed against myelin, astroglia and axons have been denoted in MS patients. B cell immortalization, that is based on the antibody-producing potential of Epstein–Barr virus (EBV) transformed B cells, can be used to expand B cells from MS patients for the production of antibodies, that ultimately can be analysed for target identification.


docid: iswxlbhb

title: Treatment of sleep apnea by ENT specialists during the COVID-19 pandemic

text: Abstract The treatment of sleep disorders has been strongly impacted by the COVID-19 pandemic. When the lockdown is over, resumption of usual patient care will require precautions to limit the risk of contamination for patients and caregivers. In this document, the French Association of Otorhinolaryngology and Sleep disorders (AFSORL) and the French Society of Otorhinolaryngology (SFORL) put forward a summary of the measures for continuing the treatment of sleep apnoea syndrome in these new practice conditions. Emphasis is placed on teleconsultation, methods of nocturnal sleep studies, the conditions for treatment by continuous positive airway pressure (CPAP) ventilation, and the postponement of more invasive treatments.


Nervous system damage after COVID-19 infection: presence or absence?