title: Applications of high-throughput genomics to antiviral research: evasion of antiviral responses and activation of inflammation during fulminant RNA virus infection

text: Host responses can contribute to the severity of viral infection, through the failure of innate antiviral mechanisms to recognize and restrict the pathogen, the development of intense systemic inflammation leading to circulatory failure or through tissue injury resulting from overly exuberant cell-mediated immune responses. High-throughput genomics methods are now being used to identify the biochemical pathways underlying ineffective or damaging host responses in a number of acute and chronic viral infections. This article reviews recent gene-expression studies of 1918 H1N1 influenza and Ebola hemorrhagic fever in cell culture and animal models, focusing on how genomics experiments can be used to increase our understanding of the mechanisms that permit those viruses to cause rapidly overwhelming infection. Particular attention is paid to how evasion of type I IFN responses in infected cells might contribute to over-activation of inflammatory responses. Reviewing recent research and describing how future studies might be tailored to understand the relationship between the infected cell and its environment, this article discusses how the rapidly growing field of high-throughput genomics can contribute to a more complete understanding of severe, acute viral infections and identify novel targets for therapeutic intervention.


title: Divergent coronaviruses detected in wild birds in Brazil, including a central park in São Paulo

text: Coronaviruses are single-stranded positive-sense RNA viruses associated with important avian diseases. Their relatively high rates of mutation and recombination frequencies allow them to adapt to new hosts and ecological niches. Although Brazil has 18% of global avian species diversity, studies regarding the presence of avian viral diseases in wild birds in South America are scarce. In this study, we performed a retrospective analysis of the presence of CoVs in 746 wild birds. Oropharyngeal and cloacal swabs were obtained and placed together in vials containing VTM transport medium collected in different regions of Brazil between 2006 and 2013. Screening for viral nucleic acid was performed using conventional RT-PCR and pancoronavirus nested PCR. Positive samples were characterized by partial sequencing of the RNA-dependent RNA polymerase (RdRp) gene, and ensuing phylogenetic analysis was performed to investigate the association between virus epidemiology and bird migration routes. Coronavirus RNA were detected and sequenced from six samples, in which three were related to gammacoronaviruses group and the other three to deltacoronavirus group. Our study documents the presence of CoVs related to avian gamma- and deltacoronaviruses circulating in both urban- and poultry-farm regions of Brazil, implicating wild birds as potential carriers of CoVs which may represent a risk to poultry farms and public health in Brazil. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42770-019-00065-7) contains supplementary material, which is available to authorized users.


title: Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner

text: [This corrects the article DOI: 10.1371/journal.ppat.1004502.].


title: COVID-19, digital privacy, and the social limits on data-focused public health responses

text: The implementation of digital contact tracing applications around the world to help reduce the spread of the COVID-19 pandemic represents one of the most ambitious uses of massive-scale citizen data ever attempted. There is major divergence among nations, however, between a “privacy-first” approach which protects citizens’ data at the cost of extremely limited access for public health authorities and researchers, and a “data-first” approach which stores large amounts of data which, while of immeasurable value to epidemiologists and other researchers, may significantly intrude upon citizens’ privacy. The lack of a consensus on privacy protection in the contact tracing process creates risks of non-compliance or deliberate obfuscation from citizens who fear revealing private aspects of their lives – a factor greatly exacerbated by recent major scandals over online privacy and the illicit use of citizens’ digital information, which have heightened public consciousness of these issues and created significant new challenges for any collection of large-scale public data. While digital contact tracing for COVID-19 remains in its infancy, the lack of consensus around best practices for its implementation and for reassuring citizens of the protection of their privacy may already have impeded its capacity to contribute to the pandemic response.


title: Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

text: During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2(1–5). Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC(50)s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.


title: Startups in times of crisis – A rapid response to the COVID-19 pandemic

text: Abstract Research summary The discovery of the coronavirus (SARS-CoV-2) and the spread of COVID-19 have led many governments to take drastic measures. The lockdown of large parts of society and economic life has come as an exogenous shock to many economic actors, not least innovative startups. This rapid response research combines a qualitative research design informed by entrepreneurial ecosystem actors with an analysis of policy measures called for, announced, and reportedly implemented in the international press. Interviews from an entrepreneurial ecosystem offer a first-hand account of the adversity startups face during a crisis and how by utilizing bricolage responses they cope, and the analysis of policy measures can serve as an inspiration to design support initiatives to protect startups from the consequences of the current lockdown and to alleviate the effects of future crises. Managerial summary The lockdown measures as a response to the spread of the new coronavirus threaten the existence of many innovative startups. Our rapid response research first illustrates the challenges entrepreneurs face as a consequence of the crisis. Second, we illustrate how entrepreneurs are dealing with the effects of the crisis and what they are doing to protect their ventures. Finally, we present measures that could be utilized by policymakers to assist entrepreneurs facing challenges. The research conducted suggests that while startups are successfully leveraging their available resources as a first response to the crisis, their growth and innovation potential are at risk. Therefore, policy measures should not only provide first aid to startups by alleviating the pressure caused by constrained cashflow, but also involve long-term measures embedded in and supported by the wider entrepreneurial ecosystem to ensure rapid recovery and growth.


title: Food security and Canada's agricultural system challenged by COVID‐19

text: The effect of COVID‐19 on Canadian food security is examined from two different perspectives. COVID‐19 creates a unique “income shock” that is expected to increase the prevalence of household food insecurity. This food insecurity can be measured by utilizing the Canadian Community Health Survey (CCHS). More fundamentally, COVID‐19 heightens household concern about the capacity of the Canadian food system to ensure food availability. Despite surges in demand and supply chain disruptions, we currently do not observe broad, rapid appreciation in food prices. This suggests that there is an adequate supply of food for the near term. There is less certainty over intermediate and longer time periods because so many factors are in flux, particularly the rate of increases in sicknesses and deaths across the country and globally. Data on these health factors and elements of the food supply chain are needed to predict beyond a short time frame. In this regard, we discuss three ongoing considerations—ease of capital flows, international exchange, and maintaining transportation—that will help ensure food availability in the longer run.


title: Pattern of patients and diseases during mass transit: The day of Arafat experience

text: BACKGROUND AND OBJECTIVE: Every year 2-3 million Muslims gather for a few days around the Holy city of Makkah in Saudi Arabia to perform Hajj. Managing enormous health issues associated with such a mass gathering requires a very vibrant health delivery plan. Related research is part of the strategy. This study was done to assess the pattern of patients and illnesses encountered at one health facility at Arafat on the 2nd day of Hajj, when all the pilgrims move from Mina and stay in Arafat for a few hours. The objective of the study was to provide input so that recommendations can be given for future improvement of health care during this mass transit. METHODS: All patients reporting sick to the Nimra Hospital on the Day of Arafat were included and documented on a detailed Performa and analyzed. RESULTS: We received 211 patients, essentially all of those were in need of acute medical intervention. Acute severe asthma and injuries were the major problems encountered. There were two deaths both related to heat stroke. Patients received were predominantly Arabic speaking. CONCLUSIONS: Only those needing acute intervention seek medical advice during transit. Well equipped and staffed health facilities are, however, needed to cater these and for any mass casualties. Pre Hajj training and mandatory Flu vaccination can help.


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title: Malaria Coinfections in Febrile Pediatric Inpatients: A Hospital-Based Study From Ghana

text: BACKGROUND: The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. METHODS: In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. RESULTS: From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. CONCLUSIONS: In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.


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title: Worldwide ACE (I/D) polymorphism may affect COVID-19 recovery rate: an ecological meta-regression

text: With the emergence of the Novel Coronavirus (2019-nCoV), researchers worldwide have started detecting the probable pathogenesis of the disease. The renin–angiotensin system (RAS) and angiotensin-converting enzymes have received a good deal of attention as possible pathways involved in 2019-nCoV pathogenesis. As the experiments seeking to find potential medications acting on these pathways are being conducted in the early phases, having an ecological worldview on the relationship between the prevalence of COVID-19 disease and the genetic differences in the genes involved in the RAS system could be valuable for the field. In this regard, we conducted a meta-analysis study of the prevalence of ACE (I/D) genotype in countries most affected by the COVID-19. In the meta-analysis, 48,758 healthy subjects from 30 different countries were evaluated in 116 studies, using the Comprehensive Meta-analysis software. The I/D allele frequency ratio was pooled by a random-effect model. The COVID-19 prevalence data of death and recovery rates were evaluated as the latitudes for the meta-regression analysis. Our results demonstrated that with the increase of the I/D allele frequency ratio, the recovery rate significantly increased (point estimate: 0.48, CI 95%: 0.05–0.91, p = 0.027). However, there was no significant difference in the case of death rate (point estimate: 1.74, CI 95%: 4.5–1.04, p = 0.22). This ecological perspective coupled with many limitations does not provide a direct clinical relevance between the COVID-19 and RAS system, but it shows potential pathophysiological associations. Our results raise concerns about ethnic and genetic differences that could affect the effectiveness of the currently investigated RAS-associated medications in different regions.


title: Generalized dermatitis associated with Malassezia overgrowth in cats: A report of six cases in France

text: We recently observed six cases of generalized dermatitis associated with Malassezia overgrowth in cats presented to the Veterinary College of Alfort, France. Elevated numbers of yeasts were observed in lesional skin by cytology and culture. Skin lesions occurred on the face, ventral neck, abdomen and ear canals and were characterized by some degree of alopecia, erythema and crusting. In most cases, pruritus was intense. The species M. pachydermatis was systematically isolated.


title: Pathobiological and Genomic Characterization of a Cold-Adapted Infectious Bronchitis Virus (BP-caKII)

text: We established a cold-adapted infectious bronchitis virus (BP-caKII) by passaging a field virus through specific pathogen-free embryonated eggs 20 times at 32 °C. We characterized its growth kinetics and pathogenicity in embryonated eggs, and its tropism and persistence in different tissues from chickens; then, we evaluated pathogenicity by using a new premature reproductive tract pathogenicity model. Furthermore, we determined the complete genomic sequence of BP-caKII to understand the genetic changes related to cold adaptation. According to our results, BP-caKII clustered with the KII genotype viruses K2 and KM91, and showed less pathogenicity than K2, a live attenuated vaccine strain. BP-caKII showed delayed viremia, resulting in its delayed dissemination to the kidneys and cecal tonsils compared to K2 and KM91, the latter of which is a pathogenic field strain. A comparative genomics study revealed similar nucleotide sequences between BP-caKII, K2 and KM91 but clearly showed different mutations among them. BP-caKII shared several mutations with K2 (nsp13, 14, 15 and 16) following embryo adaptation but acquired multiple additional mutations in nonstructural proteins (nsp3, 4 and 12), spike proteins and nucleocapsid proteins following cold adaptation. Thus, the establishment of BP-caKII and the identified mutations in this study may provide insight into the genetic background of embryo and cold adaptations, and the attenuation of coronaviruses.


title: Digital Surveillance: A Novel Approach to Monitoring the Illegal Wildlife Trade

text: A dearth of information obscures the true scale of the global illegal trade in wildlife. Herein, we introduce an automated web crawling surveillance system developed to monitor reports on illegally traded wildlife. A resource for enforcement officials as well as the general public, the freely available website, http://www.healthmap.org/wildlifetrade, provides a customizable visualization of worldwide reports on interceptions of illegally traded wildlife and wildlife products. From August 1, 2010 to July 31, 2011, publicly available English language illegal wildlife trade reports from official and unofficial sources were collected and categorized by location and species involved. During this interval, 858 illegal wildlife trade reports were collected from 89 countries. Countries with the highest number of reports included India (n = 146, 15.6%), the United States (n = 143, 15.3%), South Africa (n = 75, 8.0%), China (n = 41, 4.4%), and Vietnam (n = 37, 4.0%). Species reported as traded or poached included elephants (n = 107, 12.5%), rhinoceros (n = 103, 12.0%), tigers (n = 68, 7.9%), leopards (n = 54, 6.3%), and pangolins (n = 45, 5.2%). The use of unofficial data sources, such as online news sites and social networks, to collect information on international wildlife trade augments traditional approaches drawing on official reporting and presents a novel source of intelligence with which to monitor and collect news in support of enforcement against this threat to wildlife conservation worldwide.


Recombinant feline parvovirus infection of immunized tigers in central China


Thrombocytopenia in pregnant patients with mild COVID-19


title: Axonal neuropathy with unusual clinical course in young Snowshoe cats

text: Neuropathies in cats are mostly acquired. In comparison to the dog, only very few inherited forms have been described. This case report describes the clinical and diagnostic findings of a suspected inherited feline axonal neuropathy with a very unique clinical course. Two young related male Snowshoe cats were presented with an initially progressive history of recurrent pelvic limb weakness. Electrodiagnostic investigations suggested an axonopathy and muscle–nerve biopsies confirmed axonal degeneration. Over the following 2 years both cats stabilised without any specific treatment, and repeat electrodiagnostic investigations and muscle biopsy in one cat confirmed the tendency for remission.


title: Efficacy of Zinc Against Common Cold Viruses: An Overview

text: ABSTRACT Objective To review the laboratory and clinical evidence of the medicinal value of zinc for the treatment of the common cold. Data Sources Published articles identified through Medline (1980–2003) using the search terms zinc, rhinovirus, and other pertinent subject headings. Additional sources were identified from the bibliographies of the retrieved articles. Study Selection By the author. Data Extraction By the author. Data Synthesis Human rhinoviruses, by attaching to the nasal epithelium via the intracellular adhesion molecule-1 (ICAM-1) receptor, cause most colds. Ionic zinc, based on its electrical charge, also has an affinity for ICAM-1 receptor sites and may exert an antiviral effect by attaching to the ICAM-1 receptors in the rhinovirus structure and nasal epithelial cells. Clinical tests of zinc for treatment of common colds have been inconsistent, primarily because of study design, blinding, and lozenge contents. Early formulations of lozenges also were unpalatable. In three trials with similar study designs, methodologies, and efficacy assessments, zinc effectively and significantly shortened the duration of the common cold when it was administered within 24 hours of the onset of symptoms. Recent reports of trials with zinc gluconate administered as a nasal gel have supported these findings; in addition, they have shown that treatment with zinc nasal gel is effective in reducing the duration and severity of common cold symptoms in patients with established illness. Conclusion Clinical trial data support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms. Additional clinical and laboratory evaluations are warranted to further define the role of ionic zinc for the prevention and treatment of the common cold and to elucidate the biochemical mechanisms through which zinc exerts its symptom-relieving effects.


title: COVID-19 scenario modelling for the mitigation of capacity-dependent deaths in intensive care

text: Managing healthcare demand and capacity is especially difficult in the context of the COVID-19 pandemic, where limited intensive care resources can be overwhelmed by a large number of cases requiring admission in a short space of time. If patients are unable to access this specialist resource, then death is a likely outcome. In appreciating these ‘capacity-dependent’ deaths, this paper reports on the clinically-led development of a stochastic discrete event simulation model designed to capture the key dynamics of the intensive care admissions process for COVID-19 patients. With application to a large public hospital in England during an early stage of the pandemic, the purpose of this study was to estimate the extent to which such capacity-dependent deaths can be mitigated through demand-side initiatives involving non-pharmaceutical interventions and supply-side measures to increase surge capacity. Based on information available at the time, results suggest that total capacity-dependent deaths can be reduced by 75% through a combination of increasing capacity from 45 to 100 beds, reducing length of stay by 25%, and flattening the peak demand to 26 admissions per day. Accounting for the additional ‘capacity-independent’ deaths, which occur even when appropriate care is available within the intensive care setting, yields an aggregate reduction in total deaths of 30%. The modelling tool, which is freely available and open source, has since been used to support COVID-19 response planning at a number of healthcare systems within the UK National Health Service. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10729-020-09511-7) contains supplementary material, which is available to authorized users.


title: Modulation of cell proteome by 25-hydroxycholesterol and 27-hydroxycholesterol: A link between cholesterol metabolism and antiviral defense

text: Abstract Physiological cholesterol metabolism implies the generation of a series of oxidized derivatives, whose oxysterols are by far the most investigated ones for their potential multifaceted involvement in human pathophysiology. In this regard, noteworthy is the broad antiviral activity displayed by defined side chain oxysterols, in particular 25-hydroxycholesterol (25HC) and 27-hydroxycholesterol (27HC). Although their antiviral mechanism(s) may vary depending on virus/host interaction, these oxysterols share the common feature to hamper viral replication by interacting with cellular proteins. Here reported is the first analysis of the modulation of a cell proteome by these two oxysterols, that, besides yielding additional clues about their potential involvement in the regulation of sterol metabolism, provides novelinsights about the mechanism underlying the inhibition of virus entry and trafficking within infected cells. We show here that both 25HC and 27HC can down-regulate the junction adhesion molecule-A (JAM-A) and the cation independent isoform of mannose-6-phosphate receptor (MPRci), two crucial molecules for the replication of all those viruses that exploit adhesion molecules and the endosomal pathway to enter and diffuse within target cells.


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title: Factors associated with time to neonatal diarrhoea in French beef calves

text: Abstract A prospective study was carried out on 92 randomly selected beef herds in the Midi-Pyrénées region in France. The objective was to determine factors associated with time to neonatal gastroenteritis. By taking into account the “intra-herd” correlation in failure time (in the semiparametric Cox model), we identified 12 management risk factors associated with hazard of diarrhoea. Some previously have been identified, but “new” risk factors were feeding of corn silage and the incidence of diarrhoea in the last season. We used the two main approaches which are often reviewed: marginal and frailty Cox models. Our results show that these two models give different parameter estimates, so the choice of the model remains crucial.


title: Humoral Immunodeficiencies: Conferred Risk of Infections and Benefits of Immunoglobulin Replacement Therapy

text: Primary immune deficiency diseases (PIDDs) result from genetic defects of the immune system that increase patients’ susceptibility to infections. The types of infections that occur in PIDD patients are largely dictated by the nature of the immune deficiency, which can be defined by dysfunction of cellular or humoral defenses. An increasing number of PIDDs, including those with both cellular and humoral defects, have antibody deficiency as a major feature and can benefit from immunoglobulin replacement therapy as a result. In fact, the most common PIDDs worldwide are antibody deficiencies and include common variable immunodeficiency, congenital agammaglobulinemia, hyper IgM syndrome, specific antibody deficiency, and Good syndrome. While immunoglobulin replacement therapy is the cornerstone of treatment for the majority of these conditions, a thorough understanding of the specific infections for which these patients are at increased risk can hasten diagnosis and guide additional therapies. Moreover, the infection trends in some PIDD patients with profound defects of cellular immunity, such as autosomal dominant hyper IgE syndrome (Job’s/Buckley’s Syndrome) or dedicator of cytokinesis 8 (DOCK8) deficiency, suggest that select patients might benefit from immunoglobulin replacement therapy even if their immune deficiency is not limited to antibody defects. In this review, we provide an overview of the predisposition to infections seen in PIDDs that may benefit from immunoglobulin replacement therapy.


title: Expression and membrane integration of SARS-CoV E protein and its interaction with M protein

text: The severe acute respiratory syndrome (SARS)-CoV E gene fragment was cloned and expressed as a recombinant protein fused with a myc tag at the N-terminus in vitro and in Vero E6 cells. Similar to other N-glycosylated proteins, the glycosylation of SARS-CoV E protein occurred co-translationally in the presence of microsomes. The SARS-CoV E protein is predicted to be a double-spanning membrane protein lacking a conventional signal peptide. Both of the transmembrane regions (a.a. 11–33 and 37–59) are predicted to be α-helices, which penetrate into membranes by themselves. As expected, these two transmembrane regions inserted a cytoplasmic protein into the endoplasmic reticulum membrane. Either of these two transmembrane domains co-localized with M protein. Both the transmembrane domains of E protein are required to interact with M protein, while either of the hydrophilic regions (a.a. 1–10 or 60–76) is dispensable as shown by co-immunoprecipitation assay. These results are important for the study of SARS-CoV assembly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-009-0341-6) contains supplementary material, which is available to authorized users.


title: Hygiene: new hopes, new horizons

text: Summary Although promotion of safe hygiene is the single most cost-effective means of preventing infectious disease, investment in hygiene is low both in the health and in the water and sanitation sectors. Evidence shows the benefit of improved hygiene, especially for improved handwashing and safe stool disposal. A growing understanding of what drives hygiene behaviour and creative partnerships are providing fresh approaches to change behaviour. However, some important gaps in our knowledge exist. For example, almost no trials of the effectiveness of interventions to improve food hygiene in developing countries are available. We also need to figure out how best to make safe hygiene practices matters of daily routine that are sustained by social norms on a mass scale. Full and active involvement of the health sector in getting safe hygiene to all homes, schools, and institutions will bring major gains to public health.


title: One-step real-time RT-PCR for pandemic influenza A virus (H1N1) 2009 matrix gene detection in swine samples

text: Abstract In the spring of 2009, a novel (H1N1) influenza A virus began to spread among humans worldwide. Although the 2009 H1N1 is related genetically to swine influenza viruses, human infection has not been connected to pig exposure. Because the virus is now circulating widely in the human population, swine herds are at increased risk of becoming infected. In order to investigate potential outbreaks of the 2009 pandemic virus in pigs, a quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) for the detection of the (H1N1) 2009 RNA in clinical specimens was developed. To evaluate the applicability of the test as a diagnostic tool in the screening of field specimens from swine, 64 field isolates of North American swine, 5 equine and 48 avian influenza viruses collected during diagnostic investigations were analyzed retrospectively as well as samples collected during an experimental in vivo infection with two novel H1N1 isolates, A/California/04/2009 (H1N1)v virus and A/Mexico/4108/2009 (H1N1)v. The sensitivity of the qRT-PCR was shown to be higher with respect to standard techniques such as virus isolation and the reproducibility was satisfactory. The present unique and highly sensitive assay is able to detect as little as 1×101 copies of RNA per μl of template and it represents a rapid and useful approach for the screening and quantitation of (H1N1) 2009 RNA in porcine specimens.


title: Virus y vasculitis sistémicas

text: En la patogenia de las enfermedades autoinmunes sistémicas, incluyendo las vasculitis, siempre se ha invocado la participación de factores genéticos y factores ambientales. Entre los ambientales, las infecciones, fundamentalmente de naturaleza vírica, han sido siempre un foco de atención, máxime tras el descubrimiento de la estrecha relación existente entre la poliarteritis nudosa y el virus de la hepatitis B, por una parte, y la crioglobulinemia mixta esencial y el virus de la hepatitis C, por otra. La presente revisión pretende actualizar los conocimientos recogidos en la literatura más reciente sobre el binomio virus y vasculitis sistémicas, siguiendo la clasificación de vasculitis de Chapel-Hill. The participation of genetic and environmental factors has always been invoked in the pathogenesis of the autoimmune systemic diseases, including the primary vasculitides. Among the environmental factors, infections, fundamentally those having a viral nature, have always been focused on, especially after the discovery of the close existing relationship between the polyarteritis nodosa and the hepatitis B virus, on the one hand, and mixed cryoglobulinemia and the hepatitis C virus, on the other. The present review summarizes data from the most recent literature related to associations between virus infections and primary vasculitides, following the Chapel-Hill vasculitis classification.


title: Clinical trials for Covid‐19: can we better use the short window of opportunity?

text: The scientific community has risen to the Covid‐19 challenge, coming up with an impressive list of candidate drugs and vaccines targeting an array of pharmacological and immunological mechanisms. Yet, generating clinical evidence of efficacy and safety of these candidate treatments may be frustrated by the absence of comprehensive trial coordination mechanisms. Many small stand‐alone trials and observational studies of single‐agent interventions are currently running or in planning; many of these will likely not deliver robust results that could support regulatory and patient‐level treatment decisions. We here discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision‐relevant clinical trials.


title: Prognostication in severe acute respiratory syndrome: A retrospective time‐course analysis of 1312 laboratory‐confirmed patients in Hong Kong

text: Background and objective: The temporal importance of prognostic indicators for severe acute respiratory syndrome (SARS) has not been studied. This study identified the various clinical prognostic factors for SARS and described the temporal evolution of these factors in the course of the SARS illness in Hong Kong in 2003. Methods: A retrospective analysis of the entire Hong Kong cohort of 1312 laboratory‐confirmed SARS patients aged 15–74 years was undertaken. Demographic, clinical and laboratory data at presentation and investigative data during the first 10 days of illness from the time of symptom onset were compiled. Two adverse outcomes were examined: hospital mortality and the development of oxygenation failure based on the estimated PaO(2)/FiO(2) ratio of <200 mm Hg. Logistic regression was used to identify the association between these prognostic factors and outcomes. Results: Based on adjusted odds ratios with a P‐value of <0.05, older age, male gender, elevated pulse rate and elevated neutrophil count were all predictive of oxygenation failure and death during the 10‐day illness. Raised serum albumin and creatinine phosphokinase (CPK) levels were predictive of hospital mortality during this period. The presenting ALT and CPK level and the day 7 and day 10 platelet counts were predictive of oxygenation failure while the day 7 LDH was predictive of death. Contact exposure outside health‐care institutions also appeared to carry higher risk of death. Conclusion: This large‐scale analysis identified important discriminatory parameters related to the patients’ demographic profile (age and gender), severity of illness (pulse rate and neutrophil count), and multisystem derangement (platelet count, CPK, ALT and LDH), all of which prognosticated adverse outcomes during the SARS episode. While age, pulse rate and neutrophil count consistently remained significant prognosticators during the first 10 days of illness, the prognostic impact of other derangements was more time‐course dependent. Clinicians should be aware of the time‐course evolution of these prognosticators.


title: Viruses That Cross Borders: Factors Responsible for Global Dissemination of Viral Infections

text: OBJECTIVE: Pandemic viral infections as emerging infectious diseases are of a great global concern. However, for some viruses, particular strains are endemic to specific areas and can be genetically distinguished from strains in other regions. In contrast, for some other viruses, genetically similar strains can spread and circulate all over the world. This study addresses global dissemination of various viral infections. METHODS: We classified 34 viruses as per their ability to cross borders by review. We also described factors responsible for and the dynamics of global dissemination. We examined biological characteristics of viruses, manners or routes of transmission, host responses and epidemiological factors. RESULTS: Factors required for viruses to cross borders include ‘non-blood infection’, ‘short incubation period’, ‘short infectious period’, ’frequent re-infection’, ‘small basic reproductive number (R(0))’ and ‘high annual incidence’. CONCLUSION: Knowing the factors responsible for global dissemination of pathogens is useful for controlling and/or containing both classic and emerging infectious diseases.


title: Pneumonia—Overview

text: Pneumonia is very common and continues to exact a high burden on health. The Global Burden of Disease Study 2015 found lower respiratory infections (LRIs) were the leading infectious cause of death and the fifth leading cause of death overall. Pneumococcal pneumonia caused 55% of LRI deaths in all ages (1.5 million deaths). Novel pathogens, particularly viruses, continue to emerge as causes of pneumonia. The rise of drug-resistance among common respiratory pathogens is a further challenge. Pneumonia is commonly classified according to patient location at the time of infection, leading to the categories of community-acquired, hospital-acquired and ventilator-acquired pneumonia.


title: Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines

text: Summary Background In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people. 1,2 The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. Methods We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. Findings A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. Interpretation The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.


title: Interpatient mutational spectrum of human coronavirus‐OC43 revealed by illumina sequencing

text: Human coronaviruses (HCoV) are RNA viruses that cause respiratory tract infections with viral replication of limited duration. The host and viral population heterogeneity could influence clinical phenotypes. Employing long RT‐PCR with Illumina sequencing, we quantified the gene mutation load at 0.5% mutation frequency for the 4529 bp‐domain spanning the Spike gene (4086 bp) of HCoV‐OC43 in four upper respiratory clinical specimens obtained during acute illness. There were a total of 121 mutations for all four HCoV samples with the average number of mutations at 30.3 ± 10.2, which is significantly higher than that expected from the Illumina sequencing error rate. There were two mutation peaks, one at the 5′ end and the other near position 1 550 in the S1 subunit. Two coronavirus samples were genotype B and two were genotype D, clustering with HCoV‐OC43 strain AY391777 in neighbor‐joining tree phylogenetic analysis. Nonsynonymous mutations were 76.1 ± 14% of mutation load. Although lower than other RNA viruses such as hepatitis C virus, HCoV‐OC43 did exhibit quasi‐species. The rate of nonsynonymous mutations was higher in the HCoV‐OC43 isolates than in hepatitis C (HCV) virus genotype 1a isolates analyzed for comparison in this study. These characteristics of HCoV‐OC43 may affect viral replication dynamics, receptor binding, antigenicity, evolution, transmission, and clinical illness.


title: Development of a real time reverse transcription loop-mediated isothermal amplification method (RT-LAMP) for detection of a novel swine acute diarrhea syndrome coronavirus (SADS-CoV)

text: Abstract A novel swine acute diarrhea syndrome Coronavirus (SADS-CoV) that causes severe diarrhea in suckling piglets was identified in southern China in 2017. A simple and rapid detection test was developed for this virus using real-time RT-LAMP based on the conserved N gene of the virus. The method had a detection limit of 1.0 × 101 copies/μL with no cross-reactions with classical swine fever virus, porcine and respiratory syndrome virus NA, porcine and respiratory syndrome virus EU, transmissible gastroenteritis coronavirus, foot and mouth disease virus, porcine epidemic diarrhea virus (S-INDEL and non-S-INDEL), swine influenza virus subtype H1N1, porcine circovirus type 2, seneca valley virus, porcine parvovirus, porcine deltacoronavirus and rotavirus. This method was also reproducible. Twenty of 24 clinical samples were identified as SADS-CoV RNA-positive by the real-time RT-LAMP and the results were consistent with that of the real time RT-PCR method. This new method for detecting SADS-CoV is specific and sensitive for the detection of SADS-CoV.


title: Brief Report: Increased Addictive Internet and Substance Use Behavior During the COVID‐19 Pandemic in China

text: BACKGROUND AND OBJECTIVES: The COVID‐19 pandemic and control measures may have increased the risk of abusing addictive substances as well as addictive behaviors. METHODS: We present an initial online survey in 6416 Chinese about the relation between the COVID‐19 pandemic and addictive behavior in China. RESULTS: During the COVID‐19 pandemic, 46.8% of the subjects reported increased dependence on internet use, and 16.6% had longer hours of internet use. The prevalence (4.3%) of severe internet dependence rose up to 23% than that (3.5%) before the COVID‐19 pandemic occurred, and their dependence degree rose 20 times more often than being declined (60% vs 3%). Relapses to abuse from alcohol and smoking abstinence were relatively common at 19% and 25%, respectively. Similarly, 32% of regular alcohol drinkers and 20% of regular smokers increased their usage amount during the pandemic. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These three coping behaviors (internet, alcohol, and smoking) during this COVID‐19‐related crisis appear to have increased the risk for substance use disorders and internet addiction. (Am J Addict 2020;00:00–00)


The New Challenge of Geriatrics: Saving Frail Older People from the SARS-CoV-2 Pandemic Infection


docid: lxqcvqca

title: Sars, preschool routines and children’s behaviour: Observations from preschools in Hong Kong

text: All schools in Hong Kong were closed in April 2003 to prevent the spread of SARS. This paper considers the influence of the SARS epidemic on children’s routines and behaviour when preschools re-opened, after a six-week closure. Observations were made in 20 kindergartens and principals of another 10 kindergartens completed questionnaires. The influence of SARS was evident in all preschools, be it through teachers and students wearing masks, notices on hand washing or the provision of alcohol dispensers for hand disinfection. The outbreak impacted noticeably upon children’s routines and social exchanges. In all schools, physical contact among children and sharing of food were not allowed. Children were also prohibited from talking to their peers when they had removed their masks. The SARS outbreak provided us a “natural experiment” to consider the influence of epidemics on preschools.


title: On the origin of genomes and cells within inorganic compartments

text: Building on the model of Russell and Hall for the emergence of life at a warm submarine hydrothermal vent, we suggest that, within a hydrothermally formed system of contiguous iron-sulfide (FeS) compartments, populations of virus-like RNA molecules, which eventually encoded one or a few proteins each, became the agents of both variation and selection. The initial darwinian selection was for molecular self-replication. Combinatorial sorting of genetic elements among compartments would have resulted in preferred proliferation and selection of increasingly complex molecular ensembles – those compartment contents that achieved replication advantages. The last universal common ancestor (LUCA) we propose was not free-living but an inorganically housed assemblage of expressed and replicable genetic elements. The evolution of the enzymatic systems for (i) DNA replication; and (ii) membrane and cell wall biosynthesis, enabled independent escape of the first archaebacterial and eubacterial cells from their hydrothermal hatchery, within which the LUCA itself remained confined.


title: Newly Identified Enterovirus C Genotypes, Identified in the Netherlands through Routine Sequencing of All Enteroviruses Detected in Clinical Materials from 2008 to 2015

text: Enteroviruses (EVs) are a group of human and animal viruses that are capable of causing a variety of clinical syndromes. Different genotypes classified into species can be distinguished on the basis of sequence divergence in the VP1 capsid-coding region. Apparently new genotypes are discovered regularly, often as incidental findings in studies investigating respiratory syndromes or as part of poliovirus surveillance. Recently, some EVs have become recognized as significant respiratory pathogens, and a number of new genotypes belonging to species C have been identified. The circulation of these newly identified species C EVs, such as EV-C104, EV-C105, EV-C109, and EV-C117, nevertheless appears to be limited. In this report, we show the results of routine genotyping of all enteroviruses detected in our tertiary care hospital between January 2008 and April 2015. We detected 365 EVs belonging to 40 genotypes. Interestingly, several newly identified species C EVs were detected during the study period. Sequencing of the 5′ untranslated region (5′ UTR) of these viruses shows divergence in this region, which is a target region in many detection assays.


title: Deciphering the biology of porcine epidemic diarrhea virus in the era of reverse genetics

text: Abstract Emergence of the porcine epidemic diarrhea virus (PEDV) as a global threat to the swine industry underlies the urgent need for deeper understanding of this virus. To date, we have yet to identify functions for all the major gene products, much less grasp their implications for the viral life cycle and pathogenic mechanisms. A major reason is the lack of genetic tools for studying PEDV. In this review, we discuss the reverse genetics approaches that have been successfully used to engineer infectious clones of PEDV as well as other potential and complementary methods that have yet to be applied to PEDV. The importance of proper cell culture for successful PEDV propagation and maintenance of disease phenotype are addressed in our survey of permissive cell lines. We also highlight areas of particular relevance to PEDV pathogenesis and disease that have benefited from reverse genetics studies and pressing questions that await resolution by such studies. In particular, we examine the spike protein as a determinant of viral tropism, entry and virulence, ORF3 and its association with cell culture adaptation, and the nucleocapsid protein and its potential role in modulating PEDV pathogenicity. Finally, we conclude with an exploration of how reverse genetics can help mitigate the global impact of PEDV by addressing the challenges of vaccine development.


title: Consecutive false‐negative rRT‐PCR test results for SARS‐CoV‐2 in patients after clinical recovery from COVID‐19

text: This study reviewed the serial rRT‐PCR results of 37 patients admitted to our hospital in Wuhan, China, who had three or more sequential negative results prior to discharge. Of these 37 patients, 14 (~38%) had a positive rRT‐PCR result after a negative result during convalescence, and 5 (~14%) had a positive rRT‐PCR result after two consecutive negative results during convalescence. These results suggest that it may be necessary to require that patients have three consecutive negative results prior to discharge, to ensure that they do not spread infection among members of their household, or in the community. We believe that our study makes a significant contribution to the literature because it is not currently the standard of care to require patients to have three consecutive negative results prior to discharge. Our results suggest that a relatively high proportion of patients may continue to shed SARS‐CoV‐2 after they have clinically recovered, and thus may transmit the infection to others. This article is protected by copyright. All rights reserved.


title: Travel-Related Typhoid Fever: Narrative Review of the Scientific Literature

text: Enteric fever is a foodborne infectious disease caused by Salmonella enterica serotypes Typhi and Paratyphi A, B and C. The high incidence in low income countries can increase the risk of disease in travelers coming from high income countries. Pre-travel health advice on hygiene and sanitation practices and vaccines can significantly reduce the risk of acquiring infections. Although the majority of the cases are self-limiting, life-threatening complications can occur. Delayed diagnosis and cases of infections caused by multi-drug resistant strains can complicate the clinical management and affect the prognosis. More international efforts are needed to reduce the burden of disease in low income countries, indirectly reducing the risk of travelers in endemic settings. Surveillance activities can help monitor the epidemiology of cases caused by drug-susceptible and resistant strains.


title: The mental health of frontline and non-frontline medical workers during the coronavirus disease 2019 (COVID-19) outbreak in China: a case-control study

text: BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a new infectious disease with high transmissibility and morbidity. It has caused substantial mental distress to medical professionals. We aimed to compare the psychological impact of the COVID-19 outbreak between frontline and non-frontline medical workers in China. METHODS: This case-control study recruited 1173 frontline and 1173 age- and sex-matched non-frontline medical workers during the COVID-19 outbreak (February 11 to 26, 2020). A set of online questionnaires were used to measure mental problems (i.e., anxiety, insomnia, and depressive symptoms), and help-seeking behavior and treatment for these mental problems. RESULTS: Frontline medical workers had higher rates of any mental problem (52.6% vs 34.0%, adjusted OR=1.88, 95% CI=1.57-2.25), anxiety symptoms (15.7% vs 7.4%, adjusted OR=1.95, 95% CI=1.46-2.61), depressed mood (marginally insignificant; 14.3% vs 10.1%, adjusted OR=1.32, 95% CI=0.99-1.76) and insomnia (47.8% vs 29.1%, adjusted OR=1.96, 95% CI=1.63-2.36) than non-frontline medical workers. No significant difference was observed in terms of suicidal ideation (12.0% vs 9.0%, adjusted OR=1.25, 95% CI=0.92-1.71), help-seeking (4.5% vs 4.5%, adjusted OR=1.00, 95% CI=0.53-1.87) or treatment (3.4% vs 2.3%, adjusted OR=1.38, 95% CI=0.54-3.52) for mental problems. LIMITATIONS: The case-control nature of the data precludes causal inferences, and there is a possibility of bias related to self-reports. CONCLUSIONS: Frontline medical workers had more mental problems but comparable help-seeking behaviors and treatment for these problems than non-frontline medical workers. These findings highlight the timely mental support and intervention for medical workers, especially for those on the frontline.


First description of SARS-CoV-2 in ascites


title: Identification of group B rotavirus as an etiological agent in the gastroenteritis outbreak in Maharashtra, India

text: Acute gastroenteritis outbreak occurred at Pargaon, Maharashtra, India in 1789 cases with an attack rate of 32.5% between November to December 2015. The stool specimens (n = 32) were investigated for different enteric viral agents using conventional methods. Transmission electron microscopy and RNA polyacrylamide gel electrophoresis respectively identified morphologically distinct rotavirus particles in 28% and RNA migration pattern of Group B Rotavirus (GBR) in 72% of the specimens. Reverse transcription polymerase chain reaction and nucleotide sequencing confirmed presence of GBR in 97% of the samples analyzed. The predominance of GBR infections and absence or insignificant presence of other agents confirmed GBR as an etiological agent of the gastroenteritis outbreak occurred in Maharashtra, India.


title: Eating disorders in the age of COVID-19

text: • COVID-19 pandemic-induced psychosocial stressors and stay-at-home orders may exacerbate eating disorder-related triggers. • Appropriate management of eating disorders is crucial to help mitigate long-term impacts such as increased risk of suicide.


title: Oxidative stress indices in gastroenteritis in dogs with canine parvoviral infection

text: Abstract Gastroenteritis of viral origin has emerged as a major cause of morbidity and mortality in dogs during the last two decades. Amongst the viral etiologies responsible for gastroenteritis in dogs, canine parvovirus (CPV) is considered as the most pathogenic. The disease is characterized by hemorrhagic enteritis, bloody diarrhoea and myocarditis in young pups. The present study was carried out to examine alterations in oxidative stress indices in the erythrocytes from dogs suffering from gastroenteritis with or without canine parvoviral infection as confirmed by CPV-DNA amplification from faeces using specific primers for CPV-2 as well as CPV-2a and CPV-2b variants by polymerase chain reaction (PCR). The present investigation utilized clinical cases of dogs with signs of acute diarrhea (n =56), and 14 more apparently healthy dogs of similar age group. Erythrocytic oxidative stress indices such as lipid peroxides level and antioxidant enzymes like superoxide dismutase and catalase activity, and blood micro-mineral (iron, copper, cobalt and zinc) status were analyzed in each dog (n =70). The acute cases of gastroenteritis in dogs were associated with altered erythrocytic lipid peroxidation as evident by estimation of malonaldehyde (MDA) concentration. The activities of antioxidant enzymes catalase and superoxide dismutase, the first line of antioxidant defense against damaging effects of free radicals, were also altered. The alterations in oxidative stress indices were more pronounced in cases with involvement of canine parvovirus as compared to parvo-negative cases. Our results also revealed decreased blood zinc level in diarrhoea in dogs irrespective of involvement of canine parvovirus.


title: Association of US Households’ Disaster Preparedness With Socioeconomic Characteristics, Composition, and Region

text: IMPORTANCE: Since the terrorist attacks on September 11, 2001, the US government has promoted household disaster preparedness, but preparedness remains low. OBJECTIVE: To identify disparities in disaster preparedness among US households. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from a nationally representative sample of US households from the 2017 American Housing Survey’s topical section on preparedness to assess associations of disaster preparedness with households’ socioeconomic characteristics, composition, and region. Logistic regressions were used to assess associations of household characteristics with overall preparedness, resource- and action-based preparedness, and specific preparedness items. Data analyses were completed on March 27, 2020. EXPOSURES: Combined household income, head of household’s education level, race/ethnicity, marital status of head of household, head of household aged 65 years or older, presence of children or a household member with a disability, and region. MAIN OUTCOMES AND MEASURES: Nine actionable preparedness items, such as having an emergency carry-on kit (resource), food and water stockpiles (resource), and alternative communication plans and meeting locations (action). Items were summed for the measures of overall, resource-based, and action-based preparedness, with preparedness defined as meeting at least half of the criteria. RESULTS: Among 16 725 included households, 9103 household heads were men (54.4%), 11 687 were married (69.9%), and 10 749 (66.1%) had some college education or higher. In all, 1969 household heads (11.8%) were black, while 2696 were Hispanic/Latino (16.1%); 3579 household heads (21.4%) were 65 years or older. A total of 7163 households (42.8%) included children, and 3533 households (21.2%) included a person with a disability. Households were more likely to fulfill at least half of the criteria for resource-based preparedness (10 950 households [65.5%]) than for action-based preparedness (6876 households [41.1%]). Wealthy households and those with household heads aged 65 years or older were more likely to fulfill at least half of resource-based items (wealthy households: adjusted odds ratio [aOR] by logged income, 1.18 [95% CI, 1.13-1.22]; household heads age ≥65 years: aOR, 1.42 [95% CI, 1.29-1.55) but less likely to fulfill action-based items (wealthy households: aOR: 0.96 [95% CI, 0.93-0.99]; household heads age ≥65 years: aOR, 0.92 [95% CI, 0.84-0.99]). Households with black household heads were more likely to fulfill items directly related to emergencies (carry-on emergency kit: aOR, 1.26 [95% CI, 1.14-1.39]; alternative communication plan: aOR, 1.55 [95% CI, 1.39-1.72]; alternative meeting location: aOR, 1.18 [95% CI, 1.07-1.31]) but less likely to fulfill resource-based items (at least half of resource items: aOR, 0.89 [95% CI, 0.80-0.99]). CONCLUSIONS AND RELEVANCE: These findings suggest that types of preparedness vary by household characteristics. Targeted strategies are needed to promote preparedness across communities.


title: Infection in acute exacerbations of chronic bronchitis: a clinical perspective

text: Abstract Acute exacerbations of chronic bronchitis (AECB) is an important cause of death and morbidity in developed countries and also has significant economic impact. The disease is characterized by increased dyspnoea, sputum volume and sputum purulence; the most commonly associated pathogens are Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. H. influenzae and S. pneumoniae express virulence determinants that directly and indirectly impair mucociliary clearance and incite other consequences that are permissive to microbial persistence. Regarding the use of antibiotics, there is currently a lack of large-scale clinical trials that are sufficiently powerful to provide good evidence-based information. Nonetheless, antimicrobial chemotherapy has repeatedly been shown to confer benefit in patients with moderately severe features of AECB. Simple clinical criteria can be used to identify patients in whom there is a higher likelihood of treatment failure or mortality during AECB. These include significant cardiopulmonary co-morbidity, frequent exacerbations, advanced decline in lung function, malnutrition or other generalized debility, advanced age (> 70 years) and concurrent treatment with corticosteroids. In such patients, an aggressive antimicrobial approach to AECB may be warranted in order to prevent clinical failure or representation. From a clinical perspective, appropriate drugs include those that are stable to β-lactamases, are bactericidal against causative pathogens, penetrate diseased lung tissue in high concentrations and have a good safety profile.


title: Infection control in non‐clinical areas during the COVID‐19 pandemic

text: Large numbers of healthcare workers have acquired coronavirus disease (COVID-19) in the workplace [1]. SARS-CoV-2 is easily transmissible as each person with COVID-19 infects approximately 2.2 close contacts, and asymptomatic transmission has been reported [2,3]. SARS-CoV-2 survives in aerosols and on surfaces from hours to days, respectively [4]. Therefore, we believe non-clinical areas are potentially high-risk for transmission between healthcare workers, and often neglected by infection prevention and control protocols. To alert others to this risk and how it may be reduced, we describe our non-clinical workplace infection prevention and control measures that have been modified from those originally developed during the 2003 severe acute respiratory syndrome epidemic [5].


Coronavirus (COVID-19) infection–induced chilblains: A case report with histopathologic findings


Chloroquine-induced torsade de pointes in a COVID-19 patient


title: Detection of Plant DNA in the Bronchoalveolar Lavage of Patients with Ventilator-Associated Pneumonia

text: BACKGROUND: Hospital-acquired infections such as nosocomial pneumonia are a serious cause of mortality for hospitalized patients, especially for those admitted to intensive care units (ICUs). Despite the number of the studies reported to date, the causative agents of pneumonia are not completely known. Herein, we found by molecular technique that vegetable and tobacco DNA may be detected in the bronchoalveolar lavage from patients with ventilator-associated pneumonia (VAP). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we studied bronchoalveolar lavage (BAL) from patients admitted to ICUs with ventilator-associated pneumonia. BAL fluids were assessed with molecular tests, culture and blood culture. We successfully identified plant DNA in six patients out of 106 (6%) with ventilator-associated pneumonia. Inhalation was confirmed in four cases and suspected in the other two cases. Inhalation was significantly frequent in patients with plant DNA (four out of six patients) than those without plant DNA (three out of 100 patients) (P<0.001). Nicotiana tabacum chloroplast DNA was identified in three patients who were smokers (cases 2, 3 and 6). Cucurbita pepo, Morus bombycis and Triticum aestivum DNA were identified in cases 1, 4 and 5 respectively. Twenty-three different bacterial species, two viruses and five fungal species were identified from among these six patients by using molecular and culture techniques. Several of the pathogenic microorganisms identified are reported to be food-borne or tobacco plant-associated pathogens. CONCLUSIONS/SIGNIFICANCE: Our study shows that plants DNA may be identified in the BAL fluid of pneumonia patients, especially when exploring aspiration pneumonia, but the significance of the presence of plant DNA and its role in the pathogenesis of pneumonia is unknown and remains to be investigated. However, the identification of these plants may be a potential marker of aspiration in patients with pneumonia.


title: Two Distinct Genotypes of Porcine Epidemic Diarrhoea Virus in Vaccinated Pig Flocks in Shandong Province of China, 2012–2015

text: As one of the top pork producers in China, Shandong Province suffered frequent outbreaks of porcine epidemic diarrhoea virus (PEDV) on pig farms from January 2012 to July 2015, resulting in significant economic losses. To better understand the prevalence situation, we conducted molecular epidemiological analyses of 38 PEDV strains isolated from 13 cities in Shandong Province. The detection rate of PEDV was 71.2% (146/205) by reverse transcription polymerase chain reaction (RT‐PCR). The S genes of the 38 isolated samples were 4146 to 4161 nt in length and shared high levels of sequence identity (93.3–99.6% nt, 92.1–99.4% aa) with those of the 41 reference strains. Among the 38 strains, 31 strains that occupied 12 cities were classed into G3 genotype, while the other seven that only existed in four cities were classed into G2 genotype. In addition, the strains CH‐SDLY‐2‐2014 and CH‐SDLY‐3‐2014 isolated from Linyi were classed into the Gd subgenotype. Notably, there were multiple insertions or deletions in the S genes and several mutations in the neutralizing epitopes of the PEDV S protein. Overall, the results revealed that G2 and G3 are the predominant PEDV genotypes circulating in Shandong Province during 2012–2015, and Gd subgenotype in G3 group had already spread towards northern China in 2014.


title: African American children are at higher risk for COVID‐19 infection

text: Infection by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the viral etiology of the novel coronavirus disease 2019 (COVID‐19), was first reported in Wuhan, China in late 2019. Peculiarly, the virus has not caused significant impact on pediatric populations, unlike other coronaviruses (1). Children comprise only 1.7% of COVID‐19 positive cases in the United States (2). Furthermore, children are noted to have a milder disease course (3, 4). However, much is unknown about the age, gender and race risk factors of COVID‐19 among children. There has been recent evidence suggestive of higher rates of COVID‐19 and related fatality rates in African American adult communities around the United States(5). However, there is limited data, to our knowledge, whether any race or ethnicity group is at higher risk for COVID‐19 infection in children.


title: Brain Extracellular Matrix in Neurodegeneration

text: The role of extracellular matrix (ECM) in neurological development, function and degeneration has evolved from a simplistic physical adhesion to a system of intricate cellular signaling. While most cells require ECM adhesion to survive, it is now clear that differentiated function is intimately dependent upon cellular interaction with the ECM. Therefore, it is not surprising that the ECM is increasingly found to be involved in the enigmatic process of neurodegeneration. Descriptive studies of human neurodegenerative disorders and experimental studies of animal models of neurodegeneration have begun to define potential mechanisms of ECM disruption that can lead to synaptic and neuronal loss.


title: Isolation of a Divergent Strain of Bovine Parainfluenza Virus Type 3 (BPIV3) Infecting Cattle in China

text: Bovine parainfluenza virus type 3 (BPIV3) is one of the most important known viral respiratory pathogens of both young and adult cattle. It is also named “heat stress in transport”, causing morbidity and mass death. New variants of BPIV3 have been detected or isolated in China since 2008. Here, we isolate one BPIV3 strain (named BPIV3 BJ) in Madin-Darby bovine kidney (MDBK) cells from nasal samples collected in China. Phylogenetic analysis showed that our isolate is related to BPIV3 of the genotype A. The comparison of BPIV3-BJ and the reference Chinese isolate NM09 showed that these strains are highly divergent. We found many differences in the amino acid composition in the nucleocapsid (NP) protein among these genotype A strains. Since the NP protein has been implicated in immunization studies, our BPIV3 isolate will be useful for the development of immune assays and vaccine studies. The diversity of BPIV3 lineages that we found in China indicated ongoing evolution for immune escape. Our study highlights the importance of genetic surveillance for determining the effect of BPIV3 variability on pathogen evolution and population-scale immunity.


title: WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus

text: Summary Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.


title: Adjuvant therapy with traditional Chinese medicine in a heart failure patient complicated by hospital-acquired pneumonia: A case report

text: Abstract Objective We report a case of congestive heart failure complicated by hospital-acquired pneumonia that was successfully treated with traditional Chinese medicine (TCM) and antibiotics. Clinical features and outcome A 33-year-old man with a history of heart failure developed pneumonia during hospitalization. After the standard antibiotic therapy for 3 days, he continued to experience persistent fever and progressive cough with purulent sputum. Broad spectrum antibiotics did not relieve the fever or the purulent sputum; therefore, the patient requested TCM for integrated therapy, and was subsequently treated with a regiment of “clearing heat and damp excreting” decoction according to TCM theory. After three days of TCM combination therapy, the pneumonia patches significantly improved on chest X-ray. His sputum was obviously decreased in amount and the fever was complete remission in the 5th day of TCM adjuvant therapy. Conclusion Integrated therapy with a “clearing heat and damp excreting” decoction may have improved hospital-acquired pneumonia in a patient comorbid with congestive heart failure. The anti-pyretic, anti-inflammatory, antitussive and diuretic effects of TCM may be responsible for the observed improvement. Further experimental studies are warranted to confirm the efficacy and mechanism of TCM action in the treatment of pneumonia.


title: Briefly Noted

text: By the time this issue of ADAW is published, the final figures will be out. At press time, some $400 million in a $2 trillion stimulus package designed to combat economic problems from the coronavirus pandemic is going to the Substance Abuse and Mental Health Services Administration, according to Andrew Kessler, principal with Slingshot Solutions. Both the Senate and House versions allocated $400 million. The Senate bill proposed $425 million, while the House proposed $435 million. In both bills, $15 million goes to the Indian Health Service and $50 million to suicide prevention. In the Senate bill, $250 million is allocated to certified community behavioral health clinics (CCBHCs), while that number is $200 million in the House version. These clinics currently exist in only eight states, Kessler pointed out. The CCBHC money will allow states to apply for grants and put forth their own behavioral health priorities, said Kessler. Watch next week's issue for details.


The case for ILI surveillance


title: KDE Bioscience: Platform for bioinformatics analysis workflows

text: Abstract Bioinformatics is a dynamic research area in which a large number of algorithms and programs have been developed rapidly and independently without much consideration so far of the need for standardization. The lack of such common standards combined with unfriendly interfaces make it difficult for biologists to learn how to use these tools and to translate the data formats from one to another. Consequently, the construction of an integrative bioinformatics platform to facilitate biologists’ research is an urgent and challenging task. KDE Bioscience is a java-based software platform that collects a variety of bioinformatics tools and provides a workflow mechanism to integrate them. Nucleotide and protein sequences from local flat files, web sites, and relational databases can be entered, annotated, and aligned. Several home-made or 3rd-party viewers are built-in to provide visualization of annotations or alignments. KDE Bioscience can also be deployed in client-server mode where simultaneous execution of the same workflow is supported for multiple users. Moreover, workflows can be published as web pages that can be executed from a web browser. The power of KDE Bioscience comes from the integrated algorithms and data sources. With its generic workflow mechanism other novel calculations and simulations can be integrated to augment the current sequence analysis functions. Because of this flexible and extensible architecture, KDE Bioscience makes an ideal integrated informatics environment for future bioinformatics or systems biology research.


title: Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1

text: Background Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. Research question The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. Study Design and Methods This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. Results The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the COVID-19 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao 2/Fio 2 of 198.2 mm Hg in the COVID-19 cohort was significantly higher than the Pao 2/Fio 2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). Interpretation There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.


title: Comparative morphology of lymphoepithelial carcinoma in primary tumor, metastasis, and xenograft

text: Tissue of lymphoepithelial tumor metastasis was transplanted subcutaneously to thymus-aplastic “nude” mice. After 75 days a pea-size tumor was developing which again was transplanted to further murine passages. During the second passage the tumor was growing faster and material was taken for light and electron microscopy. The results were compaired with the datas obtained from the primary nasopharyngeal carcinoma and metastasis. The tumor cells of the metastasis and of the xenograft showed all morphological criteria of a non-ceratinizing squamous epithelial carcinoma of undifferentiated type. The ultrastructural criteria of the human NPC-tumor cells were all present including cytoplasmic deposits of Corona viruses and Herpes virus-like particles within the nuclei and the cytoplasm.


title: A shallow defence of a technocracy of artificial intelligence: Examining the political harms of algorithmic governance in the domain of government

text: Artificial intelligence (AI) has proven to be superior to human decision-making in certain areas. This is particularly the case whenever there is a need for advanced strategic reasoning and analysis of vast amounts of data in order to solve complex problems. Few human activities fit this description better than politics. In politics we deal with some of the most complex issues humans face, short-term and long-term consequences have to be balanced, and we make decisions knowing that we do not fully understand their consequences. I examine an extreme case of the application of AI in the domain of government, and use this case to examine a subset of the potential harms associated with algorithmic governance. I focus on five objections based on political theoretical considerations and the potential political harms of an AI technocracy. These are objections based on the ideas of ‘political man’ and participation as a prerequisite for legitimacy, the non-morality of machines and the value of transparency and accountability. I conclude that these objections do not successfully derail AI technocracy, if we make sure that mechanisms for control and backup are in place, and if we design a system in which humans have control over the direction and fundamental goals of society. Such a technocracy, if the AI capabilities of policy formation here assumed becomes reality, may, in theory, provide us with better means of participation, legitimacy, and more efficient government.


title: Characterization of monoclonal antibodies against feline infectious peritonitis virus type II and antigenic relationship between feline, porcine, and canine coronaviruses

text: Seven monoclonal antibodies (MAbs) with neutralizing activity against feline infectious peritonitis virus (FIPV) strain 79-1149 (type II) were prepared. When the polypeptide specificity recognized by these monoclonal antibodies (MAbs) was investigated by Western immunoblotting, all of the MAbs reacted with peplomer glycoprotein (S) of the virus. By competitive binding assay these MAbs were found to recognize at least 3 different epitopes. The reactivity of these MAbs with 6 viruses classified as FIPV type I (UCD-1, UCD-2, UCD-3, UCD-4, NW-1, and Black), feline enteric coronavirus (FECV) type II strain 79-1683, canine coronavirus (CCV) strain 1-71, and transmissible gastroenteritis virus (TGEV) strains TO-163 and SH was examined by neutralization tests. All MAbs neutralized FECV strain 79-1683, CCV strain 1-71, and TGEV strains TO-163 and SH, while they did not neutralize the 6 FIPV type I viruses. Moreover, the MAb against TGEV strain TO-163, which has strong neutralizing activity against 7 TGEV viruses, neutralized CCV strain 1-71, FECV strain 79-1683, and FIPV strain 79-1146, but did not neutralize the 6 FIPV type I viruses. These results demonstrated that there are at least 3 epitopes involved in the neutralization of FIPV type II strain 79-1146, and that these epitopes are not present in FIPV type I viruses but are present in FECV strain 79-1683 which does not induce feline infectious peritonitis, TGEV strains TO-163 and SH, and CCV strain 1-71. These results suggest the presence of 2 serotypes of FIPV which can be clearly distinguished by the neutralization test using MAbs.


docid: ikxcuczi

title: Bacterial respiratory carriage in French Hajj pilgrims and the effect of pneumococcal vaccine and other individual preventive measures: A prospective cohort survey

text: Abstract Background Viral respiratory tract infections are known to be common in Hajj pilgrims while the role of bacteria is less studied. Methods Clinical follow-up, adherence to preventive measures and PCR-based pharyngeal bacterial carriage pre- and post-Hajj, were assessed in a cohort of 119 French Hajj pilgrims. Results 55% had an indication for pneumococcal vaccination. Occurrence of respiratory symptoms was 76.5%, with cough (70.6%) and sore throat (44.5%) being the most frequent; fever was reported by 38.7% pilgrims and 42.0% took antibiotics. Respiratory symptoms, fever and antibiotic intake were significantly more frequent in pilgrims with indication for vaccination against pneumococcal infection. The prevalence of S. pneumoniae carriage (1.8% pre-, 9.8% post-Hajj), H. influenzae carriage (0.9%, 45.4%) and K. pneumoniae (2.8%, 9.8%) significantly increased post-Hajj. Pilgrims vaccinated with conjugate pneumococcal vaccine were seven time less likely to present S. pneumoniae carriage post-Hajj compared to those not vaccinated (3.2% vs. 18.0%, OR = 0.15; 95% CI [0.03–0.74], p = 0.02). Conclusions Pilgrims at risk for pneumococcal disease are more likely to suffer from febrile respiratory symptoms at the Hajj despite being immunized against pneumococcal disease and despite lowered S. pneumoniae carriage and should be targeted for reinforced prevention against respiratory infections.


title: Vaccines for Pandemic Influenza

text: Recent outbreaks of highly pathogenic avian influenza in Asia and associated human infections have led to a heightened level of awareness and preparation for a possible influenza pandemic. Vaccination is the best option by which spread of a pandemic virus could be prevented and severity of disease reduced. Production of live attenuated and inactivated vaccine seed viruses against avian influenza viruses, which have the potential to cause pandemics, and their testing in preclinical studies and clinical trials will establish the principles and ensure manufacturing experience that will be critical in the event of the emergence of such a virus into the human population. Studies of such vaccines will also add to our understanding of the biology of avian influenza viruses and their behavior in mammalian hosts.


title: Cell-free protein sorting to the regulated and constitutive secretory pathways

text: Abstract To elucidate the mechanism of secretory granule formation, we here identify the first intermediate in this process, the immature secretory granule, in the neuroendocrine cell line PC12 and demonstrate the packaging of a regulated secretory protein, secretogranin II, to immature secretory granules in a cell-free system. The formation of immature secretory granules was as fast ( t 1 2 ≈ 5 min ) as that of constitutive secretory vesicles identified by the presence of a rapidly secreted heparan sulfate proteoglycan. Using the cell-free system, the formation of post-Golgi secretory vesicles was found to be dependent upon ATP. Two distinct populations of vesicles were formed: immature secretory granules containing secretogranin II and constitutive secretory vesicles containing the heparan sulfate proteoglycan. These results show that in a cell-free system, a constitutive and a regulated secretory protein are sorted upon exit from the trans-Golgi network.


docid: brmmpwls

title: Commentary: Phosphodiesterase 4 inhibitors as potential adjunct treatment targeting the cytokine storm in COVID-19

text: The most severe presentation of COVID-19 is characterized by a hyperinflammatory state attributed to the massive pro-inflammatory cytokine release, called “cytokine storm”. Several specific anti-inflammatory/immunosuppressive agents are being evaluated by ongoing clinical trials; however, there is currently insufficient evidence for their efficacy and safety in COVID-19 treatment. Given the role of phosphodiesterase 4 (PDE) 4 and cyclic adenosine monophosphate in the inflammatory response, we hypothesize that selective PDE4 inhibition may attenuate the cytokine storm in COVID-19, through the upstream inhibition of pro-inflammatory molecules, particularly TNF-α, and the regulation of the pro-inflammatory/anti-inflammatory balance. Conversely, other anti-cytokine agents lead to the downstream inhibition of specific targets, such as IL-1, IL-6 or TNF-α, and may not be efficient in blocking the cytokine storm, once it has been triggered. Due to their mechanism of action targeting an early stage of the inflammatory response and ameliorating lung inflammation, we believe that selective PDE4 inhibitors may represent a promising treatment option for the early phase of COVID-19 pneumonia before the cytokine storm and severe multiorgan dysfunction take place. Furthermore, PDE4 inhibitors present several advantages including an excellent safety profile; the oral route of administration; the convenient dosing; and beneficial metabolic properties. Interestingly, obesity and diabetes mellitus type 2 have been reported to be risk factors for the severity of COVID-19. Therefore, randomized clinical trials of PDE4 inhibitors are necessary to explore their potential therapeutic effect as an adjunct to supportive measures and other therapeutic regiments.


title: The challenges of the COVID‐19 pandemic: Approaches for the elderly and those with Alzheimer's disease

text: Coronavirus disease 2019 (COVID‐19) is an infectious disease that since its outbreak in December 2019 has become a global pandemic. COVID‐19 is caused by the previously unknown coronavirus SARS‐CoV‐2. The elderly are the most vulnerable to COVID‐19, and have the highest mortality of the afflicted. Similar patterns have been observed in epidemics and pandemics throughout the 20th and the beginning of the 21st centuries. In this article, we review some unique challenges the elderly and people with Alzheimer's disease face during the COVID‐19 pandemic and suggest approaches that could be taken from healthcare and social approaches to better handle this pandemic.


title: Strategies to Improve Participation of Older Adults in Cancer Research

text: Cancer is a disease associated with aging. As the US population ages, the number of older adults with cancer is projected to dramatically increase. Despite this, older adults remain vastly underrepresented in research that sets the standards for cancer treatments and, consequently, clinicians struggle with how to interpret data from clinical trials and apply them to older adults in practice. A combination of system, clinician, and patient barriers bar opportunities for trial participation for many older patients, and strategies are needed to address these barriers at multiple fronts, five of which are offered here. This review highlights the need to (1) broaden eligibility criteria, (2) measure relevant end points, (3) expand standard trial designs, (4) increase resources (e.g., institutional support, interdisciplinary care, and telehealth), and (5) develop targeted interventions (e.g., behavioral interventions to promote patient enrollment). Implementing these solutions requires a substantial investment in engaging and collaborating with community-based practices, where the majority of older patients with cancer receive their care. Multifaceted strategies are needed to ensure that older patients with cancer, across diverse healthcare settings, receive the highest-quality, evidence-based care.


title: Pentraxin 3: An Immuno-Regulator in the Lungs

text: Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that is a humoral component of the innate immune system. It interacts with pathogenic moieties, infected and dying host cells and facilitates their removal through activation of appropriate innate and adaptive mechanisms. PTX3 is secreted by a diverse variety of cells, ranging from immune cells to structural cells, in response to Toll like receptor (TLR) engagement, inflammatory stimuli, and physical and chemical stress. Further, PTX3 plays an essential role in female fertility as it facilitates the organization of extracellular matrix in the cumulus oophorus. Such activity is also implicated in post-inflammation tissue repair. PTX3 is a multifunctional protein and plays a non-redundant role in providing immunity against potential immunological dangers. Thus, we assessed its role in lung immunity, as lungs are at a constant risk of infections and tissue damage that is attributable to perpetual exposure to foreign agents.


title: Upregulation of Mitochondrial Gene Expression in PBMC from Convalescent SARS Patients

text: The observations that Lymphopenia is common in severe acute respiratory syndrome (SARS) patients and that peripheral blood mononuclear cell (PBMC) could be infected by SARS-CoV indicate that PBMC could be useful in identifying the gene expression profile in convalescent patients and tracing the host response to SARS-CoV infection. In this study, the altered genes expressions in the PBMC of convalescent SARS patients were investigated with suppression subtractive hybridization (SSH). We found that genes encoded by mitochondrial DNA (mtDNA) were obviously upregulated, while mitochondria were now found to be closely connected with antiviral immunity. The identification of a viral gene, M, in SSH cDNA library shows the long-term existence of SARS-CoV in vivo. In addition, some oxidative stress sensitive genes, heat shock proteins, transcription factors, and cytokines showed remarkable elevation. Thin-section electron microscope shows increased lysosome-like granule and mitochondria in PBMC of patients. These results provide important intracellular clue for tracing host response to SARS-CoV infection and suggest a role of mitochondria in that process.


title: Molecular characterization and phylogenetic analysis of porcine epidemic diarrhea virus (PEDV) samples from field cases in Fujian, China

text: The outbreak of porcine epidemic diarrhea virus (PEDV) has been a big problem of swine industry in China in recent years. In this study, we investigated molecular diversity, phylogenetic relationships, and protein characterization of Fujian field samples with other PEDV reference strains. Sequence analysis of the S1 and sM genes showed that each sample had unique characteristics, and the sample P55 may be differentiated from the others by the unique deletions and insertions of sM gene. Phylogenetic analysis based on S1 or sM gene, which have high levels of variations, indicated that each sample was related to the specific reference strain, and this finding was consistent with the protein characterization prediction analysis. The study is useful to better understand the prevalence of PEDV and its prevention and control in Fujian.


title: The Microbiome and Its Impact on Disease in the Preterm Patient

text: Emerging technologies derived largely from the Human Genome Project are being applied to evaluating the intestinal microbiota in preterm infants. The microbial ecology of the developing intestine is highly related to health and disease and new discoveries are emerging that will help us understand disorders in the development of the intestinal microbial ecosystem and how to eventually manipulate them to prevent diseases such as necrotizing enterocolitis and late onset sepsis. Here, a brief overview of the developing microbiome as it pertains to several aspects of health and disease in the preterm infant is presented.


title: ¿Va a cambiar la neurología tras la pandemia de Covid-19 en los próximos cinco años?. Estudio de enfoque mediante informadores clave

text: ]Abstract Introduction: The COVID-19 pandemic will give rise to long-term changes in neurological care, which are not easily predictable. Material and methods: A key informant survey was used to enquire about the changes expected in the specialty over the next 5 years. The survey was completed by heads of neurology departments with broad knowledge of the situation, having been active during the pandemic. Results: Despite a low level of consensus between participants, there was strong (85%) and moderate consensus (70%) about certain subjects, mainly the increase in precautions to be taken, the use of telemedicine and teleconsultations, the reduction of care provided in in-person consultations to avoid the presence of large numbers of people in waiting rooms, the development of remote training solutions, and the changes in monitoring visits during clinical trials. There was consensus that there would be no changes to the indication of complementary testing or neurological examination. Conclusion: The key informant survey identified the foreseeable changes in neurological care after the pandemic.


title: Different roles attributed to Cav1 channel subtypes in spontaneous action potential firing and fine tuning of exocytosis in mouse chromaffin cells

text: J. Neurochem. (2011) 116, 105–121. ABSTRACT: This study examines the Cav1 isoforms expressed in mouse chromaffin cells and compares their biophysical properties and roles played in cell excitability and exocytosis. Using immunocytochemical and electrophysiological techniques in mice lacking the Cav1.3α1 subunit (Cav1.3(−/−)) or the high sensitivity of Cav1.2α1 subunits to dihydropyridines, Cav1.2 and Cav1.3 channels were identified as the only Cav1 channel subtypes expressed in mouse chromaffin cells. Cav1.3 channels were activated at more negative membrane potentials and inactivated more slowly than Cav1.2 channels. Cav1 channels, mainly Cav1.2, control cell excitability by functional coupling to BK channels, revealed by nifedipine blockade of BK channels in wild type (WT) and Cav1.3(−/−) cells (53% and 35%, respectively), and by the identical change in the shape of the spontaneous action potentials elicited by the dihydropyridine in both strains of mice. Cav1.2 channels also play a major role in spontaneous action potential firing, supported by the following evidence: (i) a similar percentage of WT and Cav1.3(−/−) cells fired spontaneous action potentials; (ii) firing frequency did not vary between WT and Cav1.3(−/−) cells; (iii) mostly Cav1.2 channels contributed to the inward current preceding the action potential threshold; and (iv) in the presence of tetrodotoxin, WT or Cav1.3(−/−) cells exhibited spontaneous oscillatory activity, which was fully abolished by nifedipine perfusion. Finally, Cav1.2 and Cav1.3 channels were essential for controlling the exocytotic process at potentials above and below −10 mV, respectively. Our data reveal the key yet differential roles of Cav1.2 and Cav1.3 channels in mediating action potential firing and exocytotic events in the neuroendocrine chromaffin cell.


title: Gastrointestinal Findings in a Patient With COVID-19

text: The novel coronavirus (severe acute respiratory syndrome coronavirus 2) that causes coronavirus disease 2019 was discovered in December 2019 in Wuhan, China, and has rapidly spread across the world becoming a pandemic and disrupting societies, economies, and public health. Digestive symptoms and gastrointestinal (GI) manifestations are increasingly being reported in patients with the virus. There is also a growing body of evidence to suggest that liver injury is frequent. We present a patient diagnosed with coronavirus who presented with several days of GI symptoms and discuss the relevance of GI disease and liver injury in these patients.


title: Ecological Traits Driving the Outbreaks and Emergence of Zoonotic Pathogens

text: Infectious diseases that are transmitted from wildlife hosts to humans, such as the Ebola virus and MERS virus, can be difficult to understand because the pathogens emerge from complex multifaceted ecological interactions. We use a wildlife–pathogen system—prairie dogs (Cynomys ludovicianus) and the plague bacterium (Yersinia pestis)—to describe aspects of disease ecology that apply to many cases of emerging infectious disease. We show that the monitoring and surveillance of hosts and vectors during the buildup to disease outbreaks are crucial for understanding pathogen-transmission dynamics and that a community-ecology framework is important to identify reservoir hosts. Incorporating multidisciplinary approaches and frameworks may improve wildlife–pathogen surveillance and our understanding of seemingly sporadic and rare pathogen outbreaks.


title: Asthma Exacerbation in Children: A Practical Review

text: Asthma is the most common chronic lower respiratory tract disease in childhood throughout the world. Despite advances in asthma management, acute exacerbations continue to be a major problem in patients and they result in a considerable burden on direct/indirect health care providers. A severe exacerbation occurring within 1 year is an independent risk factor. Respiratory tract viruses have emerged as the most frequent triggers of exacerbations in children. It is becoming increasingly clear that interactions may exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this study, we provide an overview of current knowledge about asthma exacerbations, including its definition, impact on health care providers, and associated factors. Prevention management in intermittent asthma as well as intermittent wheeze in pre-school children and those with persistent asthma are discussed. Our review findings support the importance of controlling persistent asthma, as indicated in current guidelines. In addition, we found that early episodic intervention appeared to be crucial in preventing severe attacks and future exacerbations. Besides the use of medication, timely education after an exacerbation along with a comprehensive plan in follow up is also vitally important.