title: Multiple Cis-acting elements modulate programmed -1 ribosomal frameshifting in Pea enation mosaic virus

text: Programmed -1 ribosomal frameshifting (-1 PRF) is used by many positive-strand RNA viruses for translation of required products. Despite extensive studies, it remains unresolved how cis-elements just downstream of the recoding site promote a precise level of frameshifting. The Umbravirus Pea enation mosaic virus RNA2 expresses its RNA polymerase by -1 PRF of the 5′-proximal ORF (p33). Three hairpins located in the vicinity of the recoding site are phylogenetically conserved among Umbraviruses. The central Recoding Stimulatory Element (RSE), located downstream of the p33 termination codon, is a large hairpin with two asymmetric internal loops. Mutational analyses revealed that sequences throughout the RSE and the RSE lower stem (LS) structure are important for frameshifting. SHAPE probing of mutants indicated the presence of higher order structure, and sequences in the LS may also adapt an alternative conformation. Long-distance pairing between the RSE and a 3′ terminal hairpin was less critical when the LS structure was stabilized. A basal level of frameshifting occurring in the absence of the RSE increases to 72% of wild-type when a hairpin upstream of the slippery site is also deleted. These results suggest that suppression of frameshifting may be needed in the absence of an active RSE conformation.


title: Chapter 24 Molecular Detection of Multiple Respiratory Viruses

text: Publisher Summary This chapter discusses the molecular detection of multiple respiratory viruses. Respiratory infections are very common. They are responsible for significant morbidity and mortality and are costly in terms of lost time from work, inappropriate use of antibiotics, and lengthy hospital stays. Laboratory detection of causative agents can influence treatment and allow appropriate infection control measures, potentially saving time and money, promoting quicker recovery for the patient, and lowering the risk of nosocomial transmission of the organism. Molecular testing may be the most sensitive method of detecting respiratory viruses. These methods have been shown to detect multiple viruses in a single sample more often than any of the other methods described and, in addition, can detect viruses that are difficult or impossible to grow. The detection of nonviable organisms may provide additional insight into disease but provides its own challenges in terms of determining clinical significance of positive results. Like many areas of clinical medicine and microbiology, the increasing use of molecular diagnostics for detection of respiratory viruses raises many new questions for the laboratory and the clinical diagnostician, but also promises many benefits as these methods become increasingly available for routine use.


title: Roel Coutinho—Director of the Centre for Infectious Disease Control Netherlands

text: Summary In 2005, Roel Coutinho became the first director of the Netherlands' new national coordination centre for infectious diseases. After graduating in medicine in 1972 from Amsterdam University, and a sojourn as a physician in tropical medicine in Senegal and Guinea-Bissau, Coutinho returned to the Netherlands to specialise as a medical microbiologist. Coutinho joined the Municipal Health Service of Amsterdam in 1977 as the head of the Public Health Department, where in 1984 he completed a PhD on sexually transmitted diseases among men who have sex with men. He was one of the founders of the Amsterdam cohort studies. In 1989, Coutinho was appointed Professor in the Epidemiology and Prevention of Infectious Diseases at the Academic Medical Center, University of Amsterdam. In 2000 he became General Director of the Municipal Health Service of Amsterdam, a post he occupied until joining the RIVM (National Institute for Public Health and the Environment) in 2005.


title: A Review of State Guidelines for Elective Orthopaedic Procedures During the COVID-19 Outbreak

text: BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic has resulted in widespread cancellation of elective orthopaedic procedures. The guidance coming from multiple sources frequently has been difficult to assimilate as well as dynamic, with constantly changing standards. We seek to communicate the current guidelines published by each state, to discuss the impact of these guidelines on orthopaedic surgery, and to provide the general framework used to determine which procedures have been postponed at our institution. METHODS: An internet search was used to identify published state guidelines regarding the cancellation of elective procedures, with a publication cutoff of March 24, 2020, 5:00 p.m. Eastern Daylight Time. Data collected included the number of states providing guidance to cancel elective procedures and which states provided specific guidance in determining which procedures should continue being performed as well as to orthopaedic-specific guidance. RESULTS: Thirty states published guidance regarding the discontinuation of elective procedures, and 16 states provided a definition of “elective” procedures or specific guidance for determining which procedures should continue to be performed. Only 5 states provided guidelines specifically mentioning orthopaedic surgery; of those, 4 states explicitly allowed for trauma-related procedures and 4 states provided guidance against performing arthroplasty. Ten states provided guidelines allowing for the continuation of oncological procedures. CONCLUSIONS: Few states have published guidelines specific to orthopaedic surgery during the COVID-19 outbreak, leaving hospital systems and surgeons with the responsibility of balancing the benefits of surgery with the risks to public health.


title: A Systematic Review of Technology-Assisted HIV Testing Interventions

text: PURPOSE OF REVIEW: The purpose of this review is to describe and assess the literature on mobile health (mHealth) and other technology-based HIV testing interventions published in the 5-year period from 2015 to 2020. RECENT FINDINGS: We identified 18 published technology-based studies, 6 of which were efficacy trials and the remaining 12 were either pilot randomized controlled trials (RCTs) or quasi-experimental studies. Most (n = 10) interventions were conducted outside the USA, including countries in Sub-Saharan Africa (n = 4), China (n = 3), Latin America (n = 2), and India (n = 1). All efficacy trials showed some evidence of efficacy, although uptake of HIV testing was low among in intervention trials that consisted of a low number of text messages. Most pilot RCTs demonstrated high levels of feasibility and acceptability, as well as some evidence that the intervention participants benefited more than the control group. Many non-randomized trials similarly reported positive appraisal by study participants. Recommendations for future research and practice by the authors of the studies reviewed here are summarized. SUMMARY: Technology-assisted HIV testing interventions may be an important strategy to reach national and global targets for HIV status awareness in the general population and for most at-risk groups. Although there appears to be growing evidence of their benefit, questions linger regarding how to leverage existing social media platforms to promote HIV testing, which interventions work for what populations, and best practices for scaling up mHealth and other technology-based interventions.


title: Intestinal integrity, endotoxin transport and detoxification in pigs divergently selected for residual feed intake

text: Microbes and microbial components potentially impact the performance of pigs through immune stimulation and altered metabolism. These immune modulating factors can include endotoxin from gram negative bacterial outer membrane component, commonly referred to as lipopolysaccharide (LPS). In this study, our objective was to examine the relationship between intestinal barrier integrity, endotoxin and inflammation with feed efficiency (FE), using pig lines divergently selected for residual feed intake (RFI) as a model. Twelve gilts (62 ± 3 kg BW) from the low RFI (LRFI, more efficient) and 12 from the high RFI (HRFI, less efficient) were used. Individual performance data was recorded for 5 wk. At the end of the experimental period, ADFI of LRFI pigs was less (P < 0.001), ADG not different between the 2 lines (P = 0.72) but the G:F of LRFI pigs was greater than for HRFI pigs (P = 0.019). Serum endotoxin concentration (P < 0.01) and the acute phase protein haptoglobin (P < 0.05) were greater in HRFI pigs. Transepithelial resistance of the ileum, transport of fluorescein isothiocyanate labeled-Dextran and-LPS in ileum and colon, as well as tight junction protein mRNA expression in ileum, did not differ between the lines, indicating the 2 lines did not differ in transport characteristics at the intestinal level. Ileum inflammatory markers, myeloperoxidase (P < 0.05) and IL-8 (P < 0.10), were found to be greater in HRFI pigs. Alkaline phosphatase (ALP) activity was significantly increased in the LRFI pigs in ileum and liver tissues and negatively correlated with blood endotoxin (P < 0.05). Lysozyme activity in the liver was not different between the lines; however, the LRFI pigs had a twofold greater lysozyme activity in ileum (P < 0.05). Despite the difference in their activity, ALP or lysozyme mRNA expression was not different between the lines in either tissue. Decreased endotoxin and inflammatory markers and the enhanced activities of antimicrobial enzymes in the LRFI line may not fully explain the difference in the FE between the lines, but they have the potential to prevent the growth potential in HRFI pigs. Further studies are needed to identify the other mechanisms that may contribute to the greater endotoxin and acute phase proteins in the HRFI pigs and the greater FE in the LRFI pigs.


docid: iucrorzh

title: US Public Concerns About the COVID-19 Pandemic From Results of a Survey Given via Social Media

text: This survey study assessed public concerns about symptoms of coronavirus disease 2019 and individual actions in response to the pandemic.


title: The potential of cannabidiol in the COVID‐19 pandemic: a hypothesis letter

text: Identifying candidate drugs effective in the new coronavirus disease 2019 (Covid‐19) is crucial, pending a vaccine against SARS‐CoV2. We suggest the hypothesis that Cannabidiol (CBD), a non‐psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons: 1) High‐CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS‐CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti‐inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPARγ agonist, it can display a direct antiviral activity 4) PPARγ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID‐19 pandemic.


title: Selective gene silencing by viral delivery of short hairpin RNA

text: RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells.


title: An evaluation of COVID-19 in Italy: A data-driven modeling analysis

text: The novel coronavirus (COVID-19) that has been spreading worldwide since December 2019 has sickened millions of people, shut down major cities and some countries, prompted unprecedented global travel restrictions. Real data-driven modeling is an effort to help evaluate and curb the spread of the novel virus. Lockdowns and the effectiveness of reduction in the contacts in Italy has been measured via our modified model, with the addition of auxiliary and state variables that represent contacts, contacts with infected, conversion rate, latent propagation. Results show the decrease in infected people due to stay-at-home orders and tracing quarantine intervention. The effect of quarantine and centralized medical treatment was also measured through numerical modeling analysis.


title: Reorganization Tips from a Sarcoma Unit at Time of the COVID-19 Pandemic in Italy: Early Experience from a Regional Referral Oncologic Center.

text: Since the World Health Organization declared the novel coronavirus outbreak a global health emergency, Italy's lockdown was declared on 9 March 2020. Elective orthopedic surgery was forced to stop to allow the healthcare system to face the emergency. However, many orthopedic oncology cases could not be postponed. The aim of this study was to report the experience in managing sarcoma patients and the reorganization of a cancer center in an attempt to maintain it free from COVID-19. A Coronavirus Crisis Unit was established by the health directorate coordination in order to adopt specific procedures. General rules of screening and social distancing were applied in different health settings (entrance check point, hospital inward, outpatient clinic, operative room). Regarding oncologic orthopedics, priority was given to bone and soft tissue sarcomas, metastases and aggressive benign tumors at risk of impending or pathologic fracture. Precise indications were followed to manage first outpatient visits, patients undergoing surgery and follow-up. Meticulous adherence to rules among patients and personnel and collaboration between leadership and medical staff in order to continue to perform multidisciplinary treatment protocols, maintain the availability of infrastructural spaces and source protective equipment, swabs and screening samples have been successful in the aim towards a safe cure for cancer patients.


title: Antibody Engineering & Therapeutics 2016: The Antibody Society's annual meeting, December 11–15, 2016, San Diego, CA

text: Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement. The meeting will open with keynote speakers Dennis R. Burton (The Scripps Research Institute), who will review progress toward a neutralizing antibody-based HIV vaccine; Olivera J. Finn, (University of Pittsburgh School of Medicine), who will discuss prophylactic cancer vaccines as a source of therapeutic antibodies; and Paul Richardson (Dana-Farber Cancer Institute), who will provide a clinical update on daratumumab for multiple myeloma. In a featured presentation, a representative of the World Health Organization's INN expert group will provide a perspective on antibody naming. “Antibodies to watch in 2017” and progress on The Antibody Society's 2016 initiatives will be presented during the Society's special session. In addition, two pre-conference workshops covering ways to accelerate antibody drugs to the clinic and the applications of next-generation sequencing in antibody discovery and engineering will be held on Sunday December 11, 2016.


title: From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data

text: The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.


title: Serological evidence of ebolavirus infection in bats, China

text: BACKGROUND: The genus Ebolavirus of the family Filoviridae currently consists of five species. All species, with the exception of Reston ebolavirus, have been found in Africa and caused severe human diseases. Bats have been implicated as reservoirs for ebolavirus. Reston ebolavirus, discovered in the Philippines, is the only ebolavirus species identified in Asia to date. Whether this virus is prevalent in China is unknown. FINDINGS: In this study, we developed an enzyme linked immunosorbent assay (ELISA) for ebolavirus using the recombinant nucleocapsid protein and performed sero-surveillance for the virus among Chinese bat populations. Our results revealed the presence of antibodies to ebolavirus in 32 of 843 bat sera samples and 10 of 16 were further confirmed by western blot analysis. CONCLUSION: To our knowledge, this is the first report of any filovirus infection in China.


title: Identification of Adenovirus, Influenza Virus, Parainfluenza Virus, and Respiratory Syncytial Virus by Two Kinds of Multiplex Polymerase Chain Reaction (PCR) and a Shell Vial Culture in Pediatric Patients with Viral Pneumonia

text: PURPOSE: Early identification of causative agents in lower respiratory infection of pediatric patients can reduce morbidity and prevent an overuse of antimicrobials. Two kinds of multiplex polymerase chain reaction (PCR) and a commercial shell vial viral culture were performed to identify causative agents in pediatric patients. MATERIALS AND METHODS: Nasopharyngeal aspirates of 220 children diagnosed with viral pneumonia were obtained. Two kinds of multiplex PCR (Seeplex™ RV detection kit, and Labopass™ RV detection kit), and a shell vial culture by R-Mix were performed. RESULTS: Positive samples from 220 total samples by two multiplex PCRs were 52.7% and 46.4%, respectively. We also cultured 103 samples that showed positive results of the adenovirus, influenza virus, parainfluenza virus, and respiratory syncytial virus (RSV) by two multiplex PCR. The RSV was most frequently detected in 53.0% (Seeplex) and 51.7% (Labopass) of patients. The detection rate of adenovirus (AdV) was 10.3% and 12.1%, influenza virus (IFV) A and B was 12.5% and 3.4%, and parainfluenza virus (PIFV) 1, 2, and 3 were 2.9% and 2.6%. Shell vial cultures showed concordant results with each multiplex PCR by 96.1% and 77.7%, respectively. Sequencing results were 90% consistent with multiplex PCR. CONCLUSION: Multiplex PCR showed more positivity than the shell vial culture and it can be an effective primary test. Other complementary efforts such as viral cultures and sequencing analysis could be considered, according to clinical and laboratory conditions.


docid: bnzbhetc

title: Insouciance and inexperience: A deadly combination when dealing with COVID‐19

text: This article gives key reasons for the UK's tardy and confused attempts to react to the COVID‐19 pandemic. It explains very poor outcomes in the UK (in terms of the spread of the virus and high mortality, already striking at the time of writing), in terms of an initial lack of political will to prioritise public health, itself a product of a strong Prime Minister who made the “wrong call”. It also highlights a failure to “follow the science”, except in so far as the “science” had already accepted some dubious political judgements and the lack of capacity to test as the starting‐point.


Long‐Term Care Facilities and the COVID‐19 Pandemic: Lessons Learned in Madrid


title: Combination attenuation offers strategy for live-attenuated coronavirus vaccines

text: With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live-attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2’O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the SARS-CoV mouse model, a NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2’O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2’O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live-attenuated coronavirus vaccines. Significance Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations like the aged and immune-compromised. This study illustrates that despite success in young models, the NSP16 mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the NSP16 mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for NSP16 attenuation as a major component of future live-attenuated coronavirus vaccines.


title: Metal Shadowing for Electron Microscopy

text: Metal shadowing of bacteria, viruses, isolated molecules, and macromolecular assemblies is another high-resolution method for observing the ultrastructure of biological specimens. The actual procedure for producing a metal shadow is relatively simple; a heavy metal is evaporated from a source at an oblique angle to the specimen. The metal atoms pile up on the surfaces that face the source, but the surfaces away from the source are shielded and receive little metal deposit, creating a “shadow.” However, the process of producing biological specimens that are suitable for metal shadowing can be very complex. There are a whole host of specimen preparation techniques that can precede metal shadowing, and all provide superior preservation in comparison to air drying, a required step in negative staining procedures. The physical forces present during air drying (i.e., surface tension of the water–air interface) will literally crush most biological specimens as they dry. In this chapter I explain the development of and procedures for the production of biological specimens from macromolecular assemblies (e.g., DNA and RNA), purified isolated molecules (e.g., proteins), and isolated viruses and bacteria preparations suitable for metal shadowing. A variation on this basic technique is to rotate the specimen during the metal deposition to produce a high-resolution three-dimensional rendering of the specimen.


title: Determination of the optimal penetration factor for evaluating the invasion process of aerosols from a confined source space to an uncontaminated area

text: Abstract Due to the outbreak and spread of COVID-19, SARS-CoV-2 has been proven to survive in aerosols for hours. Virus-containing aerosols may intrude into an uncontaminated area from a confined source space under certain ventilated conditions. The penetration factor, which is the most direct parameter for evaluating the invasion process, can effectively reflect the penetration fraction of aerosols and the shielding efficiency of buildings. Based on the observed concentrations of aerosols combined with a widely used concentration model, four numerical calculations of the penetration factor are proposed in this study. A theoretical time-correction P est was applied to a size-dependent P avg by proposing a correction coefficient r, and the error analysis of the real-time P(t) and the derived P d were also performed. The results indicated that P avg supplied the most stable values for laboratory penetration simulations. However, the time-correction is of little significance under current experimental conditions. P(t) and P d are suitable for rough evaluation under certain conditions due to the inevitability of particles detaching and re-entering after capture. The proposed optimal penetration factor and the error analysis of each method in this study can provide insight into the penetration mechanism, and also provide a rapid and accurate assessment method for preventing and controlling the spread of the epidemic.


title: Efficient production of recombinant SARS-CoV-2 spike protein using the baculovirus-silkworm system

text: In the case of a new viral disease outbreak, an immediate development of virus detection kits and vaccines is required. For COVID-19, we established a rapid production procedure for SARS-CoV-2 spike protein (S protein) by using the baculovirus-silkworm expression system. The baculovirus vector-derived S proteins were successfully secreted to silkworm serum, whereas those formed insoluble structure in the larval fat body and the pupal cells. The ectodomain of S protein with the native sequence was cleaved by the host furin-protease, resulting in less recombinant protein production. The S protein modified in furin protease-target site was efficiently secreted to silkworm serum and was purified as oligomers, which showed immunoreactivity for anti-SARS-CoV-2 S2 antibody. By using the direct transfection of recombinant bacmid to silkworms, we achieved the efficient production of SARS-CoV-2 S protein as fetal bovine serum (FBS)-free system. The resultant purified S protein would be useful tools for the development of immunodetection kits, antigen for immunization for immunoglobulin production, and vaccines.


title: Asma infantil e infección vírica: interacciones y posibilidades terapéuticas

text: Resumen Las infecciones por rinovirus son las causas principales de sibilancias tanto en la niñez como en la vida adulta. Estudios realizados con infecciones experimentales hablan que al menos en ciertas condiciones esta infección puede extenderse al tracto respiratorio inferior, al mismo tiempo que el virus puede actuar sobre el epitelio respiratorio. Experimentos in vitro con células del sistema inmune y del tracto respiratorio inferior sugieren mecanismos de actuación directamente ligados a la producción de citocinas proinflamatorias. Existen evidencias tanto in vivo como in vitro que muestran que los rinovirus pueden estimular a las células epiteliales bronquiales para que produzcan citocinas y quimocinas proinflamatorias. Al mismo tiempo pueden estimular el sistema nervioso colinérgico y no colinérgico, incrementan la producción de ICAM-1, y pueden dar lugar a respuestas de los linfocitos T inespecíficas o a replicación de los mismos en directa relación con la infección vírica.Por otra parte se ha comprobado una mayor producción de cistenil leucotrienos en las secreciones de los pacientes afectos de broncospasmo La infección experimental con rinovirus conduce a un aumento de la sintomatología clínica y de la hiperreactividad bronquial esta última asociada a un aumento de eosinófilos y de proteína catiónica en esputo. Todos estos hallazgos sugieren que son múltipleslas vías celulares en la inducción de exacerbacionesde asma inducida por virus, si a ello unimos el posible papel potenciador que tendría la exposición a alergenoen pacientes sensibilizados, tendríamos que la inflamaciónalérgica se vería así potenciada Teniendo en cuenta las limitaciones que tienen losesteroides en cuanto a su eficacia terapéutica en lasexacerbaciones, se necesita desarrollar nuevas estrategias de tratamiento basadas en los nuevos conocimientos fisiopatológicos sobre los virus en el asma Summary Rhinovirus infections are the main cause of wheezing in children and adults. Studies carried out with experimental infections report that at least in certain conditions, this infection may spread to the lower respiratory tract as the virus acts on the respiratory epithelium. In vitro experiments with cells from the immune system and lower respiratory tract suggest that the mechanisms of action are directly linked to the production of pro-inflammatory cytokines. Both in vivo and in vitro evidence shows that rhinoviruses may stimulate bronchial epithelial cells to produce cytokines and pro-inflammatory chemokines. They may also stimulate the cholinergic and non-cholinergic nervous system, increasing the production of ICAM-1 and may give rise to a T-lymphocyte non-specific response or to T-lymphocyte replication in direct relation with viral infection. In addition, greater production of cysteinyl leukotrienes has been observed in the secretions of patients with bronchospasm Experimental infection with Rhinovirus increases clinical symptomatology and bronchial hyperreactivity. The latter is associated with increased eosinophils and cationic proteins in sputum The above findings suggest that multiple cellular pathways are involved in the induction of exacerbations of asthma induced by the virus. In addition, the possible stimulating role of exposure to allergens in sensitized patients would also increase allergic inflammation Because of the limited therapeutic efficacy of steroids in reducing exacerbations, new treatment strategies based on greater insight into the physiopathology of the role of viruses in asthma are needed


title: Receptor Binding Domain Based HIV Vaccines

text: This paper analyzes the main trend of the development of acquired immunodeficiency syndrome (AIDS) vaccines in recent years. Designing an HIV-1 vaccine that provides robust protection from HIV-1 infection remains a challenge despite many years of effort. Therefore, we describe the receptor binding domain of gp120 as a target for developing AIDS vaccines. And we recommend some measures that could induce efficiently and produce cross-reactive neutralizing antibodies with high binding affinity. Those measures may offer a new way of the research and development of the potent and broad AIDS vaccines.


title: Action Mechanisms of Lithium Chloride on Cell Infection by Transmissible Gastroenteritis Coronavirus

text: Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus. Lithium chloride (LiCl) has been found to be effective against several DNA viruses, such as Herpes simplex virus and vaccinia virus. Recently, we and others have reported the inhibitory effect of LiCl on avian infectious bronchitis coronavirus (IBV) infection, an RNA virus. In the current study, the action mechanism of LiCl on cell infection by TGEV was investigated. Plaque assays and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenyl tetrazoliumbromide (MTT) assays showed that the cell infection by TGEV was inhibited in a dose-dependent manner, when LiCl was added to virus-infected cells; the cell infection was not affected when either cells or viruses were pretreated with the drug. The inhibition of TGEV infection in vitro by LiCl was observed at different virus doses and with different cell lines. The inhibitory effect of LiCl against TGEV infection and transcription was confirmed by RT-PCR and real-time PCR targeting viral S and 3CL-protease genes. The time-of-addition effect of the drug on TGEV infection indicated that LiCl acted on the initial and late stage of TGEV infection. The production of virus was not detected at 36 h post-infection due to the drug treatment. Moreover, immunofluorescence (IF) and flow cytometry analyses based on staining of Annexin V and propidium iodide staining of nuclei indicated that early and late cell apoptosis induced by TGEV was inhibited efficiently. The ability of LiCl to inhibit apoptosis was investigated by IF analysis of caspase-3 expression. Our data indicate that LiCl inhibits TGEV infection by exerting an anti-apoptotic effect. The inhibitory effect of LiCl was also observed with porcine epidemic diarrhea coronavirus. Together with other reports concerning the inhibitory effect of lithium salts on IBV in cell culture, our results indicate that LiCl may be a potent agent against porcine and avian coronaviruses.


title: Recent advances in the rapid diagnosis of respiratory tract infection: Childhood respiratory infections

text: Molecular techniques have enabled major advances in the speed and sensitivity of the laboratory diagnosis of respiratory infections. Although the polymerase chain reaction is the most commonly used, there are several other methods available, which have applicability across the range of microbial pathogens.


title: Countermeasures to COVID-19: Are immunomodulators rational treatment options — a critical review of the evidence

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with higher concentrations of pro-inflammatory cytokines which leads to lung damage, respiratory failure, and resultant increased mortality. Immunomodulatory therapy has the potential to inhibit cytokines and quell the immune dysregulation. Controversial data found improved oxygenation after treatment with tocilizumab, an IL-6 inhibitor, sparking a wave of interest and resultant clinical trials evaluating immunomodulatory therapies. The purpose of this article is to assess potential pro-inflammatory targets and review the safety and efficacy of immunomodulatory therapies in managing patients with acute respiratory distress syndrome associated with COVID-19.


title: Vaccination and malaria prophylaxis among Greek international travelers to Asian destinations

text: Summary Background International travel is rapidly increasing worldwide, and the greatest increases have occurred in tropical and subtropical areas. The aim of the survey was to investigate the pre-travel health-seeking practices of travelers to Asian destinations. Methods A questionnaire-based survey was conducted at the Athens International Airport between the 1st of November 2011 and the 30th of April 2013. Results A total of 1666 adult travelers participated in the study, and 69.7% were men. The mean age of the participants was 39 years. Previous travel to tropical countries was reported by 69% of the participants. The most frequent destination was the Indian subcontinent (45.0%). The main reasons for travel were visiting friends and relatives (VFRs; 36.5%) and business (32.4%). Most of the participants traveled for <1 month (51.4%). Only 24.5% pursued pre-travel consultations. Vaccinations were administered to 14.4% of the participants, and of those, 77%, 73%, and 32.5% received hepatitis A, tetanus/diphtheria, and typhoid vaccines, respectively. Malaria prophylaxis was given to 12.2% of the participants. Logistic regression analysis revealed that being male and unemployed, having an elementary level of education, traveling to visiting friends and relatives, and short durations of travel were significant determinants of not seeking pre-travel consultations. Conclusion Significant gaps were revealed in the vaccinations and malaria prophylaxes of travelers departing to Asia. Specific educational tools should be developed to improve the awareness of travelers to high-risk destinations.


title: Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles

text: [Image: see text] Worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. Colorimetric assays are a representative tool to simply identify the target molecules in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye molecules). The detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compounds at a specific wavelength. In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl(2)) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This platform is able to verify the existence of viral molecules through a localized surface plasmon resonance (LSPR) shift and color changes of AuNPs in the UV–vis wavelength range. We designed a pair of thiol-modified probes at either the 5′ end or 3′ end to organize complementary base pairs with upstream of the E protein gene (upE) and open reading frames (ORF) 1a on MERS-CoV. The dsDNA of the target and probes forms a disulfide-induced long self-assembled complex, which protects AuNPs from salt-induced aggregation and transition of optical properties. This colorimetric assay could discriminate down to 1 pmol/μL of 30 bp MERS-CoV and further be adapted for convenient on-site detection of other infectious diseases, especially in resource-limited settings.


title: The essential role of law in achieving the health-related Sustainable Development Goals

text: In this article, we examine the essential role of law in achieving the health-related Sustainable Development Goals (SDGs). Following the World Health Organization’s broad definition of health, all SDGs can be seen to impact on human health and hence the health goal (SDG3) should be right at the centre of the entire 2030 Agenda for Sustainable Development. We note recent research on the contribution of law, including international human rights law, to achieving health for all and discuss the role of law in addressing seven emerging health challenges. Law can and should play an important role in achieving all health-related SDGs, by respecting, protecting and fulfilling the right to health, ensuring that no one is left behind.


title: Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States

text: Abstract This paper presents a quantitative assessment model for the risk of entry of zoonotic bat-borne viruses into the European Union (EU). The model considers four routes of introduction: human travel, legal trade of products, live animal imports and illegal import of bushmeat and was applied to five virus outbreak scenarios. Two scenarios were considered for Zaire ebolavirus (wEBOV, cEBOV) and other scenarios for Hendra virus, Marburg virus (MARV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The use of the same framework and generic data sources for all EU Member States (MS) allows for a relative comparison of the probability of virus introduction and of the importance of the routes of introduction among MSs. According to the model wEBOV posed the highest risk of an introduction event within the EU, followed by MARV and MERS-CoV. However, the main route of introduction differed, with wEBOV and MERS-CoV most likely through human travel and MARV through legal trade of foodstuffs. The relative risks to EU MSs as entry points also varied between outbreak scenarios, highlighting the heterogeneity in global trade and travel to the EU MSs. The model has the capability to allow for a continual updating of the risk estimate using new data as, and when, it becomes available. The model provides an horizon scanning tool for use when available data are limited and, therefore, the absolute risk estimates often have high uncertainty. Sensitivity analysis suggested virus prevalence in bats has a large influence on the results; a 90% reduction in prevalence reduced the risk of introduction considerably and resulted in the relative ranking of MARV falling below that for MERS-CoV, due to this parameter disproportionately affecting the risk of introduction from the trade route over human travel.


Distance, Diffusion, and the Role of Social Media in a Time of COVID Contagion


title: Clearance of chloroquine and hydroxychloroquine by the Seraph® 100 Microbind® Affinity blood filter ‐ approved for the treatment of COVID‐19 patients

text: On April 17(th) 2020 the US Food and Drug Administration granted Coronavirus Disease 2019 (COVID‐19) emergency use authorizations for the Seraph® 100 Microbind® Affinity Blood Filter. The medical device is aimed to treat critically ill COVID‐19 patients with confirmed or imminent respiratory failure. The aim of this life size in vitro pharmacokinetic study was to investigate the in‐vitro adsorption of chloroquine and hydroxychloroquine from human plasma using equipment that is also used at the bedside. After start of the hemoperfusion Pre (C(pre)) Seraph® plasma levels were obtained at 5 (C(5)), 10 (C(10)), 15 (C(15)), 30 (C(30)), 60 (C(60)) and 120 (C(120)) minutes into the procedure. At two timepoints (5 min and 120 min) post (C(post)) Seraph® plasma levels were determined that were used to calculate the plasma clearance. Both drugs were determined using a validated HPLC method Median [IQR] plasma clearance of the Seraph for chloroquine / hydroxychloroquine was 1.71 [0.51‐4.38] ml/min / 1.79 [0.21‐3.68] ml/min respectively. The lack of elimination was also confirmed by the fact that plasma levels did not change over the 120 min treatment. As neither chloroquine nor hydroxychloroquine were removed by the treatment with the Seraph dose adjustments in COVID‐19 patients undergoing this treatment are not necessary. This article is protected by copyright. All rights reserved.


title: Difference in Bgp-independent fusion activity among mouse hepatitis viruses

text: Mouse hepatitis virus (MHV) utilizes a mouse biliary glycoprotein (Bgp) as a receptor. Co-cultivation of MHV-nonpermissive hamster BHK cells devoid of mouse Bgp with mouse DBT cells infected with MHV-A59 or JHMV induces syncytia formation on BHK cells (Bgp-independent fusion). This study shows the difference in Bgp-independent fusion activity among various MHV strains. Under a phase contrast microscopy, JHMV (cl-2, sp-4) induced the Bgp-independent syncytia on BHK cells similar to those observed on DBT cells, while such syncytia were not seen with the infection of other MHV strains (MHV-1, MHV-3, MHV-A59, MHV-S, srr7, srr11 and srr18). Tiny syncytia detectable only by immunofluorescence were produced with the latter MHV strains except for srr7 which failed to produce syncytia. MHVs except for srr7 grew in BHK cells after Bgp-independent infection. The Bgp-independent fusion by JHMV was inhibited either by anti-S1 or anti-S2 antibodies. These results showed that the JHMV spike protein had a remarkably high Bgp-independent fusion activity.


title: Isolation Precautions in the Inpatient Setting

text: This article provides an overview of the use of standard and isolation precautions in the hospital setting, including droplet, airborne, and contact precautions. The article includes the indications for use, guidance for appropriate discontinuation of precautions, and the effect of precaution use on infection control measures, patient safety and experience, health care costs, and environmental outcomes.


title: Chapter 4 Ebola Virus Disease Epidemic in Light of Other Epidemics

text: Abstract The first part of this chapter discusses the common features of various epidemics and prevailing concepts related to spread and remission of epidemics. The current Ebola virus disease epidemic is compared with epidemics that occurred over the past centuries. The second part discusses the role of community-wide preventive measures implemented in previous epidemics, the process of vaccine development, and the evolution of quarantine and current implementation across nations.


title: The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions

text: Sialic acids (Sia) are the primary receptors for influenza viruses, and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C4, C7, C8, and C9 positions, and N-acetyl or N-glycolyl at C5. They can also vary in their linkages, including α2-3 or α2-6-linkages. Here, we analyzed the distribution of modified Sia in cells and tissues of wild-type mice, or in mice lacking cytidine 5’-monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) enzyme that synthesizes N-glycolyl modifications (Neu5Gc). We also examined the variation of Sia forms on erythrocytes and saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a great degree of variability in display of modified Sia between different species. IAV HA from different virus strains showed consistently reduced binding to both Neu5Gc and O-acetyl modified Sia; however, while IAV NA were inhibited by Neu5Gc and O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV, and may affect both pathogens and the normal flora of different mucosal sites. Sialic acids (Sia) are involved in many different cellular functions and are receptors for many pathogens. Sia come in many chemically modified forms but we lack a clear understanding of how they alter the interactions with microbes. Here we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably between different animals, and their inhibitory effects on IAV NA and HA activities and on bacterial sialidases (neuraminidases) suggest a host-variable protective role in secreted mucus.


title: Acute myocarditis associated with COVID-19 infection()

text: We present the case of a 20-year-old male patient without previous history of cardiovascular disease who was admitted to our hospital with a new onset febrile sensation and chest pain. Chest computed tomography revealed a subpleural consolidation with a halo of ground-glass opacification. Blood tests revealed elevated levels of markers of myocyte necrosis (troponin I and creatine kinase–MB). Nasopharyngeal swab was positive for COVID-19. Cardiac MRI showed myocardial edema and late gadolinium enhancement compatible with myocarditis associated with COVID-19 infection. This case showed that acute myocarditis can be the initial presentation of patients with COVID-19 infection.


title: Return to sports after COVID-19: a position paper from the Dutch Sports Cardiology Section of the Netherlands Society of Cardiology

text: The coronavirus disease 2019 (COVID-19) pandemic has led to preventive measures worldwide. With the decline of infection rates, less stringent restrictions for sports and exercise are being implemented. COVID-19 is associated with significant cardiovascular complications; however there are limited data on cardiovascular complications and long-term outcomes in both competitive (elite) athletes and highly active individuals. Based on different categories of disease severity (asymptomatic, regional/systemic symptoms, hospitalisation, myocardial damage, and/or myocarditis), in this point-of-view article we offer the (sports) cardiologist or sports physician in the Netherlands a practical guide to pre-participation screening, and diagnostic and management strategies in all athletes >16 years of age after COVID-19 infection.


Spontaneous Coronary Artery Dissection in a Patient with COVID-19


title: The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia

text: Coronavirus infection, including SARS-CoV, MERS-CoV, and SARS-CoV2, causes daunting diseases that can be fatal because of lung failure and systemic cytokine storm. The development of coronavirus-evoked pneumonia is associated with excessive inflammatory responses in the lung, known as “cytokine storms,” which results in pulmonary edema, atelectasis, and acute lung injury (ALI) or fatal acute respiratory distress syndrome (ARDS). No drugs are available to suppress overly immune response-mediated lung injury effectively. In light of the low toxicity and its antioxidant, anti-inflammatory, and antiviral activity, it is plausible to speculate that curcumin could be used as a therapeutic drug for viral pneumonia and ALI/ARDS. Therefore, in this review, we summarize the mounting evidence obtained from preclinical studies using animal models of lethal pneumonia where curcumin exerts protective effects by regulating the expression of both pro- and anti-inflammatory factors such as IL-6, IL-8, IL-10, and COX-2, promoting the apoptosis of PMN cells, and scavenging the reactive oxygen species (ROS), which exacerbates the inflammatory response. These studies provide a rationale that curcumin can be used as a therapeutic agent against pneumonia and ALI/ARDS in humans resulting from coronaviral infection.


title: Newly discovered respiratory viruses: significance and implications

text: With the recent advances in molecular biology and the ability to amplify viral genomes in a non-sequence-dependent manner, several previously unidentified human respiratory viruses have been discovered. There are accumulating data that some of these new pathogens are responsible for a substantial proportion of respiratory tract diseases, particularly in children. This review will focus on several of these newly identified pathogens for which there are clinical data implicating a role of these viruses in respiratory tract disease specifically, human metapneumovirus, human coronaviruses NL63 and HKU1, and the human bocavirus. Antivirals and effective vaccines for these new agents may decrease the burden of respiratory tract diseases.


title: Severe COVID-19 during Pregnancy and Possible Vertical Transmission

text: There are few cases of pregnant women with novel corona virus 2019 (COVID-19) in the literature, most of them with a mild illness course. There is limited evidence about in utero infection and early positive neonatal testing. A 41-year-old G3P2 with a history of previous cesarean deliveries and diabetes mellitus presented with a 4-day history of malaise, low-grade fever, and progressive shortness of breath. A nasopharyngeal swab was positive for COVID-19, COVID-19 serology was negative. The patient developed respiratory failure requiring mechanical ventilation on day 5 of disease onset. The patient underwent a cesarean delivery, and neonatal isolation was implemented immediately after birth, without delayed cord clamping or skin-to-skin contact. The neonatal nasopharyngeal swab, 16 hours after delivery, was positive for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) real-time polymerase chain reaction (RT-PCR), and immunoglobulin (Ig)-M and IgG for SARS-CoV-2 were negative. Maternal IgM and IgG were positive on postpartum day 4 (day 9 after symptom onset). We report a severe presentation of COVID-19 during pregnancy. To our knowledge, this is the earliest reported positive PCR in the neonate, raising the concern for vertical transmission. We suggest pregnant women should be considered as a high-risk group and minimize exposures for these reasons. Key Points: We report a severe presentation of COVID-19 in pregnancy requiring invasive ventilatory support. This is a case of positive RT-PCR in first day of life, suggesting possible vertical transmission. There were no detectable maternal antibodies for COVID-19 until after delivery.


title: Colorimetric detection of controlled assembly and disassembly of aptamers on unmodified gold nanoparticles

text: Abstract Aptamers are nucleic acid ligands that are generated artificially by in vitro selection and behave similar to antibodies. The development of aptamer-based sensing systems or strategies has been in vogue for the past few decades, because aptamers are smaller in size, stable, cheaper and undergo easier modifications. Owing to these advantages, several facile aptamer-based colorimetric strategies have been created by controlling the assembly and disassembly of aptamers on unmodified gold nanoparticle probes. As these kinds of assay systems are rapid and can be visualized unaided by instruments, they have recently become an attractive method of choice. The formation of purple-colored aggregates (attraction) from the red dispersed (repulsion) state of GNPs in the presence of mono- or divalent ions is the key principle behind this assay. Due to its simplicity and versatility, this assay can be an alternative to existing diagnostic assays. Here, we have investigated the critical elements involved in colorimetric assays, and have screened different proteins and small ligands to evaluate biofouling on GNPs.


title: Is PEGylated G-CSF superior to G-CSF in patients with breast cancer receiving chemotherapy? A systematic review and meta-analysis

text: BACKGROUND: PEGylated granulocyte colony-stimulating factor (G-CSF) is a safe alternative to G-CSF to improve chemotherapy-induced neutropenia (CIN). This superiority has resulted in its increased use by physicians; however, the superiority of PEGylated G-CSF for CIN in breast cancer has not been conclusively determined. OBJECTIVES: To assess the superiority of PEGylated G-CSF for CIN in breast cancer in terms of effectiveness and safety via a systematic review and meta-analysis. METHODS: A literature search in PubMed, Embase, Cochrane Library, and Web of Science was performed for eligible studies published from database inception to December 2019. All studies comparing PEGylated G-CSF and G-CSF for CIN of breast cancer were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently. Meta-analysis was conducted using Revman, version 5.2. RESULTS: Nine randomized controlled trials were finally identified. The publication bias of these studies was acceptable. For the endpoint of effectiveness, analysis of the incidence/duration of grade ≥ 3 neutropenia, the duration of grade 4 neutropenia, the incidence of febrile neutropenia (FN), and the time to absolute neutrophil count recovery showed no advantage of PEGylated G-CSF over G-CSF for CIN of breast cancer (P > 0.05), with the premise of a sufficient dose of G-CSF according to the guidelines. No significant differences in grade 4 adverse events were observed between the groups (P = 0.29), and PEGylated G-CSF did not increase the incidence of skeletal and/or muscle pain compared with G-CSF (P = 0.32). CONCLUSION: PEGylated G-CSF was as effective and safe as G-CSF to reduce CIN in breast cancer but did not show an obvious superiority. However, in clinical practice, PEGylated G-CSF has an obvious advantage in terms of convenience, which could improve patient’s quality of life.


title: Clinical and biological insights from viral genome sequencing

text: Whole-genome sequencing (WGS) of pathogens is becoming increasingly important not only for basic research but also for clinical science and practice. In virology, WGS is important for the development of novel treatments and vaccines, and for increasing the power of molecular epidemiology and evolutionary genomics. In this Opinion article, we suggest that WGS of viruses in a clinical setting will become increasingly important for patient care. We give an overview of different WGS methods that are used in virology and summarize their advantages and disadvantages. Although there are only partially addressed technical, financial and ethical issues in regard to the clinical application of viral WGS, this technique provides important insights into virus transmission, evolution and pathogenesis. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.182) contains supplementary material, which is available to authorized users.


title: COVID‐19 Relief Laws Benefit Nonprofit Organizations

text: Legislation creating a $2.2 trillion economic stabilization package to combat the COVID‐19 pandemic became law on March 27, when President Trump signed the Coronavirus Aid, Relief, and Economic Security (CARES) Act (Pub. L. No. 116‐136). This was the third, and most massive, COVID‐19 emergency relief act passed by Congress in March. There are several features of the act of direct interest and import to nonprofit organizations.


title: Intracellular localization of the SARS coronavirus protein 9b: Evidence of active export from the nucleus

text: Abstract Open reading frame 9b (ORF 9b) encodes a 98 amino acid group-specific protein of severe acute respiratory syndrome (SARS) coronavirus (CoV). It has no homology with known proteins and its function in SARS CoV replication has not been determined. The N-terminal part of the 9b protein was used to raise polyclonal antibodies in rabbits, and these antibodies could detect 9b protein in infected cells. We analyzed the sub-cellular localization of recombinant 9b protein using fluorescence microscopy of live transfected cells and indirect immunofluorescence of transfected fixed cells. Our findings indicate that the 9b protein is exported outside of a cell nucleus and localizes to the endoplasmic reticulum. Our data also suggest that the 46-LRLGSQLSL-54 amino acid sequence of 9b functions as a nuclear export signal (NES).


title: SARS‐CoV‐2 Presence in seminal fluid: myth or reality

text: Great concerns have been raised on SARS‐CoV‐2 impact on men’s andrological well‐being and one of the critically unanswered questions is whether it is present or not in the seminal fluid of infected subjects. The expression of ACE2 and TMPRSS2 in the testis and in the male genital tract allows speculations about a possible testicular involvement during the infection, possibly mediated by local and/or systemic inflammation that might allow a high viral load to overcome the haemato‐testicular barrier. To date, few investigations have been carried out to ascertain the presence of SARS‐CoV‐2 in the seminal fluid with contrasting results. Furthermore, the cumulative number of subjects is far too low to answer the question unambiguously. Therefore, great caution is still needed when evaluating this data, otherwise we risk unleashing unmotivated concerns in the scientific world with troublesome consequences in reproductive medicine.


title: Robot assisted surgery during the COVID-19 pandemic, especially for gynecological cancer: a statement of the Society of European Robotic Gynaecological Surgery (SERGS)

text: All surgery performed in an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, irrespective of the known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status of the patient, should be regarded as high risk and protection of the surgical team at the bedside should be at the highest level. Robot assisted surgery (RAS) may help to reduce hospital stay for patients that urgently need complex-oncological-surgery, thus making room for COVID-19 patients. In comparison to open or conventional laparoscopic surgery, RAS potentially reduces not only contamination with body fluids and surgical gasses of the surgical area but also the number of directly exposed medical staff. A prerequisite is that general surgical precautions under COVID-19 circumstances must be taken, with the addition of prevention of gas leakage: • Use highest protection level III for bedside assistant, but level II for console surgeon. • Reduce the number of staff at the operation room. • Ensure safe and effective gas evacuation. • Reduce the intra-abdominal pressure to 8 mmHg or below. • Minimize electrocautery power and avoid use of ultrasonic sealing devices. • Surgeons should avoid contact outside theater (both in and out of the hospital).


title: Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2): A global pandemic and treatments strategies

text: The emergence and rapid spread of novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a potentially fatal disease is swiftly evolving public health crises worldwide. The origin of SARS-CoV-2 infection was first reported in people exposed to wet animal market in Wuhan City, China in December 2019. It was suggested that the infection is likely to be of zoonotic origin and transmitted to human through yet unknown intermediary. As of (22/05/2020), there are around 4,995,996 confirmed cases reported by WHO with 327,821 deaths. SARS-CoV-2 infection is transmitted via inhalation or direct contact of infected people's droplets. It has an incubation period ranging from 2 to 14 days or more. The rate of spread of SARS-CoV-2 is more than partially resembled coronavirus (SARS-CoV and MERS). The symptoms are similar to influenza like, breathlessness, sore throat and fatigue therefore, infected person is isolated and administrated with effective treatments. Infection is mild in most but in elderly (>50 years) and those with cardiac and respiratory disorder, it may progress to pneumonia, acute respiratory distress syndrome, and multi organ failure. People with strong immunity or those developed herd immunity are asymptomatic. Fatality rate ranges to 3-4% on case basis. Diagnosis of SARS-CoV-2 is recommended in respiratory secretions by special molecular tests like PCR, chest scan and common laboratory diagnosis. Currently, the existing treatment is essentially supportive and role of antiviral agents is yet to be established as there is no vaccination or therapy available. This review focuses on epidemiology, symptoms, transmission, pathogenesis, ongoing available treatments and future perspectives of SARS-CoV-2.


title: Analysis of Public Perception of the Israeli Government’s Early Emergency Instructions Regarding COVID-19: Online Survey Study

text: BACKGROUND: On March 11, 2020, the World Health Organization (WHO) officially declared coronavirus disease (COVID-19) to be a pandemic. This posed challenges to many countries, prominent among which is communication with the public to gain their cooperation. Israel faces different challenges from other countries in its management of the COVID-19 crisis because it is in the midst of a deep constitutional crisis. OBJECTIVE: The objective of this paper was to examine the response of the Israeli public to the government’s emergency instructions regarding the pandemic in terms of correlations between overall risk perception and crisis management; overall risk perception and economic threat perception; crisis management and compliance with behavioral guidelines; and crisis management and economic threat perception. We also made comparisons between crisis management and spokesperson credibility and between crisis management and the credibility of information sources. METHODS: The sample was established using an online survey that enabled rapid and effective distribution of an online questionnaire during the COVID-19 crisis. The self-selection online survey method of nonprobability sampling was used to recruit participants (N=1056) through social network posts asking the general public (aged ≥18 years) to answer the survey. RESULTS: Participants aged ≥65 years perceived higher personal risk compared to those aged 18-30 years (mean difference 0.33, 95% CI 0.04-0.61) and those aged 46-64 years (mean difference 0.38, 95% CI 0.12-0.64). Significant correlations were found between overall risk perception and attitudes toward crisis management (r=0.19, P<.001), overall risk perception and economic threat perception (r=0.22, P<.001), attitudes toward crisis management and compliance with behavioral guidelines (r=0.15, P<.001), and attitudes toward crisis management and economic threat perception (r=–0.15, P<.001). Participants who perceived that the prime minister was the most credible spokesperson evaluated the crisis management significantly higher than all other groups. The crisis management was evaluated significantly lower by participants who stated that infectious disease specialists were the most credible spokespersons. Participants for whom the Ministry of Health website was the most credible source of information evaluated the crisis management higher than all other groups. Participants for whom scientific articles were the most credible source of information evaluated the crisis management lower than those who perceived that the WHO/Centers for Disease Control and Prevention websites or Ministry of Health/hospital websites and health care workers were the most credible. CONCLUSIONS: The higher the public trust and evaluation of crisis management, the greater the compliance of the public with guidelines. It was also found that crisis management and information cannot be approached in the same way for the overall public. Furthermore, unlike other epidemics, the COVID-19 crisis has widespread economic and social consequences; therefore, it is impossible to focus only on health risks without communicating economic and social risks as well.


title: Assessment of ambulance dispatch data for surveillance of influenza-like illness in Melbourne, Australia

text: Summary Objectives Ambulance dispatch data are collated electronically in many jurisdictions and have a wide reach into the community. They may therefore be useful for syndromic surveillance and early recognition of emerging infectious diseases. This study assessed whether ambulance dispatch data are suitable for influenza surveillance. Study design Comparison of a time series of ambulance dispatch data from Melbourne, Australia for the years 1997–2005 with locum service and general practice (GP) sentinel surveillance data for influenza-like illness (ILI). Methods All data were aggregated into 1-week periods, corresponding to the data collection period used in the GP sentinel surveillance system, which was used as the reference system. Rates of ambulance dispatches classified to respiratory or breathing problems per 1000 total dispatches were compared with rates of callouts for flu or influenza per 1000 locum calls, and rates of ILI per 1000 patients from the sentinel GPs. Signals from the ambulance data were generated using the log likelihood ratio CUSUM, a method of continuous monitoring suitable for surveillance. Results The ambulance dispatch data displayed seasonal trends that were similar to those observed in locum service surveillance and GP sentinel systems, and identified the years with higher-than-expected seasonal ILI activity (1998 and 2003) and the epidemic year (1997). However, there was a high baseline rate of ambulance calls classified to respiratory or breathing problems (90–100 per 1000 calls) in months where there was minimal influenza activity. Conclusion Ambulance dispatch data have potential for syndromic surveillance, but because of the high background noise are not definitive and would need to be calibrated to suit particular local circumstances.


title: Safe surgery during the coronavirus disease 2019 crisis

text: BACKGROUND: Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has created a global pandemic. Surgical care has been impacted, with concerns raised around surgical safety, especially in terms of laparoscopic versus open surgery. Due to potential aerosol transmission of SARS‐CoV‐2, precautions during aerosol‐generating procedures and production of surgical plume are paramount for the safety of surgical teams. METHODS: A rapid review methodology was used with evidence sourced from PubMed, Departments of Health, surgical colleges and other health authorities. From this, a working group of expert surgeons developed recommendations for surgical safety in the current environment. RESULTS: Pre‐operative testing of surgical patients with reverse transcription‐polymerase chain reaction does not guarantee lack of infectivity due to a demonstrated false‐negative rate of up to 30%. All bodily tissues and fluids should therefore be treated as a potential source of COVID‐19 infection during operative management. Caution must be taken, especially when using an energy source that produces surgical plumes, and an appropriate capture device should also be used. Limiting the use of such devices or using lower energy devices is desirable. To reduce perceived risks association with desufflation of pneumoperitoneum during laparoscopic surgery, an appropriate suction irrigator system, attached to a high‐efficiency particulate air filter, should be used. Additionally, appropriate use of personal protective equipment by the surgical team is necessary during high‐risk aerosol‐generating procedures. CONCLUSIONS: As a result of the rapid review, evidence‐based guidance has been produced to support safe surgical practice.


title: A phage RNA-binding protein binds to a non-cognate structured RNA and stabilizes its core structure

text: Abstract Recent studies suggest that some RNA-binding proteins facilitate the folding of non-cognate RNAs. Here, we report that bacteriophage MS2 coat protein (MS2 CP) bound and promoted the catalytic activity of Candida group I ribozyme. Cloning of the MS2-bound RNA segments showed that this protein primarily interacts with the P5ab–P5 structure. Ultraviolet cross-linking and the T1 footprinting assay further showed that MS2 binding stabilized tertiary interactions, including the conserved L9–P5 interaction, and led to a more compact core structure. This mechanism is similar to that of the yeast mitochondrial tyrosyl-tRNA synthetase on other group I introns, suggesting that different RNA-binding proteins may use common mechanisms to support RNA structures.


title: 13 General Mechanisms of Antiviral Resistance

text: This review explores the broad mechanisms of virus resistance. This will go beyond the generally accepted concept of antiviral resistance by summarizing those evolutionary outcomes that have enabled human viruses to resist mankind’s best efforts at control. The review then focuses on how viruses acquire resistance to compounds that specifically target a virus protein (e.g., polymerase, protease, integrase, sialidase). All viruses have a principle mechanism of acquiring resistance, random point mutations. Those viruses, which have segmented genomes, have an additional mechanism, genetic reassortment. For antiviral compounds that target a key virus enzyme, there is usually a stepwise evolution of resistance. For the therapy of chronic viral infections, such as HIV, the concept of increasing the genetic barrier has been important for optimizing drug combinations for effectively delaying the appearance of resistance. In some cases, the price to the virus for gaining resistance may be reduced “fitness” but there may also be other unexpected effects. Conceptually, one way to avoid virus resistance is to use a compound to target a host protein rather than a viral protein. Such an approach seems to risk causing unacceptable toxicity, however, some instances have been identified where there can be specificity for the virus-infected cell. We end by asking the question, how will viruses respond to such an indirect challenge?


title: Facing two deadly viruses

text: As covid-19 begins to take hold, the Democratic Republic of the Congo has detected its first new Ebola cases in months, reports Peter Yeung


title: Testing Asymptomatic Emergency Department Patients for Coronavirus of 2019 (COVID‐19) in a Low Prevalence Region

text: The first cases of Coronavirus of 2019 (COVID‐19) were reported in Wuhan, China in December 2019(1). The literature demonstrates geographical variation with regards to estimates of infection incidence, suggesting that COVID‐19 has been underdiagnosed in certain regions(2,3). The rate of asymptomatic infection has been estimated to be as high as 30.8%, which may help explain variation in incidence, particularly in regions with differing screening practices (3). Transmission of COVID‐19 by asymptomatic carriers has been reported in multiple family units, indicating that this mode of infection is important in understanding disease epidemiology and population risk(4,5).


title: Management of Aerosol during Noninvasive Ventilation for Patients with Sleep-Disordered Breathing: Important Messages during the COVID-19 Pandemic

text: With the advent of COVID-19 infection and its rapid spread, preventive strategies are being developed worldwide, besides following the universal infection control guidelines. Prevention of spread through aerosol generation is one of the essential strategies in this regard, particularly for patients with sleep-disordered breathing at home and during hospital admission. Aerosols are produced, at home and in health care facilities, by natural processes and aerosol-generating procedures. To address this impinging problem, aerosol-generating procedures, like non-invasive ventilation (NIV), are to be handled meticulously, which might warrant isolation and sometimes device/interface modifications.


title: COVID-19 energy sector responses in Africa: A review of preliminary government interventions

text: The COVID-19 pandemic has unleashed unprecedented shocks across all facets of society, from strained healthcare systems to the closure of schools and economies. The energy sector is of no exception, with several concerns being raised about the ramifications that will arise for the clean energy transition. The goal of our study is to review how governments in Africa have responded to this challenge in the energy sector. We used an internet search to gather information from government policy statements/briefs, and websites of international organizations such as the IMF, WHO, KPMG, and the World Bank. Our review revealed that the majority of preliminary responses were short-term and include the provision of free electricity, waiver/suspension of bill payments, and VAT exemptions on electricity bills. These measures were more pronounced in sub-Sahara Africa while oil-rich countries of the North mostly have broad economic measures that target their oil and gas sectors. Economic stimulus packages prepared by most countries do not explicitly mention energy sector companies/institutions, especially the Renewable Energies (RE) sector. Only three countries (Nigeria, Kenya, and Burkina Faso) had specific interventions for renewables. Overall, interventions were mostly fiscal/financial and short-term, with medium to long term measures often broad without being specific to the energy sector. As governments take measures to bolster their economies, they must pay particular attention to the challenges posed by the pandemic in the energy sector and capitalize on the opportunities that it presents to drive the clean energy transition.


Assessment of Hospital Emergency Department Response to Potentially Infectious Diseases Using Unannounced Mystery Patient Drills—New York City, 2016


title: Clinical Performance of Two SARS-CoV-2 Serologic Assays

text: BACKGROUND: The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a rapid proliferation of serologic assays. However, little is known about their clinical performance. Here, we compared two commercial SARS-CoV-2 IgG assays. METHODS: 103 specimens from 48 patients with PCR confirmed SARS-CoV-2 infections and 153 control specimens were analyzed using SARS-CoV-2 serologic assays by Abbott and EUROIMMUN (EI). Duration from symptom onset was determined by medical record review. Diagnostic sensitivity, specificity, and concordance were calculated. RESULTS: The Abbott SARS-CoV-2 assay had a diagnostic specificity of 99.4% (95% CI; 96.41-99.98%), and sensitivity of 0.0% (95% CI; 0.00-26.47%) at <3 days post symptom onset, 30.0% (95% CI; 11.89-54.28) at 3-7d, 47.8% (95% CI; 26.82-69.41) at 8-13d and 93.8% (95% CI; 82.80-98.69) at ≥14d. Diagnostic specificity on the EI assay was 94.8% (95% CI; 89.96-97.72) if borderline results were considered positive and 96.7% (95% CI; 92.54-98.93) if borderline results were considered negative. The diagnostic sensitivity was 0.0% (95% CI; 0.00-26.47%) at <3d, 25.0% (95% CI; 8.66-49.10) at 3-7d, 56.5% (95% CI; 34.49-76.81) at 3-7d and 85.4% (95% CI; 72.24-93.93) at ≥14d if borderline results were considered positive. The qualitative concordance between the assays was 0.83 (95% CI; 0.75-0.91). CONCLUSIONS: The Abbott SARS-CoV-2 assay had fewer false positive and false negative results than the EI assay. However, diagnostic sensitivity was poor in both assays during the first 14 days of symptoms.


‘Age and Ageism in COVID-19’: Elderly Mental Health-care Vulnerabilities and Needs


Bréve : AIDS2020/Conférence internationale du sida


title: A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

text: Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.


Global health is more than just ‘Public Health Somewhere Else’


title: QT Interval and Arrhythmic Safety of Hydroxychloroquine Monotherapy in Coronavirus Disease 2019

text: BACKGROUND: Observational studies have suggested increased arrhythmic and cardiovascular risk with the combination use of hydroxychloroquine (HCQ) and azithromycin in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: The arrhythmic safety profile of HCQ monotherapy, which remains under investigation as a therapeutic and prophylactic agent in COVID-19, is less established and we sought to evaluate this. METHODS: In 245 consecutive patients with COVID-19 admitted to the University of Washington hospital system between March 9 and May 10, 2020, we identified 111 treated with HCQ monotherapy. Patients treated with HCQ underwent a systematic arrhythmia and QT interval surveillance protocol including serial electrocardiograms (ECG) (baseline, following second HCQ dose). The primary endpoint was in-hospital sustained ventricular arrhythmia or arrhythmic cardiac arrest. Secondary endpoints included clinically significant QTc prolongation. RESULTS: A total of 111 patients with COVID-19 underwent treatment with HCQ monotherapy (mean age 62±16 years, 44 women [39%], serum creatinine 0.9 [interquartile range 0.4] mg/dL). There were no instances of sustained ventricular arrythmia or arrhythmic cardiac arrest. In 75 patients with serial ECGs, clinically significant QTc prolongation was observed in a minority (N=5 [7%]). In patients with serial ECGs, there was no significant change in the QTc interval in pre-specified subgroups of interest, including those with prevalent cardiovascular disease or baseline use of renin-angiotensin-aldosterone axis inhibitors. CONCLUSION: In the context of a systematic monitoring protocol, HCQ monotherapy in hospitalized COVID-19 patients was not associated with malignant ventricular arrhythmia. A minority of patients demonstrated clinically significant QTc prolongation during HCQ therapy.


title: Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces

text: Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.


Management of Venous Thromboembolism During the COVID-19 Pandemic


title: On-farm biosecurity as perceived by professionals visiting Swedish farms

text: BACKGROUND: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. RESULTS: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.


title: Total phenolic content and biological activities of enzymatic extracts from Sargassum muticum (Yendo) Fensholt

text: Seaweeds are potentially excellent sources of bioactive metabolites that could represent useful leads in the development of new functional ingredients in pharmaceutical and cosmetic industries. In the last decade, new marine bioprocess technologies have allowed the isolation of substances with biological properties. The brown alga Sargassum muticum (Yendo) Fensholt (Ochrophyta) was enzymatically hydrolyzed to prepare water-soluble extracts by using six different commercially available carbohydrate-degrading enzymes and two proteases. Evaluation of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) antioxidant, tyrosinase, elastase, and biofilm inhibition, antibacterial and antiviral activities as well as evaluation of cytotoxicity were realized for each extract. Total phenolic content was measured for extract characterization, and solid-phase extraction was useful to purify the enzymatic extract. Soluble total phenolic content of S. muticum Viscozyme extract was highest with 6.4% of dry weight. Enzymatic Celluclast and Viscozyme extracts had the lowest value of DPPH IC(50) indicating a strong antiradical activity, 0.6 mg mL(−1), in comparison with other enzymes. The ferric reducing antioxidant power ranged between 48.7 μM Fe(2+) Eq, digested with Viscozyme, and 60.8 μM Fe(2+) Eq, digested with Amyloglucosidase. Tyrosinase inhibition activity of S. muticum Neutrase extract was 41.3% higher compared to other enzymes. Elastase inhibition activity of S. muticum Shearzyme extract had highest activity (32.8%). All enzymatic extracts showed no cytotoxic effect towards the kidney Vero cells. Meanwhile, only S. muticum Neutrase and Alcalase extracts exhibited potential antiviral activity. In addition, S. muticum Viscozyme and Shearzyme extracts showed promising activity in suppressing the biofilm formation against Pseudomonas aeruginosa and Escherichia coli, respectively. Purification of S. muticum Viscozyme extracts by solid-phase extraction managed to concentrate the phenolic content and improve the bioactivity. These results indicate the promising potential of enzyme-assisted followed by solid-phase extraction in recovering phenolic content and in improving its bioactivity.


title: A case series on common cold to severe bronchiolitis and pneumonia in children following human metapneumovirus infection in Sri Lanka

text: OBJECTIVES: The prevalence of hMPV infections in Sri Lanka has not been reported and here we report a case series of hMPV infection in children less than 5 years. Patients with ARTI were included from Teaching Hospital, Anuradhapura from March 2013 to August 2014. Indirect fluorescence assay was performed on nasopharyngeal aspirates for the identification of respiratory viruses [respiratory syncytial virus (RSV), parainfluenza virus 1, 2 and 3, influenza A and B and hMPV]. Moreover, reverse transcriptase-polymerase chain reaction was done to further confirm the hMPV infection. RESULTS: In this case series, hMPV infection showed a range of respiratory symptoms from common cold to life threatening lower respiratory tract infections with varying severity. In some cases, the clinical presentation of hMPV infection was similar to the ARTI caused by RSV. hMPV co-infections with of RSV have also been seen in some cases of ARTI. A child delivered through cesarean section and birth order > 3 has an Odds ratio of 3.5 and 4.3 (95% CI) for developing co-infection with RSV compared to hMPV mono-infections. Lack of diagnostic facilities to identify the viral aetiology has contributed to the use of antibiotics indicating the need for establishing viral diagnostic facilities in the country. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3239-3) contains supplementary material, which is available to authorized users.


title: Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome

text: SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a ‘cytokine storm’ have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4(+) and CD8(+) T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with ‘common cold’ coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.


Detection of SARS Coronavirus RNA in the Cerebrospinal Fluid of a Patient with Severe Acute Respiratory Syndrome


FAQ relatives à la responsabilité du médecin du travail face au Covid-19


title: Molecular evidence of tissue renin-angiotensin systems: A focus on the brain

text: Hypertension remains one of the largest human health problems, because hypertensive patients carry increased risk for ischemic heart disease, stroke, atherosclerosis, and renal failure. The renin-angiotensin system (RAS) has been intensively investigated for more than 100 years because it is a powerful regulator of blood pressure, and the antihypertensive benefits of RAS inhibitors are very clear. Despite a wealth of clinical and basic studies, the precise mechanisms by which the RAS regulates blood pressure remains incomplete. In this chapter, we review data demonstrating the existence and function of intrinsic tissue RAS, with a primary focus on the brain.


title: The association between self-perceived proficiency of personal protective equipment and objective performance: An observational study during a bioterrorism simulation drill

text: BACKGROUND: The recent Ebola virus disease outbreak emphasized the potential misuse of personal protective equipment (PPE) by health care workers (HCWs) during such an event. We aimed to compare self-perceived proficiency of PPE use and objective performance, and identify predictors of low compliance and PPE misuse. METHODS: An observational study combined with subjective questionnaires were carried out during a bioterror simulation drill. Forty-two observers evaluated performance under PPE. Mistakes were recorded and graded using a structured observational format and were correlated with the subjective questionnaires and with demographic parameters. RESULTS: One hundred seventy-eight HCWs from community clinics and hospitals were included. The mean self-perceived proficiency was high (6.1 out of 7), mean level of comfort was moderate (4.0 out of 7), and mean objective performance was intermediate (9.5 out of 13). There was no correlation between comfort and objective performance scores. Self-perceived proficiency was in correlation with donning and continuous performance with PPE but not with doffing. Clinic personnel performed better than personnel in hospitals (40.3% vs 67.8% with 3 or more mistakes, respectively; P = .001). Demographic characteristics had no correlation with objective or self-perceived performance. CONCLUSIONS: Self-perceived proficiency is a poor predictor of appropriate PPE use. The results suggest poor awareness of the possibility of PPE misuse.


title: Manipulation of human history by microbes

text: The convergence of the microbial and human worlds provides us with everyday essentials for the survival of our species, and in turn, this interaction brings painful and tragic consequences from pathogens. Looking back, it can be seen that microbes have also changed our history. Were it not for a pathogen that halted an Assyrian military campaign, we might have no Judaism, Christianity, or Islam. Microbes were there to aid adversaries in bringing about the fall of the great Greek and Roman empires. George Washington's bold orders to inoculate the Colonial Army against smallpox (20 years prior to Jenner's discovery of vaccination) were one of the most significant actions in saving the American Revolution from an early and unsuccessful end. Without the yellow fever virus and its accomplice, Aedes aegypti, those living in what was the Louisiana Territory might now have French as their native language. The potato blight caused by Phytophthora infestans changed the histories of both Ireland and those countries (especially the United States) to which victims of the famine emigrated. At the outbreak of World War I, when England was separated from its European source of acetone (needed for the navy's supply of cordite), British citizens had to make do with less gin, but acetone was available thanks to the growth of Clostridium acetobutylicum in those fermentation vessels.


Vitamin D supplementation in the COVID-19 pandemic


title: Maternal mental health in the time of the COVID‐19 pandemic

text: With the pandemic of Coronavirus disease‐19 (COVID‐19) spiraling out of control, the world is desperately frazzled at the moment. A few empirical studies related to this pandemic have reported higher prevalence of mental health problems among women compared to men.(1) In this context, pregnant women and new mothers could certainly be more vulnerable. Are there psychological repercussions of this outbreak on maternal health? Are perinatal maternal mental health disorders an inevitable burden of this pandemic? Could this be averted with a proactive, multidisciplinary, integrated health services approach targeting the vulnerable population of pregnant women?.


title: Par rapport à la vancomycine, le linézolide améliore la guérison et la survie des patients atteints de pneumonias nosocomiales à Staphylococcus aureus méthicilline-résistant (SAMR) R.G. Wunderin

text: Unknown