title: ‘It’s far too complicated’: why fragmentation persists in global health

text: BACKGROUND: Despite many efforts to achieve better coordination, fragmentation is an enduring feature of the global health landscape that undermines the effectiveness of health programmes and threatens the attainment of the health-related Sustainable Development Goals. In this paper we identify and describe the multiple causes of fragmentation in development assistant for health at the global level. The study is of particular relevance since the emergence of new global health problems such as COVID-19 heightens the need for global health actors to work in coordinated ways. Our study is part of the Lancet Commission on Synergies between Universal Health Coverage, Health Security and Health Promotion. METHODS: We used a mixed methods approach. This consisted of a non-systematic literature review of published papers in scientific journals, reports, books and websites. We also carried out twenty semi-structured expert interviews with individuals from bilateral and multilateral organisations, governments and academic and research institutions between April 2019 and December 2019. RESULTS: We identified five distinct yet interconnected sets of factors causing fragmentation: proliferation of global health actors; problems of global leadership; divergent interests; problems of accountability; problems of power relations. We explain why global health actors struggle to harmonise their approaches and priorities, fail to align their work with low- and middle-income countries’ needs and why they continue to embrace funding instruments that create fragmentation. CONCLUSIONS: Many global actors are genuinely committed to addressing the problems of fragmentation, despite their complexity and interconnected nature. This paper aims to raise awareness and understanding of the causes of fragmentation and to help guide actors’ efforts in addressing the problems and moving to more synergistic approaches.


title: Erythema multiforme and Kawasaki disease associated with COVID‐19 infection in children

text: We read with interest the publications in the JEADV which reported dermatological manifestations associated with COVID‐19, such as pityriasis rosea, urticaria, rash, vascular signs, or chilblain‐like lesions. Herein, we report two life‐threatening cases of children presenting with fever and eruptions with mucous membrane involvement – erythema multiforme and Kawasaki disease – associated with COVID‐19.


title: Profile of international air passengers intercepted with illegal animal products in baggage at Guarulhos and Galeão airports in Brazil

text: Protection against biological material entering a country or region through airports is important because, through them, infectious agents can quickly reach exotic destinations and be disseminated. Illegal products of animal origin may contain hazardous infectious agents that can compromise animal and public health. The aim of this study was to identify associations between possession of illegal animal products in baggage and demographic characteristics of the passengers, as well as characteristics of their travel plans in the two main Brazilian international airports. A total of 457 passengers were divided into two groups: passengers identified as carrying illegal animal products and control. Passengers identified as carrying illegal animal products not stated on the accompanied baggage declaration completed a questionnaire, to aid in profiling. Nationality, origin, age and residency of passengers were analyzed using chi square, logistic regression and odds ratios. Passengers from Eastern Europe were the most likely to enter with animal products as were those aged between 35 and 55 years. When evaluating the departure point, the highest frequency was seen in those coming from Portugal. Passenger group, reasons for travel, amount and type of baggage were available only for passengers identified as carrying illegal animal products, noting that they prefer traveling alone, for leisure, bringing few bags. Such information can contribute to the early identification of passengers that have illegal animal products in baggage at Brazilian airports.


The COVID-19 Registry in Rhineland-Palatinate in the context of international registry activities documenting COVID-19 outcomes


Use of multiple laboratory tests including anti-factor Xa to optimally manage anticoagulation during ECMO


title: La transmission aérienne des agents infectieux

text: Résumé La transmission aérienne est l’une des différentes modalités de transmission des agents infectieux. Elle peut avoir lieu à partir d’une source environnementale, comme pour la légionellose. Dans des conditions particulières, elle peut avoir lieu à partir d’une source humaine. Pour un agent donné, la transmission peut emprunter plusieurs modes de transmission. C’est, par exemple, le cas de la grippe dont la transmission est à la fois aérienne, directe par les sécrétions respiratoires « postillons » et indirectes par la contamination de l’environnement. Si les infections transmises par voie aérienne peuvent être, pour certaines, transmises de personne à personne (tuberculose), elles le sont le plus souvent à partir d’une source commune faisant intervenir l’environnement. Abstract Airborne transmission is one of the different ways infectious diseases spread. Airborne transmission often has an environmental source, as for legionellosis. It can also have an infectious human source. For a given infectious agent, the mode of transmission can be multiple. This is the case for influenza that can be spread by airborne transmission but also directly through respiratory secretion and indirectly through the contaminated environment. If airborne transmission may occur from person to person, it is most often a transmission from or through the environment.


Schmallenberg Virus Infection in Dogs, France, 2012


title: On-site measurement of tracer gas transmission between horizontal adjacent flats in residential building and cross-infection risk assessment

text: Abstract Airborne transmission is a main spread mode of respiratory infectious diseases, whose frequent epidemic has brought serious social burden. Identifying possible routes of the airborne transmission and predicting the potential infection risk are meaningful for infectious disease control. In the present study, an internal spread route between horizontal adjacent flats induced by air infiltration was investigated. On-site measurements were conducted, and tracer gas technique was employed. Two measurement scenarios, closed window mode and open window mode, were compared. Using the calculated air change rate and mass fraction, the cross-infection risk was estimated using the Wells–Riley model. It found that tracer gas concentrations in receptor rooms are one order lower than the source room, and the infection risks are also one order lower. Opening windows results in larger air change rate on the one hand, but higher mass fraction on the other hand. Higher mass fraction not necessarily results in higher infection risk as the pathogen concentration in the source room is reduced by the higher air change rate. In the present study, opening windows could significantly reduce the infection risk of the index room but slightly reduce the risks in receptor rooms. The mass fraction of air originated from the index room to the receptor units could be 0.28 and the relative cross-infection risk through the internal transmission route could be 9%, which are higher than the external spread through single-sided window flush. The study implicates that the horizontal transmission route induced by air infiltration should not be underestimated.


title: Remote Learning in the Time of COVID‐19

text: With the spread of SARS‐CoV‐2 in the U.S., medical schools across the nation have taken measures to protect the health and safety of their students. Notably, most schools have elected to suspend clinical experiences for medical students as the pandemic evolves. Many schools have demonstrated creativity and adaptability by developing online, non‐clinical electives for their students to engage in.


title: H5N1 infection of the respiratory tract and beyond: a molecular pathology study

text: BACKGROUND: Human infection with avian influenza H5N1 is an emerging infectious disease characterised by respiratory symptoms and a high fatality rate. Previous studies have shown that the human infection with avian influenza H5N1 could also target organs apart from the lungs. METHODS: We studied post-mortem tissues of two adults (one man and one pregnant woman) infected with H5N1 influenza virus, and a fetus carried by the woman. In-situ hybridisation (with sense and antisense probes to haemagglutinin and nucleoprotein) and immunohistochemistry (with monoclonal antibodies to haemagglutinin and nucleoprotein) were done on selected tissues. Reverse-transcriptase (RT) PCR, real-time RT-PCR, strand-specific RT-PCR, and nucleic acid sequence-based amplification (NASBA) detection assays were also undertaken to detect viral RNA in organ tissue samples. FINDINGS: We detected viral genomic sequences and antigens in type II epithelial cells of the lungs, ciliated and non-ciliated epithelial cells of the trachea, T cells of the lymph node, neurons of the brain, and Hofbauer cells and cytotrophoblasts of the placenta. Viral genomic sequences (but no viral antigens) were detected in the intestinal mucosa. In the fetus, we found viral sequences and antigens in the lungs, circulating mononuclear cells, and macrophages of the liver. The presence of viral sequences in the organs and the fetus was also confirmed by RT-PCR, strand-specific RT-PCR, real-time RT-PCR, and NASBA. INTERPRETATION: In addition to the lungs, H5N1 influenza virus infects the trachea and disseminates to other organs including the brain. The virus could also be transmitted from mother to fetus across the placenta.


title: The treatment and follow‐up of “recurrence” with discharged COVID‐19 patients: Data from Guizhou, China

text: We reported 20 cases of discharged COVID‐19 patients whose RT‐PCR test results showed “re‐positive”. After finding “re‐positive ”, these patients were admitted to hospital for the second time and were followed up until the end of May 2020. Methods: Record detailed treatment and follow‐up process, and collect relevant data. The possible causes and potential clinical significance of this phenomenon are discussed. This article is protected by copyright. All rights reserved.


title: Development of a comprehensive infection control program for a short‐term shelter serving trafficked women

text: A shelter for trafficked women has unique infection control needs that require a comprehensive infection control plan, balancing the needs of infection prevention with respect for the vulnerable population served. Using a trauma‐informed model and evidence from infection control in other shelter settings, a group of senior baccalaureate students developed a program in a short‐term shelter for commercially sexually exploited individuals that included a written infection control manual, policies and procedures, and staff training. This partnership between academia and a nonprofit agency was an experiential service learning project in the domain of public health nursing, allowing students the opportunity to apply evidence toward a sustainable intervention for the agency.


title: Forecast Possible Risk for COVID-19 Epidemic Dissemination under Current Control Strategies in Japan

text: COVID-19 has globally spread to over 4 million people and the epidemic situation in Japan is very serious. The purpose of this research was to assess the risk of COVID-19 epidemic dissemination in Japan by estimating the current state of epidemic dissemination and providing some epidemic prevention and control recommendations. Firstly, the period from 6 January to 31 March 2020 was divided into four stages and the relevant parameters were estimated according to the imported cases in Japan. The basic reproduction number of the current stage is 1.954 (95% confidence interval (CI) 1.851–2.025), which means COVID-19 will spread quickly, and the self-healing rate of Japanese is about 0.495 (95% CI 0.437–0.506), with small variations in the four stages. Secondly, the results were applied to the actual reported cases from 1 to 5 April 2020, verifying the reliability of the estimated data using the accumulated reported cases located within the 95% confidence interval and the relative error of forecast data of five days being less than [Formula: see text]. Thirdly, considering the medical resources in Japan, the times the epidemic beds and ventilators become fully occupied are predicted as 5 and 15 May 2020, respectively. Keeping with the current situation, the final death toll in Japan may reach into the millions. Finally, based on experience with COVID-19 prevention and control in China, robust measures such as nationwide shutdown, store closures, citizens isolating themselves at home, and increasing PCR testing would quickly and effectively prevent COVID-19 spread.


title: Führen in stressigen Zeiten

text: Wie Studien regelmäßig belegen, sind Pflegende dem Risiko an psychischen Belastungen zu leiden besonders ausgesetzt. Im Rahmen der Corona-Pandemie sind diese Belastungen nun noch einmal deutlich erhöht. Am Universitätsklinikum Charité in Berlin hat deshalb eine Arbeitsgruppe Empfehlungen für Führungskräfte zur Reduktion von Stress und psy- chischer Belastung bei Pflegefachpersonen im Rahmen der aktuellen Covid-19-Pandemie zusammengestellt. Insbesondere werden die Empfehlungen der Weltgesundheitsorganisation, des Internationalen Roten Kreuzes und der Vereinten Nationen berücksichtigt.


title: Court Operations during the COVID-19 Pandemic

text: This paper reviews the distinct nature of the COVID-19 pandemic and examines the resultant court responses and recommendations disseminated by various entities that support courts. Specifically, we contextualize the current environment the present pandemic has created by considering how it compares to the most-recent previous pandemics. We then review guidelines disseminated to the courts and the modifications and innovations implemented by the courts in response to the COVID-19 pandemic. Additional challenges related to these recommendations and modifications are identified and discussed.


Ventilation non invasive et insuffisance respiratoire aiguë


title: Aminopeptidase N (CD13) as a target for cancer chemotherapy

text: The enzyme aminopeptidase N (APN, also known as CD13) is a Zn(2+) dependent membrane‐bound ectopeptidase that degrades preferentially proteins and peptides with a N‐terminal neutral amino acid. Aminopeptidase N has been associated with the growth of different human cancers and suggested as a suitable target for anti‐cancerous therapy. Different approaches have been used to develop new drugs directed to this target, including enzyme inhibitors as well as APN‐targeted carrier constructs. This review discusses the prevalence and possible function of APN in malignant diseases, mainly solid tumors, as well as its “drugability” evaluated in preclinical in vivo models, and also provides a brief overview of current clinical trials focused on APN. (Cancer Sci 2011; 102: 501–508)


title: SARS‐CoV‐2 infection in kidney transplant recipients: experience of the italian marche region

text: BACKGROUND: Infection related to Coronavirus‐19 (CoV‐2) is pandemic affecting more than 4 million people in 187 countries worldwide. By May, 10 2020 it caused more than 280.000 deaths all over the world. Preliminary data reported a high prevalence of CoV‐2 infection and mortality due to severe acute respiratory syndrome‐related to CoV‐2 (SARS‐CoV‐2) in kidney transplanted patients (KTRs). Nevertheless, the outcomes and the best treatments for SARS‐CoV‐2 affected KTRs remain unclear. METHODS: In this report we describe the clinical data, the treatments and the outcomes of 5 KTRs with SARS‐CoV‐2 admitted to our hospital in Ancona, Marche region, Italy, from March, 17 to present. Due to the severity of SARS‐CoV‐2, immunosuppression with calcineurin inhibitors, antimetabolites and mTOR‐inhibitors were stopped at the admission. All KTRs were treated with low‐dose steroids. 4/5 KTRs were treated with hydroxychloroquine. All KTRs received tocilizumab up to one dose. RESULTS: Overall, the incidence of SARS‐CoV‐2 in KTRs in the Marche region was 0.85%. 3/5 were admitted in ICU and intubated. One developed AKI with the need of CRRT with Cytosorb. At present 2 patients died, 2 patients were discharged and one is still inpatient in ICU. CONCLUSIONS: The critical evaluation of all cases suggests that the timing of the administration of tocilizumab, an interleukin‐6 receptor antagonist, could be associated with a better efficacy when administered in concomitance to the drop of the oxygen saturation. Thus, in SARS‐CoV‐2 affected KTRs a close biochemical and clinical monitoring should be set up to allow physicians to hit the virus in the right moment such as a sudden reduction of the oxygen saturation and/or a significant increase of the laboratory values such as D‐Dimer.


title: Chapter 15 Nanotechnological applications for the control of pulmonary infections

text: Abstract Pulmonary infections are the major global problem. According to the global burden of disease study, lower respiratory infections were ranked third among the leading causes of death after ischaemic heart disease and cerebrovascular disease. Despite the availability of treatment options and diagnostic methods, the severity of pulmonary infections is increasing due to the emergence of multiple drug resistance and lack of sensitivity in pathogenic microbes. In this context, nanotechnology based treatment therapies have emerged as a promising approach to circumvent the limitations of conventional therapies and also manage the problem of drug resistance in pulmonary infections. The present chapter is focused on the global status of existing management strategies of pulmonary infections and their limitations. Moreover, the role of nanotechnology for the management of pulmonary infections with a special reference to different type of nanomaterials has also been discussed.


Necessity of 45-day transesophageal echocardiography after the WATCHMAN procedure amid the COVID-19 pandemic


title: Towards treatment planning of COVID-19: Rationale and hypothesis for the use of multiple immunosuppressive agents: anti-antibodies, immunoglobulins, and corticosteroids

text: Abstract The novel coronavirus, SARS-CoV2, can cause a potentially fatal disease, COVID-19, in humans. Here, we will provide an overview of therapeutic options for COVID-19. Plasma from patients recovered from COVID-19 that contains antibodies against SARS-CoV2 has shown promising results in patients with severe COVID-19. Also, IVIG, combined with moderate-dose of corticosteroids, might improve patient outcomes. Evidence links COVID-19 to variable degrees of inflammation. Studies show that the use of corticosteroids might accelerate recovery from COVID-19. There are, however, no controlled clinical trials that show whether the use of corticosteroids can reduce COVID-19-related death. Also, the pro-inflammatory cytokine IL6 is the best-documented cytokine in COVID-19 correlated with severity, criticality, viral load, and prognosis of patients with COVID-19. Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels. Essential elements that process SARS-CoV2 cell entry and specific characteristics that allow SARS-CoV2 to escape the immune system have the potential as targets for COVID-19 therapy.


title: Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study

text: Feline infectious peritonitis (FIP) is a fatal disease with no clinically effective treatment. This field study evaluated treatment with Polyprenyl Immunostimulant (PI) in cats with the non-effusive form of FIP. Because immune suppression is a major component in the pathology of FIP, we hypothesized that treatment with an immune system stimulant would increase survival times of cats with dry FIP. Sixty cats, diagnosed with dry FIP by primary care and specialist veterinarians and meeting the acceptance criteria, were treated with PI without intentional selection of less severe cases. The survival time from the start of PI treatment in cats diagnosed with dry FIP showed that of the 60 cats with dry FIP treated with PI, 8 survived over 200 days, and 4 of 60 survived over 300 days. A literature search identified 59 cats with non-effusive or dry FIP; no cat with only dry FIP lived longer than 200 days. Veterinarians of cats treated with PI that survived over 30 days reported improvements in clinical signs and behavior. The survival times in our study were significantly longer in cats who were not treated with corticosteroids concurrently with PI. While not a cure, PI shows promise in the treatment of dry form FIP, but a controlled study will be needed to verify the benefit.


title: Application of recombinant severe fever with thrombocytopenia syndrome virus nucleocapsid protein for the detection of SFTSV-specific human IgG and IgM antibodies by indirect ELISA

text: BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that was first reported in China in 2011. It is caused by SFTS virus (SFTSV) which is a member of the Phlebovirus genus in the Bunyaviridae family. SFTSV has been classified as a BSL3 pathogen. There is a need to develop safe and affordable serodiagnostic methods for proper clinical management of infected patients. METHODS: The full length nucleocapsid (N) gene of SFTSV Yamaguchi strain was amplified by RT-PCR and cloned to an expression vector pQE30. The recombinant (r) SFTSV-N protein was expressed by using Escherichia coli (E. coli) expression system and purified under native conditions. rSFTSV-N protein based indirect IgG and IgM enzyme linked immunosorbent assay (ELISA) systems were established to detect specific human IgG and IgM antibodies, respectively. One hundred fifteen serum samples from clinically suspected-SFTS patients were used to evaluate the newly established systems and the results were compared with the total antibody detecting sandwich ELISA system. RESULTS: The native form of recombinant (r) SFTSV-N protein was expressed and purified. Application of the rSFTSV-N protein based indirect IgG ELISA to the 115 serum samples showed results that perfectly matched those of the total antibody sandwich ELISA with a sensitivity and specificity of 100 %. The rSFTSV-N protein based indirect IgM ELISA missed 8 positive samples that were detected by the total antibody sandwich ELISA. The sensitivity and specificity of rSFTSV-N-IgM capture ELISA were 90.59 and 100 %, respectively. CONCLUSIONS: The rSFTSV-N protein is highly immunoreactive and a good target for use as an assay antigen in laboratory diagnosis. Its preparation is simpler in comparison with that used for the total antibody sandwich system. Our rSFTSV-N protein-based IgG and IgM ELISA systems have the advantage of distinguishing two types of antibodies and require small volume of serum sample only. They are safe to use for diagnosis of SFTS virus infection and especially fit in large-scale epidemiological investigations.


title: The Impact of Social Media on Panic During the COVID-19 Pandemic in Iraqi Kurdistan: Online Questionnaire Study

text: BACKGROUND: In the first few months of 2020, information and news reports about the coronavirus disease (COVID-19) were rapidly published and shared on social media and social networking sites. While the field of infodemiology has studied information patterns on the Web and in social media for at least 18 years, the COVID-19 pandemic has been referred to as the first social media infodemic. However, there is limited evidence about whether and how the social media infodemic has spread panic and affected the mental health of social media users. OBJECTIVE: The aim of this study is to determine how social media affects self-reported mental health and the spread of panic about COVID-19 in the Kurdistan Region of Iraq. METHODS: To carry out this study, an online questionnaire was prepared and conducted in Iraqi Kurdistan, and a total of 516 social media users were sampled. This study deployed a content analysis method for data analysis. Correspondingly, data were analyzed using SPSS software. RESULTS: Participants reported that social media has a significant impact on spreading fear and panic related to the COVID-19 outbreak in Iraqi Kurdistan, with a potential negative influence on people’s mental health and psychological well-being. Facebook was the most used social media network for spreading panic about the COVID-19 outbreak in Iraq. We found a significant positive statistical correlation between self-reported social media use and the spread of panic related to COVID-19 (R=.8701). Our results showed that the majority of youths aged 18-35 years are facing psychological anxiety. CONCLUSIONS: During lockdown, people are using social media platforms to gain information about COVID-19. The nature of the impact of social media panic among people varies depending on an individual's gender, age, and level of education. Social media has played a key role in spreading anxiety about the COVID-19 outbreak in Iraqi Kurdistan.


title: Pneumococcal co‐infection in Covid‐19 patients

text: We would like to report our experience of 2 patients co‐infected with Streptococcus pneumoniae (S. pneumoniae) and coronavirus disease 2019 (Covid‐19) in the United Kingdom. This article is protected by copyright. All rights reserved.


title: Chapter 3 Replication and Expression Strategies of Viruses

text: Summary Regardless of their genetic constitution, viral genomes are replicated, expressed, and assembled in association with living host cells. These entities do not undergo division, but rather generate new particles through the assembly of preformed components. Some viruses go further by modifying cellular metabolism to create a more favorable environment for viral gene expression. In a few instances, these clever strategies also facilitate escape from the host’s defense responses. The process of replication is typically divided into the phases of attachment, entry, uncoating, genome replication and expression, assembly, maturation, and finally, egress or release from the host cell. In this chapter, we address genome replication and expression, including the multiple strategies that serve to control gene expression and ensure preferential propagation of the virus.


title: The use of facemasks may not lead to an increase in hand–face contact

text: Advocacy of the use of facemasks by the public as a measure against the spread of COVID‐19 is controversial, with some healthcare professionals arguing that the use of a face mask may increase the rate at which people touch their faces, due to readjusting the mask. We assessed the facial touching behaviour of bus passengers in China before and after the outbreak of COVID‐19 and found that wearing a face mask does not increase the number of hand‐face contacts and is likely, therefore, to have a positive beneficial effect on suppressing the spread of COVID‐19 within populations when used in conjunction with social distancing measures.


Intracellular Transport of the S Proteins of Coronaviruses


title: Intracellular Events and Cell Fate in Filovirus Infection

text: Marburg and Ebola viruses cause a severe hemorrhagic disease in humans with high fatality rates. Early target cells of filoviruses are monocytes, macrophages, and dendritic cells. The infection spreads to the liver, spleen and later other organs by blood and lymph flow. A hallmark of filovirus infection is the depletion of non-infected lymphocytes; however, the molecular mechanisms leading to the observed bystander lymphocyte apoptosis are poorly understood. Also, there is limited knowledge about the fate of infected cells in filovirus disease. In this review we will explore what is known about the intracellular events leading to virus amplification and cell damage in filovirus infection. Furthermore, we will discuss how cellular dysfunction and cell death may correlate with disease pathogenesis.


title: Genome-wide gene–environment interaction analysis for asbestos exposure in lung cancer susceptibility

text: Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide gene–environment interactions. To determine gene–asbestos interactions in lung cancer risk, we conducted genome-wide gene–environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P-values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P-value for the most significant SNP rs13383928 was 2.17×10(–6), which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54, located on 7q32.1 (P = 8.90×10(–5)). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene–asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk. Abbreviations: CI: confidence interval E: environment FDR: false discovery rate G: gene GSEA: gene-set-enrichment analysis GWAS: genome-wide association studies i-GSEA: improved gene-set-enrichment analysis approach OR: odds ratio SNP: single nucleotide polymorphism


title: Identifying SARS-CoV Membrane Protein Amino Acid Residues Linked to Virus-Like Particle Assembly

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) membrane (M) proteins are capable of self-assembly and release in the form of membrane-enveloped vesicles, and of forming virus-like particles (VLPs) when coexpressed with SARS-CoV nucleocapsid (N) protein. According to previous deletion analyses, M self-assembly involves multiple M sequence regions. To identify important M amino acid residues for VLP assembly, we coexpressed N with multiple M mutants containing substitution mutations at the amino-terminal ectodomain, carboxyl-terminal endodomain, or transmembrane segments. Our results indicate that a dileucine motif in the endodomain tail (218LL219) is required for efficient N packaging into VLPs. Results from cross-linking VLP analyses suggest that the cysteine residues 63, 85 and 158 are not in close proximity to the M dimer interface. We noted a significant reduction in M secretion due to serine replacement for C158, but not for C63 or C85. Further analysis suggests that C158 is involved in M-N interaction. In addition to mutations of the highly conserved 107-SWWSFNPE-114 motif, substitutions at codons W19, W57, P58, W91, Y94 or F95 all resulted in significantly reduced VLP yields, largely due to defective M secretion. VLP production was not significantly affected by a tryptophan replacement of Y94 or F95 or a phenylalanine replacement of W19, W57 or W91. Combined, these results indicate the involvement of specific M amino acids during SARS-CoV virus assembly, and suggest that aromatic residue retention at specific positions is critical for M function in terms of directing virus assembly.


title: Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children

text: BACKGROUND: Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. METHODS: In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. RESULTS: The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P<0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. CONCLUSIONS: Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine.


title: Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3‐Triazole Nucleosides

text: A new strategy for the synthesis of N (3)‐benzoylated‐ and N (3)‐benzylated N (1)‐propargylquinazoline‐2,4‐diones 30a−d and 31a−d from isatoic anhydride 41 is reported. The alkynes 30a−d and 31a−d were applied in the 1,3‐dipolar cycloadditions with azides 27 and 28 to synthesize acyclic 1,2,3‐triazole nucleosides. The obtained alkynes and 1,2,3‐triazole were evaluated for antiviral activity against a broad range of DNA and RNA viruses. The alkyne 30d showed activity against adenovirus‐2 (EC(50) = 8.3 μM), while compounds 37a and 37d were also active toward herpes simplex virus‐1 wild‐type and thymidine kinase deficient (HSV‐1 TK(−)) strains (EC(50) values in the range of 4.6–13.8 μM). In addition, compounds 30a, 30b, 37b, and 37c exhibited activity toward varicella‐zoster virus (VZV) TK(+) and TK(−) strains (EC(50) = 2.1–9.5 μM). The compound 30b proved to be the most selective against VZV and displayed marginal activity against human cytomegalovirus (HCMV). Although the compound 30a had improved anti‐HCMV activity, the increase in anti‐HCMV activity was accompanied by significant toxicity. Compounds 37a and 37d showed inhibitory effects toward the human T lymphocyte (CEM) cell line (IC(50) = 21 ± 7 and 22 ± 1 μM, respectively), while compound 35 exhibited cytostatic activity toward HMEC‐1 cells (IC(50) = 28 ± 2 μM).


title: Cathepsin L promotes secretory IgA response by participating in antigen presentation pathways during Mycoplasma Hyopneumoniae infection

text: Cathepsin L (CTSL) has been proved to help contain leishmaniasis and mycoplasma infection in mice by supporting cellular immune responses, but the regulatory functions of CTSL on mucosal immune responses haven’t been tested and remain undefined. Here, we investigated the effects of CTSL on SIgA responses and invariant chain (Ii) degradations in the co-cultured swine dendritic cells (DCs) and B cells system in vitro. When the cells system were transfected with vector CTSL-GFP or incubated with recombinant CTSL (rCTSL) before they were infected with Mycoplasma hyopneumoniae (M.hp), SIgA significantly increased and Ii chain was degraded into smaller intermediates, while SIgA decreased when CTSL was knockdown or inhibited with E64. To confirm the SIgA responses promoted by CTSL contribute to the resistance to mycoplasma pneumonia, pigs injected with rCTSL before they were challenged with M.hp, showed milder clinical symptoms and histopathological damage of lungs, less mycoplasma burden together with higher secretion of SIgA, percentages of CD4(+) T cells and level of MHC II molecules comparing with the group without rCTSL. Collectively, these results suggested that rCTSL could provide effective protection for piglets against mycoplasma pneumonia by enhancing M.hp-specific mucosal immune responses through its role in antigen presentation by processing the invariant chain.


title: Unwanted pregnancies: Publicly available information for women seeking abortion care in Ontario

text: Objectives Although abortion is common, the inability to obtain a referral and social stigma often lead women to search online for abortion information. Searches may yield relevant services but may also include Crisis Pregnancy Centres (CPCs), whose mission is to dissuade women from seeking abortions. The objective of this study was to determine the type of abortion-related resources women searching for services near their community might find. Methods We included communities in Ontario with a population over 15,000 or a general hospital. Between, 07/27/2019 and 08/06/2019, we searched the community name followed by “abortion” on the anonymous Google proxy server StartPage. The first 5 Canadian resources were categorized as: sexual health resource (<200 km, ≥200 km), abortion resource (<200 km, ≥200 km), CPC or Irrelevant/Other. Descriptive statistics were generated for search results by category and the number and percent of communities with each result category. Results There were 130 communities included. Searches yielded 648 discrete results which related to abortion services (41.9%), sexual health (10.3%) and CPCs (10.2%); 37.5% were irrelevant (news articles, unrelated services). Overall, 11.5% of communities had no sexual health or abortion resource within 200km, and 29.2% had no abortion specific resource within 200km. CPCs were among the top 5 results for 41.5% of communities. Conclusions Although relevant sexual health and abortion resources comprised almost half the search results, over 10% of communities had no local resources listed and over 40% had a listed resource that could hinder timely access to abortion care


COVID-19 Quarantine in Older People: The Need to Think About Sarcopenia-Related Phenotypes


title: Middle East respiratory syndrome–related knowledge, preventive behaviours and risk perception among nursing students during outbreak

text: AIMS AND OBJECTIVES: The aim of this study was to survey nursing students’ Middle East respiratory syndrome–related knowledge, preventive behaviours and risk perception to examine the correlations among the variables during a Middle East respiratory syndrome outbreak. BACKGROUND: Middle East respiratory syndrome is a new viral respiratory illness. Nursing students who engage in clinical practice at hospitals may have been exposed to Middle East respiratory syndrome infection during the Middle East respiratory syndrome outbreak. DESIGN: This study was a descriptive cross‐sectional survey. METHODS: Participants (n = 249) were nursing students in their third or fourth year of the programme who were engaged in clinical practice for eight hours per day at the tertiary hospitals with Middle East respiratory syndrome patients. Knowledge, preventive behaviours and risk perception related to Middle East respiratory syndrome were measured using scales developed through a preliminary survey and validity testing. RESULTS: The subjects’ knowledge level of Middle East respiratory syndrome was 84·4%; their practice of preventive behaviours was rated at 44·5%; and their risk perception rating was 2·4 out of 5. Middle East respiratory syndrome–related risk perception was significantly different according to gender and Middle East respiratory syndrome education. Middle East respiratory syndrome–related knowledge was significantly correlated with preventive behaviours and risk perception. CONCLUSION: Considering the low scores for items regarding knowledge and preventive behaviours, it is necessary to develop effective and systematic publicity and education programmes for nursing students. Enhancing Middle East respiratory syndrome–related knowledge by considering cooperation between hospitals and universities will sharpen nursing students’ risk perception of the disease and effectively increase their preventive behaviours. RELEVANCE TO CLINICAL PRACTICE: Similar to other emerging infectious diseases, Middle East respiratory syndrome outbreaks may occur in other countries. The results of this study can be used to develop and apply efficient and feasible Middle East respiratory syndrome education programmes for nursing students during Middle East respiratory syndrome outbreaks.


title: Adapting Neurosurgery Practice During The Covid-19 Pandemic In The Indian Subcontinent

text: ABSTRACT Background The COVID-19 pandemic has changed the practice of neurosurgery. Significant resources have been dedicated to it. The pandemic in the Indian subcontinent, when compared to the rest of the world, is relatively delayed. The neurosurgical practice cannot remain unaffected by hugely disruptive measures such as a lockdown. The inevitable rise in covid infections with its gradual relaxation continues to pose a risk for health care providers. Therefore, it is imperative to evaluate whether the pandemic has had a discernible effect on the same especially in terms of practice modifications in private establishments and publicly funded hospitals, the emotional impact on the surgeon, and the influence of social media on the psyche of the surgeon. Material and Methods An online questionnaire-based survey was prepared, with questions related to the COVID specific themes of precautions taken in outpatient services and operation theaters, the influence of social media, the economic loss incurred, and the perceptible impact of telemedicine and webinars. The links to the survey were mailed to neurosurgeons in private and public practice all over the country. The responses were anonymized to ensure free and unbiased answers to the survey questions. Results A total of 176 responses were received from all over the Indian Sub-Continent. The median age of respondents was 39years (range 32-70 yrs) and the post-residency experience was 7years (range 0-34 yrs). Respondents were an equitable mix of public and private practitioners. 46% of the respondents were practicing restricted outpatient services, more in public institutions (p=0.22) which also had a higher incidence of tele-outpatient services(26% vs 17%). Wearing surgical masks, N-95 masks, and gloves were the most commonly practised precautionary measures in outpatient services(>60%). While private practitioners were continuing elective cases(40%), public institutes were more cautious with only emergencies being operated(29%). The greatest fear among all practitioners was passing the infection to the family (75%). Social media was helpful for brainstorming queries and updating practice modifications, but some surgeons admitted to receiving threats upon social media platforms(37.5%). Depression and economic losses were palpable for approximately 30% neurosurgeons. Conclusion The survey highlights the perception of the neurosurgeons towards the pandemic and the difference in public-private practice. Suspension of elective procedures, severe curtailment of the regular outpatient appointments, drastic modifications of the normal OPD/OR practices and apprehensions related to inadequacy of safety provided by PPE usage and financial losses of private establishments were some of the visible themes in our survey results. Though telemedicine has not been as widely adopted as expected, yet online education has been favourably received.


title: COVID19 and Headache: A Primer for Trainees

text: OBJECTIVE: To summarize for the trainee audience the possible mechanisms of headache in patients with COVID19 as well as to outline the impact of the pandemic on patients with headache disorders and headache medicine in clinical practice. BACKGROUND: COVID19 is a global pandemic caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2, of which a large subset of patients features neurological symptoms, commonly headache. The virus is highly contagious and is, therefore, changing clinical practice by forcing the limitations of in‐person visits and procedural treatments, more quickly shifting toward the widespread adaptation of telemedicine services. DESIGN/RESULTS: We review what is currently known about the pathophysiology of COVID19 and how it relates to possible mechanisms of headache, including indirect, potential direct, and secondary causes. Alternative options for the treatment of patients with headache disorders and the use of telemedicine are also explored. CONCLUSIONS: Limited information exists regarding the mechanisms and timing of headache in patients with COVID19, though causes relate to plausible direct viral invasion of the nervous system as well as the cytokine release syndrome. Though headache care in the COVID19 era requires alterations, the improved preventive treatment options now available and evidence for feasibility and safety of telemedicine well positions clinicians to take care of such patients, especially in the COVID19 epicenter of New York City.


Planning Phase Two for Endoscopic Units in Northern Italy after the COVID-19 lockdown: an exit strategy with a lot of critical issues and a few opportunities


title: Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen

text: BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression.


title: Infectious agents associated with epizootic rabbit enteropathy: Isolation and attempts to reproduce the syndrome

text: Abstract Epizootic rabbit enteropathy (ERE), a highly lethal (30–80% mortality) disease of broiler rabbits aged 6–14 weeks, first appeared in 1997 in French intensive enclosed rabbitries and is of unknown aetiology. Bacteriological, virological and parasitical examination of the intestinal contents of rabbits that had died either in spontaneous field cases or after experimental reproduction of ERE, were undertaken in an attempt to identify infectious agents that may play a role in the disease. Two bacterial strains, Clostridium perfringens and non-enteropathogenic Escherichia coli were repeatedly isolated at high faecal counts from naturally infected animals. In field cases, a correlation between typical gross lesions of epizootic enteropathy and the presence of the alpha toxin of Cl. perfringens was observed (P <0.0001; Chi-squared test). Although attempts to reproduce the disease by inoculation with different pools of cultivable bacterial strains failed, the disease was successfully reproduced by inoculation with one French and two Belgian samples of caecal contents.


title: One Health, Vaccines and Ebola: The Opportunities for Shared Benefits

text: The 2013 Ebola virus outbreak in West Africa, as of writing, is declining in reported human cases and mortalities. The resulting devastation caused highlights how health systems, in particular in West Africa, and in terms of global pandemic planning, are ill prepared to react to zoonotic pathogens. In this paper we propose One Health as a strategy to prevent zoonotic outbreaks as a shared goal: that human and Great Ape vaccine trials could benefit both species. Only recently have two phase 2/3 Ebola human vaccine trials been started in West Africa. This paper argues for a conceptual change in pandemic preparedness. We first discuss the ethics of One Health. Next, we focus on the current Ebola outbreak and defines its victims. Third, we present the notion of a ‘shared benefit’ approach, grounded in One Health, and argue for the vaccination of wild apes in order to protect both apes and humans. We believe that a creation of such inter-species immunity is an exemplar of One Health, and that it is worth pursuing as a coextensive public health approach.


title: A retrospective study of 230 consecutive patients hospitalized for presumed travel-related illness (2000–2006)

text: A good knowledge of morbidity profiles among ill-returned travelers is necessary in order to guide their management. We reviewed the medical charts of 230 patients hospitalized in one infectious diseases department in France for presumed travel-related illnesses. The male-to-female ratio was 1.6 and the median age was 33 years (interquartile range [IQR], 25–50). Most patients (70.9%) were returning from sub-Saharan Africa. The median duration of travel was 28 days (IQR, 15–60) and the median time from return of travel to hospitalization was 13 days (IQR, 7–21). Malaria was the most frequent diagnosis (49.1%), which was especially encountered in patients returning from sub-Saharan Africa (95.6%), without adequate chemoprophylaxis (78.2%). Imported diseases at risk of secondary transmission were also diagnosed, including pulmonary tuberculosis (n = 8), viral hepatitis (n = 8), typhoid fever (n = 6), human immunodeficiency virus (HIV) (six new diagnosis), non-typhoid salmonellosis (n = 5), severe acute respiratory syndrome, and Crimean-Congo hemorrhagic fever. This study underlines the need to maintain tropical expertise for infectious diseases physicians, even in Europe.


title: Brian Charlesworth

text: Brian Charlesworth is a Senior Honorary Professorial Fellow at the University of Edinburgh. His work has involved the application of population genetics to a variety of issues in evolutionary biology. His current research is on population genetics theory, molecular evolution and genome evolution. He has published over 300 papers and three books.


title: Evidence‐Based Antimicrobial Therapy in Pregnancy: Long Overdue

text: Little evidence exists to guide the clinician caring for pregnant patients with infectious morbidities. The already‐small pool of evidence shrinks rapidly as the pathogen becomes more exotic, making therapeutic decisions increasingly speculative when emerging infectious diseases appear in the pregnant patient. The current drug approval mechanisms, legal environment, and profit‐driven drug pipeline have combined to exclude pregnant women from clinical trials, paradoxically resulting in a dangerous situation for pregnant women around the world. Clinical Pharmacology & Therapeutics (2009); 86 3, 237–238. doi:10.1038/clpt.2009.123


title: Asymptomatic COVID-19 Infection in a Child with Nasal Foreign Body

text: Abstract While children, particularly infants, are susceptible to severe and critical COVID-19 disease, over 55% of pediatric cases are present in asymptomatic or mildly symptomatic children. Aerosolized SARS-CoV-2 viral particles remain viable for up to 3 hours, raising concern about risk to healthcare workers during aerosol generating procedures (APGs) in the airway and nasopharynx. Herein we describe the first case of a nasal foreign body in an asymptomatic child with SARS-CoV-2 infection. We discuss management of this child and highlight the importance of considering asymptomatic infection and preoperative testing when planning procedures of the airway in the COVID-19 era.


title: Pan-Viral Screening of Respiratory Tract Infections in Adults With and Without Asthma Reveals Unexpected Human Coronavirus and Human Rhinovirus Diversity

text: Background. Between 50% and 80% of asthma exacerbations are associated with viral respiratory tract infections (RTIs), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood because of the limited scope and throughput of conventional viral detection methods. Methods. We investigated the capability of the Virochip, a DNA microarray—based viral detection platform, to characterize viral diversity in RTIs in adults with and without asthma. Results. The Virochip detected viruses in a higher proportion of samples (65%) than did culture isolation (17%) while exhibiting high concordance (98%) with and comparable sensitivity (97%) and specificity (98%) to pathogen-specific polymerase chain reaction. A similar spectrum of viruses was identified in the RTIs of each patient subgroup; however, unexpected diversity among human coronaviruses (HCoVs) and human rhinoviruses (HRVs) was revealed. All but one of the HCoVs corresponded to the newly recognized HCoV-NL63 and HCoV-HKU1 viruses, and >20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that formed a distinct genetic subgroup. Conclusions. The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger-scale studies will be necessary to determine whether particular substrains of viruses confer an elevated risk of asthma exacerbation.


title: Isolation of two Chinese bovine enteroviruses and sequence analysis of their complete genomes

text: In this study, RNA corresponding to bovine enterovirus (BEV) was detected in 24.6 % of faecal samples (17/69) from diarrheic and healthy cattle in six different areas in China by an RT-PCR screening method. Furthermore, two cytopathic agents, designated as BHM26 and BJ50, were isolated from the bovine diarrheic fecal samples. During passage in MA104 cells, ultrathin sections of virus-infected monolayers were examined using a transmission electron microscope, and a large number of symmetrical virus crystals were seen in the cytoplasm, with monomorphic small viral particles of 27-30 nm in diameter. The full-length RNA genomes were 7433 and 7416 nucleotides long, respectively, with a genome organization analogous to that of picornaviruses. Phylogenetic analysis of the VP1 and VP3 capsid protein coding sequences suggested that the viruses BHM26 and BJ50 belong to genotype 2 of the BEV cluster B (BEV-B). In addition, sequence comparisons of the 5′ and 3′ UTRs and P1, P2 and P3 subgenomic regions of the two isolates suggested that there were intergenotypic recombination events occurring during evolution of the BHM26 and BJ50 isolates.


title: Proteomic comparison of prostate cancer cell lines LNCaP‐FGC and LNCaP‐r reveals heatshock protein 60 as a marker for prostate malignancy

text: BACKGROUND: Androgen‐sensitive prostate cancer cell‐line LNCaP‐FGC and androgen‐resistant line LNCaP‐r constitute a model for development of androgen resistance in prostate cancer. METHODS: Proteins differently expressed in the two cell‐lines were identified by two‐dimensional (2‐D) electrophoresis and mass spectrometry. HSP60, more abundant in LNCaP‐r, was studied by RT‐PCR and immunohistochemistry in specimens of human prostate cancer. RESULTS: HSP60 was upregulated in LNCaP‐r, nm23 in LNCaP‐FGC, and titin (two isoforms) in either LNCaP‐r or LNCaP‐FGC. In non‐malignant prostate, HSP60‐staining was in the glandular compartment, particularly basal epithelial cells. In prostate cancer, most epithelial cells showed moderate‐strong staining without apparent correlation between staining intensity and Gleason grade. CONCLUSIONS: The LNCaP‐FGC/LNCaP‐r model, characterized by 2‐D electrophoresis, reveals distinct proteomic alterations. With HSP60, results from cell‐lines correlated with clinical results, indicating that this model can be used for dissection of mechanisms involved in transformation to androgen resistance and assignment of protein markers in prostate cancer. Prostate © 2006 Wiley‐Liss, Inc.


title: The evaluation of online course of Traditional Chinese Medicine for MBBS international students during the COVID-19 epidemic period

text: BACKGROUND: During the COVID-19 epidemic period, Traditional Chinese Medicine (TCM) course for international students of Medical Bachelor, Bachelor of Surgery (MBBS) program in Zhejiang University has shifted from traditional classroom to online environment. This study aimed to investigate MBBS international students’ perception on online TCM course, and to assess the online learning efficacy. METHODS: A total of 84 MBBS international students attending course of “Basic Traditional Chinese Medicine” during 2020 academic years at Zhejiang University were enrolled in this study. A quantitative questionnaire was respectively completed before and after the TCM course using a pretest–post-test design. By means of two online learning platforms, Learning in ZJU and DingTalk, TCM course was broadcast in both live and archived format to students. RESULTS: A total of 48 participants completed both baseline and follow-up questionnaires. The majority of participants preferred face-to-face classroom learning (26, 54.17% of total) when compared with online learning. Students felt that the course had brought in much benefits (mean 3.88, SD 0.87), and they were satisfied with the course content (mean 3.83, SD 0.95). Students’ TCM related knowledge and their behaviors of discussion and consulting were significantly improved by online TCM course (all P < 0.001). Students’ awareness of the necessity of TCM education and their feeling of difficulty in learning TCM were significantly strengthened (P = 0.042, 0.025, respectively). CONCLUSION: Online learning is a good alternative for TCM course of MBBS international students when classroom learning is suspended, whereas it cannot replace the need for onsite and face-to-face learning.


title: The Coronavirus E Protein: Assembly and Beyond

text: The coronavirus E protein is a small membrane protein that has an important role in the assembly of virions. Recent studies have indicated that the E protein has functions during infection beyond assembly, including in virus egress and in the host stress response. Additionally, the E protein has ion channel activity, interacts with host proteins, and may have multiple membrane topologies. The goal of this review is to highlight the properties and functions of the E protein, and speculate on how they may be related.


title: Understanding the possible origin and genotyping of first Bangladeshi SARS‐CoV‐2 strain

text: The novel coronavirus, SARS‐CoV‐2, causes the unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen, the first complete genome of the virus has very recently been published. Therefore, the long awaiting questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online‐accessed data (results) regarding those issues and presented a comprehensive picture of the typing of the virus alongside the probable origin of the sub‐clade containing Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom (UK) or other European countries epidemiologically linked to the UK. According to different genotyping classification schemes, this strain belongs to A2a clade under G major clade, is of B and/or L type, and is a SARS‐CoV‐2a sub‐strain. In the forwarding days, randomized genome data will certainly voluminate in Bangladesh, however because of globalization and immigrant movements, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical interventions. This article is protected by copyright. All rights reserved.


title: On the formation of three-dimensional flows over finite-aspect-ratio wings under tip effects

text: We perform DNS of flow over finite-aspect-ratio NACA 0015 wings to characterize the tip effects on the wake dynamics. This study focuses on the development of three-dimensional separated flow over the wing, and discuss flow structures formed on the wing surface as well as in the far field wake. Vorticity is introduced into the flow in a predominantly two-dimensional manner. The vortex sheet from the wing tip rolls up around the free end to form the tip vortex. At its inception, the tip vortex is weak and its effect is spatially confined. As the flow around the tip separates, the tip effects extend farther in the spanwise direction, generating noticeable three dimensionality in the wake. For low-aspect-ratio wings, the wake remains stable due to the strong downwash over the entire span. Increasing the aspect ratio allows unsteady vortical flow to emerge away from the tip at sufficiently high angles of attack. These unsteady vortices shed and form closed vortical loops. For higher-aspect-ratio wings, the tip effects retard the near-tip shedding process, which desynchronizes from the two-dimensional shedding over the mid-span region, yielding vortex dislocation. At high angles of attack, the tip vortex exhibits noticeable undulations due to the strong interaction with the unsteady shedding vortices. The spanwise distribution of force coefficients is related to the three-dimensional wake dynamics and the tip effects. Vortical elements in the wake that are responsible for the generation of lift and drag forces are identified through the force element analysis. We note that at high angles of attack, a stationary vortical structure forms at the leading edge near the tip, giving rise to locally high lift and drag forces. The analysis performed here reveals how the vortical flow around the tip influences the separation physics, the global wake dynamics, and the spanwise force distributions.


title: Respiratory droplet generation and dispersal during nasoendoscopy and upper respiratory swab testing

text: Respiratory particle generation and dispersal during nasoendoscopy and swab testing is studied with high‐speed video and laser light illumination. Video analysis reveals droplet formation in three manoeuvres during nasoendoscopy ‐ sneezing, vocalization, and nasal decongestion spray. A capillary bridge of mucus can be seen when a nasoendoscope exits wet nares. No droplet formation is seen during oral and nasopharyngeal swab testing. We outline the following recommendations: pull the face mask down partially and keep the mouth covered, only allowing nasal access during nasoendoscopy; avoid nasal sprays if possible; if nasal sprays are used, procedurists should be in full personal protective equipment prior to using the spray; withdrawal of swabs and scopes should be performed in a slow and controlled fashion to reduce potential dispersion of droplets when the capillary bridge of mucus breaks up.


title: Seroprevalence of Dromedary Camel HEV in Domestic and Imported Camels from Saudi Arabia

text: Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, p value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels (p value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population.


title: Middle East Respiratory Syndrome – Wann daran denken?

text: Im Juni 2012 wurde erstmals eine Infektion mit Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Saudi Arabien diagnostiziert. Seither zirkuliert das Virus weiterhin im Nahen Osten und verursacht dort immer wieder größere nosokomiale Ausbrüche. Auch nach Deutschland wurde das Virus bereits importiert. So stellt sich die Frage, wann man differenzialdiagnostisch an MERS-CoV denken sollte und welche Maßnahmen zu ergreifen sind.


title: Chapter 12 Planning and Managing Health Systems

text: Abstract Health systems are complex organizations. They are often the largest single employer in a country, with expenditures of public and private money of 4–17 percent of gross domestic product. Overall and individual facility management requires mission statements, objectives, targets, budgets, activities planning, human interaction, services delivery, and quality assurance. Health organization involves a vast complex of stakeholders and participants, suppliers and purchasers, regulators and direct providers, and individual patients, and their decision-making. These include pyramidal and network organizations and ethical decision-making based on public interest, resource allocations, priority selection, and assurance of certain codes of law and ethical conduct. This chapter discusses how complex organizations work, with potential for application in health, and the motivations of workers and of the population being served. Organization theory helps in devising methods to integrate relevant factors to become more effective in defining and achieving goals and missions.


title: Use of corticosteroids in asthma and COPD patients with or without COVID-19

text: The potential detrimental effects of steroids on the immune system to fight viral infections had always been a concern for patients on long term steroids in chronic conditions. A recent warning from WHO on systemic corticosteroid use amid COVID-19 raised suspicion among public and healthcare professionals regarding the safety of steroid use during the SARS-CoV-2 pandemic. The corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients and any unsolicited changes in medications use may lead to potentially severe exacerbations and risk patient lives. This article provides a critical review of clinical evidence and offers a detailed discussion on the safety and efficacy of corticosteroids in asthma and COPD patients, both with and without COVID-19.


title: Is Nigeria prepared and ready to respond to the COVID-19 pandemic in its conflict-affected northeastern states?

text: Northeastern Nigeria has over the decade suffered from the Boko Haram insurgency and is still in the process of recovery from the complex humanitarian crisis that has displaced and subjected millions of vulnerable children, women and elderly population to poverty, disease outbreaks, hunger and malnutrition. Yet, the conflict-affected states in Northeastern Nigeria is not far away from being the worse-hit by the COVID-19 pandemic if urgent public health preventive measures are not taken to contain the spread of the deadly and highly infectious virus. The question arises, “what is Nigeria doing to tackle the burden of a COVID-19 spread and an ongoing humanitarian crisis?


title: Gender, Judicatory Respect and Pastors’ Well-Being in Closing Churches

text: This study of over 130 clergy in five old-line Protestant denominations (Episcopal, Lutheran, United Methodist, Presbyterian and UCC) who dissolved their congregations examines the relationships of gender, judicatory respect and pastors’ well-being in their experience of closing a church and vocational transition afterwards; respondents completed a written survey and most also participated in in-depth interviews. Survey results show significant gender differences in the experience of respect from and satisfaction with relationships with the middle administrative part of the wider church called here the judicatory (e.g., synod, conference, diocese or presbytery), and with the experience of stress after their churches closed. Women clergy experienced greater loneliness and isolation, financial strain and thinking that closure affected their job search; their job search was also significantly longer than that of men. Respectful judicatory relationships are negatively related to many but not all vocational stresses. Comparisons with the experience of secular professionals suggest the stigma of closing a church adversely affects women clergy’s vocational journey more than men’s. The paper closes with implications for judicatory support of clergy leading churches to closure.


title: World Economic Prospects Monthly

text: Overview: Coronavirus to cut global growth to new lows ▀ The rapid spread of coronavirus will weaken China's GDP growth sharply in the short term, causing disruption for the rest of the world. We now expect global GDP growth to slow to just 1.9% y/y in Q1 this year and have lowered our forecast for 2020 as a whole from 2.5% to 2.3%, down from 2.6% in 2019. ▀ Prior to the coronavirus outbreak, there had been signs that the worst was over for both world trade and the manufacturing sector. However, this tentative optimism has been dashed by the current disruption. ▀ While the near‐term impact of the virus is uncertain, the disruption to China will clearly be significant in Q1 – we expect Chinese GDP growth to plunge to just 3.8% y/y. Even though growth there will rebound in Q2 and Q3, it will take time for the loss in activity to be fully recovered and we now expect GDP growth of just 5.4% for 2020 as a whole, a downward revision of 0.6pp from last month. ▀ Weaker Chinese imports and tourism and disruption to global supply chains will take a toll on the rest of the world, particularly in the Asia‐Pacific region. And the shock will exacerbate the ongoing slowdown in the US and may result in the eurozone barely expanding for a second quarter running in Q1. ▀ Weaker oil demand in the short term has prompted us to lower our Brent oil price forecast. We have cut our projection for growth in crude demand in 2020 by 0.2m b/d to 0.9 mb/d and now forecast Brent crude will average $62.4pb in 2020, down from about $65pb in our January forecast. ▀ Quarterly global growth is likely to strengthen a little in H2 this year as the disruption fades and firms make up for the lost output earlier in the year and the effect of China's policy response starts to feed through. But for 2020 overall, global growth is now likely to be just 2.3%, 0.2pp weaker than previously assumed as a result of the epidemic.


title: Chapter 23 Enzymatic Production of Steviol Glucosides Using β-Glucosidase and Their Applications

text: Abstract Sweet leaf, Stevia rebaudiana Bertoni, is a perennial plant species widely known for its sweet-tastingent-kaurene type diterpenoid glycosides (steviol glucosides). Steviol glucosides include rubusoside (Ru), stevioside (Ste), and rebaudioside (Reb), which have immunomodulatory capability and protective effects against hyperglycemia, hypertension, inflammation, tumors, and diarrhea. In addition, they can enhance the solubility of epotoside, liquiritin, paclitaxel, curcuminoids, quercetin, and wheat bran flavonoids, thus increasing their permeability. The hydrolysis of three glucosyl groups at positions C13 and C19 of Ste will produce steviolbioside, steviol, isosteviol, steviol mono-glucoside, or Ru. S. rebaudiana contains these hydrolyzed products in trace amounts. This chapter describes recent advances in the preparation of various steviol glycosides from Ste by using different β-glycosidases, with particular focus on their potential industrial applications as natural solubilizers of insoluble compounds. Furthermore, the reaction mechanism of β-glycosidases and their kinetic properties are summarized.


title: Discovery of a novel canine respiratory coronavirus support genetic recombination among betacoronavirus1

text: Abstract Although canine respiratory coronavirus (CRCoV) is an important respiratory pathogen that is prevalent in many countries, only one complete genome sequence of CRCoV (South Korea strain K37) has been obtained to date. Genome-wide analyses and recombination have rarely been conducted, as small numbers of samples and limited genomic characterization have previously prevented further analyses. Herein, we report a unique CRCoV strain, denoted strain BJ232, derived from a CRCoV-positive dog with a mild respiratory infection. Phylogenetic analysis based on complete genome of all available coronaviruses consistently show that CRCoV BJ232 is most closely related to human coronavirus OC43 (HCoV-OC43) and BCoV, forming a separate clade that split off early from other Betacoronavirus 1. Based on the phylogenetic and SimPlot analysis we propose that CRCoV-K37 was derived from genetic recombination between CRCoV-BJ232 and BCoV. In detail, spike (S) gene of CRCoV-K37 clustered with CRCoV-BJ232. However orf1ab, membrane (M) and nucleocapsid (N) genes were more related to Bovine coronavirus (BCoV) than CRCoV-B232. Molecular epidemic analysis confirmed the prevalence of CRCoV-BJ232 lineage around the world for a long time. Recombinant events among Betacoronavirus 1 may have implications for CRCoV transmissibility. All these findings provide further information regarding the origin of CRCoV.


title: Correlation between antimicrobial consumption and incidence of health-care-associated infections due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci at a university hospital in Taiwan from 2000 to 2010

text: Objectives This study was conducted to investigate the correlation between antibiotic consumption and the incidence of health-care-associated infections (HCAIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) (HCAI-MRSA) and vancomycin-resistant enterococci (VREs) (HCAI-VREs) at a university hospital in Taiwan during the period from 2000 to 2010. Methods Data on annual patient-days and annual consumption (defined daily dose/1000 patient-days) of glycopeptides (vancomycin and teicoplanin), linezolid, fusidic acid, tigecycline, and daptomycin were analyzed. Yearly aggregated data on the number of nonduplicate clinical MRSA and VRE isolates causing HCAI were collected. Results Overall, the consumption of teicoplanin and linezolid significantly increased during the study period. A significant decrease in the incidence of HCAI-MRSA and a significant increase in the incidence of HCAI-VRE were found during the study period. A significant correlation was found between the increased use of teicoplanin and linezolid and the decreased incidence of HCAI-MRSA. By contrast, positive correlations were found between the consumption of teicoplanin and tigecycline and the incidence of HCAI-VRE. Conclusion This study identified various correlations between the consumption of antibiotics and the incidence of HCAI-MRSA and HCAI-VRE. Strict implementation of infection-control guidelines and reinforcement of administering appropriate antibiotic agents would be helpful in decreasing the incidence of MRSA and VRE in hospitals.


title: Protection for Otolaryngologic Surgery in the COVID-19 Pandemic

text: OBJECTIVE: The coronavirus disease 2019 (COVID-19) has placed unprecedented challenges on the world and the medical community. It is transmitted through droplets, contact, the fecal-oral route, and airborne transmission under certain conditions that allow droplets to combine with air particles to form an aerosol. Viral loads are higher in the nasal area and similar in symptomatic and asymptomatic patients. Medical situations have been classified into high and low risk of generating aerosols. Most procedures and surgery in otolaryngology correspond to high-risk medical situations. This review aims to gather the vast amount of available information and generate recommendations for different surgical procedures according to aerosolization risk and COVID-19 status, with use of specific personal protective equipment in each case. DATA SOURCES: PubMed, MEDLINE, and Embase. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, and Food and Drug Administration. REVIEW METHODS: We conducted a review on the literature on personal protective equipment for otolaryngologic surgery and surgical indication restrictions during the COVID-19 pandemic. CONCLUSIONS: SARS-CoV-2 is an easily transmitted virus. Asymptomatic and symptomatic patients with COVID-19 present an upper airway high viral load, conferring otolaryngologic procedures a high risk of aerosolization. Surgical procedures must be categorized according to aerosolization risk and the possibility of COVID-19 diagnosis, according to use of personal protective equipment. IMPLICATIONS FOR PRACTICE: This review contributes to scientific knowledge regarding the detailed description of protective personal equipment and, most important, surgical recommendations to reduce the risk of infection in the otolaryngology community during the COVID-19 pandemic.


How to risk-stratify elective surgery during the COVID-19 pandemic?


title: The Future of Business Education: A Commentary in the Shadow of the Covid-19 Pandemic

text: The Covid-19 pandemic has disrupted business schools worldwide mainly through the shift to emergency remote teaching. I provide a rudimentary framework to understand this transformation through recognizing the changes in the university, the business world and the student. This disruption is going to lead to a decade-long technology-led remaking of business education. Finally, I share a triphasic model that maps the evolution of online learning in business schools.


title: Pigment production by cold-adapted bacteria and fungi: colorful tale of cryosphere with wide range applications

text: Pigments are an essential part of everyday life on Earth with rapidly growing industrial and biomedical applications. Synthetic pigments account for a major portion of these pigments that in turn have deleterious effects on public health and environment. Such drawbacks of synthetic pigments have shifted the trend to use natural pigments that are considered as the best alternative to synthetic pigments due to their significant properties. Natural pigments from microorganisms are of great interest due to their broader applications in the pharmaceutical, food, and textile industry with increasing demand among the consumers opting for natural pigments. To fulfill the market demand of natural pigments new sources should be explored. Cold-adapted bacteria and fungi in the cryosphere produce a variety of pigments as a protective strategy against ecological stresses such as low temperature, oxidative stresses, and ultraviolet radiation making them a potential source for natural pigment production. This review highlights the protective strategies and pigment production by cold-adapted bacteria and fungi, their industrial and biomedical applications, condition optimization for maximum pigment extraction as well as the challenges facing in the exploitation of cryospheric microorganisms for pigment extraction that hopefully will provide valuable information, direction, and progress in forthcoming studies.


title: Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage

text: Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.


title: Particulate air pollution on cardiovascular mortality in the tropics: impact on the elderly

text: BACKGROUND: Air pollution has a significant health impact. Most data originate from temperate regions. We aim to study the health impact of air pollution, particularly among the elderly, in a tropical region. METHODS: A daily time-series analysis was performed to estimate excess risk (ER) of various air pollutants on daily death counts amongst the general population in Singapore from 2001 to 2013. Air pollutants included particulate matters smaller than 10 μm, and 2.5 μm (PM(10), PM(2.5)), carbon monoxide (CO), nitrogen dioxide (NO(2)), ozone (O(3)) and sulphur dioxide (SO(2)). The studied outcomes were non-accidental and cardiovascular mortality. Single-day lag and distributed lag models were studied and adjusted for confounders. RESULTS: In single-day lag models, a 10 μg/m(3) increase in particulate matter was associated with significant increases in non-accidental (PM(10) ER: 0.627%; 95% confidence interval (CI): 0.260–0.995% and PM(2.5) ER: 0.660%; 95% CI: 0.204–1.118%) and cardiovascular mortality (PM(10) ER: 0.897; 95% CI: 0.283–1.516 and PM(2.5) ER: 0.883%; 95% CI: 0.121–1.621%). This was significant in the elderly ≥ 65 years but not in those < 65 years and were seen in the acute phase of lag 0-5 days. Effects by other pollutants were minimal. For cardiovascular mortality, the effects turned protective at a cumulative lag of 30 days in the elderly and could due to “harvesting”. CONCLUSIONS: These first contemporary population-based data from an equatorial country with tropical climate show that exposure to particulate air pollution was significantly associated with non-accidental mortality and cardiovascular mortality, especially in the elderly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12940-019-0476-4) contains supplementary material, which is available to authorized users.


title: Pathogenesis of Middle East respiratory syndrome coronavirus

text: Human coronaviruses (CoVs) mostly cause a common cold that is mild and self‐limiting. Zoonotic transmission of CoVs such as the recently identified Middle East respiratory syndrome (MERS)‐CoV and severe acute respiratory syndrome (SARS)‐CoV, on the other hand, may be associated with severe lower respiratory tract infection. This article reviews the clinical and pathological data available on MERS and compares it to SARS. Most importantly, chest radiographs and imaging results of patients with MERS show features that resemble the findings of organizing pneumonia, different from the lesions in SARS patients, which show fibrocellular intra‐alveolar organization with a bronchiolitis obliterans organizing pneumonia‐like pattern. These findings are in line with differences in the induction of cytopathological changes, induction of host gene responses and sensitivity to the antiviral effect of interferons in vitro when comparing both MERS‐CoV and SARS‐CoV. The challenge will be to translate these findings into an integrated picture of MERS pathogenesis in humans and to develop intervention strategies that will eventually allow the effective control of this newly emerging infectious disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Aminopeptidase N Knockout Pigs Are Not Resistant to Porcine Epidemic Diarrhea Virus Infection


title: Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination

text: BACKGROUND: DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)-associated malignancies. However, DNA vaccines suffer from limited immunogenicity and thus strategies to enhance DNA vaccine potency are needed. We have previously demonstrated that for DNA vaccines encoding HPV-16 E7 antigen (CRT/E7) linkage with calreticulin (CRT) linked enhances both the E7-specific CD8(+) T cell immune responses and antitumor effects against E7-expressing tumors. In the current study, we aim to introduce an approach to elicit potent CD4(+) T cell help for the enhancement of antigen-specific CD8(+) T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. RESULT: We showed that co-administration of vectors containing codon-optimized bovine papillomavirus type 1 (BPV-1) L1 and L2 in combination with DNA vaccines could elicit enhanced antigen-specific CD8(+) in both CRT/E7 and ovalbumin (OVA) antigenic systems. We also demonstrated that co-administration of vectors expressing BPV-1 L1 and/or L2 DNA with CRT/E7 DNA led to the generation of L1/L2-specific CD4(+) T cell immune responses and L1-specific neutralizing antibodies. Furthermore, we showed that co-administration with DNA encoding BPV1 L1 significantly enhances the therapeutic antitumor effects generated by CRT/E7 DNA vaccination. In addition, the observed enhancement of CD8(+) T cell immune responses by DNA encoding L1 and L2 was also found to extend to HPV-16 L1/L2 system. CONCLUSION: Our strategy elicits both potent neutralizing antibody and therapeutic responses and may potentially be extended to other antigenic systems beyond papillomavirus for the control of infection and/or cancer.


title: Aerosol Risk with Noninvasive Respiratory Support in Patients with COVID‐19

text: OBJECTIVES: This study evaluates aerosol production with high flow nasal cannula (HFNC) and noninvasive positive pressure ventilation (NIPPV) compared to six liters per minute by low‐flow nasal cannula. METHODS: Two healthy volunteers were randomized to control (six liters per minute by low‐flow nasal cannula), NIPPV, or HFNC using block randomization. NIPPV conditions were studied using continuous positive airway pressures of 5, 10, and 15 cm H(2)O with an FiO(2) of 1.0 delivered via full‐face mask. HFNC conditions included flow rates of 30 and 40 liters per minute with an FiO(2) of 1.0 with and without coughing. HFNC and low‐flow nasal cannula conditions were repeated with and without participants wearing a surgical mask. Six aerosol sizes (0.3, 1.0, 2.5, 5, and 10 μm) and total aerosol mass were measured at two feet and six feet from the participant's nasopharynx. RESULTS: There was no significant difference in aerosol production between either HFNC or NIPPV and control. There was also no significant difference with the use of procedural mask over the HFNC. There was significant variation between the two participants, but in neither case was there a difference compared to control. There was an aerosol‐time trend, but there does not appear to be a difference between either flow rate, pressure, or control. Furthermore, there was no accumulation of total aerosol particles over the total duration of the experiment in both HFNC and NIPPV conditions. CONCLUSIONS: HFNC and NIPPV did not increase aerosol production compared to six liters per minute by low‐flow nasal cannula in this experiment involving healthy volunteers. This article is protected by copyright. All rights reserved


title: DA rats from two colonies differ genetically and in their arthritis susceptibility

text: The arthritis-susceptible DA rat is one of the most commonly used rat strains for genetic linkage analysis and is instrumental for the identification of many genetic loci. Even though DA rats were kept as inbred lines at different institutes and suppliers, it became obvious that the various breeding stocks differed genetically. To be able to compare the results from different linkage studies it is very import to verify the genetic background of the substrains used in those studies. We performed a genetic and phenotypic analysis of two DA substrains, DA/ZtmRhd and DA/OlaHsd, and found several genetic differences. One of the allelic differences between the DA/ZtmRhd and the DA/OlaHsd strain was located at rat chromosome 3, a 17-Mb large fragment, including the peak marker of a previously identified quantitative trait locus (QTL) for collagen-induced arthritis, Cia11. In addition, the substrains exhibited a significant difference in the susceptibility to pristane-induced arthritis (PIA) and disease severity of collagen-induced arthritis and PIA. However, by generating and testing a congenic line, we could demonstrate that phenotypic differences were not due to the contaminating fragment on chromosome 3. Nevertheless, we conclude that DA substrains show distinct genetic differences and caution should be taken when comparing arthritis data from different DA substrains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-008-9125-x) contains supplementary material, which is available to authorized users.


SARS-CoV-2–Positive Sputum and Feces After Conversion of Pharyngeal Samples in Patients With COVID-19


TREADING LIGHTLY IN A PANDEMIC: #ZENTENSIVIST REFLECTIONS ON COVID-19


Urgencias quirúrgicas no relacionadas con la pandemia COVID-19. Caso clínico: Hernia interna yeyunal complicada con necrosis intestinal en el ligamento ancho utero-ovárico (LAUO)


title: Prevalence and phylogenetic analysis of canine kobuviruses in diarrhoetic dogs in northeast China

text: Canine kobuviruses (CaKVs) are newly recognized picornaviruses that have been recently detected in dogs in the U.S.A., Italy, U.K., the Republic of Korea and Tanzania. To trace the evolution of CaKV strains, a total of 201 fecal samples from rectal swabs of diarrheic dogs, which were obtained from May 2014 to April 2015 in northeast China, were detected by reverse transcription-PCR targeting a partial (504 bp) fragment of the 3D gene. Furthermore, a phylogenetic analysis of the CaKV strains identified in northeast China was conducted based on the partial 3D gene sequence. The results indicated that 36 fecal samples (17.91%, 36/201) were positive for CaKV, in which the co-infection rates of canine coronavirus, canine parvovirus-2 and canine bocavirus were 58.33%, 41.67%, and 11.11%, respectively. Sequence comparison of the partial 3D gene revealed nucleotide homologies of 94.4–100%, 95.6–98.6%, 94.3–97.6%, 94.4–96.3% and 93.3–95.1% within the 36 Chinese CaKV strains, and between the 36 Chinese CaKV strains and four CaKV reference strains from South Korea, Italy, U.S.A. and Tanzania, respectively. A phylogenetic tree revealed that the 36 Chinese CaKV strains formed one specific CaKV lineage with CaKVs that have recently been identified in other countries. The 36 Chinese CaKV strains were closely related to CaKV reference strains from Asia and Europe, but differed genetically from CaKV reference strains from North America and Africa. This study provides evidence that CaKVs circulate in diarrhoetic dogs in China and that they exhibit substantial genetic diversity and high co-infection rates with other enteric viruses.


title: 7 Pretravel Considerations for Non-vaccine-Preventable Travel Infections

text: Abstract Pretravel advice should be tailored to the individual following a thorough review of his or her itinerary, planned activities, and host characteristics. In addition to vaccinations and malaria chemoprophylaxis, a pretravel consultation should include advice on regionally endemic or emerging non–vaccine-preventable infections that can cause severe illness or chronic morbidity. These include mosquito-borne infections such as dengue, chikungunya, and Zika, and regionally endemic severe respiratory infections such as Middle East respiratory syndrome (MERS) and some strains of avian influenza. Zika virus is notable given its capacity for sexual transmission and association with congenital birth defects. Preventive advice for other potentially relevant infections associated with specific exposures or activities (e.g., schistosomiasis and leptospirosis from freshwater exposure) should be provided where relevant. Understanding the epidemiology and prevention of these infections is crucial to providing a comprehensive pretravel consultation.


title: Response to The challenges of diagnosing heparin‐induced thrombocytopenia in patients with COVID‐19

text: We thank May et al for their comments, expanding the number of reported cases of suspected and confirmed heparin‐induced thrombocytopenia (HIT) associated with COVID‐19, and reemphasizing the complexity of the prothrombotic state observed (1). We agree that false‐positive enzyme immunoassay (EIA) detection of anti‐platelet factor 4 (PF4)/heparin antibodies could explain the results we observed in patients #2 and #3 (2), and this has been the conventional interpretation when functional testing (such as the serotonin‐release assay [SRA]) returns negative. We suggested that a false negative SRA result could have explained our findings, as opposed to the contention by May et al that we concluded they were falsely positive, to broaden our discussion about SRA‐negative HIT, a relatively new and evolving clinical condition (3‐6).


Symmetric peripheral polyarthritis developed during SARS-CoV-2 infection


Commentary: COVID-19 and Obesity: Exploring Biologic Vulnerabilities, Structural Disparities, and Weight Stigma


Hypovitaminosis D and COVID-19: Matter of Concern in India?


title: Viral Metagenomics on Cerebrospinal Fluid

text: Identifying the causative pathogen in central nervous system (CNS) infections is crucial for patient management and prognosis. Many viruses can cause CNS infections, yet screening for each individually is costly and time-consuming. Most metagenomic assays can theoretically detect all pathogens, but often fail to detect viruses because of their small genome and low viral load. Viral metagenomics overcomes this by enrichment of the viral genomic content in a sample. VIDISCA-NGS is one of the available workflows for viral metagenomics, which requires only a small input volume and allows multiplexing of multiple samples per run. The performance of VIDISCA-NGS was tested on 45 cerebrospinal fluid (CSF) samples from patients with suspected CNS infections in which a virus was identified and quantified by polymerase chain reaction. Eighteen were positive for an RNA virus, and 34 for a herpesvirus. VIDISCA-NGS detected all RNA viruses with a viral load >2 × 10(4) RNA copies/mL (n = 6) and 8 of 12 of the remaining low load samples. Only one herpesvirus was identified by VIDISCA-NGS, however, when withholding a DNase treatment, 11 of 18 samples with a herpesvirus load >10(4) DNA copies/mL were detected. Our results indicate that VIDISCA-NGS has the capacity to detect low load RNA viruses in CSF. Herpesvirus DNA in clinical samples is probably non-encapsidated and therefore difficult to detect by VIDISCA-NGS.