title: The World Health Organization (WHO) approach to healthy ageing

text: The ageing of the global population is the most important medical and social demographic problem worldwide. The World Health Organization (WHO) has defined healthy ageing as a process of maintaining functional ability to enable wellbeing in older age. The WHO, Member States and Partners for Sustainable Development Goals have created a Global Strategy and Action Plan for Ageing and Health for 2016–2020 and its continuation with the WHO programme The Decade of Healthy Ageing 2020–2030. The WHO has established main priorities such as supporting country planning and action, collecting better global data and promoting research on healthy ageing, aligning health systems to the needs of older people, laying the foundations and ensuring the human resources necessary for long-term integrated care, undertaking a global campaign to combat ageism, and enhancing the global network for age-friendly cities and communities. There are several reports of coordinated preventive health and social health initiatives in well developed countries. However, there is little evidence on the application of the active ageing frameworks in developing countries. Greater national capacities and closer monitoring of the progress through age-disaggregated data is needed to effectively implement the intended programmes on healthy ageing.


title: Coordination and resource-related difficulties encountered by Quebec's public health specialists and infectious diseases/medical microbiologists in the management of A (H1N1) - a mixed-method, exploratory survey

text: BACKGROUND: In Quebec, the influenza A (H1N1) pandemic was managed using a top-down style that left many involved players with critical views and frustrations. We aimed to describe physicians' perceptions - infectious diseases specialists/medical microbiologists (IDMM) and public health/preventive medicine specialists (PHPMS) - in regards to issues encountered with the pandemics management at the physician level and highlight suggested improvements for future healthcare emergencies. METHODS: In April 2010, Quebec IDMM and PHPMS physicians were invited to anonymously complete a web-based learning needs assessment. The survey included both open-ended and multiple-choice questions. Descriptive statistics were used to report on the frequency distribution of multiple choice responses whereas thematic content analysis was used to analyse qualitative data generated from the survey and help understand respondents' experience and perceptions with the pandemics. RESULTS: Of the 102 respondents, 85.3% reported difficulties or frustrations in their practice during the pandemic. The thematic analysis revealed two core themes describing the problems experienced in the pandemic management: coordination and resource-related difficulties. Coordination issues included communication, clinical practice guidelines, decision-making, roles and responsibilities, epidemiological investigation, and public health expert advisory committees. Resources issues included laboratory resources, patient management, and vaccination process. CONCLUSION: Together, the quantitative and qualitative data suggest a need for improved coordination, a better definition of roles and responsibilities, increased use of information technologies, merged communications, and transparency in the decisional process. Increased flexibility and less contradiction in clinical practice guidelines from different sources and increased laboratory/clinical capacity were felt critical to the proper management of infectious disease emergencies.


title: Allergy and asthma in children and adolescents during the COVID outbreak: What we know and how we could prevent allergy and asthma flares

text: Coronavirus disease 2019 (COVID-19) pandemic is affecting people at any age with a more severe course in patients with chronic diseases or comorbidities, males and elderly patients. The Center for Disease Control and Prevention (CDC) initially proposed that patients with chronic lung diseases, including moderate-severe asthma, and allergy may have a higher risk of developing severe COVID-19 than otherwise healthy people (https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/asthma.html).


title: Chapter 4 Method of Ending Disease and the Future Medical System

text: Abstract The characteristics of disease changed with the arrival of the age of chronic diseases. Now, we observe a spectrum of diverse diseases that cannot be properly managed with a simple strategy developed in the age of infectious diseases. Because our living environment changes so quickly, the response of the human body, such as the genes or epigenetic program, cannot keep up with it if we continue the current strategy. We need to find a way to enable adaptation of the human body program to change. Medical education should also be changed to focus on the harmony and balance of complexly entangled systems. Addressing such a need for changes, “systems medicine” is a new approach to achieving breakthroughs in disease prevention and treatment by obtaining and using fairly comprehensive information, such as molecular-, gene-, and cell-level information, as well as lifestyle, clinical, physiological, and environmental information.


title: Dynamic modeling of cellular response to DNA damage based on p53 stress response networks

text: Abstract Under acute perturbations from the outside, cells can trigger self-defensive mechanisms to fight against genome stress. To investigate the cellular response to continuous ion radiation (IR), a dynamic model for p53 stress response networks at the cellular level is proposed. The model can successfully be used to simulate the dynamic processes of double-strand breaks (DSBs) generation and their repair, switch-like ataxia telangiectasia mutated (ATM) activation, oscillations occurring in the p53-MDM2 feedback loop, as well as toxins elimination triggered by p53 stress response networks. Especially, the model can predict the plausible outcomes of cellular response under different IR dose regimes.


title: Celebrating TB day at the time of COVID-19

text: March 24th, the tuberculosis (TB) day, is the global call to raise awareness, celebrate successes and remind the world that TB is still the N°1 killer among the infectious causes of death [1]. TB is preventable and curable disease, and its control is a highly cost-effective health intervention. However, diagnostic delay and inadequate treatment contribute to the severity and mortality of the disease as well as the risk of transmission and development of drug resistance. Despite the fact that TB disproportionately impacts low- and middle- income countries, it does not spare any country in the world including those in the European Union/European Economic Area where more than 4000 of people still die for the disease every year [2]. Moreover, the high number of multidrug-resistant (MDR)-TB cases in some countries of the World Health Organization (WHO) European Region poses a growing public health threat. Despite the sheer numbers, TB has for too long been overshadowed by HIV and malaria, and currently by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) epidemic.


title: COVID-19 and Religious Congregations: Implications for Spread of Novel Pathogens

text: Abstract COVID-19 pandemic is ravaging the world. One of the principle preventive strategies is practicing social distancing. Congregations of the faithful at local and transnational level are strongly recommended by several world religions and religious orders. Gathering of large number of people in close approximation could be a fertile ground for the spread of novel pathogens. The refusal to suspend such gatherings could lead to potential widespread dispersal of infections.


title: The potential influence of human parainfluenza viruses detected during hospitalization among critically ill patients in Kuwait, 2013–2015

text: BACKGROUND: The four types of human parainfluenza viruses (PIV) are important causes of community-acquired pneumonia, particularly in children; however, limited information exists about the incidence of PIV in critically ill patients. The aim of this study is to describe the spectrum, incidence and clinical features of PIV-associated infections diagnosed during the hospital stay of patients admitted to pediatric intensive care unit (PICU) and intensive care unit (ICU) of 5 medical centers across Kuwait. METHODS: This was a population-based, retrospective study from 2013 to 2015. Specimens were analyzed by molecular methods. This analysis was performed using the database of Virology Unit, Mubarak Al-Kabeer Hospital. Data from 1510 admitted patients with suspected respiratory viral infections was extracted. RESULTS: The database contained a total of 39 (2.6%) patients infected with PIV (53.8% male and 46.2% females) and 20 (51.3%) were under 1 year of age. The most frequently isolated type was type 3 (28, 71.8%) followed by type 1 (9, 23.1%). At admission the most common clinical diagnosis was pneumonia in 12 patients (30.8%, p < 0.05) followed by bronchiolitis in 10 patients (25.6%). CONCLUSION: PIV plays an important yet unrecognized role in the outcomes of PIUC and ICU patients. Our results contribute to the limited epidemiologic data of PIV in PIUC and ICU in this region.


title: Psychological and Behavioral Responses in South Korea During the Early Stages of Coronavirus Disease 2019 (COVID-19)

text: Background: The psychological and behavioral responses during the early stage of Coronavirus disease 2019 (COVID-19) in South Korea were investigated to guide the public as full and active participants of public health emergency preparedness (PHEP), which is essential to improving resilience and reducing the population’s fundamental vulnerability. Methods: Data were collected through an online survey four weeks after the Korea Centers for Disease Control and Prevention (KCDC) confirmed the first case in South Korea; 973 subjects were included in the analysis. Results: Respondents’ perceived risk of COVID-19 infection; the majority of respondents reported that their perceived chance of infection was “neither high nor low” (51.3%). The average perceived severity score was higher than perceived susceptibility; 48.6 % reported that the severity would be “high,” while 19.9% reported “very high.” Many respondents reported taking precautions, 67.8% reported always practicing hand hygiene, and 63.2% reported always wearing a facial mask when outside. Approximately 50% reported postponing or canceling social events, and 41.5% were avoiding crowded places. Practicing precautionary behaviors associated strongly with perceived risk and response efficacy of the behavior. Conclusions: Our study confirmed the significance of the psychological responses, which associated with behavioral responses and significantly influenced the public’s level of public health emergency preparedness regarding the COVID-19 pandemic. This result has consequences not only for implementing public health strategies for the pandemic but also for understanding future emerging infectious diseases.


title: Endoscopic nasopharyngoscopy and ENT specialist safety in the COVID 19 era: the back endoscopy approach to the patient

text: PURPOSE: To propose a way to safely perform endoscopic nasopharyngoscopy in ENT outpatient clinic during the COVID-19 pandemic. METHODS: This manuscript highlights the importance of endoscopy in daily ENT clinical practice, which is a pivotal procedure in the diagnosis of many head and neck pathologies. However, since the beginning of the COVID-19 outbreak, the authors have witnessed a drastic reduction (91%) in the use of endoscopic nasopharyngoscopy at their institutions. In fact, it is considered at risk of contamination for healthcare professionals, as any upper airway manipulation procedure. RESULTS: In the “Back approach to the patient” for endoscopic nasopharyngoscopy, the operator positions himself behind the patient and faces the monitor. The endoscopist, not being positioned in front of the patient, should, therefore, be less exposed to airborne transmission of SARS-CoV-2 virus. CONCLUSION: This simple variation of the physician’s position during endoscopic nasopharyngoscopy could potentially reduce the risk of contagion since the operator is not in the trajectory of droplets and/or aerosols.


title: Obesity is Associated with Increased Risk for Mortality Among Hospitalized Patients with COVID‐19

text: OBJECTIVE: Obesity has been identified as a risk factor for severe COVID‐19 caused by the SARS‐CoV2 virus, however a direct association with mortality has not been reported. We sought to determine whether obesity is a risk factor for mortality among COVID‐19 patients. METHODS: The study was a retrospective cohort, including patients with COVID‐19 between March 1 and April 18, 2020. The primary objective was to determine if obesity is a predictor of mortality. RESULTS: A total of 238 patients were included, 218 patients (91.6%) were African American, 113 (47.5%) were male, and the mean age was 58.5 years. Of the included patients, 146 (61.3%) were obese (BMI >30kg/m(2)), with 63 (26.5%), 29 (12.2%), and 54 (22.7%) with class 1, 2, and 3 obesity, respectively. Obesity was identified as a predictor for mortality (OR 1.7(1.1‐2.8),p=0.016), as was male gender (OR 5.2(1.6‐16.5),p=0.01) and older age (OR 3.6(2.0‐6.3),p<0.0005). Obesity (OR 1.7(1.3‐2.1),p<0.0005) and older age (OR 1.3(1.0‐1.6),p=0.03) were also risk factors for hypoxemia. CONCLUSIONS: Obesity was found to be a significant predictor for mortality among inpatients with COVID‐19 after adjusting for age, gender, and other comorbidities. Patients with obesity were also more likely to present with hypoxemia.


The impact of COVID-19 on HIV financing in Nigeria: a call for proactive measures


title: Haplotypic diversity in human CEACAM genes: effects on susceptibility to meningococcal disease

text: Adhesion between the opacity-associated adhesin (Opa) proteins of Neisseria meningitidis and human carcino-embryonic antigen cell adhesion molecule (CEACAM) proteins is an important stage in the pathogenesis of meningococcal disease, a globally important bacterial infection. Most disease is caused by a small number of meningococcal genotypes known as hyperinvasive lineages. As these are also carried asymptomatically, acquisition of them alone cannot explain why only some hosts develop meningococcal disease. Our aim was to determine whether genetic diversity in CEACAM is associated with susceptibility to meningococcal disease. Frequency distributions of alleles, genotypes and haplotypes were compared in four CEACAM genes in 384 case samples and 190 controls. Linkage disequilibrium among polymorphic sites, haplotype structures and relationships were also analysed. A number of polymorphisms were observed in CEACAM genes but the diversity of CEACAM1, to which most Opa proteins bind, was lower, and a small number of high-frequency haplotypes were detected. Dose-dependent associations of three CEACAM haplotypes with meningococcal disease were observed, with the effect of carrying these haplotypes amplified in homozygous individuals. Two haplotypes were protective while one haplotype in CEACAM6 was associated with a twofold increase in disease susceptibility. These data imply that human CEACAM may be one determinant of human susceptibility to meningococcal disease.


title: Nitric oxide synthase Type II expression by different cell types in MHV-JHM encephalitis suggests distinct roles for nitric oxide in acute versus persistent virus infection

text: Abstract Intranasal inoculation with mouse hepatitis virus strain JHM (MHV-JHM) results in acute meningoencephalitis. We found NOS II mRNA expression in brains of acutely infected animals on days 5 through 7 after infection. In situ hybridization and immunohistochemistry demonstrated NOS II message and protein in infiltrating macrophages. Persistent infection with MHV-JHM results in chronic demyelinating encephalomyelitis. NOS II mRNA was detected in persistently infected spinal cords. In situ hybridization and immunohistochemistry showed expression of NOS II in astrocytes in and around demyelinated lesions. These results suggest the role of NO release in acute versus persistent infection with this virus, and its contribution to the resulting pathology, may be different.


title: Type I and III Interferon in the Gut: Tight Balance between Host Protection and Immunopathology

text: The intestinal mucosa forms an active interface to the outside word, facilitating nutrient and water uptake and at the same time acts as a barrier toward the highly colonized intestinal lumen. A tight balance of the mucosal immune system is essential to tolerate harmless antigens derived from food or commensals and to effectively defend against potentially dangerous pathogens. Interferons (IFN) provide a first line of host defense when cells detect an invading organism. Whereas type I IFN were discovered almost 60 years ago, type III IFN were only identified in the early 2000s. It was initially thought that type I IFN and type III IFN performed largely redundant functions. However, it is becoming increasingly clear that type III IFN exert distinct and non-redundant functions compared to type I IFN, especially in mucosal tissues. Here, we review recent progress made in unraveling the role of type I/III IFN in intestinal mucosal tissue in the steady state, in response to mucosal pathogens and during inflammation.


title: Umgang mit psychischer Belastung bei Gesundheitsfachkräften im Rahmen der Covid-19-Pandemie

text: BACKGROUND: In the current COVID-19 pandemia, health workers from all professions are facing great challenges in coping with the crisis. In this situation health professionals are confronted with specific stressors and risks not only for the physical but also for the mental health. OBJECTIVE: This article summarizes the first recommendations for the reduction of stress and psychological burden in health professionals during the current COVID-19 pandemia. METHODS: The recommendations of the World Health Organization, the United Nations and the International Red Cross Society are summarized. Recommendations for the reduction of stress and psychological distress in health professionals as well as important factors that team leaders can consider in order to reduce psychological distress in employees are presented. RESULTS: The normalization of strong emotions and stress, the fulfillment of basic needs, social support, clear communication and distribution of tasks, flexible working hours and the utilization of psychosocial and psychological help without stigmatization seem to be particularly important measures. CONCLUSION: This article presents guidelines for health professionals and team leaders in healthcare that help to maintain mental health during the COVID-19 pandemia.


title: Reducing aerosol dispersion by High Flow Therapy in COVID‐19: High Resolution Computational Fluid Dynamics Simulations of Particle Behavior during High Velocity Nasal Insufflation with a Simple Surgical Mask

text: OBJECTIVE: All respiratory care represents some risk of becoming an Aerosol Generating Procedure (AGP) during COVID‐19 patient management. Personal Protective Equipment (PPE) and Environmental Control/Engineering is advised. High Velocity Nasal Insufflation (HVNI) and High Flow Nasal Cannula (HFNC) deliver High Flow Oxygen (HFO) therapy, established as a competent means of supporting oxygenation for acute respiratory distress patients, including that precipitated by COVID‐19. Although unlikely to present a disproportionate particle dispersal risk, AGP from HFO continues to be a concern. Previously, we published a preliminary model. Here, we present a subsequent high‐resolution simulation (higher complexity/reliability) to provide a more accurate and precise particle characterization on the effect of surgical masks on patients during HVNI, Low‐Flow Oxygen therapy (LFO2), and tidal breathing. METHODS: This in‐silico modeling study of HVNI, LFO2, and tidal breathing presents ANSYS Fluent Computational Fluid Dynamics simulations that evaluate the effect of Type I surgical mask use over patient face on particle/droplet behavior. RESULTS: This in‐silico modeling simulation study of HVNI (40L∙min(‐1)) with a simulated surgical mask suggests 88.8% capture of exhaled particulate mass in the mask, compared to 77.4% in LFO2 (6L∙min(‐1)) capture, with particle distribution escaping to the room (>1m from face) lower for HVNI+Mask versus LFO2+Mask (8.23% versus 17.2%). The overwhelming proportion of particulate escape was associated with mask‐fit designed model gaps. Particle dispersion was associated with lower velocity. CONCLUSIONS: These simulations suggest employing a surgical mask over the HVNI interface may be useful in reduction of particulate mass distribution associated with AGPs. This article is protected by copyright. All rights reserved


title: The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-κB activity by blocking ubiquitination mediated proteasomal degradation of IκBα in human hepatoma cells

text: BACKGROUND: Nuclear factor kappa B (NF-κB) is a key transcription factor that plays a crucial role in host survival during infection by pathogens. Therefore, it has been a priority of many pathogens to manipulate the cellular NF-κB activity in order to create a favorable environment for their survival inside the host. RESULTS: We observed that heterologous expression of the open reading frame 2 (ORF2) protein in human hepatoma cells led to stabilization of the cellular I kappa B alpha (IκBα) pool, with a concomitant reduction in the nuclear localization of the p65 subunit of NF-κB and inhibition of NF-κB activity. Although basal or TPA induced phosphorylation of IκBα was not altered, its ubiquitination was markedly reduced in ORF2 expressing cells. Further analysis revealed that ORF2 protein could directly associate with the F-box protein, beta transducin repeat containing protein (βTRCP) and ORF2 over expression resulted in reduced association of IκBα with the SKP1 and CUL1 components of the SCF(βTRCP) complex. Chromatin immunoprecipitation (ChIP) assay of the proximal promoter regions of MHC-I heavy chain and IL-8 genes using p65 antibody and LPS stimulated ORF2 expressing cell extract revealed decreased association of p65 with the above regions, indicating that ORF2 inhibited p65 binding at endogenous promoters. CONCLUSIONS: In this report we suggest a mechanism by which ORF2 protein of HEV may inhibit host cell NF-κB activity during the course of a viral infection.


title: A nonlinear epidemiological model considering asymptotic and quarantine classes for SARS CoV-2 virus

text: In this article, we develop a mathematical model considering susceptible, exposed, infected, asymptotic, quarantine/isolation and recovered classes as in case of COVID-19 disease. The facility of quarantine/isolation have been provided to both exposed and infected classes. Asymptotic individuals either recovered without undergo treatment or moved to infected class after some duration. We have formulated the reproduction number for the proposed model. Elasticity and sensitivity analysis indicates that model is more sensitive towards the transmission rate from exposed to infected classes rather than transmission rate from susceptible to exposed class. Analysis of global stability for the proposed model is studied through Lyapunov’s function.


title: The effect of age on mortality in patients with Covid-19: a metanalysis with 611,583 subjects

text: ABSTRACT Objectives Initial data on Covid-19 infection has pointed out a special vulnerability of elderly people. Design we performed a meta-analysis with available national reports at May 7th 2020 from China, Italy, Spain, United Kingdom and New York State. Analyses were performed by a random effects model and sensitivity analyses were performed for the identification of potential sources of heterogeneity. Setting and Participants: covid-19 positive patients reported in literature and national reports. Measures all-cause mortality by age. Results A total of 611,1583 subjects were analyzed and 141,745 (23.2%) had age ≥80. The percentage of octogenarians was different in the 5 registries being the lowest in China (3.2%) and the highest and the highest in UK and New York State. The overall mortality rate was 12.10% and it varied widely between countries being the lowest in China (3.1%) and the highest in UK (20.8%) and New York State (20.99%). Mortality was <1.1% in patients with age <50 and it increased exponentially after that age in the 5 national registries. As expected, the highest mortality rate was observed in patients ≥80 years old. All age groups had significantly higher mortality compared to the inmediatelly younger age group. The largest increase in mortality risk was observed in patients with age 60-69 compared to 50-59 (OR: 3.13 95% CI 2.61-3.76). Conclusions and implications this metanalysis with more than half-million of Covid-19 patients from different countries highlights the determinant effect of age on mortality with the relevant thresholds on age >50 and, especially, >60. Elderly patients should be priorized in the implementation of preventive measures.


title: Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned

text: Unexplained pneumonia (UP) caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) emerged in China in late December 2019 and has infected more than 9000 cases by 31 January 2020. Shanghai reported the first imported case of COVID-19 (Coronavirus Disease 2019) in 20 January 2020. A combinative approach of real-time RT–PCR, CRISPR-based assay and metagenomic next-generation sequencing (mNGS) were used to diagnose this unexplained pneumonia patient. Real-time RT–PCR and CRISPR-based assay both reported positive. This sample belonged to Betacoronavirus and shared a more than 99% nucleotide (nt) identity with the Wuhan SARS-CoV-2 isolates. We further compared pros and cons of common molecular diagnostics in UP. In this study, we illustrated the importance of combining molecular diagnostics to rule out common pathogens and performed mNGS to obtain unbiased potential pathogen result for the diagnosis of UP.


title: Covid-19 pandemic and the skin - What should dermatologists know?

text: Abstract The World has changed dramatically since the COVID-19 pandemic began. Together with our social, occupational, and personal life, the new corona virus poses novel challenges for all physicians, including dermatologists. Despite the virus not being dermatotropic, several skin conditions have emerged, mainly as a result of prolonged contact to personal protective equipment and excessive personal hygiene. Pressure injury, contact dermatitis, itch, pressure urticaria, and exacerbation of pre-existing skin diseases, including seborrheic dermatitis and acne, have been described. We have focused on the dermatologic aspects of COVID-19 infection, so that dermatologist may be aware of the skin complications and the preventive measures to be taken in the COVID-19 pandemic.


title: Obesity and diabetes as high‐risk factors for severe coronavirus disease 2019 (COVID‐19)

text: The outbreak of the coronavirus disease 2019 (Covid‐19) has become an evolving worldwide health crisis. With the rising prevalence of obesity and diabetes has come an increasing awareness of their impacts on infectious diseases, including increased risk for various infections, post‐infection complications and mortality from critical infections. Although epidemiological and clinical characteristics of Covid‐19 have been constantly reported, no article has systematically illustrated the role of obesity and diabetes in Covid‐19, or how Covid‐19 affects obesity and diabetes, or special treatment in these at‐risk populations. Here, we present a synthesis of the recent advances in our understanding of the relationships between obesity, diabetes and Covid‐19 along with the underlying mechanisms, and provide special treatment guidance for these at‐risk populations.


title: Which dermatology patients attend to Dermatology Outpatient Clinics during the SARS‐CoV‐2 outbreak in Turkey and what happened to them?

text: Coronavirus disease, first emerged in Wuhan, rapidly spread all over the world since December 2019. There are concerns about elective dermatology appointments and its results. Herein, we aimed to find out which type of dermatologic patients attended to dermatology outpatient clinic. The patients visiting the clinics for elective dermatologic diseases between March 11 and 18, 2020, were included in this study. Their age, sex, diagnosis of disease, requirement for emergent intervention, and their medical records about COVID‐19 were obtained. There were 390 patients attending to the dermatology outpatient clinic in this period. The most common disease was acne (N: 94, 24%), only 19% of patients need emergent interventions or dose adjustment. There were 40 (10%) patients over the age of 65. After their visits, five patients were diagnosed as COVID‐19 in 2weeks. Dermatologic examinations may be a vector for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission since being closed to the patient. Five of our patients were diagnosed as COVID‐19 after their elective visit to hospital. Since the asymptomatic course of some young patients, most of our patients were not screened for COVID‐19. Our findings support the concerns of elective physician examinations.


title: RNA pseudoknots

text: Abstract RNA pseudoknots result from Watson-Crick base pairing involving a stretch of bases located between paired strands and a distal single-stranded region. Recently, significant advances in our understanding of their structural and functional aspects have been accomplished. At the structural level, modelling and NMR studies have shown that a defined subset of pseudoknots may be considered as tertiary motifs in RNA foldings. At the functional level, there is evidence that the realm of functions encompassed by RNA pseudoknots extends from the control of translation in prokaryotes, retroviruses and coronaviruses to the control of catalytic activity in ribozymes and the control of replication in some plant viruses.


A surge in methanol poisoning amid COVID-19 pandemic: why is this occurring?


title: Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices

text: Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR) amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed.


title: Vibrio vulnificus in aquariums is a novel threat to marine mammals and public health

text: Vibrio vulnificus is a Gram‐negative, curved, obligate halophilic marine bacterium that exclusively exists in coastal seawaters. Previous studies revealed that V. vulnificus is one of the most dangerous foodborne zoonotic pathogens for human beings. However, it remains unknown whether marine mammals can be infected by V. vulnificus. In May 2016, a captive spotted seal (Phoca largha) died due to septicemia induced by V. vulnificus. Upon post‐mortem examination, V. vulnificus was isolated, identified, and named as BJ‐PH01. Further analysis showed that BJ‐PH01 belongs to biotype 1 and the Clinical genotype. Furthermore, we performed an epidemiological investigation of V. vulnificus in six aquariums in northern China. As a result, V. vulnificus was successfully isolated from all investigated aquariums. The positive rates ranged from 20% to 100% in each investigated aquarium. During the investigation, 12 strains of V. vulnificus were isolated, and all 12 isolates were classified into biotype 1. Eleven of the 12 isolates belonged to the Clinical genotype, and one isolate belonged to the Environmental genotype. All 12 isolated V. vulnificus strains showed limited antibiotic resistance. Overall, our work demonstrated that V. vulnificus is frequently distributed in aquariums, thus constituting a threat to captive marine mammals and to public health.


title: ITP flare with mild COVID‐19 infection in pregnancy: A case report

text: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is the third zoonotic coronavirus to be identified in humans during the twenty‐first century, after severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV)(Coronaviridae Study Group of the International Committee on Taxonomy,of Viruses, 2020). The resultant disease, Coronavirus Disease (COVID‐19) (WHO, 2020), was first identified in December 2019 in Wuhan, Hubei province, China (WHO, 2020) and rapidly evolved into a pandemic (WHO, 2020) within months. In the UK, the first confirmed case was identified in late January 2020 and the first COVID‐19 related death was recorded in March 2020 (UK Government, 2020).


title: Proteomic analysis of sheep primary testicular cells infected with bluetongue virus

text: Bluetongue virus (BTV) causes a non‐contagious, arthropod‐transmitted disease in wild and domestic ruminants, such as sheep. In this study, we used iTRAQ labeling coupled with LC‐MS/MS for quantitative identification of differentially expressed proteins in BTV‐infected sheep testicular (ST) cells. Relative quantitative data were obtained for 4455 proteins in BTV‐ and mock‐infected ST cells, among which 101 and 479 proteins were differentially expressed at 24 and 48 h post‐infection, respectively, indicating further proteomic changes during the later stages of infection. Ten corresponding genes of differentially expressed proteins were validated via real‐time RT‐PCR. Expression levels of three representative proteins, eIF4a1, STAT1 and HSP27, were further confirmed via western blot analysis. Bioinformatics analysis disclosed that the differentially expressed proteins are primarily involved in biological processes related to innate immune response, signal transduction, nucleocytoplasmic transport, transcription and apoptosis. Several upregulated proteins were associated with the RIG‐I‐like receptor signaling pathway and endocytosis. To our knowledge, this study represents the first attempt to investigate proteome‐wide dysregulation in BTV‐infected cells with the aid of quantitative proteomics. Our collective results not only enhance understanding of the host response to BTV infection but also highlight multiple potential targets for the development of antiviral agents.


title: Early Introduction and Delayed Dissemination of Pandemic Influenza, Gabon

text: Active surveillance in health care centers in Gabon during 2009–2011 detected 72 clinical cases of pandemic (H1N1) 2009 (pH1N1). We found that pH1N1 virus was introduced in mid-2009 but spread throughout the country in 2010. Thus, Gabon was also affected by pH1N1.


Correction to Lancet Neurol 2020; 19: 481–82


title: Identification of host factors involved in coronavirus replication by quantitative proteomics analysis

text: In this study, we applied a quantitative proteomic approach, based on SILAC, to investigate the interactions of coronaviruses with the secretory pathway of the host cell, with the aim to identify host factors involved in coronavirus replication. Comparison of the protein profiles of Golgi‐enriched fractions of cells that were either mock infected or infected with mouse hepatitis virus revealed the significant depletion or enrichment of 116 proteins. Although ribosomal/nucleic acid binding proteins were enriched in the Golgi‐fractions of mouse hepatitis virus‐infected cells, proteins annotated to localize to several organelles of the secretory pathway were overrepresented among the proteins that were depleted from these fractions upon infection. We hypothesized that proteins, of which the abundance or distribution is affected by infection, are likely to be involved in the virus life cycle. Indeed, depletion of a small subset of the affected proteins by using small interfering RNAs identified several host factors involved in coronavirus infection. Transfection of small interfering RNAs targeting either C11orf59 or Golgi apparatus glycoprotein 1 resulted in increased virus replication, whereas depletion of vesicle‐trafficking protein vesicle‐trafficking protein sec22b enhanced the release of infectious progeny virus. Overexpression of these proteins, on the other hand, had a negative effect on virus replication. Overall, our study shows that the SILAC approach is a suitable tool to study host–pathogen interactions and to identify host proteins involved in virus replication.


title: Identifying and managing osteoporosis before and after COVID-19: rise of the remote consultation?

text: SUMMARY: The COVID-19 pandemic is influencing methods of healthcare delivery. In this short review, we discuss the evidence for remote healthcare delivery in the context of osteoporosis. INTRODUCTION: The COVID-19 pandemic has undoubtedly had, and will continue to have, a significant impact on the lives of people living with, and at risk of, osteoporosis and those caring for them. With osteoporosis outpatient and Fracture Liaison Services on pause, healthcare organisations have already moved to delivering new and follow-up consultations remotely, where staffing permits, by telephone or video. METHODS: In this review, we consider different models of remote care delivery, the evidence for their use, and the possible implications of COVID-19 on osteoporosis services. RESULTS: Telemedicine is a global term used to describe any use of telecommunication systems to deliver healthcare from a distance and encompasses a range of different scenarios from remote clinical data transfer to remote clinician-patient interactions. Across a range of conditions and contexts, there remains unclear evidence on the acceptability of telemedicine and the effect on healthcare costs. Within the context of osteoporosis management, there is some limited evidence to suggest telemedicine approaches are acceptable to patients but unclear evidence on whether telemedicine approaches support informed drug adherence. Gaps in the evidence pertain to the acceptability and benefits of using telemedicine in populations with hearing, cognitive, or visual impairments and in those with limited health literacy. CONCLUSION: There is an urgent need for further health service evaluation and research to address the impact of remote healthcare delivery during COVID-19 outbreak on patient care, and in the longer term, to identify acceptability and cost- and clinical-effectiveness of remote care delivery on outcomes of relevance to people living with osteoporosis.


title: Emerging bacterial pathogens: the past and beyond

text: Abstract Since the 1950s, medical communities have been facing with emerging and reemerging infectious diseases, and emerging pathogens are now considered to be a major microbiologic public health threat. In this review, we focus on bacterial emerging diseases and explore factors involved in their emergence as well as future challenges. We identified 26 major emerging and reemerging infectious diseases of bacterial origin; most of them originated either from an animal and are considered to be zoonoses or from water sources. Major contributing factors in the emergence of these bacterial infections are: (1) development of new diagnostic tools, such as improvements in culture methods, development of molecular techniques and implementation of mass spectrometry in microbiology; (2) increase in human exposure to bacterial pathogens as a result of sociodemographic and environmental changes; and (3) emergence of more virulent bacterial strains and opportunistic infections, especially affecting immunocompromised populations. A precise definition of their implications in human disease is challenging and requires the comprehensive integration of microbiological, clinical and epidemiologic aspects as well as the use of experimental models. It is now urgent to allocate financial resources to gather international data to provide a better understanding of the clinical relevance of these waterborne and zoonotic emerging diseases.


Known SARS‐CoV‐2 infections: The tip of an important iceberg


title: Role of Inflammation in Suicide: From Mechanisms to Treatment

text: Suicidal behavior is complex and manifests because of a confluence of diverse factors. One such factor involves dysregulation of the immune system, which has been linked to the pathophysiology of suicidal behavior. This review will provide a brief description of suicidality and discuss the contribution of upstream and downstream factors in the etiology of suicidal behavior, within the contextual framework of inflammation. The contribution of inflammatory conditions such as traumatic brain injury, autoimmune disorders, and infections to neuropsychiatric symptoms and suicidality is only beginning to be explored. We will summarize studies of inflammation in the etiology of suicide, and provide a neurobiological basis for different mechanisms by which inflammation might contribute to the pathophysiology. Finally, we will review treatments that affect upstream and downstream pathways related to inflammation in suicidality.


title: Human Rights during COVID-19 pandemic. The issue of Female Genital Mutilations

text: Abstract While SARS-CoV-2 has infected millions and claimed more than 250,000 lives, experts are warning that the impact of other diseases neglected due to the pandemic may be just as significant in the months and years to come. Specifically, when health systems are overwhelmed, and people refrain from visiting health facilities due to movement restrictions or fears about illness exposure, both direct mortality and indirect mortality from preventable and treatable conditions increase.1-3 Female genital mutilation (FGM), also named female genital cutting, is acknowledged as a violation of human rights of women.4 The United Nations Sustainable Development Goals called for the elimination of the practice by 2030.5 FGM is referred to as any procedure involving the alteration or excision of external female genitalia without medical indication,6 and 3 million women in the world are estimated to be at risk of undergoing this procedure annually.6 It is a major public health problem in several countries in Africa and Middle East,6,7 being almost universal in seven African countries (prevalence >85%).6 A report from UNICEF highlighted how this practice is still being widely carried out in 29 countries in Africa and in Middle East, despite the fact that at least 24 of these countries have legislation or some form of decrees against FGM.8 However, some evident progress is ongoing: under the new FGM amendment to the criminal law in Sudan that was approved very recently (22 April 2020), anyone who performs FGM either inside a medical establishment or elsewhere faces three years' imprisonment and fine. 9 Studies conducted in different settings have clearly showed an adverse effect of FGM on psychological, sexual and reproductive health unfavourable outcomes. 10 This includes posttraumatic stress disorder,11 dyspareunia and genitourinary complications. Adverse obstetric outcomes, such as increased risk for caesarean delivery, episiotomy and postpartum haemorrhage, are also more frequent.12 Scar tissue, especially in women with FGM type III (infibulation) can result in obstructed labour or obstetric trauma.13 It is known that in situations of conflicts and disaster, gender inequality, gender-based violence and violation of human rights are likely to increase, as protection and health system are disrupted, leaving acts of violence unpunished and condoned by the societies. This applies to health emergencies as well, including the current COVID-19 pandemic. FGM, early marriage and violence against women and girls are life-threatening, health and human rights challenge, due to the inequal relations, and patriarchal rules.14 Survivors are left no choice or right of determination over their bodies, physical, and sexual and reproductive health. Estimates provided by Avenir Health, Johns Hopkins University (USA) and Victoria University (Australia) predict that significant levels of lockdown-related disruption over 6 months may cause significant delays in programmes to end female genital mutilation, potentially leading to around 2 million more cases of FGM over the next decade than would otherwise have occurred.15 These striking figures become even more daunting when compounded with the expected additional 31 million cases of gender-based violence and the 13 million more child marriages over the next 10 years.15 Support to continued access to reproductive health care services and protection of the rights and dignity of all women and girls remains even more critical in contexts such as the current pandemic. To do so, preparedness and response plans must incorporate and integrate Female Genital Mutilation in Gender-Based Violence, and Sexual and Reproductive Health Programmes, including in community awareness initiatives and activities, thus ensuring risk mitigation as well as remote and mobile case management.


title: When Epidemics Collide: Coronavirus Disease 2019 (COVID-19) and the Opioid Crisis

text: COVID-19 could cause infection in persons with opioid use disorder, increase opioid overdose rates, reverse system-level gains in expanding access to medication for opioid use disorder, halt critical research, and prevent exacting legal reparations against opioid manufacturers. The authors call for urgent action to counteract these risks.


title: A confirmed severe case of human infection with avian-origin influenza H7N9: A case report

text: A male patient, aged 77 years, was admitted to hospital with the chief complaint of persistent hyperpyrexia that had presented for four days. The patient also suffered from hypoxemia, and a large white shadow in the left lung was observed on a chest radiograph, indicating inflammation. No therapeutic effect was observed with anti-infection treatment. The patient admitted a history of direct contact with live chickens two weeks prior to hospital admission. The day after admission to the Jingnan District Centre Hospital of Shanghai (Shanghai, China), the patient was diagnosed with severe H7N9 avian influenza infection by nasopharyngeal swab and blood sampling detection. Although the patient received anti-infective drugs, intubated assisted ventilation and circulation support, the condition of the patient continued to rapidly deteriorate. Oxygen saturation decreased and gastrointestinal bleeding occurred, with the body temperature fluctuating between 39 and 40°C. By day 6 after admission, the patient presented with circulatory failure, with liver and renal failure. On day 7, the blood pressure of the patient was unable to be measured, and the patient was diagnosed with multiple organ dysfunction. Subsequently, clinical death was declared with the patient exhibiting asystole and no spontaneous breathing.


title: Guidelines for the Laboratory Diagnosis of Middle East Respiratory Syndrome Coronavirus in Korea

text: The recent outbreak of Middle East respiratory syndrome (MERS) in Korea was unexpected that laboratory response had to be built up urgently during the outbreak. The outbreak was almost all healthcare-associated, which was aggravated by lack of availability in laboratory diagnosis of MERS-CoV on site. On behalf of the MERS joint public and private sector response committee (MERS Joint committee), the Korean Society for Laboratory Medicine (KSLM) launched a MERS response task force (MERS KSLM TF) to facilitate clinical laboratories set up MERS molecular diagnosis. MERS TF established guidelines for laboratory diagnosis of MERS-CoV and provided it to all participating laboratories as the official guidance of MERS Joint committee. This guideline was used for procedure manual of molecular diagnosis of MERS-CoV and laboratory safety manual.


Sports activities during any pandemic lockdown


Virtual Learning during the COVID-19 Pandemic: A Disruptive Technology in Graduate Medical Education


title: Inbred Strain Variant Database (ISVdb): A Repository for Probabilistically Informed Sequence Differences Among the Collaborative Cross Strains and Their Founders

text: The Collaborative Cross (CC) is a panel of recently established multiparental recombinant inbred mouse strains. For the CC, as for any multiparental population (MPP), effective experimental design and analysis benefit from detailed knowledge of the genetic differences between strains. Such differences can be directly determined by sequencing, but until now whole-genome sequencing was not publicly available for individual CC strains. An alternative and complementary approach is to infer genetic differences by combining two pieces of information: probabilistic estimates of the CC haplotype mosaic from a custom genotyping array, and probabilistic variant calls from sequencing of the CC founders. The computation for this inference, especially when performed genome-wide, can be intricate and time-consuming, requiring the researcher to generate nontrivial and potentially error-prone scripts. To provide standardized, easy-to-access CC sequence information, we have developed the Inbred Strain Variant Database (ISVdb). The ISVdb provides, for all the exonic variants from the Sanger Institute mouse sequencing dataset, direct sequence information for CC founders and, critically, the imputed sequence information for CC strains. Notably, the ISVdb also: (1) provides predicted variant consequence metadata; (2) allows rapid simulation of F1 populations; and (3) preserves imputation uncertainty, which will allow imputed data to be refined in the future as additional sequencing and genotyping data are collected. The ISVdb information is housed in an SQL database and is easily accessible through a custom online interface (http://isvdb.unc.edu), reducing the analytic burden on any researcher using the CC.


title: A Mini-Review of Adverse Lung Transplant Outcomes Associated With Respiratory Viruses

text: Due to their overall immunocompromised state, lung transplant recipients (LTRs) are at increased risk for the development of viral respiratory infections compared to the general population. Such respiratory infections often lead to poor transplant outcomes. We performed a systematic review of the last 30 years of medical literature to summarize the impact of specific respiratory viruses on LTRs. After screening 2,150 articles for potential inclusion, 39 manuscripts were chosen for final review. We found evidence for an association of respiratory viruses including respiratory syncytial virus (RSV), parainfluenza virus, and influenza viruses with increased morbidity following transplant. Through the literature search, we also documented associations of RSV and adenovirus infections with increased mortality among LTRs. We posit that the medical literature supports aggressive surveillance for respiratory viruses among this population.


Intergenerational Digital Engagement: A Way to Prevent Social Isolation During the COVID‐19 Crisis


title: Chapter 779 Birnavirus VP4 Processing Endopeptidase

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 779 is Birnavirus VP4 Processing Endopeptidase. Keywords Autoproteolytic proteinase release, birnavirus, α/β fold, multifunctional proteinase, narrow substrate specificity, polyprotein processing, RNA virus, replication control, serine-lysine proteinase, virion formation control.


title: Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy

text: This study aimed to analyse trends in notifiable infectious diseases in China, in their historical context. Both English and Chinese literature was searched and diseases were categorised according to the type of disease or transmission route. Temporal trends of morbidity and mortality rates were calculated for eight major infectious diseases types. Strong government commitment to public health responses and improvements in quality of life has led to the eradication or containment of a wide range of infectious diseases in China. The overall infectious diseases burden experienced a dramatic drop during 1975–1995, but since then, it reverted and maintained a gradual upward trend to date. Most notifiable diseases are contained at a low endemic level; however, local small-scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re-emerged since the 1990s and has become prevalent in the country. Sexually transmitted infections are in a rapid, exponential growth phase, spreading from core groups to the general population. Together human immunodeficiency virus (HIV), they account for 39% of all death cases due to infectious diseases in China in 2008. Zoonotic infections, such as severe acute respiratory syndrome (SARS), rabies and influenza, pose constant threats to Chinese residents and remain the most deadly disease type among the infected individuals. Therefore, second-generation surveillance of behavioural risks or vectors associated with pathogen transmission should be scaled up. It is necessary to implement public health interventions that target HIV and relevant coinfections, address transmission associated with highly mobile populations, and reduce the risk of cross-species transmission of zoonotic pathogens.


title: Cirugía de cardiopatías congénitas en España durante el estado de alarma por COVID-19

text: Resumen Introducción-objetivos: Vivimos tiempos excepcionales inmersos en la pandemia causada por el nuevo coronavirus SARS-CoV2. Aunque tanto la afectación clínica pediátrica como de pacientes con cardiopatías congénitas son infrecuentes, la atención prioritaria de los adultos COVID-19 prácticamente ha colapsado nuestro sistema sanitario. En consecuencia, toda actividad habitual se ha minimizado durante este período. En este trabajo analizamos la reducción de nuestra cirugía de CC durante estos 2-meses de estado de alerta sanitaria y proponemos estrategias de vuelta a la normalidad. Métodos: Desde el grupo de trabajo de cardiopatías congénitas de nuestra Sociedad se realizó una encuesta en los servicios de congénitas de nuestro país para conocer la disminución de actividad causada por la pandemia COVID-19 en el período temporal del 13-Marzo hasta el 13-Mayo-2020. Resultados: Durante la pandemia se ha disminuido parcialmente la cirugía de congénitas, interviniéndose los casos más urgentes y reduciéndose al mínimo la actividad programada. Respecto al mismo período del año anterior, se ha operado 51% menos cirugía mayor y 54% menos extracorpóreas. La colaboración en la atención directa de adultos COVID-19 ha sido del 15%, con 7% de nuestros cirujanos de baja. Antes de operar a cualquier paciente solicitamos PCR para descartar infección por SARS-CoV2, y si esta es positiva sólo consideramos intervención en los casos urgentes/emergentes. Conclusiones: La pandemia del SARS-CoV2 ha obligado a todos los servicios de congénitas del país a reestructurarse para apoyar a los compañeros con tratamiento directo del COVID-19, sin mermar la atención de nuestros propios pacientes cuya cirugía no podía demorarse. Abstract Introduction-objectives: We live in exceptional times caused by the new SARS-CoV2 coronavirus pandemic. Although clinical involvement of children and patients with congenital heart disease are not frequent, the emergency care of adults with COVID-19 has almost collapsed our healthcare system. Consequently, the whole standard activity has been minimized during this period. In this manuscript we analyse the reduction of our congenital heart surgery over these 2 months of state of alarm, and we propose strategies to return to normal. Methods: From our Society congenital heart disease working group, a survey was carried out in Spanish congenital heart disease surgery hospitals, in order to find out the decrease in activity caused by the COVID-19 pandemic during the time period from March-13 to May-13, 2020. Results: During the pandemic, congenital heart disease surgery was partially reduced, stepping with the most urgent cases and minimizing the scheduled activity. Compared to the same period in 2019, 51% less major surgery and 54% less extracorporeal surgery were performed. Collaboration in adults COVID-19 front line care has been 15%, having 7% of our specialists on quarantine. Before operating on any patient, the PCR is asked to rule out SARS-CoV2 infection and, if positive, we only consider intervention in urgent / emergency cases. Conclusions: The SARS-CoV2 pandemic has forced all the congenital heart disease services nationwide to restructure, aiming to support colleagues with direct treatment of COVID-19, without sacrificing the healthcare of our own patients whose surgery could not be delayed.


title: COVID-19: Neurology Residents’ Perspective

text: Abstract Throughout this pandemic, neurology resident education and service has, and will continue to be, affected during this unprecedented time. Balancing the safety of our residents as well as the anticipated inpatient service demands, we have, and continue to, make changes to meet the needs of our community. Education certainly has been affected but we have made great effort to maintain normalcy. We are leveraging web-based technologies to continue formal didactics. The American Academy of Neurology has provided program directors with various tools to share to provide high-yield academic education. AAN Synapse, distance learning modules, and podcasts are a few examples. Each residency training program will likely face different challenges depending on location and community structure. We have an obligation to help all of our colleagues in the hospital in providing quality and compassionate care during this time of need. Our training and education will only benefit from this experience teaching us lessons on adaptability, the importance of teamwork, and self-sacrifice.


title: Clinical characteristics of different subtypes and risk factors for the severity of illness in patients with COVID-19 in Zhejiang, China

text: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is now becoming an enormous threat to public health. The clinical spectrum of COVID-19 is extensive, of which critical cases are with rapid disease progression and high mortality. The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment. METHODS: In this retrospective study, we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020. According to the definition of clinical classification, we divided confirmed cases into four types, and summarize epidemiological and clinical characteristics, laboratory and radiograph findings, treatments, and outcomes, respectively. Moreover, we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19. RESULTS: A total of 788 patients were enrolled in our study, of whom 52 cases (6.6%) were mild type, 658 cases (83.5%) were common type, 61 cases (7.2%) were severe type, and 17 cases (2.2%) were critical type. Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2–2.6 P = 0.008), fever (OR = 3.6, 95% CI: 2.1–6.3, P < 0.001), cough (OR = 1.7, 95% CI: 1.0–2.9, P = 0.041), hemoptysis (OR = 3.4, 95% CI: 1.1–10.3, P = 0.032), gastrointestinal symptoms (OR = 1.9, 95% CI: 1.0–3.5, P = 0.047), hypertension (OR = 2.6, 95% CI: 1.2–5.6, P = 0.013). With the increase of age-grading, risk for the severity of illness was gradually higher (≤ 18 years [OR = 1.0], 19–40 years [OR = 12.7, 95% CI: 4.5–36.0, P < 0.001], 41–65 years [OR = 14.8, 95% CI: 5.2–42.1, P < 0.001], ≥ 66 years [OR = 56.5, 95% CI: 17.1–186.5, P < 0.001]). CONCLUSIONS: Clinicians should pay close attention to these features in patients with COVID-19 including older age, male, fever, cough, hemoptysis, gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.


title: Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia

text: BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.


title: Isobavachalcone inhibits post-entry stages of the porcine reproductive and respiratory syndrome virus life cycle

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen of great economic significance that impacts the swine industry globally. Since the first report of a porcine reproductive and respiratory syndrome (PRRS) outbreak, tremendous efforts to control this disease, including various national policies and plans incorporating the use of multiple modified live-virus vaccines, have been made. However, PRRSV is still a significant threat to the swine industry, and new variants continually emerge as a result of PRRSV evolution. Several studies have shown that pandemic PRRSV strains have enormous genetic diversity and that commercial vaccines can only provide partial protection against these strains. Therefore, effective anti-PRRSV drugs may be more suitable and reliable for PRRSV control. In this study, we observed that isobavachalcone (IBC), which was first isolated from Psoralea corylifolia, had potent anti-PRRSV activity in vitro. Although many biological activities of IBC have been reported, this is the first report describing the antiviral activity of IBC. Furthermore, after a systematic investigation, we demonstrated that IBC inhibits PRRSV replication at the post-entry stage of PRRSV infection. Thus, IBC may be a candidate for further evaluation as a therapeutic agent against PRRSV infection of swine in vivo.


title: The pathological effects of CCR2+ inflammatory monocytes are amplified by an IFNAR1-triggered chemokine feedback loop in highly pathogenic influenza infection

text: BACKGROUND: Highly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration of leukocytes into the lungs, high viral loads and a cytokine storm. However, the details of how these pathological features unfold in severe influenza infections remain unclear. Accumulation of Gr1 + CD11b + myeloid cells has been observed in highly pathogenic influenza infections but it is not clear how and why they accumulate in the severely inflamed lung. In this study, we selected this cell population as a target to investigate the extreme inflammatory response during severe influenza infection. RESULTS: We established H1N1 IAV-infected mouse models using three viruses of varying pathogenicity and noted the accumulation of a defined Gr1 + CD11b + myeloid population correlating with the pathogenicity. Herein, we reported that CCR2+ inflammatory monocytes are the major cell compartments in this population. Of note, impaired clearance of the high pathogenicity virus prolonged IFN expression, leading to CCR2+ inflammatory monocytes amplifying their own recruitment via an interferon-α/β receptor 1 (IFNAR1)-triggered chemokine loop. Blockage of IFNAR1-triggered signaling or inhibition of viral replication by Oseltamivir significantly suppresses the expression of CCR2 ligands and reduced the influx of CCR2+ inflammatory monocytes. Furthermore, trafficking of CCR2+ inflammatory monocytes from the bone marrow to the lung was evidenced by a CCR2-dependent chemotaxis. Importantly, leukocyte infiltration, cytokine storm and expression of iNOS were significantly reduced in CCR2−/− mice lacking infiltrating CCR2+ inflammatory monocytes, enhancing the survival of the infected mice. CONCLUSIONS: Our results indicated that uncontrolled viral replication leads to excessive production of inflammatory innate immune responses by accumulating CCR2+ inflammatory monocytes, which contribute to the fatal outcomes of high pathogenicity virus infections.


Unraveling the Mysteries of Middle East Respiratory Syndrome Coronavirus


title: Non-culturable bioaerosols in indoor settings: Impact on health and molecular approaches for detection

text: Abstract Despite their significant impact on respiratory health, bioaerosols in indoor settings remain understudied and misunderstood. Culture techniques, predominantly used for bioaerosol characterisation in the past, allow for the recovery of only a small fraction of the real airborne microbial burden in indoor settings, given the inability of several microorganisms to grow on agar plates. However, with the development of new tools to detect non-culturable environmental microorganisms, the study of bioaerosols has advanced significantly. Most importantly, these techniques have revealed a more complex bioaerosol burden that also includes non-culturable microorganisms, such as archaea and viruses. Nevertheless, air quality specialists and consultants remain reluctant to adopt these new research-developed techniques, given that there are relatively few studies found in the literature, making it difficult to find a point of comparison. Furthermore, it is unclear as to how this new non-culturable data can be used to assess the impact of bioaerosol exposure on human health. This article reviews the literature that describes the non-culturable fraction of bioaerosols, focussing on bacteria, archaea and viruses, and examines its impact on bioaerosol-related diseases. It also outlines available molecular tools for the detection and quantification of these microorganisms and states various research needs in this field.


title: Pandemic planning in pediatric care: A website policy review and national survey data

text: Abstract Objectives This study investigates current policies, key issues, and needs for pandemic planning in pediatrics in Canada. Methods Online pandemic plans from national, provincial and territorial government websites were reviewed to identify: plans for children and families, and psychosocial and ethical issues. A survey was administered to gather participants’ perspectives on the needs in pediatric planning, as well as important elements of their organizations’ and regions’ pandemic plans. A thematic analysis was conducted on qualitative survey responses. Results The majority of existing plans did not adequately address the unique needs of pediatric populations, and mainly focused on medical and policy concerns. Several gaps in plans were identified, including the need for psychosocial supports and ethical decision-making frameworks for children and families. Similarly, survey respondents identified parallel gaps, in their organization's or region's plans. Conclusions Although many plans provide guidelines for medical and policy issues in pediatrics, much more work remains in psychosocial and ethical planning. A focus on children and families is needed for pandemic planning in pediatrics to ensure best outcomes for children and families.


title: Whole-genome analysis of porcine epidemic diarrhea virus (PEDV) from eastern China

text: The complete genome sequence of a porcine epidemic diarrhea virus variant, strain SHQP/YM/2013, from China was determined and compared with those of other porcine epidemic diarrhea viruses. The full-length genome was 28,038 nucleotides (nt) in length without the poly (A) tail, and it was similar to that of other reported PEDV strains, with the characteristic gene order 5′-replicase (1a/1b) -S-ORF3-E-M-N-3′. Nucleotide sequence analysis based on individual virus genes indicated a close relationship between the S gene of SHQP/YM/2013 and those of the four Korean field strains from 2008–2009. Its ORF3 gene, however, fell into three groups. Recent prevalent Chinese PEDV field isolates were divided between group 1 and group 3, which suggests that the recent prevalent Chinese PEDV field isolates represent a new genotype that differs from the genotype that includes the vaccine strains. Based on phylogenetic analysis of the M gene, ORF3 gene and S gene, our study demonstrated that prevalent PEDV isolates in China may have originated from Korean strains. This report describes the complete genome sequence of SHQP/YM/2013, and the data will promote a better understanding of the molecular epidemiology and genetic diversity of PEDV field isolates in eastern China.


title: Candidate targets for immune responses to 2019-Novel Coronavirus (nCoV): sequence homology- and bioinformatic-based predictions

text: Effective countermeasures against the recent emergence and rapid expansion of the 2019-Novel Coronavirus (2019-nCoV) require the development of data and tools to understand and monitor viral spread and immune responses. However, little information about the targets of immune responses to 2019-nCoV is available. We used the Immune Epitope Database and Analysis Resource (IEDB) resource to catalog available data related to other coronaviruses, including SARS-CoV, which has high sequence similarity to 2019-nCoV, and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in 2019-nCoV that have high homology to SARS virus. Parallel bionformatic predictions identified a priori potential B and T cell epitopes for 2019-nCoV. The independent identification of the same regions using two approaches reflects the high probability that these regions are targets for immune recognition of 2019-nCoV. ONE SENTENCE SUMMARY We identified potential targets for immune responses to 2019-nCoV and provide essential information for understanding human immune responses to this virus and evaluation of diagnostic and vaccine candidates.


title: Environment-adjusted total-factor energy efficiency of Taiwan's service sectors

text: Abstract This study computes the pure technical efficiency (PTE) and energy-saving target of Taiwan's service sectors during 2001–2008 by using the input-oriented data envelopment analysis (DEA) approach with the assumption of a variable returns-to-scale (VRS) situation. This paper further investigates the effects of industry characteristics on the energy-saving target by applying the four-stage DEA proposed by Fried et al. (1999). We also calculate the pre-adjusted and environment-adjusted total-factor energy efficiency (TFEE) scores in these service sectors. There are three inputs (labor, capital stock, and energy consumption) and a single output (real GDP) in the DEA model. The most energy efficient service sector is finance, insurance and real estate, which has an average TFEE of 0.994 and an environment-adjusted TFEE (EATFEE) of 0.807. The study utilizes the panel-data, random-effects Tobit regression model with the energy-saving target (EST) as the dependent variable. Those service industries with a larger GDP output have greater excess use of energy. The capital–labor ratio has a significantly positive effect while the time trend variable has a significantly negative impact on the EST, suggesting that future new capital investment should also be accompanied with energy-saving technology in the service sectors.


title: Intrinsically disordered proteins of viruses: Involvement in the mechanism of cell regulation and pathogenesis

text: Abstract Intrinsically disordered proteins (IDPs) possess the property of inherent flexibility and can be distinguished from other proteins in terms of lack of any fixed structure. Such dynamic behavior of IDPs earned the name “Dancing Proteins.” The exploration of these dancing proteins in viruses has just started and crucial details such as correlation of rapid evolution, high rate of mutation and accumulation of disordered contents in viral proteome at least understood partially. In order to gain a complete understanding of this correlation, there is a need to decipher the complexity of viral mediated cell hijacking and pathogenesis in the host organism. Further there is necessity to identify the specific patterns within viral and host IDPs such as aggregation; Molecular recognition features (MoRFs) and their association to virulence, host range and rate of evolution of viruses in order to tackle the viral-mediated diseases. The current book chapter summarizes the aforementioned details and suggests the novel opportunities for further research of IDPs senses in viruses.


title: Identification of an alternative 5′‐untranslated exon and new polymorphisms of angiotensin‐converting enzyme 2 gene: Lack of association with SARS in the Vietnamese population

text: We analyzed genetic variations of angiotensin‐converting enzyme 2 (ACE2), considering that it might influence patients' susceptibility to severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) or development of SARS as a functional receptor. By cloning of the full‐length cDNA of the ACE2 gene in the lung, where replication occurs on SARS‐CoV, it was shown that there are different splicing sites. All exons including the new alternative exon, exon‐intron boundaries, and the corresponding 5′‐flanking region of the gene were investigated and 19 single nucleotide polymorphisms (SNPs) were found. Out of these, 13 SNPs including one non‐synonymous substitution and three 3′‐UTR polymorphisms were newly identified. A case control study involving 44 SARS cases, 16 anti‐SARS‐CoV antibody‐positive contacts, 87 antibody‐negative contacts, and 50 non‐contacts in Vietnam, failed to obtain any evidence that the ACE2 gene polymorphisms are involved in the disease process in the population. Nevertheless, identification of new 5′‐untranslated exon and new SNPs is considered helpful in investigating regulation of ACE2 gene expression in the future. © 2005 Wiley‐Liss, Inc.


title: A comparative study of Lonicera japonica with related species: Morphological characteristics, ITS sequences and active compounds

text: Abstract Morphological characteristics, ITS sequences, and active compounds have been used to differentiate between species of Lonicera used in the traditional Chinese medicines Flos Lonicerae Japonicae (FLJ) and Flos Lonicerae (FL). FLJ includes L. japonica whereas FJ includes Lonicera macranthoides, Lonicera hypoglauca, Lonicera confusa and Lonicera fulvotomentosa. FLJ could be distinguished from FL using four quantitative and 10 qualitative characters, ITS sequences, chlorogenic acid and luteoloside contents. Analyses revealed that L. japonica was very different from the other species. The results have implications for the identification and quality control of species of Lonicera used medicinally, suggesting that species should not be interchanged in medicinal preparations.


title: Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1(-/-) Mice

text: The Zika virus (ZIKV) can induce inflammation in immunoprivileged organs (e.g., the brain and testis), leading to the Guillain-Barré syndrome and damaging the testes. During an infection with the ZIKV, immune cells have been shown to infiltrate into the tissues. However, the cellular mechanisms that define the protection and/or immunopathogenesis of these immune cells during a ZIKV infection are still largely unknown. Herein, we describe methods to evaluate the virus-specific T-cell functionality in these immunoprivileged organs of ZIKV-infected mice. These methods include a) a ZIKV infection and vaccine inoculation in Ifnar1(-/-) mice; b) histopathology, immunofluorescence, and immunohistochemistry assays to detect the virus infection and inflammation in the brain, testes, and spleen; c) the preparation of a tetramer of ZIKV-derived T-cell epitopes; d) the detection of ZIKV-specific T cells in the monocytes isolated from the brain, testes, and spleen. Using these approaches, it is possible to detect the antigen-specific T cells that have infiltrated into the immunoprivileged organs and to evaluate the functions of these T cells during the infection: potential immune protection via virus clearance and/or immunopathogenesis to exacerbate the inflammation. These findings may also help to clarify the contribution of T cells induced by the immunization against ZIKV.


title: How law can help solve the collective action problem of antimicrobial resistance

text: Antimicrobial resistance is a global collective action problem with dire consequences for human health. This article considers how domestic and international legal mechanisms can be used to address antimicrobial resistance and overcome the governance and political economy challenges that accelerate it.


title: Plant cell factories and mucosal vaccines

text: Abstract Many advances continue to be made in the field of plant-derived vaccines. Plants have been shown capable of expressing a multicomponent vaccine that when orally delivered induces a T-helper cell subset 1 response and enables passive immunization. Furthermore, a plant-derived vaccine has been shown to protect against challenge in the target host. Increased antigen expression levels (up to 4.1% total soluble protein) have been obtained through transformation of the chloroplast genome. In view of these findings, plant-derived vaccines have been proved as valuable commodities to the world’s health system; however, before their application, studies need to focus on optimization of immunization strategies and to investigate antigen stability.


title: Mortality due to Cryptococcus neoformans and Cryptococcus gattii in low-income settings: an autopsy study

text: Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in adults living with HIV in sub-Saharan Africa. Recent estimates indicate that more than 130,000 people may die annually of cryptococcal meningitis in this region. Although complete diagnostic autopsy (CDA) is considered the gold standard for determining the cause of death, it is seldom performed in low income settings. In this study, a CDA was performed in 284 deceased patients from Mozambique (n = 223) and Brazil (n = 61). In depth histopathological and microbiological analyses were carried out in all cases dying of cryptococcosis. We determined the cryptococcal species, the molecular and sero-mating types and antifungal susceptibility. We also described the organs affected and reviewed the clinical presentation and patient management. Among the 284 cases included, 17 fatal cryptococcal infections were diagnosed. Cryptococcus was responsible for 16 deaths among the 163 HIV-positive patients (10%; 95%CI: 6–15%), including four maternal deaths. One third of the cases corresponded to C. gattii (VGI and VGIV molecular types, Bα and Cα strains) and the remaining infections typed were caused by C. neoformans var. Grubii (all VNI and Aα strains). The level of pre-mortem clinical suspicion was low (7/17, 41%), and 7/17 patients (41%) died within the first 72 hours of admission. Cryptococcosis was responsible for a significant proportion of AIDS-related mortality. The clinical diagnosis and patient management were inadequate, supporting the need for cryptococcal screening for early detection of the disease. This is the first report of the presence of C. gattii infection in Mozambique.


title: Molecular Evidence Supporting Ehrlichia canis‐Like Infection in Cats

text: Currently, the pathogenic role of Ehrlichia canis in cats has been proposed predominantly on the basis of the serologic evidence of natural infection and the infrequent detection of morulae‐like structures within the cytoplasm of leukocytes in cats. The purpose of this report was to provide molecular evidence supporting E cams‐like infection in 3 cats that had clinical manifestations consistent with canine ehrlichiosis but lacked antibodies to E canis antigens. Serum from all 3 cats contained antinuclear antibodies (ANAs). The predominant disease manifestation was polyarthritis in 1 cat and bone marrow hypoplasia or dysplasia, accompanied by pancytopenia or anemia and thrombocytopenia, in 1 cat each. The alignment of E canis partial 16S ribosomal DNA (rDNA; 382 nucleotide positions), amplified from EDTA blood samples from each cat, was identical to each other and was identical to a canine isolate of E canis (GenBank accession number AF373613). In 1 cat, concurrent treatment with corticosteroids may have interfered with the therapeutic effectiveness of doxycycline for the elimination of E canis‐like infection. To further define the spectrum of ehrlichiosis in cats, polymerase chain reaction (PCR) testing may be necessary until serologic testing is thoroughly validated in experimentally or naturally infected cats. In addition, until E canis has been isolated from cats and several tissue culture isolates are available from disparate geographic regions for detailed comparative genetic study, the molecular evidence presented in this study supporting E canis‐like infection in cats must be interpreted with caution.


title: Successful application of a simple specimen transport method for the conduct of respiratory virus surveillance in remote Indigenous communities in Australia

text: Objective Surveillance programs and research for acute respiratory infections in remote Aboriginal communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting respiratory samples from a remote setting for viral PCR compared with frozen specimens. Methods We sampled every individual who presented to a remote Aboriginal community clinic in a non‐epidemic respiratory season. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for 16 viruses was undertaken using real‐time multiplex PCR. Results A total of 140 participants were enrolled who contributed 150 study visits. Respiratory illnesses accounted for 10% of the reasons for presentation. Sixty‐one viruses were identified in 50 (33.3%) presentations for 40 (28.6%) individuals; bocavirus and rhinovirus were the most common viruses identified (14.0% and 12.6% of episodes respectively). The sensitivity for any virus detected in mailed specimens was 67.2% (95%CI 55.4, 78.9) compared to 65.6% (95%CI 53.7, 77.5) for frozen specimens. Conclusion The mailing of unfrozen nasal specimens from remote communities does not compromise the viability of the specimen for viral studies.


title: Nation‐wide surveillance of human acute respiratory virus infections between 2013 and 2015 in Korea

text: The prevalence of eight respiratory viruses detected in patients with acute respiratory infections (ARIs) in Korea was investigated through analysis of data recorded by the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) from 2013 to 2015. Nasal aspirate and throat swabs specimens were collected from 36 915 patients with ARIs, and viral nucleic acids were detected by real‐time (reverse‐transcription) polymerase chain reaction for eight respiratory viruses, including human respiratory syncytial viruses (HRSVs), influenza viruses (IFVs), human parainfluenza viruses (HPIVs), human coronaviruses (HCoVs), human rhinovirus (HRV), human adenovirus (HAdV), human bocavirus (HBoV), and human metapneumovirus (HMPV). The overall positive rate of patient specimens was 49.4% (18 236/36 915), 5% of which carried two or more viruses simultaneously. HRV (15.6%) was the most predominantly detected virus, followed by IFVs (14.6%), HAdV (7.5%), HPIVs (5.8%), HCoVs (4.2%), HRSVs (3.6%), HBoV (1.9%), and HMPV (1.6%). Most of the ARIs were significantly correlated with clinical symptoms of fever, cough, and runny nose. Although HRV and HAdV were frequently detected throughout the year in patients, other respiratory viruses showed apparent seasonality. HRSVs and IFVs were the major causative agents of acute respiratory diseases in infants and young children. Overall, this study demonstrates a meaningful relationship between viral infection and typical manifestations of known clinical features as well as seasonality, age distribution, and co‐infection among respiratory viruses. Therefore, these data could provide useful information for public health management and to enhance patient care for primary clinicians.


title: Work-related COVID-19 transmission in six Asian countries/areas: A follow-up study

text: OBJECTIVE: There is limited evidence of work-related transmission in the emerging coronaviral pandemic. We aimed to identify high-risk occupations for early coronavirus disease 2019 (COVID-19) local transmission. METHODS: In this observational study, we extracted confirmed COVID-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11(th) to 40(th) days of the following period). RESULTS: We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). CONCLUSIONS: Work-related transmission is considerable in early COVID-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.


title: A construction strategy for a baculovirus‐silkworm multigene expression system and its application for coexpression of type I and type II interferons

text: The Bombyx mori nucleopolyhedrovirus (BmNPV) baculovirus expression system (BES) is a eukaryotic expression system. It possesses great capability for post‐translation modification in expression of foreign proteins. With the counterselection cassette rpsL‐neo and phage λ‐Red recombinase, the defective‐rescue BmNPV BES reBmBac can be employed for efficient heterologous multigene coexpression at different gene sites in one baculovirus genome. In the present study, a recombinant baculovirus, reBm‐Cαγ, carrying two types of chicken interferon (IFN) genes (chIFN‐α and chIFN‐γ) was constructed using the reBmBac system. The chIFN‐α and chIFN‐γ genes were inserted into the same baculovirus genome at the polyhedron and p10 gene sites, respectively. The recombinant baculovirus was capable of coexpressing both chIFN‐α and chIFN‐γ. The expression levels of the two types of IFN in the coexpression product were exponentially high, at approximately 1.7 and 2.5 times higher, respectively, than those in the corresponding single‐expression products. The increase in expression level corresponds to replacement of the nonessential p10 gene in the reBm‐Cαγ recombinant baculovirus. This coexpression of recombinant chicken IFNs showed superior antiviral activity.


title: A comparative assessment of four serological methods used in the detection and measurement of anti-parasite antibodies in the serum of the amphibian, bufo viridis

text: Abstract Antibodies against Crithidia fasciculata choanomastigotes were detected in green toad (Bufo viridis) sera by direct agglutination, indirect haemagglutination (IHA), complement-fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), Correlation coefficients (r) were calculated for comparisons between each of the techniques and regression formulae derived in order to convert antibody levels as determined by one immunological method to that of another. The highest mean titre obtained by ELISA was approximately 1.5–3.5 times greater than those obtained by the other techniques whilst CFT gave the lowest values. IHA and ELISA titres were affected by different preparations of the crithidial antigen extracts. Highly significant r values were determined for control sera when IHA was compared to ELISA (r > 0.79), and to both CFT and ELISA with immune animals (r > 0.96). ELISA would seem most applicable for screening other lower vertebrates for anti-parasite antibodies especially in areas of human disease prevalence.


title: Bariatric Surgical Simulation: Evaluation in a Pilot Study of SimLife, a New Dynamic Simulated Body Model

text: BACKGROUND: The demand for bariatric surgery is high and so is the need for training future bariatric surgeons. Bariatric surgery, as a technically demanding surgery, imposes a learning curve that may initially induce higher morbidity. In order to limit the clinical impact of this learning curve, a simulation preclinical training can be offered. The aim of the work was to assess the realism of a new cadaveric model for simulated bariatric surgery (sleeve and Roux in Y gastric bypass). AIM: A face validation study of SimLife, a new dynamic cadaveric model of simulated body for acquiring operative skills by simulation. The objectives of this study are first of all to measure the realism of this model, the satisfaction of learners, and finally the ability of this model to facilitate a learning process. METHODS: SimLife technology is based on a fresh body (frozen/thawed) given to science associated to a patented technical module, which can provide pulsatile vascularization with simulated blood heated to 37 °C and ventilation. RESULTS: Twenty-four residents and chief residents from 3 French University Digestive Surgery Departments were enrolled in this study. Based on their evaluation, the overall satisfaction of the cadaveric model was rated as 8.52, realism as 8.91, anatomic correspondence as 8.64, and the model’s ability to be learning tool as 8.78. CONCLUSION: The use of the SimLife model allows proposing a very realistic surgical simulation model to realistically train and objectively evaluate the performance of young surgeons.


title: Prevalence of Human rhinovirus infection in young children with acute wheezing

text: Abstract Introduction Recurrent wheezing is one of the leading causes of chronic illness in childhood. We aimed to evaluate the prevalence of Human Rhinovirus (HRV) infection in the acute attack of wheezy chest which began after a respiratory illness. Methodology The study was conducted on 200 children aged 2 months to 5 years presenting to the emergency department with an acute wheezy episode either for the first time or recurrent wheeze defined as >2 reports of wheezing in the first 3 years of life. All subjects were subjected to a complete history and clinical examination. Chest X-ray was done to all subjects. Nasopharyngeal and oropharyngeal swabs were obtained from all subjects and the presence of HRV was determined by PCR examination. Results By PCR method, 163 patients (81.5%) were positive for viral infection. Due to viral co-infection, 49.5% (99 cases) were +ve for Respiratory Syncytial virus followed by HRV 43.5% (87 cases). Conclusion HRV was the second common viral infection in children with wheezes. Its prevalence was more in winter with higher incidence of recurrence. Compared to the other respiratory viruses, it had the higher mortality 43.7%.


title: The Application of a Reduced Dye Used in Orthopedics as a Novel Treatment against Coronavirus (COVID-19): A Suggested Therapeutic Protocol.

text: The severe acute respiratory syndrome caused by COVID-19 is now a global catastrophic event. Currently there is no approved drug or vaccine for the disease. Methylene blue (MB, oxidized form, blue color) has been used in many different areas of clinical medicine, ranging from malaria to orthopedics. Leucomethylene Blue (reduced form of MB, colorless) may be applied for the treatment of COVID-19 according to the scientific evidences. In severe patients, there is a cytokine storm (hyperinflammation) and high oxidative stress (OS). Inflammation and OS has a mutual correlation and exacerbate each other. In human body, MB first induces OS through absorbing electron (like a free radical) from other molecules, if the body could counteract to this OS, then reduced MB decreases OS through other mechanisms. Reduced MB could prevent inflammation, propagation of the virus RNA, and also improves hypoxia through reducing methemoglobin. Therefore, to avoid the increment of OS, we suggest using Leucomethylene Blue through the following protocol: The IV cocktail contains 50 mg MB (1mg/kg, 50-kg weight), 1000-2000 mg vitamin C, 500-1000 mg N-Acetylcysteine (or glutathione or cysteine or α-lipoic acid) and 10-20 gr urea (optional) in 100 ml dextrose 5%. Before the injection, the cocktail should be kept in a dark place for 1-2 hour to become fade or colorless.


title: Metagenomics for pathogen detection in public health

text: Traditional pathogen detection methods in public health infectious disease surveillance rely upon the identification of agents that are already known to be associated with a particular clinical syndrome. The emerging field of metagenomics has the potential to revolutionize pathogen detection in public health laboratories by allowing the simultaneous detection of all microorganisms in a clinical sample, without a priori knowledge of their identities, through the use of next-generation DNA sequencing. A single metagenomics analysis has the potential to detect rare and novel pathogens, and to uncover the role of dysbiotic microbiomes in infectious and chronic human disease. Making use of advances in sequencing platforms and bioinformatics tools, recent studies have shown that metagenomics can even determine the whole-genome sequences of pathogens, allowing inferences about antibiotic resistance, virulence, evolution and transmission to be made. We are entering an era in which more novel infectious diseases will be identified through metagenomics-based methods than through traditional laboratory methods. The impetus is now on public health laboratories to integrate metagenomics techniques into their diagnostic arsenals.