title: Progress and challenges in maternal health in western China: a Countdown to 2015 national case study

text: BACKGROUND: China is one of the few Countdown countries to have achieved Millennium Development Goal 5 (75% reduction in maternal mortality ratio between 1990 and 2015). We aimed to examine the health systems and contextual factors that might have contributed to the substantial decline in maternal mortality between 1997 and 2014. We chose to focus on western China because poverty, ethnic diversity, and geographical access represent particular challenges to ensuring universal access to maternal care in the region. METHODS: In this systematic assessment, we used data from national census reports, National Statistical Yearbooks, the National Maternal and Child Health Routine Reporting System, the China National Health Accounts report, and National Health Statistical Yearbooks to describe changes in policies, health financing, health workforce, health infrastructure, coverage of maternal care, and maternal mortality by region between 1997 and 2014. We used a multivariate linear regression model to examine which contextual and health systems factors contributed to the regional variation in maternal mortality ratio in the same period. Using data from a cross-sectional survey in 2011, we also examined equity in access to maternity care in 42 poor counties in western China. FINDINGS: Maternal mortality declined by 8·9% per year between 1997 and 2014 (geometric mean ratio for each year 0·91, 95% CI 0·91–0·92). After adjusting for GDP per capita, length of highways, female illiteracy, the number of licensed doctors per 1000 population, and the proportion of ethnic minorities, the maternal mortality ratio was 118% higher in the western region (2·18, 1·44–3·28) and 41% higher in the central region (1·41, 0·99–2·01) than in the eastern region. In the rural western region, the proportion of births in health facilities rose from 41·9% in 1997 to 98·4% in 2014. Underpinning such progress was the Government's strong commitment to long-term strategies to ensure access to delivery care in health facilities—eg, professionalisation of maternity care in large hospitals, effective referral systems for women medically or socially at high risk, and financial subsidies for antenatal and delivery care. However, in the poor western counties, substantial disparity by education level of the mother existed in access to health facility births (44% of illiterate women vs 100% of those with college or higher education), antenatal care (17% vs 69%) had at least four visits), and caesarean section (8% vs 44%). INTERPRETATION: Despite remarkable progress in maternal survival in China, substantial disparities remain, especially for the poor, less educated, and ethnic minority groups in remote areas in western China. Whether China's highly medicalised model of maternity care will be an answer for these populations is uncertain. A strategy modelled after China's immunisation programme, whereby care is provided close to the women's homes, might need to be explored, with township hospitals taking a more prominent role. FUNDING: Government of Canada, UNICEF, and the Bill & Melinda Gates Foundation.


title: Molecular characterization of a virulent canine coronavirus BGF strain

text: Abstract Molecular characterisation of a canine coronavirus (CCoV) isolate (BGF), associated with an outbreak of diarrhoea in puppies, showed 92.7% identity with attenuated Insavc-1 strain. Canine coronavirus BGF revealed a full length non-structural protein 3b (nsp 3b), associated with virulence in other coronaviruses, and a highly divergent region at the amino terminal domain of the membrane protein that may be implicated in avoiding the host immune reaction. This new canine coronavirus strain could help to identify virulence factors in coronavirus.


SARS-associated Coronavirus Infection in Teenagers


title: Perspectives: Coping with the Coronavirus fallout

text: As dentistry continues to settle into a new pattern following guidance relating to the Coronavirus, practitioners remain in a state of flux Dr Gina Vega and Dr Kunal Patel talk to BDJ In Practice about how they and their businesses are coping with the pandemic crisis


title: Shielded from harm

text: For some, covid-19 is fatal, but others have no symptoms at all. How can we predict who will get seriously sick – and how best to protect them? Carrie Arnold reports


title: An applied mathematician's perspective on Rosennean Complexity

text: Abstract The theoretical biologist Robert Rosen developed a highly original approach for investigating the question “What is life?”, the most fundamental problem of biology. Considering that Rosen made extensive use of mathematics it might seem surprising that his ideas have only rarely been implemented in mathematical models. On the one hand, Rosen propagates relational models that neglect underlying structural details of the components and focus on relationships between the elements of a biological system, according to the motto “throw away the physics, keep the organisation”. Rosen's strong rejection of mechanistic models that he implicitly associates with a strong form of reductionism might have deterred mathematical modellers from adopting his ideas for their own work. On the other hand Rosen's presentation of his modelling framework, (M, R) systems, is highly abstract which makes it hard to appreciate how this approach could be applied to concrete biological problems. In this article, both the mathematics as well as those aspects of Rosen's work are analysed that relate to his philosophical ideas. It is shown that Rosen's relational models are a particular type of mechanistic model with specific underlying assumptions rather than a fundamentally different approach that excludes mechanistic models. The strengths and weaknesses of relational models are investigated by comparison with current network biology literature. Finally, it is argued that Rosen's definition of life, “organisms are closed to efficient causation”, should be considered as a hypothesis to be tested and ideas how this postulate could be implemented in mathematical models are presented.


title: The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription

text: Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease.


title: Urologie in der Corona-Virus-Pandemie – Leitfaden 4/20

text: The coronavirus pandemic is a major challenge for healthcare systems worldwide. For urology, the expansion of the health-care structures for the treatment of patients suffering from COVID-19 should be supported as best as possible. At the same time, one should aim to ensure adequate care for urological emergencies and urgent urological treatments as far as possible, even during the pandemic. For this, patients must be prioritized individually, alternative therapy concepts must be considered and regional and supraregional cooperation must be used. Outpatient departments are of great importance in the care, examination and coordination of urological emergencies and urgent treatment. Urological clinics must prepare themselves to perform urgent operations and interventions on SARS-CoV‑2-positive patients. Here, the creation of a separate, appropriately equipped emergency operating room to perform operations and interventions on SARS-CoV‑2 patients should be considered. Furthermore strictly defined hygiene measures to protect employees in various clinical scenarios should be set up.


Practical indications for management of patients candidate to Interventional and Intraoperative Radiotherapy (Brachytherapy, IORT) during COVID-19 pandemic – A document endorsed by AIRO (Italian Association of Radiotherapy and Clinical Oncology) Interventional Radiotherapy Working Group


title: Dispositif de lutte conte le syndrome respiratoire du Moyen-Orient lors du pèlerinage 2013 en Côte d’Ivoire

text: Introduction Le pèlerinage attire environ trois millions de musulmans dans le monde dont 4500 ivoiriens. Face aux risques sanitaires dus aux conditions de regroupement, la Côte d’Ivoire a réuni tous les acteurs impliqués dans la gestion du Hadj. L’objectif était de décrire les mesures de prévention de lutte contre le Middle East Respiratory Syndrome Corona Virus (MERS-CoV). Méthodologie La mise en place des stratégies s’est déroulée du 27 août au 3 novembre 2013 dans le district d’Abidjan. Elle a concerné les candidats au Hadj, l’équipe médicale et les autres acteurs. Plusieurs activités ont été réalisées et les données recueillies ont été analysées par l’Institut national d’hygiène publique (INHP). Résultats Il est ressorti : – avant le départ : –organisation d’un atelier de formation sur la prévention et de prise en charge des cas, – distribution de matériels de protection individuelle, affichettes, posters, – sensibilisation des encadreurs médicaux, religieux et autres du Hadj, – réalisation d’une enquête CAP auprès des candidats, – élaboration de directives sur le MERS-CoV ; – pendant la préparation pour le retour : – échanges entre les encadreurs du Hadj et les responsables de la plate-forme aéroportuaire ; – au retour : – mises en place de matériel de protection individuelle, – installation d’une messagerie opérationnelle 24h/24, – suivi régulier des pèlerins, – investigation des cas suspects, – rétro-information. Conclusion La mise en place des stratégies a permis aux autorités de protéger les populations.


Evidence of human metapneumovirus in Australian children


title: Contribution of Unmeasured Anions to Acid–Base Disorders and its Association with Altered Demeanor in 264 Calves with Neonatal Diarrhea

text: BACKGROUND: The quantitative effect of strong electrolytes, unmeasured anions (UAs), p CO (2), and plasma protein concentrations in determining plasma pH and bicarbonate (HCO (3) (−)) can be demonstrated using the physicochemical approach. Demeanor of calves with diarrhea is associated with acidemia, dehydration, and hyper‐d‐lactatemia. HYPOTHESIS: Unmeasured anions are a major factor influencing changes in plasma pH and HCO (3) (−) of calves with diarrhea and UAs and strong UAs, estimated by anion gap (AG) and strong ion gap (SIG), respectively, are more strongly associated with alteration of demeanor compared to other acid–base variables. ANIMALS: A total of 264 calves with diarrhea from two data sets (DS1 and DS2). METHODS: Retrospective study. Forward stepwise regression was performed to determine the relationship between measured pH or HCO (3) (−), and physicochemical variables. A two‐way ANOVA was performed to investigate the association between acid–base variables and attitude (bright, obtunded, and stuporous), posture (standing, sternal or lateral recumbency), and strength of suckling reflex (strong, weak, or absent). RESULTS: Increased strong UAs estimated by SIG was the most important contributor to changes in measured pH and HCO (3) (−) (DS1: r (2) 66 and 59%, DS2: 39 and 42%, P < .0001). SIG and AG were correlated to deteriorating calf demeanor for all three clinical scoring categories: attitude, posture, and suckle reflex (P < .0001). CONCLUSION AND CLINICAL RELEVANCE: Elevated concentrations of strong UAs were the primary cause of acidemia and had an important influence on the demeanor of calves with diarrhea. These findings emphasize the importance of the calculation of UAs when evaluating acid–base abnormalities in calves.


title: Subarachnoid hemorrhage guidance in the era of the COVID-19 pandemic -An opinion to mitigate exposure and conserve personal protective equipment

text: Aneurysmal subarachnoid hemorrhage (SAH) patients require frequent neurological examinations, neuroradiographic diagnostic testing and lengthy intensive care unit stay. Previously established SAH treatment protocols are impractical to impossible to adhere to in the current COVID-19 crisis due to the need for infection containment and shortage of critical care resources, including personal protective equipment (PPE). Centers need to adopt modified protocols to optimize SAH care and outcomes during this crisis. In this opinion piece, we assembled a multidisciplinary, multicenter team to develop and propose a modified guidance algorithm that optimizes SAH care and workflow in the era of the COVID-19 pandemic. This guidance is to be adapted to the available resources of a local institution and does not replace clinical judgment when faced with an individual patient.


title: Expression Dynamics of Innate Immunity in Influenza Virus-Infected Swine

text: The current circulating swine influenza virus (IV) subtypes in Europe (H1N1, H1N2, and H3N2) are associated with clinical outbreaks of disease. However, we showed that pigs could be susceptible to other IV strains that are able to cross the species barrier. In this work, we extended our investigations into whether different IV strains able to cross the species barrier might give rise to different innate immune responses that could be associated with pathological lesions. For this purpose, we used the same samples collected in a previous study of ours, in which healthy pigs had been infected with a H3N2 Swine IV and four different H3N8 IV strains circulating in different animal species. Pigs had been clinically inspected and four subjects/group were sacrificed at 3, 6, and 21 days post infection. In the present study, all groups but mock exhibited antibody responses to IV nucleoprotein protein. Pulmonary lesions and high-titered viral replication were observed in pigs infected with the swine-adapted virus. Interestingly, pigs infected with avian and seal H3N8 strains also showed moderate lesions and viral replication, whereas equine and canine IVs did not cause overt pathological signs, and replication was barely detectable. Swine IV infection induced interferon (IFN)-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF) at day 3 post infection, as opposed to the other non-swine-adapted virus strains. However, IFN-alpha responses to the swine-adapted virus were not associated with an increase of the local, constitutive expression of IFN-alpha genes. Remarkably, the Equine strain gave rise to a Serum Amyloid A response in BALF despite little if any replication. Each virus strain could be associated with expression of cytokine genes and/or proteins after infection. These responses were observed well beyond the period of virus replication, suggesting a prolonged homeostatic imbalance of the innate immune system.


title: Measuring the Outreach Efforts of Public Health Authorities and the Public Response on Facebook During the COVID-19 Pandemic in Early 2020: Cross-Country Comparison

text: BACKGROUND: The coronavirus disease (COVID-19) pandemic presents one of the most challenging global crises at the dawn of a new decade. Public health authorities (PHAs) are increasingly adopting the use of social media such as Facebook to rapidly communicate and disseminate pandemic response measures to the public. Understanding of communication strategies across different PHAs and examining the public response on the social media landscapes can help improve practices for disseminating information to the public. OBJECTIVE: This study aims to examine COVID-19-related outreach efforts of PHAs in Singapore, the United States, and England, and the corresponding public response to these outreach efforts on Facebook. METHODS: Posts and comments from the Facebook pages of the Ministry of Health (MOH) in Singapore, the Centers for Disease Control and Prevention (CDC) in the United States, and Public Health England (PHE) in England were extracted from January 1, 2019, to March 18, 2020. Posts published before January 1, 2020, were categorized as pre-COVID-19, while the remaining posts were categorized as peri-COVID-19 posts. COVID-19-related posts were identified and classified into themes. Metrics used for measuring outreach and engagement were frequency, mean posts per day (PPD), mean reactions per post, mean shares per post, and mean comments per post. Responses to the COVID-19 posts were measured using frequency, mean sentiment polarity, positive to negative sentiments ratio (PNSR), and positive to negative emotions ratio (PNER). Toxicity in comments were identified and analyzed using frequency, mean likes per toxic comment, and mean replies per toxic comment. Trend analysis was performed to examine how the metrics varied with key events such as when COVID-19 was declared a pandemic. RESULTS: The MOH published more COVID-19 posts (n=271; mean PPD 5.0) compared to the CDC (n=94; mean PPD 2.2) and PHE (n=45; mean PPD 1.4). The mean number of comments per COVID-19 post was highest for the CDC (mean CPP 255.3) compared to the MOH (mean CPP 15.6) and PHE (mean CPP 12.5). Six major themes were identified, with posts about prevention and safety measures and situation updates being prevalent across the three PHAs. The themes of the MOH’s posts were diverse, while the CDC and PHE posts focused on a few themes. Overall, response sentiments for the MOH posts (PNSR 0.94) were more favorable compared to response sentiments for the CDC (PNSR 0.57) and PHE (PNSR 0.55) posts. Toxic comments were rare (0.01%) across all PHAs. CONCLUSIONS: PHAs’ extent of Facebook use for outreach purposes during the COVID-19 pandemic varied among the three PHAs, highlighting the strategies and approaches that other PHAs can potentially adopt. Our study showed that social media analysis was capable of providing insights about the communication strategies of PHAs during disease outbreaks.


title: Viriasis respiratorias. Gripe

text: Resumen Las viriasis respiratorias son un conjunto de infecciones respiratorias agudas, la mayoría benignas, causadas por virus con una importante variabilidad serotípica. La gripe es el cuadro producido por los virus influenza A y B con periodicidad epidémica estacional y, ocasionalmente, influenza A puede producir pandemias mundiales. Las complicaciones se limitan casi exclusivamente a las edades extremas de la vida y pacientes con comorbilidades, especialmente respiratorias y cardiovasculares. El tratamiento antivírico disminuye el tiempo de los síntomas y la vacunación consigue disminuir de forma eficaz el número de infecciones. El virus respiratorio sincitial es el agente causal más frecuente de la bronquiolitis aguda del lactante. Rinovirus y coronavirus son los asociados con más frecuencia al resfriado común. Coronavirus es responsable del síndrome respiratorio agudo grave descrito en China en 2002, mientras que el virus parainfluenza lo es del crup laríngeo de los niños. Abstract Respiratory viriasis are acute infectious diseases with a usually favorable course. Influenza is the disease caused by influenza viruses A and B; it could cause seasonal periodical epidemics and influenza A is implicated in worlwide pandemias. Influenza complications usually are limited to older patients and to those with comorbilities, especially those with chronic respiratory or cardiovascular diseases. Anti-influenza therapy has an effect on the duration of the symptomatic period and vaccination efficiently decreases the incidence of the infection. Respiratory syncytial virus is the more frequent cause of the acute bronchiolitis in breastfeeding patients. Rinovirus and coronavirus are implicated in the common cold. Coronavirus was the etiological agent of the severe acute respiratory syndrome, described in 2002 in China. Parainfluenza virus is the cause of the laryngeal croup in infants.


title: COVID-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 22 Cases From Belgium

text: RATIONALE & OBJECTIVE: The world is facing a global pandemic caused by Sars-CoV-2 virus. Although kidney transplant recipients are at increased risk of viral infections, the impact of their chronic immunosuppressed status on the risk of acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown. STUDY DESIGN: All cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mTOR inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients. SETTING & PARTICIPANTS: 22 COVID-19 infections were diagnosed in our cohort of 1200 kidney transplant recipients. RESULTS: Most common initial symptoms included fever, cough, or dyspnea. Eighteen patients (82%) required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Chest computerized tomography (CT) at admission (performed in 15 patients) showed mild (n=3), moderate (n=8), extensive (n=1), severe (n=2), and critical (n=1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. Eleven patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non- ICU, 1 was in ICU, and 2 patients had died. LIMITATIONS: Small sample size and short follow-up. CONCLUSIONS: Clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19.


title: Human rights and other provisions in the revised International Health Regulations (2005)

text: Summary In May 2005, the World Health Assembly of the World Health Organization (WHO) adopted the revised International Health Regulations (2005), which have now entered into force for WHO Member States across the globe. These Regulations contain a broad range of binding provisions to address the risks of international disease spread in international travel, trade and transportation. Important elements include multiple provisions, whether denominated in terms of human rights or other terminology, that are protective of interests of individuals who may be subject to public health measures in this international context. With the vast (and increasing) numbers of persons undertaking international voyages and the global coverage of these revised Regulations, they are an important development in this area. This article describes a number of these key provisions and some of the related issues they present.


title: SARS Control and Psychological Effects of Quarantine, Toronto, Canada

text: As a transmissible infectious disease, severe acute respiratory syndrome (SARS) was successfully contained globally by instituting widespread quarantine measures. Although these measures were successful in terminating the outbreak in all areas of the world, the adverse effects of quarantine have not previously been determined in a systematic manner. In this hypothesis-generating study supported by a convenience sample drawn in close temporal proximity to the period of quarantine, we examined the psychological effects of quarantine on persons in Toronto, Canada. The 129 quarantined persons who responded to a Web-based survey exhibited a high prevalence of psychological distress. Symptoms of posttraumatic stress disorder (PTSD) and depression were observed in 28.9% and 31.2% of respondents, respectively. Longer durations of quarantine were associated with an increased prevalence of PTSD symptoms. Acquaintance with or direct exposure to someone with a diagnosis of SARS was also associated with PTSD and depressive symptoms.


title: Cutting-Edge Infectious Disease Diagnostics with CRISPR

text: Three recent Science articles (Chen et al., 2018; Gootenberg et al., 2018; Myhrvold et al., 2018) describe the use of CRISPR-Cas technology to develop point-of-care diagnostics that directly detect viruses from clinical samples. These tests could radically transform approaches to diagnosing infectious diseases at the bedside and in the field.


title: Endolysosomal Ca(2+) Signalling and Cancer Hallmarks: Two-Pore Channels on the Move, TRPML1 Lags Behind!

text: The acidic vesicles of the endolysosomal (EL) system are emerging as an intracellular Ca(2+) store implicated in the regulation of multiple cellular functions. The EL Ca(2+) store releases Ca(2+) through a variety of Ca(2+)-permeable channels, including Transient Receptor Potential (TRP) Mucolipin 1-3 (TRPML1-3) and two-pore channels 1-2 (TPC1-2), whereas EL Ca(2+) refilling is sustained by the proton gradient across the EL membrane and/or by the endoplasmic reticulum (ER). EL Ca(2+) signals may be either spatially restricted to control vesicle trafficking, autophagy and membrane repair or may be amplified into a global Ca(2+) signal through the Ca(2+)-dependent recruitment of ER-embedded channels. Emerging evidence suggested that nicotinic acid adenine dinucleotide phosphate (NAADP)-gated TPCs sustain multiple cancer hallmarks, such as migration, invasiveness and angiogenesis. Herein, we first survey the EL Ca(2+) refilling and release mechanisms and then focus on the oncogenic role of EL Ca(2+) signaling. While the evidence in favor of TRPML1 involvement in neoplastic transformation is yet to be clearly provided, TPCs are emerging as an alternative target for anticancer therapies.


title: Upregulation of Bcl‐2 in nasal polyps from patients with cystic fibrosis

text: BACKGROUND: Nasal polyps in patients with cystic fibrosis (CF) are believed to be phenotypically different than polyps affecting non‐CF patients. The aim of this study was to investigate differences in cell cycle regulatory mechanisms between these 2 groups. In this prospective study at a tertiary care academic medical center, multiple techniques were used to confirm the upregulation of antiapoptotic Bcl‐2 family proteins in CF polyps. METHODS: Nasal polyps were prospectively obtained from CF and non‐CF patients. The Sigma Panorama Protein Microarray for Cell Signaling was used to identify differences in protein expression between the 2 polyp groups. Western blot analysis confirmed altered expression of a subset of these proteins. Immunohistochemical staining was performed on archived tissue to further investigate B‐cell lymphoma 2 protein (Bcl‐2) expression. Following review by a pathologist, slides were digitized using an Aperio™ ScanScope XT system and staining intensity was quantified with the Positive Pixel Count algorithm. The mean staining intensity for each polyp group was compared. RESULTS: The protein microarray suggested a greater than 2‐fold upregulation of Bcl‐xl in CF polyps relative to non‐CF polyps. Western blot analysis confirmed the upregulation in CF polyps of Bcl‐2, a more commonly studied protein analog of Bcl‐xl. The CF polyp group was noted to have a higher quantitative intensity of immunohistochemical staining for Bcl‐2 compared to the non‐CF group (p < 0.05). CONCLUSION: Through multiple modalities of protein investigation, we have demonstrated an upregulation of Bcl‐2 family proteins in CF polyps relative to polyps from non‐CF patients.


title: COVID-19: The Case of Three Patients with the Same Diagnosis but Different Clinical and Laboratory Features

text: SARS-CoV-2 is an RNA virus that causes COVID-19, which has been responsible for the pandemic that was declared in early 2020. Its pathological effect is majorly in the respiratory tract, but its full pathogenicity remains a mystery. Symptoms associated with COVID-19 include fever, cough, and shortness of breath. Some patients develop other symptoms like diarrhea. However, it is possible for other organs to be affected including the central nervous system, liver, and blood cells. The purpose of this case series is to unravel other factors associated with this disease, so we report three cases of COVID-19 that were hospitalized during the pandemic.


title: Monetary incentives and peer referral in promoting digital network-based secondary distribution of HIV self-testing among men who have sex with men in China: study protocol for a three-arm randomized controlled trial

text: BACKGROUND: Human immunodeficiency virus (HIV) testing is a crucial strategy for HIV prevention. HIV testing rates remain low among men who have sex with men (MSM) in China. Digital network-based secondary distribution is considered as an effective model to enhance HIV self-testing (HIVST) among key populations. Digital platforms provide opportunities for testers to apply for HIVST kits by themselves, and secondary distribution allows them to apply for multiple kits to deliver to their sexual partners or members within their social network. We describe a three-arm randomized controlled trial to examine the effect of monetary incentives and peer referral in promoting digital network-based secondary distribution of HIVST among MSM in China. METHODS: Three hundred MSM in China will be enrolled through a digital platform for data collection. The eligibility criteria include being biological male, 18 years of age or over, ever having had sex with another man, being able to apply for kits via the online platform, and being willing to provide personal telephone number for follow-up. Eligible participants will be randomly allocated into one of the three arms: standard secondary distribution arm, secondary distribution with monetary incentives arm, and secondary distribution with monetary incentives plus peer referral arm. Participants (defined as “index”) will distribute actual HIV self-test kits to members within their social network (defined as “alter”) or share referral links to encourage alters to apply HIV self-test kits by themselves. All index participants will be requested to complete a baseline survey and a 3-month follow-up survey. Both indexes and alters will complete a survey upon returning the results by taking a photo of the used kits with the unique identification number. DISCUSSION: HIV testing rates remain suboptimal among MSM in China. Innovative interventions are needed to further expand the uptake of HIV testing among key populations. The findings of the trial can provide scientific evidence and experience on promoting secondary distribution of HIVST to reach key populations who have not yet been covered by existing testing services. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1900025433) on 26, August 2019, http://www.chictr.org.cn/showproj.aspx?proj=42001. Prospectively registered.


title: The Link Between Bronchiolitis and Asthma

text: Bronchiolitis and asthma are common wheezing illnesses of childhood. Respiratory syncytial virus is the main causative agent of Bronchiolitis. Rhinovirus is the most common trigger of exacerbations of asthma, but also has been detected increasingly in doing children with Bronchiolitis. Reportedly, childhood asthma develops in 40% of children with a history of Bronchiolitis. No convincing link has been reported between Bronchiolitis and development of atopy, although atopy generally is regarded as the main risk factor for chronic asthma. This article focuses on the association between bronchiolitis and the development of asthma. The authors address the question how respiratory syncytial virus and rhinovirus infections in young children, together with genetics and immunologic immaturity, may contribute to the development of asthma.


title: A simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency

text: OBJECTIVES: We aimed to develop a simple algorithm to help early identification of SARS-CoV-2 infection patients with severe progression tendency. METHODS: The univariable and multivariable analysis were computed to identify the independent predictors of COVID-19 progression. The prediction model was established in a retrospective training set of 322 COVID-19 patients and was re-evaluated in a prospective validation set of 317 COVID-19 patients. RESULTS: The multivariable analysis identified age (OR = 1.061, p = 0.028), lactate dehydrogenase (LDH) (OR = 1.006, p = 0.037), and CD4 count (OR = 0.993, p = 0.006) as the independent predictors of COVID-19 progression. Consequently, the age-LDH-CD4 algorithm was derived as (age × LDH)/CD4 count. In the training set, the area under the ROC curve (AUROC) of age-LDH-CD4 model was significantly higher than that of single CD4 count, LDH, or age (0.92, 0.85, 0.80, and 0.75, respectively). In the prospective validation set, the AUROC of age-LDH-CD4 model was also significantly higher than that of single CD4 count, LDH, or age (0.92, 0.75, 0.81, and 0.82, respectively). The age-LDH-CD4 ≥ 82 has high sensitive (81%) and specific (93%) for the early identification of COVID-19 patients with severe progression tendency. CONCLUSIONS: The age-LDH-CD4 model is a simple algorithm for early identifying patients with severe progression tendency following SARS-CoV-2 infection, and warrants further validation.


title: Pathogénie de la maladie de Kawasaki : quoi de neuf ?

text: Résumé La maladie de Kawasaki (MK) est une vascularite inflammatoire aiguë survenant le plus souvent chez le nourrisson et dont le pronostic est dicté par l’atteinte coronarienne. La cause de cette maladie reste inconnue mais différentes hypothèses ont été développées ces dernières années et s’associent à des travaux de recherche pour la compréhension de la physiopathologie de la MK. La présentation clinique de la MK partage de nombreux signes avec des maladies infectieuses virales et bactériennes. La possibilité d’une maladie infectieuse à superantigène a été suggérée. La fréquence augmentée dans certaines populations, la survenue précoce à l’âge pédiatrique supporte la participation de facteurs génétiques dans le développement de la maladie. Certaines anomalies immunologiques sont également retrouvées chez les sujets présentant une MK, suggérant qu’un déséquilibre immunologique est à l’origine de la vascularite. Abstract Kawasaki disease is an acute vasculitis, which occurs most commonly in infants and toddlers. It is self-limited but prognosis depends on the development of coronary abnormalities. The aetiology is unknown, but recent research has shed some light on its pathogenesis. Epidemiologic data and clinical presentation suggest that it might be a bacterial or viral infection, but attempts to demonstrate a specific pathogen have failed so far. The possibility that a superantigen-driven process might take place in this disorder has been advocated by several groups. Ethnic preference for Asian populations and early age predilection all support a genetic predisposition. Immunological abnormalities of different kinds have also been demonstrated; therefore the current concept is that an immune-mediated pathogenesis in a genetically predisposed individual could be responsible for the disease development.


title: Liability of clinical oncologists and the COVID-19 emergency: between hopes and concerns()

text: To contain COVID-19 spread, Italy is under a global lockdown since February 21, 2020, except for health services and food supply. In this scenario, growing apprehension concerning legal consequences is rising among health professionals due to several ethical and legal questions. Even if medical ethicists may approve patients’ prioritization protocols, hospitals and health professionals remain highly exposed to liability. The so-called smart-working may be very useful, but it may harbor potential legal harms for health personnel and patients and safety. Moreover, personal umbrella policies also often exclude liability arising out of the transmission of a communicable disease, especially a pandemic state, is declared. Under the pressure of medical associations, Italian Government political forces have very recently presented an amendment to the recently released ordinances for the COVID-19 emergency aimed to reduce medical liability. Presumably, similar epidemics or other wide-scale similar events may happen again in an unpredictable future. Therefore, more articulated legal regulations are strongly needed starting from lessons learned from this epidemic.


title: Vaccines for epidemic infections and the role of CEPI

text: The author reviews the foundation of the Coalition for Epidemic Preparedness and Innovations and the choices it has made for funding of vaccine development against epidemic diseases. He comments on those decisions as well as proposing how CEPI could remain relevant for the long term.


title: IgA1 protease

text: Abstract IgA1 proteases are proteolytic enzymes that cleave specific peptide bonds in the human immunoglobulin A1 (IgA1) hinge region sequence. Several species of pathogenic bacteria secrete IgA1 proteases at mucosal sites of infection to destroy the structure and function of human IgA1 thereby eliminating an important aspect of host defence. IgA1 proteases are known as autotransporter proteins as their gene structure encodes the information to direct their own secretion out of the bacterial cell. The iga gene structure is also thought to contribute to the antigenic heterogeneity demonstrated by the IgA1 proteases during infections and the cleavage specificity of the IgA1 proteases for human IgA1. The IgA1 proteases have therefore been implicated as important virulence factors that contribute to bacterial infection and colonisation. The development of strategies to inactivate these IgA1 proteases has become the subject of recent research, as this has the potential to reduce bacterial colonisation at mucosal surfaces.


title: Increased infection severity in downstream cities in infectious disease transmission and tourists surveillance analysis

text: Abstract Infectious disease severely threatens human life. Human mobility and travel patterns influence the spread of infection between cities and countries. We find that the infection severity in downstream cities during outbreaks is related to transmission rate, recovery rate, travel rate, travel duration and the average number of person-to-person contacts per day. The peak value of the infected population in downstream cities is slightly higher than that in source cities. However, as the number of cities increases, the severity increase percentage during outbreaks between end and source cities is constant. The surveillance of important nodes connecting cities, such as airports and train stations, can help delay the occurrence time of infection outbreaks. The city-entry surveillance of hub cities is not only useful to these cities, but also to cities that are strongly connected (i.e., have a high travel rate) to them. The city-exit surveillance of hub cities contributes to other downstream cities, but only slightly to itself. Surveillance conducted in hub cities is highly efficient in controlling infection transmission. Only strengthening the individual immunity of frequent travellers is not efficient for infection control. However, reducing the number of person-to-person contacts per day effectively limits the spread of infection.


title: Increased Morbidity and Mortality in Domestic Animals Eating Dropped and Bitten Fruit in Bangladeshi Villages: Implications for Zoonotic Disease Transmission

text: We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat- or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02–1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16–1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13–2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption.


title: Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns

text: This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)—where the virus first broke out in December and spread widely from January to February 2020—was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 °C and 12 °C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4–12 °C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.


title: Genetic and pathogenic characterization of a novel reassortant mammalian orthoreovirus 3 (MRV3) from a diarrheic piglet and seroepidemiological survey of MRV3 in diarrheic pigs from east China

text: Abstract Mammalian orthoreoviruses (MRVs), which cause gastrointestinal and respiratory illness, have been isolated from a wide variety of mammalian species including bats, minks, pigs and humans. Here we report the isolation and genetic and pathogenic characterization of a novel MRV type 3 (MRV3), named MRV-ZJ2013, from the diarrheic feces of piglets in Zhejiang province, China. Genomic and phylogenetic analysis shows that MRV-ZJ2013 may have originated from reassortments among mink, bat, and pig MRVs, suggesting the hypothesis that interspecies transmission has occurred in pig herds. Neonatal piglets infected with MRV-ZJ2013 displayed mild clinical signs such as poor appetite and soft feces, but vomiting and diarrhea were not observed. Fecal virus shedding was detected only in three out of six piglets, each for one- or two-day post-infection. In contrast, piglets inoculated with a virulent porcine epidemic diarrhea virus (PEDV) strain as the control group had severe signs characterized by acute vomiting and watery diarrhea. These findings suggest that the virulence of MRV-ZJ2013, if any, was likely not significant compared to that of PEDV. A seroepidemiological survey of MRV by means of an indirect enzyme-linked immune-sorbent assay (ELISA) based on a recombinant MRV3 capsid protein sigma1 as antigen revealed a high seroprevalence (77%) in 1037 samples from diarrheic pigs of different ages from 24 herds in seven provinces of east China between 2015 and 2016, indicating that MRV3 is endemic in pig herds in China, and may contribute collectively to enteric disease along with other porcine pathogens.


title: Issues to Consider for Preparing Ferrets as Research Subjects in the Laboratory

text: The domestic or European ferret (Mustela putorius furo) has been domesticated for thousands of years. Ferrets have been used for hunting and fur production, as pets, and as models in biomedical research. Despite the relatively small numbers used in the laboratory, ferrets have some unique applications including study of human influenza and severe acute respiratory syndrome (SARS)-associated corona virus. They have served as models for peptic ulcer disease, carotenoid metabolism, cystic fibrosis, and drug emesis screening, among others. Most research ferrets are males, due to estrus-related health problems in females. They may be housed conventionally and are easy to care for when their biology and behavior are understood. Due to the small number of ferret suppliers, animals are often shipped long distances, requiring air transport and intermediate handlers. It is important to minimize shipment stress, especially with weanling and pregnant animals. Additional expertise is required for success with pregnant and whelping ferrets and for rearing of neonates. The animals have specific dietary requirements, and proper nutrition is key. Successful housing requires knowledge of ferret behaviors including social behavior, eating habits, a general inquisitive nature, and a species-typical need to burrow and hide. Regular handling is necessary to maintain well-being. A ferret health care program consists of physical examination, immunization, clinical pathology, and a working knowledge of common ferret diseases. Various research methodologies have been described, from basic procedures such as blood collection to major invasive survival surgery. Ferrets have a distinct niche in biomedical research and are hardy animals that thrive well in the laboratory.


The COVID‐19 epidemic through a gender lens: what if a gender approach had been applied to inform public health measures to fight the COVID‐19 pandemic?


title: Porcine Epidemic Diarrhoea Virus Induces Cell-cycle Arrest through the DNA Damage-signalling Pathway

text: INTRODUCTION: Porcine epidemic diarrhoea virus (PEDV) infection causes watery diarrhoea, vomiting, anorexia, and weight loss, especially among neonatal piglets, inflicting on them morbidity and mortality potentially reaching 90%–100%. Despite it being known that certain mammalian cell phases are arrested by PEDV, the mechanisms have not been elucidated, and PEDV pathogenesis is poorly understood. This study determined the effect of an epidemic PEDV strain on cell cycle progression. MATERIAL AND METHODS: We observed the effect of the PEDV SHpd/2012 strain on an infected Vero cell cycle through flow cytometry and Western blot, investigating the interrelationships of cell-cycle arrest, the DNA damage–signalling pathway caused by PEDV and the phosphorylation levels of the key molecules Chk.2 and H2A.X involved upstream and downstream in this pathway. RESULTS: PEDV induced Vero cell-cycle arrest at the G1/G0 phase. The phosphorylation levels of Chk.2 and H2A.X increased with the prolongation of PEDV infection, and no significant cell-cycle arrest was observed after treatment with ATM or Chk.2 inhibitors. The proliferation of PEDV was also inhibited by treatment with ATM or Chk.2 inhibitors. CONCLUSION: PEDV-induced cell-cycle arrest is associated with activation of DNA damage–signalling pathways. Our findings elucidate the molecular basis of PEDV replication and provide evidence to support further evaluation of PEDV pathogenesis.


title: Virus removal performance and mechanism of a submerged membrane bioreactor

text: Abstract Responding to the worldwide outbreak of SARS in 2003, virus removal performance and mechanism of a SMBR were investigated by employing phage T4 as a model virus. Two membrane modules were compared in continuous operation for about 75 days. During stable operation, SMBR achieved almost complete phage removal for both membrane modules. For the 0.22μm module, the cake layer, the gel layer and the membrane contributed 6.3log, 3.1log and 1.7log, respectively to phage removal, confirming the importance of the cake/gel layer formed on the surface of membrane. The damage of the cake/gel layer resulted in the decrease of phage removal. As for the 0.1μm one, the membrane alone played a major role in phage removal. Inactivation by activated sludge and adsorption by cake/gel layer contributed about 3.6log to phage removal everyday so that there was no phage accumulation in bulk solution. The results demonstrated that SMBR was an efficient system and recommended for treatment of virus-bearing wastewater.


title: A conversation with Thomas (Tom) R. Belin- 2020 HPSS long-term excellence award winner

text: At the 2020 International Conference on Health Policy Statistics held in San Diego, Thomas (Tom) R. Belin was awarded the Long-Term Excellence Award from the Health Policy Statistics Section of the American Statistical Association. Dr. Belin was exceptionally and uniquely qualified for this award. Highlights include his innovative statistical applications for health care research and his substantial contributions to the statistics and health policy communities through mentoring and service. In this interview, we asked Tom to share stories about his upbringing, schooling, and career phases to gain insights into his numerous achievements.


Aerosol generating procedures, dysphagia assessment and COVID‐19: A rapid review


title: Serum‐free transient protein production system based on adenoviral vector and PER.C6 technology: High yield and preserved bioactivity

text: Stable E1 transformed cells, like PER.C6, are able to grow at scale and to high cell densities. E1‐deleted adenoviruses replicate to high titer in PER.C6 cells whereas subsequent deletion of E2A from the vector results in absence of replication in PER.C6 cells and drastically lowers the expression of adenovirus proteins in such cells. We therefore considered the use of an ΔE1/ΔE2 type 5 vector (Ad5) to deliver genes to PER.C6 cells growing in suspension with the aim to achieve high protein yield. To evaluate the utility of this system we constructed ΔE1/ΔE2 vector carrying different classes of protein, that is, the gene coding for spike protein derived from the Coronavirus causing severe acute respiratory syndrome (SARS‐CoV), a gene coding for the SARS‐CoV receptor or the genes coding for an antibody shown to bind and neutralize SARS‐CoV (SARS‐AB). The ΔE1/ΔE2A‐vector backbones were rescued on a PER.C6 cell line engineered to constitutively over express the Ad5 E2A protein. Exposure of PER.C6 cells to low amounts (30 vp/cell) of ΔE1/ΔE2 vectors resulted in highly efficient (>80%) transduction of PER.C6 cells growing in suspension. The efficient cell transduction resulted in high protein yield (up to 60 picogram/cell/day) in a 4 day batch production protocol. FACS and ELISA assays demonstrated the biological activity of the transiently produced proteins. We therefore conclude that ΔE1/ΔE2 vectors in combination with the PER.C6 technology may provide a viable answer to the increasing demand for high quality, high yield recombinant protein. Biotechnol. Bioeng. 2008;100: 273–283. © 2007 Wiley Periodicals, Inc.


title: Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS

text: Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS‐CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS‐CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS‐CoV‐2 due to its similarities with SARS‐CoV, and the disease as coronavirus disease‐2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.


Coping with COVID-19 – The life changing pandemic


title: Molecular characterization of infectious bronchitis viruses isolated from broiler flocks in Bushehr province, Iran: 2014 - 2015

text: The aim of this study was to provide information on the molecular characteristic and the phylogenic relationship of infectious bronchitis viruses (IBV) strains in Bushehr province in comparison to other strains reported in the Middle East. Samples were collected from broiler flocks in Bushehr province during 2014 - 2015. These flocks had respiratory problems such as gasping, sneezing and bronchial rales. A number of 135 tracheal swabs were taken from fifteen flocks (nine swabs per flock). Each three swabs collected from each flock were pooled in one tube (finally, we had three tubes for each flock). The samples were subjected to reverse transcription polymerase chain reaction (RT-PCR). The PCR products of positive samples were analyzed by sequencing of a (392 bp) segment of the spike gene and the related results were compared with the other IBV sequences in GenBank database. Samples from twelve farms (80.0%) were found to be positive. The viruses from seven farms (46.6%) were identified as field viruses closely related to variant 2. The viruses from three farms (20.0%) were characterized as Mass type and were related to vaccine strains. Two different IB viruses (variant 2 and Mass) were detected in samples from two farms (13.3%). The variant 2 genotype detected in Bushehr had high similarity to variant 2 reported from the Middle East. These variants displayed homologies ranging from 72.9% to 76.5%, and 78.8% to 80.0% with H120 and 4/91, respectively. It is necessary to design vaccination program of poultry farms using IBV strains circulating in the region.


COVID‐19 pandemic and the quality of evidence synthesis


title: Plant Production of Veterinary Vaccines and Therapeutics

text: Plant-derived biologicals for use in animal health are becoming an increasingly important target for research into alternative, improved methods for disease control. Although there are no commercial products on the market yet, the development and testing of oral, plant-based vaccines is now beyond the proof-of-principle stage. Vaccines, such as those developed for porcine transmissible gastroenteritis virus, have the potential to stimulate both mucosal and systemic, as well as, lactogenic immunity as has already been seen in target animal trials. Plants are a promising production system, but they must compete with existing vaccines and protein production platforms. In addition, regulatory hurdles will need to be overcome, and industry and public acceptance of the technology are important in establishing successful products.


Early Lessons From World War COVID: Reinventing Our Stroke Systems of Care


When success means focusing on the oxygen delivery. A case of conventional management of severe hypoxemia in SARS-CoV-2


title: Structural and functional analysis of Oceanobacillus iheyensis macrodomain reveals a network of waters involved in substrate binding and catalysis

text: Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to hMacroD1/hMacroD2, shedding light on substrate binding and catalysis. The crystal structures of D40A, N30A and G37V mutants, and those with MES, ADPr and ADP bound, allowed us to identify five fixed water molecules that play a significant role in substrate binding. Closure of the β6–α4 loop is revealed as essential not only for pyrophosphate recognition, but also for distal ribose orientation. In addition, a novel structural role for residue D40 is identified. Furthermore, it is revealed that OiMacroD not only catalyses the hydrolysis of O-acetyl-ADP-ribose but also reverses protein mono-ADP-ribosylation. Finally, mutant G37V supports the participation of a substrate-coordinated water molecule in catalysis that helps to select the proper substrate conformation.


SARS-CoV-2 cellular tropism


title: ADN de Chlamydia trachomatis en leucocitos de sangre periférica de neonatos

text: INTRODUCTION: Diagnosis of Chlamydia trachomatis infection in newborns is difficult; however, this diagnosis is performed by cell culture or by detection of IgM antibodies against C. trachomatis. Detection of C. trachomatis DNA in peripheral blood leukocytes using polymer chain reaction (PCR) may be a better tool for the diagnosis of infection by this pathogen. MATERIAL AND METHODS: A total of 44 premature newborns, all weighing less than 2500 g, were included in the study. A blood sample and nasopharyngeal lavages were obtained from each newborn. Leukocyte DNA was obtained by phenol-chloroform extraction technique. Detection of C. trachomatis was performed by amplifying the ompA gene using the PCR endpoint. Cell culture tests and the detection of IgM antibodies against C. trachomatis by microimmunofluorescence assay were also performed. RESULTS: Twenty newborns were PCR-positive (45.5%), with this test being significantly associated with the presence of pneumonia (RR = 2.28; 95% CI: 1.01 to 5.17; P = .035). The cell culture of nasopharyngeal lavage was positive in only 7 samples and no significant association was observed with any clinical or laboratory data. The titer of IgM antibodies against C. trachomatis associated with PCR-positive was 1:32 (RR = 2.74; 95% CI: 1.21 to 6.23; P = .008), however this titer was not associated with the presence of pneumonia. CONCLUSION: DNA detection in peripheral blood leukocytes could be useful for diagnosis of C. trachomatis infection.


title: Insulin Degrading Enzyme Is a Cellular Receptor Mediating Varicella-Zoster Virus Infection and Cell-to-Cell Spread

text: Summary Varicella-zoster virus (VZV) causes chickenpox and shingles. While varicella is likely spread as cell-free virus to susceptible hosts, the virus is transmitted by cell-to-cell spread in the body and in vitro. Since VZV glycoprotein E (gE) is essential for virus infection, we postulated that gE binds to a cellular receptor. We found that insulin-degrading enzyme (IDE) interacts with gE through its extracellular domain. Downregulation of IDE by siRNA, or blocking of IDE with antibody, with soluble IDE protein extracted from liver, or with bacitracin inhibited VZV infection. Cell-to-cell spread of virus was also impaired by blocking IDE. Transfection of cell lines impaired for VZV infection with a plasmid expressing human IDE resulted in increased entry and enhanced infection with cell-free and cell-associated virus. These studies indicate that IDE is a cellular receptor for both cell-free and cell-associated VZV.


title: Nanomaterials and Nanotechnology-Associated Innovations against Viral Infections with a Focus on Coronaviruses

text: Viral infections have recently emerged not only as a health threat to people but rapidly became the cause of universal fatality on a large scale. Nanomaterials comprising functionalized nanoparticles (NPs) and quantum dots and nanotechnology-associated innovative detection methods, vaccine design, and nanodrug production have shown immense promise for interfacing with pathogenic viruses and restricting their entrance into cells. These viruses have been scrutinized using rapid diagnostic detection and therapeutic interventional options against the caused infections including vaccine development for prevention and control. Coronaviruses, namely SARS-CoV, MERS-CoV, and SARS-CoV-2, have endangered human life, and the COVID-19 (caused by SARS-CoV-2) outbreak has become a perilous challenge to public health globally with huge accompanying morbidity rates. Thus, it is imperative to expedite the drug and vaccine development efforts that would help mitigate this pandemic. In this regard, smart and innovative nano-based technologies and approaches encompassing applications of green nanomedicine, bio-inspired methods, multifunctional bioengineered nanomaterials, and biomimetic drug delivery systems/carriers can help resolve the critical issues regarding detection, prevention, and treatment of viral infections. This perspective review expounds recent nanoscience advancements for the detection and treatment of viral infections with focus on coronaviruses and encompasses nano-based formulations and delivery platforms, nanovaccines, and promising methods for clinical diagnosis, especially regarding SARS-CoV-2.


title: Health insurance coverage and sources of advice in entrepreneurship: Gender differences

text: Abstract Most of the previous literature examining health insurance and entrepreneurship focused on the effects of provisions of health insurance coverage on the decision to start or end self-employment. This paper takes a different approach and investigates the decision to purchase health insurance once self-employed. Using data from the US Federal Reserve Board’s 2016 Survey of Consumer Finances, we found that in 2016 (when full provisions of the Affordable Care Act were in place) the self-employed were less likely to be insured, especially females who in the general population are more likely to be insured. Compared to the general population, the odds of being covered by health insurance were 62% lower for self-employed males and 83% lower for self-employed females. Additionally, self-employed females were less likely to be insured when they reported using friends and family as a source of financial information.


title: Network inference from multimodal data: A review of approaches from infectious disease transmission

text: Abstract Networks inference problems are commonly found in multiple biomedical subfields such as genomics, metagenomics, neuroscience, and epidemiology. Networks are useful for representing a wide range of complex interactions ranging from those between molecular biomarkers, neurons, and microbial communities, to those found in human or animal populations. Recent technological advances have resulted in an increasing amount of healthcare data in multiple modalities, increasing the preponderance of network inference problems. Multi-domain data can now be used to improve the robustness and reliability of recovered networks from unimodal data. For infectious diseases in particular, there is a body of knowledge that has been focused on combining multiple pieces of linked information. Combining or analyzing disparate modalities in concert has demonstrated greater insight into disease transmission than could be obtained from any single modality in isolation. This has been particularly helpful in understanding incidence and transmission at early stages of infections that have pandemic potential. Novel pieces of linked information in the form of spatial, temporal, and other covariates including high-throughput sequence data, clinical visits, social network information, pharmaceutical prescriptions, and clinical symptoms (reported as free-text data) also encourage further investigation of these methods. The purpose of this review is to provide an in-depth analysis of multimodal infectious disease transmission network inference methods with a specific focus on Bayesian inference. We focus on analytical Bayesian inference-based methods as this enables recovering multiple parameters simultaneously, for example, not just the disease transmission network, but also parameters of epidemic dynamics. Our review studies their assumptions, key inference parameters and limitations, and ultimately provides insights about improving future network inference methods in multiple applications.


title: Mortality Factor Survey of Severe Acute Respiratory Syndrome in Taiwan

text: SUMMARY Background Severe acute respiratory syndrome (SARS) is a new respiratory tract infectious disease caused by the highly contagious coronavirus (SARS-CoV). Its propagation and symptom progress are very rapid. This study evaluated the clinical characteristics, laboratory results and mortality factors of probable SARS cases. Methods This study was adopted with a retrospective research design to study probable SARS cases from the Chang Gung Memorial Hospital in Linkou and Kaoshiung from August 2003 to February 2004, with a total of 78 cases (average age, 44 years; standard deviation, 18 years; age range, 13–84 years) including 24 males (30.8%) and 54 females (69.2%). Results Most of the 78 cases involved nosocomial infection (56.4%). A total of 24 patients died, and the mortality rate was as high as 30.8%. Logistic regression analysis found that intubation (odds ratio, 115; p < 0.001) was the mortality forecast factor. Conclusion The mortality rate of intubation patients was 115 times higher than that of those who did not require intubation. Therefore, special care must be taken with SARS disease with severe infiltration chest X-ray images and respiratory distress. Positive medical treatment should be performed to lower the mortality rate.


title: Faculty development program for general medicine in Taiwan: Past, present, and future

text: Abstract General medical training programs are aimed at promoting competency in general practice skills with a holistic perspective of patient-centered medicine for the new generation of physicians. The faculty development program was implemented to promote learning and application of the six core competencies established by the Accreditation Council for Graduate Medical Education. This article describes the implementation and outcome of the current faculty development program. Additional assessment tools of the faculty development program are recommended to evaluate different perspectives of outcome. Our experience suggests that OSTEs are a realistic and well-received approach for faculty development that merits further investigation. According to the clinical instructors' response, our faculty development program effectively increased familiarity with various teaching and assessment skills needed to teach PGY 1 residents and ACGME competencies, and these clinical instructors also then subsequently applied these skills.


COVID-19: A pandemic with positive and negative outcomes on resource and waste flows and stocks


Hadj ritual and risk of a pandemic


title: Return to Normal: Prioritizing Elective Surgeries With Low Resource Utilization

text: Supplemental Digital Content is available in the text.


title: Inhibition of Hepatitis C Virus Infection in Cell Culture by Small Interfering RNAs

text: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and hepatocellular carcinoma, yet fully efficacious treatments are missing. In this study, we investigated RNA interference (RNAi), a specific gene silencing process mediated by small interfering RNA (siRNA) duplexes, as an antiviral strategy against HCV. Synthetic siRNAs were designed to target conserved sequences of the HCV 5′ nontranslated region (NTR) located in a functional, stem–loop structured domain of the HCV internal ribosome entry site (IRES), which is crucial for initiation of polyprotein translation. Several siRNAs dramatically reduced or even abrogated the replication of selectable subgenomic HCV replicons upon cotransfection of human hepatoma cells with viral target and siRNAs, or upon transfection of cells supporting autonomous replication of HCV replicon with siRNAs. Importantly, three siRNAs also proved capable of strongly inhibiting virus production in cell culture. One siRNA, targeting a sequence that is highly conserved across all genotypes and forms a critical pseudoknot structure involved in translation, was identified as the most promising therapeutic candidate. These results indicate that the HCV life cycle can be efficiently blocked by using properly-designed siRNAs that target functionally important, highly conserved sequences of the HCV IRES. This finding offers a novel approach towards developing IRES-based antiviral treatment for chronic HCV infections.


title: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France

text: BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009–2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.


title: Progress Toward Polio Eradication — Worldwide, January 2018–March 2020

text: Since the Global Polio Eradication Initiative (GPEI) was established in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated.* Transmission of WPV type 1 (WPV1) remains uninterrupted only in Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2018-March 31, 2020 and updates previous reports (1,2). In 2019, Afghanistan and Pakistan reported the highest number of WPV1 cases (176) since 2014. During January 1-March 31, 2020 (as of June 19), 54 WPV1 cases were reported, an approximate fourfold increase from 12 cases during the corresponding period in 2019. Paralytic poliomyelitis can also be caused by circulating vaccine-derived poliovirus (cVDPV), which emerges when attenuated oral poliovirus vaccine (OPV) virus reverts to neurovirulence following prolonged circulation in underimmunized populations (3). Since the global withdrawal of type 2-containing OPV (OPV2) in April 2016, cVDPV type 2 (cVDPV2) outbreaks have increased in number and geographic extent (4). During January 2018-March 2020, 21 countries reported 547 cVDPV2 cases. Complicating increased poliovirus transmission during 2020, the coronavirus disease 2019 (COVID-19) pandemic and mitigation efforts have resulted in suspension of immunization activities and disruptions to poliovirus surveillance. When the COVID-19 emergency subsides, enhanced support will be needed to resume polio eradication field activities.


title: Public Opinion Polarization by Individual Revenue from the Social Preference Theory

text: Social conflicts occur frequently during the social transition period and the polarization of public opinion happens occasionally. By introducing the social preference theory, the target of this paper is to reveal the micro-interaction mechanism of public opinion polarization. Firstly, we divide the social preferences of Internet users (network nodes) into three categories: egoistic, altruistic, and fair preferences, and adopt the revenue function to define the benefits obtained by individuals with different preferences among their interaction process so as to analyze their decision-making behaviors driven by the revenue. Secondly, the revenue function is used to judge the exit rules of nodes in a network, and then a dynamic network of spreading public opinion with the node (individual) exit mechanism is built based on a BA scale-free network. Subsequently, the influences of different social preferences, as well as individual revenue on the effect of public opinion polarization, are analyzed through simulation experiments. The simulation results show that (1) Different social preferences demonstrate different influences on the evolution of public opinions, (2) Individuals tend to interact with ones with different preferences, (3) The network with a single preference or a high aggregation is more likely to form public opinion polarization. Finally, the practicability and effectiveness of the proposed model are verified by a real case.


title: Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China

text: BACKGROUND: Disaster is a serious public health issue. Health professionals and community residents are main players in disaster responses but their knowledge levels of disaster medicine are not readily available. This study aimed to evaluate knowledge levels and training needs of disaster medicine among potential disaster responders and presented a necessity to popularize disaster medicine education. METHODS: A self-reporting questionnaire survey on knowledge level and training needs of disaster medicine was conducted in Shanghai, China, in 2012. A total of randomly selected 547 health professionals, 456 medical students, and 1,526 local residents provided intact information. The total response rate was 93.7%. RESULTS: Overall, 1.3% of these participants have received systematic disaster medicine training. News media (87.1%) was the most common channel to acquire disaster medicine knowledge. Although health professionals were more knowledgeable than community residents, their knowledge structure of disaster medicine was not intact. Medical teachers were more knowledgeable than medical practitioners and health administrators (p = 0.002). Clinicians performed better than public health physicians (p<0.001), whereas public health students performed better than clinical medical students (p<0.001). In community residents, education background significantly affected the knowledge level on disaster medicine (p<0.001). Training needs of disaster medicine were generally high among the surveyed. ‘Lecture’ and ‘practical training’ were preferred teaching methods. The selected key and interested contents on disaster medicine training were similar between health professionals and medical students, while the priorities chosen by local residents were quite different from health professionals and medical students (p<0.001). CONCLUSIONS: Traditional clinical-oriented medical education might lead to a huge gap between the knowledge level on disaster medicine and the current needs of disaster preparedness. Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration.


Ventilación mecánica en la lesión pulmonar por SARS-Cov2:¿Qué puede aportar la capnografía volumétrica?


Response to letter Steroids: a therapeutic option for COVID-19 pneumonia patients with end stage-stage renal disease


Letter to the EditorCARDIAC INJURY AND PROGNOSIS IN COVID-19: METHODOLOGICAL CONSIDERATIONS AND UPDATED META-ANALYSIS


title: Lignans and Their Derivatives from Plants as Antivirals

text: Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is formed by two or more phenylpropanoid units. Lignans possess diverse pharmacological properties, including their antiviral activities that have been reported in recent years. This review discusses the distribution of lignans in nature according to their structural classification, and it provides a comprehensive summary of their antiviral activities. Among them, two types of antiviral lignans—podophyllotoxin and bicyclol, which are used to treat venereal warts and chronic hepatitis B (CHB) in clinical, serve as examples of using lignans for antivirals—are discussed in some detail. Prospects of lignans in antiviral drug discovery are also discussed.


title: Activation of c-Jun N-terminal kinase by Akabane virus is required for apoptosis

text: Abstract Akabane virus (AKAV) belongs to the Simbu serogroup of the genus Orthobunyavirus in the family Bunyaviridae. It has been shown that AKAV induces apoptosis in mammalian cells. It is necessary to understand the signaling pathways involved in AKAV-induced apoptosis to further elucidate the molecular virology of AKAV. c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) are mediators of apoptosis; therefore, we investigated the roles of JNK and p38 MAPK cascades in AKAV-infected cells. We found that JNK and p38 MAPK as well as their downstream substrates, c-Jun and heat shock protein 27 (HSP27), were phosphorylated in response to AKAV infection. A JNK inhibitor (SP600125) inhibited AKAV-mediated apoptosis whereas a p38 MAPK inhibitor (SB203580) did not. We conclude that AKAV infection activates the JNK and p38 MAPK signaling pathways, and the JNK cascade plays a crucial role in AKAV-induced apoptosis in vitro.


title: A small nonhuman primate model for filovirus-induced disease

text: Abstract Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever.


title: Extracellular barriers in respiratory gene therapy

text: Abstract Respiratory gene therapy has been considered for the treatment of a broad range of pulmonary disorders. However, respiratory secretions form an important barrier towards the pulmonary delivery of therapeutic nucleic acids. In this review we will start with a brief description of the biophysical properties of respiratory mucus and alveolar fluid. This must allow the reader to gain insights into the mechanisms by which respiratory secretions may impede the gene transfer efficiency of nucleic acid containing nanoparticles (NANs). Subsequently, we will summarize the efforts that have been done to understand the barrier properties of respiratory mucus and alveolar fluid towards the respiratory delivery of therapeutic nucleic acids. Finally, new and current strategies that can overcome the inhibitory effects of respiratory secretions are discussed.


title: Assistência perioperatória de paciente com infecção pelo SARS-CoV-2 (COVID-19) submetido a ressecção de tumor de hipófise urgente. Relato de caso e diretrizes para manejo de via aérea

text: Abstract The 2020 pandemic caused by the novel coronavirus, COVID-19, had its headquarters in China. It causes Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and presents a broad spectrum of clinical manifestations, ranging from entirely asymptomatic through severe acute respiratory failure and death. Presuming a significant quantity of ventilator-dependent patients, several institutions strategically delayed elective surgeries. Particularly procedures performed involving the nasal mucosa, such as a transsphenoidal approach of the pituitary gland, considering the tremendous level of viral shedding. Nevertheless, critical cases demand expeditious resolution. Those situations are severe pituitary apoplexy, declining consciousness level, or risk of acute visual loss. This case presents a successful urgent perioperative management of a 47 year-old male COVID-19 positive patient who presented to the Emergency Department with a left frontal headache that culminated with diplopia, left eye ptosis, and left visual acuity loss after 5 days. Transsphenoidal hypophysectomy was uneventfully performed, and the patient was discharged from the hospital on postoperative day four. It additionally describes in detail the University of Mississippi Medical Center airway management algorithm for patients infected with the novel coronavirus who need emergent surgical attention.


title: Physical activity during COVID‐19 quarantine

text: The World Health Organization recommends that children and adolescents aged 5‐17 should engage in at least 60 minutes of moderate to vigorous intensity physical activity a day. Physical activity is defined as bodily movement performed by skeletal muscles that demand energy expenditure. The physical benefits of this include musculoskeletal and cardiovascular health, a healthy body weight and neuromuscular awareness, for coordination and controlling movement. The psychological benefits include managing anxiety and building self‐esteem, which are both important for children’s psycho‐social development (1).


title: Monocytes and Macrophages as Viral Targets and Reservoirs

text: Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for dissemination, long-term persistence within tissues and virus replication. Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or membrane fusion. These processes play important roles in the mechanisms contributing to the pathogenesis of these agents and in establishing viral genome persistence and latency. Upon viral infection, monocytes respond with an elevated expression of proinflammatory signalling molecules and antiviral responses, as is shown in the case of the influenza, Chikungunya, human herpes and Zika viruses. Human immunodeficiency virus initiates acute inflammation on site during the early stages of infection but there is a shift of M1 to M2 at the later stages of infection. Cytomegalovirus creates a balance between pro- and anti-inflammatory processes by inducing a specific phenotype within the M1/M2 continuum. Despite facilitating inflammation, infected macrophages generally display abolished apoptosis and restricted cytopathic effect, which sustains the virus production. The majority of viruses discussed in this review employ monocytes/macrophages as a repository but certain viruses use these cells for productive replication. This review focuses on viral adaptations to enter monocytes/macrophages, immune escape, reprogramming of infected cells and the response of the host cells.


title: Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

text: Salmonella (S.) typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector.


title: An analysis of the current status of hospital emergency preparedness for infectious disease outbreaks in Beijing, China

text: BACKGROUND: In the event of a large-scale infectious disease outbreak, hospitals will play a critical role. The objective of our study is to understand the current status of hospitals preparedness for infectious disease outbreaks in Beijing and to provide basic information for infectious disease prevention and control in hospitals. METHODS: One hundred fifty-two secondary and tertiary care hospitals in Beijing were surveyed by a standardized questionnaire. Data related to hospital demographic information and their emergency plans, laboratory diagnosis capacity, medical treatment procedures for infectious diseases, stockpiles of drugs and personal protective equipment, and staff training were collected. RESULTS: Responses were received from 134 (88.2%) of the 152 hospitals surveyed. Overall, hospitals reported that the number of physicians and nurses in infectious disease accounted for only 1.8% of the total physicians and 2.5% of the total nurses, and surgery beds accounted for 8.5% of all the fixed beds. Approximately 93.3% of the hospitals surveyed reported that they had an emergency plan, and none of those reported that their laboratories were able to isolate and identify all 8 kinds of common pathogens of infectious diseases: 22.4% of the hospitals had medical treatment procedures for all these infectious diseases, 23.1% had stored specific drugs for treatment, 2.2% had all personal protective equipment, and 30.6% reported that their health care staff had been trained in hospital emergency preparedness for infectious diseases. In general, emergency preparedness for infectious diseases in tertiary care hospitals was better than that in secondary care hospitals; the preparedness at general hospitals was better than that at specialized hospitals; and that at teaching hospitals was better than that at nonteaching hospitals. CONCLUSION: Emergency preparedness for infectious disease at hospitals in Beijing was in an early stage of development during this survey. Comprehensive measures should be developed and implemented to enhance their capacity for infectious disease emergency.


title: Introducing One Health to the Ethical Debate About Zoonotic Diseases in Southeast Asia

text: Pandemic plans recommend phases of response to an emergent infectious disease (EID) outbreak, and are primarily aimed at preventing and mitigating human‐to‐human transmission. These plans carry presumptive weight and are increasingly being operationalized at the national, regional and international level with the support of the World Health Organization (WHO). The conventional focus of pandemic preparedness for EIDs of zoonotic origin has been on public health and human welfare. However, this focus on human populations has resulted in strategically important disciplinary silos. As the risks of zoonotic diseases have implications that reach across many domains outside traditional public health, including anthropological, environmental, and veterinary fora, a more inclusive ecological perspective is paramount for an effective response to future outbreaks.


title: Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak — United States, December 31, 2019–February 4, 2020

text: On December 31, 2019, Chinese health officials reported a cluster of cases of acute respiratory illness in persons associated with the Hunan seafood and animal market in the city of Wuhan, Hubei Province, in central China. On January 7, 2020, Chinese health officials confirmed that a novel coronavirus (2019-nCoV) was associated with this initial cluster (1). As of February 4, 2020, a total of 20,471 confirmed cases, including 2,788 (13.6%) with severe illness,* and 425 deaths (2.1%) had been reported by the National Health Commission of China (2). Cases have also been reported in 26 locations outside of mainland China, including documentation of some person-to-person transmission and one death (2). As of February 4, 11 cases had been reported in the United States. On January 30, the World Health Organization (WHO) Director-General declared that the 2019-nCoV outbreak constitutes a Public Health Emergency of International Concern.† On January 31, the U.S. Department of Health and Human Services (HHS) Secretary declared a U.S. public health emergency to respond to 2019-nCoV.§ Also on January 31, the president of the United States signed a "Proclamation on Suspension of Entry as Immigrants and Nonimmigrants of Persons who Pose a Risk of Transmitting 2019 Novel Coronavirus," which limits entry into the United States of persons who traveled to mainland China to U.S. citizens and lawful permanent residents and their families (3). CDC, multiple other federal agencies, state and local health departments, and other partners are implementing aggressive measures to slow transmission of 2019-nCoV in the United States (4,5). These measures require the identification of cases and their contacts in the United States and the appropriate assessment and care of travelers arriving from mainland China to the United States. These measures are being implemented in anticipation of additional 2019-nCoV cases in the United States. Although these measures might not prevent the eventual establishment of ongoing, widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare health care systems and the general public to be ready if widespread transmission with substantial associated illness occurs; and 3) better characterize 2019-nCoV infection to guide public health recommendations and the development of medical countermeasures including diagnostics, therapeutics, and vaccines. Public health authorities are monitoring the situation closely. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC and state and local health departments.


title: Connexins/Connexons: Cell-Free Expression

text: With a few exceptions, all secretory and plasma membrane proteins studied to date are synthesized in the endoplasmic reticulum (ER) membrane. Then, they are transported by successive vesicle budding and fusion from the ER through the Golgi stacks to the plasma membrane following the general intracellular transport route referred to as secretory pathway (originally reviewed in 1). Gap junction connexins have been shown to follow this pathway.


COVID-19 – Implications on and of Surgical Practices: Where Do We Draw the Line?


title: Immunoendocrine dysbalance during uncontrolled T. cruzi infection is associated with the acquisition of a Th-1-like phenotype by Foxp3+ T cells

text: Abstract We previously showed that Trypanosoma cruzi infection in C57BL/6 mice results in a lethal infection linked to unbalanced pro- and anti-inflammatory mediators production. Here, we examined the dynamics of CD4+Foxp3+ regulatory T (Treg) cells within this inflammatory and highly Th1-polarized environment. Treg cells showed a reduced proliferation rate and their frequency is progressively reduced along infection compared to effector T (Teff) cells. Also, a higher fraction of Treg cells showed a naïve phenotype, meanwhile Teff cells were mostly of the effector memory type. T. cruzi infection was associated with the production of pro- and anti-inflammatory cytokines, notably IL-27p28, and with the induction of T-bet and IFN-γ expression in Treg cells. Furthermore, endogenous glucocorticoids released in response to T. cruzi-driven immune activation were crucial to sustain the Treg/Teff cell balance. Notably, IL-2 plus dexamethasone combined treatment before infection was associated with increased Treg cell proliferation and expression of GATA-3, IL-4 and IL-10, and increased mice survival time. Overall, our results indicate that therapies aimed at specifically boosting Treg cells, which during T. cruzi infection are overwhelmed by the effector immune response, represent new opportunities for the treatment of Chagas disease, which is actually only based on parasite-targeted chemotherapy.


title: A new PSO-optimized geometry of spatial and spatio-temporal scan statistics for disease outbreak detection

text: Abstract The spatial and spatio-temporal scan statistics proposed by Kulldorff have been applied to a number of geographical disease cluster detection problems. As the shape of the scanning window used in these methods is circular or elliptic, they cannot find irregularly shaped clusters, say clusters occurring along river valleys or in cases where disease transmission is linked to the road network. In this study, we propose a more flexible geometric structure to be used as a spatial or spatio-temporal scanning window. A particle swarm optimization (PSO) is used to optimize the scanning window to determine disease clusters. We evaluated the proposed method over a number of spatial and spatio-temporal datasets (Breast cancer mortality in Northeastern US 1988–1992 and different types of cancer in New Mexico 1982–2007). Experimental results demonstrate that the introduced approach surpasses the results produced by the circular and elliptic scan statistics in terms of efficiency, especially when dealing with irregularly shaped clusters.