title: Chapter 4 Emergence in the functionalized carbon nanotubes as smart nanocarriers for drug delivery applications

text: Abstract Carbon nanotubes (CNTs) are the newer generation advanced materials for diverse applications, starting from physical, mechanical, chemical and biological sciences. However, the present era of healthcare industry is extensively using CNTs for exploring their applications in mitigating diverse needs. The considered attention in CNTs is due to their inimitable properties such as size and aspect ratio covering surface area to the length, and amenable electrical, thermal and mechanical properties. Available in diverse forms, viz. single-walled, double walled or multi-walled structures, CNTs of different forms possess multiple advantages in various healthcare segments, and especially in drug delivery for the treatment of diseases. CNTs have proven to be useful in specific drug delivery applications such as controlled and targeted drug delivery to desired sites such as lymphatic and ocular systems, brain and other cancerous tissues. Multiple research reports have been published till date, which unequivocally gives testimony to the potential applications of CNTs. The present book chapter, in this regard, endeavor to provide an overview on synthesis, characterization and drug delivery applications of CNTs. The chapter highlights on recent regulatory standards on commercial production and safety testing of the CNTs for translating them into market.


Reduction in emergency surgery activity during COVID‐19 pandemic in three Spanish hospitals


title: Inhibition of RNA Recruitment and Replication of an RNA Virus by Acridine Derivatives with Known Anti-Prion Activities

text: BACKGROUND: Small molecule inhibitors of RNA virus replication are potent antiviral drugs and useful to dissect selected steps in the replication process. To identify antiviral compounds against Tomato bushy stunt virus (TBSV), a model positive stranded RNA virus, we tested acridine derivatives, such as chlorpromazine (CPZ) and quinacrine (QC), which are active against prion-based diseases. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that CPZ and QC compounds inhibited TBSV RNA accumulation in plants and in protoplasts. In vitro assays revealed that the inhibitory effects of these compounds were manifested at different steps of TBSV replication. QC was shown to have an effect on multiple steps, including: (i) inhibition of the selective binding of the p33 replication protein to the viral RNA template, which is required for recruitment of viral RNA for replication; (ii) reduction of minus-strand synthesis by the tombusvirus replicase; and (iii) inhibition of translation of the uncapped TBSV genomic RNA. In contrast, CPZ was shown to inhibit the in vitro assembly of the TBSV replicase, likely due to binding of CPZ to intracellular membranes, which are important for RNA virus replication. CONCLUSION/SIGNIFICANCE: Since we found that CPZ was also an effective inhibitor of other plant viruses, including Tobacco mosaic virus and Turnip crinkle virus, it seems likely that CPZ has a broad range of antiviral activity. Thus, these inhibitors constitute effective tools to study similarities in replication strategies of various RNA viruses.


title: Small molecules with antiviral activity against the Ebola virus

text: The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus.


title: The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis

text: The endoplasmic reticulum (ER) is a cellular membrane organelle that plays important roles in virus replication and maturation. Accumulating evidence indicates that virus infection often disturbs ER homeostasis and leads to ER stress, which is associated with a variety of prevalent diseases. To cope with the deleterious effects of virus-induced ER stress, cells activate critical signaling pathways including the unfolded protein response (UPR) and intrinsic mitochondrial apoptosis, which have complex effects on virus replication and pathogenesis. In this review, we present a comprehensive summary of recent research in this field, which revealed that about 36 viruses trigger ER stress and differentially activate ER stress-related signaling pathways. We also highlight the strategies evolved by viruses to modulate ER stress-related signaling networks including immune responses in order to ensure their survival and pathogenesis. Together, the knowledge gained from this field will shed light on unveiling the mechanisms of virus replication and pathogenesis and provide insight for future research as well as antiviral development.


title: Antiviral Agents☆

text: Abstract Antiviral agents are drugs approved in the USA by the Food and Drug Administration (FDA) for the treatment or control of viral infections. Available antiviral agents mainly target stages in the viral life cycle. The target stages in the viral life cycle are; viral attachment to host cell, uncoating, synthesis of viral mRNA, translation of mRNA, replication of viral RNA and DNA, maturation of new viral proteins, budding, release of newly synthesized virus, and free virus in body fluids. Two important factors that can limit the utility of antiviral drugs are toxicity and the development of resistance to the antiviral agent by the virus. In addition, host phenotypic behaviors toward antiviral drugs because of either genomic or epigenetic factors could limit the efficacy of an antiviral agent in an individual. This article summarizes the most relevant pharmacologic and clinical properties of current antiviral agents, and targets for novel antiviral agents.


title: A global perspective on hepatitis B‐related single nucleotide polymorphisms and evolution during human migration

text: Genome‐wide association studies have indicated that human leukocyte antigen (HLA)‐DP and HLA‐DQ play roles in persistent hepatitis B virus (HBV) infection in Asia. To understand the evolution of HBV‐related single nucleotide polymorphisms (SNPs) and to correlate these SNPs with chronic HBV infection among different populations, we conducted a global perspective study on hepatitis‐related SNPs. We selected 12 HBV‐related SNPs on the HLA locus and two HBV and three hepatitis C virus immune‐related SNPs for analysis. Five nasopharyngeal carcinoma‐related SNPs served as controls. All SNP data worldwide from 26 populations were downloaded from 1,000 genomes. We found a dramatic difference in the allele frequency in most of the HBV‐ and HLA‐related SNPs in East Asia compared to the other continents. A sharp change in allele frequency in 8 of 12 SNPs was found between Bengali populations in Bangladesh and Chinese Dai populations in Xishuangbanna, China (P < 0.001); these areas represent the junction of South and East Asia. For the immune‐related SNPs, significant changes were found after leaving Africa. Most of these genes shifted from higher expression genotypes in Africa to lower expression genotypes in either Europe or South Asia (P < 0.001). During this two‐stage adaptation, immunity adjusted toward a weak immune response, which could have been a survival strategy during human migration to East Asia. The prevalence of chronic HBV infection in Africa is as high as in Asia; however, the HBV‐related SNP genotypes are not present in Africa, and so the genetic mechanism of chronic HBV infection in Africa needs further exploration. Conclusion: Two stages of genetic changes toward a weak immune response occurred when humans migrated out of Africa. These changes could be a survival strategy for avoiding cytokine storms and surviving in new environments. (Hepatology Communications 2017;1:1005–1013)


Search for Therapeutics Continues as SARS ‘Epidemic’ Abates


title: What do monitoring platelet counts in COVID‐19 teach us?

text: Yang and colleagues published the relevance of thrombocytopenia in COVID-19 patients and its association with mortality in this condition in the Journal of Thrombosis and Haemostasis.1 The authors are to be applauded for the largest so-far analysis in the epidemiology of thrombocytopenia in patients with COVID-19. In addition to the association with mortality, there may be several other findings in this interesting paper which deserves mention. First of all, the study confirms that COVID-19 is not associated with significant thrombocytopenia (only 20.7% had counts less than 125 x 109/L, the lower range in this study).2,3 The 'higher' platelet counts for an illness as severe as COVID-19 is unusual and likely points towards liver activation and thrombopoietin release.


title: Heat-Related Deaths — United States, 2004–2018

text: Deaths attributable to natural heat exposure, although generally considered preventable (1), represent a continuing public health concern in the United States. During 2004-2018, an average of 702 heat-related deaths occurred in the United States annually. To study patterns in heat-related deaths by age group, sex, race/ethnicity, and level of urbanization, and to explore comorbid conditions associated with deaths resulting from heat exposure, CDC analyzed nationally comprehensive mortality data from the National Vital Statistics System (NVSS).* The rate of heat-related mortality tended to be higher among males, persons aged ≥65 years, non-Hispanic American Indian/Alaska Natives, and persons living in noncore nonmetropolitan and large central metropolitan counties. Natural heat exposure was a contributing cause of deaths attributed to certain chronic medical conditions and other external causes. Preparedness and response initiatives directed toward extreme heat events, currently underway at local, state, and national levels, can contribute to reducing morbidity and mortality associated with natural heat exposure. Successful public health interventions† to mitigate heat-related deaths include conducting outreach to vulnerable communities to increase awareness of heat-related symptoms and provide guidance for staying cool and hydrated, particularly for susceptible groups at risk such as young athletes and persons who are older or socially isolated (2). Improved coordination across various health care sectors could inform local activities to protect health during periods of high heat. For instance, jurisdictions can monitor weather conditions and syndromic surveillance data to guide timing of risk communication and other measures (e.g., developing and implementing heat response plans, facilitating communication and education activities) to prevent heat-related mortality in the United States. CDC also recommends that federal, state, local, and tribal jurisdictions open cooling centers or provide access to public locations with air conditioning for persons in need of a safe, cool, environment during hot weather conditions. In light of the coronavirus disease 2019 (COVID-19) pandemic, CDC updated its guidance on the use of cooling centers to provide best practices (e.g., potential changes to staffing procedures, separate areas for persons with symptoms of COVID-19, and physical distancing) to reduce the risk for introducing and transmitting SARS COV-2, the virus that causes COVID-19, into cooling centers.§.


title: One-step nanomorphology control of self-organized projection coronas in uniform polymeric nanoparticles

text: Abstract Uniform polymeric nanoparticles with various morphologies of projection coronas like the viruses in the coronavirus group have been formed by the self-organization of macromolecular chains polymerizing in a dispersion system of styrene (St), acrylonitrile (AN) and poly(ethylene glycol) monomethoxymonomethacrylate (PEGm) in a polar solvent (water/ethanol). An increase in the water composition reduced the crystallization degree of AN units, resulting in a variety of the nanoparticle morphology such as the increased particle size, the reduced projection size, the increased projection number, and the decreased inter-projection distance. The difference in the projection morphology strongly affected a dispersibility in water.


title: Public enemy number one

text: The new coronavirus is no small threat, but we are starting to understand how it works, reports Michael Marshall


docid: xurmzmwj

title: A Review on Applications of Computational Methods in Drug Screening and Design

text: Drug development is one of the most significant processes in the pharmaceutical industry. Various computational methods have dramatically reduced the time and cost of drug discovery. In this review, we firstly discussed roles of multiscale biomolecular simulations in identifying drug binding sites on the target macromolecule and elucidating drug action mechanisms. Then, virtual screening methods (e.g., molecular docking, pharmacophore modeling, and QSAR) as well as structure- and ligand-based classical/de novo drug design were introduced and discussed. Last, we explored the development of machine learning methods and their applications in aforementioned computational methods to speed up the drug discovery process. Also, several application examples of combining various methods was discussed. A combination of different methods to jointly solve the tough problem at different scales and dimensions will be an inevitable trend in drug screening and design.


title: Antioxidant potential of theaflavin ameliorates the activities of key enzymes of glucose metabolism in high fat diet and streptozotocin – induced diabetic rats

text: Objectives: The present study was to evaluate the effect of theaflavin on the activities of key enzymes of carbohydrate metabolism in high fat diet and streptozotocin – induced diabetic rats. Methods: Diabetes was induced in male albino Wistar rats by feeding them with high fat diet comprising of standard laboratory rat chow 84.3%, lard 5%, egg yolk powder 10%, cholesterol 0.2% and bile salt 0.5% for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (40 mg/kg b.w). Results: Theaflavin (100 mg/kg b.w /day) was administered orally to diabetic rats for 30 days. At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats. Discussion: Oral administration of theaflavin to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The results of the present study suggest that theaflavin exhibits antidiabetic effect through its antioxidant activity.


title: Repercussions of COVID-19 pandemic on municipal solid waste management: Challenges and opportunities

text: Abstract The COVID-19 pandemic has caused global emergency and has raised social and economic concerns which will also spill over to environmental issues. Amid this natural experiment, current study evaluates prevailing municipal solid waste (MSW) management practices, with the emphasis on MSW treatment and disposal facilities in select developed and developing countries. The data and information used in this paper is collected from several scientific research papers from different disciplines, publications from governments and multilateral agencies and media reports. Despite limited literature on MSW management during such pandemics, this article presets a global backdrop of MSW management during COVID-19 outbreak and examines various aspects of MSW management. Discussion includes identifying parameters of disease transmission through solid waste handling, consequences of medical waste surge on current municipal waste treatment and disposal systems. Further, based on previous pandemic and disaster waste management studies, this study also presents challenges and opportunities in the aftermath of the ongoing pandemic. The paper recommends alternatives approaches for MSW treatment and disposal and outlines the future scope of work to achieve sustainable waste management during and aftermath of the pandemics.


title: Xylem supports community-based responses to Covid-19

text: Xylem has extended its Partner Community Grants Program to support community-level responses to Covid-19.


Susceptibility of Southwestern American Indian Tribes to Coronavirus Disease 2019 (COVID‐19)


title: Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial

text: 2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV(+)) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV(+) HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.


title: Pseudomonas aeruginosa infection increases the readmission rate of COPD patients

text: INTRODUCTION: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified. METHODS: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission. RESULTS: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296–17.041; P=0.019). CONCLUSION: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients.


title: Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets

text: The ubiquitin–proteasome system (UPS) and ubiquitin-like protein (UBL) conjugation pathways are integral to cellular protein homeostasis. The growing recognition of the fundamental importance of these pathways to normal cell function and in disease has prompted an in-depth search for small-molecule inhibitors that selectively block the function of these pathways. However, our limited understanding of the molecular mechanisms and biological consequences of UBL conjugation is a significant hurdle to identifying drug-like inhibitors of enzyme targets within these pathways. Here, we highlight recent advances in understanding the role of some of these enzymes and how these new insights may be the key to developing novel therapeutics for diseases including immuno-inflammatory disorders, cancer, infectious diseases, cardiovascular disease and neurodegenerative disorders.


New opportunities for the redesign of agricultural and food systems


title: Definition of an extended MHC class II-peptide binding motif for the autoimmune disease-associated Lewis rat RT1.BL molecule.

text: The Lewis rat, an inbred rat strain susceptible to several well-characterized experimental autoimmune diseases, provides a good model to study peptide-mediated immunotherapy. Peptide immunotherapy focussing on the modulation of T cell responses by interfering with TCR-peptide-MHC complex formation requires the elucidation of the molecular basis of TCR-peptide-MHC interactions for an efficient design of modulatory peptides. In the Lewis rat most autoimmune-associated CD4+ T cell responses are MHC class II RT1.BL restricted. In this study, the characteristics of RT1.BL-peptide interactions were explored. A series of substitution analogs of two Lewis rat T cell epitopes was examined in a direct peptide-MHC binding assay on isolated RT1.BL molecules. Furthermore, other autoimmune-related as well as non-disease-related T cell epitopes were tested in the binding assay. This has led to the definition of an extended RT1.BL-peptide binding motif. The RT1.BL-peptide binding motif established in this study is the first described rat MHC-peptide binding motif based on direct MHC-peptide binding experiments. To predict good or intermediate RT1.BL binding peptides, T cell epitope search profiles were deduced from this motif. The motif and search profiles will greatly facilitate the prediction of modulatory peptides based on autoimmune-associated T cell epitopes and the identification of target structures in experimental autoimmune diseases in Lewis rats.


title: Cameroonian fruit bats harbor divergent viruses, including rotavirus H, bastroviruses, and picobirnaviruses using an alternative genetic code

text: Most human emerging infectious diseases originate from wildlife and bats are a major reservoir of viruses, a few of which have been highly pathogenic to humans. In some regions of Cameroon, bats are hunted and eaten as a delicacy. This close proximity between human and bats provides ample opportunity for zoonotic events. To elucidate the viral diversity of Cameroonian fruit bats, we collected and metagenomically screened eighty-seven fecal samples of Eidolon helvum and Epomophorus gambianus fruit bats. The results showed a plethora of known and novel viruses. Phylogenetic analyses of the eleven gene segments of the first complete bat rotavirus H genome, showed clearly separated clusters of human, porcine, and bat rotavirus H strains, not indicating any recent interspecies transmission events. Additionally, we identified and analyzed a bat bastrovirus genome (a novel group of recently described viruses, related to astroviruses and hepatitis E viruses), confirming their recombinant nature, and provide further evidence of additional recombination events among bat bastroviruses. Interestingly, picobirnavirus-like RNA-dependent RNA polymerase gene segments were identified using an alternative mitochondrial genetic code, and further principal component analyses suggested that they may have a similar lifestyle to mitoviruses, a group of virus-like elements known to infect the mitochondria of fungi. Although identified bat coronavirus, parvovirus, and cyclovirus strains belong to established genera, most of the identified partitiviruses and densoviruses constitute putative novel genera in their respective families. Finally, the results of the phage community analyses of these bats indicate a very diverse geographically distinct bat phage population, probably reflecting different diets and gut bacterial ecosystems.


COVID ‐19 and medical staff's mental health in educational hospitals in Alborz province, Iran


title: Combined use of the neutrophil-to-lymphocyte ratio and CRP to predict 7-day disease severity in 84 hospitalized patients with COVID-19 pneumonia: a retrospective cohort study.

text: Background Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide from Wuhan. An easy-to-use index capable of the early identification of inpatients who are at risk of becoming critically ill is urgently needed in clinical practice. Hence, the aim of this study was to explore an easy-to-use nomogram and a model to triage patients into risk categories to determine the likelihood of developing a critical illness. Methods A retrospective cohort study was conducted. We extracted data from 84 patients with laboratory-confirmed COVID-19 from one designated hospital. The primary endpoint was the development of severe/critical illness within 7 days after admission. Predictive factors of this endpoint were selected by LASSO Cox regression model. A nomogram was developed based on selected variables. The predictive performance of the derived nomogram was evaluated by calibration curves and decision curves. Additionally, the predictive performances of individual and combined variables under study were evaluated by receiver operating characteristic curves. The developed model was also tested in a separate validation set with 71 laboratory-confirmed COVID-19 patients. Results None of the 84 inpatients were lost to follow-up in this retrospective study. The primary endpoint occurred in 23 inpatients (27.4%). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were selected as the final prognostic factors. A nomogram was developed based on the NLR and CRP. The calibration curve and decision curve indicated that the constructed nomogram model was clinically useful. The AUCs for the NLR, CRP and Combined Index in both training set and validation sets were 0.685 (95% CI: 0.574-0.783), 0.764 (95% CI: 0.659-0.850), 0.804 (95% CI: 0.702-0.883), and 0.881 (95% CI: 0.782-0.946), respectively. Conclusions Our results demonstrated that the nomogram and Combined Index calculated from the NLR and CRP are potential and reliable predictors of COVID-19 prognosis and can triage patients at the time of admission.


title: Making of Viral Replication Organelles by Remodeling Interior Membranes

text: Positive-stranded RNA (+RNA) viruses exploit host cell machinery by subverting host proteins and membranes and altering cellular pathways during infection. To achieve robust replication, some +RNA viruses, such as poliovirus (PV), build special intracellular compartments, called viral replication organelles. A recent work from the Altan-Bonnett laboratory [1] gave new insights into the formation of poliovirus replication organelles, which are unique subcellular structures containing many individual replication complexes as a result of dynamic cellular membrane remodeling.


title: Clinical features of children hospitalized with influenza A and B infections during the 2012–2013 influenza season in Italy

text: BACKGROUND: Influenza is a major public health issue worldwide. It is characterized by episodes of infection that involve hundreds of millions of people each year. Since that in the seasons 2010–2011 and 2011–2012 the circulation of FLUB was decreasing we evaluated the clinical presentation, demographic characteristics, admitting department, and length of stay in children who contracted influenza admitted to Bambino Gesù Children’s Hospital, during the 2012–2013 influenza season, with the aim to establish if the recover of FLUB was associated to a clinical worsening, in comparison with those due to FLUA. METHODS: A total of 133 respiratory specimens, collected from patients with symptoms of respiratory tract infections, positive for the Influenza A and B viruses (FLUA and B) were subtyped. Comparisons between the FLUA and FLUB groups were performed with the one-way ANOVA for continuous parametric variables, the Mann-Whitney test for non-parametric variables, or the Chi-Square test or Fisher’s exact test (if cells <5) for categorical variables. RESULTS: 87.09 % of the FLUA isolates were the H1N1 subtype and 12.90 % were H3N2. Among the FLUB isolates, 91.54 % were the B/Yamagata/16/88 lineage and 8.45 % were the B/Victoria/02/87 lineage. The largest number of FLUA/H1N1 cases was observed in children less than 1 years old, while the B/Yamagata/16/88 lineage was most prevalent in children 3–6 years old. Fever was a common symptom for both FLUA and B affected patients. However, respiratory symptoms were more prevalent in patients affected by FLUA. The median length of stay in the hospital was 5 days for FLUA and 3 days for FLUB. CONCLUSIONS: The clinical features correlated to different Influenza viruses, and relevant subtypes, were evaluated concluding that the increasing of FLUB in the season 2012–2013 was without any dramatic change in clinical manifestation. Our findings suggest, finally, that a stronger commitment to managing patients affected by FLUA is required, as the disease is more severe than FLUB.


title: The origin of acute respiratory epidemics

text: After studying the dependence of acute respiratory diseases of all etiologies on air temperature and population immunity dynamics, the authors proposed that the air temperature and the immunity level can affect disease resistance. Knowledge of the relationship between these factors must clarify the mechanisms that determine morbidity dynamics.


title: Community-Acquired Respiratory Viruses

text: The incidence of community-acquired respiratory viruses (CARVs) is ∼15 cases per 100 patient-years after lung transplantation (LTx). Paramyxoviruses account for almost 50% of the cases of CARV infection in LTx. Most patients will be symptomatic with a mean decline of 15 to 20% in forced expiratory volume in 1 second. The attributable death rate is low in recent years 15 to 25% CARV infected LTx patients will develop chronic lung allograft dysfunction within a year after CARV infection. This risk seems to be increased in comparison to the noninfected LTx recipient. Detection rate of CARV dependent on clinical awareness, sampling, and diagnostic method with nucleic acid testing by polymerase chain reaction in bronchoalveolar lavage is the gold standard after LTx. There is no approved treatment for paramyxoviruses, most centers use ribavirin by various routes. Toxicity of systemic ribavirin is of concern and some patients will have contraindication to this treatment modality. Treatment may reduce the risk to develop chronic lung allograft dysfunction and respiratory failure. Agents under development are inhibiting viral attachment and use silencing mechanisms of viral replication.


docid: lhlwglxo

title: Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity

text: For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not require antigen-specific recognition or a priori knowledge of the causative agent. However, it is unclear whether effective stable innate immune system activation can be achieved without triggering harmful autoimmunity or other chronic inflammatory sequelae. Here, we show that transgenic expression of a picornavirus RNA-dependent RNA polymerase (RdRP), in the absence of other viral proteins, can profoundly reconfigure mammalian innate antiviral immunity by exposing the normally membrane-sequestered RdRP activity to sustained innate immune detection. RdRP-transgenic mice have life-long, quantitatively dramatic upregulation of 80 interferon-stimulated genes (ISGs) and show profound resistance to normally lethal viral challenge. Multiple crosses with defined knockout mice (Rag1, Mda5, Mavs, Ifnar1, Ifngr1, and Tlr3) established that the mechanism operates via MDA5 and MAVS and is fully independent of the adaptive immune system. Human cell models recapitulated the key features with striking fidelity, with the RdRP inducing an analogous ISG network and a strict block to HIV-1 infection. This RdRP-mediated antiviral mechanism does not depend on secondary structure within the RdRP mRNA but operates at the protein level and requires RdRP catalysis. Importantly, despite lifelong massive ISG elevations, RdRP mice are entirely healthy, with normal longevity. Our data reveal that a powerfully augmented MDA5-mediated activation state can be a well-tolerated mammalian innate immune system configuration. These results provide a foundation for augmenting innate immunity to achieve broad-spectrum antiviral protection.


title: Virion glycosylation governs integrity and infectivity of infectious pancreatic necrosis virus

text: The possible importance of the O‐linked glycosylation in virion stability and infectivity of infectious pancreatic necrosis virus (IPNV) was analysed. Enzymatic treatment with O‐glycosidase of radiolabelled virions under different ionic conditions, to allow for possible alternative exposure of glycosidic enzyme cleavage sites, did not alter the specific infectivity of virions re‐isolated after rate‐zonal centrifugation in glycerol gradients. As an alternative method to assess the significance of carbohydrates in IPNV integrity, periodate oxidation in the presence of an aldehyde quencher was chosen. Following re‐isolation of viruses, a 3–5 (10)log‐unit reduction in specific infectivity was revealed and, at higher concentrations, a total disruption or virion aggregation was observed. The loss of infectivity of intact virions was not because of a lack of attachment to cells. Additionally, re‐evaluation of reading values from UV‐spectra of purified IPNV yielded a specific infectivity of 3 × 10(11) TCID(50)‐units mg(−1) of protein and a ratio of 40 virions per TCID(50)‐unit in the CHSE‐214 cell system.


title: Macrothrombosis and stroke in patients with mild Covid‐19 infection

text: Coronavirus disease 2019 (COVID‐19) is a pandemic disease currently affecting millions of people worldwide. Its neurological implications are poorly understood, and further study is urgently required. A hypercoagulable state has been reported in patients with severe COVID‐19, but nothing is known about coagulopathy in patients with milder disease. We describe cases of patients in New York City presenting with stroke secondary to large vessel thrombosis without occlusion, incidentally found to have COVID‐19 with only mild respiratory symptoms. This is in contrast to the venous thrombosis and microangiopathy that has been reported in patients with severe COVID‐19. Our cases suggest that even in the absence of severe disease, patients with COVID‐19 may be at increased risk of thrombus formation leading to stroke, perhaps due to viral involvement of the endothelium. Further systematic study is needed, since this may have implications for primary and secondary stroke prevention in patients with COVID‐19.


title: Examining the Moderation Effect of Political Trust on the Linkage between Civic Morality and Support for Environmental Taxation

text: Climate change and pollution are threatening sustainable environments and human life. To mitigate and adapt to the effects of such threats, governments around the world need significant financial resources. Accordingly, this study focuses on which factors are associated with individuals’ support for taxation to protect the environment and pays special attention to the direct effects of civic morality and political trust, as well as their joint effects on support for environmental taxation. Ordered probit results with a sample size of 760 demonstrate that civic morality is positively associated with individuals’ support for environmental taxation; political trust works in the same way. More importantly, political trust moderates and enhances the linkage between civic morality and support for environmental taxation, demonstrating that it can serve as a powerful tool in a government’s efforts to protect the environment.


title: Human papillomavirus: The other invisible enemy

text: • The world is working with unprecedented fervor and spending billions of dollars to find a vaccine for COVID-19. • Nearly 381,500 people worldwide died from human papillomavirus-related cancers in 2018 despite a safe and effective vaccine. • With the momentum from our fight against this pandemic, we can improve vaccine implementation.


title: Genome Organization of the SARS-CoV

text: Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or developed by ourselves. Totally, 21 open reading frames (ORFs) of genes or putative uncharacterized proteins (PUPs) were predicted. Seven PUPs had not been reported previously, and two of them were predicted to contain transmembrane regions. Eight ORFs partially overlapped with or embedded into those of known genes, revealing that the SARS-CoV genome is a small and compact one with overlapped coding regions. The most striking discovery is that an ORF locates on the minus strand. We have also annotated non-coding regions and identified the transcription regulating sequences (TRS) in the intergenic regions. The analysis of TRS supports the minus strand extending transcription mechanism of coronavirus. The SNP analysis of different isolates reveals that mutations of the sequences do not affect the prediction results of ORFs.


title: Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen-independent

text: Infection of the central nervous system by murine polyomavirus (MuPyV), a persistent natural mouse pathogen, establishes brain-resident memory CD8 T cells (bT(RM)) that uniformly and chronically express PD-1 irrespective of expression of the α(E) integrin CD103, a T(RM) cell marker. In contrast, memory antiviral CD8 T cells in the spleen are PD-1(−), despite viral loads being similar in both the brain and spleen during persistent infection. Repetitive antigen engagement is central to sustained PD-1 expression by T cells in chronic viral infections; however, recent evidence indicates that expression of inhibitory receptors, including PD-1 is part of the T(RM) differentiation program. Here, we asked whether PD-1 expression by CD8 bT(RM) cells during persistent MuPyV encephalitis is antigen-dependent. By transferring MuPyV-specific CD8 bT(RM) cells into brains of naive mice and mice infected with cognate epitope-sufficient and -deficient MuPyVs, we demonstrate that antigen and inflammation are dispensable for PD-1 maintenance. In vitro and direct ex vivo analyses indicate that CD103(−) MuPyV-specific CD8 bT(RM) retain functional competence. We further show that the Pdcd-1 promoter of anti-MuPyV bT(RM) cells is epigenetically fixed in a demethylated state in the brain. In contrast, the PD-1 promoter of splenic antiviral memory CD8 T cells undergoes remethylation after being demethylated during acute infection. These data show that PD-1 expression is an intrinsic property of brain T(RM) cells in a persistent CNS viral infection.


“SARS-CoV-2 in the peritoneal waste of patients treated with peritoneal dialysis”


Cardiopulmonary resuscitation of inpatients with severe COVID-19 pneumonia: the Wuhan experience


title: Impact of Social Vulnerability on COVID-19 Incidence and Outcomes in the United States

text: Importance: Prior pandemics have disparately affected socially vulnerable communities. Whether regional variations in social vulnerability to disasters influence COVID-19 outcomes and incidence in the U.S. is unknown. Objective: To examine the association of Social Vulnerability Index (SVI), a percentile-based measure of county-level social vulnerability to disasters, and its sub-components (socioeconomic status, household composition, minority status, and housing type/transportation accessibility) with the case fatality rate (CFR) and incidence of COVID-19. Design: Ecological study of counties with at least 50 confirmed COVID-19 cases as of April 4th, 2020. Generalized linear mixed-effects models with state-level clustering were applied to estimate county-level associations of overall SVI and its sub-component scores with COVID-19 CFR (deaths/100 cases) and incidence (cases/1000 population), adjusting for population percentage aged >65 years, and for comorbidities using the average Hierarchical Condition Category (HCC) score. Counties with high SVI (≥median) and high CFR (≥median) were identified. Setting: Population-based study of U.S. county-level data. Participants: U.S. counties with at least 50 confirmed COVID-19 cases. Main outcomes and measures: COVID-19 CFR and incidence. Results: Data from 433 counties including 283,256 cases and 6,644 deaths were analyzed. Median SVI was 0.46 [Range: 0.01-1.00], and median CFR and incidence were 1.9% [Range: 0-13.3] and 1.2 per 1000 people [Range: 0.6-38.8], respectively. Higher SVI, indicative of greater social vulnerability, was associated with higher CFR (RR: 1.19 [1.05, 1.34], p=0.005, per-1% increase), an association that strengthened after adjustment for age>65 years and comorbidities (RR: 1.63 [1.38, 1.91], p<0.001), and was further confirmed in a sensitivity analysis limited to six states with the highest testing levels. Although the association between overall SVI and COVID-19 incidence was not significant, the SVI sub-components of socioeconomic status and minority status were both predictors of higher incidence and CFR. A combination of high SVI (≥0.46) and high adjusted CFR (≥2.3%) was observed in 28.9% of counties. Conclusions and Relevance: Social vulnerability is associated with higher COVID-19 case fatality. High social vulnerability and CFR coexist in more than 1 in 4 U.S. counties. These counties should be targeted by public policy interventions to help alleviate the pandemic burden on the most vulnerable population.


title: COVID-19 stressors on migrant workers in Kuwait: cumulative risk considerations

text: As a marginalised subpopulation, migrant workers often fall short from protection by public policies, they take precarious jobs with unsafe working and living conditions and they grapple with cultural and linguistic barriers. In light of the current COVID-19 pandemic, migrant workers are now exposed to additional stressors of the virus and related responses. We applied a comprehensive qualitative cumulative risk assessment framework for migrant workers living in Kuwait. This pandemic could be one of the few examples where the stressors overlap all domains of migrant workers’ lives. No single intervention can solve all the problems; there must be a set of interventions to address all domains. Local authorities and employers must act quickly to stop the spread, ensure easy access to testing and treatment, provide adequate housing and clear communication, encourage wide social support, safeguard financial protection and mental well-being and continuously re-evaluate the situation as more data are collected.


title: What is new in otitis media?

text: The “wait and see” approach in acute otitis media (AOM), consisting of postponing the antibiotic administration for a few days, has been advocated mainly to counteract the increased bacterial resistance in respiratory infections. This approach is not justified in children less than 2 years of age and this for several reasons. First, AOM is an acute inflammation of the middle ear caused in about 70% of cases by bacteria. Redness and bulging of the tympanic membrane are characteristic findings in bacterial AOM. Second, AOM is associated with long-term dysfunction of the inflamed eustachian tube (ET), particularly in children less than 2 years of age. In this age group, the small calibre of the ET together with its horizontal direction result in impaired clearance, ventilation and protection of the middle ear. Third, recent prospective studies have shown poor long-term prognosis of AOM in children below 2 years with at least 50% of recurrences and persisting otitis media with effusion (OME) in about 35% 6 months after AOM. Viruses elicit AOM in about 30% of children. A prolonged course of AOM has been observed when bacterial and viral infections are combined because viral infection is also associated with ET dysfunction in young children. Bacterial and viral testing of the nasopharyngeal aspirate is an excellent tool both for initial treatment and recurrence of AOM. Antibiotic treatment of AOM is mandatory in children less than 2 years of age to decrease inflammation in the middle ear but also of the ET particularly during the first episode. The best choice is amoxicillin because of its superior penetration in the middle ear. Streptococci pneumoniae with intermediary bacterial resistance to penicillin are particularly associated with recurrent AOM. Therefore the dosage of amoxicillin should be 90 mg/kg per day in three doses. In recurrent AOM with β-lactamase-producing bacilli, amoxicillin should be associated with clavulanic acid at a dose of 6.4 mg/kg per day. The duration of the treatment is not established yet but 10 days is reasonable for a first episode of AOM. OME may be a precursor initiating AOM but also a complication thereof. OME needs a watchful waiting approach. When associated with deafness for 2–3 months in children over 2 years of age, an antibiotic should be given according to the results of the bacterial resistance in the nasopharyngeal aspirate. The high rate of complications of tympanostomy tube insertion outweighs the beneficial effect on hearing loss. The poor results of this procedure are due to the absence of effects on ET dysfunction. Pneumococcal vaccination has little beneficial effects on recurrent AOM and its use in infants needs further studies. Treatment with amoxicillin is indicated in all children younger than 2 years with a first episode of AOM presenting with redness and bulging of the tympanic membrane. Combined amoxicillin and clavulanic acid should be given in patients with β-lactamase-producing bacteria. The duration of treatment is estimated to be at least 10 days depending on the findings by pneumo-otoscopy and tympanometry. Bacterial and viral testing of the nasopharyngeal aspirate is highly recommended particularly in children in day care centres as well as for regular follow-up. The high recurrence rate is due to the long-lasting dysfunction of the eustachian tube and the immune immaturity of children less than 2 years of age.


Chikungunya Fever, Hong Kong


title: Characterisation of porcine epidemic diarrhea virus isolates during the 2014–2015 outbreak in the Philippines

text: The viral agent of the porcine epidemic diarrhea (PED) was investigated during the reported 2014–2015 outbreaks in commercial farms in Central Luzon, Philippines. The study covered detection of PED virus (PEDV) in fecal and intestinal samples through reverse transcription PCR and sequence analysis of the nucleocapsid (N) gene. Results showed that 10 out of 34 fecal and intestinal samples examined were positive for PEDV. The partial nucleotide sequence of the N gene of the field samples showed 98–99% homologous to PEDV sequences registered in the GenBank. It was also noted that N gene sequences between field samples were 98% homologous. Interestingly, the partial sequences of the N genes of the field samples were genetically similar to the PEDV isolates from USA, China, Mexico, Canada and Japan. The phylogenetic tree analysis revealed that the Philippine samples clustered in group 2–1 of the PEDV, wherein the isolates of this group were responsible for the outbreaks in Asia and the USA. Analysis of the partial nucleotide and amino acid sequences revealed polymorphisms, deletions and insertions in the N-gene of the PEDV. Amino acid sequence alignment also showed deletions and insertion in the PEDV detected in the Philippines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-018-0470-4) contains supplementary material, which is available to authorized users.


docid: izhzaljd

title: Epidemiology of Injuries Sustained by Civilians and Local Combatants in Contemporary Armed Conflict: An Appeal for a Shared Trauma Registry Among Humanitarian Actors

text: BACKGROUND: Conflict-related injuries sustained by civilians and local combatants are poorly described, unlike injuries sustained by US, North Atlantic Treaty Organization, and coalition military personnel. An understanding of injury epidemiology in twenty-first century armed conflict is required to plan humanitarian trauma systems capable of responding to population needs. METHODS: We conducted a systematic search of databases (e.g., PubMed, Embase, Web of Science, World Health Organization Catalog, Google Scholar) and grey literature repositories to identify records that described conflict-related injuries sustained by civilians and local combatants since 2001. RESULTS: The search returned 3501 records. 49 reports representing conflicts in 18 countries were included in the analysis and described injuries of 58,578 patients. 79.3% of patients were male, and 34.7% were under age 18 years. Blast injury was the predominant mechanism (50.2%), and extremities were the most common anatomic region of injury (33.5%). The heterogeneity and lack of reporting of data elements prevented pooled analysis and limited the generalizability of the results. For example, data elements including measures of injury severity, resource utilization (ventilator support, transfusion, surgery), and outcomes other than mortality (disability, quality of life measures) were presented by fewer than 25% of reports. CONCLUSIONS: Data describing the needs of civilians and local combatants injured during conflict are currently inadequate to inform the development of humanitarian trauma systems. To guide system-wide capacity building and quality improvement, we advocate for a humanitarian trauma registry with a minimum set of data elements. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00268-020-05428-y) contains supplementary material, which is available to authorized users.


title: Lonicerae japonicae flos and Lonicerae flos: a systematic review of ethnopharmacology, phytochemistry and pharmacology

text: Lonicerae japonicae flos (called Jinyinhua, JYH in Chinese), flowers or flower buds of Lonicera japonica Thunberg, is an extremely used traditional edible-medicinal herb. Pharmacological studies have already proved JYH ideal clinical therapeutic effects on inflammation and infectious diseases and prominent effects on multiple targets in vitro and in vivo, such as pro-inflammatory protein inducible nitric oxide synthase, toll-like receptor 4, interleukin-1 receptor. JYH and Lonicerae flos [called Shanyinhua, SYH in Chinese, flowers or flower buds of Lonicera hypoglauca Miquel, Lonicera confusa De Candolle or Lonicera macrantha (D.Don) Spreng] which belongs to the same family of JYH were once recorded as same herb in multiple versions of Chinese Pharmacopoeia (ChP). However, they were listed as two different herbs in 2005 Edition ChP, leading to endless controversy since they have close proximity on plant species, appearances and functions, together with traditional applications. In the past decades, there has no literature regarding to systematical comparison on the similarity concerning research achievements of the two herbs. This review comprehensively presents similarities and differences between JYH and SYH retrospectively, particularly proposing them the marked differences in botanies, phytochemistry and pharmacological activities which can be used as evidence of separate list of JYH and SYH. Furthermore, deficiencies on present studies have also been discussed so as to further research could use for reference.


title: Technology‐based management of neurourology patients in the COVID‐19 pandemic: Is this the future? A report from the International Continence Society (ICS) institute

text: Coronavirus disease‐2019 (COVID‐19) pandemic significantly altered our daily life as well as our professional practice. COVID‐19 has disrupted our lives both professionally and personally. We know the urological management in a neurogenic patient needs to be tailored to the individual circumstances, this is even more pertinent during these uncertain times. International Continence Society is the premier international organization in functional urology. Lately, it has established an institute to facilitate teaching and training opportunities all over the world. The School of Neurourology teamed with the School of Modern Technology and set up a Webinar—“How to manage the neuro‐urological patients in the current pandemic.” This was set up as a case‐based discussion to deliberate the management of our patients in the present climate and examine the role of modern technology in overcoming the current barriers.


title: “The COVID-19 Generation”: A Cautionary Note

text: With COVID-19 presenting as a global pandemic, we have noticed an emerging rhetoric concerning “the COVID-19 Generation,” both anecdotally and across various media outlets. The narratives advanced to support such rhetoric have distinct implications for the study of work, aging, and retirement. In this commentary, we review this emerging issue and present evidence against attempts to define “the COVID-19 Generation” as a new construct along conceptual, methodological, as well as practical lines, with a specific focus on identifying real dangers associated with investigating and potentially managing a new generation associated with this pandemic. We strongly caution against the adoption of “the COVID-19 Generation” as a concept of study and instead offer several suggestions to researchers, organizations, and practitioners seeking answers to complicated questions about links between COVID-19 and various processes relevant to work, aging, and retirement during this time of uncertainty.


Part 2 model eye simulation: aerosol generating procedures in intraocular surgery


title: Establishment and Clinical Applications of a Portable System for Capturing Influenza Viruses Released through Coughing

text: Coughing plays an important role in influenza transmission; however, there is insufficient information regarding the viral load in cough because of the lack of convenient and reliable collection methods. We developed a portable airborne particle-collection system to measure the viral load; it is equipped with an air sampler to draw air and pass it through a gelatin membrane filter connected to a cone-shaped, megaphone-like device to guide the cough airflow to the membrane. The membrane was dissolved in a medium, and the viral load was measured using quantitative real-time reverse transcriptase-polymerase chain reaction and a plaque assay. The approximate viral recovery rate of this system was 10% in simulation experiments to collect and quantify the viral particles aerosolized by a nebulizer. Using this system, cough samples were collected from 56 influenza A patients. The total viral detection rate was 41% (23/56), and the viral loads varied significantly (from <10, less than the detection limit, to 2240 viral gene copies/cough). Viable viruses were detected from 3 samples with ≤18 plaque forming units per cough sample. The virus detection rates were similar among different groups of patients infected with different viral subtypes and during different influenza seasons. Among patients who did not receive antiviral treatment, viruses were detected in one of six cases in the vaccinated group and four of six cases in the unvaccinated group. We found cases with high viral titers in throat swabs or oral secretions but very low or undetectable in coughs and vice versa suggesting other possible anatomical sites where the viruses might be mixed into the cough. Our system is easy to operate, appropriate for bedside use, and is useful for comparing the viral load in cough samples from influenza patients under various conditions and settings. However, further large-scale studies are warranted to validate our results.


title: Levodopa attenuates cellular apoptosis in steroid-associated necrosis of the femoral head

text: The present study aimed to investigate the effects of levodopa (LEV) on cellular apoptosis in a rabbit model of steroid-associated necrosis of the femoral head (SANFH). A total of 44 healthy adult Chinese rabbits were randomly divided into three groups: Group A (n=15), administered a combination of lipopolysaccharide and hormone to establish the SANFH animal model; group B (n=15), SANFH animal model as in group A orally administered LEV (0.4 g/kg/day) on the day of injection; and group C (n=14), the control group. On the 6th and 8th week of modeling, seven rabbits from each group were sacrificed to harvest bilateral femoral head specimens for hematoxylin and eosin staining and apoptosis detection by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay analysis, as well as for observing pathological changes and analyzing cellular apoptosis. Eight weeks after modeling, the serum insulin-like growth factor (IGF)-1 levels of the three groups were measured. The empty lacunae rate and apoptosis index of bone cells in the treatment group were significantly lower than that of the model group (P<0.01). Eight weeks after treatment, the serum levels of IGF-1 were significantly higher than that of the model group (P<0.01). These findings suggested that LEV was able to reduce steroid-induced bone cellular apoptosis, reduce the occurrence of necrosis of the femoral head and, through in vivo metabolism, it may promote the synthesis and release of IGF-1, which could be one of its biological pathways to prevent and treat SANFH.


docid: efpcwhnb

title: Automatisches Pollenmonitoring in Deutschland: Eine Arbeit der Sektion Umwelt- und Arbeitsmedizin der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)


docid: lfvzjkrr

title: Coronavirus Associated Fulminant Myocarditis Successfully Treated With Intravenous Immunoglobulin and Extracorporeal Membrane Oxygenation


docid: cwtdkylo

title: COVID-19 and telepsychiatry: Early outpatient experiences and implications for the future

text: The COVID-19 pandemic has dramatically transformed the U.S. healthcare landscape. Within psychiatry, a sudden relaxing of insurance and regulatory barriers during the month of March 2020 enabled clinicians practicing in a wide range of settings to quickly adopt virtual care in order to provide critical ongoing mental health supports to both existing and new patients struggling with the pandemic's impact. In this article, we briefly review the extensive literature supporting the effectiveness of telepsychiatry relative to in-person mental health care, and describe how payment and regulatory challenges were the primary barriers preventing more widespread adoption of this treatment modality prior to COVID-19. We then review key changes that were implemented at the federal, state, professional, and insurance levels over a one-month period that helped usher in an unprecedented transformation in psychiatric care delivery, from mostly in-person to mostly virtual. Early quality improvement data regarding virtual visit volumes and clinical insights from our outpatient psychiatry department located within a large, urban, tertiary care academic medical center reflect both the opportunities and challenges of virtual care for patients and providers. Finally, we provide clinical suggestions for optimizing telepsychiatry based on our experience, make a call for advocacy to continue the reduced insurance and regulatory restrictions affecting telepsychiatry even once this public health crisis has passed, and pose research questions that can help guide optimal utilization of telepsychiatry as mainstay or adjunct of outpatient psychiatric treatment now and in the future.


docid: heknhtni

title: Natural selection and infectious disease in human populations

text: The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology.


title: Artículo EspecialEl médico frente a la COVID-19: lecciones de una pandemia

text: Abstract Apart from its enormous health and economic impact, the COVID-19 pandemic has changed the way of practicing medicine and medical education. It is likely that this effect may accelerate the transformation that both activities are experiencing. The present article, written at the peak of the crisis, sets out some thoughts on four topics: 1) the publication of false and sensationalist news; 2) risks of taking medical decisions not based on the evidence; 3) the bioethical implications when there are sufficient resources available for everybody and; 4) the possible effects of the crisis on the teaching of medicine. This crisis should enable doctors, teachers and, students of medicine to draw conclusions and be better prepared for the future. Firstly, it is essential to maintain critical thinking that may protect against the “infodemic”. Furthermore, the scientific and ethical standards learned in the faculty, should not be lowered, but remain intact. Lastly, it should be remembered that, in a devastating pandemic like the current one, apart from scientific medicine, which is practised with the brain, that other medicine that is practiced with the heart must also be practised.


title: Risk factors for disease severity, unimprovement, and mortality of COVID-19 patients in Wuhan, China

text: Abstract Objective Since December 2019, coronavirus disease (COVID-19) emerged in Wuhan. However, the characteristics and risk factors associated with disease severity, unimprovement and mortality are unclear. Methods All consecutive patients diagnosed with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020 were enrolled in this retrospective cohort study. Results A total of 663 COVID-19 patients were included in this study. Among those, 247 (37.3%) had at least one kind of chronic disease. A total of 0.5% (n=3) of patients were diagnosed with mild COVID-19, while 37.8% (251/663), 47.5% (315/663), and 14.2% (94/663) were in moderate, severe, and critical condition, respectively. In our hospital during follow-up, 251 of 663 (37.9%) patients were improved and 25 patients died, leading to a mortality rate of 3.77%. Older patients (>60 years old) and those with chronic diseases were prone to have severe and critical COVID-19 conditions, show unimprovement, and die (P < 0.001, < 0.001). Multivariate logistic regression analysis identified being male (OR = 0.486, 95% CI 0.311-0.758; P = 0.001), having severe COVID-19 conditions (OR = 0.129, 95% CI 0.082-0.201; P < 0.001), expectoration (OR = 1.796, 95% CI 1.062-3.036; P = 0.029), muscle ache (OR = 0.309, 95% CI 0.153-0.626; P = 0.001), and decreased albumin (OR = 1.929, 95% CI 1.199-3.104; P = 0.007) were associated with unimprovement in COVID-19 patients. Conclusion Being male, in severe COVID-19 conditions, expectoration, muscle ache, and decreased albumin were independent risk factors which influence the improvement of COVID-19 patients.


title: Influence of extreme weather and meteorological anomalies on outbreaks of influenza A (H1N1)

text: Biological experiments and epidemiological evidence indicate that variations in environment have important effect on the occurrence and transmission of epidemic influenza. It is therefore important to understand the characteristic patterns of transmission for prevention of disease and reduction of disease burden. Based on case records, we analyzed the environmental characteristics including climate variables in Changsha, and then constructed a meteorological anomaly susceptive-infective-removal (SIR) model on the basis of the results of influenza A (H1N1) transmission. The results showed that the outbreak of influenza A (H1N1) in Changsha showed significant correlation with meteorological conditions; the spread of influenza was sensitive to meteorological anomalies, and that the outbreak of influenza A (H1N1) in Changsha was influenced by a combination of absolute humidity anomalous weather conditions, contact rates of the influenza patients and changes in population movements. These findings will provide helpful information regarding prevention strategies under different conditions, a fresh understanding of the emergence and re-emergence of influenza outbreaks, and a new perspective on the transmission dynamics of influenza.


title: SKEMPI 2.0: an updated benchmark of changes in protein–protein binding energy, kinetics and thermodynamics upon mutation

text: MOTIVATION: Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein–protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering. RESULTS: We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein–protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding. AVAILABILITY AND IMPLEMENTATION: The database is available as supplementary data and at https://life.bsc.es/pid/skempi2/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


The coronavirus pandemic and aerosols: Does COVID-19 transmit via expiratory particles?


title: Epidemiological Characteristics of Imported Influenza A (H1N1) Cases during the 2009 Pandemic in Korea

text: OBJECTIVES: Quarantine measure for prevention of epidemic disease and further evaluations of their efficiency are possible only by elaborating analyses of imported cases. The purpose of this study was to analyze descriptive epidemiological characteristics of pandemic influenza A (H1N1) cases imported to Korea. METHODS: We collected two sets of data. The first set, comprised daily reported cases of H1N1 obtained from local cities in accordance with government policy about mandatory reporting of all H1N1 cases during May 1 to August 19, 2009. The second set, including 372 confirmed imported H1N1 cases, identified from 13 National Quarantine Stations in the Korea Centers for Disease Control and Prevention from May 24 to December 31, 2009. However, given the lack of information on the nature of the imported H1N1 cases from the two data sets during the over lapping period from May 24 to August 19, we express the number of imported cases as a range for this period. RESULTS: We estimated that the number of imported H1N1 cases from May 1 to August 19, 2009, was between 1,098 and 1,291 and the total number of cases was 2,409 to 2,580. We found the number of imported cases was beginning to diminish as of August. A analysis of the second data set showed that the distribution of sex was similar (males 50.7%, females 49.3%) and the age distribution from 20 to 59 was 61.5% and that of 60 and over was 0.8% of the 372 cases. We identified 25 countries where people infected with H1N1 traveled and 67.5% were in Asia. But the proportion of cases (/1,000) by region shows Oceania (0.199), South America (0.118), Southeast Asia (0.071), North America (0.049), Europe (0.035), and Northeast Asia (0.016) in that order. The order of H1N1 peaking was the Southern Hemisphere, Tropics, and the Nothern Hemisphere. CONCLUSIONS: This study provided information that could make possible the evaluation of the government quarantine measure for stopping imported disease from causing community-acquired spread in the future.


New Design for Aerosol Protection During Endotracheal Intubation in the COVID-19 Pandemic Era: The "Anti-Aerosol Igloo" (AAI)


Simulation of the interferon-mediated protective field in lymphoid organs with their spatial and functional organization taken into consideration


title: COVID-19 pandemic: Emerging perspectives and future trends

text: World is living on the edge. The human cost of COVID pandemic could be extraordinary. We find ourselves in a time of great economic, social, and medical uncertainty. The pandemic demands action on many fronts, from prevention to testing to treatment. We need to create simple, cheap, more accessible testing for SARS-CoV-2. A faster way has to be developed to identify antibodies that neutralize the virus. More than 100 vaccines for the SARS-CoV-2 are at various stages of development. Some six groups have already begun injecting formulations into volunteers in safety trials; others have started testing in animals. The biggest challenge is to determine which vaccine is ideal. Reason and science have to guide us. There is urgent need to critically appraise evidence in deciding how to treat patients. We need a drug or combination of drugs that work. Remdesivir has generated hope. It may prove to be a magic bullet. Countries like Taiwan, Vietnam, Singapore, Hong Kong, South Korea, New Zealand have done exceptionally well to contain the spread of COVID-19. It is widely believed that during the pandemic treatment suffers. Patients with diseases like cancer, diabetes, renal failure, CAD and pregnant women need special attention. As the pandemic pushes up levels of hunger among the global poor, governments must prevent devastating nutrition and health consequences for children missing out on school meals amid school closures. Nations will have endemic SARS-CoV-2 infection for the foreseeable future. A structured and well-coordinated approach is critical for tackling this global crisis.


title: Inhibitors of signal peptide peptidase and subtilisin/kexin-isozyme 1 inhibit Ebola virus glycoprotein-driven cell entry by interfering with activity and cellular localization of endosomal cathepsins

text: Emerging viruses such as severe fever and thrombocytopenia syndrome virus (SFTSV) and Ebola virus (EBOV) are responsible for significant morbidity and mortality. Host cell proteases that process the glycoproteins of these viruses are potential targets for antiviral intervention. The aspartyl protease signal peptide peptidase (SPP) has recently been shown to be required for processing of the glycoprotein precursor, Gn/Gc, of Bunyamwera virus and for viral infectivity. Here, we investigated whether SPP is also required for infectivity of particles bearing SFTSV-Gn/Gc. Entry driven by the EBOV glycoprotein (GP) and the Lassa virus glycoprotein (LASV-GPC) depends on the cysteine proteases cathepsin B and L (CatB/CatL) and the serine protease subtilisin/kexin-isozyme 1 (SKI-1), respectively, and was examined in parallel for control purposes. We found that inhibition of SPP and SKI-1 did not interfere with SFTSV Gn + Gc-driven entry but, unexpectedly, blocked entry mediated by EBOV-GP. The inhibition occurred at the stage of proteolytic activation and the SPP inhibitor was found to block CatL/CatB activity. In contrast, the SKI-1 inhibitor did not interfere with CatB/CatL activity but disrupted CatB localization in endo/lysosomes, the site of EBOV-GP processing. These results underline the potential of protease inhibitors for antiviral therapy but also show that previously characterized compounds might exert broader specificity than initially appreciated and might block viral entry via diverse mechanisms.


title: Chapter 13 Animals and Human Health Where Do They Meet? ∗

text: Abstract Human health and animal health are closely intertwined. We share hundreds of diseases with animals, and they are vectors for many diseases that assail humans—but, at the same time, they are essential to many treatments and cures. We discuss in this chapter various aspects of intimate relationship between human and animal health, giving examples of the importance of multidisciplinary studies in understanding these connections and the fundamental aspects of strategies for promoting the health and well-being of both groups.


title: Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19

text: The outbreak of COVID-19 caused by 2019–nCov/SARS-CoV-2 has become a pandemic with an urgent need for understanding the mechanisms and identifying a treatment. Viral infections including SARS-CoV are associated with increased levels of reactive oxygen species, disturbances of Ca(++) caused by unfolded protein response (UPR) mediated by endoplasmic reticulum (ER) stress and is due to the exploitation of virus's own protein i.e., viroporins into the host cells. Several clinical trials are on-going including testing Remdesivir (anti-viral), Chloroquine and Hydroxychloroquine derivatives (anti-malarial drugs) etc. Unfortunately, each drug has specific limitations. Herein, we review the viral protein involvement to activate ER stress transducers (IRE-1, PERK, ATF-6) and their downstream signals; and evaluate combination therapies for COVID-19 mediated ER stress alterations. Melatonin is an immunoregulator, anti-pyretic, antioxidant, anti-inflammatory and ER stress modulator during viral infections. It enhances protective mechanisms for respiratory tract disorders. Andrographolide, isolated from Andrographis paniculata, has versatile biological activities including immunomodulation and determining SARS-CoV-2 binding site. Considering the properties of both compounds in terms of anti-inflammatory, antioxidant, anti-pyrogenic, anti-viral and ER stress modulation and computational approaches revealing andrographolide docks with the SARS-CoV2 binding site, we predict that this combination therapy may have potential utility against COVID-19.


title: Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review

text: Neurological manifestations and outcomes of children with the 2009 H1N1 virus infection have been reported in three American series and from smaller cohorts and case reports worldwide. Of the 83 children admitted between April 2009 and March 2010 with H1N1 virus infection to a tertiary children’s hospital in a European setting, five children aged between 2 and 10 years had neurological symptoms. Four patients had seizures and encephalopathy at presentation. One patient presented with ataxia; one developed neuropsychiatric manifestations, and two developed movement disorders during the disease course. Early neuroimaging showed evidence of acute necrotising encephalopathy (ANE) in one case and non-specific white matter changes in another. Initial neuroimaging was normal for the other three, but interval MRI showed increased signal in bilateral periventricular distribution in one and significant cerebral volume loss in the other. Clinical outcomes varied: two recovered fully while three had residual seizures and/or significant cognitive deficits. Conclusion An analysis of our patients along with all reported cases reveal that seizures and encephalopathy were common neurological presentations associated with pandemic 2009 H1N1 influenza virus infection in children requiring hospital admission. Neuroimaging suggestive of ANE, basal ganglia involvement and volume loss appears to be associated with worse neurological outcome.


title: Attitudes of consumers and live-poultry workers to central slaughtering in controlling H7N9: a cross-sectional study

text: BACKGROUND: Guangdong Province in the Pearl River Delta of Southeast China is among the areas in the country with the highest rates of avian flu cases. In order to control the outbreak of human-infected H7N9 cases, Guangdong launched a new policy on the central slaughtering of live poultry in 2015. This study aims to evaluate attitudes of consumers and live-poultry workers toward the policy. The live-poultry workers consisted of two sub-groups: live-poultry traders and poultry farm workers. METHODS: Consumers and live-poultry workers from Guangdong were enrolled by stratified multi-stage random sampling. Online and field surveys were conducted to investigate participants’ attitudes on policy implementation. Questionnaires were developed to quantify participant demographics, to collect information about attitudes toward the policy, and to identify influential factors of policy acceptability. Proportional odds logistics regression was used in the univariate and multivariate analyses. A total of 1449 consumers, 181 live-poultry traders, and 114 poultry farm workers completed the study. RESULTS: Policy acceptability percentages among consumers, live-poultry traders, and poultry farm workers were 57.1, 37.9, and 62.6%, respectively. Logistics regression shows that consumers tended not to support the policy if they were males, if they were concerned with the food safety of chilled products, and if they preferred purchasing live poultry. Live-poultry traders tended not to support if they were subsidized by the government, if they were males, if they experienced a drop in trading volume, and if they were unclear whether avian flu was a preventable disease. Finally, poultry farm workers tended not to support if they experienced a drop in trading volume, if they operated a poultry farm on a small to medium scale, and if they experienced inconvenience in their work due to the policy. CONCLUSIONS: The study reveals a substantial refusal or slowness to accept the policy. Failure to accept the policy results from varying reasons. Among consumers, concern about food safety and dietary preference are two major causes of disapproval. Policy acceptability among live-poultry workers diverges within the two sub-groups. While a large percentage of poultry farm workers accept the policy, the drop in trading and an insufficient subsidy hamper acceptance by live-poultry traders. We recommend that policy-makers promote health education and alleviate the policy impact on trading with a reformed subsidy policy to increase acceptability. These findings are crucial for the prevention of human-infected H7N9 cases in Guangdong. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-017-4374-9) contains supplementary material, which is available to authorized users.


title: A randomized multicenter clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-CoV-2 infection in high-risk contacts (MeCOVID Trial): A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: Primary objective: to evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of asymptomatic SARS-CoV-2 infection. To evaluate the efficacy of melatonin to prevent the development of severe COVID-19 in the participants enrolled in this study who develop SARS-CoV-2 infection along the trial. To evaluate the duration of COVID-19 symptoms in participants receiving melatonin before the infection. To evaluate seroconversion timing post-symptom onset. Exploratory objectives: To compare severity of COVID-19 between men and women. To evaluate the influence of sleep and diet on prevention from SARS-CoV-2 infection. To evaluate the effect of melatonin on the incidence and characteristics of lymphopenia and increase of inflammatory cytokines related to COVID-19. TRIAL DESIGN: This is a two-arm parallel randomised double-blind controlled trial to evaluate the efficacy of melatonin versus placebo in the prophylaxis of coronavirus disease 2019 among healthcare workers. PARTICIPANTS: Male or female participants ≥ 18 and ≤ 80 years of age. Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection. Not having a previous COVID19 diagnosis. Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1(st) 2020 until study enrolment. Having a negative SARS-CoV 2 reverse-transcription PCR (RT-PCR) result or a negative serologic rapid test (IgM/IgG) result before randomization. Premenopausal women must have a negative urinary pregnancy test in the 7 days before starting the trial treatment. Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method. HIV infection. Active hepatitis B infection. Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis. Osteoporosis. Myasthenia gravis. Pre-existent maculopathy. Retinitis pigmentosa. Bradycardia (less than 50 bpm). Weight less than 40 Kg. Participant with any immunosuppressive condition or hematological disease. Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone. Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption. Treatment with fluvoxamine. Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon. Pregnancy. Breastfeeding. History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis. Insulin-dependent diabetes mellitus. Known history of hypersensitivity to the study drug or any of its components. Patients that should not be included in the study at the judgment of the research team. Participants will be recruited from the following eight hospitals in Madrid, Spain: Hospital Universitario La Paz, Hospital Ramón y Cajal, Hospital Infanta Sofía, Hospital 12 de Octubre, Hospital Clínico San Carlos, Hospital Central de la defensa Gómez Ulla,Hospital de La Princesa and Hospital Infanta Leonor. INTERVENTION AND COMPARATOR: Experimental: Melatonin (Circadin®, Exeltis Healthcare, Spain): 2 mg of melatonin orally before bedtime for 12 weeks. Comparator: Identical looking placebo (Laboratorios Liconsa, Spain) orally before bedtime for 12 weeks. MAIN OUTCOMES: Number of SARS-CoV-2 (COVID-19) symptomatic infections confirmed by polymerase chain reaction (PCR) test or serologic test or according to each centre diagnosis protocol. Primary outcome will be measured until the end of treatment for each participant (until the date of the last dose taken by each patient). RANDOMISATION: Patients who meet all inclusion and no exclusion criteria will be randomised, stratified by centres, sex and age (<50 and ≥ 50 years old). The randomisation sequence was created using SAS version 9.4 statistical software (procedure ‘PROC PLAN’) with a 1:1 allocation. No randomisation seed was specified. The randomisation seed was generated taking the hour of the computer where the program was executed. Randomization will be done centrally through the electronic system RedCAP® in order to conceal the sequence until interventions are assigned BLINDING (MASKING): Participants, caregivers, and those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 450 participants are planned to be enrolled in this clinical trial, 225 in the experimental arm and 225 in the placebo arm. TRIAL STATUS: Protocol version 3.0, 17th of April 2020. Recruitment ongoing. First participant was recruited on the 21st of April 2020. The final participant is anticipated to be recruited on the 31st of May 2020. As of May 18th, 2020, a total of 312 participants have been enrolled (154 at Hospital La Paz, 85 at Hospital Infanta Sofía and 73 at Hospital 12 de Octubre). TRIAL REGISTRATION: EU Clinical Trials Register: 2020-001530-35; Date of trial registration: 13th of April 2020; https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001530-35/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: Estimation of basic reproduction number of the Middle East respiratory syndrome coronavirus (MERS-CoV) during the outbreak in South Korea, 2015

text: BACKGROUND: In South Korea, an outbreak of Middle East respiratory syndrome (MERS) occurred in 2015. It was the second largest MERS outbreak. As a result of the outbreak in South Korea, 186 infections were reported, and 36 patients died. At least 16,693 people were isolated with suspicious symptoms. This paper estimates the basic reproduction number of the MERS coronavirus (CoV), using data on the spread of MERS in South Korea. METHODS: The basic reproduction number of an epidemic is defined as the average number of secondary cases that an infected subject produces over its infectious period in a susceptible and uninfected population. To estimate the basic reproduction number of the MERS-CoV, we employ data from the 2015 South Korea MERS outbreak and the susceptible-infected-removed (SIR) model, a mathematical model that uses a set of ordinary differential equations (ODEs). RESULTS: We fit the model to the epidemic data of the South Korea outbreak minimizing the sum of the squared errors to identify model parameters. Also we derive the basic reproductive number as the terms of the parameters of the SIR model. Then we determine the basic reproduction number of the MERS-CoV in South Korea in 2015 as 8.0977. It is worth comparing with the basic reproductive number of the 2014 Ebola outbreak in West Africa including Guinea, Sierra Leone, and Liberia, which had values of 1.5–2.5. CONCLUSIONS: There was no intervention to control the infection in the early phase of the outbreak, thus the data used here provide the best conditions to evaluate the epidemic characteristics of MERS, such as the basic reproduction number. An evaluation of basic reproduction number using epidemic data could be problematic if there are stochastic fluctuations in the early phase of the outbreak, or if the report is not accurate and there is bias in the data. Such problems are not relevant to this study because the data used here were precisely reported and verified by Korea Hospital Association.


docid: vdpxhdfr

title: COVID‐19 infection may cause ketosis and ketoacidosis

text: The present study included 658 hospitalized patients with confirmed COVID‐19. Forty‐two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhoea. They had a median (interquartile range [IQR]) age of 47.0 (38.0–70.3) years, and 16 (38.1%) were men. Patients with ketosis were younger (median age 47.0 vs. 58.0 years; P = 0.003) and had a greater prevalence of fatigue (31.0% vs. 10.6%; P < 0.001), diabetes (35.7% vs. 18.5%; P = 0.007) and digestive disorders (31.0% vs. 12.0%; P < 0.001). They had a longer median (IQR) length of hospital stay (19.0 [12.8–33.3] vs. 16.0 [10.0–24.0] days; P < 0.001) and a higher mortality rate (21.4% vs. 8.9%; P = 0.017). Three (20.0%) out of the 15 patients with diabetic ketosis developed acidosis, five patients (26.7%) with diabetic ketosis died, and one of these (25.0%) presented with acidosis. Two (7.4%) and four (14.3%) of the 27 non‐diabetic ketotic patients developed severe acidosis and died, respectively, and one (25.0%) of these presented with acidosis. This suggests that COVID‐19 infection caused ketosis or ketoacidosis, and induced diabetic ketoacidosis for those with diabetes. Ketosis increased the length of hospital stay and mortality. Meanwhile, diabetes increased the length of hospital stay for patients with ketosis but had no effect on their mortality.


title: Premorbid factors and outcome associated with respiratory virus infections in a pediatric intensive care unit

text: OBJECTIVES: The purpose of this study was to report the clinical features and outcome of all children with a laboratory proven diagnosis of respiratory virus infection admitted to a university Pediatric Intensive Care Unit (PICU). METHODS: Retrospective study between January 2003 and April 2007 was carried out in the PICU. Every child with a laboratory‐confirmed viral infection was included. RESULTS: 54 viruses were identified in 49 children (27 M, 22 F) over a 52‐month period. The three respiratory virus species, respiratory syncytial virus (RSV) (n = 17), influenza (n = 13) and parainfluenza (n = 12), accounted for 86% of these 49 cases. PICU admissions due to influenza A (n = 10) were more common than influenza B (n = 3), whereas parainfluenza type 3 (n = 7) was the commonest subtype of parainfluenza infection. Comparing these three common viruses, the mean age of children admitted with RSV was lower than with influenza or parainfluenza (1.2 years vs. 5.6 years vs. 2.4 years, P = 0.003). Pre‐existing conditions such as prematurity and chronic lung disease were only present in children with RSV infection. These respiratory viruses caused both upper (croup) and lower respiratory tract diseases (bronchiolitis, pneumonia). Extrapulmonary presentations were less prevalent and included encephalitis, seizures, cardiac arrest, coexisting diabetes ketoacidosis and acute lymphoblastic leukemia. One patient with RSV and another with influenza A died during their PICU stay. Nearly half of these patients required ventilatory support or received systemic corticosteroids, and 88% received initial broad spectrum antibiotic coverage. Approximately one in five of them had nebulised adrenaline, airway endoscopies or bacterial co‐infections. Adenovirus was isolated in four patients and two (both with adenovirus type 3) died during the PICU stay. CONCLUSIONS: In PICU, respiratory viral infections were associated with significant morbidity and life‐threatening conditions. Pediatr Pulmonol. 2008; 43:275–280. © 2008 Wiley‐Liss, Inc.


Vaccine Development in the Twenty-First Century: Changing Paradigms for Elusive Viruses


title: Mechanism of baricitinib supports artificial intelligence‐predicted testing in COVID‐19 patients

text: Baricitinib, is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI)‐algorithms, to be useful for COVID‐19 infection via a proposed anti‐cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID‐19 infection. We validated the AI‐predicted biochemical inhibitory effects of baricitinib on human numb‐associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID‐19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS‐CoV‐2 viral load, inflammatory markers, and IL‐6 levels. Collectively, these data support further evaluation of the anti‐cytokine and anti‐viral activity of baricitinib and supports its assessment in randomized trials in hospitalized COVID‐19 patients.


docid: oslzprxd

title: TYPE 1 DIABETES TRIGGERED BY COVID-19 PANDEMIC: A POTENTIAL OUTBREAK?


title: Molecular Genotyping of Microbes by Multilocus PCR and Mass Spectrometry: A New Tool for Hospital Infection Control and Public Health Surveillance

text: We describe a new technology for the molecular genotyping of microbes using a platform known commercially as the Ibis T5000. The technology couples multilocus polymerase chain reaction (PCR) to electrospray ionization/mass spectrometry (PCR/ESI-MS) and was developed to provide rapid, high-throughput, and precise digital analysis of either isolated colonies or original patient specimens on a platform suitable for use in hospital or reference diagnostic laboratories or public health settings. The PCR/ESI-MS method measures digital molecular signatures from microbes, enabling real-time epidemiological surveillance and outbreak investigation. This technology will facilitate understanding of the pathways by which infectious organisms spread and will enable appropriate interventions on a time frame not previously achievable.


title: Coronavirus infection of the central nervous system: host–virus stand-off

text: Several viruses infect the mammalian central nervous system (CNS), some with devastating consequences, others resulting in chronic or persistent infections associated with little or no overt pathology. Coronavirus infection of the murine CNS illustrates the contributions of both the innate immune response and specific host effector mechanisms that control virus replication in distinct CNS cell types. Despite T-cell-mediated control of acute virus infection, host regulatory mechanisms, probably designed to protect CNS integrity, contribute to the failure to eliminate virus. Distinct from cytolytic effector mechanisms expressed during acute infection, non-lytic humoral immunity prevails in suppressing infectious virus during persistence.


title: Epidemiologic Parameters of the Middle East Respiratory Syndrome Outbreak in Korea, 2015

text: BACKGROUND: Epidemiologic parameters are important in planning infection control policies during the outbreak of emerging infections. Korea experienced an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection in 2015, which was characterized by superspreading events in healthcare settings. We aimed to estimate the epidemiologic parameters over time during the outbreak to assess the effectiveness of countermeasures. MATERIALS AND METHODS: Publicly available data pertaining to the MERS outbreak in Korea were collected. We estimated the incubation periods of 162 cases whose sources of exposure were identified and the temporal trend was evaluated. Factors influencing incubation duration were analyzed. The generational reproduction number (R(g)) and case reproduction number (R(c)) were estimated over time. RESULTS: The estimated median incubation period was 7.4 days (95% CI, 6.9-8.0). Median incubation periods tended to be longer over time as the disease generation progressed: 6.16 days (95% CI, 5.38-6.97), 7.68 days (95% CI, 7.04-8.44), and 7.95 days (95% CI, 6.25-9.88) in the first, second, and third generations, respectively. The number of days of illness in the source cases at the time of exposure inversely correlated with the incubation periods in the receiving cases (HR 0.91 [95% CI, 0.84-0.99] per one illness day increase; P=0.026). This relationship was consistent (HR 0.83 [95% CI, 0.74-0.93] per one illness day increase) in the multivariable analysis incorporating clinical characteristics, the order of generation, and a link to superspreaders. Because the third generation cases were exposed to their source cases in the early stage (median one day) compared to the second generation cases (median 6 days), the temporal trend of incubation periods appears to be influenced by early isolation of symptomatic cases and reduction of potential exposure to source cases in the later stage. R(g) declined rapidly from 28 to 0.23 in two generations. R(c) dropped below the epidemic threshold at one on May 31, 2015, which approximately coincided with the initiation of the stringent countermeasures. CONCLUSIONS: Despite the initial delay, the stringent countermeasures targeted towards second generation cases appeared to effectively contain the MERS outbreak in Korea as suggested by the decline of R(c) shortly after implementation. Except for superspreading events, the transmission potential for MERS-CoV seems to be low. Further research should be focused on characterizing superspreaders in comparison to non-transmitting cases with regard to environmental, behavioral, and virologic and host genetic factors in order to better prepare for future outbreaks of MERS-CoV.