title: The interface between coronaviruses and host cell RNA biology: Novel potential insights for future therapeutic intervention

text: Coronaviruses, including SARS‐Cov‐2, are RNA‐based pathogens that interface with a large variety of RNA‐related cellular processes during infection. These processes include capping, polyadenylation, localization, RNA stability, translation, and regulation by RNA binding proteins or noncoding RNA effectors. The goal of this article is to provide an in‐depth perspective on the current state of knowledge of how various coronaviruses interact with, usurp, and/or avoid aspects of these cellular RNA biology machineries. A thorough understanding of how coronaviruses interact with RNA‐related posttranscriptional processes in the cell should allow for new insights into aspects of viral pathogenesis as well as identify new potential avenues for the development of anti‐coronaviral therapeutics. This article is categorized under: RNA in Disease and Development > RNA in Disease.


title: Masters of manipulation: Viral modulation of the immunological synapse

text: In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse. To enable efficient replication and latency in immune cells, viruses have developed a range of strategies to manipulate cellular processes involved in immunological synapse formation to evade immune detection and control T‐cell activation. In vitro, viruses such as human immunodeficiency virus 1 and human T‐lymphotropic virus type 1 utilise structures known as virological synapses to aid transmission of viral particles from cell to cell in a process termed trans‐infection. The formation of the virological synapse provides a gateway for virus to be transferred between cells avoiding the extracellular space, preventing antibody neutralisation or recognition by complement. This review looks at how viruses are able to subvert intracellular signalling to modulate immune function to their advantage and explores the role synapse formation has in viral persistence and cell‐to‐cell transmission.


docid: fyjlheld

title: Potential of Flavonoid-Inspired Phytomedicines against COVID-19

text: Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.


title: A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques

text: Developing a vaccine to protect against the lethal effects of the many strains of coronavirus is critical given the current global pandemic. For Middle East respiratory syndrome coronavirus (MERS-CoV), we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. The vaccine protected against respiratory injury and pneumonia and reduced viral load in lung tissue by several orders of magnitude. MERS-CoV replication in type I and II pneumocytes of ChAdOx1 MERS–vaccinated animals was absent. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. We also found that antibodies elicited by ChAdOx1 MERS in rhesus macaques neutralized six different MERS-CoV strains. Transgenic human dipeptidyl peptidase 4 mice vaccinated with ChAdOx1 MERS were completely protected against disease and lethality for all different MERS-CoV strains. The data support further clinical development of ChAdOx1 MERS.


docid: tmjgmqdk

title: Coxsackievirus B3 Infection Triggers Autophagy through 3 Pathways of Endoplasmic Reticulum Stress

text: Abstract Objective Autophagy is a highly conserved intracellular degradation pathway. Many picornaviruses induce autophagy to benefit viral replication, but an understanding of how autophagy occurs remains incomplete. In this study, we explored whether coxsackievirus B3 (CVB3) infection induced autophagy through endoplasmic reticulum (ER) stress. Methods In CVB3-infected HeLa cells, the specific molecules of ER stress and autophagy were detected using Western blotting, reverse transcription polymerase chain reaction (RT-PCR), and confocal microscopy. Then PKR-like ER protein kinase (PERK) inhibitor, inositol-requiring protein-1 (IRE1) inhibitor, or activating transcription factor-6 (ATF6) inhibitor worked on CVB3-infected cells, their effect on autophagy was assessed by Western blotting for detecting microtubule-associated protein light chain 3 (LC3). Results CVB3 infection induced ER stress, and ER stress sensors PERK/eIF2α, IRE1/XBP1, and ATF6 were activated. CVB3 infection increased the accumulation of green fluorescent protein (GFP)-LC3 punctuation and induced the conversion from LC3-I to phosphatidylethanolamine-conjugated LC3-1 (LC3-II). CVB3 infection still decreased the expression of mammalian target of rapamycin (mTOR) and p-mTOR. Inhibition of PERK, IRE1, or ATF6 significantly decreased the ratio of LC3-II to LC3-I in CVB3-infected HeLa cells. Conclusion CVB3 infection induced autophagy through ER stress in HeLa cells, and PERK, IRE1, and ATF6a pathways participated in the regulation of autophagy. Our data suggested that ER stress may inhibit mTOR signaling pathway to induce autophagy during CVB3 infection.


title: Antibody Detection and Dynamic Characteristics in Patients with COVID-19

text: BACKGROUND: The corona virus disease 2019 (COVID-19) caused by the corona virus 2 (SARS-CoV-2) has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA) based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by RT-PCR. The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the 4(th) day after symptom onset. In the confirmed patients with COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, and those of IgG were 83.3.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9 %. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as complement approach for viral nucleid acid assays.


Love in the time of COVID‐19


Iloprost for COVID-19-related vasculopathy


title: SARS coronavirus Accessory Proteins

text: The emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV) has led to a renewed interest in studying the role of accessory proteins in regulating coronavirus infections in the natural host. A significant body of evidence has accumulated in the area of SARS-CoV and host interactions that indicate that the accessory proteins might play an important role in modulating the host response to virus infection and thereby, contribute to pathogenesis. In this review, we have compiled the current knowledge about SARS-CoV accessory proteins, obtained from studies in cell culture systems, reverse genetics and animal models, to shed some light into the possible role of these proteins in the propagation and virulence of SARS-CoV in its natural host. We conclude by providing some questions for future studies that will greatly advance our knowledge about the biological significance and contributions of the accessory proteins in the development of SARS in humans.


docid: gluzoods

title: Protecting vulnerable patients with inherited anaemias from unnecessary death during the COVID‐19 pandemic

text: With the developing COVID‐19 pandemic, patients with inherited anaemias require specific advice regarding isolation and changes to usual treatment schedules. The National Haemoglobinopathy Panel (NHP) has issued guidance on the care of patients with sickle cell disease, thalassaemia, Diamond Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), sideroblastic anaemia, pyruvate kinase deficiency and other red cell enzyme and membrane disorders. Cascading of accurate information for clinicians and patients is paramount to preventing adverse outcomes, such as patients who are at increased risk of fulminant bacterial infection due to their condition or its treatment erroneously self‐isolating if their fever is mistakenly attributed to a viral cause, delaying potentially life‐saving antibiotic therapy. Outpatient visits should be minimised for most patients, however some, such as first transcranial dopplers for children with sickle cell anaemia should not be delayed as known risk of stroke will outweigh the unknown risk from COVID‐19 infection. Blood transfusion programmes should be continued, but specific changes to usual clinical pathways can be instituted to reduce risk of patient exposure to COVID‐19, as well as contingency planning for possible reductions in blood available for transfusions. Bone marrow transplants for these disorders should be postponed until further notice. With the current lack of evidence on the risk and complications of COVID‐19 infection in these patients, national data collection is ongoing to record outcomes and eventually to identify predictors of disease severity, particularly important if further waves of infection travel through the population.


title: Dynamics of peripheral immune cells and their HLA‐G and receptor expressions in a patient suffering from critical COVID‐19 pneumonia to convalescence

text: OBJECTIVES: Host immune responses are indispensable to combat the disease. We report the dynamics of peripheral immune cells, cytokines, and human leucocyte antigen‐G (HLA‐G) and its receptor expressions in a patient suffering from critical COVID‐19 pneumonia to convalescence. METHODS: Clinical data of the patient were collected from medical records. The expressions of HLA‐G and receptors ILT2, ILT4 and KIR2DL4 in peripheral immune cells were measured with flow cytometry. RESULTS: From critical COVID‐19 to the convalescent stage, early lymphopenia was improved (median: 0.6 × 10(9) L(−1) vs. 0.9 × 10(9) L(−1), P = 0.009), and an obvious fluctuation in WBC and neutrophil counts was observed. Initially, low levels of CD4(+) T cells (from 120 to 528 μL(−1)) and CD8(+) T cells (from 68 to 362 μL(−1)) gradually increased to normal levels. Meanwhile, high IL‐6 (from 251.8 to 6.32 pg mL(−1)), IL‐10 (from 39.53 to 5.21 pg mL(−1)) and IFN‐γ (from 13.55 to 3.16 pg mL(−1)) levels decreased, and IL‐4 (from 2.36 to 3.19 pg mL(−1)) and TNF‐α (from 2.27 to 20.2 pg mL(−1)) levels increased quickly when the viral RNA returned negative. Moreover, the percentage of HLA‐G(+) T cells, B cells and monocytes follows high–low–high pattern, while the percentage of receptors ILT2‐, ILT4‐ and KIR2DL4‐expressing cells remained relatively stable. CONCLUSION: Our findings provide valuable information on the dynamics of early peripheral immunological responses in SARS‐CoV‐2 infection. CD4(+) and CD8(+) T cells, cytokines and HLA‐G(+) immune cells are associated with the natural history of the critical COVID‐19 patient; however, future studies are necessary.


title: Therapeutic and diagnostic implications of Hsp90 activation

text: Abstract The molecular chaperone heat-shock protein 90 (Hsp90) is involved in the stabilization and conformational maturation of many signaling proteins that are deregulated in cancers. Hsp90 inhibition results in the proteasomal degradation of these client proteins and leads to potent antitumor activity. The Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG) is presently in clinical trials. Recent work has identified the role of Hsp90 in multiple signal transduction pathways and revealed that the molecular mechanism of tumor selectivity by Hsp90 inhibitors is the result of an activated, high-affinity conformation of Hsp90 in tumors. This review discusses these recent advances in the understanding of tumor Hsp90 for the treatment and diagnosis of cancer. In addition, the role of Hsp90 in non-oncological diseases will also be discussed.


title: Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial

text: BACKGROUND: The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. METHODS: This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. RESULTS: Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. CONCLUSION: A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. TRIAL REGISTRATION: NCT01389518


docid: mkibohiw

title: Virus Morphogenesis in the Cell: Methods and Observations

text: Viruses carry out many of their activities inside cells, where they synthesise proteins that are not incorporated into viral particles. Some of these proteins trigger signals to kidnap cell organelles and factors which will form a new macro-structure, the virus factory, that acts as a physical scaffold for viral replication and assembly. We are only beginning to envisage the extraordinary complexity of these interactions, whose characterisation is a clear experimental challenge for which we now have powerful tools. Conventional study of infection kinetics using virology, biochemistry and cell biology methods can be followed by genome-scale screening and global proteomics. These are important new technologies with which we can identify the cell factors used by viruses at different stages in their life cycle. Light microscopy, electron microscopy and electron tomography, together with labelling methods for molecular mapping in situ, show immature viral intermediates, mature virions and recruited cell elements in their natural environment. This chapter describes how these methods are being used to understand the cell biology of viral morphogenesis and suggests what they might achieve in the near future.


Cloning and Characterization of Novel Isoforms of the BOULE Gene in Bats


title: Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors

text: Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.


title: Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation

text: Abstract Tylvalosin, a new broad-spectrum, third-generation macrolides, may exert a variety of pharmacological activities. Here, we report on its anti-oxidative and anti-inflammatory activity in RAW 264.7 macrophages and mouse treated with lipopolysaccharide (LPS) as well as piglet challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Tylvalosin treatment markedly decreased IL-8, IL-6, IL-1β, PGE2, TNF-α and NO levels in vitro and in vivo. LPS and PRRSV-induced reactive oxygen species (ROS) production, and the lipid peroxidation in mice lung tissues reduced after tylvalosin treatments. In mouse acute lung injury model induced by LPS, tylvalosin administration significantly attenuated tissues injury, and reduced the inflammatory cells recruitment and activation. The evaluated phospholipase A2 (PLA2) activity and the increased expressions of cPLA2-IVA, p-cPLA2-IVA and sPLA2-IVE were lowered by tylvalosin. Consistent with the mouse results, tylvalosin pretreatment attenuated piglet lung scores with improved growth performance and normal rectal temperature in piglet model induced by PRRSV. Furthermore, tylvalosin attenuated the IκBα phosphorylation and degradation, and blocked the NF-κB p65 translocation. These results indicate that in addition to its direct antimicrobial effect, tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury through suppression of NF-κB activation.


title: Les enseignements du SRAS

text: Key points Given that viruses may not have adapted to human-to-human transmission during their initial emergence in humans, they may thus be easier to control; accordingly, early detection by surveillance of unusual outbreaks is essential. Our healthcare systems are very vulnerable to viruses with a particular tropism for hospital personnel. International collaboration by teams of epidemiologists as well as virologists was the key to success against SARS (severe acute respiratory syndrome). We were lucky in the fight against SARS, the virus was in fact moderately transmissible and then only after the onset of symptoms. It was thus possible to isolate cases before they became contagious. SARS provided a good “dress rehearsal” and educated the public authorities about the issues of infectious pandemics. The specific types of new epidemics cannot be predicted but they are inevitable. Points essentiels Les virus peuvent ne pas être adaptés à la transmission interhumaine, et donc être plus faciles à maîtriser, lors de leur première émergence chez l'homme; d'où l'importance d'une détection précoce par la surveillance des foyers épidémiques inhabituels. Nos systèmes de santé sont très vulnérables face à des virus ayant un tropisme particulier pour le personnel hospitalier. La collaboration internationale, tant pour les équipes d'épidémiologistes que de virologues, a été la clef du succès de la lutte contre le SRAS (Syndrome respiratoire aigu sévère). Nous avons eu beaucoup de chance avec le SRAS: le virus était finalement peu transmissible, et seulement après le début des symptômes, permettant d'identifier et d'isoler les cas avant la période contagieuse. L'épidémie de SRAS a servi de “répétition générale”, permettant la prise de conscience par les pouvoirs publics des enjeux posés par les pandémies d'origine infectieuse. De nouvelles épidémies, quelles qu'elles soient, sont inéluctables.


title: Prediction of fatal adverse prognosis in patients with fever-related diseases based on machine learning: A retrospective study

text: BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients’ data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination (RFE) method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the Logistic regression were cardiac troponin T (CTnT) (coefficient=0.346, OR = 1.413), temperature (T) (coefficient=0.235, OR = 1.265), respiratory rate (RR) (coefficient= –0.206,OR = 0.814), serum kalium (K) (coefficient=0.137, OR = 1.146), pulse oxygen saturation (SPO(2)) (coefficient= –0.101, OR = 0.904), and albumin (ALB) (coefficient= –0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heartrate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO(2), T, ALB and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.


title: Efficacy and safety of Lian-Hua Qing-Wen granule for COVID-2019: A protocol for systematic review and meta-analysis

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Since the outbreak, the disease has caused more than 60,502 deaths worldwide. Lian-Hua Qing-Wen Granule (LHQWG) is widely used in treating COVID-19 in China. However, there is no evidence that LHQWG is effective for COVID-19. METHODS AND ANALYSIS: A comprehensive literature search will be conducted. Two methodological trained researchers will read the title, abstract and full texts and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analyses for outcomes related to COVID-19. The heterogeneity of data will be investigated by Cochrane X(2) and I(2) tests. Publication bias assessment will be conducted by funnel plot analysis and Egger test. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: Our study aims to systematically present the clinical evidence of LHQWG in treating COVID-19, which will be of significant meaning for further research and clinical practice. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/27SBU.


Please cite this paper as: Hooker et al. (20XX) Journalists’ views about reporting avian influenza and a potential pandemic: a qualitative study. Influenza and Other Respiratory Viruses 6(3), 224–229. Background The mass media is a key component of any public communication strategy for influenza or other respiratory illnesses, but coverage can be variable. In this study, we explored the factors that influenced journalists’ coverage of avian influenza as a model for coverage of a potential influenza pandemic. Methods This study involved semi‐structured interviews with 16 journalists from major Australian print, radio and television media organisations reporting on avian influenza and pandemic planning. Journalists, including reporters, editors and producers, were interviewed between October 2006 and August 2007. Thematic analysis was used to draw out major lessons for health communicators. Results Coverage of avian influenza was influenced by a small set of news values: catastrophic potential, cultural and geographical proximity, unfamiliarity and uncertainty. Lack of novelty and the absence of compelling images led to a decline in coverage. Journalists expressed concerns about the accuracy and impacts of reporting, but saw as critically important, their primary role as informants. They hence emphasised the importance of journalistic independence. Journalists all intended to continue working in a pandemic. Conclusions Health experts need to adapt their timetables and resources to journalists’ needs to improve their mutual communication. In crisis situations, journalists communicate with the public efficiently and effectively, but expert and journalistic views on the role and content of coverage may diverge in the post‐acute, reflective phase of a crisis.


title: Efficacy of Intranasal Administration of a Modified Live Feline Herpesvirus 1 and Feline Calicivirus Vaccine against Disease Caused by Bordetella bronchiseptica after Experimental Challenge

text: BACKGROUND: Studies suggest that intranasal vaccination can stimulate nonspecific immunity against agents not contained within the vaccine, but this effect is not reported for cats. HYPOTHESIS: A modified live feline herpesvirus‐1 (FHV‐1) and feline calicivirus (FCV) intranasal vaccine will reduce clinical signs of disease caused by experimental infection with Bordetella bronchiseptica. ANIMALS: Twenty specific pathogen‐free 12‐week‐old kittens. METHODS: Experimental study. Cats were randomized into 2 groups of 10 cats each. The vaccinated group was administered a single intranasal dose of a commercially available vaccine containing modified live strains of FHV‐1 and FCV, and the control group remained unvaccinated. All 20 cats were administered B. bronchiseptica by nasal inoculation 7 days later and were observed daily for clinical signs of illness for 20 days. RESULTS: In the first 10 days after B. bronchiseptica challenge, vaccinated cats were less likely to be clinically ill than control cats with a median clinical score of 0/180 (range 0–5) versus 2/180 (range 0–8) (P = .01). Nine of 10 control cats and 2 of 10 vaccinated cats were recorded as sneezing during days 1–10 after challenge (P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE: Intranasal vaccination against FHV‐1 and FCV decreased signs of illness due to an infectious agent not contained in the vaccine. This nonspecific immunity could be beneficial for protection against organisms for which vaccines are not available and as protection before development of vaccine‐induced humoral immunity.


title: The COVID‐19 Pandemic and Relationship Banking in Germany: Will Regional Banks Cushion an Economic Decline or is A Banking Crisis Looming?

text: By providing liquidity Hausbanks can support business clients to overcome the social shutdown and hence cushion the economic impacts of the COVID‐19 pandemic. Germany's regional banks demonstrated such ability in the financial crisis of 2008/09 when, in contrast to large banks, they extended lending. Revisiting research on the global financial crisis and relationship banking, this note presents hints on the soundness and lending ability of retail banks, discussing their influence in the virus‐related economic turmoil. Banks appear better prepared to resist the crisis than in 2008. Still, the (looming) turmoil of the real economy at large tends to stress all banks and regional banks in particular, owing, among other reasons, to their leading position in business lending. The crisis represents a chance for Hausbanks to prove their commitment to business clients and provides a possibility for researchers to analyse the performance of different types of banks.


title: Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin α5β1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement To Promote Its Invasion of N2a Cells

text: Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic virus that causes diffuse neuronal infection with neurological damage and high mortality. Virus-induced cytoskeletal dynamics are thought to be closely related to this type of nerve damage. Currently, the regulation pattern of the actin cytoskeleton and its molecular mechanism remain unclear when PHEV enters the host cells. Here, we demonstrate that entry of PHEV into N2a cells induces a biphasic remodeling of the actin cytoskeleton and a dynamic change in cofilin activity. Viral entry is affected by the disruption of actin kinetics or alteration of cofilin activity. PHEV binds to integrin α5β1 and then initiates the integrin α5β1-FAK signaling pathway, leading to virus-induced early cofilin phosphorylation and F-actin polymerization. Additionally, Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division cycle 42 (Cdc42), and downstream regulatory gene p21-activated protein kinases (PAKs) are recruited as downstream mediators of PHEV-induced dynamic changes of the cofilin activity pathway. In conclusion, we demonstrate that PHEV utilizes the integrin α5β1-FAK-Rac1/Cdc42-PAK-LIMK-cofilin pathway to cause an actin cytoskeletal rearrangement to promote its own invasion, providing theoretical support for the development of PHEV pathogenic mechanisms and new antiviral targets. IMPORTANCE PHEV, a member of the Coronaviridae family, is a typical neurotropic virus that primarily affects the nervous system of piglets to produce typical neurological symptoms. However, the mechanism of nerve damage caused by the virus has not been fully elucidated. Actin is an important component of the cytoskeleton of eukaryotic cells and serves as the first obstacle to the entry of pathogens into host cells. Additionally, the morphological structure and function of nerve cells depend on the dynamic regulation of the actin skeleton. Therefore, exploring the mechanism of neuronal injury induced by PHEV from the perspective of the actin cytoskeleton not only helps elucidate the pathogenesis of PHEV but also provides a theoretical basis for the search for new antiviral targets. This is the first report to define a mechanistic link between alterations in signaling from cytoskeleton pathways and the mechanism of PHEV invading nerve cells.


title: Impact of COVID-19 on surgical residency programs in Pakistan; A residents' perspective. Do programs need formal restructuring to adjust with the "new normal"? A cross-sectional survey study

text: BACKGROUND: Due to high-risk exposure of surgical residents to coronavirus, surgical residency programs have changed their training methods and working hours drastically. The purpose of this study is to find out the positive and negative impacts of the pandemic on surgical residency programs and on the lives of surgical residents. MATERIALS AND METHODS: A cross-sectional study was conducted on 112 surgical residents of a tertiary care hospital in Pakistan, with a mean age of 30.5 years from all the departments of surgery using a self-made, validated 40-point questionnaire comprising three sections. The last section also included modified Maslach Burnout inventory. RESULTS: Of all the residents, 97 (86.6%) stated that their surgical hands-on duration is adversely affected by the pandemic. As for clinical exposure, 92 (82.1%) trainees responded that their clinical exposure is affected too. Among all the subjects, 69 (61%) were concerned about transmitting it to their family members and 43 (38.4%) affirmed on being afraid of dying because of their direct exposure. On the brighter side, the average number of working hours per week for surgical residents were reduced from 81.10 +6.21 to 49.16 +6.25 (p<0.001) due to the outbreak. Modified Maslach Burnout inventory score was 8.33 + 2.34 after the outbreak, showing statistically significant reduction in burnout among the surgical residents (p< 0.001). CONCLUSION: The changes in the surgical residency programs amidst the pandemic has reduced the working hours, hands-on and clinical exposure of the surgical residents. Moreover, the situation has provided an opportunity to explore efficient methods of learning that can lead to lesser burnout. However, psychological burdens of surgical residents like fear of acquiring the infection should be appropriately addressed.


title: Emergence of new disease – how can artificial intelligence help?

text: Abstract Emergence of new disease remains a critical parameter in human health and society. Advances in artificial intelligence (AI) allow for rapid processing and analysis of massive and complex data. In this forum article we review recent applications across disease prediction and drug development with a focus on the COVID-19 pandemic.


title: HIV and AIDS: looking ahead

text: Although the future of HIV science is uncertain, we need to reappraise HIV diversity, pathogenesis and immunity. The AIDS pandemic threatens the success of existing vaccine programs and may accelerate the emergence of new infectious diseases.


title: Criminals Work from Home during Pandemics Too: a Public Health Approach to Respond to Fraud and Crimes against those 50 and above

text: This paper uses the public health framework to address the apparent impact of the coronavirus on the victimization experiences with a specific focus given to those over the age of 50. The bulk of attention is given to fraud victimization, with consideration also given to parent abuse, partner violence, and patient abuse. A review of data from the Federal Trade Commission shows that reports of most types of fraud grew significantly in the first three months of 2020 in comparison to the same time period in 2019. Differences between fraud experiences based on age are considered. Older persons lost much more to fraud than younger persons, and far more in 2020 than 2019. In addition, they reported being targeted more often for certain types of cybercrime (i.e., tech support scams). While devastating to everyone, it is concluded that the coronavirus will potentially have a more significant impact on the financial health of older persons than younger persons. It is concluded that minimizing the consequences of all forms of crimes targeting older adults will be best achieved by using a public health approach.


Respiratory infectious disease: complacency with empiricism in the age of molecular science. We can do better!


title: Risk Perception of COVID-19 Among the Portuguese Healthcare Professionals and General Population

text: Risk perception assessment of COVID-19 among Portuguese Healthcare Professionals (HCP) and General Population (GPop) was evaluated in a snowball 3 403 individual’s sample. 54.9% of HCP believed there is a high probability of becoming infected, in contrast with 24.0% of GPop (p <0.001) and, in more than 1/4, that this could happen to their family. Regarding prophylactic isolation, more than 70% agreed with its effectiveness. A large proportion perceived that health services are poorly prepared (50.1% GPop versus 63.5% HCP, p<0.001). Regarding Health Authorities’ communication, about 60% were “moderately” satisfied. 46.7% GPop and 52.8% HCP had the opinion the pandemic could be controlled in three to six months (p=0.01).


title: Human metapneumovirus in patients hospitalized with acute respiratory infections: A meta-analysis

text: Abstract This meta-analysis aimed to estimate the prevalence of human metapneumovirus (hMPV) infections in patients hospitalized for acute respiratory infection (ARI) and to study factors associated with this prevalence. Medline and ScienceDirect databases were searched for prospective observational studies that screened hospitalized patients with ARI for hMPV by RT-PCR, with data available at December 27, 2014. The risk of bias was assessed regarding participation rate, definition of ARI, description of diagnostic technique, method of inclusion identical for all subjects, standardized and identical sampling method for all subjects, analysis performed according to the relevant subgroups, and presentation of data sources. Random-effect meta-analysis with arcsine transformation and meta-regressions was used. In the 75 articles included, the prevalence of hMPV among hospitalized ARI was 6.24% (95% CI 5.25–7.30). An effect of the duration of the inclusion period was observed (p=0.0114), with a higher prevalence of hMPV in studies conducted during periods of 7–11 months (10.56%, 95% CI 5.97–16.27) or complete years (7.55%, 95% CI 5.90–9.38) than in periods of 6 months or less (5.36%, 95% CI 4.29–6.54). A significant increase in the incidence with increasing distance from the equator was observed (p=0.0384). hMPV should be taken into account as a possible etiology in hospitalized ARI.


title: A Statistical Similarity/Dissimilarity Analysis of Protein Sequences Based on a Novel Group Representative Vector

text: Similarity/dissimilarity analysis is a key way of understanding the biology of an organism by knowing the origin of the new genes/sequences. Sequence data are grouped in terms of biological relationships. The number of sequences related to any group is susceptible to be increased every day. All the present alignment-free methods approve the utility of their approaches by producing a similarity/dissimilarity matrix. Although this matrix is clear, it measures the degree of similarity among sequences individually. In our work, a representative of each of three groups of protein sequences is introduced. A similarity/dissimilarity vector is evaluated instead of the ordinary similarity/dissimilarity matrix based on the group representative. The approach is applied on three selected groups of protein sequences: beta globin, NADH dehydrogenase subunit 5 (ND5), and spike protein sequences. A cross-grouping comparison is produced to ensure the singularity of each group. A qualitative comparison between our approach, previous articles, and the phylogenetic tree of these protein sequences proved the utility of our approach.


docid: vpxubnkc

title: What is the impact of COVID-19 on head and neck squamous cell carcinoma patients?

text: Data sources It is not made clear in this review the different databases selected or how they conducted their search. The studies used are from 1975-2020 Study selection The authors have performed a scoping review using 84 studies ranging from 1975-2020. The majority of these are from before the 2019-2020 COVID-19 outbreak period. This is indicative of the lack of evidence on this topic and exemplifies why a scoping review was carried out rather than a systematic review. The studies that were reviewed were predominately cohort and case studies. With regards to previous treatment outcomes, a few systematic reviews were included, but again, the novel nature of this outbreak means that largely, there are only cohort or case studies available for review. Data extraction and synthesis There are ten authors, with no indication of how many performed the literature review or if a mediator was involved in the final decision making on what papers would be reviewed. Results Excessive consumption of alcohol, history of tobacco use, an ageing population, and comorbidities such as cardiopulmonary issues are substantial risk factors for episodes of unfavourable respiratory outcomes. The risk of these outcomes is increased by some of the toxic effects of treatments such as chemotherapy or radiotherapy. Conclusions The COVID-19 outbreak has a potentially disproportionate impact on the cohort of head and neck cancer patients, and the respiratory effects this has on these patients may increase morbidity and mortality. It is important to include alcohol and smoking cessation, along with good oral hygiene instruction in the care of these patients.


title: Future Pandemic Influenza Virus Detection Relies on the Existing Influenza Surveillance Systems: A Perspective from Australia and New Zealand

text: The anniversary of the 1918–1919 influenza pandemic has allowed a refocusing on the global burden of influenza and the importance of co-ordinated international surveillance for both seasonal influenza and the identification of control strategies for future pandemics. Since the introduction of the International Health Regulations (IHR), progress had been slow, until the emergence of the novel influenza A(H1N1)2009 virus and its global spread, which has led to the World Health Organization (WHO) developing a series of guidance documents on global influenza surveillance procedures, severity and risk assessments, and essential measurements for the determination of national pandemic responses. However, the greatest burden of disease from influenza occurs between pandemics during seasonal influenza outbreaks and epidemics. Both Australia and New Zealand utilise seasonal influenza surveillance to support national influenza awareness programs focused on seasonal influenza vaccination education and promotion. These programs also serve to promote the importance of pandemic preparedness.


title: Hydroxychloroquine Sulfate Prescribing Trends and Pharmacist-Led Outbreak Preparedness in Long Term Care Pharmacy During COVID-19

text: To address the threat posed by COVID-19 in long term care facilities, our pharmacy implemented an outbreak suppression strategy, and tracked prescriptions of anti-infectives and hydroxychloroquine sulfate in over 2,000 LTC facilities.


title: Mein Patient hat eine Warnung von seiner Corona-App — was soll ich tun?: Eindämmung der COVID-19-Pandemie

text: Nutzer der Corona-Warn-App werden bei erhöhtem Infektionsrisiko aufgefordert, einen Arzt aufzusuchen. Was das für die Praxen bedeutet, ist noch nicht abschließend geklärt. Erste Handlungsempfehlungen liegen jedoch vor.


title: Rapid and sensitive detection of canine parvovirus type 2 by recombinase polymerase amplification

text: A novel recombinase polymerase amplification (RPA)-based method for detection of canine parvovirus type 2 (CPV-2) was developed. Sensitivity analysis showed that the detection limit of RPA was 10 copies of CPV-2 genomic DNA. RPA amplified both CPV-2a and -2b DNA but did not amplify the template of other important dog viruses (CCoV, PRV or CDV), demonstrating high specificity. The method was further validated with 57 canine fecal samples. An outstanding advantage of RPA is that it is an isothermal reaction and can be performed in a water bath, making RPA a potential alternative method for CPV-2 detection in resource-limited settings.


title: Stratégie de prise en charge nutritionnelle à l’hôpital au cours de l’épidémie virale Covid-19: avis d’experts de la Société Francophone de Nutrition Clinique et Métabolisme (SFNCM)

text: Abstract The viral epidemic caused by the new Coronavirus SARS-CoV-2 is responsible for the new Coronavirus disease -2019 (Covid-19). This epidemic imposes upheavals in our organizations in healthcare centres which should not obscure the importance of nutritional care. The nutritional diagnosis and the early nutritional care management of Covid-19 infected patients must be integrated into the overall therapeutic strategy, as with any acute situation of acute illness. This document was prepared by the French speaking Society for Clinical Nutrition and Metabolism (SFNCM) in the emergency of the health crisis by a group of experts, based on the national and international recommendations available in the field of malnutrition, critical illness, metabolic stress and intensive care medicine on March 23, 2020. We hope that this article will bring to healthcare professionals, especially those not specialized in nutrition, useful landmarks to help them to manage hospitalized patients, infected or not by Covid-19 in the context of epidemic and intrahospital confinement.


title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains

text: Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Both AdAce1 and AdAce2 were highly similar (95 and 93% amino acid identity, respectively) with the Ace genes of Tribolium castaneum. Both AdAce1 and AdAce2 have the conserved residues characteristic of AChE (catalytic triad, intra‐disulfide bonds, and so on). Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. Several single nucleotide polymorphisms (SNPs) were detected, but only one non‐synonymous mutation was found (A271S in AdAce2). No SNPs were exclusively found in the resistant strains, the A271S mutation does not correspond to any mutations previously reported to alter sensitivity of AChE to organophosphates or carbamates, and the A271S was found only as a heterozygote in one individual from one of the resistant A. diaperinus strains. This suggests that tetrachlorvinphos resistance in the Kennebec and Waycross strains of A. diaperinus is not due to mutations in either AChE gene. The sequences of AdAce1 and AdAce2 provide new information about the evolution of these important genes in insects. Arch Insect Biochem Physiol. © 2007 Wiley‐Liss, Inc.


title: Conductance and amantadine binding of a pore formed by a lysine-flanked transmembrane domain of SARS coronavirus envelope protein

text: The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM α-helical bundle. We have shown previously that the topology of the α-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM α-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric α-helical bundle model.


title: Rapid, Unbiased PRRSV Strain Detection Using MinION Direct RNA Sequencing and Bioinformatics Tools

text: Prompt detection and effective control of porcine reproductive and respiratory syndrome virus (PRRSV) during outbreaks is important given its immense adverse impact on the swine industry. However, the diagnostic process can be challenging due to the high genetic diversity and high mutation rate of PRRSV. A diagnostic method that can provide more detailed genetic information about pathogens is urgently needed. In this study, we evaluated the ability of Oxford Nanopore MinION direct RNA sequencing to generate a PRRSV whole genome sequence and detect and discriminate virus at the strain-level. A nearly full length PRRSV genome was successfully generated from raw sequence reads, achieving an accuracy of 96% after consensus genome generation. Direct RNA sequencing reliably detected the PRRSV strain present with an accuracy of 99.9% using as few as 5 raw sequencing reads and successfully differentiated multiple co-infecting strains present in a sample. In addition, PRRSV strain information was obtained from clinical samples containing 10(4) to 10(6) viral copies or more within 6 hours of sequencing. Overall, direct viral RNA sequencing followed by bioinformatic analysis proves to be a promising approach for identification of the viral strain or strains involved in clinical infections, allowing for more precise prevention and control strategies during PRRSV outbreaks.


title: The Limited Sensitivity of Chest Computed Tomography Relative to Reverse Transcription Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus-2 Infection: A Systematic Review on COVID-19 Diagnostics

text: OBJECTIVES: Several studies suggest the sensitivity of chest computed tomography (CT) is far greater than that of reverse transcription polymerase chain reaction (RT-PCR) in diagnosing COVID-19 patients, and therefore, CT should be included as a primary diagnostic tool. This systematic review aims to stratify studies as high or low risk of bias to determine the true sensitivity of CT for severe acute respiratory syndrome coronavirus-2 infection according to the unbiased (low risk) studies, a topic of particular importance given the insufficient quantity of RT-PCR kits in many countries. We focus on sensitivity as that is the chief advantage perceived of CT. MATERIALS AND METHODS: This systematic review involved searching the PubMed and Google Scholar databases for articles conducted and published between January 1 and April 15, 2020. The quality assessment tool QUADAS-2 was used to stratify studies according to their risk of bias, and exclusion criteria included not providing the information deemed relevant for such a stratification, such as not indicating if the patients were symptomatic or asymptomatic, or identifying the source of the specimen for the reference standard, RT-PCR (eg, nasal, oropharyngeal, etc). Sensitivity values were then extracted, and random effects meta-analyses were performed. RESULTS: Of 641 search results, 37 studies (n = 9610 patients) were included in the analysis. The mean sensitivity of RT-PCR for COVID-19 reported by the biased studies was 70% (n = 5409/7 studies; 95% confidence interval [CI], 43–97; I(2) = 99.1%), compared with 78% by unbiased studies (n = 534/4 studies; 95% CI, 69–87, I(2) = 89.9%). For chest CT, the mean sensitivity reported by biased studies was 94% (n = 3371 patients/24 studies; 95% CI, 92–96; I(2) = 93.1%), compared with 75% by unbiased studies (n = 957/10 studies; 95% CI, 67–83; I(2) = 89.5%). CONCLUSIONS: The difference between the sensitivities of CT and RT-PCR for severe acute respiratory syndrome coronavirus-2 infection is lower than previously thought, as after stratifying the studies, the true sensitivity for CT based on the unbiased studies is limited.


title: Overviews of Pathogen Emergence: Which Pathogens Emerge, When and Why?

text: An emerging pathogen has been defined as the causative agent of an infectious disease whose incidence is increasing following its appearance in a new host population or whose incidence is increasing in an existing population as a result of long-term changes in its underlying epidemiology (Woolhouse and Dye 2001). Although we appear to be in a period where novel diseases are appearing and old diseases are spreading at an unprecedented rate, disease emergence per se is not a new phenomenon. It is almost certain that disease emergence is a routine event in the evolutionary ecology of pathogens, and part of a ubiquitous response of pathogen populations to shifting arrays of host species. While our knowledge of emerging diseases is, for the most part, limited to the time span of the human lineage, this history provides us with a modern reflection of these deeper evolutionary processes, and it is clear from this record that at many times throughout human history, demographic and behavioural changes in society have provided opportunities for pathogens to emerge.


title: The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift

text: The -1 programmed ribosomal frameshifts (PRF), which are used by many viruses, occur at a heptanucleotide slippery sequence and are currently thought to involve the tRNAs interacting with the ribosomal P- and A-site codons. We investigated here whether the tRNA occupying the ribosomal E site that precedes a slippery site influences -1 PRF. Using the human immunodeficiency virus type 1 (HIV-1) frameshift region, we found that mutating the E-site codon altered the -1 PRF efficiency. When the HIV-1 slippery sequence was replaced with other viral slippery sequences, mutating the E-site codon also altered the -1 PRF efficiency. Because HIV-1 -1 PRF can be recapitulated in bacteria, we used a bacterial ribosome system to select, by random mutagenesis, 16S ribosomal RNA (rRNA) mutations that modify the expression of a reporter requiring HIV-1 -1 PRF. Three mutants were isolated, which are located in helices 21 and 22 of 16S rRNA, a region involved in translocation and E-site tRNA binding. We propose a novel model where -1 PRF is triggered by an incomplete translocation and depends not only on the tRNAs interacting with the P- and A-site codons, but also on the tRNA occupying the E site.


title: Investigating the Congruence of Crowdsourced Information With Official Government Data: The Case of Pediatric Clinics

text: BACKGROUND: Health 2.0 is a benefit to society by helping patients acquire knowledge about health care by harnessing collective intelligence. However, any misleading information can directly affect patients’ choices of hospitals and drugs, and potentially exacerbate their health condition. OBJECTIVE: This study investigates the congruence between crowdsourced information and official government data in the health care domain and identifies the determinants of low congruence where it exists. In-line with infodemiology, we suggest measures to help the patients in the regions vulnerable to inaccurate health information. METHODS: We text-mined multiple online health communities in South Korea to construct the data for crowdsourced information on public health services (173,748 messages). Kendall tau and Spearman rank order correlation coefficients were used to compute the differences in 2 ranking systems of health care quality: actual government evaluations of 779 hospitals and mining results of geospecific online health communities. Then we estimated the effect of sociodemographic characteristics on the level of congruence by using an ordinary least squares regression. RESULTS: The regression results indicated that the standard deviation of married women’s education (P=.046), population density (P=.01), number of doctors per pediatric clinic (P=.048), and birthrate (P=.002) have a significant effect on the congruence of crowdsourced data (adjusted R (2)=.33). Specifically, (1) the higher the birthrate in a given region, (2) the larger the variance in educational attainment, (3) the higher the population density, and (4) the greater the number of doctors per clinic, the more likely that crowdsourced information from online communities is congruent with official government data. CONCLUSIONS: To investigate the cause of the spread of misleading health information in the online world, we adopted a unique approach by associating mining results on hospitals from geospecific online health communities with the sociodemographic characteristics of corresponding regions. We found that the congruence of crowdsourced information on health care services varied across regions and that these variations could be explained by geospecific demographic factors. This finding can be helpful to governments in reducing the potential risk of misleading online information and the accompanying safety issues.


title: Helicobacter Hypothesis for Idiopathic Parkinsonism: Before and Beyond

text: We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof‐of‐principle that infection can contribute to IP was provided by case studies and a placebo‐controlled efficacy study of Helicobacter eradication. “Malignant” IP appears converted to “benign”, but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating “low‐density” infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this “discriminant index” and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small‐intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity‐predominant parkinsonism.


title: Forced Disruption of Anatomy Education in Australia and New Zealand: An Acute Response to the Covid‐19 Pandemic

text: Australian and New Zealand universities commenced a new academic year in February/March 2020 largely with “business as usual.” The subsequent Covid‐19 pandemic imposed unexpected disruptions to anatomical educational practice. Rapid change occurred due to government‐imposed physical distancing regulations from March 2020 that increasingly restricted anatomy laboratory teaching practices. Anatomy educators in both these countries were mobilized to adjust their teaching approaches. This study on anatomy education disruption at pandemic onset within Australia and New Zealand adopts a social constructivist lens. The research question was “What are the perceived disruptions and changes made to anatomy education in Australia and New Zealand during the initial period of the Covid‐19 pandemic, as reflected on by anatomy educators?.” Thematic analysis to elucidate “the what and why” of anatomy education was applied to these reflections. About 18 anatomy academics from ten institutions participated in this exercise. The analysis revealed loss of integrated “hands‐on” experiences, and impacts on workload, traditional roles, students, pedagogy, and anatomists' personal educational philosophies. The key opportunities recognized for anatomy education included: enabling synchronous teaching across remote sites, expanding offerings into the remote learning space, and embracing new pedagogies. In managing anatomy education's transition in response to the pandemic, six critical elements were identified: community care, clear communications, clarified expectations, constructive alignment, community of practice, ability to compromise, and adapt and continuity planning. There is no doubt that anatomy education has stepped into a yet unknown future in the island countries of Australia and New Zealand.


Prognostic value of Carcinoembryonic antigen on outcome in patients with Coronavirus disease 2019


title: Potent and Selective Inhibition of Cysteine Proteases from Plasmodium falciparum and Trypanosoma brucei

text: Treating tropical diseases: Structure‐based design afforded highly active triazine nitrile inhibitors of the protozoan cysteine proteases falcipain‐2 and rhodesain. Optimization of the occupancy of the S1, S2, and S3 pockets of these enzymes yielded inhibitory constants in the low nanomolar activity range. The new ligands are selective against other related proteases and exhibit in vitro activities against the protozoan parasites.[Image: see text]


title: Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study

text: BACKGROUND: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population. METHODS: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ(2) test. Risk factors for mortality were identified by univariable and multivariable logistic regression models. FINDINGS: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56–70; range 14–96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59–78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56–6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16–10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57–9·50]; p=0·0033) were risk factors for death during admission to hospital. INTERPRETATION: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes. FUNDING: National Natural Science Foundation of China.


title: Reprint of: Coronavirus reverse genetic systems: Infectious clones and replicons

text: Abstract Coronaviruses (CoVs) infect humans and many animal species, and are associated with respiratory, enteric, hepatic, and central nervous system diseases. The large size of the CoV genome and the instability of some CoV replicase gene sequences during its propagation in bacteria, represent serious obstacles for the development of reverse genetic systems similar to those used for smaller positive sense RNA viruses. To overcome these limitations, several alternatives to more conventional plasmid-based approaches have been established in the last 13 years. In this report, we briefly review and discuss the different reverse genetic systems developed for CoVs, paying special attention to the severe acute respiratory syndrome CoV (SARS-CoV).


title: Weakened defences

text: The way society functions in the US has made it more vulnerable to pandemics. Could things be different, asks Chelsea Whyte


title: Modeling the variations in pediatric respiratory syncytial virus seasonal epidemics

text: BACKGROUND: Seasonal respiratory syncytial virus (RSV) epidemics occur annually in temperate climates and result in significant pediatric morbidity and increased health care costs. Although RSV epidemics generally occur between October and April, the size and timing vary across epidemic seasons and are difficult to predict accurately. Prediction of epidemic characteristics would support management of resources and treatment. METHODS: The goals of this research were to examine the empirical relationships among early exponential growth rate, total epidemic size, and timing, and the utility of specific parameters in compartmental models of transmission in accounting for variation among seasonal RSV epidemic curves. RSV testing data from Primary Children's Medical Center were collected on children under two years of age (July 2001-June 2008). Simple linear regression was used explore the relationship between three epidemic characteristics (final epidemic size, days to peak, and epidemic length) and exponential growth calculated from four weeks of daily case data. A compartmental model of transmission was fit to the data and parameter estimated used to help describe the variation among seasonal RSV epidemic curves. RESULTS: The regression results indicated that exponential growth was correlated to epidemic characteristics. The transmission modeling results indicated that start time for the epidemic and the transmission parameter co-varied with the epidemic season. CONCLUSIONS: The conclusions were that exponential growth was somewhat empirically related to seasonal epidemic characteristics and that variation in epidemic start date as well as the transmission parameter over epidemic years could explain variation in seasonal epidemic size. These relationships are useful for public health, health care providers, and infectious disease researchers.


title: Recent advances in understanding Crimean–Congo hemorrhagic fever virus

text: Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.


title: Age-related dynamics of constitutive cytokine transcription levels of feline monocytes

text: Abstract Monocytes/macrophages are central mediators of inflammation and immunity and therefore of major interest in the study of immunosenescence. In healthy adult cats, monocytes have been shown to constitutively transcribe pro- and anti-inflammatory cytokines. However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15mo to 10yr) were examined for transcription of IL-1β, IL-6, IL-10, IL-12 p40 and TNF-α by real-time PCR. Transcription levels of cytokines varied and were generally highest for IL-1β. For IL-1β, IL-6 and IL-12 p40, both young and old cats exhibited highest levels. The age association was significant. TNF-α appeared to be transcribed at similar levels over the examination period, whereas IL-10 tended to decline with age but without any statistical significant differences. The observed age association of the constitutive transcription of some cytokines indicates a drop in monocyte activities from youth to middle age, which is then followed by a (progressive) increase with increasing age. This provides evidence that monocytes are in part responsible for the pro-inflammatory status observed with ageing.


title: Wellness and resilience for college and beyond: protocol for a quasi-experimental pilot study investigating a dialectical behaviour therapy skill-infused college course

text: INTRODUCTION: College students’ mental health problems and suicidal behaviour are serious, persistent and prevalent public health issues. With the need for mental health support greatly exceeding the availability of on-campus treatment, a recent trend on college campuses is to offer courses designed to teach students strategies for developing mental health or resilience. While these courses are exceptionally popular among students, a paucity of research investigates the health outcomes associated with participation. The purpose of this study is to investigate the acceptability, appropriateness, feasibility and preliminary effectiveness of a college course grounded in skills from dialectical behaviour therapy (DBT) titled, ‘Wellness and Resilience for College and Beyond’. METHODS AND ANALYSIS: During the spring and fall 2020 semesters, the course will be offered on five campuses in Southwestern Pennsylvania and West Virginia. The course consists of 15 weekly 2.5-hour lessons, weekly homework assignments and a final examination with content drawn from DBT, acceptance and commitment therapy and positive psychology. Undergraduate students aged 18–24 will self-select into the course and control subjects receiving ‘university as usual’ will be recruited to serve as a comparison group. Students who receive the course will complete measures of course acceptability, appropriateness and feasibility. All study participants will complete measures of adaptive coping skills use, emotion dysregulation and suicidality. ETHICS AND DISSEMINATION: All of the study procedures were approved as an exempt protocol for evaluation of educational curricula by the University of Pittsburgh Human Research Protections Office (HRPO); the study was approved as a research study by the institutional review board (IRB) of the fifth study site. The University of Pittsburgh HRPO served as the IRB of record for all except one study site, which required standard IRB review. Data from this study will be disseminated via conference presentations, peer-reviewed publications and via our online stakeholder learning collaborative. TRIAL REGISTRATION NUMBER: NCT04338256.


To announce or not to announce: What is known about the 2016–2017 influenza season in Hong Kong?


title: Association of time-to-treatment with outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative patients

text: BACKGROUND: The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Therefore, this study investigated the association between the time to anti-PCP treatment and the clinical outcomes in HIV-negative patients with PCP who presented with hypoxemic respiratory failure. METHODS: A retrospective observational study was performed involving 51 HIV-negative patients with PCP who presented in respiratory failure and were admitted to the intensive care unit between October 2005 and July 2018. A logistic regression model was used to adjust for potential confounding factors in the association between the time to anti-PCP treatment and in-hospital mortality. RESULTS: All patients were treated with appropriate anti-PCP treatment, primarily involving trimethoprim/sulfamethoxazole. The median time to anti-PCP treatment was 58.0 (28.0–97.8) hours. Thirty-one (60.8%) patients were treated empirically prior to confirmation of the microbiological diagnosis. However, the hospital mortality rates were not associated with increasing quartiles of time until anti-PCP treatment (P = 0.818, test for trend). In addition, hospital mortality of patients received early empiric treatment was not better than those of patients received definitive treatment after microbiologic diagnosis (48.4% vs. 40.0%, P = 0.765). In a multiple logistic regression model, the time to anti-PCP treatment was not associated with increased mortality. However, age (adjusted OR 1.07, 95% CI 1.01–1.14) and failure to initial treatment (adjusted OR 13.03, 95% CI 2.34–72.65) were independently associated with increased mortality. CONCLUSIONS: There was no association between the time to anti-PCP treatment and treatment outcomes in HIV-negative patients with PCP who presented in hypoxemic respiratory failure.


title: Effect of Spray-Dried Plasma Form and Duration of Feeding on Broiler Performance During Natural Necrotic Enteritis Exposure

text: Abstract The effect of duration of feeding (continuous or discontinued after d 14) and form (granular vs. powder) of spray-dried plasma (SDP) on performance and mortality of broilers using used litter was evaluated with 240 Ross × Ross 308 male broilers (6 broilers per pen, 8 pens per treatment). Dietary treatments were control (no SDP) or SDP as powder or granular included in the pellet and fed continuously (d 0 to 35) or discontinued after d 14. During the experiment, broilers developed necrotic enteritis, and tissue cultures were positive for Escherichia coli and Salmonella, resulting in 50% mortality on control broilers. Addition of SDP to the feed improved (P < 0.05) average daily gain, feed intake, and feed efficiency for each period of the study (d 0 to 14, 15 to 28, 29 to 35, and 0 to 35). Continuous feeding of SDP improved (P < 0.05) average daily gain, feed intake, and feed efficiency from d 15 to 35 compared with broilers fed SDP to d 14. Liveability was improved (P < 0.05) in broilers consuming SDP either for 14 d or continuously throughout the experiment compared with control broilers. Spray-dried granular plasma was more effective than spray-dried powder plasma from d 0 to 14. The results of this experiment confirmed that SDP improved broiler growth rate, feed intake, feed efficiency, and minimized enteric challenge associated with necrotic enteritis with maximal protection afforded by continuous feeding. The response to SDP was independent of age of the broiler.


title: Diagnosis of Babesia caballi infections in horses by enzyme-linked immunosorbent assay (ELISA) and western blot

text: Abstract From Babesia caballi in vitro cultures a preparation of 100% infected erythrocytes was obtained. From this, B. caballi antigens were extracted with the detergent 3-[(3-Cholamidopropyl)-dimethylammonio]-1-propane-sulfonate (CHAPS) and used as ELISA antigens. A control antigen of normal erythrocytes from the same donor horse was prepared in an identical manner. The ELISA and Western blot were validated by testing of sera from horses experimentally infected with B. caballi or B. equi or not infected with Babesia spp. ELISA and Western blot results were compared with those obtained by the immunofluorescence antibody test (IFAT) and complement fixation test (CFT). The sensitivity of the ELISA of 98.3% obtained for sera from day 14 after infection was superior to the Western blot (94.9%), the IFAT (96.6%) and the CFT (28.8%). No positive results were obtained in the ELISA and Western blot with 106 sera from horses not infected with Babesia spp. resulting in a calculated specificity of 100% for both tests. Cross reactions of B. equi-positive sera did occur to a larger extent in the ELISA (20%) than in the IFAT (4%). No cross reactions were observed with the Western blot and the CFT. The higher sensitivity of the ELISA was also demonstrated by testing of 132 field sera: more positive results were obtained by ELISA (112) as compared to IFAT (92) or CFT (41). The validity of these results was confirmed by testing of sera by Western blot. The ELISA as the most sensitive test provides the best method for the identification of carrier horses to prevent the introduction into non-endemic areas (export testing). Positive ELISA results can be confirmed by Western blot, if a species-specific diagnosis is required.


title: Sequences, Annotation and Single Nucleotide Polymorphism of the Major Histocompatibility Complex in the Domestic Cat

text: Two sequences of major histocompatibility complex (MHC) regions in the domestic cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break (55–80 MYA) and followed by a chromosomal inversion were annotated in detail. Gene annotation of this MHC was completed and identified 183 possible coding regions, 147 human homologues, possible functional genes and 36 pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs. The first region spans 2.976 Mbp sequence, which encodes six classical class II antigens (three DRA and three DRB antigens) lacking the functional DP, DQ regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and LMP2/LMP7,TAP1/TAP2), 52 class III genes, nineteen class I genes/gene fragments (FLAI-A to FLAI-S). Three class I genes (FLAI-H, I-K, I-E) may encode functional classical class I antigens based on deduced amino acid sequence and promoter structure. The second region spans 0.362 Mbp sequence encoding no class I genes and 18 cross-species conserved genes, excluding class I, II and their functionally related/associated genes, namely framework genes, including three olfactory receptor genes. One previously identified feline endogenous retrovirus, a baboon retrovirus derived sequence (ECE1) and two new endogenous retrovirus sequences, similar to brown bat endogenous retrovirus (FERVmlu1, FERVmlu2) were found within a 140 Kbp interval in the middle of class I region. MHC SNPs were examined based on comparisons of this BAC sequence and MHC homozygous 1.9× WGS sequences and found that 11,654 SNPs in 2.84 Mbp (0.00411 SNP per bp), which is 2.4 times higher rate than average heterozygous region in the WGS (0.0017 SNP per bp genome), and slightly higher than the SNP rate observed in human MHC (0.00337 SNP per bp).


title: Epidemic characteristics of the COVID-19 outbreak in Tianjin, a well-developed city in China

text: BACKGROUND: : Coronavirus disease 2019 (COVID-19) is already a pandemic. Few studies investigated the epidemic characteristics of the COVID-19 outbreak in the well-developed cities. METHODS: : Epidemiological data of 136 confirmed COVID-19 cases were collected from the dataset of COVID-19 in Tianjin. All confirmed cases were categorized according to their potential infection sources. Daily numbers of confirmed cases of each category were plotted by date of onset, and the epidemic form of each category was inferred. RESULTS: : Among the 136 confirmed COVID-19 cases, 48 cases were categorized as imported cases and their close contacts, which were the majority of early cases. A total of 43 cases were found an epidemiological link to the Baodi department store, and they were inferred to be a common-source outbreak. Additionally, 35 cases were considered as familial clusters of COVID-19 cases, and 10 cases were sporadic. The 45 cases were inferred to be a propagated epidemic. CONCLUSIONS: : Local transmission of COVID-19 mainly occurred within families and a poorly ventilated public place in Tianjin. Besides the imported cases, the pattern of local transmission of COVID-19 was a mixture of the propagated epidemic and the common-source outbreak in Tianjin.


Understanding and Addressing Older Adults’ Needs During COVID-19


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title: Lopinavir/ritonavir use in Covid-19 infection: is it completely non-beneficial?

text: Abstract Covid-19 infection caused by the novel coronavirus SARS-COV-2 continues to be a major global health challenge. Till date, no drug has been approved for the treatment of this infection. A number of medications have been proposed and there are ongoing clinical trials around the world to find a suitable treatment. A recent randomised control trial compared lopinavir/ritonavir with standard care among 199 patients with severe Covid-19 infection and concluded that there was no significant reduction in mortality rate with lopinavir/ritonavir. However, there are a few important lessons which may be learnt from the study apart from the statistical reduction in mortality rate. There was a numerical reduction in mortality rate, less intensive care unit stay and less complications in the lopinavir-ritonavir group. This article points out some of those important lessons with some suggestions for future clinical trials.


Stalking new vaccines: Methods that target the stems of viral proteins could put universal vaccines within reach


title: Light and electron microscopic investigations of nasopharyngeal carcinomas with regard to the viral etiology of these tumors

text: Five carcinomata of the nasopharynx (four lymphoepithelial carcinomata of the Regaud type and one squamous cell carcinoma) were examined light and electron microscopically. In addition to the familiar histological and cytological features of these tumors, and because of an increased antibody titer against Epstein-Barr virus in all five patients, all those cytoplasmic and nuclear inclusions were examined which could be interpreted as indicative of a virus contact. The following structures were found: 1. Particles and microtubules which correspond in diameter, shape, and location to Corona viruses. 2. Particles surrounded by a double membrane and resembling in form and diameter Oncorna viruses. 3. Tubulo-reticular, coil-shaped cytoplasmic inclusions interpreted as an unspecific reaction of the host cell to viral attack. 4. Spherical nuclear bodies, which are frequently observed in tumors and in viral infections. 5. Intranuclear particles which correspond in diameter, structure, and distribution to viruses of the herpes type such as have been described in cell cultures of Burkitt lymphoma and nasopharyngeal carcinoma. The fifth group particularly was discussed in detail with regard to differentiation between those particles and other structures which could simulate a virus structure. Together with the appearance of increased ribosomes and of particular chromatin distribution within the tumor cell nuclei, the particles we discussed have been interpreted as morphological indications of a virus etiology of the examined tumors.


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title: Viral Diseases by Domestic Animal Species

text: This chapter presents tables that list the most important diseases and syndromes caused by viruses in each domestic animal species with their etiological associations. This listing is neither meant to substitute for a textbook of veterinary medicine or infectious diseases nor is it intended to be used for differential diagnosis, where viral and other etiologies must be considered together. Such a tabulation inevitably involves oversimplification, but page numbers have been provided to direct the reader to appropriate pages for detailed coverage of each of these viral infections. In these tables, each disease is ascribed to a measure of its importance as viewed from the perspective of veterinary medicine in countries with modern agricultural practices. There is an arbitrary element in relation to the group of diseases to which certain infections are allocated. For example, most generalized skin diseases result from generalized blood-borne infection but they have been listed as skin diseases. Where viruses cause generalized signs and also signs of particular importance in some system or in the newborn, they have been entered in both categories.


Remote management of hidradenitis suppurativa in a pandemic era of COVID‐19


title: A Simple Methodology for Conversion of Mouse Monoclonal Antibody to Human-Mouse Chimeric Form

text: Passive immunotherapy has mainly been used as a therapy against cancer and inflammatory conditions. Recent studies have shown that monoclonal antibody-(mAb-) based passive immunotherapy is a promising approach to combat virus infection. Specific mouse mAbs can be routinely generated in large amounts with the use of hybridoma technology but these cannot be used for therapy in human beings due to their immunogenicity. Therefore, the development of chimeric and humanized mAbs is important for therapeutic purpose. This is facilitated by a variety of molecular techniques like recombinant DNA technology and the better understanding of the structure and function of antibody. The human-mouse chimeric forms allow detailed analysis of the mechanism of inhibition and the potential for therapeutic applications. Here, a step-by-step description of the conversion process will be described. The commercial availability of the reagents required in each step means that this experimentation can be easily set up in research laboratories.


title: Arterial and venous abdominal thrombosis in a 79-year-old woman with COVID-19 pneumonia

text: Abstract As coronavirus pandemic continue to spread over the world, we have to be aware of potential complications on hospitalized patients. We report a case of a 79-year-old woman with COVID-19 pneumonia complicated by combined arterial and venous thrombosis of upper mesenteric vessels. As unenhanced chest-CT scan plays a key-role in managing the COVID-19 pandemic we should pay attention to indirect signs of thrombosis.


title: ROLE OF PHOTOTHERAPY IN THE ERA OF BIOLOGICS

text: ABSTRACT Phototherapy is a safe and effective treatment for many dermatologic conditions. With the advent of novel biologics and small molecule inhibitors, it is important to critically evaluate the role of phototherapy in dermatology. Surveys have shown that many dermatology residency programs do not dedicate time to teach residents how to prescribe or administer phototherapy. Limitations of phototherapy include access to a center, time required for treatments, and insurance approval. Home phototherapy, a viable option, is also underutilized. However, it should be emphasized that modern phototherapy has been in use for over 40 years, has an excellent safety profile, and does not require laboratory monitoring. It can be safely combined with many other treatment modalities including biologics and small molecule inhibitors. In addition, phototherapy costs significantly less than these novel agents. Dermatologists are the only group of physicians who have the expertise and proper training to deliver this treatment modality to our patients. Therefore, in order to continue to deliver high quality, cost-effective care, it is imperative that phototherapy be maintained as an integral part of the dermatology treatment armamentarium.


title: Does glycemic control rescue type 2 diabetic patients from COVID‐19‐related deaths?

text: Coronavirus SARS‐CoV‐2, which induced the novel coronavirus disease 2019 (COVID‐19), mainly invades respiratory tract and lung. Severe cases infected by SARS‐CoV‐2 progress to acute respiratory distress syndrome (ARDS), septic shock, and multiple organ dysfunction syndrome (MODS), which leads to death in some cases.


title: No evidence of SARS-CoV-2 in semen of males recovering from COVID-19

text: Abstract Objective To describe detection of SARS-CoV-2 in seminal fluid of patients recovering from COVID-19 and describe the expression profile of ACE2 and TMPRSS2 within the testicle. Design observational, cross-sectional study Setting Tertiary referral center Patients Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples Intervention None Main Outcome Measures Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. Results Six patients (19%) demonstrated scrotal discomfort concerning for viral orchitis around the time of COVID-19 confirmation. SARS-CoV-2 was not detected in semen after a median of 31 days (IQR: 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. Conclusions SARS-CoV-2 was not detected in the semen of patients recovering from COVID-19 one month after COVID-19 diagnosis. ACE2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.


title: Interferon-gamma levels in nasopharyngeal secretions of infants with respiratory syncytial virus and other respiratory viral infections

text: Respiratory syncytial virus (RSV) infection, one of the most common causes of hospitalization of children in developed countries, has been implicated as a cause of asthma. We aimed to characterize the cytokine profile in nasopharyngeal aspirates (NPAs) taken from infants during upper respiratory tract infection to investigate whether RSV induced a unique immune response as compared with other viruses. Additionally, we sought to determine whether this profile was influenced by the infants' atopic status. A prospective birth cohort of babies at high risk of atopy was recruited. Ratios of a T-helper 1 (Th1) cytokine, interferon gamma (IFN-γ) and a T-helper 2 (Th2)-like cytokine, interleukin-10 (IL-10), in NPAs were determined during episodes of respiratory tract infections in the first year. The viral aetiology of the respiratory tract infections was determined using polymerase chain reaction (PCR), culture and immunofluorescence. Atopic status was ascertained at 1 year of age using skin prick tests. Participants were recruited antenatally and subsequently followed in the community. Sixty babies with one or both parents atopic were enrolled into the study. IFN-γ : IL-10 ratios in NPAs during upper respiratory tract infections and their correlation with viral aetiology and atopic status were the main outcome measures. The mean IFN-γ : IL-10 ratio was significantly lower (due to lower IFN-γ) during RSV infections than during infections with other viruses (P = 0·035). The cytokine ratio, however, did not differ between infants with or without wheeze during URTIs (P = 0·44), or between infants who were atopic or non-atopic (P = 0·49). This study suggests that RSV is associated with lower IFN-γ production in young babies, regardless of their atopic status, compared to upper respiratory tract infections where either another virus is detected or where no viral identification is made.


title: Cytokine storm and leukocyte changes in mild versus severe SARS‐CoV‐2 infection: Review of 3939 COVID‐19 patients in China and emerging pathogenesis and therapy concepts

text: Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome‐coronavirus‐2 infection often results from alveolar injury that impedes airway capacity and multi‐organ failure—both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL‐6, IL‐1β, IL‐10, TNF, GM‐CSF, IP‐10 (IFN‐induced protein 10), IL‐17, MCP‐3, and IL‐1ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID‐19) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID‐19 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID‐19, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.


title: The Role of Viral Respiratory Infections in Asthma and Asthma Exacerbations

text: Viral respiratory tract infections are frequent and usually self-limited illnesses. For patients at risk for asthma, or with existing asthma, viral respiratory tract infections can have a profound effect on the expression of disease or loss of control. New evidence has shown that wheezing episodes early in life with the common cold virus, human rhinovirus, is a major risk factor for the later diagnosis of asthma at age six years. For those with existing asthma, exacerbations are a major cause of morbidity, need for acute care and, rarely, death. Viral respiratory tract infections, most frequently with rhinovirus, are the predominant microorganisms associated with asthma exacerbations. Evidence is also emerging that deficiencies in antiviral activity and the integrity of the airway epithelial barrier may make individuals with asthma more likely to have severe viral respiratory infections of the lower airway, and thus increase the risk of exacerbation. Given the influences of respiratory viruses on many aspects of asthma, efforts to understand the mechanisms and risk factors by which these airway infections cause changes in airway pathophysiology are a first step in improved treatment.


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title: Impact of Heat-Inactivation on the detection of SARS-CoV-2 IgM and IgG Antibody by ELISA

text: BACKGROUND: To establish a safe and accurate method for detecting SARS-CoV-2 IgM and IgG, we assessed the impact of sera after heat-inactivation on the SARS-CoV-2 IgM and IgG levels measured by ELISA-immunoassay. METHODS: The serum samples of 62 patients with COVID-19 and 18 healthy controls were collected in Hankou’s Hospital of Wuhan from February 27 to March 6, 2020. Before and after the samples were inactivated, the levels of IgM and IgG antibodies were measured. RESULTS: The indexes of antibodies after inactivated were significantly higher than those in fresh sera, while the positive rates in all participants or in patients with COVID-19 did not change. The positive coincidence rate, negative coincidence rate and total coincidence rate of IgM antibodies before and after inactivation were 100.00% (55/55), 96.00% (24/25) and 98.75% (79/80), respectively (κ=0.971, P<0.001), while those for IgG antibodies were 98.21% (55/56), 91.67% (22/24) and 98.75% (79/80) respectively (κ=0.910, P<0.001). These results showed a good consistency. CONCLUSIONS: Heating-activation does not decrease the diagnostic efficacy of SARS-CoV-2 IgM or IgG antibodies. Sera inactivated by heating at 56℃ for 30 minutes should be recommended to minimize the risk of virus contamination of laboratory staff.


title: Individual freedom versus collective responsibility: too many rights make a wrong?

text: Individuals might reasonably expect the freedom to make their own decisions regarding their health. However, what happens when an individual's wishes conflict with what is in that individual's best interests? How far should an individual's rights be restricted for his or her own benefit? Similarly, what limitations should be placed on an individual's behaviour when that person's wishes go against what is good for the population in general? Here we discuss the issues that can arise when the rights of individuals conflict with individual and population benefits in relation to infectious diseases.