title: Protein pI alteration related to strain variation of infectious bronchitis virus, an avian Coronavirus

text: Abstract Viral proteins of two strains of infectious bronchitis virus (IBV), which have different tissue trophism and serology, were separated on the basis of their isoelectric points (pI). The viruses have four structural proteins; the protein of greatest serological importance is found at the peplomer tip. The viral structural proteins separated by isoelectric focusing were identified by comparison to SDS-PAGE separations. Three protein bands were identical in pI and one protein band showed a difference in pI between strains. When the renatured viral proteins were Western blotted and reacted with strain-specific antiserum, antigen-antibody complexing was seen only at points corresponding to the strain-specific variant bands. For IBV strain Mass-41, antigen-antibody complexing occurred at a pI of 6.8, and, for IBV strain Ark-99, at 7.2. No cross reaction of antisera was observed for either strain. Since tissue affinities are a function of the viral peplomer-mediated attachment of virus to cells and are often directly related to pathogenicity, it appears that altered pathogenicity of strains of IBV may be detected by alteration of pI of the proteins. Classification by pI of proteins of at least the smaller viruses allows untypeable, highly pathogenic or persistent strains of these viruses to be characterized on the basis of variant proteins.


title: Evidence of intra-segmental homologous recombination in influenza A virus

text: Abstract The evolution of influenza viruses is remarkably dynamic. Influenza viruses evolve rapidly in sequence and undergo frequent reassortment of different gene segments. Homologous recombination, although commonly seen as an important component of dynamic genome evolution in many other organisms, is believed to be rare in influenza. In this study, 256 gene segments from 32 influenza A genomes were examined for homologous recombination, three recombinant H1N1 strains were detected and they most likely resulted from one recombination event between two closely rated parental sequences. These findings suggest that homologous recombination in influenza viruses tends to take place between strains sharing high sequence similarity. The three recombinant strains were isolated at different time periods and they form a clade, indicating that recombinant strains could circulate. In addition, the simulation results showed that many recombinant sequences might not be detectable by currently existing recombinant detection programs when the parental sequences are of high sequence similarity. Finally, possible ways were discussed to improve the accuracy of the detection for recombinant sequences in influenza.


title: Associations between genetics, farm characteristics and clinical disease in field outbreaks of porcine reproductive and respiratory syndrome virus

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is a disease of domestic swine characterized by exceptionally high clinical variability. This study addresses the question of whether clinical variability in PRRS results from (a) genetic variation among viral isolates and/or (b) variation in management practices among farms on which isolates are found. Genetic data (open reading frame 5 gene sequences) and data on farm characteristics and associated clinical disease signs were collected for 62 PRRS virus (PRRSV) field isolates, representing 52 farms. Clinical disease signs were interrelated — confirming that a true reproductive syndrome exists (involving abortions, infertility in sows, deaths of sows and preweaning mortality). Pairs of farms experiencing deaths in their sow populations also tended to share viral isolates which were more similar to one another than expected by chance alone. This implies that sow death (one of the more-severe manifestations of PRRS) is under genetic influence. Large herd size was a significant risk factor for the death of sows and for respiratory disease in nursery pigs. All-in–all-out management practices in the nursery were protective against reproductive signs in the sow herd. All-in–all-out management practices in the finishing stages of production were protective against respiratory disease in nursery pigs — but were paradoxically associated with an increased risk of infertility in sows. These results suggest that farm-management practices can also influence which PRRS clinical signs are manifested during an outbreak. In general, signs associated with PRRS appear to result from a combination of genetic factors and herd-management characteristics. The relative contributions of these two influences differ depending on the specific clinical sign in question.


title: Management of inpatients exposed to an outbreak of severe acute respiratory syndrome (SARS)

text: Abstract This is a prospective observational study of a cohort of inpatients exposed to a severe acute respiratory syndrome (SARS) outbreak. Strict infection control policies were instituted. The 70 patients exposed to the SARS outbreak were isolated from the rest of the hospital. They were triaged, quarantined and cohorted in three open plan wards. Selective isolation was carried out immediately when symptoms and signs suspicious of SARS manifested clinically. The patients' ages ranged from 21 to 90 years and 56% had surgery before the quarantine. Sixteen patients with unexplained fever during the period of quarantine were isolated, seven of whom were eventually diagnosed with probable SARS. The crude incidence of SARS in our cohort was 10%. The SARS case fatality was 14%. No secondary transmission of the SARS virus within the cohort was observed. Strict infection control, together with appropriate triaging, cohorting and selective isolation, is an effective and practical model of intervention in cohorts exposed to a SARS outbreak. Such a management strategy eases the logistic constraints imposed by demands for large numbers of isolation facilities in the face of a massive outbreak.


Contingency planning in the clinical laboratory: lessons learned amidst COVID-19


title: Protective role of Bruton tyrosine kinase inhibitors in patients with chronic lymphocytic leukaemia and COVID‐19

text: Severe cases of coronavirus disease 2019 (COVID-19) are usually accompanied by an exuberant immune response comparable to cytokine release syndrome (CRS), with markedly elevated serum levels of proinflammatory cytokines which are thought to be a major drivers of morbidity and mortality for these patients (Huang, et al 2020). Several drugs with anti-inflammatory properties (tocilizumab, siltuximab, sarilumab, anakinra, among others) have been suggested as adjuncts to supportive care in the management of COVID-19, and several clinical trials are underway (NCT04315298, NCT04317092, NCT04306705).


title: Two distinct cases with COVID‐19 in kidney transplant recipients

text: The fatality of novel coronavirus disease 2019 (COVID‐19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID‐19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36‐year‐old man who underwent KT 3 years ago. He was diagnosed with COVID‐19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID‐19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug‐to‐drug interaction. The second case was developed in a 56‐year‐old man without any symptoms. He received a second KT from an ABO‐incompatible donor 8 years ago. He was diagnosed with COVID‐19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.


title: miR-146a Inhibits dengue-virus-induced autophagy by targeting TRAF6

text: During dengue virus (DENV) infection, the virus manipulates different cellular pathways to assure productive replication, including autophagy. However, it remains unclear how this autophagic process is regulated. Here, we have demonstrated a novel role for the microRNA miR-146a in negatively regulating the cellular autophagic pathway in DENV-infected A549 cells and THP-1 cells. Overexpression of miR-146a significantly blocked DENV2-induced autophagy, and LNA-mediated inhibition of miR-146a counteracted these effects. Moreover, co-overexpression of TRAF6, a target of miR-146a, significantly reversed the inhibitory effect of miR-146a on autophagy. Notably, treatment with recombinant IFN-β fully restored the autophagic activity in TRAF6-silenced cells. Furthermore, our data showed that, in DENV2-infected A549 cells, autophagy promoted a pro-inflammatory response to significantly increase TNF-α and IL-6 production. Taken together, our results define a novel role for miR-146a as a negative regulator of DENV-induced autophagy and identify TRAF6 as a key target of this microRNA in modulating the DENV-autophagy interaction.


title: Containing misinformation spreading in temporal social networks

text: Many researchers from a variety of fields including computer science, network science and mathematics have focused on how to contain the outbreaks of Internet misinformation that threaten social systems and undermine societal health. Most research on this topic treats the connections among individuals as static, but these connections change in time, and thus social networks are also temporal networks. Currently there is no theoretical approach to the problem of containing misinformation outbreaks in temporal networks. We thus propose a misinformation spreading model for temporal networks and describe it using a new theoretical approach. We propose a heuristic-containing (HC) strategy based on optimizing final outbreak size that outperforms simplified strategies such as those that are random-containing (RC) and targeted-containing (TC). We verify the effectiveness of our HC strategy on both artificial and real-world networks by performing extensive numerical simulations and theoretical analyses. We find that the HC strategy greatly increases the outbreak threshold and decreases the final outbreak threshold.


title: Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis

text: BACKGROUND: The coronavirus disease 2019 (Covid-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with coronavirus disease 2019 (Covid-19) by stratifying the comorbidity status. METHODS: We analysed the data from 1590 laboratory-confirmed hospitalised patients 575 hospitals in 31 province/autonomous regions/provincial municipalities across mainland China between December 11(th), 2019 and January 31(st), 2020. We analyse the composite endpoints, which consisted of admission to intensive care unit, or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years. 686 patients (42.7%) were females. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD [hazards ratio (HR) 2.681, 95% confidence interval (95%CI) 1.424–5.048], diabetes (HR 1.59, 95%CI 1.03–2.45), hypertension (HR 1.58, 95%CI 1.07–2.32) and malignancy (HR 3.50, 95%CI 1.60–7.64) were risk factors of reaching to the composite endpoints. The HR was 1.79 (95%CI 1.16–2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61–4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory-confirmed cases of Covid-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.


Proactive measures for the pandemic COVID‐19 infection in outpatient clinics of Otolaryngology Department


title: Non‐steroidal anti‐inflammatory drugs in management of COVID‐19; a systematic review on current evidence

text: BACKGROUND: Since there is still no definitive conclusion regarding which non‐steroidal anti‐inflammatory drugs (NSAIDs) are most effective and safe in viral respiratory infections, we decided to evaluate the efficacy and safety of various NSAIDs in viral respiratory infections so that we can reach a conclusion on which NSAID is best choice for COVID‐19. METHODS: A search was performed in Medline (via PubMed), Embase, and CENTRAL databases until 23 March 2020. Clinical trials on application of NSAIDs in viral respiratory infections were included. RESULTS: Six clinical trials were included. No clinical trial has been performed on COVID‐19, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome infections. Studies show that ibuprofen and naproxen not only have positive effects in controlling cold symptoms but also do not cause serious side effects in rhinovirus infections. In addition, it was found that clarithromycin, naproxen and oseltamivir combination leads to decrease in mortality rate and duration of hospitalization in patients with pneumonia due to influenza. CONCLUSION: Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID‐19 and case‐reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID‐19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID‐19 patients until there are enough evidence. Naproxen may be a good choice for future clinical trials.


title: Detection of human rhinoviruses by reverse transcription strand invasion based amplification method (RT-SIBA)

text: Abstract Background: Rhinovirus (RV), a major cause of respiratory infection in humans, imposes an enormous economic burden due to the direct and indirect costs associated with the illness. Accurate and timely diagnosis is crucial for deciding the appropriate clinical approach and minimizing unnecessary prescription of antibiotics. Diagnosis of RV is extremely challenging due to genetic and serological variability among its numerous types and their similarity to enteroviruses. Objective: We sought to develop a rapid nucleic acid test that can be used for the detection of Rhinovirus within both laboratory and near patient settings. Study design: We developed and evaluated a novel isothermal nucleic acid amplification method called Reverse Transcription Strand Invasion-Based Amplification (RT-SIBA) to rapidly detect Rhinovirus from clinical specimens. Result: The method, RT-SIBA, detected RV in clinical specimens with high analytical sensitivity (96%) and specificity (100%). The time to positive result was significantly shorter for the RV RT-SIBA assay than for a reference RV nucleic acid amplification method (RT-qPCR). Conclusion: The rapid detection time of the RV SIBA assay, as well as its compatibility with portable instruments, will facilitate prompt diagnosis of infection and thereby improve patient care.


title: Coronavirus disease 2019 (COVID-19) in Brasil: information to physical therapists

text: The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic shows a rapid increase in cases and deaths The World Health Organization (WHO) has shown that more than 200 000 confirmed cases have been identified in more than 166 countries/territories Public health authorities in Brasil have reported 532 confirmed cases by March 19 Approximately 5% of the patients will require intensive care unit treatment with oxygen therapy and mechanical ventilation Limited data are available about rehabilitation protocols for severe illness and intensive care treatment of COVID-19 increase Thus, we aim to show current information about COVID-19, describing symptoms and the respiratory management for critical patients and preventive care Physical therapists and all health care professionals need to recognize the challenges they will face in the coming months


title: Self-reported adverse reactions in 4337 healthcare workers immunizations against novel H1N1 influenza

text: PURPOSE: The use of the 2009 H1N1 vaccine has generated much debate concerning safety issues among the general population and physicians. It was questioned if this is a safe vaccine. Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccine METHODS: We focused on the H1N1 pandemic influenza vaccine Pandemrix(® )and applied a self reporting questionnaire in a population of healthcare workers (HCWs) and medical students at a major university hospital. RESULTS: In total, 4337 individuals were vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination rate of the employees was higher than 40%. The majority of individuals were vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported to lead to one or more adverse reactions (6.7%). Local reactions were reported in 3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%. CONCLUSIONS: Our data together with available data from several national and international institutions points to a safe pandemic influenza vaccine.


title: PCR-based retrospective evaluation of diagnostic samples for emergence of porcine deltacoronavirus in US swine

text: Abstract Porcine deltacoronavirus (PDCoV) was first identified in Hong Kong in a regional surveillance study for Coronaviruses in 2012 and was detected for the first time in United States (US) swine in February 2014. However, it remains unknown if PDCoV had been introduced into the US prior to that time period. In the present study, 1734 clinical samples (903 cases) submitted to the Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) for enteric disease diagnosis between October 2012 and December 2013 were tested retrospectively for PDCoV using a virus-specific real-time reverse transcription (RT) PCR targeting conserved region of the membrane gene. PDCoV genome was first detected in a fecal sample collected on August 19th 2013 from Minnesota. Subsequently, PDCoV was observed in samples collected on August 20th and August 27th from Iowa and on August 29th from Illinois. Therefore, with available samples submitted to the ISU VDL, it can be inferred that PDCoV has been present in US swine at least since August 2013.


title: Rapidly Fatal Infections

text: Emergency physicians are trained to separate “sick” from “not sick” patients during their training. Nevertheless, every emergency physician will face situations in which early intervention is critical to their patient's outcome. Infectious diseases are responsible for many of these potentially poor outcomes. This article discusses early identification and treatment for several rapidly fatal infections, including two newly identified travel-related illnesses.


title: Vaccination with Trypanosoma rangeli reduces the infectiousness of dogs experimentally infected with Trypanosoma cruzi

text: Abstract The goal of this work was to test the efficacy of the vaccination with Trypanosoma rangeli in dogs. Mongrel dogs received three subcutaneous injections of fixed T. rangeli epimastigotes at 6-week intervals. Such immunisation induced antibodies against Trypanosoma cruzi. While both control and immunised dogs developed detectable parasitemia, this was lower and shorter in vaccinated animals. Interestingly, feeding of Triatoma infestans nymphs on vaccinated and chronically infected dogs led to a sharp reduction in the rate of bug infection. These results suggest that it might be possible to reduce the vectorial parasitemia through vaccination of dogs. As dogs are known to play a major role in the domestic cycle of T. cruzi, this might represent a strategy to reduce parasite transmission to humans.


Vitamin C, respiratory infections and the immune system


title: Possible environmental effects on the spread of COVID-19 in China

text: Abstract At the end of 2019, a novel coronavirus, designated as SARS-CoV-2, emerged in Wuhan, China and was identified as the causal pathogen of COVID-19. The epidemic scale of COVID-19 has increased dramatically, with confirmed cases increasing across China and globally. Understanding the potential affecting factors involved in COVID-19 transmission will be of great significance in containing the spread of the epidemic. Environmental and meteorological factors might impact the occurrence of COVID-19, as these have been linked to various diseases, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), whose causative pathogens belong to the same virus family as SARS-CoV-2. We collected daily data of COVID-19 confirmed cases, air quality and meteorological variables of 33 locations in China for the outbreak period of 29 January 2020 to 15 February 2020. The association between air quality index (AQI) and confirmed cases was estimated through a Poisson regression model, and the effects of temperature and humidity on the AQI-confirmed cases association were analyzed. The results show that the effect of AQI on confirmed cases associated with an increase in each unit of AQI was statistically significant in several cities. The lag effect of AQI on the confirmed cases was statistically significant on lag day 1 (relative risk (RR) = 1.0009, 95% confidence interval (CI): 1.0004, 1.0013), day 2 (RR = 1.0007, 95% CI: 1.0003, 1.0012) and day 3 (RR = 1.0008, 95% CI: 1.0003, 1.0012). The AQI effect on the confirmed cases might be stronger in the temperature range of 10 °C ≤ T < 20 °C than in other temperature ranges, while the RR of COVID-19 transmission associated with AQI was higher in the relative humidity (RH) range of 10% ≤ RH < 20%. Results may suggest an enhanced impact of AQI on the COVID-19 spread under low RH.


title: Higher levels of IL‐6 early after tocilizumab distinguish survivors from non‐survivors in COVID‐19 pneumonia: a possible indication for deeper targeting IL‐6

text: INTRODUCTION: The most serious COVID‐19 deriving from severe acute respiratory syndrome coronavirus 2 causes cytokine release storm and it is associated with worse outcomes. In COVID‐19 patients, Interleukin (IL)‐6 levels are significantly elevated. Blocking IL‐6 preliminary resulted in the improvement of this hyperinflammatory state. It is unknown which patients could require higher doses of tocilizumab to get out of the cytokine storm. MATERIALS AND METHODS: Twenty‐four patients affected by COVID‐19 pneumonia were included. All the patients underwent tocilizumab 8 mg/kg intravenously and were tested for serum IL‐6 24‐48 hours before and 12‐48 hours after tocilizumab infusion. Comparisons between survivors and non‐survivors were performed. RESULTS: Eighteen patients were discharged, while six patients died, with no clinical or laboratory differences between the two groups at baseline. IL‐6 was not different at baseline (p=0.41), while 24‐48h post‐tocilizumab IL‐6 serum levels were significantly higher in non‐survivors than in survivors [2398.5 (430.5‐9372) pg/mL vs 290.5 (58.5‐1305.5) pg/mL, p=0.022)]. Serum IL‐6 post‐tocilizumab showed a good predictive ability to discriminate survivors from non‐survivors (AUC 0.815 95%CI 0.63‐0.99, p=0.02). CONCLUSION: Repeated measurement of serum level of IL‐6 early after tocilizumab may distinguish non‐survivors from survivors and support the choice of deeper targeting IL‐6 in COVID‐19 pneumonia. This article is protected by copyright. All rights reserved.


Reply to “Clinical characteristics of COVID-19 patients with abnormal liver tests”


title: Aye Corona! The contagion effects of being named Corona during the COVID-19 pandemic

text: Abstract In the midst of the 2020 global COVID-19 pandemic and subsequent financial market collapse, corporate entities have to navigate a number of truly unforeseen contagion risks. However, one such group included those who shared their corporate identity with aspects of the rapidly evolving coronavirus. Our results indicate the existence of sharp, dynamic and new correlations between companies related to the term ‘corona’, outside of pre-existing interrelationships. We provide a number of observations as to why this situation occurred.


title: Long-Term Care, Residential Facilities, and COVID-19: An Overview of Federal and State Policy Responses

text: Abstract The COVID-19 pandemic has disproportionately affected residents and staff at long-term care (LTC) and other residential facilities in the US. The high morbidity and mortality at these facilities has been attributed to a combination of a particularly vulnerable population and a lack of resources to mitigate the risk. During the first wave of the pandemic, the federal and state governments received urgent calls for help from LTC and residential care facilities; between March and early June of 2020, policymakers responded with dozens of regulatory and policy changes. In this article, we provide an overview of these responses by first summarizing federal regulatory changes, and then reviewing state-level executive orders. The policy and regulatory changes implemented at the federal and state levels can be categorized into the following four classes: 1) preventing virus transmission, which includes policies relating to visitation restrictions, personal protective equipment (PPE) guidance, and testing requirements; 2) expanding facilities’ capacities, which includes both the expansion of physical space for isolation purposes and the expansion of workforce to combat COVID-19; 3) relaxing administrative requirements, which includes measures enacted to shift the attention of caretakers and administrators from administrative requirements to residents’ care; and 4) reporting COVID-19 data, which includes the reporting of cases and deaths to residents, families, and administrative bodies (such as state health departments). These policies represent a snapshot of the initial efforts to mitigate damage inflicted by the pandemic. Looking ahead, empirical evaluation of the consequences of these policies – including potential unintended effects – is urgently needed. The recent availability of publicly reported COVID-19 LTC data can be used to inform the development of evidence-based regulations, though there are concerns of reporting inaccuracies. Importantly, these data should also be used to systematically identify hot spots and help direct resources to struggling facilities.


title: Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics

text: Abstract Protein phosphatase 1 (PP1) catalyzes more than half of all phosphoserine/threonine dephosphorylation reactions in mammalian cells. In vivo PP1 does not exist as a free catalytic subunit but is always associated with at least one regulatory PP1-interacting protein (PIP) to generate a large set of distinct holoenzymes. Each PP1 complex controls the dephosphorylation of only a small subset of PP1 substrates. We screened the literature for genetically engineered mouse models and identified models for all PP1 isoforms and 104 PIPs. PP1 itself and at least 49 PIPs were connected to human disease-associated phenotypes. Additionally, phenotypes related to 17 PIPs were clearly linked to altered PP1 function, while such information was lacking for 32 other PIPs. We propose structural reverse genetics, which combines structural characterization of proteins with mouse genetics, to identify new PP1-related therapeutic targets. The available mouse models confirm the pleiotropic action of PP1 in health and diseases.


title: A new method to analyze protein sequence similarity using Dynamic Time Warping

text: Abstract Sequences similarity analysis is one of the major topics in bioinformatics. It helps researchers to reveal evolution relationships of different species. In this paper, we outline a new method to analyze the similarity of proteins by Discrete Fourier Transform (DFT) and Dynamic Time Warping (DTW). The original symbol sequences are converted to numerical sequences according to their physico-chemical properties. We obtain the power spectra of sequences from DFT and extend the spectra to the same length to calculate the distance between different sequences by DTW. Our method is tested in different datasets and the results are compared with that of other software algorithms. In the comparison we find our scheme could amend some wrong classifications appear in other software. The comparison shows our approach is reasonable and effective.


title: Diversity of bat astroviruses in Lao PDR and Cambodia

text: Abstract Astroviruses are known to infect humans and a wide range of animal species, and can cause gastroenteritis in their hosts. Recent studies have reported astroviruses in bats in Europe and in several locations in China. We sampled 1876 bats from 17 genera at 45 sites from 14 and 13 provinces in Cambodia and Lao PDR respectively, and tested them for astroviruses. Our study revealed a high diversity of astroviruses among various Yangochiroptera and Yinpterochiroptera bats. Evidence for varying degrees of host restriction for astroviruses in bats was found. Furthermore, additional Pteropodid hosts were detected. The astroviruses formed distinct phylogenetic clusters within the genus Mamastrovirus, most closely related to other known bat astroviruses. The astrovirus sequences were found to be highly saturated indicating that phylogenetic relationships should be interpreted carefully. An astrovirus clustering in a group with other viruses from diverse hosts, including from ungulates and porcupines, was found in a Rousettus bat. These findings suggest that diverse astroviruses can be found in many species of mammals, including bats.


title: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreak at King Abdul-Aziz Medical City-Riyadh from Emergency Medical Services Perspective

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a form of an infectious respiratory disease, discovered in November 2012 in Saudi Arabia. According to the World Health Organization (WHO; Geneva, Switzerland) reports, a total of 2,519 laboratory-confirmed cases and 866 MERS-CoV-related deaths were recorded as of March 5, 2016.(1) The majority of reported cases originated from Saudi Arabia (2,121 cases). Also, MERS-CoV is believed to be of zoonotic origin and has been linked to camels in the Arabian area.(1,2) In this report, the authors discuss the lessons learned from the MERS-CoV outbreak at King Abdul-Aziz Medical City-Riyadh (KAMC-R) from August through September 2015 from the Emergency Medical Services (EMS) perspective. The discussion includes the changes in policies and paramedic’s practice, the training and education in infection control procedures, and the process of transportation of these cases. The authors hope to share their experience in this unique situation and highlight the preparedness and response efforts that took place by the division of EMS during the outbreak.


title: Alignment independent 3D-QSAR studies and molecular dynamics simulations for the identification of potent and selective S1P1 receptor agonists

text: Abstract Sphingosine 1-phosphate type 1 (S1P1) receptors are expressed on lymphocytes and regulate immune cells trafficking. Sphingosine 1-phosphate and its analogues cause internalization and degradation of S1P1 receptors, preventing the auto reactivity of immune cells in the target tissues. It has been shown that S1P1 receptor agonists such as fingolimod can be suitable candidates for treatment of autoimmune diseases. The current study aimed to generate GRIND-based 3D-QSAR predictive models for agonistic activities of 2-imino-thiazolidin-4-one derivatives on S1P1 to be used in virtual screening of chemical libraries. The developed model for the S1P1 receptor agonists showed appropriate power of predictivity in internal (r2 acc 0.93 and SDEC 0.18) and external (r2 0.75 and MAE (95% data), 0.28) validations. The generated model revealed the importance of variables DRY-N1 and DRY-O in the potency and selectivity of these compounds towards S1P1 receptor. To propose potential chemical entities with S1P1 agonistic activity, PubChem chemicals database was searched and the selected compounds were virtually tested for S1P1 receptor agonistic activity using the generated models, which resulted in four potential compounds with high potency and selectivity towards S1P1 receptor. Moreover, the affinities of the identified compounds towards S1P1 receptor were evaluated using molecular dynamics simulations. The results indicated that the binding energies of the compounds were in the range of −39.31 to −46.18 and −3.20 to −9.75 kcal mol−1, calculated by MM-GBSA and MM-PBSA algorithms, respectively. The findings in the current work may be useful for the identification of potent and selective S1P1 receptor agonists with potential use in diseases such as multiple sclerosis.


title: A novel diagnostic approach to detecting porcine epidemic diarrhea virus: The lateral immunochromatography assay

text: Abstract Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea and dehydration in sucking piglets and has a high mortality rate. An immunochromatography (IC) assay, known as a lateral flow test, is a simple device intended to detect the presence of target pathogens. Here, we developed an IC assay that detected PEDV antigens with 96.0% (218/227) sensitivity and 98.5% (262/266) specificity when compared with real-time reverse transcriptase (RT)-PCR using FAM-labeled probes based on sequences from nucleocapsid genes. The detection limits of the real-time RT-PCR and IC assays were 1×102 and 1×103 copies, respectively. The IC assay developed herein did not detect non-specific reactions with other viral or bacterial pathogens, and the assay could be stored at 4°C or room temperature for 15 months without affecting its efficacy. Thus, the IC assay may result in improved PED detection and control on farms, and is a viable alternative to current diagnostic tools for PEDV.


title: Communicating and Monitoring Surveillance and Response Activities for Malaria Elimination: China's “1-3-7” Strategy

text: Qi Gao and colleagues describe China's 1-3-7 strategy for eliminating malaria: reporting of malaria cases within one day, their confirmation and investigation within three days, and the appropriate public health response to prevent further transmission within seven days.


Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine


title: Fluctuation analysis-based risk assessment for respiratory virus activity and air pollution associated asthma incidence

text: Abstract Asthma is a growing epidemic worldwide. Exacerbations of asthma have been associated with bacterial and viral respiratory tract infections and air pollution. We correlated the asthma admission rates with fluctuations in respiratory virus activity and traffic-related air pollution, namely particulate matter with an aerodynamic diameter ≤10μm (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3). A probabilistic risk assessment framework was developed based on a detrended fluctuation analysis to predict future respiratory virus and air pollutant associated asthma incidence. Results indicated a strong association between asthma admission rate and influenza (r =0.80, p <0.05) and SO2 level (r =0.73, p <0.05) in Taiwan in the period 2001–2008. No significant correlation was found for asthma admission and PM10, O3, NO2, and CO. The proposed fluctuation analysis provides a simple correlation exponent describing the complex interactions of respiratory viruses and air pollutants with asthma. This study revealed that there was a 95% probability of having exceeded 2987 asthma admissions per 100,000 population. It was unlikely (30% probability) that the asthma admission rate exceeded 3492 per 100,000 population. The probability of asthma admission risk can be limited to below 50% by keeping the correlation exponent of influenza to below 0.9. We concluded that fluctuation analysis based risk assessment provides a novel predictor of asthma incidence.


title: The Combination of Tocilizumab and Methylprednisolone Along With Initial Lung Recruitment Strategy in Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation: A Series of 21 Consecutive Cases

text: OBJECTIVE: To describe the outcomes with use of a combination of tocilizumab and methylprednisolone administered around the time of endotracheal intubation in patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. DATA SOURCES: Retrospective chart review. STUDY SELECTION/DATA EXTRACTION: Twenty-one consecutive patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Initial ventilator parameters were positive end-expiratory pressure 14 cm H(2)o and target plateau pressure 29 cm H(2)o to maximize lung recruitment. Methylprednisolone (125 mg every 6hr for 24 hr with tapering to 60 mg every 12 hr) was administered shortly after patients were intubated (median 11 hr after intubation). DATA SYNTHESIS: No patient in the cohort died while hospitalized (mortality, 0%; 95% CI, 0%–18%) and 18 patients have been discharged from the acute care setting. Twenty of 21 patients (95%) have been liberated from mechanical ventilation after a median duration of 8 days (range, 4–30 d). Following 48 hours of methylprednisolone, the A-a o(2) gradient decreased from 455 ± 103 to 228 ± 109 mm Hg (difference 227 ± 108 mm Hg; p < 0.01). CONCLUSIONS: Our positive experience with tocilizumab in combination with methylprednisolone started early after endotracheal intubation may be one avenue for reducing the morbidity and mortality seen with severe coronavirus disease 2019 and merits further exploration in clinical studies.


title: Antihypertensive medication uses and serum ACE2 levels: ACEIs/ARBs treatment does not raise serum levels of ACE2

text: IMPORTANCE: Recent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as animal studies indicate that these medications increase levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2. This has prompted clinicians to recommend discontinuing ACEIs and ARBs. OBJECTIVE: To examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS). DESIGN, SETTING, AND PARTICIPANTS: A single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years) stratified by ACEIs (N = 699) or ARBs (N = 753) treatment. MAIN OUTCOMES AND MEASURES: The AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m(2)), hypertension and type 2 diabetes (T2D) as well as serum levels of renin, ACE and ACE2. RESULTS: While renin and ACE levels were significantly raised in serum of individuals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected. CONCLUSIONS AND RELEVANCE: Treatment with ACEIs or ARBs does not raise ACE2 levels in serum. Therefore, the present study does not support the proposed discontinuation of these medications among patients affected with COVID-19.


title: Novel characteristics identified in two cases of feline cowpox virus infection

text: CASE SERIES SUMMARY: This case series discusses novel characteristics identified in two cases of cowpox. One presented with upper airway signs, and was identified to have a focal laryngeal lesion. The other had central neurological signs at the terminal stages, with intracytoplasmic inclusion bodies identified within the cerebral hemispheres on histopathology. RELEVANCE AND NOVEL INFORMATION: Currently, cowpox would be an unlikely consideration in patients with neurological signs or upper respiratory noise. These cases both document novel presentations of cowpox infection, which clinicians should be aware of and consider as differential diagnoses in patients with these atypical presentations.


title: The role of microglia in viral encephalitis: a review

text: Viral encephalitis is still very prominent around the world, and traditional antiviral therapies still have shortcomings. Some patients cannot get effective relief or suffer from serious sequelae. At present, people are studying the role of the innate immune system in viral encephalitis. Microglia, as resident cells of the central nervous system (CNS), can respond quickly to various CNS injuries including trauma, ischemia, and infection and maintain the homeostasis of CNS, but this response is not always good; sometimes, it will exacerbate damage. Studies have shown that microglia also act as a double-edged sword during viral encephalitis. On the one hand, microglia can sense ATP signals through the purinergic receptor P2Y12 and are recruited around infected neurons to exert phagocytic activity. Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In addition, microglia can also exert an antiviral effect by inducing autophagy or secreting cytokines. On the other hand, microglia mediate presynaptic membrane damage in the hippocampus through complement, resulting in long-term memory impairment and cognitive dysfunction in patients with encephalitis. Microglia mediate fetal congenital malformations caused by Zika virus (ZIKV) infection. The gene expression profile of microglia in HIV encephalitis changes, and they tend to be a pro-inflammatory type. Microglia inhibited neuronal autophagy and aggravated the damage of CNS in HIV encephalitis; E3 ubiquitin ligase Pellino (pelia) expressed by microglia promotes the replication of virus in neurons. The interaction between amyloid-β peptide (Aβ) produced by neurons and activated microglia during viral infection is uncertain. Although neurons can mediate antiviral effects by activating receptor-interacting protein kinases 3 (RIPK3) in a death-independent pathway, the RIPK3 pathway of microglia is unknown. Different brain regions have different susceptibility to viruses, and the gene expression of microglia in different brain regions is specific. The relationship between the two needs to be further confirmed. How to properly regulate the function of microglia and make it exert more anti-inflammatory effects is our next research direction.


title: COVID-19: Conceptos clave para el cirujano

text: Resumen Ante la pandemia por SARS-CoV-2 resulta fundamental conocer los aspectos claves de la infección: su origen epidemiológico, presentación, curso clínico, diagnóstico y los tratamientos empleados (aún experimentales en muchos casos). El conocimiento sobre el virus es limitado, pero a medida que progresa la pandemia y se conoce más su fisiopatología, se está publicando nueva evidencia de forma masiva. Los especialistas quirúrgicos se enfrentan a una situación sin precedentes: deben colaborar en plantas médicas o urgencias atendiendo a estos pacientes y además tomar decisiones sobre pacientes quirúrgicos con posible COVID-19. Esta revisión narrativa pretende resumir los aspectos más relevantes y sintetizar los conceptos básicos sobre COVID-19 para los cirujanos. Abstract In view of the current pandemic by SARS-CoV-2 it deems essential to understand the key concepts about the infection: its epidemiological origin, presentation, clinical course, diagnosis and treatment (still experimental in many cases). The knowledge about the virus is still limited, but as the pandemic progresses and the physiopathology of the disease is understood, new evidence is being massively published. Surgical specialists are facing an unprecedented situation: they must collaborate in the ER or medical wards attending these patients, while still needing to make decisions about surgical patients with probable COVID-19. The present narrative review aims to summarize the most relevant aspects and synthetize concepts on COVID-19 for surgeons.


title: Interferon-omega: Current status in clinical applications

text: Abstract Since 1985, interferon (IFN)-ω, a type I IFN, has been identified in many animals, but not canines and mice. It has been demonstrated to have antiviral, anti-proliferation, and antitumor activities that are similar to those of IFN-α. To date, IFN-ω has been explored as a treatment option for some diseases or viral infections in humans and other animals. Studies have revealed that human IFN-ω displays antitumor activities in some models of human cancer cells and that it can be used to diagnose some diseases. While recombinant feline IFN-ω has been licensed in several countries for treating canine parvovirus, feline leukemia virus, and feline immunodeficiency virus infections, it also exhibits a certain efficacy when used to treat other viral infections or diseases. This review examines the known biological activity of IFN-ω and its clinical applications. We expect that the information provided in this review will stimulate further studies of IFN-ω as a therapeutic agent.


title: Assay optimization for molecular detection of Zika virus

text: OBJECTIVE: To examine the diagnostic performance of real-time reverse transcription (RT)-polymerase chain reaction (PCR) assays for Zika virus detection. METHODS: We compared seven published real-time RT–PCR assays and two new assays that we have developed. To determine the analytical sensitivity of each assay, we constructed a synthetic universal control ribonucleic acid (uncRNA) containing all of the assays’ target regions on one RNA strand and spiked human blood or urine with known quantities of African or Asian Zika virus strains. Viral loads in 33 samples from Zika virus-infected patients were determined by using one of the new assays. FINDINGS: Oligonucleotides of the published real-time RT–PCR assays, showed up to 10 potential mismatches with the Asian lineage causing the current outbreak, compared with 0 to 4 mismatches for the new assays. The 95% lower detection limit of the seven most sensitive assays ranged from 2.1 to 12.1 uncRNA copies/reaction. Two assays had lower sensitivities of 17.0 and 1373.3 uncRNA copies/reaction and showed a similar sensitivity when using spiked samples. The mean viral loads in samples from Zika virus-infected patients were 5 × 10(4) RNA copies/mL of blood and 2 × 10(4) RNA copies/mL of urine. CONCLUSION: We provide reagents and updated protocols for Zika virus detection suitable for the current outbreak strains. Some published assays might be unsuitable for Zika virus detection, due to the limited sensitivity and potential incompatibility with some strains. Viral concentrations in the clinical samples were close to the technical detection limit, suggesting that the use of insensitive assays will cause false-negative results.


title: Prevalence, prediction and risk factors of enteropathogens in normal and non-normal faeces of young Dutch dairy calves

text: Abstract Between January and April 2007, 424 calves under 22 days of age from 108 Dutch dairy herds were sampled to estimate the prevalence of non-normal faeces (‘custard-like’—yellowish-coloured with custard consistency or diarrhoea: watery-like faeces) and the shedding of enteropathogens Escherichia coli K99 (E. coli), Coronavirus, Cryptosporidium parvum (C. parvum), Rotavirus and Clostridium perfringens (Cl. perfringens). In addition, information was collected on animal characteristics and herd-management practices. The probability of detecting each one of five enteropathogens given a calf with ‘custard-like’ faeces or diarrhoea was estimated using Bayes’ rule and was based on the predicted probabilities from a multinominal model including each of five enteropathogens as independent variables. In addition, putative risk factors for the presence of each of five enteropathogens were analysed using logistic regression models with random herd effects. Fifty-seven percent of calves had faeces of normal colour (brownish) and consistency (firm), 23.8% (95%CI: 19.8–28.2%) had ‘custard-like’ faeces and 19.1% (95%CI: 15.5–23.2%) had diarrhoea. E. coli was the least detected enteropathogen (2.6% (95%CI: 1.3–4.6%) of calves, 9% (95%CI: 5–16%) of herds) and Cl. perfringens was most detected (54.0% (95%CI: 49.1–58.8%) of calves, 85% (95%CI: 77–91%) of herds). E. coli and Coronavirus were detected incidentally in only one or two calves per herd, whereas C. parvum and Cl. perfringens were frequently detected in up to four calves per herd. For calves with ‘custard-like’ faeces, the probability of detecting Rotavirus from a calf in its first week of age was 0.31 whereas for a calf in its second week, there was a 0.66 probability of detecting C. parvum. The probabilities of detecting E. coli, Rotavirus and C. parvum in calves with diarrhoea in their first week of age were 0.10, 0.20 and 0.43, respectively. In calves with diarrhoea between 1 and 2 weeks of age, the probability of detecting enteropathogens was 0.43 for C. parvum. None of the tested enteropathogens were related to ‘custard-like’ faeces or diarrhoea in the third week of age. Putative risk factors for E. coli, Coronavirus and C. parvum included the presence of peer-calves shedding Coronavirus, C. parvum or Rotavirus, respectively. Additionally, managerial risk factors such as non-optimal hygienic housing (for Coronavirus) and the routine use of antibiotics for diarrhoeic calves (for C. parvum) were found. No animal or managerial factors were associated with shedding of Cl. perfringens.


title: Profiling of Substrate Specificity of SARS-CoV 3CL(pro)

text: BACKGROUND: The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a thorough understanding of substrate specificity of the protease, a substrate library of 19[Image: see text]8 variants was created by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer. The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high β-sheet propensity; P4 prefers small hydrophobic residues; P2 prefers hydrophobic residues without β-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated a strong structure-activity relationship between the 3CL(pro) and its substrate. The substrate specificity profiled in this study may provide insights into a rational design of peptidomimetic inhibitors.


title: A single point mutation of the influenza C virus glycoprotein (HEF) changes the viral receptor-binding activity

text: Abstract From strain JHB/1/66 of influenza C virus a mutant was derived with a change in the cell tropism. The mutant was able to grow in a subline of Madin-Darby canine kidney cells (MDCK II) which is resistant to infection by the parent virus due to a lack of receptors. Inactivation of cellular receptors by either neuraminidase or acetylesterase and generation of receptors by resialylation of cells with N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) indicated that 9-O-acetylated sialic acid is a receptor determinant for both parent and mutant virus. However, the mutant required less Neu5,9Ac2 on the cell surface for virus attachment than the parent virus. The increased binding efficiency enabled the mutant to infect cells with a low content of 9-O-acetylated sialic acid which were resistant to the parent virus. By comparing the nucleotide sequences of the glycoprotein (HEF) genes of the parent and the mutant virus only a single point mutation could be identified on the mutant gene. This mutation at nucleotide position 872 causes an amino acid exchange from threonine to isoleucine at position 284 on the amino acid sequence. Sequence similarity with a stretch of amino acids involved in the receptor-binding pocket of the influenza A hemagglutinin suggests that the mutation site on the influenza C glycoprotein (HEF) is part of the receptor-binding site.


title: Effect of 24 hours light on circadian rhythms of secretory enzymes and morphology of rat von Ebner’s glands

text: Abstract Von Ebner’s glands of the rat are minor salivary serous glands in the posterior portion of the tongue. They secrete two digestive enzymes, lingual lipase and amylase. In this investigation, circadian rhythm in feeding was established under a normal 12 h light/12 h dark cycle, with the rats eating primarily during the dark period. At lights on, the size of the acinar cells and the area of the inclusive secretory granules, and the amount of digestive enzyme activity (lingual lipase and amylase) remaining in the gland was significantly less than in the mid-afternoon, after very little daylight food consumption. However, after 7 days of continuous light the circadian rhythm was altered: the food consumption during the normal night-time hours (5 p.m. to 8 a.m.) went from 88% of total 24 h food consumption to 45%, and during normal daylight hours (8 a.m. to 5 p.m.) from 12% to 55%. These changes were correlated with histometric findings of a near reversal of the areas of acinar cells and secretory granules of a.m. and p.m. samples under continuous light. Lingual lipase activity in the glands went from 35% under 12 h light to 61% under continuous light in the a.m. and from 65% to 39% in the p.m. Amylase activity also showed nearly a reversal in activity remaining in the gland, from 36% at 12 h light to 58% at 24 h light in the a.m. and 64% to 41% for the p.m. samples. These results indicate that the von Ebner’s glands of the rat have a circadian rhythm of secretion and storage of secretory proteins that is subject to light entrainment similar to that seen in other exocrine glands such as the parotid and pancreas.


title: The coronavirus nucleocapsid protein is ADP-ribosylated

text: Abstract ADP-ribosylation is a common post-translational modification, although how it modulates RNA virus infection is not well understood. While screening for ADP-ribosylated proteins during coronavirus (CoV) infection, we detected a ~55kDa ADP-ribosylated protein in mouse hepatitis virus (MHV)-infected cells and in virions, which we identified as the viral nucleocapsid (N) protein. The N proteins of porcine epidemic diarrhea virus (PEDV), severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV were also ADP-ribosylated. ADP-ribosylation of N protein was also observed in cells exogenously expressing N protein by transduction using Venezuelan equine encephalitis virus replicon particles (VRPs). However, plasmid-derived N protein was not ADP-ribosylated following transient transfection but was ADP-ribosylated after MHV infection, indicating that this modification requires virus infection. In conclusion, we have identified a novel post-translation modification of the CoV N protein that may play a regulatory role for this important structural protein.


title: Effectiveness of intravenous immunoglobulin for children with severe COVID-19: A rapid review

text: Background: Intravenous immunoglobulin (IVIG) is usually used as supportive therapy, but the treatment of COVID-19 by IVIG is controversial. This rapid review aims to explore the clinical effectiveness and safety of IVIG in the treatment of children with severe COVID-19. Methods: We systematically searched the literature on the use of IVIG in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), including both adults and children. We assessed the risk of bias and quality of evidence and reported the main findings descriptively. Results: A total of 1,519 articles were identified by initial literature search, and finally six studies met our inclusion criteria, included one randomized controlled trial (RCT), four case series and one case report involving 198 patients. One case series showed the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS) was not improved by IVIG. One case report showed high-dose IVIG could improve the outcome of COVID-19 adults. Three observational studies showed inconsistent results of the effect of IVIG on SARS patients. One RCT showed that IVIG did not reduce mortality or the incidence of nosocomial infection in adults with severe SARS. The quality of evidence was between low and very low. Conclusions: The existing evidence is insufficient to support the efficacy or safety of IVIG in the treatment of COVID-19.


title: 1 Fixed Man, Enhanced Man, Transformed Man

text: Abstract: In the past, for a patient, any hospitalization would end in one of three ways: recovery, death or disability, also regarded as “little death”. Such was the terrible destiny of a patient. Gradually, chronic diseases have slid into the first two options, thanks to the advent of medical diagnosis. The diagnosis surpassed the symptoms. An example is the definition of diabetes obtained through medical diagnosis: according to international norms, a person suffers from diabetes if his glycaemia is 700mmol/L (126mg/dL) or more after 8hours of fasting.


title: A natural tetranortriterpenoid with immunomodulating properties as a potential anti-HSV agent

text: Abstract Meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., prevents the development of herpetic stromal keratitis (HSK) in mice by diminishing the viral load in the eye and the severity of lesions caused by a virus-induced immunopathological reaction. The tetranortriterpenoid 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA purification, displays anti-herpetic activity and impedes nuclear factor κB (NF-κB) activation in HSV-1 infected conjunctival cells. To extend our understanding about CDM biological properties, we investigated its anti-HSV-1 activity as well as the effect on NF-κB activation and cytokine secretion induced by viral (HSV-1) and no-viral (LPS) stimuli, in corneal cells and macrophages. CDM exerted a potent anti-HSV-1 effect on corneal cells and inhibited NF-κB translocation to the nucleus, leading to a decrease in IL-6 production. Besides, CDM seemed to modulate IL-6 and TNF-α responses in macrophages, whether they were infected with HSV-1 or stimulated with LPS. However, CDM did not affect NF-κB activation in these cells, suggesting that an alternative NF-κB cell signaling pathway would be involved in the modulation of cytokine production. We conclude that, in addition to its antiviral effect, CDM would be acting as an immunomodulating compound which would be responsible for the improvement of murine HSK already reported.


title: Attitudes and perception of influenza vaccines among older people in Singapore: A qualitative study

text: BACKGROUND: Despite recommendations for influenza vaccination of people aged 65 and above, uptake rate of influenza vaccines remains low. This study aims to understand barriers and motivators behind older adult’s decision on influenza vaccination. METHODS: Face to face interviews with participants aged 65 and above were conducted and audio recorded in Geylang polyclinic in Singapore. Thematic content analysis was used to organise the data. RESULTS: 15 older adults were interviewed, aged between 66 and 85 years old. 6 were vaccine refusers, 3 defaulters and 6 acceptors. A perceived lack of vulnerability, fear of side effects, and trivialisation of influenza were common reasons for not taking the vaccine. Encouragement from family and friends, travel and previous positive vaccination experiences were motivators for getting vaccinated. Healthcare workers played a role in influencing many of the participants’ decision-making. Common misconceptions included vaccines considered as necessary only before travel and as a cure rather than prevention. Most participants exhibited ambivalence, giving reasons both for and against vaccine uptake. DISCUSSION: Most older adults do not perceive influenza as a potentially serious disease nor trust in influenza vaccines’ efficacy. Misconceptions played a significant role in vaccine decline. Novel findings include the importance of the family unit in decision making, prioritization of chronic health problems over vaccination and misconception that vaccines are only needed when travelling out of country. Healthcare workers and family members appear to be important influencers in the decision making of older adults and should be actively engaged in future health promotion initiatives.


title: Simultaneous development of zanubrutinib in the USA and China

text: Zanubrutinib was recently granted expedited approval by the USA and Chinese drug regulatory authorities for the treatment of mantle cell lymphoma, thus becoming the first investigational new drug discovered in China to achieve simultaneous development in both countries. Here, we provide an overview of the regulatory processes and considerations of the two health authorities and discuss the pathways of concurrent review and approval.


title: Applications of Microfluidics for Molecular Diagnostics

text: Diagnostic assays implemented in microfluidic devices have developed rapidly over the past decade and are expected to become commonplace in the next few years. Hundreds of microfluidics-based approaches towards clinical diagnostics and pathogen detection have been reported with a general theme of rapid and customizable assays that are potentially cost-effective. This chapter reviews microfluidics in molecular diagnostics based on application areas with a concise review of microfluidics in general. Basic principles of microfabrication are briefly reviewed and the transition to polymer fabricated devices is discussed. Most current microfluidic diagnostic devices are designed to target a single disease, such as a given cancer or a variety of pathogens, and there will likely be a large market for these focused devices; however, the future of molecular diagnostics lies in highly multiplexed microfluidic devices that can screen for potentially hundreds of diseases simultaneously.


title: Weakly Labeled Data Augmentation for Deep Learning: A Study on COVID-19 Detection in Chest X-Rays

text: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in over 2.7 million infected individuals and over 190,000 deaths and growing. Assertions in the literature suggest that respiratory disorders due to COVID-19 commonly present with pneumonia-like symptoms which are radiologically confirmed as opacities. Radiology serves as an adjunct to the reverse transcription-polymerase chain reaction test for confirmation and evaluating disease progression. While computed tomography (CT) imaging is more specific than chest X-rays (CXR), its use is limited due to cross-contamination concerns. CXR imaging is commonly used in high-demand situations, placing a significant burden on radiology services. The use of artificial intelligence (AI) has been suggested to alleviate this burden. However, there is a dearth of sufficient training data for developing image-based AI tools. We propose increasing training data for recognizing COVID-19 pneumonia opacities using weakly labeled data augmentation. This follows from a hypothesis that the COVID-19 manifestation would be similar to that caused by other viral pathogens affecting the lungs. We expand the training data distribution for supervised learning through the use of weakly labeled CXR images, automatically pooled from publicly available pneumonia datasets, to classify them into those with bacterial or viral pneumonia opacities. Next, we use these selected images in a stage-wise, strategic approach to train convolutional neural network-based algorithms and compare against those trained with non-augmented data. Weakly labeled data augmentation expands the learned feature space in an attempt to encompass variability in unseen test distributions, enhance inter-class discrimination, and reduce the generalization error. Empirical evaluations demonstrate that simple weakly labeled data augmentation (Acc: 0.5555 and Acc: 0.6536) is better than baseline non-augmented training (Acc: 0.2885 and Acc: 0.5028) in identifying COVID-19 manifestations as viral pneumonia. Interestingly, adding COVID-19 CXRs to simple weakly labeled augmented training data significantly improves the performance (Acc: 0.7095 and Acc: 0.8889), suggesting that COVID-19, though viral in origin, creates a uniquely different presentation in CXRs compared with other viral pneumonia manifestations.


title: Seroprevalence of major avian respiratory diseases in broiler and sonali chicken in selected areas of Bangladesh

text: OBJECTIVE: This study was conducted to investigate different respiratory diseases in broiler and sonali birds in some selected districts of Bangladesh. MATERIALS AND METHODS: We were collected a total of 460 blood samples from 46 farms with 36 broiler farms and 10 sonali farms (cross-breed) from 2015 to 2017. All the collected serum samples were tested for determining specific antibodies of avian rhinotracheitis (ART) virus, infectious laryngotracheitis (ILT) virus, infectious bronchitis (IBV) virus, and Ornithobacterium rhinotracheale (ORT) infection using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The overall seropositivity was highest in ORT (45.9%), followed by IBV (37.6%), ART (2.6%), and ILT (0.4%). Out of 360 broiler samples, highest seropositivity was recorded in ORT (43.3%) and lowest in IBV (31.4%). Surprisingly, no broiler samples were found positive for ART and ILT. In case of sonali, the seropositivity was highest in IBV (60%) and lowest in ILT (2%). With respect to types of birds and age groups, the seropositive percentage of all four pathogens was found higher in sonali than broiler. Between two age groups of sonali, the seropositive percentage of ART (12%), ORT (55%), ILT (2%), and IBV (60%) was highest at 21–60 weeks of age compared to 5–20 weeks of age. However, based on location, the seropositive of ORT and IBV was highest in Jamalpur (63.3%) and Fulbariya and Trishal (50%) and lowest in Sreepur (16.7%) and Jamalpur (3.3%). CONCLUSION: The four pathogens are ubiquitous in nature for the sonali chickens, and the prevalence of ORT and IBV was the most prevalent viruses in the study areas. This study indicates a need for improved surveillance and characterization of ORT and ART circulating in all types of poultry in Bangladesh.


title: Google searches for the keywords of “wash hands” predict the speed of national spread of COVID-19 outbreak among 21 countries

text: Abstract This study hypothesized that national population health literacy might reflect on their keywords searching. We applied Google searches for “wash hands” and “face mask” during January 19 to February 18 as a surrogate of national population health literacy among 21 countries, and examine whether google searches for “wash hands” and “face masks” would protect from increased numbers of confirmed cases of among 21 countries We found the increased google searches for “wash hands” from January 19 to February 18, 2020, correlated with a lower spreading speed of COVID-19 from February 19 to March 10, 2020 among 21 countries (Pearson's correlation coefficient of -0.70, P < 0.001). The result highlights the importance of public awareness of hand washing in preventing COVID-19 disease spreading.


title: Bracing for impact with new 4R’s in the COVID-19 pandemic- a provincial thoracic radiation oncology consensus

text: Abstract As COVID-19 pandemic continues to explode, cancer centers worldwide are trying to adapt and are struggling with this constantly changing scenario. Intending to ensure patient safety and deliver quality care, we sought consensus on the preferred thoracic radiation regimen in a Canadian province with 4 new R’s of COVID era.


title: Impact of Covid – 19 Pandemic on Orthopaedics at Northwell Health, New York

text: Abstract The Novel Coronavirus (COVID-19) pandemicplaced an immense strain on healthcare systems and orthopedic surgeons across the world. To limit the spread, federal and state governments mandated the cancellation of all non-urgent surgical cases to address surging hospital admissions and manage workforce and resource reallocation. During the pandemic surge, thousands of surgical cancellations have been required. We outline our experience through the onset and advance of the surge, detail our incident response, and discuss the transition toward recovery.


title: Reduced nasal IL‐10 and enhanced TNFα responses during rhinovirus and RSV‐induced upper respiratory tract infection in atopic and non‐atopic infants

text: Rhinovirus and respiratory syncytial virus (RSV) are the most prevalent inducers of upper respiratory tract infections (URTI) in infants and may stimulate immune maturation. To estimate the amount of immune stimulation, nasal immune responses were examined during rhinovirus and RSV‐induced URTI in infants. Nasal brush samples were taken from infants (2–26 months; 57% atopic family) with rhinovirus‐induced URTI (N = 20), with RSV‐induced URTI (N = 7), and with rhinovirus‐induced rhinitis (N = 11), from children with asymptomatic rhinovirus infection (N = 7) and from eight non‐infected children. Numbers of nasal brush cells positive for Th1‐, Th2‐, regulatory and proinflammatory cytokines were measured by immunohistochemistry or by measuring protein levels using a cytometric bead array analysis. During rhinovirus and RSV‐induced URTI, fewer regulatory cytokine IL‐10 positive cells were found compared to non‐infected children. This fall was accompanied by an increase in levels of the Th1 cytokine TNFα. IL‐10 responses were inversely related to TNFα responses. No enhanced responses were observed for IFNγ, IL‐12 and IL‐18. Cytokine responses were comparable in children with rhinovirus‐induced URTI and in children with rhinitis, while responses in asymptomatic rhinovirus‐infected children were located between those for symptomatic and asymptomatic rhinovirus‐infected children. Cytokine responses did not depend on the age of the child or atopy in the family. In conclusion, reduced nasal IL‐10 responses during URTI in infants could facilitate the induction of a TNFα response. TNFα in turn could replace the immature production of IL‐12, IL‐18 and IFNγ during URTI to induce an effective clearance of the viral infection and which could stimulate the maturation of Th1 cytokine production in infancy. J. Med. Virol. 75:348–357, 2005. © 2004 Wiley‐Liss, Inc.


title: Clinical features and outcomes of four HIV patients with COVID‐19 in Wuhan, China

text: SARS-CoV-2 is the coronavirus that has been identified as the pathogen causing COVID-19.1 Human Immunodeficiency Virus (HIV) attacks the immune system and leads to acquired immune deficiency syndrome (AIDS) in the late stage of disease. Concerns have been raised on HIV as a risk factor for COVID-19. This article is protected by copyright. All rights reserved.


title: From high volume to “zero” proctology: Italian experience in the COVID era

text: PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic hit Italy early and strongly, challenging the whole health care system. Proctological patients and surgeons are experiencing a previously unseen change in care with unknown repercussion. Here we discuss the proctological experience of 4 Italian hospitals during the COVID-19 pandemic. METHODS: Following remote brainstorming, the authors summarised their experience in managing proctological patients during the COVID-19 pandemics and put forward some practical observations to further investigate. RESULTS: The 4 hospitals shifted from a high-volume proctological activity to almost “zero” visits and surgery. Every patient accessing the hospital must respect a specific COVID-19 protocol. Proctological patients can be stratified based on presentation and management considerations into (1) neoplastic patients, the only allowed to be surgically treated, (2) the ones requiring urgent care, operated only in highly selected cases and (3) the stable, already known patients, managed remotely. Changes in the clinical management of the proctological disease are presented together with some considerations to be explored. CONCLUSIONS: In the absence of scientific evidence, these practical considerations may be valuable to proctological surgeons starting to face the COVID-19 pandemics. Beside the more clinical considerations, this crisis produced unexpected consequences such as an improvement of the therapeutic alliance and a shift towards telemedicine that may be worth exploring also in the post-COVID-19 era.


title: Evolution of COVID‐19 infection in 4 psoriatic patients treated with biological drugs

text: Since December 2019, the pandemic coronavirus disease (2019‐nCoV; COVID‐19) has changed the approach to all dermatological diseases; in particular, psoriatic patients undergoing immunosuppressive drugs, such as biologics, can potentially show an increase risk of infection (1). However, few reports are available on the course of COVID‐19 infection in psoriatic patients treated with biological drugs (2). We describe a case series of four psoriatic patients treated with biologics who had a risk contact with COVID‐19.


State Voting Patterns in the 2016 Presidential Election and Uninsured Rates in Non-elderly Adults


title: Accuracy of IgM antibody testing, FQ-PCR and culture in laboratory diagnosis of acute infection by Mycoplasma pneumoniae in adults and adolescents with community-acquired pneumonia

text: BACKGROUND: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae in adults and adolescents is hampered by a lack of rapid and standardized tests for detection. METHODS: CAP patients from 12 teaching hospitals were prospectively and consecutively recruited. Basic and clinical information, throat swabs and paired sera were collected. Mycoplasma pneumoniae was detected by IgG and IgM antibody tests, fluorescence quantitative polymerase chain reaction (FQ-PCR) and culture. A comparative study of the diagnostic values of three methods, including sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (PLR) was conducted. A fourfold or greater increase of IgG antibody titers of paired sera was set as the diagnostic “gold standard”. RESULTS: One hundred and twenty-five CAP patients (52.8% males, median age 47 years, range 14–85) were enrolled. Twenty-seven (21.6%) patients were diagnosed with acute Mycoplasma pneumoniae infections by the “gold standard”. Specificity values of all three methods were around 90%. An increasing trend of sensitivity, positive predictive value and PLR was found, with the lowest in IgM testing (7.4%, 28.6% and 1.45), intermediate in FQ-PCR (40.7%, 50% and 3.63), and highest in culture (55.6%, 75% and 10.9). CONCLUSIONS: In the defined group of patients, there was a good agreement between positive rate of MP cultivation of throat swabs and acute M. pneumoniae infection (PLR of 10.9). Since the sensitivity is low in all of the evaluated methods, the logical approach would be to incorporate PCR, culture and serological tests for optimum diagnosis of acute Mycoplasma pneumoniae infections in adults and adolescents.


title: Inflammatory cytokines and the nuclear vitamin D receptor are implicated in the pathophysiology of dental resorptive lesions in cats

text: Abstract Dental resorptive lesions (RL) are a common oral disease in cats (Felis catus) associated with pain and tooth destruction. The aetiology of RL in cats is unknown, but inflammation is often seen in conjunction with RL. Vitamin D involvement has been suggested because 1,25-dihydroxyvitamin D (1,25(OH)2D) stimulates osteoclastogenesis, through up-regulation of the nuclear vitamin D receptor (nVDR). The aim of this study is to determine the involvement of inflammatory cytokines and the possible role of vitamin D in the pathophysiology of RL using quantitative PCR. We measured the mRNA expression of cytokines with stimulatory (IL-1β, IL-6, and TNF-α) and inhibitory effects (IL-10 and IFN-γ) on osteoclastogenesis, and the mRNA expression of the receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), and nVDR in RL samples. We found increased expression of mRNA levels for inflammatory cytokines and nVDR, but not for RANKL and OPG, in tissue from RL-affected cats compared with tissue from radiological confirmed healthy controls. The mRNA levels of nVDR were positively correlated with mRNA levels of pro-inflammatory (IL-1β, IL-6, TNF-α, and IFN-γ), anti-inflammatory (IL-10), pro-resorptive (IL-1β, IL-6, and TNF-α), and anti-resorptive (IFN-γ and IL-10) cytokines in the course of resorptive lesions. These data are consistent with our view that both inflammation and an overexpression of the nVDR are likely to be involved in RL in cats.


title: Light Microscopy and Ultrahistology of Intestinal Changes in Pigs Infected with Epizootic Diarrhoea Virus (EVD): Comparison with Transmissible Gastroenteritis (TGE) Virus and Porcine Rotavirus Infections

text: SUMMARY: Light microscopic and ultrahistological changes were investigated in the intestines of piglets naturally and experimentally infected with epizootic viral diarrhoea (EVD) virus and compared to those occuring during intestinal TGE and rotavirus infections in piglets. The course of the EVD virus infection is comparable to that of TGE. Villous atrophy develops throughout the jejunum and the ileum as in TGE. In this respect it differs from rotavirus infection. The ultrastructural picture of intestinal EVD virus infection resembles that of TGE and other enteropathogenic coronaviruses. Virus replication, however, was observed mainly in enterocytes located on the lateral walls of the villi extending to the villus/crypt border, and sometimes virus‐infected cells were demonstrated in or near the Lieberkühn's crypts. EVD virus was also demonstrated in macrophages in the intestinal lamina propria and in phagocytes in regional lymph nodes. ZUSAMMENFASSUNG: Lichtmikroskopische und ultrahistologische intestinale Veränderungen bei Ferkeln nach Infektion mit dem Epizootischen Diarrhoe‐Virus (EVD): Vergleich mit Übertragbaren Gastroenteritis (TGE) Virus‐ und Schweinerotavirusinfektionen Lichtmikroskopische und ultrahistologische Veränderungen von Därmen natürlich und experimentell mit dem Virus der Epizootischen Virusdiarrhoe (EVD) infizierten Ferkeln wurden untersucht und mit denen nach Infektion mit TGE‐Virus und Rotavirus verglichen. Der Verlauf der EVD‐Virusinfektion ist vergleichbar mit dem der TGE. Eine Zottenatrophie tritt ähnlich wie bei der TGE im gesamten Jejunum und Ileum auf. In dieser Beziehung unterscheiden sich die Befunde von der Rotavirusinfektion. Die ultrastrukturellen Darmveränderungen bei der EVD‐Virusinfektion entsprechen denen der TGE und anderen enteropathogenen Coronaviren. Virusvermehrung war jedoch hauptsächlich auf die laterale Epithelschicht der Zotten begrenzt. Sie reichte bis in den Zotten/Krypten‐Bereich. In einigen Fällen ließen sich infizierte Zellen in oder nahe den Lieberkühnschen Krypten nachweisen. EVD‐Viruspartikel wurden weiterhin in Makrophagen der Lamina propria und in Phagozyten der regionalen Lymphknoten gefunden. RÉSUMÉ: Lésions intestinales au microscope optique et ultrahistologiques chez des porcelets après une infection avec le virus diarrhéique épizootique (EVD): Comparaison avec le virus de la gastro‐entérite transmissible (TGE) et des infections à Rotavirus chez des porcs On a examiné les lésions intestinales ultrahistologiquement et au microscope optique chez des porcelets infectés naturellement et expérimentalement avec le virus épizootique de la diarrhée (EVD). On a comparé cette infection avec celle du virus TGE et Rotavirus. Le déroulement de l'infection au virus EVD est comparable à celui de TGE. Une atrophie des villosités dans tout le jejunum et l'ileum est constatée comme avec TGE. Les résultats trouvés avec une infection à Rotavirus se différencient sur ce point. Les lésions intestinales ultrastructurelles lors d'une infection avec le virus EVD correspondent à celles rencontrées avec TGE et d'autres virus Corona. La multiplication du virus fut cependant principalement localisée à la couche épithéliale latérale des villosités. Elle atteignit la région des villosités/cryptes. Des cellules infectées ont été mises en évidence dans quelques cas dans ou près des cryptes de Lieberkühn. On a trouvé des particules virales EVD dans des macrophages de Lamina propria et dans des phagocytes des ganglions régionaux. RESUMEN: Fotomicroscopía e ultrahistología de las modificaciones intestinales en lechones infectados con el virus de la diarrea virósica epizoótica (DVE): Comparación con el virus de la gastroenteritis transmisible (GET) e infecciones con el virus rota porcino Se examinaron las modificaciones fotomicroscópicas y ultrahistológicas en los intestinos de lechones infectados de forma natural y experimental con el virus de la diarrea virósica epizoótica (DVE), comparándose con las habidas tras la infección con el virus GET y el virus rota porcino. El curso de la infección con el virus de la DVE se puede comparar con el de la GET. La atrofia de villosidades aparece, tal y como en la GET, en la totalidad del yeyuno y del íleon. A este respecto se diferencian los hallazgos de la infección con el virus rota. Las modificaciones entéricas ultraestructurales en la infección con el virus de la DVE corresponden a los de la GET y otros virus corona enteropatógenos. Sin embargo, la multiplicación de virus se hallaba limitada sobre todo a la capa epitelial lateral de las villosidades. La misma alcanzaba hasta el ámbito de las villosidades/criptas. En algunos casos se pudieron identificar células infectadas en las criptas de Lieberkühn o cerca de las mismas. Partículas virales DVE se hallaron además en los macrófagos de la lámina propia y en los fagocitos de los ganglios regionales.


Alzheimer's Disease Research Enterprise in the Era of COVID‐19/SARS‐CoV‐2


title: Clinical Features of Patients with Coronavirus Disease 2019 (COVID‐19) from a Designated Hospital in Beijing, China

text: Clinical and laboratory data available on patients with coronavirus disease 2019 (COVID‐19) in Beijing, China remain extremely limited. Here, we summarized the clinical characteristics of patients with COVID‐19 in a designated hospital in Beijing, China. 55 patients with laboratory‐confirmed SARS‐CoV‐2 infection were admitted to Beijing 302 Hospital and enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. 15 (27.3%) of the patients had non‐severe symptom, the mean age was 44.0 years (interquartile range 34.0‐56.0), and median incubation period was 7.5 days (interquartile range 5.0‐11.8). 26 (47.3%) patients had exposure history in Wuhan while 20 (36.4%) were associated with familial clusters. 18 (32.7%) had underlying comorbidities including hypertension. The most common symptoms of illness were fever (45, 81.8%), 51 (92.7%) patients had abnormal findings on chest CT. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with poor prognosis. 26 patients (47.3%) were still hospitalized while 29 (52.7%) had been discharged at this point. Compared with patients in Wuhan, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with severe condition. On the basis of antiviral drugs, antibiotics treatment, appropriate dosage of corticosteroid and gamma globulin therapy significantly improve patients’ outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID‐19. This article is protected by copyright. All rights reserved.


title: Microbial sequencing to improve individual and population health

text: Recent advances in sequencing technologies are changing the face of infectious disease investigation and control. Personalized anti-infective therapies and surveillance of emergent pathogen outbreaks are just two examples of the potential benefits of merging the fields of genomics and infectious diseases.


title: 5-Ene-4-thiazolidinones – An efficient tool in medicinal chemistry

text: The presented review is an attempt to summarize a huge volume of data on 5-ene-4-thiazolidinones being a widely studied class of small molecules used in modern organic and medicinal chemistry. The manuscript covers approaches to the synthesis of 5-ene-4-thiazolidinone derivatives: modification of the C5 position of the basic core; synthesis of the target compounds in the one-pot or multistage reactions or transformation of other related heterocycles. The most prominent pharmacological profiles of 5-ene derivatives of different 4-thiazolidinone subtypes belonging to hit-, lead-compounds, drug-candidates and drugs as well as the most studied targets have been discussed. Currently target compounds (especially 5-en-rhodanines) are assigned as frequent hitters or pan-assay interference compounds (PAINS) within high-throughput screening campaigns. Nevertheless, the crucial impact of the presence/nature of C5 substituent (namely 5-ene) on the pharmacological effects of 5-ene-4-thiazolidinones was confirmed by the numerous listed findings from the original articles. The main directions for active 5-ene-4-thiazolidinones optimization have been shown: i) complication of the fragment in the C5 position; ii) introduction of the substituents in the N3 position (especially fragments with carboxylic group or its derivatives); iii) annealing in complex heterocyclic systems; iv) combination with other pharmacologically attractive fragments within hybrid pharmacophore approach. Moreover, the utilization of 5-ene-4-thiazolidinones in the synthesis of complex compounds with potent pharmacological application is described. The chemical transformations cover mainly the reactions which involve the exocyclic double bond in C5 position of the main core and correspond to the abovementioned direction of the 5-ene-4-thiazolidinone modification.


title: Detection of influenza C virus by a real‐time RT‐PCR assay

text: BACKGROUND: Influenza C virus can cause both upper and lower respiratory tract infections and has been reported to be prevalent in children. However, these infections have been under‐diagnosed, and epidemiological data available are limited due to the lack of convenient detection assays. OBJECTIVE: Design and validate a real‐time reverse‐transcriptase PCR (rt RT‐PCR) assay for the detection of influenza C. STUDY DESIGN: Respiratory samples from two primary settings, namely, children who were hospitalized or seen in the emergency department, and respiratory outbreaks for which no other viral etiology was found were used for the detection of influenza C. RESULTS AND CONCLUSIONS: The assay was sensitive and specific for the detection of influenza C. Eleven of 474 (2·32%) patients, all less than 10 years of age, were positive for influenza C. The strains clustered into two lineages, namely C/Kanagawa and C/Sao Paulo, based upon sequencing of the hemagglutinin‐esterase gene. Epidemiological data showed that a higher proportion of influenza C infections occur in younger children and during the winter months. This is the first report of the detection of influenza C in Alberta, Canada, and suggests that the detection of this virus should be included in respiratory virus testing panels.


COVID‐19 and Autism Research: Perspectives from Around the Globe