title: A gland-sparing, intraoral sialolithotomy approach for hilar and intraparenchymal multiple stones in the submandibular gland

text: Multiple intraglandular sialolithiasis for stones deep in the glandular parenchyma may require submandibulectomies, especially if sialendoscopic facilities are unavailable. We describe a gland-sparing intraoral sialolithotomy approach for both hilar and intraparenchymal multiple sialoliths. Nine patients with obstructive sialadenitis resulting from multiple sialoliths in both the deep hilar region and the submandibular gland parenchyma were selected for this study. Ultrasonography and computer tomography (CT) scans were performed to determine the location, number and sizes of the calculi and the distance between hilar and intraparenchymal sialoliths. All sialoliths were removed via gland-sparing, intraoral sialolithotomy. In all, 27 stones were found in the 9 patients. The hilar and deeper sialoliths were 4.5–11 and 0.8–4.5 mm, respectively, in diameter. The largest distance between the hilar and intraparenchymal sialoliths was 28.3 mm. Sialoliths in the hilar region were excised through an intraoral incision before deeper intraparenchymal stones were eased out of the same incision site. Postoperative follow-up imaging verified complete sialolith removal. Therefore, submandibular gland multiple sialoliths in the hilum and parenchyma can be successfully removed via an intraoral sialolithotomy under general anesthesia, thereby preserving the gland and restoring its secretory function.


title: Enhancing ‘Whole-of-Government’ Response to Biological Events in Korea: Able Response 2014

text: Since 2011, the Republic of Korea (ROK) and United States (U.S.) have been collaborating to conduct inter- and intra-governmental exercises to jointly respond to biological events in Korea. These exercises highlight U.S. interest in increasing its global biosurveillance capability and the ROK’s interest in improving cooperation among ministries to respond to crises. With Able Response (AR) exercises, the ROK and U.S. have improved coordination among US and ROK government and defense agencies responding to potential bio-threats and identified additional areas on which to apply refinements in policies and practices. In 2014, the AR exercise employed a Biosurveillance Portal (BSP) to facilitate more effective communication among participating agencies and countries including Australia. In the present paper, we seek to provide a comprehensive assessment of the AR 2014 (AR14) exercise and make recommendations for future improvements. Incorporating a more realistic response in future scenarios by integrating a tactical response episode in the exercise is recommended.


title: Reply to Letter to the Editor: COVID‐19‐Related Liver Injury and Clinical Outcomes: Does It Really Exist?

text: We appreciate Philips and colleagues’ interest in our report on the associations between liver injury markers and coronavirus 2019 (COVID‐19) mortality.((1)) They raised the question regarding the application of liver injury markers. However, several of their interpretations of our results are misleading or incorrect. We understand that use of aspartate aminotransferase (AST) in isolation cannot comprehensively characterize liver injury.


title: Cardiovascular disease in COVID-19: a systematic review and meta-analysis of 10,898 patients and proposal of a triage risk stratification tool

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has drastically affected global health. Despite several studies, there is yet a dearth of data regarding the mechanisms of cardiac injury, clinical presentation, risk factors, and treatment of COVID-19-associated cardiovascular disease. This systematic review and meta-analysis is aimed at defining the clinical, electrocardiographic, and pathologic spectrum of cardiovascular disease (CVD), frequency of elevated cardiac and inflammatory biomarkers, and their frequency and relationship with severity of the disease and mortality in COVID-19 patients and to develop a triage risk stratification tool (TRST) that can serve as a guide for the timely recognition of the high-risk patients and mechanism-targeted therapy. We conducted an online search in databases of PubMed and Embase to identify relevant studies. Data selection was in concordance with PRISMA guidelines. Results were presented as pooled frequencies, odds ratio, standardized mean difference (SMD), and forest and funnel plots. RESULTS: We gathered a total of 54 studies and included 35 of them in our meta-analysis. Acute cardiac injury occurred in more than 25% of cases, mortality was 20 times higher, and admission to intensive care unit increased by 13.5 times. Hypertension was the most common pre-existing comorbidity with a frequency of 29.2%, followed by diabetes mellitus (13.5%). The deceased group of patients had higher cardiac and inflammatory biomarkers, with statistically significant SMD, compared with survivors. Pediatric patients were predominantly mildly affected. However, less frequently, the presentation was very similar to Kawasaki disease or Kawasaki shock syndrome. This latter presentation hass been called as multisystem inflammatory syndrome in children (MIS-C). CONCLUSIONS: There is a wide spectrum of cardiac involvement in COVID-19 patients, and hence a Triage Risk Stratification Tool can serve as a guide for the timely recognition of the high-risk patients and mechanism-targeted therapy.


title: Using Time-Structured Data to Estimate Evolutionary Rates of Double-Stranded DNA Viruses

text: Double-stranded (ds) DNA viruses are often described as evolving through long-term codivergent associations with their hosts, a pattern that is expected to be associated with low rates of nucleotide substitution. However, the hypothesis of codivergence between dsDNA viruses and their hosts has rarely been rigorously tested, even though the vast majority of nucleotide substitution rate estimates for dsDNA viruses are based upon this assumption. It is therefore important to estimate the evolutionary rates of dsDNA viruses independent of the assumption of host-virus codivergence. Here, we explore the use of temporally structured sequence data within a Bayesian framework to estimate the evolutionary rates for seven human dsDNA viruses, including variola virus (VARV) (the causative agent of smallpox) and herpes simplex virus-1. Our analyses reveal that although the VARV genome is likely to evolve at a rate of approximately 1 × 10(−5) substitutions/site/year and hence approaching that of many RNA viruses, the evolutionary rates of many other dsDNA viruses remain problematic to estimate. Synthetic data sets were constructed to inform our interpretation of the substitution rates estimated for these dsDNA viruses and the analysis of these demonstrated that given a sequence data set of appropriate length and sampling depth, it is possible to use time-structured analyses to estimate the substitution rates of many dsDNA viruses independently from the assumption of host-virus codivergence. Finally, the discovery that some dsDNA viruses may evolve at rates approaching those of RNA viruses has important implications for our understanding of the long-term evolutionary history and emergence potential of this major group of viruses.


title: Molecular epidemiology and disease severity of respiratory syncytial virus in relation to other potential pathogens in children hospitalized with acute respiratory infection in Jordan

text: Human respiratory syncytial virus (HRSV) is the major viral cause of acute lower respiratory tract infections in children. Few data about the molecular epidemiology of respiratory syncytial virus in developing countries, such as Jordan, are available. The frequency and severity of infections caused by HRSV were assessed in hospitalized Jordanian children <5 years of age compared with other potential etiological agents. Overall a potential pathogen was detected in 78% (254/326) of the children. HRSV was detected in 43% (140/326) of the nasopharyngeal aspirates. HRSV was found more frequently during the winter (January/February), being less frequent or negligible by spring (March/April). Analysis of 135 HRSV‐positive strains using restriction fragment length polymorphism showed that 94 (70%) belonged to subgroup A, and 41 (30%) to subgroup B. There were also two cases of mixed genotypic infection. Only four of the six previously described N genotypes were detected with NP4 predominating. There were no associations between subgroup or N‐genogroup and disease severity. HRSV was significantly associated with more severe acute respiratory infection and the median age of children with HRSV was lower than for those without. Next in order of frequency were adenovirus (116/312: 37%), human bocavirus (57/312: 18%), rhinovirus (36/325: 11%), Chlamydia spp. (14/312: 4.5%), human metapneumovirus (8/326: 2.5%), human coronavirus NL63 (4/325: 1.2%), and influenza A virus (2/323: 0.6%). Influenza B; parainfluenza viruses 1–4, human coronavirus HKU1 and Mycoplasma pneumoniae were not detected. J. Med. Virol. 80:168–174, 2008. © 2007 Wiley‐Liss, Inc.


Correction to Lancet Psychiatry 2020; 7: e15–16


title: Infectious diarrhea

text: Abstract Infectious diarrhea is an extremely common illness that affects millions of Americans annually. For most patients, the illness is a self-limited one. Its major risk is dehydration. However, for some patients, diarrhea can lead to severe dehydration or be associated with bacteremia and metastatic infection. Patients with these conditions require prompt treatment. A large number of organisms have been associated with diarrhea in humans, and most laboratories routinely screen for Salmonella, Shigella, and Campylobacter. Other bacteria, parasites, and viruses account for a significant percentage of diarrhea cases and frequently go undetected. This article summarizes many of these pathogens and describes the settings in which they can be acquired. Food distribution networks have made the delivery of previously rare foods to remote areas a commonplace occurrence; this has also led to new challenges in the diagnosis and prevention of food-borne illnesses. Outbreaks of diarrhea now frequently extend across many states. The identification of a rare strain of a bacterial pathogen or changes in the isolation rate of common pathogens may be early clues to the cause of such an ongoing outbreak. Most enteric pathogens cause disease by either stimulating the secretion of fluids at the level of the small bowel or by irritating and invading the colon. Organisms that cause disease by the latter mechanism have the potential to invade the blood stream and spread to other parts of the body, including the bones and the central nervous system. Several organisms have been associated with specific postinfectious syndromes that are responsible for additional morbidity and mortality. The antibiotic resistance of bacterial pathogens has been increasing, and this has a limiting effect on the empiric treatment choices available for suspected bacterial diarrhea. Careful attention to local sensitivity patterns and appropriate testing of the patient's isolate are among the important factors that lead to successful treatment decisions.


title: Antiviral Immune Responses of Bats: A Review

text: Despite being the second most species‐rich and abundant group of mammals, bats are also among the least studied, with a particular paucity of information in the area of bat immunology. Although bats have a long history of association with rabies, the emergence and re‐emergence of a number of viruses from bats that impact human and animal health has resulted in a resurgence of interest in bat immunology. Understanding how bats coexist with viruses in the absence of disease is essential if we are to begin to develop therapeutics to target viruses in humans and susceptible livestock and companion animals. Here, we review the current status of knowledge in the field of bat antiviral immunology including both adaptive and innate mechanisms of immune defence and highlight the need for further investigations in this area. Because data in this field are so limited, our discussion is based on both scientific discoveries and theoretical predictions. It is hoped that by provoking original, speculative or even controversial ideas or theories, this review may stimulate further research in this important field. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Although bats appear to share most features of the immune system with other mammals, several studies have reported qualitative and quantitative differences in the immune responses of bats. These observations warrant further investigation to determine whether such differences are associated with the asymptomatic nature of viral infections in bats.


title: Slicing and dicing viruses: antiviral RNA interference in mammals

text: To protect against the harmful consequences of viral infections, organisms are equipped with sophisticated antiviral mechanisms, including cell‐intrinsic means to restrict viral replication and propagation. Plant and invertebrate cells utilise mostly RNA interference (RNAi), an RNA‐based mechanism, for cell‐intrinsic immunity to viruses while vertebrates rely on the protein‐based interferon (IFN)‐driven innate immune system for the same purpose. The RNAi machinery is conserved in vertebrate cells, yet whether antiviral RNAi is still active in mammals and functionally relevant to mammalian antiviral defence is intensely debated. Here, we discuss cellular and viral factors that impact on antiviral RNAi and the contexts in which this system might be at play in mammalian resistance to viral infection.


title: Indomethacin and resveratrol as potential treatment adjuncts for SARS‐CoV‐2/COVID‐19

text: The ongoing pandemic due to severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2, also known as COVID‐19) has led to unprecedented challenges for the global healthcare system. This novel coronavirus disease phenotype ranges from asymptomatic carriage to fulminant cytokine storm with respiratory failure, polyorgan dysfunction, and death. Severe disease is characterized by exuberant inflammation resulting from high circulating cytokines such as interleukin‐6 (IL‐6) and tumor necrosis factor (TNF). These inflammatory mediators are responsible for the detrimental effects on the immune, hematologic, respiratory, renal, gastrointestinal and other body systems. In addition to inhibition of viral replication, blunting this inflammatory response before overt cytokine storm is important to improve outcomes. Although there are upcoming promising agents such as remdesivir and convalescent plasma, inexpensive, safe, and widely available adjunct treatments to ameliorate disease burden would be welcome. Two potential antiinflammatory agents include indomethacin, which has been shown in experimental models to decrease canine coronavirus (CCoV) levels in dogs and exhibit antiviral activity against several other viruses, and the polyphenol, resveratrol, a potent antioxidant that has shown antiviral activity against several viruses.


title: Guidelines for the Antibiotic Use in Adults with Acute Upper Respiratory Tract Infections

text: These guidelines were developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. These guidelines mainly cover the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.


title: Antiviral Effect of Lithium Chloride and Diammonium Glycyrrhizinate on Porcine Deltacoronavirus In Vitro

text: Porcine deltacoronavirus (PDCoV) is an emerging global swine virus that has a propensity for interspecies transmission. It was identified in Hong Kong in 2012. Given that neither specific antiviral drugs nor vaccines are available for newly emerging porcine deltacoronavirus, searching for effective antiviral drugs is a high priority. In this study, lithium chloride (LiCl) and diammonium glycyrrhizinate (DG), which are host-acting antivirals (HAAs), were tested against PDCoV. We found that LiCl and DG inhibited PDCoV replication in LLC-PK1 cells in a dose-dependent manner. The antiviral effects of LiCl and DG occurred at the early stage of PDCoV replication, and DG also inhibited virus attachment to the cells. Moreover, both drugs inhibited PDCoV-induced apoptosis in LLC-PK1 cells. This study suggests LiCl and DG as new drugs for the treatment of PDCoV infection.


Venous thromboembolism and heparin use in COVID-19 patients: juggling between pragmatic choices, suggestions of medical societies


title: Peri-operative and critical care concerns in coronavirus pandemic

text: World Health Organization (WHO) declared novel coronavirus outbreak a “pandemic” on March 11(th), 2020. India has already reached Stage 2 (local transmission) and the Indian Government, in collaboration with the Indian Council of Medical Research (ICMR), is taking all necessary steps to halt the community transmission(Stage 3). Anaesthesiologists and intensivists around the globe are making untiring efforts akin to soldiers at the final frontier during war. All efforts pertaining to adequate staffing, Personal Protective Equipment (PPE) and strict adherence to hand hygiene measures are being stressed upon to prevent in-hospital transmission. In this article, all outbreak response measures including triaging, preparation of isolation rooms, decontamination and disinfection protocols as well as fundamental principles of critical care and anaesthetic management in Covid-19 cases is being discussed. All the recommendations have been derived from the past experiences of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) outbreak as well as upcoming guidelines from the international health fraternity and Indian Health Services.


title: A Retrospective Study Investigating Risks of Acute Respiratory Distress Syndrome and Mortality Following Human Metapneumovirus Infection in Hospitalized Adults

text: BACKGROUND: Human metapneumovirus (hMPV) is a relatively recently identified respiratory virus that induces respiratory symptoms similar to those of respiratory syncytial virus infection in children. The characteristics of hMPV-infected adults are unclear because few cases have been reported. METHODS: We conducted a retrospective review of hospitalized adult patients with a positive multiplex real-time polymerase chain reaction assay result from 2012 to 2016 at a single tertiary referral hospital in South Korea. We analyzed clinical characteristics of the enrolled patients and divided patients into an acute respiratory distress syndrome (ARDS) group and a non-ARDS group. RESULTS: In total, 110 adults were reviewed in this study. Their mean age was 61.4 years, and the majority (n = 105, 95.5%) had comorbidities or were immunocompromised. Most of the patients had pneumonia on chest X-ray (n = 88, 93.6%), 22 (20.0%) had ARDS, and 12 (10.9%) expired during hospitalization. The mortality rate for patients with ARDS was higher than that of the other patients (36.4% vs. 5.7%, P = 0.001). The risk factor for hMPV-associated ARDS was heart failure (odds ratio, 5.24; P = 0.044) and laboratory values were increased blood urea nitrogen and increased C-reactive protein. The acquisition site of infection was divided into community vs. nosocomial; 43 patients (39.1%) had a nosocomial infection. The risk factors for nosocomial infection were an immunocompromised state, malignancy and immunosuppressive treatment. CONCLUSIONS: These data suggest that hMPV is one of the important respiratory pathogens important respiratory pathogen that causes pneumonia/ARDS in elderly, immunocompromised individuals and that it may be transmitted via the nosocomial route.


title: Evaluation of Border Entry Screening for Infectious Diseases in Humans

text: In response to the severe acute respiratory syndrome (SARS) pandemic of 2003 and the influenza pandemic of 2009, many countries instituted border measures as a means of stopping or slowing the spread of disease. The measures, usually consisting of a combination of border entry/exit screening, quarantine, isolation, and communications, were resource intensive, and modeling and observational studies indicate that border screening is not effective at detecting infectious persons. Moreover, border screening has high opportunity costs, financially and in terms of the use of scarce public health staff resources during a time of high need. We discuss the border-screening experiences with SARS and influenza and propose an approach to decision-making for future pandemics. We conclude that outbreak-associated communications for travelers at border entry points, together with effective communication with clinicians and more effective disease control measures in the community, may be a more effective approach to the international control of communicable diseases.


title: Barriers to implementing infection prevention and control guidelines during crises: Experiences of health care professionals

text: BACKGROUND: Communicable disease crises can endanger the health care system and often require special guidelines. Understanding reasons for nonadherence to crisis guidelines is needed to improve crisis management. We identified and measured barriers and conditions for optimal adherence as perceived by 4 categories of health care professionals. METHODS: In-depth interviews were performed (n = 26) to develop a questionnaire for a cross-sectional survey of microbiologists (100% response), infection preventionists (74% response), public health physicians (96% response), and public health nurses (82% response). The groups were asked to appraise barriers encountered during 4 outbreaks (severe acute respiratory syndrome [SARS], Clostridium difficile ribotype 027, rubella, and avian influenza) according to a 5-point Likert scale. When at least 33% of the participants responded “strongly agree,” “agree,” or “rather agree than disagree,” a barrier was defined as “often experienced.” The common (“generic”) barriers were included in a univariate and multivariate model. Barriers specific to the various groups were studied as well. RESULTS: Crisis guidelines were found to have 4 generic barriers to adherence: (1) lack of imperative or precise wording, (2) lack of easily identifiable instructions specific to each profession, (3) lack of concrete performance targets, and (4) lack of timely and adequate guidance on personal protective equipment and other safety measures. The cross-sectional study also yielded profession-specific sets of often-experienced barriers. CONCLUSION: To improve adherence to crisis guidelines, the generic barriers should be addressed when developing guidelines, irrespective of the infectious agent. Profession-specific barriers require profession-specific strategies to change attitudes, ensure organizational facilities, and provide an adequate setting for crisis management.


title: The COVID-19 pandemic and the human rights of persons with mental and cognitive impairments subject to coercive powers in Australia

text: The purpose of this paper is to explore the effect of the COVID-19 pandemic on the human rights of persons with mental and cognitive impairments subject to coercive powers in Australia. It sets out the relevant human rights in the Convention on the Rights of Persons with Disabilities which have been engaged by the COVID-19 pandemic and the government's response to it. It examines the effect of emergency legislation on the relaxation of human rights safeguards in mental health laws, with a focus on mental health tribunals (although it is limited by a lack of published decisions and gaps in publicly available information). However, some of the issues created for persons with disabilities during the COVID-19 pandemic are evident in some decisions published by the New South Wales Guardianship Tribunal. The paper critically analyses two guardianship decisions UZX [2020] NSWCATGD 3 (3 April, 2020) and GZK [2020] NSWCATGD 5 (23 April, 2020) and some emergency South Australian legislation COVID-19 Emergency Response Act, 2020 (SA) Schedule 1 to demonstrate the ways in which the human rights of persons with mental and cognitive impairments can be more at risk than those of the general population, even when the general population is itself in “lockdown.”


title: Acute human bocavirus 1 infection in child with life-threatening bilateral bronchiolitis and right-sided pneumonia: a case report

text: BACKGROUND: Human bocavirus 1 is a commonly detected human parvovirus. Many studies have shown human bocavirus 1 as a pathogen in association with acute respiratory tract infections in children. However, because human bocavirus 1 persists in the upper airways for extensive time periods after acute infection, the definition and diagnostics of acute human bocavirus 1 infection is challenging. Until now, detection of human bocavirus 1 exclusively, high viral load in respiratory samples, and viremia have been associated with a clinical picture of acute respiratory illness. There are no studies showing detection of human bocavirus 1 messenger ribonucleic acid in the peripheral blood mononuclear cells as a diagnostic marker for acute lower respiratory tract infection. CASE PRESENTATION: We report the case of a 17-month-old Latvian boy who presented in intensive care unit with acute bilateral bronchiolitis, with a history of rhinorrhea and cough for 6 days and fever for the last 2 days prior to admission, followed by severe respiratory distress and tracheal intubation. Human bocavirus 1 was the only respiratory virus detected by a qualitative multiplex polymerase chain reaction panel. For the diagnosis of acute human bocavirus 1 infection, both molecular and serological approaches were used. Human bocavirus 1 deoxyribonucleic acid (DNA) was detected simultaneously in nasopharyngeal aspirate, stool, and blood, as well as in the corresponding cell-free blood plasma by qualitative and quantitative polymerase chain reaction, revealing high DNA-copy numbers in nasopharyngeal aspirate and stool. Despite a low-load viremia, human bocavirus 1 messenger ribonucleic acid was found in the peripheral blood mononuclear cells. For detection of human bocavirus 1-specific antibodies, non-competitive immunoglobulin M and competitive immunoglobulin G enzyme immunoassays were used. The plasma was positive for both human bocavirus 1-specific immunoglobulin M and immunoglobulin G antibodies. CONCLUSIONS: The presence of human bocavirus 1 genomic DNA in blood plasma and human bocavirus 1 messenger ribonucleic acid in peripheral blood mononuclear cells together with human bocavirus 1-specific immunoglobulin M are markers of acute human bocavirus 1 infection that may cause life-threatening acute bronchiolitis.


title: Effect of Information Disclosure Policy on Control of Infectious Disease: MERS-CoV Outbreak in South Korea

text: This study examined the effect of disclosing a list of hospitals with Middle East respiratory syndrome coronavirus (MERS-CoV) patients on the number of laboratory-confirmed MERS-CoV cases in South Korea. MERS-CoV data from 20 May 2015 to 5 July 2015 were from the Korean Ministry of Health & Welfare website and analyzed using segmented linear autoregressive error models for interrupted time series. This study showed that the number of laboratory-confirmed cases was increased by 9.632 on 5 June (p < 0.001). However, this number was significantly decreased following disclosure of a list of hospitals with MERS-CoV cases (Estimate = −0.699; p < 0.001). Disclosing the list of hospitals exposed to MERS-CoV was critical to the prevention of further infection. It reduced the number of confirmed MERS-CoV cases. Thus, providing accurate and timely information is a key to critical care response.


title: First detection and genetic characterization of canine Kobuvirus in domestic dogs in Thailand

text: BACKGROUND: Canine Kobuvirus (CaKoV) has been detected both in healthy and diarrheic dogs and in asymptomatic wild carnivores. In this study, we conducted a survey of CaKoV at small animal hospitals in Bangkok and vicinity of Thailand during September 2016 to September 2018. RESULTS: Three hundred and seven rectal swab samples were collected from healthy dogs (n = 55) and dogs with gastroenteritis symptoms (n = 252). Of 307 swab samples tested by using one-step RT-PCR specific to 3D gene, we found CaKoV positivity at 17.59% (54/307). CaKoVs could be detected in both sick (19.44%) and healthy (9.09%) animals. In relation to age group, CaKoV could be frequently detected in younger dogs (25.45%). Our result showed no seasonal pattern of CaKoV infection in domestic dogs. In this study, we characterized CaKoVs by whole genome sequencing (n = 4) or 3D and VP1 gene sequencing (n = 8). Genetic and phylogenetic analyses showed that whole genomes of Thai CaKoVs were closely related to Chinese CaKoVs with highest 99.5% amino acid identity suggesting possible origin of CaKoVs in Thailand. CONCLUSIONS: In conclusion, this study was the first to report the detection and genetic characteristics of CaKoVs in domestic dogs in Thailand. CaKoVs could be detected in both sick and healthy dogs. The virus is frequently detected in younger dogs. Thai CaKoVs were genetically closely related and grouped with Chinese CaKoVs. Our result raises the concerns to vet practitioners that diarrhea in dogs due to canine Kobuvirus infection should not be ignored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1994-6) contains supplementary material, which is available to authorized users.


title: One Health in Mongolia

text: The Asia Pacific Strategy for Emerging Diseases (APSED) requires collaboration, consensus, and partnership across all the different actors and sectors involved in different aspects of emerging disease. Guided by APSED, Mongolia has established a functional coordination mechanism between the animal and human health sectors. Surveillance, information exchange and risk assessment, risk reduction, and coordinated response capacity and collaborative research have been identified as the four pillars of the zoonoses framework. Intersectoral collaboration has been clearly shown to be a crucial tool in the prevention and control of emerging zoonotic diseases. A “One Health” strategy has been implemented under the concept of ‘Healthy animal-Healthy food-Healthy people’. An intersectoral coordination mechanism established between the veterinary and public health sectors has expanded its function to incorporate more work on food safety, emergency management, and effects of climate change on zoonotic diseases. Its membership includes the human health sector, the veterinary sector, the national emergency management agency, the environment sector, emergency management and inspection authorities, and the World Health Organization (WHO). The main outputs of the coordination mechanism have been strengthened surveillance and response activities and laboratory capacities. The coordination mechanism has also strengthened the surveillance and response capacity of neglected zoonotic diseases, such as brucellosis, anthrax, and tick-borne diseases. Through regular meetings and brainstorming sessions, both sectors have developed joint operational plans, a long-term risk reduction plan 2011–2015, initiated a prioritization exercise and risk assessment for 29 zoonotic diseases, and reviewed and revised standards, procedures, and communication strategies. In 2011, a list of experts on major zoonoses were identified from different sectors and formed into a taskforce to identify the focal points for rabies, brucellosis, and vector-borne diseases. As a result, disease control strategies are now linked to scientific research and epidemiological expertise.


title: Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China

text: IMPORTANCE: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. OBJECTIVE: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. EXPOSURES: Documented SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. RESULTS: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4(+) T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4(+) T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). CONCLUSIONS AND RELEVANCE: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4(+) T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.


COVID 19 et cancer : quelles sont les conséquences de la réorganisation des soins oncologiques?


title: COVID19-Tracker: una aplicación web para visualización de datos de la epidemia de SARS-CoV-2 en España

text: ABSTRACT Data visualization is an important tool for exploring and communicating findings in medical research, and specially in epidemiological surveillance. The COVID19-Tracker web application systematically produces daily updated data visualization and analysis of SARS-CoV-2 epidemic in Spain. It collects automatically daily data on COVID-19 diagnosed cases and mortality, from February 24th, 2020 onwards. Three applications have already been developed: 1) to analyze data trends and estimating short-term projections; 2) to estimate the case fatality rate; and 3) to assess the effect of the lockdowns on the data trends. The application may help for a better understanding of the SARS-CoV-2 epidemic data in Spain.


title: COVID 19 Pandemic: Mental health challenges of Internal migrant workers of India

text: COVID- 19, a biomedical disease has serious physical and tremendous mental health implications as the rapidly spreading pandemic. One of the most vulnerable, but neglected, an occupational community of internal migrant workers is prone for development of psychological ill-effects due to double whammy impact of COVID-19 crisis and concomitant adverse occupational scenario. Permutations and combinations of the factors viz susceptibility for new viral infections, potential to act as vectors of transmission of infection, high prevalence of pre-existing physical health morbidities such as occupational pneumoconiosis, tuberculosis, HIV infections, pre-existing psychological morbidities, adverse psychosocial factors like absence of family support and caretaker during the crisis, their limitations to follow the rules and regulations of personal safety during the crisis, social exclusion, and inability to timely access the psychiatric services; all give rise to the peri-traumatic psychological distress to internal migrant workers. Superadded, is the blow of financial constraints due to loss of work, absence or suspension of occupational safety and health-related basic laws and associated occupational hazards, which makes this occupational group highly vulnerable for the development of psychological illnesses. We attempt to draw the attention of mental health professionals, general medical practitioners and occupational health policymakers to the various, interrelated and interdependent predisposing and causative factors for the development of psychological ill-effects amongst internal migrant workers with the interventions needed to address it, from an occupational health perspective angle


NMR assignment of the protein nsp3a from SARS-CoV


title: A polycarbonate based surface plasmon resonance sensing cartridge for high sensitivity HBV loop-mediated isothermal amplification

text: Abstract In this study, we report a simple, low-cost surface plasmon resonance (SPR)-sensing cartridge based on a loop-mediated isothermal amplification (LAMP) method for the on-site detection of the hepatitis B virus (HBV). For LAMP detection, a SPR based LAMP sensing system (SPRLAMP) was constructed, including a novel SPRLAMP sensing cartridge integrating a polymethyl methacrylate (PMMA) micro-reactor with a polycarbonate (PC)-based prism coated with a 50nm Au film. First, we found that the change of refractive index of the bulk solution was approximately 0.0011 refractive index (RI) units after LAMP reaction. The PC-based prism's linearity and thermal responses were compared to those of a traditional glass prism to show that a PC-based prism can be used for SPR measurement. Finally, the HBV template mixed in the 10μl LAMP solution could be detected by SPRLAMP system in 17min even at the detection-limited concentration of 2fg/ml. We also analyzed the correlation coefficients between the initial concentrations of HBV DNA templates and the system response (ΔRU) at varying amplification times to establish an optimal amplification time endpoint of 25min (R 2 =0.98). In conclusion, the LAMP reaction could be detected with the SPRLAMP sensing cartridge based on direct sensing of the bulk refractive index.


title: Diarreas agudas del niño

text: La diarrea aguda es siempre potencialmente grave en el niño, aunque las variaciones de los cuadros clínicos son importantes. Existen numerosas recomendaciones, pero no se pueden definir indicaciones terapéuticas aplicables a todos los casos. El examen clínico y la evaluación de la deshidratación resultan cruciales. Las soluciones de rehidratación por vía oral se utilizan sistemáticamente en el niño pequeño. El tratamiento antibiótico se reserva para ciertas etiologías. Los medicamentos antidiarreicos son útiles, siempre como complemento de la rehidratación por vía oral. La realimentación precoz es sistemática. El proceso diarreico puede durar varios días, como por ejemplo en el caso de una infección por rotavirus, la causa más frecuente de diarrea. Ante una diarrea persistente debe investigarse el riesgo de paso a la cronicidad, causa de desnutrición que es necesario saber prevenir.


title: SDRA par pneumonie à EBV

text: Résumé Introduction Chez l’adulte immunocompétent, l’Epstein Barr (EBV) entraîne une maladie autolimitée spontanément résolutive. Observation Un syndrome de détresse respiratoire aigu (SDRA) compliquant une pneumonie grave à EBV est rapporté avec le recours à une ventilation artificielle prolongée. Le diagnostic était confirmé par l’usage des sérologies spécifiques et la recherche de la charge d’ADN virale par PCR. À part la stratégie protectrice de la ventilation mécanique, le traitement médical a compris l’utilisation de l’Acyclovir et les immunoglobulines polyclonales dans la phase précoce ainsi que des corticoïdes systémiques dans la phase tardive. La guérison était progressive et complète. Conclusion La pneumonie à EBV compliquée d’un SDRA chez les immunocompétents existe. Sa prise en charge est un défi diagnostique et thérapeutique. Summary Introduction In the immuno-competent adult Ebstein-Barr virus (EBV) infection is a self-limiting disease that resolves spontaneously. Case report We report a case of acute respiratory distress syndrome (ARDS) complicating severe EBV pneumonia and requiring prolonged artificial ventilation. The diagnosis was confirmed by specific serology and estimation of the viral load by PCR. Apart from supportive treatment with artificial ventilation the medical treatment included the use of Acyclovir and polyclonal immunoglobulins in the early phase and corticosteroids in the late phase. Recovery was progressive and complete. Conclusion ARDS can complicate EBV pneumonia in an immuno-competent subject. Its management represents a diagnostic and therapeutic challenge.


title: SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice

text: During the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). This family includes T cell receptor (TCR) that is critically involved in immune diseases such as autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities.


title: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

text: BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. OBJECTIVE: To estimate the length of the incubation period of COVID-19 and describe its public health implications. DESIGN: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. SETTING: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. PARTICIPANTS: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. MEASUREMENTS: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. RESULTS: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. LIMITATION: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. CONCLUSION: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. PRIMARY FUNDING SOURCE: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.


title: Detection and typing by molecular techniques of respiratory viruses in children hospitalized for acute respiratory infection in Rome, Italy

text: Detection of a broad number of respiratory viruses is not undertaken currently for the diagnosis of acute respiratory infection due to the large and always increasing list of pathogens involved. A 1‐year study was undertaken on children hospitalized consecutively for acute respiratory infection in a Pediatric Department in Rome to characterize the viruses involved. Two hundred twenty‐seven children were enrolled in the study with a diagnosis of asthma, bronchiolitis, bronchopneumonia, or laringo‐tracheo bronchitis. A molecular approach was adopted using specific reverse transcription (RT)‐PCR assays detecting 13 respiratory viruses including metapneumovirus (hMPV) and the novel coronaviruses NL63 and HKU1; most amplified fragments were sequenced to confirm positive results and differentiate the strain. Viral pathogens were detected in 97 samples (42.7%), with 4.8% of dual infections identified; respiratory syncytial virus (RSV) was detected in 17.2% of children, followed by rhinovirus (9.7%), parainfluenza virus type 3 (PIV3) (7.5%), and influenza type A (4.4%). Interestingly, more than half the patients (9/17) that have rhinovirus as the sole respiratory pathogen had pneumonia. HMPV infected children below 3 years in two peaks in March and June causing bronchiolitis and pneumonia. One case of NL63 infection is described, documenting NL63 circulation in central Italy. In conclusion, the use of a comprehensive number of PCR‐based tests is recommended to define the burden of viral pathogens in patients with respiratory tract infection. J. Med. Virol. 79:463–468, 2007. © 2007 Wiley‐Liss, Inc.


title: COVID‐19: The Immediate Response of European Academic Dental Institutions and Future Implications for Dental Education

text: The COVID‐19 pandemic has had an immediate and dramatic impact on dental education. The Association of Dental Education in Europe decided to carry out an investigation to assess the immediate response of European Academic Dental Institutions. An online survey was sent to both member and non‐member dental schools to investigate the impact on non‐clinical and clinical education, assessment and the well‐being/pastoral care measures implemented. The preliminary findings and discussion are presented in this paper, for the responses collected between the 25th March and 5th April 2020. The survey at this time of publication is ongoing and detailed results can be accessed https://adee.org/covid-19-european-dental-education%25E2%2580%2599s-immediate-response.


title: Cytochrome P4501B1 in bone marrow is co-expressed with key markers of mesenchymal stem cells. BMS2 cell line models PAH disruption of bone marrow niche development functions

text: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are metabolized to carcinogenic dihydrodiol epoxides (PAHDE) by cytochrome P450 1B1 (CYP1B1). This metabolism occurs in bone marrow (BM) mesenchymal stem cells (MSC), which sustain hematopoietic stem and progenitor cells (HSPC). In BM, CYP1B1-mediated metabolism of 7, 12-dimethylbenz[a]anthracene (DMBA) suppresses HSPC colony formation within 6 h, whereas benzo(a)pyrene (BP) generates protective cytokines. MSC, enriched from adherent BM cells, yielded the bone marrow stromal, BMS2, cell line. These cells express elevated basal CYP1B1 that scarcely responds to Ah receptor (AhR) inducers. BMS2 cells exhibit extensive transcriptome overlap with leptin receptor positive mesenchymal stem cells (Lepr+ MSC) that control the hematopoietic niche. The overlap includes CYP1B1 and the expression of HSPC regulatory factors (Ebf3, Cxcl12, Kitl, Csf1 and Gas6). MSC are large, adherent fibroblasts that sequester small HSPC and macrophage in the BM niche (Graphic abstract). High basal CYP1B1 expression in BMS2 cells derives from interactions between the Ah-receptor enhancer and proximal promoter SP1 complexes, boosted by autocrine signaling. PAH effects on BMS2 cells model Lepr+MSC niche activity. CYP1B1 metabolizes DMBA to PAHDE, producing p53-mediated mRNA increases, long after the in vivo HSPC suppression. Faster, direct p53 effects, favored by stem cells, remain possible PAHDE targets. However, HSPC regulatory factors remained unresponsive. BP is less toxic in BMS2 cells, but, in BM, CYP1A1 metabolism stimulates macrophage cytokines (Il1b > Tnfa> Ifng) within 6 h. Although absent from BMS2 and Lepr+MSC, their receptors are highly expressed. The impact of this cytokine signaling in MSC remains to be determined.


title: Reinventing community in COVID-19: a case in Canberra, Australia

text: In this essay, I share my experiences and reflections of fighting COVID-19 from the perspective of a resident and a planner living and working in Canberra, Australia. I focus on three themes of building community compassion and collaboration and regard them as potential opportunities deriving from this crisis. First, COVID-19 presents a compulsory situation for establishing a virtual community and practising smart work. Second, COVID-19 helps rediscover a local community and nurture a special community spirit under the social distancing circumstance. Third, COVID-19 creates more opportunities of engaging and understanding nature, interestingly, in a context of staying home. These three themes are in large part rooted in the local communities of a city that is known for low density and being a ‘bush capital’ and possibly suggest some rethinking about the city’s planning legacy.


Travel medicine: an American view of the Australian perspective


title: Rapid Utilization of Telehealth in a Comprehensive Cancer Center as a Response to COVID-19: Cross-Sectional Analysis

text: BACKGROUND: The emergence of the coronavirus disease (COVID-19) pandemic in March 2020 created unprecedented challenges in the provision of scheduled ambulatory cancer care. As a result, there has been a renewed focus on video-based telehealth consultations as a means to continue ambulatory care. OBJECTIVE: The aim of this study is to analyze the change in video visit volume at the University of California, San Francisco (UCSF) Comprehensive Cancer Center in response to COVID-19 and compare patient demographics and appointment data from January 1, 2020, and in the 11 weeks after the transition to video visits. METHODS: Patient demographics and appointment data (dates, visit types, and departments) were extracted from the electronic health record reporting database. Video visits were performed using a HIPAA (Health Insurance Portability and Accountability Act)-compliant video conferencing platform with a pre-existing workflow. RESULTS: In 17 departments and divisions at the UCSF Cancer Center, 2284 video visits were performed in the 11 weeks before COVID-19 changes were implemented (mean 208, SD 75 per week) and 12,946 video visits were performed in the 11-week post–COVID-19 period (mean 1177, SD 120 per week). The proportion of video visits increased from 7%-18% to 54%-72%, between the pre– and post–COVID-19 periods without any disparity based on race/ethnicity, primary language, or payor. CONCLUSIONS: In a remarkably brief period of time, we rapidly scaled the utilization of telehealth in response to COVID-19 and maintained access to complex oncologic care at a time of social distancing.


title: Chapter 3 Noniridoid Bisindole Alkaloids

text: Publisher Summary This chapter discusses that indole is a reactive nucleus prone to dimerization when it is isolated or a part of tryptamine or tryptophan, which themselves are reactive toward many functionalities. For these reasons, bisindoles, the majority of which are of iridoid origin, are frequently isolated in nature. Besides these “dimers,” there exists a growing class of noniridoid bisindoles found in the marine environment, in microorganisms, and in plant species, many of which display interesting biological activities. The chapter tries to promote research on a series of compounds worthy of attention. Marine environments are a rich source of indole and bisindole alkaloids of great structural variety. In the absence of traditional use, the chemical constituents of marine organisms are separated following bioassay-guided fractionation, and, consequently, contrary to compounds from terrestrial sources, many of the structures are associated with significant biological activity.


title: COVID-19 pandemic: stop panic abandonment of household pets

text: Panic abandonment of household pets during the COVID-19 pandemic is not justified.


title: The experiences of health care workers employed in an Australian intensive care unit during the H1N1 Influenza pandemic of 2009: A phenomenological study

text: Abstract Background The H1N1 Influenza A pandemic arrived in Australia in early May 2009. In Queensland, the highest number of H1N1 cases were admitted to the intensive care unit when compared with the other Australian states. While many recent studies examining the H1N1 pandemic have focussed on service delivery and disease epidemiology, few have explored the lived experiences of frontline health care workers caring for the patients in the intensive care unit. Objectives The purposes of this study were to: document and describe the lived experiences of the nursing and medical staff caring for patients in the intensive care unit during the H1N1 pandemic; to validate the staffs’ experiences; and to assist in informing future pandemic planning by highlighting the collective experiences of these frontline health care workers. Design A phenomenological study method was used. Setting and participants 34 staff from a tertiary referral hospital in Brisbane, Australia participated in the study. Methods Data was collected using an open ended questionnaire and focus groups. The resulting responses were analysed using Colaizzi's framework to discover regular patterns of meaning that emerged. Results Eight common themes emerged: the wearing of personal protective equipment; infection control procedures; the fear of contracting and transmitting the disease; adequate staffing levels within the intensive care unit; new roles for staff; morale levels; education regarding extracorporeal membrane oxygenation; and the challenges of patient care. These eight themes articulate the lived experience of the staff during the height of the H1N1 Influenza pandemic period. Conclusions Planning for a pandemic situation is invariably difficult due to the unpredictable nature of the event itself. Recommendations for future pandemic planning which can be drawn from this study include the appointment of a dedicated infection control representative to provide information and support regarding infection control matters; the maintenance of effective communication channels is crucial; and the increased staffing requirements across nursing, medical, allied health and ancillary staff to cope with the higher patient numbers and acuity must be anticipated and planned for.


title: Drawing on Israel’s Experience Organizing Volunteers to Operationalize Drive-Through Coronavirus Testing Centers

text: To increase the country’s capacity to test and track suspected coronavirus disease 2019 (COVID-19) cases, Israel launched drive-through testing centers in key cities, including Tel Aviv, Jerusalem, Be’er Sheva, and Haifa. This article examines the challenges that the national emergency medical services and volunteers faced in the process of implementing drive-through testing centers to offer lessons learned and direction to health-care professionals in other countries.


title: Primary bronchial carcinoma associated with bone marrow metastasis and paraneoplastic monoclonal gammopathy in a cat

text: CASE SUMMARY: Herein we describe an unusual metastatic pattern and paraneoplastic manifestation of a bronchial carcinoma in a cat. An 8 year-old cat presented with a diminished appetite, dysphagia, weight loss, lethargy and coughing. Thoracic radiographs revealed a lung mass. Bronchial carcinoma was diagnosed on the basis of histology and was associated with a lymphoplasmocytic infiltration of the fibrovascular stroma. Biochemistry showed hyperproteinaemia. Serum protein electrophoresis showed a narrow spike in the gamma region. Bone marrow cytology revealed an infiltrate with numerous clustered epithelial cells. The cat was euthanased 2 months later because of anorexia and poor general condition. RELEVANCE AND NOVEL INFORMATION: To the best of our knowledge, this is the first clinical description of primary bronchial carcinoma associated with bone marrow metastases and paraneoplastic monoclonal gammopathy in a cat.


title: Two-way antigenic cross-reactivity between porcine epidemic diarrhea virus and porcine deltacoronavirus

text: Abstract Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PdCV) cause indistinguishable clinical signs and pathological changes in swine. Here we investigated the antigenic relationship between PEDV and PdCV. We provide the first evidence that conserved epitope(s) on the respective viral nucleocapsid proteins cross-react with each other although virus neutralization cross-reactivity was not observed. As a practical matter, prevention of these two very similar diseases of swine will require the development of separate virus-specific vaccine products.


title: Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex

text: Middle East respiratory syndrome coronavirus (MERS-CoV) uses the spike (S) glycoprotein to recognize and enter target cells. In this study, we selected two epitope peptide sequences within the receptor binding domain (RBD) of the MERS-CoV S protein. We used a complex consisting of the epitope peptide of the MERS-CoV S protein and CpG-DNA encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2G10G5 and 492-1G10E4E2. The western blotting data showed that both monoclonal antibodies detected the S protein and immunoprecipitated the native form of the S protein. Indirect immunofluorescence and confocal analysis suggested strong reactivity of the antibodies towards the S protein of MERS-CoV virus infected Vero cells. Furthermore, the 506-2G10G5 monoclonal antibody significantly reduced plaque formation in MERS-CoV infected Vero cells compared to normal mouse IgG and 492-1G10E4E2. Thus, we successfully produced a monoclonal antibody directed against the RBD domain of the S protein which could be used in the development of diagnostics and therapeutic applications in the future.


title: Integration of mRNP formation and export

text: Expression of protein-coding genes in eukaryotes relies on the coordinated action of many sophisticated molecular machineries. Transcription produces precursor mRNAs (pre-mRNAs) and the active gene provides an environment in which the pre-mRNAs are processed, folded, and assembled into RNA–protein (RNP) complexes. The dynamic pre-mRNPs incorporate the growing transcript, proteins, and the processing machineries, as well as the specific protein marks left after processing that are essential for export and the cytoplasmic fate of the mRNPs. After release from the gene, the mRNPs move by diffusion within the interchromatin compartment, making up pools of mRNPs. Here, splicing and polyadenylation can be completed and the mRNPs recruit the major export receptor NXF1. Export competent mRNPs interact with the nuclear pore complex, leading to export, concomitant with compositional and conformational changes of the mRNPs. We summarize the integrated nuclear processes involved in the formation and export of mRNPs.


title: Effects of the COVID-19 pandemic on supply and use of blood for transfusion

text: The COVID-19 pandemic has major implications for blood transfusion. There are uncertain patterns of demand, and transfusion institutions need to plan for reductions in donations and loss of crucial staff because of sickness and public health restrictions. We systematically searched for relevant studies addressing the transfusion chain—from donor, through collection and processing, to patients—to provide a synthesis of the published literature and guidance during times of potential or actual shortage. A reduction in donor numbers has largely been matched by reductions in demand for transfusion. Contingency planning includes prioritisation policies for patients in the event of predicted shortage. A range of strategies maintain ongoing equitable access to blood for transfusion during the pandemic, in addition to providing new therapies such as convalescent plasma. Sharing experience and developing expert consensus on the basis of evolving publications will help transfusion services and hospitals in countries at different stages in the pandemic.


title: Molecular detection of infectious bronchitis and Newcastle disease viruses in broiler chickens with respiratory signs using Duplex RT-PCR

text: Infectious bronchitis (IB) and Newcastle disease (ND) are highly contagious and the most economically important diseases of the poultry affecting respiratory tract and causing economic losses in poultry industry throughout the world. In the present study, the simultaneous detection and differentiation of causative agents of these diseases were investigated using duplex-RT-PCR. RNA was extracted from vaccinal and reference strains of infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) and then cDNA was synthesized. Using two universal primer sets for detection of IBV and NDV, the duplex-RT-PCR was developed. In order to assess the efficiency of the developed duplex RT-PCR, a number of 12 broiler farms with the symptoms of respiratory tract infection was sampled (trachea, lung and kidney were sampled from affected birds suspicious for IBV and NDV infections). After RNA extraction from tissues and cDNA synthesis, the presence of IBV and NDV genome were investigated using duplex-PCR. The results showed that three of twelve examined broiler farms were positive for IBV and two farms were positive for NDV and IBV. The results revealed that the duplex-RT-PCR is a quick and sensitive procedure for simultaneously detecting IBV and NDV in birds with respiratory infections.


title: Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses

text: Since 1999, plasmid-based reverse genetics (RG) systems have revolutionized the way influenza viruses are studied. However, it is not unusual to encounter cloning difficulties for one or more influenza genes while attempting to recover virus de novo. To overcome some of these shortcomings we sought to develop partial or full plasmid-free RG systems. The influenza gene of choice is assembled into a RG competent unit by virtue of overlapping PCR reactions containing a cDNA copy of the viral gene segment under the control of RNA polymerase I promoter (pol1) and termination (t1) signals – herein referred to as Flu PCR amplicons. Transfection of tissue culture cells with either HA or NA Flu PCR amplicons and 7 plasmids encoding the remaining influenza RG units, resulted in efficient virus rescue. Likewise, transfections including both HA and NA Flu PCR amplicons and 6 RG plasmids also resulted in efficient virus rescue. In addition, influenza viruses were recovered from a full set of Flu PCR amplicons without the use of plasmids.


title: Improved Chiral Separation of (R,S)-Goitrin by SFC: An Application in Traditional Chinese Medicine

text: Like chemical drugs, research and development of herbal medicine also have a need to resolve enantiomers. To help illustrating the antiviral bioactivity of Isatidis Radix, a widely used traditional Chinese medicine (TCM), supercritical fluid chromatography (SFC) was used for analytical and preparative separation of (R,S)-goitrin, which was reported as the active ingredient of the herbal. Improved resolution was achieved on Chiralpak IC column, using acetonitrile as the organic modifier, representing a tenfold increase in speed, compared to the previous normal phase HPLC (NPLC) method. The newly developed chromatographic method was validated in terms of linearity, precision, limit of detection (LOD), and limit of quantitation (LOQ). Scale-up purification of (R)-goitrin and (S)-goitrin was performed on a preparative column with >90% total recovery. The absolute stereochemical assignment of the purified isomers was determined through optical rotation study. This attempt explored SFC's application in chiral research of traditional Chinese medicine.


title: Late onset of acral necrosis after SARS‐CoV‐2 infection resolution

text: SARS‐CoV‐2 has been hypothesized as the aetiologic agent of CLL, on the basis of the temporal correlation between the “burst” of skin manifestations and the viral pandemic, even though we have scarce evidence of swab‐confirmed infections. Authors have therefore suggested some pathogenetic mechanisms such as a delayed immune‐mediated reaction to the virus in genetically‐predisposed patients(1) or an early IFN‐I response in young patients, muting early viral replication but also inducing microangiopathic changes.


title: Chapter 4 Role of CD4+ T Cells in the Pathophysiology of Multiple Sclerosis

text: Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although the precise etiology of MS remains unclear, CD4+ T cells have been proposed to play not only effector but also regulatory roles in MS. CD4+ T cells can be divided into four subsets: pro-inflammatory helper T (Th) 1 and Th17 cells, anti-inflammatory Th2 cells and regulatory T cells (Tregs). The roles of CD4+ T cells in MS have been clarified by either “loss-of-function” or “gain-of-function” methods, which have been carried out mainly in autoimmune and viral models of MS: experimental autoimmune encephalomyelitis and Theiler's murine encephalomyelitis virus infection, respectively. Observations in MS patients were consistent with the mechanisms found in the MS models, that is, increased pro-inflammatory Th1 and Th17 activity is associated with disease exacerbation, while anti-inflammatory Th2 cells and Tregs appear to play a protective role.


title: Spontaneous Pneumomediastinum/Pneumothorax in Patients With COVID-19

text: No spontaneous air leak case series have been described in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patient population thus far. We described seven spontaneous air leak cases we found in our coronavirus disease 2019 (COVID-19) positive 976-patient cohort. Five out of seven patients eventually required mechanical ventilation, and one of these patients died. All of our patients who demonstrated radiological air leaks after intubation died. No other precipitating factors offered in the literature thus far played a role in our patient population. We presume that acute lung injury leading to SARS-CoV-2 with associated acute respiratory distress syndrome (ARDS) predisposes patients to this rare complication.


title: Chapter 20 Antiviral Therapy

text: Abstract Antiviral therapy is one of the most exciting aspects of virology, since it has successfully employed basic science to generate very effective treatments for serious viral infections. Table 1 lists selected examples of those human viral diseases for which there are established antiviral drugs. Therapy for human immunodeficiency virus (HIV) infection has demonstrated that the potential impact antivirals can have on a lethal, chronic infection with lifesaving therapy administered to more than 12million individuals by 2015. This dramatic advance is about to be recapitulated for the treatment of hepatitis C virus (HCV) infection. The development of new antiviral drugs is very much a work in progress, with active drug discovery programs for filoviruses, coronaviruses, dengue, and others.


title: Comparison of Nasopharyngeal and Oropharyngeal Swabs for the Diagnosis of Eight Respiratory Viruses by Real-Time Reverse Transcription-PCR Assays

text: BACKGROUND: Many acute respiratory illness surveillance systems collect and test nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few studies assessing the relative measures of performance for NP versus OP specimens. METHODS: We collected paired NP and OP swabs separately from pediatric and adult patients with influenza-like illness or severe acute respiratory illness at two respiratory surveillance sites in Kenya. The specimens were tested for eight respiratory viruses by real-time reverse transcription-polymerase chain reaction (qRT-PCR). Positivity for a specific virus was defined as detection of viral nucleic acid in either swab. RESULTS: Of 2,331 paired NP/OP specimens, 1,402 (60.1%) were positive for at least one virus, and 393 (16.9%) were positive for more than one virus. Overall, OP swabs were significantly more sensitive than NP swabs for adenovirus (72.4% vs. 57.6%, p<0.01) and 2009 pandemic influenza A (H1N1) virus (91.2% vs. 70.4%, p<0.01). NP specimens were more sensitive for influenza B virus (83.3% vs. 61.5%, p = 0.02), parainfluenza virus 2 (85.7%, vs. 39.3%, p<0.01), and parainfluenza virus 3 (83.9% vs. 67.4%, p<0.01). The two methods did not differ significantly for human metapneumovirus, influenza A (H3N2) virus, parainfluenza virus 1, or respiratory syncytial virus. CONCLUSIONS: The sensitivities were variable among the eight viruses tested; neither specimen was consistently more effective than the other. For respiratory disease surveillance programs using qRT-PCR that aim to maximize sensitivity for a large number of viruses, collecting combined NP and OP specimens would be the most effective approach.


title: SBDiEM: A new Mathematical model of Infectious Disease Dynamics

text: Abstract A worldwide multi-scale interplay among a plethora of factors, ranging from micro-pathogens and individual or population interactions to macro-scale environmental, socio-economic and demographic conditions, entails the development of highly sophisticated mathematical models for robust representation of the contagious disease dynamics that would lead to the improvement of current outbreak control strategies and vaccination and prevention policies. Due to the complexity of the underlying interactions, both deterministic and stochastic epidemiological models are built upon incomplete information regarding the infectious network. Hence, rigorous mathematical epidemiology models can be utilized to combat epidemic outbreaks. We introduce a new spatiotemporal approach (SBDiEM) for modeling, forecasting and nowcasting infectious dynamics, particularly in light of recent efforts to establish a global surveillance network for combating pandemics with the use of artificial intelligence. This model can be adjusted to describe past outbreaks as well as COVID-19. Our novel methodology may have important implications for national health systems, international stakeholders and policy makers.


title: CHAPTER 8 Epidemiologic Investigation for Public Health, Biodefense, and Forensic Microbiology

text: Publisher Summary Epidemiology is the study of the distribution and determinants of health-related states or events in specied populations and the application of this study to control health problems. It reflects that diseases are not randomly distributed in the population and that individuals have certain characteristics that predispose to, or protect against, a variety of different diseases. Disease is the result of an epidemiological triad, where disease results from the interaction of: the human host, an infectious agent or toxin, and the environment that promotes the exposure. This chapter focuses on the use of epidemiology to identify the source of diseases caused by microorganisms or toxins. Microorganisms are very efficient at infecting humans, using a number of different strategies and mechanisms. The deliberate dissemination of a biological agent by many of these mechanisms presents the latest challenge to public health. It requires a careful epidemiologic investigation to determine whether an outbreak of infectious disease is because of the intentional release of an agent, or is naturally occurring. A number of molecular techniques have been developed for sub typing bacteria, viruses, fungi, and protozoa, which will facilitate this investigation as well as identify clusters of related microorganisms.


title: Dengue and COVID‐19, overlapping epidemics? An Analysis from Colombia

text: Coronavirus Disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), has rapidly spread throughout Latin America, a region swept by multiple previous and ongoing epidemics. There are significant concerns that the arrival of COVID‐19 is currently overlapping with other viruses, particularly dengue, in various endo‐epidemic regions across South America. In this report, we analyzed trends for both viral infections in Colombia during the first 20 epidemiological weeks of 2020. From January 1st to May 16th, 2020 (epidemiological weeks, EW, 1‐20), a total of 52,679 cases of dengue and 14,943 cases of COVID‐19 have been confirmed in Colombia. As both conditions may potentially lead to fatal outcomes, especially in patients with chronic co‐morbidities, overlapping infections and co‐occurrence may increase the number of patients requiring intensive care and mechanical ventilation. In regions such as Valle del Cauca, intensified preparation for such scenarios should be pondered, and further studies should be performed to address this critical issue in a timely matter. This article is protected by copyright. All rights reserved.


title: From SARS to strategic actions reframing systems

text: Background. The developed world responds to new and re‐emerging diseases through the discovery of medications. Disease can be transmitted around the world in a day, but the development of medications does not occur at this rate. The world has one environment and the focus in health care must be on identifying factors in this environment that coalesce to produce disease. Aim. The aim of this paper is to introduce the integrative model of environmental health and explore its potential to illuminate the Toronto SARS experience. Discussion. SARS affected people on three continents in a matter of days. Response to this new disease varied from one area to another and was dependent upon the level of integration of health services and communication across services. The present focus of the health care system is on treating the results of disease rather than the causative factors. Reacting to a new disease had grave social and economic consequences. The time for a new global environmental approach to health is now. The Toronto SARS experience was examined using the integrative model of environmental health and the upstream perspective as exemplars to interrupt the traditional approach to disease. All health care providers share the responsibility to learn about and to understand how our environment creates disease. This knowledge comes through research on topics such as; chemicals, pesticides, soil erosion, killing of forests, contamination of water, destabilization of climate, and social disruption from wars. Conclusions. Health care systems in the developed world continue to focus on the treatment of disease. A global ecological initiative for an integrated disease prevention system must be negotiated among nations.


title: Application of quantitative PCR for the detection of microorganisms in water

text: The occurrence of microorganisms in water due to contamination is a health risk and control thereof is a necessity. Conventional detection methods may be misleading and do not provide rapid results allowing for immediate action. The quantitative polymerase chain reaction (qPCR) method has proven to be an effective tool to detect and quantify microorganisms in water within a few hours. Quantitative PCR assays have recently been developed for the detection of specific adeno- and polyomaviruses, bacteria and protozoa in different water sources. The technique is highly sensitive and able to detect low numbers of microorganisms. Quantitative PCR can be applied for microbial source tracking in water sources, to determine the efficiency of water and wastewater treatment plants and act as a tool for risk assessment. Different qPCR assays exist depending on whether an internal control is used or whether measurements are taken at the end of the PCR reaction (end-point qPCR) or in the exponential phase (real-time qPCR). Fluorescent probes are used in the PCR reaction to hybridise within the target sequence to generate a signal and, together with specialised systems, quantify the amount of PCR product. Quantitative reverse transcription polymerase chain reaction (q-RT-PCR) is a more sensitive technique that detects low copy number RNA and can be applied to detect, e.g. enteric viruses and viable microorganisms in water, and measure specific gene expression. There is, however, a need to standardise qPCR protocols if this technique is to be used as an analytical diagnostic tool for routine monitoring. This review focuses on the application of qPCR in the detection of microorganisms in water.


title: RNA structure: the long and the short of it

text: The database of RNA structure has grown tremendously since the crystal structure analyses of ribosomal subunits in 2000–2001. During the past year, the trend toward determining the structure of large, complex biological RNAs has accelerated, with the analysis of three intact group I introns, A- and B-type ribonuclease P RNAs, a riboswitch–substrate complex and other structures. The growing database of RNA structures, coupled with efforts directed at the standardization of nomenclature and classification of motifs, has resulted in the identification and characterization of numerous RNA secondary and tertiary structure motifs. Because a large proportion of RNA structure can now be shown to be composed of these recurring structural motifs, a view of RNA as a modular structure built from a combination of these building blocks and tertiary linkers is beginning to emerge. At the same time, however, more detailed analysis of water, metal, ligand and protein binding to RNA is revealing the effect of these moieties on folding and structure formation. The balance between the views of RNA structure either as strictly a construct of preformed building blocks linked in a limited number of ways or as a flexible polymer assuming a global fold influenced by its environment will be the focus of current and future RNA structural biology.


title: Use of viral vectors for vaccine production in plants

text: The small size of plant viral genomes, the ease with which they can be manipulated, and the simplicity of the infection process is making the viral vectors an attractive alternative to the transgenic systems for the expression of foreign proteins in plants. One use of these virus expression systems is for vaccine production. There are two basic types of viral system that have been developed for the production of immunogenic peptides and proteins in plants: epitope presentation and polypeptide expression systems. In this review, we discuss advances made in this field.


title: Evaluation of two automated and three rapid lateral flow immunoassays for the detection of anti-SARS-CoV-2 antibodies

text: Abstract Introduction Several SARS-CoV-2 immunoassays have been developed recently. The purpose of this study was to assess the performance of five immunoassays for the detection of SARS-CoV-2 antibodies. Methods Two quantitative automated immunoassays (MaglumiTM 2019-n-Cov IgG and IgM and Euroimmun Anti-SARS-CoV-2 IgG and IgA assays) and three lateral flow rapid tests were performed. This retrospective study included 200 residual sera from patients and healthy volunteers. Case serum samples (n = 128) were obtained from COVID-19 patients confirmed by RT-qPCR and CT-scan. Days since onset of symptoms was collected from their medical records. Control non-SARS-CoV-2 samples (n = 72) were obtained from anonymous stored residual serum samples. Results MaglumiTM IgG/IgM tests showed overall less sensitivity than Euroimmun IgG/IgA test (84.4% versus 64.3%). Both tests showed similar specificities of IgG at 99% and 100%, respectively. The two tests showed similar specificity for IgG at 99% and 100%, respectively. The results from the lateral flow assays were easily interpretable with unambiguous coloured reading bands. The overall sensitivity of the three tests was similar (around 70%) without any significant differences. The sensitivity of the three lateral flow assays and also of the serological quantitative assays increased during the second week after symptom onset and all reached similar values (91% to 94%) after 14 days. Conclusion This study shows accurate and equivalent performance of the five serological antibody assays (ELISA, CLIA and three lateral flow tests) in detecting SARS-CoV-2 antibodies 14 days after the onset of COVID-19 symptoms. This is compatible with their application in specific clinical contexts and in determining epidemiological strategies for the COVID-19 pandemic.


title: The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis

text: Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.


title: Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS

text: The restoration of the immune system prompted by antiretroviral therapy (ART) has allowed drastically reducing the mortality and morbidity of HIV infection. However, one main source of clinical concern is the persistence of immune hyperactivation in individuals under ART. Chronically enhanced levels of T-cell activation are associated with several deleterious effects which lead to faster disease progression and slower CD4(+) T-cell recovery during ART. In this article, we discuss the rationale, and review the results, of the use of antimalarial quinolines, such as chloroquine and its derivative hydroxychloroquine, to counteract immune activation in HIV infection. Despite the promising results of several pilot trials, the most recent clinical data indicate that antimalarial quinolines are unlikely to exert a marked beneficial effect on immune activation. Alternative approaches will likely be required to reproducibly decrease immune activation in the setting of HIV infection. If the quinoline-based strategies should nevertheless be pursued in future studies, particular care must be devoted to the dosage selection, in order to maximize the chances to obtain effective in vivo drug concentrations.


title: Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease 2019 in Wenzhou, China

text: IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 has caused a global outbreak of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 binds angiotensin-converting enzyme 2 of the rennin-angiotensin system, resulting in hypokalemia. OBJECTIVE: To investigate the prevalence, causes, and clinical implications of hypokalemia, including its possible association with treatment outcomes, among patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at Wenzhou Central Hospital and Sixth People’s Hospital of Wenzhou, Wenzhou, China, from January 11, 2020, to February 15, 2020. Participants included patients who received a diagnosis of COVID-19 according to the criteria issued by the Chinese Health Bureau and were admitted to the hospital. The patients were classified as having severe hypokalemia (plasma potassium <3 mmol/L), hypokalemia (plasma potassium 3-3.5 mmol/L), and normokalemia (plasma potassium >3.5 mmol/L). The clinical features, therapy, and outcomes were compared between the 3 groups. Data analysis was conducted in March 2020. INTERVENTIONS: The patients were given general support and antiviral therapy. Their epidemiological and clinical features were collected. MAIN OUTCOMES AND MEASURES: The prevalence of hypokalemia and response to treatment with potassium supplements were measured by analyzing plasma and urine potassium levels. RESULTS: One hundred seventy-five patients (87 female patients [50%]; mean [SD] age, 45 [14] years) were classified as having severe hypokalemia (31 patients [18%]), hypokalemia (64 patients [37%]), and normokalemia (80 patients [46%]). Patients with severe hypokalemia had statistically significantly higher body temperature (mean [SD], 37.6 °C [0.9 °C]) than the patients with hypokalemia (mean [SD], 37.2 °C [0.7 °C]; difference, 0.4 °C; 95% CI, 0.2-0.6 °C; P = .02) and the patients with normokalemia (mean [SD], 37.1 °C [0.8 °C]; difference, 0.5 °C; 95% CI, 0.3-0.7 °C; P = .005). Patients with higher levels of hypokalemia also had higher creatine kinase levels (severe hypokalemia, mean [SD], 200 [257] U/L [median, 113 U/L; interquartile range {IQR}, 61-242 U/L]; hypokalemia, mean [SD], 97 [85] U/L; and normokalemia, mean [SD], 82 [57] U/L), higher creatine kinase–MB fraction (severe hypokalemia, mean [SD], 32 [39] U/L [median, 14 U/L; IQR, 11-36 U/L]; hypokalemia, mean [SD], 18 [15] U/L; and normokalemia, mean [SD], 15 [8] U/L), higher lactate dehydrogenase levels (mean [SD], severe hypokalemia, 256 [88] U/L; hypokalemia, 212 [59] U/L; and normokalemia, 199 [61] U/L), and higher C-reactive protein levels (severe hypokalemia, mean [SD], 29 [23] mg/L; hypokalemia, mean [SD], 18 [20] mg/L [median, 12, mg/L; IQR, 4-25 mg/L]; and normokalemia, mean [SD], 15 [18] mg/L [median, 6 U/L; IQR, 3-17 U/L]). Of 40 severely and critically ill patients, 34 (85%) had hypokalemia. Patients with severe hypokalemia were given potassium at a dose of 40 mEq per day, for a total mean (SD) of 453 (53) mEq potassium chloride, during the hospital stay. The patients responded well to potassium supplements as they recovered. CONCLUSIONS AND RELEVANCE: The correction of hypokalemia is challenging because of continuous renal potassium loss resulting from the degradation of angiotensin-converting enzyme 2. The high prevalence of hypokalemia among patients with COVID-19 suggests the presence of disordered rennin-angiotensin system activity, which increases as a result of reduced counteractivity of angiotensin-converting enzyme 2, which is bound by severe acute respiratory syndrome coronavirus 2.


title: Improved detection of rhinoviruses in nasal and throat swabs by seminested RT‐PCR

text: A seminested RT‐PCR (nRT‐PCR) was used to detect picornavirus (PV) RNA in cell cultures inoculated with rhinoviruses (HRVs) and enteroviruses (EVs). PCR tests in which a primary "touchdown" PCR was followed by secondary reactions using PV or HRV specific primers were able to differentiate HRVs of 48 serotypes from EVs. PVnRT‐PCR and HRVnRT‐PCR were then used to test nasal and throat swabs from adult subjects with naturally acquired respiratory virus infections. The swabs were also analysed for respiratory viruses by cell culture techniques and the rates of PV identification by the two methods were compared. PVnRT‐PCR was found to be at least five times more sensitive than cell culture for the detection of PVs in these clinical specimens. Paired acute and convalescent serum samples were tested for complement fixing antibodies to adenovirus, influenza A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, and 3, Myco plasma pneumoniae, and Chlamydia psittaci. An enzyme‐linked immunosorbent assay (ELISA) was used to detect rises in antibody level to coronavirus types 229E and OC43. The overall rate of pathogen identification in 159 swabs from adult asthmatics increased from 28% when only cell culture and serology were used to 57% when these methods were supplemented by PVnRT‐PCR. © 1993 Wiley‐Liss, Inc.


title: Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection

text: To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G(1) phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells. Knockdown of Ccnd3 by small interfering RNA significantly enhanced virus progeny titers in cell culture supernatants. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into S phase, failed to normalize virus production. Infection by influenza A virus triggered redistribution of cyclin D3 from the nucleus to the cytoplasm, followed by its proteasomal degradation. When overexpressed in HEK 293T cells, cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection.


title: Prevalence of Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’, Bartonella species, Ehrlichia species, and Anaplasma phagocytophilum DNA in the blood of cats with anemia

text: Hemoplasmas are known causes of anemia in some cats and some Bartonella species have been associated with anemia in people and in dogs. In this retrospective study, we used polymerase chain reaction (PCR) assays to determine the prevalence rates of Mycoplasma haemofelis, ‘Candidatus M haemominutum’, A phagocytophilum, Ehrlichia species, and Bartonella species DNA in the blood of cats with anemia and a control group of healthy cats. DNA of the organisms was amplified from 22 of 89 cats with anemia (24.7%) and 20 of 87 healthy cats (23.0%). DNA of a hemoplasma was amplified from 18 of 89 cats with anemia (20.2%) and 13 of 87 healthy cats (14.9%); DNA of a Bartonella species was amplified from five of 89 cats with anemia (5.6%) and seven of 87 healthy cats (8.0%). There were no statistically significant differences detected between groups.


title: Is Global BCG Vaccination Coverage Relevant To The Progression Of SARS-CoV-2 Pandemic?

text: Abstract The lower than expected number of SARS-CoV-2 cases in countries with fragile health systems is puzzling. Herein, we hypothesize that BCG vaccination policies adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated morbidity and mortality through the vaccine’s capacity to confer heterologous protection. We also postulate that until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines to attain heterologous nonspecific protection from the new coronavirus.


title: Rinofaringitis infantiles

text: Resumen La rinofaringitis designa una inflamación moderada de las vías respiratorias superiores de origen infeccioso. Sus signos habituales son obstrucción nasal, rinorrea, estornudos, dolor faríngeo y tos. Los autores anglosajones hablan de catarro (common cold) o de infección de vías respiratorias altas para describir una inflamación de las vías respiratorias superiores, y de adenoiditis crónica (chronic adenoiditis) para designar una infección crónica de las vegetaciones adenoides que produce rinorrea febril recidivante u obstrucción de las vías respiratorias altas. Las rinofaringitis agudas no complicadas son de origen vírico. Habitualmente su evolución espontánea es rápida y sin complicaciones. Por tanto, no hay que obtener muestras bacteriológicas ni hacer un tratamiento antibiótico sistemático. Como tratamiento de primera línea, sólo precisan analgésicos y antipiréticos asociados a lavados de las fosas nasales con suero salino isotónico o hipertónico. Las complicaciones de las rinofaringitis son infecciosas –representadas esencialmente por las otitis y las sinusitis– y respiratorias obstructivas. El carácter a menudo repetitivo de las rinofaringitis a partir de los 6 meses de edad refleja un proceso fisiológico de maduración del sistema inmunitario. Cuando existen rinofaringitis frecuentes e invalidantes, los principales factores de riesgo que se deben buscar, y de ser posible erradicar, son el tabaquismo pasivo y los contactos con una población infantil. La adenoidectomía ya no está indicada si no existen complicaciones. Se están realizando investigaciones clínicas y experimentales sobre el desarrollo de fármacos antivíricos eficaces para la prevención y el tratamiento de las rinofaringitis.


title: Charities expect revenue drops, but some donors plan to boost giving

text: In response to the global COVID‐19 pandemic, some 80% of charities now believe their 2020 revenue will be lower than expected, and the vast majority of charities are concerned about maintaining a financially stable organization through the rest of the year. However, an increase in charitable giving from individuals might help to counteract that expected drop, offering some hope to pessimistic nonprofits, according to new research from the Better Business Bureau's Wise Giving Alliance.