title: Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution

text: As the global COVID-19 pandemic continues to escalate, no effective treatment has yet been developed for the severe respiratory complications of this disease. This may be due in large part to the unclear immunopathological basis for the development of immune dysregulation and acute respiratory distress syndrome (ARDS) in severe and critical patients. Specifically, it remains unknown whether the immunological features of the disease that have been identified so far are compartment-specific responses or general features of COVID-19. Additionally, readily detectable biological markers correlated with strata of disease severity that could be used to triage patients and inform treatment options have not yet been identified. Here, we leveraged publicly available single-cell RNA sequencing data to elucidate the common and compartment-specific immunological features of clinically severe COVID-19. We identified a number of transcriptional programs that are altered across the spectrum of disease severity, few of which are common between the lung and peripheral immune environments. In the lung, comparing severe and moderate patients revealed severity-specific responses of enhanced interferon, A20/IκB, IL-2, and IL-6 pathway signatures along with broad signaling activity of IFNG, SPP1, CCL3, CCL8, and IL18 across cell types. These signatures contrasted with features unique to ARDS observed in the blood compartment, which included depletion of interferon and A20/IκB signatures and a lack of IL-6 response. The cell surface marker S1PR1 was strongly upregulated in patients diagnosed with ARDS compared to non-ARDS patients in γδ T cells of the blood compartment, and we nominate S1PR1 as a potential marker for immunophenotyping ARDS in COVID-19 patients using flow cytometry. HIGHLIGHTS COVID-19 disease severity is associated with a number of compositional shifts in the cellular makeup of the blood and lung environments. Transcriptional data suggest differentially expressed cell surface proteins as markers for COVID-19 immunophenotyping from BALF and PBMC samples. Severity-specific features COVID-19 manifest at the pathway level, suggesting distinct changes to epithelia and differences between local and systemic immune dynamics. Immune-epithelial cellular communication analysis identifies ligands implicated in transcriptional regulation of proto-oncogenes in the lung epithelia of severe COVID-19 patients. Network analysis suggests broadly-acting dysregulatory ligands in the pulmonary microenvironment as candidate therapeutic targets for the treatment of severe COVID-19.


title: Bovine whey proteins – Overview on their main biological properties

text: Abstract Whey, a liquid by-product, is widely accepted to contain many valuable constituents. These include especially proteins that possess important nutritional and biological properties – particularly with regard to promotion of health, as well as prevention of diseases and health conditions. Antimicrobial and antiviral actions, immune system stimulation, anticarcinogenic activity and other metabolic features have indeed been associated with such whey proteins, as α-lactalbumin, β-lactoglobulin, lactoferrin, lactoperoxidase, and bovine serum albumin. The most important advances reported to date pertaining to biological properties of whey proteins are reviewed in this communication.


title: Evidence and future potential of mobile phone data for disease disaster management

text: Abstract Global health threats such as the recent Ebola and Zika virus outbreaks require rapid and robust responses to prevent, reduce and recover from disease dispersion. As part of broader big data and digital humanitarianism discourses, there is an emerging interest in data produced through mobile phone communications for enhancing the data environment in such circumstances. This paper assembles user perspectives and critically examines existing evidence and future potential of mobile phone data derived from call detail records (CDRs) and two-way short message service (SMS) platforms, for managing and responding to humanitarian disasters caused by communicable disease outbreaks. We undertake a scoping review of relevant literature and in-depth interviews with key informants to ascertain the: (i) information that can be gathered from CDRs or SMS data; (ii) phase(s) in the disease disaster management cycle when mobile data may be useful; (iii) value added over conventional approaches to data collection and transfer; (iv) barriers and enablers to use of mobile data in disaster contexts; and (v) the social and ethical challenges. Based on this evidence we develop a typology of mobile phone data sources, types, and end-uses, and a decision-tree for mobile data use, designed to enable effective use of mobile data for disease disaster management. We show that mobile data holds great potential for improving the quality, quantity and timing of selected information required for disaster management, but that testing and evaluation of the benefits, constraints and limitations of mobile data use in a wider range of mobile-user and disaster contexts is needed to fully understand its utility, validity, and limitations.


title: Large-scale seroprevalence analysis of human metapneumovirus and human respiratory syncytial virus infections in Beijing, China

text: BACKGROUND: Human metapneumovirus (hMPV), a recently identified virus, causes acute respiratory tract infections (ARTIs) in infants and children. However, studies on the seroepidemeology of hMPV are very limited in China. To assess the seroprevalence of hMPV infection in China, we tested a total of 1,156 serum specimens for the presence of anti-hMPV IgG antibody in children and adults free of acute respiratory illness in Beijing, China by using hMPV nucleocapsid (N) protein as an antigen. As a control, we used the human serum antibody against the N protein of human respiratory syncytial virus (hRSV), the most important viral agent responsible for ARIs in children. RESULTS: The seropositive rate for hMPV increased steadily with age from 67% at 1-6 mo to 100% at age 20. However, the rate dropped slightly between 6 mo and 1 yr of age. The seropositive rate for hRSV also increased steadily with age from 71% at 1-6 mo to 100% at age 20. In children aged six months to six years, the seropositive rates for the anti-hRSV IgG antibody were significantly higher than those for hMPV. Additionally, IgG antibody titers to hMPV and hRSV were significantly higher in adults than in young children. Consistent with the seropositive rates, the geometric mean titer of anti-hMPV IgG antibody was lower than that of anti-hRSV IgG antibody in children aged six months to six years. CONCLUSIONS: Our results indicate that similar to hRSV, exposure to hMPV is ubiquitous in the Beijing population. However, the seroprevalence of anti-hMPV IgG antibody is lower than that of hRSV in children between six months and six years old, which suggests a different number of repeat infections or a different response to infections.


title: Detection of human rhinoviruses in the lower respiratory tract of lung transplant recipients

text: The occurrence of human rhinoviruses (HRV) and its relationship to clinical and histopathological findings were investigated in 127 bronchoalveolar lavage specimens from 36 lung transplant recipients by real-time RT-PCR. In addition, 286 samples from 235 other immunocompromised and immunocompetent patients were also studied. HRV was detected in 41.7% of lung transplant recipients vs 14.5% of other patients (p < 0.0001), and no differences in viral load were observed. Acute respiratory insufficiency was found in 15 cases, three of which were HRV positive (viral load, 6.3x10(6) RNA copies/ml in one patient with chronic graft dysfunction). A diagnosis of pneumonia was made in 10 out of 127 cases, two of which were HRV positive (viral load, 10(3)-10(4) in cases of co-infection). Acute rejection was diagnosed in 12 cases, three of which were HRV positive (viral load, 10(3) in two cases of co-infection and 10(5) in a single infection). HRV infection may involve the lower respiratory tract, particularly in the presence of an impaired pulmonary background, such as a transplanted lung. Clinical evaluation should take into account the viral load, with a load of >10(5) possibly being associated with clinical symptoms, although lower loads can be detected in both symptomatic and asymptomatic patients.


title: Practical guidance for the management of adults with immune thrombocytopenia during the COVID‐19 pandemic

text: This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID‐19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.


title: Primary health care policy and vision for community pharmacy and pharmacists in Australia

text: There is evidence that the Australian Government is embracing a more integrated approach to health, with implementation of initiatives like primary health networks (PHNs) and the Government’s Health Care Homes program. However, integration of community pharmacy into primary health care faces challenges, including the lack of realistic integration in PHNs, and in service and remuneration models from government. Ideally, coordinated multidisciplinary teams working collaboratively in the community setting are needed, where expanding skills are embraced rather than resisted. It appears that community pharmacy is not sufficiently represented at a local level. Current service remuneration models encourage a volume approach. While more complex services and clinical roles, with associated remuneration structures (such as, accredited pharmacists, pharmacists embedded in general practice and residential aged care facilities) promote follow up, collaboration and integration into primary health care, they potentially marginalize community pharmacies. Community pharmacists’ roles have evolved and are being recognized as the medication management experts of the health care team at a less complex level with the delivery of MedChecks, clinical interventions and medication adherence services. More recently, vaccination services have greatly expanded through community pharmacy. Policy documents from professional bodies highlight the need to extend pharmacy services and enhance integration within primary care. The Pharmaceutical Society of Australia’s Pharmacists in 2023 report envisages pharmacists practising to full scope, driving greater efficiencies in the health system. The Pharmacy Guild of Australia’s future vision identifies community pharmacy as health hubs facilitating the provision of cost-effective and integrated health care services to patients. In 2019, the Australian Government announced the development of a Primary Health Care 10-Year Plan which will guide resource allocation for primary health care in Australia. At the same time, the Government has committed to conclude negotiations on the 7th Community Pharmacy Agreement (7CPA) with a focus on allowing pharmacists to practice to full scope and pledges to strengthen the role of primary care by better supporting pharmacists as primary health care providers. The 7CPA and the Government’s 10-year plan will largely shape the practice and viability of community pharmacy. It is essential that both provide a philosophical direction and prioritize integration, remuneration and resources which recognize the professional contribution and competencies of community pharmacy and community pharmacists, the financial implications of service roles and the retention of medicines-supply roles.


title: Evaluation Of Dermatology Consultations In The Era Of COVID19

text: It has been reported that dermatology practices may be a vector for SARS‐CoV‐2 transmission and elective cases should be postponed during the pandemic period. In this context, studies on the change of patient profile in Dermatology outpatient clinic have been conducted. However, there was no study in the literature about dermatology consultations during the pandemic period. 147 Dermatology consultation cases in the era of COVID‐19 pandemic between March 11, 2020 and May 4, 2020 were retrospectively evaluated. 24 patients (16.3%) had suspicion and signs of COVID during consultation (fever, cough, shortness of breath, etc.). 9 (37.5%) of these patients also had accompanying COVID‐19 skin lesions (2 urticarial lesions, 2 livedo and necrosis, 2 maculopapular eruption, 2 vesicular rashes, 1 pseudo‐chilblain). The number of cases that were suspected to have COVID‐19 was statistically significantly higher in consultations requested by the emergency department and intensive care unit, while there were no suspected cases in outpatient clinic consultations (P = 0.001). 2 (1.4%) of these patients were diagnosed with COVID‐19 confirmed by PCR within 2 weeks. We acknowledge that daily practice changes frequently during this period, but still our study provides a perspective to other dermatology clinics in terms of the requested dermatology consultations during the pandemic. This article is protected by copyright. All rights reserved.


title: Macromolecular prodrugs of ribavirin: Polymer backbone defines blood safety, drug release, and efficacy of anti-inflammatory effects

text: Abstract Macromolecular (pro)drugs hold much promise as broad-spectrum antiviral agents as either microbicides or carriers for intracellular delivery of antiviral drugs. Intriguing opportunity exists in combining the two modes of antiviral activity in the same polymer structure such that the same polymer acts as a microbicide and also serves to deliver the conjugated drug (ribavirin) into the cells. We explore this opportunity in detail and focus on the polymer backbone as a decisive constituent of such formulations. Fourteen polyanions (polycarboxylates, polyphosphates and polyphosphonates, and polysulfonates) were analyzed for blood pro/anti coagulation effects, albumin binding and albumin aggregation, inhibitory activity on polymerases, cytotoxicity, and anti-inflammatory activity in stimulated macrophages. Ribavirin containing monomers were designed to accommodate the synthesis of macromolecular prodrugs with disulfide-exchange triggered drug release. Kinetics of drug release was fast in all cases however enhanced hydrophobicity of the polymer significantly slowed release of ribavirin. Results of this study present a comprehensive view on polyanions as backbone for macromolecular prodrugs of ribavirin as broad-spectrum antiviral agents.


title: Predicting COVID-19 Incidence Through Analysis of Google Trends Data in Iran: Data Mining and Deep Learning Pilot Study

text: BACKGROUND: The recent global outbreak of coronavirus disease (COVID-19) is affecting many countries worldwide. Iran is one of the top 10 most affected countries. Search engines provide useful data from populations, and these data might be useful to analyze epidemics. Utilizing data mining methods on electronic resources’ data might provide a better insight into the COVID-19 outbreak to manage the health crisis in each country and worldwide. OBJECTIVE: This study aimed to predict the incidence of COVID-19 in Iran. METHODS: Data were obtained from the Google Trends website. Linear regression and long short-term memory (LSTM) models were used to estimate the number of positive COVID-19 cases. All models were evaluated using 10-fold cross-validation, and root mean square error (RMSE) was used as the performance metric. RESULTS: The linear regression model predicted the incidence with an RMSE of 7.562 (SD 6.492). The most effective factors besides previous day incidence included the search frequency of handwashing, hand sanitizer, and antiseptic topics. The RMSE of the LSTM model was 27.187 (SD 20.705). CONCLUSIONS: Data mining algorithms can be employed to predict trends of outbreaks. This prediction might support policymakers and health care managers to plan and allocate health care resources accordingly.


title: Host chemokine (C-C motif) ligand-2 (CCL2) is differentially regulated in HIV type 1 (HIV-1)-infected individuals

text: Several cytokines and chemokines including chemokine (C-C motif) ligand-2 (CCL2) are induced in HIV-1 infection. However, the impact of HIV-1 viremia on CCL2 regulation is largely unknown. We utilized a DNA oligonucleotide microarray covering 110 inflammatory genes. Five genes were induced by at least 2-fold in PBMCs of HIV-1 viremic (>100.000 RNA copies ml(−1)) as compared with aviremic (<50 RNA copies ml(−1)) individuals. These genes were CCL2, CXC chemokine ligand-10, IFN-γ, GTP-cyclohydrolase-1 and C-C chemokine receptor-1. In addition to microarray data verification by real-time PCR, analysis of independent patient samples revealed a similar expression pattern. CCL2 was the most strongly regulated gene at mRNA level and its serum concentration was significantly elevated in viremic compared with aviremic and HIV-1 seronegative controls, indicating a positive correlation between viremia and CCL2. Flow cytometric studies demonstrated a higher percentage of CCL2-expressing CD14+ monocytes in viremic compared with aviremic individuals. These results suggest a highly restricted modulation of host inflammatory gene response by HIV. Genes up-regulated in the viremic state, in particular CCL2, presumably serve as potential enhancing factors in HIV-1 replication, represented by high viral load in HIV-1 viremic patients. Inhibition of increased CCL2 production could provide a new therapeutic intervention in HIV-1 infection.


title: The impact of persistent bacterial bronchitis on the pulmonary microbiome of children

text: INTRODUCTION: Persistent bacterial bronchitis (PBB) is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of PBB. Blind, protected brushings were obtained from 20 healthy controls and 24 children with PBB, with an additional directed sample obtained from PBB patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing. RESULTS: No significant difference in bacterial diversity or community composition (R(2) = 0.01, P = 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P < 0.001) and change in community composition (R(2) = 0.08, P = 0.004) was observed among controls, in comparison with patients. Bacterial communities within patients with PBB were dominated by Proteobacteria, and indicator species analysis showed that Haemophilus and Neisseria were significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture. CONCLUSION: The bacteria present in the lungs of patients with PBB were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden.


title: Community-Based Risk Communication Survey: Risk Prevention Behaviors in Communities during the H1N1 crisis, 2010

text: OBJECTIVES: The present study aimed to investigate the prevalence of and factors associated with H1N1 preventive behaviors in a community-based population. METHODS: A cross-sectional study was conducted in three urban and two rural communities in Korea. Interviews were conducted with 3462 individuals (1608 men and 1854 women) aged ≥ 19 years during February–March 2010. Influenza-related information including anxiety, preventive behaviors and their perceived effectiveness, vaccination status, past influenza-like illness symptoms, and sources of and trust in information was obtained. RESULTS: Among 3462 participants, 173 reported experiencing influenza-like illness symptoms within the past 12 months. The mean H1N1 preventive behavior score was 25.5 ± 5.5 (out of a possible 40). The percent of participants reporting high perceived effectiveness and high anxiety was 46.2% and 21.4%, respectively. After controlling for potential confounders, H1N1 preventive behavior scores were predicted by a high (β = 3.577, p < 0.001) or moderate (β = 2.529, p < 0.001) perception of their effectiveness. Similarly, moderate (β = 1.516, p < 0.001) and high (β = 4.103, p < 0.001) anxiety scores predicted high preventive behavior scores. CONCLUSION: Effective methods of promoting population behavior change may be nationwide campaigns through mass media, as well as education and promotion by health care providers and broadcasters.


title: Risk of Infectious Gastroenteritis in Young Children Living in Québec Rural Areas with Intensive Animal Farming: Results of a Case–Control Study (2004–2007)

text: This study was designed to evaluate the epidemiology of severe gastroenteritis in children living in Québec rural areas with intensive livestock activities. From September 2005 through June 2007, 165 cases of gastroenteritis in children aged from 6 months to 5 years, hospitalized or notified to the public health department were enrolled, and 326 eligible controls participated. The parents of cases and controls were asked questions about different gastroenteritis risk factors. The quality of the drinking water used by the participants was investigated for microbial indicators as well as for four zoonotic bacterial pathogens (Campylobacter spp, Escherichia coli, Salmonella spp and Yersinia spp) and two enteric parasites (Cryptosporidium spp and Giardia spp). From 134 stool specimen analysed, viruses were detected in 82 cases (61%), while 28 (21%) were found with at least one of the bacteria investigated, and five cases were infected by parasites. Campylobacteriosis was the main bacterial infection (n = 15), followed by Salmonella sp (n = 7) and E. coli O157:H7 (n = 5) among cases with bacterial gastroenteritis. No significant difference was found between cases and controls regarding the quality of water consumed; the frequency of faecal contamination of private wells was also similar between cases and controls. Considering the total cases (including those with a virus), no link was found between severe gastroenteritis and either being in contact with animals or living in a municipality with the highest animal density (4th quartile). However, when considering only cases with a bacterial or parasite infection (n = 32), there was a weak association with pig density that was not statistically significant after adjusting for potential confounders. Contact with domestic, zoo or farm animals were the only environmental factor associated with the disease.


title: A dynamic estimation of the daily cumulative cases during infectious disease surveillance: application to dengue fever

text: BACKGROUND: In infectious disease surveillance, when the laboratory confirmation of the cases is time-consuming, there is often a time lag between the number of suspect cases and the number of confirmed cases. This study proposes a dynamic statistical model to estimate the daily number of new cases and the daily cumulative number of infected cases, which was then applied to historic dengue fever data. METHODS: The duration between the date of disease onset and date of laboratory confirmation was assumed to follow a gamma distribution or a nonparametric distribution. A conditional probability of a case being a real case among the unconfirmed cases on a given date was then calculated. This probability along with the observed confirmed cases was integrated to estimate the daily number of new cases and the cumulative number of infected cases. RESULTS: The distribution of the onset-to-confirmation time for the positive cases was different from that of the negative cases. The daily new cases and cumulative epidemic curves estimated by the proposed method have a lower absolute relative bias than the values estimated solely based on the available daily-confirmed cases. CONCLUSION: The proposed method provides a more accurate real-time estimation of the daily new cases and daily cumulative number of infected cases. The model makes use of the most recent "moving window" of information relative to suspect cases and dynamically updates the parameters. The proposed method will be useful for the real-time evaluation of a disease outbreak when case classification requires a time-consuming laboratory process to identify a confirmed case.


Interferon and Its Inducers—A Never-Ending Story: “Old” and “New” Data in a New Perspective


title: Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination

text: The primary target in multiple sclerosis (MS) is believed to be either myelin itself (myelinopathy) or the myelin-forming cell, the oligodendrocyte (oligodendrogliopathy). Although axonal injury occurs in MS, it is regarded as a secondary event to the myelin damage. Here, the lesion develops from myelin (outside) to the axon (inside) (Outside-In model). Recently, gray matter lesions and axonal injury in normal-appearing white matter have also been reported in MS. This raises two questions. 1) Is axonal injury exclusively secondary to myelin damage or from a direct insult to the axon or neurons (axonopathy)? (2) Is the injured axon regarded as only an end result of pathology or disease, or can axonal injury contribute to the spread of secondary damage, including demyelination? The former is raised from the fact that axonal damage has been reported in several virus infections, including human immunodeficiency virus, human T-lymphotropic virus 1, herpes simplex virus and coronavirus, which also cause demyelination. The latter possibility where axonal injury leads to other changes is raised from the rather unexpected similarity between spinal cord injury (SCI) and MS where axonal injury, oligodendrocyte apoptosis and demyelination are all present. In SCI, transection of axons leads to delayed oligodendrocyte apoptosis with secondary demyelination. Neurofilament immunostaining of spinal cord sections demonstrates that axonal injury with oligodendrocyte apoptosis also precedes demyelination in an animal model for MS, Theiler’s murine encephalomyelitis virus infection. This implies that axonal injury could trigger demyelination. In this instance, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).


docid: nqxdjxhh

title: State Executive Orders: Nuance in restrictions, revealing suspensions, and decisions to enforce

text: In the absence of a large‐scale federal response to the COVID‐19 pandemic, state and local elected officials have enacted executive orders that include both restrictions to public liberties as well as the suspension of rules and regulations. While these restrictive policy actions have received extensive media attention, the suspensions, including regulatory rollbacks, waivers, and extensions are lesser known. This viewpoint offers insight from a working database that captures the nuance and variation across restrictions, suspensions, and enforcement mechanisms being utilized, at the state level. This article is protected by copyright. All rights reserved.


title: The validation of a real-time RT-PCR assay which detects influenza A and types simultaneously for influenza A H1N1 (2009) and oseltamivir-resistant (H275Y) influenza A H1N1 (2009)

text: Abstract Influenza A H1N1 (2009) was declared by the World Health Organisation (WHO) as the first influenza pandemic of the 21st century. Rapid detection of influenza A and differentiation of influenza A H1N1 (2009) and seasonal influenza A is beneficial. In addition the rapid detection of antiviral resistant strains of influenza A H1N1 (2009) would be useful for clinicians to allow for change to an effective treatment at a much earlier stage if resistance is found. It was the aim of this study to develop a real-time RT-PCR that can detect all influenza A viruses and type simultaneously for influenza A H1N1 (2009) and oseltamivir resistant (H275Y) influenza A H1N1 (2009). This multiplex assay will allow laboratories to screen respiratory samples for all types of influenza A, influenza A H1N1 (2009) virus and oseltamivir resistant (H275Y) influenza A H1N1 (2009) virus in a rapid and cost effective format, ensuring that typing methods for seasonal and avian viruses are used on a smaller subset of samples. Since most virology laboratories already offer a molecular service for influenza A this assay could easily be implemented into most areas at little cost therefore increasing local access to resistance testing.


title: Positive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19)

text: Abstract Objectives To investigate the widely concerned issue about positive real-time reverse transcription polymerase chain reaction (RT-PCR) test results after discharge in patients recovered from coronavirus disease 2019 (COVID-19). Methods We identified seven cases of COVID-19 who was readmitted to hospital because of positive RT-PCR after discharge, including three pediatrics and four young adult patients. Results Six patients had positive rectal swabs but negative throat swabs, and one patient had positive throat swabs. All the patients continued to be asymptomatic and had unchanged chest computed tomography from previous images. The time from hospital discharge to positive RT-PCR after recovery was 7–11 days. The time from positive to negative rectal swabs was 5-23 days. Conclusion The study might suggest the positive RT-PCR after recovery did not mean disease relapse or virus reinfection. Adding RT-PCR test of rectal swabs to the criteria for discharge or discontinuation of quarantine might be necessary.


title: The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection

text: BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.


title: Effects of probiotic supplementation on natural killer cell function in healthy elderly individuals: a meta-analysis of randomized controlled trials

text: To evaluate evidence for the role of probiotic supplementation in enhancing natural killer (NK) cell function in healthy elderly individuals. Five electronic databases were searched, and references of included articles and eligible reviews up to December 2019, with English language and human subject restrictions, were examined. Two independent reviewers identified randomized control trials (RCTs) of probiotic supplementation influencing NK cell function in healthy elderly individuals, assessed the quality of every article, and extracted data for subsequent meta-analysis. We identified six eligible trials including 364 healthy elderly subjects. Trials were heterogeneous in study design and probiotic supplementation (including genus, strain, dose, and duration). Five trials used Lactobacillus interventions alone or in combination with Bifidobacterium. Only one trial focused on Bacillus coagulans. The duration of supplementation ranged from 3 to 12 weeks, and the doses, from 1 × 10(9) to 4 × 10(10) colony-forming units. Pooling data of eligible trials showed that probiotics significantly (P < 0.05) increased NK cell activity in healthy elderly individuals (standardized mean difference = 0.777, 95% confidence interval: 0.187‒1.366, P = 0.01, I(2) = 84.6%). Although we obtained a significant outcome, the data do not provide convincing evidence for associations between probiotic supplementation and enhancement of NK cell function, given the small final number and very large heterogeneity. More RCTs with sufficient sample sizes and long-term follow-up are needed to focus on optimal probiotic dose, species, and duration of supplementation for healthy elderly individuals.


title: Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression

text: Abstract Background and aims Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. Methods Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. Results There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I2: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I2: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I2: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I2: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I2: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age ≥55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension ≥25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) Conclusion DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.


title: Saposhnikovia divaricata—An Ethnopharmacological, Phytochemical and Pharmacological Review

text: Saposhnikovia divaricata (Turcz.) Schischk., a perennial herb belonging to the family Umbelliferae, is widely distributed in Northeast Asia. Its dried root (Radix Saposhnikoviae) is used as a Chinese herbal medicine for the treatment of immune system, nervous system, and respiratory diseases. Phytochemical and pharmacological studies have shown that the main constituents of S. divaricata are chromones, coumarins, acid esters, and polyacetylenes, and these compounds exhibited significant anti-inflammatory, analgesic, antioxidant, antiproliferative, antitumor, and immunoregulatory activities. The purpose of this review is to provide comprehensive information on the botanical characterization and distribution, traditional use and ethnopharmacology, phytochemistry, and pharmacology of S. divaricata for further study concerning its mechanism of action and development of better therapeutic agents and health products from S. divaricata. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material (Appendixes 1–10) is available in the online version of this article at 10.1007/s11655-020-3091-x.


title: Glycyrrhizin inhibits porcine epidemic diarrhea virus infection and attenuates the proinflammatory responses by inhibition of high mobility group box-1 protein

text: Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV) infection, leads to significant economic losses in the swine industry worldwide. In our studies, we found that glycyrrhizin, the major component of licorice root extracts, could moderately inhibit PEDV infection in Vero cells, when analyzed by western blot, qRT-PCR and a plaque formation assay. We also revealed that glycyrrhizin inhibited the entry and replication of PEDV. In addition, we demonstrated that glycyrrhizin decreased the mRNA levels of proinflammatory cytokines. Since glycyrrhizin is a competitive inhibitor of high mobility group box-1 (HMGB1), we confirmed that TLR4 and RAGE (£ associated with PEDV pathogenesis during the infection in Vero cells. In summary, our studies provide a molecular basis for developing novel therapeutic methods to control PEDV infection, based on glycyrrhizin and its derivatives.


docid: nbgdmavr

title: Ribavirin efficiently suppresses porcine nidovirus replication

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are porcine nidoviruses that represent emerging viral pathogens causing heavy economic impacts on the swine industry. Although ribavirin is a well-known antiviral drug against a broad range of both DNA and RNA viruses in vitro, its inhibitory effect and mechanism of action on porcine nidovirus replication remains to be elucidated. Therefore, the present study was conducted to determine whether ribavirin suppresses porcine nidovirus infection. Our results demonstrated that ribavirin treatment dose-dependently inhibited the replication of both nidoviruses. The antiviral activity of ribavirin on porcine nidovirus replication was found to be primarily exerted at early times post-infection. Treatment with ribavirin resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production in a dose-dependent manner. Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further sequencing analysis showed that the mutation frequency in ribavirin-treated cells was similar to that in untreated cells, indicating that ribavirin did not induce error-prone replication. Taken together, our data indicate that ribavirin might not only be a good therapeutic agent against porcine nidovirus, but also a potential candidate to be evaluated against other human and animal coronaviruses.


title: The Development of One Health Approaches in the Western Pacific

text: The Western Pacific Region, the most populous of six regional groupings of World Health Organization (WHO) member states, has seen the emergence of a series of novel zoonotic infections in the last decade. This has focused attention on addressing underlying risks and vulnerabilities in the complex interactions among people, animals, and environments as a better way to counter emerging diseases. This “One Health” approach is pertinent to the region because, it is a “hot spot” for the emergence of novel diseases from wildlife, because unexpected epidemics of re-emerging zoonotic diseases have caused morbidity and mortality in urban and periurban communities, and because it remains a sanctuary for well-known zoonotic infections. In this chapter, selected regional, multicountry, and national steps to operationalize One Health are discussed. While the region is well positioned to exploit the opportunities that have come with outbreaks of new diseases, the array of disconnected and overlapping initiatives from various consortia, donors, research institutes, and UN agencies is to some extent impeding the development of better ways of managing both new and old infections for the local, regional, and global good.


title: IMAGING FINDINGS IN 14 DOMESTIC FERRETS (MUSTELA PUTORIUS FURO) WITH LYMPHOMA

text: Lymphoma is the most common malignant neoplasia in domestic ferrets, Mustela putorius furo. However, imaging findings in ferrets with lymphoma have primarily been described in single case reports. The purpose of this retrospective study was to describe imaging findings in a group of ferrets with confirmed lymphoma. Medical records were searched between 2002 and 2012. A total of 14 ferrets were included. Radiographs (n = 12), ultrasound (n = 14), computed tomography (CT; n = 1), and magnetic resonance imaging (MRI; n = 1) images were available for review. Median age at the time of diagnosis was 5.2 years (range 3.25–7.6 years). Clinical signs were predominantly nonspecific (8/14). The time between the first imaging study and lymphoma diagnosis was 1 day or less in most ferrets (12). Imaging lesions were predominantly detected in the abdomen, and most frequently included intra‐abdominal lymphadenopathy (12/14), splenomegaly (8/14), and peritoneal effusion (11/14). Lymphadenopathy and mass lesions were typically hypoechoic on ultrasound. Mild peritoneal effusion was the only detected abnormality in two ferrets. Mild pleural effusion was the most common thoracic abnormality (3/12). Expansile lytic lesions were present in the vertebrae of two ferrets with T3‐L3 myelopathy and the femur in a ferret with lameness. Hyperattenuating, enhancing masses with secondary spinal cord compression were associated with vertebral lysis in CT images of one ferret. The MRI study in one ferret with myelopathy was inconclusive. Findings indicated that imaging characteristics of lymphoma in ferrets are similar to those previously reported in dogs, cats, and humans.


Development of a new detection tool by real time PCR for the detection of Middle East Respiratory Syndrome human Coronavirus (MERS-HCoV) combining specific primers, probe and a RNA internal control ready to use premix


title: Nucleotide Analogues as Inhibitors of Viral Polymerases

text: Coronaviruses such as the newly discovered virus from Wuhan, China, 2019-nCoV, and the viruses that cause SARS and MERS, have resulted in regional and global public health emergencies. Based on our molecular insight that the hepatitis C virus and the coronavirus use a similar viral genome replication mechanism, we reasoned that the FDA-approved drug EPCLUSA (Sofosbuvir/Velpatasvir) for the treatment of hepatitis C will also inhibit the above coronaviruses, including 2019-nCoV. To develop broad spectrum anti-viral agents, we further describe a novel strategy to design and synthesize viral polymerase inhibitors, by combining the ProTide Prodrug approach used in the development of Sofosbuvir with the use of 3’-blocking groups that we have previously built into nucleotide analogues that function as polymerase terminators.


title: Pandémie COVID-19 : impact sur le systeme cardiovasculaire. Données disponibles au 1er avril 2020

text: Résumé Le syndrome respiratoire aigu sévère coronavirus 2 (SARS-CoV-2) infecte les cellules hôtes par les récepteurs de l’angiotensine, conduisant à une pneumonie liée au COVID-19. À un niveau cardiaque, le virus a un double impact ; en effet, l’infection sera plus grave si l’hôte possède des comorbidités cardiovasculaires, et le virus peut causer des lésions cardiovasculaires pouvant engager le pronostic vital. Les thérapeutiques associées au COVID-19 peuvent avoir des effets indésirables cardiovasculaires. Une attention particulière doit être accordée à la protection cardiovasculaire pendant l’infection au COVID-19. Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.


title: Humanitarian Needs: The Arthroplasty Community and the COVID-19 Pandemic

text: Abstract As the world struggles with the COVID-19 pandemic, healthcare providers are on the front lines. Although hip and knee arthroplasty surgeons are not at the center of the epidemic and it may seem our role is limited, there are and will be many opportunities to contribute. During international crises such as these, the less fortunate are the most significantly affected. We highlight the value of humanitarian medical work, contributions of the hip and knee arthroplasty community to date, and future needs following the resolution of the COVID-19 pandemic. We polled members of medical mission group lead by arthroplasty surgeons to understand their efforts and benefits they have received doing humanitarian work. Google Search and PubMed were used to find articles relevant to the current environment of the COVID-19 pandemic. We sought to understand how the arthroplasty community can contribute, based on historical lessons from prior pandemics and recessions, current needs and projections of the COVID-19 impact. We conclude that there will be a great need for humanitarian work, and as in the current time, the immediate need globally may not be in our subspecialty.


title: School’s Out for COVID-19: 50 Ways BCBA Trainees in Special Education Settings Can Accrue Independent Fieldwork Experience Hours During the Pandemic

text: Due to the COVID-19 pandemic and nationwide executive orders closing schools, many trainees completing their supervised independent fieldwork in educational settings lost the ability to accrue hours linked to restricted activities of a therapeutic and instructional nature with students (i.e., clients). Given the impact on trainees of the pandemic restrictions, we present 50 suggestions for trainees in school settings to continue to accrue hours for both restricted and unrestricted activities throughout the course of the COVID-19 pandemic.


title: Isolation and identification of a canine coronavirus strain from giant pandas (Ailuropoda melanoleuca)

text: Two giant pandas (Ailuropoda melanoleuca) died of unknown causes in a Chinese zoo. The clinical disease profile suggested that the pandas may have suffered a viral infection. Therefore, a series of detection including virus isolation, electron microscopy, cytobiological assay, serum neutralization and RT-PCR were used to identify the virus. It was determined that the isolated virus was a canine coronavirus (CCV), on the basis of coronavirus, neutralization by canine anti-CCV serum, and 84.3% to 100% amino acid sequence similarity with CCV. The results suggest that the affected pandas had been infected with CCV.


docid: qkpmlkcf

title: Recombinant nucleocapsid protein is potentially an inexpensive, effective serodiagnostic reagent for infectious bronchitis virus

text: The nucleocapsid protein of the Gray strain of infectious bronchitis virus (IBV) is highly immunogenic and cross-reactive among various distinct serotypes. Recombinant nucleocapsid polypeptide expressed in bacteria with a histidine tag at the amino terminus has been used as antigen for developing an assay to detect IBV-specific antibody. This fusion protein was produced readily in bacteria and easily purified with a nickel column which bound to the histidine tag. Conditions were optimized for using these preparations for an IBV-specific ELISA. Although differences in optical densities could be detected between pre-immune and positive sera for the Ark, Mass, and Gray strains with antigen concentrations between 50 and 0.1 μg per well, the greatest differences could be detected with 3 and 1.5 μg of protein per well. Maximum differences in optical densities between pre-immune and positive sera were obtained using 2.4 μg per well of protein and sera diluted between 1:80 and 1:160. In addition, as little as 30 ng/dot of recombinant nucleocapsid consistently detected IBV-specific sera in immunoblot assays which have convenient field applications.


title: Surveillance of the Middle East respiratory syndrome (MERS) coronavirus (CoV) infection in healthcare workers after contact with confirmed MERS patients: incidence and risk factors of MERS-CoV seropositivity

text: Abstract Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.


title: What happens when we treat the “Typhoid Mary” of COVID‐19

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection was declared a pandemic on 11 March 2020. We have since seen its fast spread worldwide. A likely contributing factor was the lack of symptoms of some of the carriers, making them unaware of their risk of spreading to other more vulnerable individuals. The other important finding has been the reported cases of infectivity despite lack of symptoms. We describe the SARS‐CoV‐2 pneumonia patterns in asymptomatic individuals. The common computed tomography (CT) thorax patterns found are peripheral ground‐glass opacification (GGO) with upper or lower lobe predominance. We believe screening for 2019‐novel coronavirus (COVID‐19) in high‐risk individuals may help identify the patients needing longer follow‐up.


title: Hypoxemia IN COVID-19 Patients: An Hypothesis

text: The current SARS-Cov-2 virus pandemic challenges critical care physicians and other caregivers to find effective treatment for desperately ill patients — especially those with sudden and extreme hypoxemia. Unlike patients with other forms of Acute Respiratory Distress Syndrome, these patients do not exhibit increased lung stiffness or dramatic dyspnea., even in the presence of arterial blood oxygen levels lower than that seen normally in mixed venous blood. Urgent intubation and mechanical ventilation with high inflation pressures and raised inhaled oxygen concentration have proved unhelpful or worse, but why? Our Hypothesis is that sudden opening of a previously undetected probe-patent foramen ovale (PPFO) may explain this mystery. As hypoxemia without acidosis is a rather weak stimulus of dyspnea or increased ventilation, and opening of such an intracardiac shunt would not worsen lung mechanical properties, the absence of dramatic symptom changes would not be surprising. We point out the high frequency of PFO both in life and at autopsy, and the physiological evidence of large shunt fractions found in Covid-19 patients. Published evidence of hypercoagulability and abundant evidence of pulmonary emboli found at autopsy are in accord with our hypothesis, as they would contribute to raised pressure in the pulmonary arteries and right heart chambers, potentially causing a shunt to open. We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein. Search for an open PFO after a large drop in arterial oxygen saturation can be performed at the bedside with a variety of well-established techniques including bedside echocardiography, nitrogen washout test, and imaging studies. Potential treatments might include balloon or patch closure of the shunt, and various drug treatments to lower pulmonary vascular resistance.


title: Introduction: The Structural Basis of Virus Function

text: Viruses may be regarded as dynamic nucleoprotein assemblies capable of assisted multiplication within cells, and of propagation between cells and organisms. Infectious virus particles (virions) assembled in a host cell are dynamic, generally metastable particles: They are robust enough to protect the viral genome outside the cell, but are also poised to undergo structural changes and execute mechanochemical actions required for infection of other cells. This chapter provides an introduction to the structural and physical biology of viruses by including: (i) an elementary overview on virions and the structural basis of virus function; (ii) a concise summary on basic techniques used in structural or physical virology; (iii) brief structure-based general descriptions of the different stages in the virus cycle, especially those in which virions and/or their components are involved. These contents may facilitate a better understanding of the specialized subjects treated in the rest of the book. This chapter is also intended as a “road map” to help interconnect and integrate in a single picture the different topics described in depth in the 21 monographic chapters in this book.


title: Middle East Respiratory Syndrome and Medical Students: Letter from China

text: Objectives: The present study aimed to investigate the knowledge of Middle East Respiratory Syndrome (MERS) among Chinese medical students. Methods: A structured questionnaire on MERS was conducted among 214 medical students in China. Results: The average correction of the single question varied from 36.0% to 89.7%. There is a significant difference on MERS knowledge among different majors of medical students (p < 0.05). Management students scored significantly higher than students of other majors (p < 0.05). Conclusion: Chinese medical students had good knowledge of MERS. The MERS knowledge score varied among students of different majors. Education on disease control should be included in the school curriculum.


title: Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China

text: Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.


title: The pro-inflammatory cytokine 14-3-3ε is a ligand of CD13 in cartilage

text: Osteoarthritis is a whole-joint disease characterized by the progressive destruction of articular cartilage involving abnormal communication between subchondral bone and cartilage. Our team previously identified 14-3-3ε protein as a subchondral bone soluble mediator altering cartilage homeostasis. The aim of this study was to investigate the involvement of CD13 (also known as aminopeptidase N, APN) in the chondrocyte response to 14-3-3ε. After identifying CD13 in chondrocytes, we knocked down CD13 with small interfering RNA (siRNA) and blocking antibodies in articular chondrocytes. 14-3-3ε-induced MMP-3 and MMP-13 was significantly reduced with CD13 knockdown, which suggests that it has a crucial role in 14-3-3ε signal transduction. Aminopeptidase N activity was identified in chondrocytes, but the activity was unchanged after stimulation with 14-3-3ε. Direct interaction between CD13 and 14-3-3ε was then demonstrated by surface plasmon resonance. Using labeled 14-3-3ε, we also found that 14-3-3ε binds to the surface of chondrocytes in a manner that is dependent on CD13. Taken together, these results suggest that 14-3-3ε might directly bind to CD13, which transmits its signal in chondrocytes to induce a catabolic phenotype similar to that observed in osteoarthritis. The 14-3-3ε–CD13 interaction could be a new therapeutic target in osteoarthritis.


Essentials for Radiologists on COVID-19: An Update—Radiology Scientific Expert Panel


title: Identifying inhibitors of the SARS coronavirus proteinase

text: Abstract The Severe Acute Respiratory Syndrome (SARS) is a serious respiratory illness that has recently been reported in parts of Asia and Canada. In this study, we use molecular dynamics (MD) simulations and docking techniques to screen 29 approved and experimental drugs against the theoretical model of the SARS CoV proteinase as well as the experimental structure of the transmissible gastroenteritis virus (TGEV) proteinase. Our predictions indicate that existing HIV-1 protease inhibitors, l-700,417 for instance, have high binding affinities and may provide good starting points for designing SARS CoV proteinase inhibitors.


title: ESMO Management and treatment adapted recommendations in the COVID-19 era: Pancreatic Cancer

text: The COVID-19 pandemic is challenging the capacities of health systems in many countries. National healthcare services have to manage unexpected shortages of healthcare resources that have to be re-allocated according to the principles of fair and ethical prioritisation, in order to maintain the highest levels of care to all patients, ensure the safety of patients and healthcare workers, and save as many lives as possible. Also, cancer care services have to pursue restructuring, following the same evidence-based dispositions. In this article, we propose a guidance to the management of pancreatic cancer during the pandemic, prioritised according to a three-tiered framework, and based on expert clinical judgement and magnitude of benefit expected from specific interventions. Since the availability of resources for diagnostic procedures, surgery and postoperative care, systemic therapy and radiotherapy may differ, the authors have separated the prioritisation analyses. The impact of postponing or abrogating cancer interventions on outcomes according to a high, medium or low priority scale is outlined and discussed. The implementation of healthcare services using telemedicine is explored; it reveals itself as functional and effective for limiting patients’ need to travel to centres and thereby has the potential to reduce diffusion of SARS-CoV-2. Pancreatic cancer demands a considerable amount of medical resources. Therefore, the redefinition of its diagnostic and therapeutic algorithms with a rigorous method is crucial in order to ensure the highest quality of continuum of care in the broader context of the pandemic and the challenged healthcare systems.


title: West Nile Virus Infection Causes Endocytosis of a Specific Subset of Tight Junction Membrane Proteins

text: West Nile virus (WNV) is a blood-borne pathogen that causes systemic infections and serious neurological disease in human and animals. The most common route of infection is mosquito bites and therefore, the virus must cross a number of polarized cell layers to gain access to organ tissue and the central nervous system. Resistance to trans-cellular movement of macromolecules between epithelial and endothelial cells is mediated by tight junction complexes. While a number of recent studies have documented that WNV infection negatively impacts the barrier function of tight junctions, the intracellular mechanism by which this occurs is poorly understood. In the present study, we report that endocytosis of a subset of tight junction membrane proteins including claudin-1 and JAM-1 occurs in WNV infected epithelial and endothelial cells. This process, which ultimately results in lysosomal degradation of the proteins, is dependent on the GTPase dynamin and microtubule-based transport. Finally, infection of polarized cells with the related flavivirus, Dengue virus-2, did not result in significant loss of tight junction membrane proteins. These results suggest that neurotropic flaviviruses such as WNV modulate the host cell environment differently than hemorrhagic flaviviruses and thus may have implications for understanding the molecular basis for neuroinvasion.


title: Mouse models with human immunity and their application in biomedical research

text: Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)(null) mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Rag(null) mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.


title: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study

text: BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK–CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3 862 012 individuals (1 957 935 [50·7%] women and 1 904 077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41–4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1·5, 36 749 with an RR of 2·0, and 73 498 with an RR of 3·0. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1·5, 293 991 with an RR of 2·0, and 587 982 with an RR of 3·0. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.


title: Structural proteins of human respiratory coronavirus OC43

text: Abstract The human respiratory coronavirus OC43 was grown on a human rectal tumor cell line and was isotopically labeled with amino acids, glucosamine, and orthophosphate to analyze virion structural proteins. Four major protein species were resolved by electrophoresis and many of their properties were deduced from digestion studies using proteolytic enzymes. The four proteins are: (1) A 190 kDa protein, the presumed peplomeric protein, that was glycosylated and proteolytically cleavable by trypsin into subunits of 110 and 90 kDa. The subunits each represent a different amino acid sequence on the basis of peptide mapping; (2) a 130 kDa protein that was glycosylated and behaved as a disulfide-linked dimer of 65 kDa molecules. It is the apparent virion hemagglutinin on the basis of digestion studies with trypsin, bromelain and pronase; (3) a 55 kDa nucleocapsid protein that was phosphorylated; (4) a 26 kDa matrix protein that was glycosylated. The 190, 130, 55 and 26 kDa species can therefore be designated P, H, N and M, respectively. They exist in molar ratios of 4:1: 33 : 33, and are calculated to be present at the rate of 88, 22, 726, and 726 molecules per virion, respectively.


title: Methylene chloride: A two-year inhalation toxicity and oncogenicity study in rats and hamsters()

text: A long-term study was conducted to determine the possible chronic toxicity and oncogenicity of methylene chloride. Rats and hamsters were exposed by inhalation to 0, 500, 1500, or 3500 ppm of methylene chloride for 6 hr per day, 5 days a week, for 2 years. No exposure-related cytogenetic effects were present in male or female rats exposed to 500, 1500, or 3500 ppm. Females rats exposed to 3500 ppm had an increased mortality rate while female hamsters exposed to 1500 or 3500 ppm had decreased mortality rates. Carboxyhemoglobin values were elevated in rats and hamsters exposed to 500, 1500, or 3500 ppm with the percentage increase in hamsters greater than in rats. Minimal histopathologic effects were present in the livers of rats exposed to 500, 1500, or 3500 ppm. Decreased amyloidosis was observed in the liver and other organs in hamsters exposed to 500, 1500, or 3500 ppm. While the number of female rats with a benign tumor was not increased, the total number of benign mammary tumors was increased in female rats in an exposure-related manner. This effect was also evident in male rats in the 1500- and 3500-ppm exposure groups. Finally, male rats exposed to 1500 or 3500 ppm had an increased number of sercomas in the ventral neck region located in or around the salivary glands. Therefore, in this 2-year study, some effects were observed in male and female rats exposed to 500, 1500, or 3500 ppm of methylene chloride. In contrast, hamsters exposed to the same exposure concentrations had less extensive spontaneous geriatric changes, decreased mortality (females), and lacked evidence of definite target organ toxicity.


title: Treatment of Common Cold Patients with the Shi-Cha Capsule: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Trial

text: This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.


title: Brome Mosaic Virus

text: Brome mosaic virus (BMV) is an isometric, nonenveloped positive-strand RNA virus and a well-studied, representative member of the alphavirus-like superfamily of human, animal, and plant viruses. BMV has been extensively studied as a model for viral RNA replication, gene expression, virus–host interactions, recombination, and encapsidation. Through contributions by many different groups, these studies have not only advanced understanding of BMV, but have also revealed insights and principles extending to many other viruses and to general cellular biology. Among other advances, BMV was used to define the first ribosome binding sites in eukaryotic mRNAs, and to produce the first template-selective eukaryotic viral RNA-dependent RNA polymerase extract, the first infectious transcripts from cloned RNA virus cDNA, the first engineered RNA virus expression vectors expressing foreign genes, the first definition of subgenomic mRNA synthesis pathways and determinants, and the first demonstration of higher eukaryotic viral replication in yeast. BMV has also contributed many insights into virion assembly, virus–host interactions, RNA recombination, and RNA replication, including parallels in the replication of positive-strand RNA, reverse-transcribing, and dsRNA viruses. This article reviews the major features of the virus and selected aspects of these and other advances with BMV.


title: COVID-19. La historia se repite y seguimos tropezando con la misma piedra

text: The COVID-19 pandemic has caused a mismatch in all health systems. Most countries had forgotten how to behave in the face of such an epidemic without adequate resources. We need to take stock of everything that has happened, instruct the population and generate a new knowledge that allows us to face new epidemics.


title: Spreading of canine parvovirus type 2c mutants of Asian origin in southern Italy

text: Canine parvovirus type 2 (CPV‐2) emerged as dog pathogen in the late 1970s, causing severe and often fatal epizootics of gastroenteritis in the canine population worldwide. Although to date CPV‐2 is circulating in all continents, most of the current studies have analysed the amino acid changes accounted in the VP2 gene sequence, with limited information on virus introductions from other countries. The aim of this study was to analyse the genetic features of CPV‐2c strains currently spreading in Italy. Swabs and tissue samples were collected from dogs suspected of CPV infection. The nearly complete genome sequence from the CPV‐positive samples was obtained. The co‐circulation of two different but related CPV‐2c strains, with amino acid changes characteristic of CPV strains of Asian origin (NS1: 60V, 544F, 545F, 630P – NS2: 60V, 151N, 152V ‐ VP2: 5A/G, 267Y, 297A, 324I, 370R), were observed. The phylogenetic analyses inferred from the NS1 and VP2 gene sequences confirmed the relationship with Asian CPV‐2c strains. This study reports the spread of novel CPV‐2c mutants in Italy and supports further studies to evaluate the coexistence of genetically divergent CPV strains in the same geographical environment.


The risk of hand eczema in healthcare workers during the COVID‐19 pandemic: Do we need specific attention or prevention strategies?


title: 1,000,000 cases of COVID-19 outside of China: The date predicted by a simple heuristic

text: Abstract We forecast 1,000,000 COVID-19 cases outside of China by March 30, 2020 based on a heuristic and WHO situation reports. We do not model the COVID-19 pandemic; we model only the number of cases. The proposed heuristic is based on a simple observation that the plot of the given data is well approximated by an exponential curve. The exponential curve is used for forecasting the growth of new cases. It has been tested for the last situation report of the last day. Its accuracy has been 1.29% for the last day added and predicted by the 57 previous WHO situation reports (the date 18 March 2020). Prediction, forecast, pandemic, COVID-19, coronavirus, exponential growth curve parameter, heuristic, epidemiology, extrapolation, abductive reasoning, WHO situa- tion report.


Definition of emerging infectious diseases


Will Covid‐19 change attitudes towards the welfare state?


Theme: information on the Covid-19 Pandemic


title: Husbandry of Dairy Animals | Buffalo: Mediterranean Region

text: The buffaloes reared in the Mediterranean region are the Asian buffalo or water buffalo, that is, Bubalus bubalis. This species includes two types: (1) the river type, with 50 chromosomes, with an adult male weighing between 450 and 1000kg and with an annual milk production of 1000–3000kg; and (2) the swamp type, with 48 chromosomes, with an adult male weighing between 325 and 450kg and with an annual milk production of up to 600kg. The river buffalo is reared mainly for milk, whereas the swamp buffalo is reared mainly for draught. Only 3% of the world buffalo population is reared in the Mediterranean region. Significant numbers of buffaloes are at present found only in Italy, Romania, Egypt, Turkey, Azerbaijan, Iraq and Iran. In all these countries, buffaloes represent only a very small portion of total livestock, except in Egypt, where buffaloes are more numerous than cattle. Because of the strong market demand for buffalo cheese, the number of buffaloes has increased in Italy and there is a preference for buffalo dairy products compared to cows’ milk products in a few countries. Major morphological differences between the buffalo populations of different countries include (1) the variable size, ranging between a minimum of 280 and 300kg liveweight for adult females and males, respectively, in Egypt to a maximum of 900 and 1000kg in Iraq, the most frequent weights being 600 and 800kg; (2) the shape of the horns; and (3) the coat color, from dark gray and dark brown to black, showing white spots in some cases.


title: Chinese herbs in treatment of influenza: A randomized, double-blind, placebo-controlled trial

text: Summary Objective To investigate the efficacy and safety of Antiwei, a traditional Chinese prescription, in the treatment of influenza. Methods In a multi-center, randomized, double-blind, placebo-controlled trial, we recruited 480 adults aged 18 to 65 years within 36 h of onset of influenza-like symptoms. There were 225 patients with confirmed influenza. Eligible patients were randomly assigned 6 g of Antiwei (n = 360) or placebo (n = 120) twice daily for three days. All patients recorded their temperature and symptoms on diary cards during treatment. Analyses were performed in both the influenza-like population and the influenza-confirmed population. Results Antiwei increased patients’ recovery by 17% (P < 0.001), and reduced the severity of illness measured by the median symptom score by 50% (P < 0.001) in both the influenza-like and the influenza-confirmed populations, compared to placebo. The influenza-confirmed patients reported reductions in the severity of fever (P = 0.002), cough (P = 0.023) and expectoration (P = 0.004) after one-day of treatment with Antiwei, compared to placebo. The adverse event profiles were similar for Antiwei and placebo. Conclusion Antiwei was effective and well tolerated in treatment of natural influenza infection in adults. Antiwei represents a clinically valuable intervention in the management of influenza.


title: Reverse Transcription Cross-Priming Amplification–Nucleic Acid Test Strip for Rapid Detection of Porcine Epidemic Diarrhea Virus

text: Porcine epidemic diarrhea virus (PEDV) is a highly transmissible coronavirus that causes a severe enteric disease particularly in neonatal piglets. In this study, a rapid method for detecting PEDV was developed based on cross-priming amplification and nucleic acid test strip(CPA-NATS). Five primers specific for the N gene sequence of PEDV were used for the cross-priming amplification. Detection of amplification products based on labeled probe primers was conducted with strip binding antibody of labeled markers. The CPA method was evaluated and compared with a PCR method. The reverse transcription CPA system was further optimized for detecting PEDV RNA in clinical specimens. Results showed that the method was highly specific for the detection of PEDV, and had the same sensitivity as PCR, with detection limit of 10(−6) diluted plasmid containing the target gene of PEDV. It was also successfully applied to detecting PEDV in clinical specimens. The reverse transcription CPA-NATS detection system established in this study offers a specific, sensitive, rapid, and simple detection tool for screening PEDV, which can contribute to strategies in the effective control of PEDV in swine.


title: Influenza A Virus Infections in Dromedary Camels, Nigeria and Ethiopia, 2015–2017

text: We examined nasal swabs and serum samples acquired from dromedary camels in Nigeria and Ethiopia during 2015–2017 for evidence of influenza virus infection. We detected antibodies against influenza A(H1N1) and A(H3N2) viruses and isolated an influenza A(H1N1)pdm09–like virus from a camel in Nigeria. Influenza surveillance in dromedary camels is needed.


title: Unequal impact of structural health determinants and comorbidity on COVID-19 severity and lethality in older Mexican adults: Considerations beyond chronological aging

text: BACKGROUND: COVID-19 has had a disproportionate impact on older adults. Mexico's population is younger, yet COVID-19’s impact on older adults is comparable to countries with older population structures. Here, we aim to identify health and structural determinants that increase susceptibility to COVID-19 in older Mexican adults beyond chronological aging. METHODS: We analyzed confirmed COVID-19 cases in older adults using data from the General Directorate of Epidemiology of Mexican Ministry of Health. We modeled risk factors for increased COVID-19 severity and mortality, using mixed models to incorporate multilevel data concerning healthcare access and marginalization. We also evaluated structural factors and comorbidity profiles compared to chronological age for COVID-19 mortality risk prediction. RESULTS: We analyzed 20,804 confirmed SARS-CoV-2 cases in adults aged ≥60 years. Male sex, smoking, diabetes, and obesity were associated with pneumonia, hospitalization and ICU admission in older adults, CKD and COPD were associated with hospitalization. High social lag indexes and access to private care were predictors of COVID-19 severity and mortality. Age was not a predictor of COVID-19 severity in individuals without comorbidities and combination of structural factors and comorbidities were better predictors of COVID-19 lethality and severity compared to chronological age alone. COVID-19 baseline lethality hazards were heterogeneously distributed across Mexican municipalities, particularly when comparing urban and rural areas. CONCLUSIONS: Structural factors and comorbidity explain excess risk for COVID-19 severity and mortality over chronological age in older Mexican adults. Clinical decision-making related to COVID-19 should focus away from chronological aging onto more a comprehensive geriatric care approach.


title: A perspective on microarrays: current applications, pitfalls, and potential uses

text: With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold.


title: Molecular insight into the therapeutic potential of phytoconstituents targeting protein conformation and their expression

text: Abstract Background Native protein conformation is essential for the functional activity of the proteins and enzymes. Defects in conformation or alterations in expression of the proteins have been reported in various diseases. Purpose The aim of this study is to review the molecular insight into the therapeutic potential of phytoconstituents targeting protein conformations or expressions. Methods Published literatures were searched in PubMed, Scopus, Web of Science; Article published till Dec 2017 were extracted. The literature was assessed from the Central University of Rajasthan, India. Present study evaluate article based on the role of active plant constituents on the conformation and expression of the different proteins. Results Plant components play their role either at the molecular level or cellular level and exhibit antibacterial, antiviral, anti-neurodegenerative and other activities. Plant active compounds isolated from different plants may either stabilize or destabilize the conformation of proteins or alter expression level of the protein involved in these diseases, therefore, can play a significant role in preventing diseases caused by the alteration in these proteins. Conclusion In the present article, we have reviewed the molecular mechanism of plant active compounds, their target proteins, methods of extraction and identification, and their biological significances. Therefore, a proper understanding of the effect of these herbal molecules on the concerned proteins may help to develop new herbal-based therapeutics for various diseases.


title: Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome

text: BACKGROUND: During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance. METHODS: Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test. RESULTS: Eight patients (age range 7–14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses. CONCLUSIONS: Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.


title: Pre-Clinical and Clinical Efficiency of Complexes of Oligoribonucleotides with D-Mannitol against Respiratory Viruses

text: Oligoribonucleotides-D-mannitol (ORNs-D-M) complexes possess antiviral, anti-inflammatory, and immunomodulatory actions. The aim of the present study was to evaluated an antiviral effect of ORNs-D-M against parainfluenza virus type 3 (PIV3); influenza CA709, PR834; avian influenza virus H5N2 (AIV) in vitro by a TCID(50); hemadsorption and neuraminidase activity assays; and clinical efficiency of ORNs-D-M in patients with acute respiratory infections (ARIs) of various etiologies by PCR assay and AmpliSens test systems. It was observed that ORNs-D-M have an antiviral activity against the influenza CA709, PR834, PIV3, and AIV in vitro. The injectable dosage form of ORNs-D-M was shown to have a stronger antiviral effect compared to capsule form. It was also detected that the injectable form of ORNs-D-M significantly reduced the neuraminidase activity of influenza PR834. A complex treatment of patients with ORNs-D-M had a positive effect on the course of the disease, it accelerated patients’ recovery. Treatment with ORNs-D-M caused eradication of adeno- and influenza viruses in patients with ARI. This drug contributed to significant decrease in duration of febrile period and cough. Comprehensive treatment with ORNs-D-M improved the disease clinical findings significantly. Collectively, these results suggested that ORNs-D-M may be used at co-infection with influenza and other respiratory viruses as a medical antiviral drug.


Plexiglass barrier box to improve ERCP safety during the COVID-19 pandemic


title: When do children need kidney replacement therapy?

text: Kidney replacement therapy (KRT) can provide lifesaving support for children with severely impaired kidney function. The decision about who needs KRT and when is often complex. Many acute kidney problems will resolve with conservative maanagemenent but some children with chronic or acute kidney impairment will find themselves in a position where KRT is required either as a bridge to recovery or kidney transplantation. Less commonly, children with metabolic disorders may find that the ability of their own kidneys is overwhelmed by excessive production of certain metabolites. These children may also benefit from short term KRT. This article aims to help paediatricians in training understand which children need kidney replacement therapy, the various types of treatment available, and when they are used.


title: COVID‐19 Lockdown induced acral dermatosis in children

text: Recently, several case series of cutaneous acral manifestations in patients with suspected or confirmed coronavirus disease 2019 (COVID‐19) have been reported. A majority of these acral manifestations have a pseudo‐chilblain pattern with erythema and oedema and sometimes vesicles.


title: Mitigation of emerging implications of climate change on food production systems

text: Abstract Crops, livestock and seafood are major contributors to global economy. Agriculture and fisheries are especially dependent on climate. Thus, elevated temperatures and carbon dioxide levels can have large impacts on appropriate nutrient levels, soil moisture, water availability and various other critical performance conditions. Changes in drought and flood frequency and severity can pose severe challenges to farmers and threaten food safety. In addition, increasingly warmer water temperatures are likely to shift the habitat ranges of many fish and shellfish species, ultimately disrupting ecosystems. In general, climate change will probably have negative implications for farming, animal husbandry and fishing. The effects of climate change must be taken into account as a key aspect along with other evolving factors with a potential impact on agricultural production, such as changes in agricultural practices and technology; all of them with a serious impact on food availability and price. This review is intended to provide critical and timely information on climate change and its implications in the food production/consumption system, paying special attention to the available mitigation strategies.


Case Report: Fever Unmasking Brugada-pattern ECG in Patient with Coronavirus Disease 2019 (COVID-19)


title: Rhinovirus‐associated pulmonary exacerbations show a lack of FEV (1) improvement in children with cystic fibrosis

text: BACKGROUND: Respiratory viral infections lead to bronchial inflammation in patients with cystic fibrosis, especially during pulmonary exacerbations. The aim of this study was to determine the impact of viral‐associated pulmonary exacerbations in children with cystic fibrosis and failure to improve forced expiratory volume in 1 s (FEV (1)) after an appropriate treatment. METHODS: We lead a pilot study from January 2009 until March 2013. Children with a diagnosis of cystic fibrosis were longitudinally evaluated three times: at baseline (Visit 1), at the diagnosis of pulmonary exacerbation (Visit 2), and after exacerbation treatment (Visit 3). Nasal and bronchial samples were analyzed at each visit with multiplex viral respiratory PCR panel (qualitative detection of 16 viruses). Pulmonary function tests were recorded at each visit, in order to highlight a possible failure to improve them after treatment. Lack of improvement was defined by an increase in FEV (1) less than 5% between Visit 2 and Visit 3. RESULTS: Eighteen children were analyzed in the study. 10 patients failed to improve by more than 5% their FEV (1) between Visit 2 and Visit 3. Rhinovirus infection at Visit 2 or Visit 3 was the only risk factor significantly associated with such a failure (OR, 12; 95% CI, 1·3–111·3), P = 0·03. CONCLUSIONS: Rhinovirus infection seems to play a role in the FEV (1) recovery after pulmonary exacerbation treatment in children with cystic fibrosis. Such an association needs to be confirmed by a large‐scale study because this finding may have important implications for pulmonary exacerbation management.


title: Well‐Being and Education of Urology Residents During the COVID‐19 Pandemic: Results of an American National Survey

text: BACKGROUND: The rapid spread of COVID‐19 has placed tremendous strain on the American healthcare system. Few prior studies have evaluated the well‐being of or changes to training for American resident physicians during the COVID‐19 pandemic. We aim to study predictors of trainee well‐being and changes to clinical practice using an anonymous survey of American urology residents. METHODS: An anonymous, voluntary, 47‐question survey was sent to all ACGME‐accredited urology programs in the United States. We executed a cross‐sectional analysis evaluating risk factors of perception of anxiety and depression both at work and home and educational outcomes. Multiple linear regressions models were used to estimate beta coefficients and 95% confidence intervals. RESULTS: Among approximately 1,800 urology residents in the USA, 356 (20%) responded. Among these respondents, 24 had missing data leaving a sample size of 332. Important risk factors of mental health outcomes included perception of access to PPE, local COVID‐19 severity, and perception of susceptible household members. Risk factors for declination of redeployment included current redeployment, having children, and concerns regarding ability to reach case minimums. Risk factors for concern of achieving operative autonomy included cancellation of elective cases and higher level of training. CONCLUSIONS: Several potential actions, which could be taken by urology residency program directors and hospital administration, may optimize urology resident well‐being, morale, and education. These include advocating for adequate access to PPE, providing support at both the residency program and institutional levels, instituting telehealth education programs, and fostering a sense of shared responsibility of COVID‐19 patients.


title: Prior knowledge in learning from a non-linear electronic document: Disorientation and coherence of the reading sequences

text: Abstract A study was carried out to investigate the effects of prior knowledge on learning with a non-linear electronic document including an interactive conceptual map. Cognitive Load Theory was used as theoretical framework to investigate effects on cognitive load and disorientation in learning from non-linear documents. Forty-four future high school biology teachers were required to learn the multiplication cycle of a virus from either a hierarchical structure (organisational links) or a network structure (relational links). For the low prior knowledge learners, the results showed that the hierarchical structure supported better free recall performance and reduced feelings of disorientation. In contrast, the high prior knowledge learners performed better and followed more coherent reading sequences in the network structure. However, no interaction effect between prior knowledge and the type of structure was observed on mental effort and disorientation ratings. The results and the construct of disorientation are discussed in light of the processing demands in non-linear documents.