title: Recomendações para realização de anestesia loco-regional durante a pandemia de COVID-19

text: Resumen Desde o início da pandemia de COVID-19, muitas questões surgiram referentes à segurança do manejo anestésico de pacientes acometidos pela doença. A anestesia regional, seja esta periférica ou neuroaxial, é alternativa segura no manejo do paciente COVID-19, desde que o emprego de modalidades que minimizam o comprometimento da função pulmonar seja escolhido. A adoção desta técnica anestésica minimiza os efeitos adversos no pós-operatório e oferece segurança para o paciente e equipe, desde que sejam respeitados os cuidados com proteção individual e de contágio interpessoal. Respeito às contraindicações e emprego criterioso das técnicas e normas de segurança são fundamentais. Este manuscrito tem por objetivo revisar as evidências disponíveis sobre anestesia regional em pacientes com COVID-19 e oferecer recomendações práticas para sua realização segura e eficiente. Abstract Since the beginning of the COVID-19 pandemic, many questions have come up regarding safe anesthesia management of patients with the disease. Regional anesthesia, whether peripheral nerve or neuraxial, is a safe alternative for managing patients with COVID-19, by choosing modalities that mitigate pulmonary function involvement. Adopting regional anesthesia mitigates adverse effects in the post-operative period and provides safety to patients and teams, as long as there is compliance with individual protection and interpersonal transmission care measures. Respecting contra-indications and judicial use of safety techniques and norms are essential. The present manuscript aims to review the evidence available on regional anesthesia for patients with COVID-19 and offer practical recommendations for safe and efficient performance.


title: Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments

text: The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.


title: Convalescent plasma: A possible treatment of COVID-19 in India

text: In India, SARS-CoV-2 virus–induced coronavirus disease 2019 (COVID-19) has already infected close to 5500 people, causing the death of 164. While these numbers are not comparable with values observed for the USA, Italy, or Spain, given the population of India, and the fact that the pandemic is now in an exponential stage of growth, the risks of a contagion that affects a large sector of the Indian population are real. There are no current effective strategies to prevent the spread, other than minimizing contact through social distancing, while no fully effective drugs to prevent or treat COVID-19 exist, although several candidate drugs and repurposed antiviral and immune-modulating pharmacotherapies are being tested or in compassionate use. One postexposure prophylaxis, convalescent (immune) plasma (CP), has shown some success in China and previously in the cure and therapy of other coronaviruses, SARS-1 and Middle East respiratory syndrome. Drawn from current patients who are infected with COVID-19, its CP (human anti–SARS-CoV-2 plasma) might be one way to modulate the infectivity of this virus or its effects postinfection.


title: Serum antibody responses of neonatal and young adult pigs to transmissible gastroenteritis coronavirus

text: Abstract Serum titers of virus-neutralizing (VN) antibody were 10 to 16 times higher in neonatal pigs than in young adult pigs, after single oral doses of virulent transmissible gastroenteritis virus (TGEV). To determine the reason for this higher response, sera from neonatal and young adult pigs, 18 to 21 days after exposure to TGEV, were collected and assayed for VN antibody by plaque reduction. In addition, sera of VN-positive and VN-negative neonatal pigs were analyzed for immunoglobulin classes by radial immunodiffusion technique. The competence of neonatal pigs to produce VN antibody with increased IgG levels was demonstrated. The higher antibody response seen in neonatal pigs, when compared to sera of young adult pigs, may be attributed to the increased replication of TGEV in the intestinal tracts of neonatal pigs or to the lack of other immunogens that may interfere or compete with the production of specific antibody.


Etoposide treatment adjunctive to immunosuppressants for critically ill COVID-19 patients: Etoposide for severe COVID-19 patients


title: The association of Streptococcus equi subsp. zooepidemicus with canine infectious respiratory disease

text: Abstract Canine infectious respiratory disease (CIRD) is a multi-factorial infection that affects many kennelled dogs despite the wide use of vaccination. Current vaccines aim to protect against viral agents and a single bacterial agent, Bordetella bronchiseptica. We sought to examine the role of streptococcal species in CIRD. The isolation and identification of streptococci in the lower respiratory tract of clinically healthy dogs and those with CIRD were used to correlate the presence of specific streptococcal species with respiratory disease. In this study we report that the presence of S. equi subsp. zooepidemicus is associated with increasing severity of disease in a population of kennelled dogs with endemic CIRD.


title: Epidemiology and phylogenetic analysis of respiratory viruses from 2012 to 2015 – A sentinel surveillance report from union territory of Puducherry, India

text: Abstract Background Acute respiratory infections (ARI) are the most common illnesses affecting people of all ages worldwide. Viruses contribute to 30–70% of acute respiratory infections. Identification of these respiratory viruses is not given high priority except influenza; however, the knowledge about prevalence of non-influenza viruses, their seasonal pattern and genetic evolution have significant epidemiological value. Methods As a part of National Influenza-like illness surveillance programme, respiratory specimens were collected children and adults with symptoms of ILI or ARI, between January 2012 and March 2015 (including SARI cases). Real-time PCR was done to identify 13 respiratory viruses. Sequencing was done for representative isolates of each virus using ABI 3730 Genetic Analyzer. Results During the study period between January 2012 and March 2015, a total of 648 patients with symptoms of ARI were included in this study. The mean age of the patients was 20.2 years (SD = 19.13, median = 18); 292 (45.1%) were children (≤13 years) and 356 (54.9%) were adults. Respiratory viruses were identified in 44% (287/648) of all patients. Influenza accounted for the maximum number of cases- 179/648 (27.6%). Among the non-influenza viruses, RSV predominated with 34 cases (5.2%), followed by HMPV 24 (3.7%) and PIV-3 20 (3%). Four patients died due to INF A/H1N1 as a result of acute respiratory distress syndrome (ARDS) (CFR 3.7%). Among the non-influenza viruses, no particular seasonality pattern was observed over the different months of the study period. Conclusion Antibiotic usage in treating acute respiratory infections empirically is not justified as nearly half of ARI are due to viruses; nearly 28% of them were due to influenza viruses. Among the non-influenza viruses, RSV predominated, followed by HMPV. This study is based on an active influenza surveillance initiated after 2009 pandemic influenza outbreak, in the Union territory of Puducherry which has contributed significantly to the knowledge of the burden of influenza and non-influenza viruses among children and adults. Such surveillance network has paved the way for better diagnosis and timely therapeutic interventions.


title: Presepsin as a predictive biomarker of severity in COVID‐19: a case series

text: Guidelines for the diagnosis and treatment of the novel coronavirus disease 2019 (COVID‐19) present clear criteria, including respiratory rate, hemoglobin oxygen saturation (SaO(2)), and oxygenation indicator (PaO(2)/FiO(2))(1). This article is protected by copyright. All rights reserved.


Towards treatment of viral pathogenesis


title: Mental health problems faced by healthcare workers due to the COVID-19 pandemic- a review

text: • The current review was done to conduct systematic appraisal of studies conducted on Mental health problems faced by healthcare workers due to the COVID-19 pandemic. • Out of 23 articles selected by initial screening 6 original articles were included in the final review. • Review of all the 6 articles showed that several socio-demographic variables like gender, profession, age, place of work, department of work and certain psychological variables like poor social support, self-efficacy were found to be associated with increased reporting of stress, anxiety, depressive symptoms, insomnia in HCW. • There is increasing evidence which suggests that COVID-19 can be an independent risk factor for stress in HCW.


title: Clinical performance of different SARS‐CoV‐2 IgG antibody tests

text: SARS‐CoV‐2 serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is limited data on how commercially available tests perform with real patient samples and if positive tested samples show neutralizing abilities. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS‐CoV‐2 IgG and Vircell COVID‐19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID‐19 IgG/IgM Rapid Test Device) and two in‐house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR‐diagnosed with COVID‐19. Most of the SARS‐CoV‐2 samples were from individuals with moderate to severe clinical course, who required an in‐patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5‐9) and from 93.8 to 100% for the later period (days 10‐18). With exception of one sample, all positive tested COVID‐19 follow up‐samples, using the commercially available assays examined (including the in‐house developed IFA), demonstrated neutralizing properties in the PRNT. Regarding specificity, some samples of endemic coronavirus (HCoV‐OC43, HCoV‐229E) and Epstein Barr virus (EBV) infected individuals cross‐reacted in the ELISA assays and IFA, in one case generating a false positive result. This article is protected by copyright. All rights reserved.


Youth in a viral age: a collated auto‐ethnographic response by young people (dis)orientated in strange times


title: Acute Effusive Pericarditis: A Late Complication of COVID-19

text: As the COVID-19 pandemic evolves, the medical community continues to discover novel clinical manifestations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Often, extrapulmonary manifestations occur simultaneously with pulmonary disease. However, there is a paucity of literature describing the cardiac manifestations of COVID-19 in the absence of pulmonary findings. We report a rare case of acute pericarditis presenting with pericardial effusion and cardiac tamponade in a 43-year-old man diagnosed with COVID-19. This case emphasizes the importance of continued investigation regarding diagnosis and treatment of COVID-19 and its related symptoms.


title: Interplay between mutational and horizontally acquired resistance mechanisms and its association with carbapenem resistance amongst extensively drug-resistant Pseudomonas aeruginosa (XDR-PA)

text: Abstract Between 2003 and 2009, the prevalence of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) increased significantly in northern Taiwan from 1.0% to 2.1%. Molecular methods were used to investigate the genetic relatedness and carbapenem resistance mechanisms of a collection of 203 non-repetitive XDR-PA isolates available for study. Using pulsed-field gel electrophoresis (PFGE), 52 genotypes were observed; one predominant genotype (pulsotype 1) was found in 57.6% of the isolates. Polymerase chain reaction (PCR), sequencing and quantitative reverse-transcriptase PCR analyses demonstrated that one horizontally acquired mechanism [metallo-β-lactamase (MBL) genes] and two mutational mechanisms (efflux and porins) accounted for the carbapenem resistance. The most predominant horizontally acquired mechanism was carriage of bla VIM-3, which was found in 61.1% of isolates. Decreased expression of oprD was the most prevalent mutational mechanism and was found in 70.0% of the XDR-PA isolates, whereas overexpression of mexA was found in 27.6% of the isolates. The highlight of this study was the discovery of statistically significant relationships between certain horizontally acquired and mutational resistance mechanisms and their contribution to carbapenem susceptibility. MBL-producers expressed significantly lower MexAB and higher OprD than non-MBL-producers. Amongst isolates without an acquired β-lactamase gene, oprD expression was significantly reduced, whilst expression of efflux pumps was increased. Reduced OprD expression alone or the production of VIM-type MBLs showed similar contributions to a low to intermediate MIC50 (minimum inhibitory concentration for 50% of the organisms) for carbapenems. Isolates with reduced OprD expression that simultaneously harboured bla VIM exhibited high levels of resistance to carbapenems, which implied that these two mechanisms had a synergistic effect on the MICs.


title: The evolution of HIV: Inferences using phylogenetics

text: Abstract Molecular phylogenetics has revolutionized the study of not only evolution but also disparate fields such as genomics, bioinformatics, epidemiology, ecology, microbiology, molecular biology and biochemistry. Particularly significant are its achievements in population genetics as a result of the development of coalescent theory, which have contributed to more accurate model-based parameter estimation and explicit hypothesis testing. The study of the evolution of many microorganisms, and HIV in particular, have benefited from these new methodologies. HIV is well suited for such sophisticated population analyses because of its large population sizes, short generation times, high substitution rates and relatively small genomes. All these factors make HIV an ideal and fascinating model to study molecular evolution in real time. Here we review the significant advances made in HIV evolution through the application of phylogenetic approaches. We first examine the relative roles of mutation and recombination on the molecular evolution of HIV and its adaptive response to drug therapy and tissue allocation. We then review some of the fundamental questions in HIV evolution in relation to its origin and diversification and describe some of the insights gained using phylogenies. Finally, we show how phylogenetic analysis has advanced our knowledge of HIV dynamics (i.e., phylodynamics).


title: Consecutive pathological and immunological alterations during experimentally induced swine dysentery – A study performed by repeated endoscopy and biopsy samplings through an intestinal cannula

text: Abstract The development of intestinal lesions after inoculation with Brachyspira hyodysenteriae was followed by repeated endoscopy and biopsy sampling through a caecal cannula. Seven eight-week-old pigs were cannulated and inoculated, two were cannulated but not inoculated, and two pigs were inoculated but not cannulated. Endoscopy, biopsy, and blood sampling to determine SAA (serum amyloid A), haptoglobin, cortisol, and WBC counts were performed at scheduled time-points. At the third day of disease, endoscopy showed a hyperaemic, perturbed mucosa and excessive amount of mucus. Histologically, crypt hyperplasia, depletion of goblet cell mucus, and erosions were noted. Simultaneously, elevated acute phase proteins and circulating monocytes, and decreased number of intraepithelial CD3+ cells were observed. After five days the pigs recovered. Intestinal lesions were demarcated and interspersed among apparently normal mucosa and blood parameters returned to initial values. Endoscopy through an intestinal cannula made it possible to follow the development of intestinal alterations in vivo and describe the sequential events during the course of swine dysentery. The number of animals used in a study could thus be minimised and the precision of the experiment increased.


title: Vortex dynamics and scalar transport in the wake of a bluff body driven through a steady recirculating flow

text: The air ventilation system in wide-body aircraft cabins provides passengers with a healthy breathing environment. In recent years, the increase in global air traffic has amplified contamination risks by airborne flu-like diseases and terrorist threats involving the onboard release of noxious materials. In particular, passengers moving through a ventilated cabin may transport infectious pathogens in their wake. This paper presents an experimental investigation of the wake produced by a bluff body driven through a steady recirculating flow. Data were obtained in a water facility using particle image velocimetry and planar laser induced fluorescence. Ventilation attenuated the downward convection of counter-rotating vortices produced near the free-end corners of the body and decoupled the downwash mechanism from forward entrainment, creating stagnant contaminant regions.


title: Risk Factors for Mortality in Patients with COVID-19 in New York City

text: BACKGROUND: New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To describe the clinical characteristics and risk factors associated with mortality in a large patient population in the USA. DESIGN: Retrospective cohort study. PARTICIPANTS: 6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area MAIN MEASURES: Clinical characteristics and risk factors associated with in-hospital mortality. KEY RESULTS: A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox proportional hazard regression modeling showed an increased risk of in-hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47–3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06–1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13–1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56–2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m(2) (HR 1.80, CI 1.60–2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12–2.03), D-dimer greater than 2 mcg/mL (HR 1.19, CI 1.02–1.39), and troponin greater than 0.03 ng/mL (HR 1.40, CI 1.23–1.62). Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77–0.90), African American race (HR 0.78 CI 0.65–0.95), and hydroxychloroquine use (HR 0.53, CI 0.41–0.67). CONCLUSIONS: Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-05983-z) contains supplementary material, which is available to authorized users.


title: Comparison of two methods to clear the airways of critically ill children and adults with COVID-19 infection: a structured summary of a study protocol for a pilot randomized controlled trial

text: OBJECTIVES: As there is no treatment for COVID-19 with a proven mortality benefit at this moment in the pandemic, supportive management including mechanical ventilation is the core management in an intensive care unit (ICU). It is a challenge to provide consistent care in this situation, highly demanding and leading to potential staff shortages in ICU. We need to reduce unnecessary exposure of healthcare workers to the virus. This study aims to examine the impact of care using a non-invasive oscillating device (NIOD) for chest physiotherapy in the care of mechanically ventilated patients with COVID-19. In particular, we aim to explore if a NIOD performed by non-specialized personnel is not inferior to the standard chest physiotherapy (CPT) undertaken by physiotherapists caring for patients with COVID-19. TRIAL DESIGN: A pilot multicenter prospective crossover noninferiority randomized controlled trial. PARTICIPANTS: All mechanically ventilated patients with COVID-19 admitted to one of the two ICUs, and CPT ordered by the responsible physician. The participants will be recruited from two intensive care units in Canadian Academic Hospitals (one pediatric and one adult ICU). INTERVENTION AND COMPARATOR: We will implement NIOD and CPT alternatingly for 3 h apart over 3 h. We will apply a pragmatic design, so that other procedures including hypertonic saline nebulization, intermittent positive pressure ventilation, suctioning (e.g., oral or nasal), or changing the ventilator settings or modality (i.e., increasing positive end-expiratory pressure or changing the nasal mask to total face continuous positive airway pressure) can be provided at the direction of bedside intensivists in charge. MAIN OUTCOMES: The primary outcome measurement is the oxygenation level before and after the procedure (SpO(2)/FiO(2) ratio). For cases with invasive ventilation (i.e., the use of an endotracheal tube to deliver positive pressure) and non-invasive ventilation, we will also document expiratory tidal volume, vital signs, and any related complications such as vomiting, hypoxemia, or unexpected extubation. We will collect the data before, 10 min after, and 30 min after the procedure. RANDOMIZATION: The order of the procedures (i.e., NIOD or CPT) will be randomly allocated using manual generated random numbers for each case. Randomization will be carried out by the independent research assistant in the study coordinating center by using opaque sealed envelopes, assigning an equal number of cases to each intervention arm. Stratification will be applied for age (> 18 years or ≤ 18 years of age) and the study sites. BLINDING (MASKING): No blinding will be performed. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We estimate the necessary sample size as 25 for each arm (total 50 cases), with a power of 0.90 and an alpha of 0.05, with a non-inferiority design. TRIAL STATUS: The protocol version number 1 was approved on 27 March 2020. Currently, recruitment has not yet started, with the start scheduled by the mid-June 2020 and the end anticipated by December 2020. TRIAL REGISTRATION: ClinicalTrials.gov NCT04361435. Registered on 28 April 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional File 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


title: Characterization of the diffuse mucosal associated lymphoid tissue of feline small intestine

text: Abstract Characterization of the feline intestinal mucosal associated lymphoid tissue (MALT) will facilitate investigation of intestinal disease in the cat and promote the cat as an animal model for a range of human diseases which involve the intestinal lymphoid tissue. This includes inflammatory bowel disease, viral and non-viral associated intestinal lymphomas and immunodeficiency associated syndromes. Morphologic and phenotypic characterization of the normal small intestinal diffuse MALT in 22 SPF cats was performed using flow cytometry and cytology on isolated intestinal leukocytes from the intra-epithelial and lamina proprial compartments, as well as immunohistology on tissues from the feline duodenum, jejunum and ileum. The intra-epithelial compartment (IEC) was dominated by lymphocytes (>85%) which frequently contained intracytoplasmic granules. The most striking findings in the IEC were the elevated percentages of CD8α+ lymphocytes (40%), presumed to express CD8αα chains, and CD4−/CD8− (double negative) lymphocytes (44%), and the consistent presence of a minor subpopulation of CD3+/CD11d+ IELs (6%). Small percentages of CD4+ lymphocytes (10%) were observed such that the IEL CD4:CD8 ratio (0.25) was low. The LPC also contained a majority of T cells and few plasma cells. However, this compartment had reduced percentages of CD8α+ lymphocytes (28%) and increased percentages of CD4+ lymphocytes (27%) relative to the IEC. However, the LPL CD4:CD8 ratio (1.0) remained low compared with the ratio in peripheral blood. In feline MALT, MHC class II expression was lower than in other peripheral lymphoid compartments. The results of this study provide important reference values for future investigations involving feline intestinal lymphocytes and demonstrates that the leukocyte distribution and phenotypic characteristics of the feline diffuse MALT appear largely similar to the murine, rat and human counterparts.


title: A Mathematical Model for the Coverage Location Problem With Overlap Control

text: The Coverage Location Problem (CLP) seeks the best locations for service to minimize the total number of facilities required to meet all demands. This paper studies a new variation of this problem, called the Coverage Location Problem with Overlap Control (CLPOC). This problem models real contexts related to overloaded attendance systems, which require coverage zones with overlaps. Thus, each demand must be covered by a certain number of additional facilities to ensure that demands will be met even when the designated facility is unable to due to some facility issue. This feature is important in public and emergency services. We observe that this number of additional facilities is excessive in some demand points because overlaps among coverage zones occur naturally in CLP. The goal of the CLPOC is to control overlaps to prioritize regions with a high density population or to minimize the number of coverage zones for each demand point. In this paper, we propose a new mathematical model for the CLPOC that controls the overlap between coverage zones. We used a commercial solver to find the optimal solutions for available instances in the literature. The computational tests show that the proposed mathematical model found appropriate solutions in terms of number of demand points with minimum coverage zones and sufficient coverage zones for high demand points.


title: Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-κB activation

text: Abstract Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.


title: Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020

text: The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic’s epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65–81 cases (upper bounds: 169–507) in Guangdong and an additional 44–354 (upper bounds: 141–875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down.


RECOMMENDATIONS FOR ESSENTIAL ESOPHAGEAL PHYSIOLOGICTESTING DURING THE COVID-19 PANDEMIC


title: Influence of exogenous gonadotropin-releasing hormone on seasonal reproductive behavior of the coyote (Canis latrans)

text: Wild Canis species such as the coyote (C. latrans) express a suite of reproductive traits unusual among mammals, including perennial pair-bonds and paternal care of the young. Coyotes also are monestrous, and both sexes are fertile only in winter; thus, they depend upon social and physiologic synchrony for successful reproduction. To investigate the mutability of seasonal reproduction in coyotes, we attempted to evoke an out-of-season estrus in October using one of two short-acting gonadotropin-releasing hormone (GnRH) agents: (1) a GnRH analogue, deslorelin (6-d-tryptophan-9-(N-ethyl-l-prolinamide)-10-deglycinamide), 2.1 mg pellet sc; or (2) gonadorelin, a GnRH (5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH(2)) porcine hypothalamic extract, 2.0 μg/kg im once daily for 3 consecutive days. A transient increase in serum concentrations of estradiol and progesterone (1 and 2 wk, respectively) was detected after treatment with deslorelin but not gonadorelin. Also, socio-sexual behaviors reminiscent of winter mating (including courtship, mate-guarding, precoital mounts, and copulatory ties) were observed among the deslorelin group. During the subsequent breeding season (January and February), however, preovulatory courtship behavior and olfactory sampling appeared suppressed; emergence of mounts and copulations were delayed in both deslorelin and gonadorelin treatment groups. Furthermore, whereas 8 of 12 females treated in October ovulated and produced healthy litters in the spring, 4 naïve coyotes failed to copulate or become pregnant. Thus, perturbation of hormones prior to ovulation in species with complex mating behaviors may disrupt critical intrapair relationships, even if fertility is not impaired physiologically.


title: Epigenetic Reprogramming of Somatic Genomes by Electrofusion With Embryonic Stem Cells

text: Cell fusion is an approach for combining genetic and epigenetic information between two different types of cells. Electrofusion for generating hybrid cells between mouse embryonic stem cells and somatic cells, which is a type of nonchemically induced and nonvirus-mediated cell fusion, is introduced here as a highly effective, reproducible, and biomedically safe in vitro system. Under optimized electrofusion conditions, cells are aligned and form pearl chains between electrodes in response to AC pulse stimulation, and subsequently adjacent cytoplasmic membranes are fused by DC pulse stimulation. Hybrid cells survive as drug-resistant colonies in selection medium. Cell fusion is a technique that is applied widely in the life sciences. A recent topic of great interest in the field of stem cell research is the successful production of cloned animals via epigenetic reprogramming of somatic nuclei. Interestingly, nuclear reprogramming for conferring pluripotency on somatic nuclei also occurs via cell fusion between pluripotential stem cells and somatic cells. Furthermore, it has been shown that spontaneous cell fusion contributes to generating the intrinsic plasticity of tissue stem cells. Cell fusion technology may make important contributions to the fields of regenerative medicine and epigenetic reprogramming.


title: Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice

text: Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (Severe Acute Respiratory Syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak but early IFN-I administration ameliorates immunopathology. This delayed IFN-I signaling promotes the accumulation of pathogenic inflammatory monocyte-macrophages (IMMs), resulting in elevated lung cytokine/chemokine levels, vascular leakage and impaired virus-specific T cell responses. Genetic ablation of the IFN-αβ receptor (IFNAR) or IMM depletion protects mice from lethal infection, without affecting viral load. These results demonstrate that IFN-I and IMM promote lethal SARS-CoV infection and identify IFN-I and IMMs as potential therapeutic targets in patients infected with pathogenic coronavirus and perhaps other respiratory viruses.


title: Enzymatic pathways of the brain renin–angiotensin system: Unsolved problems and continuing challenges

text: Abstract The brain renin–angiotensin system continues to be enigmatic more than 40 years after the brain was first recognized to be a site of action of angiotensin II. This review focuses on the enzymatic pathways for the formation and degradation of the growing number of active angiotensins in the brain. A brief description and nomenclature of the peptidases involved in the processing of angiotensin peptides in the brain is given. Of primary interest is the array of enzymes that degrade radiolabeled angiotensins in receptor binding assays. This poses major challenges to studies of brain angiotensin receptors and it is debatable whether an accurate determination of brain angiotensin receptor binding kinetics has yet been made. The quandary facing the investigator of brain angiotensin receptors is the need to protect the radioligand from metabolic alteration while maintaining the characteristics of the receptors in situ. It is the tenet of this review that we have yet to fully understand the binding characteristics of brain angiotensin receptors and the extent of their distribution in the brain because of our inability to fully protect the angiotensins from metabolic alteration until equilibrium binding conditions can be attained.


title: Complete Sequence (20 Kilobases) of the Polyprotein-Encoding Gene 1 of Transmissible Gastroenteritis Virus

text: Abstract The entire nucleotide sequence of cloned cDNAs containing the 5′-untranslated region and gene 1 of Purdue-115 strain of transmissible gastroenteritis virus (TGEV) was determined. This completes the sequence of the TGEV genome, which is 28,579 nucleotides long. The gene 1 is composed of two large open reading frames, ORF1a and ORF1b, which contain 4017 and 2698 codons, respectively (stop excluded). A brief, three-codon-long ORF is present upstream of ORF1a. ORF1b overlaps ORF1a by 43 bases in the (-1) reading frame. In vitro experiments indicated that translation of the ORF1a/b polyprotein involves an efficient ribosomal frameshifting activity, as previously shown for other coronaviruses. Analysis of the predicted ORF1a and ORF1b translation products revealed that the putative functional domains identified in infectious bronchitis virus (IBV), mouse hepatitis virus (MHV) and human coronavirus 229E (HCV 229E) are all present in TGEV. The amino-terminal half of the ORFla product exhibits greater divergence then the carboxy-terminal half, including within the TGEV/HCV229E pair. The ORF1b protein is overall highly conserved among the above four coronaviruses, except a divergent region situated near the carboxy terminus.


Tropical biology and conservation in the time of the COVID‐19 pandemic


title: Multi-Organ Lesions in Suckling Mice Infected with SARS-Associated Mammalian Reovirus Linked with Apoptosis Induced by Viral Proteins μ1 and σ1

text: We reported the isolation and characterization of a novel mammalian reassortant reovirus BYD1 that may have played an accomplice role with SARS-coronavirus during the 2003 SARS pandemic. The pathogenic mechanism of this novel reovirus is unknown. Reovirus pathogenicity has been associated with virus-induced apoptosis in cultured cells and in vivo. The reovirus outer capsid protein μ1 is recognized as the primary determinant of reovirus-induced apoptosis. Here, we investigated the apoptosis induced by BYD1, its outer capsid protein μ1, and its cell-attachment protein σ1 to understand the pathogenesis of BYD1. We also investigated BYD1 caused systemic complications in suckling mice. Under electron microscopy, BYD1-infected cells showed characteristics typical of apoptosis. Notably, ectopically expressed μ1 and σ1 induced similar pathological apoptosis, independent of BYD1 infection, in host cells in which they were expressed, which suggests that μ1 and σ1 are both apoptotic virulence factors. Consistent with previous reports of reovirus pathogenicity, suckling mice intracranially inoculated with BYD1 developed central nerve damage, myocarditis, and pneumonia. Collectively, our data suggest that BYD1 μ1- and σ1-induced apoptosis is involved in the multi-organ lesions in a suckling mouse BYD1 infection model.


title: Recomendaciones Del Grupo Español De Investigación En Dermatitis De Contacto Y Alergia Cutánea (Geidac ) De La Aedv En Relación A La Realización De Pruebas Epicutáneas Durante La Pandemia Por Sars-Cov-2 ( Covid-19)

text: Abstract As the COVID-19 pandemic gradually comes under control, the members of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) have drawn up a proposed list of the requirements, limitations, and conditioning factors affecting the resumption of work in contact dermatitis units. The assumption is that the severe acute respiratory syndrome coronavirus 2 is still circulating and that occasional or seasonal outbreaks will occur. They recommend that the first step should be to assess how many patch tests each clinic can handle and review the waiting list to prioritize cases according to disease severity and urgency. Digital technologies can, where possible, be used to send and receive the documentation necessary for the patch test (information, instructions, informed consent, etc.). If the necessary infrastructure is available, patients can be offered the option of a remote initial consultation. Likewise, in selected cases, the patch test results can be read in a virtual visit using photographs taken by the patient or a video visit can be scheduled to allow the physician to evaluate the site of application remotely. These measures will reduce the number of face-to-face visits required, but will not affect the time spent on each case, which must be scheduled in the normal manner. All of these recommendations are suggestions and should be adapted to the needs and possibilities of each health centre.


title: Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin

text: Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health(1). Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)(2–10). Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96–98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013–2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.


title: Identification and characterization of a novel L-type lectin (MjLTL2) from kuruma shrimp (Marsupenaeus japonicus)

text: Abstract L-type lectins (LTLs) belong to the lectin family and are characterized by a conserved structural motif in their carbohydrate recognition domain. LTLs are homologous to leguminous lectins. In this study, we identified and functionally characterized an LTL from kuruma shrimp Marsupenaeus japonicus. We designated this LTL as MjLTL2. MjLTL2 contains a signal peptide, a Lectin_leg domain, a coiled coil, and transmembrane domain. MjLTL2 is distributed in hemocytes, heart, hepatopancreas, gill, stomach, and intestine; higher expression levels are seen in hemocytes and the hepatopancreas than in other tissues. MjLTL2 was upregulated following challenge of shrimp with Vibrio anguillarum and white spot syndrome virus (WSSV). MjLTL2 can agglutinate several bacteria without Ca2+. In addition, MjLTL2 could bind to several Gram-positive and -negative bacteria by binding to their lipopolysaccharide and peptidoglycan. However, MjLTL2 could not enhance the clearance of V. anguillarum in vivo. In the presence of WSSV infection, MjLTL2 knockdown by RNA interference resulted in a 7-day lower cumulative mortality of M. japonicus. Moreover, less VP19, VP24, VP26, and VP28 mRNAs were extracted from the hemocytes of MjLTL2 knockdown shrimp than from the control. These results suggest that MjLTL2 is involved in immune responses in shrimp.


title: Vascular endothelial growth factor induction by rhinovirus infection

text: Vascular participation manifested by a runny nose (rhinorrhea) is a prominent feature of the acute consequences of rhinovirus infection. Vascular endothelial growth factor (VEGF) is an angiogenic factor that also induces potent increases in vascular permeability; it is a candidate mediator of rhinorrhea in response to rhinovirus infection as well as contributing to enhanced vascular leakage in rhinovirus‐linked asthma exacerbations. It has been shown that rhinovirus induces significant increases in both VEGF protein and mRNA in primary airway fibroblasts [Ghildyal et al. (2005): J Med Virol 75:608–615]. The current studies assessed VEGF responses to rhinovirus in primary culture airway epithelium, in epithelial and fibroblast cell lines and in rhinovirus‐infected nasal secretions. Epithelial and fibroblast cells were infected with rhinovirus serotype 16 and VEGF protein and isoforms assessed by ELISA and RT‐PCR, respectively. VEGF protein was released by both epithelial and fibroblast cell lines and primary airway epithelial cells in culture but was not increased following rhinovirus infection. PCR products coding for four or five of the six known VEGF isoforms were produced (121, 145, 165 and 183, and/or 189 amino acids) in cell lines and primary culture cells, but no specific isoform was linked to rhinovirus infection. Nasal VEGF was also measured in a cohort of asthmatics with verified rhinovirus and respiratory syncytial virus (RSV) infection. VEGF was not raised following rhinovirus infection alone, but was increased significantly if concomitant RSV infection was present. The data suggest that fibroblasts rather than the epithelium may play a key role in VEGF mediated vascular responses after rhinovirus infection. This may aid recruitment of inflammatory cells and contribute to airway inflammation and bronchial obstruction. J. Med. Virol. 78:666–672, 2006. © 2006 Wiley‐Liss, Inc.


title: The search for a structural basis for therapeutic intervention against the SARS coronavirus

text: The 2003 outbreak of severe acute respiratory syndrome (SARS), caused by a previously unknown coronavirus called SARS‐CoV, had profound social and economic impacts worldwide. Since then, structure–function studies of SARS‐CoV proteins have provided a wealth of information that increases our understanding of the underlying mechanisms of SARS. While no effective therapy is currently available, considerable efforts have been made to develop vaccines and drugs to prevent SARS‐CoV infection. In this review, some of the notable achievements made by SARS structural biology projects worldwide are examined and strategies for therapeutic intervention are discussed based on available SARS‐CoV protein structures. To date, 12 structures have been determined by X‐ray crystallography or NMR from the 28 proteins encoded by SARS‐CoV. One key protein, the SARS‐CoV main protease (M (pro)), has been the focus of considerable structure‐based drug discovery efforts. This article highlights the importance of structural biology and shows that structures for drug design can be rapidly determined in the event of an emerging infectious disease.


title: Experimental autoimmune uveoretinitis (EAU) versus experimental allergic encephalomyelitis (EAE): a comparison of T cell-mediated mechanisms.

text: EAU is a model of ocular inflammatory disease. EAU resembles another T cell-mediated autoimmune disease--experimental allergic encephalomyelitis--since both have increased expression of MHC class II molecules in the target tissue, can be adoptively transferred by activated CD4+ T cells and are inhibited by cyclosporin A. The immunological findings will be compared to find out if the same cellular mechanisms are involved in both diseases.


title: Interferon Lambda: A New Sword in Cancer Immunotherapy

text: The discovery of the interferon-lambda (IFN-λ) family has considerably contributed to our understanding of the role of interferon not only in viral infections but also in cancer. IFN-λ proteins belong to the new type III IFN group. Type III IFN is structurally similar to type II IFN (IFN-γ) but functionally identical to type I IFN (IFN-α/β). However, in contrast to type I or type II IFNs, the response to type III IFN is highly cell-type specific. Only epithelial-like cells and to a lesser extent some immune cells respond to IFN-λ. This particular pattern of response is controlled by the differential expression of the IFN-λ receptor, which, in contrast to IFN-α, should result in limited side effects in patients. Recently, we and other groups have shown in several animal models a potent antitumor role of IFN-λ that will open a new challenging era for the current IFN therapy.


title: Feline congenital myotonia

text: FELINE infections peritonitis (FIP) is a systemic, fatal, immune‐mediated vasculitis caused by a feline coronavirus (FCoV). Historically, FIP virus (FIPV) and feline enteritis by a feline enteric coronavirus (FECV). Recent studies have shown that there is essentially only one FCoV in the field, although laboratory strains may vary in virulence.


title: Introduction—Panspermia, 2020

text: This current volume is, in many ways, a 2020 update to the important 1999–2000 compendium by Sir Fed Hoyle and Professor N. Chandra Wickramasinghe's “Astronomical Origins of life: Steps towards Panspermia.” The emerging new paradigm of biology that connects life on Earth with the wider cosmos is covered in considerable depth showing that terrestrial biological evolution is best understood as a cosmically derived habitat and an interconnected genetic system. The various chapters here discuss all aspects of this interconnectedness, particularly relevant now in this time of the coronavirus pandemic (COVID-19) as the human race reacts to the many microbes and viral pathogens that arrive regularly from space.


title: Establishing and comparing energy security trends in resource-rich exporting nations (Russia and the Caspian Sea region)

text: Abstract In the international arena, it is often the case that in countries which largely depend on foreign resources, energy security, and its key components i.e. security of energy supply, environment, technology, geopolitical and economic factors, is a subject of concern. However, due to the abundance of fossil fuel resources in resource-rich exporting nations, there is a lack of understanding of the risks around energy security and accordingly often a policy vacuum. Conceptualising energy security from different geopolitical vantage points will allow future concerns around energy supply security, climate change, and regional economic crises to be evaluated. By using policy documents and developing a time series approach and normalized z-scores for a range of comparable metrics this article compares the energy security performance in six Caspian Sea countries individually and collectively. The article results show that Azerbaijan, Iran, Kazakhstan made significant progress in energy security since 1990, while energy security indicators in Russia, Uzbekistan, and Turkmenistan regressed. Iran has a leading position in energy security performance, while Uzbekistan and Turkmenistan have the lowest level of the energy security indicators compare to other region countries. This article both contributes a replicable definition of energy security that can be undertaken for other global regions, and begins to incorporate diversification and renewables development to enhance domestic energy security assessment.


Ethics guidelines on COVID-19 triage—an emerging international consensus


title: Viral shedding and clinical illness in naturally acquired influenza virus infections

text: BACKGROUND: Volunteer challenge studies have provided detailed data on viral shedding from the respiratory tract before and through the course of experimental influenza virus infection. There are no comparable quantitative data on naturally-acquired infections. METHODS: In a community-based study in Hong Kong in 2008, we followed up initially well individuals to quantify trends in viral shedding based on culture and reverse transcription polymerase chain reaction (RT-PCR) through the course of illness associated with seasonal influenza A and B virus infection. RESULTS: Trends in symptom scores more closely matched changes in molecular viral loads measured by RT-PCR for influenza A than influenza B. For influenza A virus infections, replicating viral loads measured by culture declined to undetectable levels earlier after illness onset than molecular viral loads. Most viral shedding occurred during the first 2–3 days after illness onset and we estimated that 1–8% of infectiousness occurs prior to illness onset. Only 14% of infections with detectable shedding by RT-PCR were asymptomatic, and viral shedding was low in these cases. CONCLUSIONS: Our results suggest that ‘silent spreaders’ (i.e. individuals who are infectious while asymptomatic or pre-symptomatic) may be less important in the spread of influenza epidemics than previously thought.


title: Construction and functional test of a chicken MHC-I (BF2*15)/peptide tetramer

text: Abstract The major histocompatibility complex class I (MHC class I) peptide tetramer is a sensitive and valuable tool to evaluate antigen-specific cytotoxic T lymphocytes (CTLs) of many animal species. To date, no chicken MHC class I peptide tetramer has been reported. In this report, we describe construction and functional evaluation of a chicken MHC-I (BF2*15)/peptide tetramer. To construct the chicken MHC class I peptide tetramer, genes of the chicken MHC-I α chain (BF2*15) and β2 microglobulin (Chβ2m) were synthesized by RT-PCR from the total RNA of PBMCs and the signal sequences were deleted. The BF2*15 was then fused with the BirA substrate peptide (BSP) sequence at the C terminus. Next, the synthesized PCR products of BF2*15 and Chβ2m were cloned into the expression vector pET-28a (+) and expressed in Escherichia coli strain BL21 (DE3). Highly purified BF2*15-BSP heavy chain and Chβ2m were obtained by a Ni2+ NTA column affinity purification, yielding approximately 1.6mg of BF2*15-BSP and 2.4mg of Chβ2m per 1g of the pelleted bacteria. The purified BF2*15-BSP heavy chain and Chβ2m were refolded with synthetic peptide originated from infectious bronchitis virus nucleoprotein (IBV N71–78) in refolding buffer to generate the monomer of BF2*15/peptide complex. The monomer was then biotinylated and tetramerized using PE-labeled streptavidin. Upon functional evaluation of the construct by using flowcytometry, we observed that 3.65% of CTLs were specific to IBV nucleoprotein. This demonstrates that the CTL response of IBV-infected chicks could effectively be evaluated using the prepared MHC-I BF2*15/peptide tetramer.


title: Segmented regression analysis of emergency departments patient visits from Septicemia in Taiwan

text: Abstract Background The protocol for early goal-directed therapy (EGDT) is effective for improving both the costs and outcomes of septicemia treatment, including a significant reduction in case fatality. However, this complicated protocol may have a downside. Furthermore, the Joint Taiwan Critical Care Medicine Committee has launched a nationwide educational program after the publication of the Surviving Sepsis Campaign (SSC) to improve the overall survival rate from septicemia in the emergency care system of Taiwan. Objectives To assess the impact of the EGDT protocol and SSC education programs on island-wide septicemia-related emergency department (ED) visits. Methods Segmented regression techniques were utilized to assess the differences in annual rates and changes in septicemia-related ED visits between 1998 and 2012. We considered annual incidence of two medical comorbidities as potential confounders: metastatic malignant neoplasms and malignant neoplasms of the lymphatic and hematopoietic tissues. Results The EGDT protocol was associated with decreased septicemia-related ED visits in 2002 (level change; p < 0.001), while the SSC education program led to a slight increase in septicemia-related ED visits in 2007 (slope change; p < 0.001). For the EGDT protocol, the number of patient visits decreased by 32.9% after the protocol was implemented in 2002 compared with the expected number without the intervention. For the SSC education program, the number of patient visits increased by 20.2% (compared with the predicted number) in 2007 after the education program was implemented. Conclusions The EGDT protocol and SSC education program were associated with significant immediate changes and lagged intervention effects on island-wide septicemia-related ED visits.


title: Coalitions and Public Action in the Reshaping of Corporate Responsibility: The Case of the Retail Banking Industry

text: This paper addresses the question of whether and how public action via civil society and/or government can meaningfully shape industry-wide corporate responsibility (ICR) behaviour. We explore how, in principle, ICR can come about and what conditions might be effective in promoting more ethical behaviour. We propose a framework to understand attempts to develop more responsible behaviour at an industry level through processes of negotiation and coalition building. We suggest that any attempt to meaningfully influence ICR would require stakeholders to possess both power and legitimacy; moreover, magnitude and urgency of the issue at stake may affect the ability to influence ICR. The framework is applied to the retail banking industry, focusing on post-crisis experiences in two countries—Spain and the UK—where there has been considerable pressure on the retail banking industry by civil society and/or government to change behaviours, especially to abandon unethical practices. We illustrate in this paper how corporate responsibility at the sector level in retail banking is the product of context-specific processes of negotiation between civil society and public authorities, on behalf of customers and other stakeholders, drawing on legal and other institutions to influence industry behaviour.


title: Structural model of the SARS coronavirus E channel in LMPG micelles

text: Abstract Coronaviruses (CoV) cause common colds in humans, but are also responsible for the recent Severe Acute, and Middle East, respiratory syndromes (SARS and MERS, respectively). A promising approach for prevention are live attenuated vaccines (LAVs), some of which target the envelope (E) protein, which is a small membrane protein that forms ion channels. Unfortunately, detailed structural information is still limited for SARS-CoV E, and non-existent for other CoV E proteins. Herein, we report a structural model of a SARS-CoV E construct in LMPG micelles with, for the first time, unequivocal intermolecular NOEs. The model corresponding to the detergent-embedded region is consistent with previously obtained orientational restraints obtained in lipid bilayers and in vivo escape mutants. The C-terminal domain is mostly α-helical, and extramembrane intermolecular NOEs suggest interactions that may affect the TM channel conformation.


title: Recombinant antibodies for diagnostics and therapy against pathogens and toxins generated by phage display

text: Antibodies are valuable molecules for the diagnostic and treatment of diseases caused by pathogens and toxins. Traditionally, these antibodies are generated by hybridoma technology. An alternative to hybridoma technology is the use of antibody phage display to generate recombinant antibodies. This in vitro technology circumvents the limitations of the immune system and allows—in theory—the generation of antibodies against all conceivable molecules. Phage display technology enables obtaining human antibodies from naïve antibody gene libraries when either patients are not available or immunization is not ethically feasible. On the other hand, if patients or immunized/infected animals are available, it is common to construct immune phage display libraries to select in vivo affinity‐matured antibodies. Because the phage packaged DNA sequence encoding the antibodies is directly available, the antibodies can be smoothly engineered according to the requirements of the final application. In this review, an overview of phage display derived recombinant antibodies against bacterial, viral, and eukaryotic pathogens as well as toxins for diagnostics and therapy is given.


title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure

text: The high mutation rates of infectious bronchitis virus (IBV) pose economic threats to the poultry industry. In order to track the genetic evolutionary of IBV isolates circulating in yellow chickens, we continued to conduct the genetic analyses of the structural genes S1, E, M, and N from 64 IBV isolates in southern China during 2009–2017. The results showed that the dominant genotypes based on the four genes had changed when compared with those during 1985–2008. Based on the S1 gene phylogenetic tree, LX4-type (GI-19) was the most dominant genotype, which was different from that during 1985–2008. The second most dominant genotype was LDT3-A-type, but this genotype disappeared after 2012. New-type 1 (GVI-1) isolates showed increasing tendency and there were four aa (QKEP) located in the hypervariable region (HVR) III and one aa (S) insertion in all the New-type 1 isolates. Both the analyses of amino acid entropy and molecular evolutionary rate revealed that the variations from large to small were S1, E, M, and N. Purifying selection was detected in the S1, E, M, and N gene proteins, which was different from the positive selection during 1985–2008. Six isolates were confirmed to be recombinants, possibly generated from a vaccine virus of the 4/91-type or LDT3-A-type and a circulating virus. The estimated times for the most recent common ancestors based on the S1, E, M, and N genes were the years of 1744, 1893, 1940, and 1945, respectively. Bayesian skyline analysis revealed a sharp decrease in genetic diversity of all the four structural genes after 2010 and since late 2015, the viral population rapidly rose. In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs.


title: Impact on biometrics of Covid-19

text: At this time of global concern for the health of our loved ones, communities and workplaces, ABI Research analysts have assessed the likely short and long-term impacts that the global Covid-19 pandemic will have on the biometrics and related technology markets. Beyond the significant cost to human life due to the pandemic, it can be argued that Covid-19 will also have a significant and long-term impact on biometrics companies, developers, investors and customers.


title: The R-rich motif of Beet black scorch virus P7a movement protein is important for the nuclear localization, nucleolar targeting and viral infectivity

text: Abstract Beet black scorch virus (BBSV) encodes three movement proteins (P7a, P7b and P5′) that facilitate its cell-to-cell movement. An arginine-rich motif of P7a N-terminus was found to determine nuclear and nucleolar localization. Amino acids substitution or deletion of the R-rich motif interfered with P7a nuclear and nucleolar localization. Bimolecular fluorescence complementation (BiFC) assays revealed that P7a protein interacted with Nicotiana benthamiana nuclear import factor importin α, suggesting that P7a is translocated into the nucleus by the classical importin α/β-dependent pathway. Moreover, P7a also interacted with the nucleolar protein fibrillarin. Mutations in the R-rich motif of P7a diminished P7a interactions with importin α and fibrillarin, influenced viral replication in Nicotiana benthamiana protoplasts and altered the symptom phenotype and viral RNA accumulation in Chenopodium amaranticolor plants. These results demonstrate that the R-rich motif of P7a is correlated with nuclear and nucleolar localization, viral replication and virus infection.


title: Analysis of IFITM-IFITM Interactions by a Flow Cytometry-Based FRET Assay

text: The interferon-induced transmembrane proteins 1–3 (IFITM1–3) inhibit host cell entry of several viruses. However, it is incompletely understood how IFITM1–3 exert antiviral activity. Two phenylalanine residues, F75 and F78, within the intramembrane domain 1 (IM1) were previously shown to be required for IFITM3/IFITM3 interactions and for inhibition of viral entry, suggesting that IFITM/IFITM interactions might be pivotal to antiviral activity. Here, we employed a fluorescence resonance energy transfer (FRET) assay to analyze IFITM/IFITM interactions. For assay calibration, we equipped two cytosolic, non-interacting proteins, super yellow fluorescent protein (SYFP) and super cyan fluorescent protein (SCFP), with signals that target proteins to membrane rafts and also analyzed a SCFP-SYFP fusion protein. This strategy allowed us to discriminate background signals resulting from colocalization of proteins at membrane subdomains from signals elicited by protein–protein interactions. Coexpression of IFITM1–3 and IFITM5 fused to fluorescent proteins elicited strong FRET signals, and mutation of F75 and F78 in IFITM3 (mutant IFITM3-FF) abrogated antiviral activity, as expected, but did not alter cellular localization and FRET signals. Moreover, IFITM3-FF co-immunoprecipitated efficiently with wild type (wt) IFITM3, lending further support to the finding that lack of antiviral activity of IFITM3-FF was not due to altered membrane targeting or abrogated IFITM3-IFITM3 interactions. Collectively, we report an assay that allows quantifying IFITM/IFITM interactions. Moreover, we confirm residues F75 and F78 as critical for antiviral activity but also show that these residues are dispensable for IFITM3 membrane localization and IFITM3/IFITM3 interactions.


title: Assessing the infection prevention components of home health emergency management plans

text: BACKGROUND: Home health emergency management plans are essential and must address infection prevention issues. Few home health planning documents exist, and many of those that have been developed do not address infection prevention issues, combine them with non–infection prevention issues, or are disease/event-specific. An all-encompassing home health infection prevention emergency management planning guide is needed. METHODS: A literature review and Internet search were conducted in the summer of 2010, and data from relevant sources were extracted. A spreadsheet was created delineating home health emergency management plan components related to infection prevention. RESULTS: Of the sources screened, 41 were deemed relevant. Ten domains were identified: (1) having a plan; (2) assessing agency readiness; (3) having infection prevention policies and procedures; (4) having occupational health policies and procedures; (5) conducting surveillance and triage; (6) reporting incidents, having a communication plan, and managing information; (7) addressing surge capacity issues; (8) having anti-infective therapy and/or vaccines; (9) providing infection prevention education; and (10) managing water and waste management issues. CONCLUSION: Home health disaster planners or managers should use this article as an assessment tool for evaluating their agency’s emergency management plan and for developing policies and procedures that will decrease the risk of infection transmission during a mass casualty event.


title: Structure of the black beetle virus genome and its functional implications

text: Abstract The black beetle virus (BBV) is an isometric insect virus whose genome consists of two messenger-active RNA molecules encapsidated in a single virion. The nucleotide sequence of BBV RNA1 (3105 bases) has been determined, and this, together with the sequence of BBV RNA2 (1399 bases) provides the complete primary structure of the BBV genome. The RNA1 sequence encompasses a 5′ non-coding region of 38 nucleotides, a coding region for a protein of predicted molecular weight 101,873 (protein A, implicated in viral RNA synthesis) and a 3′ proximal region encoding RNA3 (389 bases), a subgenomic messenger RNA made in infected cells but not encapsidated into virions. The RNA3 sequence starts 16 bases inside the coding region of protein A and contains two overlapping open reading frames for proteins of molecular weight 10,760 and 11,633, one of which is believed to be protein B, made in BBV-infected cells. A limited homology exists between the sequences of RNA1 and RNA2. Sequence regions have been identified that provide energetically favorable bonding between RNA2 and RNA1 possibly to facilitate their common encapsidation, and between RNA2 and negative strand RNA1 possibly to regulate the production of RNA3.


title: Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa

text: BACKGROUND: Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. METHODS: Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. RESULTS: We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. CONCLUSION: Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.


title: The θ-defensin retrocyclin 101 inhibits TLR4- and TLR2-dependent signaling and protects mice against influenza infection

text: Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection. In this study, RC-101, a variant of the humanized θ-defensin RC-1, blocked TLR4-mediated gene expression in mouse and human macrophages in response to LPS, targeting both MyD88- and TRIF-dependent pathways. In a cell-free assay, RC-101 neutralized the biologic activity of LPS at doses ranging from 0.5 to 50 EU/ml, consistent with data showing that RC-101 binds biotinylated LPS. The action of RC-101 was not limited to the TLR4 pathway because RC-101 treatment of macrophages also inhibited gene expression in response to a TLR2 agonist, Pam3CSK4, but failed to bind that biotinylated agonist. Mouse macrophages infected in vitro with mouse-adapted A/PR/8/34 influenza A virus (PR8) also produced lower levels of proinflammatory cytokine gene products in a TLR4-independent fashion when treated with RC-101. Finally, RC-101 decreased both the lethality and clinical severity associated with PR8 infection in mice. Cumulatively, our data demonstrate that RC-101 exhibits therapeutic potential for the mitigation of influenza-related morbidity and mortality, potentially acting through TLR-dependent and TLR-independent mechanisms.


title: COVID-19 and Heart: From Clinical Features to Pharmacological Implications.

text: A highly pathogenic human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized in Wuhan, China, as the cause of the coronavirus disease 2019 (COVID-19) outbreak which has spread rapidly from China to other countries in the world, causing a pandemic with alarming morbidity and mortality. The emerging epidemiological data about COVID-19 patients suggest an association between cardiovascular diseases (CVD) and SARS-CoV-2 infection, in term of clinical features at hospital admission and prognosis for disease severity. The aim of our review is to describe the cardiological features of COVID-19 patients at admission, the acute cardiac presentation, the clinical outcome for patients with underlying CVD and the pharmacological implications for disease management.


title: Timely identification of optimal control strategies for emerging infectious diseases

text: Abstract Background Health authorities must rely on quarantine, isolation, and other non-pharmaceutical interventions to contain outbreaks of newly emerging human diseases. Methods We modeled a generic disease caused by a pathogen apparently transmitted by close interpersonal contact, but about which little else is known. In our model, people may be infectious while incubating or during their prodrome or acute illness. We derived an expression for ℜ , the reproduction number, took its partial derivatives with respect to control parameters, and encoded these analytical results in a user-friendly Mathematica™ notebook. With biological parameters for SARS estimated from the initial case series in Hong Kong and infection rates from hospitalizations in Singapore, we determined ℜ 's sensitivity to control parameters. Results Stage-specific infection rate estimates from cases hospitalized before quarantine began exceed those from the entire outbreak, but are qualitatively similar: infectiousness was negligible until symptom onset, and increased 10-fold from prodrome to acute illness. Given such information, authorities might instead have emphasized a strategy whose efficiency more than compensates for any possible reduction in efficacy. Conclusions In future outbreaks of new human diseases transmitted via close interpersonal contact, it should be possible to identify the optimal intervention early enough to facilitate effective decision-making.


title: Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis

text: Abstract Aim The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. Methods A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. Results Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2 : 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2 : 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2 : 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2 : 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2 : 52.4%). Conclusions Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.


title: Association between Angiotensin-Converting Enzyme Inhibitors and Lung Cancer—A Nationwide, Population-Based, Propensity Score-Matched Cohort Study

text: Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged ≥ 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36; 95% confidence interval [CI]. = 1.11–1.67). Duration–response and dose–response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87; 95% CI = 1.48–2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80; 95% CI = 1.43–-2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.


title: Reorganization of a large academic hospital to face COVID‐19 outbreak: The model of Parma, Emilia‐Romagna region, Italy

text: COVID-19 outbreak is challenging for hospital care. Development of lean, adaptable algorithms for managing patient flows may be pivotal for handling and adapting to a situation of uncertainty and evolving crisis. Here, we present the model of care adopted at Parma University-Hospital, a large teaching hospital facility located in Northern Italy, to face a massive overflow of COVID-19 patients presenting to the Emergency Department.


Late miscarriage as a presenting manifestation of COVID-19


Mycobacterium avium ssp. paratuberculosis High Shedding in an Adult Female Alpaca, and its Implications for the Rest of the Herd


title: The role of high cholesterol in age-related COVID19 lethality

text: Coronavirus disease 2019 (COVID19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan China in 2019. The disease is notably severe in elderly and those with underlying chronic conditions. A molecular mechanism that explains why the elderly are vulnerable and why children are resistant is largely unknown. Understanding these differences is critical for safeguarding the vulnerable and guiding effective policy and treatments. Here we show loading cells with cholesterol from blood serum using the cholesterol transport protein apolipoprotein E (apoE) enhances the endocytic entry of pseudotyped SARS-CoV-2. Super resolution imaging of the SARS-CoV-2 entry point with high cholesterol showed almost twice the total number of viral entry points. The cholesterol concomitantly traffics angiotensinogen converting enzyme (ACE2) to the viral entry site where SARS-CoV-2 docks to properly exploit entry into the cell. Cholesterol also increased binding of SARS-CoV-2 receptor binding domains. In mouse lung we found age and high fat diet induced cholesterol loading into lung tissue by up to 40%. Based on these findings, we propose a cholesterol dependent model for COVID19 lethality in elderly and the chronically ill. As cholesterol increases with age and inflammation (e.g. obesity, smoking, and diabetes), the cell surface is coated with viral entry points, optimally assembled viral entry proteins, and optimal furin priming. Importantly our model suggests problems arise when cholesterol levels are high in the tissue, not the blood. In fact, rapidly dropping cholesterol in the blood may indicate severe loading of cholesterol in peripheral tissue and a dangerous situation for escalated SARS-CoV-2 infectivity. Molecules that remove cholesterol from tissue or disrupt ACE2 localization with viral entry points or furin localization for priming in the producer cells, likely reduce the severity of COVID19 in critically ill patients.


title: DEAD-Box Helicases: Sensors, Regulators, and Effectors for Antiviral Defense

text: DEAD-box helicases are a large family of conserved RNA-binding proteins that belong to the broader group of cellular DExD/H helicases. Members of the DEAD-box helicase family have roles throughout cellular RNA metabolism from biogenesis to decay. Moreover, there is emerging evidence that cellular RNA helicases, including DEAD-box helicases, play roles in the recognition of foreign nucleic acids and the modulation of viral infection. As intracellular parasites, viruses must evade detection by innate immune sensing mechanisms and degradation by cellular machinery while also manipulating host cell processes to facilitate replication. The ability of DEAD-box helicases to recognize RNA in a sequence-independent manner, as well as the breadth of cellular functions carried out by members of this family, lead them to influence innate recognition and viral infections in multiple ways. Indeed, DEAD-box helicases have been shown to contribute to intracellular immune sensing, act as antiviral effectors, and even to be coopted by viruses to promote their replication. However, our understanding of the mechanisms underlying these interactions, as well as the cellular roles of DEAD-box helicases themselves, is limited in many cases. We will discuss the diverse roles that members of the DEAD-box helicase family play during viral infections.


title: Temperature and precipitation associate with Covid-19 new daily cases: A correlation study between weather and Covid-19 pandemic in Oslo, Norway

text: Abstract This study aims to analyze the correlation between weather and covid-19 pandemic in the capital city of Norway, Oslo. This study employed a secondary data analysis of covid-19 surveillance data from the Norwegian public health institute and weather data from the Norwegian Meteorological institute. The components of weather include minimum temperature (°C), maximum temperature (°C), temperature average (°C), normal temperature (°C), precipitation level (mm) and wind speed (m/s). Since normality was not fulfilled, a non-parametric correlation test was used for data analysis. Maximum temperature (r = 0.347; p = .005), normal temperature(r = 0.293; p = .019), and precipitation level (r = −0.285; p = .022) were significantly correlated with covid-19 pandemic. The finding serves as an input to a strategy making against the prevention of covid-19 as the country prepare to enter into a new weather season.


title: Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody

text: We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG(HeV)). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG(HeV). One of the selected antibody Fab clones, m102.4, had affinity of binding to sG(HeV) that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sG(HeV) and sG(NiV). m102.4 bound a soluble form of NiV G (sG(NiV)) better than it bound sG(HeV), and it neutralized NiV better than HeV, despite being originally selected against sG(HeV). These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent


title: The influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis

text: The ageing-associated decline of biological functions represents an important contributor to the increase in morbidity and mortality of human beings. Of these biological functions deterioration; there is a significant decline in the heart function, impairments in the lungs gas exchange, and impairments in the immune function. Many alterations in the body humeral and cellular immune response were observed with ageing process: The circulating pro-inflammatory cytokines are increased, the naive lymphocytes are decreased, the numbers of the antigen-presenting cells areelevated and the overall response is impaired. In addition, ageing is associated with a progressive restriction in the telomere length. Telomeres are located at chromosomes ends and play an essential role in preserving chromosome stability. Also, telomere length is very important to the immune system, because of the high sensitivity of the immune cells to the shortening of telomeres. Telomeres shortening adversely affect the immune cells’ function and developments. These adverse changes increased the susceptibility for severe infection, risk of hospitalization, and even death. Elderly COVID-19 patients are at a real risk of complications due to impaired immune function, cytokine storm and defective respiratory function. Administration of anti-ageing immunomodulation factors like Nicotinamide Adenine Dinucleotide NAD+ can minimize these changes through its potent immunomodulation and longevity effects. NAD+ has a direct inhibitory effect on PARP-1 and can prevent pro-inflammatory cytokines over-activation. Increasing the NAD+ level will also result in stabilizing telomeres and this has a positive impact on immune cells function.


title: Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19

text: Background Type 2 diabetes (T2DM) and obesity are significant risks for mortality in Covid19. Metformin has been hypothesized as a treatment for COVID19. Metformin has sex specific immunomodulatory effects which may elucidate treatment mechanisms in COVID-19. In this study we sought to identify whether metformin reduced mortality from Covid19 and if sex specific interactions exist. Methods De-identified claims data from UnitedHealth were used to identify persons with at least 6 months continuous coverage who were hospitalized with Covid-19. Persons in the metformin group had at least 90 days of metformin claims in the 12 months before hospitalization. Unadjusted and multivariate models were conducted to assess risk of mortality based on metformin as a home medication in individuals with T2DM and obesity, controlling for pre-morbid conditions, medications, demographics, and state. Heterogeneity of effect was assessed by sex. Results 6,256 persons were included; 52.8% female; mean age 75 years. Metformin was associated with decreased mortality in women by logistic regression, OR 0.792 (0.640, 0.979); mixed effects OR 0.780 (0.631, 0.965); Cox proportional-hazards: HR 0.785 (0.650, 0.951); and propensity matching, OR of 0.759 (0.601, 0.960). TNF-alpha inhibitors were associated with decreased mortality in the 38 persons taking them, by propensity matching, OR 0.19 (0.0378, 0.983). Conclusions Metformin was significantly associated with reduced mortality in women with obesity or T2DM in observational analyses of claims data from individuals hospitalized with Covid-19. This sex-specific finding is consistent with metformin reducing TNF-alpha in females over males, and suggests that metformin conveys protection in Covid-19 through TNF-alpha effects. Prospective studies are needed to understand mechanism and causality.


title: In vitro rapid clearance of infectious bursal disease virus in peripheral blood mononuclear cells of chicken lines divergent for antibody response might be related to the enhanced expression of proinflammatory cytokines

text: Abstract Infectious bursal disease (IBD) is an acute and highly contagious viral disease of young chickens caused by infectious bursal disease virus (IBDV). An effective way to control IBDV would be to breed chickens with a reduced susceptibility to IBDV infection. In the present work, we used chickens selected for high and low specific responses to sheep red blood cells (SRBC) (H and L, respectively) to assess the susceptibility of differential immune competent animals to IBDV infection. The peripheral blood mononuclear cells (PBMCs) of high SRBC line (HL) and low SRBC line (LL) were infected with IBDV and viral RNA loads were determined at different time post-IBDV infection. Chicken orthologues of the T helper 1 (Th1) cytokines, interferon-γ (IFN-γ) and interleukin-2 (IL-2); a Th2 cytokine, IL-10; a pro inflammatory cytokine, IL-6; the CCL chemokines, chCCLi2, chCCLi4 and chCCLi7; colony stimulating factor, GM-CSF; and a anti-inflammatory cytokine, transforming growth factor β-2 (TGFβ-2) were quantified. The expression of chCCLi2, chCCLi4 and chCCLi7 was significantly higher in L line as compared to H line. However, in H line the viral RNA loads were significantly lower than in L line. Therefore, the upregulated chemokines might be associated with the susceptibility to IBDV. The expression of IFN-γ, IL-2 and IL-6 was significantly higher in H line as compared to L line. We assume that the higher proinflammatory cytokines expression in H line might be related to the rapid clearance of virus from PBMCs. Significantly higher levels of IL-10 and TGFβ-2 mRNAs in L line might be related to the pathogenesis of IBDV. In conclusion, selection for antibody responses appears to influence the expression profiles of chemokines and cytokines against IBDV. Further, the selection for high SRBC response might improve the immuno-competence of chickens against IBDV.


title: Hepatitis C Virus and Cellular Stress Response: Implications to Molecular Pathogenesis of Liver Diseases

text: Infection with hepatitis C virus (HCV) is a leading risk factor for chronic liver disease progression, including steatosis, cirrhosis, and hepatocellular carcinoma. With approximately 3% of the human population infected worldwide, HCV infection remains a global public health challenge. The efficacy of current therapy is still limited in many patients infected with HCV, thus a greater understanding of pathogenesis in HCV infection is desperately needed. Emerging lines of evidence indicate that HCV triggers a wide range of cellular stress responses, including cell cycle arrest, apoptosis, endoplasmic reticulum (ER) stress/unfolded protein response (UPR), and autophagy. Also, recent studies suggest that these HCV-induced cellular responses may contribute to chronic liver diseases by modulating cell proliferation, altering lipid metabolism, and potentiating oncogenic pathways. However, the molecular mechanism underlying HCV infection in the pathogenesis of chronic liver diseases still remains to be determined. Here, we review the known stress response activation in HCV infection in vitro and in vivo, and also explore the possible relationship of a variety of cellular responses with the pathogenicity of HCV-associated diseases. Comprehensive knowledge of HCV-mediated disease progression shall shed new insights into the discovery of novel therapeutic targets and the development of new intervention strategy.


title: Bovine coronavirus

text: Summary This review aims to summarize current data describing the characteristics of bovine coronavirus (BCV) and the three clinical syndromes with which this virus is associated. The first half of this paper consists of a general description of the virus, commencing with a brief outline of the methods used for in vitro growth. The structure of the virus is then described in more detail, with particular reference to the structure and functions of the four major viral proteins. This is followed by an outline of the unique replication strategy adopted by coronaviruses. The second half of this review discusses the clinical significance of the virus, beginning with a detailed account of BCV-induced neonatal calf diarrhoea, the clinical syndrome with which this virus is most commonly associated. The clinical and epidemiological importance of BCV respiratory tract infection is then discussed, and finally the evidence supporting the aetiological role of BCV in outbreaks of winter dysentery in adult cattle is examined.


CS16.1 Management of the complications of liver cirrhosis


title: Full coding hepatitis E virus genotype 3 genome amplification method

text: Abstract Hepatitis E virus (HEV) genotype 3 produces zoonotic infection associated with the consumption of infected animals. HEV infections can become chronic in immunocompromised (IC) patients. The viral genome has three well defined open reading frames (ORF1, ORF2 and ORF3) within which various domains and functions have been described. This paper (i) describes a new method of complete sequencing of the HEV coding region through overlapping PCR systems, (ii) establishes a consensus sequence and polymorphic positions (PP) for each domain, and (iii) analyzes the complete coding sequence of an IC patient. With regard to the consensus, a high percentage of PP was observed in protease (PP=19%) and the X domain (PP=22%) within ORF1, the N-terminal region of the S domain (PP=22%) in ORF2, and the P1 (PP=35%) and P2 (PP=25%) domains in ORF3. In contrast, the ORF1 Y, ORF2 S, ORF2 M and ORF3 D1 domains were conserved in the reference sequences (0.40, 1, 0.70 and 0% of PP, respectively). The sequence from the IC patient had more mutations in the RpRp (D1235G, Q1242R, S1454T, V1480I, I1502 V, K1511R, G1373 V, E1442D, V1693 M), the terminal ORF2 S- domain (F10L, S26T, G36S, S70P, A105 V, I113 V), the X domain (T938 M, T856 V, S898A) and the helicase (S1014N, S975T, Q1133 K).


The Impact of COVID-19 on Radiation Oncology Clinics and Patients With Cancer in the United States


title: Distribution of infectious bronchitis virus strains in different organs and evidence of vertical transmission in natural infection

text: On the basis of partial sequencing of the infectious bronchitis virus (IBV) S1 gene, this study investigated the molecular diversity of the virus in two life periods of a batch of breeding hens at the field level. The chicks were vaccinated against IBV on the second day of life with the vaccine Ma5, but at the age of 18 days, they exhibited clinical signs and macroscopic lesions compatible with avian infectious bronchitis (IB). In the clinical disease stage, the Ma5 vaccine strain was detected in the trachea, lungs, and small intestine of the chicks, while IBV variants were detected in the bursa of Fabricius and kidneys. Subsequently, new samples were collected from the same batch at the end of the production cycle. In this phase, the Ma5 vaccine strain was detected in the kidneys, small intestine, and oviduct of the hens. However, a previously unidentified IBV variant was found in the cecal tonsils. Additionally, a fragment of viral RNA with that was completely identical to the corresponding region of the Ma5 vaccine was detected in the allantoic fluid of viable embryos from the hens under study after 18 days of incubation. These findings suggest that, in addition to the Ma5 vaccine, other strains of IBV variants can coexist, seeming to establish a chronic infection in the chickens, and that they can potentially be transmitted vertically. These results may assist in immunoprophylaxis control programs against IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-016-3030-5) contains supplementary material, which is available to authorized users.