title: Performance of spring-calving beef suckler cows and their progeny to slaughter on intensive and extensive grassland management systems

text: Abstract The performance of rotationally grazed beef suckler cows and their progeny to slaughter on two lowland grassland management systems differing in stocking rate (SR) and fertiliser nitrogen (N) level was compared over eight years. The two Systems were 1) Intensive (INT): SR of 0.56 (bull production) or 0.71 (steer production) ha cow−1 unit, 211 kg fertiliser N ha−1, two silage harvests, and 2) Extensive (EXT): SR of 0.69 (bull production) or 0.88 (steer production) ha cow−1 unit, 97 kg fertiliser N ha−1 and one staggered silage harvest. A cow unit was defined as a cow plus progeny to slaughter. On the silage harvesting area, the mean application rate for fertiliser N was 110 and 80 kg ha−1 for first and second harvests, respectively. Herbage dry matter digestibility both pre- and post-grazing was similar (P >0.05) for the two systems, whereas herbage crude protein concentrations were generally significantly lower for the EXT than the INT system. There was no difference (P >0.05) between the Systems in cow live weight, body condition score or their changes or in calf live weight gain from birth to weaning. Post-weaning, live weight gain, slaughter weight, carcass weight, kill-out proportion, estimated carcass gain, carcass conformation score or carcass fat score did not differ (P >0.05) between the systems for heifer, steer or bull progeny. It can be concluded that similar animal performance levels can be expected in an extensive grassland-based suckler calf-to-beef system compatible with the EU, Rural Environmental Protection Scheme as that attained in a more intensive System comprising of both a moderately high SR (~1.25 higher) and fertiliser N application (~2.1 higher).


title: Epitranscriptomic marks: Emerging modulators of RNA virus gene expression

text: Epitranscriptomics, the study of posttranscriptional chemical moieties placed on RNA, has blossomed in recent years. This is due in part to the emergence of high‐throughput detection methods as well as the burst of discoveries showing biological function of select chemical marks. RNA modifications have been shown to affect RNA structure, localization, and functions such as alternative splicing, stabilizing transcripts, nuclear export, cap‐dependent and cap‐independent translation, microRNA biogenesis and binding, RNA degradation, and immune regulation. As such, the deposition of chemical marks on RNA has the unique capability to spatially and temporally regulate gene expression. The goal of this article is to present the exciting convergence of the epitranscriptomic and virology fields, specifically the deposition and biological impact of N7‐methylguanosine, ribose 2′‐O‐methylation, pseudouridine, inosine, N6‐methyladenosine, and 5‐methylcytosine epitranscriptomic marks on gene expression of RNA viruses. This article is categorized under: RNA in Disease and Development > RNA in Disease. RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications.


title: Community-acquired viral respiratory infections amongst hospitalized inpatients during a COVID-19 outbreak in Singapore: co-infection and clinical outcomes

text: AIMS: During the ongoing COVID-19 outbreak, co-circulation of other common respiratory viruses can potentially result in co-infections; however, reported rates of co-infections for SARS-CoV-2 vary. We sought to evaluate the prevalence and etiology of all community acquired viral respiratory infections requiring hospitalization during an ongoing COVID-19 outbreak, with a focus on co-infection rates and clinical outcomes. METHODS: Over a 10-week period, all admissions to our institution, the largest tertiary hospital in Singapore, were screened for respiratory symptoms, and COVID-19 as well as a panel of common respiratory viral pathogens were systematically tested for. Information was collated on clinical outcomes, including requirement for mechanical ventilation and in hospital mortality. RESULTS: One-fifth (19.3%, 736/3807) of hospitalized inpatients with respiratory symptoms had a PCR-proven viral respiratory infection; of which 58.5% (431/736) tested positive for SARS-CoV-2 and 42.2% (311/736) tested positive for other common respiratory viruses. The rate of co-infection with SARS-CoV-2 was 1.4% (8/431); all patients with co-infection had mild disease and stayed in communal settings. The in-hospital mortality rate and proportion of COVID-19 patients requiring invasive ventilation was low, at around 1% of patients; these rates were lower than patients with other community-acquired respiratory viruses admitted over the same period (p < 0.01). CONCLUSION: Even amidst an ongoing COVID-19 outbreak, common respiratory viruses still accounted for a substantial proportion of hospitalizations. Coinfections with SARS-CoV-2 were rare, with no observed increase in morbidity or mortality.


Adults with congenital heart disease during the coronavirus disease 2019 (COVID-19) pandemic: are they at risk?


Making State Public Health Laws Work for SARS Outbreaks


title: Immune‐Mediated Neutropenia in 2 Dogs

text: Immune‐mediated neutropenia, also termed autoimmune neutropenia (AIN), is an uncommon event, rarely documented within veterinary literature, although the clinical profile and probable pathogenesis have been outlined in detail within medical literature. In this paper, we review 2 different manifestations of this disorder. The 1st case primarily involved peripheral destruction of mature neutrophils, with little impact on marrow precursors, whereas the 2nd case resulted in suppression of neutrophilic granulopoiesis within marrow. In both cases, absolute neutrophil counts dropped below 200/mL.


docid: tahmgsas

title: On the impact of epidemic severity on network immunization algorithms

text: Abstract There has been much recent interest in the prevention and mitigation of epidemics spreading through contact networks of host populations. Here, we investigate how the severity of epidemics, measured by its infection rate, influences the efficiency of well-known vaccination strategies. In order to assess the impact of severity, we simulate the SIR model at different infection rates on various real and model immunized networks. An extensive analysis of our simulation results reveals that immunization algorithms, which efficiently reduce the nodes’ average degree, are more effective in the mitigation of weak and slow epidemics, whereas vaccination strategies that fragment networks to small components, are more successful in suppressing severe epidemics.


title: Impact of COVID‐19 on the mental health of surgeons and coping strategies

text: Unprecedented times call for extraordinary measures. While surgeons across the globe try to comprehend the evolving facade of the COVID‐19 pandemic and improvise surgical practice to the best of their ability, the psychological impact of the stress on their own mental health and well‐being has been underestimated. This paper aims to review the indirect and overt factors that may affect the mental health of a surgeon in the present circumstances. Furthermore, it will aim to highlight key coping mechanisms at an individual and institutional level, so as to mitigate the negative psychological impact on surgeons.


title: Intact Brain Network Function in an Unresponsive Patient with COVID‐19

text: Many patients with severe coronavirus disease 2019 (COVID‐19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID‐19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID‐19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness.


Herausforderungen und Chancen für die Arbeit der Akademie für Ethik in der Medizin angesichts der COVID-19-Pandemie


Response to COVID -19 and Diabetes: Can DPP4 Inhibition Play a Role? – GLP-1 Might Play One Too


title: Chapter 3 Biology and Diseases of Mice

text: Today’s laboratory mouse, Mus musculus, has its origins as the ‘house mouse’ of North America and Europe. Beginning with mice bred by mouse fanciers, laboratory stocks (outbred) derived from M. musculus musculus from eastern Europe and M. m. domesticus from western Europe were developed into inbred strains. Since the mid-1980s, additional strains have been developed from Asian mice (M. m. castaneus from Thailand and M. m. molossinus from Japan) and from M. spretus which originated from the western Mediterranean region.


title: Analysis of interactions between SNARE proteins using imaging ellipsometer coupled with microfluidic array

text: The soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins are small and abundant membrane-bound proteins, whose specific interactions mediate membrane fusion during cell fusion or cellular trafficking. In this study, we report the use of a label-free method, called imaging ellipsometer to analyze the interactions among three SNAREs, namely Sec22p, Ykt6p and Sso2p. The SNAREs were immobilized on the silicon wafer and then analyzed in a pairwise mode with microfluidic array, leading us to discover the interactions between Ykt6p and Sso2p, Sec22p and Sso2p. Moreover, by using the real-time function of the imaging ellipsometer, we were able to obtain their association constants (K(A)) of about 10(4) M(−1). We argue that the use of imaging ellipsometer coupled with microfluidic device will deepen our understanding of the molecular mechanisms underlying membrane fusion process.


title: High-flow nasal cannula for COVID-19 patients: low risk of bio-aerosol dispersion

text: Human-to-human SARS-COV2 transmission has been established with more than 3300 clinicians reported to be infected in China and more than 1116 clinicians infected in Italy where 13 882 cases were confirmed by 13 March 2020. Room surfaces in the vicinity of COVID-19 symptomatic patients and clinician's protection equipment were found to be contaminated [1]. The primary strategy for COVID-19 patients is supportive care, including oxygen therapy for hypoxemic patients, in which high-flow nasal cannula (HFNC) was reported as effective in improving oxygenation. Among patients with acute hypoxemic respiratory failure, HFNC was proven to avoid intubation compared to conventional oxygen device [2, 3].


title: Anticoagulant and antiarrhythmic effects of heparin in the treatment of COVID‐19 patients

text: Most severe manifestations of COVID‐19 cases, such as multiple organ failure and death, have been linked to coagulation dysfunction markers, such as platelet reduction and increases in prothrombin time, fibrin degradation products and, mainly, D‐dimer [1]. A recent paper by Tang et al. [2] in this journal reported that heparin treatment reduced mortality of COVID‐19 patients with elevated D‐dimer; similar preliminary results have been reported elsewhere [3]. A mounting body of evidence shows that SARS‐CoV‐2 causes a “cytokine storm” [1,4] that activates the coagulation cascade, leading to thrombosis. Similar to the findings in severe sepsis, generalized deposition of intravascular thrombi compromises the blood supply of several organs, leading to organ failure [5].


title: Olfactory and Gustatory Dysfunction as an Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study

text: OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)–confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.


title: COVID‐19 in Italian pediatric patients: the experience of a tertiary children’s hospital

text: Coronavirus disease (COVID‐19) caused by the novel SARS‐CoV‐2 has spread worldwide since its onset in Wuhan in December 2019. In Italy COVID‐19 rapidly increased in February 2020 and by 12 May 2020, 2.0 % of the confirmed cases were under 18 years and 3.7% of those had been hospitalized. This case series report reviews the demographic characteristics, clinical course, laboratory findings, radiologic features and treatment of children admitted with COVID‐19 to a tertiary care hospital in Italy.


title: Chapter 22 Nose, Larynx, and Trachea

text: Abstract Chapter 22 outlines the morphology of the nose, larynx, and trachea. The text includes descriptions of spontaneous and treatment-related lesions observed in the tissues in toxicity and carcinogenicity studies. The text begins with a description of the normal upper respiratory tract through the stages of embryonic development. Anatomy and histology are discussed before delving into the various degenerative, regenerative, and adaptive lesions found in toxicology studies. Included in the text is information on inflammatory and vascular lesions, and how trauma and injury, as well as exposure to irritants, can elicit inflammatory responses. Molecular pathology of the upper respiratory tract is investigated, as well as an examination of the molecular alterations within specific cell types, providing a better understanding of the mechanisms of tissue injury.


Hydroxychloroquine: balancing the needs of LMICs during the COVID-19 pandemic


docid: rqjeacow

title: Multiple organ infection and the pathogenesis of SARS

text: After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.


Intraventricular recombinant alpha-interferon in subacute sclerosing panencephalitis


title: Nano-based anti-tubercular drug delivery: an emerging paradigm for improved therapeutic intervention

text: Tuberculosis (TB) classified as one of the most fatal contagious diseases is of prime concern globally. Mycobacterium tuberculosis is the causative agent that ingresses within the host cells. The approved conventional regimen, though the only viable option available, is unfavorably impacting the quality of life of the affected individual. Despite newer antibiotics gaining light, there is an unending demand for more therapeutic alternatives. Therefore, substantial continuous endeavors are been undertaken to come up with novel strategies to curb the disease, the stepping stone being nanotechnology. This approach is instrumental in overcoming the anomalies associated with conventional therapy owing to their intriguing attributes and leads to optimization of the therapeutic effect to a certain extent. This review focusses on the different types of nanocarrier systems that are being currently explored by the researchers for the delivery of anti-tubercular drugs, the outcomes achieved by them, and their prospects. [Figure: see text]


Quelle conduite à tenir pour la prise en charge de pathologies chirurgicales vitréo-rétiniennes en cette période d’épidémie de Covid-19 à virus SARS-CoV-2?#


title: Developments, applications, and prospects of cryo‐electron microscopy

text: Cryo‐electron microscopy (cryo‐EM) is a structural biological method that is used to determine the 3D structures of biomacromolecules. After years of development, cryo‐EM has made great achievements, which has led to a revolution in structural biology. In this article, the principle, characteristics, history, current situation, workflow, and common problems of cryo‐EM are systematically reviewed. In addition, the new development direction of cryo‐EM—cryo‐electron tomography (cryo‐ET), is discussed in detail. Also, cryo‐EM is prospected from the following aspects: the structural analysis of small proteins, the improvement of resolution and efficiency, and the relationship between cryo‐EM and drug development. This review is dedicated to giving readers a comprehensive understanding of the development and application of cryo‐EM, and to bringing them new insights.


title: A synthesis of (±)-thia-calanolide A, its resolution and in vitro biological evaluation

text: Abstract A synthesis of (±)-thia-calanolide A 3 has been successfully accomplished starting from 3,5-dimethoxythiophenol 4, in six steps in an overall yield of 4.5%. The key reaction involved Friedel–Crafts tigloylation of 5,7-dihydroxy-4-n-propyl thiocoumarin 6 employing an appropriate solvent of CS2–PhNO2 in a ratio of 7:3. In its biological evaluation for anti-HIV activity, (±)-thia-calanolide A 3 demonstrated comparatively less activity with calanolide A and its synthetic analogue aza-calanolide. Further, (±)-3 has been resolved by chiral HPLC to (+) and (−)-3.


title: Relapsing subacute demyelinating encephalomyelitis in rats during the course of coronavirus JHM infection

text: Abstract Temperature-sensitive mutants of the murine coronavirus JHM induced a subacute demyelinating encephalomyelitis (SDE) in young rats. Neurological symptoms were associated with marked lesions of primary demyelination in the white matter of the central nervous system (CNS), and developing after an incubation time of several weeks to months. Many rats survived this infection and recovered completely from this CNS disease. Among 43 survivors of SDE, 9 rats developed a relapse 27–153 days after onset of the first attack. Neuropathological examination of these animals revealed areas of fresh demyelination together with old remyelinated lesions. Viral antigens were detectable in the neighbourhood of fresh lesions and in some cases infectious virus was re-isolated from rats revealing low antibody titers to JHM virus. These results demonstrate that mutants of JHM virus can induce a relapsing demyelinating disease process, associated with a persistent infection, which possesses some similarities to chronic experimental allergic encephalomyelitis.


docid: ikptxviu

title: US-like isolates of porcine epidemic diarrhea virus from Japanese outbreaks between 2013 and 2014

text: Since late 2013, outbreaks of porcine epidemic diarrhea virus (PEDV) have reemerged in Japan. In the present study, we observed a high detection rate of PEDV, with 72.5 % (148/204) of diarrhea samples (suckling, weaned, and sows) and 88.5 % (77/87) of farms experiencing acute diarrhea found to be positive for PEDV by reverse transcription PCR. Sequencing and phylogenic analyses of the partial spike gene and ORF3 of PEDV demonstrated that all prevailing Japanese PEDV isolates belonged to novel genotypes that differed from previously reported strains and the two PEDV vaccine strains currently being used in Japan. Sequence and phylogenetic analysis revealed prevailing PEDV isolates in Japan had the greatest genetic similarity to US isolates and were not vaccine-related. Unlike vaccine strains, all prevailing field PEDV isolates in Japan were found to have a number of amino acid differences in the neutralizing epitope domain, COE, which may affect antigenicity and vaccine efficacy. The present study indicates recent PEDV isolates may have been introduced into Japan from overseas and highlights the urgent requirement of novel vaccines for controlling PEDV outbreaks in Japan.


title: Memory of mice and men: CD8(+) T‐cell cross‐reactivity and heterologous immunity

text: Summary: The main functions of memory T cells are to provide protection upon re‐exposure to a pathogen and to prevent the re‐emergence of low‐grade persistent pathogens. Memory T cells achieve these functions through their high frequency and elevated activation state, which lead to rapid responses upon antigenic challenge. The significance and characteristics of memory CD8(+) T cells in viral infections have been studied extensively. In many of these studies of T‐cell memory, experimental viral immunologists go to great lengths to assure that their animal colonies are free of endogenous pathogens in order to design reproducible experiments. These experimental results are then thought to provide the basis for our understanding of human immune responses to viruses. Although these findings can be enlightening, humans are not immunologically naïve, and they often have memory T‐cell populations that can cross‐react with and respond to a new infectious agent or cross‐react with allo‐antigens and influence the success of tissue transplantation. These cross‐reactive T cells can become activated and modulate the immune response and outcome of subsequent heterologous infections, a phenomenon we have termed heterologous immunity. These large memory populations are also accommodated into a finite immune system, requiring that the host makes room for each new population of memory cell. It appears that memory cells are part of a continually evolving interactive network, where with each new infection there is an alteration in the frequencies, distributions, and activities of memory cells generated in response to previous infections and allo‐antigens.


docid: yugpjgjj

title: N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting

text: BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.


title: Standard and AEGIS nicking molecular beacons detect amplicons from the Middle East respiratory syndrome coronavirus

text: Abstract This paper combines two advances to detect MERS-CoV, the causative agent of Middle East Respiratory Syndrome, that have emerged over the past few years from the new field of “synthetic biology”. Both are based on an older concept, where molecular beacons are used as the downstream detection of viral RNA in biological mixtures followed by reverse transcription PCR amplification. The first advance exploits the artificially expanded genetic information systems (AEGIS). AEGIS adds nucleotides to the four found in standard DNA and RNA (xNA); AEGIS nucleotides pair orthogonally to the A:T and G:C pairs. Placing AEGIS components in the stems of molecular beacons is shown to lower noise by preventing unwanted stem invasion by adventitious natural xNA. This should improve the signal-to-noise ratio of molecular beacons operating in complex biological mixtures. The second advance introduces a nicking enzyme that allows a single target molecule to activate more than one beacon, allowing “signal amplification”. Combining these technologies in primers with components of a self-avoiding molecular recognition system (SAMRS), we detect 50 copies of MERS-CoV RNA in a multiplexed respiratory virus panel by generating fluorescence signal visible to human eye and/or camera.


title: Impact of MicroRNA in Normal and Pathological Respiratory Epithelia

text: Extensive sequencing efforts, combined with ad hoc bioinformatics developments, have now led to the identification of 1222 distinct miRNAs in human (derived from 1368 distinct genomic loci) and of many miRNAs in other multicellular organisms. The present chapter is aimed at describing a general experimental strategy to identify specific miRNA expression profiles and to highlight the functional networks operating between them and their mRNA targets, including several miRNAs deregulated in cystic fibrosis and during differentiation of airway epithelial cells.


title: Early decrease in blood platelet count is associated with poor prognosis in COVID-19 patients—indications for predictive, preventive, and personalized medical approach

text: BACKGROUND: Changes in platelet count are common in COVID-19 patients. The platelet count reflects the thrombocyte turnover, acting as a sensitive indicator of illness severity that is of great clinical utility to monitor a quickly changing health condition of patients affected by aggressive viral infections. This study aims to investigate the significance of platelet count during the progression of the disease in COVID-19 patients. METHODS: A total of 532 COVID-19 patients were involved in the cohort study from the First People’s Hospital of Jiangxia District in Wuhan from January 7, 2020, to February 28, 2020. We collected the clinical characteristics and laboratory data of patients. Patients still hospitalized before February 29, 2020, died on admission, with malignant tumors, previous gastrointestinal surgery, missing baseline platelet count, or platelet count detected only once, were excluded. We used a generalized additive model and generalized additive mixed model to compare trends in platelet count over time among survivors and non-survivors, with an adjustment for potential confounders. RESULTS: During the follow-up, twenty-nine subjects died (mortality rate, 5.45%). The platelets among non-survivors decreased and among survivors increased gradually within 1 week after admission. In addition, the difference between the two groups showed an increasing trend during 1 week after admission. This difference increased by an average of 5.3 × 10^9/L daily. CONCLUSIONS: In the early stage, platelet count can dynamically reflect the pathophysiological changes in COVID-19 patients. Early decrease in platelet count was associated with mortality in patients with COVID-19. Causality, however, cannot be deduced from our data.


title: Internet-based surveillance systems for monitoring emerging infectious diseases

text: Emerging infectious diseases present a complex challenge to public health officials and governments; these challenges have been compounded by rapidly shifting patterns of human behaviour and globalisation. The increase in emerging infectious diseases has led to calls for new technologies and approaches for detection, tracking, reporting, and response. Internet-based surveillance systems offer a novel and developing means of monitoring conditions of public health concern, including emerging infectious diseases. We review studies that have exploited internet use and search trends to monitor two such diseases: influenza and dengue. Internet-based surveillance systems have good congruence with traditional surveillance approaches. Additionally, internet-based approaches are logistically and economically appealing. However, they do not have the capacity to replace traditional surveillance systems; they should not be viewed as an alternative, but rather an extension. Future research should focus on using data generated through internet-based surveillance and response systems to bolster the capacity of traditional surveillance systems for emerging infectious diseases.


title: Was WHO SARS-related Travel Advisory for Toronto Ethical?

text: Freedom of movement is undoubtedly a fundamental international right. However, circumstances may arise where that right must be curtailed. Was the 2003 SARS outbreak in Toronto one such circumstance? Guénaël R.M. Rodier thinks WHO’s decision to impose a SARS-related travel advisory was justifiable, even reasonable, though it caused a loss of over $1.1 billion in the Greater Toronto Area. That travel to an infected area was the most common epidemiological link with SARS infections supports Rodier’s position. However, as suggested in the Naylor report, issuing a travel advisory does not keep infected individuals from leaving Toronto and such individuals account for 5 of 6 cases where SARS was spread from Canada. That alone would discount Rodier’s argument and the WHO decision on purely logistical grounds. But there is an ethical question as well. Was the travel advisory implemented fairly? This question is best judged using Nancy E. Kass’s framework for public health. From that framework, two points are placed in immediate relief. First, the Toronto authorities were not given an opportunity to state their case to WHO before the travel advisory was implemented. Second, the framework requires that burdens be distributed fairly and the travel advisory did not do that, or even attempt to do so.


Anthroponotic risk of SARS-CoV-2, precautionary mitigation, and outbreak management


title: Variability in transmissibility of the 2009 H1N1 pandemic in Canadian communities

text: BACKGROUND: The prevalence and severity of the 2009 H1N1 pandemic appeared to vary significantly across populations and geographic regions. We sought to investigate the variability in transmissibility of H1N1 pandemic in different health regions (including urban centres and remote, isolated communities) in the province of Manitoba, Canada. METHODS: The Richards model was used to fit to the daily number of laboratory-confirmed cases and estimate transmissibility (referred to as the basic reproduction number, R(0)), doubling times, and turning points of outbreaks in both spring and fall waves of the H1N1 pandemic in several health regions. RESULTS: We observed considerable variation in R(0 )estimates ranging from 1.55 to 2.24, with confidence intervals ranging from 1.45 to 2.88, for an average generation time of 2.9 days, and shorter doubling times in some remote and isolated communities compared to urban centres, suggesting a more rapid spread of disease in these communities during the first wave. For the second wave, R(e), the effective reproduction number, is estimated to be lower for remote and isolated communities; however, outbreaks appear to have been driven by somewhat higher transmissibility in urban centres. CONCLUSIONS: There was considerable geographic variation in transmissibility of the 2009 pandemic outbreaks. While highlighting the importance of estimating R(0 )for informing health responses, the findings indicate that projecting the transmissibility for large-scale epidemics may not faithfully characterize the early spread of disease in remote and isolated communities.


title: Pathogen inactivation and removal procedures used in the production of intravenous immunoglobulins

text: Abstract Patients with immunodeficiencies or some types of autoimmune diseases rely on a safe therapy with intravenous immunoglobulins (IVIGs) manufactured from human plasma, the only available source for this therapeutic. Since plasma is predisposed to contamination by a variety of blood-borne pathogens, ascertaining and ensuring the pathogen safety of plasma-derived therapeutics is a priority among manufacturers. State-of-the-art manufacturing processes provide a high safety standard by incorporating virus elimination procedures into the manufacturing process. Based on their mechanism these procedures are grouped into three classes: partitioning, inactivation, and virusfiltration.


Antipsoriatic treatments during COVID‐19 outbreak


title: Social support and HIV/STDs infections among a probability-based sample of rural married migrant women in Shandong Province, China

text: BACKGROUND: The increasing population of marriage-based migrant women is disproportionally affected by AIDS/STDs in China, and social support plays a critical role. This study aims to describe the social support level received by married migrant women in rural areas in Shandong province in comparison to non-migrant local women, identifies the relevant factors of this social support condition among married migrant women, and observes the correlation between social support level and infection status of AIDS and STDs among this group. METHODS: A probability-based sample of 1,076 migrant and 1,195 local women were included in the study. A pre-tested field questionnaire was administered to participants through a direct face-to-face interview. Questionnaire contained questions on socio-demographic information, AIDS and STDs prevalence information and Social Support Rating Scale (SSRS) which measures objective support, subjective support, and utilization of social support. RESULTS: Compared to local women, married migrant women had lower levels of social support in most dimensions. Multi-variable analysis revealed that relationship with spouse, family average income, number of children, education, engagement and claimed reasons of moving have various correlations with one or all dimensions of social support scores. Higher social support is also related to awareness of infection status of HIV and STDs among this group. CONCLUSION: Our findings provide further evidence that married migrant women have lower levels of social support which may be related to some social characteristics and their awareness status of AIDS and STDs infection status and that targeted interventions need to be developed for this population.


title: Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now?

text: Abstract Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19), has posed a serious threat to global health and is currently causing a major pandemic. While patients typically present with fever and a respiratory illness, mounting evidence indicates that patients might also report extra-pulmonary manifestations, including those affecting the liver and gastrointestinal tract. This involvement may have important implications to the disease management, transmission, and prognosis, especially in patients with pre-existing hepatic or digestive co-morbidities. In this review, the characteristics and possible explanations of hepatic and gastrointestinal involvement caused by SARS-CoV-2 infection are summarized, adding to our knowledge of the spectrum of COVID-19. In addition, preventive measures implemented in endoscopy departments to prevent further dissemination of SARS-CoV-2 infection are proposed.


title: An Overview of Patent Law as Applied to the Field of Veterinary Medicine

text: This article analyzes some of the challenges that can arise when patent law is applied to the field of veterinary medicine. Topics covered in this article include an overview of the different kinds of inventions that can be patented in the veterinary field; a review of recent legal developments that may affect the patenting of veterinary pharmaceuticals; a discussion of some potential issues related to patents covering assays; and an identification of some special situations where the law affecting veterinary pharmaceuticals is actually different from the law affecting human pharmaceuticals.


Caught in the crossfire: hepato‐bilio‐pancreatic cancer surgery in the midst of COVID‐19


title: Expanded skin virome in DOCK8-deficient patients

text: Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation(1–3), mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunedeficient patients manifest with various viral bacterial, fungal and parasitic infections, including skin infections(4). Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility(5). DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues, such as skin(6). Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity as compared to healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.


title: The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

text: Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins—whose aberrant activities govern the reprogramed state of coronavirus-infected cells—presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to established treatments. Specifically, we propose that a small module of host cell Master Regulator proteins (ViroCheckpoint) is hijacked by the virus to support its efficient replication and release. Conventional methodologies are not well suited to elucidate these potentially targetable proteins. By using the VIPER network-based algorithm, we successfully interrogated 12h, 24h, and 48h signatures from Calu-3 lung adenocarcinoma cells infected with SARS-CoV, to elucidate the time-dependent reprogramming of host cells and associated Master Regulator proteins. We used the NYS CLIA-certified Darwin OncoTreat algorithm, with an existing database of RNASeq profiles following cell perturbation with 133 FDA-approved and 195 late-stage experimental compounds, to identify drugs capable of virtually abrogating the virus-induced Master Regulator signature. This approach to drug prioritization and repurposing can be trivially extended to other viral pathogens, including SARS-CoV-2, as soon as the relevant infection signature becomes available.


title: Evaluation of bioaerosol samplers for the detection and quantification of influenza virus from artificial aerosols and influenza virus–infected ferrets

text: BACKGROUND: Bioaerosol sampling devices are necessary for the characterization of infectious bioaerosols emitted by naturally‐infected hosts with acute respiratory virus infections. Assessment of these devices under multiple experimental conditions will provide insight for device use. OBJECTIVES: The primary objective of this study was to assess and compare bioaerosol sampling devices using a) an in vitro, environmentally‐controlled artificial bioaerosol system at a range of different RH conditions and b) an in vivo bioaerosol system of influenza virus‐infected ferrets under controlled environmental conditions. Secondarily, we also sought to examine the impact of NSAIDs on bioaerosol emission in influenza virus‐infected ferrets to address its potential as a determinant of bioaerosol emission. METHODS: We examined the performance of low and moderate volume bioaerosol samplers for the collection of viral RNA and infectious influenza virus in vitroand in vivo using artificial bioaerosols and the ferret model of influenza virus infection. The following samplers were tested: the polytetrafluoroethylene filter (PTFE filter), the 2‐stage National Institute of Occupational Safety and Health cyclone sampler (NIOSH cyclone sampler) and the 6‐stage viable Andersen impactor (Andersen impactor). RESULTS: The PTFE filter and NIOSH cyclone sampler collected similar amounts of viral RNA and infectious virus from artificially‐generated aerosols under a range of relative humidities (RH). Using the ferret model, the PTFE filter, NIOSH cyclone sampler and the Andersen impactor collected up to 3.66 log(10)copies of RNA/L air, 3.84 log(10)copies of RNA/L air and 6.09 log(10)copies of RNA/L air respectively at peak recovery. Infectious virus was recovered from the PTFE filter and NIOSH cyclone samplers on the peak day of viral RNA recovery. CONCLUSION: The PTFE filter and NIOSH cyclone sampler are useful for influenza virus RNA and infectious virus collection and may be considered for clinical and environmental settings.


title: Concerns and Fears of Indian Dentists on Professional Practice During the Coronavirus Disease‐2019 (COVID‐19) Pandemic

text: The Coronavirus disease‐2019 (COVID‐19) pandemic, due to the Severe Acute Respiratory Syndrome Virus 2 (SARS‐CoV‐2) was declared a public health emergency of international concern by the World Health Organization on 30(th) of January 2020 (World Health Organization, 2020). The first case of COVID‐19 was reported in India on the same day, and at the time of writing, on 20(th) May 2020, India has reported over 106,000 patients, with over 3,300 related deaths. The country is under a state of lockdown since 25(th) March, 2020, and over 600 health care providers have been infected.


title: Challenges of the Unknown: Clinical Application of Microbial Metagenomics

text: Availability of fast, high throughput and low cost whole genome sequencing holds great promise within public health microbiology, with applications ranging from outbreak detection and tracking transmission events to understanding the role played by microbial communities in health and disease. Within clinical metagenomics, identifying microorganisms from a complex and host enriched background remains a central computational challenge. As proof of principle, we sequenced two metagenomic samples, a known viral mixture of 25 human pathogens and an unknown complex biological model using benchtop technology. The datasets were then analysed using a bioinformatic pipeline developed around recent fast classification methods. A targeted approach was able to detect 20 of the viruses against a background of host contamination from multiple sources and bacterial contamination. An alternative untargeted identification method was highly correlated with these classifications, and over 1,600 species were identified when applied to the complex biological model, including several species captured at over 50% genome coverage. In summary, this study demonstrates the great potential of applying metagenomics within the clinical laboratory setting and that this can be achieved using infrastructure available to nondedicated sequencing centres.


title: Using DNA Shuffling to Create Novel Infectious Bronchitis Virus S1 Genes: Implications for S1 Gene Recombination

text: We employed the staggered extension process (StEP) to shuffle the S1 genes from four infectious bronchitis virus (IBV) strains representing four unique serotypes. Upon creating a shuffled S1 gene library, we randomly selected 25 clones and analyzed them by DNA sequencing. In total, eleven clones contained novel S1 gene recombinants. Based on sequence data, each recombinant was unique and contained a full-length open reading frame. The average number of crossovers per recombinant was 5 and the average number of point mutations was 1.3, leading mostly to non-synonymous amino acid changes. No recombinant contained sequences from all four parental genes and no recombinant contained any sequence from the distantly related Delaware 072 strain. Our data suggests that recombination between distantly related IBV strains within the S1 gene probably does not readily occur. This finding is extremely important in light of the common industry vaccination practice of mixing different live-attenuated IBV strains.


title: Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes

text: Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.


docid: riwurvmg

title: Avian cholera outbreaks threaten seabird species on Amsterdam Island

text: Infectious diseases may be particularly critical for the conservation of endangered species. A striking example is the recurrent outbreaks that have been occurring in seabirds on Amsterdam Island for the past 30 years, threatening populations of three Endangered seabird species and of the endemic, Critically Endangered Amsterdam albatross Diomedea amsterdamensis. The bacteria Pasteurella multocida (avian cholera causative agent), and to a lesser extent Erysipelothrix rhusiopathiae (erysipelas causative agent), were both suspected to be responsible for these epidemics. Despite this critical situation, demographic trends were not available for these threatened populations, and the occurrence and characterization of potential causative agents of epizootics remain poorly known. The aims of the current study were to (i) provide an update of population trends for four threatened seabird species monitored on Amsterdam Island, (ii) assess the occurrence of P. multocida, and E. rhusiopathiae in live birds from five species, (iii) search for other infectious agents in these samples and, (iv) isolate and genotype the causative agent(s) of epizooties from dead birds. Our study shows that the demographic situation has worsened substantially in three seabird species during the past decade, with extremely low reproductive success and declining populations for Indian yellow-nosed albatrosses Thalassarche carteri, sooty albatrosses Phoebetria fusca, and northern rockhopper penguins Eudyptes moseleyi. Pasteurella multocida or E. rhusiopathiae were detected by PCR in live birds of all five investigated species, while results were negative for eight additional infectious agents. A single strain of P. multocida was repeatedly cultured from dead birds, while no E. rhusiopathiae could be isolated. These results highlight the significance of P. multocida in this particular eco-epidemiological system as the main agent responsible for epizootics. The study stresses the urgent need to implement mitigation measures to alter the course of avian cholera outbreaks threatening the persistence of seabird populations on Amsterdam Island.


title: All lesions great and small, part 2. Diagnostic cytology in veterinary medicine

text: This is the second in a two‐part review of diagnostic cytopathology in veterinary medicine. As in human medicine, cytopathology is a minimally invasive, rapid, and cost‐effective diagnostic modality with broad utilization. In this second part, the diagnostic applications of cytology in respiratory, gastrointestinal, genitourinary, endocrine, ocular, and central nervous system tissues are discussed with a section describing fluid analysis in veterinary medicine. As noted in the previous manuscript, which characterized the cytology of the skin/subcutis, musculoskeletal, and lymphoid tissues, the interpretation of veterinary cytology samples must be undertaken with extensive knowledge of the breadth of animal species, including familiarity with the frequency and clinical progression of diseases, both of which can be influenced by species, breed, and husbandry conditions. Similar to part one, this review focuses on the most common domestic companion animal species (dog, cat, and horse) and highlights lesions that are either unique to veterinary species or have relevant correlates in people. The cytologic features and biological behavior of similar lesions are compared, and selected mechanisms of disease and ancillary diagnostics are reviewed when appropriate. Supporting figures illustrate a subset of lesions. While not an exhaustive archive of veterinary cytology, the goal is to give cytopathologists working in human medicine a general impression of correlates and unique entities in veterinary practice. Diagn. Cytopathol. 2014;42:544–552. © 2014 Wiley Periodicals, Inc.


title: Inhibition of porcine hemagglutinating encephalomyelitis virus replication by short hairpin RNAs targeting of the nucleocapsid gene in a porcine kidney cell line

text: Abstract Porcine hemagglutinating encephalomyelitis virus (PHEV), which causes porcine encephalomyelitis and is widespread among swine worldwide. RNA interference (RNAi) pathways have emerged as important regulators of virus–host cell interactions. In this study, two siRNA expression plasmids (shN1 and shN2) were generated to target two different coding regions of the nucleocapsid protein (N) of PHEV. The shRNAs were transiently transfected into a porcine kidney cell line, PK-15, to determine whether these constructs inhibited PHEV production. Our results revealed that both shRNAs were highly capable of inhibiting viral RNA genome replication, especially shN2. Next, stable transfection of shN2 was used to produce two siRNA stably expressing PK-15 cell clones (shN2-1 and shN2-2), and these two lines were infected with PHEV. The analysis of cytopathic effects (CPE) demonstrated that shN2-1 and shN2-2 were capable of protecting cells against PHEV infection with high specificity and efficiency. Furthermore, effective inhibition of viral replication persisted for up to 120h by a TCID50 assay. These results indicated that RNAi targeting of the N gene could facilitate studies of the specific function of viral genes associated with PHEV replication and may have potential therapeutic applications.


title: The Role of CXCR3 in Neurological Diseases

text: BACKGROUND: Neurological diseases have become an obvious challenge due to insufficient therapeutic intervention. Therefore, novel drugs for various neurological disorders are in desperate need. Recently, compelling evidence has demon-strated that chemokine receptor CXCR3, which is a G protein-coupled receptor in the CXC chemokine receptor family, may play a pivotal role in the development of neurological diseases. The aim of this review is to provide evidence for the potential of CXCR3 as a therapeutic target for neurological diseases. METHODS: English journal articles that focused on the invovlement of CXCR3 in neurological diseases were searched via PubMed up to May 2017. Moreover, reference lists from identified articles were included for overviews. RESULTS: The expression level of CXCR3 in T cells was significantly elevated in several neurological diseases, including multiple sclerosis (MS), glioma, Alzheimer’s disease (AD), chronic pain, human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and bipolar disorder. CXCR3 antagonists showed therapeutic effects in these neurological diseases. CONCLUSION: These studies provided hard evidence that CXCR3 plays a vital role in the pathogenesis of MS, glioma, AD, chronic pain, HAM/TSP and bipolar disorder. CXCR3 is a crucial molecule in neuroinflammatory and neurodegenerative diseases. It regulates the activation of infiltrating cells and resident immune cells. However, the exact functions of CXCR3 in neurological diseases are inconclusive. Thus, it is important to understand the topic of chemokines and the scope of their ac-tivity in neurological diseases.


title: Utilization of Physiologically Based Pharmacokinetic Modeling in Clinical Pharmacology and Therapeutics: an Overview

text: The purpose of this review was to assess the advancement of applications for physiologically based pharmacokinetic (PBPK) modeling in various therapeutic areas. We conducted a PubMed search, and 166 articles published between 2012 and 2018 on FDA-approved drug products were selected for further review. Qualifying publications were summarized according to therapeutic area, medication(s) studied, pharmacokinetic model type utilized, simulator program used, and the applications of that modeling. The results showed a 13-fold increase in the number of papers published from 2012 to 2018, with the largest proportion of articles dedicated to the areas of infectious diseases, oncology, and neurology, and application extensions including prediction of drug-drug interactions due to metabolism and/or transporter-mediated effects and understanding drug kinetics in special populations. In addition, we profiled several high-impact studies whose results were used to guide package insert information and formulate dose recommendations. These results show that while utilization of PBPK modeling has drastically increased over the past several years, regulatory support, lack of easy-to-use systems for clinicians, and challenges with model validation remain major challenges for the widespread adoption of this practice in institutional and ambulatory settings. However, PBPK modeling will continue to be a useful tool in the future to assess therapeutic drug monitoring and the growing field of personalized medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40495-020-00212-x) contains supplementary material, which is available to authorized users.


It Will Be a Different World for Surgeons Post-COVID-19 Lockdown


Assistance Publique–Hôpitaux de Paris' response to the COVID-19 pandemic


Mechanisms of increased morbidity and mortality of SARS-CoV-2 infection in individuals with diabetes: what this means for an effective management strategy


title: Active Replication of Middle East Respiratory Syndrome Coronavirus and Aberrant Induction of Inflammatory Cytokines and Chemokines in Human Macrophages: Implications for Pathogenesis

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infection caused severe pneumonia and multiorgan dysfunction and had a higher crude fatality rate (around 50% vs 10%) than SARS coronavirus (SARS-CoV) infection. To understand the pathogenesis, we studied viral replication, cytokine/chemokine response, and antigen presentation in MERS-CoV–infected human monocyte–derived macrophages (MDMs) versus SARS-CoV–infected MDMs. Only MERS-CoV can replicate in MDMs. Both viruses were unable to significantly stimulate the expression of antiviral cytokines (interferon α [IFN-α] and IFN-β) but induced comparable levels of tumor necrosis factor α and interleukin 6. Notably, MERS-CoV induced significantly higher expression levels of interleukin 12, IFN-γ, and chemokines (IP-10/CXCL-10, MCP-1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5, and interleukin 8) than SARS-CoV. The expression of major histocompatibility complex class I and costimulatory molecules were significantly higher in MERS-CoV–infected MDMs than in SARS-CoV–infected cells. MERS-CoV replication was validated by immunostaining of infected MDMs and ex vivo lung tissue. We conclusively showed that MERS-CoV can establish a productive infection in human macrophages. The aberrant induction of inflammatory cytokines/chemokines could be important in the disease pathogenesis.


title: Virus Databases

text: As tools and technologies for the analysis of biological organisms (including viruses) have improved, the amount of raw data generated by these technologies has increased exponentially. Today's challenge, therefore, is to provide computational systems that support data storage, retrieval, display, and analysis in a manner that allows the average researcher to mine this information for knowledge pertinent to his or her work. Every article in this encyclopedia contains knowledge that has been derived in part from the analysis of such large data sets, which in turn are directly dependent on the databases that are used to organize this information. Fortunately, continual improvements in data-intensive biological technologies have been matched by the development of computational technologies, including those related to databases. This work forms the basis of many of the technologies that encompass the field of bioinformatics. This article provides an overview of database structure and how that structure supports the storage of biological information. The different types of data associated with the analysis of viruses are discussed, followed by a review of some of the various online databases that store general biological, as well as virus-specific, information.


title: The use of hepatitis C virus NS3/4A and secreted alkaline phosphatase to quantitate cell–cell membrane fusion mediated by severe acute respiratory syndrome coronavirus S protein and the receptor angiotensin-converting enzyme 2

text: Abstract The membrane fusion process mediated by severe acute respiratory syndrome coronavirus (SARS–CoV) S protein and its cellular receptor angiotensin-converting enzyme 2 (ACE2) had been reconstituted using two Chinese hamster ovary (CHO) cell lines that constitutively express these recombinant proteins separately. This system was applied to develop a quantitative measurement of cell–cell fusion using hepatitis C virus (HCV) NS3/4A protease and a secretion-blocked EGFP-4A/4B-SEAP (EGFP: enhanced green fluorescent protein; 4A/4B: a decapeptide substrate of NS3/4A protease; SEAP: secreted alkaline phosphatase) fusion gene. Both genes were transiently expressed in either of the CHO cell lines, followed by fusion treatment. Significant SEAP activity could be detected in the culture medium only after cell–cell fusion occurred. Cell–cell fusion provides an environment in which the protease encounters its substrate 4A/4B, thereby releasing SEAP from the fusion protein. In this study, we developed a simple, sensitive, and quantitative assay to study the membrane fusion process by measuring the extracellular activity of SEAP.


title: Infection of porcine precision cut intestinal slices by transmissible gastroenteritis coronavirus demonstrates the importance of the spike protein for enterotropism of different virus strains

text: Abstract TGEV is a coronavirus that is still widely spread in pig farming. On molecular level this virus has been studied in detail. However, studying TGEV infection within the complexity of the porcine intestinal epithelium reveals difficulties due to limiting infection models. Here we established a new ex vivo model to analyze the enterotropism of TGEV in porcine intestinal tissue. Precision cut intestinal slices (PCIS) were produced and ATP level was measured to proof vitality of the slices. ATP measurements and HE staining revealed living tissue in culture for up to 24h. PCIS were infected with three different TGEV strains. TGEV PUR 46-MAD is a commonly used TGEV strain that is known to be attenuated. TGEV Miller was passaged in piglets several times to reveal high infection. Finally, TGEV GFP is a recombinant strain that obtained its main body from TGEV PUR 46-MAD, but its spike protein from TGEV PUR-C11 that showed high mortality in piglets in vivo. Our results were in complete consensus of these statements. TGEV Miller mildly and TGEV GFP extensively infected the cells in the jejunum based on the amount of positive stained epithelial cells. However, for TGEV PUR 46-MAD no nucleocapsid protein was detected in the epithelial cells of the tissue. This shows that differences in TGEV strains and their infectious potential are highly dependent on their S protein.


title: 4.3 Nanomechanical Sensors

text: Abstract This chapter introduces nanomechanical sensors and their applications. All molecules have “volume” and “mass.” Direct measurement of these fundamental parameters can realize label-free and real-time measurements. Nanomechanical sensors have been emerging as a key device for such label-free and real-time measurements with their multiple operation modes; static and dynamic modes for detecting volume- and mass-related features, respectively. A cantilever array sensor is a representative example among various geometries, while structural optimization can enhance the scope of nanomechanical sensors in both academic and industrial applications. One of the most advanced sensing platforms is a membrane-type surface stress sensor (MSS), which realizes both high sensitivity and compact system at the same time. The MSS is also expected to contribute to addressing nanomechanical behavior of living cells and their network.


title: Chest X-ray severity index as a predictor of in-hospital mortality in coronavirus disease 2019: A study of 302 patients from Italy

text: Abstract Objectives This study aimed to assess the usefulness of a new chest X-ray scoring system, the Brixia score, to predict the risk of in-hospital mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) Methods Between March 4, 2020 and March 24, 2020, all CXR reports containing the Brixia score were retrieved. We enrolled only hospitalized Caucasian patients with COVID-19 for whom the final outcome was available. For each patient, age, sex, underlying comorbidities, immunosuppressive therapies and the CXR report containing the highest score were considered for the analysis. These independent variables were analyzed using a multivariable logistic regression model to extract the predictive factors for in-hospital mortality. Results 302 Caucasian patients who were hospitalized for COVID-19 were enrolled. In the multivariable logistic regression model, only Brixia score, patient age, and conditions that induced immunosuppression were the significant predictive factors for in-hospital mortality. On receiver operating characteristic curve analyses, the optimal cutoff values for Brixia score and patient age were 8 points and 71 years, respectively. Three different models that included the Brixia score showed excellent predictive power. Conclusions Patients with high Brixia score and at least one other predictive factor had the highest risk of in-hospital death.


title: West Nile Virus Core Protein Tetramer Structure and Ribbon Formation

text: Abstract We have determined the crystal structure of the core (C) protein from the Kunjin subtype of West Nile virus (WNV), closely related to the NY99 strain of WNV, currently a major health threat in the U.S. WNV is a member of the Flaviviridae family of enveloped RNA viruses that contains many important human pathogens. The C protein is associated with the RNA genome and forms the internal core which is surrounded by the envelope in the virion. The C protein structure contains four α helices and forms dimers that are organized into tetramers. The tetramers form extended filamentous ribbons resembling the stacked α helices seen in HEAT protein structures.


docid: lzgxfsue

title: Guidelines on processing and clinical use of skin allografts

text: Abstract Processing methods used for banking of skin for subsequent therapeutic use depend on whether the skin is to retain viability or not. For viable skin grafts, sterilisation techniques cannot be applied, however antibiotics and antimycotics may be used to disinfect the tissue with respect to bacteria and fungi. Nevertheless, strict standards are applied to avoid disease transmission from donor to recipient involving donor medical history, donor testing for viral diseases, aseptic retrieval and processing, and control of storage temperature. Cryopreservation is the preferred method for long term storage of viable skin grafts. If viability is not required, then additional long term preservation methods may be used including deep-freezing, freeze-drying or high concentration solute preservation. All three methods work by reducing water activity. In addition it is possible to apply certain sterilisation techiques that have been shown not to damage the tissue. It is important that sterilisation methods are validated in accordance with precise definitions of sterilisation, and for the initial levels of “bioburden” expected to be present immediately prior to application of the sterilisation method. The application of improved and refined methodologies in accordance with defined standards has ensured improved graft performance while reducing risk to the recipient.


12 Biodefense and Special Pathogen Vaccines


title: Pathogenic Role for Virus-Specific CD4 T Cells in Mice with Coronavirus-Induced Acute Encephalitis

text: Acute viral encephalitis is believed to result from direct virus destruction of infected cells and from virus-induced host immune response, but the relative contribution of each remains largely unknown. For example, C57BL/6 (B6) mice infected with mouse hepatitis virus (JHM strain, JHMV) develop severe encephalitis, with death occurring within 7 days. Here, we show that the host response to a single JHMV-specific immunodominant CD4 T-cell epitope is critical for severe disease. We engineered a recombinant JHMV with mutations in the immunodominant CD4 T-cell epitope (rJ.M(Y135Q)). Infection of naïve B6 mice with this virus resulted in mild disease with no mortality. However, introduction of a CD4 T-cell epitope from Listeria monocytogenes into rJ.M(Y135Q) generated a highly virulent virus. The decrease in disease severity was not due to a switch from Th1 to Th2 predominance in rJ.M(Y135Q)-infected mice, an effect on CD8 T-cell function, or differential expression of tumor necrosis factor-α by JHMV-specific CD4 T cells. These results show that the response to a single virus-specific CD4 T-cell epitope may contribute to a pathogenic host response in the setting of acute viral disease and that abrogation of this response ameliorates clinical disease without diminishing virus clearance.


title: Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection

text: BACKGROUND: Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms. METHODS: We performed RNA sequencing on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample. RESULTS: Our first study showed that a signature of 3 mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% confidence interval [CI], 0.9–1.0), and identified proteins correlating with virus detection. In a second study, elevated CXCL11 or CXCL10 protein levels identified samples containing respiratory viruses, including viruses not on the initial test panel. Overall area under the curve (AUC) values were: CXCL11 AUC = 0.901 (95% CI, 0.86–0.94); CXCL10 AUC = 0.85 (95% CI, 0.80–0.91). CONCLUSIONS: Host antiviral mRNAs and single host proteins detectable using nasopharyngeal swabs accurately predict the presence of viral infection. This approach holds promise for developing rapid, cost-effective tests to improve management of patients with respiratory illnesses.


title: Diagnostic et traitement des viroses émergentes : comment aller de l’avant ?

text: SUMMARY Virus emergence episodes follow one another at a steady pace. The medical and scientific community responds to needs as and when they arise but finds difficult to propose a global strategy in the medium and long term. Regarding diagnosis, priority should be given to anticipating the management of re-emerging pathogens, to developing capacities of real-time molecular diagnosis, and to preserving reference expertise and reference biological materials. This effort should also include sero-epidemiological studies aiming at obtaining a more accurate mapping of the circulation of potentially re-emerging pathogens. Regarding therapeutics (with the exception of vaccines which are addressed in another presentation), the expected improvements are the advance implementation of ready-to-use protocol frames for clinical trials and that of an ambitious strategy aiming at gradually covering the taxonomic spectrum of evolutionary virus groups infecting vertebrates.


title: Complement as a target in COVID-19?

text: There is an urgent need to develop effective therapies for COVID-19. Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients.


title: 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis

text: The current synthesis of the ‘hygiene hypothesis’ suggests that the recent increase in chronic inflammatory disorders is at least partly attributable to immunodysregulation resulting from lack of exposure to microorganisms that have evolved an essential role in the establishment of the immune system. This document provides a background for discussion of the following propositions. 1. The essential role of these organisms is an example of ‘evolved dependence’. 2. The most relevant organisms are those that co-evolved with mammals, and already accompanied early hominids in the Paleolithic. 3. More recently evolved ‘childhood infections’ are not likely to have evolved this role, and recent epidemiology supports this contention. 4. This mechanism is interacting with other modern environmental changes that also lead to enhanced inflammatory responses [inappropriate diet, obesity, psychological stress, vitamin D deficiency, pollution (dioxins), etc.]. 5. The range of chronic inflammatory disorders that is affected is potentially larger than usually assumed [allergies, autoimmunity, inflammatory bowel disease, but also vascular disease, some cancers, depression/anxiety (when accompanied by raised inflammatory cytokines), and perhaps neurodegenerative disorders and type 2 diabetes].


Chapter 59 Antigen Delivery Systems III: Use of Recombinant Plant Viruses


title: Reply to: “Reporting of all cardiac medications and their outcome in COVID‐19”

text: We thank Dr. Ajay Kumar Mishra and his colleagues for their attention to our review.(1, 2) We strongly agree with them that it is inappropriate for COVID‐19 patients to discontinue ACEIs /ARBs without weighing up the pros and cons.(3, 4) Whether the RAAS inhibitors may affect the prognosis of COVID‐19 patients still needs more clinical trials to confirm. This article is protected by copyright. All rights reserved.


title: Chapter 3 Ethnomedicinal Wisdom An Approach for Antiviral Drug Development

text: Abstract Nature has its own way of protecting mankind from the atrocities of illness and diseases by producing natural products of diverse structures and bioactivities, not only necessary for good health but also to combat diverse life-style and infectious diseases including microbial infections caused by virus, bacteria, fungi, protozoa, and other parasites. The problems of emerging and emerging diseases with drug resistance, latency, and reactivation along with the shorter life span of most synthetic agents or drugs have directed scientists to look into the treasure chests of nature to find out and explore the natural metabolites of plants for the management of diverse diseases including viral diseases. This chapter explains the treasure of “Ethnomedicine” and its journey through time, which reveals the importance of this branch of “natural science” in the current scenario, its potential as “alternative or complementary” medicine, especially against viral diseases with a detailed account of identified antivirals, their isolation and identification as “natural antiviral” to make the readers realize the need to accept “ethnomedicine” as appropriate alternatives to “synthetic chemistry.”


title: A Multi-function Public Health Surveillance System and the Lessons Learned in Its Development: The Alberta Real Time Syndromic Surveillance Net

text: Objective: We describe a centralized automated multi-function detection and reporting system for public health surveillance–the Alberta Real Time Syndromic Surveillance Net (ARTSSN). This improves upon traditional paper-based systems which are often fragmented, limited by incomplete data collection and inadequate analytical capacity, and incapable of providing timely information for public health action. Methods: ARTSSN concurrently analyzes multiple electronic data sources in real time to describe results in tables, charts and maps. Detected anomalies are immediately disseminated via alerts to decision-makers for action. Results: ARTSSN provides richly integrated information on a variety of health conditions for early detection of and prompt action on abnormal events such as clusters, outbreaks and trends. Examples of such health conditions include chronic and communicable disease, injury and environmentmediated adverse incidents. Discussion: Key advantages of ARTSSN over traditional paper-based methods are its timeliness, comprehensiveness and automation. Public health surveillance of communicable disease, injury, environmental hazard exposure and chronic disease now occurs in a single system in real time year round. Examples are given to demonstrate the public health value of this system, particularly during Pandemic (H1N1) 2009.


title: Virus infection in exacerbations of chronic obstructive pulmonary disease requiring ventilation

text: OBJECTIVES: We aimed to characterise and quantify the incidence of common infectious agents in acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring ventilation, with a focus on respiratory viruses. DESIGN: An epidemiological study conducted over 3 years. SETTING: A 12-bed intensive care unit (ICU). PARTICIPANTS: ICU patients over 45 years of age with a primary diagnosis of COPD exacerbation requiring non-invasive ventilation (NIV) or ventilation via endotracheal tube (ETT). MATERIALS AND METHODS: Nasopharyngeal aspirates (NPA) and posterior pharyngeal swabs (PS) were tested for viruses with immunofluorescence assay (IFA), virus culture (VC) and polymerase chain reaction (PCR). Paired virus and atypical pneumonia serology assays were taken. Blood, sputum and endotracheal aspirates were cultured for bacteria. RESULTS: 107 episodes in 105 patients were recorded. Twenty-three (21%) died within 28 days. A probable infectious aetiology was found in 69 patient episodes (64%). A virus was identified in 46 cases (43%), being the sole organism in 35 cases (33%) and part of a mixed infection in 11 cases (10%). A probable bacterial aetiology was found in 25 cases (23%). There was no statistically significant difference in clinical characteristics or outcomes between the group with virus infections and that without. CONCLUSION: Forty-six (43%) of the patients with COPD exacerbation requiring mechanical ventilation had a probable viral pathogen. Prodromal, clinical and outcome parameters did not distinguish virus from non-virus illness. PCR was the most sensitive whilst virus culture was the least of virus assays. ELECTRONIC SUPPLEMENTARY MATERIAL: The electronic reference of this article is http://dx.doi.org/10.1007/s00134-006-0202-x. The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.


title: Epidemiology of human coronavirus NL63 infection among hospitalized patients with pneumonia in Taiwan

text: Abstract Background/Purpose Human coronavirus (HCoV) NL63 is recognized in association with upper or lower respiratory tract illnesses in children. This study surveyed the prevalence of HCoV-NL63 and influenza viruses in patients with influenza-like illness in Taiwan during 2010–2011. Methods Throat samples from 107 hospitalized patients with pneumonia and 175 outpatients with influenza-like illness were examined using real-time polymerase chain reaction assays with virus-specific primers, and then virus-positive specimens were confirmed by sequencing the polymerase chain reaction products. Results HCoV-NL63 infection was identified in 8.4% (9/107) of hospitalized patients with pneumonia, but not found in outpatients with influenza-like illness. Age distribution of HCoV-NL63 infection in hospitalized patients with pneumonia indicated that the group aged 16–25 years (20%) had the highest positive rate compared with the other groups, and exhibited a similar age-specific pattern to influenza A/H1N1 infection, but not influenza A/H3N2 and B infections in hospitalized patients. Seasonal prevalence of HCoV-NL63 infection was late winter, overlapping the highest peak of the influenza A/H1N1 epidemic during December 2010 to March 2011 in Taiwan. Co-infection of HCoV-NL63 and influenza A/H1N1 was detected in three hospitalized patients. Clinical manifestation analysis indicated that the main symptoms for HCoV-NL63 infection included fever (88.9%), cough (77.8%), and pneumonia (100%). Co-infection caused significantly higher rates of breathing difficulties, cough, and sore throat than those of single infection with HCoV-NL63 and influenza A/H1N1. Phylogenetic analysis indicated a low level of heterogeneity between Taiwan and global HCoV-NL63 strains. Conclusion Understanding epidemiology of HCoV-NL63 in Taiwan provides an insight for worldwide surveillance of HCoV-NL63 infection.


Gastroenteritis associated with Helicobacter‐like organisms and rotavirus in a reindeer (Rangifer tarandus)


title: Patchless administration of canine influenza vaccine on dog’s ear using insertion-responsive microneedles (IRMN) without removal of hair and its in vivo efficacy evaluation

text: Microneedles provide the advantages of convenience and compliance by avoiding the pain and fear of needles that animals often experience. Insertion-responsive microneedles (IRMN) were used for administration to a hairy dog without removing the dog’s hair. Canine H3N2 vaccine was administered with IRMN attached to the dog’s ears ex vivo and the conventional microneedle system (MN) was administered for 15 min to compare puncture performance and delivery efficiency. The vaccine was also administered to compare antibody formation using IRMN with the use of intramuscular injection. The veterinarian observed the behavior of the dog during the course of the administration and compared the response to IRMN with that of intramuscular administration. The tips of IRMN were separated from the base and delivered into the hairy skin successfully. Puncture performance of IRMN were the same as that of coated microneedles (95%), but delivery efficiency of IRMN were 95% compared to less than 1% for coated microneedles. The H3N2 vaccine inoculated into the dog's ears showed the same antibody formation as the intramuscular injection. The dog appeared to be more comfortable with IRMN administration compared to syringe administration. IRMN are the first microneedle system to deliver a canine vaccine successfully into a hairy dog without removal of the dog’s hair. The use of IRMN can provide both convenience and compliance for both the dog and the owner.


title: Testing times in Coronavirus disease (Covid-19): A tale of two nations

text: The Coronavirus Disease (Covid-19) pandemic is caused by the severe acute respiratory syndrome virus 2 and was first identified in Wuhan, China, in December 2019. The disease spread globally, leading to the World Health Organization declaring it a pandemic in March 2020. The condition is often fatal in its severe form. As it is a previously unknown virus, no treatment is identified or any vaccine available. The burden of disease control and containment, therefore, falls upon a robust and geographically appropriate testing strategy. Testing policies are modified, in turn, by the rapidly evolving patterns of the disease in various nations and by the evolving nature of tests in development. It is, therefore, helpful to study different national models to learn from the experience of different countries. This article compares testing strategies in the UK and India as the two countries travel different paths in controlling the pandemic. The UK is one of the most severely affected countries in the world. Initially restricted to hospitalised patients, the UK has broadened the scope of testing to many categories of individuals. In contrast, India appears to have a lower prevalence of the infection. However, the large Indian population and relatively insufficient testing capacities so far have led India to adopt a different testing trajectory, with the testing currently focused on high-risk groups in the community and hospitals. Owing to the rapidly changing nature of the disease, there can be no ‘one-size-fits-all’ policy but should be based on country-specific circumstances.


Assessing Psychological Response to the COVID-19: The Fear of COVID-19 Scale and the COVID Stress Scales


title: Developmental toxicity in rats of a hemoglobin-based oxygen carrier results from impeded function of the inverted visceral yolk sac

text: Abstract HBOC-201 is a bovine-derived, cross-linked, and stabilized hemoglobin (250kDa) in physiological saline. Daily intravenous infusions of HBOC (1.95, 3.90, or 5.85g/kg/day) during gestational days (GDs) 6–18 in Sprague-Dawley rats caused fetal mortality, reduced birth weight, and malformations. Subsequent single-day infusions (5.85g/kg/day) showed that developmental toxicity was limited to GDs 7–9 when histiotrophic nutrition via the inverted visceral yolk sac (invVYS) is essential. Histiotrophic nutrition is receptor-mediated endocytosis of bulk maternal proteins and subsequent lysosomal degradation providing amino acids and other nutrients for embryonic growth. Controls for protein content, oncotic properties, and hemoglobin content indicated that toxicity was due to hemoglobin. Rat whole embryo cultures verified HBOC interference with invVYS transport capacity and resultant deficient embryonic nutrition. These mechanisms of action are not expected to impact human development based on differences in VYS morphology and function, although a complete understanding of early human embryonic nutrition is lacking.


title: Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the main olfactory bulb

text: Abstract Several neurotropic viruses enter the brain after peripheral inoculation and spread transneuronally along pathways known to be connected to the initial site of entry. In this study, the pathways utilized by two such viruses, herpes simplex virus type 1 and mouse hepatitis virus strain JHM, were compared using in situ hybridization following inoculation into either the nasal cavity or the main olfactory bulb of the mouse. The results indicate that both viruses spread to infect a unique and only partially overlapping set of connections of the main olfactory bulb. Both quantitative and qualitative differences were observed in the patterns of infection of known primary and secondary main olfactory bulb connections. Using immunohistochemistry for tyrosine hydroxylase combined with in situ hybridization, it was shown that only herpes simplex virus infected noradrenergic neurons in the locus coeruleus. In contrast, both viruses infected dopaminergic neurons in the ventral tegmental area, although mouse hepatitis virus produced a more widespread infection in the A10 group, as well as infecting A8 and A9. The results suggest that differential virus uptake in specific neurotransmitter systems contributes to the pattern of viral spread, although other factors, such as differences in access to particular synapses on infected cells and differences in the distribution of the cellular receptor for the two viruses, are also likely to be important. The data show that neural tracing with different viruses may define unique neural pathways from a site of inoculation. The data also demonstrate that two viruses can enter the brain via the olfactory system and localize to different structures, suggesting that neurological diseases involving disparate regions of the brain could be caused by different viruses, even if entry occurred at a common site.


title: Enhanced growth of influenza A virus by coinfection with human parainfluenza virus type 2

text: It has been reported that dual or multiple viruses can coinfect epithelial cells of the respiratory tract. However, little has been reported on in vitro interactions of coinfected viruses. To explore how coinfection of different viruses affects their biological property, we examined growth of influenza A virus (IAV) and human parainfluenza virus type 2 (hPIV2) during coinfection of Vero cells. We found that IAV growth was enhanced by coinfection with hPIV2. The enhanced growth of IAV was not reproduced by coinfection with an hPIV2 mutant with reduced cell fusion activity, or by ectopic expression of the V protein of hPIV2. In contrast, induction of cell fusion by ectopic expression of the hPIV2 HN and F proteins augments IAV growth. hPIV2 coinfection supported IAV growth in cells originated from the respiratory epithelium. The enhancement correlated closely with cell fusion ability of hPIV2 in those cells. These results indicate that cell fusion induced by hPIV2 infection is beneficial to IAV replication and that enhanced viral replication by coinfection with different viruses can modify their pathological consequences.


title: Gastro-entérites virales des animaux domestiques et zoonoses

text: SUMMARY Etiologic investigations of infectious diarrhea were long limited to bacteria and protozoa. The advent of electron microscopy and molecular biology showed that diarrhea could also be caused by viruses, both in humans and in other animals. In 1969, electron microcopy was used to show, for the first time, the responsibility of a virus in a case of calf diarrhea. This “ reo-like virus ” was subsequently identified as a rotavirus, and was shown only four years later to be responsible for severe diarrhea in young children. Noroviruses, and particularly the human virus Norwalk, were subsequently discovered, followed by coronavirus, sapovirus, pestivirus, astrovirus, enteric adenoviruses, torovirus, and picobirnavirus. Some of viruses found in animals, and particularly rotaviruses, can also infect humans. Rotaviruses have been identified in numerous animal species and are generally host-specific, but zoonotic transmission has been suggested by cross-infection (especially in experimental models), by genetic studies showing a close relationship between certain human and animal rotaviruses, and by the discovery of new animal genotypes during epidemiological surveillance of human rotaviroses. Some animal strains of norovirus, sapovirus, picobirnavirus and astrovirus are genetically related to human strains, but their human transmission has not been demonstrated.


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title: Thromboembolic events and apparent heparin resistance in patients infected with SARS‐CoV‐2

text: In March 2020, the global healthcare system is overwhelmed by patients infected with SARS‐CoV‐2, which is the cause of the coronavirus pandemic (Covid‐2019). A large number of these patients end up in the intensive care units (ICU) with critical illness requiring mechanical ventilation. One of the most important clinical features of the infection is a profound coagulopathy. In a recent cohort study 71% of patients who eventually died matched the ISTH criteria for disseminated intravascular coagulation (DIC), while this percentage was only 0.6% in patients who survived.


Letter: Transmission of COVID-19 During Neurosurgical Procedures—Some Thoughts From the United Kingdom


title: Enquête sérologique par immunofluorescence indirecte, sur les infections à coronavirus OC43

text: Summary Four-hundred seventy-two sera were examined by the indirect immunofluorescence test against Coronavirus strain OC43 adapted to the HRT18 cell culture. Sera were from children and adults hospitalized over a 4-year period, from 1979 to 1982, at the CHRU of Clermont-Ferrand (France) for different clinical reasons. Of the 446 sera tested, 61 % showed antibodies against OC43; 90 % of adult sera were positive. Coronavirus infections are very common in France. Immunity appears early in life, and infection is frequent in children from 12–36 months of age.


title: Health system resilience: Lebanon and the Syrian refugee crisis

text: BACKGROUND: Between 2011 and 2013, the Lebanese population increased by 30% due to the influx of Syrian refugees. While a sudden increase of such magnitude represents a shock to the health system, threatening the continuity of service delivery and destabilizing governance, it also offers a unique opportunity to study resilience of a health system amidst ongoing crisis. METHODS: We conceptualized resilience as the capacity of a health system to absorb internal or external shocks (for example prevent or contain disease outbreaks and maintain functional health institutions) while sustaining achievements. We explored factors contributing to the resilience of the Lebanese health system, including networking with stakeholders, diversification of the health system, adequate infrastructure and health human resources, a comprehensive communicable disease response and the integration of the refugees within the health system. RESULTS: In studying the case of Lebanon we used input–process–output–outcome approach to assess the resilience of the Lebanese health system. This approach provided us with a holistic view of the health system, as it captured not only the sustained and improved outcomes, but also the inputs and processes leading to them. CONCLUSION: Our study indicates that the Lebanese health system was resilient as its institutions sustained their performance during the crisis and even improved.


Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients


title: Impact of Covid-19 on training and wellbeing in subspecialty surgery: a national survey of cardiothoracic trainees in the United Kingdom.

text: Structured Abstract Objectives The Covid-19 pandemic has overwhelmed healthcare systems and disrupted routine care internationally. Healthcare workers face disruption to their work routines and professional development, as well as an elevated risk of infection and morbidity. We sought to establish the impact of the Covid-19 pandemic on the wellbeing, practice and progression of all trainees in cardiothoracic surgery in the United Kingdom. Methods A 31-item questionnaire was designed, validated, and disseminated via email and an instant-messaging platform. Results 76 (of 118, 64%) cardiothoracic surgical trainees responded, representing all training grades and programmes nationally. 48 (63%) and 24 (32%) were concerned about their physical and mental health respectively. 25 (33%) had taken time off work due to Covid-19. 65 (86%) had treated Covid-19 patients, 36 of whom (55%) were wearing satisfactory personal protective equipment at the time. 41 (54%) remain concerned about PPE provision at their institution. 42 (55%) had been redeployed to cover other specialties. 23 (30%) had encountered ethical dilemmas related to care of patients. There was a significant impact on time spent in outpatient clinics (44% reduction), multidisciplinary team meetings (79% reduction) and operating theatres (78% reduction). 67 (88%) of respondents were concerned about the impact on their training, and 54 (71%) felt that the deviation may require an extension in their planned training time. Conclusions The duration and impact of the current pandemic is, as yet, uncertain. Timely sharing of experiences, concerns and expectations will inform healthcare and education policy, and influence practice in the pandemic era and beyond.