title: Virus associated immune and pharmacologic mechanisms in disorders of respiratory and cutaneous atopy

text: Abstract Anaphylaxis represents non-atopic immediate hypersensitivity, whereas manifestations of atopic immediate hypersensitivity include bronchial asthma, hay fever, allergic rhinitis, chronic urticaria, and atopic dermatitis. In spite similar antigen exposure, only a minority of the population shown some form of atopic disease. Atopic disease with its spontaneous pattern of familial occurrence cannot be induced at will. The exact pathogenesis of atopy is yet to be elucidated. Two theories prevail: 1) atopy is a primary disorder of the immune system with sequelae in the various effector tissues; and 2) a concept of atopy as a primary autonomic imbalance, essentially beta adrenergic in character, with sequelae in effector cells, including those engaged in the production of antibodies. The autonomic imbalance is perceived as caused not by some disorder of the autonomic nervous system itself but by a defector functioning of its effector cells. These two concepts are not mutually exclusive. The IgE antibody, which mediates allergic reactions, is essentially identical with atopic reagin in various animal species. The beta adrenergic theory regards atopic disorders (i.e., perennial and seasonal allergic rhinitis, bronchial asthma, and atopic dermatitis) not as immunologic diseases but as unique patterns of altered reactivities to a broad spectrum of immunologic, psychic, infectious, chemical and physical stimuli. The antigen-antibody interaction is given the same role as that of a broad category of nonspecific stimuli that function only to trigger the same defective homeostatic mechanism in the various effector cells involved in immediate hypersensitivities. Current evidence favors the possibility that there are inherited and/or acquired multiple abnormalities in the receptor—adenylate cyclase—cyclic AMP system of all effector cells that are critical in the organization of immune reactivities. Atopic abnormality may be 1) acquired by functional receptor regulatory shifts caused by hormonal changes, infection (viral, bacterial, etc), allergic tissue injury or other event; 2) genetically determined; or 3) caused by autoimmune disease. One, two or all three of these effector mechanisms may be operative in a particular disease. There is an important relationship between asthma and viral respiratory infection. A history of childhood viral respiratory illness is a risk factor for the development of chronic obstructive airway syndromes in later life. Asthmatic attacks occurred only when the infection produced fever, malaise, cough or coryza. The dominant role of fever in these episodes immediately suggests the profound involvement of adrenergic effector mechanisms. The presence of autoantibodies to beta-adrenoceptors in patients correlated well with a reduced beta—and an increased alpha-adrenergic responsiveness. Virus infections can elicit autoantibody formation. In patients with atopic dermatitis an increased susceptibility and abnormal host response to viral infections in general. Defective cytotoxic T cells, abnormally functioning macrophages and natural killer cells, a reduced production of IFNα in children, and of IFNγ in atopic patients with food allergy has recently been demonstrated. Lymphocytic cyclic AMP-phosphodiesterase, that destroys cyclic AMP, is increased in atopic dermatitis and in allergic respiratory disease of adults, and this increased activity correlated closely with histamine release from basophils. Peripheral blood leukocytes and lymphocytes in atopic dermatitis have frequently demonstrated impaired beta adrenergic reactivity. Allergic tissue injury may be initiated by antigen-specific IgE antibodies that combine with Fcε receptors on various cell types and trigger mediator release upon encounter with the antigen. Various noxious agents that are capable of triggering asthma are capable of releasing inflammatory mediators from the same target cells. Accounting only for those pharmacologic mediators where the cell-type has been identified, the spectrum of mediator-storing, synthesizing, or transporting cells includes neutrophil leucocytes, basophilic leucocytes eosinophilic leucocytes; mast cells, “chromaffin-positive” mast cells, enterochromaffin cells, chromaffin cells; platelets, neurosecretory cells and nerve cells that potentially produce all amine-mediators as well as prostaglandins and kinins.


EPIDEMIOLOGY OF PARKINSON'S DISEASE


title: Rapid development and evaluation of a live-attenuated QX-like infectious bronchitis virus vaccine

text: Infectious bronchitis (IB) is an acute, highly contagious disease, which causes economic losses to the poultry industry worldwide. To control the disease, biosecurity and vaccination are required. In the current research, we rapidly attenuated a QX-like IBV field strain ZYY-2014 using passage in embryos at limiting dilution and tested the safety and efficacy of the attenuated Chinese QX-like IBV strain ZYYR-2014 in 1-day-old specific-pathogen-free (SPF) chickens through spray route. Our result revealed that the attenuated strain presented a decreased pathogenicity in 1-day-old chickens. The strain ZYY-2014 inoculated birds presented typical IBV clinical signs with a mortality of 43%, while the attenuated strain ZYYR-2014 inoculated birds remained healthy. The strain ZYYR-2014 also presented stronger antibody responses and lower viral loads in tracheas, lungs and kidneys. When vaccinated through spray route into 1-day-old SPF chickens, our data suggest a potential of the attenuated ZYYR-2014 strain as a vaccine candidate applied in hatchery, which can contribute in preventing the QX-like IBV infections. Furthermore, attenuation by passage at limiting dilution could be applied for rapid vaccine development against emerging strains.


title: Cybercrime in America amid COVID-19: the Initial Results from a Natural Experiment

text: The COVID-19 pandemic has radically altered life, killing hundreds of thousands of people and leading many countries to issue “stay-at-home” orders to contain the virus’s spread. Based on insights from routine activity theory (Cohen & Felson 1979), it is likely that COVID-19 will influence victimization rates as people alter their routines and spend more time at home and less time in public. Yet, the pandemic may affect victimization differently depending on the type of crime as street crimes appear to be decreasing while domestic crimes may be increasing. We consider a third type of crime: cybercrime. Treating the pandemic as a natural experiment, we investigate how the pandemic has affected rates of cybervictimization. We compare pre-pandemic rates of victimization with post-pandemic rates of victimization using datasets designed to track cybercrime. After considering how the pandemic may alter routines and affect cybervictimization, we find that the pandemic has not radically altered cyberroutines nor changed cybervictimization rates. However, a model using routine activity theory to predict cybervictimization offers clear support for the theory’s efficacy both before and after the pandemic. We conclude by considering plausible explanations for our findings.


title: Digital privacy in mental healthcare: current issues and recommendations for technology use

text: Mental healthcare providers increasingly use technology for psychotherapy services. This progress enables professionals to communicate, store information, and rely on digital software and hardware. Emails, text messaging, telepsychology/telemental health therapy, electronic medical records, cloud-based storage, apps/applications, and assessments are now available within the provision of services. Of those mentioned, some are directly utilized for psychotherapy while others indirectly aid providers. Whereas professionals previously wrote notes locally, technology has empowered providers to work more efficiently with third-party services and solutions. However, the implementation of these advancements in mental healthcare involves consequences to digital privacy and might increase clients’ risk of unintended breaches of confidentiality. This manuscript reviews common technologies, considers the vulnerabilities therein, and proposes suggestions to strengthen privacy.


COVID-19 Epidemic and Enhancing China’s National Biosecurity System


title: Being a front-line dentist during the Covid-19 pandemic: a literature review

text: Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.


title: Evaluation of green tea extract as a safe personal hygiene against viral infections

text: BACKGROUND: Viral infections often pose tremendous public health concerns as well as economic burdens. Despite the availability of vaccines or antiviral drugs, personal hygiene is considered as effective means as the first-hand measure against viral infections. The green tea catechins, in particular, epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity. In this study, we evaluated the green tea extract as a safe personal hygiene against viral infections. RESULTS: Using the influenza virus A/Puerto Rico/8/34 (H1N1) as a model, we examined the duration of the viral inactivating activity of green tea extract (GTE) under prolonged storage at various temperature conditions. Even after the storage for 56 days at different temperatures, 0.1% GTE completely inactivated 10(6) PFU of the virus (6 log(10) reduction), and 0.01% and 0.05% GTE resulted in 2 log(10) reduction of the viral titers. When supplemented with 2% citric acid, 0.1% sodium benzoate, and 0.2% ascorbic acid as anti-oxidant, the inactivating activity of GTE was temporarily compromised during earlier times of storage. However, the antiviral activity of the GTE was steadily recovered up to similar levels with those of the same concentrations of GTE without the supplements, effectively prolonging the duration of the virucidal function over extended period. Cryo-EM and DLS analyses showed a slight increase in the overall size of virus particles by GTE treatment. The results suggest that the virucidal activity of GTE is mediated by oxidative crosslinking of catechins to the viral proteins and the change of physical properties of viral membranes. CONCLUSIONS: The durability of antiviral effects of GTE was examined as solution type and powder types over extended periods at various temperature conditions using human influenza A/H1N1 virus. GTE with supplements demonstrated potent viral inactivating activity, resulting in greater than 4 log(10) reduction of viral titers even after storage for up to two months at a wide range of temperatures. These data suggest that GTE-based antiviral agents could be formulated as a safe and environmentally friendly personal hygiene against viral infections.


Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a cross-reactive environmental antigen


title: Cancer and COVID-19 — potentially deleterious effects of delaying radiotherapy

text: Radiotherapy can be safely delivered during the coronavirus disease 2019 (COVID-19) pandemic, often through use of hypofractionated regimens, which minimize the number of visits to treatment centres while also avoiding potentially detrimental delays in the delivery of cancer care.


title: Evidence for Human Norovirus Infection of Dogs in the United Kingdom

text: Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential.


title: A Randomized Study of Immune Plasma for the Treatment of Severe Influenza

text: BACKGROUND: Influenza causes significant morbidity and mortality despite currently available treatments. Anecdotal reports suggest plasma with high antibody titers towards influenza may be of benefit in the treatment of severe influenza. METHODS: We conducted a randomized, open-label, multicenter phase 2 trial at 29 academic medical centers in the United States to assess the safety and efficacy of anti-influenza plasma with hemagglutination inhibition (HAI) antibody titers of ≥ 1:80 to the infecting strain. Hospitalized children and adults (including pregnant women) with severe influenza A or B (defined as hypoxia or tachypnea) were randomly assigned to receive either 2 units (or pediatric equivalent) of anti-influenza plasma plus standard care (P+S), versus standard care alone (S), and were followed for 28 days. The primary endpoint was time to normalization of patients’ respiratory status (respiratory rate of ≤ 20 for adults or age defined thresholds of 20–38 for children), and a room air saturation of oxygen ≥ 93%. ClinicalTrials.gov Identifier: NCT01052480 FINDINGS: Between January 13, 2011 and March 2, 2015, 113 participants were screened, and 98 were randomized. Of the participants with confirmed influenza, 28 of 42 (67%) of P+S participants normalized their respiratory status by Day 28, as compared to 24 of 45 (53%) of S participants (p=0·069). The estimated hazard ratio comparing P+S to S was 1·71 (95% CI: 0·96 to 3·06). Six participants died, 1 (2%) and 5 (10%) from the P+S and S arms respectively (p=0·093). P+S participants had non-significant reductions in days in hospital (median 6 vs. 11 days, p=0·13) and days on mechanical ventilation (median 0 vs. 3 days, p=0·14), and significantly improved clinical status at Day 7 (p=0·020). Fewer P+S participants experienced SAEs compared to S recipients (20% vs. 38%, p= 0·041), the most frequent of which were acute respiratory distress syndrome (1 [2%] vs 2 [4%]) and stroke (1 [2%] vs 2 [4%]). INTERPRETATION: Results from this Phase II randomized trial of immune plasma for the treatment of severe influenza provides support for a possible benefit of immunotherapy across the primary and secondary endpoints. A Phase III randomized trial is now underway to further evaluate this intervention.


title: Quantitative structure‐activity relationship and molecular docking revealed a potency of anti‐hepatitis C virus drugs against human corona viruses

text: A number of human coronaviruses (HCoVs) were reported in the last and present centuries. Some outbreaks of which (eg, SARS and MERS CoVs) caused the mortality of hundreds of people worldwide. The problem of finding a potent drug against HCoV strains lies in the inability of finding a drug that stops the viral replication through inhibiting its important proteins. In spite of its limited efficacy and potential side effects, Ribavirin is extensively used as a first choice against HCoVs. Therefore, scientists reverted towards the investigation of different drugs that can more specifically target proteins. In this study, four anti‐HCV drugs (one approved by FDA and others under clinical trials) are tested against HCoV polymerases. Quantitative Structure‐Activity Relationship (QSAR) and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and Ribavirin. Both QSAR and molecular docking showed that IDX‐184 is superior compared to Ribavirin against MERS CoV, a result that was also reported for HCV. MK‐0608 showed a performance that is comparable to Ribavirin. We strongly suggest an in vitro study on the potency of these two drugs against MERS CoV.


Editorial overview: Preventive and therapeutic vaccines: Vaccination against viral disease — current advances and challenges


What is new in the nucleolus?: Workshop on the Nucleolus: New Perspectives


title: Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes

text: SUMMARY: Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY: https://www.genomedetective.com/app/typingtool/cov SUPPLEMENTARY INFORMATION:


title: The societal impact of ion beam therapy

text: Ion beam therapy should be"democratized"through model-based patient selection, innovative technologies for better and faster treatment delivery, and substantial size and cost reduction. The disability-adjusted life year (DALY) concept can be used to quantify the societal benefit.


Diagnostic Criteria during SARS Outbreak in Hong Kong


title: Analysis of Synonymous Codon Usage Bias in Flaviviridae Virus

text: BACKGROUND: Flaviviridae viruses are single-stranded, positive-sense RNA viruses, which threat human constantly mediated by mosquitoes, ticks, and sandflies. Considering the recent increase in the prevalence of the family virus and its risk potential, we investigated the codon usage pattern to understand its evolutionary processes and provide some useful data to develop the medications for most of Flaviviridae viruses. RESULTS: The overall extent of codon usage bias in 65 Flaviviridae viruses is low with the average value of GC contents being 50.5% and the highest value being 55.9%; the lowest value is 40.2%. ENC values of Flaviviridae virus genes vary from 48.75 to 57.83 with a mean value of 55.56. U- and A-ended codons are preferred in the Flaviviridae virus. Correlation analysis shows that the positive correlation between ENC value and GC content at the third nucleotide positions was significant in this family virus. The result of analysis of ENC, neutrality plot analysis, and correlation analysis revealed that codon usage bias of all the viruses was affected mainly by natural selection. Meanwhile, according to correspondence analysis (CoA) based on RSCU and phylogenetic analysis, the Flaviviridae viruses mainly are made up of two groups, Group I (Yellow fever virus, Apoi virus, Tembusu virus, Dengue virus 1, and others) and Group II (West Nile virus lineage 2, Japanese encephalitis virus, Usutu virus, Kedougou virus, and others). CONCLUSIONS: All in, the bias of codon usage pattern is affected not only by compositional constraints but also by natural selection. Phylogenetic analysis also illustrates that codon usage bias of virus can serve as an effective means of evolutionary classification in Flaviviridae virus.


title: ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

text: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.


title: The piglet as a model for B cell and immune system development

text: The ability to identify factors responsible for disease in all species depends on the ability to separate those factors which are environmental from those that are intrinsic. This is particularly important for studies on the development of the adaptive immune response of neonates. Studies on laboratory rodents or primates have been ambiguous because neither the effect of environmental nor maternal factors on the newborn can be controlled in mammals that: (i) transmit potential maternal immunoregulatory factors in utero and (ii) are altricial and cannot be reared after birth without their mothers. Employing the newborn piglet model can address each of these concerns. However, it comes at the price of having first to characterize the immune system of swine and its development. This review focuses on the porcine B cell system, especially on the methods used for its characterization in fetal studies and neonatal piglets. Understanding these procedures is important in the interpretation of the data obtained. Studies on neonatal piglets have (a) provided valuable information on the development of the adaptive immune system, (b) lead to important advances in evolutionary biology, (c) aided our understanding of passive immunity and (d) provided opportunities to use swine to address specific issues in veterinary and biomedical research and immunotherapy. This review summarizes the history of the development of the piglet as a model for antibody repertoire development, thus providing a framework to guide future investigators.


title: Alteraciones Del Olfato En El Covid-19, Revisión De La Evidencia E Implicaciones En El Manejo De La Pandemia

text: Resumen Existe debate sobre si las alteraciones en el olfato deberían considerarse un síntoma de infección por COVID-19, dadas las implicaciones en el manejo del propio síntoma, en la realización de pruebas diagnósticas y en la aplicación de medidas de aislamiento. Se realizó una revisión sistemática bibliográfica de los artículos indexados en PubMed sobre alteraciones del olfato en cuadros virales de vías respiratorias, con especial énfasis en el COVID-19. El objetivo principal fue encontrar evidencia de interés clínico que apoye la relación entre ansomia y COVID-19. Las alteraciones del olfato en procesos infecciosos de vías altas son frecuentes, en su mayoría responden a una causa obstructiva por edema de la mucosa nasal. Ocasionalmente aparece una disfunción olfatoria post-viral de tipo neurosensorial, de pronóstico variable. La evidencia acerca de la anosmia en pacientes con COVID-19 es muy limitada, correspondiente a un grado 5 o D del Centre for Evidence-Based Medicine. En acuerdo con las distintas sociedades médicas que han emitido comunicados al respecto, parece razonable aplicar medidas de aislamiento, higiene y distanciamiento social a los pacientes con alteraciones del olfato de reciente aparición como único síntoma, aunque se debería estudiar la utilidad de la realización de pruebas diagnósticas a este tipo de pacientes. Abstract There is debate as to whether olfactory dysfunction should be considered a symptom of COVID-19 infection, given the implications for managing the symptom itself, for diagnostic testing, and for implementing isolation measures. We undertook a systematic literature review of the articles indexed in PubMed on olfactory disorders in viral respiratory tract conditions, with special emphasis on COVID-19. The main objective was to find evidence of clinical interest to support the relationship between anosmia and COVID-19. Olfactory disorders in upper respiratory tract infections are frequent, most caused by obstruction due to oedema of the nasal mucosa. Occasionally, post-viral sensorineural olfactory dysfunction occurs, with a variable prognosis. The evidence on anosmia in COVID-19 patients is extremely limited, corresponding to a level 5 or D of the Centre for Evidence-Based Medicine. According to the various medical societies that have issued reports on the subject, it seems reasonable to apply isolation, hygiene and social distancing measures in patients with recent olfactory disorders as the only symptom, although the usefulness of diagnostic tests for this type of patient should be studied.


title: Captive Red Panda Medicine

text: As with many captive animals, red panda health problems can be categorized into two age-based groups: paediatric and adult. This chapter addresses the broad health concerns of those two groups, followed by discussion on parasites, infectious diseases, and vaccination, and concludes with suggestions for chemical restraint and anaesthesia of red pandas. Several drugs and drug combinations have been used to chemically restrain red pandas for short procedures or for the induction of general anaesthesia. Neonates are usually “masked down,” by placing a face mask over their face, and having them breathe 5% isoflurane in oxygen. Alternatively, an induction chamber can be used in all age groups. Anaesthesia is induced by flowing 5% isoflurane in oxygen into the box. A combination of ketamine HCl, a dissociative anaesthetic and medetomidine, an alpha-2-adrenergicagonist works well in red pandas for short, non-noxious procedures, such as blood collection, teeth cleaning, orradiology. Typically, the animal is transferred from a crate to a small squeeze cage and the drugs are given intramuscularly, via hand injection. The effects of the medetomidine can be reversed with atipamezole and recoveries are usually rapid and smooth. Other drug combinations that have been used in juvenile and adult red pandas are: ketamine and xylazine; ketamine with xylazine i.m. and followed by i.v. diazepam; and tiletamine/zolazepam.


Brachytherapy during the COVID-19– Lessons from Iran


title: SARS‐CoV‐2: a new aetiology for atypical lymphocytes

text: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a newly emerging coronavirus, SARS-CoV-2. COVID-19 has a very variable clinical picture, ranging from asymptomatic to severe acute respiratory syndrome that can lead to death. Our case, a 74-year-old female patient, presented with fever, moderate dyspnoea and leucocytosis (white blood cell count 21.6 × 109 /l, neutrophils 16.8 × 109 /l, lymphocytes 3.67 × 109 /l). RT-PCR for SARS-CoV-2 was performed, which confirmed COVID-19.


ST-elevation acute myocardial infarction during COVID-19 pandemic: Are we missing the boat?


title: C-E1 Fusion Protein Synthesized by Rubella Virus DI RNAs Maintained During Serial Passage

text: Rubella virus (RUB) replicons are derivatives of the RUB infectious cDNA clone that retain the nonstructural open reading frame (NS-ORF) that encodes the replicase proteins but not the structural protein ORF (SP-ORF) that encodes the virion proteins. RUB defective interfering (DI) RNAs contain deletions within the SP-ORF and thus resemble replicons. DI RNAs often retain the 5′ end of the capsid protein (C) gene which has been shown to modulate virus-specific RNA synthesis. However, when replicons either with or without the C gene were passaged serially in the presence of wt RUB as a source of the virion proteins, it was found that neither replicon was maintained and DI RNAs were generated. The majority DI RNA species contained in-frame deletions in the SP-ORF leading to a fusion between the 5′ end of the C gene and the 3′ end of the E1 glycoprotein gene. DI infectious cDNA clones were constructed and transcripts from these DI infectious cDNA clones were maintained during serial passage with wt RUB. The C-E1 fusion protein encoded by the DI RNAs was synthesized and was required for maintenance of the DI RNA during serial passage. This is the first report of a functional novel gene product resulting from deletion during DI RNA generation. Thus far, the role of the C-E1 fusion protein in maintenance of DI RNAs during serial passage remained elusive as it was found that the fusion protein diminished rather than enhanced DI RNA synthesis and was not incorporated into virus particles.


title: The French Infectious Diseases Society's readiness and response to epidemic or biological risk–the current situation following the Middle East respiratory syndrome coronavirus and Ebola virus disease alerts

text: Abstract Context In 2012, the French Infectious Diseases Society (French acronym SPILF) initiated the “Coordination of epidemic and biological risk” (SPILF-COREB - Emergences [SCE]) group to support the readiness and response of healthcare workers (HCWs) to new alerts. Objective To present the SCE group, its functioning, and the main support it provided for frontline HCWs. Methods A multidisciplinary group of heads of infectious disease departments from reference hospitals was created to build a network of clinical expertise for care, training, and research in the field of epidemic and biological risk (EBR). The network developed a set of standardized operational procedures (SOPs) to guide interventions to manage EBR-suspect patients. Results A working group created the SOP aimed at frontline HCWs taking care of patients. Priority was given to the development of a generic procedure, which was then adapted according to the current alert. Five key steps were identified and hierarchized: detecting, protecting, caring for, alerting, and referring the EBR patient. The interaction between clinicians and those responsible for the protection of the community was crucial. The SOPs validated by the SPILF and its affiliates were disseminated to a wide range of key stakeholders through various media including workshops and the SPILF's website. Conclusion SPILF can easily adapt and timely mobilize the EBR expertise in case of an alert. The present work suggests that sharing and discussing this experience, initiated at the European level, can generate a new collective expertise and needs to be further developed and strengthened.


Orthopedic Surgery Post COVID-19: An Opportunity for Innovation and Transformation


title: Tracking Australian Hajj pilgrims' health behavior before, during and after Hajj, and the effective use of preventive measures in reducing Hajj-related illness: A cohort study

text: This study assessed Australian Hajj pilgrims' knowledge, attitude and practices throughout their Hajj journey to understand their health behaviors, use of preventative measures and development of illness symptoms. A prospective cohort study with data collection at three phases (before, during and after Hajj) was conducted among Australian pilgrims between August and December 2015. Baseline datawere collected from421 pilgrims beforeHajj, with 391 providing follow-up data duringHajj and 300 after their home return. Most participants (78% [329/421]) received one or more recommended vaccines; travel agents' advice was the main factor affecting vaccination uptake. Most participants (69% [270/391]) practiced hand hygiene with soap and sanitizers frequently, followed by disposable handkerchief use (36% [139/391]) and washing hands with water only (28% [111/391]). During Hajj 74% (288/391) of participants reported one or more illness symptoms, 86% (248/288) of these symptoms were respiratory. Cough was less often reported among pilgrims who received vaccinations, cleaned their hands with soap or alcoholic hand rubs, while a runny nose was less common among those who frequently washed their hands with plain water but was more common among those who used facemasks. This study reveals that most Australian Hajj pilgrims complied with key preventative measures, and that tour group operators' advice played an important role in compliance. Pilgrims who were vaccinated and practiced hand hygiene were less likely to report infection symptoms.


title: Immune Responses to rAAV6: The Influence of Canine Parvovirus Vaccination and Neonatal Administration of Viral Vector

text: Recombinant adeno-associated viral (rAAV) vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV). rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV-vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, 1 month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice.


title: Chicken egg yolk antibodies (IgY) modulate the intestinal mucosal immune response in a mouse model of Salmonella typhimurium infection

text: Abstract This study determined the effects of chicken egg yolk antibodies (IgY) on immune responses in the intestinal mucosal of mice infected with Salmonella typhimurium. Sixty, 28-day-old mice were divided into 4 groups and treated with streptomycin or sterile water for 2days followed by 1day without treatment. The control group was unchallenged whereas the mice in the other three groups were treated twice with 109 CFUmL−1 S. typhimurium. For the next 3days, control mice continued to receive no treatment whereas the mice in the remaining three groups were orally administered with 20mgmL−1 of specific IgY, 20mgmL−1 of nonspecific IgY or PBS. S. typhimurium activated gut-associated lymphoid tissue, increasing the release of IFN-γ and TNF-α in the mucosa and increased the number of activated T-lymphocytes and cytotoxic T-γδ. Specific IgY attenuated the increase in IFN-γ and TNF-α and the decrease in IL-10. S. typhimurium induced mobilization of CD8+ and CD8+ TCRγδ T cells in the epithelium and CD4+ and CD8+ T cells in the lamina propria reflecting an inflammatory process that was attenuated by IgY. These results suggest that specific IgY modulates intestinal mucosal immune responses during a S. typhimurium infection.


Gastrointestinal endoscopy operation——A potential transmission risk for SARS-CoV-2


title: Malaria in Zhejiang Province, China, from 2005 to 2014

text: To summarize the changing epidemiological characteristics of malaria in Zhejiang Province, China, we collected data on malaria from the Chinese Notifiable Disease Reporting System (NDRS) and analyzed them. A total of 2,738 malaria cases were identified in Zhejiang Province from 2005 to 2014, of which 2,018 were male and 720 were female. Notably, only 7% of malaria cases were indigenous and the other cases were all imported. The number of malaria cases increased from 2005 to 2007, peaked in 2007, and then decreased from 2007 to 2011. There were no indigenous cases from 2012 to 2014. Of all cases, 68% of cases contracted Plasmodium vivax, 27% of cases contracted P. falciparum, and two cases contracted P. malariae. About 88% of malaria cases during 2005–2011 occurred yearly between May and October, but the number of malaria cases in different months during 2012–2014 was similar. The median age was 33 years, and 1,892 cases occurred in persons aged 20–50 years. The proportion of businessmen increased and the proportion of migrant laborers decreased in recent years. The median time from illness onset to confirmation of malaria cases was 5 days and it decreased from 2005 to 2014. Some epidemiological characteristics of malaria have changed, and businessmen are the emphases to surveillance in every month.


title: What do Patients Want From Their Radiation Oncologist? Initial Results From a Prospective Trial

text: Purpose To assess patients' initial physician preferences using a newly developed instrument. Methods and Materials A total of 182 patients with a primary diagnosis of prostate, breast, or lung cancer referred for consultation to the University of Pittsburgh Cancer Institute Department of Radiation Oncology enrolled in our institutional review board–approved protocol. All patients completed patient preference instrument surveys before meeting their radiation oncologist. Survey responses to 10 statements were categorized into three groups (agree, neutral, or disagree), and the association of survey responses by cancer site was tested with chi-squared tests. Results Ninety-nine percent of all patients preferred to be addressed by their first name in encounters with their radiation oncologist. There were significant associations of Item 3 (hand holding) with gender (p = 0.039) and education (p = 0.028). The responses to Item 5, a statement that patients would feel uncomfortable if the radiation oncologist offered to hug them at the end of treatment, was significantly associated with disease site (p < 0.0001). Further analysis was performed for Item 5 and revealed that the male lung cancer patients had a much higher rate of disagreement with Item 5 compared with prostate cancer patients (37% vs. 18%). Conclusions Results of this study may afford greater insight and foster better understanding of what patients want from their radiation oncologist. For breast, lung, and prostate cancer patients, initial preferences for their radiation oncologist are generally similar, according to this tool. However, there are important difference among cancer sites (and gender) regarding physical contact at the end of treatment.


title: The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases?

text: Currently, our world is facing the 2019 Novel Coronavirus (COVID-19) outbreak and tremendous efforts are made for developing drugs to treat and vaccines to prevent the disease. At present, there is no specific antiviral drug or vaccine for COVID-19. The pathogenic infectivity of the virus requires the S1 subunit of the spike (S) protein to bind the host cell receptor, angiontensin converting enzyme (ACE2). While the binding to host cell receptor is the first step of infection, the entrance of the virus into the cell needs the cleavage of S1–S2 subunits to expose S2 for fusion to cell membrane via host proteases including cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, trypsin and factor Xa. Previous in vitro studies have shown that factor Xa inhibition can decrease viral infectivity. We suppose that host cell proteases including furin (as expressed highly in lungs), factor Xa and cathepsin are possible targets to decrease viral burden, therefore unfractioned heparin and low molecular weight heparin-LMWH (specifically dalteparin and tinzaparin for their anti inflammatory action) can be potential inhibitors of multiple endoproteases involved in virus infectivity. Our hypothesis needs to be tested in in vitro and clinical studies, however as we are in an urgent situation as the burden of SARS-CoV2 is increasing all around the world, we recommend the usage of unfractioned heparin or LMWH in intensive care unit (ICU) and non-ICU hospitalized patients with the risk–benefit judgement of the clinician. Whether our hypothesis is clinically applicable and successful in decreasing viral infection will be evaluated for further studies.


title: Codon usage similarity between viral and some host genes suggests a codon-specific translational regulation

text: Abstract The codon usage pattern is a specific characteristic of each species; however, the codon usage of all of the genes in a genome is not uniform. Intriguingly, most viruses have codon usage patterns that are vastly different from the optimal codon usage of their hosts. How viral genes with different codon usage patterns are efficiently expressed during a viral infection is unclear. An analysis of the similarity between viral codon usage and the codon usage of the individual genes of a host genome has never been performed. In this study, we demonstrated that the codon usage of human RNA viruses is similar to that of some human genes, especially those involved in the cell cycle. This finding was substantiated by its concordance with previous reports of an upregulation at the protein level of some of these biological processes. It therefore suggests that some suboptimal viral codon usage patterns may actually be compatible with cellular translational machineries in infected conditions.


title: The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain

text: The porcine epidemic diarrhea virus (PEDV) poses a great threat to the global swine industries and the unreliable protection induced by the currently available vaccines remains a major challenge. We previously generated a genogroup 2b (G2b) PEDV Taiwan Pintung 52 (PEDVPT) strain, PEDVPT-P96, and determined its promising host immune response against the virulent PEDVPT-P5 strain. To study the attenuation determinants of PEDVPT-P96 and establish a PEDVPT-P96-based recombinant vector as a vaccine platform for further antigenicity modification, iPEDVPT-P96, a full-length cDNA clone of PEDVPT-P96, was established. Comparing to the parental PEDVPT-P96 virus, the iPEDVPT-P96 virus showed efficient replication kinetics with a delayed decline of viral load and similar but much more uniform plaque sizes in Vero cells. In the 5-week-old piglet model, fecal viral shedding was observed in the PEDVPT-P96-inoculated piglets, whereas those inoculated with iPEDVPT-P96 showed neither detectable fecal viral shedding nor PEDV-associated clinical signs. Moreover, inoculation with iPEDVPT-P96 elicited comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA, neutralizing antibody titers, and similar but less effective immunoprotection against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was successfully generated for the first time, and the in vitro and in vivo data indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared to its parental PEDVPT-P96 viral stock. The successful development of the iPEDVPT-P96 cDNA clone could allow for the manipulation of the viral genome to study viral pathogenesis and facilitate the rapid development of effective vaccines.


title: A welcome burst of human antibodies

text: A new method allows rapid identification of human monoclonal antibodies from immune or vaccinated individuals.


title: Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement

text: Abstract The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.


title: Human Rhinovirus/Enterovirus in Pediatric Acute Respiratory Distress Syndrome

text: The role of human rhinovirus/enterovirus (HRV/HEV) in severe lower respiratory tract infections remains unclear. We characterized the respiratory status of children admitted to a large academic pediatric intensive care unit (PICU) who tested positive for only HRV/HEV. One hundred and fifty-five children met inclusion criteria with 62% requiring positive pressure respiratory support of 5 cm of water pressure or more within the first 24 hours of admission. Among them, 34% had SaO (2) to FiO (2) ratios of 264 or less with 22 patients (14%) meeting criteria for pediatric acute respiratory distress syndrome. HRV/HEV is associated with significant respiratory disease in children admitted to the PICU.


Our Health is the Public’s Health: Pain Management Leadership in the COVID-19 Pandemic


title: Expression of Hemagglutinin/Esterase by a Mouse Hepatitis Virus Coronavirus Defective–Interfering RNA Alters Viral Pathogenesis

text: Abstract A defective-interfering (DI) RNA of mouse hepatitis virus (MHV) was developed as a vector for expressing MHV hemagglutinin/esterase (HE) protein. The virus containing an expressed HE protein (A59-DE-HE) was generated by infecting cells with MHV-A59, which does not express HE, and transfecting thein vitro-transcribed DI RNA containing the HE gene. A similar virus (A59-DE-CAT) expressing the chloramphenicol acetyltransferase (CAT) was used as a control. These viruses were inoculated intracerebrally into mice, and the role of the HE protein in viral pathogenesis was evaluated. Results showed that all mice infected with parental A59 or A59-DE-CAT succumbed to infection by 9 days postinfection (p.i.), demonstrating that inclusion of the DI did not by itself alter pathogenesis. In contrast, 60% of mice infected with A59-DE-HE survived infection. HE- or CAT-specific subgenomic mRNAs were detected in the brains at days 1 and 2 p.i. but not later, indicating that the genes in the DI vector were expressed only in the early stage of viral infection. No significant difference in virus titer or viral antigen expression in brains was observed between A59-DE-HE- and A59-DE-CAT-infected mice, suggesting that virus replication in brain was not affected by the expression of HE. However, at day 3 p.i. there was a slight increase in the extent of inflammatory cell infiltration in the brains of the A59-DE-HE-infected mice. Surprisingly, virus titers in the livers of A59-DE-HE-infected mice were 3 log10lower than that of the A59-DE-CAT-infected mice at day 6 p.i. Also, substantially less necrosis and viral antigen were detected in the livers of the A59-DE-HE-infected mice. This may account for the reduced mortality of these mice. The possible contribution of the host immune system to this difference in pathogenesis was analyzed by comparing the expression of four cytokines. Results showed that both tumor necrosis factor-α and interleukin-6 mRNAs increased in the brains of the A59-DE-HE-infected mice at day 2 p.i., whereas interferon-γ and interleukin-1α mRNAs were similar between A59-DE-HE- and A59-DE-CAT-infected mice. These data suggest that the transient expression of HE protein enhances an early innate immune response, possibly contributing to the eventual clearance of virus from the liver. This study indicates the feasibility of the DI expression system for studying roles of viral proteins during MHV infection.


title: Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway()

text: Apoptosis plays an important role in the pathogenesis of viral infections. In this study, we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms. Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis. HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria. The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly (ADP-ribose) polymerase, which is known to be an important substrate for activated caspase-3. Caspase-9 was activated significantly in HHV-6A-infected cells, whereas caspase-8 was not activated obviously. Moreover, HHV-6A infection upregulated Bax and downregulated Bcl-2. This is the first demonstration of mitochondrion-mediated, caspase-dependent apoptosis in HHV-6A-infected cells.


Review of Rosi Braidotti (2019). Posthuman Knowledge: Cambridge, UK: Polity Press. 210 pp. ISBN 9781509535255 (Hardcover)


title: Epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in Mexico

text: BACKGROUND: Respiratory syncytial virus (RSV) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. However, little information is available regarding RSV infections in Latin American countries, particularly among adult patients. OBJECTIVE: To describe the epidemiology of RSV infection and to analyze the factors associated with severe infections in children and adults in Mexico. METHODS: Patients ≥1 month old, who presented with an influenza‐like illness (ILI) to six hospitals in Mexico, were eligible for participation in the study. Multiplex reverse‐transcriptase polymerase chain reaction identified viral pathogens in nasal swabs from 5629 episodes of ILI. Patients in whom RSV was detected were included in this report. RESULTS: Respiratory syncytial virus was detected in 399 children and 171 adults. RSV A was detected in 413 cases and RSV B in 163, including six patients who had coinfection with both subtypes; 414 (72.6%) patients required hospital admission, including 96 (16.8%) patients that required admission to the intensive care unit. Coinfection with one or more respiratory pathogens other than RSV was detected in 159 cases. Young age (in children) and older age (in adults) as well as the presence of some underlying conditions were associated with more severe disease. CONCLUSIONS: This study confirms that RSV is an important respiratory pathogen in children in Mexico. In addition, a substantial number of cases in adults were also detected highlighting the relevance of this virus in all ages. It is important to identify subjects at high risk of complications who may benefit from current or future preventive interventions.


Surprise Billing in Surgical Care Episodes – Overview, Ethical Concerns, and Policy Solutions in Light of COVID-19


title: The RNA Virus Database

text: http://virus.zoo.ox.ac.uk/rnavirusdb; http://hivweb.sanbi.ac.za/rnavirusdb; http://bioinf.cs.auckland.ac.nz/rnavirusdb; http://tree.bio.ed.ac.uk/rnavirusdb.


Neuroradiological features in COVID-19 patients: first evidence in a complex scenario


title: Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection

text: Insights into the host antiviral strategies as well as viral disease manifestations can be achieved through the elucidation of host‐ and virus‐mediated transcriptional responses. An oligo‐based microarray was employed to analyse mRNAs from rhabdomyosarcoma cells infected with the MS/7423/87 strain of enterovirus 71 (EV71) at 20 h post infection. Using Acuity software and LOWESS normalization, 152 genes were found to be downregulated while 39 were upregulated by greater than twofold. Altered transcripts include those encoding components of cytoskeleton, protein translation and modification; cellular transport proteins; protein degradation mediators; cell death mediators; mitochondrial‐related and metabolism proteins; cellular receptors and signal transducers. Changes in expression profiles of 15 representative genes were authenticated by real‐time reverse transcription polymerase chain reaction (RT‐PCR), which also compared the transcriptional responses of cells infected with EV71 strain 5865/Sin/000009 isolated from a fatal case during the Singapore outbreak in 2000. Western blot analyses of APOB, CLU, DCAMKL1 and ODC1 proteins correlated protein and transcript levels. Two‐dimensional proteomic maps highlighted differences in expression of cellular proteins (CCT5, CFL1, ENO1, HSPB1, PSMA2 and STMN1) following EV71 infection. Expression of several apoptosis‐associated genes was modified, coinciding with apoptosis attenuation observed in poliovirus infection. Interestingly, doublecortin and CaM kinase‐like 1 (DCAMKL1) involved in brain development, was highly expressed during infection. Thus, microarray, real‐time RT‐PCR and proteomic analyses can elucidate the global view of the numerous and complex cellular responses that contribute towards EV71 pathogenesis.


title: Acute Exacerbations of Asthma: Epidemiology, Biology and the Exacerbation-Prone Phenotype

text: Asthma is a highly prevalent chronic respiratory disease affecting 300 million people worldwide. A significant fraction of the cost and morbidity of asthma derives from acute care for asthma exacerbations. In the United States alone, there are approximately 15.0 million outpatient visits, 2 million emergency room visits, and 500,000 hospitalizations each year for management of acute asthma. Common respiratory viruses, especially rhinoviruses, cause the majority of exacerbations in children and adults. Infection of airway epithelial cells with rhinovirus causes the release of pro-inflammatory cytokines and chemokines, as well as recruitment of inflammatory cells, particularly neutrophils, lymphocytes, and eosinophils. The host response to viral infection is likely to influence susceptibility to asthma exacerbation. Having had at least one exacerbation is an important risk factor for recurrent exacerbations suggesting an “exacerbation-prone” subset of asthmatics. Factors underlying for the “exacerbation-prone” phenotype are incompletely understood but include extrinsic factors: cigarette smoking, medication noncompliance, psychosocial factors, and co-morbidities such as gastroesophageal reflux disease, rhinosinusitis, obesity, and intolerance to non-steroidal anti-inflammatory medications; as well as intrinsic factors such as deficient epithelial cell production of the anti-viral type I interferons (IFN-α and IFN-β). A better understanding of the biologic mechanisms of host susceptibility to recurrent exacerbations will be important for developing more effective preventions and treatments aimed at reducing the significant cost and morbidity associated with this important global health problem.


title: New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?

text: ABSTRACT Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.


title: Inhibitors of c-Jun N-terminal kinases—JuNK no more?

text: Abstract The c-Jun N-terminal kinases (JNKs) have been the subject of intense interest since their discovery in the early 1990s. Major research programs have been directed to the screening and/or design of JNK-selective inhibitors and testing their potential as drugs. We begin this review by considering the first commercially-available JNK ATP-competitive inhibitor, SP600125. We focus on recent studies that have evaluated the actions of SP600125 in lung, brain, kidney and liver following exposure to a range of stress insults including ischemia/reperfusion. In many but not all cases, SP600125 administration has proved beneficial. JNK activation can also follow infection, and we next consider recent examples that demonstrate the benefits of SP600125 administration in viral infection. Additional ATP-competitive JNK inhibitors have now been described following high throughput screening of small molecule libraries, but information on their use in biological systems remains limited and thus these inhibitors will require further evaluation. Peptide substrate-competitive ATP-non-competitive inhibitors of JNK have also now been described, and we discuss the recent advances in the use of JNK inhibitory peptides in the treatment of neuronal death, diabetes and viral infection. We conclude by raising a number of questions that should be considered in the quest for JNK-specific inhibitors.


title: Viral metagenomics

text: Characterisation of new viruses is often hindered by difficulties in amplifying them in cell culture, limited antigenic/serological cross‐reactivity or the lack of nucleic acid hybridisation to known viral sequences. Numerous molecular methods have been used to genetically characterise new viruses without prior in vitro replication or the use of virus‐specific reagents. In the recent metagenomic studies viral particles from uncultured environmental and clinical samples have been purified and their nucleic acids randomly amplified prior to subcloning and sequencing. Already known and novel viruses were then identified by comparing their translated sequence to those of viral proteins in public sequence databases. Metagenomic approaches to viral characterisation have been applied to seawater, near shore sediments, faeces, serum, plasma and respiratory secretions and have broadened the range of known viral diversity. Selection of samples with high viral loads, purification of viral particles, removal of cellular nucleic acids, efficient sequence‐independent amplification of viral RNA and DNA, recognisable sequence similarities to known viral sequences and deep sampling of the nucleic acid populations through large scale sequencing can all improve the yield of new viruses. This review lists some of the animal viruses recently identified using sequence‐independent methods, current laboratory and bioinformatics methods, together with their limitations and potential improvements. Viral metagenomic approaches provide novel opportunities to generate an unbiased characterisation of the viral populations in various organisms and environments. Copyright © 2007 John Wiley & Sons, Ltd.


Novel coronavirus (2019-nCoV): Update on 3rd Coronavirus Outbreak of 21st Century


title: Oncolytic viruses: a new class of immunotherapy drugs

text: Oncolytic viruses represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumour cell killing and the induction of systemic anti-tumour immunity. The molecular and cellular mechanisms of action are not fully elucidated but are likely to depend on viral replication within transformed cells, induction of primary cell death, interaction with tumour cell antiviral elements and initiation of innate and adaptive anti-tumour immunity. A variety of native and genetically modified viruses have been developed as oncolytic agents, and the approval of the first oncolytic virus by the US Food and Drug Administration (FDA) is anticipated in the near future. This Review provides a comprehensive overview of the basic biology supporting oncolytic viruses as cancer therapeutic agents, describes oncolytic viruses in advanced clinical trials and discusses the unique challenges in the development of oncolytic viruses as a new class of drugs for the treatment of cancer. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd4663) contains supplementary material, which is available to authorized users.


title: Ibuprofen, a traditional drug that may impact the course of COVID-19 New effective formulation in nebulizable solution

text: The traditional formulation of ibuprofen is poorly soluble in water, so the administered dose must be 10 times higher than the dose required for a therapeutic effect. The development of a hydrosoluble form of ibuprofen can be a strategy to reach a high concentration in the lungs by using modern inhalation devices. Therefore, the development of an inhalable formulation with high bioavailability in the lungs was the leitmotiv of our investigation. The hypertonic ibuprofen solution to be nebulized (NIH) presents great relevant characteristics: bactericidal, virucidal, mucolytic and has a known anti-inflammatory property. Bactericidal and virucidal effects are related to the physico-chemical properties of Na-ibuprofenate as an amphipathic molecule. It has the capability to insert into the bilayer membranes destabilizing the structure, altering its biological properties and avoiding the duplication or infection. Our preliminary results indicate that the presence of this high ionic strength solution reduces 10 times the amount of ibuprofen necessary to kill bacteria, but also the time to kill 1x10(6) bacteria, from 4 hours (in its absence) to only three minutes (in its presence). That was observed using Pseudomona aeruginosa, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia. Also, “in vitro'' ibuprofen demonstrated virucidal activity against the so-called enveloped virus, a family that includes coronavirus strain (2019-nCoV). We observed too, the markedly reduced local inflammation in the airways after administering NIH lays on its ability to inhibit the enzyme cyclooxygenase and to markedly diminish reactive oxygen species (ROS). Other investigators also showed the importance of actin in the rapid spread of virus infection. Furthermore, reorganization of the actin filaments is a key step in lung inflammation induced by systemic inflammatory responses caused by SARS-CoV-2. These findings suggest that the interaction between actin proteins and S1 is involved in the 2019-nCoV infection and pathogenesis. Consequently, the possibility of interfering in this interaction could represent a valid hypothesis for the development of promising therapeutic and prevention strategies. In conclusion, we consider that treating people with COVID-19 with NIH may be beneficial and an opportunity to contribute for the current global health emergency.


Infectious diseases know no borders: A plea for more collaboration between researchers in human and veterinary vaccines


title: Growth characteristics of canine pathogenic viruses in MDCK cells cultured in RPMI 1640 medium without animal protein

text: Madin Darby canine kidney (MDCK) cells were adapted to serum-free RPMI 1640 medium and used for cultivation of canine viruses. RPMI 1640 medium was supplemented with a soybean peptone, l-glutamine and antibiotics, so that the protein concentration was less than 5 μg/ml (RPMI/SP medium). The resulting adapted MDCK-SP cells showed steady growth after the twenty-eighth passage in RPMI/SP medium (MDCK-SP cell culture). Canine distemper virus, canine parvovirus, canine adenoviruses and canine parainfluenza virus, which are the principal components of canine combined virus vaccines, grew in the MDCK-SP cell culture as efficiently as the parental MDCK cells cultured in the conventional Eagle's MEM containing fetal bovine serum. Consequently, the use of MDCK-SP cell culture can make current canine vaccine products much safer, of higher quality and at lower cost.


title: GmPHD5 acts as an important regulator for crosstalk between histone H3K4 di-methylation and H3K14 acetylation in response to salinity stress in soybean

text: BACKGROUND: Accumulated evidence suggest that specific patterns of histone posttranslational modifications (PTMs) and their crosstalks may determine transcriptional outcomes. However, the regulatory mechanisms of these "histone codes" in plants remain largely unknown. RESULTS: In this study, we demonstrate for the first time that a salinity stress inducible PHD (plant homeodomain) finger domain containing protein GmPHD5 can read the "histone code" underlying the methylated H3K4. GmPHD5 interacts with other DNA binding proteins, including GmGNAT1 (an acetyl transferase), GmElongin A (a transcription elongation factor) and GmISWI (a chromatin remodeling protein). Our results suggest that GmPHD5 can recognize specific histone methylated H3K4, with preference to di-methylated H3K4. Here, we illustrate that the interaction between GmPHD5 and GmGNAT1 is regulated by the self-acetylation of GmGNAT1, which can also acetylate histone H3. GmGNAT1 exhibits a preference toward acetylated histone H3K14. These results suggest a histone crosstalk between methylated H3K4 and acetylated H3K14. Consistent to its putative roles in gene regulation under salinity stress, we showed that GmPHD5 can bind to the promoters of some confirmed salinity inducible genes in soybean. CONCLUSION: Here, we propose a model suggesting that the nuclear protein GmPHD5 is capable of regulating the crosstalk between histone methylation and histone acetylation of different lysine residues. Nevertheless, GmPHD5 could also recruit chromatin remodeling factors and transcription factors of salt stress inducible genes to regulate their expression in response to salinity stress.


title: Acute Lung Infections in Normal and Immunocompromised Hosts

text: Pulmonary infections are among the most common causes of morbidity and mortality worldwide, and contribute substantially to annual medical expenditures in the United States. Despite the availability of antimicrobial agents, pneumonia constitutes the sixth most common cause of death and the number one cause of death from infection. Pneumonia can be particularly life-threatening in the elderly, in individuals who have pre-existing heart and lung conditions, in patients who have suppressed or weakened immunity, and in pregnant women. This article discusses some of the important causes of acute lung infections in normal and immunocompromised hosts. Because there often is considerable overlap, infections are categorized by the host immune status that is most likely to be associated with a particular pathogen.


title: Analysis of mRNA expression for genes associated with regulatory T lymphocytes (CD25, FoxP3, CTLA4, and IDO) after experimental infection with bovine viral diarrhea virus of low or high virulence in beef calves

text: Abstract Immunosuppression caused by bovine viral diarrhea virus (BVDV) has been associated with lymphocyte depletion, leukopenia and impairment of leukocyte function; however, no work has been done on the relationship between BVDV and regulatory T lymphocytes (Tregs). The objective of this study was to compare the mRNA expression of genes associated with Tregs (CD25, FoxP3, CTLA4, and IDO), after experimental infection of beef calves with low (LV) or high (HV) virulence BVDV. Thirty BVDV-naïve calves were randomly assigned to three groups. Calves were intra-nasally inoculated with LV (n =10, strain SD-1) or HV (n =10, strain 1373) BVDV or BVDV-free cell culture medium (control, n =10). Quantitative RT-PCR was used to determine the expression of target genes in tracheo-bronchial lymph nodes and spleen on day 5 post-infection. The mRNA expression of CD25 was up-regulated in tracheo-bronchial lymph nodes of LV (P <0.05), but not in HV compared to the control group. The expression of FoxP3 and CTLA4 was not increased in tracheo-bronchial lymph nodes of either of the BVDV-inoculated groups. A dramatic up-regulation of IDO mRNA was observed in tracheo-bronchial lymph nodes of LV (P <0.05), but not HV compared to the control calves. In conclusion, experimental infection with BVDV did not provide evidence of Treg activation based on expression of FoxP3 and CTL4. Differential expression of CD25 and IDO mRNA on day 5 post-infection with HV or LV BVDV might reflect temporal differences in transcription occurring during the immune response elicited by these viral strains, or differences in viral infectivity of the host cells.


title: In vitro study of the effect of a probiotic bacterium Lactobacillus rhamnosus against herpes simplex virus type 1

text: Abstract Background Due to the emergence of drug resistance in herpes simplex virus type 1 (HSV-1), researchers are trying to find other methods for treating herpes simplex virus type 1 infections. Probiotic bacteria are effective in macrophage activation and may have antiviral activities. Objective This study aimed at verifying the direct effect of Lactobacillus rhamnosus, a probiotic bacterium, in comparison with Escherichia coli, a non-probiotic one, on HSV-1 infection, and determining its effect on macrophage activation for in vitro elimination of HSV-1 infection. Methods The above bacteria were introduced into HSV-1 infected Vero cells, and their effects were examined using both MTT and plaque assay. To determine macrophage activation against in vitro HSV-1 infection, J774 cells were exposed to these bacteria; then, macrophage viability was examined with the MTT method, and tumor necrosis factor alpha (TNF-α), Interferon-gamma (IFN-γ), and nitric oxide (NO) assessments were performed using the ELISA method. Results A significant increased viability of macrophages was observed (p<0.05) in the presence of Lactobacillus rhamnosus before and after HSV-1 infection when compared with Escherichia coli as a non-probiotic bacterium. However, tumor necrosis factor α concentration produced by Escherichia coli-treated J774 cells was significantly higher than Lactobacillus rhamnosus-treated J774 cells (p<0.05). Interferon-gamma and NO production were not different in the groups treated with Escherichia coli or with Lactobacillus rhamnosus. Conclusion The results of this study indicate that Lactobacillus rhamnosus enhances macrophage viability for HSV-1 elimination and activation against HSV-1 more effectively, when compared with non-probiotic Escherichia coli. It also seems that receptor occupation of macrophage sites decreases HSV-1 infectivity by both of the studied bacteria.


A call to action : the need for autopsies to determine the full extent of organ involvement associated with COVID-19 infections


title: Provision of care through telemedicine during a natural disaster: a case study

text: INTRODUCTION: As the frequency and intensity of natural disasters increases, disaster preparedness is necessary for individuals with disabilities, including those with spinal cord injury (SCI). However, despite vulnerability to poorer outcomes, disaster preparedness for individuals with SCI is inadequate. Telemedicine has been effectively used to mitigate the impact of natural disasters. In this case study, we describe the provision of clinical care, via telemedicine, to an individual with SCI who was affected by the California Valley Fire in 2015. CASE PRESENTATION: The individual described was an adult who sustained a SCI. Before discharge from acute inpatient rehabilitation, they enrolled in a research study, through which they received outpatient SCI-specific care via telemedicine (teleSCI). The participant attended several teleSCI visits prior to the start of the Valley Fire. In the midst and immediate aftermath of prolonged wildfire, and despite experiencing significant personal loss as a result of the fire, the participant continued to receive teleSCI services. TeleSCI was used to address emergent and extant medical concerns and to facilitate replacement of medical supplies and equipment destroyed by fire. DISCUSSION: TeleSCI was used to provide continuity of care and was responsive to the needs of an individual with SCI severely affected by wildfire. Emergency preparedness that meets the needs of persons with disabilities is critical during times of crisis. Telemedicine may be an effective tool that can be applied to meet the medical needs of individuals with SCI and to mitigate the impact of disasters.


title: The determinants of the 1999 and 2007 Chinese Golden Holiday System: A content analysis of official documentation

text: Abstract This study examines the factors that lay behind the development of the Golden Week holiday system in China in 1999 and 2007. It does so by evaluating three dimensions, namely (a) dominant government policy, (b) the pattern of tourism demand and (c) the degree of public participation in the policy making process. Both quantitative and qualitative methodologies are used in a content analysis of 45 related documents. The results indicate that while little relationship existed between the demands of tourism and public policy in both 1999 and 2007, the requirements of social policies and a greater role being attributed to public participation in the policy making were more emphasized in 2007. The theoretical contributions and practical implications of this study are also addressed.


title: Fate of Selected Bacterial Pathogens and Indicators in Fractionated Poultry Litter During Storage

text: Abstract A study of broiler litter re-utilization potential was conducted with the goal of determining if storage of litter significantly reduced potential pathogens to levels safe for re-utilization. Litter from four broiler houses was separated into a fine fraction for fertilizer use and a coarse fraction for use as a supplement to wood shavings in growing subsequent flocks of birds. Fractions and whole litter were stored in indoor piles for four months with periodic analysis for culturable pathogenic and indicator bacteria. Significant reductions in microbial concentrations occurred in a majority of samples tested during four months of storage (in most cases to below detection limits of approximately 30 CFU/g dry weight). Poultry feed was found to be one possible source of litter contamination.


title: Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease

text: Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as high-throughput surface plasmon resonance (SPR), that we also describe.


title: Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus

text: Abstract This paper concerns study of the genome of the Wuhan Seafood Market isolate believed to represent the causative agent of the disease COVID-19. This is to find a short section or sections of viral protein sequence suitable for preliminary design proposal for a peptide synthetic vaccine and a peptidomimetic therapeutic, and to explore some design possibilities. The project was originally directed towards a use case for the Q-UEL language and its implementation in a knowledge management and automated inference system for medicine called the BioIngine, but focus here remains mostly on the virus itself. However, using Q-UEL systems to access relevant and emerging literature, and to interact with standard publically available bioinformatics tools on the Internet, did help quickly identify sequences of amino acids that are well conserved across many coronaviruses including 2019-nCoV. KRSFIEDLLFNKV was found to be particularly well conserved in this study and corresponds to the region around one of the known cleavage sites of the SARS virus that are believed to be required for virus activation for cell entry. This sequence motif and surrounding variations formed the basis for proposing a specific synthetic vaccine epitope and peptidomimetic agent. The work can, nonetheless, be described in traditional bioinformatics terms, and readily reproduced by others, albeit with the caveat that new data and research into 2019-nCoV is emerging and evolving at an explosive pace. Preliminary studies using molecular modeling and docking, and in that context the potential value of certain known herbal extracts, are also described.


title: Molecular Epidemiology of Paramyxoviruses in Frugivorous Eidolon helvum Bats in Zambia

text: In this study, we describe the detection of novel paramyxoviruses from the Eidolon helvum species of fruit bats. We extracted RNA from 312 spleen samples from bats captured in Zambia over a period of 4 years (2008–2011). Semi-nested RT-PCR detected a total of 25 (8%) positive samples for paramyxoviruses which were then directly sequenced and analyzed using phylogenetic analysis. Among the positive samples, seven novel paramyxoviruses were detected. Five viruses were closely related to the genus Henipavirus, while two viruses were related to the unclassified Bat paramyxoviruses from Ghana and Congo Brazzaville. Our study identified novel Henipavirus-related and unrelated viruses using RT-PCR in fruit bats from Kansaka National Park and indicated the presence of similar Bat paramyxoviruses originating from wide geographic areas, suggesting the ability of bats to harbor and transmit viruses. The presence of these viruses in fruit bats might pose a public health risk.


title: Infectome: A platform to trace infectious triggers of autoimmunity

text: Abstract The “exposome” is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the “infectome”, which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the “immunome” and “microbiome” projects.


title: Author response to Letter to the Editor: Potential implications of COVID‐19 in non‐alcoholic fatty liver disease

text: We are grateful to Grietje h. Prins and his colleagues for their interest in our recent article regarding the characteristics and mechanisms of liver damage caused by three highly pathogenic coronavirus infections and for their valuable insights on the liver injury among COVID‐19.


Cardiovascular Disease in the Post-COVID-19 Era – the Impending Tsunami?


title: Locked-In with COVID-19

text: Coronavirus Disease 2019 (COVID-19) can be associated with various neurological manifestations including acute strokes. Hyper acute diagnosis and treatment are key factors which decrease mortality and morbidity in stroke patients. The COVID-19 pandemic has introduced a great strain on the healthcare system, and as a result clinicians are facing several barriers in diagnosing and treating stroke. Delayed presentation of strokes is a problem as some in the general population defer the decision to seek immediate medical attention fearing contracting the virus. Also playing a role is the paucity of healthcare professionals available during a pandemic. Recent literature demonstrates the association of acute strokes in young patients with COVID-19. Lack of clear pathophysiology of the neurological manifestations from COVID-19 intensifies the problem. A thorough examination of the intensive care unit patient has always been a challenge owing to several factors including use of sedatives, sepsis, uremia, and encephalopathy secondary to medications. Locked-In Syndrome (LIS) secondary to stroke is much more challenging to diagnose as patients are unable to communicate or elicit any motor functions apart from certain ocular movements. We present the case of a 25 year old patient with no known history of coagulopathy, but had developed COVID-19 cytokine storm which culminated in LIS secondary to pontine strokes.


title: Human defensins and LL‐37 in mucosal immunity

text: Defensins are widespread in nature and have activity against a broad range of pathogens. Defensins have direct antimicrobial effects and also modulate innate and adaptive immune responses. We consider the role of human defensins and the cathelicidin LL‐37 in defense of respiratory, gastrointestinal, and genitourinary tracts and the oral cavity, skin, and eye. Human β‐defensins (hBDs) and human defensins 5 and 6 (HD5 and −6) are involved most obviously in mucosal responses, as they are produced principally by epithelial cells. Human α‐defensins 1–4 (or HNPs 1–4) are produced principally by neutrophils recruited to the mucosa. Understanding the biology of defensins and LL‐37 is the beginning to clarify the pathophysiology of mucosal inflammatory and infectious diseases (e.g., Crohn's disease, atopic dermatitis, lung or urinary infections). Challenges for these studies are the redundancy of innate defense mechanisms and the presence and interactions of many innate defense proteins in mucosal secretions.


title: Functional and Homeostatic Impact of Age-Related Changes in Lymph Node Stroma

text: Adults over 65 years of age are more vulnerable to infectious disease and show poor responses to vaccination relative to those under 50. A complex set of age-related changes in the immune system is believed to be largely responsible for these defects. These changes, collectively termed immune senescence, encompass alterations in both the innate and adaptive immune systems, in the microenvironments where immune cells develop or reside, and in soluble factors that guide immune homeostasis and function. While age-related changes in primary lymphoid organs (bone marrow, and, in particular, the thymus, which involutes in the first third of life) have been long appreciated, changes affecting aging secondary lymphoid organs, and, in particular, aging lymph nodes (LNs) have been less well characterized. Over the last 20 years, LN stromal cells have emerged as key players in maintaining LN morphology and immune homeostasis, as well as in coordinating immune responses to pathogens. Here, we review recent progress in understanding the contributions of LN stromal cells to immune senescence. We discuss approaches to understand the mechanisms behind the decline in LN stromal cells and conclude by considering potential strategies to rejuvenate aging LN stroma to improve immune homeostasis, immune responses, and vaccine efficacy in the elderly.


title: Severe acute respiratory syndrome (SARS) in children: epidemiology, presentation and management

text: Abstract Severe acute respiratory syndrome (SARS) is a newly recognised and highly contagious respiratory infection caused by a new strain of coronavirus. The disease can result in progressive respiratory failure in adults and the mortality rate has been reported to be 8–15%. This infection spreads by droplet transmission and children appear to acquire SARS through close household contact exposure to infected adults. Disease severity is, however, much milder in the paediatric age group. The common laboratory findings in infected children and adolescents include lymphopaenia and elevated levels of lactate dehydrogenase and creatinine phosphokinase. Air space consolidation is commonly seen during the course of the illness although chest radiographs are normal on presentation in half of the cases. The pathophysiology of SARS appears to be related to immunological dysregulation in response to the coronavirus infection. The optimal treatment of SARS in children remains to be determined. No case fatality in infected children has been reported. The early and proper isolation of infected adults, meticulous infection control measures in the hospital setting, exhaustive contact tracing and quarantine measures are important steps in preventing the spread of the disease among health care workers and into the community. The development of a sensitive and rapid test for early diagnosis is underway. Further controlled trials are necessary to define the optimal treatment of this infection in children.


title: Are we equal in adversity? Does Covid-19 affect women and men differently?

text: BACKGROUND & OBJECTIVES: This article examines whether women are less prone than men to Covid-19 infections and their complications. DATA SOURCES: We reviewed available databases and searched systematically for publications. To be taken into account, data had to be broken down by gender. There was no study evaluation nor quantification synthesis, due to the large heterogeneity of the studies. Nineteen databases were selected. 73 publications were considered and 33 were selected, to which 12 more were added. RESULTS: Globally, the proportion of men and women who tested positive is comparable. However, men are about 60% more likely to be severely ill or to die from the complications of Covid-19 than are women. LIMITATIONS: The study was hampered by a large heterogeneity in testing and reporting of the data. CONCLUSIONS: Although in the pandemic men die more frequently than women from Covid-19, it is not clear whether this is due to biological differences between men and women, differences in behavioral habits, or differences in the rates of co-morbidities. IMPLICATIONS OF KEY FINDINGS: Countries and studies should report their data by age, gender and co-morbidities. This may have implications in terms of vaccination strategies, the choice of treatments and future consequences for long-term health issues concerning gender equality.


title: Dyspnea: the vanished warning symptom of COVID‐19 pneumonia

text: Since December 2019, the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has rapidly spread worldwide, challenging the clinician and focusing the entire globe on critical illness high mortality. This article is protected by copyright. All rights reserved.


title: Why is it difficult to accurately predict the COVID-19 epidemic?

text: Since the COVID-19 outbreak in Wuhan City in December of 2019, numerous model predictions on the COVID-19 epidemics in Wuhan and other parts of China have been reported. These model predictions have shown a wide range of variations. In our study, we demonstrate that nonidentifiability in model calibrations using the confirmed-case data is the main reason for such wide variations. Using the Akaike Information Criterion (AIC) for model selection, we show that an SIR model performs much better than an SEIR model in representing the information contained in the confirmed-case data. This indicates that predictions using more complex models may not be more reliable compared to using a simpler model. We present our model predictions for the COVID-19 epidemic in Wuhan after the lockdown and quarantine of the city on January 23, 2020. We also report our results of modeling the impacts of the strict quarantine measures undertaken in the city after February 7 on the time course of the epidemic, and modeling the potential of a second outbreak after the return-to-work in the city.


Effects of lockdown on retinal detachment incidence in Scotland


title: New human virus from SARS family

text: A virus never before seen in humans has infected two people, killing one. There is so far no evidence that it can spread readily between people


title: Effect of sulfhydryl reagents on the infectivity of vesicular stomatitis virus

text: Abstract The infectivity of vesicular stomatitis virus (VSV) was moderately affected by iodoacetic acid and drastically affected by N-ethylmaleimide; the antiviral effect of these sulfhydryl reagents was enhanced somewhat by the reducing agent, 2-mercaptoethanol. Reducing and/or alkylating reagents did not affect VSV hemagglutination and the impermeable sulfhydryl reagent, dextran-maleimide, did not significantly influence VSV infectivity. These data indicate that glycoprotein spikes are not the major sites for the antiviral activity of sulfhydryl reagents. [14C]Iodoacetic acid was able to penetrate the virion membrane to bind covalently to the free sulfhydryl groups of all five virion proteins, particularly the reduced disulfides of the L protein. The RNA polymerase activity of intact VSV was inhibited by iodoacetic acid and to a greater extent by N-ethylmaleimide, which probably accounts for the loss of viral infectivity caused by the permeable sulfhydryl reagents.


title: Evaluation of the reinforced integrated disease surveillance and response strategy using short message service data transmission in two southern regions of Madagascar, 2014–15

text: BACKGROUND: The Integrated Disease Surveillance and Response (IDSR) strategy was introduced in Madagascar in 2007. Information was collected by Healthcare structures (HS) on paper forms and transferred to the central level by post or email. Completeness of data reporting was around 20% in 2009–10. From 2011, in two southern regions data were transmitted through short messages service using one telephone provider. We evaluated the system in 2014–15 to determine its performance before changing or expanding it. METHODS: We randomly selected 80 HS and interviewed their representatives face-to-face (42) or by telephone (38). We evaluated knowledge of surveillance activities and selected case definitions, number of SMS with erroneous or missing information among the last ten transferred SMS, proportion of weekly reports received in the last 4 weeks and of the last four health alerts notified within 48 h, as well as mobile phone network coverage. RESULTS: Sixty-four percent of 80 interviewed HS representatives didn’t know their terms of reference, 83% were familiar with the malaria case definition and 32% with that of dengue. Ninety percent (37/41) of visited HS had five or more errors and 47% had missing data in the last ten SMS they transferred. The average time needed for weekly IDSR data compilation was 24 min in the Southern and 47 in the South-eastern region. Of 320 expected SMS 232 (73%) were received, 136 (43%) of them in time. Out of 38 alerts detected, four were notified on time. Nine percent (7/80) of HS had no telephone network with the current provider. CONCLUSIONS: SMS transfer has improved IDSR data completeness, but timeliness and data quality remain a problem. Healthcare staff needs training on guidelines and case definitions. From 2016, data are collected and managed electronically to reduce errors and improve the system’s performance.


title: Glial Responses to Virus Infection

text: Astroctyes, microglia, and oligodendrocytes of the central nervous system support neurons and their functions and are the main line of defense against pathogens such as bacteria and viruses. Viral infections trigger broad glial activation and the concomitant release of proinflammatory molecules, stimulating both the innate and the adaptive immune systems. If sustained, in some instances these responses may be deleterious rather than protective of the nervous system. Immunomodulatory mechanisms that limit activation and proinflammatory responses may be more effective at maintaining a balance between the proper response to infection and the preservation or recovery of tissue homeostasis. HIV-1 infection of the central nervous system is used as an example to characterize the glial response to viral infection.


title: On the global stability of a delayed epidemic model with transport-related infection

text: Abstract We study the global dynamics of a time delayed epidemic model proposed by Liu et al. (2008) [J. Liu, J. Wu, Y. Zhou, Modeling disease spread via transport-related infection by a delay differential equation, Rocky Mountain J. Math. 38 (5) (2008) 1525–1540] describing disease transmission dynamics among two regions due to transport-related infection. We prove that if an endemic equilibrium exists then it is globally asymptotically stable for any length of time delay by constructing a Lyapunov functional. This suggests that the endemic steady state for both regions is globally asymptotically stable regardless of the length of the travel time when the disease is transferred between two regions by human transport.


title: Seroconversion to HCoV-NL63 in Rhesus Macaques

text: HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63.


How to manage obsessive-compulsive disorder (OCD) under COVID-19: A clinician's guide from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) and the Obsessive-Compulsive Research Network (OCRN) of the European College of Neuropsychopharmacology


title: Comment on “Encephalopathy in patients with COVID‐19: A review”

text: I read with great interest the article by Garg and colleagues on "Encephalopathy in patients with COVID-19: A review". The authors performed a review of published reports on COVID-19-associated encephalitis and encephalopathy. This article is protected by copyright. All rights reserved.