title: COVID‐19 polyradiculitis in 24 patients without SARS‐CoV‐2 in the cerebro‐spinal fluid

text: OBJECTIVES to summarise and discuss current knowledge about COVID-19-associated Guillain-Barre syndrome (GBS). METHOD literature review RESULTS: altogether 18 articles were found, which reported 23 patients with COVID-19-associated GBS. A further patient came to our attention by personal communication. Among these 24 included patients age ranged from 20 to 76y. There was male preponderance. Fourteen patients presented with acute inflammatory demyelinating polyneuropathy (AIDP), 4 with acute motor axonal neuropathy (AMAN), 3 with Miller-Fisher syndrome (MFS), and 2 with acute motor and sensory axonal neuropathy (AMSAN). In one patient the subtype was not specified. The cerebrospinal fluid (CSF) was tested for SARS-CoV-2 in 15 patients but was negative for the virus in all of them. Seven patients required artificial ventilation. Twenty-one patients received intravenous immunoglobulines (IVIG). Thirteen patients recovered, 6 did not, and 2 patients died. CONCLUSIONS SARS-CoV-2 can cause GBS. SARS-CoV-2-associated GBS occurs in the absence of the virus in the CSF. Clinical presentation, course, response to treatment, and outcome do not vary between SARS-CoV-2-associated GBS and GBS due to other triggers. This article is protected by copyright. All rights reserved.


title: Coronaviruses and Central Nervous System Manifestations

text: SARS-CoV-2 is a highly pathogenic coronavirus that has caused an ongoing worldwide pandemic. Emerging in Wuhan, China in December 2019, the virus has spread rapidly around the world. Corona virus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has resulted in significant morbidity and mortality. The most prominent symptoms of SARS-CoV-2 infection are respiratory. However, accumulating evidence highlights involvement of the central nervous system (CNS). This includes headache, anosmia, meningoencephalitis, acute ischemic stroke, and several presumably post/para-infectious syndromes and altered mental status not explained by respiratory etiologies. Interestingly, previous studies in animal models emphasized the neurotropism of coronaviruses; thus, these CNS manifestations of COVID-19 are not surprising. This minireview scans the literature regarding the involvement of the CNS in coronavirus infections in general, and in regard to the recent SARS-CoV-2, specifically.


Anesthesia, ethics, and severe acute respiratory syndrome


title: Molecular detection and genotypic characterization of Toxoplasma gondii infection in bats in four provinces of China

text: BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that infects a wide variety of warm-blooded hosts, including humans. Limited information about T. gondii infection in bats is available in China. The objective of the present study was to determine prevalence and genetic characterization of T. gondii infection in bats in Jilin, Liaoning, Jiangxi and Guangdong provinces, China. METHODS: During May 2005 to August 2013, bats were sampled from Jilin, Liaoning, Jiangxi, and Guangdong provinces, China, and liver tissues were collected for the detection of T. gondii by a nested PCR targeting the B1 gene. The positive samples were genotyped at 11 genetic markers (SAG1, 5′-and 3′-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A total of 626 bats representing 10 species were examined for T. gondii infection, 38 (6.1%) were tested positive with by PCR, 8 positive DNA samples were completely genotyped, of which 3 samples (2 from Cynopterus sphinx, and 1 from Murina leucogaster) represented ToxoDB#10, and 5 samples (2 from Murina leucogaster, 2 from Myotis chinensis, and 1 from Rhinolophus ferrumequinum) belonged to ToxoDB#9 (http://toxodb.org/toxo/). CONCLUSIONS: The present study revealed an overall T. gondii prevalence of 6.1% in bats from Jilin, Liaoning, Jiangxi and Guangdong provinces in China, and reported two T. gondii genotypes (ToxoDB#9 and #10) having a wide geographical distribution in China. These results provide new genetic information about T. gondii infection in bats, and have implications for better understanding of the genetic diversity of T. gondii in China and elsewhere.


Assessing the psychological response to the COVID-19: A response to Bitan et al. “Fear of COVID-19 scale: Psychometric characteristics, reliability and validity in the Israeli population”


title: Mechanical Ventilator Using Motorized Bellow

text: The present work describes the state of art in India with respect to the development of low-cost mechanical ventilators. It highlights the bare minimum specifications that are required in a ventilator to fight the COVID-19 menace. With respect to this, CSIR-CMERI is developing a motorized bellow-based ventilator, which has inbuilt intelligence to assist a patient who is trying to breathe or supply a prescribed volume at a defined pressure to a passive patient.


title: Host Src controls gallid alpha herpesvirus 1 intercellular spread in a cellular fatty acid metabolism-dependent manner

text: Abstract Viral spread is considered a promising target for antiviral therapeutics, but the associated mechanisms remain unclear for gallid alpha herpesvirus 1 (ILTV). We previously identified proto-oncogene tyrosine-protein kinase Src (Src) as a crucial host determinant of ILTV infection. The present study revealed accelerated spread of ILTV upon Src inhibition. This phenomenon was independent of either viral replication or the proliferation of infected cells and could not be compromised by neutralizing antibody. Neither extracellular vesicles nor the direct cytosol-to-cytosol connections between adjacent cells contributed to the enhanced spread of ILTV upon Src inhibition. Further genome-wide transcriptional profile analyses in combination with functional validation identified fatty acid metabolism as an essential molecular event during modulation of the intercellular spread and subsequent cytopathic effect of ILTV by Src. Overall, these data suggest that Src controls the cell-to-cell spread of ILTV in a cellular fatty acid metabolism-dependent manner, which determines the virus's cytopathic effect.


title: SmartPDT®: smartphone enabled real-time dosimetry via satellite observation for daylight photodynamic therapy

text: BACKGROUND: Actinic keratosis (AK) affects one quarter of over 60 s in Europe with the risk of transforming into invasive squamous cell carcinoma. Daylight photodynamic therapy (dPDT) is an effective and patient preferred treatment that uses sunlight to clear AK. Currently, there is no standardised method for measuring the light received during treatment. METHODS: SmartPDT® is a smartphone-based application and web-portal, developed by siHealth Ltd, enabling remote delivery of dPDT. It uses satellite imagery and computational algorithms to provide real-time determination of exposure to PpIX-effective solar radiation (“light dose”). The application also provides forecast of expected radiant exposures for 24- and 48 -hs prior to the treatment period. Validation of the real-time and forecasted radiant exposure algorithms was performed against direct ground-based measurement under all weather conditions in Chilton, UK. RESULTS: Agreement between direct ground measurements and satellite-determined radiant exposure for 2 -h treatment was excellent at -0.1% ± 5.1% (mean ± standard deviation). There was also excellent agreement between weather forecasted radiant exposure and ground measurement, 1.8% ± 17.7% at 24 -hs and 1.6% ± 25.2% at 48 -hs. Relative Root Mean Square of the Error (RMSE(r)) demonstrated that agreement improved as time to treatment reduced (RMSE(r) = 22.5% (48 -hs), 11.2% (24 -hs), 5.2% (real-time)). CONCLUSION: Agreement between satellite-determined, weather-forecasted and ground-measured radiant exposure was better than any existing published literature for dPDT. The SmartPDT® application and web-portal has excellent potential to assist with remote delivery of dPDT, an important factor in reducing risk in an elderly patient population during the Covid-19 pandemic.


title: SARS virus infection of cats and ferrets

text: The reservoir of the coronavirus isolated from patients with severe acute respiratory syndrome (SARS)(1,2) is still unknown, but is suspected to have been a wild animal species. Here we show that ferrets (Mustela furo) and domestic cats (Felis domesticus) are susceptible to infection by SARS coronavirus (SCV) and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. The observation that these two distantly related carnivores can so easily be infected with the virus indicates that the reservoir for this pathogen may involve a range of animal species. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/425915a) contains supplementary material, which is available to authorized users.


title: Chest CT findings of COVID-19 pneumonia by duration of symptoms

text: Abstract Purpose To evaluate lung abnormalities on thin-section computed tomographic (CT) scans in patients with COVID-19 and correlate findings to duration of symptoms. Methods In total, 348 CT scans in 112 patients were classified according to the time after the onset of the initial symptoms, namely stage-1 (0–4 days); stage-2 (5–9 days); stage-3 (10–14 days); stage-4 (15–21 days); stage-5 (22–28 days); and stage-6 (＞28 days). Each lung lobe was evaluated for extent affected by ground-glass opacities (GGO), crazy-paving pattern and consolidation, in five categories of percentual severity. Summation of scores from all five lung lobes provided the total CT score (maximal CT score, 25). Results The predominant patterns of lung abnormalities were GGOs, crazy-paving pattern, consolidation and linear opacities. The frequency of crazy-paving pattern, consolidation and linear opacities peaked at stage-3 (62.7 %), stage-4 (75.0 %) and stage-5 (83.1 %), respectively, and decreased thereafter. Total CT scores increased from stage-1 to stage-2 (2.8 ± 3.1, vs. 6.5 ± 4.6, respectively, P < 0.01), and thereafter remained high. The lower lobes were more inclined to be involved with higher CT scores except for stage-1. At stage-6 98.1 % of CT scans still showed abnormalities (CT score 7.5 ± 4.1). Conclusion Thin-section CT could provide semi-quantitative analysis of pulmonary damage severity. This disease changed rapidly at the early stage, then tended to be stable and lasted for a long time.


The traps of calling the public health response to COVID-19 “an unexpected war against an invisible enemy”


Étiologie virale des infections respiratoires aiguës de l’enfant à Bangui


Aus- und Weiterbildung – auch in Zeiten der Coronaviruspandemie


title: Toona sinensis: a comprehensive review on its traditional usages, phytochemisty, pharmacology and toxicology

text: Toona sinensis (Juss.) M.Roem, Meliaceae, a deciduous plant native to eastern and southeastern Asia, is widely used in Traditional Chinese Medicine. This paper was aimed to summarize the current advances in traditional usage, phytochemistry, pharmacology and toxicology of T. sinensis. In this review, various types of data of T. sinensis are discussed in the corresponding parts of this paper, and perspectives for possible future studies of this plant are discussed. The main constituents of T. sinensis are terpenoids, phenylpropanoids and flavonoids, etc., and its pharmacological activities include anti-tumor effects, antioxidant activities, anti-diabetic effects and anti-inflammatory effects. Although a series of phytochemical and pharmacological researches of this plant have been conducted, the active constituents and action mechanism of these activities should be also further explored. Furthermore, the present review also indicates that T. sinensis has potentials to develop into drugs for treating various diseases with high efficacy and low toxicity, particularly in cancer, diabetes and inflammatory disorders. In conclusion, the paper provides a full-scale profile of the traditional usage, phytochemistry, pharmacology and toxicology of T. sinensis, and also provides potential therapeutic uses and drug development prospects of this plant.


title: Navigating crisis from the backseat? How top managers can support radical change initiatives by middle managers

text: Abstract We advance the premise that to navigate crisis, rather than reactively cutting costs by culling middle management, top managers can benefit from enabling radical change initiatives by middle managers. Contextualizing this idea to the marketing function and the COVID-19 crisis, we ask: How can Chief Marketing Officers (CMOs) support marketing middle managers (MMMs) in initiating radical change in crisis situations? We take the position that marketing managers' distinctive functional influence on radical change is in driving product and service innovations that are new-to-the-firm. We then argue that crisis situations present an opportunity for top and middle managers to rethink assumptions about ‘who does what’ in radical change initiatives from the marketing function, focusing on the underemphasized possibility of MMMs initiating change and CMOs implementing. Building on recent findings on ‘change role reversal’, we unpack the notion that change initiatives may be most effective when middle managers initiate, while top managers implement. This unconventional change route would see CMOs taking a deliberate and supportive back seat in navigating crisis, while MMMs take the wheel in driving radical change initiatives. We identify duties and hurdles to a change role reversal— approach faced by MMMs throughout three stages of innovation-enabled radical change proposed by Burgelman (1991; variation-selection-retention) and chart corresponding roles that CMOs can play to support MMMs: advisor, judge, and guardian. Three tangible final questions addressed to CMOs guide managerial applications, while considerations outside scope are also discussed.


title: Pathogenesis of oral type I feline infectious peritonitis virus (FIPV) infection: Antibody-dependent enhancement infection of cats with type I FIPV via the oral route

text: Feline infectious peritonitis virus (FIPV) causes a severe, immune-mediated disease called FIP in domestic and wild cats. It is unclear whether FIP transmits from cat to cat through the oral route of FIPV infection, and the reason for this includes that FIP is caused by oral inoculation with some FIPV strains (e.g., type II FIPV WSU 79-1146), but is not caused by other FIPV (e.g., type I FIPV KU-2 strain: FIPV-I KU-2). In this study, when cats passively immunized with anti-FIPV-I KU-2 antibodies were orally inoculated with FIPV-I KU-2, FIP was caused at a 50% probability, i.e., FIPV not causing FIP through oral infection caused FIP by inducing antibody-dependent enhancement. Many strains of type I FIPV do not cause FIP by inoculation through the oral route in cats. Based on the findings of this study, type I FIPV which orally infected cats may cause FIP depending on the condition.


title: Current strategies against COVID-19

text: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently was declared a pandemic by world health organization (WHO) Due to sudden outbreaks, currently, no completely effective vaccine or drug is clinically approved. Several therapeutic strategies can be envisaged to prevent further mortality and morbidity. Based on the past contribution of traditional Chinese medicines (TCM) and immune-based therapies as a treatment option in crucial pathogen outbreaks, we aimed to summarize potential therapeutic strategies that could be helpful to stop further spread of SARS-CoV-2 by effecting its structural components or modulation of immune responses. Several TCM with or without modification could be effective against the structural protein, enzymes, and nucleic acid should be tested from available libraries or to identify their immune-stimulatory activities to enhance several antiviral biological agents for effective elimination of SARS-CoV-2 from the host. TCM is not only effective in the direct inhibition of virus attachment and internalization in a cell but can also prevent their replication and can also help to boost up host immune response. Immune-modulatory effects of TCMs may lead to new medications and can guide us for the scientific validity of drug development. Besides, we also summarized the effective therapies in clinical for controlling inflammation. This review will be not only helpful for the current situation of COVID-19, but can also play a major role in such epidemics in the future.


title: Isolation of rhinoviruses and coronaviruses from 38 colds in adults

text: Nasal washings were collected from 27 normal adults during 38 naturally acquired colds. The washings were exhaustively tested using tissue cultures, organ cultures and electron microscopy. Washings yielding no identifiable agent were inoculated into human volunteers, and further specimens obtained from the latter were examined by the same techniques in vitro. Viruses were identified in association with 25 of the original 38 colds (65.7%). Fifteen were rhinoviruses (39.5%), seven coronaviruses (18.4%), two were parainfluenza viruses, and one was influenza virus. Use of organ cultures and of volunteers significantly increased the isolation rate. No agent was cultivated from the remaining 13 specimens, although tests in volunteers showed that cold‐producing agents were present in five of them (13%). Three specimens gave doubtful results in volunteers, and five others, all collected within a period of six weeks in December and January, apparently contained no infectious agent.


title: How to approach and treat viral infections in ICU patients

text: Patients with severe viral infections are often hospitalized in intensive care units (ICUs) and recent studies underline the frequency of viral detection in ICU patients. Viral infections in the ICU often involve the respiratory or the central nervous system and can cause significant morbidity and mortality especially in immunocompromised patients. The mainstay of therapy of viral infections is supportive care and antiviral therapy when available. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host proteins that regulate immunity and are involved in the viral life cycle. These novel treatments need to be further validated in animal and human randomized controlled studies.


title: Virus-Induced Aggregates in Infected Cells

text: During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review.


title: Inflammation et virus: déclenchement,contournements et détournements de la réponse inflammatoire au cours des infections virales

text: Summary The inflammatory process aims at opposing an early responseto the viral infections. Inflammation is supposed to delay or limit viral multiplication and dissemination until a specific immune response can be raised. This review introduces the basis of virus-induced inflammation and presents various strategies that are used by viruses to circumvent or exploit inflammation for their own benefit.


title: Endoprotector: Protective box for safe endoscopy use during COVID-19 outbreak

text: Background and study aim Outbreak of COVID-19 began in Wuhan in December 2019 and has rapidly spread from China to the rest of the world. Although it is primarily transmitted by contact and droplets, aerosol-generating procedures also seem to carry the possibility of airborne viral transmission. As such, upper gastrointestinal endoscopy can be considered a risky procedure, with several position statements recommending the adoption of safe practices in endoscopic procedures. This article aims to describe an additional tool to protect healthcare personnel during endoscopy. Methods A covering box made of acrylic plastic, named Endoprotector, was designed to cover the patient’s head, while taking into consideration movements performed by patients and healthcare staff during an endoscopic procedure. Results A cough simulation using fluorescent dye confirmed the potential benefit of the box during endoscopy, thus protecting healthcare staff from air droplets. The feasibility and practicality of the box was also tested with patients during endoscopy. Conclusion The reusable Endoprotector is easily and affordably manufactured and may reduce air droplets and airborne transmission of SARS-CoV-2 and other microorganisms during endoscopy.


title: Multiple functions of USP18

text: Since the discovery of the ubiquitin system and the description of its important role in the degradation of proteins, many studies have shown the importance of ubiquitin-specific peptidases (USPs). One special member of this family is the USP18 protein (formerly UBP43). In the past two decades, several functions of USP18 have been discovered: this protein is not only an isopeptidase but also a potent inhibitor of interferon signaling. Therefore, USP18 functions as 'a' maestro of many biological pathways in various cell types. This review outlines multiple functions of USP18 in the regulation of various immunological processes, including pathogen control, cancer development, and autoimmune diseases.


title: Aciertos y errores en la gestión de las crisis de salud pública en España

text: Health crises shock the population and overwhelm the health services. This article analyzes 30 years of health crises in Spain from a multifaceted perspective: population, patients, clinicians, public health practitioners, politicians, the media and other groups involved. The interaction among all stakeholders shapes the response and management of any health crisis. Heterogeneity of management and of health effects–contributing to inequalities in health-is common. The participation and coordination of the health services is crucial in detection of the crisis and in modulating the population reactions. Public health services characterized by their low public profile could gain public influence by their role in coordinating politicians and the media when solving important health problems. Analyzing the mistakes and successes in previous crises together with risk and vulnerability assessments, research and drills are essential to give a quick and adequate response to future crises.


title: How host genetics dictates successful viral zoonosis

text: Viruses of wild and domestic animals can infect humans in a process called zoonosis, and these events can give rise to explosive epidemics such as those caused by the HIV and Ebola viruses. While humans are constantly exposed to animal viruses, those that can successfully infect and transmit between humans are exceedingly rare. The key event in zoonosis is when an animal virus begins to replicate (one virion making many) in the first human subject. Only at this point will the animal virus first experience the selective environment of the human body, rendering possible viral adaptation and refinement for humans. In addition, appreciable viral titers in this first human may enable infection of a second, thus initiating selection for viral variants with increased capacity for spread. We assert that host genetics plays a critical role in defining which animal viruses in nature will achieve this key event of replication in a first human host. This is because animal viruses that pose the greatest risk to humans will have few (or no) genetic barriers to replicating themselves in human cells, thus requiring minimal mutations to make this jump. Only experimental virology provides a path to identifying animal viruses with the potential to replicate themselves in humans because this information will not be evident from viral sequencing data alone.


title: Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B

text: Feline coronavirus (FCoV) causes the fatal disease feline infectious peritonitis, which is currently incurable by drug treatment, and no effective vaccines are available. Cyclosporin A (CsA), a cyclophilin (Cyp) inhibitor, inhibits the replication of FCoV in vitro and in vivo as well as the replication of human and animal coronaviruses. However, the mechanism underlying the regulation of coronavirus replication by CsA is unknown. In this study, we analysed the role of Cyps in FCoV replication using knockdown and knockout cells specific to Cyps. Inhibition of CypA and CypB reduced FCoV replication, with replication in knockout cells being much less than that in knockdown cells. Furthermore, the proteins expressed by CypA and CypB harbouring mutations in their respective predicted peptidyl-prolyl cis–transisomerase active sites, which also alter the affinities between Cyps and CsA, inhibited FCoV replication. These findings indicate that the peptidyl-prolyl cis–transisomerase active sites of Cyps might be required for FCoV replication.


title: Nursing shortage in China: State, causes, and strategy

text: This article describes the nursing shortage situation in China and the causes for it. China is a major donor of nurses to other parts of the world and this article discusses the solutions China has implemented to address its nursing shortage, and the challenges that it is currently facing. The strategies that have been employed include: improving the health care system, improving work cultures for increased retention through policy and regulation, making greater investments in nursing education to build sustainable nursing education infrastructures, and enhancing the image of the nursing profession. These solutions may serve as a reference to other countries to deal with the crisis of a nursing shortage.


title: GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic

text: BACKGROUND: Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. METHODOLOGY/PRINCIPAL FINDINGS: This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. CONCLUSIONS/SIGNIFICANCE: It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood.


COVID19 meets the Antivaccine Movement


title: Clinical trial on the effects of a free-access acidified milk replacer feeding program on the health and growth of dairy replacement heifers and veal calves

text: Abstract The objectives of this study were to evaluate the effects of free-access acidified milk replacer feeding on the pre- and postweaning health of dairy and veal calves. Individually housed calves were systematically assigned at birth to 1 of 2 feeding programs: free-access feeding (ad libitum) of acidified milk replacer (ACD, n=249) or traditional restricted feeding (3L fed twice daily) of milk replacer (RES, n=249). Calves were fed milk replacer containing 24% crude protein and 18% fat. Acidified milk replacer was prepared to a target pH between 4.0 and 4.5 using formic acid. Calves were weaned off milk replacer at approximately 6wk of age. Weaning occurred over 5d, and during this weaning period, ACD calves had access to milk replacer for 12h/d and RES calves were offered only one feeding of milk replacer (3 L) daily. Calves were monitored daily for signs of disease. Fecal consistency scores were assigned each week from birth until weaning. A subset of calves was systematically selected for fecal sampling at 3 time points between 7 and 27d of age. Fecal samples were analyzed for enterotoxigenic Escherichia coli F5, Cryptosporidium parvum, rotavirus, and coronavirus. Hip width, hip height, body length, heart girth, and body weight were measured at birth and weaning. Postweaning body weight measurements were collected from the heifers at approximately 8mo of age. Postweaning body weight and carcass grading information was collected from the veal calves at slaughter once a live weight between 300 and 350kg had been achieved. The odds of ACD calves being treated for a preweaning disease event tended to be lower than that of the RES calves (1.2 vs. 5.2%, respectively). Preweaning mortality, postweaning disease treatment, and postweaning mortality did not differ between feeding treatments. The ACD feeding treatment supported greater preweaning average daily gain (0.59 vs. 0.43kg/d) and structural growth than RES feeding. Postweaning average daily gain and carcass characteristics were similar for ACD and RES calves. These results indicate that free-access acidified milk replacer feeding tended to support improved health, and greater body weight gain and structural growth during the preweaning period; these effects did not persist in the postweaning period. The growth advantage observed before weaning in the ACD calves likely disappeared due to the weaning methods used.


title: Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial

text: BACKGROUND: COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. STUDY DESIGN AND METHODS: This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function. This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48–72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators. Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.


High-throughput bead based suspension array for the detection of acute respiratory viral pathogens among children aged <5 years in Pakistan


China coronavirus: mild but infectious cases may make it hard to control outbreak, report warns.


title: Room ventilation and the risk of airborne infection transmission in 3 health care settings within a large teaching hospital

text: BACKGROUND: Room ventilation is a key determinant of airborne disease transmission. Despite this, ventilation guidelines in hospitals are not founded on robust scientific evidence related to the prevention of airborne transmission. METHODS: We sought to assess the effect of ventilation rates on influenza, tuberculosis, and rhinovirus infection risk within 3 distinct rooms in a major urban hospital: a lung function laboratory, an emergency department negative-pressure isolation room, and an outpatient consultation room. Air-exchange rate measurements were performed in each room using CO(2) as a tracer. The model developed by Gammaitoni and Nucci was used to estimate infection risk. RESULTS: Current outdoor air-exchange rates in the lung function laboratory and emergency department isolation room limited infection risks to 0.1%-3.6%. Influenza risk for individuals entering an outpatient consultation room after an infectious individual departed ranged from 3.6% to 20.7%, depending on the duration for which each person occupied the room. CONCLUSION: Given the absence of definitive ventilation guidelines for hospitals, air-exchange measurements combined with modeling afford a useful means of assessing, on a case-by-case basis, the suitability of room ventilation for preventing airborne disease transmission.


title: The pandemic paradox: The consequences of COVID‐19 on domestic violence

text: COVID-19 (the new strain of coronavirus) has been declared a global pandemic. Measures announced over recent weeks to tackle it have seen people's day-to-day life drastically altered. These changes are essential to beat coronavirus and protect health systems (UK Home Office 2020). However, there are unintended, negative consequences. As the virus continues to spread across the world, it brings with it multiple new stresses, including physical and psychological health risks, isolation and loneliness, the closure of many schools and businesses, economic vulnerability and job losses. Through all of that, children (and their mothers) are particularly vulnerable (End Violence against Children, 2020) to the risk of domestic violence. Domestic violence refers to a range of violations that happen within a domestic space. It is a broad term that encompasses intimate partner violence (IPV), a form of abuse that is perpetrated by a current or ex-partner.


title: Impact of viral upper respiratory tract infection on the concentration of nasopharyngeal pneumococcal carriage among Kenyan children

text: Viral upper respiratory tract infection (URTI) predisposes to bacterial pneumonia possibly by facilitating growth of bacteria such as Streptococcus pneumoniae colonising the nasopharynx. We investigated whether viral URTI is temporally associated with an increase in nasopharyngeal pneumococcal concentration. Episodes of symptomatic RSV or rhinovirus URTI among children <5 years were identified from a longitudinal household study in rural Kenya. lytA and alu PCR were performed on nasopharyngeal samples collected twice-weekly, to measure the pneumococcal concentration adjusted for the concentration of human DNA present. Pneumococcal concentration increased with a fold-change of 3.80 (95%CI 1.95–7.40), with acquisition of RSV or rhinovirus, during 51 URTI episodes among 42 children. In repeated swabs from the baseline period, in the two weeks before URTI developed, within-episode variation was broad; within +/−112-fold range of the geometric mean. We observed only a small increase in nasopharyngeal pneumococcal concentration during RSV or rhinovirus URTI, relative to natural variation. Other factors, such as host response to viral infection, may be more important than nasopharyngeal pneumococcal concentration in determining risk of invasive disease.


title: Pathogenic characteristics of persistent feline enteric coronavirus infection in cats

text: Feline coronaviruses (FCoV) comprise two biotypes: feline enteric coronaviruses (FECV) and feline infectious peritonitis viruses (FIPV). FECV is associated with asymptomatic persistent enteric infections, while FIPV causes feline infectious peritonitis (FIP), a usually fatal systemic disease in domestic cats and some wild Felidae. FIPV arises from FECV by mutation. FCoV also occur in two serotypes, I and II, of which the serotype I viruses are by far the most prevalent in the field. Yet, most of our knowledge about FCoV infections relates to serotype II viruses, particularly about the FIPV, mainly because type I viruses grow poorly in cell culture. Hence, the aim of the present work was the detailed study of the epidemiologically most relevant viruses, the avirulent serotype I viruses. Kittens were inoculated oronasally with different doses of two independent FECV field strains, UCD and RM. Persistent infection could be reproducibly established. The patterns of clinical symptoms, faecal virus shedding and seroconversion were monitored for up to 10 weeks revealing subtle but reproducible differences between the two viruses. Faecal virus, i.e. genomic RNA, was detected during persistent FECV infection only in the large intestine, downstream of the appendix, and could occasionally be observed also in the blood. The implications of our results, particularly our insights into the persistently infected state, are discussed.


COVID-19 and systemic lupus erythematosus: a case series


title: Bronconeumopatías agudas del niño

text: Las infecciones infantiles afectan con frecuencia al aparato respiratorio inferior. Las clasificaciones convencionales, basadas en el tipo de afección anatómica, radiológica y etiopatogénica, permiten definir entidades clínicas (bronquitis, bronquiolitis, neumopatía); sin embargo, la evaluación de la gravedad del proceso es lo más útil para decidir el tipo y la rapidez del tratamiento. Aunque la etiología viral es la más frecuente, la estrategia fundamental para reducir la morbilidad e incluso la mortalidad de las infecciones respiratorias bajas se basa en el tratamiento adecuado de las neumonías bacterianas. Ante la ausencia de especificidad, es indispensable, cuando esté indicado, recurrir a una antibioticoterapia inicial probabilística que incluya el neumococo. En el niño, las muestras no suelen proceder del parénquima pulmonar y, además, la recogida de las secreciones bronquiales durante los primeros años de vida no es de buena calidad. Al contrario de lo que ocurre con los virus, el examen bacteriológico de las secreciones de las vías respiratorias altas es poco útil, porque los niños suelen ser portadores de gérmenes que pueden causar neumopatías. Los datos clínicos y radiológicos sólo pueden sugerir el diagnóstico. El desarrollo de técnicas que detectan antígenos microbianos o la búsqueda de material genético por biología molecular han permitido mejorar de manera significativa la identificación del patógeno responsable y la elección del tratamiento adecuado. Algunos grupos particulares de pacientes pueden padecer una afección respiratoria por agentes infecciosos inusuales o, incluso, oportunistas. Una proporción importante de la afectación respiratoria del adulto puede atribuirse a las agresiones pulmonares sufridas durante su infancia. La aplicación de vacunas, en especial, la antigripal y la antineumocócica, es fundamental para la prevención de estas afecciones respiratorias.


title: Negative regulation of TBK1-mediated antiviral immunity

text: TANK-binding kinase 1 (TBK1) plays pivotal roles in antiviral innate immunity. TBK1 mediates the activation of interferon regulatory factor (IRF) 3, leading to the induction of type I IFNs (IFN-α/β) following viral infections. TBK1 must be tightly regulated to effectively control viral infections and maintain immune homeostasis. TBK1 activity can be regulated in a variety of ways, such as phosphorylation, ubiquitination, kinase activity modulation and prevention of functional TBK1-containing complexes formation. Furthermore, multiple viruses have evolved elaborate strategies to circumvent IFN responses by targeting TBK1. Here we provide an overview of TBK1 in antiviral immunity and recent developments on the regulation of TBK1 activity.


title: Genetic diversity and recombination of murine noroviruses in immunocompromised mice

text: Murine noroviruses (MNV) are newly identified pathogens which infect laboratory mice. In this study, we found a high prevalence (64.3%) of MNV in various breeding colonies of immunocompromised, transgenic and wild-type mouse lines. All mice survived infection with no signs of clinical disease. Faeces samples were collected from animals housed in two separate laboratory mouse colonies in Berlin, Germany, and screened using quantitative reverse transcription (RT)-PCR. We have determined the complete nucleotide sequences of 3 novel MNV strains. Furthermore, we sequenced two subgenomic regions within open reading frames (ORFs) 1 and 2 that are suitable for genotyping. Sequence analysis of the full-length and partial genomes obtained from naturally infected mice yielded valuable data on genetic diversity of murine noroviruses. The discordance of genotype affiliation of some MNVs shown in ORF1 and ORF2 suggests intertypic recombination events in vivo.


Drought and Covid-19 in the Eastern Mediterranean Region of the WHO


title: Development of a Mouse-Adapted MERS Coronavirus

text: First identified in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that can cause acute respiratory distress syndrome (ARDS), multiorgan failure, and death, with a case fatality rate of ~35%. An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. The murine dipeptidyl peptidase 4 (Dpp4) protein is not a functional receptor for MERS-CoV; thus, mice are resistant to MERS-CoV infection. We generated human DPP4 knock-in (hDPP4 KI) mice by replacing exons 10–12 at the mouse Dpp4 locus with exons 10–12 from the human DPP4 gene. The resultant human DPP4 KI mice are permissive to MERS-CoV (HCoV-EMC/2012 strain) infection but develop no disease. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. After 30 in vivo passages, an adapted virus clone was isolated and designated MERS(MA)6.1.2. This virus clone produced significantly higher titers than the parental clone in the lungs of hDPP4 KI mice and caused diffuse lung injury and a fatal respiratory infection. In this chapter, we will describe in detail the procedures used to mouse adapt MERS-CoV by serial passage of the virus in lungs. We also describe the methods used to isolate virus clones and characterize virus infection.


title: Chapter 57 Infections Associated with Retinal Autoimmunity

text: Abstract Autoimmune reactivity and autoimmune disease in the eye is a rapidly expanding area of research and therapy. We present evidence implicating three distinct classes of infectious agents in the development of an autoimmune process within the retina. We highlight two human diseases triggered by Onchocerca volvulus or Toxoplasma gondii and an experimental model of retinal degenerative disease, referred to as experimental coronavirus retinopathy (ECOR). Analysis of these systems revealed distinct pathogenic mechanisms involved in the induction of autoimmunity triggered by each organism. In T. gondii infections, the chronic reactivation is probably responsible for the presentation of sequestered retinal epitopes of the immune system. In O. volvulus infections, molecular mimicry between the organism and the human RPE protein may contribute to retinal pathology. In ECOR, differences in time of induction, duration, and intensity of innate immune reactivity may contribute to autoimmune reactivity in BALB/c mice.


title: Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

text: Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.


title: Broad-spectrum antivirals against viral fusion

text: Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This ‘one bug–one drug’ approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry.


title: Novel Coronavirus Disease 2019 Infection in Children: The Dark Side of a Worldwide Outbreak

text: In this pediatric perspectives article, we discuss current limits in the understanding of novel coronavirus infection. In our opinion, the burden of novel coronavirus infections is underestimated because not actively looked for. We discuss the basis of our observations and what this can generate, suggesting a different approach for the search of the virus in children.


title: Chapter 15 A Global Approach to Energy and the Environment The G-Cubed Model

text: Abstract G-Cubed is a multi-country, multi-sector, intertemporal general equilibrium model that has been used to study a variety of policies in the areas of environmental regulation, tax reform, monetary and fiscal policy, and international trade. It is designed to bridge the gaps between three areas of research – econometric general equilibrium modeling, international trade theory, and modern macroeconomics – by incorporating the best features of each. This chapter describes the theoretical and empirical structure of the model, summarizes its applications and contributions to the literature, and discusses two example applications in detail.


title: The novel coronavirus 2019-nCoV: Its evolution and transmission into humans causing global COVID-19 pandemic

text: A novel coronavirus strain 2019-nCoV has caused a rapid global pandemic-COVID-19. Scientists have taken onto the task of characterizing this new virus and understanding how this virus has transmitted to humans. All preliminary studies have found some striking similarities between this new virus and the SARS-CoV that caused a similar kind of epidemic in 2002–2003. Through bioinformatics tools, a great deal of information has been gathered about the origin, evolution and zoonosis of this virus. We, in this review, report the symptoms, mode of transmission and available and putative treatments to tackle 2019-nCoV infections. We also comprehensively summarize all the information so far made available regarding the genome, evolution and zoonosis of this virus.


GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY AND COVID-19 INFECTION


title: Dynamic relationships between industry returns and stock market returns

text: Abstract Different from prior studies which concentrate on the unidirectional impact of industry leading, this study examines the bi-directional dynamical causal relation between industry returns and stock market returns by considering multiple structural breaks for ten major eastern and southern Asia countries. Our results show that finance and consumer service industry returns have significant power in explaining the movements of market returns. Further, we apply logit regressions to explore the determinants of the leading hypotheses and find exchange rate and interest rate are important in explaining the industry–market nexus. In a developed market the industry and the market have feedback relations, but in a highly controlled economy the influence from the stock market dominates.


title: Evolution of research in health geographics through the International Journal of Health Geographics (2002–2015)

text: Health geographics is a fast-developing research area. Subjects broached in scientific literature are most varied, ranging from vectorial diseases to access to healthcare, with a recent revival of themes such as the implication of health in the Smart City, or a predominantly individual-centered approach. Far beyond standard meta-analyses, the present study deliberately adopts the standpoint of questioning space in its foundations, through various authors of the International Journal of Health Geographics, a highly influential journal in that field. The idea is to find space as the common denominator in this specialized literature, as well as its relation to spatial analysis, without for all that trying to tend towards exhaustive approaches. 660 articles have being published in the journal since launch, but 359 articles were selected based on the presence of the word “Space” in either the title, or the abstract or the text over 13 years of the journal’s existence. From that database, a lexical analysis (tag cloud) reveals the perception of space in literature, and shows how approaches are evolving, thus underlining that the scope of health geographics is far from narrowing.


title: Recombinant fowlpox virus vaccines for poultry

text: The intensive poultry industries rely heavily upon the use of vaccines for disease control. Viral vector based vaccines offer new avenues for the development of vaccines for effective disease control in poultry. Techniques developed for the construction of recombinant vaccinia viruses have been readily adapted to the construction of recombinant viruses based on fowlpox virus (rFPV). The ability to insert several genes into the large genome of fowlpox may enable the development of multivalent vaccines and vaccines incorporating immune response modifiers such as lymphokines. Newcastle disease, avian influenza, infectious bursal disease and Marek's disease antigens expressed by rFPV have been shown to be effective vaccines in poultry. None appear, however, to provide a substantial improvement in vaccine efficacy. Recombinant FPV will be a valuable adjunct to conventional vaccines currently in widespread use. Whether rFPV or other vector based vaccines can circumvent the problems of vaccination in the presence of high maternally derived antibodies is yet to be resolved. The observation that avipoxvirus recombinants may be suitable for the vaccination of non‐avian species provides an added dimension to vaccines based on FPV or other avipoxviruses. Recombinant FPV will find a useful role in poultry disease control when used in conjunction with conventional vaccines.


title: Gene silencing of β-galactosamide α-2,6-sialyltransferase 1 inhibits human influenza virus infection of airway epithelial cells

text: BACKGROUND: Human influenza virus hemagglutinin prefers to use sialic acid (SA) receptors via α-2,6 linkages. The β-galactoside α-2,6-sialyltransferase I (ST6Gal I) protein is encoded by the ST6GAL1 gene and is responsible for the addition of α-2,6 linked SA to the Galβ1-4GlcNAc disaccharide of glycans and glycoproteins found on the cellular surface. Therefore, ST6GAL1 could be a potential target for anti-influenza therapeutics. We used specific small interfering RNAs (siRNAs) to block expression of ST6GAL1 and limit distribution of SA receptors on the surface of airway epithelial cells. RESULTS: The siRNA duplexes we used inhibited ST6GAL1 mRNA expression and subsequent expression of the encoding protein. As a result, synthesis of α-2,6 SA galactose was inhibited. Adsorption of influenza virus particles to the surface of cells transfected with appropriate specific siRNAs was significantly reduced. Intracellular viral genome copy number and virus titer within the supernatant of cells transfected with siRNAs was significantly reduced in a dose-dependent manner compared with those for untransfected cells and cells transfected with non-specific siRNAs. CONCLUSIONS: We used siRNAs targeting ST6GAL1 to inhibit the expression of certain cell surface receptors, thereby preventing virus adsorption. This resulted in the inhibition of human influenza virus infection. Our findings are a significant development in the identification of potential new anti-influenza drug targets.


title: The impact of host genetic background in the Pseudomonas aeruginosa respiratory infections

text: Understanding the significance of human genetic diversity in modulating host susceptibility to opportunistic infections is an emerging challenge in the field of respiratory illnesses. While it is recognized that diverse bacterial strains account for differential disease manifestations, emerging data indicate that host genetic diversity is an important determinant factor that influences the severity of opportunistic infections. With particular regard to respiratory illnesses mediated by the gram-negative bacterium Pseudomonas aeruginosa, diverse genetic background is also emerging as a key contributor. Human-genome-wide association studies are a common approach for determining the inter-individual genetic variation associated with variability of the pulmonary infections. Historically, diverse murine inbred mouse strains and ex-vivo cellular models were considered complementary to human studies for establishing the contribution of genetic background to P. aeruginosa respiratory infections. More recently, the development of a new mouse model of infection, mirroring human airway diseases, combined with innovative murine resource populations, modelling human genetic variation, provides additional insights into the mechanisms of genetic susceptibility. In this review, we cover the recent state of the art of human and animal studies and we discuss future potential challenges in the field of P. aeruginosa respiratory infections.


title: COVID-19 and vaping: risk for increased susceptibility to SARS-CoV-2 infection?

text: With great interest we read and commend the study done by Russo and colleagues, highlighting their findings that nicotine induces an increase in angiotensin-converting enzyme-2 (ACE2) expression in human bronchial epithelial cells (HBEpC) and is mediated by α7-subtype nicotinic receptors (α7-nAChR) [1]. It raises the concern that all electronic nicotine-delivery systems may put users at greater risk of succumbing to COVID-19.


title: Construction and next-generation sequencing analysis of a large phage-displayed V(NAR) single-domain antibody library from six naïve nurse sharks

text: BACKGROUND: Shark new antigen receptor variable domain (V(NAR)) antibodies can bind restricted epitopes that may be inaccessible to conventional antibodies. METHODS: Here, we developed a library construction method based on polymerase chain reaction (PCR)-Extension Assembly and Self-Ligation (named “EASeL”) to construct a large V(NAR) antibody library with a size of 1.2 × 10(10) from six naïve adult nurse sharks (Ginglymostoma cirratum). RESULTS: The next-generation sequencing analysis of 1.19 million full-length V(NAR)s revealed that this library is highly diversified because it covers all four classical V(NAR) types (Types I–IV) including 11% of classical Type I and 57% of classical Type II. About 30% of the total V(NAR)s could not be categorized as any of the classical types. The high variability of complementarity determining region (CDR) 3 length and cysteine numbers are important for the diversity of V(NAR)s. To validate the use of the shark V(NAR) library for antibody discovery, we isolated a panel of V(NAR) phage binders to cancer therapy-related antigens, including glypican-3, human epidermal growth factor receptor 2 (HER2), and programmed cell death-1 (PD1). Additionally, we identified binders to viral antigens that included the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) spike proteins. The isolated shark single-domain antibodies including Type I and Type II V(NAR)s were produced in Escherichia coli and validated for their antigen binding. A Type II V(NAR) (PE38-B6) has a high affinity (K(d) = 10.1 nM) for its antigen. CONCLUSIONS: The naïve nurse shark V(NAR) library is a useful source for isolating single-domain antibodies to a wide range of antigens. The EASeL method may be applicable to the construction of other large diversity gene expression libraries.


title: The management of coronavirus infections with particular reference to SARS

text: The human coronaviruses (HCoV) OC43 and 229E are common causes of upper respiratory tract infections. Severe diseases were rare, however, until the emergence of the severe acute respiratory syndrome (SARS)-CoV in 2003. Since then, other novel CoV (NL63 and HKU1) have been described, and they have caused respiratory infections worldwide. Potentially exposed laboratory workers or animal handlers with rapidly progressive pneumonia not responding to standard antibacterial coverage must be isolated with contact and droplet, and for specific situations, airborne precautions, till rapid tests of respiratory and faecal samples are negative for SARS-CoV. Generally, the viral loads collected at different anatomical sites correlate with the severity of symptoms and mortality. Shedding of SARS-CoV peaks at day 10 after the onset of symptoms, which theoretically allows ample time for antiviral treatment. The disease is characterized by uncontrolled replication of the virus and a prominent pro-inflammatory response. No randomized controlled trials with a specific anti-coronavirus agent have been conducted with respect to therapy or prophylaxis. Reports using historical matched controls have suggested that treatment with interferon alfacon-1 (a synthetic interferon) combined with steroid, protease inhibitors together with ribavirin, or convalescent plasma containing neutralizing antibody, could be useful. Prophylaxis with interferon or hyperimmune globulin may be considered for unprotected exposure. The role of immunomodulators to decrease excessive inflammation remains elusive. Other non-SARS-CoV infections are generally milder in immunocompetent hosts, and scientific data on antiviral treatment of these viruses are scarce.


title: COVID-19 Assessment with Bedside Lung Ultrasound in a Population of Intensive Care Patients Treated with Mechanical Ventilation and ECMO

text: The COVID-19 pandemic has increased the need for an accessible, point-of-care and accurate imaging modality for pulmonary assessment COVID-19 pneumonia is mainly monitored with chest X-ray, however, lung ultrasound (LUS) is an emerging tool for pulmonary evaluation In this study, patients with verified COVID-19 disease hospitalized at the intensive care unit and treated with ventilator and extracorporal membrane oxygenation (ECMO) were evaluated with LUS for pulmonary changes LUS findings were compared to C-reactive protein (CRP) and ventilator settings Ten patients were included and scanned the day after initiation of ECMO and thereafter every second day until, if possible, weaned from ECMO In total 38 scans adding up to 228 cineloops were recorded and analyzed off-line with the use of a constructed LUS score The study indicated that patients with a trend of lower LUS scores over time were capable of being weaned from ECMO LUS score was associated to CRP (R = 0 34;p < 0 03) and compliance (R = 0 60;p < 0 0001), with the strongest correlation to compliance LUS may be used as a primary imaging modality for pulmonary assessment reducing the use of chest X-ray in COVID-19 patients treated with ventilator and ECMO


title: Global profiling of megalocytivirus-induced proteins in tongue sole (Cynoglossus semilaevis) spleen identifies cellular processes essential to viral infection

text: Abstract Megalocytivirus is a DNA virus with a broad host range among farmed fish including tongue sole (Cynoglossus semilaevis). In this study, label-free proteomics was performed to examine protein expression in tongue sole spleen induced by megalocytivirus at 8 and 12 days post infection (dpi). Compared to uninfected control fish, virus-infected fish displayed 315 up-regulated proteins and 111 down-regulated proteins at 8 dpi, and 48 up-regulated proteins and 43 down-regulated proteins at 12 dpi. The expressions of five differentially expressed proteins were confirmed by Western blot. The differentially expressed proteins were enriched in the pathways and processes associated with innate immune response and viral infection. Interference with the expression of two up-regulated proteins of the ubiquitin proteasome system (UPS), i.e. proteasome assembly chaperone 2 and proteasome maturation protein, significantly reduced viral propagation in fish, whereas overexpression of these two proteins significantly enhanced viral propagation. Consistently, inhibition of the functioning of proteasome significantly impaired viral replication in vivo. This study provided the first global protein profile responsive to megalocytivirus in tongue sole, and revealed an essential role of UPS in viral infection.


title: Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

text: The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.


title: Pathogen screening and prognostic factors in children with severe ARDS of pulmonary origin

text: BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most lethal diseases encountered in the pediatric intensive care unit (PICU). The etiological pathogens and prognostic factors of severe ARDS of pulmonary origin in children with respiratory virus infections were prospectively investigated. METHODS: Enrolled children fulfilled the following criteria: (1) PICU admission; (2) age of 1 month to 16 years; (3) diagnosis of infectious pneumonia and respiratory virus infection; and (4) development of severe ARDS within 72 h after PICU admission. Pathogens were detected in the blood and tracheal lavage fluid using molecular techniques and a conventional culture system. The serum levels of inflammatory mediators on the day of PICU admission were examined. RESULTS: Fifty‐seven patients (32 boys; median age, 9 months) were enrolled. Multiple virus infections, co‐infection with bacteria/fungus, and bacteremia/fungemia were observed in 60%, 49%, and 32% of children, respectively. Adenovirus‐B, measles virus, and cytomegalovirus were detected predominantly in tracheal lavage fluid. There were no statistically significant differences between non‐survivors and survivors regarding the types of pathogen, incidence of multiple virus infection, gender, age, clinical features, and treatment. The serum levels of interferon (IFN)‐γ and the IFN‐γ/interleukin (IL)‐10 ratio were higher in non‐survivors. CONCLUSIONS: IFN‐γ upregulation as detected on the day of PICU admission was found to be one of the possible prognostic factors affecting a fatal outcome. These results suggest that modulation of inflammatory responses is critical for the clinical management of children with ARDS.


title: Guideline for diagnosis and treatment of spine trauma in the epidemic of COVID-19

text: Outbreak of COVID-19 is ongoing all over the world. Spine trauma is one of the most common types of trauma and will probably be encountered during the fight against COVID-19 and resumption of work and production Patients with unstable spine fractures or continuous deterioration of neurological function require emergency surgery. The COVID-19 epidemic has brought tremendous challenges to the diagnosis and treatment of such patients. To coordinate the diagnosis and treatment of infectious disease prevention and spine trauma to formulate a rigorous diagnosis and treatment plan and to reduce the disability and mortality of the disease, multidisciplinary collaboration is needed. To prevent and control the epidemic, to diagnose and treat patients with spine trauma reasonably, and to reduce the risk of cross-infection between patients and medical personnel during the treatment, this expert consensus is formulated.


title: Surveillance for Avian Influenza A(H7N9), Beijing, China, 2013

text: During surveillance for pneumonia of unknown etiology and sentinel hospital–based surveillance in Beijing, China, we detected avian influenza A(H7N9) virus infection in 4 persons who had pneumonia, influenza-like illness, or asymptomatic infections. Samples from poultry workers, associated poultry environments, and wild birds suggest that this virus might not be present in Beijing.


Gastroenterological Society of Australia, Annual Scientific Meeting, May 1980


title: Model Membrane Platforms for Biomedicine: Case Study on Antiviral Drug Development

text: As one of the most important interfaces in cellular systems, biological membranes have essential functions in many activities such as cellular protection and signaling. Beyond their direct functions, they also serve as scaffolds to support the association of proteins involved in structural support, adhesion, and transport. Unfortunately, biological processes sometimes malfunction and require therapeutic intervention. For those processes which occur within or upon membranes, it is oftentimes difficult to study the mechanism in a biologically relevant, membranous environment. Therefore, the identification of direct therapeutic targets is challenging. In order to overcome this barrier, engineering strategies offer a new approach to interrogate biological activities at membrane interfaces by analyzing them through the principles of the interfacial sciences. Since membranes are complex biological interfaces, the development of simplified model systems which mimic important properties of membranes can enable fundamental characterization of interaction parameters for such processes. We have selected the hepatitis C virus (HCV) as a model viral pathogen to demonstrate how model membrane platforms can aid antiviral drug discovery and development. Responsible for generating the genomic diversity that makes treating HCV infection so difficult, viral replication represents an ideal step in the virus life cycle for therapeutic intervention. To target HCV genome replication, the interaction of viral proteins with model membrane platforms has served as a useful strategy for target identification and characterization. In this review article, we demonstrate how engineering approaches have led to the discovery of a new functional activity encoded within the HCV nonstructural 5A protein. Specifically, its N-terminal amphipathic, α-helix (AH) can rupture lipid vesicles in a size-dependent manner. While this activity has a number of exciting biotechnology and biomedical applications, arguably the most promising one is in antiviral medicine. Based on the similarities between lipid vesicles and the lipid envelopes of virus particles, experimental findings from model membrane platforms led to the prediction that a range of medically important viruses might be susceptible to rupturing treatment with synthetic AH peptide. This hypothesis was tested and validated by molecular virology studies. Broad-spectrum antiviral activity of the AH peptide has been identified against HCV, HIV, herpes simplex virus, and dengue virus, and many more deadly pathogens. As a result, the AH peptide is the first in class of broad-spectrum, lipid envelope-rupturing antiviral agents, and has entered the drug pipeline. In summary, engineering strategies break down complex biological systems into simplified biomimetic models that recapitulate the most important parameters. This approach is particularly advantageous for membrane-associated biological processes because model membrane platforms provide more direct characterization of target interactions than is possible with other methods. Consequently, model membrane platforms hold great promise for solving important biomedical problems and speeding up the translation of biological knowledge into clinical applications.


title: WCTECGdb: A 12-Lead Electrocardiography Dataset Recorded Simultaneously with Raw Exploring Electrodes’ Potential Directly Referred to the Right Leg

text: With this paper we communicated the existence of a surface electrocardiography (ECG) recordings dataset, named WCTECGdb, that aside from the standard 12-lead signals includes the raw electrode biopotential for each of the nine exploring electrodes refereed directly to the right leg. This dataset, comprises of 540 ten second segments recorded from 92 patients at Campbelltown Hospital, NSW Australia, and is now available for download from the Physionet platform. The data included in the dataset confirm that the Wilson’s Central Terminal (WCT) has a relatively large amplitude (up to 247% of lead II) with standard ECG characteristics such as a p-wave and a t-wave, and is highly variable during the cardiac cycle. As further examples of application for our data, we assess: (1) the presence of a conductive pathway between the legs and the heart concluding that in some cases is electrically significant and (2) the initial assumption about the limbs potential stating the dominance of the left arm concluding that this is not always the case and that might requires case to case assessment.


title: Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV)

text: The International Committee on Taxonomy of Viruses (ICTV) is charged with the task of developing, refining, and maintaining a universal virus taxonomy. This task encompasses the classification of virus species and higher-level taxa according to the genetic and biological properties of their members; naming virus taxa; maintaining a database detailing the currently approved taxonomy; and providing the database, supporting proposals, and other virus-related information from an open-access, public web site. The ICTV web site (http://ictv.global) provides access to the current taxonomy database in online and downloadable formats, and maintains a complete history of virus taxa back to the first release in 1971. The ICTV has also published the ICTV Report on Virus Taxonomy starting in 1971. This Report provides a comprehensive description of all virus taxa covering virus structure, genome structure, biology and phylogenetics. The ninth ICTV report, published in 2012, is available as an open-access online publication from the ICTV web site. The current, 10th report (http://ictv.global/report/), is being published online, and is replacing the previous hard-copy edition with a completely open access, continuously updated publication. No other database or resource exists that provides such a comprehensive, fully annotated compendium of information on virus taxa and taxonomy.


title: Determining the dynamics of influenza transmission by age

text: BACKGROUND: It is widely accepted that influenza transmission dynamics vary by age; however methods to quantify the reproductive number by age group are limited. We introduce a simple method to estimate the reproductive number by modifying the method originally proposed by Wallinga and Teunis and using existing information on contact patterns between age groups. We additionally perform a sensitivity analysis to determine the potential impact of differential healthcare seeking patterns by age. We illustrate this method using data from the 2009 H1N1 Influenza pandemic in Gauteng Province, South Africa. RESULTS: Our results are consistent with others in showing decreased transmission with age. We show that results can change markedly when we make the account for differential healthcare seeking behaviors by age. CONCLUSIONS: We show substantial heterogeneity in transmission by age group during the Influenza A H1N1 pandemic in South Africa. This information can greatly assist in targeting interventions and implementing social distancing measures.


title: Stock markets’ reaction to COVID-19: cases or fatalities?

text: Abstract In this paper, we examine the stock markets’ response to the COVID-19 pandemic. Using daily COVID-19 confirmed cases and deaths and stock market returns data from 64 countries over the period January 22, 2020 to April 17, 2020, we find that stock markets responded negatively to the growth in COVID-19 confirmed cases. That is, stock market returns declined as the number of confirmed cases increased. We further find that stock markets reacted more proactively to the growth in number of confirmed cases as compared to the growth in number of deaths. Our analysis also suggests negative market reaction was strong during early days of confirmed cases and then between 40 to 60 days after the initial confirmed cases. Overall, our results suggest that stock markets quickly respond to COVID-19 pandemic and this response varies over time depending on the stage of outbreak.


title: Collateral damage: Fear from SARS-CoV2-infection causing Takotsubo cardiomyopathy

text: An 84-year-old male patient with known ischemic cardiomy-opathy was admitted to the emergency department of Leip-zig University Hospital with typical signs and symptoms of an acute coronary syndrome in the midst of the SARS-Cov2 pandemic on April 22, 2020 His angina rapidly resolved after angioplasty of a sub-total proximal occlusion of his right coronary artery However, 12 h later his 81-year-old wife was brought to a secondary care hospital by the emergency doctor because of acute and severe shortness of breath and typical angina Elevated Troponin, ECG-and echocar-diographic abnormalities led to her urgent transfer to our hospital with the suspected diagnosis of acute myocardial infarction Her medical history included chronic renal insufficiency and hypertension Otherwise, the patient was previously well, mobile and in very good general condition Clinical examination showed an obese woman (163 cm, 97 kg, blood pressure 130/73 mmHg, heart rate 78/min, and body temperature 37 2 °C) The laboratory findings are presented in Table 1 The 12-lead-ECG at admission displayed a sinus rhythm with a previously known right bundle branch block and new negative T-waves in II, III, aVF and V3-6 (Fig 1) Echocardiography (Fig 2) showed wall motion abnormalities with apical septal dyskinesis, mid ubiquitous akinesia and basal septal and anterior hypokinesis Left ventricular ejection fraction was reduced to 45% Global longitudinal strain with a typical strain pattern of apical balloning was −8% (Fig 3) Coronary angiogram revealed no signs of artery disease (CAD), as shown in Fig 4 Cardiac MR (Fig 5) showed wall motion abnormalities corresponding to the echocardiography The tissue characterization by T2STIR sequences documented severe edema (Fig 6) T1TFE sequences showed diffuse late enhancement T1-and T2-mapping showed severely increased T1 and T2 values (1660 ms and 68 ms), respectively Extracellular volume was ~ 37% In summary, the findings fulfill the criteria of a Takotsubo (stress) cardiomyopathy [1] Focused evaluation of potential emotional or physical triggers revealed that the patient suffered from psychologic stress during the last few weeks Due to media reports, she was highly afraid of SARS-CoV2 infections for her husband and herself, because age and hypertension were communicated as high risk for a severe course of COVID-19 Furthermore, she felt severely affected by the lockdown measures Her condition acutely and severely exacerbated when her husband was admitted to the hospital, which she felt would place him at a high risk of death, and because she was not allowed to visit him due to the SARS-CoV2-specific regulations The patient was provided with psychological support and the SARS-CoV2-negative couple was allowed to meet Heart failure therapy including an angiotensin receptor blocker, beta blocker, mineraloreceptor antagonist and a loop diuretic Table 1 Laboratory results on admission Reference range CK 1 79 µkat/l (0 43-2 34 µkat/l) CK-MB 0 47 µkat/l ( 90 ml/min/1 73m 2) Urea 12 6 mmol/l (< 11 9 mmol/l) LDH 4 82 µkat/l (2 25-3 55 µkat/l)


title: A systematic review of emerging respiratory viruses at the Hajj and possible coinfection with Streptococcus pneumoniae

text: Abstract Background The annual Hajj to the Kingdom of Saudi Arabia attracts millions of pilgrims from around the world. International health community's attention goes towards this mass gathering and the possibility of the development of any respiratory tract infections due to the high risk of acquisition of respiratory viruses. Method We searched MEDLINE/PubMed and Scopus databases for relevant papers describing the prevalence of respiratory viruses among Hajj pilgrims. Results The retrieved articles were summarized based on the methodology of testing for these viruses. A total of 31 studies were included in the quantitative/qualitative analyses. The main methods used for the diagnosis of most common respiratory viruses were polymerase chain reaction (PCR), culture and enzyme-linked immunosorbent assay (ELISA). Influenza, rhinovirus and parainfluenza were the most common viruses detected among pilgrims. Coronaviruses other than MERS-CoV were also detected among pilgrims. The acquisition of MERS-CoV remains very limited and systematic screening of pilgrims showed no infections. Conclusions Well conducted multinational follow-up studies using the same methodology of testing are necessary for accurate surveillance of respiratory viral infections among Hajj pilgrims. Post-Hajj cohort studies would further evaluate the impact of the Hajj on the acquisition of respiratory viruses.


title: Positron Emission Tomography With (18)F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome

text: The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with (18)F-fluorodeoxyglucose [18F-fluorodeoxyglucose ((18)F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS. Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with (18)F-FDG emission scans for quantification of regional (18)F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung (18)F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed. Seventeen patients with ACS (mean age 28.3 ± 6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1–2.9] vs 0.8 [0.6–1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R(2) = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6–11] vs 4 [3–6] days; P = 0.016). Lungs of patients with ACS exhibited higher (18)F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower (18)F-FDG uptake than lung bases, but higher (18)F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung (18)F-FDG uptake had longer ICU stay than others.


title: A Global Health Elective for US Medical Students: The 35 Year Experience of the State University of New York, Downstate Medical Center, School of Public Health

text: The School of Public Health at the State University of New York, Downstate Medical Center has sponsored a 6–8 week global health elective for fourth year medical students since 1980. The purpose of this elective is to provide students with an opportunity to observe the health care and public health delivery systems in low-income countries, provide medical service and have a cross-cultural experience. Over the course of the past 35 years, 388 students have participated in this global health elective in more than 41 low-income countries. The most popular sites include the Dominican Republic, Guatemala, India, Kenya and Thailand. Overall, interest in this elective has persisted throughout the course of time, sometimes temporarily increasing or decreasing with outside factors, such as the events of 11 September 2001 and the outbreak of Severe Acute Respiratory Syndrome in Asia. Recent annual applications for this elective have been as high as 44 out of a class of 200 students. Over the past 10 years, annual acceptance rates have varied, ranging from a low of 32 % in 2007–2008 to a high of 74 % in 2010–2011 and 2013–2014. Careful screening, including a written application, review of academic records and personal interviews has resulted in the selection of highly mature, adaptable and dedicated students who have performed well at overseas sites. Student rated satisfaction levels with this elective are almost universally high, with most rating it the best experience of their medical school years. Students undergo extensive preparation prior to their travel overseas, including a review of individual health and safety issues, travel and lodging, and the nature of the host country culture, health care system and assignment site. Downstate medical students are especially experienced in cross-cultural understanding because of the unusual diversity of the patient population in Brooklyn, and the diversity of local hospital staff and the medical school class. The Alumni Fund of the College of Medicine has steadfastly supported this elective with both a philosophical commitment and financial grants to help defray costs since the very early years. The Dr. Michael and Lona B. Kennéy Endowment, the Joshua H. Weiner endowment, and the LSK Foundation have also provided financial support for this elective. Throughout the course of this elective, overseas preceptors have willingly given of their time and institutional resources to make these experiences available and meaningful for our students.


(71) Respiratory Viral Infections Are Common in the First Year After Pediatric Lung Transplantation: A Multi-Center Prospective Study


title: Critical Differences between the Binding Features of the Spike Proteins of SARS-CoV-2 and SARS-CoV

text: [Image: see text] The COVID-19 caused by SARS-CoV-2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse-grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS-CoV-2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS-CoV antibody m396 and SARS-CoV-2, it is found that the remote energetic contribution is missing, which might explain the absence of cross-reactivity of such antibodies.


title: On the frontline against COVID-19: Community pharmacists’ contribution during a public health crisis

text: The global spread of COVID-19 is placing unprecedented demands on healthcare services. In this time of crisis, innovative and adaptive methods of practising will be required across all health professions. In order to maximise the use of current available resources, it is vital that existing services are comprehensively reviewed and full use is made of any unrealised potential among healthcare providers. Community pharmacy is one of a number of health professions that has a key role to play in responding to the current pandemic. As the scope of community pharmacy practice varies considerably across countries, it is important to examine ways in which the profession can assist with the public health response to COVID-19 and maintaining the continuity of healthcare services. This article seeks to highlight roles and activities that community pharmacists can undertake to help in relieving pressure on other areas of the health service, such as general practice. This information could help to inform future decisions about the restructuring of existing health services by governments, public health bodies and policy makers in response to public health crises such as COVID-19.


title: Plague: Past, Present, and Future

text: The authors argue that plague should be taken much more seriously by the international health community.


title: Extended models for nosocomial infection: parameter estimation and model selection

text: We consider extensions to previous models for patient level nosocomial infection in several ways, provide a specification of the likelihoods for these new models, specify new update steps required for stochastic integration, and provide programs that implement these methods to obtain parameter estimates and model choice statistics. Previous susceptible-infected models are extended to allow for a latent period between initial exposure to the pathogen and the patient becoming themselves infectious, and the possibility of decolonization. We allow for multiple facilities, such as acute care hospitals or long-term care facilities and nursing homes, and for multiple units or wards within a facility. Patient transfers between units and facilities are tracked and accounted for in the models so that direct importation of a colonized individual from one facility or unit to another might be inferred. We allow for constant transmission rates, rates that depend on the number of colonized individuals in a unit or facility, or rates that depend on the proportion of colonized individuals. Statistical analysis is done in a Bayesian framework using Markov chain Monte Carlo methods to obtain a sample of parameter values from their joint posterior distribution. Cross validation, deviance information criterion and widely applicable information criterion approaches to model choice fit very naturally into this framework and we have implemented all three. We illustrate our methods by considering model selection issues and parameter estimation for data on methicilin-resistant Staphylococcus aureus surveillance tests over 1 year at a Veterans Administration hospital comprising seven wards.


title: Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission

text: The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.


title: Focusing on Families and Visitors Reduces Healthcare Associated Respiratory Viral Infections in a Neonatal Intensive Care Unit

text: Healthcare-associated respiratory viral infections (HARVIs) result in significant harm to infants in the neonatal intensive care unit (NICU). Healthcare workers and visitors can serve as transmission vectors to patients. We hypothesized that improved family and visitor hand hygiene (FVHH) and visitor screening would reduce HARVIs by at least 25%. METHODS: This quality improvement project took place in a large tertiary NICU to reduce HARVIs. Interventions primarily focused on improving FVHH and reducing visitation by symptomatic family members and visitors. We defined correct FVHH as hand hygiene performed immediately before touching their child. Hand hygiene observations were performed by direct observation by NICU staff using a standardized tool. Interventions to improve FVHH included education of staff and visitors, reminder signs, and immediate reminders to families to prevent lapses in hand hygiene. Staff screened family and visitors before NICU entry. Symptomatic individuals were asked to defer visitation until symptoms resolved. HARVIs were identified during prospective surveillance by infection preventionists using standard definitions. RESULTS: Baseline FVHH was 27% in 2015. After May 2017, the average FVHH remained at 85%. When reminded, family members and visitors performed hand hygiene 99% of the time. Staff screened ~129,000 people for FVHH. Between January 2013 and March 2019, there were 74 HARVIs; 80% were rhinovirus/enterovirus. After the implementation of improved FVHH, the HARVI rate decreased from 0.67 to 0.23/1,000 patient days. CONCLUSIONS: Adding interventions to improve FVHH and visitor management to existing healthcare worker prevention efforts can help reduce HARVIs in the NICU.


Factores de riesgo y predictores de gravedad en pacientes hospitalizados por COVID-19: análisis de 52 casos


title: Chapter 19 Advances in structure-assisted antiviral discovery for animal viral diseases

text: Abstract The latest advancements in drug development are structure-assisted and computer-aided identification, design, and synthesis of target-specific antiviral. Structural virology of animal viruses has made valuable contribution to our understanding of viruses in general, replication, evolution, and interaction with the host. Structure–function relation studies are definitely the need of the hour for rational design of drugs and vaccines to effectively treat animal viral diseases. These studies are important for economical, veterinary, and human medical perspectives. X-ray crystallography, nuclear magnetic resonance and cryo-electron microscopy techniques elaborate the structure–function relation studies by utilizing various computational approaches for structure-assisted designing of drug molecules and antiviral against viruses. Availability of protein three-dimensional structures, high-performance computing, data management software, and internet are enhancing the modern day drug discovery process. Computational tools offer the advantage of delivering new drug candidates more quickly and at a lower cost. Various viral proteins that are necessary for the survival of the virus inside the host are discussed in this chapter such as viral polymerase, helicase, protease, etc. Various antiviral drug molecules identified and designed on the basis of the structure of viral proteins which are highlighted, and disclosed details of the available inhibitors and potential antiviral are discussed. Further improvement in identified inhibitors, the need of novel structure-based drugs and their clinical testing is emphasized. This chapter describes briefly the structural techniques and advances made in animal virology toward structure-based identification and development of antiviral for treatment of animal viruses. In the future, the studies discussed may serve as the basis for development of potential antiviral against animal viral diseases.


The Bundeskartellamt in times of COVID-19: adaption of workflows and implications for our enforcement practice


title: First data analysis about possible COVID-19 virus airborne diffusion due to air particulate matter (PM): the case of Lombardy (Italy)

text: Abstract The severe cases of COVID-19 infections in Italy, and notably in Lombardy (mainly in Brescia and Bergamo areas), registered at the beginning of March 2020, occurred after a period of PM10 pollution, that exceeded the concentration of 50 μg/m3 (the attention limit) for several days. The two events were supposed to be correlated, also based on the limited information available about the new virus. Despite that clear indications about the role of particulate matter (PM) in the virus mechanism dispersion cannot be found in literature, some researchers supposed that PM can act as virus carrier, promoting its diffusion through the air. This paper, for the first time, analyses the PM10 situation in Lombardy (from 10th February to 27th March 2020), several days before the sanitary emergency explosion. The data of the detected infection cases are reported and discussed parallelly. As a comparison, the situation of Piedmont, located near to the Lombardy is also presented. Data are reported for Brescia, Bergamo, Cremona, Lodi, Milano, Monza-Brianza, Pavia (Lombardy), Alessandria, Vercelli, Novara, Biella, Asti, and Torino (Piedmont). The results show that it is not possible to conclude that COVID-19 diffusion mechanism also occurs through the air, by using PM10 as a carrier. In particular, it is shown that Piedmont cities, presenting lower detected infections cases in comparison to Brescia and Bergamo in the investigated period, had most sever PM10 pollution events in comparison to Lombardy cities. This first study may serve as a reference to better understand and predict the factors affecting the COVID-19 diffusion and transmission routes, focusing on the role of air particulate matter in the atmosphere.