title: An experimental study quantifying pulmonary ventilation on inhalation of aerosol under steady and episodic emission

text: Abstract Estimating inhalation dose accurately under realistic conditions can enhance the accuracy of risk assessment. Conventional methods to quantify aerosol concentration that susceptible victims in contaminated environments are exposed to use real time particle counters to measure concentrations in environments without occupancy. Breathing-induced airflow interacts and influences concentration around nostrils or mouth and alter the ultimate exposure. This subject has not yet been systematically studied, particularly under transient emission. In this work, an experimental facility comprising two manikins was designed and fabricated. One of them mimicked realistic breathing, acting as a susceptible victim. Both steady and episodic emissions were generated in an air-conditioned environmental chamber in which two different ventilation schemes were tested. The scaled-dose of the victim under different expiratory velocities and pulmonary ventilation was measured. Inferring from results obtained from comprehensive tests, it can be concluded that breathing has very significant influence on the ultimate dose compared with that without breathing. Majority of results show that breathing reduces inhalation quantity and the reduction magnitude increases with breathing rate. This is attributed to the fact that the exhalation process plays a more significant role in reducing the dose level than the enhanced effect during inhalation period. The higher the breathing rate, the sharper the decline of the resultant concentration would be leading to lower dose. Nevertheless, under low pulmonary ventilation, results show that breathing increases dose marginally. Results also reveals that ventilation scheme also affects the exposure.


title: Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013–14

text: Abstract Background Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. Objectives To describe the spectrum and clinical impact of co-infections. Study design Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. Results Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23–0.73], p=0.003), leukocytosis (>11K/μl, OR 3.7 [2.2–6.2], p<0.001; reference: normal WBC 3.5–11K/μl) at ICU admission and a higher ICU admission SOFA score (for each increase by 1 in SOFA score, OR 1.1 [1.0–1.2], p=0.001). Bacterial co-infections (OR 2.2 [1.4–3.6], p=0.001) and viral co-infections (OR 3.1 [1.3–7.4], p=0.010) were both associated with death in bivariable analysis. Patients with a bacterial co-infection had a longer hospital stay, a longer ICU stay and were likely to have had a greater delay in the initiation of antiviral administration than patients without co-infection (p<0.05) in bivariable analysis. Conclusions Bacterial co-infections were common, resulted in delay of antiviral therapy and were associated with increased resource allocation and higher mortality.


title: Limited transmissibility of coronavirus (SARS‐1, MERS, and SARS‐2) in certain regions of Africa

text: A novel coronavirus disease (COVID‐19) was first identified in Wuhan, China in December 2019 [1], and after a few weeks, the World Health Organization (WHO) declared the outbreak as a global pandemic [2]. Scientifically, the virus was named “severe acute respiratory syndrome (SARS‐2) coronavirus” [3]. High‐level endemic transmissions occurred in several countries, and while yet very limited, have spread in certain regions of the globe, particularly in Africa [4]. This article is protected by copyright. All rights reserved.


title: Viral Infections, an Overview with a Focus on Prevention of Transmission

text: Abstract Viruses are obligatory intracellular pathogens with a simple structure consisting of assembled proteins enclosing the nucleic acid genome with or without a lipid envelope. Despite increasing availability of rapid nucleic acid amplification assays for laboratory diagnosis, effective antivirals, and safe vaccines, the control of most viral infections depends on time-honored surveillance and infection control measures. Moreover most viruses can be readily destroyed by common disinfectants. This article is focused on the epidemiology, diagnosis, and control of common and emerging viral diseases.


title: Ramsay Hunt syndrome and zoster laryngitis with multiple cranial nerve involvement

text: Ramsay Hunt syndrome is characterized by varicella zoster virus infection affecting the geniculate ganglion of the facial nerve. It typically presents with vesicles in the external auditory canal associated with auricular pain and peripheral facial nerve paralysis. Although vestibulocochlear nerve is frequently co-involved during the course of Ramsay Hunt syndrome, multiple lower cranial nerve involvement has rarely been described in the literature. In addition, laryngitis due to varicella zoster virus is a diagnostic challenge due to its unfamiliarity among clinicians. We report a case of Ramsay Hunt syndrome with laryngitis involving multiple lower cranial nerves.


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title: Estimation of the Basic Reproductive Number and Mean Serial Interval of a Novel Pathogen in a Small, Well-Observed Discrete Population

text: BACKGROUND: Accurately assessing the transmissibility and serial interval of a novel human pathogen is public health priority so that the timing and required strength of interventions may be determined. Recent theoretical work has focused on making best use of data from the initial exponential phase of growth of incidence in large populations. METHODS: We measured generational transmissibility by the basic reproductive number R(0) and the serial interval by its mean T(g). First, we constructed a simulation algorithm for case data arising from a small population of known size with R(0) and T(g) also known. We then developed an inferential model for the likelihood of these case data as a function of R(0) and T(g). The model was designed to capture a) any signal of the serial interval distribution in the initial stochastic phase b) the growth rate of the exponential phase and c) the unique combination of R(0) and T(g) that generates a specific shape of peak incidence when the susceptible portion of a small population is depleted. FINDINGS: Extensive repeat simulation and parameter estimation revealed no bias in univariate estimates of either R(0) and T(g). We were also able to simultaneously estimate both R(0) and T(g). However, accurate final estimates could be obtained only much later in the outbreak. In particular, estimates of T(g) were considerably less accurate in the bivariate case until the peak of incidence had passed. CONCLUSIONS: The basic reproductive number and mean serial interval can be estimated simultaneously in real time during an outbreak of an emerging pathogen. Repeated application of these methods to small scale outbreaks at the start of an epidemic would permit accurate estimates of key parameters.


Acute generalized exanthematous pustulosis following paracetamol ingestion in a child


Odyssean Education Plays the Coronavirus: Ideation and the Immune Institution


title: Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review

text: At present more than 250 FDA approved chlorine containing drugs were available in the market and many pharmaceutically important drug candidates in pre-clinical trials. Thus, it is quite obvious to expect that in coming decades there will be an even greater number of new chlorine-containing pharmaceuticals in market. Chlorinated compounds represent the family of compounds promising for use in medicinal chemistry. This review describes the recent advances in the synthesis of chlorine containing heterocyclic compounds as diverse biological agents and drugs in the pharmaceutical industries for the inspiration of the discovery and development of more potent and effective chlorinated drugs against numerous death-causing diseases.


title: Infecciones respiratorias

text: Resumen Las infecciones respiratorias son una de las principales causas de mortalidad y hospitalización en personas ingresadas en residencies de ancianos. Como resultado de ello hay un creciente interés en su epidemiología aunque todavía diversos aspectos no han sido evaluados de manera sistemática debido a la falta de ensayos clínicos. Pocos estudios han comparado diferentes estrategias terapéuticas antibióticas y resultados. Los ancianos institucionalizados que presentan neumonía son habitualmente hospitalizados y estos ingresos están asociados con los múltiples riesgos inherentes a la propia hospitalización, así como con importantes costes económicos. Se han desarrollado diferentes modelos predictivos para identificar a los residentes con bajo y alto riesgo de mortalidad. El siguiente trabajo revisa la literatura e intenta ayudar en las decisiones diarias en una residencia. Abstract Respiratory tract infection is a leading cause of mortality and hospitalization in nursing home residents. As a result, interest has increased in the epidemiology of these infections. However, several issues remain to be systematically evaluated due to the lack of clinical trials. Few studies have compared different antibiotic treatment strategies and outcomes. Nursing home residents with pneumonia are frequently hospitalized and these transfers are associated with the multiple hazards of hospitalization as well as with economic costs. Several predictive models have been developed to help clinicians identify residents at low and high risk of mortality. This present article analyzes the relevant literature and attempts to provide information of help in dayto-day decision-making in nursing homes.


title: Effective Suckling C57BL/6, Kunming, and BALB/c Mouse Models with Remarkable Neurological Manifestation for Zika Virus Infection

text: Since 2015, 84 countries and territories reported evidence of vector-borne Zika Virus (ZIKV) transmission. The World Health Organization (WHO) declared that ZIKV and associated consequences especially the neurological autoimmune disorder Guillain–Barré syndrome (GBS) and microcephaly will remain a significant enduring public health challenge requiring intense action. We apply a standardization of the multi-subcutaneous dorsal inoculation method to systematically summarize clinical neurological manifestation, viral distribution, and tissue damage during the progress of viremia and systemic spread in suckling mouse models. We found that C57BL/6 and Kunming mice (KM) both showed remarkable and uniform neurologic manifestations. C57BL/6 owned the highest susceptibility and pathogenicity to the nervous system, referred to as movement disorders, with 100% incidence, while KM was an economic model for a Chinese study characterized by lower limb weakness with 62% morbidity. Slight yellow extraocular exudates were observed in BALB/c, suggesting the association with similar ocular findings to those of clinical cases. The virus distribution and pathological changes in the sera, brains, livers, kidneys, spleens, and testes during disease progression had strong regularity and uniformity, demonstrating the effectiveness and plasticity of the animal models. The successful establishment of these animal models will be conducive to expound the pathogenic mechanism of GBS.


title: Potential implication of new torque teno mini viruses in parapneumonic empyema in children

text: An unexplained increase in the incidence of parapneumonic empyema (PPE) in pneumonia cases has been reported in recent years. The present study investigated the genetic and biological specifications of new isolates of torque teno mini virus (TTMV) detected in pleural effusion samples from children hospitalised for severe pneumonia with PPE. A pathogen discovery protocol was applied in undiagnosed pleural effusion samples and led to the identification of three new isolates of TTMV (TTMV-LY). Isolated TTMV-LY genomes were transfected into A549 and human embryonic kidney 293T cells and viral replication was assessed by quantitative real-time PCR and full-length genome amplification. A549 cells were further infected with released TTMV-LY virions and the induced-innate immune response was measured by multiplex immunoassays. Genetic analyses of the three TTMV-LY genomes revealed a classic genomic organisation but a weak identity (<64%) with known sequences. We demonstrated the in vitro replication of TTMV-LY in alveolar epithelial cells and the effective release of infectious viral particles. We also showed a selective production of inflammatory mediators in response to TTMV infection. This study reports the description of replicative TTMV-LY isolated from parapneumonic effusions of children hospitalised with PPE, suggesting a potential role of the virus in the pathogenesis of pneumonia.


title: New Diagnostic Tests for Pneumonia: What is Their Role in Clinical Practice?

text: The utility of diagnostic studies to determine the etiologic agents of community-acquired pneumonia has been controversial in part because of the lack of rapid, accurate, easily performed, and cost-effective methods. Advancements in molecular testing methods and biological markers are becoming available with marked expansion of diagnostic capability for infectious diseases. Subsequent studies and clinical experience will clarify their real clinical value.


title: The Acute Respiratory Distress Syndrome Biomarker Pipeline: Crippling Gaps between Discovery and Clinical Utility

text: Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into “personalized” medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19-infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies.


title: Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions

text: BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for severe combined immunodeficiency (SCID); although, there is a high incidence of severe infections and an increased risk of graft-versus host-disease (GvHD) with HSCT. Early intervention is a crucial prognostic factor and a HLA-haploidentical parental donor is often available. Haploidentical HSCT protocols utilizing extensively ex vivo T-cell depleted grafts (CliniMACs system) have proven efficient in preventing GvHD, but cause a delay in early T-cell recovery that increases the risk of viral infections. Here, we present a novel approach for treating SCID that combines selective depletion of GvHD-inducing alpha/beta (α/β) T-cells from the haploidentical HSCT graft with a subsequent donor lymphocyte infusion (DLI) enriched for CD45RO+ memory T-cells. RESULTS: Our patient was diagnosed with SCID (T-B + NK+ phenotype). At 9 months of age, he received a T cell receptor(TCR)α/β-cell depleted graft from his haploidentical mother, following a reduced intensity conditioning regimen with no additional GvHD prophylaxis. Engraftment was rapid with complete donor chimerism and no signs of GvHD. However, at 12 weeks post HSCT, the patient was still T-cell lymphopenic with clinical symptoms of multiple severe viral infections. Consequently, therapeutic DLIs were initiated for enhanced anti-viral immunity. The patient was treated with CD45RA+ depleted haploidentical maternal donor lymphocytes enriched from unmobilized whole blood, and a total T-cell dose of no more than 25 x10(3) CD3+ cells/kg with >99.9 % purity of CD3 + CD45RO+ memory T-cells was transferred. Following the DLI, a prompt increase in CD3 + CD4+ and CD3 + CD8+ counts was observed with a subsequent clearance of viral infections. No acute or chronic GvHD was observed. CONCLUSIONS: Automated depletion of CD45RA+ naïve T-cells from unmobilized whole blood is a simple and rapid strategy to provide unmanipulated DLIs, with a potentially broad repertoire of pathogen specific memory T-cells. In the haploidentical setting, CD45RA+ depleted DLIs can be safely administered at low T-cell doses for efficient enhancement of viral immunity and limited risk of GvHD. We demonstrate the successful use of this approach following TCR-α/β-cell depleted HSCT for the treatment of SCID.


title: Attitudes of patients with relapsing-remitting form of multiple sclerosis using disease-modifying drugs in Montenegro regarding COVID-19 pandemic

text: BACKGROUND: : In the days of the reorganization of healthcare systems due to SARS-Cov2 pandemic, patients suffering from chronic diseases are being often neglected. The aim of our study was to examine the attitudes and behaviors of patient suffering from relapsing-remitting form of multiple sclerosis using disease-modifying drugs in Montenegro in relation to the current pandemic. METHODS: : The research was conducted through an online-generated questionnaire during the peak of the pandemic. RESULTS: : There is a high level of concern about COVID-19 (3.22±1.23), especially about safety behavior intensification (3.80±1.29). Possibility of relapse during pandemic was considered as moderate (2.06±1.42), but relapse symptoms would be reported by the majority of subjects (1.55±1.23). Our unemployed patients statistically more often reported that they had more frequent mood changes, but also that they felt more energy loss. Surprisingly, there was no difference among the subjects according to smoking status. According therapy groups there was significant difference between the groups regarding some variables: patients using ocrelizumab are most concerned about COVID-19; patients using interferon beta 1a i.m. statistically more often have frequent changes in their mood, memory problems, poor appetite, feeling of nausea or upset stomach and patients on fingolimod have bigger afraid of coming to regular visits. CONCLUSION: : Our patients showed concern about their disease future status in the current epidemic era, but also showed a high degree of trust in physicians and the overall health system.


title: Management of Rodent Viral Disease Outbreaks: One Institution's (R)Evolution

text: At first blush, an outbreak of mouse hepatitis virus or epizootic diarrhea of infant mice virus in a research colony of laboratory mice may not seem like a “disaster.” However, irrespective of magnitude, such an outbreak at an academic institution is disruptive for researchers at all levels. It can be a disaster for the graduate student who may have just a few experiments to finish before writing the thesis or for the postdoctoral fellow who is in the lab for only 1 or 2 years. Infectious disease outbreaks also limit the ability of principal investigators to share their animals with collaborators at their home institution as well as with those at extramural sites, thereby thwarting the expectation that research materials supported by federal funds will be made readily available to colleagues. This article traces the evolution of a change in “culture” at a large, well-funded academic institution with over 1,800 active IACUC protocols, more than 1,000 of which include mice. During a period of less than 5 years, the institution evolved from virtual paralysis in the face of such outbreaks to the implementation of policies and practices that enable effective outbreak management and the timely resumption of research functionality. This evolution required not only support from the highest levels of leadership in the university and its school of medicine but also a huge outlay of financial resources.


COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features


title: Epizootology and experimental infection of Yokose virus in bats

text: Abstract To reveal whether bats serve as an amplifying host for Yokose virus (YOKV), we conducted a serological survey and experimentally infected fruit bats with YOKV isolated from microbats in Japan. YOKV belongs to the Entebbe bat virus group of vector unknown group within the genus Flavivirus and family Flaviviridae. To detect antibodies against YOKV, we developed an enzyme-linked immunosorbent assay (ELISA) using biotinylated anti-bat IgG rabbit sera. Serological surveillance was conducted with samples collected in the Philippines and the sera supplied from Malaysia. One of the 36 samples from the Philippines (2.7%) and 5 of the 26 samples from Malaysia (19%) had detectable ELISA antibodies. In the experimental infections, no clinical signs of disease were observed. Moreover, no significant viral genome amplification was detected. These findings revealed that YOKV replicates poorly in the fruit bat, suggesting that fruit bats do not seem to serve as an amplifying host for YOKV.


title: Loop-mediated isothermal amplification as an emerging technology for detection of Yersinia ruckeri the causative agent of enteric red mouth disease in fish

text: BACKGROUND: Enteric Redmouth (ERM) disease also known as Yersiniosis is a contagious disease affecting salmonids, mainly rainbow trout. The causative agent is the gram-negative bacterium Yersinia ruckeri. The disease can be diagnosed by isolation and identification of the causative agent, or detection of the Pathogen using fluorescent antibody tests, ELISA and PCR assays. These diagnostic methods are laborious, time consuming and need well trained personnel. RESULTS: A loop-mediated isothermal amplification (LAMP) assay was developed and evaluated for detection of Y. ruckeri the etiological agent of enteric red mouth (ERM) disease in salmonids. The assay was optimised to amplify the yruI/yruR gene, which encodes Y. ruckeri quorum sensing system, in the presence of a specific primer set and Bst DNA polymerase at an isothermal temperature of 63°C for one hour. Amplification products were detected by visual inspection, agarose gel electrophoresis and by real-time monitoring of turbidity resulted by formation of LAMP amplicons. Digestion with HphI restriction enzyme demonstrated that the amplified product was unique. The specificity of the assay was verified by the absence of amplification products when tested against related bacteria. The assay had 10-fold higher sensitivity compared with conventional PCR and successfully detected Y. ruckeri not only in pure bacterial culture but also in tissue homogenates of infected fish. CONCLUSION: The ERM-LAMP assay represents a practical alternative to the microbiological approach for rapid, sensitive and specific detection of Y. ruckeri in fish farms. The assay is carried out in one hour and needs only a heating block or water bath as laboratory furniture. The advantages of the ERM-LAMP assay make it a promising tool for molecular detection of enteric red mouth disease in fish farms.


title: Automated extraction protocol for quantification of SARS-Coronavirus RNA in serum: an evaluation study

text: BACKGROUND: We have previously developed a test for the diagnosis and prognostic assessment of the severe acute respiratory syndrome (SARS) based on the detection of the SARS-coronavirus RNA in serum by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In this study, we evaluated the feasibility of automating the serum RNA extraction procedure in order to increase the throughput of the assay. METHODS: An automated nucleic acid extraction platform using the MagNA Pure LC instrument (Roche Diagnostics) was evaluated. We developed a modified protocol in compliance with the recommended biosafety guidelines from the World Health Organization based on the use of the MagNA Pure total nucleic acid large volume isolation kit for the extraction of SARS-coronavirus RNA. The modified protocol was compared with a column-based extraction kit (QIAamp viral RNA mini kit, Qiagen) for quantitative performance, analytical sensitivity and precision. RESULTS: The newly developed automated protocol was shown to be free from carry-over contamination and have comparable performance with other standard protocols and kits designed for the MagNA Pure LC instrument. However, the automated method was found to be less sensitive, less precise and led to consistently lower serum SARS-coronavirus concentrations when compared with the column-based extraction method. CONCLUSION: As the diagnostic efficiency and prognostic value of the serum SARS-CoV RNA RT-PCR test is critically associated with the analytical sensitivity and quantitative performance contributed both by the RNA extraction and RT-PCR components of the test, we recommend the use of the column-based manual RNA extraction method.


Viral Infections in Immunocompromised Patients


title: Conventional and unconventional mechanisms for capping viral mRNA

text: In the eukaryotic cell, capping of mRNA 5′ ends is an essential structural modification that allows efficient mRNA translation, directs pre-mRNA splicing and mRNA export from the nucleus, limits mRNA degradation by cellular 5′–3′ exonucleases and allows recognition of foreign RNAs (including viral transcripts) as 'non-self'. However, viruses have evolved mechanisms to protect their RNA 5′ ends with either a covalently attached peptide or a cap moiety (7-methyl-Gppp, in which p is a phosphate group) that is indistinguishable from cellular mRNA cap structures. Viral RNA caps can be stolen from cellular mRNAs or synthesized using either a host- or virus-encoded capping apparatus, and these capping assemblies exhibit a wide diversity in organization, structure and mechanism. Here, we review the strategies used by viruses of eukaryotic cells to produce functional mRNA 5′-caps and escape innate immunity.


title: Molecular characterization of Cryptosporidium isolates from beef calves under one month of age over three successive years in one herd in western France

text: Abstract Cohorts of pre-weaned calves were studied for Cryptosporidium infection over three successive years (2010–2012) in one beef cattle herd in western France. Each year 25–34 calves were sampled weekly from 3 days to one month of age in order to characterize oocyst output, Cryptosporidium species and clinical features associated with infection. Faecal samples were screened for the presence of oocysts using immunofluorescence analysis. DNA was extracted from positive samples and a PCR SSU rRNA followed by RFLP or sequencing was performed. For the subtyping of C. parvum, a gp60 PCR was carried out. Regardless of the year, 92–100% of the animals excreted oocysts on at least one sampling date. Depending on the year of observation, the age of highest prevalence varied. In contrast, the peak of excretion was systematically observed almost at the same age (2nd–3rd week of life) with excretion levels ranging from between 100 and 1.7×107 oocysts/g of faeces. Differences concerning clinical signs depending on the year of sampling were observed. Different species patterns were observed, with a predominance of C. bovis in the 1st year and a predominance of C. parvum in the last year. Moreover, two zoonotic subtypes of C. parvum, IIaA15G2R1 and IIaA18G2R1, were recorded in different years. This study shows that, in a given farm, the Cryptosporidium species and C. parvum subtypes identified as well as the prevalence of infection and level of excretion may vary greatly and show distinct patterns according to the year.


title: Biosecurity practices in Belgian veal calf farming: Level of implementation, attitudes, strengths, weaknesses and constraints

text: Abstract The shift from cure toward prevention in veterinary medicine involves the implementation of biosecurity. In cattle farming, the application of biosecurity measures has been described to a limited degree, yet no data on biosecurity on veal farms is available. A high degree of commingling of veal calves from multiple farms causes frequent disease outbreaks, and thereby high antimicrobial usage and increased risk of antimicrobial resistance. Therefore, this study aimed to describe the current implementation of biosecurity on veal farms in Belgium. To this extent, a list of the most important calf diseases (n = 34) was created, and risk factors and related biosecurity measures for these diseases were determined and included in a questionnaire. Herd visits and face-to-face interviews were conducted on 20 randomly selected veal farms, comprising 8.3% of the target population. A categorical principal component and clustering analysis were performed to determine the influence of the veal companies on the farms’ biosecurity level. Awareness of biosecurity was very low among the farmers. All farms used an “all-in, all-out” production system with calves originating from multiple farms without quarantine. On average, farms were filled in 11.4 days (range 2–52). The degree of commingling for these farms was 1.24, meaning that, on average, 124 calves originated from 100 farms. Veterinarians wore farm-specific boots on eight farms (40%) and farm-specific clothes on six farms (30%), while technical advisors wore farm-specific boots on six farms (30%) and farm-specific clothes on four farms (20%). Disinfection footbaths were only used in five farms (25%) despite being present in all farms in the sample. Concerning internal biosecurity, none of the farmers isolated sick animals; only one farmer (5%) had a physically separated hospital pen, and only 11 farmers (55%) both cleaned and disinfected the stables after each production cycle. In most farms, animals were of comparable age. Healthy calves generally remained in the same compartment during the entire production cycle, limiting the risks associated with the movement of animals. No influence of the integrations on the biosecurity level could be determined. It can be concluded that a few biosecurity measures, such as “‘all-in, all-out” and compartmentation, are implemented relatively well, while other measures, such as good cleaning and disinfection and proper entrance measures for visitors and personnel can easily be improved. The improvement of measures regarding the introduction of animals of different origins will require more fundamental changes in the veal industry.


title: Coronaviruses SD and SK share extensive nucleotide homology with murine coronavirus MHV-A59, more than that shared between human and murine coronaviruses

text: A cDNA probe representing the genome of mouse hepatitis virus (MHV) strain A59 (MHV-A59) was used to measure nucleotide sequence homologies among murine and human coronaviruses and the SD and SK coronaviruses isolated by Burks et al. Since SD and SK were isolated by inoculation of multiple sclerosis (MS) central nervous system (CNS) tissue into mice or cultured mouse cells, it is important to determine their relationships to other murine and human coronavirus isolates. Our results indicate that SD and SK share almost complete nucleotide homology (approximately 90%) with MHV-A59 and generate subgenomic RNAs of the same sizes as MHV-A59. The human coronavirus (HCV) strains tested show less homology with MHV-A59. The immunologically unrelated HCV-229 E shows no nucleotide homology with MHV-A59. The immunologically crossreactive HCV-OC43 shows nucleotide homology with MHV-A59 by blot hybridization but not when hybridized in solution and assayed by S1 nuclease digestion.


Electron microscopy studies of the coronavirus ribonucleoprotein complex


RAPID SALIVARY TEST SUITABLE FOR A MASS SCREENING PROGRAM TO DETECT SARS-COV-2: A DIAGNOSTIC ACCURACY STUDY


title: Epitopes on the peplomer protein of infectious bronchitis virus strain M41 as defined by monoclonal antibodies

text: Abstract Sixteen monoclonal antibodies (Mcabs) were prepared against infectious bronchitis virus strain M41, all of them reacting with the peplomer protein. One of them, Mcab 13, was able to neutralize the virus and to inhibit hemagglutination. Competition binding assays allowed the definition of five epitopes, designated as A, B, C, D, and E, of which epitopes A and B are overlapping. Furthermore, the binding of Mcab 13 (epitope E) could be enhanced by the addition of Mcabs from group B, C, and D. A dot immunoblot assay was used to analyze the effect of denaturation on antibody recognition of the epitopes. Only the binding of Mcab 13 was affected, indicating that the epitope involved in neutralization and hemagglutination is conformation dependent. The epitopes A to D were highly conserved among IBV strains, while epitope E was specific for strains M41 and D3896. In this last strain, however, this epitope was not involved in neutralization.


title: Evaluation of the filtration performance of 21 N95 filtering face piece respirators after prolonged storage

text: BACKGROUND: Organizations are stockpiling respirators to prepare for an influenza pandemic. To understand better the effects of prolonged storage, this investigation evaluated the filtration efficiency of 21 different models of National Institute for Occupational Safety and Health (NIOSH)-certified disposable N95 filtering face piece respirators. These respirators had been stored in their original packaging for a period of at least 6 years in research laboratories and dry warehouse facilities, ranging in temperature between 15°C and 32°C and relative humidity between 20% and 80%. METHODS: Filter penetration was measured using an abbreviated version of the NIOSH respirator certification test incorporating a polydisperse sodium chloride aerosol at 85 L/min. RESULTS: Of the 21 respirator models tested, 19 models had both average penetration results of less than 5%. Mean initial penetration values ranged from 0.39% to 5.83%, whereas mean maximum penetration values ranged from 0.95% to 5.83%. There did not appear to be any correlation between the length of storage and failure to pass the filtration test. CONCLUSION: Results indicate that most N95 filtering face piece respirators stored for up to 10 years at warehouse conditions will likely have expected levels of filtration performance and that the degree of filtration efficiency degradation is likely model specific.


title: A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

text: BACKGROUND: The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. METHODS: PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. RESULTS: We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. CONCLUSIONS: The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.


title: Non-plaque-forming virions of Modified Vaccinia virus Ankara express viral genes

text: Abstract In cell culture infections with vaccinia virus the number of counted virus particles is substantially higher than the number of plaques obtained by titration. We found that standard vaccine preparations of recombinant Modified Vaccinia virus Ankara produce only about 20–30% plaque-forming virions in fully permissive cell cultures. To evaluate the biological activity of the non-plaque-forming particles, we generated recombinant viruses expressing fluorescent reporter proteins under transcriptional control of specific viral early and late promoters. Live cell imaging and automated counting by fluorescent microscopy indicated that virtually all virus particles can enter cells and switch on viral gene expression. Although most of the non-plaque-forming infections are arrested at the level of viral early gene expression, we detected activation of late viral transcription in 10–20% of single infected cells. Thus, non-plaque-forming particles are biologically active, and likely contribute to the immunogenicity of vaccinia virus vaccines.


title: Pediatric Fluid Therapy

text: Many conditions of pediatric patients require fluid therapy. Depending on the veterinarian's assessment of hydration and perfusion status, fluids can be administered orally, subcutaneously, intraperitoneally, intravenously, or by the intraosseous route. Pediatric patients are prone to hypothermia, hypovolemia, hypoglycemia, and hypokalemia, which must be addressed during fluid therapy in pediatric patients. Typical parameters used to assess hydration status in adult animals do not always apply to pediatric patients. Veterinarians should be aware of differences between pediatric patients and adult animals in terms of physical assessment, common presentations, and fluid requirements for resuscitation and maintenance needs.


title: Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 During the Pandemic Crisis

text: Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB’s instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial’s scientific integrity.


title: Sars-cov-2 host entry and replication inhibitors from Indian ginseng: an in-silico approach

text: COVID-19 has ravaged the world and is the greatest of pandemics in modern human history, in the absence of treatment or vaccine, the mortality and morbidity rates are very high. The present investigation identifies potential leads from the plant Withania somnifera (Indian ginseng), a well-known antiviral, immunomodulatory, anti-inflammatory and a potent antioxidant plant, using molecular docking and dynamics studies. Two different protein targets of SARS-CoV-2 namely NSP15 endoribonuclease and receptor binding domain of prefusion spike protein from SARS-CoV-2 were targeted. Molecular docking studies suggested Withanoside X and Quercetin glucoside from W. somnifera have favorable interactions at the binding site of selected proteins, that is, 6W01 and 6M0J. The top-ranked phytochemicals from docking studies, subjected to 100 ns molecular dynamics (MD) suggested Withanoside X with the highest binding free energy (ΔG(bind) = −89.42 kcal/mol) as the most promising inhibitor. During MD studies, the molecule optimizes its conformation for better fitting with the receptor active site justifying the high binding affinity. Based on proven therapeutic, that is, immunomodulatory, antioxidant and anti-inflammatory roles and plausible potential against n-CoV-2 proteins, Indian ginseng could be one of the alternatives as an antiviral agent in the treatment of COVID 19. Communicated by Ramaswamy H. Sarma


title: Fetal programming of schizophrenia: Select mechanisms

text: Abstract Mounting evidence indicates that schizophrenia is associated with adverse intrauterine experiences. An adverse or suboptimal fetal environment can cause irreversible changes in brain that can subsequently exert long-lasting effects through resetting a diverse array of biological systems including endocrine, immune and nervous. It is evident from animal and imaging studies that subtle variations in the intrauterine environment can cause recognizable differences in brain structure and cognitive functions in the offspring. A wide variety of environmental factors may play a role in precipitating the emergent developmental dysregulation and the consequent evolution of psychiatric traits in early adulthood by inducing inflammatory, oxidative and nitrosative stress (IO&NS) pathways, mitochondrial dysfunction, apoptosis, and epigenetic dysregulation. However, the precise mechanisms behind such relationships and the specificity of the risk factors for schizophrenia remain exploratory. Considering the paucity of knowledge on fetal programming of schizophrenia, it is timely to consolidate the recent advances in the field and put forward an integrated overview of the mechanisms associated with fetal origin of schizophrenia.


title: Synthesis and pharmacological evaluation of (2-oxaadamant-1-yl)amines

text: The synthesis of several (2-oxaadamant-1-yl)amines is reported. They were evaluated as NMDA receptor antagonists and several of them were more active than amantadine, but none was more potent than memantine. None of the tested compounds displayed antiviral activity. Two of the derivatives showed a significant level of trypanocidal activity.


title: Dinámica de anticuerpos neutralizantes contra el virus respiratorio sincicial bovino

text: Abstract Bovine respiratory syncytial virus (BRSV) is one of the most relevant agents responsible for respiratory disease in cattle from both dairy and beef farms. BRSV is spread by horizontal contact causing a constant presence of seropositive animals that favors viral circulation throughout the year. Moreover, reinfections with BRSV are frequent between animals regardless of their age as BRSV does not confer long-lasting protective immunity. Several studies have demonstrated the circulation of BRSV in cattle from different regions of the world; however, little is known about the dynamics of BRSV infection in cows before and after they begin lactation. The aim of this work was to study the dynamics of BRSV neutralizing antibodies from birth up to 36 months of age in a closed dairy herd of Argentina specifically around the lactation period. Passive maternal antibodies against BRSV started to decrease monthly and became almost undetectable at 8 months of age. We detected two potential infection points at months 11 and 27 after birth, in which 30% and 45% of the animals showed seroconversion, respectively. Specifically, an increase in the proportion of seropositive cows after the start of lactation suggests that they became reinfected around the time they began lactating. We demonstrate the importance of understanding BRSV dynamics in a closed dairy herd to review the vaccination schedule of the animals to achieve protection against BRSV infection.


title: Generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies

text: Indoor air can be an important vehicle for a variety of human pathogens. This review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. The following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (Aspergillus, Penicillium, and Cladosporium spp and Stachybotrys chartarum), enteric viruses (noro- and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (Clostridium difficile and Bacillus anthracis). An overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. Available guidelines from the U.S. Environmental Protection Agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. Recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under field-relevant conditions. Furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed.


docid: gduhterq

title: Cardiovascular Clinical Trials in a Pandemic: Immediate Implications of Coronavirus Disease 2019

text: The coronavirus disease 2019 (COVID-19) pandemic started in Wuhan, Hubei Province, China, in December 2019, and by 24 April 2020, it had affected >2.73 million people in 185 countries and caused >192,000 deaths. Despite diverse societal measures to reduce transmission of the severe acute respiratory syndrome coronavirus 2, such as implementing social distancing, quarantine, curfews and total lockdowns, its control remains challenging. Healthcare practitioners are at the frontline of defence against the virus, with increasing institutional and governmental supports. Nevertheless, new or ongoing clinical trials, not related to the disease itself, remain important for the development of new therapies, and require interactions among patients, clinicians and research personnel, which is challenging, given isolation measures. In this article, the authors summarise the acute effects and consequences of the COVID-19 pandemic on current cardiovascular trials.


title: High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl

text: Coronaviruses (CoVs) are found in a wide variety of wild and domestic animals, and constitute a risk for zoonotic and emerging infectious disease. In poultry, the genetic diversity, evolution, distribution and taxonomy of some coronaviruses have been well described, but little is known about the features of CoVs in wild birds. In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. The highest prevalence was found in the diving ducks—mainly Greater Scaup (Aythya marila; 51.5%)—and the dabbling duck Mallard (Anas platyrhynchos; 19.2%). Sequences from two of the Greater Scaup CoV fell into an infrequently detected lineage, shared only with a Tufted Duck (Aythya fuligula) CoV. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. A single Black-headed Gull represented the only positive sample from the order Charadriiformes. Globally, Anas species represent the largest fraction of avian CoV sequences, and there seems to be no host species, geographical or temporal structure. To better understand the eitiology, epidemiology and ecology of these viruses more systematic surveillance of wild birds and subsequent sequencing of detected CoV is imperative.


title: Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1) Formulated with Alum Induces Protective Immunity and Reduces Immune Enhancement

text: We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a highyielding, yeast- engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high-level neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ~ 30% mortality in mice when immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and other emerging and re-emerging beta-CoVs such as SARS-CoV-2.


title: SARS CORONAVIRUS AND INNATE IMMUNITY

text: The emergence of the highly pathogenic SARS coronavirus (SARS-CoV) has reignited interest in coronavirus biology and pathogenesis. An emerging theme in coronavirus pathogenesis is that the interaction between specific viral genes and the host immune system, specifically the innate immune system, functions as a key determinant in regulating virulence and disease outcomes. Using SARS-CoV as a model, we will review the current knowledge of the interplay between coronavirus infection and the host innate immune system in vivo, and then discuss the mechanisms by which specific gene products antagonize the host innate immune response in cell culture models. Our data suggests that the SARS-CoV uses specific strategies to evade and antagonize the sensing and signaling arms of the interferon pathway. We summarize by identifying future points of consideration that will contribute greatly to our understanding of the molecular mechanisms governing coronavirus pathogenesis and virulence, and the development of severe disease in humans and animals.


title: The effect of intranasal nedocromil sodium on viral upper respiratory tract infections in human volunteers

text: Two studies involving double‐blind group comparative trials in human volunteers compared the effects of intranasal nedocromil sodium (2·6 mg active drug per nostril, q.i.d.) with placebo on clinical symptoms and performance impairment associated with the common cold. In the first study volunteers were challenged with rhinoviruses (RV9 and RV14), and in the second study with respiratory coronavirus. In both studies, active and placebo groups of volunteers were demographically similar. Infection rates in both groups were also similar. There were no withdrawals resulting from unusual symptoms related to either treatment. In the rhinovirus study (19, placebo; 20, nedocromil sodium) daily symptom scores and daily mean nasal secretion weights were significantly lower in the nedocromil sodium‐treated group. In the coronavirus study (26, placebo; 27, nedocromil sodium) there was little difference in the severity of colds between the active and placebo‐treated groups, but trends favoured nedocromil sodium. In both studies the impairment of performance in volunteers who developed a cold was significantly less in those treated with nedocromil sodium than in those treated with placebo.


docid: arujgzog

title: Porcine hemagglutinating encephalomyelitis virus induces apoptosis in a porcine kidney cell line via caspase-dependent pathways

text: Abstract Porcine hemagglutinating encephalomyelitis is an acute, highly contagious disease in piglets that is caused by the porcine hemagglutinating encephalomyelitis virus (PHEV). However, the pathogenesis of PHEV and the relationship between PHEV and the host cells are not fully understood. In this study, we investigated whether the PHEV-induced cytopathic effect (CPE) was caused by apoptosis. Replication of PHEV in a porcine kidney-derived cell line (PK-15 cells) caused an extensive CPE, leading to the destruction of the entire monolayer and the death of the infected cells. Staining with Hoechst 33,342 revealed morphological changes in the nuclei and chromatin fragmentation. In addition, PHEV caused DNA fragmentation detectable by agarose gel electrophoresis 48h post-infection, increasing with the incubation time. The percentage of apoptotic cells increased with the incubation time and reached a maximum at 96h post-infection, as determined using flow cytometry and fluorescence microscopy of cells that were stained with annexin V-FITC and propidium iodide (PI). Moreover, as is commonly observed for coronavirus infections of other animals, the activities of the effecter caspase, caspase-3, and the initiator caspases, caspase-8 and caspase-9, which are representative factors in the death receptor-mediated apoptotic pathway and the mitochondrial apoptotic pathway, respectively, were increased in PHEV-infected PK-15 cells. Moreover, the tripeptide pan-ICE (caspase) inhibitor Z-VAD-FMK blocked PHEV-induced apoptosis but did not have an effect on virus production by 96h post-infection. These results suggested that PHEV induces apoptosis in PK-15 cells via a caspase-dependent pathway. Apoptotic death of infected cells is detrimental to animals because it causes cell and tissue destruction. Although the pathological characteristics of PHEV are largely unknown, apoptosis may be the pathological basis of the lesions resulting from PHEV infection.


title: Chatbots in the fight against the COVID-19 pandemic

text: We are all together in a fight against the COVID-19 pandemic. Chatbots, if effectively designed and deployed, could help us by sharing up-to-date information quickly, encouraging desired health impacting behaviors, and lessening the psychological damage caused by fear and isolation. Despite this potential, the risk of amplifying misinformation and the lack of prior effectiveness research is cause for concern. Immediate collaborations between healthcare workers, companies, academics and governments are merited and may aid future pandemic preparedness efforts.


title: Novel insights into bat influenza A viruses

text: In 2012 and 2013, influenza virus genome sequences of two new influenza A virus (IAV) subtypes were discovered in bat specimens, but further characterization was largely impeded by the lack of infectious virus. With the identification of highly susceptible cell lines, reconstitution of infectious bat IAV by reverse genetics recently succeeded and allowed a first insight into the life cycle of these viruses. Although there is a certain degree of functional compatibility between bat and conventional influenza A virus proteins, there are striking differences, including receptor usage, polarity of infection and reassortment potential.


title: Where are we with understanding of COVID-19?

text: Coronavirus disease 2019 caused by SARS-CoV-2 originated from China and spread across every corner of the world. The scientific interest on COVID-19 increased after WHO declared it a pandemic in the early February of 2020. In fact, this pandemic has had a worldwide impact on economy, health, and lifestyle like no other in the last 100 years. SARS-CoV-2 belongs to Coronaviridae family and causes the deadliest clinical manifestations when compared to other viruses in the family. COVID-19 is an emerging zoonotic disease that has resulted in over 383,000 deaths around the world. Scientists are scrambling for ideas to develop treatment and prevention strategies to thwart the disease condition. In this review, we have attempted to summarize the latest information on the virus, disease, prevention, and treatment strategies. The future looks promising.


title: Translocation of proteins across the endoplasmic reticulum

text: Abstract The past year has seen significant advances in the field of protein translocation: the roles of the signal recognition particle and its receptor have been understood in greater detail; many membrane components responsible for translocation have been identified; and insight has been gained into how proteins cross membranes.


title: I heard it through the grapevine: On herd immunity and why it is important

text: A. David Napier has been studying immunology and immunologists for more than three decades. In this article, he argues that the medicalization of viral epidemics has distracted us from the importance of their true social drivers: that is, the behaviour of people when they are together – what epidemiologists call human herds. On their own, viruses cannot ‘invade’ us. Our cells bring them to life and make them infectious through our social actions. Confusing viruses with invasive microbes not only leads us to misuse antibiotics, but fosters xenophobic responses towards outside carriers – as even our neighbours become categorical ‘others’ in the face of a foreign threat. Indeed, new work in viral epidemiology indicates that many viruses have infectious potential long before an epidemic develops. It is not only changes within viruses that cause epidemics, but also the condition of human herds – how we behave socially – that ignites the rapid circulation of viral information.


title: The COVID-19 pandemic in Africa: What can we expect?

text: In this paper we discuss the particularities of the COVID-19 pandemic in Africa, we comment on the first available data concerning the evolution of mortality rates. We think that our comments will help the decision-makers in Africa in their choices related to COVID-19 pandemic management.


docid: bjvuxcov

title: IFNL4-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections

text: Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the IFNL4 gene encoding interferon λ4. Since the IFNL4-ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an IFNL4-ΔG-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of IFNL4-ΔG have a significantly increased risk of prostate cancer while those with the same number of partners but lacking IFNL4-ΔG do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and IFNL4-ΔG in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene–environment interaction between IFNL4-ΔG and sexual activity may increase the risk of prostate cancer.


title: Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis

text: Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2′O-methyltransferase (2′O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2′O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and in vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2′O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. IMPORTANCE Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′O-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2′O-MTase function across CoVs.


Commentary: Let’s start again!


title: Companion animal disease surveillance: A new solution to an old problem?

text: Abstract Infectious disease surveillance in companion animals has a long history. However, it has mostly taken the form of ad hoc surveys, or has focused on adverse reactions to pharmaceuticals. In 2006 a Blue Ribbon Panel was convened by the U.S. White House Office of Science and Technology Policy to discuss the potential utility of a national companion animal health surveillance system. Such a system could provide fundamental information about disease occurrence, transmission and risk factors; and could facilitate industry-supported pharmaco-epidemiological studies and post-market surveillance. Disease WatchDog, a prospective national disease surveillance project, was officially launched in January 2010 to capture data on diseases in dogs and cats throughout Australia. Participation is encouraged by providing registrants real-time disease maps and material for improved communication between veterinarians and clients. From January to mid-November 2010, an estimated 31% of veterinary clinics Australia-wide joined the project. Over 1300 disease cases – including Canine Parvovirus (CPV), Canine Distemper, Canine Hepatitis, Feline Calicivirus, Feline Herpesvirus, and Tick Paralysis – were reported. In New South Wales alone, 552 CPV cases in dogs were reported from 89 postcode locations. New South Wales data was scanned using the space–time permutation test. Up to 24 clusters (P <0.01) were identified, occurring in all months except March. The greatest number of clusters (n =6) were identified in April. The most likely cluster was identified in western Sydney, where 36 cases of CPV were reported from a postcode in February. Although the project is still in its infancy, already new information on disease distribution has been produced. Disease information generated could facilitate targeted control and prevention programs.


title: Anti-dengue virus serotype 2 activity of tannins from porcupine dates

text: BACKGROUND: Dengue fever is currently endemic in tropical and subtropical countries worldwide and effective drug against DENV infection is still unavailable. Porcupine dates, which are traditionally used to treat dengue fever, might contain potential anti-dengue compounds. Two porcupine dates, black date (BD) and powdery date (PD) from Himalayan porcupine (Hystrix brachyura), were investigated for their antiviral activities against DENV-2 in vitro. METHODS: The methanol crude extracts (MBD and MPD) were prepared from the raw material of porcupine dates. The tannin-rich fractions (BDTF and PDTF) were isolated from their methanol crude extracts using column chromatography. The presence of tannins in BDTF and PDTF extracts was determined by fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analyses. The cytotoxicity and anti-DENV-2 activities including virus yield inhibition, virucidal, virus attachment and pre-treatment assays of the extracts were examined in Vero cells. RESULTS: Our findings revealed that all the extracts of porcupine dates exhibited antiviral activity against DENV-2 in Vero cells. The IC(50) of BDTF and PDTF were 25 µg/mL and 11 µg/mL respectively, while their methanol crude extracts demonstrated lower antiviral efficacy (IC(50) ≈ 101–107 µg/mL). BDTF and PDTF also exerted a similar higher virucidal effect (IC(50) of 11 µg/mL) than methanol crude extracts (IC(50) ≈ 52–66 µg/mL). Furthermore, all the extracts inhibited the attachment of DENV-2 by at least 80%. Pre-treatments of cells with BDTF and PDTF markedly prevented DENV-2 infection when compared to methanol crude extracts. CONCLUSION: This study suggests that porcupine dates possess antiviral properties against DENV-2, which is attributed to its tannin compounds.


title: Anti-inflammatory and antipyretic properties of Kang 601 heji, a traditional Chinese oral liquid dosage form

text: Abstract Objective To evaluate the scientific basis for the use of Kang 601 heji (K-601) as an anti-inflammatory and antipyretic agent using appropriate animal models. Methods Carrageenan-induced rat paw and xylene-induced ear oedemas were models used to investigate anti-inflammatory actions of K-601. Lipopolysaccharide-induced pyrexia model was used to evaluate antipyretic activity in Wistar rats. The anti-inflammatory and antipyretic mechanisms were evaluated by detecting prostaglandins E2, nitric oxide, interleukin-1β and tumour necrosis factor-α levels using appropriate reagents and ELISA kits. Results The results revealed that K-601 reduced the level of inflammations in both anti-inflammatory models in a dose-dependent manner. The same was true for the antipyretic model. The possible mechanisms of actions were through the inhibition of prostaglandins E2, interleukin-1β, tumour necrosis factor-α and nitric oxide. Conclusions K-601 has proven anti-inflammatory and antipyretic actions. The findings provide a scientific basis for the use of K-601 as anti-inflammatory and antipyretic agent in traditional Chinese medicinal practice.


COVID-19–related Mortality During the First 60 Days After Kidney Transplantation


title: Benzylidene/2-chlorobenzylidene hydrazides: Synthesis, antimicrobial activity, QSAR studies and antiviral evaluation

text: A series of benzylidene hydrazides (1–20) was synthesized and tested, in vitro, for antibacterial, antifungal and antiviral activities. The microbial screening results indicated that compounds having chloro and nitro substituents were the most active ones. The antiviral evaluation depicted that compounds 9 and 19 were active against Vesicular stomatitis virus (VSV) in HeLa cell cultures. QSAR investigations indicated that the multi-target QSAR model was effective in describing the antimicrobial (antibacterial and antifungal) activity over the one-target QSAR models. Further the mt-QSAR model indicated that the topological parameters, second order molecular connectivity index ((2)χ) and third order Kier's alpha shape index (κα(3)) are effective in describing the antimicrobial activity of synthesized hydrazides.


title: Severe COVID-19 in the young and healthy: monogenic inborn errors of immunity?

text: Severe COVID-19 is rare in previously healthy individuals who are less than 50 years of age, affecting probably no more than 1 in 1,000 such infected individuals. We suggest that these patients may become critically ill because of monogenic inborn errors that disrupt protective immunity to SARS-CoV-2.


docid: jcnausya

title: Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China

text: BACKGROUND: Appropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus. METHODS: We collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure. RESULTS: Demographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou. CONCLUSIONS: We demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.


title: Doxycycline Induces Mitophagy and Suppresses Production of Interferon-β in IPEC-J2 Cells

text: Previous reports have demonstrated that the second-generation tetracycline derivative doxycycline (DOX) interrupts mitochondrial proteostasis and physiology, inhibits proliferation of many cell types, and induces apoptosis. However, the effects of DOX, which is widely used in porcine husbandry by feed, on the porcine intestinal epithelium are unclear. In this study, we demonstrated that DOX damaged mitochondrial morphology and induced the co-localization of mitochondria with autophagosomes, suggesting that DOX induces mitophagy in IPEC-J2 cells. We also found evidence that DOX increased intracellular levels of reactive oxygen species (ROS) or mitochondrial-specific ROS in a dose dependent manner. Moreover, 50 μg/ml DOX significantly decreased production of interferon-β and facilitated replication of transmissible gastroenteritis coronavirus in IPEC-J2 cells. These results demonstrated that DOX induced mitophagy and ROS production, which damaged the intestinal epithelium. As DOX is used extensively in pig husbandry, uncontrolled application poses a significant threat of viral infection, so stricter policies on its usage should be required.


title: A role for Streptococcus pneumoniae in virus-associated pneumonia

text: Here we show, in a double-blind, randomized, placebo-controlled trial in 37,107 fully immunized infants in Soweto, South Africa, that a 9-valent pneumococcal conjugate vaccine, PncCV, prevents 31% (95% confidence interval = 15–43%) of pneumonias associated with any of seven respiratory viruses in children in hospital. These data suggest that the pneumococcus has a major role in the development of pneumonia associated with these viruses and that viruses contribute to the pathogenesis of bacterial pneumonia. NOTE: In the version of this article originally published online, the species name was misspelled Streptococcus pnemoniae in the title of the article. The name should be Streptococcus pneumoniae . This error has been corrected for the HTML and print versions of the article. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1077) contains supplementary material, which is available to authorized users.


title: Evolution of genomes, host shifts and the geographic spread of SARS‐CoV and related coronaviruses

text: Severe acute respiratory syndrome (SARS) is a novel human illness caused by a previously unrecognized coronavirus (CoV) termed SARS‐CoV. There are conflicting reports on the animal reservoir of SARS‐CoV. Many of the groups that argue carnivores are the original reservoir of SARS‐CoV use a phylogeny to support their argument. However, the phylogenies in these studies often lack outgroup and rooting criteria necessary to determine the origins of SARS‐CoV. Recently, SARS‐CoV has been isolated from various species of Chiroptera from China (e.g., Rhinolophus sinicus) thus leading to reconsideration of the original reservoir of SARS‐CoV. We evaluated the hypothesis that SARS‐CoV isolated from Chiroptera are the original zoonotic source for SARS‐CoV by sampling SARS‐CoV and non‐SARS‐CoV from diverse hosts including Chiroptera, as well as carnivores, artiodactyls, rodents, birds and humans. Regardless of alignment parameters, optimality criteria, or isolate sampling, the resulting phylogenies clearly show that the SARS‐CoV was transmitted to small carnivores well after the epidemic of SARS in humans that began in late 2002. The SARS‐CoV isolates from small carnivores in Shenzhen markets form a terminal clade that emerged recently from within the radiation of human SARS‐CoV. There is evidence of subsequent exchange of SARS‐CoV between humans and carnivores. In addition SARS‐CoV was transmitted independently from humans to farmed pigs (Sus scrofa). The position of SARS‐CoV isolates from Chiroptera are basal to the SARS‐CoV clade isolated from humans and carnivores. Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS‐CoV, the structural biology of the spike protein of SARS‐CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS‐CoV, angiotensin‐converting enzyme 2 (ACE2). In SARS‐CoV we study, both visually and statistically, labile genomic fragments and, putative key mutations of the spike protein that may be associated with host shifts. We display host shifts and candidate mutations on trees projected in virtual globes depicting the spread of SARS‐CoV. These results suggest that more sampling of coronaviruses from diverse hosts, especially Chiroptera, carnivores and primates, will be required to understand the genomic and biochemical evolution of coronaviruses, including SARS‐CoV. © The Willi Hennig Society 2008.


title: Rethinking the need for overnight admission after robotic-assisted laparoscopic prostatectomy

text: Robotic-assisted laparoscopic prostatectomy (RALP) is the gold standard for the surgical management of localized prostate cancer (PCa). Multi-institutional series have demonstrated complications and readmissions in less than 5% of patients and most are now discharged within 24 h of surgery. Recently, several high-volume surgeons demonstrated the safety of same-day discharge (SDD) after RALP. The main benefits include lower costs and reduced exposure to nosocomial infections and hospital errors. The leading arguments for criticism include potential suboptimal postoperative care and the risk of missing a catastrophic event. In recent years, important advances have further strengthened the argument for SDD including more structured perioperative care, integration of single-port robotic systems, and new challenges presented by the coronavirus 2019 (COVID-19) pandemic. Here, we provide further evidence demonstrating the safety of SDD in a multi-institutional cohort of patients and review the main arguments supporting the expanded use of this approach.


title: Real time detection of farm-level swine mycobacteriosis outbreak using time series modeling of the number of condemned intestines in abattoirs

text: Mycobacteriosis in swine is a common zoonosis found in abattoirs during meat inspections, and the veterinary authority is expected to inform the producer for corrective actions when an outbreak is detected. The expected value of the number of condemned carcasses due to mycobacteriosis therefore would be a useful threshold to detect an outbreak, and the present study aims to develop such an expected value through time series modeling. The model was developed using eight years of inspection data (2003 to 2010) obtained at 2 abattoirs of the Higashi-Mokoto Meat Inspection Center, Japan. The resulting model was validated by comparing the predicted time-dependent values for the subsequent 2 years with the actual data for 2 years between 2011 and 2012. For the modeling, at first, periodicities were checked using Fast Fourier Transformation, and the ensemble average profiles for weekly periodicities were calculated. An Auto-Regressive Integrated Moving Average (ARIMA) model was fitted to the residual of the ensemble average on the basis of minimum Akaike’s information criterion (AIC). The sum of the ARIMA model and the weekly ensemble average was regarded as the time-dependent expected value. During 2011 and 2012, the number of whole or partial condemned carcasses exceeded the 95% confidence interval of the predicted values 20 times. All of these events were associated with the slaughtering of pigs from three producers with the highest rate of condemnation due to mycobacteriosis.


title: Low incidence of severe respiratory syncytial virus infections in lung transplant recipients despite the absence of specific therapy

text: Background Respiratory syncytial virus (RSV) infections in lung transplant recipients (LTRs) have been associated with significant morbidity and mortality. Immunoglobulins, ribavirin, and palivizumab are suggested treatments for both pre-emptive and therapeutic purposes. However, in the absence of randomized, placebo-controlled trials, efficacy is controversial and there is toxicity as well as cost concerns. Methods We retrospectively reviewed cases of lower respiratory tract RSV infections in adult LTRs. Diagnosis was based on clinical history, combined with a positive polymerase chain reaction (PCR) and/or viral cultures of bronchoalveolar lavage (BAL) specimens. Results Ten symptomatic patients were identified (7 men and 3 women, age range 28 to 64 years). All were hospitalized for community-acquired respiratory tract infections. Two patients had a concomitant acute Grade A3 graft rejection, and 1 patient had a concomitant bacterial pneumonia. Eight patients did not receive a specific anti-RSV treatment because of clinical stability and/or improvement at the time of RSV diagnosis. Only 2 patients (1 with Grade A3 allograft rejection and 1 requiring mechanical ventilation) received ribavirin and palivizumab. All patients recovered without complications and with no persistent RSV infection. However, bronchiolitis obliterans (BOS) staging worsened in 6 patients during the mean follow-up of 45 months. Conclusions Our data suggest that mild RSV infections in LTRs might evolve favorably in the absence of specific anti-viral therapy. However, this observation needs confirmation in a large clinical trial specifically investigating the development of BOS in untreated vs treated patients.


title: Suppression of immune response induction in Peyer's patch lymphoid cells from mice infected with mouse hepatitis virus

text: Abstract Multiple previous studies have demonstrated significant alterations of immunologic parameters associated with mouse hepatitis virus (MHV) infection, but effects of the virus on mucosal lymphoid cells have not been examined. Coincident with a natural outbreak of MHV at our institution, we noted alterations in immunoglobulin secretion by mature Peyer's patch B cells under an inductive stimulus provided by dendritic cells and mitogen-activated T cells (DC-T). MHV was isolated from mice affected during the outbreak, and experimental infection of mice with the isolate consistently resulted in failures of immunoglobulin secretion by cocultures of Peyer's patch DC-T and B cells. In subsequent experiments, MHV appeared to negatively affect DC-T more than B cells. Therefore, the effects of inapparent MHV infection on experimental mucosal immune responses can result from natural infection and can be experimentally reproduced.


title: Effect of proactive infection control measures on benchmarked rate of hospital outbreaks: An analysis of public hospitals in Hong Kong over 5 years

text: BACKGROUND: Hospital outbreaks of epidemiologically important pathogens are usually caused by lapses in infection control measures and result in increased morbidity, mortality, and cost. However, there is no benchmark to compare the occurrence of hospital outbreaks across hospitals. METHODS: We implemented proactive infection control measures with an emphasis on timely education of health care workers and hospitalized patients at Queen Mary Hospital, a teaching hospital. Our benchmarked performance (outbreak episodes per 1 million patient discharges and 1 million patient-days) was compared with those of other regional public hospitals without these additional proactive measures in place between 2010 and 2014. RESULTS: During the study period, Queen Mary Hospital had 1 hospital outbreak resulting in 1.48 and 0.45 outbreak episodes per 1 million patient discharges and patient-days, respectively, values significantly lower than the corresponding overall rates in the 7 acute regional hospitals (24.26 and 6.70 outbreak episodes per 1 million patient discharges and patient-days, respectively; P < .001) and that of all 42 public hospitals in Hong Kong (41.62 and 8.65 outbreak episodes per 1 million patient discharges and patient-days, respectively; P < .001). CONCLUSIONS: The results of this large study on benchmarked rate of hospital outbreaks per patient discharges or patient-days suggests that proactive infection control interventions may minimize the risk of hospital outbreaks.


title: SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex

text: SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.


title: 15 Nanocomposite biosensors for point-of-care—evaluation of food quality and safety

text: Abstract Nanosensors have wide applications in the food industry. Nanosensors based on quantum dots for heavy metal and organophosphate pesticides detection, and nanocomposites as indicators for shelf life of fish/meat products, have served as important tools for food quality and safety assessment. Luminescent labels consisting of NPs conjugated to aptamers have been popular for rapid detection of infectious and foodborne pathogens. Various detection technologies, including microelectromechanical systems for gas analytes, microarrays for genetically modified foods, and label-free nanosensors using nanowires, microcantilevers, and resonators are being applied extensively in the food industry. An interesting aspect of nanosensors has also been in the development of the electronic nose and electronic tongue for assessing organoleptic qualities, such as, odor and taste of food products. Real-time monitoring of food products for rapid screening, counterfeiting, and tracking has boosted ingenious, intelligent, and innovative packaging of food products. This chapter will give an overview of the contribution of nanotechnology-based biosensors in the food industry, ongoing research, technology advancements, regulatory guidelines, future challenges, and industrial outlook.


title: Editorial: low population mortality from COVID‐19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity

text: LINKED CONTENT This article is linked to Al‐Ani et al and Garg et al papers. To view these articles, visit https://doi.org/10.1111/apt.15779 and https://doi.org/10.1111/apt.15796.


title: Optimizing your telemedicine visit during the COVID‐19 pandemic: Practice guidelines for patients with head and neck cancer

text: The COVID‐19 epidemic has resulted in many hospitals and practices to cancel in‐person outpatient clinic visits, where head and neck patients receive their critical longitudinal care. Out of necessity, most practices have been encouraged to use telemedicine as a method to maintain a continuum of care with their patients. As a result, the prevalence of telemedicine has grown rapidly during this pandemic, without allowing the physicians and patients to be adequately educated on how best to utilize the services. There is a steep learning curve as we have learned, and our goal is to provide guidelines for both patients and physicians, as well as a valuable patient handout in preparation for their visit.


title: Meeting report: 32nd International Conference on Antiviral Research

text: Abstract The 32nd International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held in Baltimore, Maryland, USA, on May 12–15, 2019. This report gives an overview of the conference on behalf of the Society. It provides a general review of the meeting and awardees, summarizing the presentations, and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development. As in past years, ICAR promoted and showcased the most recent progress in antiviral research, and continued to foster collaborations and interactions in drug discovery and development. The 33rd ICAR will be held in Seattle, Washington, USA, March 30th-April 3rd, 2020.


title: Molecular characterization of a canine respiratory coronavirus strain detected in Italy

text: Abstract Coronaviruses (CoVs) are positive-stranded, non-segmented RNA viruses generally responsible for the emergence of respiratory and enteric disease in humans, companion animals and livestock. Their aptitude to evolve by genetic recombination and/or point mutation is recognized, thus giving rise to new viral genotypes and mutants with different tissues or host tropism. In particular, a probable origin from the strictly related bovine coronavirus (BCoV) or, alternatively, from a common ancestor has been suggested for some group 2a CoVs, including canine respiratory coronavirus (CRCoV). In this study, we report the sequence analysis of the viral RNA 3′-end of an Italian CRCoV, strain 240/05, together with the sequence comparison with extant bovine-like viruses including the sole CRCoV strain 4182 previously described. Interestingly, although the structural proteins show the same features of CRCoV 4182, the genomic region between the spike and the envelope protein genes of CRCoV 240/05 encodes for three distinct products, including the equivalent bovine 4.9kDa non-structural protein and a truncated form of the 4.8kDa protein, whereas CRCoV 4182 has a unique 8.8kDa protein.


Evaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV Vaccine


title: High frequency of polyoma BK virus shedding in the gastrointestinal tract after hematopoietic stem cell transplantation: a prospective and quantitative analysis

text: The polyoma BK virus (BKV) remains latent after primary infection and may reactivate during immunosuppression. The uroepithelium is the main latency site defined. This study addressed whether the gastrointestinal tract might be another latency site. To test this hypothesis, we prospectively quantified fecal BKV by quantitative PCR reaction in 40 patients undergoing hematopoietic SCT (HSCT). Urinary BKV was similarly quantified. Fecal BKV excretion was positive in 16/40 patients, of whom 10 were transient (<3 consecutively positive samples), six were persistent (⩾3 consecutively positive samples) and three were persistent with peaking (⩾10(3)-fold increase in viral load over baseline, reaching 5.11 × 10(6), 4.68 × 10(7) and 2.75 × 10(8) copies/sample at 14, 14 and 21 days post-HSCT, respectively). Urinary BKV excretion was positive in 25/40 patients. Fecal BKV excretion was significantly correlated with that of the urine (P=0.036) and was significantly associated with allogeneic HSCT (P=0.037) and persistent and peaking of urinary BKV excretion (P<0.001). Binary logistic regression showed that BKV viruria was the only significant risk factor for fecal BKV excretion (P=0.021). Fecal BKV excretion occurred in 40% patients undergoing HSCT, implicating the gastrointestinal tract as a BKV latency site.


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title: Viral-bacterial co-infection in Australian Indigenous children with acute otitis media

text: BACKGROUND: Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation. METHODS: A total of 366 nasopharyngeal swabs from 114 Indigenous children were retrospectively examined. A panel of 17 respiratory viruses was screened by PCR, and densities of S. pneumoniae, H. influenzae and M. catarrhalis were estimated by quantitative real time PCR. Data are reported by clinical ear state. RESULTS: M. catarrhalis (96%), H. influenzae (91%), S. pneumoniae (89%) and respiratory viruses (59%) were common; including rhinovirus (HRV) (38%), polyomavirus (HPyV) (14%), adenovirus (HAdV) (13%), bocavirus (HBoV) (8%) and coronavirus (HCoV) (4%). Geometric mean bacterial loads were significantly higher in children with acute otitis media (AOM) compared to children without evidence of otitis media. Children infected with HAdV were 3 times more likely (p < 0.001) to have AOM with or without perforation. CONCLUSION: This study confirms a positive association between nasopharyngeal bacterial load and clinical ear state, exacerbated by respiratory viruses, in Indigenous children. HAdV was independently associated with acute ear states.


The Root Causes of COVID-19 Screech for Compassion


title: Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate, and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3–5].


title: Role of pharmacists during the COVID‐19 pandemic in China ‐ Shanghai Experiences

text: The roles and contributions of pharmacists in Shanghai during the coronavirus disease 2019 (COVID‐19) pandemic are described in this report. Five pharmacists have been appointed as members of an expert interdisciplinary health care team tasked with taking care of all adult COVID‐19 patients in Shanghai in a designated hospital, the Shanghai Public Health Clinical Center (SPHCC). They work with pharmacists at SPHCC, having responsibilities that include drug supplies, dispensing, pharmacy intravenous admixture services (PIVAS), prescription audits, medication reconciliations, pharmacotherapy, therapeutic drug monitoring, and patient education. Due to the pandemic, pharmacy operations in all hospitals are modified to adhere to guidelines for infection risk mitigation and personnel protection. Community pharmacies serve as the public access point to health care and medical supplies, providing services beyond dispensing and medication counselling. The establishment of internet hospitals (telehealth facilities) provide new opportunities for delivering pharmaceutical care and working with health care professionals. Pharmacists also participate in evaluating new treatments and keeping health care teams informed of new findings for potential treatment considerations. In response to the critical need for health care professionals in Wuhan, 68 pharmacists from Shanghai went there to work with the local pharmacists. Through assuming new roles and adapting existing practice, pharmacists have acquired invaluable experiences for future practice advancement. In order to assume these responsibilities effectively, pharmacists need to be equipped with the necessary skills for meeting the evolving health care challenges. This article is protected by copyright. All rights reserved.


COVID-19 must catalyse key global natural experiments