title: Emergence of a Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2: Biology and Therapeutic Options

text: The new decade of the 21(st) century (2020) started with the emergence of a novel coronavirus known as SARS-CoV-2 that caused an epidemic of coronavirus disease (COVID-19) in Wuhan, China. It is the third highly pathogenic and transmissible coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in humans. The source of origin, transmission to humans, and mechanisms associated with the pathogenicity of SARS-CoV-2 are not yet clear, however, its resemblance to SARS-CoV and several other bat coronaviruses was recently confirmed through genome sequencing-related studies. The development of therapeutic strategies is necessary in order to prevent further epidemics and cure infections. In this review, we summarize current information about the emergence, origin, diversity, and epidemiology of three pathogenic coronaviruses with a specific focus on the current outbreak in Wuhan, China. Furthermore, we discuss the clinical features and potential therapeutic options that may be effective against SARS-CoV-2.


title: Amid COVID-19: the importance of developing an positive adverse drug reaction (ADR) and medical device incident (MDI) reporting culture for Global Health and public safety

text: Amid COVID-19 Crisis, reporting adverse drug reactions (ADRs) and medical device incidents (MDIs) to Health Canada or health authorities in every country is crucial for monitoring medication safety and improving public health. Health Canada, for example, through their online database, has facilitated the process of reporting side effects relating to drugs and medical devices. However, several patients and health care professionals still fail to voluntarily report adverse events. For health care providers, some barriers to reporting may include fear of negative feedback, apathy, legal concerns, and uncertainty about whether an incident qualifies as an ADR. In the current COVID-19 Crisis, it is especially important for health care providers to be diligent about reporting Adverse Drug Reactions (ADRs), since misinformation propagated by the media is causing patients to misuse certain medications. We need to shift the current thought process about ADR reporting in order to encourage a positive reporting culture by patients and health care providers.


title: Multilingual chief complaint classification for syndromic surveillance: An experiment with Chinese chief complaints

text: Abstract Purpose Syndromic surveillance is aimed at early detection of disease outbreaks. An important data source for syndromic surveillance is free-text chief complaints (CCs), which may be recorded in different languages. For automated syndromic surveillance, CCs must be classified into predefined syndromic categories to facilitate subsequent data aggregation and analysis. Despite the fact that syndromic surveillance is largely an international effort, existing CC classification systems do not provide adequate support for processing CCs recorded in non-English languages. This paper reports a multilingual CC classification effort, focusing on CCs recorded in Chinese. Methods We propose a novel Chinese CC classification system leveraging a Chinese-English translation module and an existing English CC classification approach. A set of 470 Chinese key phrases was extracted from about one million Chinese CC records using statistical methods. Based on the extracted key phrases, the system translates Chinese text into English and classifies the translated CCs to syndromic categories using an existing English CC classification system. Results Compared to alternative approaches using a bilingual dictionary and a general-purpose machine translation system, our approach performs significantly better in terms of positive predictive value (PPV or precision), sensitivity (recall), specificity, and F measure (the harmonic mean of PPV and sensitivity), based on a computational experiment using real-world CC records. Conclusions Our design provides satisfactory performance in classifying Chinese CCs into syndromic categories for public health surveillance. The overall design of our system also points out a potentially fruitful direction for multilingual CC systems that need to handle languages beyond English and Chinese.


title: Suppression and resolution of autoimmune arthritis by rhesus θ-defensin-1, an immunomodulatory macrocyclic peptide

text: θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θ-defensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture. RTD-1 significantly reduced joint IL-1β levels compared with controls. RTD-1 dose-dependently inhibited fibroblast-like synoviocyte (FLS) invasiveness and FLS IL-6 production. Consistent with the inhibition of FLS invasiveness, RTD-1 was a potent inhibitor of arthritogenic proteases including ADAMs 17 and 10 which activate TNFα, and inhibited matrix metalloproteases, and cathepsin K. RTD-1 was non-toxic, non-immunogenic, and effective when administered as infrequently as once every five days. Thus θ-defensins, which are absent in humans, have potential as retroevolutionary biologics for the treatment of RA.


Surgical and Clinical Reactivation for Elective Procedures during the COVID Era: A Global Perspective


title: Acute Stroke Care Algorithm in a Private Tertiary Hospital in the Philippines During the COVID-19 Pandemic: A Third World Country Experience

text: BACKGROUND AND PURPOSE: Since the declaration of the Novel Coronavirus Disease (COVID-19) pandemic, ensuring the safety of our medical team while delivering timely management has been a challenge. Acute stroke patients continue to present to the emergency department and they may not have the usual symptoms of COVID-19 infection. Stroke team response and management must be done within the shortest possible time to minimize worsening of the functional outcome without compromising safety of the medical team. METHODS: Infection control recommendations, emergency department protocols and stroke response pathways utilized prior to the COVID 19 pandemic within our institution were evaluated by our stroke team in collaboration with the multidisciplinary healthcare services. Challenges during the COVID-19 scenario were identified, from which a revised acute stroke care algorithm was formulated to adapt to this pandemic. RESULTS: We formulated an algorithm that incorporates practices from internationally devised protocols while tailoring certain aspects to suit the available resources in our system locally. We highlighted the significance of the following: team role designation, coordination among different subspecialties and departments, proper use of personal protective equipment and resources, and telemedicine use during this pandemic. CONCLUSIONS: This pandemic has shaped the stroke team's approach in the management of acute stroke patients. Our algorithm ensures proper resource management while optimizing acute stroke care during the COVID-19 pandemic in our local setting. This algorithm may be utilized and adapted for local practice and other third world countries who face similar constraints.


title: Chapter 3 Clinical Biochemistry and Hematology

text: The sparse information available for multiple less commonly used species have been compiled with references. Clinical problems in animals are usually associated with changes in the blood and urine and core values are recommended for research, safety, and toxicity studies in laboratory animals. The core panel includes glucose, blood urea nitrogen, creatinine, total protein, albumin globulin, calcium, sodium, potassium, chloride, and total cholesterol; hematology tests includes total leukocyte count, erythrocyte count, erythrocyte morphology, platelet count, hemoglobin concentration, hematocrit or packed cell volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Urinalysis tests are also recommended. Stress associated with restraint and handling may cause changes; anesthesia may produce changes in clinical biochemistry or hematology parameters, including decreased hematocrit, hemoglobin level, and red blood cell count. Techniques for blood and urine collection are described.


title: Lactococcus lactis-expressing listeriolysin O (LLO) provides protection and specific CD8(+) T cells against Listeria monocytogenes in the murine infection model

text: Lactococcus lactis has previously been proposed as a vaccine platform for the safe delivery of heterologous antigens. Here we utilized L. lactis as a live vector for expression of listeriolysin O (LLO), a major Listeria monocytogenes antigen and virulence factor. A variety of plasmid constructs were designed to permit either constitutive or nisin-inducible expression of secreted or non-secreted LLO in L. lactis. Recombinant strains were subsequently tested in a murine model for vaccination efficacy against L. monocytogenes infection. CD8(+) T lymphocytes specific for the LLO(91–99) epitope were detected when strains were administered via the intraperitoneal (IP) but not the oral route. Challenge with live L. monocytogenes revealed different levels of protection among the three vaccine strains tested with the nisin-inducible LLO-secreting L. lactis strain providing the greatest protection against secondary infection. This work highlights the usefulness of the GRAS (Generally Regarded As Safe) organism L. lactis as the basis of a live vaccine vector against L. monocytogenes. The work suggests that LLO-expressing L. lactis strains may also have the potential to act as a platform for directing other co-expressed antigens towards the cytosolic MHC class I pathway for enhanced stimulation of the CD8(+) T-cell response.


title: Syncope, Brugada syndrome, and COVID‐19 lung disease

text: A 52‐year‐old male with no history of familiar sudden death arrived at our Emergency Department after syncope with loss of consciousness occurred during high fever. The thoracic high‐resolution computed tomography demonstrated bilateral multiple ground‐glass opacities. The nose‐pharyngeal swab resulted positive for SARS‐CoV‐2. The 12‐lead ECG presented a “coved‐type” aspect in leads V1 and V2 at the fourth intercostal space and a first degree atrio‐ventricular block. As soon as the temperature went down, the 12‐lead ECG resumed a normal aspect, maintaining a long PR interval.


Chapter 45 Autoimmunity – Multiple Sclerosis


title: Highly infectious SARS-CoV pseudotyped virus reveals the cell tropism and its correlation with receptor expression

text: Abstract Studies of SARS coronavirus (SARS-CoV)—the causative agent of severe acute respiratory syndrome (SARS)—have been hampered by its high transmission rate and the pathogenicity of this virus. To permit analysis of the host range and entry mechanism of SARS-CoV, we incorporated the humanized SARS-CoV spike (S) glycoprotein into HIV particles to generate a highly infectious SARS-CoV pseudotyped virus. The infection on Vero E6—a permissive cell line to SARS-CoV—could be neutralized by sera from convalescent SARS patients, and the entry was a pH-dependent process. With these highly infectious SARS-CoV pseudotypes, several cell lines derived from various tissues were revealed as susceptible to SARS-CoV, which were highly corresponding to the expression pattern of virus’s receptor angiotensin-converting enzyme 2 (ACE2). In addition, we also demonstrated angiotensin 1 converting enzyme (ACE)—the homologue of ACE2 could not function as a receptor for SARS-CoV.


title: Coronaviruses: Propagation, Quantification, Storage, and Construction of Recombinant Mouse Hepatitis Virus

text: The focus of this protocol is mouse hepatitis virus (MHV), with occasional references to other coronaviruses. Many of these protocols can be easily adapted to other coronaviruses. Basic protocols for propagating MHV in DBT and 17CL-1 cells; the storage, and titration of viral stocks; purification of MHV on sucrose gradients; and the generation of recombinant viruses by a cDNA assembly method and by targeted recombination, will be presented. Support protocols for the propagation of DBT, 17CL-1, and L2 cells used for growing and titrating MHV, for the growth of BHK-R cells and FCWF cells. The latter two cell lines are used for regenerating infectious MHV by an in vitro cDNA assembly protocol and by a targeted recombination protocol, respectively, allowing reverse genetic manipulation of these viruses. An additional support protocol for the maintenance of the large plasmids used for generating recombinant MHVs will also be presented.


title: Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)

text: Abstract Purpose Lianhuaqingwen (LH) as traditional Chinese medicine (TCM) formula has been used to treat influenza and exerted broad-spectrum antiviral effects on a series of influenza viruses and immune regulatory effects Ding et al. (2017). The goal of this study is to demonstrate the antiviral activity of LH against the novel SARS-CoV-2 virus and its potential effect in regulating host immune response. Methods The antiviral activity of LH against SARS-CoV-2 was assessed in Vero E6 cells using CPE and plaque reduction assay. The effect of LH on virion morphology was visualized under transmission electron microscope. Pro-inflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. Results LH significantly inhibited SARS-CoV-2 replication in Vero E6 cells and markedly reduced pro-inflammatory cytokines (TNF-α, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Furthermore, LH treatment resulted in abnormal particle morphology of virion in cells. Conclusions LH significantly inhibits the SARS-COV-2 replication, affects virus morphology and exerts anti-inflammatory activity in vitro. These findings indicate that LH protects against the virus attack, making its use a novel strategy for controlling the COVID-19 disease.


title: Correction to: COVID-19 and importance of environmental sustainability

text: The original version of this article unfortunately contains a mistake


title: Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients

text: Abstract Apart from the core (21kD), a novel hepatitis C virus (HCV) frame shift protein (F1) is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frame shift into the −2/+1 reading frame. To date, no information is available on F1 protein of Indian isolates, and hence detection of antibodies for F1 protein in Indian patients assumes great relevance. Specific primers have been designed to amplify sequence coding for 120aa of truncated F1 (tF1). The amplified tF1 has been cloned in bacterial expression vector, pET21b for expression in Escherichia coli. Partially purified expressed protein has been subjected to western blot analysis using patients’ sera. Three HCV positive sera employed in western analysis showed positive signals to tF1, while sera from uninfected individuals failed to give any signals. Further, results of western blots, carried out with patients sera titrated with purified core protein, confirmed the presence of antibodies specific to F1. The positive signal observed for F1 in western analysis with HCV infected sera suggests that F1 protein is synthesized in the natural course of HCV infection in Indian patients as well. Presence of antibodies against F1 protein of subtype 1c has been demonstrated, for the first time, in Indian patients.


title: COVID-19 epidemic: Proposed alternatives in the management of digestive cancers: A French intergroup clinical point of view (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR)

text: INTRODUCTION: Patients treated for malignancy are considered at risk of severe COVID-19. This exceptional pandemic has affected countries on every level, particularly health systems which are experiencing saturation. Like many countries, France is currently greatly exposed, and a complete reorganization of hospitals is ongoing. We propose here adaptations of diagnostic procedures, therapies and care strategies for patients treated for digestive cancer during the COVID-19 epidemic. METHODS: French societies of gastroenterology and gastrointestinal (GI) oncology carried out this study to answer two main questions that have arisen (i) how can we limit high-risk situations for GI-cancer patients and (ii) how can we limit contact between patients and care centers to decrease patients’ risk of contamination while continuing to treat their cancer. All recommendations are graded as experts’ agreement according to the level of evidence found in the literature until March 2020. RESULTS: A proposal to adapt treatment strategies was made for the main GI oncology situations. Considering the level of evidence and the heterogeneous progression of the COVID-19 epidemic, all proposals need to be considered by a multidisciplinary team and implemented with patient consent. CONCLUSION: COVID-19 epidemic may significantly affect patients treated for digestive malignancies. Healthcare teams need to consider adapting treatment sequences when feasible and according to the epidemic situation.


title: Necrotoxigenic Escherichia coli type-2 invade and cause diarrhoea during experimental infection in colostrum-restricted newborn calves

text: Abstract There exists experimental evidence that necrotoxigenic Escherichia coli (NTEC) strains producing the cytotoxic necrotising factor 1 cause intestinal and extra-intestinal disease in piglets. On the other hand, no experimental model has been developed with NTEC strains producing the cytotoxic necrotising factor 2. In all, 14 colostrum-restricted calves were orally challenged with two strains isolated from the faeces of a diarrheic calf (B20a) or from the heart blood of a septicaemic calf (1404). All calves had diarrhoea which lasted until euthanasia in eight of them. In those calves, diarrhoea was correlated with the faecal excretion of the challenge strains. At necropsy, vascular congestion of the intestinal mucosa, hypertrophy of the mesenteric lymph nodes (MLN) and some congestion of the lungs were observed. Bacteriology confirmed the colonisation of the intestine by the challenge strains which were also recovered from the heart blood, the lungs and/or the liver. Histological sections confirmed enterocolitis, lymphadenitis and limited bronchopneumonia. In the intestinal tissue sections, bacteria testing positive in an in situ DNA hybridisation assay with a CNF2 probe were observed. Those results were confirmed by immunohistochemistry with a polyclonal anti-O78 and a monoclonal anti-F17b antisera. Three of the five control calves receiving either saline or a CNF−, F17a strain (25KH09) had no clinical signs or lesions. The other two presented a profuse liquid diarrhoea but those calves were positive for the presence of K99+ E. coli. In this model, both NTEC2 strains were thus, able to colonise the intestine, to cause long-lasting diarrhoea and to invade the blood stream with localisation in various internal organs in colostrum-restricted conventional newborn calves.


title: Infection and blood transfusion: a guide to donor screening

text: Abstract In recent years, blood-component therapy has become more accessible in veterinary practice. As with human medicine, care must be taken to minimize the risk of disease transmission from donor to recipient. Determining the appropriate diseases to screen for is complicated by regional variations in disease incidence, the existence of chronic carrier states for some diseases, the difficulty in screening-test selection, and testing cost. The feline diseases considered include retroviral infections, feline coronaviruses, ehrlichiosis (Ehrlichia canis-like), anaplasmosis (Anaplasma phagocytophilum), neorickettsiosis (Neorickettsia risticii), hemoplasmosis (Mycoplasma hemofelis and M. hemominutum, previously feline hemobartonellosis), and cytauxzoonosis (Cytauxzoon felis). The canine diseases considered in this paper include babesiosis (Babesia canis and B. gibsonii,) ehrlichiosis (E. canis and E. ewingii), anaplasmosis (A. phagocytophilum), neorickettsiosis (N. risticii var. atypicalis), leishmaniasis (Leishmania donovani complex), brucellosis (Brucella canis), hemoplasmosis (M. hemocanis, previously canine hemobartonellosis), and bartonellosis (Bartonella vinsonii).


title: Diagnostic histologique des infections bactériennes nécrosantes extensives du poumon Étude de 4 observations d’évolution fulminante

text: Résumé Nous rapportons les aspects anatomo-cliniques et histologiques de 4 observations d’infection bactérienne pulmonaire associée à des lésions de nécrose extensive, dont l’évolution a été foudroyante en quelques heures (2 cas d’infections à streptocoque béta hémolytique du groupe A, 1 cas d’infection à Staphylococcus aureus et un cas d’infection à Haemophilus influenzae). Ces infections bactériennes nécrosantes extensives (IBNE) sont gravissimes compte tenu de la production de toxines nécrosantes. Les aspects histologiques sont stéréotypés, combinant une nécrose hémorragique extensive et diffuse, des nappes de bactéries et une réaction inflammatoire cellulaire quasi inexistante. Ces infections sont extrêmement rares et elles surviennent sans cause apparente, chez le sujet immunodéficient ou immunocompétent. Elles posent des problèmes de diagnostic différentiel parfois difficile à résoudre en histologie faisant discuter une infection virale associée. Le diagnostic positif repose sur une confontation anatomopathologique et microbiologique. Summary We report the clinical and histopathological features of four cases of pulmonary bacterial infections associated with extensive necrosis, which were fatal within a few hours (two cases of group A Streptococcus, one case of Staphyloccocus aureus and one case of Haemophilus influenzae infection). These bacterial infections are extremely severe conditions due to the production of necrotizing toxins. Histological findings are distinctive, showing extensive hemorrhagic necrosis, widespread layers of bacteria, and very few or no inflammatory cell components. These dramatic infections are extremely rare, occuring with no apparent underlying disease, both in immunodeficient and immunocompetent patients. The main differential diagnosis is a viral infection, difficult to diagnose on histological examination alone. The diagnosis is based on histological and microbiological results.


title: Monocytes and B cells support active replication of Chandipura virus

text: BACKGROUND: Interaction between immune system and Chandipura virus (CHPV) during different stages of its life cycle remain poorly understood. The exact route of virus entry into the blood and CNS invasion has not been clearly defined. The present study was undertaken to assess the population in PBMC that supports the growth of virus and to detect active virus replication in PBMC as well as its subsets. METHODS: PBMC subsets viz.: CD3(+), CD14(+), CD19(+), CD56(+)cells were separated and infected with CHPV. The infected cells were then assessed for transcription (N gene primer) and replication (NP gene primer) of CHPV by PCR. The supernatant collected from infected cells were titrated in Baby Hamster Kidney (BHK) cells to assess virus release. The cytokine and chemokine expression was quantified by flow cytometry. RESULTS: Amplification of N and NP gene was detected in CD14(+) (monocyte) and CD19(+) (B cell), significant increase in virus titre was also observed in these subsets. It was observed that, although the levels of IL-6 and IL-10 were elevated in CD14(+) cells as compared to CD19(+)cells, the differences were not significant. However the levels of TNFα and IL-8 were significantly elevated in CD14(+) cells than in CD19(+)cells. The levels of chemokine (CXCL9, CCL5, CCL2, CXCL10) were significantly elevated in CHPV infected PBMC as compared to uninfected cells. CCL2 and CXCL9 were significantly increased in CHPV infected CD14(+)cells as compared to CD19(+) cells. CONCLUSION: CD14(+)and CD19(+)cells support active replication of CHPV. High viral load was detected in CD14(+) cells infected with CHPV hence it might be the primary target cells for active replication of CHPV. An elevated levels of cytokines and chemokines observed in CD14(+) cells may help in predicting the pathogenecity of CHPV and possible entry into the central nervous system.


title: Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in Vivo by monoclonal antibody

text: Abstract Monoclonal hybridoma antibodies directed against the polypeptides of murine hepatitis virus-4 (JHM strain) were tested for their ability to alter the course of a normally lethal intracerebral virus challenge. Three monoclonal antibodies directed against two distinct epitopes on the E2 glycoprotein of MHV-4 protected mice against lethal virus challenge and converted the infection from fatal encephalomyelitis to demyelination. A single neutralizing antibody directed against a third epitope on E2 as well as seven nonneutralizing antibodies to E2, E1, and N polypeptides did not protect against challenge. In mice which received protective antibody, MHV-4 infection was not blocked, however, virus grew to lower titers in liver and brain, and virus replication in the CNS was more restricted than in unprotected mice. Decreased involvement of neurons in the brains of protected mice was observed, and no evidence of neuronal infection in the spinal cords was found. In contrast, oligodendrocytes were infected in the presence of protective antibody, and evidence of demylination associated with mononuclear cell infiltration was found. These studies demonstrate that antibody to a single epitope on a viral glycoprotein can substantially alter the course and phenotype of disease.


title: Clinical Features, Severity, and Incidence of RSV Illness During 12 Consecutive Seasons in a Community Cohort of Adults ≥60 Years Old

text: BACKGROUND: The epidemiology and burden of respiratory syncytial virus (RSV) illness are not well defined in older adults. METHODS: Adults ≥60 years old seeking outpatient care for acute respiratory illness were recruited from 2004–2005 through 2015–2016 during the winter seasons. RSV was identified from respiratory swabs by multiplex polymerase chain reaction. Clinical characteristics and outcomes were ascertained by interview and medical record abstraction. The incidence of medically attended RSV was estimated for each seasonal cohort. RESULTS: RSV was identified in 243 (11%) of 2257 enrollments (241 of 1832 individuals), including 121 RSV type A and 122 RSV type B. The RSV clinical outcome was serious in 47 (19%), moderate in 155 (64%), and mild in 41 (17%). Serious outcomes included hospital admission (n = 29), emergency department visit (n = 13), and pneumonia (n = 23) and were associated with lower respiratory tract symptoms during the enrollment visit. Moderate outcomes included receipt of a new antibiotic prescription (n = 144; 59%), bronchodilator/nebulizer (n = 45; 19%), or systemic corticosteroids (n = 28; 12%). The relative risk of a serious outcome was significantly increased in persons aged ≥75 years (vs 60–64 years) and in those with chronic obstructive pulmonary disease or congestive heart failure. The average seasonal incidence was 139 cases/10 000, and it was significantly higher in persons with cardiopulmonary disease compared with others (rate ratio, 1.89; 95% confidence interval, 1.44–2.48). CONCLUSIONS: RSV causes substantial outpatient illness with lower respiratory tract involvement. Serious outcomes are common in older patients and those with cardiopulmonary disease.


title: Production of specific antibodies against SARS-coronavirus nucleocapsid protein without cross reactivity with human coronaviruses 229E and OC43

text: Severe acute respiratory syndrome (SARS) is a life-threatening disease for which accurate diagnosis is essential. Although many tools have been developed for the diagnosis of SARS, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. We have raised polyclonal and monoclonal antibodies (Abs) using a recombinant form of the SARS virus nucleocapsid protein. Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.


title: Prospects for control of emerging infectious diseases with plasmid DNA vaccines

text: Experiments almost 20 years ago demonstrated that injections of a sequence of DNA encoding part of a pathogen could stimulate immunity. It was soon realized that "DNA vaccination" had numerous potential advantages over conventional vaccine approaches including inherent safety and a more rapid production time. These and other attributes make DNA vaccines ideal for development against emerging pathogens. Recent advances in optimizing various aspects of DNA vaccination have accelerated this approach from concept to reality in contemporary human trials. Although not yet licensed for human use, several DNA vaccines have now been approved for animal health indications. The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Because of recent advances in DNA vaccination, this approach has the potential to be a powerful new weapon in protecting against emerging and potentially pandemic human pathogens.


title: Assessment of nursing students perceptions of their training hospital's infection prevention climate: A multi-university study in Saudi Arabia

text: Abstract Background The risk of acquiring and spreading infection must be minimized in nursing students because they are exposed to healthcare-associated infections during clinical training. To achieve this goal, students should be knowledgeable and competent in infection control practice before proceeding to their training hospitals. Objectives This study assessed the nursing students' perception of the infection prevention climate in training hospitals in Saudi Arabia. It also examined the predictors of the students' perceptions. Design A quantitative, cross-sectional design was used. Methods This investigation was part of a large study conducted in six Saudi universities. A total of 829 Saudi nursing students were included in this study. Data were collected using the Leading Culture of Quality in Infection Prevention scale and analyzed using descriptive and inferential statistics. Ethical approval was obtained from the King Saud University, and permission was given by the administration of each participating university. Results The overall perception of nursing students indicated a modest infection prevention climate. Prioritization of quality and improvement orientation was rated as the highest dimensions, whereas psychological safety and supportive environment were the lowest. The nursing students in University F had the poorest perceptions among the six universities. The predictors of nursing student perception of their training hospitals' infection prevention climates were the university where they studied, their age, and participation in infection prevention seminars. Conclusions This article describes nursing students' perception of the infection prevention climate of their training hospitals in Saudi Arabia. Results may provide a unique theoretical underpinning on the perception and factors that effect an infection prevention climate. Thereby, previous knowledge and literature may be expanded. Results can be used as a guide in establishing clinical policies in efforts toward improving the infection prevention climate.


Neumomediastino espontáneo en pacientes con COVID-19: una serie de cuatro casos


title: Neglected dorsolateral dislocation of the first metatarsophalangeal joint: A case report

text: INTRODUCTION: Although the first metatarsophalangeal (MTP) joint is frequently injured, Complete dislocation of the first MTP joint represents a relatively rare traumatic injury. PRESENTATION OF CASE: A 46-year-old gentleman presented with a traumatic first MTP joint dislocation resulting from an automobile accident. Due to coronavirus outbreak in the hospital at that time, patient was referred to another hospital. Six months later, reduction was achieved surgically and fixation of the MTP with K-wires was done. DISCUSSION: Only few case reports have described the injury, and the ideal treatment along with the long-term result of the injury has yet to be further studied because reports are rare in this regard. CONCLUSION: Functional range of motion may result even after 6 months of delayed treatment with ORIF and osteopenia may result.


title: Attitudes of ageing passengers to air travel since the coronavirus pandemic

text: The coronavirus pandemic has had a devastating impact on the demand for air transport. One passenger segment that has received relatively little attention is ageing passengers (defined as aged 65+), in spite of the fact that this group has been disproportionately affected by COVID-19, and in recent years has been viewed as a potential growth market. Therefore, the aim of this brief paper is to analyse the attitudes of ageing passengers by assessing air travel plans in the next 12 months, examining the factors influencing future flying decisions, and investigating the impact of the coronavirus pandemic on perceived risks and experiences associated with flying. The findings show that over 60% of ageing passengers are planning to travel by air in the next 12 months, although the nature of their trips may change. Factors such as flexible ticket booking and quarantine rules do not appear to be key drivers affecting travel decisions and within the different stages of the air journey, getting to/from the airport is perceived as the safest stage. The findings suggest that there are various COVID-19 implications for airlines and airports serving this market segment, ranging from the use of self-service technology, the generation of commercial/ancillary revenues and the design of surface access policies.


title: Establishment of reverse transcription loop-mediated isothermal amplification for rapid detection and differentiation of canine distemper virus infected and vaccinated animals

text: Abstract Although widespread vaccination against canine distemper virus (CDV) has been conducted for many decades, several canine distemper outbreaks in vaccinated animals have been reported frequently. In order to detect and differentiate the wild-type and vaccine strains of the CDV from the vaccinated animals, a novel reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was developed. A set of four primers—two internal and two external—were designed to target the H gene for the specific detection of wild-type CDV variants. The CDV-H RT-LAMP assay rapidly amplified the target gene, within 60min, using a water bath held at a constant temperature of 65°C. The assay was 100-fold more sensitive than conventional RT-PCR, with a detection limit of 10−1 TCID50 ml−1. The system showed a preference for wild-type CDV, and exhibited less sensitivity to canine parvovirus, canine adenovirus type 1 and type 2, canine coronavirus, and canine parainfluenza virus. The assay was validated using 102 clinical samples obtained from vaccinated dog farms, and the results were comparable to a multiplex nested RT-PCR assay. The specific CDV-H RT-LAMP assay provides a simple, rapid, and sensitive tool for the detection of canines infected with wild-type CDV from canines vaccinated with attenuated vaccine.


title: Saliva—Friend and Foe in the COVID-19 Outbreak

text: The coronavirus disease 2019 (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global ongoing pandemic. Timely, accurate and non-invasive SARS-CoV-2 detection in both symptomatic and asymptomatic patients, as well as determination of their immune status, will facilitate effective large-scale pandemic control measures to prevent the spread of COVID-19. Saliva is a biofluid whose anatomical source and location is of particularly strategic relevance to COVID-19 transmission and monitoring. This review focuses on the role of saliva as both a foe (a common mode of viral transmission via salivary droplets and potentially aerosols) and a friend (as a non-invasive diagnostic tool for viral detection and immune status surveillance) in combating COVID-19.


title: Transmission dynamics of the COVID‐19 outbreak and effectiveness of government interventions: A data‐driven analysis

text: Using the parameterized susceptible‐exposed‐infectious‐recovered model, we simulated the spread dynamics of coronavirus disease 2019 (COVID‐19) outbreak and impact of different control measures, conducted the sensitivity analysis to identify the key factor, plotted the trend curve of effective reproductive number (R), and performed data fitting after the simulation. By simulation and data fitting, the model showed the peak existing confirmed cases of 59 769 arriving on 15 February 2020, with the coefficient of determination close to 1 and the fitting bias 3.02%, suggesting high precision of the data‐fitting results. More rigorous government control policies were associated with a slower increase in the infected population. Isolation and protective procedures would be less effective as more cases accrue, so the optimization of the treatment plan and the development of specific drugs would be of more importance. There was an upward trend of R in the beginning, followed by a downward trend, a temporary rebound, and another continuous decline. The feature of high infectiousness for severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2) led to an upward trend, and government measures contributed to the temporary rebound and declines. The declines of R could be exploited as strong evidence for the effectiveness of the interventions. Evidence from the four‐phase stringent measures showed that it was significant to ensure early detection, early isolation, early treatment, adequate medical supplies, patients’ being admitted to designated hospitals, and comprehensive therapeutic strategy. Collaborative efforts are required to combat the novel coronavirus, focusing on both persistent strict domestic interventions and vigilance against exogenous imported cases.


title: AEG-SEED position paper for the resumption of endoscopic activity after the peak phase of the COVID-19 pandemic

text: Abstract Introduction The COVID-19 pandemic has led to the suspension of programmed activity in most of the Endoscopy Units in our environment. The aim of this document is to facilitate the resumption of elective endoscopic activity in an efficient and safe manner. Material and methods A series of questions considered to be of clinical and logistical relevance were formulated. In order to elaborate the answers, a structured bibliographic search was carried out in the main databases and the recommendations of the main Public Health and Digestive Endoscopy institutions were reviewed. The final recommendations were agreed upon through telematic means. Results A total of 33 recommendations were made. The main aspects discussed are: 1) Reassessment and prioritization of the indication, 2) Restructuring of spaces, schedules and health personnel, 3) Screening for infection, 4) Hygiene measures and personal protective equipment. Conclusion The AEG and SEED recommend restarting endoscopic activity in a phased, safe manner, adapted to local resources and the epidemiological situation of SARS-CoV-2 infection.


title: Rational monoclonal antibody development to emerging pathogens, biothreat agents and agents of foreign animal disease: The antigen scale

text: Abstract Many factors influence the choice of methods used to develop antibody to infectious agents. In this paper, we review the current status of the main technologies used to produce monoclonal antibodies (mAbs) from the B cells of antigen-sensitized animals. While companies are adopting advanced high-throughput methods, the major technologies used by veterinary and medical research laboratories are classical hybridoma fusion and recombinant library selection techniques. These methods have inherent advantages and limitations but have many common aspects when using immunized rodents. Laboratories with expertise in both methods of antibody development have a distinct advantage in their ability to advance mAb technology. New and re-emerging infectious threats in today’s world emphasize the need for quality immunoreagents and the need to maintain expertise in mAb development. We provide examples of some common applications for mAb reagents used to identify pathogens such as the SARS-coronavirus (SARS-CoV), Bacillus anthracis, and foot-and-mouth disease (FMD) virus. We also outline a framework for investigators to make rational decisions concerning which method to use to develop mAbs based upon characteristics of the pathogen under study and the intended downstream application. Lastly, we provide parameters for the immunisation of mice and a classification system which describes the expected outcome for mAb development strategies when using classes of immunogens to generate mAbs with desired activities.


title: Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection

text: The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions.


title: COVID-19 in Hemodialysis Patients: A Report of 5 Cases

text: In December 2019, an outbreak of coronavirus disease (COVID-19) due to the novel SARS-CoV-2 virus began in China and spread rapidly worldwide. It is unknown whether hemodialysis patients represent a distinct group of patients with certain characteristics that may make them susceptible to infection or severe disease. In this Case Report, we describe the clinical and epidemiological features of COVID-19 in 201 maintenance hemodialysis patients in Zhongnan Hospital of Wuhan university, including 5 maintenance hemodialysis patients who contracted COVID-19 disease. Of the 5 patients with COVID-19, one had a definite history of contact with an infected person. The age range of the patients was 47–67 years. Diarrhea (80%), fever (60%), and fatigue (60%) were the most common symptoms. Lymphopenia occurred in all patients.Chest computerized tomography (CT) scans showed ground glass opacity in the lungs of all patients. Up to February 13, 2020, none of the patients had developed severe complications (acute respiratory distress syndrome, shock, multiple organ dysfunction) or died.


title: Repeated detection of European bat lyssavirus type 2 in dead bats found at a single roost site in the UK

text: In August 2007, European bat lyssavirus type 2 (EBLV-2) was isolated from a Daubenton’s bat found at Stokesay Castle. In September 2008, another bat from the same vicinity of Stokesay Castle also tested positive for EBLV-2. This is the first occurrence of repeated detection of EBLV-2 from a single site. Here, we report the detection of low levels of viral RNA in various bat organs by qRT-PCR and detection of viral antigen by immunohistochemistry. We also report sequence data from both cases and compare data with those derived from other EBLV-2 isolations in the UK.


title: The Emerging Role of Rhinoviruses in Lower Respiratory Tract Infections in Children – Clinical and Molecular Epidemiological Study From Croatia, 2017–2019

text: Rhinoviruses (RVs) are increasingly implicated not only in mild upper respiratory tract infections, but also in more severe lower respiratory tract infections; however, little is known about species diversity and viral epidemiology of RVs among the infected children. Therefore, we investigated the rhinovirus (RV) infection prevalence over a 2-year period, compared it with prevalence patterns of other common respiratory viruses, and explored clinical and molecular epidemiology of RV infections among 590 children hospitalized with acute respiratory infection in north-western and central parts of Croatia. For respiratory virus detection, nasopharyngeal and pharyngeal flocked swabs were taken from each patient and subsequently analyzed with multiplex RT-PCR. To determine the RV species in a subset of positive children, 5′UTR in RV-positive samples has been sequenced. Nucleotide sequences of referent RV strains were retrieved by searching the database with Basic Local Alignment Tool, and used to construct alignments and phylogenetic trees using MAFFT multiple sequence alignment tool and the maximum likelihood method, respectively. In our study population RV was the most frequently detected virus, diagnosed in 197 patients (33.4%), of which 60.4% was detected as a monoinfection. Median age of RV-infected children was 2.25 years, and more than half of children infected with RV (55.8%) presented with lower respiratory tract infections. Most RV cases were detected from September to December, and all three species co-circulated during the analyzed period (2017–2019). Sequence analysis based on 5′UTR region yielded 69 distinct strains; the most prevalent was RV-C (47.4%) followed by RV-A (44.7%) and RV-B (7.9%). Most of RV-A sequences formed a distinct phylogenetic group; only strains RI/HR409-18 (along with a reference strain MF978777) clustered with RV-C strains. Strains belonging to the group C were the most diverse (41.6% identity among strains), while group B was the most conserved (71.5% identity among strains). Despite such differences in strain groups (hitherto undescribed in Croatia), clinical presentation of infected children was rather similar. Our results are consistent with newer studies that investigated the etiology of acute respiratory infections, especially those focused on children with lower respiratory tract infections, where RVs should always be considered as potentially serious pathogens.


title: Acute and Chronic Otitis Media

text: Otitis media (OM) is a common illness in young children. OM has historically been associated with frequent and severe complications. Nowadays it is usually a mild condition that often resolves without treatment. For most children, progression to tympanic membrane perforation and chronic suppurative OM is unusual (low-risk populations); this has led to reevaluation of many interventions that were used routinely in the past. Evidence from a large number of randomized controlled trials can help when discussing treatment options with families. Indigenous children in the United States, Canada, Northern Europe, Australia, and New Zealand experience more OM than other children. In some places, Indigenous children continue to suffer from the most severe forms of the disease. Communities with more than 4% of the children affected by chronic tympanic membrane perforation have a major public health problem (high-risk populations). Higher rates of invasive pneumococcal disease, pneumonia, and chronic suppurative lung disease (including bronchiectasis) are also seen. These children will often benefit from effective treatment of persistent (or recurrent) bacterial infection.


title: Effects of fractionated colostrum replacer and vitamins A, D, and E on haptoglobin and clinical health in neonatal Holstein calves challenged with Mycobacterium avium ssp. paratuberculosis

text: Abstract Thirty Holstein calves were obtained from 2 dairy farms in central Iowa at birth and randomly assigned to 1 of 6 treatment groups: (1) colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D3; (5) CR, vitamin E; and (6) CR, vitamins A, D3, E, with 5 calves per treatment in a 14-d study. Calves were fed pasteurized whole milk (CD) or fractionated colostrum replacer (CR) at birth (d 0) and injected with vitamins according to treatment group. From d 1 through d 14 of the study, all calves were fed pasteurized whole milk (PWM) supplemented with vitamins as assigned. All calves were inoculated with Mycobacterium avium ssp. paratuberculosis on d 1 and 3 of age. Calves fed CR acquired IgG1 and haptoglobin in serum within 24 h of birth, whereas CD calves did not. The CR-fed calves were 2.5 times less likely to develop scours, and CR calves supplemented with vitamins D3 and E also demonstrated a decreased incidence of scours. Serum vitamin levels of A, D, and E increased within treatment group by d 7 and 14 of the study. Interestingly, synergistic effects of supplemental vitamins A, D3, and E on serum 25-(OH)-vitamin D were observed at d 7, resulting in higher levels than in calves administered vitamin D only. Further, vitamin D3 deficiency was observed in CD and CR calves fed a basal diet of pasteurized whole milk and no supplemental vitamins. Colonization of tissues with Mycobacterium avium ssp. paratuberculosis was negligible and was not affected by colostrum feeding or vitamin supplementation. Results demonstrated passive transfer of haptoglobin to neonatal calves, and potential health benefits of supplemental vitamins D3 and E to calves fed pasteurized whole milk.


title: Application of the Updated CDC Isolation Guidelines for Health Care Facilities

text: THE CENTERS FOR DISEASE CONTROL and Prevention has published updated guidelines for isolation precautions that outline how health care workers can prevent the transmission of infectious agents to their patients and to themselves. THE GUIDELINES RE-EMPHASIZE standard precautions, which guide clinicians in the use of appropriate personal protective equipment (PPE), depending on the expected type of exposure. Respiratory hygiene/cough etiquette is incorporated into infection control practices as a new component of standard precautions. THE ARTICLE PROVIDES information on the new guidelines as well as information on newly emerging patho gens and methods to prevent disease transmission in health care settings.


title: Evaluation of nCoV-QS (MiCo BioMed) for RT-qPCR detection of SARS-CoV-2 from nasopharyngeal samples using CDC FDA EUA qPCR kit as a gold standard: an example of the need of validation studies

text: BACKGROUND: Several qPCR kits are available for SARS-CoV-2 diagnosis, mostly lacking of evaluation due to covid19 emergency. OBJECTIVE: We evaluated nCoV-QS (MiCo BioMed) kit using CDC kit as gold standard. RESULTS: We found limitations for nCoV-QS: 1) lower sensitivity 2) lack of RNA quality control probe. CONCLUSIONS: Validation studies should be implemented for any SARS-CoV-2 RT-qPCR commercial kit to prevent unreliable diagnosis.


title: Preparedness planning and care of patients under investigation for or with Ebola virus disease: A survey of physicians in North America

text: The West African Ebola virus disease (EVD) epidemic of 2014-2015 required North American hospitals to undertake comprehensive planning and training for the potential need to care for patients with EVD. Here we describe physician contributions to EVD preparedness planning and the care of persons under investigation for or patients with EVD.


title: An Activated GOPS‐poly‐L‐Lysine‐ Coated Glass Surface for the Immobilization of 60mer Oligonucleotides

text: To explore a method for enhancing the immobilization and hybridization efficiency of oligonucleotides on DNA microarrays, conventional protocols of poly‐L‐lysine coating were modified by means of surface chemistry, namely, the slides were prepared by the covalently coupling of poly‐L‐lysine to a glycidoxy‐modified glass surface. The modified slides were then used to print microarrays for the detection of the SARS coronavirus by means of 60mer oligonucleotide probes. The characteristics of the modified slides concerning immobilization efficiency, hybridization dynamics, and probe stripping cycles were determined. The improved surface exhibited high immobilization efficiency, a good quality uniformity, and satisfactory hybridization dynamics. The spotting concentration of 10 μmol/L can meet the requirements of detection; the spots were approximately 170 nm in diameter; the mean fluorescence intensity of the SARS spots were between 3.2 × 10(4) and 5.0 × 10(4) after hybridization. Furthermore, the microarrays prepared by this method demonstrated more resistance to consecutive probe stripping cycles. The activated GOPS‐PLL slide could undergo hybridization stripping cycles for at least three cycles, and the highest loss in fluorescence intensity was found to be only 11.9 % after the third hybridization. The modified slides using the above‐mentioned method were superior to those slides treated with conventional approaches, which theoretically agrees with the fact that modification by surface chemistry attaches the DNA covalently firmly to the slides. This protocol may have great promise in the future for application in large‐scale manufacture.


title: The Impact of COVID-19 on People with Diabetes in Brazil

text: Abstract The present study aims atidentifying main barriers faced by people living with diabetes in Brazil during the COVID-19 pandemic. Methods In a convenience sampling study, data were collected from 1701 individuals, aged 18 or above; 75.54% female participants; 60.73% T1D and 30.75% T2D, between April 22nd and May 4th, using an anonymous and untraceable survey containing 20 multiple choice questions (socio-demographic; health status and habits of life during COVID-19 pandemic). Relationship between variables was established using the multiple correspondence analysis technique. Results 95.1% of respondents reduced their frequency of going outside of their homes; among those who monitored blood glucose at home during the pandemic (91.5%), the majority (59.4%) experienced an increase, a decrease or a higher variability in glucose levels; 38.4% postponed their medical appointments and/or routine examinations; and 59.5% reduced their physical activity. T1D, the youngest group, was more susceptible to presenting COVID-19 symptoms despite not being testing; whilst the TD2 group had higher frequency of comorbidities that are additional risk factors for COVID-19 severity. Conclusions This study provides a firsthand revelation of the severity of COVID-19 on individuals with diabetes in Brazil, altering their habits, which impacted their glycemia, potentially increasing their risk of poor outcomes if infected by SARS-CoV-2.


title: Myeloid C-Type Lectin Receptors in Viral Recognition and Antiviral Immunity

text: Recognition of viral glycans by pattern recognition receptors (PRRs) in innate immunity contributes to antiviral immune responses. C-type lectin receptors (CLRs) are PRRs capable of sensing glycans present in viral pathogens to activate antiviral immune responses such as phagocytosis, antigen processing and presentation, and subsequent T cell activation. The ability of CLRs to elicit and shape adaptive immunity plays a critical role in the inhibition of viral spread within the host. However, certain viruses exploit CLRs for viral entry into host cells to avoid immune recognition. To block CLR interactions with viral glycoproteins, antiviral strategies may involve the use of multivalent glycan carrier systems. In this review, we describe the role of CLRs in antiviral immunity and we highlight their dual function in viral clearance and exploitation by viral pathogens.


title: Neurosyphilis revealed by compressive cervical spine syphilitic gumma: a case report

text: INTRODUCTION: Neurosyphilis is a sexually transmitted disease secondary to the invasion of the central nervous system by the Treponema pallidum. The spinal syphilitic gumma is rare. CASE PRESENTATION: We report a case of extradural cervical spinal syphilitic gumma revealed by spinal cord compression in a 58-year-old male. The epidural lesion was removed via a posterior approach. Histological examination revealed syphilis. Syphilis serologies were positive. Brain MRI showed an associated cerebro-meningeal syphilitic gumma. Antibiotic regime based on aqueous penicillin G was introduced for 14 days. DISCUSSION: Currently, there is an increase in the frequency of syphilis and changes in its clinical manifestations. Neurosyphilis can take atypical forms. Spinal syphilitic gumma is a rare manifestation and its association with cerebral involvement is exceptional. Diagnosis is based on serologies in the blood and cerebrospinal fluid. The place of imagery, especially magnetic resonance imaging, is essential. Neurosyphilis should be discussed as a possible differential diagnosis in evaluation of spinal and cerebral lesions.


title: Rna Viruses Redirect Host Factors to Better Amplify Their Genome

text: Publisher Summary This chapter provides an updated view of the host factors that are, at present, believed to participate in replication/transcription of RNA viruses. One of the major hurdles faced when attempting to identify host factors specifically involved in viral RNA replication/transcription is how to discriminate these factors from those involved in translation. Several of the host factors shown to affect viral RNA synthesis are factors known to be involved in protein synthesis, for example, translation factors. In addition, some of the factors identified to date appear to influence viral RNA amplification as well as viral protein synthesis, and translation and replication are frequently tightly associated. Several specific host factors actively participating in viral RNA transcription/replication have been identified and the regions of host protein/replicase or host protein/viral RNA interaction have been determined. The chapter centers exclusively on those factors that appear functionally important for viral amplification. It presents a list of the viruses for which a specific host factor associates with the polymerase, affecting viral genome amplification. It also indicates the usually accepted cell function of the factor and the viral polymerase or polymerase subunit to which the host factor binds.


title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis

text: Human metapneumovirus (hMPV) causes severe airway infection in children that may be caused by an unfavorable immune response. The nature of the innate immune response to hMPV in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. We examined nasopharynx aspirates and blood samples from hMPV-infected children without detectable co-infections. The expression of inflammatory and antiviral genes were measured in nasal airway secretions by relative mRNA quantification while blood plasma proteins were determined by a multiplex immunoassay. Several genes were significantly up-regulated at mRNA and protein level in the hMPV infected children. Most apparent was the expression of the chemokine IP-10, the pro-inflammatory cytokine IL-18 in addition to the interferon inducible gene ISG54. Interestingly, children experiencing more severe disease, as indicated by a severity index, had significantly more often up-regulation of the inflammasome-associated genes IL-1β and NLRP3. Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. Our study is the first to demonstrate that inflammasome components are associated with increased illness severity in hMPV-infected children.


title: Infectious Bursal Disease Virus: Ribonucleoprotein Complexes of a Double-Stranded RNA Virus

text: Abstract Genome-binding proteins with scaffolding and/or regulatory functions are common in living organisms and include histones in eukaryotic cells, histone-like proteins in some double-stranded DNA (dsDNA) viruses, and the nucleocapsid proteins of single-stranded RNA viruses. dsRNA viruses nevertheless lack these ribonucleoprotein (RNP) complexes and are characterized by sharing an icosahedral T =2 core involved in the metabolism and insulation of the dsRNA genome. The birnaviruses, with a bipartite dsRNA genome, constitute a well-established exception and have a single-shelled T =13 capsid only. Moreover, as in many negative single-stranded RNA viruses, the genomic dsRNA is bound to a nucleocapsid protein (VP3) and the RNA-dependent RNA polymerase (VPg). We used electron microscopy and functional analysis to characterize these RNP complexes of infectious bursal disease virus, the best characterized member of the Birnaviridae family. Mild disruption of viral particles revealed that VP3, the most abundant core protein, present at ∼450 copies per virion, is found in filamentous material tightly associated with the dsRNA. We developed a method to purify RNP and VPg–dsRNA complexes. Analysis of these complexes showed that they are linear molecules containing a constant amount of protein. Sensitivity assays to nucleases indicated that VP3 renders the genomic dsRNA less accessible for RNase III without introducing genome compaction. Additionally, we found that these RNP complexes are functionally competent for RNA synthesis in a capsid-independent manner, in contrast to most dsRNA viruses.


Tocilizumab in COVID-19: beware of risk of intestinal perforation


title: Incidence and comparison of retrospective and prospective data on respiratory and gastrointestinal infections in German households

text: BACKGROUND: Acute respiratory infections (ARI) and acute gastrointestinal infections (AGI) are the most common childhood infections, and corresponding data can either be collected prospectively or retrospectively. The aim of this study was to estimate the incidence of respiratory and gastrointestinal episodes in German households with children attending day care and to compare results of prospective and retrospective data collection. METHODS: We conducted a 4 months prospective cohort study in the winter period 2014/2015 and recruited parents of children aged 0–6 years in 75 day care centers in Braunschweig, Lower Saxony, Germany. For all household members, we collected information on episodes of ARI and AGI. We applied prospective data collection in one study arm and retrospective data collection with a reporting period of 2 months in the other. Poisson regression was used to model monthly incidence rates for both study arms. RESULTS: In total, 100 households (including 404 persons) participated in the retrospective group and 77 households (282 persons) in the prospective group. Incidence estimates for ARI (retrospective group: 0.52 per person month, prospective group: 0.47) were higher than for AGI (retrospective group: 0.14, prospective group: 0.13). The adjusted incidence estimates were similar in both study arms for ARI (incidence rate ratio for retrospective versus prospective data collection: 1.11 [confidence interval (CI) 95% 0.99; 1.24], p = 0.42) as well as for AGI (1.10 [CI 95% 0.89; 1.37], p = 0.27). CONCLUSION: If there is no need to collect biomaterials or data on severity of the diseases, incidence of infections in the household setting over a short time period (2 months) can be assessed retrospectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2434-5) contains supplementary material, which is available to authorized users.


title: N95 filtering facepiece respirators do not reliably afford respiratory protection during chest compression: A simulation study

text: Abstract Background N95 filtering facepiece respirators (N95 respirators) may not provide adequate protection against respiratory infections during chest compression due to inappropriate fitting. Methods This was a single-center simulation study performed from December 1, 2016, to December 31, 2016. Each participant underwent quantitative fit test (QNFT) of N95 respirators according to the Occupational Safety and Health Administration protocol. Adequacy of respirator fit was represented by the fit factor (FF), which is calculated as the number of ambient particles divided by the number inside the respirator. We divided all participants into the group that passed the overall fit test but failed at least one individual exercise (partially passed group [PPG]) and the group that passed all exercises (all passed group [APG]). Then, the participants performed three sessions of continuous chest compressions, each with a duration of 2 min, while undergoing real-time fit testing. The primary outcome was any failure (FF < 100) of the fit test during the three bouts of chest compression. Results Forty-four participants passed the QNFT. Overall, 73% (n = 32) of the participants failed at least one of the three sessions of chest compression; the number of participants who failed was significantly higher in the PPG than in the APG (94% vs. 61%; p = 0.02). Approximately 18% (n = 8) of the participants experienced mask fit failures, such as strap slipping. Conclusions Even if the participants passed the QNFT, the N95 respirator did not provide adequate protection against respiratory infections during chest compression.


title: Probiotics and Paraprobiotics in Viral Infection: Clinical Application and Effects on the Innate and Acquired Immune Systems

text: Recently, the risk of viral infection has dramatically increased owing to changes in human ecology such as global warming and an increased geographical movement of people and goods. Howev-er, the efficacy of vaccines and remedies for infectious diseases is limited by the high mutation rates of viruses, especially, RNA viruses. Here, we comprehensively review the effectiveness of several probiot-ics and paraprobiotics (sterilized probiotics) for the prevention or treatment of virally-induced infectious diseases. We discuss the unique roles of these agents in modulating the cross-talk between commensal bacteria and the mucosal immune system. In addition, we provide an overview of the unique mechanism by which viruses are eliminated through the stimulation of type 1 interferon production by probiotics and paraprobiotics via the activation of dendritic cells. Although further detailed research is necessary in the future, probiotics and/or paraprobiotics are expected to be among the rational adjunctive options for the treatment of various viral diseases.


title: Inhibition of SARS-CoV-2 Infection by the Cyclophilin Inhibitor Alisporivir (Debio 025)

text: Cyclophilins play a key role in the life cycle of coronaviruses. Alisporivir (Debio 025) is a nonimmunosuppressive analogue of cyclosporine with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in Vero E6 cells, with a 50% effective concentration (EC(50)) of 0.46 ± 0.04 μM. Alisporivir inhibited a postentry step of the SARS-CoV-2 life cycle. These results justify rapidly conducting a proof-of-concept phase 2 trial with alisporivir in patients with SARS-CoV-2 infection.


title: Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak

text: The 2019-nCoV infection that is caused by a novel strain of coronavirus was first detected in China in the end of December 2019 and declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Community pharmacists in one of the first areas that had confirmed cases of the viral infection, Macau, joined the collaborative force in supporting the local health emergency preparedness and response arrangements. This paper aimed to improve the understanding of community pharmacists’ role in case of 2019-CoV outbreak based on the practical experiences in consultation with the recommendations made by the International Pharmaceutical Federation on the Coronavirus 2019-nCoV outbreak.


title: Racial Differences in Time to Treatment for Melanoma

text: Abstract Background Longer time from diagnosis to definitive surgery (TTDS) is associated with increased melanoma-specific mortality. Although Black patients present with later stage melanoma and have worse survival than non-Hispanic white (NHW) patients, the association between race and TTDS is unknown. Objective To investigate racial differences in time to melanoma treatment. Methods Retrospective review of the National Cancer Database (2004-2015). Multivariable logistic regression was used to evaluate the association of race with TTDS controlling for sociodemographic/disease characteristics. Results Of the 233,982 melanoma patients identified, 1,221 (0.52%) were Black. Black patients had longer TTDS for stage I-III melanoma (p<0.001) and time to immunotherapy (p=0.01), but not for TTDS for stage IV melanoma or time to chemotherapy (p>0.05 for both). Controlling for sociodemographic characteristics, Black patients had over twice the odds of having TTDS between 41-60 days, over three times the odds of having TTDS between 61-90 days, and over five times the odds of having TTDS over 90 days. Racial differences in TTDS persisted within each insurance type. Patients with Medicaid had the longest TTDS (mean 60.4 days), and those with private insurance had the shortest TTDS (mean 44.6 days; p<0.001 for both). Conclusions Targeted approaches to improve TTDS for Black patients are integral in reducing racial disparities in melanoma outcomes.


title: Induction of immature dendritic cell apoptosis by foot and mouth disease virus is an integrin receptor mediated event before viral infection

text: Foot and mouth disease virus (FMDV) has been demonstrated to infect dendritic cells (DC) and reduced its ability to stimulate host immune responses. This study aimed to determine whether non‐replicating FMDV could induce apoptosis of the host immune cells. In this study, we have demonstrated that bone morrow derived dendritic cells (BMDCs) were induced to undergo apoptosis in a dose‐dependent manner, which was determined by the annexin‐V staining, DNA fragmentation, and TUNEL staining methods, after they were treated with the chemically inactivated FMDV in vitro. The initiation of apoptosis was apparently via an interaction of the integrin receptor on BMDCs and the RGD motif within the VP1 capsid protein of FMDV. The initiation activated a cascade of apoptotic pathway including reduced expression of Bcl‐2, activation of caspases, and release of cytochrome c from mitochondria. Pretreatment with BMDCs with LPS prevented the inactivated FMDV induced apoptosis, suggesting immature BMDCs are susceptible to such apoptosis. Taken together, the data demonstrate that the inactivated FMDV induces the apoptosis in BMDCs via the integrin receptor and subsequently triggers the apoptosis signal, suggesting that such induction of apoptosis is likely to impair immune responses against FMDV infection. J. Cell. Biochem. 102: 980–991, 2007. © 2007 Wiley‐Liss, Inc.


Identification of an ER retrieval signal in a retroviral glycoprotein


title: COVID‐19 knowledge prevents biologics discontinuation: Data from an Italian multicenter survey during RED‐ZONE declaration

text: SARS‐CoV‐2 become pandemics and there is still a dearth of data about its the potentially among dermatological patients under biologics. We aimed to assess health literacy, disease knowledge, treatment dissatisfaction and biologics attitudes toward COVID‐19. We performed a cross‐sectional, questionnaire‐based survey on 98/105 consecutive dermatological patients treated with biologics—51 suffering from plaque psoriasis, 22 from atopic dermatitis, and 25 from hidradenitis suppurativa. An ad hoc, validated questionnaire has 44 items investigating the following domains: knowledge of COVID‐19 related to (a) epidemiology, (b) pathogenesis, (c) clinical symptoms, (d) preventive measures, and (e) attitudes. Patients data and questionnaires were collected. Despite only 8.1% thought that biologics may increase the risk of COVID‐19, 18.4% and 21.4% of the patients were evaluating the possibility to discontinue or modify the dosage of the current biologic therapy, respectively. Globally, male patients (P = .001) with higher scholarity level (P = .005) displayed higher knowledge of COVID‐19. Patients with lower DLQI (P = .006), longer disease duration (P = .051) and lower scholarity (P = .007) have thought to discontinue/modify autonomously their biologic therapy. At the multivariate logistic regression, only the knowledge of epidemiology and preventive measures resulted independent predictors of continuation vs discontinuation and modification vs no modification, respectively. Dermatologists should promote COVID‐19 knowledge to prevent biologics disruption.


Alopecia areata not due by isotretinoin. A thought in COVID‐19 time


title: Indirect effects of severe acute respiratory syndrome coronavirus 2 on the kidney in coronavirus disease patients

text: Among patients hospitalized for novel coronavirus disease (COVID-19), between 10 and 14% develop an acute kidney injury and around half display marked proteinuria and haematuria. Post-mortem analyses of COVID-19 kidney tissue suggest that renal tubular cells and podocytes are affected. Here we report two cases of collapsing glomerulopathy and tubulointerstitial lesions in living COVID-19 patients. Despite our use of sensitive reverse transcription polymerase chain reaction techniques in this study, we failed to detect the virus in blood, urine and kidney tissues. Our observations suggest that these kidney lesions are probably not due to direct infection of the kidney by severe acute respiratory syndrome coronavirus 2.


Lower detection rates of SARS-COV2 antibodies in cancer patients vs healthcare workers after symptomatic COVID-19


title: Transitive Sequencing Medical Records for Mining Predictive and Interpretable Temporal Representations

text: Electronic health records (EHRs) contain important temporal information about the progression of disease and treatment outcomes. This paper proposes a transitive sequencing approach for constructing temporal representations from EHR observations for downstream machine learning. Using clinical data from a cohort of patients with congestive heart failure, we mined temporal representations by transitive sequencing of EHR medication and diagnosis records for classification and prediction tasks. We compared the classification and prediction performances of the transitive sequential representations (bag-of-sequences approach) with the conventional approach of using aggregated vectors of EHR data (aggregated vector representation) across different classifiers. We found that the transitive sequential representations are better phenotype “differentiators” and predictors than the “atemporal” EHR records. Our results also demonstrated that data representations obtained from transitive sequencing of EHR observations can present novel insights about the progression of the disease that are difficult to discern when clinical data are treated independently of the patient's history.


title: Human metapneumovirus and respiratory syncytial virus: subtle differences but comparable severity

text: Human metapneumovirus (hMPV) is a recently discovered virus that causes respiratory illness in children that can lead to hospitalization. Our study was undertaken to further understand hMPV-associated illness, compare clinical characteristics of hMPV and respiratory syncytial virus (RSV), and establish the utility of routine screening for hMPV. We retrospectively identified hMPV-associated illnesses described among children with respiratory symptoms admitted to a tertiary care center in southeast Michigan during the 2006–2007 respiratory viral season. A convenience sample of 256 nasopharyngeal specimens was subjected to nucleic acid extraction and amplification to identify those specimens positive for hMPV. A medical record review was undertaken to retrieve demographic and clinical data of patients with hMPV, comparing them to RSV-positive patients and patients evaluated for respiratory symptoms who were negative for hMPV and RSV. We found that hMPV was the second most commonly identified virus after RSV. hMPV-positive patients were older than RSV-positive patients. Among hMPV-positive patients, pneumonia was diagnosed in 37.5% and bronchiolitis in 31.2%, peribronchial cuffing was present on chest radiographs of 37.5%, antibiotic treatment was used in 81.2%, and admission to the ICU was seen in 37.5%. Finally, hMPV-positive patients were more likely to have fever than RSV-positive patients or patients negative for hMPV and RSV. We concluded that hMPV is a major pathogen associated with hospitalization of children and with the same severity of illness as RSV but in a slightly older population. Because of the apparent prevalence and severity of illness, routine screening should be implemented.


title: Translating COVID-19 Evidence to Maximize Physical Therapists’ Impact and Public Health Response

text: Coronavirus disease 2019 (COVID-19) has sounded alarm bells throughout global health systems. Late May, 2020, over 100,000 COVID-19 related deaths were reported in the United State, the highest number of any country. This article describes COVID-19 as the next historical turning point in the physical therapy profession’s growth and development. The profession has had over a 100-year tradition of responding to epidemics including poliomyelitis; two world wars and geographical regions experiencing conflicts and natural disasters; and the epidemic of noncommunicable diseases (NCDs). The evidence-based role of non-invasive interventions (non-pharmacologic/non-surgical) that hallmark physical therapist practice has emerged as being highly relevant today in addressing COVID-19 in two primary ways. First, despite some unique features, COVID-19 presents as acute respiratory distress syndrome (ARDS) in its severe acute stage. ARDS is well familiar to physical therapists in intensive care units. Body positioning and mobilization, prescribed based on comprehensive assessments/examinations, counter the negative sequelae of recumbency and bedrest; augment gas exchange and reduce airway closure, deconditioning and critical illness complications; and maximize long-term functional outcomes. Physical therapists have an indisputable role across the COVID-19 care continuum. Second, over 90% of individuals who contract and die from COVID-19 have co-morbidities, most notably cardiovascular disease, hypertension, chronic lung disease, type 2 diabetes mellitus, and obesity. Physical therapists need to redouble their efforts to address NCDs by assessing patients for risk factors and manifestations and institute evidence-based health education (smoking cessation, whole-food plant-based nutrition, weight control, physical activity/exercise), and/or support patients’ efforts when these are managed by other professionals. Effective health education is a core competency for addressing risk of COVID-19 as well as NCDs. COVID-19 is a wake-up call to the profession, an opportunity to assert its role throughout the COVID-19 care continuum and augment public health initiatives by reducing the impact of the current pandemic.


title: Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics

text: Elevated low-density lipoprotein cholesterol (LDL-C) is one of the major contributors to cardiovascular heart disease (CHD), the leading cause of death worldwide. Due to severe side effects of statins, alternative treatment strategies are required for statin-intolerant patients. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown great efficacy in LDL-C reduction. Limitations for this approach include the need for multiple injections as well as increased costs associated with patient management. Here, we engineered a DNA-encoded mAb (DMAb) targeting PCSK9 (daPCSK9), as an alternative approach to protein-based lipid-lowering therapeutics, and we characterized its expression and activity. A single intramuscular administration of mouse daPCSK9 generated expression in vivo for over 42 days that corresponded with a substantial decrease of 28.6% in non-high-density lipoprotein cholesterol (non-HDL-C) and 10.3% in total cholesterol by day 7 in wild-type mice. Repeated administrations of the DMAb plasmid led to increasing expression, with DMAb levels of 7.5 μg/mL at day 62. daPCSK9 therapeutics may provide a novel, simple, less frequent, cost-effective approach to reducing LDL-C, either as a stand-alone therapy or in combination with other LDL-lowering therapeutics for synergistic effect.


Delayed management of Staphyloccocus aureus infective endocarditis in a Middle East respiratory syndrome coronavirus possible case hospitalized in 2015 in Paris, France


title: The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein

text: Abstract Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a severe outbreak in several regions of the world in 2003. The SARS-CoV genome is predicted to contain 14 functional open reading frames (ORFs). The first ORF (1a and 1b) encodes a large polyprotein that is cleaved into nonstructural proteins (nsp). The other ORFs encode for four structural proteins (spike, membrane, nucleocapsid and envelope) as well as eight SARS-CoV-specific accessory proteins (3a, 3b, 6, 7a, 7b, 8a, 8b and 9b). In this report we have cloned the predicted nsp8 gene and the ORF6 gene of the SARS-CoV and studied their abilities to interact with each other. We expressed the two proteins as fusion proteins in the yeast two-hybrid system to demonstrate protein–protein interactions and tested the same using a yeast genetic cross. Further the strength of the interaction was measured by challenging growth of the positive interaction clones on increasing gradients of 2-amino trizole. The interaction was then verified by expressing both proteins separately in-vitro in a coupled-transcription translation system and by coimmunoprecipitation in mammalian cells. Finally, colocalization experiments were performed in SARS-CoV infected Vero E6 mammalian cells to confirm the nsp8–ORF6 interaction. To the best of our knowledge, this is the first report of the interaction between a SARS-CoV accessory protein and nsp8 and our findings suggest that ORF6 protein may play a role in virus replication.


title: Biometric Fingerprinting for Visa Application: Device and Procedure Are Risk Factors for Infection Transmission

text: BACKGROUND: Biometric fingerprint identity verification is currently introduced in visa application and entry screening at border control. The system implies physical contact between the skin and the surface of the fingerprint‐capturing and reading devices. AIM: To assess the risk of infection transmission through fingerprinting. METHODS: The medical literature was reviewed for the potential of microorganisms to be carried on the skin of hands in the community, to be transferred from hands to inanimate surfaces, to survive on surfaces, and to be transferred in doses exceeding the infectious dose. The fingerprinting procedures as currently applied were reviewed. RESULTS: Factors that favor transfer of microorganisms are large skin–surface contact between flat fingers (2 × 20 cm(2)) and fingerprint‐capturing device, nonporous contact surface, large overlap of contact surface and short turnaround time between successive applicants, high contact pressure, and difficulties to disinfect devices. Transmission risk exists for enteric viruses (rotavirus, norovirus, and hepatitis A virus), respiratory viruses (respiratory syncytial virus, rhinovirus, influenzavirus, etc.), and enteropathogenic bacteria with low infectious doses (Shigella dysenteriae, Enterohemorrhagic Escherichia coli, etc.). Using Monte Carlo risk analysis on US data, transmission of human rotavirus is estimated at 191 [95% credible intervals (CI) 0–289] per million fingerprint‐capturing procedures. Application of 70% isopropyl hand rub and 85% ethanol hand gel reduces the risk to 77 (95% CI 0–118) and 0.3 (95% CI 0–0.3) transmissions per million procedures, respectively. CONCLUSIONS: The fingerprinting procedure as currently used is associated with a risk of infection transmission. Simple hygienic measures can considerably reduce this transmission risk.


Povidone iodine gargle and mouthwash


title: The impact of attachment insecurity and sleep disturbance on symptoms and sick days in hospital-based health-care workers

text: Abstract Objective Adult attachment insecurity is associated with many health outcomes and may be associated with sleep disturbance. The purpose of this study was to test the hypothesis that sleep disturbance mediates the relationship between attachment insecurity and three measures of health (perceived general health, physical symptoms and sick days) in a group that is at high risk of sleep disturbance: hospital based health-care workers. Methods One hundred thirty-one nondepressed female hospital workers completed self-report measures of adult attachment, sleep disturbance, depressive symptoms (excluding sleep-related items) and health outcomes. The hypothesis of mediation was tested with sequential regression analyses. Results Both attachment anxiety and attachment avoidance were significantly associated with impairment in global sleep quality (ρ=.20 and .19, respectively, P<.05) and physical symptoms (ρ=.21 and .19, P<.05). Attachment anxiety was also associated with depressive symptoms (ρ=.33, P<.001) and sick days (ρ=.21, P<.05). For both physical symptoms and sick days, mediation analyses were consistent with global sleep quality acting as a partial mediator of the relationship between attachment anxiety and physical health. Non-sleep-related depressive symptoms were a stronger mediator. Conclusions This study corroborates evidence that attachment insecurity is associated with sleep disturbance and extends this association to the occurrence of physical symptoms and time off work due to sickness among workers in a high-stress occupation.


title: Fecal microbiota transplantation as a tool to treat and reduce susceptibility to disease in animals

text: Abstract Fecal microbiota transplantation (FMT) is the process by which fecal microbiota are donated from a healthy individual and subsequently transplanted into a diseased or young individual. The mechanism by which FMT is effective is believed to be due to enhanced beneficial microbes, increased microbiome diversity, and restored normal flora. Beneficial gut microorganisms not only play a role in maintaining an intestinal barrier and metabolizing nutrients, but importantly, these microbes help regulate local and systemic immune function. Although FMT has been described for several centuries, only recently has it been utilized as a mainstream therapy in humans and significantly considered for applications in other species. In humans and animals, gastrointestinal diseases are by far the most widely accepted FMT-treatable conditions; however, recent research has shown exceptional promise for FMT being used to treat or prevent other conditions, including those outside of the gastrointestinal tract. Overall, FMT is likely an underutilized, widely-available, and inexpensive tool for improving the health and response to disease in animals. In this review, the effects of FMT on veterinary diseases and potential applications for FMT in animals are discussed.


title: Potential for the replication of the betanodavirus redspotted grouper nervous necrosis virus in human cell lines

text: The determination of the host ranges of viruses is important because of the possible emergence of infectious agents, which may result from the zoonotic transmission of animal viruses to humans. The family Nodaviridae, whose members are non-enveloped, positive-stranded bipartite RNA viruses, is comprised of the genera Alphanodavirus and Betanodavirus, whose members predominantly infect insects and fish, respectively. The alphanodaviruses can also infect suckling mice and suckling hamsters, resulting in paralysis and death. Pigs near the site of isolation of the Nodamura virus (NoV), an alphanodavirus, have been reported to have high levels of NoV neutralizing antibody, suggesting that they may be part of the natural host range of this virus. Betanodaviruses are the causative agents of viral nervous necrosis, which occurs in several species of fish. However, little is known regarding the mechanism of infection of these viruses. Whether betanodaviruses can infect hosts other than fish remains unclear. In this study, we examined the possibility that a betanodavirus, redspotted grouper nervous necrosis virus (RGNNV), can infect human cell lines and showed that this virus can attach to the cells but cannot penetrate them, although human cells can support the replication of the betanodavirus when viral RNAs are transfected. The betanodavirus in its present form cannot infect human cells.


title: Eye-Catching Microbes—Polyphasic Analysis of the Microbiota on Microscope Oculars Verifies Their Role as Fomites

text: Microscopes are used in virtually every biological and medical laboratory. Previous cultivation-based studies have suggested that direct contact with microscope eyepieces increases the risk of eye infections. To obtain a deeper insight into the microbiota on oculars, we analysed 10 recently used university microscopes. Their left oculars were used for a cultivation-based approach, while the right oculars served for massive gene sequencing. After cleaning with isopropyl alcohol, the oculars were re-sampled and analysed again. All oculars were found to be contaminated with bacteria, with a maximum load of 1.7 × 10(3) CFU cm(−2). MALDI Biotyping revealed mainly Cutibacterium (68%), Staphylococcus (14%) and Brevibacterium (10%), with the most abundant species being Cutibacterium acnes (13%) and Staphylococcus capitis (6%). Cleaning reduced the microbial load by up to 2 log scales. Within 10 uncleaned and 5 cleaned samples, 1480 ASVs were assigned to 10 phyla and 262 genera. The dominant genera before cleaning were Cutibacterium (78%), Paracoccus (13%), Pseudomonas (2%) and Acinetobacter (1%). The bacteriota composition on the cleaned oculars was similar; however, it probably largely represented dead bacteria. In summary, used oculars were significantly contaminated with skin and environmental bacteria, including potential pathogens. Regular cleaning is highly recommended to prevent eye and skin infections.


Erythematous‐oedematous type of chilblain‐like lesions and COVID‐19 : an Indian perspective


title: Role of the chronic air pollution levels in the Covid-19 outbreak risk in Italy()

text: After the initial outbreak in China, the diffusion in Italy of SARS-CoV-2 is exhibiting a clear regional trend with more elevated frequency and severity of cases in Northern areas. Among multiple factors possibly involved in such geographical differences, a role has been hypothesized for atmospheric pollution. We provide additional evidence on the possible influence of air quality, particularly in terms of chronicity of exposure on the spread viral infection in Italian regions. Actual data on Covid-19 outbreak in Italian provinces and corresponding long-term air quality evaluations, were obtained from Italian and European agencies, elaborated and tested for possible interactions. Our elaborations reveal that, beside concentrations, the chronicity of exposure may influence the anomalous variability of SARS-CoV-2 in Italy. Data on distribution of atmospheric pollutants (NO(2), O(3), PM(2.5) and PM(10)) in Italian regions during the last 4 years, days exceeding regulatory limits, and years of the last decade (2010–2019) in which the limits have been exceeded for at least 35 days, highlight that Northern Italy has been constantly exposed to chronic air pollution. Long-term air-quality data significantly correlated with cases of Covid-19 in up to 71 Italian provinces (updated April 27, 2020) providing further evidence that chronic exposure to atmospheric contamination may represent a favourable context for the spread of the virus. Pro-inflammatory responses and high incidence of respiratory and cardiac affections are well known, while the capability of this coronavirus to bind particulate matters remains to be established. Atmospheric and environmental pollution should be considered as part of an integrated approach for sustainable development, human health protection and prevention of epidemic spreads but in a long-term and chronic perspective, since adoption of mitigation actions during a viral outbreak could be of limited utility.


title: Viral–bacterial interactions–therapeutic implications

text: Viral and bacterial respiratory tract infections are a leading cause of morbidity and mortality worldwide, despite the development of vaccines and potent antibiotics. Frequently, viruses and bacteria can co‐infect the same host, resulting in heightened pathology and severity of illness compared to single infections. Bacterial superinfections have been a significant cause of death during every influenza pandemic, including the 2009 H1N1 pandemic. This review will analyze the epidemiology and global impact of viral and bacterial co‐infections of the respiratory tract, with an emphasis on bacterial infections following influenza. We will next examine the mechanisms by which viral infections enhance the acquisition and severity of bacterial infections. Finally, we will discuss current management strategies for diagnosing and treating patients with suspected or confirmed viral‐bacterial infections of the respiratory tract. Further investigation into the interactions between viral and bacterial infections is necessary for developing new therapeutic approaches aimed at mitigating the severity of co‐infections.


title: Rapid generation of a human monoclonal antibody to combat Middle East respiratory syndrome

text: Summary The last century has witnessed the emergence of several previously unknown viruses as life-threatening human pathogens. Several examples include HIV, Ebola, Lujo, and, most recently, the Middle East respiratory syndrome (MERS) and Ebola. In this study, we describe a method for the swift generation of a human-derived monoclonal antibody, known as LCA60, as a treatment for MERS infections. LCA60 antibody was generated using the Cellclone Technology from the immortalized B cells of a human donor recovering from MERS. Only four months were required from the initial screening of B cells to the development of a stable CHO cell line suitable for the production of clinical grade antibody, thereby delineating a rapid pathway for the development of antiviral therapies against emerging viruses. Currently, the LCA60 antibody is being considered for clinical development, which includes prophylaxis in individuals at risk and a treatment for severe MERS-CoV infections.