title: Insectivorous bats carry host specific astroviruses and coronaviruses across different regions in Germany

text: Abstract Recently several infectious agents with a zoonotic potential have been detected in different bat species. However, there is still a lack of knowledge on the transmission dynamics within and between bat species, as well as from bats to other mammals. To better understand these processes, it is important to compare the phylogenetic relationships between different agents to that of their respective hosts. In this study, we analysed more than 950 urine, faeces and oral swab samples collected from 653 bats from mainly four species (Myotis nattereri, Myotis bechsteinii, Myotis daubentonii, and Plecotus auritus) for the presence of coronavirus, paramyxovirus and astrovirus related nucleic acids located in three different regions of Germany. Using hemi-nested reverse transcriptase (RT)-PCR amplification of fragments within the highly conserved regions of the respective RNA dependent RNA polymerase (RdRp) genes, we detected astrovirus sequences at an overall detection rate of 25.8% of the analysed animals, with a maximum of 65% in local populations. The detection rates for coronaviruses and paramyxoviruses were distinctly lower, ranging between 1.4% and 3.1%. Interestingly, the sequence similarities in samples collected from the same bat species in different geographical areas were distinctly larger than the sequence similarities between samples from different species sampled at the same location. This indicates that host specificity may be more important than host ecology for the presence of certain viruses in bats.


title: Erratum to “Complete genome comparison of porcine reproductive and respiratory syndrome virus parental and attenuated strains”

text: Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. Of the 41 nucleotide changes, 12 resulted in conservative changes and 18 produced non-conservative changes. The results suggest that key amino acids in ORF1 may contribute to the phenotype of RespPRRS, which includes increased growth rate on MA-104 cells and decreased virulence in swine. The results provide a genetic basis for future manipulation of a PRRSV reverse genetics system.


title: Parasite diversity of European Myotis species with special emphasis on Myotis myotis (Microchiroptera, Vespertilionidae) from a typical nursery roost

text: BACKGROUND: Bats belong to one of the most species-rich orders within the Mammalia. They show a worldwide distribution, a high degree of ecological diversification as well as a high diversity of associated parasites and pathogens. Despite their prominent and unique role, the knowledge of their parasite-host-relationships as well as the mechanisms of co-evolutionary processes are, partly due to strict conservation regulations, scarce. METHODS: Juvenile specimens of the greater mouse-eared bat (Myotis myotis) from a roosting colony in Gladenbach (Hesse, Germany) were examined for their metazoan endo-and ectoparasite infections and pathogens. Morphometric data were recorded and the individuals were checked for Lyssavirus-specific antigen using a direct immunofluorescence test. For unambiguous species identification, the bats were analysed by cyt-b sequence comparison. RESULTS: Myotis myotis were parasitized by the six insect and arachnid ectoparasite species, i.e. Ixodes ricinus, Ischnopsyllus octactenus, Ichoronyssus scutatus, Steatonyssus periblepharus, Spinturnix myoti and Cimex dissimilis. Additionally, the nematode Molinostrongylus alatus and the cestode Vampirolepis balsaci were recorded. Each bat was parasitized by at least four species. The parasites showed partially extreme rates of infection, never recorded before, with more than 1,440 parasites per single host. Ichoronyssus scutatus, Steatonyssus periblepharus, Vampirolepis balsaci and Molinostrongylus alatus are recorded for the first time in Germany. A checklist for Europe is presented containing records of 98 parasite species of 14 Myotis species. CONCLUSIONS: The Myotis myotis from Gladenbach (Hesse, Germany) were parasitized by a diverse parasite fauna with high infestation rates. We assume that in juvenile Myotis the number of parasites is generally higher than in adults due to only later acquired immune competence and behavioural adaptations. Our results revealed new insights into parasite fauna of M. myotis and European bats in general. The finding of endoparasitic cyclophyllidean cestodes that have a two-host lifecycle is, considering the stationary behaviour of the juvenile bats, rather unusual and suggests a non-predatory transmission mechanism (e.g. via autoinfection). A new insight gained from the collated literature was that the European wide composition of the Myotis parasite fauna is dominated by a few specific taxonomic groups in Europe.


title: All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus

text: A recent outbreak of novel coronavirus (SARS-CoV-2), the causative agent of COVID-19, has spread rapidly all over the world. Human immunodeficiency virus (HIV) is another deadly virus and causes acquired immunodeficiency syndrome (AIDS). Rapid and early detection of these viruses will facilitate early intervention and reduce disease transmission risk. Here, we present an All-In-One Dual CRISPR-Cas12a (termed “AIOD-CRISPR”) assay method for simple, rapid, ultrasensitive, one-pot, and visual detection of coronavirus SARS-CoV-2 and HIV virus. In our AIOD CRISPR assay, a pair of crRNAs was introduced to initiate dual CRISPR-Cas12a detection and improve detection sensitivity. The AIOD-CRISPR assay system was successfully utilized to detect nucleic acids (DNA and RNA) of SARS-CoV-2 and HIV with a sensitivity of few copies. Also, it was evaluated by detecting HIV-1 RNA extracted from human plasma samples, achieving a comparable sensitivity with real-time RT-PCR method. Thus, our method has a great potential for developing next-generation point-of-care molecular diagnostics.


title: Telemedicine for head and neck ambulatory visits during COVID‐19: Evaluating usability and patient satisfaction

text: BACKGROUND: In light of the COVID‐19 pandemic, there has been a rapid increase in telemedicine visits. Otolaryngology patient satisfaction with these visits has not yet been extensively studied using a validated survey. METHODS: All patients who had telemedicine visits with three head and neck surgeons, by phone or video‐based platform, between March 25, 2020 and April 24, 2020. Retrospective chart reviews were conducted to determine demographic, disease, and treatment information. Patients who had a video visit were contacted by telephone and, if they could be reached and consented, were administered the telehealth usability questionnaire (TUQ). RESULTS: Hundred surveys were completed. The average score across all questions was 6.01 on a scale from 1 to 7, where 7 indicated the highest level of patient agreement. The highest scores were for questions related to satisfaction with telehealth (6.29), while the lowest were related to reliability (4.86). CONCLUSIONS: Patients are generally highly satisfied with telemedicine.


title: Mycoplasma felis-associated meningoencephalomyelitis in a cat

text: Mycoplasmas are frequently isolated from many animal species. In domestic cats, mycoplasmas may be isolated from respiratory and ocular mucosae, but other sites are also occasionally colonized by these organisms. No cases of Mycoplasma species-associated neurologic disease have been reported in cats. We describe a case of Mycoplasma felis-associated meningoencephalitis in a 10-month-old domestic shorthair cat.


title: Experiencing SARS(): Perspectives of the elderly residents and health care professionals in a Hong Kong nursing home

text: Severe acute respiratory syndrome (SARS) has affected many areas of the world recently and is becoming a global problem. Hong Kong and China have been most severely affected by this new infectious disease. The elderly population is highly vulnerable, and mortality in those older than 65 years is more than 50%. In our study, 27 health care workers and 40 elderly residents in a nursing home were interviewed to investigate their level of knowledge of SARS and its prevention. Most of the elderly residents knew little regarding SARS and prevention strategies, despite access to outside news by TV, radio, and visitors. Also, the worry and fear of an outbreak of SARS among staff working in the nursing home was considered to be high. Tailored education programs to promote awareness and prevention of SARS for the elderly are needed. Also, more in-service training, support, and counseling are strongly indicated for staff to promote disease prevention and improve quality of care.


title: Author Correction: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

text: An amendment to this paper has been published and can be accessed via a link at the top of the paper.


title: Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection

text: Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains. IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.


title: Patterns of muscle strength loss with age in the general population and patients with a chronic inflammatory state

text: Abstract Background There is growing recognition of the serious consequences of sarcopenia on the functionality and autonomy in old age. Recently, the age-related changes in several inflammatory mediators have been implicated in the pathogenesis of sarcopenia. The purposes of this systematic review were two-fold: (1) to describe the patterns of muscle strength loss with age in the general population, and (2) to quantify the loss of muscle strength in rheumatoid arthritis as representative for an underlying inflammatory state. Handgrip strength was used as a proxy for overall muscle strength. Results Results from 114 studies (involving 90,520 subjects) and 71 studies (involving 10,529 subjects) were combined in a meta-analysis for the general and rheumatoid arthritis population respectively and standardized at an equal sex distribution. For the general population we showed that between the ages of 25 years and 95 years mean handgrip strength declined from 45.5kg to 23.2kg for males and from 27.1kg to 12.8kg for females. We noted a steeper handgrip strength decline after 50 years of age (rate of 0.37kg/year). In the rheumatoid arthritis population handgrip strength was not associated with chronological age between the ages of 35 years and 65 years and was as low as 20.2kg in male and 15.1 in female. Rheumatoid arthritis disease duration was inversely associated with handgrip strength. Conclusions This meta-analysis shows distinct patterns of age-related decrease of handgrip strength in the general population. Handgrip strength is strongly associated with the presence and duration of an inflammatory state as rheumatoid arthritis. The putative link between age-related inflammation and sarcopenia mandates further study as it represents a potential target for intervention to maintain functional independence in old age.


title: Diabetes, Obesity and COVID‐19: A Complex Interplay

text: With the accumulation of observational data showing association of metabolic comorbidities with adverse outcomes from COVID‐19, there is a need to disentangle the contributions of pre‐existing macro‐ and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID‐19, the clinical and research questions that arise from these; and the types of studies needed to answer them. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience or interest in management of COVID‐19. This article is protected by copyright. All rights reserved.


title: Lives or livelihood: Insights from locked-down India due to COVID19

text: • India is the second most populous country of the world, counted among the most rapidly growing economies of the world. • Realizing that a fast spread of COVID19 in India would wipe-out a huge part of the world population, the government of India found itself in a dilemma of whether to save lives or livelihoods. • Prioritizing lives for livelihood, the government announced a 21-day lockdown. • This measure is supposed to leave a lasting impact on the economy of the country, which is evident from a cut in the GDP growth forecast by Moody’s (from 5.3 per cent to 2.5 per cent for calendar year 2020) within ten days of the earlier projection. • This article suggests measures to the government of India to balance between saving lives and sustaining the economy.


title: Methods for preparation of low abundance glycoproteins from mammalian cell supernatants()

text: Proteins secreted to mammalian cell supernatants are usually in a low concentration and purity, due to the limitation of the expression systems or the presence of a large amount of contaminant proteins from the cell medium. So, initial protein recovery from cell supernatants requires of a highly specific chromatography step. We compared several purification methods based on affinity chromatography for purification of proteins from cell culture supernatants: metal chelate affinity, strep-tag and immunopurification with a monoclonal antibody. Soluble receptor glycoproteins were engineered with the corresponding peptide tag at their C-terminal end. The proteins were expressed in 293T cells and secreted to the cell supernatant, as monitored by sandwich ELISA. Supernatants were run through the different chromatography columns and several purification-related parameters determined. While all column-retained proteins were easily eluted, the chelating and immunopurification chromatography gave the highest yield and the latest method provided a sample with the highest purity. So, in spite of its cost, immunopurification chromatography gave optimal results for purification of a low abundance protein from a cell supernatant. Finally, we applied a protein expression system together with immunopurification chromatography for preparation of a glycoprotein for crystallization.


title: Report on WHO meeting on immunization in older adults: Geneva, Switzerland, 22–23 March 2017

text: Many industrialized countries have implemented routine immunization policies for older adults, but similar strategies have not been widely implemented in low- and middle-income countries (LMICs). In March 2017, the World Health Organization (WHO) convened a meeting to identify policies and activities to promote access to vaccination of older adults, specifically in LMICs. Participants included academic and industry researchers, funders, civil society organizations, implementers of global health interventions, and stakeholders from developing countries with adult immunization needs. These experts reviewed vaccine performance in older adults, the anticipated impact of adult vaccination programs, and the challenges and opportunities of building or strengthening an adult and older adult immunization platforms. Key conclusions of the meeting were that there is a need for discussion of new opportunities for vaccination of all adults as well as for vaccination of older adults, as reflected in the recent shift by WHO to a life-course approach to immunization; that immunization in adults should be viewed in the context of a much broader model based on an individual’s abilities rather than chronological age; and that immunization beyond infancy is a global priority that can be successfully integrated with other interventions to promote healthy ageing. As WHO is looking ahead to a global Decade of Healthy Ageing starting in 2020, it will seek to define a roadmap for interdisciplinary collaborations to integrate immunization with improving access to preventive and other healthcare interventions for adults worldwide.


title: Increasing resilience by creating an adaptive salesforce

text: Abstract During disruptions such as the COVID-19 pandemic, the resilience of any commercial organization becomes a critical characteristic. This paper examines the flexibility of the sales process—that is, adaptive selling—as an analog to resiliency, and recommends that firms create an adaptive salesforce to increase resilience. By examining the extant research and conducting interviews with sales leaders, the findings of this paper suggest that an adaptive salesforce should focus on three areas of change within team structures. The first is an increase in flexibility and adaptiveness for the functions that the salesforce performs. The second area is an improvement of the adaptiveness of scale in which sales functions can be rapidly insourced or outsourced. The final area is technology adaptiveness, in which the salesforce adopts the use of technologies that are most relevant to customers. Implications for the firm, sales function, and individual salespeople are also derived.


Coronavirus: need for a therapeutic approach


docid: ygoywgyq

title: Implications for cancer care in iran during COVID-19 pandemic


title: Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses

text: Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH(4)Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC(50 )of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents.


Body mass index and risk of COVID‐19 across ethnic groups: analysis of UK Biobank study


title: DNA hybridization biosensors using polylysine modified SPCEs

text: Two electrochemical DNA hybridization biosensors (genosensors) for the detection of a 30-mer sequence unique to severe acute respiratory syndrome (SARS) virus are described in this work. Both genosensors rely on the hybridization of the oligonucleotide target with its complementary probe, which is immobilized on positively charged polylysine modified screen-printed carbon electrodes (SPCEs), through electrostatic interactions. In one design, a biotinylated target is used and the detection of the hybridization reaction is monitored using alkaline phosphatase labeled streptavidin (S-AP). This enzyme catalyzes the hydrolysis of the substrate 3-indoxyl phosphate (3-IP) to indigo, which is then solubilized to indigo carmine and detected by means of cyclic voltammetry (CV). In the other design, the target is labeled using an Au(I) complex, sodium aurothiomalate, and the duplex formation is detected by measuring, for first time, the current generated by the hydrogen evolution catalyzed by the gold label. Using 30 min of hybridization time, a detection limit of 8 pM is calculated for the enzymatic genosensor. Although this good sensitivity cannot be reached with the metal label (0.5 nM), the use of this label allows a considerable decrease of the analysis time. Both genosensors do not require the modification of the oligonucleotide probe and using stringent experimental conditions (60 min of hybridization time and 50% formamide in the hybridization buffer) can discriminate between a complementary oligonucleotide and an oligonucleotide with a three-base mismatch.


title: Fiebre en el viajero retornado del trópico

text: Resumen El incremento de los viajes internacionales, la creciente presencia de vectores transmisores de arbovirus en nuestro país, las alertas de fiebres hemorrágicas, como el actual brote de ébola en la R. D. del Congo y los casos autóctonos de fiebre hemorrágica de Crimea-Congo en nuestro país, ponen de nuevo en primer plano las enfermedades tropicales. El aislamiento de los casos sospechosos de enfermedades de alta transmisibilidad y letalidad ha de ser una prioridad (fiebres hemorrágicas, MERS-CoV). Al valorar al paciente, una cuidadosa historia clínica basada en los aspectos epidemiológicos de la zona de procedencia, las actividades realizadas, el tiempo de estancia en el mismo y el inicio de los síntomas nos ayudarán finalmente, si no al diagnóstico definitivo, sí al menos a descartar las enfermedades que signifiquen una amenaza para él. Por su frecuencia y gravedad la malaria debe ser descartada, sin olvidar las otras causas habituales de fiebre con las que el médico de urgencias debe estar familiarizado también. Abstract The increase in international travel, the growing presence of arbovirus vectors in our country, and notifications of haemorrhagic fever such as the current outbreak of Ebola in D.R. Congo and the cases of Crimea-Congo haemorrhagic fever in our country have again cast the spotlight on tropical diseases Isolating suspected cases of highly contagious and lethal diseases must be a priority (Haemorrhagic fever, MERS-CoV). Assessing the patient, taking a careful medical history based on epidemiological aspects of the area of origin, activities they have carried out, their length of stay in the area and the onset of symptoms, will eventually help us, if not to make a definitive diagnosis, at least to exclude diseases that pose a threat to these patients. Malaria should be ruled out because of its frequency, without forgetting other common causes of fever familiar to emergency doctors.


title: Analysis of cis-Acting Sequences Essential for Coronavirus Defective Interfering RNA Replication

text: Abstract Mouse hepatitis virus (MHV) defective interfering (DI) RNA was used to determine the cis-acting sequences required for MHV RNA replication. A 2.2-kb-long cDNA clone of the MHV DI RNA DIssE was used to test the effect of deletions throughout the DI RNA on replication in DI RNA-transfected, MHV-infected cells. Data from a series of deletion mutants demonstrated that about 470 nucleotides at the 5′ terminus, 460 nucleotides at the 3′ terminus, and about 135 nucleotides in an internal position approximately 0.9 kb from the 5′ end of DI RNA were necessary for DI RNA replication. These data suggested that cis-acting sequences which were necessary for MHV RNA replication required not only terminal sequences but also an internal sequence present at about 3.2 kb from the 5′ end of the genome.


title: Pharmacology, Physiology, and Mechanisms of Action of Dipeptidyl Peptidase-4 Inhibitors

text: Dipeptidyl peptidase-4 (DPP4) is a widely expressed enzyme transducing actions through an anchored transmembrane molecule and a soluble circulating protein. Both membrane-associated and soluble DPP4 exert catalytic activity, cleaving proteins containing a position 2 alanine or proline. DPP4-mediated enzymatic cleavage alternatively inactivates peptides or generates new bioactive moieties that may exert competing or novel activities. The widespread use of selective DPP4 inhibitors for the treatment of type 2 diabetes has heightened interest in the molecular mechanisms through which DPP4 inhibitors exert their pleiotropic actions. Here we review the biology of DPP4 with a focus on: 1) identification of pharmacological vs physiological DPP4 substrates; and 2) elucidation of mechanisms of actions of DPP4 in studies employing genetic elimination or chemical reduction of DPP4 activity. We review data identifying the roles of key DPP4 substrates in transducing the glucoregulatory, anti-inflammatory, and cardiometabolic actions of DPP4 inhibitors in both preclinical and clinical studies. Finally, we highlight experimental pitfalls and technical challenges encountered in studies designed to understand the mechanisms of action and downstream targets activated by inhibition of DPP4.


The explosive epidemic outbreak of novel coronavirus disease 2019 (COVID-19) and the persistent threat of respiratory tract infectious diseases to global health security


title: The clinical and immunological features of pediatric COVID-19 patients in China

text: Abstract In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3–4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.


title: A novel cause of chronic viral meningoencephalitis: Cache Valley virus

text: OBJECTIVE: Immunodeficient patients are particularly vulnerable to neuroinvasive infections that can be challenging to diagnose. Metagenomic next generation sequencing can identify unusual or novel microbes and is therefore well suited for investigating the etiology of chronic meningoencephalitis in immunodeficient patients. METHODS: We present the case of a 34‐year‐old man with X‐linked agammaglobulinemia from Australia suffering from 3 years of meningoencephalitis that defied an etiologic diagnosis despite extensive conventional testing, including a brain biopsy. Metagenomic next generation sequencing of his cerebrospinal fluid and brain biopsy tissue was performed to identify a causative pathogen. RESULTS: Sequences aligning to multiple Cache Valley virus genes were identified via metagenomic next generation sequencing. Reverse transcription polymerase chain reaction and immunohistochemistry subsequently confirmed the presence of Cache Valley virus in the brain biopsy tissue. INTERPRETATION: Cache Valley virus, a mosquito‐borne orthobunyavirus, has only been identified in 3 immunocompetent North American patients with acute neuroinvasive disease. The reported severity ranges from a self‐limiting meningitis to a rapidly fatal meningoencephalitis with multiorgan failure. The virus has never been known to cause a chronic systemic or neurologic infection in humans. Cache Valley virus has also never previously been detected on the Australian continent. Our research subject traveled to North and South Carolina and Michigan in the weeks prior to the onset of his illness. This report demonstrates that metagenomic next generation sequencing allows for unbiased pathogen identification, the early detection of emerging viruses as they spread to new locales, and the discovery of novel disease phenotypes. Ann Neurol 2017;82:105–114


title: In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing

text: BACKGROUND: The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 M(pro) (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding. METHODS: For the study, we have targeted the SARS-CoV-2 M(pro) for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 M(pro) active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries. RESULTS: The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 M(pro) protein. CONCLUSIONS: In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.


title: The population genetics of Trypanosoma cruzi revisited in the light of the predominant clonal evolution model

text: Abstract Comparing the population structure of Trypanosoma cruzi with that of other pathogens, including parasitic protozoa, fungi, bacteria and viruses, shows that the agent of Chagas disease shares typical traits with many other species, related to a predominant clonal evolution (PCE) pattern: statistically significant linkage disequilibrium, overrepresented multilocus genotypes, near-clades (genetic subdivisions somewhat blurred by occasional genetic exchange/hybridization) and “Russian doll” patterns (PCE is observed, not only at the level of the whole species, but also, within the near-clades). Moreover, T. cruzi population structure exhibits linkage with the diversity of several strongly selected genes, with gene expression profiles, and with some major phenotypic traits. We discuss the evolutionary significance of these results, and their implications in terms of applied research (molecular epidemiology/strain typing, analysis of genes of interest, vaccine and drug design, immunological diagnosis) and of experimental evolution. Lastly, we revisit the long-term debate of describing new species within the T. cruzi taxon.


title: Education and scientific dissemination during the COVID‐19 pandemic

text: The COVID‐19 pandemic has produced unique challenges for society in general and healthcare workers in particular. For intensivists and anaesthetists the clinical workload has been incomparable, with multiple challenges for those providing frontline care. This has included staffing dramatically expanded intensive care units, redeployment, cross‐skilling and embracing new ways of working. It has also included involvement in many less high profile roles, such as hospital logistics planning, risk management and supply chain management to ensure critical care and emergency anaesthesia and surgery had space, staff, systems and equipment.


title: Impact of lockdown measures to combat Covid-19 on air quality over western Europe

text: Abstract Recent studies based on observations have shown the impact of lockdown measures taken in various European countries to contain the Covid-19 pandemic on air quality. However, these studies are often limited to compare situations without and with lockdown measures, which correspond to different time periods and then under different meteorological conditions. We propose a modelling study with the WRF-CHIMERE modelling suite for March 2020, an approach allowing to compare atmospheric composition with and without lockdown measures without the biases of meteorological conditions. This study shows that the lockdown effect on atmospheric composition, in particular through massive traffic reductions, has been important for several short-lived atmospheric trace species, with a large reduction in NO2 concentrations, a lower reduction in Particulate Matter (PM) concentrations and a mitigated effect on ozone concentrations due to non-linear chemical effects.


title: All Hands on Deck: A Synchronized Whole-of-World Approach for COVID-19 Mitigation

text: Abstract The COVID-19 pandemic can no longer be mitigated by nationwide approach of individual nations alone. Given its scale and accelerating expansion COVID-19 behooves a coordinated and simultaneous Whole- of-World approach that galvanizes clear global leadership and solidarity from all governments of the world. Considering an ‘all hands-on deck’ concept, we present a comprehensive list of tools and entities responsible for and enabling them, as well a conceptual framework to achieve the maximum impact. The list is drawn from pandemic mitigation tools developed in response to past outbreaks including influenza, coronaviruses, and Ebola and includes tools to minimize transmission in various settings including person-to-person, crowd, funerals, travel, workplace, and events and gatherings including business, social and religious venues. Included are the roles of individuals, communities, government and other sectors such as school system, health, institutions, and business. While individuals and communities have significant responsibilities to prevent person-to-person transmission, other entities can play a significant role to enable individuals and communities to make use of the tools. Historic and current data indicate the role of political will, whole-of-government approach, and the role of early introduction of mitigation measures. There is also an urgent need to further elucidate the immunologic mechanisms underlying the epidemiological characteristics such as the low disease burden among women, and role of COVID-19 in inducing Kawasaki like syndromes in children. Understanding the role of and development of anti-inflammatory strategies based on our understanding pro-inflammatory cytokines (IL1, IL-6) is also critical. Similarly, the role of oxygen therapy as an anti-inflammatory strategy is evident and access to oxygen therapy should be prioritized to avoid the aggravation of COVID-19 infection. We highlight the need for global solidarity to share both mitigation commodities and infrastructure between countries. Given the global reach ofCOVID-19 and potential for repeat waves of outbreaks, we call on all countries and communities to act synergistically and emphasize the need for synchronized pan-global mitigation efforts to minimize everyone's risk, maximize collaboration and to commit to shared progress.


docid: uiizoqff

title: IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein

text: The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus strain-dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection, and provides insight into the specialized role of IFITMs in HIV infection.


title: Worldwide Outbreak Database: the largest collection of nosocomial outbreaks

text: Epidemiological findings of a single outbreak event may not be generalized; however, the characteristics of a typical outbreak can be determined on the basis of a large number of similar events. The Outbreak Database (http://www.outbreak-database.com) is the largest collection of nosocomial outbreaks currently available—and is still expanding. Articles are filed systematically, enabling those on a specific parameter of interest to be retrieved quickly. As such, this database is an extremely valuable tool on many medically related fronts, such as for educating other medical personnel, providing relevant information during the investigation of an acute outbreak, or addressing scientific-oriented questions. Several systematic reviews on a wide range of subjects, including sources of infections, types of pathogens, routes of transmission, appropriate infection control measures, and patients at risk of infection, have already been published based on information contained in this database. As this database may be used free of charge, all medical staff in the field of infection control, hygiene, and hospital epidemiology should be aware of its existence.


docid: zqhpkhfz

title: Mobile and accurate detection system for infection by the 2009 pandemic influenza A (H1N1) virus with a pocket‐warmer reverse‐transcriptase loop‐mediated isothermal amplification

text: The 2009 pandemic H1N1 influenza A virus spread quickly worldwide in 2009. Since most of the fatal cases were reported in developing countries, rapid and accurate diagnosis methods that are usable in poorly equipped laboratories are necessary. In this study, a mobile detection system for the 2009 H1N1 influenza A virus was developed using a reverse‐transcriptase loop‐mediated isothermal amplification (RT‐LAMP) kit with a disposable pocket‐warmer as a heating device (designated as pwRT‐LAMP). The pwRT‐LAMP can detect as few as 100 copies of the virus—which is nearly as sensitive as real‐time reverse‐transcription polymerase chain reaction (RT‐PCR)—and does not cross‐react with RNA of seasonal influenza viruses. To evaluate the usefulness of the pwRT‐LAMP system, nasal swab samples were collected from 56 patients with flu‐like symptoms and were tested. Real‐time RT‐PCR confirmed that the 2009 H1N1 influenza A virus was present in 27 of the 56 samples. Of these 27 positive samples, QuickVue Influenza A + B immunochromatography detected the virus in only 11 samples (11/27; 40.7%), whereas the pwRT‐LAMP system detected the virus in 26 of the 56 samples (26/27 of the positive samples; 96.3%). These findings indicate that the mobile pwRT‐LAMP system is an accurate diagnostic system for the 2009 H1N1 influenza A virus, and has great potential utility in diagnosing future influenza pandemics. J. Med. Virol. 83:568–573, 2011. © 2011 Wiley‐Liss, Inc.


To the Editor


title: Stopping Covid-19: A pandemic-management service value chain approach

text: A logical strategy to contain the Covid-19 pandemic is to completely isolate everyone for 2 weeks (the incubation period of the virus). However, such a strategy can have prohibitive economic and social costs and, therefore, will be difficult to implement. At the same time, the current situation is leading to an expanding humanitarian, health and economic crisis. Based on principles of the Theory of Constraints, we propose in this article the “Shutting-down Transmission Of Pandemic” (STOP Covid-19) plan that would reliably contain the pandemic, mitigate its economic consequences, and boost societal confidence. This plan requires the implementation of four strategies over 90 days: (a) stop all international, domestic passenger air and intercity bus/train travel; (b) create administrative zones of about 1 million people; (c) stop all non-emergency cross-zonal travel except for transportation of goods, and (d) deploy an information-driven service value chain to control the spread of the pandemic within a zone.


Reinventar el proceso radiológico. ¡¡Un verdadero reto!!


title: Coinfection with Haemophilus parasuis serovar 4 increases the virulence of porcine circovirus type 2 in piglets

text: BACKGROUND: Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine. Pigs with PMWS are often infected with a variety of other pathogens, including bacteria, viruses and mycoplasm, in addition to porcine circovirus type 2 (PCV2). PCV2 and Haemophilus parasuis serovar 4 (HPS4) coinfection remain epidemic in China. METHODS: Here we report construction of a three-week-old naturally farrowed, colostrum-deprived (NFCD) piglet’s infection model and demonstrate that PCV2-infected piglets with the HPS4 coinfection increased the virulence of PCV2 and these pathogens interact acquired PMWS. RESULTS: All the single infected piglets were transiently bacteremic or viremic. All the PCV2/HPS4 coinfected piglets developed PMWS, characterized by dyspnea, anorexia, prostration and lose weight severely. Co-infection with PCV2 and HPS4 resulted in an increased amount of virus in serum and tissues, presented a slower generation and lower levels of antibodies against PCV2. Co-infection with PCV2 and HPS4 resulted in further reductions in total and differential peripheral blood leukocyte counts. Meantime, PCV2/ HPS4 coinfection potentiated the severity of lung and lymphoid lesions by PCV2-associated, increased the virulence of PCV2-antigen and enhanced the incidence of PMWS in piglets. CONCLUSION: Co-infection with PCV2 and HPS4 induce the exacerbation of system injuries and enhance the pathogenicity of PCV2 in piglets.


title: The Short-run and Long-run Effects of Covid-19 on Energy and the Environment

text: Summary/Abstract We explore how the short-run effects of Covid-19 in reducing CO2 and local air pollutant emissions can easily be outweighed by the long-run effects of a slowing of clean energy innovation. Focusing on the United States, we show that in the short run, Covid-19 has reduced consumption for jet fuel and gasoline dramatically, by 50% and 30% respectively, while electricity demand has declined by less than 10%. CO2 emissions have declined by 15%, while local air pollutants have also declined, saving about 200 lives per month. However, there could be a deep impact on long-run innovation in clean energy, leading to an additional 2,500 MMT CO2 and 40 deaths per month on average to 2035. Even pushing back renewable electricity generation investments by one year would outweigh the emission reductions and avoided deaths from March-June 2020. The policy response will determine how Covid-19 ultimately influences the future path of emissions.


title: The role of testing in infectious disease control: A case of COVID-19 in Africa

text: Abstract The dramatic increase in COVID-19 suspected cases in Africa has placed enormous burden on public and private clinical facilities. Till date, the most commonly used method for the identification and confirmation of the virus is the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) testing. Unfortunately, testing capacities have been limited in many parts of Africa because of inadequate test kits which have restricted scaling up beyond the few public health laboratories at designated locations. We present in this mini-review Africa’s preparedness and readiness toward testing, why testing is crucial, the need to immediately strengthen existing facilities and what it involves as combined approaches for managing the COVID-19 crisis. The review highlights the urgent need for speedy expansion and distribution of several laboratory testing platforms to public health facilities and fully accredited private clinical laboratories, including real-time PCR and serological assays.


title: Causative agents and epidemiology of diarrhea in Korean native calves

text: Calf diarrhea caused by infectious agents is associated with economic losses in the cattle industry. The purpose of this study was to identify the causative agents and epidemiological characteristics of diarrhea in Korean native calves (KNC). In total, 207 diarrheal KNC aged less than 7 months were investigated. Fecal samples collected from the rectum were examined for causative agents using polymerase chain reaction (PCR) or real-time PCR and the number of oocysts were counted. Fourteen causative agents were detected from 164 of the 207 diarrheal KNC. Rotavirus was the most common agent (34.8%), followed by Eimeria spp. (31.7%), Escherichia coli (22.0%), Giardia spp. (14.0%), Clostridium difficile (9.8%), bovine viral diarrhea virus (8.5%), coronavirus (7.9%), Cryptosporidium spp. (7.3%), torovirus (6.7%), parvovirus (5.5%), norovirus (4.9%), kobuvirus (1.8%), adenovirus (1.2%), and Salmonella spp. (0.6%). About 95 (57.9%) of 164 calves were infected with a single causative agent and 42.1% were infected by multiple agents. No significant difference was observed in mortality between calves infected with a single agent and multiple agents. The occurrence of diarrhea caused by rotavirus, Eimeria spp., kobuvirus, and Giardia spp. was significantly different based on onset age, and the prevalence of diarrhea caused by rotavirus or C. difficile was significantly different between seasons. This study help the understanding of KNC diarrhea for the development of an effective strategy for disease prevention and control, especially in Eastern provinces of South Korea.


title: Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony

text: Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks.


title: COVID-19 Outcomes among People with Intellectual and Developmental Disability Living in Residential Group Homes in New York State

text: BACKGROUND: People with intellectual and developmental disabilities (IDD) may be at higher risk of severe outcomes from COVID-19. OBJECTIVE: To describe COVID-19 outcomes among people with IDD living in residential groups homes in the state of New York and the general population of New York State. METHODS: Data for people with IDD are from a coalition of organizations providing over half of the residential services for the state of New York, and from the New York State Department of Health. Analysis describes COVID-19 case rates, case-fatality, and mortality among people with IDD living in residential group homes and New York State through May 28, 2020. RESULTS: People with IDD living in residential group homes were at greater risk of severe COVID-19 outcomes: case rates – 7,841 per 100,000 for people with IDD compared to 1,910 for New York State; case-fatality – 15.0% for people with IDD compared to 7.9% for New York State; and mortality rate – 1,175 per 100,000 for people with IDD compared to 151 per 100,000 for New York State. Differences in cases and mortality rate were confirmed across regions of the state, but case-fatality rate was only higher for people with IDD in and around the New York City region. CONCLUSIONS: COVID-19 appears to present a greater risk to people with IDD, especially those living in congregate settings. A full understanding of the severity of this risk will not be possible until US states begin publicly sharing all relevant data they have on COVID-19 outcomes among this population.


title: The therapy of gastrointestinal infections associated with the acquired immunodeficiency syndrome

text: Although there have been dramatic strides in the therapy of human immunodeficiency virus infection over the last few years, the number of infected people world‐wide is tremendous and, at least in developing countries, continues to expand. Complications which involve the gastrointestinal tract are common in these patients, because the gut is a major site for involvement by opportunistic infections and neoplasms in patients with the acquired immunodeficiency syndrome. It is important to recognize the clinical spectrum of gastrointestinal diseases, as well as the appropriate and most cost‐effective diagnostic strategies, as therapies for a number of these disorders are both widely available and highly effective. This review summarizes the major gastrointestinal infections which are seen in patients with the acquired immunodeficiency syndrome, and their treatment.


title: Practical experience of high throughput real time PCR in the routine diagnostic virology setting

text: Abstract The advent of PCR has transformed the utility of the virus diagnostic laboratory. In comparison to traditional gel based PCR assays, real time PCR offers increased sensitivity and specificity in a rapid format. Over the past 4 years, we have introduced a number of qualitative and quantitative real time PCR assays into our routine testing service. During this period, we have gained substantial experience relating to the development and implementation of real-time assays. Furthermore, we have developed strategies that have allowed us to increase our sample throughput while maintaining or even reducing turn around times. The issues resulting from this experience (some of it bad) are discussed in detail with the aim of informing laboratories that are only just beginning to investigate the potential of this technology.


title: Infective disorders of the gastrointestinal tract

text: Gastrointestinal infections are a major cause of morbidity and mortality worldwide. Infectious organisms are often recovered by microbiological methods, but surgical pathologists may play a very valuable role in diagnosis. This review will focus on infective disorders of the gastrointestinal tract with an emphasis on enterocolitides caused by food‐ and water‐borne pathogens. Diagnostic histological features of selected enteric infections will be emphasized, including those that mimic other inflammatory conditions of the gut (such as ischaemia or idiopathic inflammatory bowel disease), along with available diagnostic methods that can aid in diagnosis.


title: The influence of cold weather on the usage of emergency link calls: a case study in Hong Kong

text: BACKGROUND: In response to an unexpected long cold spell in February 1996 which killed more than 100 older adults (mostly living alone) in Hong Kong, the Hong Kong Senior Citizen Home Safety Association established a Personal Emergency Link Service to provide emergency contact to the older adults, which uses a telephone system to render emergency relief and total care service around the clock. To facilitate the dynamic and efficient allocation of service resources, it is crucial to understand the factors linked with use of the services and number of hospital admissions arising from PE link service. METHODS: We initially use the Poisson generalized linear model (GLM) with polynomial effect functions of relevant covariates. If the time series of residuals from fitting the Poisson GLM reveals significant serial correlation, a Poisson generalized linear autoregressive moving average (GLARMA) model is refitted to the data to account for the auto-correlation among the time series of daily call numbers. If the data is overdispersed relative to the best fitting Poisson GLARMA model, then the negative binomial GLARMA model is refitted to account for any overdispersion. In all the models, dummy variables for weekdays and months are included to account for any cyclic trends due weekday effect or month of the year effect. The secular time trend is modeled by a polynomial function of calendar time over the study period. Finally any critical temperatures are identified by visually inspecting the graph of the effect function of temperature. RESULTS: The weekday and month effects are both significant with Monday seeing more PE Link calls than Sunday and June seeing less than January. Temperature has significant effect on the PE Link call rate with the effect highly nonlinear. A critical temperature, below which excessive increase in PE link calls that lead to hospital admissions, is identified to be around 15 °C. CONCLUSION: Identifying a threshold temperature which generates an excessive increase in the expected number of PE Link calls would be useful in service provision planning and support for elderly in need of hospital admission.


title: Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: A case series

text: BACKGROUND: Mechanically ventilated patients with coronavirus disease 2019 (COVID-19) have a mortality of 24–53%, in part due to distal mucopurulent secretions interfering with ventilation. Dornase alfa is recombinant human DNase 1 and digests DNA in mucoid sputum. Nebulized dornase alfa is FDA-approved for cystic fibrosis treatment. DNA from neutrophil extracellular traps (NETs) contributes to the viscosity of mucopurulent secretions. NETs are found in the serum of patients with severe COVID-19, and targeting NETs reduces mortality in animal models of acute respiratory distress syndrome (ARDS). Thus, dornase alfa may be beneficial to patients with severe COVID-19—acting as a mucolytic and targeting NETs. However, delivery of nebulized drugs can aerosolize SARS-CoV-2, which causes COVID-19, increasing the infection risk for staff. Here, we report a single center case series where dornase alfa was administered through an in-line nebulizer system to minimize risk of virus aerosolization. METHODS: Demographic, clinical data, and outcomes were collected from the electronic medical records of five mechanically ventilated patients with COVID-19—including three requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO)—treated with nebulized in-line endotracheal dornase alfa co-administered with albuterol (used to increase delivery to the alveoli), between March 31 and April 24, 2020. Data on tolerability and responses, including longitudinal values capturing respiratory function and inflammatory status, were analyzed. RESULTS: Following nebulized in-line administration of dornase alfa with albuterol, the fraction of inspired oxygen requirements was reduced for all five patients. All patients remain alive and two patients have been discharged from the intensive care unit. No drug associated toxicities were identified. CONCLUSIONS: The results presented in this case series suggest that dornase alfa will be well-tolerated by critically ill patients with COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and two have recently been registered (NCT04359654 and NCT04355364). With this case series, we hope to contribute to the development of management approaches for critically ill patients with COVID-19.


title: A follow-up of Beagle dogs intradermally infected with Leishmania chagasi in the presence or absence of sand fly saliva

text: In this study, we compare the development of infection and/or disease in Beagle dogs intradermally infected with Leishmania chagasi, in the presence or absence of Lutzomyia longipalpis saliva, with those of intravenously infected animals. Spleen samples of all the animals inoculated with parasites had positive polymerase chain reaction tests for Leishmania DNA. Positive spleen cultures for Leishmania were detected earlier (P≤0.018) and were more frequent (five out of the five animals) in intravenously infected animals than in the intradermally infected animals, in presence (two out of the six animals) or absence (three out of the five animals) of salivary gland lysate of L. longipalpis. Significant increase in serum antibodies against Leishmania was observed only in the intravenously infected group (P=0.004). In addition, dogs with infection confirmed by isolation of amastigotes or detection of parasite DNA were, nevertheless, negative for anti-Leishmania antibodies up to 5 months or more after infection. Only animals of the intravenously infected group developed progressive decreases in hematocrit (Pearson r=−0.8076, P=0.0026) and hemoglobin (Pearson r=−0.8403, P=0.0012) during the infection period. No significant difference in the course of infection was observed between groups of intradermally infected animals. The data presented herein confirms that the intradermal inoculation of dogs with Leishmania produces an asymptomatic form of infection. It also fails to show an advantage in using L. longipalpis saliva as an infection-enhancing agent in experimental canine leishmaniasis.


title: SARS-CoV-2: fear versus data

text: ABSTRACT SARS-CoV-2, the novel coronavirus from China, is spreading around the world, causing a huge reaction despite its current low incidence outside China and the Far East. Four common coronaviruses are in current circulation and cause millions of cases worldwide. This article compares the incidence and mortality rates of these four common coronaviruses with those of SARS-CoV-2 in Organisation for Economic Co-operation and Development countries. It is concluded that the problem of SARS-CoV-2 is probably being overestimated, as 2.6 million people die of respiratory infections each year compared with less than 4000 deaths for SARS-CoV-2 at the time of writing.


title: A One Health Approach to Tackle Cryptosporidiosis

text: Cryptosporidiosis is a significant diarrhoeal disease in both people and animals across the world and is caused by several species of the protozoan parasite Cryptosporidium. Recent research has highlighted the longer-term consequences of the disease for malnourished children, involving growth stunting and cognitive deficits, and significant growth and production losses for livestock. There are no vaccines currently available to prevent the disease and few treatment options in either humans or animals, which has been a significant limiting factor in disease control to date. A One Health approach to tackle zoonotic cryptosporidiosis looking at new advances in veterinary, public, and environmental health research may offer several advantages and new options to help control the disease.


docid: iiniecga

title: Metabolic associated fatty liver disease increases coronavirus disease 2019 disease severity in nondiabetic patients

text: BACKGROUND AND AIM: Coronavirus disease 2019 (COVID‐19) has attracted increasing worldwide attention. While diabetes is known to aggravate COVID‐19 severity, it is not known whether nondiabetic patients with metabolic dysfunction are also more prone to more severe disease. The association of metabolic associated fatty liver disease (MAFLD) with COVID‐19 severity in nondiabetic patients was investigated here. METHODS: The study cohort comprised 65 patients with (i.e. cases) and 65 patients without MAFLD (i.e. controls). Each case was randomly matched with one control by sex (1:1) and age (±5 years). The association between the presence of MAFLD (as exposure) and COVID‐19 severity (as the outcome) was assessed by binary logistic regression analysis. RESULTS: In nondiabetic patients with COVID‐19, the presence of MAFLD was associated with a four‐fold increased risk of severe COVID‐19; the risk increased with increasing numbers of metabolic risk factors. The association with COVID‐19 severity persisted after adjusting for age, sex, and coexisting morbid conditions. CONCLUSION: Health‐care professionals caring for nondiabetic patients with COVID‐19 should be cognizant of the increased likelihood of severe COVID‐19 in patients with MAFLD.


title: Recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay for detection of antibody to turkey coronavirus

text: Abstract Nucleocapsid (N) protein gene of turkey coronavirus (TCoV) was expressed in a prokaryotic system and used to develop an enzyme-linked immunosorbent assay (ELISA) for detection of antibody to TCoV. Anti-TCoV hyperimmune turkey serum and normal turkey serum were used as positive or negative controls for optimization of the ELISA. Goat anti-turkey IgG (H+L) conjugated with horseradish peroxidase was used as detector antibody. Three hundred and twenty two turkey sera from the field were used to evaluate the performance of ELISA and determine the cut-off point of ELISA. The established ELISA was also examined with serum samples obtained from turkeys experimentally infected with TCoV. Those serum samples were collected at various time intervals from 1 to 63 days post-infection. The optimum conditions for differentiation between anti-TCoV hyperimmune serum and normal turkey serum were recombinant TCoV N protein concentration at 20μg/ml, serum dilution at 1:800, and conjugate dilution at 1:10,000. Of the 322 sera from the field, 101 were positive for TCoV by immunofluorescent antibody assay (IFA). The sensitivity and specificity of the ELISA relative to IFA test were 86.0% and 96.8%, respectively, using the optimum cut-off point of 0.2 as determined by logistic regression method. Reactivity of anti-rotavirus, anti-reovirus, anti-adenovirus, or anti-enterovirus antibodies with the recombinant N protein coated on the ELISA plates was not detected. These results indicated that the established antibody-capture ELISA in conjunction with recombinant TCoV N protein as the coating protein can be utilized for detection of antibodies to TCoV in turkey flocks.


Risk factors for severe COVID-19: evidence from 167 hospitalized patients in Anhui, China


title: Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection

text: OBJECTIVE: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. METHODS: We included patients hospitalized at the University Hospital of Rome Tor Vergata, medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. RESULTS: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. CONCLUSIONS: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms were present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.


title: Treatment and prevention of acute respiratory infections among Iranian hajj pilgrims: a 5-year follow up study and review of the literature

text: Background Respiratory diseases/syndromes are the most common causes of referring to physicians among pilgrims in Hajj. They lead to high morbidity, impose high costs on the health system and are among the major obstacles for pilgrims to perform Hajj duties. The main aim of our study was to determine types, frequencies, etiologies, and epidemiologic factors of respiratory diseases among Iranian Hajj pilgrims and to suggest some preventive and treatment strategies. Methods: To determine the types and frequencies of respiratory syndromes, we implemented a syndromic surveillance method in Iranian health care system for Hajj during 5 consecutive years. To achieve the etiology of these diseases, we performed 4 concurrent before and after studies. We also evaluated efficacy of the flu and pneumovax vaccines among Iranian Hajj pilgrims in 2 studies. To determine some other epidemiological factors, we conducted 4 additional studies. Results: The most common problem was common cold like syndrome. Origins of the most upper respiratory problems were infections, and allergies were less involved. Among infectious agents, viruses were the most common agents and their frequencies were as follows respectively: Adenoviruses 38 (36.2 %), Rhinoviruses 31 (30%), Influenza type B virus 21 (20%). Bacteria were often the secondary causes and their frequencies were as follows respectively: Intestine bacillus 69 (19.4%), Chlamydia pneumonia 20(15.8%), Haemophiluses 32 (9.1%) and Streptococcus (A,C and G) 30 ( 8.5%). We introduced some epidemiological factors as effective in creating respiratory diseases. Conclusion: In this paper, we suggested some applied points for prevention, treatment, and correction of common malpractices in the treatment of respiratory diseases of the pilgrims.


title: Establishing and Applying a Schistosomiasis Early Warning Index (SEWI) in the Lower Yangtze River Region of Jiangsu Province, China

text: BACKGROUND: China has made remarkable progress in schistosomiasis control over the past decades. Transmission control has replaced morbidity control as the country moves towards the goal of elimination and the current challenge is to find a sensitive measure capable of gauging transmission risk in low-prevalence areas. The study aims to develop a Schistosomiasis Early Warning Index (SEWI) and demonstrate its use in Jiangsu Province along the lower Yangtze River. METHODOLOGY/PRINCIPAL FINDINGS: The Delphi approach, a structured communication technique, was used to develop the SEWI. Two rounds of interviews with 30 public health experts specialized in schistosomiasis control were conducted using 40 indicators that reflected different aspects of schistosomiasis transmission and control. The necessity, feasibility, and sensitivity of each indicator were assessed and the weight value of each indicator determined based on these experts' judgment. The system included 3 first-order indicators, 7 second-order indicators, and 30 third-order indicators. The 3 first-order indicators were endemic status, control measures, social and environmental factors, with the weight values 0.366, 0.343 and 0.291, respectively. For the 7 second-order indicators, the highest weight value was for control measures for snails (0.175) and the lowest for transmission route (0.110). We estimated and mapped the SEWI for endemic areas at the county scale in Jiangsu Province finding that the majority of the endemic areas were characterized as medium transmission risk (SEWI risk values between 0.3 and 0.6), while areas where transmission interruption had been officially declared showed SEWI values <0.30. A few isolated areas (e.g. endemic islands in the Yangtze River) produced SEWI values >0.60. These estimates are largely in agreement with the endemicity levels based on recent epidemiological surveys. CONCLUSIONS/SIGNIFICANCE: The SEWI should be useful for estimation of schistosomiasis transmission surveillance, particularly with reference to the elimination of the disease in China.


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


docid: bmwdpzqe

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.