title: Demographics and husbandry of pet cats living in Sydney, Australia: results of cross-sectional survey of pet ownership

text: Our aim was to collect baseline data on the age, gender, breed, reproductive status and husbandry (housing, diet, vaccination, veterinary attention) of pet cats living in Sydney. Accordingly, a cross-sectional survey of 2768 households was conducted using a postal questionnaire. The 2006 Sydney residential phone book was used as the sampling frame. Non-responders were re-mailed the questionnaire on two further occasions, 2 and 4 weeks after the first posting. Completed questionnaires were received from 884 households. No pets were kept by 387 (43.8%) respondents. Dogs and cats were owned by 295 (33.4%) and 198 (22.5%) of households, respectively, with 7.8% of households having both cat(s) and dog(s). Fish and birds were the next most popular pets. Of the 198 cat-owning households, 54.0% kept only cat(s), while 46.5% kept cats with other pets. The distribution of cat ownership across Sydney was non-uniform. Each cat-owning household kept 1.3 cats on average, with the majority keeping one (75.8% households) or two (18.7%). For the 260 cats, the mean age was 7.1 years, the median 6 years, with a range of 3 months to 22 years. There were significantly more female (143; 55%) than male cats (117; 45%). Only seven cats (2.7%) were sexually entire, and these were all ≤6 years. Crossbred cats outnumbered pedigree cats by a ratio of 3.3:1. The Burmese was the most common breed, followed by the Persian. The median age of pedigree cats (5.5 years) was significantly lower than for domestic crossbred cats (7.0 years). Most cats were housed both indoors and outdoors (72.6%), with 19.7% being restricted to indoors and/or ‘pet park enclosures’. Pedigree cats were significantly more likely than crossbreds to be housed indoors. Most owners fed their cats a combination of commercial dry and canned food (38.1%), although fresh meat was popular also and either fed alone (1.6%) or in combination with dry food (14.4%), tinned food (1.6%) or canned and dry food (25.8%). A diet consisting of dry food alone was fed to cats in 13.4% of households. Ninety percent of cats had been vaccinated at least once, while 72.2% received a vaccination in the last 3 years. Older cats were less likely to have been vaccinated recently than younger cats. Only 5.8% of cats had never visited a veterinarian. For the 243 cats that had received veterinary attention, the average number of years since the last visit was 1.5.


title: Neither B cells nor T cells are required for CNS demyelination in mice persistently infected with MHV-A59

text: Murine hepatitis virus A59 infection of the central nervous system (CNS) results in CNS demyelination in susceptible strains of mice. In infected B-cell-deficient mice, demyelination not only occurred but was also more severe than in parental C57BL/6 animals. This increase may be due to the persistence of virus in the CNS in the absence of B cells. In mice lacking antibody receptors or complement pathway activity, virus did not persist yet demyelination was similar to parental mice. In infected RAG1(−/−) mice, moderately sized, typical demyelinating lesions were identified. Therefore, demyelination can occur in the absence of B and T cells.


title: Type 1 interferons as a potential treatment against COVID-19

text: Abstract Type 1 interferons have a broad antiviral activity in vitro and are currently evaluated in a clinical trial to treat MERS-CoV. In this review, we discuss preliminary data concerning the potential activity of type 1 interferons on SARS-CoV-2, and the relevance of evaluating these molecules in clinical trials for the treatment of COVID-19.


title: Covid-19 in Flüchtlingsunterkünften: ÖGD jetzt weiter stärken

text: The Covid-19 pandemic poses a major challenge for the management of collective accommodation centres for refugees. The often-overcrowded facilities hinder satisfactory implementation of social distancing and hygiene practices. Adequate information policies as well as a rapid, efficient management of suspected and confirmed Covid-19 cases are essential. However, scientific evidence on this is largely lacking. Besides partially implemented approaches, such as isolation areas or cluster quarantine, plans to evacuate overcrowded facilities should also be considered. The German Public Health Service (ÖGD) plays a vital role in the current Covid-19 pandemic. In order to fulfil their routine tasks of infection control and support health services management for refugee accommodation centres, the ÖGD urgently needs to be strengthened in terms of personnel and material. Additionally, means for a rapid exchange of best practice examples of Covid-19 interventions across federal states as well as collaborative structures and capacity within the ÖGD for accompanying operational research are needed. Refugees, their housing situation and their access to health care need to be included in pandemic plans. Only an integrative health care system can achieve regional and international targets for the control of Covid-19 and other infectious diseases.


title: Retrospective serological survey on selected viral pathogens in wild boar populations in Germany

text: The objective of this study was to retrospectively evaluate the occurrence of porcine parvovirus (PPV), Aujeszky’s disease virus (ADV), transmissible gastroenteritis virus (TGEV), porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV) in selected wild boar populations in Germany (n = 1,221). Commercial enzyme linked immunosorbent assay and hemagglutination inhibition tests were used for serological monitoring. The serosurvey revealed seroprevalence rates of 64.28%, 11.26%, 7.87%, 7.84%, 3.82% and 1.59% for PPV, ADV, PRCV, SIV, PRRSV and TGEV, respectively. The seroprevalence rates differed between populations and age classes with the highest number of antibody-positive wild boars in older animals (>1 year old). No antibodies to TGEV were found in Baden–Wuerttemberg and in Mecklenburg–Western Pomerania (investigation period 1997/1998). In addition, sera collected in Mecklenburg–Western Pomerania in 1997/1998 were negative for SIV. Even though the seroprevalence rates established for these viruses, except for PPV, were relatively low, wild boars may act as a reservoir for pathogens and a source of infection for domestic pigs and humans. Based on the epidemiological situation, no risk of a spread of these viruses should emanate from wild boars, neither for wildlife nor for livestock. However, effective and science-based disease monitoring programmes should continuously be carried out in wild boar populations.


title: Vaccination with recombinant adenovirus expressing multi-stage antigens of Toxoplasma gondii by the mucosal route induces higher systemic cellular and local mucosal immune responses than with other vaccination routes

text: Toxoplasmosis caused by Toxoplasma gondii, an obligate intracellular protozoan, is a cause of congenital disease and abortion in humans and animals. Various vaccination strategies against toxoplasmosis in rodent models have been used in the past few decades; however, effective vaccines remain a challenge. A recombinant adenovirus vaccine expressing ubiquitin-conjugated multi-stage antigen segments (Ad-UMAS) derived from different life-cycle stages of T. gondii was constructed previously. Here, we compared the immune responses and protection effects in vaccination of mice with Ad-UMAS by five vaccination routes including intramuscular (i.m.), intravenous (i.v.), subcutaneous (s.c.), intraoral (i.o.), and intranasal (i.n.). Much higher levels of T. gondii-specific IgG and IgA antibodies were detected in the sera of the intraoral and intranasal vaccination groups on day 49 compared with controls (p < 0.05). The percentages of CD8(+) T-cells in mice immunized intranasally and intraorally were larger than in mice immunized intramuscularly (p < 0.05). The highest level of IL-2 and IFN-γ was detected in the group with nasal immunization, and splenocyte proliferation activity was significantly enhanced in mice immunized via the oral and nasal routes. Furthermore, the higher survival rate (50%) and lower cyst numbers observed in the intraoral and intranasal groups all indicate that Ad-UMAS is far more effective in protecting mice against T. gondii infection via the mucosal route. Ad-UMAS could be an effective and safe mucosal candidate vaccine to protect animals and humans against T. gondii infection.


title: The Spike but Not the Hemagglutinin/Esterase Protein of Bovine Coronavirus Is Necessary and Sufficient for Viral Infection

text: Abstract The spike (S) and hemagglutinin/esterase (HE) of bovine coronavirus (BCV) are the two envelope proteins that recognize the same receptor-determinant of 9-O-acetylneuraminic acid on host cells. However, the precise and relative roles of the two proteins in BCV infectivity remain elusive. To unequivocally determine their roles in viral cytopathogenicity, we developed a system in which phenotypically chimeric viruses were generated by infecting a closely related mouse hepatitis virus (MHV) in cells that stably express an individual BCV protein (S or HE). The chimeric viruses were then used to infect human rectal tumor (HRT)-18 cells that are permissive to BCV but are nonsusceptible to MHV. Using this approach, we found that the chimeric virus containing the BCV S protein on the virion surface entered and replicated in HRT-18 cells; this was specifically blocked by prior treatment of the virus with a neutralizing antibody specific to the BCV S protein, indicating that the BCV S protein is responsible for initiating chimeric virus infection. In contrast, chimeric viruses that contain biologically active and functional BCV HE protein on the surface failed to enter HRT-18 cells, indicating that the BCV HE protein alone is not sufficient for BCV infection. Taken together, these results demonstrate that the S protein but not the HE protein of BCV is necessary and sufficient for infection of the chimeric viruses in HRT-18 cells, suggesting that BCV likely uses the S protein as a primary vehicle to infect permissive cells.


title: Virus-mediated autoimmunity in Multiple Sclerosis

text: Epidemiological data suggest the notion that in Multiple Sclerosis (MS) is an acquired autoimmune disease and the cause may be an environmental factor(s), probably infectious, in genetically susceptible individuals. Several cases of viral induced demyelinatimg encephalomyelitis in human beings and in experimental models as well as the presence of IgG oligoclonal bands in the cerebrospinal fluid indicate that the infectious factor may be viral. However, the absence of a specific virus identification in MS central nervous system may hardly support this notion. On the other hand, the partial response of patients with MS to immunosuppressive and immunomodulatory therapy support the evidence of an autoimmune etiology for MS. However, the autoimmune hypothesis shares the same criticism with the infectious one in that no autoantigen(s) specific to and causative for MS has ever been identified. Nevertheless, the absence of identifiable infectious agent, especially viral does not rule out its presence at a certain time – point and the concomitant long term triggering of an autoimmune cascade of events thereafter. Several concepts have emerged in an attempt to explain the autoimmune mechanisms and ongoing neurodegeneration in MS on the basis of the infectious – viral hypothesis.


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title: Integrated microdevice of reverse transcription-polymerase chain reaction with colorimetric immunochromatographic detection for rapid gene expression analysis of influenza A H1N1 virus

text: An integrated microdevice of a reverse transcription-polymerase chain reaction (RT-PCR) reactor and an immunochromatographic strip was constructed for colorimetric detection of gene expression of influenza A virus subtype H1N1. An RT-PCR cocktail, which included Texas Red-labeled primers, dNTP including biotin-labeled dUTP, and RNA templates of influenza A H1N1 virus, was filled in the PCR chamber through the micropump, and the RT-PCR was performed to amplify the target H1 gene (102 bp). The resultant amplicons bearing biotin moieties and Texas Red haptens were subsequently eluted to the immunochromatographic strip, in which they were first conjugated with the gold nanoparticle labeled anti-hapten antibody in the conjugation pad, and then captured on the streptavidin coated test line through the biotin–streptavidin interaction. By observing a violet color in the test line which was derived from the gold nanoparticle, we confirmed the H1N1 target virus. The entire process on the integrated microdevice consisting of a micropump, a 2 μL PCR chamber, and an immunochromatographic strip was carried out on the portable genetic analyzer within 2.5 h, enabling on-site colorimetric pathogen identification with detection sensitivity of 14.1 pg RNA templates.


title: Viral security proteins: counteracting host defences

text: Interactions with host defences are key aspects of viral infection. Various viral proteins perform counter-defensive functions, but a distinct class, called security proteins, is dedicated specifically to counteracting host defences. Here, the properties of the picornavirus security proteins L and 2A are discussed. These proteins have well-defined positions in the viral polyprotein, flanking the capsid precursor, but they are structurally and biochemically unrelated. Here, we consider the impact of these two proteins, as well as that of a third security protein, L(*), on viral reproduction, pathogenicity and evolution. The concept of security proteins could serve as a paradigm for the dedicated counter-defensive proteins of other viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro2452) contains supplementary material, which is available to authorized users.


title: Human Coronavirus Infections—Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and SARS-CoV-2

text: Three novel coronaviruses have emerged as new lethal zoonotic pathogens of humans during the past 17 years: The Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS-CoV), the Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV), and most recently SARS-CoV-2. SARS-CoV first surfaced as a human pathogen in Guangdong, China in November 2002 and rapidly spread worldwide with 8098 cases and 774 deaths before the end of the epidemic. SARS-like CoVs have been detected in horseshoe bats with high sequence homology with human or civet isolates, suggesting that bats could be a natural reservoir of a close ancestor of SARS-CoV. No cases of SARS have been reported since January 2004. MERS-CoV was first reported in September 2012, after it was isolated from respiratory samples from a patient in Jeddah, Saudi Arabia who died in June 2012. How humans acquire MERS-CoV infection is not yet known although bats and dromedary camels are intermediary reservoirs. MERS-CoV continues to circulate in the Middle East. As of May 22, 2019, 2428 cases of laboratory-confirmed MERS-CoV cases reported to the World Health Organization, including 838 deaths (34.5% mortality) have been reported from 27 countries. While the majority of MERS cases occur in the Middle East, travel related MERS cases have been reported from all continents. Large health care associated outbreaks of MERS-CoV have occurred in Saudi Arabia, United Arab Emirates, and the Republic of Korea. SARS-CoV-2 emerged from Wuhan, China in December 2019, and by March 2020 had established as a pandemic which has caused massive disruption in multiple countries. The eventual mortality caused by this virus remains to be seen. All three viruses cause a similar wide range of nonspecific clinical manifestations from mild upper respiratory tract illness to severe respiratory, gastrointestinal and other extra-pulmonary disease. Early recognition of cases, improved compliance with internationally recommended infection control protocols, and rapid implementation of infection control measures are required to prevent health care facility-associated outbreaks, and in the case of SARS-CoV-2 for control of community spread as well. Treatment is supportive and there are no specific antivirals or vaccines available for both SARS and MERS.


title: Human Metapneumovirus: A Largely Unrecognized Threat to Human Health

text: Human metapneumovirus (HMPV) infects most children by five years of age. The virus can cause both upper and lower respiratory tract disease and can be life threatening. High-risk populations include young children who are exposed to virus for the first time and the elderly. Currently, there is no standard treatment nor licensed vaccine for HMPV, although several attractive vaccine candidates have been developed for pre-clinical studies. A raised awareness of the impact of HMPV on public health is needed to drive research, complete vaccine development, and thereby prevent significant virus-associated morbidities and mortalities worldwide.


title: Prevalence of viral infection detected by PCR and RT‐PCR in patients with acute exacerbation of COPD: A systematic review

text: Background and objective: Viruses are important aetiological agents of acute exacerbation of COPD (AECOPD). Their reported prevalence varies from region to region. This systematic review calculated the prevalence of respiratory viral infections in AECOPD. Methods: A systematic search was performed using Medline, and references of relevant articles and conference proceedings were hand searched. Articles for review were selected based on the following criteria: (i) prospective or cross‐sectional study, (ii) original research, (iii) viral detection used the highly sensitive techniques of PCR and/or Reverse Transcriptase PCR (RT‐PCR), (iv) viral prevalence in AECOPD defined, and (v) full paper available in English. We assessed the study quality and extracted data independently and in duplicate using a pre‐defined data extraction form. Weighted mean prevalence (WMP) was calculated and a forest plot was constructed to show the dispersion. Results: Eight studies met the inclusion criteria. The WMP of respiratory viral infection in AECOPD was 34.1% (95% CI: 23.9–44.4). picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2–27.3), followed by influenza; 7.4% (95% CI: 2.9–12.0), respiratory syncytial virus; 5.3% (95% CI: 1.6–9.0), corona viruses; 3.1% (95% CI: 0.4–5.8), parainfluenza; 2.6% (95% CI: 0.4–4.8), adenovirus; 1.1% (95% CI: −1.1 to 3.3), and human metapneumovirus; 0.7% (95% CI: −0.3 to 1.8). Maximum WMP was observed in studies from Europe followed by the USA, Australia and Asia. Picorna was the most common virus detected in Western countries whereas influenza was most common in Asia. Conclusions: This systematic review demonstrated that viruses are strongly associated with AECOPD, with the highest detection rates of viruses being in Europe. The geographical epidemiology of viruses may have important therapeutic implications for management of AECOPD.


title: Ebola virus convalescent blood products: Where we are now and where we may need to go

text: Abstract The world is regularly exposed to emerging infections with the potential to burst into a pandemic. One possible way to treat patients, when no other treatment is yet developed, is passive immunization performed by transfusing blood, plasma or plasma immunoglobulin fractions obtained from convalescent donors who have recovered from the disease and have developed protective antibodies. The most recent on-going epidemic is caused by the Ebola virus, a filovirus responsible for Ebola virus disease, a severe, often lethal, hemorrhagic fever. Recently, the use of convalescent blood products was proposed by the WHO as one early option for treating patients with Ebola virus disease. This publication provides an overview of the various convalescent blood products and technological options that could theoretically be considered when there is a need to rely on this therapeutic approach. In countries without access to advanced blood-processing technologies, the choice may initially be restricted to convalescent whole blood or plasma. In technologically advanced countries, additional options for convalescent blood products are available, including virally inactivated plasma and fractionated immunoglobulins. The preparation of minipool immunoglobulins is also a realistic option to consider.


title: Ross River virus envelope glycans contribute to disease through activation of the host complement system

text: Abstract Mannose binding lectin (MBL) generally plays a protective role during viral infection, yet MBL-mediated complement activation promotes Ross River virus (RRV)-induced inflammatory tissue destruction, contributing to arthritis and myositis. As MBL binds to carbohydrates, we hypothesized that N-linked glycans on the RRV envelope glycoproteins act as ligands for MBL. Using a panel of RRV mutants lacking the envelope N-linked glycans, we found that MBL deposition onto infected cells was dependent on the E2 glycans. Moreover, the glycan-deficient viruses exhibited reduced disease and tissue damage in a mouse model of RRV-induced myositis compared to wild-type RRV, despite similar viral load and inflammatory infiltrates within the skeletal muscle. Instead, the reduced disease induced by glycan-deficient viruses was linked to decreased MBL deposition and complement activation within inflamed tissues. These results demonstrate that the viral N-linked glycans promote MBL deposition and complement activation onto RRV-infected cells, contributing to the development of RRV-induced myositis.


title: Microarrays and gene expression profiling in microbiology and infectious diseases: a clinician's perspective

text: Advances in molecular biology, bioinformatics, and robotics have allowed microarray technology to be used for in-depth, basic science studies in all fields of microbiology. Recently, translation of these basic science applications to clinical microbiology and infectious diseases has also progressed. From a clinical infectious disease perspective, genome-based organism identification, pathogen discovery, and antimicrobial susceptibility testing of problematic organisms offer the potential to yield diagnostic information that may not otherwise become available. Moreover, microarray-based studies have the ability to provide “signatures” of host cell transcriptional responses for individual pathogens and/or groups of pathogens. This type of information has the potential to confirm difficult diagnoses, to monitor responses to therapeutic intervention, or even to predict prognosis and sequelae following an infectious disease. Examples are presented to illustrate ways in which microarray technology has already impacted these areas of clinical microbiology.


title: The Public Health Response to the COVID-19 Pandemic for People with Disabilities()

text: With the rapidly changing landscape of the Covid-19 outbreak, how to best address the needs and continue to protect the health and well-being of people with disabilities (PwDs) is a global public health priority. In this commentary we identify three public health areas of ongoing need and offer possible strategies to address each. These areas include: the types of data that would help clarify risks for PwDs and help assure their safety long term; the prevention, treatment and mitigation measures for PwDs that are needed through the duration of the outbreak; and the issues of equity in access to and quality of medical care for PwDs. Because of the rapid nature of the public health response, it is critical to reassess and readjust our approach to best address the needs of PwDs in the months and years to come and to incorporate these new practices into future emergency preparedness responses.


title: The GAIT Translational Control System

text: The interferon (IFN)-γ-activated inhibitor of translation (GAIT) system directs transcript-selective translational control of functionally-related genes. In myeloid cells, IFN-γ induces formation of a multiprotein GAIT complex that binds structural GAIT elements in the 3' untranslated regions (UTR) of multiple inflammation-related mRNAs, including ceruloplasmin and VEGF-A, and represses their translation. The human GAIT complex is a heterotetramer containing glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), ribosomal protein L13a (L13a), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). A network of IFN-γ-stimulated kinases regulates recruitment and assembly of GAIT complex constituents. Activation of Cdk5, mTORC1, and S6K1 kinases induces EPRS release from its parental multi-aminoacyl tRNA synthetase complex to join NSAP1 in a “pre-GAIT” complex. Subsequently, the DAPK-ZIPK kinase axis phosphorylates L13a, inducing release from the 60S ribosomal subunit and binding to GAPDH. The subcomplexes join to form the functional GAIT complex. Each constituent has a distinct role in the GAIT system. EPRS binds the GAIT element in target mRNAs, NSAP1 negatively regulates mRNA binding, L13a binds eIF4G to block ribosome recruitment, and GAPDH shields L13a from proteasomal degradation. The GAIT system is susceptible to genetic and condition-specific regulation. An N-terminus EPRS truncate is a dominant-negative inhibitor ensuring a “translational trickle” of target transcripts. Also, hypoxia and oxidatively-modified lipoproteins regulate GAIT activity. Mouse models exhibiting absent or genetically-modified GAIT complex constituents are beginning to elucidate the physiological role of the GAIT system, particularly in the resolution of chronic inflammation. Finally, GAIT-like systems in proto-chordates suggests an evolutionarily conserved role of the pathway in innate immunity.


title: The promise and pitfalls of social science research in an emergency: lessons from studying the Zika epidemic in Brazil, 2015–2016

text: Social science generates evidence necessary to control epidemics. It can help to craft appropriate public health responses, develop solutions to the epidemic impacts and improve understanding of why the epidemic occurred. Yet, there are practical constraints in undertaking this international research in a way that produces quality, ethical and appropriate data, and that values all voices and experiences, especially those of local researchers and research participants. In this paper, we reflected on the experience of undertaking social science research during the 2015/2016 Zika epidemic in Brazil. This experience was considered from the perspective of this paper’s authors: three Brazilian academics, two UK academics and two mothers of children affected by congenital Zika syndrome. This group came together through the conduct of the Social and Economic Impact of Zika study, a mixed-methods social science study. The key findings highlight practical issues in the achievement of three goals: the conduct of high-quality social science in emergencies and efforts towards the decolonisation of global health in terms of levelling the power between Brazilian and UK researchers and optimising the role of patients within research. From our perspective, the information collected through social science was valuable, providing detailed insight into the programmatic needs of mothers and their affected children (eg, economic and social support and mental health services). Social science was considered a low priority within the Zika epidemic despite its potential importance. There were logistical challenges in conducting social science research, foremost of which are the difficulties in developing a trusting and balanced power relationship between the UK and Brazilian researchers in a short time frame. When these issues were overcome, each partner brought unique qualities, making the research stronger. The mothers of affected children expressed dissatisfaction with research, as they were involved in many studies which were not coordinated, and from which they did not see a benefit. In conclusion, the importance of social science in epidemics must continue to be promoted by funders. Funders can also set in place mechanisms to help equalise the power dynamics between foreign and local researchers, researchers and participants, both to promote justice and to create best quality data.


title: Comparison of electrocardiographic parameters and serum electrolytes and microelements between single infection of rotavirus and coronavirus and concurrent infection of Cryptosporidium parvum with rotavirus and coronavirus in diarrheic dairy calves

text: To study the effects of concurrent infection of Cryptosporidium parvum with rotavirus and coronavirus in comparison to single infection of rotavirus and coronavirus, electrocardiographic parameters and serum electrolytes and microelements are compared between eight calves with concurrent infection and ten calves with single infection. Calves with single infections had higher serum concentrations of sodium and calcium, and less potassium, copper, and iron, which was not statistically significant. They also had significantly shorter P and QRS wave amplitudes and longer T wave duration in electrocardiogram patterns.


title: Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins

text: Abstract Bunyaviridae and Arenaviridae virus families include an important number of highly pathogenic viruses for humans. They are enveloped viruses with negative stranded RNA genomes divided into three (bunyaviruses) or two (arenaviruses) segments. Each genome segment is coated by the viral nucleoproteins (NPs) and the polymerase (L protein) to form a functional ribonucleoprotein (RNP) complex. The viral RNP provides the necessary context on which the L protein carries out the biosynthetic processes of RNA replication and gene transcription. Decades of research have provided a good understanding of the molecular processes underlying RNA synthesis, both RNA replication and gene transcription, for these two families of viruses. In this review we will provide a global view of the common features, as well as differences, of the molecular biology of Bunyaviridae and Arenaviridae. We will also describe structures of protein and protein-RNA complexes so far determined for these viral families, mainly focusing on the L protein, and discuss their implications for understanding the mechanisms of viral RNA replication and gene transcription within the architecture of viral RNPs, also taking into account the cellular context in which these processes occur. Finally, we will discuss the implications of these structural findings for the development of antiviral drugs to treat human diseases caused by members of the Bunyaviridae and Arenaviridae families.


title: Clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms: A report of 164 cases

text: Abstract Objective To explore the clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms. Methods The clinical data of 164 COVID-19 patients with gastrointestinal symptoms were extracted and analysed retrospectively. Results In total, 505 COVID-19 patients were divided into two groups: those with gastrointestinal symptoms (G group) and those without gastrointestinal symptoms (NG group). Common gastrointestinal symptoms included inappetence, diarrhoea, nausea, abdominal pain, and vomiting. Significantly higher proportions of patients with fever, dizziness, myalgia, and fatigue were noted in group G than in group NG. Compared with patients without fever, there was a significant difference between G group and NG group in moderate fever or above, while there was no significant difference between the two groups in low fever. The laboratory results showed that patients in the G group had significantly higher C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase levels than those in the NG group. Moreover, the proportion of patients with severe pneumonia was significantly higher in the G group than in the NG group. Conclusion In Wuhan, the proportion of COVID-19 patients who experience gastrointestinal symptoms is relatively high. Patients who experience gastrointestinal symptoms are more likely to suffer from severe pneumonia, which may help clinicians identify patients at high risk of COVID-19 and thus reduce the incidence of this condition.


title: ATENCIÓN DE LA URGENCIA QUIRÚRGICA DURANTE LA PANDEMIA COVID-19. RECOMENDACIONES DE LA ASOCIACIÓN ESPAÑOLA DE CIRUJANOS

text: RESUMEN La infección por el nuevo coronavirus SARS-CoV-2 (enfermedad por coronavirus 2019 -covid-19-) ha determinado la necesidad de la reorganización de muchos centros hospitalarios en el mundo. España, como uno de los epicentros de la enfermedad, ha debido asumir cambios en la práctica totalidad de su territorio. Sin embargo, y desde el inicio de la pandemia, en todos los centros que atienden urgencias quirúrgicas ha sido necesario el mantenimiento de su cobertura, aunque igualmente ha sido inevitable introducir directrices especiales de ajuste al nuevo escenario que permitan el mantenimiento de la excelencia en la calidad asistencial. Este documento desarrolla una serie de indicaciones generales para la cirugía de urgencias y la atención al politraumatizado, desarrolladas desde la literatura disponible y consensuadas por un subgrupo de profesionales desde el grupo general Cirugía-AEC-COVID19. Estas medidas van encaminadas a contemplar un riguroso control de la exposición en pacientes y profesionales, a tener en cuenta las implicaciones de la pandemia sobre diferentes escenarios perioperatorios relacionados con la urgencia y a una adaptación ajustada a la situación del centro en relación con la atención a pacientes infectados. ABSTRACT New coronavirus SARS-CoV-2 infection (coronavirus disease 2019 -covid-19-) has determined the necessity of reorganization in many centers all over the world. Spain, as an epicenter of the disease, has been forced to assume health policy changes in all the territory. However, and from the beginning of the pandemic, every center attending surgical urgencies had to guarantee the continuous coverage adopting correct measures to maintain the excellence of quality of care. This document resumes general guidelines for emergency surgery and trauma care, obtained from the available bibliography and evaluated by a subgroup of professionals designated from the general group of investigators Cirugía-AEC-COVID19 from the Spanish Association of Surgeons, directed to minimize professional exposure, to contemplate pandemic implications over different urgent perioperative scenarios and to adjust decision making to the occupational pressure caused by covid-19 patients.


title: Tuberculosis-associated Immune Thrombocytopenia: A Case Report

text: Various hematological manifestations are known to occur with tuberculosis (TB), but its association with immune thrombocytopenia is uncommon and not well recognized. Here, the case of a 39-year-old male who presented with a history of epistaxis and hematuria is described. The patient was found to have diffuse lymphadenopathy both clinically and radiologically. He was diagnosed with immune thrombocytopenia; however, there was a delay in the diagnosis of TB because of the patient's refusal of lymph node biopsy and late recognition of the association between TB and immune thrombocytopenia. Treatment with steroids without antituberculosis medications may have led to reactivation and dissemination of tuberculous infection in this patient. Later, the patient was readmitted with a suspected community-acquired pneumonia and the sputum smear was positive for acid-fast bacilli. Unfortunately, the patient died after he developed sepsis and multiorgan failure. The purpose of this case report is to highlight this rare combination and create awareness among clinicians to consider TB as an underlying etiology of immune thrombocytopenia, especially if there are other associated physical findings such as the presence of lymphadenopathy.


title: A Participatory System for Preventing Pandemics of Animal Origins: Pilot Study of the Participatory One Health Disease Detection (PODD) System

text: BACKGROUND: Aiming for early disease detection and prompt outbreak control, digital technology with a participatory One Health approach was used to create a novel disease surveillance system called Participatory One Health Disease Detection (PODD). PODD is a community-owned surveillance system that collects data from volunteer reporters; identifies disease outbreak automatically; and notifies the local governments (LGs), surrounding villages, and relevant authorities. This system provides a direct and immediate benefit to the communities by empowering them to protect themselves. OBJECTIVE: The objective of this study was to determine the effectiveness of the PODD system for the rapid detection and control of disease outbreaks. METHODS: The system was piloted in 74 LGs in Chiang Mai, Thailand, with the participation of 296 volunteer reporters. The volunteers and LGs were key participants in the piloting of the PODD system. Volunteers monitored animal and human diseases, as well as environmental problems, in their communities and reported these events via the PODD mobile phone app. LGs were responsible for outbreak control and provided support to the volunteers. Outcome mapping was used to evaluate the performance of the LGs and volunteers. RESULTS: LGs were categorized into one of the 3 groups based on performance: A (good), B (fair), and C (poor), with the majority (46%,34/74) categorized into group B. Volunteers were similarly categorized into 4 performance groups (A-D), again with group A showing the best performance, with the majority categorized into groups B and C. After 16 months of implementation, 1029 abnormal events had been reported and confirmed to be true reports. The majority of abnormal reports were sick or dead animals (404/1029, 39.26%), followed by zoonoses and other human diseases (129/1029, 12.54%). Many potentially devastating animal disease outbreaks were detected and successfully controlled, including 26 chicken high mortality outbreaks, 4 cattle disease outbreaks, 3 pig disease outbreaks, and 3 fish disease outbreaks. In all cases, the communities and animal authorities cooperated to apply community contingency plans to control these outbreaks, and community volunteers continued to monitor the abnormal events for 3 weeks after each outbreak was controlled. CONCLUSIONS: By design, PODD initially targeted only animal diseases that potentially could emerge into human pandemics (eg, avian influenza) and then, in response to community needs, expanded to cover human health and environmental health issues.


title: Animal Models of Cardiac Disease and Stem Cell Therapy

text: Animal models that mimic cardiovascular diseases are indispensable tools for understanding the mechanisms underlying the diseases at the cellular and molecular level. This review focuses on various methods in preclinical research to create small animal models of cardiac diseases, such as myocardial infarction, dilated cardiomyopathy, heart failure, myocarditis and cardiac hypertrophy, and the related stem cell treatment for these diseases.


title: Optimization of group size in pool testing strategy for SARS‐CoV‐2: A simple mathematical model

text: Coronavirus disease (Covid‐19) has reached unprecedented pandemic levels and is affecting almost every country in the world. Ramping up the testing capacity of a country supposes an essential public health response to this new outbreak. A pool testing strategy where multiple samples are tested in a single reverse transcriptase‐polymerase chain reaction (RT‐PCR) kit could potentially increase a country's testing capacity. The aim of this study is to propose a simple mathematical model to estimate the optimum number of pooled samples according to the relative prevalence of positive tests in a particular healthcare context, assuming that if a group tests negative, no further testing is done whereas if a group tests positive, all the subjects of the group are retested individually. The model predicts group sizes that range from 11 to 3 subjects. For a prevalence of 10% of positive tests, 40.6% of tests can be saved using testing groups of four subjects. For a 20% prevalence, 17.9% of tests can be saved using groups of three subjects. For higher prevalences, the strategy flattens and loses effectiveness. Pool testing individuals for severe acute respiratory syndrome coronavirus 2 is a valuable strategy that could considerably boost a country's testing capacity. However, further studies are needed to address how large these groups can be, without losing sensitivity on the RT‐PCR. The strategy best works in settings with a low prevalence of positive tests. It is best implemented in subgroups with low clinical suspicion. The model can be adapted to specific prevalences, generating a tailored to the context implementation of the pool testing strategy.


title: Chapter Seventeen The structures and biological functions of polysaccharides from traditional Chinese herbs

text: Abstract Most of traditional Chinese medicine substances come from herbal plants. The medicinal quality of herbal plants varies with the locations of cultivation, the parts of the herb collected, the season of the herb collected, and the herb processing method. Polysaccharides are major components of the herb plants and their biosynthesis is partly controlled by the genes but mostly influenced by the availability of the nutrition and determined by the various environmental factors. In recent decades, polysaccharides isolated from different kinds of Chinese herbs have received much attention due to their important biological activities, such as anti-tumor, anti-oxidant, anti-diabetic, radiation protecting, antiviral, hypolipidemic, and immunomodulatory activities. Interestingly, different batches of the same herb can obtain different polysaccharide fractions with subtle differences in molecular weight, monosaccharide compositions, glycosidic linkages, and biological functions. Even with these variations, a large number of bioactive polysaccharides from different kinds of traditional Chinese herbs have been purified, characterized, and reported. This review provides a comprehensive summary of the latest polysaccharide extraction methods and the strategies used for monosaccharide compositional analysis plus polysaccharide structural characterization. Most importantly, the reported chemical characteristics and biological activities of the polysaccharides from the famous traditional Chinese herbs including Astragalus membranaceus, Ginseng, Lycium barbarum, Angelica sinensis, Cordyceps sinensis, and Ophiopogon japonicus will be reviewed and discussed. The published studies provide evidence that polysaccharides from traditional Chinese herbs play an important role in their medical applications, which forms the basis for future research, development, and application of these polysaccharides as functional foods and therapeutics in modern medicine.


title: Navigating telemedicine for facial trauma during the COVID‐19 pandemic

text: IMPORTANCE: The COVID‐19 pandemic is changing how health care providers practice. As some telemedicine and telecommunication support tools have been incorporated into the otolaryngology practice in response to safety and access demands, it is essential to review how these tools and services can help facilitate facial trauma evaluation during a time when clinical resources are limited. OBJECTIVE: To review applications of telemedicine for the evaluation of facial trauma to better direct utilization of these methods and technologies during times of limited access to clinical resources such as the COVID‐19 pandemic. METHODS: A systematic review was conducted using PubMed, Embase, and Web of Science. RESULTS: After screening 158 titles and abstracts, we identified 16 eligible studies involving facial trauma evaluation using telemedicine. Telemedicine opportunities for facial trauma evaluation have the potential to be developed in the areas of multidisciplinary remote consultations, facial trauma triage, patient engagement, and postoperative follow‐up. CONCLUSION: The COVID‐19 pandemic is posing obstacles for both providers and patients in the delivery of health care at a time of limited clinical resources. Telemedicine may provide a potential useful tool in the evaluation and triage of facial injuries and patient engagement.


Known drugs and small molecules in the battle for COVID-19 treatment


title: Dietary supplementation with olive mill wastewaters induces modifications on chicken jejunum epithelial cell transcriptome and modulates jejunum morphology

text: BACKGROUND: The Mediterranean diet is considered one of the healthier food habits and olive oil is one of its key components. Olive oil polyphenols are known to induce beneficial effects in several pathological conditions, such as inflammatory bowel disease, and to contrast the proliferation of cancer cells or hypercholesterolemia. Polyphenols are also present in waste products derived from the olive industry: olive mill wastewaters (OMWW) are rich in polyphenols and there is an increasing interest in using OMWW in animal nutrition. OMWW are attributed with positive effects in promoting chicken performance and the quality of food-derived products. However, a tissue-specific transcriptome target analysis of chickens fed with OMWW has never been attempted. RESULTS: We explored the effect of dietary OMWW on the intestinal function in broilers. A morphological analysis of the jejunum revealed that OMWW reduced crypt depth, whereas no significant modifications were observed for villus height and the villus height/crypt depth ratio. An RNA Sequencing analysis was performed on isolated, intestinal, epithelial cells and 280 differentially expressed genes were found using a count-based approach. An enrichment analysis revealed that the majority of up regulated genes in the OMWW group were over-represented by the regulation of viral genome replication-related GO-Terms, whereas down regulated genes were mainly involved in cholesterol and lipid metabolism. CONCLUSIONS: Our study showed how an industrial waste product can be recycled as a feed additive with a positive relapse. OMWW dietary supplementation can be a nutritional strategy to improve chicken performance and health, prevent intestinal damage, enhance innate immunity and regulate cholesterol metabolism and fat deposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4962-9) contains supplementary material, which is available to authorized users.


Covid-19: Portugal closes all medical schools after 31 cases confirmed in the country.


title: [Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia].

text: Objective: To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). Methods: The correlation between ALT, AST and other liver enzyme changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of ACE2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion: We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.


title: Association of Mycoplasma pneumoniae and asthma among Indian children

text: The role of Mycoplasma pneumoniae infection as a trigger for asthma exacerbations is well supported in previous studies. This study was designed to investigate the role of M. pneumoniae infection in acute exacerbation of asthma in children. A total of 150 patients (110 males, 40 females) were studied and immunoglobulin M (IgM) antibodies to M. pneumoniae were detected by enzyme-linked immunosorbent assay (ELISA), and PCR amplification was performed for the P1 gene to associate M. pneumoniae infection with asthma. As compared with 33 children with asthma, only two of the control subjects had positive IgM titers for M. pneumoniae, which was statistically significant (P=0.002). A total of 15 children with asthma were positive by PCR for the P1 gene while none of the controls had a positive PCR. Of these positive cases, 24 cases were positive only by ELISA, six were positive only by PCR and nine patients were found to be positive by both ELISA and PCR. All the clinical characteristics of the patients at baseline were comparable between the moderate and the severe group of patients statistically, except for the peak expiratory flow rate. Mycoplasma pneumoniae infection was found to have a significant association with acute exacerbation in the moderate group of asthma patients by PCR (P=0.01). These data suggest that M. pneumoniae infection may contribute to asthma exacerbation.


title: Phylogenetic characterization of circulating Dengue and Alkhumra Hemorrhagic Fever viruses in western Saudi Arabia and lack of evidence of Zika virus in the region: A retrospective study, 2010‐2015

text: Flaviviruses represent a global public health concern. They consist of ∼70 viruses with almost half of them causing human diseases with unspecified febrile illnesses. Cities in western Saudi Arabia are endemic for viruses (DENV) with sporadic infections due to Alkhumra hemorrhagic fever virus (AHFV). They also represent a major destination for travelers coming for annual religious pilgrimages (Hajj and Umrah) from all over the world. However, whether other flaviviruses are circulating is not known because of the limited number of surveillance studies. Here, we retrospectively screened 690 samples for flaviviruses in samples from patients with unexplained febrile illnesses between 2010 and 2015 in western Saudi Arabia using a pan‐flaviviruses RT‐PCR assay. Despite Zika virus RNA was not detected, this study confirms circulation and/or sporadic spread of DENV‐2, DENV‐3, and AHFV, higher prevalence of DENV‐2, and a role for visitors from DENV endemic countries in DENV importation into the Kingdom. Further analysis also showed very low genetic diversity of AHFV confirming its slow microevolution. Accordingly, continuous and prospective surveillance for flaviviruses using such assay are warranted in Saudi Arabia which receives millions of Muslims annually to implement effective control measures in light of the global widespread and outbreaks of several flaviviruses.


Genomes and evolution


title: Affective psychosis after COVID-19 infection in a previously healthy patient: a case report

text: • Patients COVID19 new-onset psychiatric symptoms because treatments or virus itself.


title: High-Containment Pathogen Preparation in the Intensive Care Unit

text: The recent Ebola virus disease outbreak highlighted the need to build national and worldwide capacity to provide care for patients with highly infectious diseases. Specialized biocontainment units were successful in treating a number of critically ill patients with Ebola virus disease both in the United States and Europe. Several key principles underlie the care of critically ill patients in a high containment environment. Environmental factors, staffing, equipment, training, laboratory testing, procedures and waste management each present unique challenges. A multidisciplinary approach is key to developing effective systems and protocols to maintain the safety of patients, staff and communities.


title: Chapter 11 Rhinovirus RNA Polymerase Structure, Function, and Inhibitors

text: Abstract Human rhinovirus is responsible for causing 50% of common cold infections in infants and adults. It belongs to the picornavirus family of nonenveloped positive-strand RNA viruses. The RNA synthesis of rhinovirus is carried out by RNA-dependent RNA polymerase, also known as 3DPol. It catalyzes the synthesis of negative-strand RNA using a positive-strand template. The structure of the enzyme consists of three domains: palm, fingers, and thumb domains and Mg2+ in the active site. These conserved structural features of the enzyme help in catalyzing phosphodiester bond formation between the two consecutive nucleotide units complimentary to the template RNA using a VPg primer. Owing to the presence of over 100 serotypes of the enzyme, designing specific inhibitors targeting the polymerase is a challenging task and until now no clinically approved antirhino viral drug is reported. In this review, we have given detailed information about the structure and function of the enzyme and also discussed some of the inhibitors and their in vivo activity against 3DPol.


title: Epidemiology and clinical profile of pathogens responsible for the hospitalization of children in Sousse area, Tunisia

text: This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1–3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient’s demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1–4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia.


title: Immunity and the Endocrine System

text: Abstract The immune system is highly receptive to endocrine signals due to the expression of hormone receptors on immune cells. The impact of this immune–endocrine cross talk and related immune responses becomes clearly evident when assessing immunity from a sex-specific perspective. We here describe the effect of hormones, primarily sex- and stress-related steroid hormones, on cells of the innate and adaptive immune system in men and women. We specify how these effects are operational throughout the life span and also during periods of dramatic hormonal changes, such as pregnancy.


Animal Models for Sars


title: Structure of a Protozoan Virus from the Human Genitourinary Parasite Trichomonas vaginalis

text: The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves −2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date.


title: Association of RSV-A ON1 genotype with Increased Pediatric Acute Lower Respiratory Tract Infection in Vietnam

text: Since the initial discovery of RSV-A ON1 in Canada in 2010, ON1 has been reported worldwide, yet information regarding its clinical impact and severity has been controversial. To investigate the clinical relevance of RSV-A ON1,acute respiratory infection (ARI) cases enrolled to our population-based prospective pediatric ARI surveillance at Khanh Hoa General Hospital, Central Vietnam from January 2010 through December 2012 were studied. Clinical-epidemiological information and nasopharyngeal samples were collected. Multiplex PCR assays were performed for screening 13 respiratory viruses. RSV-positive samples were further tested for subgroups (A/B) and genotypes information by sequencing the G-glycoprotein 2nd hypervariable region. Statistical analysis was performed to evaluate the clinical-epidemiological characteristics of RSV-A ON1. A total of 1854 ARI cases were enrolled and 426 (23.0%) of them were RSV-positive. During the study period, RSV-A and B had been co-circulating. NA1 was the predominant RSV-A genotype until the appearance of ON1 in 2012. RSV-related ARI hospitalization incidence significantly increased after the emergence of ON1. Moreover, multivariate analysis revealed that risk of lower respiratory tract infection was 2.26 (95% CI: 1.37–3.72) times, and radiologically-confirmed pneumonia was 1.98 (95% CI: 1.01–3.87) times greater in ON1 compared to NA1 cases. Our result suggested that ON1 ARI cases were clinically more severe than NA1.


title: In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding

text: Abstract The early cytokines interferon-α (IFN-α), tumour necrosis factor-α (TNF-α), interleukin-1, -6 and -8 (IL-1, -6, -8) are produced during the most early stage of an infection. The activities of these cytokines have been studied extensively in vitro and in rodents, but in vivo studies on the role of these cytokines in infectious diseases of food animals are few. This review concentrates on in vivo studies of cytokine involvement in infectious respiratory diseases of swine, with an emphasis on viral infections. First evidence for the role of early cytokines in pneumonia in swine came from experimental infections with Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. The role of TNF-α and IL-1 in the symptoms and pathology of porcine pleuropneumonia has recently been proven by use of an adenovirus vector expressing the anti-inflammatory IL-10. In the authors’ laboratory, studies were undertaken to investigate the relationship between viral respiratory disease and bioactive lung lavage levels of IFN-α, TNF-α, IL-1 and IL-6. Out of three respiratory viruses—porcine respiratory coronavirus (PRCV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV)—only SIV induced acute respiratory disease and severe lung damage by itself. Disease and lung pathology were tightly associated with the simultaneous production of IFN-α, TNF-α, IL-1 and IL-6. In challenge studies of SIV-vaccinated pigs, levels of IFN-α, TNF-α and IL-6, but not IL-1 were correlated with clinical and virological protection. Multifactorial respiratory disease was reproduced by combined inoculations with PRCV or PRRSV followed by LPS from Escherichia coli. In comparison with the respective single inoculations, which were subclinical, there was a true potentiation of disease and production of TNF-α, IL-1 and IL-6. TNF-α and IL-6 were best correlated with disease. In further studies, we will use more specific strategies to dissect the role of cytokines during viral infections.


Unexpected favourable course of Coronavirus Disease 2019 in chronic thromboembolic pulmonary hypertension patients


title: Type I interferon receptor knockout mice as models for infection of highly pathogenic viruses with outbreak potential

text: Due to their inability to generate a complete immune response, mice knockout for type I interferon (IFN) receptors (Ifnar(–/–)) are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.


title: SEIR modeling of the COVID-19 and its dynamics

text: In this paper, a SEIR epidemic model for the COVID-19 is built according to some general control strategies, such as hospital, quarantine and external input. Based on the data of Hubei province, the particle swarm optimization (PSO) algorithm is applied to estimate the parameters of the system. We found that the parameters of the proposed SEIR model are different for different scenarios. Then, the model is employed to show the evolution of the epidemic in Hubei province, which shows that it can be used to forecast COVID-19 epidemic situation. Moreover, by introducing the seasonality and stochastic infection the parameters, nonlinear dynamics including chaos are found in the system. Finally, we discussed the control strategies of the COVID-19 based on the structure and parameters of the proposed model.


title: Social media engagement analysis of U.S. Federal health agencies on Facebook

text: BACKGROUND: It is becoming increasingly common for individuals and organizations to use social media platforms such as Facebook. These are being used for a wide variety of purposes including disseminating, discussing and seeking health related information. U.S. Federal health agencies are leveraging these platforms to ‘engage’ social media users to read, spread, promote and encourage health related discussions. However, different agencies and their communications get varying levels of engagement. In this study we use statistical models to identify factors that associate with engagement. METHODS: We analyze over 45,000 Facebook posts from 72 Facebook accounts belonging to 24 health agencies. Account usage, user activity, sentiment and content of these posts are studied. We use the hurdle regression model to identify factors associated with the level of engagement and Cox proportional hazards model to identify factors associated with duration of engagement. RESULTS: In our analysis we find that agencies and accounts vary widely in their usage of social media and activity they generate. Statistical analysis shows, for instance, that Facebook posts with more visual cues such as photos or videos or those which express positive sentiment generate more engagement. We further find that posts on certain topics such as occupation or organizations negatively affect the duration of engagement. CONCLUSIONS: We present the first comprehensive analyses of engagement with U.S. Federal health agencies on Facebook. In addition, we briefly compare and contrast findings from this study to our earlier study with similar focus but on Twitter to show the robustness of our methods.


title: Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity

text: The ubiquitin-proteasome system (UPS) is the primary mechanism by which intracellular proteins, transcription factors, and many proteotoxic proteins with aggregation-prone structures are degraded. The UPS is reportedly downregulated in various neurodegenerative disorders, with increased proteasome activity shown to be beneficial in many related disease models. Proteasomes function under tonic inhibitory conditions, possibly via the ubiquitin chain-trimming function of USP14, a proteasome-associated deubiquitinating enzyme (DUB). We identified three specific RNA aptamers of USP14 (USP14-1, USP14-2, and USP14-3) that inhibited its deubiquitinating activity. The nucleotide sequences of these non-cytotoxic USP14 aptamers contained conserved GGAGG motifs, with G-rich regions upstream, and similar secondary structures. They efficiently elevated proteasomal activity, as determined by the increased degradation of small fluorogenic peptide substrates and physiological polyubiquitinated Sic1 proteins. Additionally, proteasomal degradation of tau proteins was facilitated in the presence of the UPS14 aptamers in vitro. Our results indicate that these novel inhibitory UPS14 aptamers can be used to enhance proteasome activity, and to facilitate the degradation of proteotoxic proteins, thereby protecting cells from various neurodegenerative stressors.


title: Role of protease in mouse hepatitis virus-induced cell fusion Studies with a cold-sensitive mutant isolated from a persistent infection

text: Abstract A plaque mutant was isolated from Kirsten mouse sarcoma virus-transformed BALB/c cells persistently infected with a mouse hepatitis virus strain MHV-S. While the wild type produced large plaques consisting of fused cells (fusion type) both at 39 and at 32°, the mutant produced small fusion-type plaques at 39°, and at 32°, only after longer incubation, plaques consisting of round dead cells (non-fusion type) were obtained. The mutant grew equally well at both temperatures. Thus, the mutant was cold sensitive in inducing cell fusion, but not in replication or in ultimate cell killing. The cold sensitivity was overcome by the addition of trypsin (0.04 to 0.05%) to the culture medium, but not by treating the virions with trypsin. SDS-polyacrylamide gel electrophoresis of the virion proteins failed to detect differences between the wild type and the mutant. In intracellular viral proteins immunoprecipitated with anti-MHV-S rabbit serum, a protein of 68,000 daltons (68K protein) which was present in the wild type-infected cells was absent in the mutant-infected cells, but trypsin treatment or incubation at 39° of the mutant-infected cells failed to induce the 68K protein. After six to seven undiluted passages, the mutant segregated varieties of mutants which were partially or totally reverted to the wild type in phenotype, and also those whose cell fusion induction was absent even at 39°. All these mutants failed to induce the 68K protein in the infected cells. Thus, there was no linkage between the presence of 68K protein and the fusion induction. Trypsin treatment of the infected cells enabled MHV-S to form fusion plaques on otherwise resistant cells, and MHV-2, a producer of non-fusion-type plaques, to form fusion-type plaques. Protease appears to play an important role in MHV-induced cell fusion in general.


Literature Highlights in Combinatorial Science: QSAR Comb. Sci. 9/2005


title: Customised structural, optical and antibacterial characteristics of cinnamon nanoclusters produced inside organic solvent using 532 nm Q-switched Nd:YAG-pulse laser ablation

text: Biomedical values of organic natural cinnamon that are buried in their bulk counterpart can be exposed and customised via nanosizing. Based on this factor, a new type of spherical cinnamon nanoclusters (Cin-NCs) were synthesised using eco-friendly nanosecond pulse laser ablation in liquid (PLAL) approach. As-grown nontoxic Cin-NCs suspended in the citric acid of pH 4.5 (acted as organic solvent) were characterised thoroughly to evaluate their structural, optical and bactericidal properties. The effects of various laser fluences (LF) at the fixed wavelength (532 nm) on the physiochemical properties of these Cin-NCs were determined. The FTIR spectra of the Cin-NCs displayed the symmetric-asymmetric stretching of the functional groups attached to the heterocyclic/cinnamaldehyde compounds. The HR-TEM image of the optimum sample revealed the nucleation of the crystalline spherical Cin-NCs with a mean diameter of approximately 10 ± 0.3 nm and lattice fringe spacing around 0.14 nm. In addition, the inhibition zone diameter (IZD) and optical density (OD(600)) of the proposed Cin-NCs were measured to assess their antibacterial potency against the Staphylococcus aureus (IZD ≈ 24 mm) and Escherichia coli (IZD ≈ 25 mm) bacterial strains. The strong UV absorption (in the range of 269 and 310 nm) shown by these NCs was established to be useful for the antibacterial drug development and food treatment.


title: Functional peptide microarrays for specific and sensitive antibody diagnostics

text: Peptide microarrays displaying biologically active small synthetic peptides in a high‐density format provide an attractive technology to probe complex samples for the presence and/or function of protein analytes. We present a new approach for manufacturing functional peptide microarrays for molecular immune diagnostics. Our method relies on the efficiency of site‐specific solution‐phase coupling of biotinylated synthetic peptides to NeutrAvidin (NA) and localized microdispensing of peptide‐NA‐complexes onto activated glass surfaces. Antibodies are captured in a sandwich manner between surface immobilized peptide probes and fluorescence‐labeled secondary antibodies. Our work includes a total of 54 peptides derived from immunodominant linear epitopes of the T7 phage capsid protein, Herpes simplex virus glycoprotein D, c‐myc protein, and three domains of the Human coronavirus polymerase polyprotein and their cognate mAbs. By using spacer molecules of different type and length for NA‐mediated peptide presentation, we show that the incorporation of a minimum spacer length is imperative for antibody binding, whereas the peptide immobilization direction has only secondary importance for antibody affinity and binding. We further demonstrate that the peptide array is capable of detecting low‐picomolar concentrations of mAbs in buffered solutions and diluted human serum with high specificity.


title: Update: Recommendations for Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

text: On June 11, 2013, CDC issued interim infection prevention and control recommendations for hospitalized patients with known or suspected Middle East respiratory syndrome coronavirus (MERS-CoV) infection in U.S. hospitals. To date, no MERS-CoV cases have been reported in the United States; however, cases have been reported in eight other countries. Recent published reports have described limited health-care transmission of MERS-CoV, including cases among health-care personnel in international settings. These published reports highlight the need for rapid detection of infectious patients and adherence to correct infection prevention measures to prevent transmission of the virus among patients, health-care personnel, and visitors.


title: Chapter 6 Biology and Diseases of Guinea Pigs

text: The guinea pig (Cavia porcellus), the only New World rodent used commonly in research, has contributed to studies of anaphylaxis, asthma, gnotobiotics, immunology, infectious and nutritional disease, and otology, among others. Several outbred and inbred strains were used historically, but at present, only outbred pigmented stocks, albino Hartley stocks, and IAF hairless stock are available commercially in the United States (Fig. 6.1). Husbandry considerations include noninjurious housing, appropriate food, prevention of intraspecies aggression, environmental stability, and reproductive aspects, including a long gestation. Although guinea pigs are susceptible to a wide range of diseases, current breeding and housing conditions have reduced the occurrence of many spontaneous infectious diseases in these animals. Diseases of concern that do occur in research colonies include respiratory diseases (especially those caused by Bordetella, Streptococcus, and adenovirus), chlamydiosis, pediculosis, dermatophytosis, hypovitaminosis C, pregnancy toxemia, urolithiasis, traumatic lesions, dental malocclusion, ovarian cysts, and antibiotic-induced intestinal dysbiosis.


title: Relationship between the treatment and the evolution of the clinical course in scouring Merino lambs from “La Serena” (Southwest Spain)

text: Abstract This work investigated the link between the type of treatment and the clinical evolution of lambs suffering from diarrhoea attributed to non-enterotoxigenic Escherichia coli. Two hundred and forty scouring lambs, and 25 healthy lambs selected as control, were used in this trial. The faecal samples from the scouring lambs were positive to non-enterotoxigenic E. coli. All the scouring lambs received supportive care and they were randomly allotted to two groups of 120 animals (treated group and untreated group). The lambs in the treated group were given two daily doses of 20mg/kg live weight spectinomycin for 3 days, while the other group of lambs (untreated group) did not receive any antibiotic. Serum endotoxin was higher in the treated lambs. The combined infection of E. coli + Proteus mirabilis was the most frequent microbiological result in the deceased treated lambs, while the only enteric pathogen isolated in the untreated lambs submitted to necroscopy was E. coli. The pathological findings most commonly recorded in the untreated lambs were suggestive of a generalized inflammatory process attributed to colibacilosis, while the lesions in the treated lambs might correspond to an enterotoxoemic process. The overproduction of P. mirabilis might be consequence of the antibiotic treatment and it would be the most probable cause of the endotoxemia, the high mortality rate and the pathological findings in the treated lambs. Therefore, a supportive care without antibiotics does not lead to a poorer chance of survival in lambs with diarrhoea attributed to non-enterotoxigenic E. coli.


The Tsinghua–Lancet Commission on Healthy Cities in China: unlocking the power of cities for a healthy China


title: Update: Severe Respiratory Illness Associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) — Worldwide, 2012–2013

text: CDC continues to work in consultation with the World Health Organization (WHO) and other partners to better understand the public health risk posed by the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), formerly known as novel coronavirus, which was first reported to cause human infection in September 2012. The continued reporting of new cases indicates that there is an ongoing risk for transmission to humans in the area of the Arabian Peninsula. New reports of cases outside the region raise concerns about importation to other geographic areas. Nosocomial outbreaks with transmission to health-care personnel highlight the importance of infection control procedures. Recent data suggest that mild respiratory illness might be part of the clinical spectrum of MERS-CoV infection, and presentations might not initially include respiratory symptoms. In addition, patients with comorbidities or immunosuppression might be at increased risk for infection, severe disease, or both. Importantly, the incubation period might be longer than previously estimated. Finally, lower respiratory tract specimens (e.g., sputum, bronchoalveolar lavage, bronchial wash, or tracheal aspirate) should be collected in addition to nasopharyngeal sampling for evaluation of patients under investigation. An Emergency Use Authorization (EUA) was recently issued by the Food and Drug Administration (FDA) to allow for expanded availability of diagnostic testing in the United States.


title: The incidence of Clostridioides difficile and Clostridium perfringens netF-positive strains in diarrheic dogs

text: Abstract The aim of this study was to examine the incidence of Clostridioides (previously Clostridium) difficile and Clostridium perfringens in the feces of diarrheic and non-diarrheic dogs. Also, the presence of other common canine enteropathogens was examined. Toxigenic C. difficile and C. perfringens positive for the NetF-encoding gene (netF) were detected in 11 (11.9%) and seven (7.6%) diarrheic dogs, respectively. Three dogs were diagnosed simultaneously with toxigenic C. difficile and netF-positive C. perfringens. Among other enteropathogens, Giardia sp. was the most common agent detected in dogs positive for toxigenic C. difficile or netF-positive C. perfringens. The results suggest that C. difficile and C. perfringens occur more frequently as a primary cause of diarrhea.


title: Management of Transplant Patients outside Hospital during COVID‐19 Epidemic: a Chinese Experience

text: Coronavirus disease 2019 (COVID‐19) pandemic poses an increasing challenge for transplant community. Aggressive management measures are conductive to improve compliance and to lower the risk of intra‐hospital infection. In this Personal Viewpoint essay, we shared experiences about management strategies of transplant patients outside hospital amid the epidemic. With the aid of Cloud Clinic service and telemedicine care, transplant patients could be regularly followed up and get medical consultation online. Furthermore, personal health education and mental health assistance are enrolled in our practice.


title: Randomized controlled trial of the effect of regular paracetamol on influenza infection

text: BACKGROUND AND OBJECTIVE: Anti‐pyretic treatment is recommended in the management of influenza infection. In animal models anti‐pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection. METHODS: This is a randomized, double‐blind, placebo‐controlled trial of adults aged 18–65 years with influenza‐like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT‐PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5–14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log(10) viral load from Baseline to Day 5. RESULTS: A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR‐positive in placebo and in paracetamol groups respectively. Mean (SD) AUC PCR log(10) viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was −0.24, 95% CI: −0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR. CONCLUSION: Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR‐confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection. Clinical trial registration: ACTRN12611000497909 at the Australian New Zealand Clinical Trials Registry.


title: Global dynamics of a fractional order model for the transmission of HIV epidemic with optimal control

text: In this paper, a nonlinear fractional order epidemic model for HIV transmission is proposed and analyzed by including extra compartment namely exposed class to the basic SIR epidemic model. Also, the infected class of female sex workers is divided into unaware infectives and the aware infectives. The focus is on the spread of HIV by female sex workers through prostitution, because in the present world sexual transmission is the major cause of the HIV transmission. The exposed class contains those susceptible males in the population who have sexual contact with the female sex workers and are exposed to the infection directly or indirectly. The Caputo type fractional derivative is involved and generalized Adams-Bashforth-Moulton method is employed to numerically solve the proposed model. Model equilibria are determined and their stability analysis is considered by using fractional Routh-Hurwitz stability criterion and fractional La-Salle invariant principle. Analysis of the model demonstrates that the population is free from the disease if [Formula: see text] and disease spreads in the population if [Formula: see text]. Meanwhile, by using Lyapunov functional approach, the global dynamics of the endemic equilibrium point is discussed. Furthermore, for the fractional optimal control problem associated with the control strategies such as condom use for exposed class, treatment for aware infectives, awareness about disease among unaware infectives and behavioral change for susceptibles, we formulated a fractional optimality condition for the proposed model. The existence of fractional optimal control is analyzed and the Euler-Lagrange necessary conditions for the optimality of fractional optimal control are obtained. The effectiveness of control strategies is shown through numerical simulations and it can be seen through simulation, that the control measures effectively increase the quality of life and age limit of the HIV patients. It significantly reduces the number of HIV/AIDS patients during the whole epidemic.


title: Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample

text: Summary Objectives Many adult patients hospitalised with acute respiratory illness have viruses detected but the overall importance of viral infection compared to bacterial infection is unclear. Methods Patients were recruited from two acute hospital sites in Leicester (UK) over 3 successive winters. Samples were taken for viral and bacterial testing. Results Of the 780 patients hospitalised with acute respiratory illness 345 (44%) had a respiratory virus detected. Picornaviruses were the most commonly isolated viruses (detected in 23% of all patients). Virus detection rates exceeded 50% in patients with exacerbation of asthma (58%), acute bronchitis and Influenza-like-illness (64%), and ranged from 30 to 50% in patients with an exacerbation of COPD (38%), community acquired pneumonia (36%) and congestive cardiac failure (31%). Bacterial detection was relatively frequent in patients with exacerbation of COPD and pneumonia (25% and 33% respectively) but was uncommon in all other groups. Antibiotic use was high across all clinical groups (76% overall) and only 21% of all antibiotic use occurred in patients with detectable bacteria. Conclusions Respiratory viruses are the predominant detectable aetiological agents in most hospitalised adults with acute respiratory illness. Antibiotic usage in hospital remains excessive including in clinical conditions associated with low rates of bacterial detection. Efforts at reducing excess antibiotic use should focus on these groups as a priority. Registered International Standard Controlled Trial Number: 21521552.


title: Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post-pandemic influenza seasons, 2010/11–2012/13

text: BACKGROUND: Previous influenza surveillance at paediatric intensive care units (PICUs) in Germany indicated increased incidence of PICU admissions for the pandemic influenza subtype A(H1N1)pdm09. We investigated incidence and clinical characteristics of influenza in children admitted to PICUs during the first three post-pandemic influenza seasons, using active screening. METHODS: We conducted a prospective surveillance study in 24 PICUs in Bavaria (Germany) from October 2010 to September 2013. Influenza cases among children between 1 month and 16 years of age admitted to these PICUs with acute respiratory infection were confirmed by PCR analysis of respiratory secretions. RESULTS: A total of 24/7/20 influenza-associated PICU admissions were recorded in the post-pandemic seasons 1/2/3; incidence estimates per 100,000 children were 1.72/0.76/1.80, respectively. Of all 51 patients, 80 % had influenza A, including 65 % with A(H1N1)pdm09. Influenza A(H1N1)pdm09 was almost absent in season 2 (incidence 0.11), but dominated PICU admissions in seasons 1 (incidence 1.35) and 3 (incidence 1.17). Clinical data was available for 47 influenza patients; median age was 4.8 years (IQR 1.6–11.0). The most frequent diagnoses were influenza-associated pneumonia (62 %), bronchitis/bronchiolitis (32 %), secondary bacterial pneumonia (26 %), and ARDS (21 %). Thirty-six patients (77 %) had underlying medical conditions. Median duration of PICU stay was 3 days (IQR 1–11). Forty-seven per cent of patients received mechanical ventilation, and one patient (2 %) extracorporeal membrane oxygenation; 19 % were treated with oseltamivir. Five children (11 %) had pulmonary sequelae. Five children (11 %) died; all had underlying chronic conditions and were infected with A(H1N1)pdm09. In season 3, patients with A(H1N1)pdm09 were younger than in season 1 (p = 0.020), were diagnosed more often with bronchitis/bronchiolitis (p = 0.004), and were admitted to a PICU later after the onset of influenza symptoms (p = 0.041). CONCLUSIONS: Active screening showed a continued high incidence of A(H1N1)pdm09-associated PICU admissions in the post-pandemic seasons 1 and 3, and indicated possible underestimation of incidence in previous German studies. The age shift of severe A(H1N1)pdm09 towards younger children may be explained by increasing immunity in the older paediatric population. The high proportion of patients with underlying chronic conditions indicates the importance of consistent implementation of the current influenza vaccination recommendations for risk groups in Germany.


title: Clinical features of familial clustering in patients infected with 2019 novel coronavirus in Wuhan, China

text: An epidemic caused by SARS-Coronavirus-2 (SARS-CoV-2) infection has appeared in Wuhan City in December 2019 and subsequently spread in China. The disease has shown a "clustering epidemic" pattern, and family-clustered onset has been the main characteristic. We collected data from 130 cases from 35 cluster-onset families (COFs) and 41 cases from 16 solitary-onset families (SOFs). The incidence 2019 coronavirus disease (COVID-19) in COFs was significantly higher than that of SOFs. Our study also showed that patients with exposure to high-risk factors (respiratory droplets and close contact), advanced age, and comorbidities were more likely to develop COVID-19 in the COFs. In addition, advanced age and elevated neutrophil/lymphocyte ratio (NLR) were risk factors for death in patients with SARS-CoV-2 infection in the COFs.


title: Changes in sexual behaviors of young women and men during the coronavirus disease 2019 outbreak: a convenience sample from the epidemic area

text: Abstract Background In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Currently, data on changes in sexual behavior during the COVID-19 outbreak are limited. Aim The present study aimed to obtain a preliminary understanding of the changes in people’s sexual behavior, as a result of the pandemic and explore the context in which they manifest. Methods A convenience sample of 270 men and 189 women who completed an online survey consisting of 12 items plus an additional question were included in the study. Outcomes The study outcomes were obtained using a study-specific questionnaire to assess the changes in people’s sexual behavior. Results While there was a wide range of individual responses, our results showed that 44% of participants reported a decrease in the number of sexual partners and about 37% of participants reported a decrease in sexual frequency. Multiple regression analysis showed that age, partner relationship and sexual desire were closely related to sexual frequency. In addition, we found that most individuals with risky sexual experiences had a rapid reduction in risky sexual behavior. Clinical Implications The current findings contribute to identifying another potential health implication associated with the COVID-19 pandemic and report preliminary evidence of the need to provide potential interventions for the population. Strength & Limitations This study is the first to perform a preliminary exploration of sexual behavior during the COVID-19 outbreak. The generalizability of the results is limited, given that only a small convenience sample was used. Conclusion During the height of the COVID-19 outbreak, overall sexual activity, frequency, and risky behaviors declined significantly among young men and women in China.


title: Schneller Ausstieg oder bedachte Lockerung?: Zur Zukunft von Kontaktbeschränkungen in der COVID-19-Krise

text: How important is the relaxation of contact restrictions for the recovery of the German economy and what conclusions can be drawn for the appropriate level of contact restrictions in the coming months? In considering these issues, an attempt will be made to assess what significance the contact restriction measures introduced by the federal and state governments since mid-March 2020 will actually have for the current slump in economic activity in Germany. In addition, the various plausible scenarios for the spread and containment of infection are presented with different options for easing contact restrictions.


title: lncRNA-mediated regulation of the interferon response

text: The interferon (IFN) response is a critical arm of the innate immune response and a major host defense mechanism against viral infections. Following microbial encounter, a series of signaling events lead to transcriptional activation of the IFN genes, which in turn leads to significant changes in the cellular transcriptome by altering the expression of hundreds of target genes. Emerging evidence suggest that long non-coding RNAs (lncRNAs) constitute a major subgroup of the IFN target genes, and further, that the IFN response is subject to regulation by a large number of host- and pathogen-derived lncRNAs. While the vast majority of lncRNAs with potential roles in the IFN response remain unstudied, analysis of a very small subset provides a glimpse of the regulatory impact of this class of RNAs on IFN response.


title: Identification of a Gamma Interferon-Activated Inhibitor of Translation-Like RNA Motif at the 3′ End of the Transmissible Gastroenteritis Coronavirus Genome Modulating Innate Immune Response

text: A 32-nucleotide (nt) RNA motif located at the 3′ end of the transmissible gastroenteritis coronavirus (TGEV) genome was found to specifically interact with the host proteins glutamyl-prolyl-tRNA synthetase (EPRS) and arginyl-tRNA synthetase (RRS). This RNA motif has high homology in sequence and secondary structure with the gamma interferon-activated inhibitor of translation (GAIT) element, which is located at the 3′ end of several mRNAs encoding proinflammatory proteins. The GAIT element is involved in the translation silencing of these mRNAs through its interaction with the GAIT complex (EPRS, heterogeneous nuclear ribonucleoprotein Q, ribosomal protein L13a, and glyceraldehyde 3-phosphate dehydrogenase) to favor the resolution of inflammation. Interestingly, we showed that the viral RNA motif bound the GAIT complex and inhibited the in vitro translation of a chimeric mRNA containing this RNA motif. To our knowledge, this is the first GAIT-like motif described in a positive RNA virus. To test the functional role of the GAIT-like RNA motif during TGEV infection, a recombinant coronavirus harboring mutations in this motif was engineered and characterized. Mutations of the GAIT-like RNA motif did not affect virus growth in cell cultures. However, an exacerbated innate immune response, mediated by the melanoma differentiation-associated gene 5 (MDA5) pathway, was observed in cells infected with the mutant virus compared with the response observed in cells infected with the parental virus. Furthermore, the mutant virus was more sensitive to beta interferon than the parental virus. All together, these data strongly suggested that the viral GAIT-like RNA motif modulates the host innate immune response.


title: Genetic determinants of HIV‐1 infection and progression to AIDS: susceptibility to HIV infection

text: Interindividual variability in susceptibility to HIV‐1 infection, its transmission, disease progression, and response to antiviral therapy has been attributed to host determinants and variability in multiple genes. Although most people exposed to the virus go on to develop full‐blown disease at variable intervals, a proportion of them, labeled as long‐term nonprogressors or exposed uninfected, possess ‘natural resistance’ to infection. A better understanding of genetic and immunologic basis of such a natural resistance to infection would bear important implications in designing therapeutic vaccine designs. The genetic variants that could influence susceptibility to HIV‐1 and limit AIDS vary in different populations and among individuals. Meta‐analyses of large cohort studies have identified numerous ‘AIDS restriction genes’ that regulate HIV cell entry (particularly chemokine coreceptors and their ligands), acquired and innate immunity (major histocompatibility complex, killer cell immunoglobulin‐like receptor, and cytokines), and others [tripartite interaction motif 5 α (TRIM5α) and apolipoprotein B mRNA‐editing enzyme, catalytic polypeptide‐like 3G] that influence outcome of HIV infection. Studies carried out in the Indian population with regard to genetic polymorphisms in chemokine receptors have shown that (i) the protective CCR5 Δ32 variant is rare, (ii) CCR5HHE carrying *59402A is associated with increased likelihood of infection and development of AIDS, and (iii) the Indian population generally has low CCL3L1 copy numbers (∼2.3). These data have implications in developing screening tests that could identify people at higher or lower risk of infection and rate of disease progression, predict vaccine responsiveness in clinical trials and understand the pathogenic mechanisms.


title: Mapping genetic determinants of viral traits with F ST and quantitative trait locus (QTL) approaches

text: Abstract The genetic determinism of viral traits can generally be dissected using either forward or reverse genetics because the clonal reproduction of viruses does not require the use of approaches based on laboratory crosses. Nevertheless, we hypothesized that recombinant viruses could be analyzed as sexually reproducing organisms, using either a quantitative trait loci (QTL) approach or a locus-by-locus fixation index (F ST). Locus-by-locus F ST analysis, and four different regressions and interval mapping algorithms of QTL analysis were applied to a phenotypic and genotypic dataset previously obtained from 47 artificial recombinant genomes generated between two begomovirus species. Both approaches assigned the determinant of within-host accumulation—previously identified using standard virology approaches—to a region including the 5׳ end of the replication-associated protein (Rep) gene and the upstream intergenic region. This study provides a proof of principle that QTL and population genetics tools can be extended to characterize the genetic determinants of viral traits.