title: Cholecystectomy or Gallbladder In Situ After Endoscopic Sphincterotomy and Bile Duct Stone Removal in Chinese Patients

text: Background & Aims: In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. Methods: We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. Results: One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). Conclusions: In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.


title: Immunological properties of gold nanoparticles

text: In the past decade, gold nanoparticles have attracted strong interest from the nanobiotechnological community owing to the significant progress made in robust and easy-to-make synthesis technologies, in surface functionalization, and in promising biomedical applications. These include bioimaging, gene diagnostics, analytical sensing, photothermal treatment of tumors, and targeted delivery of various biomolecular and chemical cargos. For the last-named application, gold nanoparticles should be properly fabricated to deliver the cargo into the targeted cells through effective endocytosis. In this review, we discuss recent progress in understanding the selective penetration of gold nanoparticles into immune cells. The interaction of gold nanoparticles with immune cell receptors is discussed. As distinct from other published reviews, we present a summary of the immunological properties of gold nanoparticles. This review also summarizes what is known about the application of gold nanoparticles as an antigen carrier and adjuvant in immunization for the preparation of antibodies in vivo. For each of the above topics, the basic principles, recent advances, and current challenges are discussed. Thus, this review presents a detailed analysis of data on interaction of gold nanoparticles with immune cells. Emphasis is placed on the systematization of data over production of antibodies by using gold nanoparticles and adjuvant properties of gold nanoparticles. Specifically, we start our discussion with current data on interaction of various gold nanoparticles with immune cells. The next section describes existing technologies to improve production of antibodies in vivo by using gold nanoparticles conjugated with specific ligands. Finally, we describe what is known about adjuvant properties of bare gold or functionalized nanoparticles. In the Conclusion section, we present a short summary of reported data and some challenges and perspectives.


title: Esophageal, Gastric, and Intestinal Disorders of Young Dogs and Cats

text: Digestive tract disorders are common diagnostic and therapeutic problems in young dogs and cats. Prompt and effective symtomatic therapy is necessary in all such cases and is sufficient in many. Some infectious, parasitic, and protozoal diseases require alterations in kennel management as well as individual treatment. Congenital disorders are frequently challenging diagnostic dilemmas.


title: Synthesis and inhibitory properties of a thiomethylmercuric sialic acid with application to the X-ray structure determination of 9-O-acetylsialic acid esterase from influenza C virus

text: Abstract 2-α-Thiomethylmercuryl 9-acetamido-9-deoxy-sialoside was prepared and found to inhibit the 9-O-acetylsialic acid esterase from influenza C virus in a competitive manner with a K i of 4.2±0.5 mM. The inhibitor is being used in the X-ray determination of the crystal structure of the esterase.


title: Zika virus infection in Collaborative Cross mice

text: The 2015-2016 emergence of Zika virus (ZIKV) in the Americas, and recognition that ZIKV infection during pregnancy can result in birth defects, revealed a need for small animal models to study ZIKV pathogenic mechanisms and evaluate candidate vaccines and antivirals. Mice would be an attractive system for such studies, but ZIKV replicates poorly in laboratory mice because it fails to antagonize murine STAT2 and STING. To address this, most ZIKV pathogenesis studies have used mice with impaired interferon signaling (e.g. Ifnar1−/− or treatment with IFNAR1-blocking antibodies). However, using mice with severe defects in innate antiviral signaling confounds studies of viral pathogenic mechanisms. Collaborative Cross (CC) mice have proven to be a valuable system for developing new mouse pathogenesis models for viral infections that are not well modeled in conventional laboratory mouse lines. To test whether CC mice could provide an immune-competent model for ZIKV pathogenesis, we infected CC lines with ZIKV and assessed weight loss, viremia, and production of neutralizing antibodies. We tested 21 CC lines (CC001, CC002, CC003, CC004, CC005, CC006, CC011, CC012, CC013, CC019, CC024, CC028, CC040, CC041, CC042, CC046, CC051, CC059, CC061, CC068, and CC072, 13 of which have non-functional alleles of the flavivirus restriction factor Oas1b) and 3 ZIKV strains (MR766, H/PF/2013, and a mouse-adapted variant of Dakar 41525). ZIKV infection did not induce weight loss compared to mock-infected controls and accordingly only low levels of viral RNA were detected in serum. Only a subset of mice developed neutralizing antibodies to ZIKV, likely due to overall low levels of infection and viremia. Our results are consistent with other studies demonstrating poor ZIKV infection in interferon-intact mice and suggest that the tested CC lines do not include polymorphic host genes that greatly increase susceptibility to ZIKV infection.


title: Controversial treatments: An updated understanding of the coronavirus disease 2019

text: An outbreak of severe acute respiratory syndrome‐related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case‐fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.


title: Purification and characterization of angiotensin converting enzyme 2 (ACE2) from murine model of mesangial cell in culture

text: Angiotensin converting enzyme 2 (ACE2) is a component of the renin–angiotensin system (RAS) which converts Ang II, a potent vasoconstrictor peptide into Ang 1–7, a vasodilator peptide which may act as a negative feedback hormone to the actions of Ang II. The discovery of this enzyme added a new level of complexity to this system. The mesangial cells (MC) have multiple functions in glomerular physiology and pathophysiology and are able to express all components of the RAS. Despite of being localized in these cells, ACE2 has not yet been purified or characterized. In this study ACE2 from mice immortalized MC (IMC) was purified by ion-exchange chromatography. The purified enzyme was identified as a single band around 60–70 kDa on SDS-polyacrylamide gel and by Western blotting using a specific antibody. The optima pH and chloride concentrations were 7.5 and 200 mM, respectively. The N-terminal sequence was homologous with many species ACE2 N-terminal sequences as described in the literature. ACE2 purified from IMC was able to hydrolyze Ang II into Ang 1–7 and the K(m) value for Ang II was determined to be 2.87 ± 0.76 μM. In conclusion, we purified and localized, for the first time, ACE2 in MC, which was able to generate Ang 1–7 from Ang II. Ang 1–7 production associated to Ang II degradation by ACE2 may exert a protective effect in the renal hemodynamic.


title: The role of CXCL10 in the pathogenesis of experimental septic shock

text: INTRODUCTION: The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice. METHODS: Septic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer’s solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival. RESULTS: CXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions. CONCLUSIONS: CXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock.


title: A typology of beliefs and misperceptions about the influenza disease and vaccine among older adults in Singapore

text: Access to the influenza vaccine pose little barriers in developed countries such as Singapore and vaccination against influenza is highly recommended for at-risk populations including older adults. However, vaccination rates are much lower than recommended despite the significant morbidity and mortality associated with the disease among this vulnerable population. Given timely goals to increase vaccine acceptance and uptake, we explored Singaporean older adults’ misperceptions about influenza disease and vaccine. Qualitative semi-structured interviews were conducted among 76 Singaporean adults aged 65 and above with no focus on a specific area in Singapore. Data were analyzed with grounded theory methods to understand participants’ attitudes, perceptions, and knowledge. We developed in vivo codes that reflect the verbiage used by participants and exhaustively catalogued themes through a constant comparison coding method. Focusing specifically on older adults’ misperceptions, seven main themes about influenza disease or vaccine emerged from our data analysis: familiarity with influenza, misperceptions about influenza, personal susceptibility to influenza, familiarity with the influenza vaccine, misperceptions about the influenza vaccine, misperceptions about influenza vaccine usage, and opinions about and barriers to influenza vaccine uptake. Notably, there is a lack of adequate knowledge and motivation in vaccinating against influenza among older adults in Singapore. Health communication needs to be more tailored toward older adults’ message processing systems and engage health professionals’ involvement in addressing the influenza disease and vaccine misperceptions identified in this study.


title: Nano-capillary electrophoresis for environmental analysis

text: Many analytical techniques have been used to monitor environmental pollutants. But most techniques are not capable to detect pollutants at nanogram levels. Hence, under such conditions, absence of pollutants is often assumed, whereas pollutants are in fact present at low but undetectable concentrations. Detection at low levels may be done by nano-capillary electrophoresis, also named microchip electrophoresis. Here, we review the analysis of pollutants by nano-capillary electrophoresis. We present instrumentations, applications, optimizations and separation mechanisms. We discuss the analysis of metal ions, pesticides, polycyclic aromatic hydrocarbons, explosives, viruses, bacteria and other contaminants. Detectors include ultraviolet–visible, fluorescent, conductivity, atomic absorption spectroscopy, refractive index, atomic fluorescence spectrometry, atomic emission spectroscopy, inductively coupled plasma, inductively coupled plasma–mass spectrometry, mass spectrometry, time-of-flight mass spectrometry and nuclear magnetic resonance. Detection limits ranged from nanogram to picogram levels.


title: Sialic acids as regulators of molecular and cellular interactions

text: The wide occurrence of sialic acids (Sia) in various chemical forms linked as monomers or polymers in an outstanding position in a multitude of complex carbohydrates of animals and microorganisms renders them as most versatile function modulators in cell biology and pathology. A survey is presented of recent advances in the study of the influences that Sias have as bulky hydrophilic and electronegatively charged monosaccharides on animal cells and on their interaction with microorganisms. Some highlights are: sialylation leads to increased anti-inflammatory activity of IgG antibodies, facilitates the escape of microorganisms from the host's immune system, and in polymeric form is involved in the regulation of embryogenesis and neuronal growth and function. The role of siglecs in immunoregulation, the dynamics of lymphocyte binding to selectins and the interactions of toxins, viruses, and other microorganisms with the host's Sia are now better understood. N-Glycolylneuraminic acid from food is antigenic in man and seems to have pathogenic potential. Sia O-acetylation mediated by various eukaryotic and prokaryotic O-acetyltransferases modulates the affinity of these monosaccharides to mammalian and microbial receptors and hinders apoptosis. The functionally versatile O-acetylated ganglioside GD3 is an onco-fetal antigen.


title: The 5' and 3' ends of alphavirus RNAs – non-coding is not non-functional

text: The non-coding regions found at the 5' and 3' ends of alphavirus genomes regulate viral gene expression, replication, translation and virus-host interactions, which have significant implications for viral evolution, host range, and pathogenesis. The functions of these non-coding regions are mediated by a combination of linear sequence and structural elements. The capped 5' untranslated region (UTR) contains promoter elements, translational regulatory sequences that modulate dependence on cellular translation factors, and structures that help to avoid innate immune defenses. The polyadenylated 3' UTR contains highly conserved sequence elements for viral replication, binding sites for cellular miRNAs that determine cell tropism, host range, and pathogenesis, and conserved binding regions for a cellular protein that influences viral RNA stability. Nonetheless, there are additional conserved elements in non-coding regions of the virus (e.g., the repeated sequence elements in the 3' UTR) whose function remains obscure. Thus, key questions remain as to the function of these short yet influential untranslated segments of alphavirus RNAs.


title: IκB kinase ɛ (IKKɛ): A therapeutic target in inflammation and cancer

text: Abstract The innate immune system forms our first line of defense against invading pathogens and relies for a major part on the activation of two transcription factors, NF-κB and IRF3. Signaling pathways that activate these transcription factors are intertwined at the level of the canonical IκB kinases (IKKα, IKKβ) and non-canonical IKK-related kinases (IKKɛ, TBK1). Recently, significant progress has been made in understanding the function and mechanism of action of IKKɛ in immune signaling. In addition, IKKɛ impacts on cell proliferation and transformation, and is thereby also classified as an oncogene. Studies with IKKɛ knockout mice have illustrated a key role for IKKɛ in inflammatory and metabolic diseases. In this review we will highlight the mechanisms by which IKKɛ impacts on signaling pathways involved in disease development and discuss its potential as a novel therapeutic target.


title: Visualizing the replication of respiratory syncytial virus in cells and in living mice

text: Respiratory syncytial virus (RSV) is the most important cause of severe lower-respiratory tract disease in calves and young children, yet no human vaccine nor efficient curative treatments are available. Here we describe a recombinant human RSV reverse genetics system in which the red fluorescent protein (mCherry) or the firefly luciferase (Luc) genes are inserted into the RSV genome. Expression of mCherry and Luc are correlated with infection rate, allowing the monitoring of RSV multiplication in cell culture. Replication of the Luc-encoding virus in living mice can be visualized by bioluminescent imaging, bioluminescence being detected in the snout and lungs of infected mice after nasal inoculation. We propose that these recombinant viruses are convenient and valuable tools for screening of compounds active against RSV, and can be used as an extremely sensitive readout for studying effects of antiviral therapeutics in living mice. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms6104) contains supplementary material, which is available to authorized users.


title: Developing a Measure of the Impact of COVID‐19 Social Distancing on Household Conflict and Cohesion

text: This report introduces the COVID‐19 Family Environment Scale (CHES), which aims to measure the impact of social distancing due to COVID‐19 on household conflict and cohesion. Existing measures do not capture household experiences relevant to the pandemic, in which families are largely confined to their homes while sharing a life‐threatening situation. Using best practice guidelines, we developed a pool of items and revised them with review by a panel of experts, and cognitive interviewing with community respondents. We administered the CHES by online survey to 3,965 adults. The CHES consists of 15 items for each of two subscales, Household Conflict (α = .847), and Household Cohesion (α = .887). Exploratory factor analysis yielded two factors, corresponding to the intended conflict and cohesion items, which accounted for 22% of variance. Confirmatory factor analysis partially supported the 2‐factor model (RMSEA = .057; CFI = .729, TLI = .708, and SRMR = .098). The CHES also contains 25 optional items to describe respondent and household characteristics, and household‐level COVID‐19 exposure. The CHES, publicly available at https://elcentro.sonhs.miami.edu/research/measures-library/covid-19/index.html,provides a tool for measuring the impact of the COVID‐19 pandemic on important determinants of resilience in the face of major stressful events. Further work is needed to address the factor structure and establish validity of the CHES.


Fasting plasma glucose associated with mortality rate


title: 6-Thioguanine inhibits rotavirus replication through suppression of Rac1 GDP/GTP cycling

text: Abstract Rotavirus infection has emerged as an important cause of complications in organ transplantation recipients and might play a role in the pathogenesis of inflammatory bowel disease (IBD). 6-Thioguanine (6-TG) has been widely used as an immunosuppressive drug for organ recipients and treatment of IBD in the clinic. This study aims to investigate the effects and mode-of-action of 6-TG on rotavirus replication. Human intestinal Caco2 cell line, 3D model of human primary intestinal organoids, laboratory rotavirus strain (SA11) and patient-derived rotavirus isolates were used. We have demonstrated that 6-TG significantly inhibits rotavirus replication in these intestinal epithelium models. Importantly, gene knockdown or knockout of Rac1, the cellular target of 6-TG, significantly inhibited rotavirus replication, indicating the supportive role of Rac1 for rotavirus infection. We have further demonstrated that 6-TG can effectively inhibit the active form of Rac1 (GTP-Rac1), which essentially mediates the anti-rotavirus effect of 6-TG. Consistently, ectopic over-expression of GTP-Rac1 facilitates but an inactive Rac1 (N17) or a specific Rac1 inhibitor (NSC23766) inhibits rotavirus replication. In conclusion, we have identified 6-TG as an effective inhibitor of rotavirus replication via the inhibition of Rac1 activation. Thus, for transplantation patients or IBD patients infected with rotavirus or at risk of rotavirus infection, the choice of 6-TG as a treatment appears rational.


title: Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection

text: Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection.


title: Sows infected in pregnancy with porcine respiratory coronavirus show no evidence of protecting their sucking piglets against transmissible gastroenteritis

text: Eighteen litters of sucking piglets were challenged with one of two strains of transmissible gastroenteritis virus (TGEV). During pregnancy, their seronegative dams had been either inoculated intranasally with porcine respiratory coronavirus (PRCV), inoculated orally with TGEV or left untreated. On the basis of weight gain, clinical signs and survival, no differences in response to challenge was detected when piglets suckled by PRCV inoculated sows were compared with those suckled by uninoculated sows. Such a difference was evident when the litters of sows successfully pre-immunized with TGEV were compared with those of unicoculated or PRCV-inoculated sows. The possibility of transplacental transmission of PRCV was investigated in two litters born to sows that had been inoculated with this virus in late pregnancy. All sixteen live-born piglets were seronegative for the virus at birth and PRCV was not isolated from tissues taken from two stillborn piglets.


title: Integrating the resources of Korean disaster management research via the Johari window

text: Abstract It is not widely known that quite a few researchers are faced with difficulties in using various resources of disaster management research in Korea. The article aims to assess how rigorously the Korean field of disaster management research resources has been managed or how it can be improved for the ultimate goal of disaster management. Descriptive content analysis has been used as the major methodology by referring to the Johari window. In doing so, electronic research resources have been systematically compared with integrated research resources via the perspective of Korean-speaking researchers and that of English-speaking researchers. The conclusion is that two researchers have to be integrated with all four research resources (open, blind, hidden, and unknown resources) by implementing assigned responsibilities as well as freely asking questions. Ultimately, this will be conducive to reducing down the impacts of disaster in Korea.


title: A virocentric perspective on the evolution of life

text: Viruses and/or virus-like selfish elements are associated with all cellular life forms and are the most abundant biological entities on Earth, with the number of virus particles in many environments exceeding the number of cells by one to two orders of magnitude. The genetic diversity of viruses is commensurately enormous and might substantially exceed the diversity of cellular organisms. Unlike cellular organisms with their uniform replication-expression scheme, viruses possess either RNA or DNA genomes and exploit all conceivable replication-expression strategies. Although viruses extensively exchange genes with their hosts, there exists a set of viral hallmark genes that are shared by extremely diverse groups of viruses to the exclusion of cellular life forms. Coevolution of viruses and host defense systems is a key aspect in the evolution of both viruses and cells, and viral genes are often recruited for cellular functions. Together with the fundamental inevitability of the emergence of genomic parasites in any evolving replicator system, these multiple lines of evidence reveal the central role of viruses in the entire evolution of life.


title: Autoimmune phenotypes in schizophrenia reveal novel treatment targets

text: Abstract Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuries-old roots is gaining traction in psychiatric research circles and may represent a new frontier for drug discovery in schizophrenia. At the forefront of this investigative effort is the immune system and its many components, pathways and phenotypes, which are now known to actively engage the brain. Studies in schizophrenia reveal an intricate association of environmentally-driven immune activation in concert with a disrupted genetic template. A consistent conduit through this gene-environmental milieu is the gut-brain axis, which when dysregulated can generate pathological autoimmunity. In this review, we present epidemiological and biochemical evidence in support of an autoimmune component in schizophrenia and depict gut processes and a dysbiotic microbiome as a source and perpetuator of autoimmune dysfunction in the brain. Within this framework, we review the role of infectious agents, inflammation, gut dysbioses and autoantibody propagation on CNS pathologies such as neurotransmitter receptor hypofunction and complement pathway-mediated synaptic pruning. We then review the new pharmacotherapeutic horizon and novel agents directed to impact these pathological conditions. At the core of this discourse is the understanding that schizophrenia is etiologically and pathophysiologically heterogeneous and thus its treatment requires individualized attention with disease state variants diagnosed with objective biomarkers.


title: Molecular characterization of a novel bovine group A rotavirus

text: Abstract In this study, by partial sequence analysis of the genome segments encoding VP5* and VP7, we characterized a novel bovine group A rotavirus, namely, Tak2, that was detected from adult cattle diarrhea in Tochigi Prefecture, Japan. The nucleotide (nt) and deduced amino acid (aa) sequences of the genome segments encoding VP5* and half of the amino terminal portion of VP7 of Tak2 revealed a low identity with those of group A rotaviruses carrying previously published P and G type specificities (VP5*: nt identity, 61.6%–67.6% and aa identity, 58.0%–71.4%; half of the amino terminal portion of VP7: nt identity, 57.8%–73.5% and aa identity, 61.2%–70.9%). Additionally, phylogenetic analysis of the nt sequences of the genome segments encoding VP5* and half of the amino terminal portion of VP7 revealed that Tak2 formed a branch separate from the established P and G types. These results suggested that Tak2 could possess novel P and G types yet not reported among group A rotaviruses.


title: Yeast as a promising heterologous host for steroid bioproduction

text: With the rapid development of synthetic biology and metabolic engineering technologies, yeast has been generally considered as promising hosts for the bioproduction of secondary metabolites. Sterols are essential components of cell membrane, and are the precursors for the biosynthesis of steroid hormones, signaling molecules, and defense molecules in the higher eukaryotes, which are of pharmaceutical and agricultural significance. In this mini-review, we summarize the recent engineering efforts of using yeast to synthesize various steroids, and discuss the structural diversity that the current steroid-producing yeast can achieve, the challenge and the potential of using yeast as the bioproduction platform of various steroids from higher eukaryotes.


title: Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles

text: [Image: see text] The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ignored to date. In this Perspective, we present a rationale for an urgent need to investigate this possible impact and therapeutic options for COVID-19 based on dietary and microbiome modifications. The mitigating role of nanotechnology with relation to the impact of SARS-CoV-2 virus is highlighted.


title: Three-dimensional cell culture models for investigating human viruses

text: Three-dimensional (3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover, these models bridge the gap between traditional two-dimensional (2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition, 3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.


title: A pilot survey of the U.S. medical waste industry to determine training needs for safely handling highly infectious waste

text: BACKGROUND: The recent Ebola outbreak led to the development of Ebola virus disease (EVD) best practices in clinical settings. However, after the care of EVD patients, proper medical waste management and disposal was identified as a crucial component to containing the virus. Category A waste—contaminated with EVD and other highly infectious pathogens—is strictly regulated by governmental agencies, and led to only several facilities willing to accept the waste. METHODS: A pilot survey was administered to determine if U.S. medical waste facilities are prepared to handle or transport category A waste, and to determine waste workers' current extent of training to handle highly infectious waste. RESULTS: Sixty-eight percent of survey respondents indicated they had not determined if their facility would accept category A waste. Of those that had acquired a special permit, 67% had yet to modify their permit since the EVD outbreak. This pilot survey underscores gaps in the medical waste industry to handle and respond to category A waste. Furthermore, this study affirms reports a limited number of processing facilities are capable or willing to accept category A waste. CONCLUSIONS: Developing the proper management of infectious disease materials is essential to close the gaps identified so that states and governmental entities can act accordingly based on the regulations and guidance developed, and to ensure public safety.


title: Development of fluorescent reverse transcription loop-mediated isothermal amplification (RT-LAMP) using quenching probes for the detection of the Middle East respiratory syndrome coronavirus

text: Abstract Clinical detection of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) in patients is achieved using genetic diagnostic methods, such as real-time RT-PCR assay. Previously, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of MERS-CoV [Virol J. 2014. 11:139]. Generally, amplification of RT-LAMP is monitored by the turbidity induced by precipitation of magnesium pyrophosphate with newly synthesized DNA. However, this mechanism cannot completely exclude the possibility of unexpected reactions. Therefore, in this study, fluorescent RT-LAMP assays using quenching probes (QProbes) were developed specifically to monitor only primer-derived signals. Two primer sets (targeting nucleocapsid and ORF1a sequences) were constructed to confirm MERS cases by RT-LAMP assay only. Our data indicate that both primer sets were capable of detecting MERS-CoV RNA to the same level as existing genetic diagnostic methods, and that both were highly specific with no cross-reactivity observed with other respiratory viruses. These primer sets were highly efficient in amplifying target sequences derived from different MERS-CoV strains, including camel MERS-CoV. In addition, the detection efficacy of QProbe RT-LAMP was comparable to that of real-time RT-PCR assay using clinical specimens from patients in Saudi Arabia. Altogether, these results indicate that QProbe RT-LAMP assays described here can be used as powerful diagnostic tools for rapid detection and surveillance of MERS-CoV infections.


CoViD-19 epidemic in“Establishments for dependent elderly people”


title: Clinical Characterization of Epilepsy of Unknown Cause in Cats

text: BACKGROUND: The diagnosis of feline epilepsy of unknown cause (EUC) requires a thorough diagnostic evaluation, otherwise the prevalence of EUC could be overestimated. HYPOTHESIS: Feline EUC is a clinically defined disease entity, which differs from feline hippocampal necrosis by the absence of magnetic resonance imaging (MRI) signal alteration of the hippocampus. The objectives of this study were (1) to evaluate the prevalence of EUC in a hospital population of cats by applying well‐defined inclusion criteria, and (2) to describe the clinical course of EUC. ANIMALS: Eighty‐one cats with recurrent seizures. METHODS: Retrospective study—medical records were reviewed for cats presented for evaluation of recurrent seizures (2005–2010). Inclusion criteria were a defined diagnosis based on laboratory data, and either MRI or histopathology. Final outcome was confirmed by telephone interview with the owner. Magnetic resonance images were reviewed to evaluate hippocampal morphology and signal alterations. RESULTS: Epilepsy of unknown cause was diagnosed in 22% of cats with epilepsy. Physical, neurologic, and laboratory examinations, and either 1.5 T MRI and cerebrospinal fluid analysis or postmortem examination failed to identify an underlying cause. Cats with EUC had a higher survival rate (P < .05) and seizure remission occurred frequently (44.4%). CONCLUSION AND CLINICAL IMPORTANCE: A detailed clinical evaluation and diagnostic imaging with MRI is recommended in any cat with recurrent seizures. The prognosis of cats with normal MRI findings and a clinical diagnosis of EUC are good. Standardized imaging guidelines should be established to assess the hippocampus in cats.


title: A spike-specific whole-porcine antibody isolated from a porcine B cell that neutralizes both genogroup 1 and 2 PEDV strains

text: Abstract Porcine epidemic diarrhea (PED), caused by an alpha coronavirus, is a highly contagious disease and causes high morbidity and mortality in suckling piglets. Isolating PEDV neutralizing antibodies from porcine B cells is critical to elucidate the development of PEDV neutralizing antibodies and the protective mechanism of PEDV infection. Here, we described the isolation of a PEDV-neutralizing antibody from the B cell of a vaccinated pig. The antibody, named PC10, was demonstrated to target the conformational epitope of PEDV spike protein, specifically bind to the infected cells of PEDV genogroup 1 and 2 strains, and potently neutralize PEDV infection. PC10 neutralized PEDV infection through interfering with the viral life stages after cellular attachment instead of blocking the attachment of PEDV to cells. These results suggest that PC10 could be a promising candidate for passive protection and inform PEDV vaccine design because of its specificity and substantial neutralization potency.


title: Recombinant protein‐based ELISA and immuno‐cytochemical assay for the diagnosis of SARS

text: A new Coronavirus (SARS‐CoV) is the aetiological agent of the severe acute respiratory syndrome (SARS). Because of the critical role played by serological assays for SARS diagnosis, an in‐house ELISA based on SARS‐CoV recombinant antigens was developed. The SARS‐CoV nucleocapsid protein (N), three N fragments (N1, N2, and N3) and the intraviral domain of the membrane protein (M2) were cloned and expressed in Escherichia coli as histidine‐tagged proteins. Six reference sera from SARS patients were used to detect virus‐specific IgG in an ELISA using each recombinant protein as coating antigen. High‐titre positive reactions were detected in all SARS positive sera. The specificity of the assay appears to be high as no positive reaction was detected in the sera of 20 healthy subjects and 73 patients with non‐SARS, low‐tract respiratory infections. Specific hyper‐immune sera to SARS‐CoV and the recombinant proteins, N, N1, N2, N3, and M2 were also generated in mice and rabbits. The specificity of these sera was confirmed by an immunocytochemical assay on biochips of SARS‐CoV infected and uninfected cells. J. Med. Virol. 76:137–142, 2005. © 2005 Wiley‐Liss, Inc.


title: Overview of Trends in the Application of Metagenomic Techniques in the Analysis of Human Enteric Viral Diversity in Africa’s Environmental Regimes

text: There has been an increase in the quest for metagenomics as an approach for the identification and study of the diversity of human viruses found in aquatic systems, both for their role as waterborne pathogens and as water quality indicators. In the last few years, environmental viral metagenomics has grown significantly and has enabled the identification, diversity and entire genome sequencing of viruses in environmental and clinical samples extensively. Prior to the arrival of metagenomics, traditional molecular procedures such as the polymerase chain reaction (PCR) and sequencing, were mostly used to identify and classify enteric viral species in different environmental milieu. After the advent of metagenomics, more detailed reports have emerged about the important waterborne viruses identified in wastewater treatment plant effluents and surface water. This paper provides a review of methods that have been used for the concentration, detection and identification of viral species from different environmental matrices. The review also takes into consideration where metagenomics has been explored in different African countries, as well as the limitations and challenges facing the approach. Procedures including sample processing, experimental design, sequencing technology, and bioinformatics analysis are discussed. The review concludes by summarising the current thinking and practices in the field and lays bare key issues that those venturing into this field need to consider and address.


title: Focus on Middle East respiratory syndrome coronavirus (MERS-CoV)

text: Abstract Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.


Risk Factors Associated with Disease Severity and Length of Hospital Stay in COVID-19 Patients


title: Synthesis and characterization of glycyrrhizin-decorated graphene oxide for hepatocyte-targeted delivery

text: Abstract The present work was to investigate graphene oxide (GO) decorated with glycyrrhizin (GL) which were conjugated via strong hydrogen-bonding interaction as a new hepatocyte-targeted delivery vehicle. The hydrogen-bonding interaction, simplified as a non-covalent type of functionalization, enables high drug loading and subsequent controlled release of the drug. An effective loading of GL on GO as high as 5.19mg/mg was obtained at initial GL concentration of 0.6mg/mL. The release of GL on GO showed strong pH dependence and the extent of release at pH 5.5 and 7.4 is 58.4% and 17.6% over 30h in vitro respectively. The results show that the GO-GL complex seems to be a very promising vehicle for loading of drugs under neutral conditions and releasing under acidic environment. Furthermore, GO-GL can be obtained under mild conditions without addition of any organic solvents and surfactants, which is very suitable for pharmaceutical applications as a promising hepatocyte-targeted delivery carrier.


title: Integrative omics of Lonicera japonica Thunb. Flower development unravels molecular changes regulating secondary metabolites

text: Abstract Lonicera japonica Thunb. is an important medicinal plant. The secondary metabolites in L. japonica are diverse and vary in levels during development, leading to the ambiguous evaluation for its medical value. In order to reveal the regulatory mechanism of secondary metabolites during the flowering stages, transcriptomic, proteomic, and metabolomic analyses were performed. The integration analysis of omic-data illustrated that the metabolic changes over the flower developmental stages were mainly involved in sugar metabolism, lipopolysaccharide biosynthesis, carbon conversion, and secondary metabolism. Further proteomic analysis revealed that uniquely identified proteins were mainly involved in glycolysis/phenylpropanoids and tricarboxylic acid cycle/terpenoid backbone pathways in early and late stages, respectively. Transketolase was commonly identified in the 5 developmental stages and 2-fold increase in gold flowering stage compared with juvenile bud stage. Simple phenylpropanoids/flavonoids and 1-deoxy-D-xylulose-5-phosphate were accumulated in early stages and upregulated in late stages, respectively. These results indicate that phenylpropanoids were accumulated attributing to the activated glycolysis process in the early stages, while the terpenoids biosynthetic pathways might be promoted by the transketolase-contained regulatory circuit in the late stages of L. japonica flower development. Biological Significance Lonicera japonica Thunb. is a native species in the East Asian and used in traditional Chinese medicine. In order to reveal the regulatory mechanism of secondary metabolites during the flowering stages, transcriptomic, proteomic, and metabolomic analyses were performed. The integration analysis of omic-data illustrated that the metabolic changes over the flower developmental stages were mainly involved in sugar metabolism, lipopolysaccharide biosynthesis, carbon conversion, and secondary metabolism. Our results indicate that phenylpropanoids were accumulated attributing to the activated glycolysis process in the early stages, while the terpenoids biosynthetic pathways might be promoted by the transketolase-contained regulatory circuit in the late stages of L. japonica flower development.


title: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond

text: The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, together with the current knowledge about their connection to disease.


title: Strategic decision making about travel during disease outbreaks: a game theoretical approach

text: Visitors can play an important role in the spread of infections. Here, we incorporate an epidemic model into a game theoretical framework to investigate the effects of travel strategies on infection control. Potential visitors must decide whether to travel to a destination that is at risk of infectious disease outbreaks. We compare the individually optimal (Nash equilibrium) strategy to the group optimal strategy that maximizes the overall population utility. Economic epidemiological models often find that individual and group optimal strategies are very different. By contrast, we find perfect agreement between individual and group optimal strategies across a wide parameter regime. For more limited regimes where disagreement does occur, the disagreement is (i) generally very extreme; (ii) highly sensitive to small changes in infection transmissibility and visitor costs/benefits; and (iii) can manifest either in a higher travel volume for individual optimal than group optimal strategies, or vice versa. The simulations show qualitative agreement with the 2003 severe acute respiratory syndrome (SARS) outbreak in Beijing, China. We conclude that a conflict between individual and group optimal visitor travel strategies during outbreaks may not generally be a problem, although extreme differences could emerge suddenly under certain changes in economic and epidemiological conditions.


title: Discordant Biological and Toxicological Species Responses to TLR3 Activation

text: Toll-like receptors (TLRs) are highly conserved type 1 membrane proteins that initiate a multiplicity of transient gene transcriptions, resulting in innate and adaptive immune responses. These essential immune responses are triggered by common TLR pattern recognition receptors of microbial products expressed through the cytoplasmic carboxy-terminal Toll/IL-1 domain. Toll/IL-1 adapter protein cascades are induced by an activated Toll/IL-1 to induce transient transcription responses. All TLRs, with the exception of TLR3, use an MyD88 adapter to Toll/IL-1 to initiate a proinflammatory cascade. TLR3 uses the toll receptor 3/4 induction factor adapter to initiate a different cytosolic adapter cascade with double-stranded RNA agonists. This non-MyD88 pathway induces both NF-κB and type 1 interferon responses. By using a TLR3-restricted double-stranded RNA agonist, rintatolimod, we demonstrate significant unexpected differences in toxic responses between rats and primates. The mechanism of this differential response is consistent with a relative down-regulation of the NF-κB inflammatory cytokine induction pathway in the cynomolgus monkey and humans, but not observed systemically in rat. Our findings suggest evaluation of TLR3 agonists in drug therapy.


title: Persistent Human Cosavirus Infection in Lung Transplant Recipient, Italy

text: Human cosavirus is a novel picornavirus recently identified in feces from children in southern Asia. We report infection with human cosavirus in a patient in the Mediterranean area. The patient was an adult double lung transplant recipient who had chronic diarrhea associated with persistent infection with human cosavirus.


title: Laboratory findings and a combined multifactorial approach to predict death in critically ill patients with COVID-19: a retrospective study

text: To describe the laboratory findings of cases of death with coronavirus disease 2019 (COVID-19) and to establish a scoring system for predicting death, we conducted this single-centre, retrospective, observational study including 336 adult patients (≥18 years old) with severe or critically ill COVID-19 admitted in two wards of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, who had definite outcomes (death or discharge) between 1 February 2020 and 13 March 2020. Single variable and multivariable logistic regression analyses were performed to identify mortality-related factors. We combined multiple factors to predict mortality, which was validated by receiver operating characteristic curves. As a result, in a total of 336 patients, 34 (10.1%) patients died during hospitalisation. Through multivariable logistic regression, we found that decreased lymphocyte ratio (Lymr, %) (odds ratio, OR 0.574, P < 0.001), elevated blood urea nitrogen (BUN) (OR 1.513, P = 0.009), and raised D-dimer (DD) (OR 1.334, P = 0.002) at admission were closely related to death. The combined prediction model was developed by these factors with a sensitivity of 100.0% and specificity of 97.2%. In conclusion, decreased Lymr, elevated BUN, and raised DD were found to be in association with death outcomes in critically ill patients with COVID-19. A scoring system was developed to predict the clinical outcome of these patients.


title: Detectable SARS‐CoV‐2 viral RNA in feces of three children during recovery period of COVID‐19 pneumonia

text: Coronavirus Disease 2019 (COVID‐19) is a newly emerging infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). After its first occurrence in Wuhan of China from December 2019, COVID‐19 rapidly spread around the world. According to the World Health Organization statement on 13 March 2020, there had been over 132 500 confirmed cases globally. Nevertheless, the case reports of children are rare, which results in the lack of evidence for preventing and controlling of children's infection. Here, we report three cases of SARS‐CoV‐2 infected children diagnosed from 3 February to 17 February 2020 in Tianjin, China. All of these three cases experienced mild illness and recovered soon after the treatment, with the nucleic acid of throat swab turning negative within 14, 11, and 7 days after diagnosis, respectively. However, after been discharged, all three cases were tested SARS‐CoV‐2 positive in the stool samples within 10 days, in spite of their remained negative nucleic acid in throat swab specimens. Therefore, it is necessary to be aware of the possibility of fecal‐oral transmission of SARS‐CoV‐2 infection, especially for children cases.


title: SARS-CoV-2 (COVID-19) Vaccine Development and Production: An Ethical Way Forward

text: The world awaits a SARS-CoV-2 virus (i.e., COVID-19 disease) vaccine to keep the populace healthy, fully reopen their economies, and return their social and healthcare systems to “normal.” Vaccine safety and efficacy requires meticulous testing and oversight; this paper describes how despite grandiose public statements, the current vaccine development, testing, and production methods may prove to be ethically dubious, medically dangerous, and socially volatile. The basic moral concern is the potential danger to the health of human test subjects and, eventually, many vaccine recipients. This is further complicated by economic and political pressures to reduce government oversight on rushed vaccine testing and production, nationalistic distribution goals, and failure to plan for the widespread immunization needed to produce global herd immunity. As this paper asserts, the public must be better informed to assess promises about the novel vaccines being produced and to tolerate delays and uncertainty.


title: Can orthodontic care be safely delivered during the COVID-19 pandemic? Recommendations from a literature review

text: Data sources Five electronic databases were searched: COVID-19 Open Research Dataset (CORD-19-2020); PubMed; MEDLINE; Scopus; and Google Scholar. Study selection Titles of articles and abstracts were identified during the electronic database searches and then screened for relevance. Publications up until the date of the literature search, 19th March 2020, were used. All articles with the appropriate topics pertaining to COVID-19, dentistry, orthodontics, and infection control were used irrespective of language. The author did not state whether they were selective about the study type or design of articles screened. References of these articles were also screened, via the 'snowballing technique', to obtain as much relevant literature as possible. Data extraction and synthesis Articles were reviewed by the cited author, and one research assistant. Data was extracted from each study by this author. The data obtained was combined and discussed narratively, in a qualitative manner. Due to the broad scope of studies included, it was not possible to conduct a meta-analysis. Results This literature review describes ways to reduce COVID-19 transmission in orthodontic practice. Overview of the literature discusses how the virus may be transmitted in the orthodontic setting: by human-human contact; saliva; aerosols; and use of orthodontic instruments. The literature review illustrates the need for optimum infection control and strict cleaning, detailing surface disinfection and sterilisation protocols. It highlights the need for optimal hand hygiene, use of high standard personal protective equipment, controlling aerosol use, appropriate ventilation, and treating emergency cases only. Conclusions While there are no known cases of COVID-19 cross-transmission within the dental setting currently reported, utmost vigilance is required by orthodontic professionals to reduce risk of transmission. The review reinforces crucial measures required to reduce infection, as outlined in the Results section above. While the virus is still emerging, knowledge is limited and as such it is difficult to provide robust and complete recommendations for best practice. Further studies to inform future practice are required.


title: May Polyphenols Have a Role Against Coronavirus Infection? An Overview of in vitro Evidence

text: The coronavirus infection is constantly diffusing worldwide and the incidence of death is dramatically increasing, representing one of the greatest disasters in human history. Nowadays, no effective therapeutic approaches have been licensed, despite the rising interest of the scientific research in this specific field, and the daily growing number of publications, while the need to find novel strategies is urgent. Evidence in the literature reported the antiviral activity of polyphenols, the largest class of bioactive compounds in nature. Interestingly, a limited number of studies investigated the efficacy of polyphenols from different raw materials, directly against coronaviruses. The present manuscript aimed to report this evidence and provide a viewpoint on the possibility to use it as a start point for the development of novel natural approaches against this viral infection, eventually designing further appropriate researches.


title: The Use of NanoTrap Particles as a Sample Enrichment Method to Enhance the Detection of Rift Valley Fever Virus

text: BACKGROUND: Rift Valley Fever Virus (RVFV) is a zoonotic virus that is not only an emerging pathogen but is also considered a biodefense pathogen due to the threat it may cause to public health and national security. The current state of diagnosis has led to misdiagnosis early on in infection. Here we describe the use of a novel sample preparation technology, NanoTrap particles, to enhance the detection of RVFV. Previous studies demonstrated that NanoTrap particles lead to both 100 percent capture of protein analytes as well as an improvement of more than 100-fold in sensitivity compared to existing methods. Here we extend these findings by demonstrating the capture and enrichment of viruses. RESULTS: Screening of NanoTrap particles indicated that one particle, NT53, was the most efficient at RVFV capture as demonstrated by both qRT-PCR and plaque assays. Importantly, NT53 capture of RVFV resulted in greater than 100-fold enrichment from low viral titers when other diagnostics assays may produce false negatives. NT53 was also capable of capturing and enhancing RVFV detection from serum samples. RVFV that was inactivated through either detergent or heat treatment was still found bound to NT53, indicating the ability to use NanoTrap particles for viral capture prior to transport to a BSL-2 environment. Furthermore, both NP-40-lysed virus and purified RVFV RNA were bound by NT53. Importantly, NT53 protected viral RNA from RNase A degradation, which was not observed with other commercially available beads. Incubation of RVFV samples with NT53 also resulted in increased viral stability as demonstrated through preservation of infectivity at elevated temperatures. Finally, NanoTrap particles were capable of capturing VEEV and HIV, demonstrating the broad applicability of NanoTrap particles for viral diagnostics. CONCLUSION: This study demonstrates NanoTrap particles are capable of capturing, enriching, and protecting RVFV virions. Furthermore, the use of NanoTrap particles can be extended to a variety of viruses, including VEEV and HIV.


title: Risk factors for neonatal calf diarrhoea and enteropathogen shedding in New Zealand dairy farms

text: Abstract To investigate the risk factors for neonatal calf diarrhoea, a cross-sectional study was conducted on 97 New Zealand dairy farms. Faecal specimens from 1283 calves were scored as liquid, semi-solid or solid, and analysed for bovine rotavirus (BRV) and coronavirus (BCV), enterotoxigenic K99+ Escherichia coli (K99), Salmonella spp. and Cryptosporidium parvum. Calf- and farm-level data were collected by means of a questionnaire and the odds of liquid faeces calculated using mixed effects logistic regression models. Among the infectious agents, only C. parvum (odds ratio [OR] = 2.6; 95% confidence interval [CI], 1.3–5.6; P = 0.02), BRV (OR = 2.7; 95% CI, 1.3–5.9; P = 0.01) and co-infection with more than one agent (compared with mono-infection: OR = 2.5; 95% CI, 1.3–4.8; P = 0.01) were associated with increased odds of liquid faeces in calves which were 9 to 21 days old. Housing of calves in open barns so exposing them to the weather was also associated with increased odds of liquid faeces compared with closed barns (OR = 2.1; 95% CI, 1.1–12.2; P = 0.03). Vaccinating cows against calf enteropathogens (OR = 0.2; 95% CI, 0.1–0.9; P = 0.03), administering waste milk (from mastitis and/or containing antibiotics; OR = 0.4; 95% CI, 0.1–0.8; P = 0.01), the sex of calves (females compared to males OR = 0.2, 95% CI, 0.07–0.7; P < 0.01), and the use of straw for bedding (OR = 0.2; 95% CI, 0.03–0.9; P = 0.03) decreased the odds of liquid faeces. Conversely, in calves that were 1 to 5 days old, only K99 was associated with liquid faeces (OR = 4.6; 95% CI, 1.2–16.1; P = 0.02). In this age group, the odds of liquid faeces were smaller on farms where females took care of the calves, compared with males (OR = 0.4; 95% CI, 0.01–0.9; P = 0.04).


The first case of acquired hemophilia A associated with SARS‐CoV‐2 infection


title: Impact of comorbidities on patients with COVID‐19: A large retrospective study in Zhejiang, China

text: BACKGROUND: Coronavirus disease 2019 (COVID‐19) has become a serious public health problem worldwide. Here, we stratified COVID‐19 patients based on their comorbidities to assess their risk of serious adverse outcomes. METHODS: We collected 856 hospitalized cases diagnosed with COVID‐19 from January 17 to February 7, 2020, in Zhejiang Province, and analyzed their comorbidities and composite endpoint (including admission to intensive care unit owing to disease progression, shock, invasive ventilation, and death) to determine the relationship between comorbidities and adverse outcomes. RESULTS: The median age of patients was 46 (36‐56) years; 439 (51.3%) were men, 242 (28.3%) had comorbidities, and 152 (17.8%) had two or more comorbidities. The most common comorbidity was hypertension (142 [16.6%]), followed by diabetes (64 [7.5%]). Of the 856 patients, there are 154 (18.0%) severe cases.32(3.7%) reached composite endpoints, of which 22 (9.1%) were from the comorbidity group and 10 (1.6%) from the non‐comorbidity group (p < 0.001). After adjusting for age and gender status, the risk of reaching the composite endpoint was higher in the group with comorbidity than in that without comorbidity (hazard ratio [HR] 3.04, 95% confidence interval [CI]: 1.40‐6.60). HR values for patients with one, two, and three or more comorbidities were 1.61 (95% CI: 0.44‐5.91), 3.44 (95% CI: 1.31‐9.08), and 6.90 (95% CI: 2.69‐17.69), respectively. CONCLUSIONS: COVID‐19 patients with comorbidities had worse clinical outcomes as compared to those without any comorbidity. The higher the number of comorbidities, the greater was the risk of serious adverse outcomes. This article is protected by copyright. All rights reserved.


title: Enhanced Surveillance for Detection and Management of Infectious Diseases: Regional Collaboration in the Middle East

text: Formed before international negotiations of the revised International Health Regulations (IHR), the Middle East Consortium for Infectious Disease Surveillance (MECIDS) is a regional collaboration aimed at facilitating implementation of the revised IHR and, more broadly, improving the detection and control of infectious disease outbreaks among neighboring countries in an area of continuous dispute. Initially focused on enhancing foodborne disease surveillance, MECIDS has expanded the scope of its work to also include avian and pandemic influenza and other emerging and re-emerging infectious diseases. Here, we describe the history and governance of MECIDS, highlighting key achievements over the consortium's seven-year history, and discuss the future of MECIDS.


Coronavirus Disease 2019: Epidemiological Factors During Aerosol-Generating Medical Procedures


title: Development of a novel real-time RT-PCR assay with LUX primer for the detection of swine transmissible gastroenteritis virus

text: Abstract Real-time RT-PCR assay, based on light upon extension (LUX) fluorogenic primer and LightCycle technology, was developed for rapid detection of transmissible gastroenteritis virus (TGEV). Viral RNA from different TGEV isolates and clinical specimens was detected. To evaluate the sensitivity of the assay, a gel-based RT-PCR method targeted at the same 101bp sequence was also developed. Serial 10-fold dilutions of TGEV RNA were detected by the two methods. Although the real time method used only 2μl RNA for each reaction, a 10-fold increase of sensitivity over that of the gel-based method, which used 10μl RNA was demonstrated. The study indicates that the LUX assay reported below is rapid, reliable and sensitive and it has the potential for use as an alternative molecular method for TGEV diagnosis.


Covid-19 mortality in Italian Doctors


Pandemic positives – a seroepidemiology consortium has formed and significant A(H1N1)pdm09 research continues to flow and demand journal pages


title: Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses

text: BACKGROUND: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL(pro)), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: Here, we profiled the substrate specificities of 3CL(pro) from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19×8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL(pro) prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL(pro) from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL(pro) prefers P4-Pro and SARS-CoV 3CL(pro) prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences ‘VARLQ↓SGF’ that can be cleaved efficiently by all 3CL(pro) with relative activity of 1.7 to 3.2, and ‘VPRLQ↓SGF’ that can be cleaved specifically by IBV 3CL(pro) with relative activity of 4.3. CONCLUSIONS/SIGNIFICANCE: The comprehensive substrate specificities of 3CL(pro) from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.


title: International Health Regulations—What Gets Measured Gets Done

text: The global spread of severe acute respiratory syndrome highlighted the need to detect and control disease outbreaks at their source, as envisioned by the 2005 revised International Health Regulations (IHR). June 2012 marked the initial deadline by which all 194 World Health Organization (WHO) member states agreed to have IHR core capacities fully implemented for limiting the spread of public health emergencies of international concern. Many countries fell short of these implementation goals and requested a 2-year extension. The degree to which achieving IHR compliance will result in global health security is not clear, but what is clear is that progress against the threat of epidemic disease requires a focused approach that can be monitored and measured efficiently. We developed concrete goals and metrics for 4 of the 8 core capacities with other US government partners in consultation with WHO and national collaborators worldwide. The intent is to offer an example of an approach to implementing and monitoring IHR for consideration or adaptation by countries that complements other frameworks and goals of IHR. Without concrete metrics, IHR may waste its considerable promise as an instrument for global health security against public health emergencies.


title: Forty Years of Basic and Translational Heparanase Research

text: This review summarizes key developments in the heparanase field obtained 20 years prior to cloning of the HPSE gene and nearly 20 years after its cloning. Of the numerous publications and review articles focusing on heparanase, we have selected those that best reflect the progression in the field as well as those we regard important accomplishments with preference to studies performed by scientists and groups that contributed to this book. Apart from a general ‘introduction’ and ‘concluding remarks’, the abstracts of these studies are presented essentially as published along the years. We apologize for not being objective and not being able to include some of the most relevant abstracts and references, due to space limitation. Heparanase research can be divided into two eras. The first, initiated around 1975, dealt with identifying the enzyme, establishing the relevant assay systems and investigating its biological activities and significance in cancer and other pathologies. Studies performed during the first area are briefly introduced in a layman style followed by the relevant abstracts presented chronologically, essentially as appears in PubMed. The second era started in 1999 when the heparanase gene was independently cloned by 4 research groups [1–4]. As expected, cloning of the heparanase gene boosted heparanase research by virtue of the readily available recombinant enzyme, molecular probes, and anti-heparanase antibodies. Studies performed during the second area are briefly introduced followed by selected abstracts of key findings, arranged according to specific topics.


title: Epitope Mapping: The First Step in Developing Epitope-Based Vaccines

text: Antibodies are an effective line of defense in preventing infectious diseases. Highly potent neutralizing antibodies can intercept a virus before it attaches to its target cell and, thus, inactivate it. This ability is based on the antibodies’ specific recognition of epitopes, the sites of the antigen to which antibodies bind. Thus, understanding the antibody/epitope interaction provides a basis for the rational design of preventive vaccines. It is assumed that immunization with the precise epitope, corresponding to an effective neutralizing antibody, would elicit the generation of similarly potent antibodies in the vaccinee. Such a vaccine would be a ‘B-cell epitope-based vaccine’, the implementation of which requires the ability to backtrack from a desired antibody to its corresponding epitope. In this article we discuss a range of methods that enable epitope discovery based on a specific antibody. Such a reversed immunological approach is the first step in the rational design of an epitope-based vaccine. Undoubtedly, the gold standard for epitope definition is x-ray analyses of crystals of antigen: antibody complexes. This method provides atomic resolution of the epitope; however, it is not readily applicable to many antigens and antibodies, and requires a very high degree of sophistication and expertise. Most other methods rely on the ability to monitor the binding of the antibody to antigen fragments or mutated variations. In mutagenesis of the antigen, loss of binding due to point modification of an amino acid residue is often considered an indication of an epitope component. In addition, computational combinatorial methods for epitope mapping are also useful. These methods rely on the ability of the antibody of interest to affinity isolate specific short peptides from combinatorial phage display peptide libraries. The peptides are then regarded as leads for the definition of the epitope corresponding to the antibody used to screen the peptide library. For epitope mapping, computational algorithms have been developed, such as Mapitope, which has recently been found to be effective in mapping conformational discontinuous epitopes. The pros and cons of various approaches towards epitope mapping are also discussed.


title: From Individuals to Groups and Back: The Evolutionary Implications of Group Phenotypic Composition

text: There is increasing interest in understanding the processes that maintain phenotypic variation in groups, populations, or communities. Recent studies have investigated how the phenotypic composition of groups or aggregations (e.g., its average phenotype or phenotypic variance) affects ecological and social processes, and how multi-level selection can drive phenotypic covariance among interacting individuals. However, we argue that these questions are rarely studied together. We present a unified framework to address this gap, and discuss how group phenotypic composition (GPC) can impact on processes ranging from individual fitness to population demography. By emphasising the breadth of topics affected, we hope to motivate more integrated empirical studies of the ecological and evolutionary implications of GPC.


title: Vasculitis in children

text: Primary systemic vasculitides of the young are relatively rare diseases, but can have a significant morbidity and mortality. The purpose of this review is to provide an overview of the paediatric vasculitides. Vasculitides that predominantly affect children will be considered in more detail than vasculitic diseases that although are seen in children affect adults more commonly, such as the ANCA associated vasculitides. New classification criteria for childhood vasculitis have recently been proposed and are currently undergoing validation. Epidemiological clues continue to implicate infectious triggers in Kawasaki Disease and Henoch Schönlein purpura. Several genetic polymorphisms have now been described in the vasculitides that may be relevant in terms of disease predisposition or development of disease complications. Treatment regimens continue to improve, with the use of different immunosuppressive medications and newer therapeutic approaches such as biologic agents. However new challenges are looming in regards to the role of inflammation in endothelial health and the long term cardiovascular morbidity for children with primary systemic vasculitis. International multicenter collaboration is of utmost importance in order for us to further advance our understanding and improve the treatment and outcome of systemic vasculitis in the young.


title: Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management

text: When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.


Phosphodiesterase Type 5 Inhibitors and COVID-19: Are They Useful In Disease Management?


title: Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease

text: One hypothesis for the etiology of central nervous system (CNS) autoimmune disease is that infection by a virus sharing antigenic epitopes with CNS antigens (molecular mimicry) elicits a virus-specific immune response that also recognizes self-epitopes. To address this hypothesis, transgenic mice were generated that express the nucleoprotein or glycoprotein of lymphocytic choriomeningitis virus (LCMV) as self in oligodendrocytes. Intraperitoneal infection with LCMV strain Armstrong led to infection of tissues in the periphery but not the CNS, and the virus was cleared within 7–14 d. After clearance, a chronic inflammation of the CNS resulted, accompanied by upregulation of CNS expression of MHC class I and II molecules. A second LCMV infection led to enhanced CNS pathology, characterized by loss of myelin and clinical motor dysfunction. Disease enhancement also occurred after a second infection with unrelated viruses that cross-activated LCMV-specific memory T cells. These findings indicate that chronic CNS autoimmune disease may be induced by infection with a virus sharing epitopes with a protein expressed in oligodendrocytes and this disease may be enhanced by a second infection with the same or an unrelated virus. These results may explain the association of several different viruses with some human autoimmune diseases.


title: Adverse skin reactions among healthcare workers during the coronavirus disease 2019 outbreak: a survey in Wuhan and its surrounding regions

text: During the outbreak of coronavirus disease 2019 (COVID-19), healthcare workers (HCWs) caring for COVID-19 patient have to wear personal protective equipment (PPE) and are therefore susceptible to PPE-related adverse skin reactions. However, little is known about the prevalence and characteristics of these adverse skin reactions and their associated risk factors.


title: A Long-Term Study of a Lipid-Buprenorphine Implant in Rats

text: Animal models to study opiates are of growing interest. We have examined the short-term safety of buprenorphine implants in Fischer F344/NTac rats treated with excess doses of a cholesterol-triglyceride suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of analgesia for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Here we report the results of a long-term follow-up study of female rats injected with 0.65 and 1.3 mg/kg. The 14-month evaluation showed no abnormal findings that could be attributed to the drug or lipid suspension. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery in laboratory animals and suggest that this model may be used to study long-term effects of opiate therapy.


title: Therapeutic Targeting of RIG-I and MDA5 Might Not Lead to the Same Rome

text: RIG-I and MDA5 receptors are key sensors of pathogen-associated molecular pattern (PAMP)-containing viral RNA and transduce downstream signals to activate an antiviral and immunomodulatory response. Fifteen years of research have put them at the center of an ongoing hunt for novel pharmacological pan-antivirals, vaccine adjuvants, and antitumor strategies. Current knowledge testifies to the redundant, but also distinct, functions mediated by RIG-I and MDA5, opening opportunities for the use of specific and potent nucleic acid agonists. We critically discuss the evidence and remaining knowledge gaps that have an impact on the choice and design of optimal RNA ligands to achieve an appropriate immunostimulatory response, with limited adverse effects, for prophylactic and therapeutic interventions against viruses and cancer in humans.


title: Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

text: Abstract The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies. Reported here is the X-ray crystal structure of the RBD in complex with the Fab of a neutralizing mouse monoclonal antibody, F26G19, elicited by immunization with chemically inactivated SARS-CoV. The RBD–F26G19 Fab complex represents the first example of the structural characterization of an antibody elicited by an immune response to SARS-CoV or any fragment of it. The structure reveals that the RBD surface recognized by F26G19 overlaps significantly with the surface recognized by ACE2 and, as such, suggests that F26G19 likely neutralizes SARS-CoV by blocking the virus–host cell interaction.


title: Use of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in COVID-19

text: BACKGROUND: As the pandemic of coronavirus disease 2019 (COVID-19) continues, prognostic markers are now being identified. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily accessible values that have been known to correlate with inflammation and prognosis in several conditions. We used the available data to identify the association of NLR and PLR with the severity of COVID-19. METHODS: A literature search using EMBASE, MEDLINE, and Google Scholar for studies reporting the use of NLR and PLR in COVID-19 published until April 28, 2020, was performed. Random effects meta-analysis was done to estimate standard mean difference (SMD) of NLR and PLR values with 95% confidence interval (CI) between severe and non-severe COVID-19 cases. RESULTS: A total of 20 studies with 3,508 patients were included. Nineteen studies reported NLR values, while five studies reported PLR values between severe and non-severe COVID-19 patients. Higher levels of NLR (SMD: 2.80, 95% CI: 2.12 - 3.48, P < 0.00001) and PLR (SMD: 1.82, 95% CI: 1.03 - 2.61, P < 0.00001)) were seen in patients with severe disease compared to non-severe disease. CONCLUSIONS: NLR and PLR can be used as independent prognostic markers of disease severity in COVID-19.


title: Prevalence and molecular characterization of WU/KI polyomaviruses isolated from pediatric patients with respiratory disease in Thailand

text: Abstract WU and KI polyomaviruses represent novel viruses discovered in respiratory secretions from human patients with acute respiratory tract infection. However, the association between WU/KI polyomaviruses and human disease has remained unclear. In this study, the prevalence of these two novel viruses and occurrence of co-infection with other respiratory viruses were determined in Thai pediatric patients with respiratory disease. Previously described PCR assays were applied to detect WU/KI polyomaviruses as well as other respiratory viruses in 302 nasopharyngeal suction specimens collected from February 2006 through February 2007. The results revealed the anneal prevalence of WU and KI polyomaviruses in the Thai population was 6.29% and 1.99%, respectively. The frequency of co-detection of WU and KI polyomaviruses with other respiratory viral pathogens was 42.11% and 33.33%, respectively. Moreover, each of the two complete genome sequences of WU (CU_295 and CU_302) and KI (CU_255 and CU_258) polyomaviruses were genetically and phylogenetically characterized. Sequence analysis showed that they contained features common to those found in previous studies. However, there were several nucleotide variations within the non-coding regulatory regions and various non-synonymous mutations within the coding regions which may influence virulence and pathogenesis of these viruses. Nevertheless, it is still possible that these viruses are not the causative agents of clinical respiratory disease. Therefore, judging the association of WU/KI polyomavirus infections with a particular disease will be challenging and require more comprehensive case control investigations.


title: Clostridial Abomasitis and Enteritis in Ruminants

text: Clostridial abomasitis and enteritis are important alimentary diseases observed in all domestic ruminant species. These diseases most commonly result from overgrowth of Clostridium perfringens types A, B, C, D, and E with the associated release of bacterial exotoxins that result in necrosis of the abomasal or intestinal mucosa. Clostridium difficile may also be associated with enteritis in calves but is much less common than disease caused by C perfringens. This article reviews the causes, pathophysiology, clinical signs, diagnosis, treatment, and prevention of clostridial gastrointestinal diseases in ruminants. Particular emphasis is given to describing the various forms of disease and treatment of individual cases.


title: Natural Foci Diseases as a Stable Biological Threat

text: The key aspects of the natural foci of especially dangerous diseases as a type of biological threats are presented. Approaches to epidemiological surveillance and control to the spread of the agents of especially dangerous diseases on endemic areas are described for zoonosis that has a medical value. The knowledge of specific design of tools for the implementation of epidemiological surveillance, monitoring and evaluation of natural foci diseases in developing countries is low; accordingly, little is known on the ecology and transmission dynamics for the agents of especially dangerous diseases. Important is to know the effectiveness of serological monitoring of the indigenous population to determine the activity of natural foci of hemorrhagic fever with renal syndrome, tick-borne encephalitis, tularemia, Q-fever, Lyme disease and West Nile disease. The main species of reservoirs and vectors for these agents have been determined in different regions of Ukraine. New tick-borne agents that were unknown for certain regions have been detected. These data indicate the spreading of different pathogens in combination with natural foci.


title: Phosphorylation of p38 MAPK and its downstream targets in SARS coronavirus-infected cells

text: Abstract Severe acute respiratory syndrome (SARS) has become a global public health emergency. Understanding the molecular mechanisms of SARS-induced cytopathic effects (CPEs) is a rational approach for the prevention of SARS, and an understanding of the cellular stress responses induced by viral infection is important for understanding the CPEs. Polyclonal antibodies, which recognized nucleocapsid (N) and membrane (M) proteins, detected viral N and M proteins in virus-infected Vero E6 cells at least 6 and 12h post-infection (h.p.i.), respectively. Furthermore, detection of DNA ladder and cleaved caspase-3 in the virus-infected cells at 24h.p.i. indicated that SARS-CoV infection induced apoptotic cell death. Phosphorylation of p38 MAPK was significantly up-regulated at 18h.p.i. in SARS-CoV-infected cells. The downstream targets of p38 MAPK, MAPKAPK-2, HSP-27, CREB, and eIF4E were phosphorylated in virus-infected cells. The p38 MAPK inhibitor, SB203580, inhibited effectively phosphorylation of HSP-27, CREB, and eIF4E in SARS-CoV-infected cells. However, viral protein synthesis was not affected by treatment of SB203580.


title: miR-146a-5p promotes replication of infectious bronchitis virus by targeting IRAK2 and TNFRSF18

text: Abstract Avian infectious bronchitis virus (IBV) is a coronavirus which infects chickens (Gallus gallus) of all ages and causes significant economic losses to the poultry industry worldwide. The present study aims to analyze the miRNAs related to pathogenicity of nephropathogenic IBVs. It was found that four miRNAs (miR-1454, miR-3538, miR-146a-5p and miR-215-5p) were related to the infection of virulent nephropathogenic IBV with transcript per million (TPM) > 500 and more than a 2-fold alteration. In vitro study results showed that the alterations of these four miRNAs were consistent with in vivo data. In vitro, we found that high levels of miR-146a-5p could enhance the replication of IBV at the early stage of infection, and its down regulated level could slow down the replication of IBV. Finally, high levels of exogenous miR-146a-5p in HD11 cells led to down regulation of IL-1 receptor associated kinase-2 (IRAK2) and Tumor necrosis factor receptor superfamily member 18 (TNFRSF18) genes. Luciferase reporter assays revealed that miR-146a-5p could bind to the 3′-UTRs of IRAK2 and TNFRSF18. This is the first study demonstrating that IBV induced miR-146a-5p is related to virus pathogenesis by down regulating IRAK2 and TNFRSF18, which may serve as a therapeutic strategy for the prevention of IBV infections.


ISNI 2006 Abstracts


title: Porcine epidemic diarrhea virus introduction into the United States: Root cause investigation

text: Abstract Porcine epidemic diarrhea (PED) was identified in the United States in the spring of 2013, and professionals from many parts of the U.S. swine industry responded rapidly to understand and control the newly emerging disease. In less than two months, the disease had spread to more than 200 herds in thirteen states. Experts from the US Department of Agriculture (USDA) engaged in laboratory diagnostics, analytic support, epidemiology expertise, and data management to facilitate the effort. By 2014, a great deal had been learned about the disease; however, the question of how it entered the United States remained unanswered. In 2014, USDA formed an investigative group to address the question and leverage current knowledge with resources and partnerships not readily available to non-federal investigators. The group formed collaborations with other government and non-government organizations and individuals, and followed many avenues of inquiry; ultimately arriving at a small number of scenarios that describe possible mechanisms for PED introduction. For a scenario to be plausible, it had to explain: contamination of a person or product in the source country, its transit and entry to the United States, rapid dispersal across a wide geographic area, and exposure/infection of pigs. It had to be compatible with findings of swine herd investigations and research studies. Potential products had to have been imported legally during the time prior to the beginning of the epidemic, or delivered to the United States through prohibited channels. Follow-up studies were initiated to gather more evidence for the most plausible scenarios. Of the scenarios, flexible intermediate bulk containers (“feed totes”) used to transport bulk feed serving as fomites for movement of PED virus provided the simplest explanation for the accumulated findings of the investigation.


title: One Health: Zoonoses in the Exotic Animal Practice

text: Zoonoses make up approximately ¾ of today’s emerging infectious diseases; many of these zoonoses come from exotic pets and wildlife. Recent outbreaks in humans associated with nondomestic animals include Sudden Acute Respiratory Syndrome, Ebola virus, salmonellosis, and monkeypox. Expanding human populations, increased exotic pet ownership and changes in climate may contribute to increased incidence of zoonoses. Education and preventive medicine practices can be applied by veterinarians and other health professionals to reduce the risk of contracting a zoonotic disease. The health of humans, animals, and the environment must be treated as a whole to prevent the transmission of zoonoses.


title: Three tachykinins in mammalian brain

text: Two polypeptide precursors to the neuropeptide substance P have recently been identified. One of them (β-preprotachykinin) contains amino acid sequences corresponding not only to substance P but also to substance K, a novel, related peptide. A third substance P-like peptide, neuromedin K, has recently been isolated from spinal cord. The existence in vertebrates of three members of the tachykinin family of peptides may account for pharmacological observations suggesting the presence of more than one type of substance P receptor in the nervous system.


title: The Mental Health Burden of the COVID-19 Pandemic on Physical Therapists

text: We evaluated the mental health burden of coronavirus disease (COVID-19) on physical therapists, including their stress and anxiety levels, who were at risk of developing psychological distress and other mental health symptoms. A questionnaire survey was conducted with physical therapists of three university hospitals in South Korea on 10 April 2020. The questionnaires evaluated the presence of anxiety and depression in the respondents. Among the 65 physical therapists who completed our survey, 21 (32.3%) and 12 (18.5%) physical therapists reported having symptoms of anxiety and depression, respectively. If a physical therapist was living with a ≤6-year-old infant or child, the possibility of the presence of anxiety was significantly higher. The risk of depression among those who were in their 30 s and 50 s was significantly higher than among those in their 20 s. Thus, physical therapists living with a ≤6-year-old infant or child and those in their 30 s and 50 s need special attention.


title: Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets

text: Abstract Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Passive immunotherapy via either convalescent plasma or mAbs has proven to be effective for other infectious agents. Following infection with MERS-CoV, common marmosets were treated with high titer hyperimmune plasma or the mAb m336, at 6 and 48 h post inoculation. Both treatments reduced signs of clinical disease, but reduction in viral loads in the respiratory tract were only found in the hyperimmune plasma group. A decrease in gross pathology was found only in the mAb-treated group, but no histological differences were observed between treated and control animals. While both hyperimmune plasma and the m336 treatments reduced the severity of disease in the common marmoset, neither treatment resulted in full protection against disease.


title: CD147 promotes IKK/IκB/NF-κB pathway to resist TNF-induced apoptosis in rheumatoid arthritis synovial fibroblasts

text: ABSTRACT: TNF is highly expressed in synovial tissue of rheumatoid arthritis (RA) patients, where it induces proinflammatory cytokine secretion. However, in other cases, TNF will cause cell death. Considering the abnormal proliferation and activation of rheumatoid arthritis synovioblasts, the proper rate of synovioblast apoptosis could possibly relieve arthritis. However, the mechanism mediating TNF-induced synovioblast survival versus cell death in RA is not fully understood. Our objective was to study the role of CD147 in TNF downstream pathway preference in RA synovioblasts. We found that overexpressing TNF in synovial tissue did not increase the apoptotic level and, in vitro, TNF-induced mild synovioblast apoptosis and promoted IL-6 secretion. CD147, which was highly expressed in rheumatoid arthritis synovial fibroblasts (RASFs), increased the resistance of synovioblasts to apoptosis under TNF stimulation. Downregulating CD147 both increased the apoptotic rate and inhibited IκB kinase (IKK)/IκB/NF-κB pathway-dependent proinflammatory cytokine secretion. Further, we determined that it was the extracellular portion of CD147 and not the intracellular portion that was responsible for synovioblast apoptosis resistance. CD147 monoclonal antibody inhibited TNF-induced proinflammatory cytokine production but had no effect on apoptotic rates. Thus, our study indicates that CD147 is resistant to TNF-induced apoptosis by promoting IKK/IκB/NF-κB pathway, and the extracellular portion of CD147 is the functional region. KEY MESSAGES: CD147 inhibits TNF-stimulated RASF apoptosis. CD147 knockdown decreases IKK expression and inhibits NF-κB-related cytokine secretion. CD147’s extracellular portion is responsible for apoptosis resistance. CD147 antibody inhibits TNF-related cytokine secretion without additional apoptosis.


title: Haemorrhagic conjunctivitis with pseudomembranous related to SARS-CoV-2

text: Abstract Purpose To describe the multiplicity of ocular manifestations of COVID-19 patients, we report a case of pseudomembranous and hemorrhagic conjunctivitis related with SARS-CoV-2 pneumonia in a patient of intensive care unit (ICU). Observations A 63-year-old male was admitted in intensive care unit (ICU), seven days after the beginning of an influenza-like symptoms, to manage an acute respiratory syndrome related with SARS-CoV-2. Chest scan showed interstitial pneumonia with “crazy paving” patterns. At day 19, ocular examination at the patient's bed described petechias and tarsal hemorrhages, mucous filaments and tarsal pseudomembranous. Conjunctival scrapings and swabs did not identify any bacteria or virus. To our knowledge, we described the first case of pseudomembranous conjunctivitis in a COVID-19 patient. Conclusion and importance Considering that SARS-CoV-2 is present in tears and conjunctival secretions, external ocular infections could be factors of infectious spreading. Physicians should be aware of late (>2 weeks) ocular complications in COVID-19 patients to prevent sequelae.