title: Yupingfeng polysaccharides enhances growth performance in Qingyuan partridge chicken by up‐regulating the mRNA expression of SGLT1, GLUT2 and GLUT5

text: The ban on the use of antibiotic in feed encouraged nutritionists to using alternatives to maintain growth performance and intestinal function of broilers. This study was conducted to evaluate the effects of Yupingfeng polysaccharides (YP) supplementation on growth performance and expression of SGLT1, GLUT2 and GLUT5 in Qingyuan partridge chicken. Experiment 1: a total of 540 chickens were randomly allocated to five groups with six replication. Dietary treatments were: (1) CON (control group), basal diet; (2) T1, CON + 0.5 g kg(−1) YP; (3) T2, CON + 1 g kg(−1) YP; (4) T3, CON + 2 g kg(−1) YP; (5) T4, CON + 4 g kg(−1) YP. Experiment 2, a total of 162 were randomly allocated to three groups with three replication. Dietary treatments were: (1) CON, basal diet; (2) T1, CON + 0.5 g kg(−1) YP; (3) T2, CON + 1 g kg(−1) YP. From days 1 to 14 and overall, chicken fed T1 diet had higher ADG. On day 42, there was increased villus height of jejunum in T1 group. On days 14 and 28, there was decreased villus height of duodenum and jejunum in T2 group. In duodenum, the expression of SGLT1 (days 21, 35 and 42), GLUT2 (days 7, 14, 21, 28, 35 and 42) and GLUT5 (days 7, 14, 21 and 28) was increased with YP supplementation. In jejunum, the expression of SGLT1 (days 7, 14, 21, 28 and 35), GLUT2 (days 14, 21, 28, 35 and 42) and GLUT5 (days 7, 14, 21, 28, 35 and 42) was increased with YP supplementation. In ileum, the expression of SGLT1 (days 7, 21, 35 and 42), GLUT2 (days 7, 14, 21 and 42) and GLUT5 (days 7, 14, 21, 28, 35 and 42) was increased with YP supplementation. Dietary YP supplementation improves growth performance and expression of SGLT1, GLUT2 and GLUT5 in intestine.


title: OAS single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine

text: Interferon (IFN)-induced antiviral genes are crucial players in innate antiviral defense and potential determinants of immune response heterogeneity. We selected 114 candidate SNPs from 12 antiviral genes using an LD tagSNP selection approach and genotyped them in a cohort of 738 schoolchildren immunized with two doses of rubella vaccine. Associations between SNPs/haplotypes and rubella virus-specific immune measures were assessed using linear regression methodologies. We identified 23 significant associations (p<0.05) between polymorphisms within the 2′-5′-oligoadenylate synthetase (OAS) gene cluster, and rubella virus-specific IL-2, IL-10, IL-6 secretion and antibody levels. The minor allele variants of three OAS1 SNPs (rs3741981/Ser162Gly, rs1051042/Thr361Arg, rs2660), located in a linkage disequilibrium block of functional importance, were significantly associated with an increase in rubella virus-specific IL-2/Th1 response (p≤0.024). Seven OAS1 and OAS3 promoter/regulatory SNPs were similarly associated with IL-2 secretion. Importantly, two SNPs (rs3741981 and rs10774670), independently cross-regulated rubella virus-specific IL-10 secretion levels (p≤0.031). Furthermore, both global tests and individual haplotype analyses revealed significant associations between OAS1 haplotypes and rubella virus-specific cytokine secretion. Our results suggest that innate immunity and OAS genetic variations are likely involved in modulating the magnitude and quality of the adaptive immune responses to live attenuated rubella vaccine.


title: Panique et pandémie: revue de la littérature sur les liens entre le trouble panique et l'épidémie à SARS-CoV-2

text: Résumé L’état de panique associé à la pandémie liée au SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) incite à s’interroger sur les troubles anxieux que cette situation pourrait générer ou aggraver. Si la littérature a déjà fourni des projections généralistes en la matière, les données concrètes concernent à ce stage davantage le trouble de stress post-traumatique et le trouble obsessionnel compulsif, tandis que quelques évaluations s’intéressent au cadre nosographie du trouble anxieux généralisé. Le trouble panique ne se voit que peu ou pas cité et l’évocation de la « panique », au sens social, la supplante largement. Bien que d’une légitimité clinique encore débattue, le trouble panique qualifié de « respiratoire » pourrait se voir augmenter en nombre et/ou être intensifié chez les patients qui en présentent déjà. D’éventuelles situations co-morbides entre un tel trouble et la COVID-19 (coronavirus disease 2019) doivent inciter à certaines précautions en matière de prescriptions médicamenteuses, notamment en lien avec les traitements, ou situations, sources d’hypokaliémie : (i) le salbutamol, source potentielle de surconsommation, notamment chez les patients anxieux, (ii) l’infection par le SARS-CoV-2 et plus encore en cas de diarrhées et/ou vomissements. L’hypokaliémie est associée à un risque accru de torsade de pointe, il convient donc également d’être prudent en matière de prescription de psychotropes à risque : comme avec le citalopram et l’escitalopram, des antidépresseurs indiqués dans le trouble panique, ou encore l’hydroxyzine, à visée anxiolytique. Ces données sont de nature à resituer l’importance de la prise en considération du trouble panique dans le cadre de la pandémie en cours. Abstract Although the ‘panic’ word has been abundantly linked to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific literature very few studies have considered whether the current epidemic could predispose to the onset or the aggravation of panic attacks or panic disorder. Indeed, most studies thus far have focused on the risk of increase and aggravation of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic disorder, especially the subtype with prominent respiratory symptoms, which is characterized by a fear response conditioning to interoceptive sensations (e.g., respiratory), and hypervigilance to these interoceptive signals, could be expected in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea, are among the most commonly associated with the SARS-CoV-2 (59-82 % and 31-55 %, respectively), and respiratory symptoms are associated with a poor illness prognosis. Hence given that some etiological and maintenance factors associated with panic disorder – i.e., fear conditioning to abnormal breathing patterns attributable or not to the COVID-19 (coronavirus disease 2019), as well as hypervigilance towards breathing abnormalities – are supposedly more prevalent, one could expect an increased risk of panic disorder onset or aggravation following the COVID-19 epidemic in people who were affected by the virus, but also those who were not. In people with the comorbidity (i.e., panic disorder or panic attacks and the COVID-19), it is particularly important to be aware of the risk of hypokalemia in specific at-risk situations or prescriptions. For instance, in the case of salbutamol prescription, which might be overly used in patients with anxiety disorders and COVID-19, or in patients presenting with diarrhea and vomiting. Hypokalemia is associated with an increased risk of torsade de pointe, thus caution is required when prescribing specific psychotropic drugs, such as the antidepressants citalopram and escitalopram, which are first-line treatments for panic disorder, but also hydroxyzine, aiming at anxiety reduction. The results reviewed here highlight the importance of considering and further investigating the impact of the current pandemic on the diagnosis and treatment of panic disorder (alone or comorbid with the COVID-19).


title: Alongshan virus in Russia

text: In recent decades, many new flavivirus-like viruses have been discovered predominantly in different invertebrates and, as was recently shown, some of them may cause disease in humans. The Jingmen tick virus (JMTV) group holds a special place among flavivirus-like viruses because, in contrast to the “classic” flaviviruses and other flavivirus-like viruses, they have a segmented ssRNA(+) genome. Two segments of the JMTV genome have homology with regions of the flavivirus genome encoding polymerase and helicase-protease proteins. JMTVs have several open reading frames (ORF) in segments encoding glycoprotein and capsid protein and these ORF are specific only to them. JMTVs greatly differ in virion size. We isolated three strains of Alongshan virus (ALSV), which is a representative of the JMTV group, from adult Ixodes persulcatus ticks collected in two geographically-separated Russian regions into the tick cell line IRE/CTVM19. One of the strains persisted in the IRE/CTVM19 cells without cytopathic effect for three years. Most virions purified from tick cells were spherical with a diameter of approximately 40.5 nm. In addition, we found smaller particles of approximately 13.1 nm in diameter with either electron-translucent or electron-dense cores. We obtained full genome sequences of all four segments of two of the isolated ALSV strains, and partial sequences of one segment from the third strain. Phylogenetic analysis on genome segment 2 of the JMTV group clustered our novel strains with other ALSV strains. We found evidence for the existence of a novel upstream ORF in the glycoprotein-coding segment of Alongshan and Jingmen tick viruses.


title: Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus

text: Nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a major pathological determinant in the host that may cause host cell apoptosis, upregulate the proinflammatory cytokine production, and block innate immune responses. Therefore, N gene has long been thought an ideal target for the design of small interference RNA (siRNA). siRNA is a class of small non-coding RNAs with a size of 21-25nt that functions post-transcriptionally to block targeted gene expression. In this study, we analyzed the N gene coding sequences derived from 16 different isolates, and found that nucleotide deletions and substitutions are mainly located at the first 440nt sequence. Combining previous reports and the above sequence information, we create three novel siRNAs that specifically target the conserved and unexploited regions in the N gene. We show that these siRNAs could effectively and specifically block the isolated N gene expression in mammal cells. Furthermore, we provide evidence to show that N gene can effectively up-regulate M gene mediated interferon β (IFNβ) production, while blocking N gene expression by specific siRNA significantly reduces IFNβ gene expression. Our data indicate that the inhibitory effect of siRNA on the isolated N gene expression might be influenced by the sequence context around the targeted sites.


title: Subversion of host stress granules by coronaviruses: Potential roles of π‐rich disordered domains of viral nucleocapsids

text: Coronavirus nucleocapsids (CoV N's) play both structural and non‐structural roles in viral life‐cycle. Here, we propose a mechanism for host stress granule (SG) subversion by CoV N proteins. We posit that disordered domains of CoV N's can engage in π‐π intermolecular fuzzy interactions with host SG proteins and are crucial to the viral hijacking of host machineries. This article is protected by copyright. All rights reserved.


title: Challenges in Preparing and managing the critical care services for a large urban area during COVID-19 outbreak: Perspective from Delhi

text: Abstract The Coronavirus disease-2019 (Covid-19) pandemic has put the healthcare services all over the world into a challenging situation. The contagious nature of the disease and the respiratory failure necessitating ventilatory care of these patients has put extra burden on the intensive care unit (ICU) services. India has been no exception and by March 2020, the number of covid-19 patients started increasing in India. This article describes the measures taken and challenges faced in creating the ICU beds to cater to the anticipated load of patients in the state of Delhi, India. The main challenges faced among others were, estimating the number of ICU beds to be created; deciding the dedicated Covid hospitals; procurement of ventilators, personal protection equipment and other related material; mobilizing the human resource and their training; and providing isolated in-house accommodation to the staff on duty. The authors acknowledge and agree that the methodology proposed in this article is, but one way of dealing with this difficulty scenario, and that there could be other, perhaps better methods of dealing with such a problem.


title: Chapter 11 Kawasaki Disease

text: Publisher Summary Kawasaki disease (KD) is an acute febrile systemic vasculitis usually occurring in children younger than five years, and rarely reported in neonates and adults. This chapter discusses the epidemiology, etiology, pathogenesis, clinical manifestations, and treatments of KD. The etiology still remains unknown, although epidemiological and clinical features strongly suggest an infectious cause. Immunological abnormalities in the acute phase of the disease reflect activation of immune system and marked production of cytokines by activated cells. KD has some similarities to toxin-mediated diseases, both from a clinical and an immunological point of view. The role of one or more superantigens competent of stimulating large numbers of T cells produced by certain strains of Staphylococcus or Streptococcus is discussed in the chapter, in the context of the etiology of KD. Atypical cases are those with fever, acute surgical symptoms, or neurological manifestations as presenting signs. Medical history, physical examination, and laboratory tests including elevated white-blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and low hemoglobin, sodium and albumin levels may help to rule out illnesses mimicking KD. Oral or pulsed corticosteroids in children refractory to intravenous immunoglobulins (IVIG) are an alternative and safe treatment.


title: 5.20 Antiviral Drugs for Acute Infections

text: Abstract After the great success of the research and development of antiviral drugs to treat chronic infections like HIV and hepatitis C, attention is turning to treatment of acute viral infections. In this article, we illustrate the potential for developing antiviral drugs to treat such infections. Four distinct clinical problems caused by four different viruses allow exploration of the problems associated with each disease. Targets for each virus are evaluated, and the progress made to date in identifying suitable clinical candidates is discussed. Finally, we consider the problem of emerging acute virus infections and improving rapidity of responses to them.


title: Adaptive mechanism between dynamical synchronization and epidemic behavior on complex networks

text: Many realistic epidemic networks display statistically synchronous behavior which we will refer to as epidemic synchronization. However, to the best of our knowledge, there has been no theoretical study of epidemic synchronization. In fact, in many cases, synchronization and epidemic behavior can arise simultaneously and interplay adaptively. In this paper, we first construct mathematical models of epidemic synchronization, based on traditional dynamical models on complex networks, by applying the adaptive mechanisms observed in real networks. Then, we study the relationship between the epidemic rate and synchronization stability of these models and, in particular, obtain the conditions of local and global stability for epidemic synchronization. Finally, we perform numerical analysis to verify our theoretical results. This work is the first to draw a theoretical bridge between epidemic transmission and synchronization dynamics and will be beneficial to the study of control and the analysis of the epidemics on complex networks.


title: The Safety of an Adjuvanted Autologous Cancer Vaccine Platform in Canine Cancer Patients

text: Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each canine patient were combined with Advax™, a novel non-inflammatory immunomodulator and vaccine adjuvant and were tested for safety in a diverse range of patient presentations alone or in combination with other treatments. Canine patients had their tumor biopsied, debulked or resected and the tumor antigens were processed into an autologous vaccine formulated with Advax™ adjuvant with or without rhizavidin as an additional immune stimulant. Patients treated early in the trial received two intramuscular (IM) doses, 2 weeks apart. As the study progressed and no issues of safety were observed, the protocol was changed to weekly vaccinations for 4 weeks followed by monthly booster shots. Over the 150 I.M injections delivered to date, the vaccine was found to be very safe and no significant adverse reactions were observed. These results justify ongoing development and future controlled studies of this autologous vaccine approach.


title: COVID-19: Development of a robust mathematical model and simulation package with consideration for ageing population and time delay for control action and resusceptibility

text: The current global health emergency triggered by the pandemic COVID-19 is one of the greatest challenges mankind face in this generation. Computational simulations have played an important role to predict the development of the current pandemic. Such simulations enable early indications on the future projections of the pandemic and is useful to estimate the efficiency of control action in the battle against the SARS-CoV-2 virus. The SEIR model is a well-known method used in computational simulations of infectious viral diseases and it has been widely used to model other epidemics such as Ebola, SARS, MERS, and influenza A. This paper presents a modified SEIRS model with additional exit conditions in the form of death rates and resusceptibility, where we can tune the exit conditions in the model to extend prediction on the current projections of the pandemic into three possible outcomes; death, recovery, and recovery with a possibility of resusceptibility. The model also considers specific information such as ageing factor of the population, time delay on the development of the pandemic due to control action measures, as well as resusceptibility with temporal immune response. Owing to huge variations in clinical symptoms exhibited by COVID-19, the proposed model aims to reflect better on the current scenario and case data reported, such that the spread of the disease and the efficiency of the control action taken can be better understood. The model is verified using two case studies for verification and prediction studies, based on the real-world data in South Korea and Northern Ireland, respectively.


title: Diversity of upper respiratory tract infections and prevalence of Streptococcus pneumoniae colonization among patients with fever and flu-like symptoms

text: BACKGROUND: Many upper respiratory pathogens cause similar symptoms. In China, routine molecular tests for upper respiratory pathogens are not widely performed and antibiotics abuse in treating upper respiratory tract infections (URTIs) is a major public health concern. METHODS: We performed qualitative real-time PCR tests to detect common upper respiratory tract pathogens including 9 viruses and 3 bacteria in 1221 nasopharyngeal swabs from patients with fever and influenza-like symptoms in a Chinese city. A quantitative real-time PCR was also performed to measure the bacterial density of the colonizing Streptococcus pneumoniae in these samples. RESULTS: We found very diverse pathogens including 81.7% viruses, 11.6% bacteria and 6.7% mixed viruses and bacteria. S. pneumoniae colonization was found in 8.0% of the cases but most of them had low bacterial density (Mean = 3.9 log cfu/ml). We also discovered an increase of S. pneumoniae colonization frequency (but not the density) in patients with detectable upper respiratory tract pathogens, in a pathogen variety-dependent manner. CONCLUSIONS: Our study provided strong evidence against empiric antibiotic use for treating URTIs, and highlighted a strong need for improving the diagnostic capacity for URTIs by using more molecular testing in China.


title: Characteristics of Parker's rat coronavirus (PRC) replicated in L-2 cells

text: Parker's rat coronavirus (PRC) is a naturally-occurring viral infection of the laboratory rat. On the first passage, ATCC strain 8190 of PRC replicated in L-2 cells. Using the tenth passage of PRC in L-2 cells, the characteristics of the virus were compared with previous studies of sialodacryoadenitis virus (SDAV) replicated in L-2 cells. Based on light and immunofluorescence microscopic examination of control and inoculated cell cultures, PRC-associated CPE was frequently confined primarily to individual cells, and there were relatively few syncytial giant cells. Maximum titers were recovered at 36h post inoculation (pi). Infectious virus was demonstrated at pH values ranging from 6.0 to 9.0 and a pH of 7.5 was determined to produce the highest titers of PRC. The optimum temperature for viral replication was 33°C. Up to 15 passages of PRC in L-929 cells failed to produce detectable virus. However, after adaptation in L-2 cells (20th passage), PRC replicated to high titers in L-929 cells. Previously, in vitro studies of rat coronaviruses have been hampered by the lack of an identified continuous cell line to replicate these viruses in the laboratory. L-2 cells represent a readily-available continuous cell line that can support the replication of relatively high titers of PRC.


Hyperinflammatory shock related to COVID‐19 in a patient presenting with multisystem inflammatory syndrome in children: First case from Iran


title: Virus‐derived small RNAs: molecular footprints of host–pathogen interactions

text: Viruses are obligatory intracellular parasites that require the host machinery to replicate. During their replication cycle, viral RNA intermediates can be recognized and degraded by different antiviral mechanisms that include RNA decay, RNA interference, and RNase L pathways. As a consequence of viral RNA degradation, infected cells can accumulate virus‐derived small RNAs at high levels compared to cellular molecules. These small RNAs are imprinted with molecular characteristics that reflect their origin. First, small RNAs can be used to reconstruct viral sequences and identify the virus from which they originated. Second, other molecular features of small RNAs such as size, polarity, and base preferences depend on the type of viral substrate and host mechanism of degradation. Thus, the pattern of small RNAs generated in infected cells can be used as a molecular footprint to identify and characterize viruses independent on sequence homology searches against known references. Hence, sequencing of small RNAs obtained from infected cells enables virus discovery and characterization using both sequence‐dependent strategies and novel pattern‐based approaches. Recent studies are helping unlock the full application of small RNA sequencing for virus discovery and characterization. WIREs RNA 2016, 7:824–837. doi: 10.1002/wrna.1361 1.. RNA Processing > Processing of Small RNAs; 2.. RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms; 3.. RNA Methods > RNA Analyses In Vitro and In Silico.


title: Using Ontario's "Telehealth" health telephone helpline as an early-warning system: a study protocol

text: BACKGROUND: The science of syndromic surveillance is still very much in its infancy. While a number of syndromic surveillance systems are being evaluated in the US, very few have had success thus far in predicting an infectious disease event. Furthermore, to date, the majority of syndromic surveillance systems have been based primarily in emergency department settings, with varying levels of enhancement from other data sources. While research has been done on the value of telephone helplines on health care use and patient satisfaction, very few projects have looked at using a telephone helpline as a source of data for syndromic surveillance, and none have been attempted in Canada. The notable exception to this statement has been in the UK where research using the national NHS Direct system as a syndromic surveillance tool has been conducted. METHODS/DESIGN: The purpose of our proposed study is to evaluate the effectiveness of Ontario's telephone nursing helpline system as a real-time syndromic surveillance system, and how its implementation, if successful, would have an impact on outbreak event detection in Ontario. Using data collected retrospectively, all "reasons for call" and assigned algorithms will be linked to a syndrome category. Using different analytic methods, normal thresholds for the different syndromes will be ascertained. This will allow for the evaluation of the system's sensitivity, specificity and positive predictive value. The next step will include the prospective monitoring of syndromic activity, both temporally and spatially. DISCUSSION: As this is a study protocol, there are currently no results to report. However, this study has been granted ethical approval, and is now being implemented. It is our hope that this syndromic surveillance system will display high sensitivity and specificity in detecting true outbreaks within Ontario, before they are detected by conventional surveillance systems. Future results will be published in peer-reviewed journals so as to contribute to the growing body of evidence on syndromic surveillance, while also providing an non US-centric perspective.


title: Presenting characteristics, comorbidities, and outcomes of patients coinfected with COVID‐19 and Mycoplasma pneumoniae in the USA

text: Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS‐CoV‐2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID‐19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%‐50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C‐reactive protein, lactate dehydrogenase, interleukin‐6, serum ferritin, and D‐dimer in all six (100%) patients. The chest X‐ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course.


title: Surveillance for respiratory syncytial virus and parainfluenza virus among patients hospitalized with pneumonia in Sarawak, Malaysia

text: BACKGROUND: Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are frequent causes of pneumonia and death among children at Sibu and Kapit Hospitals in Sarawak, Malaysia. OBJECTIVES: To determine the prevalence and risk factors for RSV subtypes A and B and PIV types 1–4 among patients hospitalized with pneumonia. METHODS: In a cross-sectional, pilot study nasopharyngeal swabs were studied with real-time reverse transcription polymerase chain reaction assays. Concurrently, we helped Sibu and Kapit Hospitals adapt their first molecular diagnostics for RSV and PIV. RESULTS: Of 129 specimens collected (June to July 2017), 39 tested positive for RSV-A (30.2%), two were positive for RSV B (1.6%), one was positive for PIV-3 (0.8%) and one was positive for PIV-4 (0.8%). No samples were positive for PIV-1 or PIV-2. Of the 39 RSV-A positive specimens, 46.2% were collected from children under one year of age and only 5.1% were from patients over the age of 18. A multivariable analysis found the odds of children <1 year of age testing positive for RSV-A were 32.7 (95% CI: 3.9, 276.2) times larger than >18 years of age, and the odds of patients hospitalized at Kapit Hospital testing positive for RSV-A were 3.2 (95% CI: 1.3, 7.8) times larger than patients hospitalized at Sibu Hospital. CONCLUSION: This study found an unusually high prevalence of RSV-A among pneumonia patients admitted to the two hospitals. Subsequently, Sibu Hospital adapted the molecular assays with the goal of providing more directed care for such pneumonia patients.


title: Effect of Health Education on Healthcare-Seeking Behavior of Migrant Workers in China

text: Health education is considered to be an effective way to improve the healthcare-seeking behavior of migrant workers. This study examined the impact of health education on healthcare-seeking behavior of migrant workers in China and explored the differences in different health education methods. This paper used the 2017 China Migrants Dynamic Survey (CMDS) to analyze the relationship between health education and healthcare-seeking behavior. Our results indicated that health education could significantly improve the healthcare-seeking behavior of migrant workers, but there was still ample space for improvement. From the perspective of different health education methods, lectures, public consultation, and online education were positively correlated to healthcare-seeking behavior, while publicity materials and bulletin boards were not. Although the effects of publicity materials and bulletins were limited, these two health education methods were still the most widely used. Our results emphasized the necessity of increasing investment in lectures, public consultation, online education, and other similar health education methods. This change in health education methods can play an effective role in the spread of health education to improve the healthcare-seeking behavior of migrant workers.


title: Selection for 3′-End Triplets for Polymerase Chain Reaction Primers

text: Primer extension by thermostable DNA polymerase in PCR starts from the 3′-end of a primer. If the PCR starting process fails, the entire PCR fails. Primer sequences at the 3′-end often interfere with success in PCR experiments. Over 2000 primer sequences from successful PCR experiments used with varieties of templates and conditions were analyzed for finding frequencies of the 3′-end triplets. This chapter discusses a trend in 3′-end triplet frequencies in primers used in successful PCR experiments and proposes requirements for the 3′-end of a primer. Finally, a method break to select primers with the best 3′-end triplets is introduced based on the 3′-end analysis result.


title: Genotyping of infectious bronchitis viruses from broiler farms in Iraq during 2014-2015

text: Infectious bronchitis virus (IBV) is one of the most critical pathogens in the poultry industry, causing serious economic losses in all countries including Iraq. IBV has many genotypes that do not confer any cross-protection. This virus has been genotyped by sequence analysis of the S1 glycoprotein gene. A total of 100 tracheal and kidney tissue specimens from different commercial broiler flocks in the middle and south of Iraq were collected from September 2013 to September 2014. Thirty-two IBV-positive samples were selected from among the total and were further characterized by nested PCR. Phylogenetic analysis revealed that isolates belong to four groups (group I, variant 2 [IS/1494-like]; group II, 793/B-like; group III, QX-like; group IV, DY12-2-like). Sequence analysis revealed nucleotide sequence identities within groups I, II, and III of 99.68 %-100 %, 99.36 %-100 %, and 96.42 %-100 %, respectively. Group I (variant 2) was the dominant IBV genotype. One Chinese-like recombinant virus (DY12-2-like) that had not been reported in the Middle East was detected. In addition, the presence of QX on broiler chicken farms in the area studied was confirmed. This is the first comprehensive study on the genotyping of IBV in Iraq with useful information regarding the molecular epidemiology of IBV. The phylogenetic relationship of the strains with respect to different time sequences and geographical regions displayed complexity and diversity. Further studies are needed and should include the isolation and full-length molecular characterization of IBV in this region.


RELACIÓN ENTRE OBESIDAD, DIABETES E INGRESO EN UCI EN PACIENTES COVID-19


title: Mouse hepatitis virus

text: Abstract Inoculation of mice with most neurotropic strains of the coronavirus mouse hepatitis virus results in an immune response-mediated demyelinating disease that serves as an excellent animal model for the human disease multiple sclerosis. Recent work has shown that either virus-specific CD4+ or CD8+ T cells are able to mediate demyelination and also that the antibody response is crucial for clearing infectious virus. Another exciting advance is the development of recombinant coronaviruses, which, for the first time, will allow genetic manipulation of the entire viral genome.


title: Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada

text: BACKGROUND: In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission. METHODS: A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission. RESULTS: 45 laboratory-confirmed intubated SARS patients were identified. Of the 697 HCWs involved in their care, 624 (90%) participated in the study. SARS-CoV was transmitted to 26 HCWs from 7 patients; 21 HCWs were infected by 3 patients. In multivariate GEE logistic regression models, presence in the room during fiberoptic intubation (OR = 2.79, p = .004) or ECG (OR = 3.52, p = .002), unprotected eye contact with secretions (OR = 7.34, p = .001), patient APACHE II score ≥20 (OR = 17.05, p = .009) and patient Pa0(2)/Fi0(2) ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients. CONCLUSION: Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients.


title: Experimental study of gaseous and particulate contaminants distribution in an aircraft cabin

text: Abstract The environment of the aircraft cabin greatly influences the comfort and health of passengers and crew members. Contaminant transport has a strong effect on disease spreading in the cabin environment. To obtain the complex cabin contaminant distribution fields accurately and completely, which is also essential to provide solid and precise data for computational fluid dynamics (CFD) model validation, this paper aimed to investigate and improve the method for simultaneous particle and gaseous contaminant fields measurement. The experiment was conducted in a functional MD-82 aircraft. Sulfur hexafluoride (SF6) was used as tracer gas, and Di-Ethyl-Hexyl-Sebacat (DEHS) was used as particulate contaminant. The whole measurement was completed in a part of the economy-class cabin without heating manikins or occupied with heating manikins. The experimental method, in terms of pollutant source setting, sampling points and schedule, was investigated. Statistical analysis showed that appropriately modified sampling grid was able to provide reasonable data. A small difference in the source locations can lead to a significant difference in cabin contaminant fields. And the relationship between gaseous and particulate pollutant transport was also discussed through tracking behavior analysis.


title: Cómo la pandemia por COVID-19 ha cambiado la forma de atender a las pacientes en una unidad de uroginecología

text: RESUMEN La actual pandemia ocasionada por el SARS-coronavirus tipo 2 ha generado, en pocas semanas, cambios importantes en el funcionamiento del sistema sanitario y la forma en cómo se realiza la atención a las pacientes. La patología Uroginecológica afecta a la calidad de vida, pero sin riesgo vital en la mayoría de casos, por lo que suele ser demorable. Además afecta a un alto porcentaje de mujeres >65 años (población de riesgo ante la infección por Covid-19). En este manuscrito se resume la evidencia que existe sobre la efectividad de la telemedicina aplicada en las disfunciones de suelo pélvico, así como recomendaciones de las sociedades científicas Uroginecológicas durante el estado de alarma. Describimos el abordaje de las disfunciones de suelo pélvico durante la pandemia por Covid-19 y una propuesta de cómo organizar las agendas para el diagnóstico (visitas y pruebas diagnósticas) y tratamiento (conservador, farmacológico y la cirugía) en el periodo interpandemia y futuro. SUMMARY The current SARS-coronavirus type 2 pandemic caused, in few weeks, important changes in the health system organization and in the way we attend the patients. Urogynaecological diseases affect quality of life, but without life risk in most cases, so it is possible to delay. Moreover, urogynaecological diseases affect mostly women over 65 years old (a high risk population for contracting COVID-19). In this manuscript we summarise the current evidence about telemedicine efectivity to manage to pelvic floor dysfunctions and, in addition, the recommendations of Urogynaecological scientific societies during state of alarm. We describe the management of the different pelvic floor dysfunctions during COVID-19 pandemic and a proposal to organize the urogynaecological services to diagnose (visits and diagnostic investigations) and to treat (conservative, pharmacological or surgery) in the interpandemic period and in the future.


title: Are countries’ self-reported assessments of their capacity for infectious disease control reliable? Associations among countries’ self-reported international health regulation 2005 capacity assessments and infectious disease control outcomes

text: BACKGROUND: This study aimed to evaluate associations among countries’ self-reported International Health Regulation 2005 (IHR 2005) capacity assessments and infectious disease control outcomes. METHODS: Countries’ self-reported assessments implemented by percentages as IHR Monitoring Tools (IHRMT) in 2016 and 2017 were used to represent national capacity regarding infectious disease control. WHO Disease Outbreak News and matched diseases reports on ProMED-mail were collected in 2016 to represent disease control outcomes of countries. Disease control outcomes were divided in good, normal and bad groups based on the development of outbreaks listed in the reports. The Human Development Index (HDI), density of physicians and nurses, health expenditure, number of arrivals of international tourists were also collected for control. Chi-square test and logistic regression were applied for analysis. RESULTS: A total of 907 cases occurred in 92 countries. For all diseases, cases occurring in high international travel volume countries presented twice the risk of having a bad disease control outcomes than cases occurring in low international travel volume countries (OR = 2.19 for IHR 2016, OR = 2.97 for IHR 2017). Cases occurring in low IHR average score countries had significant higher risk (OR = 7.83 for IHR 2016 and OR = 2.23 for IHR 2017) of having a bad disease control outcomes than countries with high IHR average scores. For only human diseases, cases occurring in high international travel volume countries presented twice the risk of having a bad disease control outcomes than cases occurring in low international travel volume countries for IHR 2017 (OR = 2.79). Cases occurring in low IHR average score countries had significant higher risk (OR = 11.16 for IHR 2016 and OR = 3.45 for IHR 2017) of having a bad disease control outcomes than countries with high IHR average scores. The HDI, health workforce density and total health expenditure were all positively associated with disease control outcomes. CONCLUSIONS: Countries’ self-reported infectious disease control capacities positively correlated with their disease control outcomes. While the self-reported IHR scores were accountable to some degree, this approach was useful for understanding global capacity in infectious disease control and in allocating resources for future preparedness.


An address to the European immunology community concerning the Coronavirus pandemic


The possibility of COVID‐19 transmission from eye to nose


title: COVID-19 Outbreak Perception in Italian Dentists

text: The aim of this study is an evaluation of the Italian dentists’ knowledge regarding COVID-19 and their perception of the risks associated with COVID-19, their attitude in resuming their activities, and how they judge the institutional intervention on a health and economic basis. Methods: This research evaluated Italian dentists from 11 to 18 April 2020, using a questionnaire submitted via Google Forms (Alphabet, Mountain View, CA, USA). It consisted of different investigations about sociodemographic aspects, profession-related characteristics, knowledge about COVID-19 infection transmission modalities, symptoms, and attitude in treating potentially infected patients. Statistical analysis was performed using the Pearson chi(2) test and Student t-test. The α-level was fixed at p = 0.05. All data were analyzed with STATA 16 (StataCorp LP, College Station, TX, USA). Results: 1500 dentists (664 men and 836 women) completed the questionnaire. The majority of respondents declared having been trained in infection prevention procedures (64.3%) but not specifically to prevent the spread of COVID-19 (48.7%). A total of 57.2% declared that they were not trained sufficiently to restart working after lockdown, with a significantly higher prevalence (Pearson chi(2) test, p < 0.001) among women (62.3%) than men (50.9%). Conclusion: Italian dentists were informed correctly on the mode of transmission but partially missed COVID-19 symptoms. Dentists considered the virus infection highly dangerous, and they were not confident in being able to work safely. The lack of precise operating guidelines creates uncertainties on infection control measures and appropriate personal protective equipment (PPE) use. The participants revealed apprehension for their health and the current and future economic situation of their practices.


title: A decade of the sharing economy: Concepts, users, business and governance perspectives

text: Sharing economy platforms have been transforming production and consumption systems in cities around the world. While the sharing economy may contribute to addressing sustainability issues, its actual economic, social and environmental impacts remain poorly understood. Advancing more sustainably promising forms of sharing and leveraging its benefits, while circumventing its pitfalls, is becoming increasingly important in the era of Covid-19 and climate crisis, economic downturn and uncertainty, and loss of social connectedness, particularly in anonymous urban environments. The ways to capitalise on strengths of the sharing economy are still poorly understood. In particular, the roles and perspectives of users, businesses and municipal governments in institutionalising the sharing economy in various geographical contexts are essential to examine. This volume seeks to advance the research field by focusing on four research areas: 1) understanding the sharing economy conceptually; 2) user perspectives on the sharing economy; 3) business perspective on the sharing economy; and 4) urban governance perspective on the sharing economy. The twenty articles in this volume discuss sustainability implications of the sharing economy from different perspectives, in various geographical contexts, and drawing on a range of disciplines. The volume makes a significant contribution by bringing in empirical findings from emerging and developing economies, including Brazil, China, Indonesia, Poland, the Philippines, South Korea, Thailand and Vietnam, thereby supplementing more frequently discussed perspectives from high-income countries. The volume also outlines the course for future research.


title: Imiquimod suppresses respiratory syncytial virus (RSV) replication via PKA pathway and reduces RSV induced-inflammation and viral load in mice lungs

text: Abstract Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children, as well as an important cause of morbidity and mortality in elderly and immunocompromised individuals. However, there is no safe and efficacious RSV vaccine or antiviral treatment. Toll Like Receptors (TLR) are important molecular mediators linking innate and adaptive immunity, and their stimulation by cognate agonists has been explored as antiviral agents. Imiquimod is known as a TLR7 agonist, but additionally acts as an antagonist for adenosine receptors. In this study, we demonstrate that imiquimod, but not resiquimod, has direct anti-RSV activity via PKA pathway in HEp-2 and A549 cells, independently of an innate response. Imiquimod restricts RSV infection after viral entry into the host cell, interfering with viral RNA and protein synthesis. Probably as a consequence of these anti-RSV properties, imiquimod displays cytokine modulating activity in RSV infected epithelial cells. Moreover, in a murine model of RSV infection, imiquimod treatment improves the course of acute disease, evidenced by decreased weight loss, reduced RSV lung titers, and attenuated airway inflammation. Consequently, imiquimod represents a promising therapeutic alternative against RSV infection and may inform the development of novel therapeutic targets to control RSV pathogenesis.


title: A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern

text: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016-2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible and actionable the information produced by these studies was. To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE and grey literature review, we identified studies that forecasted, predicted or simulated ecological or epidemiological phenomenon related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility and clarity by independent reviewers. 2034 studies were identified, of which n = 73 met eligibility criteria. Spatial spread, R0 (basic reproductive number) and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barré Syndrome burden (4%), sexual transmission risk (4%) and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%) and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions and 54% provided sufficient methodological detail allowing complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median 119 days sooner than journal publication dates, they were used in only 30% of studies. Many ZIKV predictions were published during the 2016-2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response, it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics and pandemics. Researchers published many studies which sought to predict and forecast important features of Zika virus (ZIKV) infections and their spread during the 2016-2017 ZIKV pandemic. We conducted a comprehensive review of such ZIKV prediction studies and evaluated their aims, the data sources they used, which methods were used, how timely they were published, and whether they provided sufficient information to be used or reproduced by others. Of the 73 studies evaluated, we found that the accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. We identified that the release of study findings before formal journal publication (‘pre-prints’) increased the timeliness of Zika prediction studies, but note they were infrequently used during this public health emergency. Addressing these areas can improve our understanding of Zika and other outbreaks and ensure that forecasts can inform preparedness and response to future outbreaks, epidemics and pandemics.


title: Deciphering of the Human Interferon-Regulated Proteome by Mass Spectrometry-Based Quantitative Analysis Reveals Extent and Dynamics of Protein Induction and Repression

text: Interferons (IFNs) are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative, and immune stimulatory capacities, recombinant IFNs are frequently prescribed as drugs to treat different diseases. IFNs act by changing the gene expression profile of cells. Due to characteristics such as rapid gene induction and signaling, IFNs also represent prototypical model systems for various aspects of biomedical research (e.g., signal transduction). In regard to the signaling and activated promoters, IFNs can be subdivided into two groups. Here, alterations of the cellular proteome of human cells treated with IFNα and IFNγ were elucidated in a time-resolved manner by quantitative proteome analysis. The majority of protein regulations were strongly IFN type and time dependent. In addition to the expected upregulation of IFN-responsive proteins, an astonishing number of proteins became profoundly repressed especially by IFNγ. Thus, our comprehensive analysis revealed important insights into the human IFN-regulated proteome and its dynamics of protein induction and repression. Interestingly, the new class of IFN-repressed genes comprises known host factors for highly relevant pathogens such as HIV, dengue virus, and hepatitis C virus.


title: Epidemiology of the first 100 cases of COVID-19 in Taiwan and its implications on outbreak control

text: Abstract Purpose To describe the epidemiology and outcome of the first 100 COVID-19 cases in Taiwan. Methods We included the first 100 patients with laboratory-confirmed SARS-CoV-2 infection in Taiwan. Demographic, clinical, epidemiological and laboratory data were extracted from outbreak investigation reports and medical records. Results Illness onset of the 100 patients was during January 11 to March 16, 2020. Twenty-nine (29%) had at least one underlying condition and ten (10%) were asymptomatic. Seventy-one were imported, including four clusters. Twenty-nine were locally-acquired, including four clusters. The median days from onset to report was longer in locally-acquired cases (10 vs 3 days). Three patients died (case fatality rate 3%) and all of them had underlying conditions. As of May 13, 2020, 93 had been discharged in stable condition; the median hospital stay was 30 days (range, 10‒79 days). Conclusion The first 100 cases of COVID-19 in Taiwan showed the persistent threat of imported cases from different countries. Even though sporadic locally-acquired disease has been identified, through contact investigation, isolation, quarantine and implementation of social distancing measures, the epidemic is contained to a manageable level with minimal local transmission.


title: This time is indeed different: A study on global market reactions to public health crisis()

text: This paper studies the differences in stock market reactions to the same kind of disease-related news by analyzing abnormal returns of global stock markets during Public Health Risk Emergency of International Concern (PHEIC) announcements. Drawing the data from 26 stock market indices over the period from 22 April 2008 to 12 March 2020, we compare stock market reactions to all six PHEIC announcements made by the World Health Organization since 2009. Although the PHEIC announcements can be categorized as the same type of event, we found no consistent patterns in market reactions. The markets did not show significant reactions in a 30-day event window, which suggests a relatively low economic impact of the diseases on a global scale during this time, except for Covid-19. Among all diseases included in our study, only Covid-19 had a significant negative effect on stock markets at least lasting 30 days.


title: Deubiquitinases and cancer: A snapshot

text: Abstract Ubiquitination is the vital system for controlling protein degradation and regulation of basic cellular processes. Deubiquitinases (DUBs) are emerging as an important regulator of several pathways related to cancer and other diseases. Their ability to detach ubiquitin from the target substrate and regulation of signaling makes it potential target to treat cancer and other fatal diseases. In the current review, we are trying to summarize deubiquitination, and their role in cancer and potential small molecules DUBs inhibitors which can be used as drugs for cancer treatment.


title: Quantitative Temporal in Vivo Proteomics Deciphers the Transition of Virus-Driven Myeloid Cells into M2 Macrophages

text: [Image: see text] Myeloid cells play a central role in the context of viral eradication, yet precisely how these cells differentiate throughout the course of acute infections is poorly understood. In this study, we have developed a novel quantitative temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of temporally transitioning virus-driven myeloid cells directly in situ, thus taking into consideration host–virus interactions throughout the course of an infection. QTiPs, in combination with phenotypic, functional, and metabolic analyses, elucidated a pivotal role for inflammatory CD11b(+), Ly6G(–), Ly6C(high-low) cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b(+), Ly6G(–), Ly6C(high-low) cells into M2-like macrophages, which displayed increased antigen-presentation capacities and bioenergetic demands late in infection. We elucidated the pivotal role of myeloid cells in virus clearance and show how these cells phenotypically, functionally, and metabolically undergo a timely transition from inflammatory to M2-like macrophages in vivo. With respect to the growing appreciation for in vivo examination of viral–host interactions and for the role of myeloid cells, this study elucidates the use of quantitative proteomics to reveal the role and response of distinct immune cell populations throughout the course of virus infection.


title: Full-Length Genome Sequence of a Variant Porcine Epidemic Diarrhea Virus Strain, CH/GDZQ/2014, Responsible for a Severe Outbreak of Diarrhea in Piglets in Guangdong, China, 2014

text: The full-length genome sequence of a variant porcine epidemic diarrhea virus (PEDV) strain, CH/GDZQ/2014, was determined. The isolate was a variant strain with a relatively far relationship with the PEDV strains previously identified in the same area between 2011 and 2012 and was genetically distinct from the CV777-based vaccine strain currently being used in China.


title: Re-examining risk premiums in the Fama–French model: The role of investor sentiment

text: Abstract This paper reconstructs the Fama–French three-factor (F–F) model as a panel smooth transition regression (PSTR) framework to investigate the differentiated effects of investor sentiment proxies-the volatility index (VIX), credit default swap (CDS), and TED spread-on the three risk premiums. Sample period spans from 2003: 1Q to 2013: 4Q. Sample objects are 58 semiconductor companies listed on Taiwan Security Exchange Corporation. The empirical results report that stock returns display a nonlinear path, and the three risk premiums are time-varying, depending on different proxies of investor sentiment in different regimes. Market premiums fall as investors in stock markets show extreme optimism or extreme pessimism. Except in rare situations, the size premium is significant and decreases with the increase in the VIX. Returns in holding growth stocks dominate holding value stocks when the investors show extreme pessimism or optimism. However, in normal sentiment of investment, value stocks earn more returns than growth stocks.


Letters Published in the June Issue


title: DC-SIGN and L-SIGN: the SIGNs for infection

text: Two closely related trans-membrane C-type lectins dendritic cell-specific intracellular adhesion molecules (ICAM)-3 grabbing non-integrin (DC-SIGN or CD209) and liver/lymph node-specific ICAM-3 grabbing non-integrin (L-SIGN also known as DC-SIGNR, CD209L or CLEC4M) directly recognize a wide range of micro-organisms of major impact on public health. Both genes have long been considered to share similar overall structure and ligand-binding characteristics. This review presents more recent biochemical and structural studies, which show that they have distinct ligand-binding properties and different physiological functions. Of importance in both these genes is the presence of an extra-cellular domain consisting of an extended neck region encoded by tandem repeats that support the carbohydrate-recognition domain, which plays a crucial role in influencing the pathogen-binding properties of these receptors. The notable difference between these two genes is in this extra-cellular domain. Whilst the tandem-neck-repeat region remains relatively constant size for DC-SIGN, there is considerable polymorphism for L-SIGN. Homo-oligomerization of the neck region of L-SIGN has been shown to be important for high-affinity ligand binding, and heterozygous expression of the polymorphic variants of L-SIGN in which neck lengths differ could thus affect ligand-binding affinity. Functional studies on the effect of this tandem-neck-repeat region on pathogen-binding, as well as genetic association studies for various infectious diseases and among different populations, are discussed. Worldwide demographic data of the tandem-neck-repeat region showing distinct differences in the neck-region allele and genotype distribution among different ethnic groups are presented. These findings support the neck region as an excellent candidate acting as a functional target for selective pressures exerted by pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-008-0350-2) contains supplementary material, which is available to authorized users.


title: COVID-19 Disease: Non-Invasive Ventilation and High Frequency Nasal Oxygenation

text: Abstract Severe COVID-19 causes significant numbers of patients to develop respiratory symptoms that require increasing interventions. Initially, the treatment for severe respiratory failure included early intubation and invasive ventilation, as this was deemed preferable to be more effective than Non-Invasive Ventilation (NIV). However, emerging evidence has shown that NIV may have a more significant and positive role than initially thought. NIV includes Continuous Positive Airway Pressure (CPAP) and Bi-Level Positive Airway Pressure (BiPAP). CPAP is the method of choice with the use of BiPAP for those with complex respiratory conditions who contract COVID-19. The use of High Flow Nasal Oxygen (HFNO) remains contentious with different perspectives in how this modality can be used to treat respiratory failure in COVID-19. Current thinking suggests that NIV and HFNO may be an appropriate bridging adjunct in the early part of the disease progress and may prevent the need for intubation or invasive ventilation. Patients requiring NIV or HFNO may be nursed in locations outside of the critical care unit. Therefore, this article reviews the different types of NIV and HFNO, indications and the nursing care.


title: Pteropine orthoreovirus infection among out‐patients with acute upper respiratory tract infection in Malaysia

text: This study aims to assess the incidence rate of Pteropine orthreovirus (PRV) infection in patients with acute upper respiratory tract infection (URTI) in a suburban setting in Malaysia, where bats are known to be present in the neighborhood. Using molecular detection of PRVs directly from oropharyngeal swabs, our study demonstrates that PRV is among one of the common causative agents of acute URTI with cough and sore throat as the commonest presenting clinical features. Phylogenetic analysis on partial major outer and inner capsid proteins shows that these PRV strains are closely related to Melaka and Kampar viruses previously isolated in Malaysia. Further study is required to determine the public health significance of PRV infection in Southeast Asia, especially in cases where co‐infection with other pathogens may potentially lead to different clinical outcomes. J. Med. Virol. 87:2149–2153, 2015. © 2015 Wiley Periodicals, Inc.


title: Local disease–ecosystem–livelihood dynamics: reflections from comparative case studies in Africa

text: This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human–ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples’ interactions with ecosystems and animals affect their exposure to disease. Cross-case analysis highlights how these dynamics vary by ecosystem type, across a range from humid forest to semi-arid savannah; the significance of interacting temporal and spatial scales; and the importance of mosaic and patch dynamics. Ecosystem interactions and services central to different people's livelihoods and well-being include pastoralism and agro-pastoralism, commercial and subsistence crop farming, hunting, collecting food, fuelwood and medicines, and cultural practices. There are synergies, but also tensions and trade-offs, between ecosystem changes that benefit livelihoods and affect disease. Understanding these can inform ‘One Health’ approaches towards managing ecosystems in ways that reduce disease risks and burdens. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.


title: Arboviral diseases and COVID‐19 in Brazil: Concerns regarding climatic, sanitation and endemic scenario

text: Brazil is witnessing a massive increase of COVID‐19 cases and may face some difficulties, not only regarding to other respiratory pathogens, but also to other relevant issues parallelly occurring, for instance, the beggining of autumn and winter seasons, which provides a longer period with high transmissibility of respiratory viroses. Additionally, Brazil is localized in a geographical tropical area with relevant arboviral diseases, where Dengue fever presented highest incidence during March‐June, mainly at Southeast and Midwest regions, where probably it will occur overlapping curves of arboviruses and COVID‐19, which will overload our public health system. The main affected áreas by COVID‐19 in Brazil were the same that presented 66% of the Dengue fever cases in Brazil. Moreover, it is importante to highlight the difficulty found to distinguish Dengue fever and COVID‐19 and its implications, which present similar laboratorial and clinical characteristics. Besides that, it has been pointed out false‐positive results in serological tests for Dengue fever, which later were confirmed as COVID‐19. These issues demand urgent attention,once they culminate in serious and devastating impacts in the Brazilian health system, public health, and social conditions. This article is protected by copyright. All rights reserved.


title: Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)

text: BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1–3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9–38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3–163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12072-020-10072-8) contains supplementary material, which is available to authorized users.


title: Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro

text: BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike) of the severe acute respiratory syndrome coronavirus (SARS-CoV) to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: Purified triSpike proteins were readily cleaved in vitro by three different airway proteases: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC) and amino acid sequencing analyses identified two arginine residues (R667 and R797) as potential protease cleavage site(s). The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A). Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV.


title: Comparison of an injectable toltrazuril-gleptoferron (Forceris®) and an oral toltrazuril (Baycox®) + injectable iron dextran for the control of experimentally induced piglet cystoisosporosis

text: BACKGROUND: Cystoisospora suis causes diarrhoeal disease and reduced weight gain in suckling piglets, and a toltrazuril-based oral suspension is available for treatment. Recently a combinatorial product with toltrazuril plus iron has been developed for parenteral application. In this study we compared the efficacy of the injectable product with the oral suspension against experimentally induced piglet cystoisosporosis. METHODS: In a randomised controlled study, three groups of piglets (n = 10–13) were treated either with a fixed dose of 45 mg toltrazuril + 200 mg gleptoferron i.m. per piglet (Forceris®) on the second day of life (study day 2; SD 2) or with 20 mg toltrazuril/kg body weight as an oral suspension (Baycox® 5%) on SD 4 or left untreated (Control group). The Baycox® and the Control group received 200 mg of iron dextran/piglet on SD 2. All piglets were infected with 1000 sporulated C. suis oocysts on SD 3. Faecal samples were taken daily from SD 7 to SD 20 to determine faecal consistency, oocyst shedding and other diarrhoeal pathogens. Body weight was recorded on SD 1 and then weekly until SD 29. Animals were observed daily for general health and after treatment for possible adverse events. RESULTS: In the Control group all animals shed oocysts for 3.1 days on average and all animals showed diarrhoea for an average of five days. Excretion peaked on SD 9 (max. 48,618 oocysts per gram of faeces). Treatment with Forceris® completely suppressed oocyst excretion. In the Baycox® group, low levels of excretion could be detected. Diarrhoea was reduced to single piglets in the treated groups. Body weight development was reduced in the Control group compared to the treated groups. Enteropathogenic bacteria (Escherichia coli, Clostridium perfringens) could be detected. All parameters related to oocyst excretion, faecal consistency and weight gain were significantly improved in the treated groups compared to the Control group without significant differences between the treated groups. Both products were safe to use. CONCLUSIONS: Treatment with both the injectable (Forceris®) and the oral (Baycox®) formulation of toltrazuril in the prepatent period were safe and highly effective against experimental infection with C. suis in newborn piglets.


title: Protein Chip Array Profiling Analysis in Patients with Severe Acute Respiratory Syndrome Identified Serum Amyloid A Protein as a Biomarker Potentially Useful in Monitoring the Extent of Pneumonia

text: Background: A new strain of coronavirus (CoV) has caused an outbreak of severe acute respiratory syndrome (SARS), with 8098 individuals being infected and 774 deaths worldwide. We carried out protein chip array profiling analysis in an attempt to identify biomarkers that might be useful in monitoring the clinical course of SARS patients. Methods: We performed surface-enhanced laser desorption ionization time-of-flight mass spectrometry on 89 sera collected from 28 SARS patients, 72 sera from 51 control patients with various viral or bacterial infections, and 10 sera from apparently healthy individuals. Results: Nine significantly increased and three significantly decreased serum biomarkers were discovered in the SARS patients compared with the controls. Among these biomarkers, one (11 695 Da) was identified to be serum amyloid A (SAA) protein by peptide mapping and tandem mass spectrometric analysis. When we monitored the SAA concentrations longitudinally in 45 sera from four SARS patients, we found a good correlation of SAA concentration with the extent of pneumonia as assessed by a serial chest x-ray opacity score. Increased SAA occurred in three of four patients at the time of extensive pneumonia as indicated by high x-ray scores. Over the course of gradual recovery in two patients, as assessed clinically and radiologically, SAA concentrations gradually decreased. In the third patient, the concentrations were initially increased, but were further increased with superimposed multiple bacterial infections. SAA was not markedly increased in the fourth patient, who had low x-ray scores and whose clinical course was relatively mild. Conclusions: Protein chip array profiling analysis could be potentially useful in monitoring the severity of disease in SARS patients.


Transfusion transmitted infections: How many more?


title: SARS-CoV heptad repeat 2 is a trimer of parallel helices

text: In severe acute respiratory syndrome coronavirus, the envelope heptad repeat 2 (HR2) plays a critical role in viral entry. Moreover, HR2 is both the target for novel antiviral therapies and, as an isolated peptide, presents a potential antiviral therapeutic. The structure of HR2, as determined by NMR spectroscopy in the presence of the co-solvent trifluoroethanol (TFE), is a trimer of parallel helices, whereas the structure of HR2, as determined by X-ray crystallography, is a tetramer of anti-parallel helices. In this work, we added a nitroxide spin label to the N-terminal region of HR2 and used paramagnetic relaxation enhancement to assess the orientation of the HR2 helices under different solution conditions. We find that the relaxation effects are consistent with an orientation corresponding to a trimer of parallel helices in both the presence and absence of TFE. This work suggests that the different orientation and oligomerization states observed by NMR and X-ray are due to the 11 additional residues present at the N-terminus of the NMR construct.


title: Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT

text: BACKGROUND: Despite its high sensitivity in diagnosing COVID-19 in a screening population, chest CT appearances of COVID 19 pneumonia are thought to be non-specific. PURPOSE: To assess the performance of United States (U.S.) and Chinese radiologists in differentiating COVID-19 from viral pneumonia on chest CT. METHODS: A total of 219 patients with both positive COVID-19 by RT-PCR and abnormal chest CT findings were retrospectively identified from 7 Chinese hospitals in Hunan Providence, China from January 6 to February 20, 2020. A total of 205 patients with positive Respiratory Pathogen Panel for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia by original radiology interpretation within 7 days of each other were identified from Rhode Island Hospital in Providence, RI. Three Chinese radiologists blindly reviewed all chest CTs (n=424) to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched cases was randomly selected and evaluated by 4 U.S. radiologists in a similar fashion. Different CT features were recorded and compared between the two groups. RESULTS: For all chest CTs, three Chinese radiologists correctly differentiated COVID-19 from non-COVID-19 pneumonia 83% (350/424), 80% (338/424), and 60% (255/424) of the time, respectively. The seven radiologists had sensitivities of 80%, 67%, 97%, 93%, 83%, 73% and 70% and specificities of 100%, 93%, 7%, 100%, 93%, 93%, 100%. Compared to non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs. 57%, p<0.001), ground-glass opacity (91% vs. 68%, p<0.001), fine reticular opacity (56% vs. 22%, p<0.001), and vascular thickening (59% vs. 22%, p<0.001), but less likely to have a central+peripheral distribution (14.% vs. 35%, p<0.001), pleural effusion (4.1 vs. 39%, p<0.001) and lymphadenopathy (2.7% vs. 10.2%, p<0.001). CONCLUSION: Radiologists in China and the United States distinguished COVID-19 from viral pneumonia on chest CT with high specificity but moderate sensitivity. A translation of this abstract in Farsi is available in the supplement. - ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.


title: LC-APCI-MS method for detection and analysis of tryptanthrin, indigo, and indirubin in Daqingye and Banlangen

text: Abstract A rapid, selective, and sensitive LC-APCI-MS method is developed in this study for detecting and analyzing tryptanthrin, indigo, and indirubin in Daqingye and Banlangen, which are, respectively, the leaves and roots of Isatis indigotica and Strobilanthes cusia in traditional Chinese medicine. The detection of the three active components is linear in concentrations ranging from 100 to 1500ng/mL, the squared correlation coefficient is higher than 0.996, the precision as measured by the relative standard deviation is no larger than 9.5%, and the recovery is greater than 86.6%. The analysis of the 21 Banlangen samples led to considerably different conclusions on the contents of tryptanthrin, indigo, and indirubin in fresh leaves versus those in dried leaves. These results should shed some light on future plant selection and breeding. Compared with the traditional TLC and HPLC-UV methods, the new LC-APCI-MS approach has proven to be an optimal tool for detecting and analyzing the three marker compounds in the Chinese herbal medicines of Daqingye and Banlangen.


Respiratory viruses in the intensive care unit: More frequent than expected


title: New angiotensins

text: Accumulation of a large body of evidence during the past two decades testifies to the complexity of the renin–angiotensin system (RAS). The incorporation of novel enzymatic pathways, resulting peptides, and their corresponding receptors into the biochemical cascade of the RAS provides a better understanding of its role in the regulation of cardiovascular and renal function. Hence, in recent years, it became apparent that the balance between the two opposing effector peptides, angiotensin II and angiotensin-(1-7), may have a pivotal role in determining different cardiovascular pathophysiologies. Furthermore, our recent studies provide evidence for the functional relevance of a newly discovered rat peptide, containing two additional amino acid residues compared to angiotensin I, first defined as proangiotensin-12 [angiotensin-(1-12)]. This review focuses on angiotensin-(1-7) and its important contribution to cardiovascular function and growth, while introducing angiotensin-(1-12) as a potential novel angiotensin precursor.


title: Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses

text: Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of chronic infections caused by HIV, hepatitis B or C viruses, and herpes viruses. High antiviral potency and favorable pharmacokinetics parameters make some nucleoside analogs suitable also for the treatment of acute infections caused by other medically important RNA and DNA viruses. This review summarizes available information on antiviral research of nucleoside analogs against arthropod-borne members of the genus Flavivirus within the family Flaviviridae, being primarily focused on description of nucleoside inhibitors of flaviviral RNA-dependent RNA polymerase, methyltransferase, and helicase/NTPase. Inhibitors of intracellular nucleoside synthesis and newly discovered nucleoside derivatives with high antiflavivirus potency, whose modes of action are currently not completely understood, have drawn attention. Moreover, this review highlights important challenges and complications in nucleoside analog development and suggests possible strategies to overcome these limitations.


title: Comparing the Cobas Liat Influenza A/B and respiratory syncytial virus assay with multiplex nucleic acid testing

text: Influenza virus and respiratory syncytial virus (RSV) detection with short turn‐around‐time (TAT) is pivotal for rapid decisions regarding treatment and infection control. However, negative rapid testing results may come from poor assay sensitivity or from influenza‐like illnesses caused by other community‐acquired respiratory viruses (CARVs). We prospectively compared the performance of Cobas Liat Influenza A/B and RSV assay (LIAT) with our routine multiplexNAT‐1 (xTAG Respiratory Pathogen Panel; Luminex) and multiplexNAT‐2 (ePlex‐RPP; GenMark Diagnostics) using 194 consecutive nasopharyngeal swabs from patients with influenza‐like illness during winter 2017/2018. Discordant results were reanalyzed by specific in‐house quantitative nucleic acid amplification testing (NAT). LIAT was positive for influenza virus‐A, ‐B, and RSV in 18 (9.3%), 13 (6.7%), and 55 (28.4%) samples, and negative in 108 samples. Other CARVs were detected by multiplexNAT in 66 (34.0%) samples. Concordant results for influenza and RSV were seen in 190 (97.9%), discordant results in 4 (2.1%), which showed low‐level RSV (<40 000 copies/mL). Sensitivity and specificity of LIAT for influenza‐A, ‐B, and RSV were 100%, 100% and 100%, and 100%, 99.5% and 100%, respectively. The average TAT of LIAT was 20 minutes compared to 6 hours and 2 hours for the multiplexNAT‐1 and ‐2, respectively. Thus, LIAT demonstrated excellent sensitivity and specificity for influenza and RSV, which together with the simple sample processing and short TAT renders this assay suitable for near‐patient testing.


title: Complete Genome Sequence of Porcine Deltacoronavirus Strain CH/JXJGS01/2016, Isolated in Jiangxi Province, China, 2016

text: The complete genome sequence of a variant of porcine deltacoronavirus, isolated from a diarrheal piglet and designated CH/JXJGS01/2016, was sequenced and analyzed. Phylogenetic analysis demonstrated that CH/JXJGS01/2016 shares the highest nucleotide and amino acid identities with the Chinese strain NH (GenBank accession number KU981059).


title: Invasive strategy for COVID patients presenting with acute coronary syndrome: The first multicenter Italian experience

text: OBJECTIVE: To report our initial experience of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)/acute coronary syndrome (ACS) patients undergoing standard of care invasive management. BACKGROUND: The rapid diffusion of the SARS‐CoV‐2 together with the need for isolation for infected patients might be responsible for a suboptimal treatment for SARS‐CoV‐2 ACS patients. Recently, the group of Sichuan published a protocol for COVID/ACS infected patients that see the thrombolysis as the gold standard of care. METHODS: We enrolled 31 consecutive patients affected by SARS‐COV‐2 admitted to our emergencies room for suspected ACS. RESULTS: All patients underwent urgent coronary angiography and percutaneous coronary intervention (PCI) when required except two patients with severe hypoxemia and unstable hemodynamic condition that were conservatively treated. Twenty‐one cases presented diffuse ST‐segment depression while in the remaining cases anterior and inferior ST‐elevation was present in four and six cases, respectively. PCI was performed in all cases expect two that were diagnosed as suspected myocarditis because of the absence of severe coronary disease and three with apical ballooning at ventriculography diagnostic for Tako‐Tsubo syndromes. Two patients conservatively treated died. The remaining patients undergoing PCI survived except one that required endotracheal intubation (ETI) and died at Day 6. ETI was required in five more patients while in the remaining cases CPAP was used for respiratory support. CONCLUSIONS: Urgent PCI for ACS is often required in SARS‐CoV‐2 patients improving the prognosis in all but the most advanced patients. Complete patient history and examination, routine ECG monitoring, echocardiography, and careful evaluation of changes in cardiac enzymes should be part of the regular assessment procedures also in dedicated COVID positive units.


title: Human gene and disease associations for clinical‐genomics and precision medicine research

text: We are entering the era of personalized medicine in which an individual's genetic makeup will eventually determine how a doctor can tailor his or her therapy. Therefore, it is becoming critical to understand the genetic basis of common diseases, for example, which genes predispose and rare genetic variants contribute to diseases, and so on. Our study focuses on helping researchers, medical practitioners, and pharmacists in having a broad view of genetic variants that may be implicated in the likelihood of developing certain diseases. Our focus here is to create a comprehensive database with mobile access to all available, authentic and actionable genes, SNPs, and classified diseases and drugs collected from different clinical and genomics databases worldwide, including Ensembl, GenCode, ClinVar, GeneCards, DISEASES, HGMD, OMIM, GTR, CNVD, Novoseek, Swiss‐Prot, LncRNADisease, Orphanet, GWAS Catalog, SwissVar, COSMIC, WHO, and FDA. We present a new cutting‐edge gene‐SNP‐disease‐drug mobile database with a smart phone application, integrating information about classified diseases and related genes, germline and somatic mutations, and drugs. Its database includes over 59 000 protein‐coding and noncoding genes; over 67 000 germline SNPs and over a million somatic mutations reported for over 19 000 protein‐coding genes located in over 1000 regions, published with over 3000 articles in over 415 journals available at the PUBMED; over 80 000 ICDs; over 123 000 NDCs; and over 100 000 classified gene‐SNP‐disease associations. We present an application that can provide new insights into the information about genetic basis of human complex diseases and contribute to assimilating genomic with phenotypic data for the availability of gene‐based designer drugs, precise targeting of molecular fingerprints for tumor, appropriate drug therapy, predicting individual susceptibility to disease, diagnosis, and treatment of rare illnesses are all a few of the many transformations expected in the decade to come.


title: Small Interfering RNA Effectively Inhibits the Expression of SARS Coronavirus Membrane Gene at Two Novel Targeting Sites

text: Small interfering RNA (siRNA) is a class of duplex RNA molecules of 21-25 nt nucleotides in length functioning post-transcriptionally to downregulate targeted gene expression. The membrane (M) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is highly abundant during viral infections and is a critical element for viral assembly. Nucleotide substitution in the viral genome occurs frequently during SARS-CoV infection. In the current study, we analyzed the M gene sequences derived from 15 SARS-CoV isolates and uncovered six nucleotide substitutions among these isolates. Interestingly, these nucleotide substitutions are all located at the 5’ half of the M gene. Based on this information and previous reports, we created two novel siRNAs targeting two unexplored and well conserved regions in the M gene. The effects of these two siRNAs were tested by semi-quantitative RT-PCR and EGFP-M fusion gene expression. The results demonstrated that both siRNAs effectively and specifically blocked the targeted gene expression. Real time quantitative RT-PCR (qRT-PCR) revealed that siRNA targeting the 3’ half of the M gene (si-M2) induced more potent inhibition than that targeting the 5’ half (si-M1). Both si-M1 and si-M2 significantly downregulated M gene mediated upregulation of interferon β expression. Thus, our results indicate that SARS-CoV M gene specific siRNA might function in a sequence-dependent manner.


title: Development of oligonucleotide microarray for accurate and simultaneous detection of avian respiratory viral diseases

text: BACKGROUND: Avian influenza virus (AIV), infectious bronchitis virus (IBV), and Newcastle disease virus (NDV) are important avian pathogens that can cause enormous economic loss on the poultry industry. Different respiratory etiological agents may induce similar clinical signs that make differential diagnosis difficult. Importantly, AIV brings about severe threat to human public health. Therefore, a novel method that can distinguish these viruses quickly and simultaneously is urgently needed. RESULTS: In this study, an oligonucleotide microarray system was developed. AIV, including H5, H7, and H9 subtypes; NDV; and IBV were simultaneously detected and differentiated on a microarray. Three probes specific for AIV, NDV, and IBV, as well as three other probes for differentiating H5, H7, and H9 of AIV, were first designed and jet-printed to predetermined locations of initiator-integrated poly(dimethylsiloxane) for the synchronous detection of the six pathogens. The marked multiplex reverse transcription polymerase chain reaction (PCR) products were hybridized with the specific probes, and the results of hybridization were read directly with the naked eyes. No cross-reaction was observed with 10 other subtypes of AIV and infectious bursal disease virus, indicating that the oligonucleotide microarray assay was highly specific. The sensitivity of the method was at least 100 times higher than that of the conventional PCR, and the detection limit of NDV, AIV, H5, H7, and H9 can reach 0.1 EID(50) (50% egg infective dose), except that of IBV, which was 1 EID(50) per reaction. In the validation of 93 field samples, AIV, IBV, and NDV were detected in 53 (56.99%) samples by oligonucleotide microarray and virus isolation and in 50 (53.76%) samples by conventional PCR. CONCLUSIONS: We have successfully developed an approach to differentiate AIV, NDV, IBV, H5, H7, and H9 subtypes of AIV using oligonucleotide microarray. The microarray is an accurate, high-throughput, and relatively simple method for the rapid detection of avian respiratory viral diseases. It can be used for the epidemiological surveillance and diagnosis of AIV, IBV, and NDV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-019-1985-7) contains supplementary material, which is available to authorized users.


title: COVID‐19 and Liver Dysfunction: a systematic review and meta‐analysis of retrospective studies

text: BACKGROUND: Recently, Coronavirus Disease 2019 (COVID‐19) pandemic is the most significant global health crisis. In this study, we conducted a meta‐analysis to find the association between liver injuries and the severity of COVID‐19 disease. METHODS: Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to April 16, 2020. Depending on the heterogeneity between studies, a fixed‐ or random‐effects model was applied to pool data. Publication bias Egger's test was also performed. RESULTS: Meta‐analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID‐19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID‐19. CONCLUSION: Liver dysfunction was associated with a severe outcome of COVID‐19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes. This article is protected by copyright. All rights reserved.


title: Transmission maternofœtale des coronavirus humains. Étude prospective pilote

text: Human coronaviruses (HCoV) have been implicated in neonatal nosocomial respiratory infection. Prior to our study, several cases of neonatal infection were observed in infants born at our hospital. This prospective pilot monocentric pilot study investigates the possibility of maternofetal transmission of HCoV responsible for cases of neonatal infection observed within the first 24 hours of life. MATERIALS AND METHODS: Three samples from mother–child couples, maternal vaginal (VM) and respiratory (RM) samples during labor; newborn gastric sample (GNN), were assessed for viral analysis using real time RT-PCR for the detection of HCoV 229-E and OC43. Clinical follow-up of infants and mothers was up to Day 3 after birth. RESULTS: One hundred (and) fifty-nine mother–child couples were included between July 2003 and August 2005. HCoV 229-E only was detected in 11 samples from 6 mother–child couples. For 2 couples, all 3 samples (VM, RM and GNN) were tested positive (cases 1 and 2). For case 3, both VM and GNN were positive. For 2 couples, only RM was positive (cases 4 and 5). In case 6, only VM was positive. Of the 3 positive GNN, no infant was symptomatic. CONCLUSION: Possible vertical transmission of HCoV was evidenced in this pilot study and requires further investigation on a larger scale. Equally indicated is the inclusion of tests to detect recently identified human coronaviruses HCoV NL63 and HKU1, as well as genomic profile analysis of HCoV 229-E detected in the 3 positive mother-child couples.


title: Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses

text: Reverse genetics, an approach to rescue infectious virus entirely from a cloned cDNA, has revolutionized the field of positive-strand RNA viruses, whose genomes have the same polarity as cellular mRNA. The cDNA-based reverse genetics system is a seminal method that enables direct manipulation of the viral genomic RNA, thereby generating recombinant viruses for molecular and genetic studies of both viral RNA elements and gene products in viral replication and pathogenesis. It also provides a valuable platform that allows the development of genetically defined vaccines and viral vectors for the delivery of foreign genes. For many positive-strand RNA viruses such as Japanese encephalitis virus (JEV), however, the cloned cDNAs are unstable, posing a major obstacle to the construction and propagation of the functional cDNA. Here, the present report describes the strategic considerations in creating and amplifying a genetically stable full-length infectious JEV cDNA as a bacterial artificial chromosome (BAC) using the following general experimental procedures: viral RNA isolation, cDNA synthesis, cDNA subcloning and modification, assembly of a full-length cDNA, cDNA linearization, in vitro RNA synthesis, and virus recovery. This protocol provides a general methodology applicable to cloning full-length cDNA for a range of positive-strand RNA viruses, particularly those with a genome of >10 kb in length, into a BAC vector, from which infectious RNAs can be transcribed in vitro with a bacteriophage RNA polymerase.


title: Expect the Unexpected: A Rare Case of Pseudomonas aerguinosa Endocarditis

text: Infective endocarditis (IE) caused by Pseudomonas aeruginosa is extremely uncommon. Reported cases have usually been associated with intravenous drug use, prosthetic heart valves, and/or implanted cardiac devices. Traditionally, successful treatment has necessitated a combination of antimicrobial(s) and valve replacement. Yet, P. aeruginosa IE remains difficult to manage, especially in cases where valve replacement may not be an immediate option. We present such a case of P. aeruginosa IE, highlighting that medical management with 2 antipseudomonal synergistic agents may be an alternative to surgery in particularly complicated cases.