title: Development of a rapid immunochromatographic strip test for the detection of porcine epidemic diarrhea virus specific SIgA in colostrum

text: Abstract Porcine epidemic diarrhea virus (PEDV) causes very high mortality in newborn piglets. The mucosal immune system in the gut must eliminate potential pathogens while maintaining a mutually beneficial relationship with the commensal microbiota. Antibodies derived from the secretory immunoglobulin A (SIgA) class, act as the first line of antigen-specific immunity in the gut by recognizing both pathogens and commensals. Therefore, the measurement of SIgA levels is an important index in evaluating PEDV infections and immune status. A simple and rapid method for the detection of PEDV-specific SIgA using an immunochromatographic test strip has been developed; incorporating a colloidal gold-labeled anti-SIgA secretory component (SC) mAb probe for the detection of anti-PEDV-specific SIgA in swine. On the strip, a gold-labeled anti-SIgA SC mAb was applied to a conjugate pad; purified PEDV particles and goat anti-mouse antibodies were blotted onto a nitrocellulose membrane to form the test and control lines, respectively. Results showed that the immunochromatographic test strip had high sensitivity and specificity. When compared with enzyme-linked immunosorbent assay, kappa value suggesting that the strip could be used to detect PEDV specific SIgA in colostrum samples. Furthermore, the strip assay is rapid and easy to perform with no requirement for professional-level skills or equipment. We found that the immunochromatographic test strip was a rapid, sensitive, and reliable method for the identification of PEDV specific SIgA, indicating its suitability for epidemiological surveillance as well as vaccine immunity when studying PEDV.


title: Synthesis and evaluation of isatin derivatives as effective SARS coronavirus 3CL protease inhibitors

text: Abstract N-Substituted isatin derivatives were prepared from the reaction of isatin and various bromides via two steps. Bioactivity assay results (in vitro tests) demonstrated that some of these compounds are potent and selective inhibitors against SARS coronavirus 3CL protease with IC50 values ranging from 0.95 to 17.50μM. Additionally, isatin 4o exhibited more potent inhibition for SARS coronavirus protease than for other proteases including papain, chymotrypsin, and trypsin.


title: ssICAM-1, IL-21 and IL-23 in patients with tick borne encephalitis and neuroborreliosis

text: Abstract Objective There have been few reports on the role of Intercellular Adhesion Molecule 1 (ICAM-1), but not interleukin-21 (IL-21) and interleukin-23 (IL-23) in tick-borne encephalitis (TBE) and neuroborreliosis (NB). We postulate that these two interleukins may participate in the early phase of TBE and NB. The aim of the study was to measure serum and cerebrospinal fluid (CSF) concentration of ICAM-1, IL-21 and IL-23 in patients with TBE and NB before treatment and to assess their usefulness in the diagnosis and monitoring of inflammatory process in TBE and NB. Methods Forty-three patients hospitalized in The Department of Infectious Diseases and Neuroinfections of Medical University in Bialystok, Poland, were included in the study. Patients were divided into three groups: TBE, NB and CG. Pre-treatment blood and CSF samples were obtained from all patients. ELISA kits (DRG Instruments, Germany) were used to measure the concentration of IL-21, IL-23 and sICAM-1. Results Significant differences between TBE/CG and NB/CG concentration of sICAM-1 were found only in the CSF. CSF IL-21 levels in NB were lower than in TBE. In TBE, a strong negative correlation between CSF concentration of IL-21 and IL-23 and monocyte count in CSF was observed. Negative correlation between IL-21 in CSF and neutrophil count was also noted. Serum IL-23 correlated positively with leukocytes and platelet count in serum. In NB, a strong positive correlation between serum IL-21 and platelet count and negative correlation between IL-21 in serum and CSF with pleocytosis was observed. Conclusions Increased sICAM-1 concentration in TBE and NB may be a proof of brain–blood barrier disturbances in the early phase of these diseases. IL-21 and IL-23 do not appear to play an important role in the pathogenesis of the early stages of TBE and NB.


title: Effect on Thromboprophylaxis among Hospitalized Patients Using a System-wide Multifaceted Quality Improvement Intervention: Rationale and Design for a Multicenter Cluster Randomized Clinical Trial in China

text: ABSTRACT Background Venous thromboembolism (VTE) is a life-threatening disease that can affect each hospitalized patient. But the current in-hospital thromboprophylaxis remains suboptimal and there exists a large gap between clinical practice and guideline-recommended care in China. Methods To facilitate implementation of guideline recommendations, we conduct a multicenter, adjudicator-blinded, cluster-randomized clinical trial, aiming to assess the effectiveness of a system-wide multifaceted quality improvement (QI) strategy on VTE prophylaxis improvement and thromboembolism reduction in clinical setting. Hospitals are randomized into intervention or control group. In intervention group, hospitals receive the concept of appropriate in-hospital thromboprophylaxis plus a multifaceted QI which encompasses four components: (1) an electronic alert combining computer-based clinical decision support system and electronic reminders, (2) appropriate prophylaxis based on dynamic VTE and bleeding risk assessments, (3) periodical audit and interactive feedback on performance, (4) strengthened training and patient education. In control, hospitals receive the concept of recommended prophylaxis alone without QI. Thromboprophylaxis will be at the discretion of hospitals and conducted as usual. With a final sample size of 5760 hospitalized patients in 32 hospitals on mainland China, this trial will examine the effect of QI on improvement in thromboprophylaxis and patient-centered outcomes. This is an open-label trial that patients and healthcare professionals will know group allocation after enrollment, but endpoint adjudicators and statisticians will be blinded. RCT# NCT04211181 Conclusions The system-wide multifaceted QI intervention is expected to facilitate implementation of recommended VTE prophylaxis in hospital, thereafter reducing VTE incidence and relevant adverse events among hospitalized patients in China.


title: Isolation of the Fathead Minnow Nidovirus from Muskellunge Experiencing Lingering Mortality

text: In 2011, the Fathead Minnow nidovirus (FHMNV; Genus Bafinivirus, Family Coronaviridae, Order Nidovirales) was isolated from pond‐raised juvenile Muskellunge Esox masquinongy suffering from lingering mortality at the Wild Rose Hatchery in Wild Rose, Wisconsin. Moribund Muskellunge exhibited tubular necrosis in the kidneys as well as multifocal coalescing necrotizing hepatitis. The FHMNV was also isolated from apparently healthy juvenile Muskellunge at the Wolf Lake State Fish Hatchery in Mattawan, Michigan. The identity of the two syncytia‐forming viruses (designated MUS‐WR and MUS‐WL from Wild Rose Hatchery and Wolf Lake State Fish Hatchery, respectively) as strains of FHMNV was determined based on multiple‐gene sequencing and phylogenetic analyses. The pathogenicity of the MUS‐WL FHMNV strain was determined by experimentally infecting naive juvenile Muskellunge through intraperitoneal injection with two viral concentrations (63 and 6.3 × 10(3) TCID(50)/fish). Both doses resulted in 100% mortality in experimentally infected fish, which exhibited severely pale gills and petechial hemorrhaging in eyes, fins, and skin. Histopathological alterations in experimentally infected fish were observed mainly in the hematopoietic tissues in the form of focal areas of necrosis. Phylogenetic analysis of concatenated partial spike glycoprotein and helicase gene sequences revealed differences between the MUS‐WL FHMNV, MUS‐WR FHMNV, and two other FHMNV originally isolated from moribund Fathead Minnows Pimephales promelas including the index FHMNV strain (GU002364). Based on a partial helicase gene sequence, a reverse transcriptase PCR assay was developed that is specific to FHMNV. These results give evidence that the risks posed to Muskellunge by FHMNV should be taken seriously. Received May 1, 2015; accepted February 8, 2016


title: Pro con debates in clinical medicine Infection prevention and control in cystic fibrosis: One size fits all? The argument in favour

text: This article advocates for a universal approach to infection control measures in cystic fibrosis. The central tenets of infection control include hand hygiene, contact precautions, regular microbiological surveillance and adopting inpatient, outpatient, domestic and social practices to minimise acquisition of common CF pathogens. Infection control measures should be proactive and prospective, assuming all patients harbour aggressive pathogens, and not relying on past culture results. The challenges of implementing these policies include cost, equipment, education, consistency, meticulousness all whilst balancing additional procedures to a busy clinical workload.


title: Broadly targeted multiprobe QPCR for detection of coronaviruses: Coronavirus is common among mallard ducks (Anas platyrhynchos)

text: Abstract Coronaviruses (CoVs) can cause trivial or fatal disease in humans and in animals. Detection methods for a wide range of CoVs are needed, to understand viral evolution, host range, transmission and maintenance in reservoirs. A new concept, “Multiprobe QPCR”, which uses a balanced mixture of competing discrete non- or moderately degenerated nuclease degradable (TaqMan®) probes was employed. It provides a broadly targeted and rational single tube real-time reverse transcription PCR (“NQPCR”) for the generic detection and discovery of CoV. Degenerate primers, previously published, and the new probes, were from a conserved stretch of open reading frame 1b, encoding the replicase. This multiprobe design reduced the degree of probe degeneration, which otherwise decreases the sensitivity, and allowed a preliminary classification of the amplified sequence directly from the QPCR trace. The split probe strategy allowed detection of down to 10 viral nucleic acid equivalents of CoV from all known CoV groups. Evaluation was with reference CoV strains, synthetic targets, human respiratory samples and avian fecal samples. Infectious-Bronchitis-Virus (IBV)-related variants were found in 7 of 35 sample pools, from 100 wild mallards (Anas platyrhynchos). Ducks may spread and harbour CoVs. NQPCR can detect a wide range of CoVs, as illustrated for humans and ducks.


title: Molecular screening and risk factors of enterotoxigenic Escherichia coli and Salmonella spp. in diarrheic neonatal calves in Egypt

text: Abstract The aim of the present study was to carry out molecular epidemiological investigation on enterotoxigenic Escherichia coli (ETEC) K99 and Salmonella spp. in diarrheic neonatal calves. Fecal samples were obtained from 220 diarrheic calves at 9 farms related to four governorates in central and northern Egypt. E. coli and Salmonella spp. isolates were examined for E. coli K99 and Salmonella spp. using PCR. ETEC K99 was recovered from 20 (10.36 %) out of 193 isolates, whereas Salmonella spp. was recovered from nine calves (4.09%). Multivariable logistic regression was used to evaluate the risk factors associated with both infections. ETEC K99 was significantly affected by age (P <0.01; OR: 1.812; CI 95%: 0.566–1.769), colostrum feeding practice (P <0.01; OR: 5.525; CI 95%: 2.025–15.076), rotavirus infection (P <0.001; OR: 2.220; CI 95%: 0.273–1.251), vaccination of pregnant dams with combined vaccine against rotavirus, coronavirus and E. coli (K99) (P <0.001; OR: 4.753; CI 95%: 2.124–10.641), and vitamin E and selenium administration to the pregnant dam (P <0.01; OR: 3.933; CI 95%: 0.703–1.248). Infection with Salmonella spp. was found to be significantly affected by the animal age (P <0.05; OR: 0.376; CI 95%: 0.511–1.369), Hygiene (P <0.05; OR: 0.628; CI 95%: 1.729–5.612), and region (P <0. 01; OR: 0.970; CI 95%: 0.841–1.624). The results of the present study indicate the importance of PCR as rapid, effective and reliable tool for screening of ETEC and Salmonella spp. when confronted with cases of undifferentiated calf diarrhea. Moreover, identification of the risk factors associated with the spreading of bacteria causing diarrhea may be helpful for construction of suitable methods for prevention and control.


title: The incidence of pneumonia in rural Thailand

text: Summary Background Pneumonia continues to be a leading infectious disease killer, yet accurately measuring incidence remains a challenge. In 2002, Thailand began active, population-based surveillance for radiographically confirmed pneumonia in Sa Kaeo Province. Methods Full-time surveillance officers conducted active case ascertainment at every hospital, and routine audits and a community cluster survey promoted complete and accurate reporting. A case of pneumonia was defined as acute infection with signs or symptoms of lower respiratory tract infection and evidence of new infiltrates. An independent panel of radiologists reviewed digital images of all radiographs. Results Between September 2002 and August 2003, 777 patients met the case definition. The measured minimum incidence was 177/100000 but the estimated incidence was as high as 580/100000 with full adjustment for incomplete chest radiography and access to health care. Seventy-two (9%) patients died and 28% were known to be HIV positive. Fifteen (2%) patients had pneumonia twice during the year. The average cost of hospitalization for an episode of pneumonia ranged from US$490.80 to $628.60. Conclusions Pneumonia is a significant and costly public health problem in Thailand. This surveillance system allows precise assessment and monitoring of radiologically confirmed pneumonia and lays the groundwork for the introduction of new vaccines against pneumonia pathogens.


title: Combination siRNA therapy against feline coronavirus can delay the emergence of antiviral resistance in vitro

text: Abstract Virulent biotypes of feline coronavirus (FCoV), commonly referred to as feline infectious peritonitis virus (FIPV), can result in the development of feline infectious peritonitis (FIP), a typically fatal immune mediated disease for which there is currently no effective antiviral treatment. We previously reported the successful in vitro inhibition of FIPV replication by synthetic siRNA mediated RNA interference (RNAi) in an immortalised cell line (McDonagh et al., 2011). A major challenge facing the development of any antiviral strategy is that of resistance, a problem which is particularly acute for RNAi based therapeutics due to the exquisite sequence specificity of the targeting mechanism. The development of resistance during treatment can be minimised using combination therapy to raise the genetic barrier or using highly potent compounds which result in a more rapid and pronounced reduction in the viral replication rate, thereby reducing the formation of mutant, and potentially resistant viruses. This study investigated the efficacy of combination siRNA therapy and its ability to delay or prevent viral escape. Virus serially passaged through cells treated with a single or dual siRNAs rapidly acquired resistance, with mutations identified in the siRNA target sites. Combination therapy with three siRNA prevented viral escape over the course of five passages. To identify more potent silencing molecules we also compared the efficacy, in terms of potency and duration of action, of canonical versus Dicer-substrate siRNAs for two previously identified effective viral motifs. Dicer-substrate siRNAs showed equivalent or better potency than canonical siRNAs for the target sites investigated, and may be a more appropriate molecule for in vivo use. Combined, these data inform the potential therapeutic application of antiviral RNAi against FIPV.


title: Phylodynamic analysis and molecular diversity of the avian infectious bronchitis virus of chickens in Brazil

text: Abstract Avian infectious bronchitis virus (IBV) is the etiological agent of a highly contagious disease, which results in severe economic losses to the poultry industry. The spike protein (S1 subunit) is responsible for the molecular diversity of the virus and many sero/genotypes are described around the world. Recently a new standardized classification of the IBV molecular diversity was conducted, based on phylogenetic analysis of the S1 gene sequences sampled worldwide. Brazil is one of the biggest poultry producers in the world and the present study aimed to review the molecular diversity and reconstruct the evolutionary history of IBV in the country. All IBV S1 gene sequences, with local and year of collection information available on GenBank, were retrieved. Phylogenetic analyses were carried out based on a maximum likelihood method for the classification of genotypes occurring in Brazil, according to the new classification. Bayesian phylogenetic analyses were performed with the Brazilian clade and related international sequences to determine the evolutionary history of IBV in Brazil. A total of 143 Brazilian sequences were classified as GI-11 and 46 as GI-1 (Mass). Within the GI-11 clade, we have identified a potential recombinant strain circulating in Brazil. Phylodynamic analysis demonstrated that IBV GI-11 lineage was introduced in Brazil in the 1950s (1951, 1917–1975 95% HPD) and population dynamics was mostly constant throughout the time. Despite the national vaccination protocols, our results show the widespread dissemination and maintenance of the IBV GI-11 lineage in Brazil and highlight the importance of continuous surveillance to evaluate the impact of currently used vaccine strains on the observed viral diversity of the country.


title: Extracellular Matrix: Surface Proteoglycans

text: Cell surface proteoglycans, such as syndecans and glypicans, regulate molecular interactions that mediate cell adhesion, migration, proliferation, and differentiation. Through these activities, surface proteoglycans modulate critical biological processes of development, inflammation, infection, tissue repair, and cancer metastasis. Proteoglycans are unique glycoproteins comprised of one or several glycosaminoglycans attached covalently to core proteins. Glycosaminoglycans mediate the majority of ligand-binding functions of proteoglycans. Accumulating evidence indicates that surface proteoglycans regulate the onset, progression, and outcome of lung diseases, including lung injury, infection, fibrosis, and cancer. This article will review key features of surface proteoglycan biology in lung health and disease.


title: I-ACTSS-COVID-19—the Italian acute care and trauma surgery survey for COVID-19 pandemic outbreak

text: ABSTRACT: The sudden COVID-19 outbreak in Italy has challenged our health systems and doctors faced the challenge of treating a large number of critically ill patients in a short time interval. Acute care surgeons, although not directly involved in treating COVID-19 + patients, have often modified their daily activity to help in this crisis. We have designed the first Italian survey on the effect of COVID-19 outbreak on Acute Care Surgery activity and submitted it to emergency surgeons in all the country to evaluate the experiences, trends, attitudes and possible educational outcomes that this emergency brought to light. A total of 532 valid surveys were collected during the study period. Lombardy and Lazio had the major answer rate. 96% of responders noticed a decrease in surgical emergencies. The outbreak affected regions and hospitals in different ways depending on the local incidence of infection. Half of responders modified their approach to intra-abdominal infections towards a more conservative treatment. 43% of responders, mainly in the North, were shifted to assist non-surgical patients. There has been a direct but non-homogeneous involvement of emergency surgeons. Almost all hospitals have responded with specific pathways and training. Both emergency surgery and trauma activity have changed and generally decreased but the majority of surgeons have operated on suspected COVID-19 patients. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13304-020-00832-4) contains supplementary material, which is available to authorized users.


Modelling the impact of COVID‐19 on intensive care services in New South Wales


title: 206 Transcriptional signatures of pathogenesis and successful type I interferon and ribavirin therapy in a rhesus macaque model of MERS-CoV infection

text: A novel betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), emerged on the Arabian Peninsula in 2012. MERS-CoV was found to produce severe respiratory illness with case-fatality rates near 50%, and may be transmitted person-to-person in instances of close physical contact, such as among family members and to health care workers. As mice, hamsters, ferrets, and cynomolgus macaques are either not susceptible to MERS-CoV infection or do not develop observable clinical disease, we sought to determine whether rhesus macaques (Macaca mulatta) can be used as a model of MERS-CoV infection and disease. Animals challenged with MERS-CoV via multiple combined infection routes rapidly developed pneumonia, and we observed other clinical signs of illness, virus shedding, and virus replication in respiratory tissues. Using microarrays to compare transcripts associated with histopathologic lesions removed from the lungs of infected animals, we identified 173 significant differentially expressed genes (DEG) associated with lung lesions on day 3 post-infection concurrent with peak clinical signs. Functional analysis indicated that these genes were predominantly associated with proinflammatory processes, recruitment and chemotaxis of inflammatory cells, and antiviral immunity. Using singular value decomposition coupled multidimensional scaling (SVD-MDS), we also identified changes in similar inflammatory genes in peripheral blood mononuclear cells, suggesting a rapid activation of innate immune and inflammatory processes in leukocytes after infection. These data were consistent with cytokine and chemokine profiles in the blood of animals. Due to the urgent need for an effective therapeutic means of treating MERS-CoV patients, we used this rhesus macaque model to evaluate post-exposure treatment with combination interferon (IFN)-a2b and ribavirin (RBV), and identified key transcriptional signatures associated with disease severity and treatment efficacy. Animals treated with IFN-a2b/RBV beginning 8h post-infection did not develop significant clinical or severe histopathologic signs of disease, breathing abnormalities, or radiographic evidence of pneumonia, and showed reduced viral loads and lower levels of serum proinflammatory cytokines. Microarray analysis of treated animals showed significant induction of interferon-stimulated genes (ISGs) and fewer upregulated transcripts associated with inflammatory processes. Additionally, we identified a subset of statistically significant DEGs associated with signaling pathways such as hedgehog, which has been linked to airway function and protection against pulmonary injury. Together, these data indicate that treatment of MERS-CoV-infected rhesus macaques with IFN-a2b and ribavirin reduces virus replication and improves clinical outcome, and suggests a transcriptomic basis for therapeutic efficacy. As these two drugs are already used together in the clinic, IFN-a2b and ribavirin may be useful for therapeutic intervention and patient management of new human MERS-CoV cases.


title: Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records Chen H, Gun J, Wang C, et al. Lancet 2020; 395: 809–15.

text: Multiple reports have been published recently on characteristics of patients with COVID-19 in the general population, but there is little information on pregnancy-related presenting symptoms and outcomes. The goal of this study was to report clinical data as well as incidence of vertical transmission in pregnant patients with COVID-19. This retrospective chart review was performed on pregnant women admitted to Zhongnan Hospital of Wuhan University in China with confirmed COVID-19 between January 20 through January 31, 2020. Clinical, laboratory, and radiologic records were reviewed by two investigators. Additionally, analyses from amniotic fluid, cord blood samples, and neonatal throat samples from the time of delivery were included. Vertical transmission was defined as positive testing for COVID-19 in these samples. Descriptive statistics were used. There were nine patients included in the analysis. All were in the third trimester on admission, the earliest presenting at 36 weeks, 2 days and all had a known source of exposure to COVID-19. None of the patients had baseline comorbidities, but one patient had gestational hypertension and another developed pre-eclampsia. The most common symptoms of COVID-19 were fever on admission (78%), postpartum fever (67%), cough (44%), myalgia (33%), and sore throat (22%). Most had low or normal leukocyte count (78%) and 5 (56%) had lymphopenia. C-reactive protein was greater than 10mg/L in 75% of patients. One was found to be co-infected with influenza, and all were diagnosed with COVID-19 pneumonia and required oxygen therapy and antibiotics. Many (67%) also received antivirals. Regarding delivery, all nine were live births delivered via cesarean section with 1-min Apgar scores of 8-9 and 5-min Apgar scores of 9-10. Four of the 9 were delivered prematurely at 36 weeks (44%) for a variety of reasons including premature rupture of membranes, pre-eclampsia, or pneumonia. None of the fluid samples at birth were positive for COVID-19. Additionally, all of the mothers and babies were discharged from the hospital. Limitations discussed include the retrospective nature of data abstraction and small sample size. Additionally all patients enrolled were in the third trimester. The authors concluded that pregnant patients with COVID-19 present with similar symptoms as nonpregnant patients. Also, based on this limited sample, the mothers had a low risk of complications and all of the infants tested negative for COVID-19 after birth, suggesting that vertical transmission is unlikely. Comment: There are still many uncertainties about the disease course of COVID-19 in pregnant patients. This review is reassuring, however this is a very small sample size so caution should be used in applying these results to our day to day patients, especially those at earlier gestational ages. More studies should be conducted on pregnant patients with COVID-19 in all trimesters to have a more accurate picture of how this virus affects pregnancy-related outcomes.


title: Factors Contributing to Healthcare Professional Burnout During the COVID-19 Pandemic: A Rapid Turnaround Global Survey

text: BACKGROUND: Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload, and stress. Understanding HCPs’ risk for burnout is critical to supporting HCPs and maintaining the quality of healthcare during the pandemic. METHODS: To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs’ self-assessment of burnout and other experiences and attitudes associated with working during the COVID-19 pandemic. FINDINGS: A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR=1·57, 95% CI=1·39–1·78, P<0·001), feeling pushed beyond training (RR=1·32, 95% CI=1·20–1·47, P<0·001), exposure to COVID-19 patients (RR=1·18, 95% CI=1·05–1·32, P=0·005), making life prioritizing decisions (RR=1·16, 95% CI=1·02–1·31, P=0·03). Adequate personal protective equipment (PPE) was protective against burnout (RR=0·88, 95% CI=0·79–0·97, P=0·01). Burnout was higher in high-income countries (HICs) compared to low- and middle-income countries (LMICs) (RR=1·18; 95% CI=1·02–1·36, P=0·018). INTERPRETATION: Burnout is prevalent at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, support for family, PPE, and mental health resources. FUNDING: N/A


title: Emission strength of airborne pathogens during toilet flushing

text: The flushing of toilets generates contaminated aerosols, the transmission of which may cause the spread of disease, particularly in the immunocompromised or the elderly. This study investigated the emission strength of three types of airborne bacteria, namely Staphylococcus epidermidis, Escherichia coli, and Pseudomonas alcaligenes, during toilet flushing in a custom‐built toilet under a controlled environment. Flushing was activated by a flushometer operated at two pressure levels, 400 kPa (high pressure [HP]) and 200 kPa (low pressure [LP]), and by a water cistern tank placed 95 cm (high tank [HT]) and 46 cm (low tank [LT]) above the toilet seat. The pathogens emitted by the first flush were calculated, with the correlations between airborne pathogen emissions and droplet concentration (HP, r=0.944, P<.001; LP, r=0.803, P<.001, HT, r=0.885, P<.05) and bacterial size (HP, r=−0.919, P<.001; LP, r=−0.936, P<.001; HT, r=−0.967, P<.05) in the different conditions then tested. The emission strength in the HP condition was statistically greater than that in the LP condition, whereas the cistern tank system produced less emissions than the flushometer system, and tank height was not found to be a sensitive parameter.


title: Evidence for important COVID-19 community transmission in Somalia using a clinical case definition

text: • Current COVID-19 surveillance strategies, as recommended by the World Health Organization (WHO), may be underestimating the real burden of the disease. • A clinical definition taking into account anosmia as a diagnostic symptom increases the sensitivity of the WHO clinical definition. • The proposed clinical definition can complement existing COVID-19 surveillance measures particularly in resource-poor settings where testing and contact tracing capacities are limited.


title: A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV

text: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans and camels, calling for efficient, cost-effective, and broad-spectrum strategies to control its spread. Nanobodies (Nbs) are single-domain antibodies derived from camelids and sharks and are potentially cost-effective antivirals with small size and great expression yield. In this study, we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version (NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding domain (RBD). We further tested their receptor-binding affinity, recognizing epitopes, cross-neutralizing activity, half-life, and efficacy against MERS-CoV infection. Both Nbs can be expressed in yeasts with high yield, bind to MERS-CoV RBD with high affinity, and block the binding of MERS-CoV RBD to the MERS-CoV receptor. The binding site of the Nbs on the RBD was mapped to be around residue Asp539, which is part of a conserved conformational epitope at the receptor-binding interface. NbMS10 and NbMS10-Fc maintained strong cross-neutralizing activity against divergent MERS-CoV strains isolated from humans and camels. Particularly, NbMS10-Fc had significantly extended half-life in vivo; a single-dose treatment of NbMS10-Fc exhibited high prophylactic and therapeutic efficacy by completely protecting humanized mice from lethal MERS-CoV challenge. Overall, this study proves the feasibility of producing cost-effective, potent, and broad-spectrum Nbs against MERS-CoV and has produced Nbs with great potentials as anti-MERS-CoV therapeutics. IMPORTANCE Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the in vivo half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.


title: A “One Health” Approach to Address Emerging Zoonoses: The HALI Project in Tanzania

text: Jonna Mazet and colleagues describe their work in the Tanzania-based HALI Project, which adopts the “One Health” approach to address emerging zoonoses and that recognizes the interconnectedness of human, animal, and environmental health.


title: Coronaviridae, pathogenetic and clinical aspects: An update

text: Abstract A review is given about pathogenetic and clinical aspects of the well-known as well as of recently detected members of the family Coronaviridae. Special attention is paid to coronavirus infections of domestic cattle and pets, whereas avian, murine, rat and human coronaviruses are summarized briefly.


title: Genetic characterization of S1 gene of infectious bronchitis virus isolated from commercial poultry flocks in West Java, Indonesia

text: BACKGROUND AND AIM: Infectious bronchitis (IB) is still a major problem among poultry industry in Indonesia, IB outbreaks continue to happen even in vaccinated flocks. The emergence of new IB virus (IBV) variants might lead to mismatching between vaccine virus strain and circulating virus strain, this may be a reason of vaccination failure. Information about circulating IBV in a region is important to decide which IB vaccine should be used. However, information about recent IBV strains which circulated in Indonesia and their genetic characters were limited; therefore, the aim of our research was to determine the genetic characterization of S1 gene of IBV isolated from commercial poultry flocks in West Java, Indonesia. MATERIALS AND METHODS: A total of 47 viral isolate samples collected from chickens with clinical sign and reduced in egg production. Six IB live vaccines were used as control, the reference vaccines represent IBV strains including H120, H52, 4/91, CR88, 233A, and 1-96. Primers XCe2+ and XCe2- were used to amplify S1 gene partially. RESULTS: Twenty-six of 47 samples showed positive result to S1 gene of IBV by reverse transcription-polymerase chain reaction. Three IBV isolates, Indonesia/K233A31/18, Indonesia/K4A9/17, and Indonesia/P3/17, were selected for nucleotide sequencing. Phylogenetic analysis of 352 nucleotides of the partial S1 gene shows that isolates Indonesia/K4A9/17 and Indonesia/K233A31/18 have 100% homology with IBV vaccine strain 4/91, while isolate Indonesia/P3/17 has 100% homology with IBV vaccine strain 233A. CONCLUSION: Our result indicates that at least two IBV strains were circulating among poultry in West Java, Indonesia, which is IBV close to vaccine strain 4/91 and 233A. The present study provides updates on the circulating IBV in commercial poultry flocks in West Java, Indonesia, and might use as guidance on selecting a proper IB vaccine strain to improve IB vaccination efficacy in certain region.


title: Efferocytosis and Its Associated Cytokines: A Light on Non-tumor and Tumor Diseases?

text: Billions of cells undergo turnover and die via apoptosis throughout our lifetime. A prompt clearance of these apoptotic cells and debris by phagocytic cells, a process known as efferocytosis, is important in maintaining tissue homeostasis. Accordingly, impaired efferocytosis due to the defective clearance and disrupted stages can lead to a growing number of inflammation- and immune-related diseases. Although numerous studies have shown the mechanisms of efferocytosis, its role in disorders, such as non-tumor and tumor diseases, remains poorly understood. This review summarizes the processes and signal molecules in efferocytosis, and efferocytosis-related functions in non-tumor (e.g., atherosclerosis, lung diseases) and tumor diseases (e.g., breast cancer, prostate cancer), as well as describes the role of involved cytokines. Of note, there is a dual role of efferocytosis in the abovementioned disorders, and a paradoxical effect among non-tumor and tumor diseases in terms of inflammation resolution, immune response, and disease progression. Briefly, intact efferocytosis and cytokines promote tissue repair, while they contribute to tumor progression via the tumor microenvironment and macrophage politzerization. Additionally, this review provides potential targets associated with TAM (TYRO3, AXL, MERTK) receptors and cytokines, such as tumor necrosis factor α and CXCL5, suggesting potential novel therapeutic ways in treating diseases.


title: Reply to letter: Acute‐onset smell and taste disorders in the context of Covid‐19: a pilot multicenter PCR‐based case‐control study

text: We thank our colleagues for their constructive discussion on our recently published study(1). Regarding prevalence, indeed, growing literature yields a variable frequency of loss of smell (LOS) in Covid‐19 patients, that may be hypothetically due to differences in the location and amount of viral load, to the different immune response between younger mild‐symptomatic outpatients (higher prevalence) and more severely affected inpatients (lower prevalence)(1,2), and to the variable methods of measurement.


Pregnant, uninfected, stressed, and confined in the COVID-19 period: what can we expect in the near future?


title: Advances in anti-viral immune defence: revealing the importance of the IFN JAK/STAT pathway

text: Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection. ISGs mark an elegant mechanism of anti-viral host defence that warrants renewed research focus in our global efforts to treat existing and emerging viruses. By understanding the mechanistic role of individual ISGs we anticipate the discovery of a new “treasure trove” of anti-viral mediators that may pave the way for more effective, targeted and less toxic anti-viral therapies. Therefore, with the aim of highlighting the value of the innate type 1 IFN response in our battle against viral infection, this review outlines both historic and recent advances in understanding the IFN-α JAK/STAT pathway, with a focus on new research discoveries relating to specific ISGs and their potential role in curing existing and future emergent viral infections.


title: Early risk factors of the exacerbation of Coronavirus disease 2019 pneumonia

text: The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID‐19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with SARS‐CoV‐2, including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest CT. All laboratory examination were measured within first 24 hours after admission, and chest CT were performed before admission. 56 (65.9%) patients had a history of exposure to Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID‐2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (p=0.003) and coronary heart disease (p=0.017). All severe and critical patients infected with SARS‐CoV‐2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (p<0.001). Severe and critical patients showed higher WBC count (p=0.006), NEU count (p=0.001), NEU% (p=0.002), PCT (p=0.011), CRP (p=0.003), PT (p=0.035), D‐dimer (p=0.025), AST (p=0.006), and lower LYM count (p=0.019), LYM% (p=0.001), ALB (p<0.001). Logistic regression analysis showed NEU count is a independent risk factor for deterioration, with the threshold of 6.5×10(9)·L(‐1). We concluded that the laboratory independent risk factor for the progression of COVID‐19 pneumonia is NEU count. In addition, COVID‐19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease. This article is protected by copyright. All rights reserved.


title: Antiproliferative and apoptosis inducing effect of essential oil extracted from Cyrtomium fortumei (J.) Smith leaves

text: Cyrtomium fortumei (J.) Smith is an endemic species in China, which has been proved to be an important Chinese herbal medicine. However, chemical composition and bioactivity of essential oil (EO) of C. fortumei (J.) Smith leaves remain unclear. In present study, we isolated EO from the plant by supercritical carbon dioxide extraction assay (SFE-CO(2)), and investigated on cancer cells MGC-803, MCF-7, BGC-823, Bcap-37, A375, and A549 in vitro by MTT assay. 26 compounds were identified by GC–MS analysis, and the EO showed significant antitumor activities against MGC-803, Bcap-37, and A549 cancer cell lines (IC(50) values ranging from 0.15 to 0.24 mg/mL), and the activities of its main component were also studied. Subsequent fluorescence staining and flow cytometry analysis indicated that the EO could induce apoptosis in MGC-803, Bcap-37, and A549 cell lines, and the apoptosis ratios reached 26.44 % after 48 h of treatment at 0.15 mg/mL in MGC-803 cells. Caspase 3 activity in MGC-803 cells was also determined when the cells treated with the oil, and the activity of caspase 3 enzyme was increased compared to the control. This study suggests that the EO isolated from C. fortumei (J.) Smith could inhibit the growth of human carcinoma cells, and it could induce apoptosis of cancer cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-014-1244-1) contains supplementary material, which is available to authorized users.


Current Applications of Artificial Intelligence for COVID‐19


title: An Evaluation of Neurosurgical Resident Education and Sentiment During the COVID-19 Pandemic: A North American Survey

text: ABSTRACT Background The COVID-19 pandemic has had a tremendous impact on the healthcare system. Due to restrictions in elective surgery and social distancing guidelines, the training curriculum for neurosurgical trainees is rapidly evolving. This evolution may have significant long-term effects on the training of neurosurgery residents. Objective To assess the impact of COVID-19 on neurosurgical training programs and residents. Methods A survey consisting of thirty-one questions assessing changes to resident clinical and educational workload and their sentiment on how these changes may affect their careers was distributed electronically to neurosurgery residents in the United States and Canada. Results The survey respondents were spread over 29 states and Canada and were relatively evenly spread across all levels of residency. Nearly 82% reported that the inpatient and outpatient volumes were either greatly (44.0%) or moderately (37.8%) reduced. Greater than 91% reported that their work responsibilities or access to the hospital had been reduced with a significant reduction in work hours and a significant increase in resident didactics (p <.001). Senior residents expressed concern about their educational experience as well as their future career prospects as a result of the pandemic. Conclusion Universally, residents have experienced reduced work hours and reduction in their operative case volumes. Programs have adapted by increasing didactic time and using electronic platforms. It is quite possible that this remarkable time period will prompt a critical re-appraisal of the pre-COVID-19 adequacy of educational content in our training programs, and that enhanced educational efforts driven by this pandemic may be lasting.


title: Airborne pathogen isolation capability in emergency departments of US children's hospitals

text: The requirement for negative pressure isolation procedures has been an accepted component of pediatric care to protect patients and staff from highly infectious respiratory agents. Surveys regarding airborne isolation were distributed to 43 pediatric emergency departments at US children's hospitals with 26 responses. There was a median of 5 airborne isolation rooms, a median of 4 of those with negative pressure, and 61% without an ante-room. Capacity to manage pediatric patients infected with a highly pathogenic airborne-transmitted organism during an epidemic is limited.


title: Contagion modeling between the financial and insurance markets with time changed processes

text: Abstract This study analyzes the impact of contagion between financial and non-life insurance markets on the asset–liability management policy of an insurance company. The indirect dependence between these markets is modeled by assuming that the assets return and non-life insurance claims are led respectively by time-changed Brownian and jump processes, for which stochastic clocks are integrals of mutually self-exciting processes. This model exhibits delayed co-movements between financial and non-life insurance markets, caused by events like natural disasters, epidemics, or economic recessions.


title: Emergence and control of infectious diseases in China

text: Summary Infectious diseases remain the major causes of morbidity and mortality in China despite substantial progress in their control. China is a major contributor to the worldwide infectious disease burden because of its population size. The association of China with the rest of the world through travel and trade means that events in the country can affect distant populations. The ecological interaction of people with animals in China favours the emergence of new microbial threats. The public-health system has to be prepared to deal with the challenges of newly emerging infectious diseases and at the same time try to control existing diseases. To address the microbial threats, such as severe acute respiratory syndrome, the government has committed substantial resources to the implementation of new strategies, including the development of a real-time monitoring system as part of the infectious-disease surveillance. This strategy can serve as a model for worldwide surveillance and response to threats from infectious diseases.


title: Are antiphospholipid antibodies associated with thrombotic complications in critically ill COVID-19 patients?

text: • The prevalence of aPL antibodies is poorly documented in ICU COVID-19 patients. • LA based on dRVVT system was positive in 85% of critically ill COVID-19 patients. • LA was not associated with thrombotic complications. • The prevalence of elevated anticardiolipin IgG/M/anti-beta2-GPI IgG was of 12%.


title: Surgical Helmets and SARS Infection

text: Performance testing of two brands of surgical helmets indicated that their efficiency at in vivo filtration of sub–micrometer-sized particles is inadequate for their use as respirators. These helmets are not marketed for respiratory protection and should not be used alone for protection against severe acute respiratory syndrome when performing aerosol-generating procedures.


title: HTLV-3/4 and simian foamy retroviruses in humans: Discovery, epidemiology, cross-species transmission and molecular virology

text: Abstract Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons.


title: Pandemic Influenza and Excess Intensive-Care Workload

text: In the Netherlands a major part of preparedness planning for an epidemic or pandemic consists of maintaining essential public services, e.g., by the police, fire departments, army personnel, and healthcare workers. We provide estimates for peak demand for healthcare workers, factoring in healthcare worker absenteeism and using estimates from published epidemiologic models on the expected evolution of pandemic influenza in relation to the impact on peak surge capacity of healthcare facilities and intensive care units (ICUs). Using various published scenarios, we estimate their effect in increasing the availability of healthcare workers for duty during a pandemic. We show that even during the peak of the pandemic, all patients requiring hospital and ICU admission can be served, including those who have non–influenza-related conditions. For this rigorous task differentiation, clear hierarchical management, unambiguous communication, and discipline are essential and we recommend informing and training non-ICU healthcare workers for duties in the ICU.


title: Infection control and biosecurity in equine disease control

text: Infectious diseases are an important cause of morbidity and mortality in horses, along with economic costs and broader impacts associated with the loss of members of a species that generates income, acts as a working animal and is a companion. Endemic diseases continue to challenge, emerging diseases are an ever‐present threat and outbreaks can be both destructive and disruptive. While infectious diseases can never be completely prevented, measures can be introduced to restrict the entry of pathogens into a population or limit the implications of the presence of a pathogen. Objective research regarding infection control and biosecurity in horses is limited, yet a variety of practical infection prevention and control measures can be used. Unfortunately, infection control can be challenging, because of the nature of the equine industry (e.g. frequent horse movement) and endemic pathogens, but also because of lack of understanding or motivation to try to improve practices. Recognition of the basic concepts of infection control and biosecurity, and indeed the need for measures to control infectious diseases, is the foundation for successful infection prevention and control.


title: MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells

text: RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C), a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions.


Open data in a deeply connected world


title: Influenza A(H1N1)pdm09 epidemiology in the Eastern Province of Saudi Arabia

text: Abstract Objectives The influenza A(H1N1)pdm09 virus caused a worldwide pandemic in 2009–2010 and has since remained in seasonal circulation. This study was conducted to determine any variations in the influenza A(H1N1)pdm09 status according to sex, age group, sample type, or location within the Eastern Province of the Kingdom of Saudi Arabia. Methods Samples from 749 patients with suspected Middle East respiratory coronavirus who presented to Johns Hopkins Aramco Healthcare facilities in the Eastern Province of Saudi Arabia were tested reflexively for influenza A/H1N1 2009 by the Ministry of Health using the RealTime ready Influenza A/H1N1 Detection Set for real-time PCR. The sample types included nasopharyngeal swabs (n=677), expectorated deep cough sputum (n=32), induced sputum (n=17), and tracheal aspirates (n=23). Results The incidence of influenza A(H1N1)pdm09 was higher among younger patients; 27.94% of patients in the 0–19-year age group tested positive compared to only 3.51% of patients in the ≥80-year age group. The incidence of influenza A(H1N1)pdm09 was higher in Ras Tanura city compared to other locations in the Eastern Province. Conclusions Younger individuals in the Eastern Province of the Kingdom of Saudi Arabia had a relatively higher risk of influenza A(H1N1)pdm09 infection. Additionally, an outbreak of influenza A(H1N1)pdm09 may have occurred in Ras Tanura city between April 2015 and February 2016.


title: Cutaneous manifestations of SARS‐CoV‐2 infection: a clinical update

text: On March 11(th), 2020, the World Health Organization (WHO) has declared the novel coronavirus disease (COVID‐19) a global pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 virus). A consistent number of case reports and clinical series have been already published describing a complex spectrum of skin manifestations associated with the SARS‐CoV‐2 infection. We carried out a review of the English‐language literature up to May 20th 2020, reporting original cases or case series of the cutaneous manifestations of SARS‐CoV‐2 virus infection. The following databases were consulted PubMed, Embase, Google Scholar, ResearchGate. The search of papers was conducted by using the key term ‘COVID‐19’ or ‘SARS‐CoV‐2’ or ‘coronavirus’ combined with each of the following: ‘skin’, ‘cutaneous’, ’dermatologic’ or ‘dermatology’, ‘manifestation’, ‘lesions,’ or ‘rash.’ The patterns of dermatological manifestations associated with SARS‐CoV‐2 infection could be classified into four categories: exanthema (varicella‐like, papulo‐vesicular and morbilliform rash), vascular (chilblain‐like, purpuric/petechial and livedoid lesions), urticarial and acro‐papular eruption. Lastly, other skin manifestations to be considered are the cutaneous adverse reactions to the drugs prescribed for the treatment of COVID‐19. Whether SARS‐CoV‐2 infection can directly cause a worsening of chronic inflammatory diseases such as psoriasis or atopic dermatitis remains to be determined. Dermatology’s outlook in the COVID‐19 pandemic is multidimensional.


title: IFN-γ– and IL-10–expressing virus epitope-specific Foxp3(+) T reg cells in the central nervous system during encephalomyelitis

text: Foxp3(+) CD4 regulatory T cells (T reg cells) are important in limiting immunopathology in infections. However, identifying pathogen-specific epitopes targeted by these cells has been elusive. Using MHC class II/peptide tetramers and intracellular cytokine staining, we identify T reg cells recognizing two virus-specific CD4 T cell epitopes in the coronavirus-infected central nervous system as well as naive T cell precursor pools. These T reg cells are detected at the same time as effector T cells (T eff cells) exhibiting the same specificity and can suppress T eff cell proliferation after stimulation with cognate peptide. These virus-specific T reg cells may be especially effective in inhibiting the immune response during the peak of infection, when virus antigen is maximal. Furthermore, these T reg cells express both IL-10 and IFN-γ after peptide stimulation. IFN-γ expression is maintained during both acute and chronic phases of infection. Identification of T reg cell target epitopes by cytokine production is also applicable in autoimmune disease because myelin oligodendrocyte glycoprotein–specific Foxp3(+) T reg cells express IL-10 and IL-17 at the peak of disease in mice with experimental autoimmune encephalomyelitis. These results show that pathogen epitope-specific Foxp3(+) T reg cells can be identified on the basis of cytokine production.


title: First-time Diabetic Ketoacidosis in Type 2 Diabetics with COVID-19 Infection: A Novel Case Series

text: Abstract Background SARS-CoV-2 is a novel coronavirus first diagnosed in US hospitals in January 2020. Typical presenting symptoms include fever, dry cough, dyspnea, and hypoxia. However, several other symptoms have been reported, including fatigue, weakness, diarrhea, and abdominal pain. We have identified a series of patients with diabetic ketoacidosis (DKA) likely precipitated by COVID-19. Case Series We describe five patients with previously known type 2 diabetes and no history of DKA, who presented to the emergency department with new-onset DKA and COVID-19. Why should an emergency physician be aware of this? Diabetes mellitus is a known risk factor for poor outcomes in viral respiratory illnesses, including COVID-19. Infection may precipitate DKA in patients with type 2 diabetes. Aggressive management of these patients is recommended; however, management guidelines have not yet been put forth for this unique subset of patients.


title: Pharmaceutical and preclinical evaluation of Advax adjuvant as a dose-sparing strategy for ant venom immunotherapy

text: Abstract A major challenge in broader clinical application of Jack Jumper ant venom immunotherapy (JJA VIT) is the scarcity of ant venom which needs to be manually harvested from wild ants. Adjuvants are commonly used for antigen sparing in other vaccines, and thereby could potentially have major benefits to extend JJA supplies if they were to similarly enhance JJA VIT immunogenicity. The purpose of this study was to evaluate the physicochemical and microbiological stability and murine immunogenicity of low-dose JJA VIT formulated with a novel polysaccharide adjuvant referred to as delta inulin or Advax™. Jack Jumper ant venom (JJAV) protein stability was assessed by UPLC-UV, SDS-PAGE, SDS-PAGE immunoblot, and ELISA inhibition. Diffraction light scattering was used to assess particle size distribution of Advax; pH and benzyl alcohol quantification by UPLC-UV were used to assess the physicochemical stability of JJAV diluent, and endotoxin content and preservative efficacy test was used to investigate the microbiological properties of the adjuvanted VIT formulation. To assess the effect of adjuvant on JJA venom immunogenicity, mice were immunised four times with JJAV alone or formulated with Advax adjuvant. JJA VIT formulated with Advax was found to be physicochemically and microbiologically stable for at least 2 days when stored at 4 and 25 °C with a trend for an increase in allergenic potency observed beyond 2 days of storage. Low-dose JJAV formulated with Advax adjuvant induced significantly higher JJAV-specific IgG than a 5-fold higher dose of JJAV alone, consistent with a powerful allergen-sparing effect. The pharmaceutical data provides important guidance on the formulation, storage and use of JJA VIT formulated with Advax adjuvant, with the murine immunogenicity studies providing a strong rationale for a planned clinical trial to test the ability of Advax adjuvant to achieve 4-fold JJAV dose sparing in JJA-allergic human patients.


Post-Intensive Care Syndrome and COVID-19: crisis after a crisis?


title: Molecular epidemiology of infectious bronchitis virus and avian metapneumovirus in Greece

text: Respiratory diseases like infectious bronchitis virus (IBV) and avian metapneumovirus (aMPV) have been held accountable for major losses for poultry production. Nevertheless, scarce information was present dealing with the prevalence and molecular epidemiology of these infections in Greece and the efficacy of currently applied control strategies. To fill this gap, a specific epidemiological study was designed. A total of 106 broiler and layer farms, including 10 backyard and 96 commercial flocks, were sampled between March 2016 and May 2017, and the obtained tracheal swabs were tested for IBV and aMPV using RT-PCR based techniques followed by sequencing. For each farm, data regarding production type, flock features, clinical signs, and vaccination program were also recorded. Different associations between vaccination protocol, production type, animal category, birds density, age, presence of clinical signs, and IBV and/or aMPV infection were tested. Both IBV and aMPV field strain prevalence were proven high, approximately 20 and 30%, respectively, being the GI-19 lineage (14 out of 19; 73.6%) and B subtype (30 out of 30; 100%), the most commonly detected IBV and aMPV genetic types. Infection with IBV field strains was significantly associated with clinical sign presence (odds ratio = 8.55 [95CI = 2.17–42.90]). Remarkably, only the vaccination protocol involving a double vaccination at 1 D of age was proven protective against IBV-induced symptomatology, with the odds of developing disease being 4.14 [95CI = 1.34–14.51] times lower. No association was demonstrated between aMPV infection and clinical outbreaks or between aMPV and IBV detection, suggesting the marginal role of the former pathogen in poultry farming. Globally, the present study provides the first detailed investigation of the epidemiological scenario of 2 viruses traditionally considered of pivotal relevance in poultry farming and demonstrates that remarkable benefits could be obtained with just minor adjustments in vaccination protocols.


title: Indian Publications on SARS-CoV-2: A bibliometric study of WHO COVID-19 database

text: BACKGROUND & AIMS: Nowadays, the whole World is under threat of Coronavirus disease (COVID-19). The ongoing COVID-19 pandemic has resulted in many fatalities and forced scientific communities to foster their Research and Development (R&D) activities. As a result, there is an enormous growth of scholarly literature on the subject. We here in this study have assessed the Indian publications contributions on COVID-19. METHODS: WHO is curating global scientific literature on coronavirus since it declared COVID-19 a global pandemic through Global Research Database on COVID-19. The present study analyzed Indian publications on SARS-CoV-2 as found in WHO COVID-19 database. The research data was restricted for the period of March 2, 2020 to May 12, 2020. RESULTS: The study found that there is a considerable and constant growth of Indian publications on COVID-19 from mid-April. It is interesting to note that, the most prolific authors belong to either AIIMS or ICMR institutes. Delhi state contributed highest number of publications on COVID-19. The AIIMS, New Delhi was the most productive institution in terms of publications. The Indian Journal of Medical Research has emerged as the productive journal contributing highest number of the publications. In terms of research area, the majority of the publications were related to Epidemiology. CONCLUSIONS: The highly cited publications were of evidenced based studies. It is observed that the studies pertaining to virology, diagnosis and treatment, clinical features etc. have received highest citations than general studies on epidemiology or pandemic.


title: Isolation of a novel viral agent associated with porcine reproductive and neurological syndrome and reproduction of the disease

text: Abstract Disease outbreaks characterized by reproductive failure and/or neurologic disorders, which are commonly referred as “Porcine Reproductive and Neurologic Syndrome (PRNS)”, were observed in many swine farms in Iowa and other states. Although an infectious cause was suspected to account for the disease, no conclusive diagnosis had been reached with respect to conventional infectious agents. Extensive laboratory diagnostic investigation on suspect cases repeatedly resulted in the isolation of a cytopathic enveloped virus of 50–60nm in size from nervous and second lymphoid tissues and sera and, to reflect its unknown identity, named “Virus X”. The presence of virus particle with morphological characteristics similar to Virus X in tissues from affected animals was also observed on thin-section positive-staining electron microscopy. Isolates of Virus X were not readily recognized by antibodies raised against any known viruses pathogenic to swine but by antisera collected from animals surviving clinical episode, indicating that Virus X is likely a previously unrecognized agent. Pregnant sows experimentally inoculated with Virus X (ISUYP604671) or homogenate (filtrate) of tissues from a clinically affected animal developed clinical signs and pathological changes similar to field observations including the loss of pregnancy. Furthermore, caesarian-derived, colostrum-deprived young pigs developed mild encephalomyelitis lesions in brains after experimental inoculation with the virus or the tissue homogenate although clinical neurologic signs were not observed. More importantly, Virus X was re-isolated from all inoculated animals while control pigs remained negative for the virus during the study. Collectively, Virus X is a novel viral agent responsible for PRNS and remains to be further characterized for taxonomical identity.


title: Clinical Outcomes Associated With Respiratory Virus Detection Before Allogeneic Hematopoietic Stem Cell Transplant

text: Background. The management of respiratory virus infections prior to hematopoietic cell transplant (HCT) is difficult. We examined whether respiratory virus detection before HCT influenced the requirement for bronchoscopy, hospitalization, and overall survival following HCT. Methods. Pre-HCT and weekly post-HCT nasal washes were collected through day 100 from patients with and without symptoms. Samples were tested by multiplex polymerase chain reaction for respiratory syncytial virus, parainfluenza viruses 1–4, influenza A and B, human metapneumovirus, adenovirus, and human rhinoviruses, coronaviruses, and bocavirus. Results. Of 458 patients, 116 (25%) had respiratory viruses detected pre-HCT. Overall, patients with viruses detected pre-HCT had fewer days alive and out of the hospital and lower survival at day 100 (adjusted hazard ratio [aHR], 2.4; 95% confidence interval [CI], 1.3–4.5; P = .007) than patients with negative samples; this risk was also present with rhinovirus alone (aHR for mortality, 2.6; 95% CI, 1.2–5.5; P = .01). No difference in bronchoscopy incidence was seen in patients with and without respiratory viruses (aHR, 1.3; 95% CI, .8–2.0; P = .32). In symptomatic patients, those with respiratory viruses detected had increased overall mortality compared with patients without viruses detected (unadjusted HR, 3.5; 95% CI, 1.0–12.1; P = .05); among asymptomatic patients, detection of respiratory viruses was not associated with increased mortality. Conclusions. These data support routine testing for respiratory viruses among symptomatic patients before HCT, and delay of transplant with virus detection when feasible, even for detection of rhinovirus alone. Further study is needed to address whether asymptomatic patients should undergo screening for respiratory virus detection before HCT.


title: YouTube as a source of information on COVID-19: a pandemic of misinformation?

text: INTRODUCTION: The COVID-19 pandemic is this century’s largest public health emergency and its successful management relies on the effective dissemination of factual information. As a social media platform with billions of daily views, YouTube has tremendous potential to both support and hinder public health efforts. However, the usefulness and accuracy of most viewed YouTube videos on COVID-19 have not been investigated. METHODS: A YouTube search was performed on 21 March 2020 using keywords ‘coronavirus’ and ‘COVID-19’, and the top 75 viewed videos from each search were analysed. Videos that were duplicates, non-English, non-audio and non-visual, exceeding 1 hour in duration, live and unrelated to COVID-19 were excluded. Two reviewers coded the source, content and characteristics of included videos. The primary outcome was usability and reliability of videos, analysed using the novel COVID-19 Specific Score (CSS), modified DISCERN (mDISCERN) and modified JAMA (mJAMA) scores. RESULTS: Of 150 videos screened, 69 (46%) were included, totalling 257 804 146 views. Nineteen (27.5%) videos contained non-factual information, totalling 62 042 609 views. Government and professional videos contained only factual information and had higher CSS than consumer videos (mean difference (MD) 2.21, 95% CI 0.10 to 4.32, p=0.037); mDISCERN scores than consumer videos (MD 2.46, 95% CI 0.50 to 4.42, p=0.008), internet news videos (MD 2.20, 95% CI 0.19 to 4.21, p=0.027) and entertainment news videos (MD 2.57, 95% CI 0.66 to 4.49, p=0.004); and mJAMA scores than entertainment news videos (MD 1.21, 95% CI 0.07 to 2.36, p=0.033) and consumer videos (MD 1.27, 95% CI 0.10 to 2.44, p=0.028). However, they only accounted for 11% of videos and 10% of views. CONCLUSION: Over one-quarter of the most viewed YouTube videos on COVID-19 contained misleading information, reaching millions of viewers worldwide. As the current COVID-19 pandemic worsens, public health agencies must better use YouTube to deliver timely and accurate information and to minimise the spread of misinformation. This may play a significant role in successfully managing the COVID-19 pandemic.


title: Endoscopy during the Covid-19 outbreak: experience and recommendations from a single center in a high-incidence scenario

text: Abstract A dramatic SARS-Cov-2 outbreak is hitting Italy hard. To face the new scenario all the hospitals have been re-organised in order to reduce all the outpatient services and to devote almost all their personnel and resources to the management of Covid-19 patients. As a matter of fact, all the services have undergone a deep re-organization guided by: the necessity to reduce exams, to create an environment that helps reduce the virus spread, and to preserve the medical personnel from infection. In these days a re-organization of the endoscopic unit, sited in a high-incidence area, has been adopted, with changes to logistics, work organization and patients selection. With the present manuscript, we want to support gastroenterologists and endoscopists in the organization of a “new” endoscopy unit that responds to the “new” scenario, while remaining fully aware that resources availability and local circumstances may extremely vary from unit to unit.


title: The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets

text: An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.


title: The Crisis Close at Hand: How COVID-19 Challenges Long-Term Care Planning for Adults with Intellectual Disability

text: Whether cared for in the community or in a facility, adults with intellectual disability are among the most vulnerable individuals in the United States. Families caring for these individuals face financial, social, and emotional stress as they navigate long-term care choices for their loved ones. COVID-19 has stressed an already overwhelmed and disparate system.


title: Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

text: Middle East respiratory syndrome coronavirus (MERS‐CoV) is caused by a novel betacoronavirus that was isolated in late 2012 in Saudi Arabia. The viral infections have been reported in more than 1700 humans, ranging from asymptomatic or mild cases to severe pneumonia with a mortality rate of 40%. It is well documented now that dromedary camels contract the infection and shed the virus without notable symptoms, and such animals had been infected by at least the early 1980s. The mechanism of camel to human transmission is still not clear, but several primary cases have been associated with camel contact. There is no approved antiviral drug or vaccine against MERS‐CoV despite the active research in this area. Vaccine candidates have been developed using various platforms and regimens and have been tested in several animal models. Here, this article reviews the published studies on MERS‐CoV vaccines with more focus on vaccines tested in large animals, including camels. It is foreseeable that the 1‐health approach could be the best way of tackling the MERS‐CoV endemic in the Arabian Peninsula, by using the mass vaccination of camels in the affected areas to block camel to human transmission. Camel vaccines can be developed in a faster time with fewer regulations and lower costs and could clear this virus from the Arabian Peninsula if accompanied by efficient public health measures.


title: Roadblocks to translational challenges on viral pathogenesis

text: Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the “Herrenhausen Symposia” series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind—to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.


title: Benserazide, the first allosteric inhibitor of Coxsackievirus B3 3C protease

text: Abstract Coxsackievirus B3 is the main cause of human viral myocarditis and cardiomyopathy. Virally encoded Coxsackievirus 3C protease (3Cpro) plays an essential role in viral proliferation. Here, benserazide was discovered as a novel inhibitor from a drug library screen targeting Coxsackievirus 3Cpro using a FRET-based enzyme assay. Benserazide, whose chemical structure has no electrophilic functional groups, was characterized as a non-competitive inhibitor by enzyme kinetic studies. A molecular docking study with benserazide and its analogs indicated that a novel putative allosteric binding site was involved. Specifically, a 2,3,4-trihydroxybenzyl moiety was determined to be a key pharmacophore for the enzyme’s inhibitory activity. We suggest that the putative allosteric binding site may be a novel target for future therapeutic strategies.


title: Treatment of cats with feline infectious peritonitis

text: Abstract Feline infectious peritonitis (FIP) infection resulting in clinical signs is invariably fatal despite clinical intervention. As FIP is an immune-mediated disease, treatment is mainly aimed at controlling the immune response triggered by the infection with the feline coronavirus (FCoV). Immune suppressive drugs such as prednisone or cyclophosphamide may slow disease progression but do not produce a cure. In nearly every published case report of attempted therapy for clinical FIP, glucocorticoids have been used; there are, however, no controlled studies that evaluate the effect of glucocorticoids as a therapy for FIP. Some veterinarians prescribe immune modulators to treat cats with FIP with no documented controlled evidence of efficacy. It has been suggested that these agents may benefit infected animals by restoring compromised immune function, thereby allowing the patient to control viral burden and recover from clinical signs. However, a non-specific stimulation of the immune system may be contraindicated as clinical signs develop and progress as a result of an immune-mediated response to the mutated FCoV.


title: Structural characterization of Mumps virus fusion protein core

text: Abstract The fusion proteins of enveloped viruses mediating the fusion between the viral and cellular membranes comprise two discontinuous heptad repeat (HR) domains located at the ectodomain of the enveloped glycoproteins. The crystal structure of the fusion protein core of Mumps virus (MuV) was determined at 2.2Å resolution. The complex is a six-helix bundle in which three HR1 peptides form a central highly hydrophobic coiled-coil and three HR2 peptides pack against the hydrophobic grooves on the surface of central coiled-coil in an oblique antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human respiratory syncytium virus, forms typical 3-4-4-4-3 spacing. The similar charecterization in HR1 regions, as well as the existence of O–X–O motif in extended regions of HR2 helix, suggests a basic rule for the formation of the fusion core of viral fusion proteins.


Rice revitalization and food sovereignty in Sabah


title: Early computed tomography for acute post-traumatic diffuse axonal injury: a systematic review

text: PURPOSE: Diffuse axonal injury (DAI) is the rupture of multiple axons due to acceleration and deceleration forces during a closed head injury. Most traumatic brain injuries (TBI) have some degree of DAI, especially severe TBI. Computed tomography (CT) remains the first imaging test performed in the acute phase of TBI, but has low sensitivity for detecting DAI, since DAI is a cellular lesion. The aim of this study is to search in the literature for CT signs, in the first 24 h after TBI, that may help to differentiate patients in groups with a better versus worst prognosis. METHODS: We searched for primary scientific articles in the PubMed database, in English, indexed since January 1st, 2000. RESULTS: Five articles were selected for review. In the DAI group, traffic accidents accounted 70% of the cases, 79% were male, and the mean age was 41 years. There was an association between DAI and intraventricular hemorrhage (IVH) and traumatic subarachnoid hemorrhage (tSAH); an association between the IVH grade and number of corpus callosum lesions; and an association between blood in the interpeduncular cisterns (IPC) and brainstem lesions. CONCLUSION: In closed TBI with no tSAH, severe DAI is unlikely. Similarly, in the absence of IVH, any DAI is unlikely. If there is IVH, patients generally are clinically worse; and the more ventricles affected, the worse the prognosis.


title: Coding-Complete Genome Sequence of SARS-CoV-2 Isolate from Bangladesh by Sanger Sequencing.

text: A coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate was revealed. The sample for the virus was isolated from a female patient from Dhaka, Bangladesh, suffering from coronavirus disease-2019 (COVID-19).


title: 6. Asthma

text: Abstract The increasing incidence and prevalence of asthma in many parts of the world continue to make it a global health concern. The heterogeneous nature of the clinical manifestations and therapeutic responses of asthma in both adult and pediatric patients indicate that it may be more of a syndrome rather than a specific disease entity. Numerous triggering factors including viral infections, allergen and irritant exposure, and exercise, among others, complicate both the acute and chronic treatment of asthma. Therapeutic intervention has focused on the appreciation that airway obstruction in asthma is composed of both bronchial smooth muscle spasm and variable degrees of airway inflammation characterized by edema, mucus secretion, and the influx of a variety of inflammatory cells. The presence of only partial reversibility of airflow obstruction in some patients indicates that structural remodeling of the airways may also occur over time. Choosing appropriate medications depends on the disease severity (intermittent, mild persistent, moderate persistent, severe persistent), extent of reversibility, both acutely and chronically, patterns of disease activity (exacerbations related to viruses, allergens, exercise, etc), and the age of onset (infancy, childhood, adulthood). (J Allergy Clin Immunol 2003;111:S502-19.)


title: Early efforts in modeling the incubation period of infectious diseases with an acute course of illness

text: The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period. After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.


title: The vital role of science in global policy decision-making: An analysis of past, current, and forecasted trends and issues in global red meat trade and policy

text: Abstract As global populations and economies change, the dynamics of global trade and policy change as well. In analyzing the past trends and projections for global populations, economic developments, animal product production and consumption, global trade policy, and current issues being faced, one can begin to make some predictions or projections as to how the global red meat and poultry infrastructure will change and, more importantly, point to areas where a proactive approach is necessary to shape these changes to meet the most globally beneficial end. Many issues face the global red meat industry, from food safety to animal disease, and are becoming more and more complicated as consumer knowledge increases and as politics intervene. Internationalized science is key and vital in the future of global trade policy as science can address the more informed consumer in a manner, which reduces anxiety over unknowns. The role of the industry is to provide the information and knowledge to the consumer necessary to convey the validity of globally accepted standards, which relate to ensuring consumer safety, animal welfare, and provide assurances that these standards are being met within the production sector.


title: The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes

text: G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Evaluation of the thermal stability of the LTR G-quadruplexes in different-length oligonucleotides showed that the protein is fit to be most active in the LTR full-length environment. When hnRNP A2/B1 was silenced in cells, LTR activity decreased, indicating that the protein acts as a HIV-1 transcription activator. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. These findings provide a deeper understanding of the viral transcription mechanism and may pave the way to the development of drugs effective against the integrated HIV-1, present both in actively and latently infected cells.


Tocilizumab En Niño Con Leucemia Linfoblástica Aguda Y Síndrome De Liberación De Citoquinas Asociado A Covid-19


title: Oral efficacy of Vero cell attenuated porcine epidemic diarrhea virus DR13 strain

text: Abstract A Vero cell attenuated porcine epidemic diarrhea virus (PEDV) strain, DR13, was distinguished from wild-type PEDV using restriction enzyme fragment length polymorphism (RFLP). Cell attenuated DR13 was orally or intramuscularly (IM) administered to late-term pregnant sows, and mortality resulting from the highly virulent PEDV challenge was investigated in passively immunized suckling piglets of the two different groups. The mortality rate of the oral group (13%) was lower than that of the IM group (60%). In particular, the concentration of IgA against PEDV was higher in piglets of sows in the oral group, compared to the IM group. The attenuated DR13 virus remained safe, even after three backpassages in piglets. The findings of this study support the theory that the Vero cell attenuated DR13 virus may be applied as an oral vaccine for inducing specific immunity in late-term pregnant sows with a high margin of protection against PEDV infection.


title: Determinants of the Taiwanese tourist hotel industry cycle

text: This paper contributes to the tourism literature by examining determinants of the Taiwanese tourist hotel industry (THI) cycle. This study uses a Markov-switching model (MSM) proposed by Hamilton (1989) to analyze the Taiwanese tourist hotel industry cycle. The MSM decomposes the tourist hotel industry cycle into two distinct states: high-growth and low-growth (HGS and LGS). The mean growth rate of HGS is 1.5% and the average growth rate of LGS is 0.07% during the period from December 1999 to February 2011. The corresponding standard deviations in the two regimes are 0.008% and 0.038%, implying that HGS is more stable than LGS. Moreover, the probability of staying in HGS is 94% and the probability of remaining in LGS is 65%. The expected durations of HGS and LGS are about 16 and 3 months, respectively. Further, the paper investigates the factors that keep the THI in HGS. Empirical test results show that growth in the international tourism market and industrial production growth rate are two key factors that keep the THI in HGS, but the SARS outbreak in 2003 has had an adverse effect.


title: Reemergence of an Unusual Disease: The Chikungunya Epidemic

text: Since the beginning of 2006, a crippling mosquito-borne disease has shown an explosive emergence in nations in the Indian Ocean area. By March 7, 2006, 157,000 people had been infected in the French island La Réunion, and the disease had spread to the islands of Seychelles, Mauritius, and Mayotte (French). Subsequently, the disease appeared in India, China, and European countries. The World Health Organization is taking measures to assist in fighting the epidemic. This article describes the disease, its recent emergence, and the current epidemic.


World Health Organization Global Conference on Severe Acute Respiratory Syndrome


title: The Role of Lung and Gut Microbiota in the Pathology of Asthma

text: Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.


title: Novel 1-[5-(4-bromophenoxy)pentyl]-3-(2-arylamino- 2-oxoethyl)uracils and their antiviral properties

text: The title compounds were prepared from 1-[5-(4-bromophenoxy) pentyl]uracil by the introduction of N-arylacetamide moiety at the 3-position, the better approach involving the use of N-aryl-2-chloroacetamides as the reactants. Antiviral activity of the obtained compounds was estimated.


title: Self-management strategies to consider to combat endometriosis symptoms during the COVID-19 pandemic

text: The care of patients with endometriosis has been complicated by the coronavirus disease 2019 (COVID-19) pandemic. Medical and allied healthcare appointments and surgeries are being temporarily postponed. Mandatory self-isolation has created new obstacles for individuals with endometriosis seeking pain relief and improvement in their quality of life. Anxieties may be heightened by concerns over whether endometriosis may be an underlying condition that could predispose to severe COVID-19 infection and what constitutes an appropriate indication for presentation for urgent treatment in the epidemic. Furthermore, the restrictions imposed due to COVID-19 can impose negative psychological effects, which patients with endometriosis may be more prone to already. In combination with medical therapies, or as an alternative, we encourage patients to consider self-management strategies to combat endometriosis symptoms during the COVID-19 pandemic. These self-management strategies are divided into problem-focused and emotion-focused strategies, with the former aiming to change the environment to alleviate pain, and the latter address the psychology of living with endometriosis. We put forward this guidance, which is based on evidence and expert opinion, for healthcare providers to utilize during their consultations with patients via telephone or video. Patients may also independently use this article as an educational resource. The strategies discussed are not exclusively restricted to consideration during the COVID-19 pandemic. Most have been researched before this period of time and all will continue to be a part of the biopsychological approach to endometriosis long after COVID-19 restrictions are lifted.


title: COVID-19 and Fake News in the Dominican Republic

text: The first case of novel coronavirus disease (COVID-19) in the Dominican Republic coincided with a period of political crisis. Distrust in governmental institutions shaped the critical phase of early response. Having a weak public health infrastructure and a lack of public trust, the Ministry of Health (MoH) began the fight against COVID-19 with a losing streak. Within 45 days of the first reported case, the political crisis and turmoil caused by “fake news” are limiting the capacity and success of the MoH response to the pandemic.


title: RNA binding property and RNA chaperone activity of dengue virus core protein and other viral RNA‐interacting proteins

text: In this study we showed that the dengue virus (DENV) core protein forms a dimer with an α‐helix‐rich structure, binds RNA and facilitates the strand annealing process. To assess the RNA chaperone activity of this core protein and other dengue viral RNA‐interacting proteins, such as NS3 helicase and NS5 proteins, we engineered cis‐ and trans‐cleavage hammerhead ribozyme constructs carrying DENV genomic RNA elements. Our results indicate that DENV core protein facilitates typical hammerhead structure formation by acting as an RNA chaperone and DENV NS5 has a weak RNA chaperone activity, while DENV NS3 helicase failed to refold RNA with a complex secondary structure.


title: A Novel High-Throughput Vaccinia Virus Neutralization Assay and Preexisting Immunity in Populations from Different Geographic Regions in China

text: BACKGROUND: Pre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China. METHODOLOGY/PRINCIPAL FINDINGS: A new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, cross-sectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30–55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significant difference observed for titer or prevalence by gender, age range and geographic origin. CONCLUSION: A simplified, sensitive, standardized, reproducible, and high-throughput assay was developed for the quantitation of NAbs against different Vaccinia strains. The current study provides useful insights for the future development of VTT-based vaccination in Beijing and Anhui provinces of China.