title: Haematological parameters in severe acute respiratory syndrome

text: Clinical presentation of severe acute respiratory syndrome (SARS) is non‐specific and isolation of all suspected patients is difficult because of the limited availability of isolation facilities. We studied changes in haematological parameters in SARS patients using median values analysed according to the day of symptom onset. White cell (WCC), absolute neutrophil, absolute lymphocyte (ALC) and platelet counts followed a v‐shaped trend with the nadir at day 6 or 7 after symptom onset except for ALC in the ICU group that had not reached the nadir by day 12. None of our patients had a platelet count < 80 × 10(9)/l and WCC < 2 × 10(9)/l in the first 5 days of symptoms and these parameters may allow early stratification of febrile patients into likely and unlikely SARS cases to allow effective utilization of isolation facilities. On multivariate analysis, age is the only independent predictor for ICU admission.


title: Antimicrobial and Antioxidant Activities of Essential Oils of Satureja thymbra Growing Wild in Libya

text: The composition of essential oil isolated from Satureja thymbra, growing wild in Libya, was analyzed by GC and GC-MS. The essential oil was characterized by γ-terpinene (39.23%), thymol (25.16%), p-cymene (7.17%) and carvacrol (4.18%) as the major constituents. Antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. It possessed strong antioxidant activity (IC50 = 0.0967 mg/mL). The essential oil was also screened for its antimicrobial activity against eight bacterial and eight fungal species, showing excellent antimicrobial activity against the microorganisms used, in particular against the fungi. The oil of S. thymbra showed bacteriostatic activity at 0.001–0.1 mg/mL and was bactericidal at 0.002–0.2 mg/mL; fungistatic effects at 0.001–0.025 mg/mL and fungicidal effects at 0.001–0.1 mg/mL. The main constituents thymol, carvacrol and γ-terpinene also showed strong antimicrobial activity. The commercial fungicide bifonazole showed much lower antifungal activity than the tested oil.


Effects of age and sex on recovery from COVID-19: Analysis of 5,769 Israeli patients


title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes

text: Human coronavirus OC43 (HCoV-OC43) is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.


title: Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression

text: BACKGROUND: Recurrent respiratory infections are one of the most important causes of morbidity in childhood. When immune functions are still largely immature, the airway epithelium plays a primary defensive role since, besides providing a physical barrier, it is also involved in the innate and the adaptive immune responses. A study was therefore designed to evaluate in vitro whether pidotimod, a synthetic dipeptide able to stimulate the inflammatory and immune effector cells, could activate bronchial epithelial cell functions involved in response to infections. METHODS: BEAS-2B cell line (human bronchial epithelial cells infected with a replication-defective Adenovirus 12-SV40 virus hybrid) were cultured in the presence of pidotimod, with or without tumor necrosis factor (TNF)-α or zymosan to assess: a) intercellular adhesion molecule (ICAM)-1 expression, by flow cytometry; b) toll-like receptor (TLR)-2 expression and production, by immunofluorescence flow cytometry and western blotting; d) interleukin (IL)-8 release, by enzyme-linked immunosorbent assay (ELISA); e) activated extracellular-signal-regulated kinase (ERK1/2) phosphorylation and nuclear factor-kappa B (NF-kB) activation, by western blotting. RESULTS: The constitutive expression of ICAM-1 and IL-8 release were significant up-regulated by TNF-α (ICAM-1) and by TNF-α and zymosan (IL-8), but not by pidotimod. In contrast, an increased TLR-2 expression was found after exposure to pidotimod 10 and 100 μg/ml (p < 0.05) and to the association pidotimod 100 μg/ml + TNF-α (p < 0.05). Western blot analysis substantiated that the constitutive TLR-2 expression was significantly increased after exposure to all the stimuli. Finally, while a remarkable inhibition of TNF-α -induced ERK1/2 phosphorylation was observed in the presence of pidotimod, both TNF-α and pidotimod were effective in inducing NF-kB protein expression in the cytoplasm and its nuclear translocation. CONCLUSION: Through different effects on ERK1/2 and NF-kB, pidotimod was able to increase the expression of TLR-2 proteins, surface molecules involved in the initiation of the innate response to infectious stimuli. The lack of effect on ICAM-1 expression, the receptor for rhinovirus, and on IL-8 release, the potent chemotactic factor for neutrophils (that are already present in sites of infection), may represent protective functions. If confirmed in vivo, these activities may, at least in part, clarify the mechanism of action of this molecule at airway level.


title: Patent pools and clearinghouses in the life sciences

text: The biopharmaceutical industry is slowly absorbing the idea of collaborative patent licensing models. Recently, two patent pools for developing countries have been launched: the Pool for Open Innovation against Neglected Tropical Diseases initiated by GlaxoSmithKline (GSK), which is referred to as the BIO Ventures for Global Health (BVGH) pool, and the Medicines Patent Pool (MPP) initiated by UNITAID. Various organizations have recommended using pools or clearinghouses beyond the humanitarian dimension where many patents are owned by many different actors. As a first attempt, MPEG LA, which administers patent pools in various technology fields, is now setting up a clearinghouse for patents related to molecular diagnostics. These examples as well as the results from an empirical study provide useful insights for the design and administration of future pools and clearinghouses in the life sciences.


title: Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.


title: To mask or not to mask children to overcome COVID-19

text: It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child’s will must not be forced. Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation.


Psychological trauma of Middle East Respiratory Syndrome victims and bereaved families


Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Background Severe acute respiratory syndrome (SARS) is a newly emerged infection from a novel coronavirus (SARS-CoV). Apart from fever and respiratory complications, acute renal impairment has been observed in some patients with SARS. Herein, we describe the clinical, pathologic, and laboratory features of the acute renal impairment complicating this new viral infection. Methods We conducted a retrospective analysis of the plasma creatinine concentration and other clinical parameters of the 536 SARS patients with normal plasma creatinine at first clinical presentation, admitted to two regional hospitals following a major outbreak in Hong Kong in March 2003. Kidney tissues from seven other patients with postmortem examinations were studied by light microscopy and electron microscopy. Results Among these 536 patients with SARS, 36 (6.7%) developed acute renal impairment occurring at a median duration of 20 days (range 5–48 days) after the onset of viral infection despite a normal plasma creatinine level at first clinical presentation. The acute renal impairment reflected the different prerenal and renal factors that exerted renal insult occurring in the context of multiorgan failure. Eventually, 33 SARS patients (91.7%) with acute renal impairment died. The mortality rate was significantly higher among patients with SARS and acute renal impairment compared with those with SARS and no renal impairment (91.7% vs. 8.8%) (P < 0.0001). Renal tissues revealed predominantly acute tubular necrosis with no evidence of glomerular pathology. The adjusted relative risk of mortality associated with the development of acute renal impairment was 4.057 (P < 0.001). By multivariate analysis, acute respiratory distress syndrome and age were the most significant independent risk factors predicting the development of acute renal impairment in SARS. Conclusion Acute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS.


title: Modelling the transmission of healthcare associated infections: a systematic review

text: BACKGROUND: Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time. METHODS: MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings. RESULTS: In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries. The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data. CONCLUSIONS: Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models.


title: Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis)

text: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.


title: Methods for the recovery of a model virus from healthcare personal protective equipment

text: Aims: To develop methods for recovering a model virus (bacteriophage MS2) from healthcare personal protective equipment (PPE). Methods and Results: Nine eluents were evaluated for recovery of infectious MS2 from PPE: 1·5% beef extract (BE) pH 7·5 with and without 0·1% Tween 80, 1·5% BE pH 9·0 with and without 0·1% Tween 80, 3% BE pH 7·5 with and without 0·1% Tween 80, 3% BE pH 9·0 with and without 0·1% Tween 80 and PBS with 0·1% Tween 80. Methods were applied to experimentally contaminated PPE. Elution followed by two‐step enrichment assay could recover virus inputs as low as 1·5 log(10), and could recover >90% of inoculated virus from used items of experimentally contaminated PPE worn by human volunteers. Conclusions: BE was effective for recovering infectious viruses from a range of PPE materials. Significance and Impact of the Study: PPE plays a crucial role in interrupting transmission of infectious agents from patients to healthcare workers (HCWs). The fate of micro‐organisms when PPE is removed and disposed of has important consequences for infection control. Methods described here can be used to conduct rigorous studies of viral survival and transfer on PPE for risk assessments in infection control and HCW protection.


docid: thsmrnrc

title: The role of RNA pseudoknot stem 1 length in the promotion of efficient −1 ribosomal frameshifting 1 1 Edited by D. E. Draper

text: Abstract The ribosomal frameshifting signal present in the genomic RNA of the coronavirus infectious bronchitis virus (IBV) contains a classic hairpin-type RNA pseudoknot that is believed to possess coaxially stacked stems of 11 bp (stem 1) and 6 bp (stem 2). We investigated the influence of stem 1 length on the frameshift process by measuring the frameshift efficiency in vitro of a series of IBV-based pseudoknots whose stem 1 length was varied from 4 to 13 bp in single base-pair increments. Efficient frameshifting depended upon the presence of a minimum of 11 bp; pseudoknots with a shorter stem 1 were either non-functional or had reduced frameshift efficiency, despite the fact that a number of them had a stem 1 with a predicted stability equal to or greater than that of the wild-type IBV pseudoknot. An upper limit for stem 1 length was not determined, but pseudoknots containing a 12 or 13 bp stem 1 were fully functional. Structure probing analysis was carried out on RNAs containing either a ten or 11 bp stem 1; these experiments confirmed that both RNAs formed pseudoknots and appeared to be indistinguishable in conformation. Thus the difference in frameshifting efficiency seen with the two structures was not simply due to an inability of the 10 bp stem 1 construct to fold into a pseudoknot. In an attempt to identify other parameters which could account for the poor functionality of the shorter stem 1-containing pseudoknots, we investigated, in the context of the 10 bp stem 1 construct, the influence on frameshifting of altering the slippery sequence-pseudoknot spacing distance, loop 2 length, and the number of G residues at the bottom of the 5′-arm of stem 1. For each parameter, it was possible to find a condition where a modest stimulation of frameshifting was observable (about twofold, from seven to a maximal 17 %), but we were unable to find a situation where frameshifting approached the levels seen with 11 bp stem 1 constructs (48-57 %). Furthermore, in the next smaller construct (9 bp stem 1), changing the bottom four base-pairs to G·C (the optimal base composition) only stimulated frameshifting from 3 to 6 %, an efficiency about tenfold lower than seen with the 11 bp construct. Thus stem 1 length is a major factor in determining the functionality of this class of pseudoknot and this has implications for models of the frameshift process.


title: Clinical Features of Coronavirus Disease 2019 Patients With Mechanical Ventilation: A Nationwide Study in China

text: OBJECTIVES: The outbreak of coronavirus disease 2019 is becoming a worldwide pandemic. Mechanical ventilation is lifesaving for respiratory distress, this study was designed to delineate the clinical features of the coronavirus disease 2019 patients with mechanical ventilation from a national cohort in China. DESIGN: Prospective observational study. SETTING: The rapid spread of severe acute respiratory syndrome coronavirus 2 has infected more than 7.7 million people and caused more than 423,000 deaths. PATIENTS: Adult hospitalized coronavirus disease 2019 patients with mechanical ventilation from 557 hospitals from China. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From a nationwide cohort, 141 coronavirus disease 2019 cases with mechanical ventilation were extracted from 1,590 cases. Cigarette smoke, advanced age, coexisting chronic illness, elevated systolic blood pressure, high body temperature, and abnormal laboratory findings are common in these ventilated cases. Multivariate regression analysis showed that higher odds of in-hospital death was associated with invasive mechanical ventilation requirement (hazard ratio: 2.95; 95% CI, 1.40–6.23; p = 0.005), and coexisting chronic obstructive pulmonary disease (hazard ratio, 4.57; 95% CI, 1.65–12.69; p = 0.004) and chronic renal disease (hazard ratio, 5.45; 95% CI, 1.85–16.12; p = 0.002). Compared with patients with noninvasive mechanical ventilation, patients who needs invasive mechanical ventilation showed higher rate of elevated d-dimer (> 1.5 mg/L) at admission (hazard ratio, 3.28, 95% CI, 1.07–10.10; p = 0.039). CONCLUSIONS: The potential risk factors of elevated d-dimer level could help clinicians to identify invasive mechanical ventilation requirement at an early stage, and coexisting chronic obstructive pulmonary disease or chronic renal disease are independent risk factors associated with fatal outcome in coronavirus disease 2019 patients with mechanical ventilation.


title: Did viral disease of humans wipe out the Neandertals?

text: Neandertals were an anatomically distinct hominoid species inhabiting a vast geographical area ranging from Portugal to western Siberia and from northern Europe to the Middle East. The species became extinct 28,000 years ago, coinciding with the arrival of anatomically modern humans (AMHs) in Europe 40,000 years ago. There has been considerable debate surrounding the main causes of the extinction of Neandertals. After at least 200,000 years of successful adaption to the climate, flora and fauna of Eurasia, it is not clear why they suddenly failed to survive. For many years, climate change or competition with anatomically modern human (AMH) have been the leading hypotheses. Recently these hypotheses have somewhat fallen out of favour due to the recognition that Neandertals were a highly developed species with complex social structure, culture and technical skills. Were AMHs lucky and survived some catastrophe that eradicated the Neandertals? It seems unlikely that this is the case considering the close timing of the arrival of AMHs and the disappearance of Neandertals. Perhaps the arrival of AMHs also brought additional new non-human microscopic inhabitants to the regions where Neandertals lived and these new inhabitants contributed to the disappearance of the species. We introduce a medical hypothesis that complements other recent explanations for the extinction of Neandertals. After the ancestors of Neandertals left Africa, their immune system adapted gradually to the pathogens in their new Eurasian environment. In contrast, AMHs continued to co-evolve with east African pathogens. More than 200,000 years later, AMHs carried pathogens that would have been alien to pre-historic Europe. First contact between long separated populations can be devastating. Recent European and American history provides evidence for similar events, where introduction of viral, protozoan or bacterial pathogens to immunologically naïve populations lead to mass mortality and local population extinction. We propose that a virus, possibly from the family Herpesviridae, contributed to Neandertal extinction.


title: Presence of rhinovirus in the respiratory tract of adolescents and young adults with asthma without symptoms of infection

text: Abstract Background Viral respiratory infections have been associated with up to 80% of wheezing episodes and asthma exacerbations. However, studies on the role of these viruses in asthmatic patients in the interval between exacerbations are sparse. This study aimed to determine the presence of respiratory viruses, without symptoms of infection, in the airways of young asthmatics as compared to healthy controls. Material and Methods Patients 10–35 years of age with stable asthma and a group of healthy controls were analyzed regarding the presence of RNA from common respiratory viruses in nasopharyngeal aspirates by PCR. Self-reported asthma control and quality of life, fraction of exhaled nitric oxide (FeNO), spirometry, and bronchial responsiveness to methacholine were recorded. Blood samples were collected to assess IgE sensitisation and eosinophil cationic protein (ECP) levels. Results In 354 patients with asthma and 108 healthy controls, human rhinovirus (HRV) was the only virus detected (4.5% of asthmatics vs. 0.9% of controls; p = 0.08). HRV+ asthma patients had a higher degree of aeroallergen IgE sensitisation (median 37.7 vs. 10.4 kUA/L, p = 0.04), and a tendency for higher levels of serum ECP (median 17.2 vs. 12.6 μg/L, p = 0.07), as compared to their HRV− counterparts. Conclusions Absence of symptoms of respiratory tract infection notwithstanding, HRV seems to be more prevalent in the airways of adolescents and young adults with asthma and a high degree of aeroallergen IgE sensitisation than in controls. The presence of HRV seems also to be related to systemic eosinophilic inflammation despite ongoing treatment with inhaled corticosteroids.


title: Commentary on ‘Interventions to improve antibiotic prescribing practices in ambulatory care’

text: This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Arnold SR, Straus SE. Interventions to improve antibiotic prescribing practices in ambulatory care. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD003539. DOI: 10.1002/14651858.CD003539.pub2. Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Characteristics and Key Findings Tables articles. Copyright © 2006 John Wiley & Sons, Ltd.


title: Management of COVID-19 Outbreak in Argentina: The Beginning

text: The aim of this study was to analyze the impact coronavirus disease 2019 (COVID-19) had in Argentina during its initial stage, identify the measures taken to try to mitigate its impact, and briefly compare it with the influenza A H1N1 pandemic in 2009. This is a descriptive study. Pandemics constitute a serious problem to global health with a major impact on the affected countries’ populations. The recent COVID-19 outbreak represents one of the most important viral pandemics lately. It reached Argentina 64 days after the first case was identified in China. Since then, several measures were taken by the Argentinian government to try to mitigate its impact in this initial stage. An updated report of the current situation and its management in different countries is of vital importance regarding global health issues and may serve for feedback and decision-making.


title: A serological survey of canine respiratory coronavirus in New Zealand

text: Aims: To determine the seroprevalence of canine respiratory coronavirus (CRCoV) in New Zealand dogs, and to explore associations with age, sex, breed, month, and geographical region of sampling and reported presence of clinical signs suggestive of respiratory disease. Methods: A total of 1,015 canine serum samples were randomly selected from submissions to a diagnostic laboratory between March and December 2014, and were analysed for CRCoV antibodies using a competitive ELISA. Logistic regression analysis was used to determine associations between seroprevalence of CRCoV and breed category, age, sex, sampling month, region, and reported health status of dogs. Results: Overall, 538/1,015 (53.0%) samples were seropositive for CRCoV, with 492/921 (53.4%) positive dogs in the North Island and 46/94 (49%) in the South Island. Age of dog, sampling month, region, and presence of abnormal respiratory signs were included in the initial logistic regression model. Seroprevalence was higher in dogs aged ≥3 compared with ≤2 years (p < 0.01). The lowest seroprevalence was observed in July (30/105; 28.5%) and August (32/100; 32%), and the highest in June (74/100; 74%). Seroprevalence in dogs from Auckland was higher than in dogs from the Hawkes Bay, Manawatu, Marlborough, and Waikato regions (p < 0.05). Abnormal respiratory signs (coughing, nasal discharge, or sneezing) were reported for 28/1,015 (2.8%) dogs sampled. Seroprevalence for CRCoV tended to be higher among dogs with respiratory signs (67.9 (95% CI = 47.6–83.4)%) than dogs with no reported respiratory signs (52.6 (95% CI = 49.5–55.7)%). Conclusions: Serological evidence of infection with CRCoV was present in more than half of the dogs tested from throughout New Zealand. Differences in CRCoV seroprevalence between regions and lack of seasonal pattern indicate that factors other than external temperatures may be important in the epidemiology of CRCoV in New Zealand. Clinical relevance: Our data suggest that CRCoV should be included in investigations of cases of infectious canine tracheobronchitis, particularly if these occur among dogs vaccinated with current vaccines, which do not include CRCoV antigens.


title: Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis

text: Abstract Objectives To provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)—BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays—on the detection of viral respiratory infections. Methods A comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay. Results Twenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848–0.949), 0.949 (95% confidence interval, 0.882–0.979) and 0.954 (95% confidence interval, 0.871–0.985), respectively. The three mPCRs were comparable in terms of detection of FluA. Conclusions Point estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.


title: Frequency of tuberculosis among diabetic patients in the People’s Republic of China

text: The People’s Republic of China has nearly the highest incidence of both diabetes mellitus (DM) and tuberculosis (TB) worldwide. DM increases the risk of TB by two to three times and adversely affects TB treatment outcomes. The increasing epidemic of DM in the People’s Republic of China is due to decreased physical activity, unhealthy diet, and obesity. Over the last 20 years, the excellent free China National Tuberculosis Program has been set up, and the “DOTS” (directly observed treatment + short-course chemotherapy) model for TB control has successfully reduced the burden of TB, but the disease is still a considerable problem. Given the high burden of TB and DM in the People’s Republic of China and the relationship between the two diseases, it is sensible to screen DM patients for TB. A bidirectional screening of the two diseases was conducted in the People’s Republic of China from 2011 to 2012, which identified a TB incidence in patients with DM of about 958 per 100,000. Here, we report the findings of our recent study on the incidence of TB among diabetic patients in the People’s Republic of China. The data agree with those of previous reports.


title: A pilot study of the antiviral activity of anionic and cationic polyamidoamine dendrimers against the Middle East respiratory syndrome coronavirus

text: The Middle East respiratory syndrome coronavirus (MERS‐CoV) is an emerging virus that causes infection with a potentially fatal outcome. Dendrimers are highly branched molecules that can be added to antiviral preparations to improve their delivery, as well as their intrinsic antiviral activity. Studies on identifying anti‐MERS‐CoV agents are few. Three types of polyanionic dendrimers comprising the terminal groups sodium carboxylate (generations 1.5, 2.5, 3.5, and 4.5), hydroxyl (generations 2, 3, 4, and 5), and succinamic acid (generations 2, 3, 4, and 5) and polycationic dendrimers containing primary amine (generations 2, 3, 4, and 5) were used to assess their antiviral activity with the MERS‐CoV plaque inhibition assay. The hydroxyl polyanionic set showed a 17.36% to 29.75% decrease in MERS‐CoV plaque formation. The most potent inhibition of MERS‐CoV plaque formation was seen by G(1.5)‐16COONa (40.5% inhibition), followed by G(5)‐128SA (39.77% inhibition). In contrast, the cationic dendrimers were cytotoxic to Vero cells. Polyanionic dendrimers can be added to antiviral preparations to improve the delivery of antivirals, as well as the intrinsic antiviral activity.


title: Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle

text: Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts.


title: The potential of RNA interference-based therapies for viral infections

text: RNA interference (RNAi) is a natural mechanism in cells that suppresses or silences the expression of aberrant or foreign genes. This activity is being developed as a potential antiviral therapeutic strategy. Studies in vitro, and some in vivo, appear to show the feasibility of using RNAi to treat virus infection. Therapeutic use of RNAi seems to be promising when directed against viruses that cause localized acute infections in accessible target cells. Therapeutic strategies using RNAi against viruses that cause chronic infections, such as HIV, hepatitis B virus, or hepatitis C virus, are more difficult to design, but studies have begun to address identifiable problems. Two clinical trials using RNAi have recently been initiated—one phase II trial against respiratory syncytial virus and a phase I trial against HIV. It will be of much interest to see whether nucleic acid therapies can offer another route to treating viral infection.


title: Deciphering desirable immune responses from disease models with resistant and susceptible chickens

text: Coccidiosis and necrotic enteritis (NE) are among the most significant diseases affecting the poultry industry. These diseases have become more prominent in the wake of policies to reduce the use of antibiotics in animal production. This has led to more research focused on better understanding the immune system and its responses to pathogen challenge, and thus developing informed strategies to exploit immune responses that can support enhanced disease resistance and growth performance. Some chicken breeds and lines show greater resistance or susceptibility to various diseases, and thus these birds maybe able to shed light on immune processes or pathways that contribute to the more resistant/susceptible state. This review attempts to identify potentially important genes that show some consistency in (relative) up or downregulation in key tissues between the resistant and susceptible chickens. For coccidiosis and NE, relative downregulation of IL-10 and (slightly less consistently) upregulation of IFN-γ appear to be features of more resistant birds. Data for IFN-α, IL-12, and IL-17D are currently less consistent. Gene expression data from NE studies have identified some potentially interesting, perhaps less well understood, immune-related genes (e.g., TCF12, BCL2, IRF2, TRAF3, TAB3, etc.,) that maybe associated with the resistant and/or susceptible phenotype. Salmonella and Campylobacter are important foodborne pathogens harbored by the chicken intestinal tract, while infectious bursal disease and infectious bronchitis are also important viral diseases of poultry. We, therefore, consider whether there are consistent features from resistant/susceptible disease models with these pathogens that relate to findings from the coccidiosis and NE studies. It is not anticipated that ideal immune responses to these pathogens will be identical but rather that consistent elements maybe identified that could help inform breeding or alternative strategies to support general disease resistance and enhanced (and efficient) flock productivity.


title: 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members

text: Cellular mRNA of higher eukaryotes and many viral RNA are methylated at the N-7 and 2′-O positions of the 5′ guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability 1, the function of 2′-O methylation has remained uncertain since its discovery 35 years ago 2-4. Here, we show that a West Nile virus (WNV) mutant (E218A) that lacks 2′-O MTase activity was attenuated in wild type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signaling. 2′-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISG) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2′-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and specifically, IFIT proteins. Our results demonstrate that the 2′-O methylation of the 5′ cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2′-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA likely serves as a paradigm for pattern recognition and restriction of propagation of foreign viral RNA in host cells.


docid: xbszmiql

title: An in vitro study of theaflavins extracted from black tea to neutralize bovine rotavirus and bovine coronavirus infections

text: Abstract Crude theaflavin was extracted from black tea and then fractionated by HPLC into five components (initial peaks (IP), TF1, TF2A, TF2B, and TF3). The crude extract and the various fractions of theaflavin were collected and tested, individually and in combination, for antirotaviral activity. The mean effective concentration (EC50) was calculated and compared. Activity varied from the most active being the uncharacterized theaflavin-like initial peaks (IP) with an EC50 of 0.125μg/ml to the least active being theaflavin-3 monogallate (TF2A) with an EC50 of 251.39μg/ml. The combination of TF1+TF2A+TF2B+TF3 was more active than the sum of the activities of these four fractions individually, indicating synergism among the peaks. Only the crude extract was assayed for activity against coronavirus; the EC50 was 34.7μg/ml.


title: Determination and analysis of the full-length chicken parvovirus genome

text: Abstract Viral enteric disease in poultry is an ongoing problem in many parts of the world. Many enteric viruses have been identified in turkeys and chickens, including avian astroviruses, rotaviruses, reoviruses, and coronaviruses. Through the application of a molecular screening method targeting particle-associated nucleic acid (PAN), we recently described the detection and partial characterization of a novel enteric parvovirus in chickens. Subsequent surveys of intestinal homogenates from turkeys and chickens in the United States revealed widespread occurrence of parvovirus in poultry. Here we report the first full genome sequence of a novel chicken parvovirus, ChPV ABU-P1. ChPV ABU-P1 genome organization, predicted amino acid sequence, and phylogenetic relationships with other described parvoviruses are discussed.


title: Response to: Sore throat in COVID‐19: comment on “Clinical characteristics of hospitalized patients with SARS‐CoV‐2 infection: A single arm meta‐analysis”

text: We thank Andrea Lovato et al for their letter, which was written in response to our recent meta-analysis published in the journal[1] . From the news, we learned that the heroic Italian people are fighting the Corona Virus Disease 2019 (COVID-19) tenaciously. We wish you a great victory in this battle. This article is protected by copyright. All rights reserved.


title: The Boeing 737 MAX: Lessons for Engineering Ethics

text: The crash of two 737 MAX passenger aircraft in late 2018 and early 2019, and subsequent grounding of the entire fleet of 737 MAX jets, turned a global spotlight on Boeing’s practices and culture. Explanations for the crashes include: design flaws within the MAX’s new flight control software system designed to prevent stalls; internal pressure to keep pace with Boeing’s chief competitor, Airbus; Boeing’s lack of transparency about the new software; and the lack of adequate monitoring of Boeing by the FAA, especially during the certification of the MAX and following the first crash. While these and other factors have been the subject of numerous government reports and investigative journalism articles, little to date has been written on the ethical significance of the accidents, in particular the ethical responsibilities of the engineers at Boeing and the FAA involved in designing and certifying the MAX. Lessons learned from this case include the need to strengthen the voice of engineers within large organizations. There is also the need for greater involvement of professional engineering societies in ethics-related activities and for broader focus on moral courage in engineering ethics education.


COVID-19, syphilis and biologic therapies for psoriasis and psoriatic arthritis: A word of caution


Relevance of SARS-CoV E Protein Ion Channel Activity in Virus Pathogenesis


title: Rapid implementation of an evidence‐based remote triaging system for assessment of suspected referrals and patients with head and neck cancer on follow‐up after treatment during the COVID‐19 pandemic: Model for international collaboration

text: BACKGROUND: Outpatient telemedicine consultations are being adopted to triage patients for head and neck cancer. However, there is currently no established structure to frame this consultation. METHODS: For suspected referrals with cancer, we adapted the Head and Neck Cancer Risk Calculator (HaNC‐RC)‐V.2, generated from 10 244 referrals with the following diagnostic efficacy metrics: 85% sensitivity, 98.6% negative predictive value, and area under the curve of 0.89. For follow‐up patients, a symptom inventory generated from 5123 follow‐up consultations was used. A customized Excel Data Tool was created, trialed across professional groups and made freely available for download at http://www.entintegrate.co.uk/entuk2wwtt, alongside a user guide, protocol, and registration link for the project. Stakeholder support was obtained from national bodies. RESULTS: No remote consultations were refused by patients. Preliminary data from 511 triaging episodes at 13 centers show that 77.1% of patients were discharged directly or have had their appointments deferred. DISCUSSION: Significant reduction in footfall can be achieved using a structured triaging system. Further refinement of HaNC‐RC‐V.2 is feasible and the authors welcome international collaboration.


title: Isotope-edited IR spectroscopy for the study of membrane proteins

text: Fourier transform infrared (FTIR) spectroscopy has long been a powerful tool for structural analysis of membrane proteins. However, because of difficulties in resolving contributions from individual residues, most of the derived measurements tend to yield average properties for the system under study. Isotope editing, through its ability to resolve individual vibrations, establishes FTIR as a method that is capable of yielding accurate structural data on individual sites in a protein.


title: The role of transplant during a pandemic

text: This month's installment of “The AJT Report” explores the role of the transplant community in the wider healthcare framework as both entities navigate the challenges of COVID‐19. We also report on the Centers for Medicare & Medicaid Services’ recently proposed updates to the Organ Procurement Organization Conditions for Coverage.


title: Impact of multiplex molecular assay turn-around-time on antibiotic utilization and clinical management of hospitalized children with acute respiratory tract infections

text: Abstract Background Empiric antibiotic treatment is common among children with acute respiratory tract infections (ARTI), despite infections being predominately viral. The use of molecular respiratory panel assays has become increasingly common for medical care of patients with ARTIs. Study design This was a 6-year retrospective, single-centered study of pediatric inpatients who tested positive for an ARTI respiratory pathogen. We examined the relationship between clinical outcomes and whether the patient was tested using the Luminex Respiratory Viral Panel ([RVP]; in-use: Dec. 2009 – Jul. 2012) or Biofire Respiratory Pathogen Panel ([RP]; in-use Aug. 2012 – Jun. 2016). The prevalence and duration of pre-test empiric antibiotics, post-test oseltamivir administration to influenza patients, chest x-rays and length of stay between the two assays was compared. Results A total of 5142 patients (1264 RVP; 3878 RP) were included. The median laboratory turn-around-time for RP was significantly shorter than RVP (1.4 vs. 27.1 h, respectively; p < .001). Patients tested with RP were less likely to receive empiric antibiotics (OR: 0.45; p < .001; 95% CI: 0.39, 0.52) and had a shorter duration of empiric broad-spectrum antibiotics (6.4 h vs. 32.9 h; p < .001) compared to RVP patients. RP influenza patients had increased oseltamivir use post- test compared to RVP influenza patients (OR: 13.56; p < .001; 95% CI: 7.29, 25.20). Conclusions Rapid molecular testing positively impacts patient management of ARTIs. Adopting assays with a shorter turn-around-time improves decision making by decreasing empirical antibiotic use and duration, decreasing chest x-rays, increasing timely oseltamivir administration, and reducing length of stay.


title: Managing childhood allergies and immunodeficiencies during respiratory virus epidemics – The 2020 COVID‐19 pandemic: A statement from the EAACI‐section on pediatrics

text: While the world is facing an unprecedented pandemic with COVID‐19, patients with chronic diseases need special attention and if warranted adaptation of their regular treatment plan. In children, allergy and asthma are among the most prevalent non‐communicable chronic diseases, and healthcare providers taking care of these patients need guidance. At the current stage of knowledge, children have less severe symptoms of COVID‐19, and severe asthma and immunodeficiency are classified as risk factors. In addition, there is no evidence that currently available asthma and allergy treatments, including antihistamines, corticosteroids, and bronchodilators, increase the risk of severe disease from COVID‐19. Most countries affected by COVID‐19 have opted for nationwide confinement, which means that communication with the primary clinician is often performed by telemedicine. Optimal disease control of allergic, asthmatic, and immunodeficient children should be sought according to usual treatment guidelines. This statement of the EAACI Section on Pediatrics puts forward six recommendations for the management of childhood allergies and immunodeficiencies based on six underlying facts and existing evidence.


title: Anesthetic Management of Patients Undergoing Aortic Dissection Repair With Suspected Severe Acute Respiratory Syndrome Coronavirus-2 Infection

text: Severe acute respiratory syndrome coronavirus-2 is still active in Wuhan, China, and is spreading to the rest of the world. Recently, perioperative anesthetic management in patients with suspected or confirmed coronavirus-2 has been reported. However, little has been reported on the anesthetic management of patients undergoing aortic dissection repair in patients with suspected severe acute respiratory syndrome coronavirus-2 infection. During the outbreak in Wuhan, the authors’ team completed 4 cases of aortic dissection repair successfully in patients with suspected severe acute respiratory syndrome coronavirus-2 infection. The purpose of the present report is to summarize current knowledge and experiences on anesthetic management in this patient population and to provide clinical practice guidelines on anesthetic management and infection prevention and control in these critically ill patients.


title: Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy

text: The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to April 28(th) 2020 Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy Selected patients were referred from the North of Italy The aim of our study was to evaluate the clinical course of COVID-19 in this setting We evaluated 385 consecutive patients (220 males, 57%;median age 61 years, IQR 48-69);331 (86%) received solid organ transplantation and 54 (14%) had a RMD CNIs were the only immunosuppressant administered in 47 patients (12%) We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%) Twelve patients were hospitalized and two of them died, both with severe comorbidities No patients developed acute respiratory distress syndrome or infectious complications The surviving 10 patients are now fully recovered The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low


docid: hzfawetp

title: N-Propargylated isatin-Mannich mono- and bis-adducts: Synthesis and preliminary analysis of in vitro activity against Tritrichomonas foetus

text: Cu(I)Cl promoted synthesis of N-propargylated-isatin Mannich mono- and bis-adducts with an extension towards the synthesis of N-propargylated-isatin-7-chloroquinoline conjugates was described. The synthesized scaffolds were evaluated for their in vitro activity against the veterinary protozoal pathogen Tritrichomonas foetus and cytotoxicity against human prostate (PC-3) cancer cell line. The preliminary evaluation data revealed the enhancement in the activity profiles with the introduction of 7-chloroquinoline ring with the most active conjugates 7a, 7c and 7d exhibiting an IC(50) of 22.2, 11.3 and 24.5 μM respectively against T. foetus and minimal toxicity against human prostate (PC-3) cell lines.


title: Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways

text: Early innate and cell-intrinsic responses are essential to protect host cells against pathogens. In turn, viruses have developed sophisticated mechanisms to establish productive infections, counteracting the host innate immune responses. Increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication, as well as by sensing and transmitting signals to induce antiviral cytokines. Recent studies have pointed at new, unappreciated mechanisms of viral evasion of host innate protective responses including manipulating the host ubiquitin system. Viral inhibition of antiviral factors by ubiquitin-dependent degradation is emerging as critical evasion mechanism of the antiviral response. In addition, recent studies have uncovered new mechanisms by which viral encoded proteins inhibit ubiquitin and ubiquitin-like modification of host proteins involved innate immune signaling pathways. Here we discuss recent findings and novel strategies that viruses have developed to counteract these early innate antiviral defenses.


title: Persistent viral RNA shedding after COVID‐19 symptom resolution in older convalescent plasma donors

text: INTRODUCTION: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is responsible for a worldwide pandemic. While the medical community understands the mode of viral transmission, less is known about how long viral shedding occurs once viral symptoms have resolved. Our objective was to determine how long the SARS‐CoV‐2 remains detectable following self‐reporting of viral symptom resolution. METHODS: This study was approved by the University of Wisconsin Institutional Review Board. A cohort of patients who were previously SARS‐CoV‐2 positive less than 28 days after self‐reported symptom resolution were retested for proof of viral recovery by nasal swab reverse transcriptase polymerase chain reaction for SARS‐CoV‐2 RNA. RESULTS: A total of 152 potential participants were screened, of which 5 declined, 54 were ineligible, and 93 were recruited; 86 of 93 completed testing. Eleven of 86 (13%) were still positive at a median of 19 days (range, 12‐24 days) after symptom resolution. Positive participants were significantly older than negative participants (mean, 54 years; 95% confidence interval [CI], 44‐63 vs 42 years; 95% CI, 38‐46; P = .024). C (T) values were significantly, inversely associated with age (β = −.04; r (2) = 0.389; P = .04). The number of days since symptom recovery was not apparently different between positive and negative participants. CONCLUSION: We found evidence of persistent viral shedding in nasopharyngeal secretions more than 2 weeks after resolution of symptoms from confirmed COVID‐19 infection. Persistent shedding was more common in older participants, and viral load was higher among older positive participants. These results underscore the necessity of testing COVID‐19 convalescent plasma donors less than 28 days after symptom resolution.


title: Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

text: G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5′-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NFκB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5′-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place.


title: Gene cloning, sequencing, expression and biological activity of giant panda (Ailuropoda melanoleuca) interferon-α

text: Abstract The giant panda (Ailuropoda melanoleuca) is an endangered species and indigenous to China. In mammals, multiple subtypes of interferon-α (IFN-α) exist, most of which possess antiviral activity. Little is known about giant panda IFN-α genes and the role they may play in giant panda immunological responses to viruses. We have cloned genes encoding 12 giant panda IFN-α (AmIFN-α or AmIFNA) subtypes that share from 90 to 99% amino acid sequence identity. AmIFN-α12 has one additional amino acid at position 57, which is not present in other subtypes. Sequence identity of the AmIFN-α proteins encoded by the 12 genes compared to human IFN-α2 is approximately 58%. Unlike most of the human subtypes, each of the 12 giant panda IFN sequences has an N-glycosylation recognition site. Expression of all 12 AmIFN-α subtypes in 293 cells was confirmed by SDS-PAGE and Western blotting analysis. The antiviral activity and antiproliferative activity of each AmIFN-α subtype produced in transiently transfected 293 cell cultures were tested in vitro. All AmIFN-α subtypes were found to be stable at pH 2 or 65°C and to exhibit antiviral activity. Some IFN subtypes (AmIFN-α8 and AmIFN-α4) showed higher biological activity levels than others, whereas AmIFN-α11 exhibited lower activity. AmIFN-α had various antiproliferative activities to different target cells. To B16 cells, AmIFN-α3, AmIFN-α4, AmIFN-α8 had the highest activities, while to K562 cells, AmIFN-α3, AmIFN-α7, AmIFN-α10 had the highest activities. The various IFN-α subtypes displayed a good correlation between their antiviral and antiproliferative potencies.


title: Nearest neighbor parameters for Watson–Crick complementary heteroduplexes formed between 2′-O-methyl RNA and RNA oligonucleotides

text: Results from optical melting studies of Watson–Crick complementary heteroduplexes formed between 2′-O-methyl RNA and RNA oligonucleotides are used to determine nearest neighbor thermodynamic parameters for predicting the stabilities of such duplexes. The results are consistent with the physical model assumed by the individual nearest neighbor-hydrogen bonding model, which contains terms for helix initiation, base pair stacking and base pair composition. The sequence dependence is similar to that for Watson–Crick complementary RNA/RNA duplexes, which suggests that the sequence dependence may also be similar to that for other backbones that favor A-form RNA conformations.


title: Genotypes and antimicrobial profiles of Shigella sonnei isolates from diarrheal patients circulating in Beijing between 2002 and 2007

text: Abstract Shigella sonnei has become the dominant serotype causing shigellosis in Asian countries in recent years. In this study, we characterize the increasing trend of antibiotic resistance profiles and genotypes of S. sonnei isolates in the Beijing area. From January 2002 to December 2007, a total of 1108 Shigella isolates including 362 S. sonnei were recovered from diarrhea patients at the 302nd Hospital in Beijing. While the frequency of S. flexneri gradually decreased, S. sonnei gradually increased and became the dominant species. A total of 362 S. sonnei isolates were further analyzed for their antimicrobial profiles and 272 revived isolates were selected for genotyping analysis, respectively. High-level antimicrobial resistances were observed in sulfamethoxazole/trimethoprim (94.5%), ampicillin (40.3%), piperacillin (36.5%), and ceftriaxone (12.8%) with significant single- and multiple-drug resistance increase trends from 2002 to 2007 (P = 0.0000). Pulsed-field gel electrophoresis analysis indicated that 263 (96.7%) S. sonnei belonged to 1 clonal genotype A, which were further divided into A1–A6 subtypes. While subtype A2 was dominant in the early stage of study years, subtype A4 started to emerge and increased significantly in later years. Antimicrobial resistance rates are statistically different among the 6 subtypes (P = 0.0000), and A4 possessed the highest resistance rates to ampicillin (83.7%) and piperacillin (81.4%). Subtype A3 was highly clustered in inpatients compared to other subtypes (P = 0.0145). This study indicates that a clonal S. sonnei strain has become dominant in the Beijing area, and subtype A4 is responsible for increased antibiotic resistance.


title: Demyelinating strain of mouse hepatitis virus infection bridging innate and adaptive immune response in the induction of demyelination

text: Abstract The presence of immunoglobulin oligoclonal bands in the cerebrospinal fluid of Multiple Sclerosis (MS) patients supports the hypothesis of an infectious etiology, although the antigenic targets remain elusive. Neurotropic mouse hepatitis virus (MHV) infection in mice provides a useful tool for studying mechanisms of demyelination in a virus-induced experimental model of MS. This study uses Affymetrix microarray analysis to compare differential spinal cord mRNA levels between mice infected with demyelinating and non-demyelinating strains of MHV to identify host immune genes expressed in this demyelinating disease model. The study reveals that during the acute stage of infection, both strains induce inflammatory innate immune response genes, whereas upregulation of several immunoglobulin genes during chronic stage infection is unique to infection with the demyelinating strain. Results suggest that the demyelinating strain induced an innate-immune response during acute infection that may promote switching of Ig isotype genes during chronic infection, potentially playing a role in antibody-mediated progressive demyelination even after viral clearance.


docid: aosgiinu

title: Molecular Diagnosis of Viral Respiratory Infections

text: In clinical practice, a rapid and accurate identification of pathogens causing viral respiratory tract infections can be problematic because of nonspecific clinical presentations, lack of rapid and sensitive tests, and the emergence of new and mutating viral pathogens. Nucleic acid-targeted molecular techniques are increasingly being used to provide high sensitivity and specificity, short test turnaround time, and automatic and high-throughput processing. In-house and commercially available molecular methods have been developed to qualitatively and quantitatively detect and identify a single or a panel of clinically encountered respiratory tract viruses in a single reaction. Molecular techniques are being gradually introduced in routine laboratory diagnosis of viral respiratory tract infections. However, their performance characteristics and limitations must be clearly understood by both laboratory personnel and clinicians to ensure proper utilization and interpretation.


title: Generation of improved humanized mouse models for human infectious diseases

text: The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rg(null)) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of “next generation” humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines.


Adolescent Life in the Early Days of the Pandemic: Less and More Substance Use


title: Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay

text: Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.


title: Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis

text: Abstract Necrotizing enterocolitis remains one of the most vexing problems in the neonatal intensive care unit. Risk factors for NEC include prematurity, formula feeding, and inappropriate microbial colonization of the GI tract. The pathogenesis of NEC is believed to involve weakening of the intestinal barrier by perinatal insults, translocation of luminal bacteria across the weakened barrier, an exuberant inflammatory response, and exacerbation of the barrier damage by inflammatory factors, leading to a vicious cycle of inflammation-inflicted epithelial damage. Nitric oxide (NO), produced by inducible NO synthase (iNOS) and reactive NO oxidation intermediates play a prominent role in the intestinal barrier damage by inducing enterocyte apoptosis and inhibiting the epithelial restitution processes, namely enterocyte proliferation and migration. The factors that govern iNOS upregulation in the intestine are not well understood, which hampers efforts in developing NO/iNOS-targeted therapies. Similarly, efforts to identify bacteria or bacterial colonization patterns associated with NEC have met with limited success, because the same bacterial species can be found in NEC and in non-NEC subjects. However, microbiome studies have identified the three important characteristics of early bacterial populations of the GI tract: high diversity, low complexity, and fluidity. Whether NEC is caused by specific bacteria remains a matter of debate, but data from hospital outbreaks of NEC strongly argue in favor of the infectious nature of this disease. Studies in Cronobacter muytjensii have established that the ability to induce NEC is the property of specific strains rather than the species as a whole. Progress in our understanding of the roles of bacteria in NEC will require microbiological experiments and genome-wide analysis of virulence factors.


title: MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing

text: In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18–22 nucleotide), non-coding RNA transcripts called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.


title: Maintaining a scientific community while social distancing

text: The “Aging Science Talks: Science for the Community” daily online seminar series was established in reaction to the cancellation of a myriad of regional, national, and international meetings focused on the biology of aging due to the COVID-19 pandemic. The inability to attend scientific meetings has far-reaching implications for our field, as we lose the ability to 1) disseminate both published and non-published data through talks and posters; 2) network and establish new collaborations to produce innovative science in the aging field; and 3) continue the career development of early career researchers (ECRs). Through these virtual seminars, we hope to offset the negative effects of these canceled meetings. We established the program rapidly using a “lean” approach, making use of existing technologies broadly available at academic institutions. Here, we provide an initial description of how this program was developed and implemented. We discuss advantages and limitations of this approach, including “real-time” participation and the creation of an on/off-line community of inquiry (CoI). In the future, we hope to formally evaluate the success of this program in building engagement, creating a community, and enhancing the development of ECRs, and to capture metrics associated with the continued progress of science. Our approach to building a CoI may be applied across multiple scientific disciplines during this time of uncertainty, and may offer a valuable example of how to continue to advance science during pandemics or similar events.


Networking for BSL-3/4 laboratory scientist training


Fatal fruit bat virus sparks epidemics in southern Asia


title: Infectivity of an Asymptomatic Patient With Middle East Respiratory Syndrome Coronavirus Infection

text: During the MERS outbreak in Korea, one case of asymptomatic or mild MERS-CoV infection was noted. Eighty-two persons were exposed to the case without protection. They were isolated and RT-PCR and serology for MERS were performed. There was no transmission through an asymptomatic MERS case in this study.


title: Experimental confirmation of recombination upstream of the S1 hypervariable region of infectious bronchitis virus

text: Abstract Chimeric infectious bronchitis virus (IBV) genomes with cross-over sites in the S1 gene were generated by co-infection with two distinct IBV strains. Recombinant viruses were collected from chicken embryos, embryonic cultured cells and chickens co-infected with Ark99 and Mass41 strains and purified by differential centrifugation. The recombinant S1 genes were identified by reverse transcription polymerase chain reaction (RTPCR) using heterologous primers and confirmed by nucleotide sequencing. The recombinants with Ark99 5′ and Mass41 3′ sequences were identified following the in vitro, in ovo and in vivo co-infections. Mixed RNA extracted from Ark99 and Mass41 did not produce RTPCR products with these primers at the PCR conditions used. Cross-over sites within the amplified 580 (Mass41) or 604 (Ark99) bases of the 5′ S1 gene could only be detected between nucleotides 50 and 155. While this region, lying upstream of the S1 hypervariable region, corresponded with sites commonly identified in naturally occurring isolates, recombination sites identified in these studies could not be detected within the HVR of S1 of the genomes of chimeric viruses.


title: Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer

text: Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5’ flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA, and unwind a 5’ flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation, or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1.


title: Evolving Gene Targets and Technology in Influenza Detection

text: Influenza viruses cause recurring epidemic outbreaks every year associated with high morbidity and mortality. Despite extensive research and surveillance efforts to control influenza outbreaks, the primary mitigation treatment for influenza is the development of yearly vaccine mixes targeted for the most prevalent virus strains. Consequently, the focus of many detection technologies has evolved toward accurate identification of subtype and understanding the evolution and molecular determinants of novel and pathogenic forms of influenza. The recent availability of potential antiviral treatments are only effective if rapid and accurate diagnostic tests for influenza epidemic management are available; thus, early detection of influenza infection is still important for prevention, containment, patient management, and infection control. This review discusses the current and emerging technologies for detection and strain identification of influenza virus and their specific gene targets, as well as their implications in patient management.


title: Telemedicine and COVID‐19: 6 tips to ace your first visit

text: The COVID‐19 crisis has seen some dramatic changes to health care as we know it. In particular, one area that has seen rapid changes is the area of telemedicine. Telemedicine is not a new phenomenon. Quite the opposite. For some time now, telemedicine has been used to connect those in rural areas to providers for both medical care and behavioral health care services. Unfortunately, the conditions surrounding it have been fairly stringent and have even gone so far as to require that specific audiovisual equipment be used in order for it to qualify for reimbursement from the Centers for Medicare & Medicaid Services (CMS) and other health insurers.


Novel coronavirus (COVID‑19) epidemic: a veterinary perspective.


title: Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry

text: OBJECTIVES: COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. METHODS: Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. RESULTS: A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. CONCLUSIONS: We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.


title: Differential mortality in COVID-19 patients from India and western countries

text: BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as ‘COVID-19’, ‘Pandemics’, ‘disease outbreaks’ and ‘India’ on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.


title: MicroRNA miR-320a and miR-140 inhibit mink enteritis virus infection by repression of its receptor, feline transferrin receptor

text: Mink enteritis virus (MEV) is one of the most important pathogens in the mink industry. Recent studies have shed light into the role of microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt), as critical modulators in the host-pathogen interaction networks. We previously showed that miRNA miR-181b can inhibit MEV replication by repression of viral non-structural protein 1 expression. Here, we report that two other miRNAs (miR-320a and miR-140) inhibit MEV entry into feline kidney (F81) cells by downregulating its receptor, transferrin receptor (TfR), by targeting the 3′ untranslated region (UTR) of TfR mRNA, while being themselves upregulated.


title: Navigating environmental constraints to injection preparation: the use of saliva and other alternatives to sterile water among unstably housed PWID in London

text: BACKGROUND: The United Kingdom is experiencing an increase in drug-related deaths and serious bacterial infections among its most vulnerable citizens. Cuts to essential services, coupled with a growing homeless population, create a challenging environment to tackle this public health crisis. In this paper, we highlight an underexplored environmental constraint faced by people living and injecting drugs on the streets. Access to water for injection is restricted in the UK, due to legislative and financial barriers. Austerity measures, such as public toilet closures, further restrict the ability of people made homeless to access clean water and protect themselves from health harms. METHODS: We generated questionnaire (n = 455) and in-depth qualitative interview (n = 32) data with people who inject drugs in London for the Care and Prevent study. Participants provided detail on their life history; drug use, injecting and living environments; health conditions and care seeking practices. FINDINGS: A high proportion of the survey sample reported lifetime history of street homelessness (78%), bacterial infections (65%) and related hospitalisation (30%). Qualitative accounts highlight unsafe, potentially dangerous, injection practices in semi-public spaces. Multiple constraints to sourcing sterile water for injection preparation were reported. Alternatives to sterile water included puddle water, toilet cistern water, whisky, cola soda and saliva. Participants who injected heroin and crack cocaine together unanimously reported adding water at two stages during injection preparation: first, adding water as a vehicle for heroin (which was then heated); second, adding cold water to the heroin mixture prior to adding the crack cocaine. This new finding of a stage addition of solvent may represent an additional risk of infection. CONCLUSION: Currently, harm reduction equipment and resources for safe injecting are not meeting the needs of people who inject drugs who are street homeless or unstably housed. Preparation of injections with non-sterile water sources could precipitate bacterial and fungal infections, particularly when used without the application of heat. It is crucial that water for injection, also skin cleaning, is made available for the unstably housed and that harm reduction messaging is tailored to speak to the everyday realities of people who prepare and inject drugs in public spaces.


docid: cxyndepl

title: Multiple sclerosis: Possible immunological mechanisms

text: Abstract Multiple sclerosis is the principal demyelinating disease of the central nervous system. Although the prevalence of the disease is moderately low, averaging about 40 cases per 100,000 people in high risk areas, it is a particularly devastating disease. It primarily affects young adults, is chronic, and has an unpredictable course. Most discouraging, the cause of the disease is not known and an effective treatment has not been identified. Recently, however, research has yielded some important findings concerning the etiology of MS. Much evidence now points to an immunological process as one of the major elements in the disease. It is also likely that an environmental influence, possibly an infectious process, may contribute to the disease. Finally, it is now certain that genetic makeup influences susceptibility to the disease. At present, the strongest evidence is for a polygenic effect, not the effect of a single gene or gene locus. This review will examine some of the possible immunologically mediated disease processes that could be involved in MS, especially those that could account for a role for infectious and genetic factors in the disease.


docid: emkjwhgk

title: Leçons et perspectives concernant la prise en charge des grippes sévères depuis 2009

text: Résumé Depuis la pandémie grippale de 2009, la prise en charge des grippes sévères en réanimation a évolué : modalité de ventilation mécanique, utilisation des inhibiteurs de la neuramidase, recours précoces à l’assistance respiratoire extracorporelle. De nombreux états organisent des réseaux de surveillance épidémiologiques et un réseau de soins autour de centres référents et d’unités mobiles d’assistance. La lutte contre la grippe nosocomiale associe isolement et vaccination des personnels. Summary Since 2009 pandemic influenza, the management of severe flu has evolved in intensive care units: mechanical ventilation modalities, use of antiviral agents, early support with extracorporeal membrane oxygenation. Many countries are implementing epidemiologic monitoring and health care networks including ECMO centers. Patient's isolation and influenza vaccination prevent nosocomial outbreak of influenza.


title: Hypoglycemia at the time of Covid-19 pandemic

text: BACKGROUND: Hypoglycemia is the limiting factor in the glycemic management of diabetes, which need to be addressed critically to avoid complications. Lockdown because of new coronavirus strain (COVID-19) pandemic has further complicated the issue of hypoglycemia due to limitations in access to food, outpatient clinics, pathological services and medicines. AIM: To assess the factors associated with the risk of hypoglycemia during April–May 2020 lockdown in people with type 2 diabetes mellitus. METHODOLOGY: We analyzed the data retrospectively from 146 patients of type 2 diabetes mellitus (T2DM) reporting to the emergency department (ED) during lockdown period with symptoms suggestive of hypoglycemia. RESULTS: The majority of patients were male (90/146) with a mean age of 59.88 ± 10.09 years and a mean random blood glucose level of 57.67 ± 9.00 mg/dL. Two-third of patients (70.83%) had level 1 hypoglycemia, while level 2 hypoglycemia was reported in 29.16% of patients. A combination of Metformin and Sulfonylureas (SU) was most commonly associated with the risk of hypoglycemia (65.75%) followed by insulin (33.56%). Subjects who received insulin reported a lower blood glucose value (50.75 ± 8.20 mg/dL) as compared to those receiving a combination of metformin and SU (60.95 ± 7.10 mg/dl). 330.56% of patients who had received prophylaxis hydroxychloroquine (HCQ) 400 mg twice a day along with the routine anti-hyperglycemic agents without their dose adjustment reported hypoglycemia. Patients with hypertension, micro-vascular, macro-vascular complications, and coexistent with each other had a higher propensity to the risk of hypoglycemia (46.58%, 33.56%, 23.29%, and 32.88%) respectively. CONCLUSION: The COVID-19 lockdown has shown to influence the risk of hypoglycemia in patients with T2DM, especially those receiving SU, insulin, HCQ especially in patients with associated co-morbidities. Patient education, support, and telemedicine plays a pivotal role to prevent hypoglycemia.


title: FilmArray respiratory panel assay: An effective method for detecting viral and atypical bacterial pathogens in bronchoscopy specimens

text: Abstract The BioFire FilmArray Respiratory Panel (FA RP) is a rapid multiplexed molecular assay approved for detection of viral and atypical bacterial pathogens in nasopharyngeal specimens. This study aimed to evaluate the performance of the BioFire FilmArray Respiratory Panel v1.7 on bronchoscopy specimens. We tested 133 bronchial specimens (87 archived and 46 prospectively collected) with the FA RP and compared the results to the Luminex NxTAG Respiratory Pathogen Panel (NxTAG RPP). After discordant analysis, 123 specimens gave concordant results using the FA RP and the NxTAG RPP for an overall agreement of 93.9% (kappa = 0.88 [95% CI 0.80–0.96]), a positive percent agreement of 93.7% (95% CI 83.7–97.7) and a negative percent agreement of 94.1% (95% CI 84.9–98.1). In conclusion, the BioFire FilmArray RP performed reliably to detect a broad range of respiratory pathogens in bronchoscopy specimens.


title: Peptides from the SARS-associated coronavirus as tags for protein expression and purification

text: Abstract Protein tagging with a peptide is a commonly used technique to facilitate protein detection and to carry out protein purification. Flexibility with respect to the peptide tag is essential since no single tag suites all purposes. This report describes the usage of two short peptides from the SARS-associated coronavirus nucleocapsid (SARS-N) protein as protein tags. Plasmids for the generation of tagged proteins were generated by ligating synthetic oligonucleotides for the peptide-coding regions downstream of the protein coding sequence. The data show recognition of prokaryotically expressed HIV-1 Gag/p24 fusion protein by Western blot and efficient affinity purification using monoclonal antibodies against the tags. The SARS peptide antibody system described presents an alternative tagging opportunity in the growing field of protein science.


title: The Application Of Plasmapheresis For Covid‐19 Patients

text: Coronaviruses are known human and animal pathogens, but a novel type of coronavirus, designated as severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2) is defined by World Health Organisation(WHO).This novel type has created a pandemia throughout the world most notably causing death owing to pneumonia.Nowadays the entire world is searching the curative treatment but outcomes are discouraging for intensive care critical patients. In this article we'd like to highlight that plasmapheresis,although it’ s an unproven strategy, could be a useful approach by the mechanism of alleviating the cytokine storm and decreasing the viral load. This article is protected by copyright. All rights reserved.


title: The impact of the activities of Ghana AIDS Commission on new HIV infections in Ghana: An intervention time series analysis

text: Abstract The study examines the impact of Ghana AIDS Commission (GAC) activities on new HIV infections. Secondary data from 1 January 1996 to 31 December 2007 were obtained from the Ghana National AIDS Control Programme and Biostatistics Department of the Health Ministry. Intervention time series analysis was applied separately to the data from the northern and southern sectors due to data collection mechanism and location of two tertiary teaching hospitals. The impact of GAC activities is measured by the statistical significance of the coefficients of the intervention variable. The intervention variable is coded as zero (0) for the period before and one (1), the period after the GAC activities commenced. It was shown that the HIV incidence in the northern follows an integrated moving average model, whilst in the southern sectors an autoregressive integrated moving average model was the appropriate model. No significant impact of GAC activities was observed in the northern sector. In contrast the GAC activities in the southern sector were associated with a reduction in new HIV infections (male=−0.20±0.13, p <0.05; female=0.14±0.10, p <0.05), corresponding to a 15% and 18% reduction in male and female new HIV infections respectively in the sector. It can therefore be concluded that the GAC activities were a success. However, greater focus of GAC efforts in the northern sector is required to ensure that its activities have an impact on the incidence there.


title: Phylogenetic analysis of human coronavirus NL63 circulating in Italy

text: Abstract Background Five known human coronaviruses infect the human respiratory tract: HCoV-OC43, HCoV-229E, SARS-CoV, HCoV-NL63 and HCoV-HKU1. Objectives To evaluate the prevalence of HCoV-NL63 in hospitalized adult patients and to perform molecular characterization of Italian strains. Study Design HCoV-NL63 was sought by RT-PCR in 510 consecutive lower respiratory tract (LRT) samples, collected from 433 Central-Southern Italy patients over a 1-year period. Phylogenetic analysis was performed by partial sequencing of S and ORF1a. Additional S sequences from Northern Italy were included in the phylogenetic trees. Results HCoV-NL63 was detected in 10 patients (2.0%) with symptomatic respiratory diseases, mainly during winter. Phylogenetic analysis indicated a certain degree of heterogeneity in Italian isolates. The ORF1a gene clustering in phylogenetic trees did not match with that of the S gene. Conclusions As observed by others, HCoV-NL63 is often associated with another virus. Phylogenetic characterization of HCoV-NL63 circulating in Italy indicates that this virus circulates as a mixture of variant strains, as observed in other countries.


title: Using Biosecurity Measures to Combat Respiratory Disease in Cattle: The Norwegian Control Program for Bovine Respiratory Syncytial Virus and Bovine Coronavirus

text: Bovine respiratory disease (BRD) cause important health problems in all cattle husbandry systems. It contributes substantially to the use of antimicrobial substances and compromises animal welfare and the sustainability of the cattle industry. The existing preventive measures of BRD focus at the individual animal or herd level and include vaccination, mass treatment with antimicrobials and improvement of the animal's environment and general health status. Despite progress in our understanding of disease mechanism and technological development, the current preventive measures are not sufficiently effective. Thus, there is a need for alternative, sustainable strategies to combat the disease. Some of the primary infectious agents in the BRD complex are viruses that are easily transmitted between herds such as bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV). This conceptual analysis presents arguments for combatting BRD through improved external biosecurity in the cattle herds. As an example of a population-based approach to the control of BRD, the Norwegian BRSV/BCoV control-program is presented. The program is voluntary and launched by the national cattle industry. The core principle is classification of herds based on antibody testing and subsequent prevention of virus-introduction through improved biosecurity measures. Measures include external herd biosecurity barriers and regulations in the organization of animal trade to reduce direct and indirect transmission of virus. Improved biosecurity in a large proportion of herds will lead to a considerable effect at the population level. Positive herds are believed to gain freedom by time if new introduction is avoided. Vaccination is not used as part of the program. Dissemination of information to producers and veterinarians is essential. We believe that reducing the incidence of BRD in cattle is essential and will lead to reduced antimicrobial usage while at the same time improving animal health, welfare and production. Alternative approaches to the traditional control measures are needed.