title: Bovine respiratory syncytial virus infection enhances Pasteurella multocida adherence on respiratory epithelial cells

text: Abstract Primary infection with bovine respiratory syncytial virus (BRSV) predisposes cattle to secondary infection with bacteria that cause bovine respiratory disease complex (BRDC). However, the interaction between BRSV and bacteria is unclear. This in vitro study examined the adherence of Pasteurella multocida (PM) to BRSV-infected cells was assessed in colony forming unit assays, by flow cytometry analysis, and by indirect immunofluorescence analysis (IFA) of epithelial cells (A549, HEp-2, and MDBK). An in vitro model based on infection of BRSV-infected epithelial cells revealed that PM adherence to BRSV-infected cells was 2- to 8-fold higher than uninfected cells. This was confirmed by flow cytometry analysis and IFA. Epithelial cell expression of mRNA encoding cytokines and chemokines increased after exposure to PM, but increased further after co-infection with BRSV and PM. BRSV-mediated adherence of PM to epithelial cells may underlie the serious symptoms of BRDC.


title: Structural characterization of the HCoV-229E fusion core

text: Abstract HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis. The overall structures, especially the residues in some positions of HR2 are highly conserved. Fourteen hydrophobic and three polar residues from each HR1 peptide are packed in layers at the coiled-coil interface. These core amino acids can be grouped into seven heptad repeats. Analysis of hydrophobic and hydrophilic interactions between HR2 helix and HR1 helices, shows that the HR1 and HR2 polypeptides are highly complementary in both shape and chemical properties. Furthermore, the available knowledge concerning HCoV-229E fusion core may make it possible to design small molecule or polypeptide drugs targeting membrane fusion, a crucial step of HCoV-229E infection.


title: Efficacy and safety of current therapeutic options for COVID-19 - lessons to be learnt from SARS and MERS epidemic: A systematic review and meta-analysis

text: Abstract The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I 2 = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I 2 = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.


docid: shmfieok

title: Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank

text: BACKGROUND: Understanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study. METHODS: The UK Biobank study recruited 40–70-year-olds in 2006–2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including area-level socioeconomic deprivation and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health. RESULTS: Amongst 392,116 participants in England, 2658 had been tested for SARS-CoV-2 and 948 tested positive (726 in hospital) between 16 March and 3 May 2020. Black and south Asian groups were more likely to test positive (RR 3.35 (95% CI 2.48–4.53) and RR 2.42 (95% CI 1.75–3.36) respectively), with Pakistani ethnicity at highest risk within the south Asian group (RR 3.24 (95% CI 1.73–6.07)). These ethnic groups were more likely to be hospital cases compared to the white British. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.19 for most deprived quartile vs least (95% CI 1.80–2.66) and RR 2.00 for no qualifications vs degree (95% CI 1.66–2.42)). CONCLUSIONS: Some minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study, which was not accounted for by differences in socioeconomic conditions, baseline self-reported health or behavioural risk factors. An urgent response to addressing these elevated risks is required.


Transporting Patient with Suspected SARS


title: Recommendations for Cardiopulmonary Resuscitation (CPR) of patients with suspected or confirmed COVID-19

text: Abstract The care for patients suffering from cardiopulmonary arrest in a context of a COVID-19 pandemic has particularities that should be highlighted. The following recommendations from the Brazilian Association of Emergency Medicine (ABRAMEDE), the Brazilian Society of Cardiology (SBC) and the Brazilian Association of Intensive Medicine (AMIB) and the Brazilian Society of Anesthesiology (SBA), associations and societies official representatives of specialties affiliated to the Brazilian Medical Association (AMB), aim to guide the various assistant teams, in a context of little solid evidence, maximizing the protection of teams and patients. It is essential to wear full Personal Protective Equipment (PPE) for aerosols during the care of Cardiopulmonary Resuscitation (CPR) and it is imperative to consider and treat the potential causes in these patients, especially hypoxia and arrhythmias caused by changes in the QT interval or myocarditis. The installation of an advanced invasive airway must be obtained early and the use of High Efficiency Particulate Arrestance (HEPA) filters at the interface with the valve bag is mandatory; situations of occurrence of CPR during mechanical ventilation and in a prone position demand peculiarities that are different from the conventional CPR pattern. Faced with the care of a patient diagnosed or suspected of COVID-19, the care follows the national and international protocols and guidelines 2015 ILCOR (International Alliance of Resuscitation Committees), AHA 2019 Guidelines (American Heart Association) and the Update of the Cardiopulmonary Resuscitation and Emergency Care Directive of the Brazilian Society of Cardiology 2019.


docid: udzywajm

title: Virological and Epidemiological Situation in the Influenza Epidemic Seasons 2016/2017 and 2017/2018 in Poland

text: The World Health Organization estimates that influenza virus infects 3–5 million people worldwide every year, of whom 290,000 to 650,000 die. In the 2016/2017 epidemic season in Poland, the incidence of influenza was 1,692 per 100,000 population. The influenza A virus, subtype A/H3N2/, was the predominant one in that season. However, in the most recent 2017/2018 epidemic season, the incidence exceeded 1,782 per 100,000 already by August of 2018. In this season, influenza B virus predominated, while the A/H1N1/pdm09 strain was most frequent among the influenza A subtypes. The peak incidence, based on the number of clinical specimens tested, was in weeks 4–5 of 2017 and week 8 of 2018 in the 2016/2017 and 2017/2018 epidemic seasons, respectively. As of the 2017/2018 season, a quadrivalent vaccine, consisting of two antigens of influenza A subtypes and another two of influenza B virus, was available in Poland. Nonetheless, the vaccination rate remained at one of the lowest level in Europe, fluctuating between 3% and 4% of the general Polish population.


title: Fact-finding survey of nosocomial infection control in hospitals in Vietnam and application to training programs

text: Abstract Nosocomial infection control is crucial for improving the quality of medical care. It is also indispensable for implementing effective control measures for severe acute respiratory syndrome (SARS) and the possible occurrence of a human influenza pandemic. The present authors, in collaboration with Vietnamese hospital staff, performed a fact-finding survey of nosocomial infection control in hospitals in northern Vietnam and compared the results with those of a survey conducted 4 years previously. Remarkable improvement was recognized in this period, although there were considerable differences between the central hospitals in Hanoi and local hospitals. In the local hospitals, basic techniques and the systems for infection control were regarded as insufficient, and it is necessary to improve these techniques and systems under the guidance of hospitals in the central area. Based on the results of the survey, programs were prepared and training courses were organized in local hospitals. Evaluation conducted after the training courses showed a high degree of satisfaction among the trainees. The results of the survey and the training courses conducted during the study period are expected to contribute to the improvement of nosocomial infection control in remote areas of Vietnam


title: Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity

text: [Image: see text] We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.


title: Armillifer-Infected Snakes Sold at Congolese Bushmeat Markets Represent an Emerging Zoonotic Threat

text: African pythons (Pythonidae) and large vipers (Bitis spp.) act as definitive hosts for Armillifer armillatus and Armillifer grandis parasites (Crustacea: Pentastomida) in the Congo Basin. Since the proportion of snakes in bushmeat gradually increases, human pentastomiasis is an emerging zoonotic disease. To substantiate the significance of this threat, we surveyed snakes offered for human consumption at bushmeat markets in the Kole district, Democratic Republic of the Congo, for the presence of adult pentastomids. In Bitis vipers (n = 40), Armillifer spp. infestations exhibited an 87.5% prevalence and 6.0 median intensity. Parasite abundance covaried positively with viper length, but not with body mass. In pythons (n = 13), Armillifer spp. exhibited a 92.3% prevalence and 3.5 median intensity. The positive correlations between parasite abundance and python length or mass were statistically nonsignificant. Ninety-one percent of A. grandis were discovered in vipers and 97% of infected vipers hosted A. grandis, whereas 81% of A. armillatus specimens were found in pythons and 63% of infected pythons hosted A. armillatus. Thus, challenging the widespread notion of strict host specificity, we found ‘reversed’ infections and even a case of coinfection. In this study, we also gathered information about the snake consumption habits of different tribal cultures in the area. Infective parasite ova likely transmit to humans directly by consumption of uncooked meat, or indirectly through contaminated hands, kitchen tools or washing water.


title: Coronavirus Disease 2019 (Covid-19) presenting as purulent fulminant myopericarditis and cardiac tamponade: a case report and literature review.

text: The vast majority of patients in the ongoing coronavirus Disease 2019 (Covid-19) pandemic primarily present with severe respiratory illness. We report a Covid-19 patient who presented with findings of acute coronary syndrome and was found to have purulent fulminant myopericarditis and cardiac tamponade. We compare our case to the previously reported instances of Covid-19-associated myocarditis. Through review of the available literature, we also highlight the potential mechanisms of cardiac injury in Covid-19. We hope to increase awareness amongst clinicians about this unusual presentation of Covid-19.


docid: bvihscxo

title: Paramyxovirus F1 protein has two fusion peptides: implications for the mechanism of membrane fusion 1 1 Edited by A. R.Fersht

text: Abstract Viral fusion proteins contain a highly hydrophobic segment, named the fusion peptide, which is thought to be responsible for the merging of the cellular and viral membranes. Paramyxoviruses are believed to contain a single fusion peptide at the N terminus of the F1 protein. However, here we identified an additional internal segment in the Sendai virus F1 protein (amino acids 214–226) highly homologous to the fusion peptides of HIV-1 and RSV. A synthetic peptide, which includes this region, was found to induce membrane fusion of large unilamellar vesicles, at concentrations where the known N-terminal fusion peptide is not effective. A scrambled peptide as well as several peptides from other regions of the F1 protein, which strongly bind to membranes, are not fusogenic. The functional and structural characterization of this active segment suggest that the F1 protein has an additional internal fusion peptide that could participate in the actual fusion event. The presence of homologous regions in other members of the same family suggests that the concerted action of two fusion peptides, one N-terminal and the other internal, is a general feature of paramyxoviruses.


title: Characterization of San Miguel Sea Lion Virus populations using pyrosequencing-based methods

text: Abstract San Miguel Sea Lion Virus (SMSV) is a small RNA virus in the genus Vesivirus with an unusually broad host range. Three populations of SMSV were examined by PCR amplification of the capsid precursor and putative helicase genes, followed by pyrosequencing. The populations were nasal swabs from two SMSV infected California sea lions (Zalophus californianus) from two different years, and a virus isolate from the earlier swab that was passaged in cell culture five times. In the capsid precursor, extensive deletions were prevalent in the passaged virus but uncommon in the clinical samples. A greater prevalence of point mutations was seen in the capsid precursor gene than in the putative helicase gene. In culture, the minority sequence in the capsid precursor at nucleotide position 5826 rapidly shifted after five passages to become the majority sequence. Levels of diversity at individual sites showed much more similarity between the two clinical samples than between the earlier clinical sample and the passaged culture from the same sample. SMSV appears to behave as a quasispecies. Assessment of original patient samples is preferable for understanding clinical SMSV populations.


title: Essential Role of Patient Blood Management in a Pandemic: A Call for Action

text: The World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and “flattening the curve” while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient’s own blood. This multinational and diverse group of authors issue this “Call to Action” underscoring “The Essential Role of Patient Blood Management in the Management of Pandemics” and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.


title: Molecular survey of enteric viruses in commercial chicken farms in Korea with a history of enteritis

text: Abstract Several enteric viruses have increasingly received attention as potential causative agents of runting-stunting syndrome (RSS) in chickens. A molecular survey was performed to determine the presence of a broad range of enteric viruses, namely chicken astrovirus (CAstV), avian nephritis virus (ANV), chicken parvovirus (ChPV), infectious bronchitis virus (IBV), avian rotavirus (AvRV), avian reovirus (ARV), and fowl adenovirus (FAdV), in intestinal samples derived from 34 commercial chicken flocks that experienced enteritis outbreaks between 2010 and 2012. Using techniques such as PCR and reverse-transcription PCR, enteric viruses were identified in a total of 85.3% of investigated commercial chicken flocks in Korea. Furthermore, diverse combinations of 2 or more enteric viruses were simultaneously identified in 51.7% of chicken farms positive for enteric viruses. The rank order of positivity for enteric viruses was as follows: ANV (44.1%), CAstV (38.2%), ChPV (26.5%), IBV (20.6%), ARV (8.8%), AvRV (5.9%), and FAdV (2.9%). Additionally, other pathogens such as Escherichia coli, Salmonella spp., Eimeria spp., and FAdV were detected in 79% of chicken flocks positive for enteric viruses using PCR, bacterial isolation, and microscopic examination. The results of our study indicate the presence of several enteric viruses with various combinations in commercial chicken farms that experienced enteritis outbreaks. Experimental studies are required to further understand the roles of enteric viruses in RSS in commercial chickens.


Infectious disease trends in China since the SARS outbreak


Educación Remota En Médicos Residentes En Tiempos Del Covid-19


title: The Effect of The COVID-19 Pandemic On Electively Scheduled HIP and KNEE Arthroplasty Patients in THE United States

text: Abstract In response to the COVID-19 pandemic, US hospitals stopped performing elective procedures. This led to cancellation of a large number of hip and knee arthroplasty cases. We aimed to assess the effect this had on our elective primary arthroplasty patients by distributing a specifically designed survey to patients across six institutions identified through the AAHKS Research Committee. Surveys were completed by 360 patients over the course of one week. Patients were most anxious about the uncertainty of when their operation could be rescheduled. Although 85% of patients understood and agreed with the cancellation of elective surgeries as part of public health measures to curb the spread of pandemic, almost 90% of patients plan to reschedule as soon as possible. Financial concerns were minimal in this cohort. Patients suffering from pain of hip and knee arthritis continue to struggle with their end-stage disease and despite anxiety about the COVID-19 pandemic, plan to undergo arthroplasty as soon as possible.


title: Inhibition of porcine circovirus type 1 and type 2 production in PK-15 cells by small interfering RNAs targeting the Rep gene

text: Abstract Porcine circovirus type 1 (PCV1) and type 2 (PCV2) are two genotypes of porcine circovirus. Both of them are presumed to be widespread in the swine population. Currently, there is no specific treatment for their infections. RNA interference (RNAi) is a sequence-specific RNA degradation mechanism mediated by small interfering RNA (siRNA), which represents a possible therapeutic application for the treatment of viral infections. In this study, three siRNA expression plasmids (pS-RepA, pS-RepB and pS-RepC) were generated to target three different coding regions of the Rep protein (Rep) of PCV. These siRNAs were used to inhibit PCV production in a porcine kidney cell line, PK-15 cells. Our results revealed that Rep gene expression was inhibited by pS-RepA, pS-RepB and pS-RepC to different degrees. Moreover, our study also showed that the production of PCV1 and PCV2 was reduced by these siRNAs. pS-RepC, which targets the middle region of Rep gene, proved to be the most efficient siRNA for inhibition of Rep expression and viral production. Taken together, our data suggest that RNAi could be investigated as a potential treatment for PCV infection.


title: Occurrence of enterotoxigenic and nonenterotoxigenic Bacteroides fragilis in calves and evaluation of their antimicrobial susceptibility

text: Bacteroides fragilis is considered an important clinical pathogen and the most common anaerobe isolated from human and animal clinical specimens; enterotoxigenic strains produce diarrhea. The presence of enterotoxigenic (ETBF) and nonenterotoxigenic B. fragilis in stool samples from calves with or without acute diarrhea and the antimicrobial susceptibility of the strains were evaluated. The stool samples were plated onto a selective B. fragilis–bile–esculin agar, and incubated anaerobically (10% CO(2)/90% N(2)), at 37°C, for 72 h. Species of the B. fragilis group were identified by using the API 32-A kit. Enterotoxigenic strains were detected by PCR and the cytotoxic assay. From 54 diarrhea and 54 nondiarrhea stools, 124 and 92 members of the B. fragilis group, respectively, were recovered. Only two ETBF strains were isolated from two different diarrhea samples and the bft gene was detected in both. Moreover, the bft gene was detected in DNA from four different diarrheal stools samples but no ETBF strain was recovered. All the bacteria were susceptible to chloramphenicol, imipenem, moxifloxacin, piperacillin/tazobactam, metronidazole and tigecycline. Most of the isolates from both calves with and without diarrhea were resistant to all metals. Our results are of concern, and suggest the need to increase the surveillance of antibiotic and metal resistance of this microbial group isolated from animal production such as calves.


title: The cloning and sequencing of the virion protein genes from a British isolate of porcine respiratory coronavirus: comparison with transmissible gastroenteritis virus genes

text: Abstract Previous analysis of porcine respiratory coronavirus (PRCV) mRNA species showed that mRNAs 2 and 3 were smaller than the corresponding transmissible gastroenteritis virus (TGEV) mRNA species (Page et al. (1991) J. Gen. Virol. 72, 579–587). Sequence analysis showed that mRNA 3 was smaller due to the presence of a new putative RNA-leader binding site upstream of the PRCV ORF-3 gene. However, this observation did not explain the deletion observed in PRCV mRNA 2. Polymerase chain reaction (PCR) was used to generate cDNA from the 3' coding region of the putative polymerase gene to the poly (A) tail of PRCV for comparison to the equivalent region from TGEV. The PRCV S protein was found to consist of 1225 amino acids, which had 98% similarity to the TGEV S protein. However, the PRCV S gene contained a 672 nucleotide deletion, corresponding to 224 amino acids (residues 21 to 245 in TGEV S protein), 59 nucleotides downstream of the S gene initiation codon. The PRCV genome from the ORF-3 gene to the poly (A) tail was sequenced for comparison to TGEV in order to identify other potential differences between the two viruses. Four ORFs were identified that showed 98% similarity to the TGEV ORF-4, M, N and ORF-7 genes. No other deletions or any PRCV specific sequences were identified.


title: GLIPR1L1 is an IZUMO-binding protein required for optimal fertilization in the mouse

text: BACKGROUND: The sperm protein IZUMO1 (Izumo sperm-egg fusion 1) and its recently identified binding partner on the oolemma, IZUMO1R, are among the first ligand-receptor pairs shown to be essential for gamete recognition and adhesion. However, the IZUMO1-IZUMO1R interaction does not appear to be directly responsible for promoting the fusion of the gamete membranes, suggesting that this critical phase of the fertilization cascade requires the concerted action of alternative fusogenic machinery. It has therefore been proposed that IZUMO1 may play a secondary role in the organization and/or stabilization of higher-order heteromeric complexes in spermatozoa that are required for membrane fusion. RESULTS: Here, we show that fertilization-competent (acrosome reacted) mouse spermatozoa harbor several high molecular weight protein complexes, a subset of which are readily able to adhere to solubilized oolemmal proteins. At least two of these complexes contain IZUMO1 in partnership with GLI pathogenesis-related 1 like 1 (GLIPR1L1). This interaction is associated with lipid rafts and is dynamically remodeled upon the induction of acrosomal exocytosis in preparation for sperm adhesion to the oolemma. Accordingly, the selective ablation of GLIPR1L1 leads to compromised sperm function characterized by a reduced ability to undergo the acrosome reaction and a failure of IZUMO1 redistribution. CONCLUSIONS: Collectively, this study characterizes multimeric protein complexes on the sperm surface and identifies GLIPRL1L1 as a physiologically relevant regulator of IZUMO1 function and the fertilization process.


docid: vufephkg

title: Mathematical epidemiology is not an oxymoron

text: A brief description of the importance of communicable diseases in history and the development of mathematical modelling of disease transmission is given. This includes reasons for mathematical modelling, the history of mathematical modelling from the foundations laid in the late nineteenth century to the present, some of the accomplishments of mathematical modelling, and some challenges for the future. Our purpose is to demonstrate the importance of mathematical modelling for the understanding and management of infectious disease transmission.


title: Hemorrhagic Fever Viruses

text: This article reviews the epidemiology, pathophysiology, and clinical management of patients with suspected or confirmed viral hemorrhagic fever infection. The focus is on clinical management based on case series from naturally occuring outbreaks of viral hemorrhagic fever infection as well as imported cases of viral hemorrhagic fever encountered in industrialized nations. The potential risk of bioterrorism involving these agents is discussed as well as emergency department and critical care management of isolated cases or larger outbreaks. Important aspects of management, including recognition of infected patients, isolation and decontamination procedures, as well as available vaccines and therapies are emphasized.


Suicides related to the COVID-19 outbreak in India: a pilot study of media reports


title: Metallothionein (I+II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration

text: Abstract Because of its similarity to ageing in impaired immune efficiency 48 h after surgical procedures on young partially hepatectomised mice, partial hepatectomy/liver regeneration (pHx) provides a good model for the study of inflammation in ageing. In old age, high metallothionein (I+II) (MT) sequesters a substantial number of intracellular zinc ions consequently leading to low zinc ion bioavailability for an adequate immune response. Corticosterone and IL-6 affect MTmRNA induction in inflammation and after pHx against oxidative damage. The aim of this study was to investigate the role played by MT in conferring immune plasticity in ageing and in very old age using the pHx model. 48 h after their partial hepatectomy, the crude zinc balance was negative in young, old and very old mice coupled with increased MT, corticosterone, sIL-6R and IL-6. Concomitantly, Natural Killer (NK) cell activity and IL-2 production decreased. Complete restoration of the nutritional–endocrine–immune parameters occurred 15 days from the surgical procedures in young and very old mice, but not in old or transgenic mice overexpressing MT. A significant positive or inverse correlation among nutritional–endocrine–immune parameters exists in young and very old mice, but not in old mice during liver regeneration. Since MT also affects c-myc, the gene expression of c-myc declines from 48 h to days 7 and 15 after pHx in young and very old mice, but remains constantly high in old pHx mice for the same days. This circumstance leads to the appearance of tumours in the long run in old pHx mice and survival times that are shorter than old sham controls. Because complete remodelling also occurs in IL-6 and in sIL-6R in very old mice during liver regeneration, the pre-existing inflammation is not detrimental in very old age. As such, very old mice are still responsive to large inflammation, such as pHx, thanks to correct MT homeostasis. Correct MT homeostasis, via c-myc, is therefore pivotal in both suitable liver regeneration and in conferring immune plasticity with subsequent successful ageing. High MT plays an extremely harmful role in ageing: on one hand it lowers zinc ion bioavailability levels required for immune efficiency and on the other hand it increases c-myc expression. The combination of immune depression and enhanced c-myc, via high MT, may trigger the appearance of age-related degenerative diseases.


Sierra Leone – Pandemic Politics


title: The role of viruses in the induction and progression of asthma

text: Viral respiratory infections have been related to asthma in several ways. It is well established that viral common colds precipitate exacerbations of asthma. Severe bronchiolitis in early life is related to subsequent wheezing and therefore may represent a marker of susceptibility to asthma; alternatively, it could be involved in the initiation of the disease. Finally, it is possible that some infections may protect from the development of asthma and allergies by promoting a type-1 host response. However, whether respiratory or other viruses could mediate such a protective effect is debated. The design and implementation of novel anti- or proviral strategies targeting asthma depends on the resolution of these questions. This review presents current evidence on the epidemiologic correlations and proposed mechanisms for the involvement of viral infections in the development and progression of asthma.


At the epicenter of severe acute respiratory syndrome


title: The clinical feature of silent infections of novel coronavirus infection (COVID‐19) in Wenzhou

text: Here were reported clinical features of silent infected COVID‐19 patients. Our study showed that the prevalence of the silent infection of COVID‐19 is 5.8% (95% CI: 3.4‐9.9%), which is much higher than 1.2% which from the report in China CDC. The silent infection patients were more likely to be young adults, the patients without chronic disease. All of the cases in the presented study was found because they were traced as close contact of confirmed cases. Our study indicated that traced the close contract of confirmed case, long time self‐quarantine, and screening is necessary to prevent the secondary cases in community. This article is protected by copyright. All rights reserved.


Editorial: Challenges to Opioid Use Disorders During COVID‐19


title: The pivotal link between ACE2 deficiency and SARS-CoV-2 infection

text: Abstract Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7. In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.


docid: olfpcndb

title: Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: Design, synthesis, biological evaluation, and docking studies

text: We report the design and synthesis of a series of dipeptide-type inhibitors with novel P3 scaffolds that display potent inhibitory activity against SARS-CoV 3CL(pro). A docking study involving binding between the dipeptidic lead compound 4 and 3CL(pro) suggested the modification of a structurally flexible P3 N-(3-methoxyphenyl)glycine with various rigid P3 moieties in 4. The modifications led to the identification of several potent derivatives, including 5c–k and 5n with the inhibitory activities (K(i) or IC(50)) in the submicromolar to nanomolar range. Compound 5h, in particular, displayed the most potent inhibitory activity, with a K(i) value of 0.006 μM. This potency was 65-fold higher than the potency of the lead compound 4 (K(i) = 0.39 μM). In addition, the K(i) value of 5h was in very good agreement with the binding affinity (16 nM) observed in isothermal titration calorimetry (ITC). A SAR study around the P3 group in the lead 4 led to the identification of a rigid indole-2-carbonyl unit as one of the best P3 moieties (5c). Further optimization showed that a methoxy substitution at the 4-position on the indole unit was highly favorable for enhancing the inhibitory potency.


title: Point of care and intensive care lung ultrasound: A reference guide for practitioners during COVID-19

text: Abstract Objectives Current events with the recent COVID-19 outbreak are necessitating steep learning curves for the NHS workforce. Ultrasound, although not used in the diagnosis of COVID-19 may be utilised by practitioners at the point of care (POC) or on the intensive care units (ITUs) where rapid assessment of the lung condition may be required. The aim of this article was to review current literature surrounding the use of lung ultrasound in relation to COVID-19 and provide Sonographers with a quick and digestible reference guide for lung pathologies. Key findings Ultrasound is being used in Italy and China to help review lung condition during the COVID-19 outbreak however not strictly as a diagnostic tool as Computed Tomography (CT) of the chest and chest radiographs are currently gold standard. Ultrasound is highly sensitive in the detection of multiple lung pathologies which can be demonstrated in conjunction with COVID-19 however to date there are no specific, nor pathognomonic findings which relate to COVID-19 on ultrasound. Conclusion Lung ultrasound is highly sensitive and can quickly and accurately review lung condition creating potential to assess for changes or resolution over time, especially in the ITU and POC setting. However it should not be used as a diagnostic tool for COVID-19 due to low specificity in relation to the virus. Implications for practice The adoption of lung ultrasound to monitor lung condition during the COVID-19 outbreak may reduce the need for serial exposure to ionising radiation on the wards and in turn reduce the number of radiographers required to attend infected wards and bays, protecting both patients and the workforce.


title: Comparative Evaluation of Three Homogenization Methods for Isolating Middle East Respiratory Syndrome Coronavirus Nucleic Acids From Sputum Samples for Real-Time Reverse Transcription PCR

text: BACKGROUND: Real-time reverse transcription PCR (rRT-PCR) of sputum samples is commonly used to diagnose Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Owing to the difficulty of extracting RNA from sputum containing mucus, sputum homogenization is desirable prior to nucleic acid isolation. We determined optimal homogenization methods for isolating viral nucleic acids from sputum. METHODS: We evaluated the following three sputum-homogenization methods: proteinase K and DNase I (PK-DNase) treatment, phosphate-buffered saline (PBS) treatment, and N-acetyl-L-cysteine and sodium citrate (NALC) treatment. Sputum samples were spiked with inactivated MERS-CoV culture isolates. RNA was extracted from pretreated, spiked samples using the easyMAG system (bioMérieux, France). Extracted RNAs were then subjected to rRT-PCR for MERS-CoV diagnosis (DiaPlex Q MERS-coronavirus, SolGent, Korea). RESULTS: While analyzing 15 spiked sputum samples prepared in technical duplicate, false-negative results were obtained with five (16.7%) and four samples (13.3%), respectively, by using the PBS and NALC methods. The range of threshold cycle (Ct) values observed when detecting upE in sputum samples was 31.1–35.4 with the PK-DNase method, 34.7–39.0 with the PBS method, and 33.9–38.6 with the NALC method. Compared with the control, which were prepared by adding a one-tenth volume of 1:1,000 diluted viral culture to PBS solution, the ranges of Ct values obtained by the PBS and NALC methods differed significantly from the mean control Ct of 33.2 (both P<0.0001). CONCLUSIONS: The PK-DNase method is suitable for homogenizing sputum samples prior to RNA extraction.


title: Failure in initial stage containment of global COVID‐19 epicenters

text: With multiple virus epicenters, COVID‐19 has been declared a pandemic by the World Health Organization. Consequently, many countries have implemented different policies to manage this crisis including curfew and lockdown. However, the efficacy of individual policies remains unclear with respect to COVID‐19 case development. We analyzed available data on COVID‐19 cases of eight majorly affected countries, including China, Italy, Iran, Germany, France, Spain, South Korea, and Japan. Growth rates and doubling time of cases were calculated for the first 6 weeks after the initial cases were declared for each respective country and put into context with implemented policies. Although the growth rate of total confirmed COVID‐19 cases in China has decreased, those for Japan have remained constant. For European countries, the growth rate of COVID‐19 cases considerably increased during the second time interval. Interestingly, the rates for Germany, Spain, and France are the highest measured in the second interval and even surpass the numbers in Italy. Although the initial data in Asian countries are encouraging with respect to case development at the initial stage, the opposite is true for European countries. Based on our data, disease management in the 2 weeks following the first reported cases is of utmost importance.


COVID-19: a multifaceted threat to refugee camps


title: Fever and the Rational Use of Antimicrobials in the Emergency Department

text: Any patient presenting to the emergency department (ED) with fever triggers consideration of the administration of an antimicrobial. Empiric antimicrobial therapy has become a cornerstone of treatment. Frequently, the decision to initiate empiric treatment needs to be made before the definitive diagnosis is known. In such cases, an organized approach is helpful. This article aims to provide a systems-based approach to prescribing antimicrobials to patients presenting to the ED with fever, while understanding the risk associated with overutilization. An understanding of the key considerations is needed to ensure that decisions are made well and appropriate treatment begins promptly.


title: Evaluation of Four Commercial Multiplex Molecular Tests for the Diagnosis of Acute Respiratory Infections

text: Acute Respiratory Infections (ARIs) are responsible for considerable morbidity and mortality worldwide. Documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. Here, we compared the performances of four commercial multiplex kits used in French University Hospital diagnostic microbiology laboratories for the detection of ARI pathogens (i.e., the xTAG Respiratory Viral Panel Fast, RespiFinder SMART 22, CLART PneumoVir and Fast Track Diagnostics Respiratory Pathogen 33 kits). We used a standardised nucleic acids extraction protocol and a comprehensive comparative approach that mixed reference to well established real-time PCR detection techniques and analysis of convergent positive results. We tested 166 respiratory clinical samples and identified a global high degree of correlation for at least three of the techniques (xTAG, RespiFinder and FTD33). For these techniques, the highest Youden’s index (YI), positive predictive (PPV) and specificity (Sp) values were observed for Core tests (e.g., influenza A [YI:0.86–1.00; PPV:78.95–100.00; Sp:97.32–100.00] & B [YI:0.44–1.00; PPV:100.00; Sp:100.00], hRSV [YI:0.50–0.99; PPV:85.71–100.00; Sp:99.38–100.00], hMPV [YI:0.71–1.00; PPV:83.33–100.00; Sp:99.37–100.00], EV/hRV [YI:0.62–0.82; PPV:93.33–100.00; Sp:94.48–100.00], AdV [YI:1.00; PPV:100.00; Sp:100.00] and hBoV [YI:0.20–0.80; PPV:57.14–100.00; Sp:98.14–100.00]). The present study completed an overview of the multiplex techniques available for the diagnosis of acute respiratory infections.


title: Digital Approaches to Remote Pediatric Health Care Delivery During the COVID-19 Pandemic: Existing Evidence and a Call for Further Research

text: The global spread of the coronavirus disease (COVID-19) outbreak poses a public health threat and has affected people worldwide in various unprecedented ways, both personally and professionally. There is no question that the current global COVID-19 crisis, now more than ever, is underscoring the importance of leveraging digital approaches to optimize pediatric health care delivery in the era of this pandemic. In this perspective piece, we highlight some of the available digital approaches that have been and can continue to be used to streamline remote pediatric patient care in the era of the COVID-19 pandemic, including but not limited to telemedicine. JMIR Pediatrics and Parenting is currently publishing a COVID-19 special theme issue in which investigators can share their interim and final research data related to digital approaches to remote pediatric health care delivery in different settings. The COVID-19 pandemic has rapidly transformed health care systems worldwide, with significant variations and innovations in adaptation. There has been rapid expansion of the leveraging and optimization of digital approaches to health care delivery, particularly integrated telemedicine and virtual health. Digital approaches have played and will play major roles as invaluable and reliable resources to overcome restrictions and challenges imposed during the COVID-19 pandemic and to increase access to effective, accessible, and consumer-friendly care for more patients and families. However, a number of challenges remain to be addressed, and further research is needed. Optimizing digital approaches to health care delivery and integrating them into the public health response will be an ongoing process during the current COVID-19 outbreak and during other possible future pandemics. Regulatory changes are essential to support the safe and wide adoption of these approaches. Involving all relevant stakeholders in addressing current and future challenges as well as logistical, technological, and financial barriers will be key for success. Future studies should consider evaluating the following research areas related to telemedicine and other digital approaches: cost-effectiveness and return on investment; impact on quality of care; balance in use and number of visits needed for the management of both acute illness and chronic health conditions; system readiness for further adoption in other settings, such as inpatient services, subspecialist consultations, and rural areas; ongoing user-centered evaluations, with feedback from patients, families, and health care providers; strategies to optimize health equity and address disparities in access to care related to race and ethnicity, socioeconomic status, immigration status, and rural communities; privacy and security concerns for protected health information with Health Insurance Portability and Accountability Act (HIPAA)–secured programs; confidentiality issues for some specific populations, especially adolescents and those in need of mental health services; early detection of exposure to violence and child neglect; and integration of training into undergraduate and graduate medical education and subspecialty fellowships. Addressing these research areas is essential to understanding the benefits, sustainability, safety, and optimization strategies of telemedicine and other digital approaches as key parts of modern health care delivery. These efforts will inform long-term adoption of these approaches with expanded dissemination and implementation efforts.


title: Diagnostic System for Rapid and Sensitive Differential Detection of Pathogens

text: Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences and report its application for detecting 22 respiratory pathogens in clinical samples.


title: Frequency of PRRS live vaccine virus (European and North American genotype) in vaccinated and non-vaccinated pigs submitted for respiratory tract diagnostics in North-Western Germany

text: Abstract The frequency of PRRSV corresponding to live vaccines and wild-type was determined in 902 pigs from North-Western Germany submitted for post-mortem examination. Overall, 18.5% of the samples were positive for the EU wild-type virus. EU genotype vaccine virus was detected in 1.3% and the NA genotype vaccine virus in 8.9% of all samples. The detection of the EU vaccine was significantly higher in pigs vaccinated with the corresponding vaccine (OR=9.4). Pigs vaccinated with NA genotype had significantly higher detection chances for the corresponding vaccine virus when compared to non-vaccinated animals (OR=3.34) animals, however, NA vaccine was also frequently detected in non-vaccinated pigs. Concluding, the dynamics of NA genotype vaccine and EU wild-type virus corresponds with studies on PRRSV spread in endemically infected herds. The potential of spontaneous spread of the NA genotype vaccine should be considered in the planning of eradication programs.


title: Intestinal lymphatic transport for drug delivery

text: Abstract Intestinal lymphatic transport has been shown to be an absorptive pathway following oral administration of lipids and an increasing number of lipophilic drugs, which once absorbed, diffuse across the intestinal enterocyte and while in transit associate with secretable enterocyte lipoproteins. The chylomicron-associated drug is then secreted from the enterocyte into the lymphatic circulation, rather than the portal circulation, thus avoiding the metabolically-active liver, but still ultimately returning to the systemic circulation. Because of this parallel and potentially alternative absorptive pathway, first-pass metabolism can be reduced while increasing lymphatic drug exposure, which opens the potential for novel therapeutic modalities and allows the implementation of lipid-based drug delivery systems. This review discusses the physiological features of the lymphatics, enterocyte uptake and metabolism, links between drug transport and lipid digestion/re-acylation, experimental model (in vivo, in vitro, and in silico) of lymphatic transport, and the design of lipid- or prodrug-based drug delivery systems for enhancing lymphatic drug transport.


title: Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease

text: BACKGROUND: Acute viral respiratory infections are an important cause of morbidity and mortality in humans worldwide. The etiological backgrounds of these infections remain unconfirmed in most clinical cases. The aim of this study was to estimate the prevalence of human coronavirus infections in a series of children hospitalized with symptoms of acute respiratory tract disease in a one-year period in Slovenia. METHODS: The 664 specimens from 592 children under six years of age hospitalized at the University Children’s Hospital in Ljubljana were sent for the routine laboratory detection of respiratory viruses. Respiratory viruses were detected with a direct immunofluorescence assay and human coronaviruses were detected with a modified real-time RT–PCR. RESULTS: HCoV RNA was detected in 40 (6%, 95% CI: 4.3%–8.1%) of 664 samples. Of these specimens, 21/40 (52.5%) were identified as species HKU1, 7/40 (17.5%) as OC43, 6/40 (15%) as 229E, and 6/40 (15%) as NL63. Infection with HCoV occurred as a coinfection with one or more other viruses in most samples (70%). Of the HCoV-positive children, 70.3% had lower respiratory tract infections. CONCLUSION: The results of our study show that HCoV are frequently detected human pathogens, often associated with other respiratory viruses and acute respiratory tract infections in hospitalized children. An association between age and the viral load was found. The highest viral load was detected in children approximately 10 months of age.


title: Palmitoylation of the feline immunodeficiency virus envelope glycoprotein and its effect on fusion activity and envelope incorporation into virions

text: Abstract The feline immunodeficiency virus (FIV) envelope glycoprotein (Env) possesses a short cytoplasmic domain of 53 amino acids containing four highly conserved cysteines at Env positions 804, 811, 815 and 848. Since palmitoylation of transmembrane proteins occurs at or near the membrane anchor, we investigated whether cysteines 804, 811 and 815 are acylated and analyzed the relevance of these residues for Env functions. Replacement of cysteines 804, 811 and 815 individually or in combination by serine residues resulted in Env glycoproteins that were efficiently expressed and processed. However, mutations C804S and C811S reduced Env fusogenicity by 93% and 84%, respectively, compared with wild-type Env. By contrast, mutant C815S exhibited a fusogenic capacity representing 50% of the wild-type value. Remarkably, the double mutation C804S/C811S abrogated both Env fusion activity and Env incorporation into virions. Finally, by means of Click chemistry assays we demonstrated that the four FIV Env cytoplasmic cysteines are palmitoylated.


title: Recommendations on the use of radiation therapy in managing patients with gastrointestinal malignancies in the era of COVID-19

text: Abstract As of April 6, 2020, there are over 1,200,000 reported cases and 70,000 deaths worldwide due to COVID-19, the disease caused by the SARS-CoV-2 virus, and these numbers rise exponentially by the day.[1] According to the Centers for Disease Control (CDC), the most effective means of minimizing the spread of the virus is through reducing interactions between individuals.[2] We performed a review of the literature, as well as national and international treatment guidelines, seeking data in support of the RADS principle (Remote visits, Avoid radiation, Defer radiation, Shorten radiation)[3] as it applies to gastrointestinal cancers. The purpose of the present work is to guide radiation oncologists managing patients with gastrointestinal cancers during the COVID-19 crisis in order to maintain the safety of our patients, while minimizing the impact of the pandemic on cancer outcomes.


docid: uspvbyqc

title: Pharyngitis: Certain clinico-pictorial differentiators

text: Abstract Pharyngitis is an acute inflammatory infection of pharynx and/or tonsils, most cases are caused by viruses and occur as part of common cold syndromes. As there is marked overlap between clinical findings of viral and bacterial pharyngitis and it is difficult to distinguish GABHS from viral causes clinicians tend to prescribe antibiotics for any sore throat and therefore pharyngitis has become the raison d'être for antibiotic misuses. Although clinical findings may not specifically differentiate the various pharyngitis pathogens yet many of these pathogens have clinical markers which could give us some clues to clinical suspicion. A good picture is equal to thousand words, believing in this axiom article presents few simple clinico-pictorial clues which could help suspecting pharyngitis pathogens, this in turn may boost clinical confidence to avoid unnecessary antibiotic prescriptions.


title: Characteristics and outcomes of oral antibiotic treated pulmonary exacerbations in children with cystic fibrosis

text: Abstract Background Pulmonary exacerbations (PEx) in children with cystic fibrosis (CF) are frequently treated in the outpatient setting with oral antibiotics. However, little is known about the characteristics of PEx managed on an outpatient basis and the effectiveness of oral antibiotic therapy. We sought to prospectively evaluate clinical and laboratory changes associated with oral antibiotic treatment for PEx. Methods Children with CF between 8 and 18 years of age prescribed two weeks of oral antibiotics for a PEx were eligible to enroll. The study consisted of a visit within 48 h of starting antibiotics and a second visit within one week of antibiotic completion. Twenty-eight participants were evaluated by exacerbation score, quality of life measurements, lung function, sputum microbiology and inflammation. Results Oral antibiotic treatment was associated with a significant improvement in exacerbation score and quality of life measured by the CF Questionnaire-Revised (CFQ-R) respiratory domain. Following treatment, forced expiratory volume in 1 s (FEV1) % predicted increased [median (range)] 9% (−8%, 31%), and 22 (81%) subjects returned to 90% or higher of baseline FEV1. Bacterial density of the primary organism identified on sputum culture decreased significantly with a median (range) decrease of 0.8 log10 cfu/mL (−8 log10, 2 log10, p = 0.03). Sputum neutrophil elastase [−37 μg/mL (−464, 272), p = 0.02] and IL-1β [−2.8 × 103μg/mL (−6.9 × 104, 3.3 × 104), p = 0.03] decreased significantly following treatment in this cohort. Conclusions Treatment of PEx with oral antibiotics was associated with measurable improvements in patient reported outcomes, lung function, bacterial density and sputum inflammatory markers.


title: Chapter 1 Nanomaterials in Biosensors Fundamentals and Applications

text: Abstract With the recent advancement of nanomaterials and nanostructured materials, the point-of-care biosensor devices have shown a potential growth to revolutionize the future personalized health care diagnostics and therapy practices. This chapter deals with the fundamentals of nanomaterials-based biosensors. The first chapter covers the brief details of nanotechnology with its types and an introduction to the synthesis of nanomaterials and their importance to construct transducers. The different components of transducers such as electrochemical, optical, piezoelectric, thermal, surface plasmon resonance, and so on for biosensors have been explained in this chapter. Various principles utilized for development of enzymatic biosensors, immunosensors, DNA, and whole-cell biosensors have been included in this chapter. Immobilization of bioreceptors is a crucial step to fabricate biosensors and their stepwise demonstration and conjugation of nanomaterials with nanomaterials have been described.


title: Effects of ribavirin on cytokine production of recall antigens and phytohemaglutinin-stimulated peripheral blood mononuclear cells. (Inhibitory effects of ribavirin on cytokine production)

text: Abstract Aim: To evaluate the effects of ribavirin on cytokine production of recall antigen and PHA-stimulated PBMC obtained from healthy individuals. Materials and methods: PBMC were challenged with tetanus toxoid (5μg/mL) and PHA (10 μmL) in absence or presence of ribavirin at different concentrations (1, 10 and 100 (μM). Parallel sets of wells containing PBMC exposed to medium alone were used as negative controls. On day 3 after initiation of the cultures, IL-2, IFN-γ, IL-4, IL-10, TNF-α content were determined in supernatants of PBMC from the different individuals. Results: The effects of ribavirin on cytokine released by human PBMC in response to PHA and TT showed a great variation among individuals. No significant changes were observed between 1-10μ M concentrations in the production of TNF-α, IFN-γ and IL-10 by both PHA and TT-stimulated PBMC. Ribavirin inhibited TNF-α, IFN-γ, and IL-10 in both PHA and TT-stimulated PBMC at 100 μM (p <0.05). At this concentration, ribavirin induced an increase of 124% in the production of IL-2 by PHA-stimulated PBMC (p <0.05). Conclusions: The present data suggest that ribavirin may cause diverse effects on immunoregulatory cytokine secretion with changes in the Th1/Th2 balance.


title: HIV virions sense plasma membrane heterogeneity for cell entry

text: It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing cholesterol-rich ordered and cholesterol-poor fluid lipid domains, we demonstrate that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries. We also show that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries. Ordered/disordered lipid domain coexistence is not required for HIV attachment but is a prerequisite for successful fusion. We propose that HIV virions sense and exploit membrane discontinuities to gain entry into cells. This study provides surprising answers to the long-standing question about the roles of cholesterol and ordered lipid domains in cell entry of HIV and perhaps other enveloped viruses.


title: Translational Recoding Induced by G-Rich mRNA Sequences That Form Unusual Structures

text: Abstract We investigated a herpesvirus mutant that contains a single base insertion in its thymidine kinase (tk) gene yet expresses low levels of TK via a net +1 translational recoding event. Within this mutant gene, we defined a G-rich signal that is sufficient to induce recoding. Unlike other translational recoding events, downstream RNA structures or termination codons did not stimulate recoding, and paused ribosomes were not detected. Mutational analysis indicated that specific tRNAs or codon–anticodon slippage were unlikely to account for recoding. Rather, recoding efficiency correlated with the G-richness of the signal and its ability to form unusual structures. These findings identify a mechanism of translational recoding with unique features and potential implications for clinical drug resistance and other biological systems.


title: Genetic dissection of lymphopenia from autoimmunity by introgression of mutated Ian5 gene onto the F344 rat

text: Abstract Peripheral T cell lymphopenia (lyp) in the BioBreeding (BB) rat is linked to a frameshift mutation in Ian5, a member of the Immune Associated Nucleotide (Ian) gene family on rat chromosome 4. This lymphopenia leads to type 1 (insulin-dependent) diabetes mellitus (T1DM) at rates up to 100% when combined with the BB rat MHC RT1 u/u genotype. In order, to better study the lymphopenia phenotype without possible confounding effects of diabetes or other autoimmune disease, we generated congenic F344.lyp rats by introgression of lyp on diabetes-resistant MHC RT1 lv1/lv1 F344 rats. Analysis of thymic CD4 and CD8 T lymphocytes revealed no difference in the percentage of CD4−CD8+and CD4+CD8−subsets in lyp/lyp compared to +/+ F344 rats. The same subsets was however dramatically reduced in blood (P=0.005), spleen (P=0.019) and mesenteric lymph nodes (MLN) (P<0.0001). Compared to F344 +/+ rats double positive CD4+CD8+T cells were increased only in lyp/lyp spleen (P=0.034) while double negative CD4−CD8−were increased in thymus (P=0.033), spleen (P=0.012), MLN (P<0.0001), and peripheral blood (P<0.0001). There were no signs of inflammatory lesions in organs and tissues in F344.lyp/lyp rats examined at 120 days of age or older. We thus conclude that the lymphopenia phenotype was reconstituted by introgression of lyp on to F344 rats without subsequent development of organ-specific autoimmunity. The congenic F344.lyp rat should prove useful to dissect the mechanisms by which the Ian5 frameshift mutation affects T cell selection, differentiation and maturation without organ-specific autoimmunity.


title: Distributed data processing for public health surveillance

text: BACKGROUND: Many systems for routine public health surveillance rely on centralized collection of potentially identifiable, individual, identifiable personal health information (PHI) records. Although individual, identifiable patient records are essential for conditions for which there is mandated reporting, such as tuberculosis or sexually transmitted diseases, they are not routinely required for effective syndromic surveillance. Public concern about the routine collection of large quantities of PHI to support non-traditional public health functions may make alternative surveillance methods that do not rely on centralized identifiable PHI databases increasingly desirable. METHODS: The National Bioterrorism Syndromic Surveillance Demonstration Program (NDP) is an example of one alternative model. All PHI in this system is initially processed within the secured infrastructure of the health care provider that collects and holds the data, using uniform software distributed and supported by the NDP. Only highly aggregated count data is transferred to the datacenter for statistical processing and display. RESULTS: Detailed, patient level information is readily available to the health care provider to elucidate signals observed in the aggregated data, or for ad hoc queries. We briefly describe the benefits and disadvantages associated with this distributed processing model for routine automated syndromic surveillance. CONCLUSION: For well-defined surveillance requirements, the model can be successfully deployed with very low risk of inadvertent disclosure of PHI – a feature that may make participation in surveillance systems more feasible for organizations and more appealing to the individuals whose PHI they hold. It is possible to design and implement distributed systems to support non-routine public health needs if required.


title: COVID-19 provides an opportunity to advance a sustainable UK fisheries policy in a post-Brexit brave new world

text: Brexit creates a systemic shock that provides a unique opportunity for the UK to implement a new sustainable Fisheries Policy to better manage the multiple stocks on which future fishers will depend on leaving the European Union. At the same time, the global slowdown of commercial fishing as a result of COVID-19 has reduced pressure on some threatened stocks to levels not seen since the Second World War. In combination, Brexit and the COVID-19 slowdown have created a unique opportunity to facilitate the recovery of a threatened resource. Nevertheless, challenges remain as fisheries represent only 0.12% of UK economic output, presenting a risk that opportunities for more sustainable management will be lost during wider trade negotiations. Reduced fishing pressure during the COVID-19 era will enable stocks an opportunity to recover if supported by a new UK Fisheries Policy that focuses on: (a) re-establishing the role of Maximum Sustainable Yield to set limits that enable the recovery of fish populations initiated during the COVID-19 era; (b) ensuring that catch targets are set with the aim to maintain biomass at 120% of that which will achieve Maximum Sustainable Yield; (c) improving coherent resource management that also considers the expensive use of carbon associated with unsustainable fishing, and the need to protect fish throughout their life-cycle; and (d) constructing and effectively enforcing protection of a resilient network of Marine Protected Areas despite potential protests from EU member states.


title: The emergence of enterovirus D68 in a Dutch University Medical Center and the necessity for routinely screening for respiratory viruses

text: Abstract Background Since August 2014, an increase in infections caused by enterovirus D68 (EV-D68) was reported in the USA and Canada, for the most part in children presenting with severe respiratory symptoms. Objectives To determine whether an increase in severe EV-D68 respiratory infections was observed in our region. Study design Samples from patients with respiratory symptoms were screened for viral pathogens, including rhinovirus and enterovirus. Subsequently, samples positive for rhinovirus and enterovirus were routinely sequenced for phylogenetic analysis. Furthermore, an additional method was used to detect EV-D68 specifically. Results During the first three quarters of the year 2014, 1896 respiratory samples were analyzed; 39 (2%) of them tested positive for enterovirus. Eighteen samples tested positive for EV-D68, obtained from 16 different patients admitted to our hospital. Eleven were children below the age of 18, of whom five children needed intensive care treatment. The remaining five samples were from adults, who all had an underlying disease; three were transplant patients (heart, lung and renal transplantation), the other two had an underlying lung condition (COPD, asthma). Phylogenetic analysis showed a close relationship with the strains circulating currently in the USA, all belonging to the known EV-D68 genetic subtypes. Conclusions We observed an increase of EV-D68 infections in our population, both in children as well as in adult. In 2014 there have been 16 cases so far, compared to none in 2011 and 2013 and a single case in 2012. Phylogenetic analysis identified two similar clusters as shown in the USA and Canada.


title: Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

text: BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.


title: Antiviral activity of an aqueous extract derived from Aloe arborescens Mill. against a broad panel of viruses causing infections of the upper respiratory tract

text: Abstract Background A number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. But these therapies are very often of limited efficacy or have severe side effects. Therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin. Hypothesis Since an aqueous extract of Aloe arborescens Mill. shows antiviral activity against viruses causing infections of the upper respiratory tract in vitro we hypothesised that a product containing it such as Biaron C® could have an antiviral activity too. Study design Antiviral activity of Bioaron C®, an herbal medicinal product consisting of an aqueous extract of Aloe arborescens Mill., Vitamin C, and Aronia melanocarpa Elliot. succus, added as an excipient, was tested in vitro against a broad panel of viruses involved in upper respiratory tract infections. Methods These studies included human adenovirus and several RNA viruses and were performed either with plaque reduction assays or with tests for the detection of a virus-caused cytopathic effect. Results Our studies demonstrated an impressive activity of Bioaron C® against members of the orthomyxoviridae – influenza A and influenza B viruses. Replication of both analysed influenza A virus strains – H1N1 and H3N2 – as well as replication of two analysed influenza B viruses – strains Yamagatal and Beiying – was significantly reduced after addition of Bioaron C® to the infected cell cultures. In contrast antiviral activity of Bioaron C® against other RNA viruses showed a heterogeneous pattern. Bioaron C® inhibited the replication of human rhinovirus and coxsackievirus, both viruses belonging to the family of picornaviridae and both representing non-enveloped RNA viruses. In vitro infections with respiratory syncytial virus and parainfluenza virus, both belonging to the paramyxoviridae, were only poorly blocked by the test substance. No antiviral activity of Bioaron C® was detected against adenovirus – a non-enveloped DNA virus. Conclusions These results represent the first proof of a selective antiviral activity of Bioaron C® against influenza viruses and create basis for further analyses of type and molecular mechanisms of the antiviral activity of this herbal medicine.


title: Nonparametric methods for the analysis of single-color pathogen microarrays

text: BACKGROUND: The analysis of oligonucleotide microarray data in pathogen surveillance and discovery is a challenging task. Target template concentration, nucleic acid integrity, and host nucleic acid composition can each have a profound effect on signal distribution. Exploratory analysis of fluorescent signal distribution in clinical samples has revealed deviations from normality, suggesting that distribution-free approaches should be applied. RESULTS: Positive predictive value and false positive rates were examined to assess the utility of three well-established nonparametric methods for the analysis of viral array hybridization data: (1) Mann-Whitney U, (2) the Spearman correlation coefficient and (3) the chi-square test. Of the three tests, the chi-square proved most useful. CONCLUSIONS: The acceptance of microarray use for routine clinical diagnostics will require that the technology be accompanied by simple yet reliable analytic methods. We report that our implementation of the chi-square test yielded a combination of low false positive rates and a high degree of predictive accuracy.


title: Longitudinal survey of two serotine bat (Eptesicus serotinus) maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1): Assessment of survival and serological status variations using capture-recapture models

text: This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1) antibodies in serotine bat (Eptesicus serotinus) maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying. Five bats have been found with EBLV-1 RNA in the saliva at the start of the study, suggesting they were caught during virus excretion period. Among these bats, one was interestingly recaptured one year later and harbored a seropositive status. Along the survey, some others bats have been observed to both seroconvert (i.e. move from a negative to a positive serological status) and serorevert (i.e. move from a positive to a negative serological status). Peak of seroprevalence reached 34% and 70% in site A and B respectively. On one of the 2 sites, global decrease of seroprevalence was observed all along the study period nuanced by oscillation intervals of approximately 2–3 years supporting the oscillation infection dynamics hypothesized during a previous EBLV-1 study in a Myotis myotis colony. Seroprevalence were affected by significantly higher seroprevalence in summer than in spring. The maximum time observed between successive positive serological statuses of a bat demonstrated the potential persistence of neutralizing antibodies for at least 4 years. At last, EBLV-1 serological status transitions have been shown driven by age category with higher seroreversion frequencies in adults than in juvenile. Juveniles and female adults seemed indeed acting as distinct drivers of the rabies virus dynamics, hypothesis have been addressed but their exact role in the EBLV-1 transmission still need to be specified.


Corrigendum to “Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases’’ [J. Clin. Virol. 61 (2014) 275–278]


title: Communication between S1N330 and a Region in S2 of Murine Coronavirus Spike Protein Is Important for Virus Entry into Cells Expressing CEACAM1b Receptor

text: Abstract The soluble receptor-resistant (srr) mutants, srr7 and srr11, isolated from a murine coronavirus, mouse hepatitis virus (MHV) JHMV, have an amino acid mutation at positions 1114 (Leu to Phe) and 65 (Leu to His), respectively, in the spike (S) protein. These mutants failed to efficiently infect BHK cells expressing CEACAM1b (BHK-R2), due to their low entry into this cell line, although they infected cells expressing CEACAM1a (BHK-R1) in a manner similar to that of wild-type (wt) JHMV cl-2 (Matsuyama and Taguchi, Virology 273, 80–89, 2000). Following the repeated passage of these mutants through BHK-R2 cells, viruses were no longer isolated from srr11-infected cells, while two distinct mutants, srr7A and srr7B, were obtained from srr7-infected cells. Srr7A and srr7B grew 2 log10 higher than srr7 and induced fusion in BHK-R2 cells, being similar to wt virus. In addition to the amino acid change at position 1114 that stemmed from parental srr7, srr7A and srr7B had mutations around position 280, corresponding to the third region of the S1N330 receptor-binding site (S1N330-III) common to all MHV strains examined thus far. Srr7A and srr7B S proteins showed high fusogenicity in both BHK-R1 and BHK-R2 cells, like the wt virus, while srr7Aa and srr7Ba S proteins, which had mutations in S1N330-III but not at amino acid 1114, exhibited profoundly reduced fusion activity in these cell lines. These findings suggest that communication between S1N330-III and the amino acid at position 1114 is important for efficient fusion activity in BHK-R2 cells. S1N330-III is a possible region in the S1 involved in viral entry into cells.


title: Quality vaccines for all people(): Report on the 16th annual general meeting of the Developing Countries Vaccine Manufacturers' Network, 05–07th October 2015, Bangkok, Thailand

text: The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed.


title: Personal Protective Equipment and COVID-19: A Review for Surgeons

text: There is a long history of personal protective equipment (PPE) used by the surgeon to minimize the transmission of various pathogens. In the context of the present coronavirus disease 2019 pandemic there is significant controversy as to what forms of PPE are appropriate or adequate. This review aims to describe the pathogenic mechanism and route of spread of the causative virus, severe acute respiratory syndrome coronavirus, as it pertains to accumulated published data from experienced centers globally. The various forms of PPE that are both available and appropriate are addressed. There are options in the form of eyewear, gloves, masks, respirators, and gowns. The logical and practical utilization of these should be data driven and evolve based on both experience and data. Last, situations specific to surgical populations are addressed. We aim to provide granular collective data that has thus far been published and that can be used as a reference for optimal PPE choices in the perioperative setting for surgical teams.


title: A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

text: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.


title: Nutraceuticals An Alternative Strategy for the Use of Antimicrobials

text: Livestock industries strive to improve the health of their animals and, in the future, they are going to be required to do this with a continued reduction in antimicrobial use. Nutraceuticals represent a group of compounds that may help fill that void because they exert some health benefits when supplemented to livestock. This review is focused on the mechanisms of action, specifically related to the immune responses and health of ruminants. The nutraceutical classes discussed include probiotics, prebiotics, phytonutrients (essential oils and spices), and polyunsaturated fatty acids.


title: Secondary Photoreceptor Degenerations*

text: Secondary photoreceptor degenerations can be partially distinguished from primary photoreceptor degenerations based upon whether or not correction of the defect in the photoreceptors themselves would be sufficient to arrest photoreceptor death. The distinction is by no means perfect, since there can be genetic mutations that affect directly the survival of photoreceptors as well as the survival of adjacent retinal or retinal pigment epithelium cells that could secondarily be critical for photoreceptor survival. As we attempt to distinguish intrinsic and extrinsic causes of both primary and secondary photoreceptor degenerations, it is increasingly clear that complex interactions and mechanisms can be involved.


Traditional chinese medicine and COVID-19: should emergency practitioners use it?


title: Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study

text: In recent years, several studies based on the interaction of self-assembling short peptides derived from viroporins with model membranes, have improved our understanding of the molecular mechanism of corona virus (CoV) infection under physiological conditions. In this study, we have characterized the mechanism of membrane interaction of a short, 9-residue peptide TK9 (T(55)VYVYSRVK(63)) that had been derived from the carboxyl terminal of the Severe Acute Respiratory Syndrome (SARS) corona virus (SARS CoV) envelope (E) protein. The peptide has been studied for its physical changes in the presence of both zwitterionic DPC and negatively charged SDS model membrane micelles, respectively, with the help of a battery of biophysical techniques including two-dimensional solution state NMR spectroscopy. Interestingly, in both micellar environments, TK9 adopted an alpha helical conformation; however, the helical propensities were much higher in the case of DPC compared to those of SDS micelle, suggesting that TK9 has more specificity towards eukaryotic cell membrane than the bacterial cell membrane. The orientation of the peptide TK9 also varies in the different micellar environments. The peptide's affinity was further manifested by its pronounced membrane disruption ability towards the mammalian compared to the bacterial membrane mimic. Collectively, the in-depth structural information on the interaction of TK9 with different membrane environments explains the host specificity and membrane orientation owing to subsequent membrane disruption implicated in the viral pathogenesis.


title: Identification of a novel recombinant virulent avian infectious bronchitis virus

text: Abstract The emergence of new infectious bronchitis virus (IBV) variants is often disastrous in the poultry industry. In this study, an IBV, CK/CH/2010/JT-1, was isolated from an H120- and 4/91-IBV-vaccinated flock in China. Antisera against vaccine strains H120 and 4/91 could not provide effective protection against CK/CH/2010/JT-1 in virus neutralization assays. CK/CH/2010/JT-1 could cause 43.75% mortality with respiratory and severe renal lesions in inoculated chickens. Phylogenetic analysis of the S1 gene showed that CK/CH/2010/JT-1 and 31 other isolates could be grouped as a new genotypic cluster. Recombination analysis revealed that three recombination events could be found in the genome of CK/CH/2010/JT-1 at positions 24709-365, 17160-19811 and 21136-21770. Whole-genome sequence analysis showed that CK/CH/2010/JT-1 originated from multiple template switches among QX-like, CK/CH/LSC/99I-, tl/CH/LDT3/03- and 4/91-type IBVs. All of these data demonstrated that CK/CH/2010/JT-1 is a new recombinant genotype IBV with high virulence. Our findings suggest that the surveillance of new genotype strains of IBV is very important for developing more effective anti-IBV strategies.


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title: Potential airborne pathogen transmission in a hospital with and without surge control ventilation system modifications

text: Abstract To better understand the transport of airborne particulate matter (PM) in hospital environments when surge control strategies are implemented, tests were conducted in a recently decommissioned hospital during a one-week period. An aerosol was released within a patient room and concentrations measured in the room and hallway with and without surge control ventilation system modifications. The average hallway protection efficiencies were high (>98%) both for the baseline ventilation configuration and when the ventilation system was modified for whole floor negative pressure, indicating very little PM reached the hallway. During entry/exit events through the patient room door into the hallway, the average minimum hallway protection efficiencies were lower during the modified ventilation operation (93–94%) than for the baseline operation (98–99%). These lower hallway protection efficiencies may be explained by the 52% reduction in the outdoor air ventilation being supplied to the hallway during the modified operation mode. This suggests that patient room doors should remain closed to control PM movement into the hallway. In addition, if there is concern about airborne infection transmission, an anteroom may be used to further reduce the transport of particles from the patient rooms to the hallways of the ward.


title: Kidney transplantation with pre‐symptomatic COVID‐19 positive surgeon

text: In Italy the Coronavirus Disease 2019 (COVID‐19) outbreak caused by SARS‐CoV‐2 is testing the national health system and the intensive care unit are at the limits of their capacity. Severe travel limitation and containment at home were applied, such as in the Chinese experience and isolation of the diseased patients to control the exponential trend of the infection spread.


title: Transcriptional profiles of PBMCs from pigs infected with three genetically diverse porcine reproductive and respiratory syndrome virus strains

text: Porcine reproductive and respiratory syndrome virus is the cause of reproductive failure in sows and respiratory disease in young pigs, which has been considered as one of the most costly diseases to the worldwide pig industry for almost 30 years. This study used microarray-based transcriptomic analysis of PBMCs from experimentally infected pigs to explore the patterns of immune dysregulation after infection with two East European PRRSV strains from subtype 2 (BOR and ILI) in comparison to a Danish subtype 1 strain (DAN). Transcriptional profiles were determined at day 7 post infection in three tested groups of pigs and analysed in comparison with the expression profile of control group. Microarray analysis revealed differential regulation (> 1.5-fold change) of 4253 and 7335 genes in groups infected with BOR and ILI strains, respectively, and of 12518 genes in pigs infected with Danish strain. Subtype 2 PRRSV strains showed greater induction of many genes, especially those involved in innate immunity, such as interferon stimulated antiviral genes and inflammatory markers. Functional analysis of the microarray data revealed a significant up-regulation of genes involved in processes such as acute phase response, granulocyte and agranulocyte adhesion and diapedesis, as well as down-regulation of genes enrolled in pathways engaged in protein synthesis, cell division, as well as B and T cell signaling. This study provided an insight into the host response to three different PRRSV strains at a molecular level and demonstrated variability between strains of different pathogenicity level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-018-4204-x) contains supplementary material, which is available to authorized users.


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title: The envelope protein of severe acute respiratory syndrome coronavirus interacts with the non-structural protein 3 and is ubiquitinated

text: Abstract To analyze the proteins interacting with the severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein, a SARS-CoV was engineered including two tags associated to the E protein. Using this virus, complexes of SARS-CoV E and other proteins were purified using a tandem affinity purification system. Several viral and cell proteins including spike, membrane, non-structural protein 3 (nsp3), dynein heavy chain, fatty acid synthase and transmembrane protein 43 bound E protein. In the present work, we focused on the binding of E protein to nsp3 in infected cells and cell-free systems. This interaction was mediated by the N-terminal acidic domain of nsp3. Moreover, nsp3 and E protein colocalized during the infection. It was shown that E protein was ubiquitinated in vitro and in cell culture, suggesting that the interaction between nsp3 and E protein may play a role in the E protein ubiquitination status and therefore on its turnover.


title: The Global One Health Paradigm: Challenges and Opportunities for Tackling Infectious Diseases at the Human, Animal, and Environment Interface in Low-Resource Settings

text: Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.


title: Genetic diversity and phylogenetic analysis of newly discovered bat astroviruses in Korea

text: Bats have been identified as a natural reservoir for several potentially zoonotic viruses. Recently, astroviruses have been reported in bats in many countries, but not Korea. We collected 363 bat samples from thirteen species at twenty-nine sites in Korea across 2016 and tested them for astrovirus. The detection of the RNA-dependent RNA polymerase (RdRp) gene in bat astroviruses was confirmed in thirty-four bats across four bat species in Korea: twenty-five from Miniopterus fuliginosusi, one from Myotis macrodactylus, four from M. petax, and four from Rhinolophus ferrumequinum. The highest detection rates for astrovirus were found in Sunchang (61.5%, 8/13 bats), and in the samples collected in April (63.2%, 12/19 bats). The amino acid identity of astroviral sequences identified from bat samples was ≥ 46.6%. More specifically, the amino acid identity within multiple clones from individual bats was ≥ 50.8%. Additionally, the phylogenetic topology between astroviruses from different bat families showed a close relationship. Furthermore, phylogenetic analysis of the partial ORF2 sequence of bat astroviruses was found to have a maximum similarity of 73.3–74.8% with available bat astrovirus sequences. These results indicate potential multiple-infection by several bat astrovirus species in individual bats, or hyperpolymorphism in the astrovirus strains, as well as the transmission of astroviruses across bat families; furthermore, our phylogenetic analysis of the partial ORF2 implied that a novel astrovirus may exist. However, the wide diversity of astroviral sequences appeared to have no significant correlation with bat species or the spatiotemporal distribution of Korean bat astroviruses.