The NlpD Lipoprotein Is a Novel Yersinia pestis Virulence Factor Essential for the Development of Plague

Yersinia pestis is the causative agent of plague. Previously we have isolated an attenuated Y. pestis transposon insertion mutant in which the pcm gene was disrupted. In the present study, we investigated the expression and the role of pcm locus genes in Y. pestis pathogenesis using a set of isogenic surE, pcm, nlpD and rpoS mutants of the fully virulent Kimberley53 strain. We show that in Y. pestis, nlpD expression is controlled from elements residing within the upstream genes surE and pcm. The NlpD lipoprotein is the only factor encoded from the pcm locus that is essential for Y. pestis virulence. A chromosomal deletion of the nlpD gene sequence resulted in a drastic reduction in virulence to an LD50 of at least 107 cfu for subcutaneous and airway routes of infection. The mutant was unable to colonize mouse organs following infection. The filamented morphology of the nlpD mutant indicates that NlpD is involved in cell separation; however, deletion of nlpD did not affect in vitro growth rate. Trans-complementation experiments with the Y. pestis nlpD gene restored virulence and all other phenotypic defects. Finally, we demonstrated that subcutaneous administration of the nlpD mutant could protect animals against bubonic and primary pneumonic plague. Taken together, these results demonstrate that Y. pestis NlpD is a novel virulence factor essential for the development of bubonic and pneumonic plague. Further, the nlpD mutant is superior to the EV76 prototype live vaccine strain in immunogenicity and in conferring effective protective immunity. Thus it could serve as a basis for a very potent live vaccine against bubonic and pneumonic plague

Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

Abstract Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991 . Registered on November 6, 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/146186/1/12879_2018_Article_3444.pd

Collaboration networks and scientific quality among behavioural ecologists

Quantifying an author’s scientific impact is becoming increasingly important for evaluation and comparison purposes (e.g., for university recruitment and advancement or the award of grants). To this end, a number of quantitative metrics have been proposed that (in principle) allow the comparison of individuals’ scientific quality or impact (Cartwright and McGhee 2005; Cheek et al. 2006; Meho 2007; although for a discussion on the potential pitfalls of this approach, see e.g., Garfield 1979; MacRoberts and MacRoberts 1996). These generally fall into the categories of reputation, yield or productivity, and influence or impact (Avital and Collopy 2001). Commonly used metrics include the total number of papers published, which is commonly used to gauge basal productivity and is likely to be positively correlated with factors such as funding obtained and research group size; the mean or total number of citations received, which are assumed to indicate the scientific utility of a study and can thus be used as a partial indicator of a study’s quality and impact (Lawani 1986); and the journals where the papers were published and these journals’ impact parameter (e.g., Steinpreis et al. 1999). In particular, publication productivity and measures of citation frequency are commonly used to assess influence, although other metrics have also been proposed that incorporate both measures into a single metric. For example, the h-index, developed by Hirsch (2005), aims to measure the cumulative impact of a researcher’s output by looking at the quantity of papers published along with the number citations his/her work has received. The effective evaluation of such metrics is likely to require an understanding of factors such as visibility, the size of citing community, and the extent of integration into social and professional networks (Ward et al. 1992). However, the relationship between these factors and scientific impact is unclear. Here, I investigate how variation in individual scientific impact is related to the structure of the scientific collaboration network (specifically, the coauthorship network) of which they are a part

Prospective cohort study of influenza vaccine effectiveness among healthcare personnel in Lima, Peru: Estudio Vacuna de Influenza Peru, 2016-2018

© 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd. Background: The Estudio Vacuna de Influenza Peru (VIP) cohort aims to describe the frequency of influenza virus infection, identify predictors of vaccine acceptance, examine the effects of repeated influenza vaccination on immunogenicity, and evaluate influenza vaccine effectiveness among HCP. Methods: The VIP cohort prospectively followed HCP in Lima, Peru, during the 2016-2018 influenza seasons; a fourth year is ongoing. Participants contribute blood samples before and after the influenza season and after influenza vaccination (for vaccinees). Weekly surveillance is conducted to identify acute respiratory or febrile illnesses (ARFI). When an ARFI is identified, participants self-collect nasal swabs that are tested for influenza viruses by real-time reverse transcriptase-polymerase chain reaction. Influenza vaccination status and 5-year vaccination history are ascertained. We analyzed recruitment and enrollment results for 2016-2018 and surveillance participation for 2016-2017. Results: In the first 3 years of the cohort, VIP successfully contacted 92% of potential participants, enrolled 76% of eligible HCP, and retained \u3e90% of participants across years. About half of participants are medical assistants (54%), and most provide “hands-on” medical care (76%). Sixty-nine percent and 52% of participants completed surveillance for \u3e70% of weeks in years 1 and 2, respectively. Fewer weeks of completed surveillance was associated with older age (≥50 years), being a medical assistant, self-rated health of fair or poor, and not receiving the influenza vaccine during the current season (P-values \u3c.05). Conclusions: The VIP cohort provides an opportunity to address knowledge gaps about influenza virus infection, vaccination uptake, effectiveness and immunogenicity among HCP

Performance of the VERSANT (R) HIV-1 Resistance Assays (LiPA) for detecting drug resistance in therapy-naive patients infected with different HIV-1 subtypes

In this study we evaluated the performance of the VERSANT((R)) HIV-1 Resistance Assays (LiPA) in detecting drug resistance in therapy-naive HIV-infected patients diagnosed in Belgium in 2000. We compared the results with population sequencing and found concordance to be in line with previous studies in treatment-experienced patients (86.87% for reverse transcriptase (RT); 92.77% for protease (PRO)). Discordance was mainly due to indeterminate reactions on LiPA (8.45% for RT; 6.85% for PRO) and minor discordances (4.13% for RT; 0.25% for PRO). Major discordances were rare (0.46% for RT; 0.12% for PRO). Indeterminate reactions were significantly associated with strains belonging to non-B subtypes. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V.. All rights reserved

Inflammatory response and long-term behavioral assessment after neonatal CO2-pneumothorax: study in a rodent model

Background: Carbon-dioxide (CO2)-pneumothorax during minimally invasive surgery induces well-known metabolic changes. However, little is known about its impact on the central nervous system.The aim of this work is to evaluate the acute impact of CO2-pneumothorax over central cytokine response and its long-term effect on animal behavior.Methods: This is an experimental study where neonatal Sprague-Dawley rats are submitted to CO2-pneumothorax. Peripheral and central cytokine response was evaluated 24 h after insufflation, and peripheral immune cell phenotyping was evaluated 24 h and 4 weeks post-insufflation. Progenitor cell survival was evaluated in the hippocampal dentate gyrus, and the behavioral analysis was performed in adulthood to test cognition, anxious-like, and depressive-like behavior.Results: Significantly increased 11-10 levels were observed in the cerebrospinal-fluid (CSF) of animals submitted to CO2-pneurnothorax, while no differences were found in serum. Regarding pro-inflammatory cytokines, no differences were observed in the periphery or centrally. CO2-pneumothorax event did not alter the survival of newborn cells in the hippocampal dentate gyrus, and no impact on long-term behavior was observed.Conclusions: Neonatal animals submitted to CO2-pneumothorax present acutely increased CSF IL-10 levels. The CO2 pneumothorax seems to result in no significant outcome over neurodevelopment as no functional behavioral alterations were observed in adulthood.FEDER through the Operational Programme Competitiveness Factors - COMPETE and National Funds through the Foundation for Science and Technology -FCT under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We also acknowledge the FCT for providing a doctoral fellowship to A. Miranda (SFRH/BD/52059/2012) and to C. Serre-Miranda (SFRH/BD/112494/2015) and a post-doctoral fellowship to S. Roque (SFRH/BPD/72710/2010). The funders have not been involved in manuscript writing or the decision to submit the article for publicationinfo:eu-repo/semantics/publishedVersio

Prospective cohort study of influenza vaccine effectiveness among healthcare personnel in Lima, Peru: Estudio Vacuna de Influenza Peru, 2016- 2018

BackgroundThe Estudio Vacuna de Influenza Peru (VIP) cohort aims to describe the frequency of influenza virus infection, identify predictors of vaccine acceptance, examine the effects of repeated influenza vaccination on immunogenicity, and evaluate influenza vaccine effectiveness among HCP.MethodsThe VIP cohort prospectively followed HCP in Lima, Peru, during the 2016- 2018 influenza seasons; a fourth year is ongoing. Participants contribute blood samples before and after the influenza season and after influenza vaccination (for vaccinees). Weekly surveillance is conducted to identify acute respiratory or febrile illnesses (ARFI). When an ARFI is identified, participants self- collect nasal swabs that are tested for influenza viruses by real- time reverse transcriptase- polymerase chain reaction. Influenza vaccination status and 5- year vaccination history are ascertained. We analyzed recruitment and enrollment results for 2016- 2018 and surveillance participation for 2016- 2017.ResultsIn the first 3 years of the cohort, VIP successfully contacted 92% of potential participants, enrolled 76% of eligible HCP, and retained >90% of participants across years. About half of participants are medical assistants (54%), and most provide - hands- on- medical care (76%). Sixty- nine percent and 52% of participants completed surveillance for >70% of weeks in years 1 and 2, respectively. Fewer weeks of completed surveillance was associated with older age (- ¥50 years), being a medical assistant, self- rated health of fair or poor, and not receiving the influenza vaccine during the current season (P- values < .05).ConclusionsThe VIP cohort provides an opportunity to address knowledge gaps about influenza virus infection, vaccination uptake, effectiveness and immunogenicity among HCP.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155966/1/irv12737.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155966/2/irv12737_am.pd