bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Profiling of Mycobacterium tuberculosis Exposed toIn VitroLysosomal Stress
Authors: Lin Wenwei , de Sessions Paola Florez , Teoh Garrett Hor Keong , Mohamed Ahmad Naim Nazri , Zhu Yuan O. , Koh Vanessa Hui Qi , Ang Michelle Lay Teng , Dedon Peter C. , Hibberd Martin Lloyd , Alonso Sylvie 
Published: June 2016

ABSTRACTIncreasing experimental evidence supports the idea thatMycobacterium tuberculosishas evolved strategies to survive within lysosomes of activated macrophages. To further our knowledge ofM. tuberculosisresponse to the hostile lysosomal environment, we profiled the global transcriptional activity ofM. tuberculosiswhen exposed to the lysosomal soluble fraction (SF) prepared from activated macrophages. Transcriptome sequencing (RNA-seq) analysis was performed using various incubation conditions, ranging from noninhibitory to cidal based on the mycobacterial replication or killing profile. Under inhibitory conditions that led to the absence of apparent mycobacterial replication,M. tuberculosisexpressed a unique transcriptome with modulation of genes involved in general stress response, metabolic reprogramming, respiration, oxidative stress, dormancy response, and virulence. The transcription pattern also indicates characteristic cell wall remodeling with the possible outcomes of increased infectivity, intrinsic resistance to antibiotics, and subversion of the host immune system. Among the lysosome-specific responses, we identified theglgE-mediated 1,4 α-glucan synthesis pathway and a defined group of VapBC toxin/anti-toxin systems, both of which represent toxicity mechanisms that potentially can be exploited for killing intracellular mycobacteria. A meta-analysis including previously reported transcriptomic studies in macrophage infection andin vitrostress models was conducted to identify overlapping and nonoverlapping pathways. Finally, the Tap efflux pump-encoding geneRv1258cwas selected for validation. AnM. tuberculosis ΔRv1258cmutant was constructed and displayed increased susceptibility to killing by lysosomal SF and the antimicrobial peptide LL-37, as well as attenuated survival in primary murine macrophages and human macrophage cell line THP-1.
The Type Three Secretion System 2-Encoded Regulator EtrB Modulates Enterohemorrhagic Escherichia coli Virulence Gene Expression
Authors: Luzader Deborah H. , Willsey Graham G. , Wargo Matthew J. , Kendall Melissa M. 
Published: June 2016

ABSTRACT

Enterohemorrhagic
Escherichia coli
O157:H7 (EHEC) is a foodborne pathogen that causes bloody diarrhea and hemolytic uremic syndrome throughout the world. A defining feature of EHEC pathogenesis is the formation of attaching and effacing (AE) lesions on colonic epithelial cells. Most of the genes that code for AE lesion formation, including a type three secretion system (T3SS) and effectors, are carried within a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE). In this study, we report that a putative regulator, which is encoded in the cryptic
E. coli
type three secretion system 2 (ETT2) locus and herein renamed EtrB, plays an important role in EHEC pathogenesis. The
etrB
gene is expressed as a monocistronic transcript, and EtrB autoregulates expression. We provide evidence that EtrB directly interacts with the
ler
regulatory region to activate LEE expression and promote AE lesion formation. Additionally, we mapped the EtrB regulatory circuit in EHEC to determine a global role for EtrB. EtrB is regulated by the transcription factor QseA, suggesting that these proteins comprise a regulatory circuit important for EHEC colonization of the gastrointestinal tract.
AlgU Controls Expression of Virulence Genes in Pseudomonas syringae pv. tomato DC3000
Authors: Markel Eric , Stodghill Paul , Bao Zhongmeng , Myers Christopher R. , Swingle Bryan 
Published: June 2016

ABSTRACTPlant-pathogenic bacteria are able to integrate information about their environment and adjust gene expression to provide adaptive functions. AlgU, an extracytoplasmic function (ECF) sigma factor encoded byPseudomonas syringae, controls expression of genes for alginate biosynthesis and genes involved with resisting osmotic and oxidative stress. AlgU is active while these bacteria are associated with plants, where its presence supports bacterial growth and disease symptoms. We found that AlgU is an important virulence factor forP. syringaepv. tomato DC3000 but that alginate production is dispensable for disease in host plants. This implies that AlgU regulates additional genes that facilitate bacterial pathogenesis. We used transcriptome sequencing (RNA-seq) to characterize the AlgU regulon and chromatin immunoprecipitation sequencing (ChIP-seq) to identify AlgU-regulated promoters associated with genes directly controlled by this sigma factor. We found that in addition to genes involved with alginate and osmotic and oxidative stress responses, AlgU regulates genes with known virulence functions, including components of the Hrp type III secretion system, virulence effectors, and thehrpLandhrpRStranscription regulators. These data suggest thatP. syringaepv. tomato DC3000 has adapted to use signals that activate AlgU to induce expression of important virulence functions that facilitate survival and disease in plants.IMPORTANCEPlant immune systems produce antimicrobial and bacteriostatic conditions in response to bacterial infection. Plant-pathogenic bacteria are adapted to suppress and/or tolerate these conditions; however, the mechanisms controlling these bacterial systems are largely uncharacterized. The work presented here provides a mechanistic explanation for howP. syringaepv. tomato DC3000 coordinates expression of multiple genetic systems, including those dedicated to pathogenicity, in response to environmental conditions. This work demonstrates the scope of AlgU regulation inP. syringaepv. tomato DC3000 and characterizes the promoter sequence regulated by AlgU in these bacteria.
The Na
+
-Translocating NADH:Quinone Oxidoreductase Enhances Oxidative Stress in the Cytoplasm of Vibrio cholerae
Authors: Muras Valentin , Dogaru-Kinn Paul , Minato Yusuke , Häse Claudia C. , Steuber Julia 
Published: June 2016

ABSTRACT

We searched for a source of reactive oxygen species (ROS) in the cytoplasm of the human pathogen
Vibrio cholerae
and addressed the mechanism of ROS formation using the dye 2′,7′-dichlorofluorescein diacetate (DCFH-DA) in respiring cells. By comparing
V. cholerae
strains with or without active Na
+
-translocating NADH:quinone oxidoreductase (Na
+
-NQR), this respiratory sodium ion redox pump was identified as a producer of ROS
in vivo
. The amount of cytoplasmic ROS detected in
V. cholerae
cells producing variants of Na
+
-NQR correlated well with rates of superoxide formation by the corresponding membrane fractions. Membranes from wild-type
V. cholerae
showed increased superoxide production activity (9.8 ± 0.6 μmol superoxide min
−1
mg
−1
membrane protein) compared to membranes from the mutant lacking Na
+
-NQR (0.18 ± 0.01 μmol min
−1
mg
−1
). Overexpression of plasmid-encoded Na
+
-NQR in the
nqr
deletion strain resulted in a drastic increase in the formation of superoxide (42.6 ± 2.8 μmol min
−1
mg
−1
). By analyzing a variant of Na
+
-NQR devoid of quinone reduction activity, we identified the reduced flavin adenine dinucleotide (FAD) cofactor of cytoplasmic NqrF subunit as the site for intracellular superoxide formation in
V. cholerae
. The impact of superoxide formation by the Na
+
-NQR on the virulence of
V. cholerae
is discussed.

IMPORTANCE
In several studies, it was demonstrated that the Na
+
-NQR in
V. cholerae
affects virulence in a yet unknown manner. We identified the reduced FAD cofactor in the NADH-oxidizing NqrF subunit of the Na
+
-NQR as the site of superoxide formation in the cytoplasm of
V. cholerae
. Our study provides the framework to understand how reactive oxygen species formed during respiration could participate in the regulated expression of virulence factors during the transition from aerobic to microaerophilic (intestinal) habitats. This hypothesis may turn out to be right for many other pathogens which, like
V. cholerae
, depend on the Na
+
-NQR as the sole electrogenic NADH dehydrogenase.
Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies
Authors: Fayaz A , Croft P , Langford R M , Donaldson L J , Jones G T 
Published: June 2016

ObjectivesThere is little consensus regarding the burden of pain in the UK. The purpose of this review was to synthesise existing data on the prevalence of various chronic pain phenotypes in order to produce accurate and contemporary national estimates.DesignMajor electronic databases were searched for articles published after 1990, reporting population-based prevalence estimates of chronic pain (pain lasting >3 months), chronic widespread pain, fibromyalgia and chronic neuropathic pain. Pooled prevalence estimates were calculated for chronic pain and chronic widespread pain.ResultsOf the 1737 articles generated through our searches, 19 studies matched our inclusion criteria, presenting data from 139 933 adult residents of the UK. The prevalence of chronic pain, derived from 7 studies, ranged from 35.0% to 51.3% (pooled estimate 43.5%, 95% CIs 38.4% to 48.6%). The prevalence of moderate-severely disabling chronic pain (Von Korff grades III/IV), based on 4 studies, ranged from 10.4% to 14.3%. 12 studies stratified chronic pain prevalence by age group, demonstrating a trend towards increasing prevalence with increasing age from 14.3% in 18–25 years old, to 62% in the over 75 age group, although the prevalence of chronic pain in young people (18–39 years old) may be as high as 30%. Reported prevalence estimates were summarised for chronic widespread pain (pooled estimate 14.2%, 95% CI 12.3% to 16.1%; 5 studies), chronic neuropathic pain (8.2% to 8.9%; 2 studies) and fibromyalgia (5.4%; 1 study). Chronic pain was more common in female than male participants, across all measured phenotypes.ConclusionsChronic pain affects between one-third and one-half of the population of the UK, corresponding to just under 28 million adults, based on data from the best available published studies. This figure is likely to increase further in line with an ageing population.
Direct inpatient burden caused by foot-related conditions: a multisite point-prevalence study
Authors: Lazzarini Peter A , Hurn Sheree E , Kuys Suzanne S , Kamp Maarten C , Ng Vanessa , Thomas Courtney , Jen Scott , Kinnear Ewan M , d'Emden Michael C , Reed Lloyd 
Published: June 2016

ObjectiveThe aims of this point-prevalence study were to investigate a representative inpatient population to determine the prevalence of people admitted to hospital for the reason of a foot-related condition, and identify associated independent factors.MethodsParticipants were adult inpatients in 5 different representative hospitals, admitted for any reason on the day of data collection. Maternity, mental health and cognitively impaired inpatients were excluded. Participants were surveyed on a range of self-reported demographic, social determinant, medical history, foot disease history, self-care, footwear, past foot treatment prior to hospitalisation and reason for admission variables. Physical examinations were performed to clinically diagnose a range of foot disease and foot risk factor variables. Independent factors associated with being admitted to hospital for the primary or secondary reason of a foot-related condition were analysed using multivariate logistic regression.ResultsOverall, 733 participants were included; mean (SD) age 62 (19) years, male 55.8%. Foot-related conditions were the primary reason for admission in 54 participants (7.4% (95% CI 5.7% to 9.5%)); 36 for foot disease (4.9%), 15 foot trauma (2.1%). Being admitted for the primary reason of a foot-related condition was independently associated with foot infection, critical peripheral arterial disease, foot trauma and past foot treatment by a general practitioner and surgeon (p<0.01). Foot-related conditions were a secondary reason for admission in 28 participants (3.8% (2.6% to 5.6%)), and were independently associated with diabetes and current foot ulcer (p<0.01).ConclusionsThis study, the first in a representative inpatient population, suggests the direct inpatient burden caused by foot-related conditions is significantly higher than previously appreciated. Findings indicate 1 in every 13 inpatients was primarily admitted because of a foot-related condition with most due to foot disease or foot trauma. Future strategies are recommended to investigate and intervene in the considerable inpatient burden caused by foot-related conditions.
Disclosing victimisation to healthcare professionals in Sweden: a constructivist grounded theory study of experiences among men exposed to interpersonal violence
Authors: Simmons Johanna , Brüggemann Adrianus Jelmer , Swahnberg Katarina 
Published: June 2016

ObjectiveTo develop a theoretical model concerning male victims' processes of disclosing experiences of victimisation to healthcare professionals in Sweden.DesignQualitative interview study.SettingInformants were recruited from the general population and a primary healthcare centre in Sweden.ParticipantsInformants were recruited by means of theoretical sampling among respondents in a previous quantitative study. Eligible for this study were men reporting sexual, physical and/or emotional violence victimisation by any perpetrator and reporting that they either had talked to a healthcare provider about their victimisation or had wanted to do so.MethodConstructivist grounded theory. 12 interviews were performed and saturation was reached after 9.ResultsSeveral factors influencing the process of disclosing victimisation can be recognised from previous studies concerning female victims, including shame, fear of negative consequences of disclosing, specifics of the patient–provider relationship and time constraints within the healthcare system. However, this study extends previous knowledge by identifying strong negative effects of adherence to masculinity norms for victimised men and healthcare professionals on the process of disclosing. It is also emphasised that the process of disclosing cannot be separated from other, even seemingly unrelated, circumstances in the men's lives.ConclusionsThe process of disclosing victimisation to healthcare professionals was a complex process involving the men's experiences of victimisation, adherence to gender norms, their life circumstances and the dynamics of the actual healthcare encounter.
Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children
Authors: Zanella Sara , De Leo Luigina , Nguyen-Ngoc-Quynh Le , Nguyen-Duy Bo , Not Tarcisio , Tran-Thi-Chi Mai , Phung-Duc Son , Le-Thanh Hai , Malaventura Cristina , Vatta Serena , Ziberna Fabiana , Mazzocco Martina , Volpato Stefano , Phung-Tuyet Lan , Le-Thi-Minh Huong , Borgna-Pignatti Caterina 
Published: June 2016

ObjectiveThe prevalence of coeliac disease (CD) in Vietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi.SettingThe outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam.ParticipantsChildren having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years).OutcomesPrimary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG.ResultsThe IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative.ConclusionsCoeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings.
β-Adrenoreceptor agonists in the management of pain associated with renal colic: a systematic review
Authors: Tabner Andrew John , Johnson Graham David , Fakis Apostolos , Surtees Jane , Lennon Robert Iain 
Published: June 2016

ObjectivesTo determine whether β-adrenoreceptor agonists are effective analgesics for patients with renal colic through a systematic review of the literature.SettingAdult emergency departments or acute assessment units.ParticipantsHuman participants with proven or suspected renal colic.Interventionsβ-adrenoreceptor agonists.Outcome measuresPrimary: level of pain at 30 min following administration of the β-agonist.Secondary: level of pain at various time points following β-agonist administration; length of hospital stay; analgesic requirement; stone presence, size and position; degree of hydronephrosis.Results256 records were screened and 4 identified for full-text review. No articles met the inclusion criteria.Conclusions and implicationsThere is no evidence to support or refute the proposed use of β-agonists for analgesia in patients with renal colic. Given the biological plausibility and existing literature base, clinical trials investigating the use of β-adrenoreceptor agonists in the acute setting for treatment of the pain associated with renal colic are recommended.Trial registration numberCRD42015016266.
Consultants as victims of bullying and undermining: a survey of Royal College of Obstetricians and Gynaecologists consultant experiences
Authors: Shabazz Tariq , Parry-Smith William , Oates Sharon , Henderson Steven , Mountfield Joanna 
Published: June 2016

ObjectiveTo explore incidents of bullying and undermining among obstetrics and gynaecology (O&G) consultants in the UK, to add another dimension to previous research and assist in providing a more holistic understanding of the problem in medicine.DesignQuestionnaire survey.SettingRoyal College of Obstetricians and Gynaecologists (RCOG).ParticipantsO&G consultant members/fellows of the RCOG working in the UK.Main outcome measuresMeasures included a typology of 4 bullying and undermining consequences from major to coping.ResultsThere was a 28% (664) response rate of whom 44% (229) responded that they had been persistently bullied or undermined. Victims responded that bullying and undermining is carried out by those senior or at least close in the hierarchy. Of the 278 consultants who answered the question on ‘frequency of occurrence’, 50% stated that bullying and undermining occurs on half, or more, of all encounters with perpetrators and two-thirds reported that it had lasted more than 3 years. The reported impact on professional and personal life spans a wide spectrum from suicidal ideation, depression and sleep disturbance, and a loss of confidence. Over half reported problems that could compromise patient care. When victims were asked if the problem was being addressed, 73% of those that responded stated that it was not.ConclusionsSignificant numbers of consultants in O&G in the UK are victims of bullying and undermining behaviour that puts their own health and patient care at risk. New interventions to tackle the problem, rather than its consequences, are required urgently, together with greater commitment to supporting such interventions.
Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration ProjectPRELUDE
Authors: Vaccher S , Grulich A , McAllister J , Templeton D J , Bloch M , McNulty A , Holden J , Poynten I M , Prestage G , Zablotska I 
Published: June 2016

IntroductionDespite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. ThePRELUDEstudy aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults.Methods and analysisPRELUDEis an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants—mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV.Ethics and disseminationThe study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete.Trial registration numberNCT02206555; Pre-results.