bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane Curvature and the Tol-Pal Complex Determine Polar Localization of the Chemoreceptor Tar in Escherichia coli
Authors: Saaki Terrens N. V. , Strahl Henrik , Hamoen Leendert W. 
Published: February 2018

ABSTRACT

Chemoreceptors are localized at the cell poles of
Escherichia coli
and other rod-shaped bacteria. Over the years, different mechanisms have been put forward to explain this polar localization, including stochastic clustering, membrane curvature-driven localization, interactions with the Tol-Pal complex, and nucleoid exclusion. To evaluate these mechanisms, we monitored the cellular localization of the aspartate chemoreceptor Tar in different deletion mutants. We did not find any indication for either stochastic cluster formation or nucleoid exclusion. However, the presence of a functional Tol-Pal complex appeared to be essential to retain Tar at the cell poles. Interestingly, Tar still accumulated at midcell in
tol
and in
pal
deletion mutants. In these mutants, the protein appears to gather at the base of division septa, a region characterized by strong membrane curvature. Chemoreceptors, like Tar, form trimers of dimers that bend the cell membrane due to a rigid tripod structure. The curvature approaches the curvature of the cell membrane generated during cell division, and localization of chemoreceptor tripods at curved membrane areas is therefore energetically favorable, as it lowers membrane tension. Indeed, when we introduced mutations in Tar that abolish the rigid tripod structure, the protein was no longer able to accumulate at midcell or the cell poles. These findings favor a model where chemoreceptor localization in
E. coli
is driven by strong membrane curvature and association with the Tol-Pal complex.

IMPORTANCE
Bacteria have exquisite mechanisms to sense and adapt to the environment they live in. One such mechanism involves the chemotaxis signal transduction pathway, in which chemoreceptors specifically bind certain attracting or repelling molecules and transduce the signals to the cell. In different rod-shaped bacteria, these chemoreceptors localize specifically to cell poles. Here, we examined the polar localization of the aspartate chemoreceptor Tar in
E. coli
and found that membrane curvature at cell division sites and the Tol-Pal protein complex localize Tar at cell division sites, the future cell poles. This study shows how membrane curvature can guide localization of proteins in a cell.
Simple limbal epithelial transplantation (SLET) in failed cultivated limbal epithelial transplantation (CLET) for unilateral chronic ocular burns
Authors: Basu Sayan , Mohan Sashwanthi , Bhalekar Swapnil , Singh Vivek , Sangwan Virender 
Published: February 2018

AimsCultivated limbal epithelial transplantation (CLET) fails in around 20%–30% of cases. This study aimed to report the clinical outcomes of autologous simple limbal epithelial transplantation (SLET) in eyes with recurrent unilateral limbal stem cell deficiency (LSCD) due to failure of CLET.MethodsThis was a prospective case series which included 30 eyes of 30 patients who underwent SLET between 2010 and 2016 after failure of one (n=24) or two (n=6) previous CLET procedures for chronic unilateral ocular burns. The primary outcome measure was success of SLET defined on the basis of relative improvement in five objective criteria: best corrected visual acuity (BCVA), and grades of symblepharon, corneal conjunctivalisation, vascularisation and opacification.ResultsAt a mean follow-up of 2.3 years, 24 (80%) of the 30 eyes maintained a successful outcome. Kaplan-Meier analysis showed a 5-year survival probability of 77%±8%. At 1 year postoperatively statistically significant improvement was noted in BCVA (logarithm of the minimum angle of resolution of 3 to 1) and in the median grades of corneal conjunctivalisation (2 to 0), vascularisation (2 to 0) and opacification (2 to 1) (P≤0.0026). In 62.5% of successful cases, BCVA improved to 20/200 or better. The success rate of SLET in failed CLET was better than that of repeat CLET (53.5%, P=0.011). None of the donor eyes developed any complications.ConclusionSLET is an effective alternative to CLET in eyes with recurrence of LSCD after previously failed CLET procedures. Since SLET is single-staged and less expensive, it is probably preferable to repeating CLET.
Can lay health workers support the management of hypertension? Findings of a cluster randomised trial in South Africa
Authors: Goudge Jane , Chirwa Tobias , Eldridge Sandra , Gómez-Olivé Francesc Xavier F , Kabudula Chodziwadziwa , Limbani Felix , Musenge Eustasius , Thorogood Margaret 
Published: February 2018

IntroductionIn low/middle-income countries with substantial HIV and tuberculosis epidemics, health services often neglect other highly prevalent chronic conditions, such as hypertension, which as a result are poorly managed. This paper reports on a study to assess the effect on hypertension management of lay health workers (LHW) working in South African rural primary healthcare clinics to support the provision of integrated chronic care.MethodsA pragmatic cluster randomised trial with a process evaluation in eight rural clinics assessed the effect of adding two LHWs supporting nurses in providing chronic disease care in each intervention clinic over 18 months. Control clinics continued with usual care. The main outcome measure was the change in the difference of percentage of clinic users who had elevated cardiovascular risk associated with high blood pressure (BP) before and after the intervention, as measured by two cross-sectional population surveys.ResultsThere was no improvement in BP control among users of intervention clinics as compared with control clinics. However, the LHWs improved clinic functioning, including overall attendance, and attendance on the correct day. All clinics faced numerous challenges, including rapidly increasing number of users of chronic care, unreliable BP machines and cuffs, intermittent drug shortages and insufficient space.ConclusionLHWs improved the process of providing care but improved BP control required improved clinical care by nurses which was compromised by large and increasing numbers of patients, the dominance of the vertically funded HIV programme and the poor standards of equipment in clinics.Trial registration numberISRCTN12128227.
Does insurance enrolment increase healthcare utilisation among rural-dwelling older adults? Evidence from the National Health Insurance Scheme in Ghana
Authors: van der Wielen Nele , Channon Andrew Amos , Falkingham Jane 
Published: February 2018

IntroductionThis paper examines the relationship between national health insurance enrolment and the utilisation of inpatient and outpatient healthcare for older adults in rural areas in Ghana. The Ghanaian National Health Insurance Scheme (NHIS) aims to improve affordability and increase the utilisation of healthcare. However, the system has been criticised for not being responsive to the needs of older adults. The majority of older adults in Ghana live in rural areas with poor accessibility to healthcare. With an ageing population, a specific assessment of whether the scheme has benefitted older adults, and also if the benefit is equitable, is needed.MethodsUsing the Ghanaian Living Standards Survey from 2012 to 2013, this paper uses propensity score matching to estimate the effect of enrolment within the NHIS on the utilisation of inpatient and outpatient care among older people aged 50 and over.ResultsThe raw results show higher utilisation of healthcare among NHIS members, which persists after matching. NHIS members were 6% and 9% more likely to use inpatient and outpatient care, respectively, than non-members. When these increases were disaggregated for outpatient care, the non-poor and females were seen to benefit more than their poor and male counterparts. For inpatient care, the benefits of enrolment were equal by poverty status and sex. However, overall, poor older adults use health services much less than the non-poor older adults even when enrolled.ConclusionThe results indicate that NHIS coverage does increase healthcare utilisation among rural older adults but that inequalities remain. The poor are still at a great disadvantage in their use of health services overall and benefit less from enrolment for outpatient care. The receipt of healthcare is significantly influenced by a set of auxiliary barriers to access to healthcare even where insurance should remove the financial burden of ad hoc out of pocket payments.
’Well, it literally stops me from having a life when it’s really bad': a nested qualitative interview study of patient views on the use of self-management treatments for the management of recurrent sinusitis (SNIFS trial)
Authors: Leydon Geraldine M , McDermott Lisa , Thomas Tammy , Halls Amy , Holdstock-Brown Ben , Petley Stephen , Wiseman Clare , Little Paul 
Published: February 2018

ObjectiveTo explore the experience and perceptions of illness, the decision to consult a general practitioner and the use of self-management approaches for chronic or recurrent sinusitis.DesignQualitative semistructured interview study.SettingUK primary care.Participants32 participants who had been participating in the ‘SNIFS’ (Steam inhalation and Nasal Irrigation For recurrent Sinusitis) trial in the South of England.MethodThematic analysis of semistructured telephone interviews.ResultsParticipants often reported dramatic impact on both activities and their quality of life. Participants were aware of both antibiotic side effects and resistance, but if they had previously been prescribed antibiotics, many patients believed that they would be necessary for the future treatment of sinusitis. Participants used self-help treatments for short and limited periods of time only. In the context of the trial, steam inhalation used for recurrent sinusitis was described as acceptable but is seen as having limited effectiveness. Nasal irrigation was viewed as acceptable and beneficial by more patients. However, some participants reported that they would not use the treatment again due to the uncomfortable side effects they experienced, which outweighed any symptom relief, which may have resulted had they continued.ConclusionsSteam inhalation is acceptable but seen as having limited effectiveness. Nasal irrigation is generally acceptable and beneficial for symptoms, but detailed information on the correct procedure and potential benefits of persisting may increase acceptability and adherence in those patients who find it uncomfortable.Trial registration numberISRCTN 88204146.
Impact of variation in functions and delivery on the effectiveness of behavioural and mood management interventions for smoking cessation in people with depression: protocol for a systematic review and meta-analysis
Authors: Taylor Gemma , Aveyard Paul , Meer Regina Van der , Toze Daniel , Stuijfzand Bobby , Kessler David , Munafò Marcus 
Published: February 2018

IntroductionTobacco is the world’s leading preventable cause of disease and death. People with depression are twice as likely to smoke and are less responsive to standard tobacco treatments as compared with the general population. A Cochrane systematic review of randomised controlled trials of smoking cessation treatment for smokers with current or historical depression found that adding mood management to usual smoking treatment improved quit rates. However, the review did not examine if variation in intervention delivery or intervention functions impacted on treatment effectiveness.With the aim of providing information to develop tailored approaches to treating smoking for people with current depression, we will add-on to the Cochrane review in three ways: (1) use the Template for Intervention Description and Replication checklist to determine if variations in mood management delivery have impact on intervention effectiveness, (2) use the Taxonomy of Behaviour Change techniques for smoking cessation to examine which behaviour change functions are most effective for smoking cessation in people with current depression and (3) examine the difference in change in depression scores between intervention and control arms.Methods and analysisWe will include randomised controlled trials of smokers with current depression as identified by a previous Cochrane review and the in-progress update of this Cochrane review. We will use meta-regression to examine (1) if variations in delivery of mood management impact on smoking cessation intervention effectiveness, (2) determine which behaviour change functions are most effective for smoking cessation and (3) use meta-analysis of the difference in change in depression scores between treatment arms from baseline to follow-up to determine if offering smoking cessation treatment causes psychological harm.Ethics anddisseminationEthical approval is not required for this study. We will disseminate the findings of this work at national and international conferences, and to relevant patient panels.PROSPERO registration numberCRD42017070741.
Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China
Authors: Li Cheng-Wei , Tao Ru-Jia , Zou Dan-Feng , Li Man-Hui , Xu Xin , Cao Wei-Jun 
Published: February 2018

ObjectivesSarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China.MethodsData from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement.ResultsTwo hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05).ConclusionsExtrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.
Characteristics and publication fate of unregistered and retrospectively registered clinical trials submitted toThe BMJover 4 years
Authors: Loder Elizabeth , Loder Stephen , Cook Sophie 
Published: February 2018

ObjectivesWe sought to evaluate the characteristics and publication fate of improperly registered clinical trials submitted to a medical journal (The BMJ) over a 4-year period to identify common types of registration issues and their relation to publication outcomes.DesignResearch articles submitted toThe BMJand identified as unregistered or retrospectively registered by editors were included if they reported outcomes of a clinical trial. Relevant data regarding the trials were then extracted from each paper. Trials were categorised as prospectively registered, registered in an unapproved registry, unregistered or other, and explanations for registration deficiencies were grouped into six categories. We searched PubMed and Google to determine whether, where and when improperly registered studies were subsequently published and whether registration issues were disclosed.Results123 research papers reporting apparently unregistered or retrospectively registered clinical trials were identified. 110 studies (89.4%) were retrospectively registered, nine (7.3%) were unregistered, three (2.4%) had been registered in an unapproved registry and one study originally lacking registration details was later discovered to have been prospectively registered. 82 studies (66.6%) were funded entirely or in part by government sources, and only seven studies (5.7%) received funding from industry. Of those papers submitted toThe BMJthrough the end of 2015, 67 of the 70 papers rejected for registration problems (95.7%) were subsequently published in another journal. The registration problem was disclosed in only 2 (2.9%).ConclusionsImproper registration remains a problem, particularly for clinical trials that are government or foundation-funded. Nonetheless, improperly registered trials are almost always published, suggesting that medical journal editors may not actively enforce registration requirements.
Identifying positively deviant elderly medical wards using routinely collected NHS Safety Thermometer data: an observational study
Authors: Baxter Ruth , Taylor Natalie , Kellar Ian , Pye Victoria , Mohammed Mohammed A , Lawton Rebecca 
Published: February 2018

ObjectiveThe positive deviance approach seeks to identify and learn from exceptional performers. Although a framework exists to apply positive deviance within healthcare organisations, there is limited guidance to support its implementation. The approach has also rarely explored exceptional performance on broad outcomes, been implemented at ward level, or applied within the UK. This study develops and critically appraises a pragmatic method for identifying positively deviant wards using a routinely collected, broad measure of patient safety.DesignA two-phased observational study was conducted. During phase 1, cross-sectional and temporal analyses of Safety Thermometer data were conducted to identify a discrete group of positively deviant wards that consistently demonstrated exceptional levels of safety. A group of matched comparison wards with above average performances were also identified. During phase 2, multidisciplinary staff and patients on the positively deviant and comparison wards completed surveys to explore whether their perceptions of safety supported the identification of positively deviant wards.Setting34 elderly medical wards within a northern region of England, UK.ParticipantsMultidisciplinary staff (n=161) and patients (n=188) clustered within nine positively deviant and comparison wards.ResultsPhase 1: A combination of analyses identified five positively deviant wards that performed best in the region, outperformed their organisation and performed consistently well over 12 months. Five above average matched comparator wards were also identified. Phase 2: Staff and patient perceptions of safety generally supported the identification of positively deviant wards using Safety Thermometer data, although patient perceptions of safety were less concordant with the routinely collected data.ConclusionsThis study tentatively supports a pragmatic method of using routinely collected data to identify positively deviant elderly medical wards; however, it also highlights the various challenges that are faced when conducting the first stage of the positive deviance approach.Trial registration numberUK Clinical Research Network Portfolio (reference-18050).
Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
Authors: Gao Xue , Yuan Yong-Yi , Lin Qiong-Fen , Xu Jin-Cao , Wang Wei-Qian , Qiao Yue-Hua , Kang Dong-Yang , Bai Dan , Xin Feng , Huang Sha-Sha , Qiu Shi-Wei , Guan Li-Ping , Su Yu , Wang Guo-Jian , Han Ming-Yu , Jiang Yi , Liu Han-Kui , Dai Pu 
Published: February 2018

Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder.Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL).Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism.Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL. Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level.ConclusionIFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
Protection from vascular dysfunction in female rats with chronic stress and depressive symptoms
Authors: Brooks Steven D. , Hileman Stanley M. , Chantler Paul D. , Milde Samantha A. , Lemaster Kent A. , Frisbee Stephanie J. , Shoemaker J. Kevin , Jackson Dwayne N. , Frisbee Jefferson C. 
Published: February 2018

The increasing prevalence and severity of clinical depression are strongly correlated with vascular disease risk, creating a comorbid condition with poor outcomes but demonstrating a sexual disparity whereby female subjects are at lower risk than male subjects for subsequent cardiovascular events. To determine the potential mechanisms responsible for this protection against stress/depression-induced vasculopathy in female subjects, we exposed male, intact female, and ovariectomized (OVX) female lean Zucker rats to the unpredictable chronic mild stress (UCMS) model for 8 wk and determined depressive symptom severity, vascular reactivity in ex vivo aortic rings and middle cerebral arteries (MCA), and the profile of major metabolites regulating vascular tone. While all groups exhibited severe depressive behaviors from UCMS, severity was significantly greater in female rats than male or OVX female rats. In all groups, endothelium-dependent dilation was depressed in aortic rings and MCAs, although myogenic activation and vascular (MCA) stiffness were not impacted. Higher-resolution results from pharmacological and biochemical assays suggested that vasoactive metabolite profiles were better maintained in female rats with normal gonadal sex steroids than male or OVX female rats, despite increased depressive symptom severity (i.e., higher nitric oxide and prostacyclin and lower H2O2and thromboxane A2levels). These results suggest that female rats exhibit more severe depressive behaviors with UCMS but are partially protected from the vasculopathy that afflicts male rats and female rats lacking normal sex hormone profiles. Determining how female sex hormones afford partial vascular protection from chronic stress and depression is a necessary step for addressing the burden of these conditions on cardiovascular health.NEW & NOTEWORTHY This study used a translationally relevant model for chronic stress and elevated depressive symptoms to determine how these factors impact conduit and resistance arteriolar function in otherwise healthy rats. While chronic stress leads to an impaired vascular reactivity associated with elevated oxidant stress, inflammation, and reduced metabolite levels, we demonstrated partial protection from vascular dysfunction in female rats with normal sex hormone profiles compared with male or ovariectomized female rats.