bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis of Functional Diversification of the HD-GYP Domain Revealed by the Pseudomonas aeruginosa PA4781 Protein, Which Displays an Unselective Bimetallic Binding Site
Authors: Rinaldo Serena , Paiardini Alessandro , Stelitano Valentina , Brunotti Paolo , Cervoni Laura , Fernicola Silvia , Protano Carmela , Vitali Matteo , Cutruzzolà Francesca , Giardina Giorgio 
Published: February 2015

ABSTRACT

The intracellular level of the bacterial secondary messenger cyclic di-3′,5′-GMP (c-di-GMP) is determined by a balance between its biosynthesis and degradation, the latter achieved via dedicated phosphodiesterases (PDEs) bearing a characteristic EAL or HD-GYP domain. We here report the crystal structure of PA4781, one of the three
Pseudomonas aeruginosa
HD-GYP proteins, which we have previously characterized
in vitro
. The structure shows a bimetallic active site whose metal binding mode is different from those of both HD-GYP PDEs characterized so far. Purified PA4781 does not contain iron in the active site as for other HD-GYPs, and we show that it binds to a wide range of transition metals with similar affinities. Moreover, the structural features of PA4781 indicate that this is preferentially a pGpG binding protein, as we previously suggested. Our results point out that the structural features of HD-GYPs are more complex than predicted so far and identify the HD-GYP domain as a conserved scaffold which has evolved to preferentially interact with a partner GGDEF but which harbors different functions obtained through diversification of the active site.

IMPORTANCE
In bacteria, the capability to form biofilms, responsible for increased pathogenicity and antibiotic resistance, is almost universally stimulated by the second messenger cyclic di-GMP (c-di-GMP). To design successful strategies for targeting biofilm formation, a detailed characterization of the enzymes involved in c-di-GMP metabolism is crucial. We solved the structure of the HD-GYP domain of PA4781 from
Pseudomonas aeruginosa
, involved in c-di-GMP degradation. This is the third structure of this class of phosphodiesterases to be solved, and with respect to its homologues, it shows significant differences both in the nature and in the binding mode of the coordinated metals, indicating that HD-GYP proteins are able to fine-tune their function, thereby increasing the chances of the microorganism to adapt to different environmental needs.
BolA Is a Transcriptional Switch That Turns Off Motility and Turns On Biofilm Development
Authors: Dressaire Clémentine , Moreira Ricardo Neves , Barahona Susana , Alves de Matos António Pedro , Arraiano Cecília Maria 
Published: February 2015

ABSTRACT

Bacteria are extremely versatile organisms that rapidly adapt to changing environments. When bacterial cells switch from planktonic growth to biofilm, flagellum formation is turned off and the production of fimbriae and extracellular polysaccharides is switched on. BolA is present in most Gram-negative bacteria, and homologues can be found from proteobacteria to eukaryotes. Here, we show that BolA is a new bacterial transcription factor that modulates the switch from a planktonic to a sessile lifestyle. It negatively modulates flagellar biosynthesis and swimming capacity in
Escherichia coli
. Furthermore, BolA overexpression favors biofilm formation, involving the production of fimbria-like adhesins and curli. Our results also demonstrate that BolA is a protein with high affinity to DNA and is able to regulate many genes on a genome-wide scale. Moreover, we show that the most significant targets of this protein involve a complex network of genes encoding proteins related to biofilm development. Herein, we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation.

IMPORTANCE
Escherichia coli
cells possess several mechanisms to cope with stresses. BolA has been described as a protein important for survival in late stages of bacterial growth and under harsh environmental conditions. BolA-like proteins are widely conserved from prokaryotes to eukaryotes. Although their exact function is not fully established at the molecular level, they seem to be involved in cell proliferation or cell cycle regulation. Here, we unraveled the role of BolA in biofilm development and bacterial motility. Our work suggests that BolA actively contributes to the decision of bacteria to arrest flagellar production and initiate the attachment to form structured communities, such as biofilms. The molecular studies of different lifestyles coupled with the comprehension of the BolA functions may be an important step for future perspectives, with health care and biotechnology applications.
Complication characteristics between young-onset type 2 versus type 1 diabetes in a UK population
Authors: Song Soon H 
Published: February 2015

BackgroundIn the UK, the care of young people with diabetes has focused predominantly on type 1 diabetes (T1D). However, young-onset T2D has become increasingly prevalent. At present, it is unclear which type of diabetes represents the more adverse phenotype to develop complications. This study aims to determine the complication burden and its predictive factors in young-onset T2D compared with T1D.MethodsA cross-sectional study using a hospital diabetes register to identify patients with young-onset T2D and T1D. Young-onset T2D was defined as age of diagnosis below 40 years. The T1D cohort with a similar age of diagnosis was used as a comparator. Data from the last clinic visit was used for analysis. Clinical characteristics and diabetes complications were evaluated at diabetes durations <10, 10–20, and >20 years. Predictive factors for diabetes complications (age, sex, glycated hemoglobin, creatinine, diabetes duration, hypertension, dyslipidemia, and body mass index >25) were determined by logistic regression analysis.ResultsData were collected on 1287 patients, of which 760 and 527 had T1D and T2D, respectively. In all diabetes durations, the T2D cohort had an older age of onset (p<0.0005) with a higher prevalence of obesity, hypertension, and dyslipidemia (all p<0.0005) while glycemic control was similar in both groups. Cardiovascular disease (p<0.005) and neuropathy (p<0.05) were more prevalent in the young-onset T2D cohort in all diabetes durations. There was no difference in retinopathy. Cardiovascular disease was predominantly due to ischemic heart disease. Stroke and peripheral vascular disease became significantly higher in T2D after 20 years duration. After controlling for traditional risk factors, young-onset T2D was an independent predictor for cardiovascular disease (p<0.005) and neuropathy (p<0.05) but not for retinopathy.ConclusionsYoung-onset T2D is a more aggressive phenotype than T1D to develop diabetes complications, particularly for ischemic heart disease and neuropathy.
Improving outcomes in patients with coexisting multimorbid conditions—the development and evaluation of the combined diabetes and renal control trial (C-DIRECT): study protocol
Authors: Griva Konstadina , Mooppil Nandakumar , Khoo Eric , Lee Vanessa Yin Woan , Kang Augustine Wee Cheng , Newman Stanton P 
Published: February 2015

IntroductionDiabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD). Patients with diabetes on dialysis have worse clinical outcomes and increased psychological burden. The need to manage the combined treatment demands for both conditions is particularly challenging yet there is paucity of data of the barriers preventing optimal management to combined therapy for diabetes and kidney failure. The study aims to explore needs of patients and develop an intervention to enable people with diabetes and ESRD to better manage both their conditions.Methods and analysisA two-phase study comprising a mixed method observational study (phase I) and a feasibility trial (phase II). Phase I will seek to document outcomes and needs of the population (patients with DM-ESRD) and seek input on preferred delivery/implementation for the programme. Data will be collected with in-depth interviews with patients, caregivers and healthcare providers (N=50), and from a questionnaire-based survey (N=170). Phase 2 will build on these data to design and test the feasibility of a practical, low-intensity, clinic-integrated intervention using a self-management paradigm. The intervention will primarily seek to support behavioural change so as to improve adherence and clinical outcomes for DM as well as for ESRD. For the feasibility trial, we will be evaluating acceptability, retention and completion rates of the programme.Ethics and disseminationThe study protocol has been approved by the local ethics committee and written informed consent is required from every participant. Findings will be disseminated through journals, conferences and will be used to create a fully manualised intervention (materials) and training course for facilitators.
A randomised controlled study of the long-term effects of exercise training on mortality in elderly people: study protocol for the Generation 100 study
Authors: Stensvold Dorthe , Viken Hallgeir , Rognmo Øivind , Skogvoll Eirik , Steinshamn Sigurd , Vatten Lars J , Coombes Jeff S , Anderssen Sigmund A , Magnussen Jon , Ingebrigtsen Jan Erik , Fiatarone Singh Maria A , Langhammer Arnulf , Støylen Asbjørn , Helbostad Jorunn L , Wisløff Ulrik 
Published: February 2015

IntroductionEpidemiological studies suggest that exercise has a tremendous preventative effect on morbidity and premature death, but these findings need to be confirmed by randomised trials. Generation 100 is a randomised, controlled study where the primary aim is to evaluate the effects of 5 years of exercise training on mortality in an elderly population.Methods and analysisAll men and women born in the years 1936–1942 (n=6966), who were residents of Trondheim, Norway, were invited to participate. Between August 2012 and June 2013, a total of 1567 individuals (790 women) were included and randomised to either 5 years of two weekly sessions of high-intensity training (10 min warm-up followed by 4×4 min intervals at ∼90% of peak heart rate) or, moderate-intensity training (50 min of continuous work at ∼70% of peak heart rate), or to a control group that followed physical activity advice according to national recommendations. Clinical examinations, physical tests and questionnaires will be administered to all participants at baseline, and after 1, 3 and 5 years. Participants will also be followed up by linking to health registries until year 2035.Ethics and disseminationThe study has been conducted according to the SPIRIT statement. All participants signed a written consent form, and the study has been approved by the Regional Committee for Medical Research Ethics, Norway. Projects such as this are warranted in the literature, and we expect that data from this study will result in numerous papers published in world-leading clinical journals; we will also present the results at international and national conferences.Trial registration numberClinical trial govNCT01666340.
The relationship between social, policy and physical venue features and social cohesion on condom use for pregnancy prevention among sex workers: a safer indoor work environment scale
Authors: Duff Putu , Shoveller Jean , Dobrer Sabina , Ogilvie Gina , Montaner Julio , Chettiar Jill , Shannon Kate 
Published: February 2015

BackgroundThis study aims to report on a newly developedSafer Indoor Work Environmental Scalethat characterises the social, policy and physical features of indoor venues and social cohesion; and using this scale, longitudinally evaluate the association between these features on sex workers’ (SWs’) condom use for pregnancy prevention.MethodsDrawing on a prospective open cohort of female SWs working in indoor venues, a newly developedSafer Indoor Work Environment Scalewas used to build six multivariable models with generalised estimating equations (GEE), to determine the independent effects of social, policy and physical venue-based features and social cohesion on condom use.ResultsOf 588 indoor SWs, 63.6% used condoms for pregnancy prevention in the last month. In multivariable GEE analysis, the following venue-based features were significantly correlated with barrier contraceptive use for pregnancy prevention: managerial practices and venue safety policies (adjusted OR (AOR)=1.09; 95% CI 1.01 to 1.17), access to sexual and reproductive health services/supplies (AOR=1.10; 95% CI 1.00 to 1.20), access to drug harm reduction (AOR=1.13; 95% CI 1.01 to 1.28) and social cohesion among workers (AOR=1.05; 95% CI 1.03 to 1.07). Access to security features was marginally associated with condom use (AOR=1.13; 95% CI 0.99 to 1.29).ConclusionsThe findings of the current study highlight how work environment and social cohesion among SWs are related to improved condom use. Given global calls for the decriminalisation of sex work, and potential legislative reforms in Canada, this study points to the critical need for new institutional arrangements (eg, legal and regulatory frameworks; labour standards) to support safer sex workplaces.
Socioeconomic status is positively associated with measures of adiposity and insulin resistance, but inversely associated with dyslipidaemia in Colombian children
Authors: Buitrago-Lopez Adriana , van den Hooven Edith H , Rueda-Clausen Christian F , Serrano Norma , Ruiz Alvaro J , Pereira Mark A , Mueller Noel T 
Published: February 2015

BackgroundLow socioeconomic status (SES) has been associated with higher risk of cardiometabolic diseases in developed societies, but investigation of SES and cardiometabolic risk in children in less economically developed populations is sparse. We aimed to examine associations among SES and cardiometabolic risk factors in Colombian children.MethodsWe used data from a population-based study of 1282 children aged 6–10 years from Bucaramanga, Colombia. SES was classified according to household wealth, living conditions and access to public utilities. Anthropometric and biochemical parameters were measured at a clinic visit. Cardiometabolic risk factors were analysed continuously using linear regression and as binary outcomes—according to established paediatric cut points—using logistic regression to calculate OR and 95% CIs.ResultsMean age of the children was 8.4 (SD 1.4) and 51.1% of the sample were boys. Odds of overweight/obesity, abdominal obesity and insulin resistance were greater among higher SES. Compared with the lowest SES stratum, children in the highest SES had higher odds of overweight/obesity (OR=3.25, 95% CI 1.89 to 5.57), abdominal obesity (OR=2.74, 95% CI 1.41 to 5.31) and insulin resistance (OR=2.60, 95% CI 1.81 to 3.71). In contrast, children in the highest SES had lower odds of hypertriglyceridaemia (triglycerides ≥90th centile; OR=0.28, 95% CI 0.14 to 0.54) and low (≤10th centile) high-density lipoprotein (HDL) cholesterol (OR=0.35, 95% CI 0.15 to 0.78).ConclusionsIn Colombian children, SES is directly associated with obesity and insulin resistance, but inversely associated with dyslipidaemia (hypertriglyceridaemia and low HDL cholesterol). Our findings highlight the need to analyse cardiometabolic risk factors separately in children and to carefully consider a population's level of economic development when studying their social determinants of cardiometabolic disease.
Socioeconomic marginalisation in the structural production of vulnerability to violence among people who use illicit drugs
Authors: Richardson Lindsey A , Long Cathy , DeBeck Kora , Nguyen Paul , Milloy M-J S , Wood Evan , Kerr Thomas H 
Published: February 2015

ObjectiveMany people who use illicit drugs (PWUD) face challenges to their financial stability. Resulting activities that PWUD undertake to generate income may increase their vulnerability to violence. We therefore examined the relationship between income generation and exposure to violence across a wide range of income generating activities among HIV-positive and HIV-negative PWUD living in Vancouver, Canada.MethodsData were derived from cohorts of HIV-seropositive and HIV-seronegative PWUD (n=1876) between December 2005 and November 2012. We estimated the relationship between different types of income generation and suffering physical or sexual violence using bivariate and multivariate generalised estimating equations, as well as the characteristics of violent interactions.ResultsExposure to violence was reported among 977 (52%) study participants over the study period. In multivariate models controlling for sociodemographic characteristics, mental health status, and drug use patterns, violence was independently and positively associated with participation in street-based income generation activities (ie, recycling, squeegeeing and panhandling; adjusted OR (AOR)=1.39, 95% CI 1.23 to 1.57), sex work (AOR=1.23, 95% CI 1.00 to 1.50), drug dealing (AOR=1.63, 95% CI 1.44 to 1.84), and theft and other acquisitive criminal activity (AOR=1.51, 95% CI 1.27 to 1.80). Engagement in regular, self-employment or temporary employment was not associated with being exposed to violence. Strangers were the most common perpetrators of violence (46.7%) and beatings the most common type of exposure (70.8%).ConclusionsThese results suggest that economic activities expose individuals to contexts associated with social and structural vulnerability to violence. The creation of safe economic opportunities which can minimise vulnerability to violence among PWUD is therefore urgently required.
A systematic review of ICD complications in randomised controlled trials versus registries: is our ‘real-world’ data an underestimation?
Authors: Ezzat Vivienne A , Lee Victor , Ahsan Syed , Chow Anthony W , Segal Oliver , Rowland Edward , Lowe Martin D , Lambiase Pier D 
Published: February 2015

Implantable cardioverter defibrillator (ICD) implantation carries a significant risk of complications, however published estimates appear inconsistent. We aimed to present a contemporary systematic review using meta-analysis methods of ICD complications in randomised controlled trials (RCTs) and compare it to recent data from the largest international ICD registry, the US National Cardiovascular Data Registry (NCDR).PubMed was searched for any RCTs involving ICD implantation published 1999–2013; 18 were identified for analysis including 6433 patients, mean follow-up 3 months–5.6 years. Exclusion criteria were studies of children, hypertrophic cardiomyopathy, congenital heart disease, resynchronisation therapy and generator changes.Total pooled complication rate from the RCTs (excluding inappropriate shocks) was 9.1%, including displacement 3.1%, pneumothorax 1.1% and haematoma 1.2%. Infection rate was 1.5%.There were no predictors of complications but longer follow-up showed a trend to higher complication rates (p=0.07). In contrast, data from the NCDR ICD, reporting on 356 515 implants (2006–2010) showed a statistically significant threefold lower total major complication rate of 3.08% with lead displacement 1.02%, haematoma 0.86% and pneumothorax 0.44%.The overall ICD complication rate in our meta-analysis is 9.1% over 16 months. The ICD complication reported in the NCDR ICD registry is significantly lower despite a similar population. This may reflect under-reporting of complications in registries. Reporting of ICD complications in RCTs and registries is very variable and there is a need to standardise classification of complications internationally.
Recurrent thrombo-embolic episodes: the association of cholangiocarcinoma with antiphospholipid syndrome
Authors: Samadian S , Estcourt L 
Published: February 2015

SummaryAntiphospholipid syndrome is a disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently elevated levels of antiphospholipid antibodies. It was first described in a group of patients with systemic lupus erythematosus but has since been associated with a wide range of conditions, including other autoimmune disorders and malignancy. It can also occur in isolation, the so-called primary antiphospholipid syndrome. We describe an elderly woman with the antiphospholipid syndrome thought to be associated with a cholangiocarcinoma.
Osmosis, osmometry, and osmoregulation
Authors: Lord R C C 
Published: February 2015

Summary
The maintenance of adequate body fluid volume and the correct distribution of this fluid between the body compartments is a critical part of homeostasis. The process of osmosis plays an important role in movement of fluid within the body and the use of osmometry is an important part of the management of many patients. In addition to the application of osmometry to the measurement of body fluids, most commonly plasma and urine, osmotic action plays a part in some therapeutic actions of drugs and its strength needs to be quantified in fluids administered to patients. Unfortunately confusion often exists in the various terms that are used in the field of osmometry. This review aims to explain the different terms used, the laboratory methodology involved in osmometry, and the clinical application and interpretation of the results obtained.
Delays by patients in seeking treatment for acute chest pain: implications for achieving earlier thrombolysis
Authors: Mumford Andrew D , Warr Kim V , Owen Sandra J , Fraser Alan G 
Published: February 2015

SummaryA study was set up to identify why patients delay seeking medical assistance after myocardial infarction. The study was performed in 100 consecutive patients with suspected acute myocardial infarction admitted to either the University Hospital of Wales, Cardiff, UK, or the Royal Jubilee Hospital, Victoria, British Columbia, Canada (50 patients from each centre). The main outcome measure was the delay from the onset of symptoms to admission to hospital. The mean total delay before admission was 385 minutes (SEM 45). The mean delay incurred by the patient in seeking assistance was 172 minutes (SEM 27), representing 45% of the total. Delay was longer in patients with crescendo angina and shorter in those later confirmed to have myocardial infarction. Patients with prior ischaemic heart disease (74% of patients) presented later than those with no such history. No other demographic or clinical factors predicted early or late presentation.Delays in seeking medical assistance after the onset of severe chest pain contribute significantly to total delays in patients' hospital admission and thrombolysis. The unexpected observation that patients with known ischaemic heart disease delay longer before seeking help in spite of their frequent contact with doctors, suggests that opportunities for educating patients are being wasted. Major efforts are needed to understand and modify behaviour of patients with chest pain to further reduce delays in treatment.
Lack of response to octreotide in Cushing's syndrome due to metastatic adrenocortical carcinoma
Authors: Chan N N , Isaacs A J 
Published: February 2015

Summary
Functional metastatic adrenocortical carcinoma is an uncommon cause of Cushing's syndrome, which rarely responds to conventional treatment. A patient presenting with Cushing's syndrome secondary to adrenocortical carcinoma underwent surgical resection. Post-operatively, she developed metastatic disease resistant to conventional chemotherapy. Octreotide, a somatostatin analogue which is effective in the treatment of several types of neuroendocrine tumour, was tried to ameliorate her secretory symptoms, but without any therapeutic effect.