bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vacuolar ATPase is required for ERK‐dependent wound healing in the Drosophila embryo
Authors: Fraire‐Zamora Juan J. , Simons Matias 
Published: February 2018

AbstractEpithelia have the ability to repair injuries through an evolutionary conserved wound healing mechanism. Wound healing events can be classified into the transcription‐independent signals involving mobilization of ionic currents and cytoskeletal rearrangements or the transcription‐dependent response with activation of repair genes. The vacuolar H+‐ATPase (V‐ATPase) has been implicated in the regeneration of vertebrate structures, but the underlying cellular mechanisms remain unclear. Here, we use wounding assays on the epidermis of Drosophila embryos to assess the role of the V‐ATPase in the healing response. We show that a deficient V‐ATPase induces a defective wound healing response by delaying re‐epithelialization and preventing the ERK‐dependent transcriptional activation of repair around the wound site. Our data suggests that the V‐ATPase plays an evolutionary conserved role in the activation of genes necessary for the wound healing response.
Balancing tonic and phasic inhibition in hypothalamic corticotropin‐releasing hormone neurons
Authors: Colmers Phillip L.W. , Bains Jaideep S. 
Published: February 2018

Key points
GABA transporter (GAT) blockade recruits extrasynaptic GABAA receptors (GABAARs) and amplifies constitutive presynaptic GABABR activity.
Extrasynaptic GABAARs contribute to a tonic current.
Corticosteroids increase the tonic current mediated by extrasynaptic GABAARs.
AbstractCorticotropin‐releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) are integratory hubs that regulate the endocrine response to stress. GABA inputs provide a basal inhibitory tone that constrains this system and circulating glucocorticoids (CORT) are important feedback controllers of CRH output. Surprisingly little is known about the direct effects of CORT on GABA synapses in PVN. Here we used whole‐cell patch clamp recordings from CRH neurons in mouse hypothalamic brain slices to examine the effects of CORT on synaptic and extrasynaptic GABA signalling. We show that GABA transporters (GATs) limit constitutive activation of presynaptic GABAB receptors and ensure high release probability at GABA synapses. GATs in combination with GABAB receptors also curtail extrasynaptic GABAAR signalling. CORT has no effect on synaptic GABA signalling, but increases extrasynaptic GABA tone through upregulation of postsynaptic GABAA receptors. These data show that efficient GABA clearance and autoinhibition control the balance between synaptic (phasic) and extrasynaptic (tonic) inhibition in PVN CRH neurons. This balance is shifted towards increased extrasynaptic inhibition by CORT.
In Vitro
Study of the Susceptibility of Clinical Isolates of Trichomonas vaginalis to Metronidazole and Secnidazole
Authors: Ghosh Arindam P. , Aycock Cheri , Schwebke Jane R. 
Published: February 2018

ABSTRACT

Nitroimidazoles (metronidazole [MTZ] and tinidazole [TNZ]) are the only drugs recommended for treatment of
Trichomonas vaginalis
infections. MTZ resistance occurs in 4% to 10% of cases of vaginal trichomoniasis (R. D. Kirkcaldy et al., Emerg Infect Dis 18:939–943, 2012; J. R. Schwebke and F. J. Barrientes, Antimicrob Agents Chemother 50:4209–4210, 2006) and TNZ resistance in 1% of cases (J. R. Schwebke and F. J. Barrientes, Antimicrob Agents Chemother 50:4209–4210, 2006). Emerging nitroimidazole-resistant trichomoniasis is concerning, because few alternatives to standard therapy exist. We assessed the prevalence of
in vitro
aerobic MTZ and secnidazole resistance among
T. vaginalis
isolates collected in 2015 to 2016 from 100 women in Birmingham, Alabama, with positive cultures. Archived specimens were treated with secnidazole or MTZ (0.2 to 400 μg/ml) for 48 h, according to U.S. Centers for Disease Control and Prevention protocols. Ninety-six (96%) of the 100 clinical
Trichomonas
isolates tested demonstrated lower minimum lethal concentrations for secnidazole than for MTZ, suggesting that secnidazole has better
in vitro
activity than MTZ.
Detection and Serogrouping of Dichelobacter nodosus Infection by Use of Direct PCR from Lesion Swabs To Support Outbreak-Specific Vaccination for Virulent Footrot in Sheep
Authors: McPherson Andrew S. , Dhungyel Om P. , Whittington Richard J. 
Published: February 2018

ABSTRACT

Virulent footrot is an economically significant disease in most sheep-rearing countries. The disease can be controlled with vaccine targeting the fimbriae of virulent strains of the essential causative agent,
Dichelobacter nodosus
. However, the bacterium is immunologically heterogeneous, and 10 distinct fimbrial serogroups have been identified. Ideally, in each outbreak the infecting strains would be cultured and serogrouped so that the appropriate serogroup-specific mono- or bivalent vaccine could be administered, because multivalent vaccines lack efficacy due to antigenic competition. If clinical disease expression is suspected to be incomplete, culture-based virulence tests are required to confirm the diagnosis, because control of benign footrot is economically unjustifiable. Both diagnosis and vaccination are conducted at the flock level. The aims of this study were to develop a PCR-based procedure for detecting and serogrouping
D. nodosus
directly from foot swabs and to determine whether this could be done accurately from the same cultured swab. A total of 269 swabs from the active margins of foot lesions of 261 sheep in 12 Merino sheep flocks in southeastern Australia were evaluated. DNA extracts taken from putative pure cultures of
D. nodosus
and directly from the swabs were evaluated in PCR assays for the 16S rRNA and
fimA
genes of
D. nodosus
. Pure cultures were tested also by the slide agglutination test. Direct PCR using extracts from swabs was more sensitive than culture for detecting and serogrouping
D. nodosus
strains. Using the most sensitive sample collection method of the use of swabs in lysis buffer,
D. nodosus
was more likely to be detected by PCR in active than in inactive lesions, and in lesions with low levels of fecal contamination, but lesion score was not a significant factor. PCR conducted on extracts from swabs in modified Stuart's transport medium that had already been used to inoculate culture plates had lower sensitivity. Therefore, if culture is required to enable virulence tests to be conducted, it is recommended that duplicate swabs be collected from each foot lesion, one in transport medium for culture and the other in lysis buffer for PCR.
Sociodemographic and behavioral characteristics associated with self-reported diagnosed diabetes mellitus in adults aged 50+ years in Ghana and South Africa: results from the WHO-SAGE wave 1
Authors: Tarekegne Fitsum Eyayu , Padyab Mojgan , Schröders Julia , Stewart Williams Jennifer 
Published: February 2018

ObjectiveThe objective is to identify and describe the sociodemographic and behavioral characteristics of adults, aged 50 years and over, who self-reported having been diagnosed and treated for diabetes mellitus (DM) in Ghana and South Africa.Research design and methodsThis is a cross-sectional study based on the WHO Study on global AGEing and adult health (SAGE) wave 1. Information on sociodemographic factors, health states, risk factors and chronic conditions is captured from questionnaires administered in face-to-face interviews. Self-reported diagnosed and treated DM is confirmed through a ‘yes’ response to questions regarding1having previously been diagnosed with DM, and2having taken insulin or other blood sugar lowering medicines. Crude and adjusted logistic regressions test associations between candidate variables and DM status. Analyses include survey sampling weights. The variance inflation factor statistic tested for multicollinearity.ResultsIn this nationally representative sample of adults aged 50 years and over in Ghana, after adjusting for the effects of sex, residence, work status, body mass index, waist-hip and waist-height ratios, smoking, alcohol, fruit and vegetable intake and household wealth, WHO-SAGE survey respondents who were older, married, had higher education, very high-risk waist circumference measurements and did not undertake high physical activity, were significantly more likely to report diagnosed and treated DM. In South Africa, respondents who were older, lived in urban areas and had high-risk waist circumference measurements were significantly more likely to report diagnosed and treated DM.ConclusionsCountries in sub-Saharan Africa are challenged by unprecedented ageing populations and transition from communicable to non-communicable diseases such as DM. Information on those who are already diagnosed and treated needs to be combined with estimates of those who are prediabetic or, as yet, undiagnosed. Multisectoral approaches that include socioculturally appropriate strategies are needed to address diverse populations in SSA countries.
Interventions that enhance health services for parents and infants to improve child development and social and emotional well-being in high-income countries: a systematic review
Authors: Hurt Lisa , Paranjothy Shantini , Lucas Patricia Jane , Watson Debbie , Mann Mala , Griffiths Lucy J , Ginja Samuel , Paljarvi Tapio , Williams Jo , Bellis Mark A , Lingam Raghu 
Published: February 2018

BackgroundExperiences in the first 1000 days of life have a critical influence on child development and health. Health services that provide support for families need evidence about how best to improve their provision.MethodsWe systematically reviewed the evidence for interventions in high-income countries to improve child development by enhancing health service contact with parents from the antenatal period to 24 months postpartum. We searched 15 databases and trial registers for studies published in any language between 01 January 1996 and 01 April 2016. We also searched 58 programme or organisation websites and the electronic table of contents of eight journals.ResultsPrimary outcomes were motor, cognitive and language development, and social-emotional well-being measured to 39 months of age (to allow the interventions time to produce demonstrable effects). Results were reported using narrative synthesis due to the variation in study populations, intervention design and outcome measurement. 22 of the 12 986 studies identified met eligibility criteria. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group criteria, the quality of evidence overall was moderate to low. There was limited evidence for intervention effectiveness: positive effects were seen in 1/6 studies for motor development, 4/11 for language development, 4/8 for cognitive development and 3/19 for social-emotional well-being. However, most studies showing positive effects were at high/unclear risk of bias, within-study effects were inconsistent and negative effects were also seen. Intervention content and intensity varied greatly, but this was not associated with effectiveness.ConclusionsThere is insufficient evidence that interventions currently available to enhance health service contacts up to 24 months postpartum are effective for improving child development. There is an urgent need for robust evaluation of existing interventions and to develop and evaluate novel interventions to enhance the offer to all families.PROSPERO registration numberCRD42015015468.
Effect of an increased dosage of statins on spinal degenerative joint disease: a retrospective cohort study
Authors: Cheng Yuan-Yang , Kao Chung-Lan , Lin Shih-Yi , Chang Shin-Tsu , Wei Tz-Shiang , Chang Shih-Ni , Lin Ching-Heng 
Published: February 2018

ObjectivesIt has been proven that statin can protect synovial joints from developing osteoarthritis through its anti-inflammatory effects. However, studies on the effect of statins on spinal degenerative joint diseases are few and limited to in vitro studies. Therefore, we investigated the relationship between the statin dosage and the development of spinal degenerative joint diseases.DesignA retrospective cohort study.SettingPatients registered in Taiwan National Health Insurance Research Database.ParticipantsPatients aged 40–65 years old from 2001 to 2010 were included. Those who received statin treatment before 2001, were diagnosed with spinal degenerative joint diseases or received any spinal surgery before 2004 or had any spinal trauma before 2011 were excluded. A total of 7238 statin users and 164 454 non-users were identified and followed up for the next 7 years to trace the development of spinal degenerative joint disease.Outcome measuresThe incident rate of spinal degenerative joint diseases and HRs among the groups treated with different statin dosages.ResultsA higher dosage of statins was associated with a significantly lower risk of developing spinal degenerative joint disease in patients with hypercholesterolaemia. Compared with the group receiving less than 5400 mg of a statin, the HR of the 11 900–28 000 mg group was 0.83 (95% CI 0.70 to 0.99), and that of the group receiving more than 28 000 mg was 0.81 (95% CI 0.68 to 0.97). Results of subgroup analysis showed a significantly lower risk in men, those aged 50–59 years and those with a monthly income less than US$600.ConclusionsOur study’s findings clearly indicated that a higher dosage of statins can reduce the incidence of spinal degenerative joint disease in patients with hypercholesterolaemia, and it can be beneficial for people with a higher risk of spine degeneration.
Economic burden of schizophrenia in Italy: a probabilistic cost of illness analysis
Authors: Marcellusi Andrea , Fabiano Gianluca , Viti Raffaella , Francesa Morel Pier Cesare , Nicolò Giuseppe , Siracusano Alberto , Mennini Francesco Saverio 
Published: February 2018

ObjectivesSchizophrenia is a chronic, debilitating psychiatric disease with highly variable treatment pathways and consequent economic impacts on resource utilisation. The aim of the study was to estimate the economic burden of schizophrenia in Italy for both the societal and Italian National Healthcare perspective.MethodsA probabilistic cost of illness model was applied. A systematic literature review was carried out to identify epidemiological and economic data. Direct costs were calculated in terms of drugs, hospitalisations, specialist services, residential and semiresidential facilities. Indirect costs were calculated on the basis of patients’ and caregivers’ loss of productivity. In addition, the impact of disability compensation was taken into account using a database from the Italian National Social Security Institute —Italy (INPS).ResultsOverall, 303 913 prevalent patients with schizophrenia were estimated. Of these, 212 739 (70%) were diagnosed and 175 382 (82%) were treated with antipsychotics. The total economic burden was estimated at €2.7 billion (95% CI €1771.93 to €3988.65), 50.5% due to indirect costs and 49.5% to direct costs. Drugs corresponded to 10% of direct costs and hospitalisations (including residential and semiresidential facilities) accounted for 81%.ConclusionsThis study highlighted that indirect costs and hospitalisations (including residential and semiresidential facilities) play a major role within the expenses associated with schizophrenia in Italy, and this may be considered as a tool for public decision-makers.
Cross-sectional analysis of the prevalence and predictors of statin utilisation in Ireland with a focus on primary prevention of cardiovascular disease
Authors: Byrne Paula , Cullinan John , Murphy Catríona , Smith Susan M 
Published: February 2018

ObjectiveTo describe the prevalence of statin utilisation by people aged over 50 years in Ireland and the factors associated with the likelihood of using a statin, focusing particularly on those using statins for primary prevention of cardiovascular disease (CVD).MethodsThis is a cross-sectional analysis of cardiovascular risk and sociodemographic factors associated with statin utilisation from wave 1 of The Irish Longitudinal Study on Ageing. A hierarchy of indications for statin utilisation, consisting of eight mutually exclusive levels of CVD-related diagnoses, was created. Participants were assigned one level of indication. The prevalence of statin utilisation was calculated. The likelihood that an individual was using a statin was estimated using a multivariable logistic regression model, controlling for cardiovascular risk and sociodemographic factors.ResultsIn this nationally representative sample (n=5618) of community-dwelling participants aged 50 years and over, 1715 (30.5%) were taking statins. Of these, 65.0% (57.3% of men and 72.7% of women) were doing so for the primary prevention of CVD. Thus, almost two-thirds of those taking statins did so for primary prevention and there was a notable difference between women and men in this regard. We also found that statin utilisation was highest among those with a prior history of CVD and was significantly associated with age (compared with the base category 50–64 years; 65–74 years OR 1.38 (95% CI 1.16 to 1.65); 75+ OR 1.33 (95% CI 1.04 to 1.69)), living with a spouse or partner (compared with the base category living alone; OR 1.35 (95% CI 1.10 to 1.65)), polypharmacy (OR 1.74 (95% CI 1.39 to 2.19)) and frequency of general practitioner visits (compared with the base category 0 visits per year; 1–2 visits OR 2.46 (95% CI 1.80 to 3.35); 3–4 visits OR 3.24 (95% CI 2.34 to 4.47); 5–6 visits OR 2.98 (95% CI 2.08 to 4.26); 7+ visits OR 2.51 (95% CI 1.73 to 3.63)), even after controlling for clinical need. There was no association between using statins and gender, education, income, social class, health insurance status, location or Systematic Coronary Risk Evaluation (SCORE) risk in the multivariable analysis.ConclusionStatin utilisation among those with no history of CVD accounted for almost two-thirds of all statin use, in part reflecting the high proportion of the population with no history of CVD, although utilisation rates were highest among those with a history of CVD.
‘Because my brain isn’t as active as it should be, my eyes don’t always see’: a qualitative exploration of the stress process for those living with posterior cortical atrophy
Authors: Harding Emma , Sullivan Mary Pat , Woodbridge Rachel , Yong Keir X X , McIntyre Anne , Gilhooly Mary L , Gilhooly Kenneth J , Crutch Sebastian J 
Published: February 2018

ObjectivesTo explore the stress process for individuals living with posterior cortical atrophy (PCA) and their families.DesignA qualitative study using in-depth semi-structured dyadic and individual interviews with people living with a diagnosis of PCA and a family carer. Interview transcripts were thematically analysed.SettingParticipants’ homes.Participants20 individuals in the mild to moderate stages of PCA and 20 family carers.FindingsThree major themes were identified: (1) the diagnostic journey: mostly an unsettling and convoluted process, owing to the early age of onset, rarity and atypical symptom profile of PCA. (2) Interactions with the physical environment: profound difficulties with functional and leisure activities were usually compensated for with adaptations maximising familiarity or simplicity. (3) Implications within the psychosocial environment: symptoms impacted individuals’ sense of independence and identity and required reallocations of roles and responsibilities. Ongoing uncertainties and the progressive nature of PCA caused most dyads to take a ‘one day at a time’ approach to coping. Relatively well-preserved insight and memory were a benefit and burden, as individuals shared the illness experience with family members and also compared their current situation to pre-diagnosis. The experience was framed by background and contextual factors and understood within an ever-changing temporal context.ConclusionThe stress process in PCA is characterised by uncertainty and unpredictability from diagnosis through to ongoing management. The provision of tailored information about cortical visual problems and associated functional difficulties, time-sensitive environmental adaptations to help those with PCA to identify what and where things are and psychosocial interventions for the marital/family unit as a whole would be useful to improve both functional status and psychological well-being. Future research exploring (1) stress and coping in the later stages of PCA and (2) the nature and impact of visual impairment(s) in typical Alzheimer’s disease would be worthwhile.
Impact of the New Cooperative Medical Scheme on the trend of catastrophic health expenditure in Chinese rural households: results from nationally representative surveys from 2003 to 2013
Authors: Xie Biao , Huo Minghe , Wang Zhiqiang , Chen Yongjie , Fu Rong , Liu Meina , Meng Qun 
Published: February 2018

ObjectiveTo evaluate the trend of catastrophic health expenses (CHE) for inpatient care in relation to the commencement of the New Cooperative Medical Scheme (NCMS) in rural China from 2003 to 2013, and the roles of NCMS in protecting affected households from CHE.MethodsWe assessed the 10-year trend of the incidence and severity of CHE in rural households with hospitalised members using data from the Chinese National Health Services Survey. Generalised estimating equations were used to estimate the OR and 95% CI of the association between incidence rates of CHE (RCHE) and NCMS reimbursement.ResultsThe incidence and severity of CHE after NCMS reimbursement both decreased and their changes increased rapidly from 2003 to 2013. After adjustment of the covariates,RCHEbefore reimbursement was significantly higher than that after reimbursement, and the OR (95% CI) was 1.50 (1.24 to 1.81), 1.79 (1.69 to 1.90) and 2.94 (2.77 to 3.11) in 2003, 2008 and 2013, respectively.ConclusionThe incidence and severity of CHE both reduced after NCMS reimbursements in each year. Excluding some confounding factors,RCHEwas significantly associated with NCMS reimbursement. NCMS partly protected the rural households with hospitalised members from CHE. However, the inequalities between different income groups still existed.RCHEin rural households with hospitalised members was still rather high in 2003, 2008 and 2013 even though they were covered by NCMS. This study will provide suggestions for further reforms in China and guidance for other low-income/middle-income countries.
Association of common comorbidities with osteonecrosis: a nationwide population-based case–control study in Denmark
Authors: Dima Alina , Pedersen Alma Becic , Pedersen Lars , Baicus Cristian , Thomsen Reimar Wernich 
Published: February 2018

ObjectiveTo examine recent time trends in the incidence of osteonecrosis (ON) in Denmark and to investigate different common comorbidities association with ON in a population-based setting.MethodsUsing Danish medical databases, we included all patients with a first-time hospital diagnosis of ON during 1995–2012. Each ON case was matched with 10 randomly selected population control subjects from general population. For all participants, we obtained a complete hospital history of comorbidities included in the CharlsonComorbidity Index 5 years preceding the inclusion date.Results4107 ON cases and 41 063 controls were included. The incidence of ON increased from 3.9 in 1995 to 5.5 in 2012 per 100 000 inhabitants. Solid cancer was the most common comorbidity, associated with an adjusted OR (aOR) for ON of 2.0 (95% CI 1.7 to 2.2). For advanced metastatic cancer, leukaemia and lymphoma, aORs of ON were 3.4 (95% CI 2.5 to 4.5), 4.3 (95% CI 2.7 to 7.0) and 5.8 (95% CI 4.3 to 7.8), respectively. Among other chronic conditions, aORs were 3.5 (95% CI 3.0 to 4.1) for connective tissue diseases and 2.3 (95% CI 2.0 to 2.7) for chronic pulmonary diseases. aORs were also increased at 2.8 (95% CI 1.9 to 4.1) and 4.5 (95% CI 2.5 to 8.2) for mild and moderate-to-severe liver disease, respectively, and 4.2 (95% CI 3.4 to 5.2) for renal disease.ConclusionThis large population-based study provides evidence for an increasing ON incidence in the general population and documents an association between several common comorbid conditions and risk of ON.