bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethanol drives aversive conditioning through dopamine 1 receptor and glutamate receptor‐mediated activation of lateral habenula neurons
Authors: Zuo Wanhong , Fu Rao , Hopf Frederic Woodward , Xie Guiqin , Krnjević Kresimir , Li Jing , Ye Jiang‐Hong 
Published: August 2015

AbstractThere has been increasing interest in the lateral habenula (LHb) given its potent regulatory role in many aversion‐related behaviors. Interestingly, ethanol can be rewarding as well as aversive; we therefore investigated whether ethanol exposure alters pacemaker firing or glutamate receptor signaling in LHb neurons in vitro and also whether LHb activity in vivo might contribute to the acquisition of conditioned place aversion to ethanol. Surprisingly, in epithalamic slices, low doses of ethanol (1.4 mM) strongly accelerated LHb neuron firing (by ~60%), and ethanol's effects were much reduced by blocking glutamate receptors. Ethanol increased presynaptic glutamate release, and about half of this effect was mediated by dopamine subtype 1 receptors (D1Rs) and cyclic adenosine monophosphate (cAMP)‐dependent signaling pathways. In agreement with these findings, c‐Fos immunoreactivity in LHb regions was enhanced after a single administration of a low dose of ethanol (0.25 g/kg i.p.). Importantly, the same dose of ethanol in vivo also produced strong conditioned place aversion, and this was prevented by inhibiting D1Rs or neuronal activity within the LHb. By contrast, a higher dose (2 g/kg) led to ethanol conditioned place preference, which was enhanced by inhibiting neuronal activity or D1Rs within the LHb and suppressed by infusing aminomethylphosphonic acid or the D1R agonist SKF38393 within the LHb. Our in vitro and in vivo observations show, for the first time, that ethanol increases LHb excitation, mediated by D1R and glutamate receptors, and may underlie a LHb aversive signal that contributes to ethanol‐related aversion.
Relating off‐premises alcohol outlet density to intentional and unintentional injuries
Authors: Morrison Christopher , Smith Karen , Gruenewald Paul J. , Ponicki William R. , Lee Juliet P. , Cameron Peter 
Published: August 2015

AbstractAimsThis study investigated the hypotheses that (i) intentional and unintentional injuries occur more frequently in areas with greater density of off‐premises alcohol outlets; and (ii) larger and chain outlets selling cheaper alcohol contribute more substantially to injury risk than smaller and independent outlets.DesignEcological cross‐sectional.SettingFrom the 256 Statistical Area level 2 (SA2) census units in Melbourne, Australia, we selected a random sample of 62 units. There were 2119 Statistical Area level 1 (SA1) units nested within the selected SA2 units.ParticipantsThe selected units contained 295 off‐premises outlets.MeasurementsTwo independent observers conducted premises assessments in all off‐premises outlets, assessing the volume of alcohol available for sale (paces of shelf space), price (least wine price) and other operating characteristics (chain versus independent, drive‐through). Outlet counts, assessed outlet characteristics and other area characteristics (population density, median age, median income, retail zoning) were aggregated within SA1 units. Dependent variables were counts of ambulance attended intentional injuries (assaults, stabbings, shootings) and unintentional injuries (falls, crush injuries and object strikes).FindingsIn univariable analyses, chain outlets were larger (r = 0.383; P < 0.001) and sold cheaper alcohol (r = −0.484; P < 0.001) compared with independent outlets. In Bayesian spatial Poisson models, off‐premises outlet density was positively related to both intentional [incidence rate ratio (IRR) = 1.38; 95% credible interval (CI) = 1.19, 1.60] and unintentional injuries (IRR = 1.18; 95% CI = 1.06, 1.30). After disaggregation by outlet characteristics, chain outlet density was also related to both intentional (IRR = 1.35; 95% CI = 1.11, 1.64) and unintentional injuries (IRR = 1.20; 95% CI = 1.08, 1.38).ConclusionsGreater off‐premises outlet density is related to greater incidence of traumatic injury, and chain outlets appear to contribute most substantially to traumatic injury risk.
Sodium channel haploinsufficiency and structural change in ventricular arrhythmogenesis
Authors: Jeevaratnam K. , Guzadhur L. , Goh Y. M. , Grace A. A. , Huang C. L.‐H. 
Published: August 2015

AbstractNormal cardiac excitation involves orderly conduction of electrical activation and recovery dependent upon surface membrane, voltage‐gated, sodium (Na+) channel α‐subunits (Nav1.5). We summarize experimental studies of physiological and clinical consequences of loss‐of‐function Na+ channel mutations. Of these conditions, Brugada syndrome (BrS) and progressive cardiac conduction defect (PCCD) are associated with sudden, often fatal, ventricular tachycardia (VT) or fibrillation. Mouse Scn5a+/− hearts replicate important clinical phenotypes modelling these human conditions. The arrhythmic phenotype is associated not only with the primary biophysical change but also with additional, anatomical abnormalities, in turn dependent upon age and sex, each themselves exerting arrhythmic effects. Available evidence suggests a unified binary scheme for the development of arrhythmia in both BrS and PCCD. Previous biophysical studies suggested that Nav1.5 deficiency produces a background electrophysiological defect compromising conduction, thereby producing an arrhythmic substrate unmasked by flecainide or ajmaline challenge. More recent reports further suggest a progressive decline in conduction velocity and increase in its dispersion particularly in ageing male Nav1.5 haploinsufficient compared to WT hearts. This appears to involve a selective appearance of slow conduction at the expense of rapidly conducting pathways with changes in their frequency distributions. These changes were related to increased cardiac fibrosis. It is thus the combination of the structural and biophysical changes both accentuating arrhythmic substrate that may produce arrhythmic tendency. This binary scheme explains the combined requirement for separate, biophysical and structural changes, particularly occurring in ageing Nav1.5 haploinsufficient males in producing clinical arrhythmia.
Chronic intermittent toluene inhalation in adolescent rats results in metabolic dysfunction with altered glucose homeostasis
Authors: Dick A L W , Simpson A , Qama A , Andrews Z , Lawrence A J , Duncan J R 
Published: August 2015

Background and PurposeAbuse of toluene‐containing inhalants is an increasing public health problem, especially among adolescents. Abuse during adolescence is associated with emaciation, while industrial exposure leads to altered glycaemic control suggesting metabolic instability. However, the relationship between adolescent inhalant abuse and metabolic dysfunction remains unknown.Experimental ApproachTo model human abuse patterns, we exposed male adolescent Wistar rats [postnatal day (PND) 27] to chronic intermittent inhaled toluene (CIT, 10 000 ppm) or air (control) for 1 h·day−1, three times a week for 4 weeks. Feeding and body composition were monitored. After 4 weeks, circulating metabolic hormone concentrations and responses to a glucose tolerance test (GTT) were measured. Dietary preference was measured by giving animals access to either a ‘western diet’ plus standard chow (WC + SC) or standard chow alone during 4 weeks of abstinence. Metabolic hormones and GTT were subsequently measured.Key ResultsAdolescent CIT exposure significantly retarded weight gain, altered body composition, circulating metabolic hormones and responses to a GTT. While reduced body weight persisted, responses to a GTT and circulating hormones appeared to normalize for animals on standard chow following abstinence. In CIT‐exposed WC + SC rats, we observed impaired glucose tolerance associated with altered metabolic hormones. Analysis of hypothalamic genes revealed differential expression profiles in CIT‐exposed rats following both the exposure period and abstinence, suggesting a central contribution to inhalant‐induced metabolic dysfunction.Conclusion and ImplicationsCIT exposure during adolescence has long‐term effects on metabolic function, which may increase the risk of disorders related to energy balance and glycaemic control.
24‐Month‐Old Children With Larger Oral Vocabularies Display Greater Academic and Behavioral Functioning at Kindergarten Entry
Authors: Morgan Paul L. , Farkas George , Hillemeier Marianne M. , Hammer Carol Scheffner , Maczuga Steve 
Published: August 2015

Data were analyzed from a population‐based, longitudinal sample of 8,650 U.S. children to (a) identify factors associated with or predictive of oral vocabulary size at 24 months of age and (b) evaluate whether oral vocabulary size is uniquely predictive of academic and behavioral functioning at kindergarten entry. Children from higher socioeconomic status households, females, and those experiencing higher quality parenting had larger oral vocabularies. Children born with very low birth weight or from households where the mother had health problems had smaller oral vocabularies. Even after extensive covariate adjustment, 24‐month‐old children with larger oral vocabularies displayed greater reading and mathematics achievement, increased behavioral self‐regulation, and fewer externalizing and internalizing problem behaviors at kindergarten entry.
Impact of co‐existent thyroiditis on clinical outcome in papillary thyroid carcinoma with high preoperative serum antithyroglobulin antibody: a retrospective cohort study
Authors: Nam H.‐Y. , Lee H.Y. , Park G.C. 
Published: August 2015

ObjectivesThe aim of this study was to investigate the impact of co‐existent chronic lymphocytic thyroiditis (CLT) on changes in serum antithyroglobulin antibody (TgAb) and clinical outcome in papillary thyroid carcinoma (PTC) patients with high preoperative serum TgAb.DesignA retrospective cohort study.SettingUniversity teaching hospital.ParticipantsThirty‐seven PTC patients with high preoperative serum TgAb level (≥100 U/mL) were evaluated. All patients underwent total thyroidectomy followed by high‐dose I‐131 ablation.Main outcome measuresPer cent changes of TgAb between pre‐treatment and post‐treatment, and disease‐free survival were calculated.ResultsTwenty‐two patients (59.5%) had co‐existent CLT, and seven had residual/recurrent tumours. There was a higher proportion of females among the patients with CLT compared to those without CLT (95.5% versus 66.7%; P = 0.0306). There were trends towards more aggressive pathologies, such as tumour size, extrathyroidal extension, surgical margin and lymph node stage, in PTC without CLT than in that with co‐existent CLT. Pre‐treatment and post‐treatment TgAb were all higher in PTC with co‐existent CLT. But, per cent changes of TgAb between pre‐treatment and post‐treatment were no significant difference between PTC with and without CLT (P < 0.05). Patients with co‐existent CLT showed a significantly lower residual/recurrent tumour rate than those without CLT (4.5% versus 40%; P = 0.0113).ConclusionResidual/recurrent tumour rate was lower in PTC patients with co‐existent CLT than in those without CLT.
Objectively measured sedentary time, physical activity and kidney function in people with recently diagnosed Type 2 diabetes: a prospective cohort analysis
Authors: Guo V. YW. , Brage S. , Ekelund U. , Griffin S. J. , Simmons R. K. ,   the ADDITION‐Plus study team
Published: August 2015

AbstractAimTo assess the prospective association between objectively measured physical activity and kidney function over 4 years in people with Type 2 diabetes.MethodsIndividuals (120 women and 206 men) participating in the ADDITION‐Plus trial underwent assessment of sedentary time (SED‐time), time spent in moderate‐to‐vigorous‐intensity physical activity (MVPA) and total physical activity energy expenditure (PAEE) using a combined heart rate and movement sensor, and kidney function [estimated glomerular filtration rate (eGFR), serum creatinine and urine albumin‐to‐creatinine ratio (ACR)] at baseline and after 4 years of follow‐up. Multivariate regression was used to quantify the association between change in SED‐time, MVPA and PAEE and kidney measures at four‐year follow‐up, adjusting for change in current smoking status, waist circumference, HbA1c, systolic blood pressure, triglycerides and medication usage.ResultsOver 4 years, there was a decline in eGFR values from 87.3 to 81.7 ml/min/1.73m2 (P < 0.001); the prevalence of reduced eGFR (eGFR < 60 ml/min/1.73m2) increased from 6.1 to 13.2% (P < 0.001). There were small increases in serum creatinine (median: 81–84 μmol/l, P < 0.001) and urine ACR (median: 0.9–1.0 mg/mmol, P = 0.005). Increases in SED‐time were associated with increases in serum creatinine after adjustment for MVPA and cardiovascular risk factors (β = 0.013, 95% CI: 0.001, 0.03). Conversely, increases in PAEE were associated with reductions in serum creatinine (β = –0.001, 95% CI: –0.003, –0.0001).ConclusionReducing time spent sedentary and increasing overall physical activity may offer intervention opportunities to improve kidney function among individuals with diabetes. (Trial Registry no. ISRCTN 99175498)
The prevalence of migraine in university students: a systematic review and meta‐analysis
Authors: Wang X. , Zhou H. B. , Sun J. M. , Xing Y. H. , Zhu Y. L. , Zhao Y. S. 
Published: August 2015

Our aim was to determine the prevalence of migraine amongst university students. Migraine is highly prevalent amongst university students, but the exact frequency remains inconsistent between studies. PubMed, Embase and Google Scholar databases were used to identify studies dealing with the prevalence of migraine amongst university students published between 1 January 1988 and 31 August 2014. The pooled migraine prevalence was calculated using DerSimonian and Laird's random‐effects model. Heterogeneity of the results was investigated using subgroup analysis and the trend of migraine prevalence according to the publication year and sample size was determined by cumulative analysis. Data were combined from 56 independent studies, analysing a total of 34 904 students. The pooled migraine prevalence was 16.1% [95% confidence interval (CI) 13.6%–18.9%]: 11.3% (95% CI 8.8%–14.4%) amongst male students and 21.7% (95% CI 18.0%–25.8%) amongst female students. Subgroup analysis revealed that diagnostic criteria (P < 0.0001) and gender distribution (P = 0.004) significantly affected migraine prevalence. Cumulative analysis found that the 95% CI became narrower with ascending publication year and sample size. Many studies agree that migraine is highly prevalent amongst university students, but diverse methodologies lead to substantial heterogeneity in the results. It is shown that gender and diagnostic criteria significantly influence the migraine prevalence and may partially explain the heterogeneity between studies.
The HLA‐A*2402/Cw*0102 haplotype is associated with lamotrigine‐induced maculopapular eruption in the Korean population
Authors: Moon Jangsup , Park Han‐Ki , Chu Kon , Sunwoo Jun‐Sang , Byun Jung‐Ick , Lim Jung‐Ah , Kim Tae‐Joon , Shin Jung‐Won , Lee Soon‐Tae , Jung Keun‐Hwa , Jung Ki‐Young , Jeon Daejong , Kim Dong Wook , Yu Kyung‐Sang , Jang In‐Jin , Kang Hye‐Ryun , Park Heung‐Woo , Lee Sang Kun 
Published: August 2015

SummaryThe use of lamotrigine (LTG) can be limited by the occurrence of cutaneous adverse drug reactions (cADRs) that range from maculopapular eruption (MPE) to the more severe Stevens‐Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen (HLA)–related genetic risk factors for carbamazepine‐induced cADR have been identified. However, the HLA‐related genetic risk factors associated with LTG‐induced cADR are not yet well known. We performed HLA genotyping in 50 Korean patients with epilepsy, including 21 patients presenting LTG‐induced MPE and 29 LTG‐tolerant patients. A significant association between the HLA‐A*2402 allele and LTG‐induced MPE was identified, in comparison with the LTG‐tolerant group (odds ratio [OR] 4.09, p = 0.025) and the general Korean population (OR 3.949, p = 0.005). The frequencies of the Cw*0102 or Cw*0702 alleles were significantly higher in the LTG‐MPE group than in the Korean population, whereas the frequency of the A*3303 allele was lower. The coexistence of the A*2402 and Cw*0102 alleles was significantly associated with the LTG‐MPE group when compared to the LTG‐tolerant group (OR 7.88, p = 0.007). In addition, the Cw*0701 allele was more frequent in the LTG‐tolerant group than in the Korean population. These findings suggest the presence of HLA‐related genetic risk factors for LTG‐induced MPE in the Korean population.
Duration of tetanus immunoglobulin G titres following basic immunisation of horses
Authors: Kendall A. , Anagrius K. , Gånheim A. , Rosanowski S. M. , Bergström K. 
Published: August 2015

SummaryReasons for performing studyRecommendations for prophylactic vaccination against tetanus in horses vary greatly between countries and have scarce scientific support in the peer‐reviewed literature. In human medicine, recommended booster vaccination intervals are also very variable, but are considerably longer than for horses. More information is needed about the duration of immunity induced by modern vaccines.ObjectivesTo investigate if the duration of antibody titres previously determined to be protective against tetanus differ from what is indicated by recommended vaccination intervals for horses.Study designProspective seroconversion study.MethodsThirty‐four horses were enrolled for basic immunisation with an ISCOM Matrix‐combination vaccine (Equilis Prequenza Te). Horses received the first vaccination at age 5–11 months, and the second dose 4 weeks later. A third vaccine dose was given 15–17 months after the second dose. Serum tetanus antibody titres were analysed by toxin‐binding enzyme‐linked immunosorbent assay 2 weeks as well as 14–16 months after the second dose. After the third vaccine dose, titres were checked once yearly for 3 years. Results were described by age and level of antibody titre at first sampling.ResultsTwo weeks after the second dose, all horses (34/34) had antibody levels that exceeded the limit of detection, 0.04 iu/ml. After 16 months the levels were above 0.04 iu/ml in 28/33 horses, the remaining 5 horses potentially had suboptimal protection against tetanus. After the third vaccine dose antibody levels remained above 0.04 iu/ml in 25/26 horses for 1 year, 16/16 horses for 2 years, and 8/8 horses for 3 years.ConclusionsHorses that undergo basic immunisation with 3 doses of vaccine after age 5 months are likely to have serum antibody titres consistent with protection against tetanus for more than 3 years. Current guidelines for tetanus prophylaxis should be revised.
The dynamic anatomy and patterning of skin
Authors: Wong Richard , Geyer Stefan , Weninger Wolfgang , Guimberteau Jean‐Claude , Wong Jason K. 
Published: August 2015

AbstractThe skin is often viewed as a static barrier that protects the body from the outside world. Emphasis on studying the skin's architecture and biomechanics in the context of restoring skin movement and function is often ignored. It is fundamentally important that if skin is to be modelled or developed, we do not only focus on the biology of skin but also aim to understand its mechanical properties and structure in living dynamic tissue. In this review, we describe the architecture of skin and patterning seen in skin as viewed from a surgical perspective and highlight aspects of the microanatomy that have never fully been realized and provide evidence or concepts that support the importance of studying living skin's dynamic behaviour. We highlight how the structure of the skin has evolved to allow the body dynamic form and function, and how injury, disease or ageing results in a dramatic changes to the microarchitecture and changes physical characteristics of skin. Therefore, appreciating the dynamic microanatomy of skin from the deep fascia through to the skin surface is vitally important from a dermatological and surgical perspective. This focus provides an alternative perspective and approach to addressing skin pathologies and skin ageing.
A two‐level detector of short‐term unique changes in time series based on a similarity method
Authors: Pełech‐Pilichowski Tomasz , Duda Jan T. 
Published: August 2015

AbstractIn the paper, a novel two‐level algorithm of time‐series change detection is presented. In the first level, to identify non‐stationary sequences in a processed signal, preliminary detection of events is performed with a short‐term prediction comparison. In the second stage, to confirm the changes detected in the first level, a similarity method aimed at identification of unique changes is employed. The detection of changes in a non‐stationary time series is discussed, implemented algorithms are described and the results produced on a sample four financial time series are shown. General conditions for implementing the proposed algorithm as an immune‐like event detector are discussed.
Reaction of pyranose dehydrogenase from Agaricus meleagris with its carbohydrate substrates
Authors: Graf Michael M.H. , Sucharitakul Jeerus , Bren Urban , Chu Dinh Binh , Koellensperger Gunda , Hann Stephan , Furtmüller Paul G. , Obinger Christian , Peterbauer Clemens K. , Oostenbrink Chris , Chaiyen Pimchai , Haltrich Dietmar 
Published: August 2015

Monomeric Agaricus meleagris pyranose dehydrogenase (AmPDH) belongs to the glucose–methanol–choline family of oxidoreductases. An FAD cofactor is covalently tethered to His103 of the enzyme. AmPDH can double oxidize various mono‐ and oligosaccharides at different positions (C1 to C4). To study the structure/function relationship of selected active‐site residues of AmPDH pertaining to substrate (carbohydrate) turnover in more detail, several active‐site variants were generated, heterologously expressed in Pichia pastoris, and characterized by biochemical, biophysical and computational means. The crystal structure of AmPDH shows two active‐site histidines, both of which could take on the role as the catalytic base in the reductive half‐reaction. Steady‐state kinetics revealed that His512 is the only catalytic base because H512A showed a reduction in (kcat/KM)glucose by a factor of 105, whereas this catalytic efficiency was reduced by two or three orders of magnitude for His556 variants (H556A, H556N). This was further corroborated by transient‐state kinetics, where a comparable decrease in the reductive rate constant was observed for H556A, whereas the rate constant for the oxidative half‐reaction (using benzoquinone as substrate) was increased for H556A compared to recombinant wild‐type AmPDH. Steady‐state kinetics furthermore indicated that Gln392, Tyr510, Val511 and His556 are important for the catalytic efficiency of PDH. Molecular dynamics (MD) simulations and free energy calculations were used to predict d‐glucose oxidation sites, which were validated by GC‐MS measurements. These simulations also suggest that van der Waals interactions are the main driving force for substrate recognition and binding.