bluuebunny/crossref_metadata_2025_split huggingface dataset:
The new KCNQ2 activator 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid displays anticonvulsant potential
Authors: Boehlen A , Schwake M , Dost R , Kunert A , Fidzinski P , Heinemann U , Gebhardt C 
Published: November 2012

Background and PurposeKCNQ2‐5 channels are voltage‐gated potassium channels that regulate neuronal excitability and represent suitable targets for the treatment of hyperexcitability disorders. The effect of Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid was tested on KCNQ subtypes for its ability to alter neuronal excitability and for its anticonvulsant potential.Experimental ApproachThe effect of 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid was evaluated using whole‐cell voltage‐clamp recordings from CHO cells and Xenopus laevis oocytes expressing different types of KCNQ channels. Epileptiform afterdischarges were recorded in fully amygdala‐kindled rats in vivo. Neuronal excitability was assessed using field potential and whole cell recording in rat hippocampus in vitro.Key Results4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid caused a hyperpolarizing shift of the activation curve and a pronounced slowing of deactivation in KCNQ2‐mediated currents, whereas KCNQ3/5 heteromers remained unaffected. The effect was also apparent in the Retigabine‐insensitive mutant KCNQ2‐W236L. In fully amygdala‐kindled rats, it elevated the threshold for induction of afterdischarges and reduced seizure severity and duration. In hippocampal CA1 cells, 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid strongly damped neuronal excitability caused by a membrane hyperpolarization and a decrease in membrane resistance and induced an increase of the somatic resonance frequency on the single cell level, whereas synaptic transmission was unaffected. On the network level, 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid caused a significant reduction of γ and θ oscillation peak power, with no significant change in oscillation frequency.Conclusion and ImplicationsOur data indicate that 4‐Chlor‐N‐(6‐chlor‐pyridin‐3‐yl)‐benzamid is a potent KCNQ activator with a selectivity for KCNQ2 containing channels. It strongly reduces neuronal excitability and displays anticonvulsant activity in vivo.
Engaging in cyberspace: seeking help for sexual assault
Authors: Webber Ruth , Moors Rosetta 
Published: November 2012

AbstractMany young people who have been sexually assaulted are accessing the Internet through question and answer (Q&A) social networking sites in order to obtain information, advice and counselling on sexual assault. This paper reports on a study that was conducted on the Q&As on sexual assault that were posted on Yahoo! Answers. It focuses on comparing answers supplied by counsellors who work at a sexual assault centre with those posted by other Yahoo members. It reports on an analysis of content, tone and ‘best’ answer. Sixty‐five questions and 392 answers were analysed using interpretive description which is an inductive analytic approach. The responses by counsellors were voted ‘best’ by posters of questions (Askers) in the majority of cases. Their responses were dispassionate, accurate and systematic and contained information about how and where Askers could access help. In contrast, the answers by general Yahoo members were inconsistent and lacked specificity. While most of their responses contained supportive comments, many contained condemnatory remarks about perpetrators and Askers, which were potentially damaging to both Askers and other Yahoo members who were accessing the site.
Determination of lingual vascular canals in the interforaminal region before implant surgery to prevent life‐threatening bleeding complications
Authors: Kilic Erdem , Doganay Selim , Ulu Murat , Çelebi Nükhet , Yikilmaz Ali , Alkan Alper 
Published: November 2012

AbstractObjectivesProfuse hemorrhage and airway obstruction may occur during or after the implant surgery in the interforaminal region. The prevention from this complication requires identifying the location of the mandibular lingual vascular canals (MLVCs). The purpose of this study was to evaluate the anatomical variations of MLVCs and to determine the safety margins for implant placement in interforaminal region.Materials and methodsComputer tomography (CT) images of 200 consecutive patients were reexamined retrospectively by a radiologist and a maxillofacial surgeon to evaluate the presence of the MLVCs entering the mandible. The diameter and the number of the canals, the distance between the entrance of the canal and mandibular midline, and the height of the entrances of the canals from the inferior mandibular margin were measured.ResultsTwo hundred and thirty‐six median lingual canals (MLCs) and 159 lateral lingual canals (LLCs) were found in 200 patients. Significant differences were found between the number of lingual canals in the midline and canine regions (P < 0.001).ConclusionThere is a potential risk of complications due to the injuries of the vessels entering the lingual cortical bone through a number of bone canals during implant placement in the interforaminal region.
Human cadaveric histomorphological and metallurgical analysis of dental implants following 12.5 years of service
Authors: Abbott John R. , Marino Victor , Bartold P. Mark 
Published: November 2012

AbstractObjectivesTo provide a metallurgical and histomorphological analysis of hybrid bridgework and associated dental implants which have been in a clinical load bearing situation for a period of 12.5 years.Material and methodsThe physical integrity of the hybrid framework was examined with stereoimaging microscopy and scanning electron microscopy for signs of wear, fatigue cracks, corrosion. Elemental spectra and maps of the surface were analysed with anEDAX®DetectingUnit (AMETEK,Inc,Mahwah,NJ,USA). Similarly, the supporting titanium abutments screwed into the implants were examined for fatigue and corrosion. Bone density scans and bone trabecular patterns were obtained from radiographs. Microcomputer tomography was used to assess the bone–implant interface and bone architecture around the implants. Histological sections were stained with 1% basic fuchsin to assess osseous microdamage.ResultsThe study demonstrated that the gold alloy framework to be in satisfactory condition with little indication of corrosion or cracking. The interface between the gold alloy and the titanium abutments likewise demonstrated no obvious corrosion cells. No radiographic evidence of any adverse loss of bone around the implants was noted. Bone mineral density was related to implant position, being higher between the implants. Scanning electron micrograph images confirmed the good bone integration with the implant threads with a high level of organisation, maturation and adaptation for the entire length of the implant. There was no evidence of any microdamage.ConclusionsThe implants, abutments and hybrid framework were in remarkably good condition considering their length of service.
The multiple origins of Type 1 diabetes
Authors: Pugliese A. 
Published: November 2012

AbstractIt is widely accepted that Type 1 diabetes is a complex disease. Genetic predisposition and environmental factors favour the triggering of autoimmune responses against pancreatic β‐cells, eventually leading to β‐cell destruction. Over 40 susceptibility loci have been identified, many now mapped to known genes, largely supporting a dominant role for an immune‐mediated pathogenesis. This role is also supported by the identification of several islet autoantigens and antigen‐specific responses in patients with recent onset diabetes and subjects with pre‐diabetes. Increasing evidence suggests certain viruses as a common environmental factor, together with diet and the gut microbiome. Inflammation and insulin resistance are emerging as additional cofactors, which might be interrelated with environmental factors. The heterogeneity of disease progression and clinical manifestations is likely a reflection of this multifactorial pathogenesis. So far, clinical trials have been mostly ineffective in delaying progression to overt diabetes in relatives at increased risk, or in reducing further loss of insulin secretion in patients with new‐onset diabetes. This limited success may reflect, in part, our incomplete understanding of key pathogenic mechanisms, the lack of truly robust biomarkers of both disease activity and β‐cell destruction, and the inability to assess the relative contributions of various pathogenic mechanisms at various time points during the course of the natural history of Type 1 diabetes. Emerging data and a re‐evaluation of histopathological, immunological and metabolic findings suggest the hypothesis that unknown mechanisms of β‐cell dysfunction may be present at diagnosis, and may contribute to the development of hyperglycaemia and clinical symptoms.
Differential associations between depressive symptoms and glycaemic control in outpatients with diabetes
Authors: Bot M. , Pouwer F. , de Jonge P. , Tack C. J. , Geelhoed‐Duijvestijn P. H. L. M. , Snoek F. J. 
Published: November 2012

AbstractAimsDepression is common in people with diabetes, and related to higher HbA1c levels. Depression, however, is a heterogeneous construct that involves a variety of symptoms. As little is known about the associations of individual depressive symptoms with HbA1c, we explored these associations in outpatients with diabetes.MethodsThe study was conducted in three tertiary diabetes clinics in the Netherlands. At baseline, the presence of the nine depressive symptoms that are listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was assessed with the nine‐item Patient Health Questionnaire (PHQ‐9). At baseline and after a 1‐year follow‐up, HbA1c was derived from the medical charts.ResultsA total of 288 out of 646 subjects with diabetes (45%) reported one or more depressive symptom(s). Depressed mood (β = 0.11, P = 0.005), sleeping difficulties (β = 0.16, P < 0.001), appetite problems (β = 0.15, P < 0.001) and suicidal ideation (β = 0.14, P = 0.001) were significantly related to higher baseline HbA1c values. Furthermore, depressed mood (β = 0.09, P = 0.03) sleeping difficulties (β = 0.12, P = 0.004), appetite problems (β = 0.11, P = 0.01) and psychomotor agitation/retardation (β = 0.09, P = 0.04) were significantly related to higher HbA1c values at 1‐year follow‐up. Associations were more pronounced in Type 1 diabetes than in Type 2 diabetes. None of the depressive symptoms were related to change in HbA1c over time, except suicidal ideation.ConclusionIn people with diabetes, several individual depressive symptoms were related to higher HbA1c levels. These associations persisted over time. More research is needed to investigate potential mechanistic pathways.
Small platelet microparticle levels are increased in pulmonary arterial hypertension
Authors: Nadaud Sophie , Poirier Odette , Girerd Barbara , Blanc Catherine , Montani David , Eyries Mélanie , Imbert‐Bismut Françoise , Pacheco Antoine , Vigne Jacques , Tregouet David‐Alexandre , Humbert Marc , Soubrier Florent 
Published: November 2012

Eur J Clin Invest 2012AbstractBackground  The various aetiologies and risk factors for pulmonary arterial hypertension (PAH) lead to close phenotypes with small differences. Plasma microparticles have been shown to be increased in vascular pathologies including PAH. The aim of this study was to determine whether the levels of endothelial and platelet‐derived microparticles could vary between different forms of PAH: idiopathic PAH (iPAH), heritable PAH associated with BMPR2 (Bone morphogenetic protein receptor, type II) mutation (hPAH) and PAH associated with connective tissue diseases (aPAH).Materials and methods  Microparticles were analysed using flow cytometry in plasma from controls and iPAH, hPAH and aPAH patients. Platelet‐derived MP (PMP) were defined as CD31+/CD41+ and endothelial‐derived MP (EMP) as CD31+/CD41−. Two populations of PMP were isolated according to their size, defining small PMP (0·3–0·5 μm) and large PMP (0·5–0·9 μm). BMPR2 genotype, clinical and biologic parameters were recorded.Results  EMP and small PMP levels in iPAH, hPAH and aPAH were similar and were significantly increased as compared with controls. No differences in large PMP levels were observed. After adjusting for age, sex, proBNP and CRP, EMP and small PMP levels did not correlate with clinical parameters.Conclusions  iPAH, hPAH and aPAH were characterized by increased levels of EMP and of small PMP, a new class of PMP which seems to be differentially produced than large PMP.
Endothelial function does not relate to haemoglobin or serum erythropoietin concentrations and these do not explain the gender difference in endothelial function in healthy middle‐aged men and women
Authors: Tilling Lindsey , Hunt Joanne , Jiang Benyu , Sanders Thomas A. B. , Clapp Brian , Chowienczyk Philip 
Published: November 2012

AbstractBackgroundHaemoglobin scavenges nitric oxide, and a previous study has shown a negative association between flow‐mediated vasodilation (FMD), a measure of nitric oxide (NO)‐dependent vasomotor function and haemoglobin concentrations [Hb]. Circulating erythropoietin (EPO) is also negatively associated with [Hb] and could influence availability of NO. The purpose of this study was to examine the association of FMD with [Hb] and EPO concentrations and to determine whether these contribute to the sex difference in FMD. FMD (by high‐resolution ultrasound), [Hb], circulating immunoreactive EPO and cardiovascular risk factors were measured in 317 healthy middle‐aged men and women (183 women, 33 premenopausal, mean age ± SD, 55 ± 6·8 years) participating in a dietary study.ResultsIn the whole mixed‐sex group, FMD was negatively correlated with [Hb] (R = −0·23, P < 0·001). However, in a multivariable model, incorporating sex and other confounding factors, FMD was independently negatively correlated only with age, male sex and systolic blood pressure: standardized regression coefficients −0·21 (P < 0·01), −0·17 (P < 0·05) and −0·20 (P < 0·05) respectively and not with [Hb]. Similarly, when the analysis was restricted to men or to postmenopausal women, there was no significant relationship between FMD and Hb. There was no significant correlation between FMD and EPO on either univariate analysis in the whole group, in each sex, or in multivariate analysis.ConclusionThese results suggest that in healthy middle‐aged subjects, FMD is not influenced by [Hb] or EPO and these do not contribute to the gender difference in FMD.
The changing role of education in the distribution of earnings and household income
Authors: Večerník Jiří 
Published: November 2012

AbstractThis article draws on income surveys from the last two decades to report on trends in earnings disparities and household income inequality in the Czech Republic. Education has been the main axis of change in this area, having acquired a much greater role in the entire process of collecting and distributing income. First, an increasing influence of education is evident in the personal earnings of employees, returns to education having doubled. Second, in couples, education has an important impact on both women’s employment and their earnings. Third, the importance of marital partners’ education levels on household income grew even more than its effect on earnings.
Offspring investment in wild Atlantic salmon (Salmo salar): relationships with smolt age and spawning condition
Authors: Burton Tim , McKelvey Simon , Stewart Dave C. , Armstrong John D. , Metcalfe Neil B. 
Published: November 2012

AbstractWe investigated the independent effects of age at smolting and body condition at the time of spawning on egg production by female Atlantic salmon (Salmo salar). For a given body size, female salmon that had smolted as juveniles after 2 years in fresh water produced smaller, more numerous eggs than females that smolted 1 year later. Furthermore, fecundity (but not egg size) was related positively to maternal body condition at spawning. Given that age at smolting is closely related to juvenile growth rate; results from this study suggest that conditions experienced by female Atlantic salmon during both early life and adulthood have implications for the size and number of eggs that they produce.
Infection patterns and hosts ofArceuthobium oxycedri(DC.)M.Bieb. inSlovenia
Authors: Gajšek D. , Jarni K. , Brus R. 
Published: November 2012

SummaryEleven mixed populations ofJuniperus oxycedrusL. andJuniperus communisL. were inventoried for the presence of parasitic woody speciesArceuthobium oxycedri(DC.)M. Bieb. infections. BothJ. oxycedrusandA. oxycedriare rare and distributed in marginal populations inSlovenia. To our knowledge, this is the first detailed research on the host species as well as on the infection and spreading patterns ofA. oxycedriinEurope. Assessment of the infection rate was based on theHawksworth six‐class dwarf mistletoe rating system (DMR). The dimensions ofA. oxycedrispecimens were surprisingly large and often exceeded 25 cm in diameter, the largest even measuring up to 40 cm. Six juniper populations of 11 were infected, and the proportion of infected host individuals in these ranged between 29.17 and 82.93%. The proportion of infectedJ. oxycedrusspecimens in infected populations was 76.56%, while this percentage forJ. communiswas 54.90%, which is surprisingly high for this species. A different pattern of infection was observed for the two hosts. A typical infection onJ. communiswas more localized. Usually, only a single infection was present and was most common on the trunk in the middle third of the crown and much less common on the branches. InJ. oxycedrus, infections were also most common in the middle third, but also frequent in other areas of the trunk as well as on the branches. Mostly, we observed a dotted pattern of infection with uninfected areas in between. We assume thatA. oxycedriwill continue to slowly spread in Slovenia, primarily in areas where it is already present. However, its control is probably not yet necessary.
Modelling the evolution of genetic instability during tumour progression
Authors: S. Datta Ruchira , Gutteridge Alice , Swanton Charles , Maley Carlo C. , Graham Trevor A. 
Published: November 2012

AbstractThe role of genetic instability in driving carcinogenesis remains controversial. Genetic instability should accelerate carcinogenesis by increasing the rate of advantageous driver mutations; however, genetic instability can also potentially retard tumour growth by increasing the rate of deleterious mutation. As such, it is unclear whether genetically unstable clones would tend to be more selectively advantageous than their genetically stable counterparts within a growing tumour. Here, we show the circumstances where genetic instability evolves during tumour progression towards cancer. We employ a Wright–Fisher type model that describes the evolution of tumour subclones. Clones can acquire both advantageous and deleterious mutations, and mutator mutations that increase a cell's intrinsic mutation rate. Within the model, cancers evolve with a mutator phenotype when driver mutations bestow only moderate increases in fitness: very strong or weak selection for driver mutations suppresses the evolution of a mutator phenotype. Genetic instability occurs secondarily to selectively advantageous driver mutations. Deleterious mutations have relatively little effect on the evolution of genetic instability unless selection for additional driver mutations is very weak or if deleterious mutations are very common. Our model provides a framework for studying the evolution of genetic instability in tumour progression. Our analysis highlights the central role of selection in shaping patterns of mutation in carcinogenesis.
Exogenous NAD+ supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1‐p53 pathway
Authors: Liu Ling , Wang Ping , Liu Xinwei , He Dongwei , Liang Canxin , Yu Ying 
Published: November 2012

AbstractNicotinamide adenine dinucleotide (NAD+) not only transfers electrons in mitochondrial respiration, but also acts as an indispensable cosubstrate for Sirt1, the class III histone/nonhistone deacetylase. However, NAD+ is depleted in myocardial ischemia/reperfusion (IR) injury. The objective of this study was to investigate the role of exogenous NAD+ supplementation in hypoxia/reoxygenation (HR)‐stressed H9c2 cardiac myoblasts. Firstly, the effects of distinct treating time points and doses of NAD+ supplementation on the viability of HR‐stressed H9c2 cells were detected. Secondly, intracellular NAD+ levels in HR‐stressed H9c2 cells at various extracellular NAD+ concentrations were determined. Thirdly, the role of NAD+ supplementation in HR‐induced cell apoptosis and its relevance to Sirtuin 1‐p53 pathway were investigated. Exogenous NAD+ supplementation elevated intracellular NAD+ level and reduced HR‐induced cell death in both time‐ and concentration‐dependent manners. It appeared that NAD+ supplementation exerted the greatest protection when extracellular concentration ranged from 500 to 1000 μm and when NAD+ was added immediately after reoxygenation began. NAD+ replenishment restored Sirt1 activity, reduced the acetylation level of p53 (Lys373 & 382), and attenuated cell apoptosis in HR‐stressed H9c2 cells, whereas inhibition of Sirt1 activity alleviated the effects of NAD+ replenishment. These results indicated that exogenous NAD+ supplementation attenuated HR‐induced cell apoptosis, which was at least partly mediated by restoring Sirt1 activity and subsequently inhibiting p53 activity via deacetylating p53 at lysine 373 and 382.
Association between low renal function and tooth loss over 5 years
Authors: Yoshihara Akihiro , Iwasaki Masanori , Miyazaki Hideo , Nakamura Kazutoshi 
Published: November 2012

ObjectivesThis longitudinal study evaluated the relationship between low renal function and tooth loss in elderly subjects.Material and methodsSubjects comprised 406 female subjects (55–74 years old) who agreed to participate in a baseline examination and a follow‐up examination after 5 years. Serum cystatin C levels were used to assess renal function. Multiple logistic regression analysis was used to evaluate the relationship between tooth loss and change in serum cystatin C levels over 5 years. Tooth loss over 5 years (0: no, 1: yes) was used as the dependent variable. Seven variables were used as independent variables, including change in serum cystatin C levels over 5 years.ResultsResults of multiple logistic regression analysis showed that cystatin C change over 5 years, age, number of remaining teeth at baseline, number of sites with ≥4 mm clinical attachment level at baseline and serum 25‐hydroxyvitamin D levels at baseline were significantly associated with tooth loss. The odds ratio for tooth loss with cystatin C change over 5 years was 7.70 (p = 0.029).ConclusionThis study indicates a relationship between serum cystatin C levels and number of missing teeth, and thus suggests that low renal function is associated with tooth loss.