bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation of the filaggrin gene adds to the risk of eczema associated with loss‐of‐function variants
Authors: Ziyab A.H. , Karmaus W. , Holloway J.W. , Zhang H , Ewart S. , Arshad S.H. 
Published: September 2012

AbstractBackground  Loss‐of‐function variants within the filaggrin gene (FLG) are associated with a dysfunctional skin barrier that contributes to the development of eczema. Epigenetic modifications, such as DNA methylation, are genetic regulatory mechanisms that modulate gene expression without changing the DNA sequence.Objectives  To investigate whether genetic variants and adjacent differential DNA methylation within the FLG gene synergistically act on the development of eczema.Methods  A subsample (n = 245, only females aged 18 years) of the Isle of Wight birth cohort participants (n = 1456) had available information for FLG variants R501X, 2282del4 and S3247X and DNA methylation levels for 10 CpG sites within the FLG gene. Log‐binomial regression was used to estimate the risk ratios (RRs) of eczema associated with FLG variants at different methylation levels.Results  The period prevalence of eczema was 15.2% at age 18 years and 9.0% of participants were carriers (heterozygous) of FLG variants. Of the 10 CpG sites spanning the genomic region of FLG, methylation levels of CpG site ‘cg07548383’ showed a significant interaction with FLG sequence variants on the risk for eczema. At 86% methylation level, filaggrin haploinsufficient individuals had a 5.48‐fold increased risk of eczema when compared to those with wild type FLG genotype (P‐value = 0.0008).Conclusions  Our novel results indicated that the association between FLG loss‐of‐function variants and eczema is modulated by DNA methylation. Simultaneously assessing the joint effect of genetic and epigenetic factors within the FLG gene further highlights the importance of this genomic region for eczema manifestation.
Development of NMR spectroscopic methods for dynamic detection of acetylcholine synthesis by choline acetyltransferase in hippocampal tissue
Authors: Hall Hélène , Cuellar‐Baena Sandra , Denisov Vladimir , Kirik Deniz 
Published: September 2012

AbstractCholine acetyltransferase (ChAT) is the key enzyme for acetylcholine (ACh) synthesis and constitutes a reliable marker for the integrity of cholinergic neurons. Cortical ChAT activity is decreased in the brain of patients suffering from Alzheimer's and Parkinson's diseases. The standard method used to measure the activity of ChAT enzyme relies on a very sensitive radiometric assay, but can only be performed on post‐mortem tissue samples. Here, we demonstrate the possibility to monitor ACh synthesis in rat brain homogenates in real time using NMR spectroscopy. First, the experimental conditions of the radiometric assay were carefully adjusted to produce maximum ACh levels. This was important for translating the assay to NMR, which has a low intrinsic sensitivity. We then used 15N‐choline and a pulse sequence designed to filter proton polarization by nitrogen coupling before 1H‐NMR detection. ACh signal was resolved from choline signal and therefore it was possible to monitor ChAT‐mediated ACh synthesis selectively over time. We propose that the present approach using a labeled precursor to monitor the enzymatic synthesis of ACh in rat brain homogenates through real‐time NMR represents a useful tool to detect neurotransmitter synthesis. This method may be adapted to assess the state of the cholinergic system in the brain in vivo in a non‐invasive manner using NMR spectroscopic techniques.
Splanchnic net balance of oxygen and metabolites in response to a discontinuous mesenteric vein infusion of ammonium in sheep
Authors: Recavarren M. I. , Milano G. D. 
Published: September 2012

SummaryTo simulate daily episodes of high absorption associated with the intake of diets with high N content, four wethers (42 ± 3.4 kg body weight), fitted with permanent catheters in the femoral artery and splanchnic vessels, were infused with 340 μmol into the mesenteric vein for 3 h, during the morning meal, over seven consecutive days. On the 7th day, mass transfers of , urea, glucose, lactate, ß‐OH‐butyrate and O2 were measured across portal‐drained viscera (PDV), liver and splanchnic tissues during the last 90 min of the infusion. Measurements were repeated on the following day, at the same time, without the infusion. Plasma concentration in the portal vein (+332 μm; p = 0.006), portal absorption (+424 μmol/min; p < 0.001), liver uptake (+375 μmol/min; p = 0.003) and urea N production (+338 μmol/min; p = 0.059) were higher during infusion. Mass transfers of urea, glucose, lactate, ß‐OH‐butyrate and O2 across the PDV, and glucose, lactate, ß‐OH‐butyrate and O2 across the liver, were not altered by the infusion. Results suggest that a daily, discontinuous increase in portal flow during a meal stimulates liver removal and urea N production but does not significantly affect liver glucose production and O2 consumption in sheep.
Asymptomatic groin dermatophyte carriage detected during routine gynaecologic examinations
Authors: Küçükgöz‐Güleç Ümran , Gümral Ramazan , Güzel Ahmet B. , Khatib Ghanim , Karakaş Mehmet , Ilkit Macit 
Published: September 2012

SummaryWe investigated the epidemiological characteristics of both symptomatic and asymptomatic dermatophytic groin infections in 1970 women (age: 36.2 ± 12.5) during routine gynaecologic examinations. Bilateral groin samples were collected with sterile cotton swabs premoistened with sterile physiological saline. The samples were then separately inoculated onto Sabouraud glucose agar. Fungi were identified by sequencing the rDNA internal transcribed spacer region. Dermatophytes were recovered from five patients (four Trichophyton rubrum and one Arthroderma vanbreuseghemii, 0.25%) with a diagnosis of asymptomatic carriers (four) and tinea inguinalis (one). In one case, groin carriage converted into tinea inguinalis after 3 weeks. Analysis of risk factors indicated that patients of at least 49 years were more likely to be positive for dermatophyte isolation (P = 0.002). In conclusion, groin dermatophyte carriage is more common than tinea inguinalis and can potentially convert into a symptomatic infection.
A novel phosphotransferase system of Streptococcus mutans is responsible for transport of carbohydrates with α‐1,3 linkage
Authors: Ajdic D. , Chen Z. 
Published: September 2012

SummaryThe most common type of carbohydrate‐transport system in Streptococcus mutans is the phosphoenolpyruvate–sugar phosphotransferase system (PTS). Fourteen PTS exist in S. mutans UA159. Several studies have shown that microorganisms growing in biofilms express different genes compared with their planktonic counterparts. In this study, we showed that one PTS of S. mutans was expressed in sucrose‐grown biofilms. Furthermore, the same PTS was also responsible for the transport and metabolism of disaccharide nigerose (3‐O‐α‐d‐glucopyranosyl‐d‐glucose). Additionally, the results indicate that the studied PTS might be involved in the transport and metabolism of carbohydrates synthesized by glucosyltransferase B and glucosyltransferase C of S. mutans. To our knowledge, this is the first report that shows PTS transport of a disaccharide (and possibly extracellular oligosaccharides) with α‐1,3 linkage.
Family and social aspects associated with depression among older persons in aChinese context
Authors: Zeng Wen , North Nicola , Kent Bridie 
Published: September 2012

AimThis study aims to explore the factors associated with depression among older persons inMacau, in relation to family and social aspects.BackgroundDepression among community‐dwelling older persons inMacau has been shown to be present at high rates. InChinese culture, depression leads to social stigmatisation, suggesting a need to better understand depression as a sociocultural phenomenon.MethodsA mixed methods study was undertaken to identify the key influences on depression amongChinese older persons inMacau. Quantitative (standardised tests) and qualitative (collection of narratives) data were collected from 31 purposively selected participants, all community‐dwelling older persons with depression.ResultsDepression was common among the participants. The paper reports on the family and social aspects, one of the findings of the study. Informants readily described their thoughts and judgements of themselves in graphic language. As they explored their life stories, family and social aspects emerged as significant influences that associated with depression. In a society and culture that relies on and values filial support, experiences of being widowed, having poor family support and weak social networks appeared to compound and exacerbate depression.ConclusionsThese findings highlight that filial support, valued inChinese culture, is seriously strained by the realities of contemporary society. Yet current government policies rely on and confirm the role of family support. Findings from this study suggest a need for such policies to be reviewed to address the realities of family and social support.Implications for practiceThe findings have several implications for clinical practice. Firstly, the cultural context ofChinese older persons should be considered and emphasised in nursing practice. Secondly, the root of depression among Chinese older persons is seen to lie in their social, family, cultural and day‐to‐day living issues.
Comparison of the bronchodilating effects of albuterol delivered by valved vs. non‐valved spacers in pediatric asthma
Authors: Rodriguez‐Martinez Carlos E. , Sossa‐Briceño Mónica P. , Castro‐Rodriguez Jose A. 
Published: September 2012

AbstractIntroductionInhaled therapy using a metered‐dose inhaler (MDI) with attached valved holding chamber has been increasingly recognized as the optimal method for delivering bronchodilators for asthma treatment. However, mainly due to the high cost of these valved holding chambers in many developing countries, the use of non‐valved spacers is frequent, despite the scarce evidence that supports their efficacy. The aim of this study was to compare the bronchodilator response to albuterol administered by MDI with and without a valved spacer.MethodsIn a randomized, two‐period, two‐sequence crossover clinical trial, we analyzed 31 stable asthmatic children (6–18 yrs of age) on two consecutive days, who were randomly assigned to receive 100 μg of albuterol MDI through either a locally produced valved spacer or a non‐valved spacer. The next day, a crossover treatment was employed through the use of the other spacer. Spirometry was recorded before and after each albuterol administration.ResultsAs we were not able to identify any sequence or carryover effect, we tested for treatment effects in both periods. No significant differences in the absolute change in FEV1 (0.20 ± 0.17 vs. 0.18 ± 0.16, p = 0.63), FVC (0.07 ± 0.13 vs. 0.07 ± 0.16, p = 0.88), or MMEF (0.49 ± 0.31 vs. 0.43 ± 0.39, p = 0.53) after bronchodilator administration were found between the use of valved and non‐valved spacers.ConclusionsIn stable asthmatic children, albuterol administered through MDI using a non‐valved spacer produces a bronchodilator response similar to that of a spacer with a valve that requires an inhalatory opening pressure (with flows between 2 and 32 l/min) that even toddlers with bronchial obstruction can easily generate.
Comparison of success rate of ultrasound‐guided sciatic and femoral nerve block and neurostimulation in children with arthrogryposis multiplex congenita: a randomized clinical trial
Authors: Ponde Vrushali , Desai Ankit P. , Shah Dipal 
Published: September 2012

SummaryBackground and objectivesArthrogryposis multiplex congenital is hallmarked with immobile joints and muscle fibrosis. The main objective of this study was to compare the success rate of ultrasound‐guided sciatic and femoral nerve blocks with nerve stimulations in children diagnosed with distal arthrogryposis multiplex congenita.MethodSixty children aged 8 months to 2 years posted for foot surgery were randomly assigned to group NS and group US of 30 each. Under general anesthesia, femoro‐sciatic block was performed with nerve stimulator guidance in group NS and ultrasound guidance in group US.ResultsGroup NS: 23 of 30 (76.7%) children showed ankle movement with sciatic neurostimulation. In 7 (23.6%), distal motor response could not be elicited and the block was abandoned. Out of 23 children who could be given femoral block, in 12 (52%) patients quadriceps contractions were not elicited and fascia iliaca block was given. All 23 blocks were successful. CHIPPS score at 1, 4, 6, 8, and 10 h was 1.05 ± 0.90, 1.82 ± 1.18, 3.36 ± 1.65, 2.23 ± 2.02, and 1.18 ± 1.14, respectively. Group US: In 29 of 30 patients (96.6%), sciatic nerve was visualized with ultrasonography. All 29 children received femoral block, and they were successful. The odds of success in group US were 8.9 (95% confidence interval [1.0, 77.9]) as compared with NS group. The difference in success rate was statistically significant (P = 0.026). The analgesic duration difference in the US and NS groups was a mean 7.62 ± 0.57 h in group NS and 8.60 ± 0.66 h in group US (statistically significant [P < 0.001]). CHIPPS score at 1, 4, 6, 8, and 10 h was 0.79 ± 0.96, 1.61 ± 0.92, 2.96 ± 1.04, 2.36 ± 2.54, and 1.14 ± 1.01, respectively. The difference between the CHIPPS score was not statistically significant.ConclusionUltrasonography significantly increases the success rate of sciatic and femoral block in arthrogryposis.
Nonylphenol Polyethoxylates Degraded by Three Different Wavelengths of UV and Their Genotoxic Change—Detected by Generation of γ‐H2AX
Authors: Kubota Toru , Toyooka Tatsushi , Ibuki Yuko 
Published: September 2012

AbstractUV rays in sunlight are an important factor in the degradation of chemicals. In this study, we investigated the degradation of nonionic surfactants, nonylphenol polyethoxylates (NPEOs) with 10 or 70 ethylene oxide (EO) units using UVA, B and C, and their genotoxic change based on phosphorylation of histone H2AX (γ‐H2AX), a marker of DNA damage. NPEOs were degraded dependent on the energy of UV, that is, UVC having the highest energy was most effective, whereas UVA having the lowest energy caused little change. The EO side chain of NPEO(70) was broken near the benzene ring by UV, producing NPEOs with a shortened EO chain (around 10 units). The generation of γ‐H2AX reflected the pattern of degradation; shortening of the EO chain changed NPEO(70) into an inducer for γ‐H2AX, and degradation of NPEO(10) attenuated the genotoxicity. The γ‐H2AX generated by NPEO(10) and UV‐degraded NPEO(70) was independent of the cell cycle. The formation of DNA double strand breaks detected by gel electrophoresis was consistent with the results for γ‐H2AX. These results suggested that UV rays can make NPEOs harmless or genotoxic according to the degradation of the EO side chain, the effects being dependent on wavelength.
Descriptive Epidemiology of Non‐syndromic Complete Atrioventricular Canal Defects
Authors: Agopian A. J. , Moulik Mousumi , Gupta‐Malhotra Monesha , Marengo Lisa K. , Mitchell Laura E. 
Published: September 2012

AbstractBackground:  Complete atrioventricular canal defects (CAVC) are a common heart defect, but few epidemiologic studies have evaluated non‐syndromic CAVC. Risk factors for non‐syndromic CAVC have not been well established.Methods:  To assess the relationship between risk for non‐syndromic CAVC in offspring and several sociodemographic and reproductive parental factors, including maternal diabetes and obesity, we conducted Poisson regression analyses, using data ascertained through the Texas Birth Defects Registry, a large, population‐based birth defects registry. Data were evaluated for 563 non‐syndromic cases with CAVC.Results:  Significant associations were observed between non‐syndromic CAVC in offspring and maternal pregestational diabetes (adjusted prevalence ratio (aPR) 6.74; 95% confidence interval (CI) 3.67, 12.37), gestational diabetes (aPR 1.69; 95% CI 1.03, 2.79) and obesity (aPR 1.69; 95% CI 1.24, 2.30).Conclusions:  Our findings add non‐syndromic CAVC to the growing list of birth defects that appear to be associated with maternal diabetes and obesity.
Graftula: A Composite Access Consisting of a Graft Used to Repair a Dysfunctional Hemodialysis Fistula
Authors: Ramani Karthik , Kallam Ajay , Zibari Gazi , Caldito Gloria , Ram Sunanda J. , Abreo Kenneth D. , Sequeira Adrian 
Published: September 2012

AbstractNonmaturing or dysfunctional hemodialysis fistulas are often repaired with interposition grafts placed either within the fistula (fistula‐to‐fistula configuration), or connected to another vein (fistula‐to‐vein configuration). The goal of this study was to compare the survival and usefulness of the composite accesses thus created, which we call “graftulas,” with upperarm grafts. This was a retrospective study wherein we determined the survival and thrombosis rates of graftulas (n = 24) and upper arm grafts (n = 31) placed 1/1/07 through 12/31/09 and followed through 11/30/10. Graftulas resembled grafts as most (96%) were successfully cannulated in 65 ± 43 days. Survival of graftulas was also similar to grafts (58%, 47%, and 32% vs. 56%, 47%, and 39% at 1, 2, and 3 years respectively, p = 0.60). However, graftulas had a lower thrombosis rate than grafts (0.5 vs. 1.2 per patient year, p = 0.04), and in the fistula‐to‐fistula configuration, a 2‐year thrombosis‐free survival of 78%. Total survival of the access site (fistula + graftula) was 92%, 73%, and 42% at 1, 3, and 5 years, respectively. Graftulas possess certain beneficial properties of fistulas and grafts that allows for continued use of the original access site.
Blood Pressure and Blood Volume: Acute and Chronic Considerations in Hemodialysis
Authors: Lewicki Michelle C. , Kerr Peter G. , Polkinghorne Kevan R. 
Published: September 2012

AbstractHypertension is highly prevalent yet poorly controlled in the majority of dialysis patients and represents a significant burden of disease, with rates of morbidity and mortality greater than those in the general population. In dialysis, blood volume plays a critical role in the pathogenesis of hypertension, with expansion of extracellular volume increasingly recognized as an independent risk factor for morbidity and mortality. Within the current paradigm of dialysis prescription the majority of patients remain chronically volume expanded. However, management of blood pressure and volume state is difficult for clinicians with a paucity of randomized evidence adding to the complexity of nonlinear morbidity and mortality associations. With dialysis itself as a significant cardiac stressor, control of volume state is critical to minimize intradialytic hemodynamic instability, aid in preservation of cardiac anatomy and prevent progression to cardiovascular morbidity and mortality. This review explores the relationship of blood volume to blood pressure and potential targets for management in this at risk population.
Dihydropyridine receptors actively control gating of ryanodine receptors in resting mouse skeletal muscle fibres
Authors: Robin Gaëlle , Allard Bruno 
Published: September 2012

Key points
Depolarization of the skeletal muscle membrane elicits a change in the configuration of dihydropyridine receptors that in turn triggers sarcoplasmic reticulum (SR) Ca2+ release through ryanodine receptors.
At rest, it is assumed, but never demonstrated in adult muscle fibres, that dihydropyridine receptors exert a repressive action on ryanodine receptors that keeps them in a closed state.
By measuring Ca2+ changes in the SR in voltage‐clamp conditions, we report that any interventions designed to alter the conformation of dihydropyridine receptors at rest induce an SR Ca2+ efflux.
These results show that dihydropyridine receptors maintain a strict control upon ryanodine receptors in resting skeletal mouse muscle fibres.
Abstract  Contraction of skeletal muscle is triggered by the release of Ca2+ from the sarcoplasmic reticulum (SR) in response to depolarization of the muscle membrane. Depolarization is known to elicit a conformational change of the dihydropyridine receptor (DHPR) in the tubular membrane that controls in a time‐ and voltage‐dependent manner the opening of the ryanodine receptor (RyR), the SR Ca2+ release channel. At rest, it is assumed that RyRs are kept in a closed state imposed by the repressive action of DHPRs; however, a direct control of the RyR gating by the DHPR has up to now never been demonstrated in resting adult muscle. In this study, we monitored slow changes in SR Ca2+ content using the Ca2+ indicator fluo‐5N loaded in the SR of voltage‐clamped mouse muscle fibres. We first show that external Ca2+ removal induced a reversible SR Ca2+ efflux at −80 mV and prevented SR Ca2+ refilling following depolarization‐evoked SR Ca2+ depletion. The dihydropyridine compound nifedipine induced similar effects. The rate of SR Ca2+ efflux was also shown to be controlled in a time‐ and voltage‐dependent manner within a membrane potential range more negative than −50 mV. Finally, intracellular addition of ryanodine produced an irreversible SR Ca2+ efflux and kept the SR in a highly depleted state following depolarization‐evoked SR Ca2+ depletion. The fact that resting SR Ca2+ efflux is modulated by conformational changes of DHPRs induced by external Ca2+, nifedipine and voltage demonstrates that DHPRs exert an active control on gating of RyRs in resting skeletal muscle.
Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients
Authors: Muller Matthew D. , Drew Rachel C. , Blaha Cheryl A. , Mast Jessica L. , Cui Jian , Reed Amy B. , Sinoway Lawrence I. 
Published: September 2012

Key points
Peripheral arterial disease (PAD) is a common and debilitating condition linked with heightened risk of cardiovascular mortality.
Dynamic exercise elicits augmented blood pressure responses in PAD that could put the patient at risk for adverse event but the underlying mechanisms are unknown.
The exercise pressor reflex is comprised of group III and group IV muscle afferents that increase their discharge in response to mechanical and/or chemical stimulation.
In this study, we demonstrate that mechanically sensitive muscle afferents cause augmented reflex elevations in blood pressure during dynamic plantar flexion exercise in PAD. These responses occur prior to claudication pain, are related to disease severity and can be partly reduced by acute antioxidant infusion.
Abstract  Exaggerated blood pressure (BP) responses to dynamic exercise predict cardiovascular mortality in patients with peripheral arterial disease (PAD). However, the underlying mechanisms are unclear and no attempt has been made to attenuate this response using antioxidants. Three physiological studies were conducted in patients with PAD and controls. In Protocol 1, subjects underwent 4 min of low‐intensity (0.5–2.0 kg), rhythmic plantar flexion in the supine posture. In Protocol 2, patients with PAD received high‐dose ascorbic acid intravenously before exercise. In Protocol 3, involuntary exercise was conducted via electrical stimulation of the tibial nerve. The primary outcome measure was Δ mean arterial pressure (MAP) during the first 20 s of exercise (i.e. the onset of sympathoexcitation by muscle afferents). Compared to controls, patients with PAD had significantly greater ΔMAP during plantar flexion, particularly at 0.5 kg with the most affected leg (11 ± 2 vs. 2 ± 1 mmHg) as well as the least affected leg (7 ± 1 vs. 1 ± 1 mmHg). This augmented response occurred before the onset of claudication pain and was attenuated by ∼50% with ascorbic acid. Electrically evoked exercise also elicited larger haemodynamic changes in patients with PAD compared to controls. Further, the ΔMAP during 0.5 kg plantar flexion inversely correlated with the ankle–brachial index, indicating that patients with more severe resting limb ischaemia have a larger BP response to exercise. The BP response to low‐intensity exercise was enhanced in PAD. Chronic limb ischaemia may sensitize muscle afferents and potentiate the BP response to muscle contraction in a dose‐dependent manner.