bluuebunny/crossref_metadata_2025_split huggingface dataset:
DA‐9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study
Authors: Kim Su Young , Woo Hyun Sun , Kim Kyoung Oh , Choi Sung Han , Kwon Kwang An , Chung Jun‐Won , Kim Yoon Jae , Kim Jung Ho , Kim Su Ji , Park Dong Kyun 
Published: April 2017

AbstractBackground and AimDA‐9701, a newly developed prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has been shown to effectively treat functional dyspepsia. Recently, it has also been suspected to improve gastrointestinal motor function. The aims of this study were to assess the effect of DA‐9701 on colonic transit time (CTT) and symptoms of functional constipation.MethodsThirty‐three patients with functional constipation based on the Rome III criteria were prospectively enrolled. The patients received 30‐mg DA‐9701 three times a day for 24 days. CTT was estimated initially and at the end of treatment. Symptoms such as spontaneous bowel movements, straining, stool form, feeling of incomplete emptying and anorectal blockage, abdominal discomfort and pain, overall defecation satisfaction, and incidence of adverse events were also analyzed.ResultsTwenty‐seven patients completed the study. DA‐9701 was associated with a significantly reduced CTT from 34.9 ± 17.6 to 23.7 ± 19.1 h (P = 0.001). Segmental CTT also significantly decreased after treatment (right CTT: from 16.8 [0.0–28.8] to 6.0 [0.0–25.2] hours, P < 0.001; rectosigmoid transit time: from 13.2 [0.0–38.4] to 6.0 [0.0–33.6] hours, P = 0.021). In addition, all constipation‐related subjective symptoms, including spontaneous bowel movement frequency, significantly improved compared with those before treatment. Serious adverse events did not occur.ConclusionsDA‐9701 accelerates colonic transit and safely improves symptoms in patients with functional constipation. Therefore, we suggest that this novel agent could help to treat patients with this condition.
ARALAR/AGC1 deficiency, a neurodevelopmental disorder with severe impairment of neuronal mitochondrial respiration, does not produce a primary increase in brain lactate
Authors: Juaristi Inés , García‐Martín María L. , Rodrigues Tiago B. , Satrústegui Jorgina , Llorente‐Folch Irene , Pardo Beatriz 
Published: April 2017

AbstractARALAR/AGC1 (aspartate‐glutamate mitochondrial carrier 1) is an important component of the NADH malate‐aspartate shuttle (MAS). AGC1‐deficiency is a rare disease causing global cerebral hypomyelination, developmental arrest, hypotonia, and epilepsy (OMIM ID #612949); the aralar‐KO mouse recapitulates the major findings in humans. This study was aimed at understanding the impact of ARALAR‐deficiency in brain lactate levels as a biomarker. We report that lactate was equally abundant in wild‐type and aralar‐KO mouse brain in vivo at postnatal day 17. We find that lactate production upon mitochondrial blockade depends on up‐regulation of lactate formation in astrocytes rather than in neurons. However, ARALAR‐deficiency decreased cell respiration in neurons, not astrocytes, which maintained unchanged respiration and lactate production. As the primary site of ARALAR‐deficiency is neuronal, this explains the lack of accumulation of brain lactate in ARALAR‐deficiency in humans and mice. On the other hand, we find that the cytosolic and mitochondrial components of the glycerol phosphate shuttle are present in astrocytes with similar activities. This suggests that glycerol phosphate shuttle is the main NADH shuttle in astrocytes and explains the absence of effects of ARALAR‐deficiency in these cells.
image
Haplodeficiency of Cathepsin D does not affect cerebral amyloidosis and autophagy in APP/PS1 transgenic mice
Authors: Cheng Shaowu , Wani Willayat Y. , Hottman David A. , Jeong Angela , Cao Dongfeng , LeBlanc Kyle J. , Saftig Paul , Zhang Jianhua , Li Ling 
Published: April 2017

AbstractAutophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. This study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β‐amyloidosis in amyloid‐β precursor protein (APP)sw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease in Cat D level in APP/PS1/Ctsd+/− compared with APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain. There were also no differences in APP processing, the levels of two other Aβ‐degrading proteases, the levels of autophagy related protein, such as LAMP2, P62, LC3‐I, LC3‐II, and Beclin‐1, or the markers of neuroinflammation, observed between the APP/PS1/Ctsd+/+ and APP/PS1/Ctsd+/− mice. Our findings demonstrate that in wild‐type mice, Cat D protein levels are either in excess or redundant with other factors in the brain, and at least one allele of Ctsd is dispensable for cerebral β‐amyloidosis and autophagy in APP/PS1 transgenic mice.
image
The role of charged residues in independent glycine receptor folding domains for intermolecular interactions and ion channel function
Authors: Langlhofer Georg , Villmann Carmen 
Published: April 2017

AbstractGlycine receptor (GlyR) truncations in the intracellular TM3‐4 loop, documented in patients suffering from hyperekplexia and in the mouse mutant oscillator, lead to non‐functionality of GlyRs. The missing part that contains the TM3‐4 loop, TM4 and C‐terminal sequences is essential for pentameric receptor arrangements. In vitro co‐expressions of GlyRα1‐truncated N‐domains and C‐domains were able to restore ion channel function. An ionic interaction between both domains was hypothesized as the underlying mechanism. Here, we analysed the proposed ionic interaction between GlyR N‐ and C‐domains using C‐terminal constructs with either positively or negatively charged N‐termini. Charged residues at the N‐terminus of the C‐domain did interfere with receptor surface expression and ion channel function. In particular, presence of negatively charged residues at the N‐terminus led to significantly decreased ion channel function. Presence of positive charges resulted in reduced maximal currents possibly as a result of repulsion of both domains. If the C‐domain was tagged by a myc‐epitope, low maximal current amplitudes were detected. Intrinsic charges of the myc‐epitope and charged N‐terminal ends of the C‐domain most probably induce intramolecular interactions. These interactions might hinder the close proximity of C‐domains and N‐domains, which is a prerequisite for functional ion channel configurations. The remaining basic subdomains close to TM3 and 4 were sufficient for domain complementation and functional ion channel formation. Thus, these basic subdomains forming α‐helical elements or an intracellular portal represent attractants for incoming negatively charged chloride ions and interact with the phospholipids thereby stabilizing the GlyR in a conformation that allows ion channel opening.
image
A device to measure secretion of individual sweat glands for diagnosis of peripheral neuropathy
Authors: Loavenbruck Adam J. , Hodges James S. , Provitera Vincenzo , Nolano Maria , Wendelshafer‐Crabb Gwen , Kennedy William R. 
Published: April 2017

AbstractThere is a need for quantitative, precise assessment of small fiber peripheral nerve function. We tested a customized camera device and protocol designed to quantify secretions of individual sweat glands (SGs). Testing was performed on 178 healthy controls and 20 neuropathy subjects. Sweating was stimulated on a 2.25 cm2 skin area by iontophoresis of pilocarpine. The camera imaged sweat from 50 to 400 sweat ducts. We calculated secretion rate of individual SGs, total sweat volume, and number of secreting SGs at four body sites. Neuropathy subjects were tested at the two distal sites to demonstrate the device's capability to detect abnormal sudomotor function. Normal ranges were calculated for each body site. Neuropathy subjects had lower sweat rates per SG, lower total sweat, and lower SG density. The normal values decreased with advancing age, were lower in females, and differed between body sites. There was good agreement with repeat testing. The device provides reliable, precise quantitative measures of sweat secretion from single SGs for characterization of sudomotor nerve function in healthy control subjects and in subjects with known peripheral neuropathy. The test combines the capabilities of existing tests of sudomotor function while providing additional capabilities.
Variation in brain anatomy in frogs and its possible bearing on their locomotor ecology
Authors: Manzano Adriana S. , Herrel Anthony , Fabre Anne‐Claire , Abdala Virginia 
Published: April 2017

AbstractDespite the long‐standing interest in the evolution of the brain, relatively little is known about variation in brain anatomy in frogs. Yet, frogs are ecologically diverse and, as such, variation in brain anatomy linked to differences in lifestyle or locomotor behavior can be expected. Here we present a comparative morphological study focusing on the macro‐ and micro‐anatomy of the six regions of the brain and its choroid plexus: the olfactory bulbs, the telencephalon, the diencephalon, the mesencephalon, the rhombencephalon, and the cerebellum. We also report on the comparative anatomy of the plexus brachialis responsible for the innervation of the forelimbs. It is commonly thought that amphibians have a simplified brain organization, associated with their supposedly limited behavioral complexity and reduced motor skills. We compare frogs with different ecologies that also use their limbs in different contexts and for other functions. Our results show that brain morphology is more complex and more variable than typically assumed. Moreover, variation in brain morphology among species appears related to locomotor behavior as suggested by our quantitative analyses. Thus we propose that brain morphology may be related to the locomotor mode, at least in the frogs included in our analysis.
The development, evidence, and current use of ATX‐101 for the treatment of submental fat
Authors: Georgesen Corey , Lipner Shari R. 
Published: April 2017

SummaryATX‐101 (deoxycholic acid) is the first pharmaceutical therapy approved by the FDA for the reduction in submental fat. Deoxycholic acid is an endogenous secondary bile acid that normally solubilizes dietary fat, contributing to its breakdown and absorption within the gut. This article reviews the identification of deoxycholic acid as a lipolytic agent, and the mechanism of action, pharmacokinetics, and pharmacodynamics of ATX‐101. In addition to phase I/II trials, four Phase III clinical trials have evaluated safety and efficacy of ATX‐101. These studies helped establish the appropriate dosage, administration techniques, warnings, and side effects of ATX‐101. ATX‐101 is effective in treating submental fat. Adverse events, although common, are mild and transient.
Ibn Khaldun and Philosophy: Causality in History
Authors: Çaksu Ali 
Published: April 2017

AbstractIbn Khaldun was a statesman, diplomat, scholar and judge. His masterpiece Muqaddimah bears testimony to his skills in some other fields like economy and poetry too. As an intellectual of his time, he was naturally interested in philosophy as well. He had an education in philosophy and had a considerable knowledge in both Greek and Islamic philosophy. In fact, he is considered a philosopher of history and even the first one. This article will display an aspect of Ibn Khaldun's interest and relation to philosophy. It will discuss his conception of causation and analyze how it works in his history.
Khaldunian studies today: The contributions of Syed Farid Alatas
Authors: Ardıç Nurullah 
Published: April 2017

AbstractThe growing interest in the 14th‐century Muslim scholar Ibn Khaldun's ideas and his essentially historical‐sociological perspective implies a promise of a critical appraisal of the Eurocentric nature of the classical and contemporary social theory. An important role is played in this endeavor by Syed Farid Alatas whose work has been important not only in terms of further introducing Ibn Khaldun's theory to the Western audience but also making it more relevant to the contemporary theoretical debates and historical sociology. This article reviews Alatas' work on Ibn Khaldun with a view to demonstrate that his contributions to the Khaldunian studies today take at least five different forms: a critical examination of Ibn Khaldun's theory in general, and reconstruction of it as a theory of the state, and of religious revival in particular; demonstrating its significance for the modern social sciences; its application to a number of premodern and modern empirical cases; and a theoretical integration of his model with some modern Western theories, which is a rare occurrence in both Khaldunian studies and sociology in general.
Long Hours and Longings: Australian Children's Views of Fathers' Work and Family Time
Authors: Strazdins Lyndall , Baxter Jennifer A. , Li Jianghong 
Published: April 2017

AbstractUsing two waves of paired data from a population sample of 10‐ to 13‐year‐old Australian children (5,711 father–child observations), the authors consider how the hours, schedules, intensity, and flexibility of fathers' jobs are associated with children's views about fathers' work and family time. A third of the children studied considered that their father works too much, one eighth wished that he did not work at all, and one third wanted more time with him or did not enjoy time together. Logistic regression modeling revealed that working on weekends, being time pressured, being unable to vary start and stop times, and working long hours generated negative views in children about fathers' jobs and time together. The time dilemmas generated by fathers' work devotions and demands are salient to and subjectively shared by their children.
Assessment of disease‐specific knowledge in Australian children with inflammatory bowel disease and their parents
Authors: Day Andrew S , Mylvaganam Gaithri , Shalloo Nollaig , Clarkson Cathy , Leach Steven T , Lemberg Daniel A 
Published: April 2017

AimsDisease‐specific knowledge may influence disease outcome and quality of life in children with inflammatory bowel disease (IBD). This prospective study aimed to define IBD‐related knowledge in a group of Australian children with IBD and their parents using a validated measure of disease‐specific knowledge, the Inflammatory Bowel Disease Knowledge Inventory Device (IBD‐KID).MethodsChildren (less than 18 years) diagnosed with IBD who were members of the Australian patient support organisation were identified. Each family was sent copies of the IBD‐KID. Children aged 10–18 years and all parents were asked to complete the IBD‐KID and to also provide demographic details and disease characteristics.ResultsReplies were received from 196 families: 262 parents and 128 children completed questionnaires. Most children had a diagnosis of Crohn disease (65%) and 51% were male. Children diagnosed in the preceding 6 years scored higher than those with longer time since diagnosis. Parents had better scores in the IBD‐KID than the children (P < 0.0001). Overall, parents and children had poor understanding of key management issues for IBD (such as side effects of steroids), important outcomes (e.g. growth) and the use of complementary therapies.ConclusionsConsistent patterns of IBD‐related knowledge were noted in this large group of Australian children with IBD and their parents. Measurement of disease‐related knowledge with the IBD‐KID can identify gaps in understanding, thereby permitting focused educational activities. Although these knowledge gaps may impact upon outcomes, further prospective studies are now required to elucidate the relationships between enhanced knowledge and specific outcomes.
Increased levels of soluble HLA‐G molecules in Tunisian patients with chronic hepatitis B infection
Authors: Laaribi A. B. , Bortolotti D. , Hannachi N. , Mehri A. , Hazgui O. , Ben Yahia H. , Babay W. , Belhadj M. , Chaouech H. , Yacoub S. , Letaief A. , Ouzari H. I. , Boudabous A. , Di Luca D. , Boukadida J. , Rizzo R. , Zidi I. 
Published: April 2017

SummaryHepatitis B virus (HBV) infection is a global health problem. The mechanisms of immune tolerance in HBV infection are still unclear. The host immune response plays a critical role in determining the outcome of HBV infection. Human leucocyte antigen‐G (HLA‐G) is involved in immunotolerogenic process and infectious diseases. This study aimed to explore the implication of soluble HLA‐G (sHLA‐G) and its isoforms in HBV infection. Total sHLA‐G (including shedding HLA‐G1 and HLA‐G5) was analysed by ELISA in 95 chronic HBV patients, 83 spontaneously resolvers and 100 healthy controls (HC). To explore the presence of sHLA‐G dimers, we performed an immunoprecipitation and a Western blot analysis on positive samples for sHLA‐G in ELISA. The serum levels of sHLA‐G were significantly increased in patients with chronic HBV patients compared to spontaneously resolvers and HC (P<.0001). Interestingly, we found an increased level of sHLA‐G1 in chronic HBV patients than in spontaneously resolvers and HC (P<.001). In addition, the expression of HLA‐G5 seems to be higher in the sera of chronic HBV patients than spontaneously resolvers (P=.026). The analysis of HLA‐G dimers showed the presence of homodimers in 93% of chronic HBV patients, 67% in spontaneously resolvers and 60% in HC. These results provide evidence that sHLA‐G may have a crucial role in the outcome of HBV infection and could be proposed as a biomarker for infection outcome. Based on its tolerogenic function, HLA‐G might be considered as a new promising immunotherapeutic approach to treat the chronic infection with HBV.
Staphylococcus aureus nitric oxide synthase (saNOS) modulates aerobic respiratory metabolism and cell physiology
Authors: Mogen Austin B. , Carroll Ronan K. , James Kimberly L. , Lima Genevy , Silva Dona , Culver Jeffrey A. , Petucci Christopher , Shaw Lindsey N. , Rice Kelly C. 
Published: April 2017

SummaryNitric oxide (NO) is generated from arginine and oxygen via NO synthase (NOS). Staphylococcus aureus NOS (saNOS) has previously been shown to affect virulence and resistance to exogenous oxidative stress, yet the exact mechanism is unknown. Herein, a previously undescribed role of saNOS in S. aureus aerobic physiology was reported. Specifically, aerobic S. aureus nos mutant cultures presented with elevated endogenous reactive oxygen species (ROS) and superoxide levels, as well as increased membrane potential, increased respiratory dehydrogenase activity and slightly elevated oxygen consumption. Elevated ROS levels in the nos mutant likely resulted from altered respiratory function, as inhibition of NADH dehydrogenase brought ROS levels back to wild‐type levels. These results indicate that, in addition to its recently reported role in regulating the switch to nitrate‐based respiration during low‐oxygen growth, saNOS also plays a modulatory role during aerobic respiration. Multiple transcriptional changes were also observed in the nos mutant, including elevated expression of genes associated with oxidative/nitrosative stress, anaerobic respiration and lactate metabolism. Targeted metabolomics revealed decreased cellular lactate levels, and altered levels of TCA cycle intermediates, the latter of which may be related to decreased aconitase activity. Collectively, these findings demonstrate a key contribution of saNOS to S. aureus aerobic respiratory metabolism.
Non‐response to fluconazole maintenance treatment (ReCiDiF regimen) for recurrent vulvovaginal candidosis is not related to impaired glucose metabolism
Authors: Grinceviciene Svitrigaile , Bellen Gert , Ruban Kateryna , Donders Gilbert 
Published: April 2017

SummaryIs non‐response to maintenance treatment for recurrent vulvovaginal candidosis (RCVV) related to the impaired glucose metabolism? In the ReCiDiF trial, women with RCVV were given a degressive regimen with fluconazole according to their clinical, microscopic and mycologic response. Data obtained from optimal, suboptimal and non‐reponding patients were used for secondary analysis of medical history, physical status and family history for potential glucose impairment. Results were presented in means and percentages. Pearson chi‐square, Fisher exact, Mann‐Whitney U, Kruskal‐Wallis and Spearman's correlation coefficient was calculated. P<.05 were interpreted as statistically significant. Sociodemographic characteristics and family and personal history of diabetes were not different between optimal, suboptimal and non‐responders. The average HbA1c concentration was 5.1±0.3% in optimal, 5.0±0.4% in sub‐optimal, and 5.1±0.3% in non‐responding patients (P=1.0). There are no statistical differences between optimal, sub‐optimal and non‐respondents to treatment in all deciles of HbA1c among patients with recurrent candidosis (P=1.0). There was no difference among groups in fasting glucose concentration, nor after 30 min, 60 min or 120 min during the oral glucose tolerance test (OGTT) (P=.6). Area under the OGTT curve did not differ within groups (P=.8), nor was the deviation from the normal cut‐off value any different (P=.8). Glucose concentration in vaginal rinsing fluid showed no correlation with responsiveness to treatment (P=.7). Glucose metabolism, BMI, personal or family history of diabetes are not related to non‐response to maintenance treatment with fluconazole for patients with RVVC.
The incidence and costs of bacteremia due to lack of gentamicin lock solutions for dialysis catheters
Authors: Goh Tze Liang , Wei Jason , Semple David , Collins John 
Published: April 2017

AbstractThe use of antibiotic lock solutions as prophylaxis for catheter‐associated blood stream infection (CRBSI) has been shown to be effective in previous randomized controlled trials. However, the cost‐effectiveness of this approach had not been studied. In 2012, the routine gentamicin‐heparin lock solution used in Auckland City Hospital was withdrawn from the market, leading to a change to heparin‐only lock. This was then replaced with gentamicin‐citrate lock in 2014. This situation allowed review of the CRBSI rate and financial impact of different catheter lock solutions. A retrospective audit was performed from 1 January 2011 to 31 December 2015 to investigate the rate of culture‐proven CRBSI in patients with tunneled cuffed dialysis catheters. There were 89 cases of CRBSI involving 64 patients in the 5‐year period. In comparison with the heparin‐only lock, both gentamicin‐heparin and gentamicin‐citrate locks had a significantly lower rate of bacteremia, with rate ratios of 0.46 (confidence interval 0.30‐0.72) and 0.11 (confidence interval 0.05‐0.22), respectively. The inpatient costs as a consequence of the CRBSI were NZ$27 792 per 1000 catheter days for heparin‐only lock, NZ$10 608.56 per 1000 catheter days for gentamicin‐heparin lock, and NZ$ 1898.45 per 1000 catheter days for gentamicin‐citrate lock. The lack of antibiotic lock solutions led to an increase in bacteremia rates and higher financial cost for inpatient management of bacteremia. Our findings highlight the importance of consistent supply of pharmaceuticals.