bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression of liver disease in non‐alcoholic fatty liver disease: A prospective clinicopathological follow‐up study
Authors: Chan Wah‐Kheong , Ida Normiha Hilmi , Cheah Phaik‐Leng , Goh Khean‐Lee 
Published: July 2014

ObjectiveTo perform a follow‐up study on non‐alcoholic fatty liver disease (NAFLD) patients in our previous study using paired liver biopsy.MethodsPatients who were included in our previous study on NAFLD and agreed to receive a repeat liver biopsy were included in the study. Their clinical characteristics, laboratory examination results and histological analysis on the repeat liver biopsied specimens were prospectively collected and compared with those in the previous study.ResultsData from 35 patients (mean age 47.5 ± 10.9 years, male 40.0%) were analyzed. The mean interval between the liver biopsies was 6.4 ± 0.8 years. NAFLD activity score (NAS) worsened in 13, remained unchanged in 9 and ameliorated in 13. Fibrosis worsened in 18 and remained unchanged in 17. Two patients who were confirmed with cirrhosis at baseline developed decompensated cirrhosis. On multivariate analysis, elevated serum aspartate aminotransferase (AST) (odds ratio [OR] 10.74, 95% confidence interval [CI] 1.00–115.86, P = 0.050) and γ‐glutamyl transpeptidase (γ‐GT) (OR 16.10, 95% CI 1.30–198.90, P = 0.030) at follow‐up were associated with worsened NAS. Patients with borderline NASH at baseline were more likely to have worsened NAS at follow‐up than those with definite NASH (OR 12.67, 95% CI 2.29–70.02, P = 0.004). However, both groups had a similar likelihood of having worsened fibrosis at follow‐up. No plausible factors were found to be associated with worsened fibrosis.ConclusionsNAFLD patients with persistently elevated serum AST and γ‐GT levels during follow‐up should be suspected of having worsened NAS. NASH patients can have significant disease progression over a relatively short period of time and fibrosis might be irreversible without specific interventions.
miR‐125a‐5p impairs endothelial cell angiogenesis in aging mice via RTEF‐1 downregulation
Authors: Che Peng , Liu Jun , Shan Zhen , Wu Ridong , Yao Chen , Cui Jin , Zhu Xiaonan , Wang Junwei , Burnett Mary Susan , Wang Shenming , Wang JinSong 
Published: July 2014

SummaryIncreasing evidence suggests that microRNAs (miRNAs) play important roles in impaired endothelial cell (EC) angiogenesis during aging. However, their exact roles in the aging process remain unclear. We aimed to determine whether miRNAs cause angiogenesis defects in ECs during aging and to uncover the underlying mechanisms. To study the miRNA‐induced changes in ECs during aging, we performed microarray analyses on arterial ECs collected from young and aging mice. Using qRT–PCR, we showed that microRNA‐125a‐5p (mir‐125a‐5p) expression was approximately 2.9 times higher in old endothelial cells (OECs) compared with samples collected from young animals. Western blot assays showed a lower expression level of an mir‐125a‐5p target known as related transcriptional enhancer factor‐1 (RTEF‐1) in OECs compared with its expression levels in young cells. Overexpression of mir‐125a‐5p in young endothelial cells (YECs) using pre‐mir‐125a‐5p caused the downregulation of RTEF‐1, endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) and resulted in impaired angiogenesis, as evidenced by spheroid sprouting and tube formation assays in vitro. Conversely, repression of mir‐125a‐5p in OECs using anti‐mir‐125a‐5p increased RTEF‐1, eNOS and VEGF expression and improved EC angiogenesis. Importantly, impaired angiogenesis caused by knock‐down of RTEF‐1 was not efficiently rescued by anti‐mir‐125a‐5p. Dual‐luciferase reporter gene analysis showed that RTEF‐1 is a direct target of mir‐125a‐5p, which regulates angiogenesis by repressing RTEF‐1 expression and modulating eNOS and VEGF expression. These findings indicate that mir‐125a‐5p and RTEF‐1 are potential therapeutic targets for improving EC‐mediated angiogenesis in elderly individuals.
Fibroblasts derived from long‐lived insulin receptor substrate 1 null mice are not resistant to multiple forms of stress
Authors: Page Melissa M. , Sinclair Amy , Robb Ellen L. , Stuart Jeffrey A. , Withers Dominic J. , Selman Colin 
Published: July 2014

SummaryReduced signalling through the insulin/insulin‐like growth factor‐1 signalling (IIS) pathway is a highly conserved lifespan determinant in model organisms. The precise mechanism underlying the effects of the IIS on lifespan and health is currently unclear, although cellular stress resistance may be important. We have previously demonstrated that mice globally lacking insulin receptor substrate 1 (Irs1−/−) are long‐lived and enjoy a greater period of their life free from age‐related pathology compared with wild‐type (WT) controls. In this study, we show that primary dermal fibroblasts and primary myoblasts derived from Irs1−/− mice are no more resistant to a range of oxidant and nonoxidant chemical stressors than cells derived from WT mice.
Predictors for outcomes after super‐selective mesenteric embolization for lower gastrointestinal tract bleeding
Authors: Chan Dedrick Kok Hong , Soong Junwei , Koh Frederick , Tan Ker Kan , Lieske Bettina 
Published: July 2014

AbstractBackgroundThe optimal management of bleeding from the lower gastrointestinal tract (LGIB) remains controversial. We aim to evaluate the efficacy of mesenteric embolization for LGIB and to identify predictors for re‐bleeding after the procedure.MethodsWe conducted a retrospective review of all patients who underwent mesenteric embolizations for LGIB in our institution over a 6‐year period (from August 2007 to August 2013). Technical success was defined as the absence of contrast extravasation on post‐embolization angiogram. Clinical success was defined as the absence of overt LGIB (clinical bleeding with >1 g/dL decrease in haemoglobin) within 30 days post‐embolization.ResultsMesenteric embolization was performed in 26 patients with LGIB. Technical success rate was 100%, with no occurrence of post‐embolization ischaemia. Clinical success rate was 65.4%, with nine patients re‐bleeding within 30 days post‐embolization. Three underwent surgery, one underwent re‐embolization and five were treated conservatively. Mortality rate was 19.3% (five patients), with two bleeding‐associated mortalities. Site and aetiology of LGIB, platelet count and coagulation status prior to embolization, number of packed red blood cells and fresh frozen plasma transfusion were found to be predictors of clinical failure. After Bonferroni's correction (P < 0.005), platelet count of ≤140 × 109/L prior to embolization was the only statistically significant factor associated with re‐bleeding (odds ratio = 17.5, 95% confidence interval: 2.364–129.57; P = 0.004).ConclusionMesenteric embolization was found to be safe and effective in treating LGIB (100% technical success, no post‐embolization ischaemia), with 65.4% of cases not requiring further intervention. Low platelet count prior to embolization appears to be associated with clinical failure.
Reconstruction of perineoscrotal defects in Fournier's gangrene with pedicle anterolateral thigh perforator flap
Authors: Lin Chin‐Ta , Chang Shun‐Cheng , Chen Shyi‐Gen , Tzeng Yuan‐Sheng 
Published: July 2014

AbstractBackgroundFournier's gangrene is an acute and potentially lethal necrotizing fasciitis that involves the scrotum and perineum. This disease can result in the extensive loss of skin and soft tissues of the perineoscrotal area with exposure of the testes. To reconstruct the large defects of scrotal and perineal remains a surgical challenge.MethodsBetween January 2008 and December 2012, 26 patients were admitted with a diagnosis of Fournier's gangrene. The Division of Plastic and Reconstructive Surgery at our hospital was consulted about patients who needed reconstructive procedures after initial debridement was performed in the Division of Colorectal Surgery or the Division of Urology. Of the 26 patients, 10 patients with large perineoscrotal defects who underwent the reconstructive surgery using pedicle anterolateral thigh (ALT) perforator flaps were enrolled in this series.ResultsWe carried out the perineoscrotal reconstruction in these 10 patients using the pedicled ALT perforator flaps. They were all male with a mean age of 59.1 years (ranged from 39 to 82 years). The size of the flaps ranged from 72 to 198 cm2. All flaps survived completely but one hematoma was noticed postoperatively. All patients mobilized well with no limitation of motion, and the scrotal contour appeared to be natural.ConclusionEarly debridement and wound coverage in Fournier's gangrene are mandatory to allow patients to return to normal life. Pedicle ALT perforator flaps provide pliable and reliable soft‐tissue coverage for large perineoscrotal defects with adequate contour that result in satisfactory function and cosmesis.
Perimortem cesarean section for maternal and fetal salvage: concise review and protocol
Authors: Drukker Lior , Hants Yael , Sharon Einav , Sela Hen Y. , Grisaru‐Granovsky Sorina 
Published: July 2014

AbstractCardiopulmonary arrest is a rare event during pregnancy and labor. Perimortem cesarean section has been resorted to as a rare event since ancient times; however, greater awareness regarding this procedure within the medical community has only emerged in the past few decades. Current recommendations for maternal resuscitation include performance of the procedure after five minutes of unsuccessful cardiopulmonary resuscitation. If accomplished in a timely manner, perimortem cesarean section can result in fetal salvage and is also critical for maternal resuscitation. Nevertheless, deficits in knowledge about this procedure are common. We have reviewed publications on perimortem cesarean section and present the most recent evidence on this topic, as well as recommending our “easy‐to‐access protocol” adapted for resuscitation following maternal collapse.
Is there an association between sonographically determined occipito‐transverse position in the second stage of labor and operative delivery?
Authors: Phipps Hala , Hyett Jon A. , Graham Kathy , Carseldine Wendy J. , Tooher Jane , de Vries Bradley 
Published: July 2014

AbstractObjectiveTo evaluate if ultrasound‐determined occipito‐transverse position early in the second stage of labor is associated with operative delivery.DesignRetrospective review of two prospective cohort studies.SettingAn Australian tertiary referral hospital.PopulationWomen with term, cephalic singleton pregnancies.MethodsRetrospective analysis of data from two prospective studies. Logistic regression was undertaken to assess the independent contribution of the occipito‐transverse position to operative delivery.Main outcome measureOperative delivery (cesarean section, forceps or vacuum extraction).ResultsAmong 422 women included, the occipito‐transverse position was present in 80, occipito‐anterior in 303 and the occipito‐posterior in 39. Compared with occipito‐anterior, the adjusted odds ratio for operative delivery was 2.1 (95% confidence interval 1.2–3.8, p = 0.02) for the occipito‐transverse position, and 7.4 (95% confidence interval 3.2–17) for the occipito‐posterior position. Factors that independently predicted operative delivery were nulliparity, abnormal second stage cardiotocography, maternal place of birth and epidural analgesia. The length of second stage of labor was longer for the occipito‐transverse group than for the occipito‐anterior group (median 2 h 7 min vs. 1 h 36 min, p = 0.003).ConclusionThe occipito‐transverse position early in the second stage of labor was associated with an increased operative delivery rate.
Contrast sensitivity measured by two different test methods in healthy, young adults with normal visual acuity
Authors: Koefoed Vilhelm F. , Baste Valborg , Roumes Corinne , Høvding Gunnar 
Published: July 2014

AbstractPurposeThis study reports contrast sensitivity (CS) reference values obtained by two different test methods in a strictly selected population of healthy, young adults with normal uncorrected visual acuity. Based on these results, the index of contrast sensitivity (ICS) is calculated, aiming to establish ICS reference values for this population and to evaluate the possible usefulness of ICS as a tool to compare the degree of agreement between different CS test methods.MethodsMilitary recruits with best eye uncorrected visual acuity 0.00 LogMAR or better, normal colour vision and age 18–25 years were included in a study to record contrast sensitivity using Optec 6500 (FACT) at spatial frequencies of 1.5, 3, 6, 12 and 18 cpd in photopic and mesopic light and CSV‐1000E at spatial frequencies of 3, 6, 12 and 18 cpd in photopic light. Index of contrast sensitivity was calculated based on data from the three tests, and the Bland–Altman technique was used to analyse the agreement between ICS obtained by the different test methods.ResultsA total of 180 recruits were included. Contrast sensitivity frequency data for all tests were highly skewed with a marked ceiling effect for the photopic tests. The median ICS for Optec 6500 at 85 cd/m2 was −0.15 (95% percentile 0.45), compared with −0.00 (95% percentile 1.62) for Optec at 3 cd/m2 and 0.30 (95% percentile 1.20) FOR CSV‐1000E. The mean difference between ICSFACT85 and ICSCSV was −0.43 (95% CI −0.56 to −0.30, p < 0.00) with limits of agreement (LoA) within −2.10 and 1.22. The regression line on the difference of average was near to zero (R2 = 0.03).ConclusionThe results provide reference CS and ICS values in a young, adult population with normal visual acuity. The agreement between the photopic tests indicated that they may be used interchangeably. There was little agreement between the mesopic and photopic tests. The mesopic test seemed best suited to differentiate between candidates and may therefore possibly be useful for medical selection purposes.
Verapamil decreases the glucose‐lowering effect of metformin in healthy volunteers
Authors: Cho Sung Kweon , Kim Choon Ok , Park Eun Seok , Chung Jae‐Yong 
Published: July 2014

AimThe organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose‐lowering effect. A recent non‐clinical study reported that metformin uptake into hepatocytes is regulated via OCT1, and that uptake was strongly inhibited by verapamil. Therefore, we investigated the effects of verapamil co‐administration on the pharmacokinetics and pharmacodynamics of metformin in humans.MethodsWe evaluated the pharmacokinetics and the anti‐hyperglycaemic effects of metformin using an oral glucose tolerance test (OGTT) in 12 healthy participants, before (day 1) and after metformin treatment (day 2), and again on days 15 and 16 after co‐administration with verapamil.ResultsVerapamil inhibited the ability of metformin to reduce maximum blood glucose concentrations (ΔGmax) by 62.5% (P = 0.008) and decreased the area under the glucose concentration–time curve (ΔAUCgluc) by 238% (P = 0.015). However, verapamil did not significantly alter the Cmax and the AUC of metformin, nor its renal clearance.ConclusionsOur results suggest that verapamil remarkably decreases the glucose‐lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1.
The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: a phase II trial
Authors: Durgam Suresh , Starace Anju , Li Dayong , Migliore Raffaele , Ruth Adam , Németh György , Laszlovszky István 
Published: July 2014

ObjectivesCariprazine, an orally active and potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is being developed for the treatment of schizophrenia and bipolar mania. This Phase II trial evaluated the efficacy, safety, and tolerability of cariprazine versus placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder.MethodsThis was a multinational, randomized, double‐blind, placebo‐controlled, flexible‐dose study of cariprazine 3–12 mg/day in patients with acute manic or mixed episodes associated with bipolar I disorder. Following washout, patients received three weeks of double‐blind treatment. The primary and secondary efficacy parameters were change from baseline to Week 3 in Young Mania Rating Scale (YMRS) and Clinical Global Impressions–Severity (CGI‐S) scores, respectively. Post‐hoc analysis evaluated changes on YMRS single items.ResultsIn each group, 118 patients received double‐blind treatment; 61.9% of placebo and 63.6% of cariprazine patients completed the study. The overall mean daily dose of cariprazine was 8.8 mg/day. At Week 3, cariprazine significantly reduced YMRS and CGI‐S scores versus placebo, with least square mean differences of −6.1 (p < 0.001) and −0.6 (p < 0.001), respectively. On each YMRS item, change from baseline to Week 3 was significantly greater for cariprazine versus placebo (all, p < 0.05). A significantly greater percentage of cariprazine patients than placebo patients met YMRS response (48% versus 25%; p < 0.001) and remission (42% versus 23%; p = 0.002) criteria at Week 3. Adverse events (AEs) led to discontinuation of 12 (10%) placebo and 17 (14%) cariprazine patients. The most common AEs (> 10% for cariprazine) were extrapyramidal disorder, headache, akathisia, constipation, nausea, and dyspepsia. Changes in metabolic parameters were similar between groups, with the exception of fasting glucose; increases in glucose were significantly greater for cariprazine versus placebo (p < 0.05). Based on Barnes Akathisia Rating Scale and Simpson–Angus Scale scores, more cariprazine than placebo patients experienced treatment‐emergent akathisia (cariprazine: 22%; placebo: 6%) or extrapyramidal symptoms (parkinsonism) (cariprazine: 16%; placebo: 1%).ConclusionCariprazine demonstrated superior efficacy versus placebo and was generally well tolerated in patients experiencing acute manic or mixed episodes associated with bipolar I disorder.
Doing more, feeling better: A behavioural approach to helping a woman overcome low mood and anxiety
Authors: Stuart Simon , Graham Christopher D. , Butler Sarah 
Published: July 2014

Accessible summary

Much has been written about how best to help people with learning disabilities if they feel sad or worried.

Often this is about thinking. But it might be better to look at doing instead.

This is the story of how we tried to help a lady feel happier, and worry less.

SummaryA substantial body of literature exists concerning the adaptation of Cognitive Behavioural Therapy for people with learning disabilities. However, it is possible that cognitive approaches have been prioritised at the expense of behavioural techniques that are simpler and more effective. This case conceptualisation considers a behaviourally focused approach to helping a woman with a mild learning disability who was experiencing low mood and anxiety, delivered by a trainee clinical psychologist working within a multidisciplinary team.
Up Regulation of Liver‐enriched Transcription Factors HNF4a and HNF6 and Liver‐Specific MicroRNA (miR‐122) by Inhibition of Let‐7b in Mesenchymal Stem Cells
Authors: Alizadeh Effat , Akbarzadeh Abolfazl , Eslaminejad Mohamadreza Baghaban , Barzegar Abolfazl , Hashemzadeh Shahryar , Nejati‐Koshki Kazem , Zarghami Nosratollah 
Published: July 2014

MicroRNAs are small non‐coding RNAs that regulate key processes of the stem cells. Although, microRNAs have emerged as powerful regulators of differentiation, few studies have been focused on the post‐transcriptional regulation of hepatic differentiation in mesenchymal stem cells (MSCs) by microRNAs. The aim of this study was to evaluate the specific effect of let‐7 microRNAs in particular let‐7b in hepatic commitment of human adipose tissue‐derived mesenchymal stem cells (hAT‐MSCs). The dynamic expression profile of let‐7a, b, c microRNAs and two liver‐enriched transcription factors (LETFs) HNF4a and HNF6 was studied during in vitro hepatic differentiation of hAT‐MSCs. Let‐7b was used for transient overexpression and knockdown investigations. It was shown that the expression of LETFs is inversely correlated with those of let‐7 miRNAs during differentiation progress (p < 0.05). Inhibition of let‐7b caused upregulation of LETFs, an increase in the expression of miR‐122 (p < 0.01) emulating the features of functional hepatocytes, and accumulation of hAT‐MSCs in the G0/G1 phase of cell cycle, triggering initiation of hepatic commitment. In conclusion, transient inhibition of let‐7b activates hepatic differentiation of hAT‐MSCs. The findings of this work might help optimization of in vitro hepatogenic differentiation utilizing microRNAs and hAT‐MSCs that could be used for therapeutic purposes.
The Role of Reflection in the Effects of Community Service on Adolescent Development: A Meta‐Analysis
Authors: van Goethem Anne , van Hoof Anne , Orobio de Castro Bram , Van Aken Marcel , Hart Daniel 
Published: July 2014

This meta‐analysis assessed the effect of community service on adolescent development and the moderation of this effect by reflection, community service, and adolescent characteristics to explicate the mechanisms underlying community service effects. Random effects analyses, based on 49 studies (24,477 participants, 12–20 years old), revealed that community service had positive effects on academic, personal, social, and civic outcomes. Moderation analyses indicated that reflection was essential; the effect for studies that include reflection was substantial (mean ES = .41) while community service in the absence of reflection yielded negligible benefits (mean ES = .05). Effects increased when studies include more frequent reflection and community service, reflection on academic content, and older adolescents. These findings have implications for understanding and improving community service.
Value of whole exome sequencing for syndromic retinal dystrophy diagnosis in young patients
Authors: Prokudin Ivan , Li Dong , He Sijie , Guo Yiran , Goodwin Linda , Wilson Meredith , Rose Loreto , Tian Lifeng , Chen Yulan , Liang Jinlong , Keating Brendan , Xu Xun , Jamieson Robyn V , Hakonarson Hakon 
Published: July 2014

AbstractBackgroundSeveral retinal dystrophies are associated with syndromic features including such conditions as Bardet–Biedl and Joubert syndromes. Cohen syndrome is an autosomal recessive disorder associated with multiple clinical manifestations including developmental delay, acquired microcephaly, myopia, pigmentary retinopathy, joint hypermobility, truncal obesity, friendly disposition and intermittent neutropenia. In young patients, diagnosis is difficult, because several of the characteristic features may not be present until school age or later years and the intermittent neutropenia is not always detectable.DesignThis was a prospective study using whole exome sequencing in syndromic retinal dystrophy. It was undertaken in a hospital and research institute setting.ParticipantsParticipants in this study were members of a consanguineous Australian family of Lebanese ethnicity with two siblings with retinal dystrophy, microcephaly and developmental delay.MethodsDetailed clinical evaluation was undertaken. Whole exome capture and sequencing of patient genomic DNA samples was followed by sequence alignment, variant detection, comparison and prioritization.Main Outcome MeasuresPathogenic variant identification in the disease‐causing gene in affected individuals.ResultsWe identified a novel homozygous deletion leading to a frameshift mutation in VPS13B, c.11327del, p.(Asn3776Thrfs*102), the disease gene associated with Cohen syndrome.ConclusionsThis report emphasizes the value of a broad‐based whole exome sequencing approach in disease gene identification in the syndromic retinal dystrophies, where all disease characteristics may not be present in young patients to allow a clinical diagnosis. This facilitates improved prognostic and genetic information for patients and families.