bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes after metformin failure: A randomized controlled trial
Authors: Yang Wenying , Han Ping , Min Kyung‐Wan , Wang Bei , Mansfield Traci , T'Joen Caroline , Iqbal Nayyar , Johnsson Eva , Ptaszynska Agata 
Published: November 2015

AbstractBackgroundDapagliflozin, a highly selective sodium–glucose cotransporter 2 inhibitor, reduces hyperglycemia, body weight, and blood pressure in patients with type 2 diabetes (T2D).MethodsThis randomized double‐blind placebo‐controlled parallel‐group 24‐week study assessed the efficacy, safety, and tolerability of dapagliflozin added to metformin in Asian patients with inadequately controlled T2D (HbA1c 7.5%–10.5%). Patients were randomized to receive placebo (n = 145) or dapagliflozin 5 (n = 147) or 10 mg (n = 152).ResultsMost participants were Chinese (86.0%), with a mean age of 53.8 years and mean T2D duration of 4.9 years; 92.1% completed the study. Adjusted mean HbA1c changes from baseline at Week 24 (primary endpoint) were −0.23%, −0.82%, and −0.85% in the placebo, dapagliflozin 5 and 10 mg groups, respectively, resulting in dapagliflozin 5 and 10 mg versus placebo differences of −0.59% and −0.62%, respectively (both P < 0.0001). Dapagliflozin 5 and 10 mg differences versus placebo were, respectively: –1.2 and −1.5 mmol/L for fasting plasma glucose; −1.1 and −1.8 kg for weight; and −2.3 and −2.7 mmol/L for 2‐h postprandial glucose (all P <0.0001). In the placebo, dapagliflozin 5 and 10 mg groups, respectively: adverse events (AEs) occurred in 52.4%, 52.4%, and 55.3% of patients; serious AEs occurred in 4.1%, 2.0%, and 2.0%; urinary tract infections occurred in 4.8%, 4.1%, and 6.6%; and genital infections occurred in 0%, 2.0%, and 1.3%. No AEs of pyelonephritis or renal failure occurred.ConclusionsDapagliflozin 5 or 10 mg as add‐on to metformin was well tolerated in Asian patients with T2D and significantly improved glycemic control with the additional benefit of weight reduction.
Role of Pleiotropic Properties of Peroxisome Proliferator‐Activated Receptors in the Heart: Focus on the Nonmetabolic Effects in Cardiac Protection
Authors: Barlaka Eleftheria , Galatou Eleftheria , Mellidis Kyriakos , Ravingerova Tanya , Lazou Antigone 
Published: November 2015

SummaryPeroxisome proliferator‐activated receptors, PPARα, PPARβ/δ, and PPARγ, are a group of nuclear receptors that function as transcriptional regulators of lipid metabolism, energy homeostasis, and inflammation. Given the role of metabolism imbalance under pathological states of the heart, PPARs have emerged as important therapeutic targets, and accumulating evidence highlights their protective role in the improvement of cardiac function under diverse pathological settings. Although the role of PPARs in the regulation of cardiac substrate utilization preference and energy homeostasis is well documented, their effects related to the regulation of cellular inflammatory and redox responses in the heart are less studied. In this review, we provide an overview on recent progress with respect to understanding the role of the nonmetabolic effects of PPARs in cardiac dysfunction, namely during ischemia/reperfusion injury, hypertrophy, and cardiac failure, and highlight the mechanisms underlying the protective effects against inflammation, oxidative stress, and cell death. The role of receptor‐independent, nongenomic effects of PPAR agonists is also discussed.
Pilot randomised trial of a brief intervention for comorbid substance misuse in psychiatric in‐patient settings
Authors: Graham H. L. , Copello A. , Griffith E. , Freemantle N. , McCrone P. , Clarke L. , Walsh K. , Stefanidou C. A. , Rana A. , Birchwood M. 
Published: November 2015

ObjectiveThis proof of principle study evaluated the effectiveness and feasibility of a brief motivational intervention, delivered in mental health in‐patient settings, to improve engagement in treatment for drug and alcohol misuse.MethodA randomised controlled trial using concealed randomisation, blind, independent assessment of outcome at 3 months. Participants were 59 new adult admissions, to six acute mental health hospital units in one UK mental health service, with schizophrenia related or bipolar disorder diagnoses, users of community mental health services and also misusing alcohol and/or drugs. Participants were randomised to Brief Integrated Motivational Intervention (BIMI) with Treatment As Usual (TAU), or TAU alone. The BIMI took place over a 2‐week period and encouraged participants to explore substance use and its impact on mental health.ResultsFifty‐nine in‐patients (BIMI n = 30; TAU n = 29) were randomised, the BIMI was associated with a 63% relative odds increase in the primary outcome engagement in treatment [OR 1.63 (95% CI 1.01–2.65; P = 0.047)], at 3 months. Qualitative interviews with staff and participants indicated that the BIMI was both feasible and acceptable.ConclusionMental health hospital admissions present an opportunity for brief motivational interventions focussed on substance misuse and can lead to improvements in engagement.
The Role of Social Contact in the Experience of Discrimination: Implications for Subjective Health Among Marriage Migrant Women in South Korea
Authors: Cheon Yuen Mi , Chung Grace H. 
Published: November 2015

Several studies have found that various social contexts could serve a protective role for minorities facing discrimination. One of these contexts is frequency of social contact, which is known to be positively associated with health outcomes. The purpose of this study was to examine the frequency of social contact with various social groups as a protective factor against the negative association between perceived discrimination and subjective health. Using data from the 2009 Korean National Survey of Multicultural Families, a total of 27,083 marriage migrant women were analyzed via hierarchical multiple regression. After controlling for socio‐demographic factors and Korean proficiency, the experience of discrimination was found to be significantly associated with lower levels of subjective health (B = −0.22; P < 0.001). More frequent meetings with one's family of origin (B = 0.02; P < 0.01) and in‐laws (B = 0.06; P < 0.001) were associated with higher levels of subjective health, while more frequent meetings with neighbors were negatively associated (B = −0.02; P < 0.001). More frequent contact with one's family of origin (B = 0.03; P < 0.05), rather than with other groups, such as friends from their country of origin, in‐laws, and neighbors, seemed to reduce the negative influence of discrimination on subjective health.
Longitudinal Effects of Economic Preparation and Social Activities on Life and Family Relationship Satisfaction among Retirees
Authors: Park Jihyun , Park Aely 
Published: November 2015

This longitudinal study examined the long‐term effects of economic preparation and social activity on life and family relationship satisfaction among retirees, particularly baby boomers. Data was obtained from the 2009 and 2011 Korean Retirement & Income Panel Study. A fixed effects model was employed to estimate unobservable individual‐specific effects and to control for study participants’ individual characteristics. The results show that both economic preparation and social activities have long‐term effects on baby boomers’ life and family relationship satisfaction. This study reveals that multidimensional aspects of preparation increase the long‐term impact of life satisfaction for retirees.
Pharmacological management of anticholinergic delirium ‐ theory, evidence and practice
Authors: Dawson Andrew H. , Buckley Nicholas A. 
Published: November 2015

The spectrum of anticholinergic delirium is a common complication following drug overdose. Patients with severe toxicity can have significant distress and behavioural problems that often require pharmacological management. Cholinesterase inhibitors, such as physostigmine, are effective but widespread use has been limited by concerns about safety, optimal dosing and variable supply. Case series support efficacy in reversal of anticholinergic delirium. However doses vary widely and higher doses commonly lead to cholinergic toxicity. Seizures are reported in up to 2.5% of patients and occasional cardiotoxic effects are also recorded.This article reviews the serendipitous path whereby physostigmine evolved into the preferred anticholinesterase antidote largely without any research to indicate the optimal dosing strategy. Adverse events observed in case series should be considered in the context of pharmacokinetic/pharmacodynamic studies of physostigmine which suggest a much longer latency before the maximal increase in brain acetylcholine than had been previously assumed. This would favour protocols that use lower doses and longer re‐dosing intervals. We propose based on the evidence reviewed that the use of cholinesterase inhibitors should be considered in anticholinergic delirium that has not responded to non‐pharmacological delirium management. The optimal risk/benefit would be with a titrated dose of 0.5 to 1 mg physostigmine (0.01–0.02 mg kg−1 in children) with a minimum delay of 10–15 min before re‐dosing. Slower onset and longer acting agents such as rivastigmine would also be logical but more research is needed to guide the appropriate dose in this setting.
Factors affecting parathyroid hormone levels in different types of primary aldosteronism
Authors: Jiang Yiran , Zhang Cui , Ye Lei , Su Tingwei , Zhou Weiwei , Jiang Lei , Zhang Yifei , Wang Weiqing 
Published: November 2015

SummaryBackgroundRecent studies have found that mild secondary hyperparathyroidism might be another clinical feature of patients with primary aldosteronims (PA), but whether serum parathyroid hormone level (PTH) is correlated with subtypes of PA and what contributes to the elevated PTH level remains unclear.ObjectiveTo illustrate the changes of PTH in PA and to partly explain the mechanism of how the effects of aldosterone regulating the secretion of PTH in PA.MethodsWe enrolled a total of 120 patients with primary hypertension (PH) and 242 patients with PA, which included 89 APAs (aldosterone‐producing adenoma), 119 IHAs (idiopathic hyperaldosteronism) and 34 UAHs (unilateral adrenal hyperplasia). The plasma levels of aldosterone, renin activity, parathyroid hormone and markers associated with calcium metabolism were measured.ResultsWe found serum PTH level was significantly elevated in patients with PA compared with primary hypertension [9·0 (6·6, 11·7) vs 5·7 (4·4, 7·0)] pmol/l, P < 0·001]. However, no difference was found between the three PA subtypes (P > 0·05). Stepwise multiple regression analysis showed that in patients with PA, serum levels of K+ and Ca2+ were independently associated with serum PTH level. More importantly, elevated PTH level could be corrected either by unilateral adrenalectomy [9·9 (7·5, 12·8) vs 5·2 (4·4, 7·0) pmol/l, P < 0·001] or mineralocorticoid receptor (MR) antagonists treatment [11·7 (9·1, 13·4) vs 6·3 (5·1, 7·8) pmol/l, P < 0·001].ConclusionsPTH level is elevated in PA patients and irrelevant with subtypes of PA. Serum K+ and serum Ca2+ level are main factors influence the plasma PTH level in PA patients. After medical or surgical treatment, PTH levels return to normal.
Analysis of caveolin‐1 and phosphoinositol‐3 kinase expression in primary uveal melanomas
Authors: Stenzel Miriam , Tura Aysegül , Nassar Khaled , Rohrbach Jens Martin , Grisanti Salvatore , Lüke Matthias , Lüke Julia 
Published: November 2015

AbstractBackgroundTo evaluate the regulation of blood supply in primary uveal melanomas through caveolin‐1 (Cav‐1)/phosphoinositol‐3 kinase (PI3K).MethodsThe expression of Cav‐1 and PI3K was analysed in 51 paraffin sections of metastatic (n = 30) and non‐metastastic uveal melanomas (n = 21). Two trained observers quantified Cav‐1 and PI3K immunofluorescensce expression by determining intensity of staining and percentage of positive cells. The expression was correlated with known prognostic factors. Besides angiogenesis by means of endoglin expression, the normal vasculature (von Willebrand Factor expression) was evaluated semi‐quantitatively. Vasculogenic mimicry (VM) was analysed by CD31/PAS staining.ResultsAll examined specimens expressed Cav‐1 with a mean of 90.34% Cav‐1 positive cells (range, 3.23–100%). Metastatic disease was associated with a higher Cav‐1 expression. The correlation of Cav‐1 with well‐established prognostic factors showed a significant association between Cav‐1 expression and largest tumour diameter (P = 0.022), tumour node metastasis classification (P = 0.008) and invasion of optic nerve head (P = 0.048). PI3K was expressed by all uveal melanomas with a mean of 87.28% cells showing PI3K expression. A higher level of PI3K was significantly associated with larger height (P = 0.042) and progressed tumour node metastasis stage (P = 0.016). The percentage of PI3K and Cav‐1 positive cells were significantly associated (P = 0.034). For PI3K and Cav‐1 expression a non‐significant association with VM was shown (P = 0.064 and P = 0.072, respectively). No correlation of PI3K or Cav‐1 with angiogenesis or mature vasculature was seen (P > 0.05).ConclusionsCav‐1 expression may be especially up‐regulated in larger uveal melanomas. As it was correlated with PI3K expression and VM in this series of uveal melanoma, Cav‐1 might induce the formation of VM via the PI3K‐signalling cascade.
In vivo assessment of tumour angiogenesis in colorectal cancer: the role of confocal laser endomicroscopy
Authors: De Palma G. D. , Maione F. , Esposito D. , Luglio G. , Giglio M. C. , Siciliano S. , Gennarelli N. , Cassese G. , Campione S. , D'Armiento F. P. , Bucci L. 
Published: November 2015

AbstractAimTumour neoangiogenesis is a key factor in tumour progression and metastatic spread and the possibility to assess tumour angiogenesis might provide prognostic information. The aim of this study was to establish the role of probe‐based confocal laser endomicroscopy (p‐CLE) in the identification of vascular architecture and specific morphological patterns in normal colorectal mucosa and malignant lesions during routine endoscopy.MethodFourteen consecutive patients with colorectal cancer were included. The following features were identified and then compared between normal and neoplastic mucosa on p‐CLE images: vessel shape (straight vs irregular) vessel diameter the ‘branching patterns’ vessel permeability (fluorescein leakage) and blood flow (normal vs defective flux). Immunohistochemistry was used to confirm the presence and to study the morphology of vascular structures (CD‐34 staining) and ‘neo‐vessels’ (WT‐1 staining) on tumour and normal mucosal sections.ResultsTumour vessels appeared as irregular, ectatic and with a highly variable calibre and branching patterns on p‐CLE images. The mean diameter of tumour vessels was significantly larger than those in normal mucosa (weighted mean difference 3.38, 95% CI 2.65–4.11, P = 0.01). Similarly, ‘vessel branching’ (OR 2.74, 95% CI 1.23–6.14, P = 0.01), fluorescent dye ‘extravasation’ (OR 3.46, 95% CI 1.39–8.57, P = 0.01) were significantly more frequent in colorectal cancer than in normal colorectal mucosa. Immunohistochemistry corroborated the p‐CLE findings, showing higher vascularity in tumour sections due to neoformed vessels, presenting irregular patterns.ConclusionProbe‐based confocal laser endomicroscopy provides a noninvasive characterization of the microvascular architecture of colonic mucosa. Different morphological patterns have been described, discriminating normal and malignant microvascular networks in colorectal mucosa.
Characterization of thrombopoietin kinetics within 60 days after allogeneic hematopoietic stem cell transplantation and its correlation with megakaryocyte ploidy distribution
Authors: Fu Haixia , Zhang Xiaohui , Xu Lanping , Liu Kaiyan , Huang Xiaojun 
Published: November 2015

AbstractThrombopoietin (TPO) has been identified as a key cytokine for both megakaryogenesis and thrombopoiesis. We attempt to characterize the kinetics of TPO and its correlation with megakaryocytes (MKs) ploidy distribution pattern within 60 d after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Forty‐six consecutive patients undergoing allo‐HSCT from October 2008 to December 2008 were included. TPO levels and ploidy distribution patterns of MKs were measured using ELISA and flow cytometric analysis, respectively. The results indicated that TPO levels and the platelet count followed opposite trends after allo‐HSCT. The preconditioning TPO levels and the number of transplanted CD34+ cells were significant predisposing factors for rapid platelet engraftment (p = 0.010 and 0.007, respectively) by multivariate analysis. There was a reduction of ploidy and an increase in immature MKs in patients with higher endogenous TPO levels (>250 pg/mL) on day 60 after allo‐HSCT. Moreover, lower TPO levels (≤250 pg/mL) on day 60 after allo‐HSCT were associated with significantly improved five‐yr overall survival (p = 0.021) and reduced transplant‐related mortality (p = 0.033). In conclusion, endogenous TPO levels may be associated with platelet recovery and have prognostic significance during allo‐HSCT.
Injection frequency of botulinum toxin A for spastic equinus: a randomized clinical trial
Authors: Hastings‐Ison Tandy , Blackburn Christine , Rawicki Barry , Fahey Michael , Simpson Pam , Baker Richard , Graham Kerr 
Published: November 2015

AimWe compared two botulinum toxin A (BoNT‐A) injection frequency regimens, 12‐monthly versus 4‐monthly, for spastic equinus in a randomized clinical trial. The primary outcome measure was passive ankle dorsiflexion.MethodForty‐two ambulant children with spastic equinus, secondary to cerebral palsy (23 males and 19 females; mean age 3y 6mo, SD 13mo; GMFCS levels I [n=20], II [n=19], III [n=3]) were randomized to receive either 12‐monthly or 4‐monthly BoNT‐A injections to the calf, over a 26‐month period. Twenty‐one children had spastic hemiplegia, 21 children had spastic diplegia. A fixed 6U/kg dose of Botox was injected into the gastrocnemius muscle of both limbs in children with diplegia and the gastrocsoleus of the affected limb in children with hemiplegia, under mask anaesthesia.ResultsForty‐two children entered the trial with 21 participants randomized to each group. There were three withdrawals and two children received serial casting midway through the trial. There was no significant difference in passive dorsiflexion between 12‐monthly and 4‐monthly regimens (p=0.41). There were also no significant between group differences on secondary outcome measures. There were no serious adverse events – the rate was 1.2 adverse events per child per year in the 12‐monthly group and 2.2 adverse events per child per year in the 4‐monthly group. Subgroup analysis revealed a significant difference in passive dorsiflexion between children with hemiplegia and diplegia (p=0.01).InterpretationThere was no significant difference between 12‐monthly and 4‐monthly injection regimens on passive dorsiflexion or secondary outcome measures. BoNT‐A injections for spastic equinus may be recommended on a 12‐monthly basis.
Quantifying insect predation with predator exclusion cages: the role of prey antipredator behavior as a source of bias
Authors: Castellanos Ignacio , Barbosa Pedro , Zuria Iriana , Caldas Astrid 
Published: November 2015

AbstractThere are limitations imposed by current methodologies to detect and quantify insect predation. However, there has been relatively little effort to experimentally document the sources of biases associated with the various methodologies. In this study, we examined how predation estimates in the field using predator exclusion cages may be biased when one fails to account for antipredator behavioral responses. To do this, we did the usual comparison of the number of insects missing from plants where predators were allowed access to the number missing from plants where predators were excluded, but also determined how many of the missing insects reacted to predators by dropping from plants and how many were actually preyed upon. Our results provide evidence that estimates of insect mortality in the field are significantly reduced if prey antipredator behavior is taken into account. As it is commonly assumed that prey missing in the field are predated, documenting the incidence of predator‐mediated ‘disappearance’ and capturing insect prey before they escape can provide with a relevant estimate of bias.
Industrial pollution affects behaviour of the leafmining moth Stigmella lapponica
Authors: Kozlov Mikhail V. , Zvereva Elena L. 
Published: November 2015

AbstractWe explored the impacts of industrial air pollution on the behaviour of the leafmining moth Stigmella lapponica (Wocke) (Lepidoptera: Nepticulidae) by comparing the characteristics of larval gallery mines in mountain birch [Betula pubescens ssp. czerepanovii (Orlova) Hämet‐Ahti (Betulaceae)] leaves collected from unpolluted forests and from heavily polluted industrial barrens surrounding the copper‐nickel smelter in Monchegorsk in north‐western Russia. Population density of S. lapponica, survival of larvae, length of the completed mine, and width of its terminal part did not differ between polluted and unpolluted sites. Females in unpolluted sites only rarely (16%) oviposited on the apical half of the leaf and the larval mortality in mines that started in the apical part of the leaf was 83%. A significantly larger (38%) proportion of mines started in the apical half of the leaves in polluted sites, and the larval mortality in these mines was only 45%. The between‐habitat difference in the choice of the oviposition sites by S. lapponica is the first demonstration of the adaptive plasticity of oviposition behaviour in a leafmining insect. This difference was not explained by specific leaf weight which did not vary within leaves. Larvae mining in polluted leaves extended 25% farther between turns, and the galleries turned more sharply than in unpolluted leaves. This result confirms the abilities of leafmining larvae to evaluate the quality of the ingested food and adjust their behaviour accordingly. Thus, pollution modifies both the preference of S. lapponica females for oviposition sites within a birch leaf and the behaviour of S. lapponica larvae mining these leaves. This is one of the first records of changes in insect behaviour in natural environment disturbed by industrial pollution.
Liver function may play an uneven role in haemorrhagic transformation for stroke subtypes after acute ischaemic stroke
Authors: Tan G. , Lei C. , Hao Z. , Chen Y. , Yuan R. , Liu M. 
Published: November 2015

Background and purposeHaemorrhagic transformation (HT) is common after acute ischaemic stroke. Whether liver function plays a role in HT remains an open question.MethodsAcute ischaemic stroke patients within 7 days from stroke onset were included. Baseline data including liver function tests were collected. An independent association between liver function and HT was identified by multivariate regression analysis for stroke overall and stroke subtypes.ResultsA total of 2788 patients were included. HT occurred in 277 patients (9.9%), with 32 patients (1.1%) with symptomatic HT and 245 patients (8.8%) with asymptomatic HT. On multivariate regression analysis, aspartate aminotransferase (AST) and bilirubin (BILI) were independently associated with HT for stroke overall. In different stroke subtypes, AST was independently associated with HT for cardioembolic stroke, BILI for stroke of undetermined aetiology, and no liver function indicators for stroke of large‐artery atherosclerosis and small‐artery occlusion.ConclusionsLiver function played an uneven role in HT for different stroke subtypes. Indicators of liver function independently associated with HT were AST for cardioembolic stroke, BILI for stroke of undetermined aetiology and none for stroke of large‐artery atherosclerosis and small‐artery occlusion.