bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global development and adaptive behaviour in children with early‐onset epilepsy: a population‐based case–control study
Authors: Reilly Colin , Atkinson Patricia , Memon Ayesha , Jones Chloe , Dabydeen Lyvia , Das Krishna B , Gillberg Christopher , Neville Brian G R , Mahoney J Matthew , Scott Rod C 
Published: June 2018

AimThere are limited population‐based data on global development and adaptive behaviour in children with early‐onset epilepsy. The aims of this study were: (1) to identify the prevalence of deficits in global development and adaptive behaviour experienced by children with early‐onset epilepsy; (2) to identify factors associated with such deficits; and (3) to compare the relationship between measures of neurodevelopment in the group with epilepsy to a group without epilepsy who had other neurological or neurodevelopmental difficulties.MethodThe Sussex Early Epilepsy and Neurobehaviour study is a prospective, community‐based study involving children (1–7y) with epilepsy. We undertook comprehensive psychological assessment with participants, including measures of global development and adaptive behaviour. We compared the children with epilepsy with a sex, age, and developmentally‐matched group of children without epilepsy who had neurodevelopmental or neurological difficulties using correlation matrices.ResultsForty‐eight children (91% of the eligible population) with epilepsy underwent assessment. Seventy‐one per cent of children displayed delayed global development (<2SD) and 56% showed significant deficits (<2SD) in adaptive behaviour. Our analysis revealed that non‐white ethnicity and use of polytherapy were independently associated with decreased scores on measures of global development and adaptive behaviour. The correlations between measures of developmental functioning were higher in children with epilepsy than in those without.InterpretationChildren with early‐onset epilepsy frequently have difficulties with global development and adaptive behaviour. The higher correlations between neurodevelopmental measures in children with epilepsy suggest that the profile in children with epilepsy is different. This may have significant implications for both neuropathology and interventions.What this paper adds

Children with early‐onset epilepsy are at significant risk of intellectual disability.

Developmental impairment is associated with use of polytherapy but not with any seizure parameters.

Developmental profiles in young children with epilepsy differ from other conditions.
Short‐ and long‐term administration of the non‐steroidal mineralocorticoid receptor antagonist finerenone opposes metabolic syndrome‐related cardio‐renal dysfunction
Authors: Lachaux Marianne , Barrera‐Chimal Jonatan , Nicol Lionel , Rémy‐Jouet Isabelle , Renet Sylvanie , Dumesnil Anais , Wecker Didier , Richard Vincent , Kolkhof Peter , Jaisser Frederic , Ouvrard‐Pascaud Antoine , Mulder Paul 
Published: June 2018

AimTo determine whether non‐steroidal mineralocorticoid receptor (MR) antagonists oppose metabolic syndrome‐related end‐organ, i.e. cardiac, damage.Materials and methodsIn Zucker fa/fa rats, a rat model of metabolic syndrome, we assessed the effects of the non‐steroidal MR antagonist finerenone (oral 2 mg/kg/day) on left ventricular (LV) function, haemodynamics and remodelling (using echocardiography, magnetic resonance imaging and biochemical methods).ResultsLong‐term (90 days) finerenone modified neither systolic blood pressure nor heart rate, but reduced LV end‐diastolic pressure and LV end‐diastolic pressure‐volume relationship, without modifying LV end‐systolic pressure and LV end‐systolic pressure‐volume relationship. Simultaneously, long‐term finerenone reduced both LV systolic and diastolic diameters, associated with reductions in LV weight and LV collagen density, while proteinuria and renal nGAL expression were reduced. Short‐term (7 days) finerenone improved LV haemodynamics and reduced LV systolic diameter, without modifying LV diastolic diameter. Moreover, short‐term finerenone increased myocardial tissue perfusion and reduced myocardial reactive oxygen species, while plasma nitrite levels, an indicator of nitric oxide (NO) bio‐availability, were increased.ConclusionsIn rats with metabolic syndrome, the non‐steroidal MR antagonist finerenone opposed metabolic syndrome‐related diastolic cardiac dysfunction and nephropathy. This involved acute effects, such as improved myocardial perfusion, reduced oxidative stress/increased NO bioavailability, as well as long‐term effects, such as modifications in the myocardial structure.
Efficacy and safety of ipragliflozin as an add‐on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial
Authors: Han Kyung‐Ah , Chon Suk , Chung Choon Hee , Lim Soo , Lee Kwan‐Woo , Baik SeiHyun , Jung Chang Hee , Kim Dong‐Sun , Park Kyong Soo , Yoon Kun‐Ho , Lee In‐Kyu , Cha Bong‐Soo , Sakatani Taishi , Park Sumi , Lee Moon‐Kyu 
Published: June 2018

AimTo evaluate the efficacy and safety of ipragliflozin vs placebo as add‐on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM).MethodsThis double‐blind, placebo‐controlled, multi‐centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT).ResultsIn total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add‐on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were −0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference −0.83% [95% CI −1.07 to −0.59]; P < .0001). More ipragliflozin‐treated patients than placebo‐treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference −1.64 mmol/L, −1.50 μU/mL, −1.72 kg, and −0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted.ConclusionsIpragliflozin as add‐on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.
Mapping of biguanide transporters in human fat cells and their impact on lipolysis
Authors: Arner Peter , Kulyté Agné , Batchelor Kenneth , Laurencikiene Jurga , Livingston James , Rydén Mikael 
Published: June 2018

AimTo examine the cell membrane transporters involved in mediating the antilipolytic effect of biguanides in human fat cells.Materials and methodsGene expression of biguanide transporters was mapped in human subcutaneous adipose tissue and in adipocytes before and after differentiation. Those expressed in mature fat cells were knocked down by RNA interference (RNAi) and the antilipolytic effects of metformin and two novel, highly potent biguanides, NT1014 and NT1044, were examined.ResultsAnalysis of the transporter affinity of biguanides in HEK293 cells overexpressing individual transporters showed that NT1014 and NT1044 had >10 times higher affinity than metformin. Animal studies showed that NT1014 was >5 times more potent than metformin in lowering plasma glucose in mice. In human fat cells, the novel biguanides displayed higher AMP‐activated protein kinase activation and antilipolytic efficacy than metformin. Five transporters, organic cation transporter (OCT)1 (SLC22A1), organic cation transporter novel type 1 (OCTN1; SLC22A4), OCT3 (SLC22A3), plasma membrane monoamine transporter (PMAT; SLC29A4) and multidrug and toxin extrusion transporter (MATE1; SLC47A1), were detectable in fat cells but only OCT3, PMAT and MATE1 increased during adipogenesis in vitro and were enriched in fat cells compared with other adipose cell types. Gene knockdown by RNAi showed that MATE1 and PMAT reduction attenuated the antilipolytic effect of metformin but only PMAT knockdown decreased the effect of all three biguanides.ConclusionsWhile human fat cells primarily express three biguanide transporters, our data suggest that PMAT is the primary target for development of fat cell‐specific antilipolytic biguanides with high sensitivity and potency.
Contribution of basal and postprandial hyperglycaemia in type 2 diabetes patients treated by an intensified insulin regimen: Impact of pump therapy in the OPT2mise trial
Authors: Reznik Yves , Habteab Aklilu , Castaneda Javier , Shin John , Joubert Michael 
Published: June 2018

AimsThe relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) in type 2 diabetes patients treated with multiple daily injections (MDI) of insulin is poorly documented. In this study, the BHG and PPHG of patients from the OPT2mise study who were initially treated with MDI were assessed before randomization and again after 6 months of continuous subcutaneous insulin infusion (CSII).Materials and MethodsBlinded continuous glucose monitoring (CGM) data were collected in 259 MDI patients after completion of an 8‐week run‐in period. The hyperglycaemic area under the curve (AUC) during the 24‐hour basal period (AUC‐B) and the postprandial period (AUC‐P) were compared with analysis of variance based on contribution to total hyperglycaemia in HbA1c groups (Group 1, <8%; Group 2, 8%‐8.4%; Group 3, 8.5%‐8.9%; Group 4, 9%‐9.4%; Group 5, ≥9.5%). Changes in AUC‐B and AUC‐P were assessed after 6 months of pump therapy in 131 randomized participants with available CGM recordings.ResultsIn patients undergoing MDI therapy, AUC‐B was 21.6% to 54.8% lower in Group 4 to 1 (P = .0138 and P = .0002, respectively) in comparison to Group 5. In contrast, AUC‐P did not differ among HbA1c groups (P = .1009). HbA1c correlated with AUC‐B, but not with AUC‐P. After switching to CSII, AUC‐B and AUC‐P decreased by 21% and 17%, respectively. When comparing responders with non‐responders to CSII therapy, no between‐group differences were observed in AUC‐B and AUC‐P.ConclusionsBasal hyperglycaemia is the major determinant of overall exposure to hyperglycaemia in type 2 diabetes with MDI failure.
Application of double low dose combined low flow injection in coronary dual‐source coronary computed tomography angiography
Authors: Tang Zhenhua 
Published: June 2018

PurposeThis study was aimed to explore the feasibility of lower tube voltage, low volumes of contrast medium, and low flow injection in prospective electrocardiogram (ECG)‐triggered high‐pitch dual‐source coronary computed tomography angiography (CCTA) for coronary artery imaging.Material and MethodsA total of 140 patients with body mass index (BMI) ranging from 18.5 to 24.3 kg/m2 and heart rate (HR) lower than 65 times/min underwent CCTA were divided randomly into two groups. The enhanced CT value and noise as well as signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) were calculated. Coronary artery was evaluated by double‐blind method using a four‐point grading scale.ResultsNo significant differences were found in the average enhanced CT value, noise, SNR, and CNR of all segments between the two groups (P > .05). Meanwhile, effective radiation dosages in group A were markedly lower than those in group B (P < .01).ConclusionThe prospective ECG‐triggered high‐pitch dual‐source CCTA with low voltage, contrast medium, and flow rate injection using sinogram affirmed iterative reconstruction is feasible which can observably reduce radiation and obtain satisfactory images.
‘Stop‐go’ policy and the restriction of postwar British house‐building
Authors: Scott Peter M. , Walker James T. 
Published: June 2018

AbstractFrom the mid‐1950s to the early 1980s the Treasury and the Bank of England successfully advocated a policy of restricting both private and public sector house‐building, as a key but covert instrument of their wider ‘stop‐go’ macroeconomic policy framework. While the intensity of restrictions varied over the economic cycle, private house‐building was restricted (through limiting mortgage availability) for almost all this period. This was achieved by keeping building society interest rates low relative to other interest rates and thus starving the building society movement of mortgage funds. Mortgage restriction was never publicly discussed and sometimes operated alongside ambitious housing targets and well‐publicized policy initiatives to boost housing demand. This article outlines the evolution of house‐building restriction, together with its impacts on the housing sector and the wider economy. We review the evolution of the policy framework and its consequences, compare the level and stability of British house‐building during this period—historically and relative to other countries—and undertake time‐series econometric analysis of its impacts on both house‐building and house prices. Finally, implications for debates regarding stop‐go policy, Britain's housing problem, and the distributional consequences of government macroeconomic policy are discussed.
Contribution of early Alzheimer's disease‐related pathophysiology to the development of acquired epilepsy
Authors: Gschwind Tilo , Lafourcade Carlos , Gfeller Tim , Zaichuk Mariana , Rambousek Lukas , Knuesel Irene , Fritschy Jean‐Marc 
Published: June 2018

AbstractAberrant epileptic activity is detectable at early disease stages in Alzheimer's disease (AD) patients and in AD mouse models. Here, we investigated in young ArcticAβ mice whether AD‐like pathology renders neuronal networks more susceptible to the development of acquired epilepsy induced by unilateral intrahippocampal injection of kainic acid (IHK). In this temporal lobe epilepsy model, IHK induces a status epilepticus followed after two weeks by spontaneous recurrent seizures (SRS). ArcticAβ mice exhibited more severe status epilepticus and early onset of SRS. This hyperexcitable phenotype was characterized in CA1 neurons by decreased synaptic strength, increased kainic acid‐induced LTP and reduced frequency of spontaneous inhibitory currents. However, no difference in neurodegeneration, neuroinflammation, axonal reorganization or adult neurogenesis was observed in ArcticAβ mice compared to wild‐type littermates following IHK‐induced epileptogenesis. Neuropeptide Y (NPY) expression was reduced at baseline and its IHK‐induced elevation in mossy fibres and granule cells was attenuated. However, although this alteration might underlie premature seizure onset, neutralization of soluble Aβ species by intracerebroventricular Aβ‐specific antibody application mitigated the hyperexcitable phenotype of ArcticAβ mice and prevented early SRS onset. Therefore, the development of seizures at early stages of AD is mediated primarily by Aβ species causing widespread changes in synaptic function.
Reading memory formation from the eyes
Authors: Bergt Anne , Urai Anne E. , Donner Tobias H. , Schwabe Lars 
Published: June 2018

AbstractAt any time, we are processing thousands of stimuli, but only few of them will be remembered hours or days later. Is there any way to predict which ones? Here, we tested whether the pupil response to ongoing stimuli, an indicator of physiological arousal known to be relevant for memory formation, is a reliable predictor of long‐term memory for these stimuli, over at least 1 day. Pupil dilation was tracked while participants performed visual and auditory encoding tasks. Memory was tested immediately after encoding and 24 hr later. Irrespective of the encoding modality, trial‐by‐trial variations in pupil dilation predicted reliably which stimuli were recalled in the immediate and 24 hr‐delayed tests, in particular for emotionally arousing stimuli. These results show that our eyes may provide a window into the formation of long‐term memories. Furthermore, our findings underline the important role of central arousal systems in the rapid formation of memories in the brain, possibly by gating synaptic plasticity mechanisms in the neocortex.
Resurrecting Discontinued Bonds: A Comparative Study of Israeli Holocaust and Cambodian Genocide Trauma Descendant Relations with the Genocide Dead
Authors: Kidron Carol A. 
Published: June 2018

AbstractThis comparative study examines the way Israeli Holocaust descendants and Cambodian genocide descendants differentially reconstitute “discontinued” descendant‐ancestor relations with the genocide dead they never knew. Empirically examining the way distant bonds “discontinued” in contexts of warfare and mass suffering are restored in everyday life, this study fills a lacuna in the scholarship on genocide legacies, continuing bonds, and person‐dead contact. Descendants depict channels of engagement with the dead entailing person‐ person‐dead contact, person‐object interaction, and imaginal conversations, constituting copresence and intersubjectivity. Contrary to trauma theory, Holocaust and genocide studies, and the anthropology of absence that reduce relations with the dead to maladaptive identification or the burdensome presence of voided absence, the data points to normalized and empowering relations. Comparative findings contribute to our understanding of the way cross‐cultural meaning making differentially conceptualizes the porous border between the living and their ancestors and informs the restoration of (dis)‐continued bonds.
Constructing “The Middle”: The Socialization of Monastic Youth in Buddhist Northern Thailand
Authors: Chladek Michael R. 
Published: June 2018

AbstractTemporary Buddhist monasticism is an important institution in Thailand for the socialization of boys and young men. By ordaining for some time, they learn the ideals of Thai Buddhist morality. Scholarship on youth's socialization into cultural models has often suggested a linear, unidirectional process in which “agents of socialization” instill in younger generations notions of what it means to be morally good. Such models presume consistent reinforcement of cultural models, often with the help of socially entrenched institutions. How young monastics experience divergent notions of what it means to be a good monastic, though, demonstrates that such a unidirectional model does not adequately address the ways in which morality and cultural models are constructed within interactions. I argue that religious institutions act as not only sites for the cultural reproduction of moral ideals but also as sites of everyday interactions where young monastics and their lay supporters reconstruct moral ideals anew. [morality, cultural models, youth, Thailand]
Control of cell death‐associated danger signals during cornification prevents autoinflammation of the skin
Authors: Eckhart Leopold , Tschachler Erwin 
Published: June 2018

AbstractThe function of the skin as a barrier to the environment is mainly achieved by the outermost layers of the epidermis. In the granular layer, epidermal keratinocytes undergo the last steps of their terminal differentiation program resulting in cornification. The coordinated conversion of living keratinocytes into corneocytes, the building blocks of the cornified layer, represents a unique form of programmed cell death. Recent studies have identified numerous genes that are specifically expressed in terminally differentiated keratinocytes and, surprisingly, this genetic program does not only include mediators of cornification but also suppressors of pyroptosis, another mode of programmed cell death. Pyroptosis is activated by inflammasomes, leads to the release of interleukin‐1 (IL‐1) family cytokines, and thereby activates inflammation. In addition, inhibitors of potentially pro‐inflammatory proteases and enzymes removing danger‐associated cytoplasmic DNA are expressed in differentiated keratinocytes. We propose the concept of cornification as an inherently hazardous process in which damaging side effects are actively suppressed by protective mechanisms. In support of this hypothesis, loss‐of‐function mutations in epidermal protease inhibitors and IL‐1 family antagonists suffice to induce autoinflammation. Similarly, exogenous disturbances of either cornification or its accompanying control mechanisms may be starting points for skin inflammation. Further studies into the relationship between cornification, pyroptosis and other forms of cell death will help to define the initiation phase of inflammatory skin diseases and offer new targets for disease prevention and therapy.
Molecular pathogenesis of cutaneous lymphomas
Authors: Stadler Rudolf , Stranzenbach René 
Published: June 2018

AbstractPrimary cutaneous T‐cell lymphoma (CTCL) comprises the second most common group of extra‐nodal non‐Hodgkin's lymphoma. They represent incurable primary extra‐nodal lymphomas of major T cells, uniformly present in the skin with 1%‐2% risk of systemic dissemination in mycosis fungoides (MF), which represents the most common subtype of CTCL. In general, long‐term antigen stimulation is thought, through key cytokine signalling pathways, to induce an inflammatory response with T‐cell proliferation, leading to a clonal malignant T cell with continuous expansion. However, in recent years, using data harvested from high‐throughput transcriptional profiling, substantial advances in the understanding of the molecular pathogenesis were made to understand the complex pathogenesis of CTCL. In this review, the actual data are summarised.
Ursodeoxycholic acid suppresses the formation of fructose/streptozotocin‐induced diabetic cataract in rats
Authors: Abdel‐Ghaffar Amany , Ghanem Hala M. , Ahmed Emad K. , Hassanin Olfat A. , Mohamed Rawda G. 
Published: June 2018

AbstractThe main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin‐induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.5% solution, four times/day) or orally (100 mg/kg b.w.). Cataract formation was monitored biweekly and scored into four stages. After 12 weeks of treatment, rats were subjected to ophthalmological examination, and then, their blood and lenses were prepared for biochemical analysis of glucose, insulin, reduced glutathione, total antioxidant capacity, malondialdehyde, hydrogen peroxide, caspase‐12, and lenticular total proteins. In addition, tertiary structure and conformational changes of lenticular soluble proteins were analyzed using SDS–PAGE and UV absorption while changes in lenticular α‐crystallin structure were investigated using intrinsic tryptophan fluorescence. Results demonstrated that both local and oral UDCA restored the normal levels of lens T‐AOC, MDA, H2O2, and caspase‐12 and improved noticeably the levels of the lens GSH and total proteins. In addition, conformational and tertiary structure changes of soluble lens proteins were significantly reduced in UDCA‐treated groups. Morphological examination of lenses revealed decreased score of cataract progression in UDCA‐treated groups compared to DM animals. It was concluded that UDCA decreased the incidence of diabetic cataract by maintaining the antioxidant status, reducing the endoplasmic reticulum stress, and suppressing the structural changes of soluble lens proteins.