bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoids exert differential effects on the endothelium in an in vitro model of the blood–retinal barrier
Authors: van der Wijk Anne‐Eva , Canning Paul , van Heijningen Rutger P. , Vogels Ilse M.C. , van Noorden Cornelis J.F. , Klaassen Ingeborg , Schlingemann Reinier O.
Published: August 2018

Purpose

Glucocorticoids (GCs) are used as treatment in diabetic macular oedema, a condition caused by blood–retinal barrier (BRB) disruption. The proposed mechanisms by which GCs reduce macular oedema are indirect anti‐inflammatory effects and inhibition of VEGF production, but direct effects on the BRB endothelium may be equally important. Here, we investigated direct effects of GCs on the endothelium to understand the specific pathways of GC action, to enable development of novel therapeutics lacking the adverse side‐effects of the presently used GCs.

Methods

Primary bovine retinal endothelial cells (BRECs) were grown on Transwell inserts and treated with hydrocortisone (HC), dexamethasone (Dex) or triamcinolone acetonide (TA). Molecular barrier integrity of the BRB was determined by mRNA and protein expression, and barrier function was assessed using permeability assays. In addition, we investigated whether TA was able to prevent barrier disruption after stimulation with VEGF or cytokines.

Results

Treatment of BRECs with GCs resulted in upregulation of tight junction mRNA (claudin‐5, occludin, ZO‐1) and protein (claudin‐5 and ZO‐1). In functional assays, only TA strengthened the barrier function by reducing endothelial permeability. Moreover, TA was able to prevent cytokine‐induced permeability in human retinal endothelial cells and VEGF‐induced expression of plasmalemma vesicle‐associated protein (PLVAP), a key player in VEGF‐induced retinal vascular leakage.

Conclusion

Glucocorticoids have differential effects in an experimental in vitro BRB model. TA is the most potent in improving barrier function, both at the molecular and functional levels, and TA prevents VEGF‐induced expression of PLVAP.
Non–exposed endoscopic wall‐inversion surgery for pediatric gastrointestinal stromal tumor: A case report
Authors: Matsumoto Shiro , Hosoya Yoshinori , Lefor Alan K , Ino Yuji , Haruta Hidenori , Kurashina Kentaro , Saito Shin , Kitayama Joji , Sata Naohiro
Published: August 2018

Gastrointestinal stromal tumors (GIST) in patients under 18 years of age are classified as pediatric GIST. Pediatric GIST are extremely rare, and there are no reports of laparoscopic‐endoscopic cooperative surgery for these lesions. We report the use of non‐exposed endoscopic wall‐inversion surgery as a laparoscopic‐endoscopic cooperative surgery‐related procedure for the treatment of a pediatric GIST. The case involved a 17‐year‐old male patient who presented with anemia and was found to have a bleeding gastric tumor. The tumor was resected transorally using the non‐exposed endoscopic wall‐inversion surgery technique. No gene mutation of c‐Kit or Platelet‐Derived Growth Factor Receptor α (PDGFRα) was found, and the final pathological diagnosis was epithelial‐type GIST due to a succinate dehydrogenase abnormality. Follow‐up included a CT scan every 4 months. No recurrence has occurred to date.
Morphological study for understanding the sexual pattern in ghost shrimp Callichirus major (Crustacea: Axiidea)
Authors: Souza Tugstênio L. , Braga Adriane A. , López Greco Laura S. , Bertini Giovana , Nunes Erika T.
Published: August 2018

Callichirus major is a species of ghost shrimp that has burrowing habits, building underground galleries in the intertidal region of beaches. This study aimed to analyse some morphological parameters to verify its type of sexual pattern. A sample of 79 individuals, collected at the beach of Corujão, Espírito Santo, Brazil, was used. Data on the external morphology, presence of gonopores, carapace length (CL) and cheliped lengths (Lch) were obtained. In addition, the gonads were processed for histological analysis. The animals were divided into three categories: A, individuals with male characteristics; B, those presenting exclusively female characteristics; C, animals with characteristics of intersex, which presented supernumerary gonopores. Positive allometries were found for Lch versus CL only for category A, characterizing the group's marked heterochely. Histologically, it was possible to observe the presence of oocytes in category A and one case of male tissue in an intersex individual (category C). However, no genital ducts of both sexes were found in that individual. Callichirus major presents controversial sexual characters, which makes it difficult to understand the reproductive parameters and sexual pattern. However, maybe that species can develop a sexual system of hermaphroditism.
Meta‐analysis of the Influence of UGT Genetic Polymorphisms on Lamotrigine Concentration
Authors: Kim Su Cheol , Kim Myeong Gyu
Published: August 2018

Uridine 5′‐diphospho‐glucuronosyltransferases (UGTs) are involved in the metabolism of lamotrigine, but whether the UGT1A4 and UGT2B7 genetic polymorphisms affect lamotrigine concentration remains controversial. Thus, the objective of this meta‐analysis was to analyse the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration. Through searching, screening, selection, data extraction and quantitative analyses, the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration‐to‐dose ratio (CDR) was assessed by meta‐analysis of nine studies. Neither UGT1A4 70C>A nor 142T>G significantly affected lamotrigine CDR values (standardized difference in means [SDM] = 0.433, 95% confidence interval [CI] = −0.380‐1.302; SDM = −0.458, 95% CI = −1.141‐0.224, respectively). Only the UGT2B7 ‐161C>T homozygous variant had significantly higher CDR values than the wild‐type (WT) and heterozygous variant (SDM = 0.634, 95% CI = 0.056‐1.222). In conclusion, CDR of lamotrigine was significantly higher for the UGT2B7 ‐161C>T homozygous variant than for the WT and heterozygous variant. Thus, UGT2B7 ‐161C>T homozygous variant needs to receive reduced dose.
Prospective study of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi‐agent chemotherapy
Authors: Walewski Jan , Hellmann Andrzej , Siritanaratkul Noppadol , Ozsan Guner Hayri , Ozcan Muhit , Chuncharunee Suporn , Goh Ai Sim , Jurczak Wojciech , Koren Jan , Paszkiewicz‐Kozik Ewa , Wang Bingxia , Singh Shalini , Huebner Dirk , Engert Andreas , von Tresckow Bastian
Published: August 2018

Some patients with relapsed/refractory Hodgkin lymphoma (HL) are not considered suitable for stem cell transplant (SCT) and have a poor prognosis. This phase IV study (NCT01990534) evaluated brentuximab vedotin (1·8 mg/kg intravenously once every 3 weeks) in 60 patients (aged ≥18 years) with CD30‐positive relapsed/refractory HL, a history of ≥1 prior systemic chemotherapy regimen, who were considered unsuitable for SCT/multi‐agent chemotherapy. Primary endpoint was overall response rate (ORR) per independent review facility (IRF). Secondary endpoints included duration of response (DOR), progression‐free survival (PFS) per IRF, overall survival (OS), proportion proceeding to SCT and safety. The ORR was 50%, with 12% CR; 47% proceeded to SCT. Median DOR was 4·6 months and median duration of CR was 6·1 months. After a median follow‐up of 6·9 and 16·6 months, median PFS and OS were 4·8 months (95% confidence interval, 3·0–5·3) and not reached, respectively; estimated OS rate was 86% at 12 months. Most common adverse events (≥10%) were peripheral neuropathy (35%), pyrexia (18%), diarrhoea and neutropenia (each 10%). Brentuximab vedotin showed notable activity with a safety profile consistent with known toxicities, and may act as a bridge to SCT, enabling high‐risk patients who achieve suboptimal response to frontline/salvage chemotherapy/radiotherapy to receive potentially curative SCT.
Resibufogenin suppresses transforming growth factor‐β‐activated kinase 1‐mediated nuclear factor‐κB activity through protein kinase C‐dependent inhibition of glycogen synthase kinase 3
Authors: Liu Lu , Liu Yang , Liu Xiaojia , Zhang Na , Mao Genxiang , Zeng Qingxuan , Yin Mingxiao , Song Danqing , Deng Hongbin
Published: August 2018

Resibufogenin (RB), one of the major active compounds of the traditional Chinese medicine Chansu, has received considerable attention for its potency in cancer therapy. However, the anticancer effects and the underlying mechanisms of RB on pancreatic cancer remain elusive. Here, we found that RB inhibited the viability and induces caspase‐dependent apoptosis in human pancreatic cancer cells Panc‐1 and Aspc. Resibufogenin‐induced apoptosis was through inhibition of constitutive nuclear factor‐κB (NF‐κB) activity and its target genes’ expression, which was caused by downregulation of transforming growth factor‐β‐activated kinase 1 (TAK1) levels and suppression of IκB kinase activity in Panc‐1 and Aspc cells. This induction of TAK1‐mediated NF‐κB inactivation by RB was associated with increased glycogen synthase kinase‐3 (GSK‐3) phosphorylation and subsequent suppression of its activity. Moreover, RB‐induced GSK‐3 phosphorylation/inactivation acted through activation of protein kinase C but not Akt. Finally, RB suppressed human pancreatic tumor xenograft growth in athymic nude mice. Thus, our findings reveal a novel mechanism by which RB suppresses TAK1‐mediated NF‐κB activity through protein kinase C‐dependent inhibition of GSK‐3. Our findings provide a rationale for the potential application of RB in pancreatic cancer therapy.
Fatigue and the wear-off effect in adult patients with common variable immunodeficiency
Authors: Hajjar J , Kutac C , Rider N L , Seeborg F O , Scalchunes C , Orange J
Published: August 2018

Patients with common variable immunodeficiency (CVID) have increased fatigue compared with the general population. Fatigue is associated with lower quality of life (QoL), which is associated with higher mortality in CVID. This study aimed to determine the prevalence of self-reported fatigue for patients with CVID and to identify its possible drivers and burden on QoL. We analysed data from the 2013 Immune Deficiency Foundation (IDF) treatment survey. Answers were included from 873 CVID patients who responded (respondents). Of the 873 respondents included in the analysis, 671 (76·9%) reported fatigue, of whom 400 (83·7%) were receiving intravenous (i.v.) immunoglobulins (IVIG) and 271 (68·6%) were receiving subcutaneous (s.c.) immunoglobulins. This difference in fatigue between patients receiving IVIG and SCIG was statistically significant (P < 0·001). Dose and frequency of immunoglobulin replacement therapy (IgGRT) did not affect fatigue prevalence. Fatigued patients on IVIG reported greater infection rates and required more anti-microbials during the wear-off period. Fatigued patients reported worse health status than non-fatigued patients, and had lower rates of employment, education, household income and school attendance than their non-fatigued counterparts. Fatigue is increased in CVID, especially among patients receiving IVIG, compared to SCIG. Fatigue has a significant impact on QoL and productivity in patients with CVID. Further studies to identify the mechanisms of fatigue are warranted to help advance therapeutic measures to treat this disease and improve patients’ QoL and wellbeing.
Implant‐associated gene expression in the jaw bone of smokers and nonsmokers: A human study using quantitativeqPCR
Authors: Sayardoust Shariel , Omar Omar , Norderyd Ola , Thomsen Peter
Published: August 2018

Objectives

This study aimed to compare the molecular events in implant‐adherent cells and in peri‐implant bone during the osseointegration of machined and oxidized titanium implants in smokers and nonsmokers.

Materials and Methods

Twenty‐four smokers and 24 nonsmokers each received machined and anodically oxidized mini‐implants. The mini‐implants and the surrounding bone were retrieved after 1, 7, and 28 days, for gene expression analysis of selected factors using quantitative polymerase chain reaction (qPCR).

Results

Differences between machined and oxidized implants were more evident in the implant‐adherent cells than the peri‐implant bone. The machined implants revealed higher expression of proinflammatory cytokines, interleukin‐8 (IL‐8) (in nonsmokers), and tumor necrosis factor‐alpha (in nonsmokers and smokers), compared with the oxidized implants. Conversely, the expression of bone formation genes, alkaline phosphatase and osteocalcin, was generally higher at the oxidized implants. In smokers, the temporal pattern revealed the delayed and initial inhibition of osteoblastic and osteoclastic gene expression, respectively, mainly at the machined implants. In contrast, oxidized implants revealed higher expression of bone remodeling, cathepsin K (CatK) and calcitonin receptor, and coupling, receptor activator of nuclear factor kappa‐B ligand (RANKL) and osteoprotegerin, genes after 7 day in smokers.

Conclusions

The implant‐adherent cells are more sensitive to surface properties and smoking conditions than the cells in the peri‐implant bone. Smoking imposes inhibitory effects on the initial molecular events of osseointegration in the human bone–implant interface. The surface properties of oxidized implants appear to have a beneficial effect on osseointegration by mitigating the smoking‐induced negative effects.
Modifiable vascular risk factors, white matter disease and cognition in early Parkinson's disease
Authors: Chahine L. M. , Dos Santos C. , Fullard M. , Scordia C. , Weintraub D. , Erus G. , Rosenthal L. , Davatzikos C. , McMillan C. T.
Published: August 2018

Background and purpose

Dementia in Parkinson's disease (PD) is common and disabling. Identification of modifiable risk factors for it is essential. Vascular risk factors (VRFs) may be associated with cognitive decline in early PD. Biomarkers that serve as surrogates of the long‐term effect of VRFs on PD are needed. To that end, we aimed to quantitate white matter hyperintensities (WMH) in early PD, measure associations with VRFs and examine relationships between WMH and longitudinal cognition.

Methods

Participants in the Parkinson's Progression Markers Initiative study (141 patients with PD, 63 healthy controls) with adequate baseline structural brain magnetic resonance imaging data were included. Hypertension and diabetes history, and body mass index were combined to create a vascular risk score. WMH were quantitated via automated methods. Cognition was assessed annually with a comprehensive test battery.

Results

In the PD group, vascular risk score was associated with WMH for total brain (β = 0.210; P = 0.021), total white matter (β = 0.214; P = 0.013), frontal (β = 0.220; P = 0.002) and temporal (β = 0.212; P = 0.002) regions. Annual rate of change in global cognition was greater in those with higher vascular risk score (β = −0.040; P = 0.007) and greater WMH (β = −0.029; P = 0.049). Higher temporal WMH burden was associated with great decline over time in verbal memory (β = −0.034; P = 0.031).

Conclusions

In early PD, modifiable VRFs are associated with WMH on brain magnetic resonance imaging. Temporal WMH burden predicts decline in verbal memory. WMH may serve as a surrogate marker for the effect of VRFs on cognitive abilities in PD.
Abnormal sleep in patients with epileptic or dissociative (non‐epileptic) seizures: a polysomnography study
Authors: Popkirov S. , Stone J. , Derry C. P.
Published: August 2018

Background and purpose

The aim of this study was to identify the prevalence of sleep disorders and measure the objective sleep quality in patients with seizure disorders.

Methods

Patients admitted for video electroencephalography monitoring were prospectively recruited and polysomnography was performed on the third night of monitoring.

Results

A total of 4/44 (9%) patients with epilepsy and 2/22 (9%) patients with dissociative seizures were found to have mild sleep‐disordered breathing. Three (7%) patients with epilepsy were found to have mild or moderate obstructive sleep apnea–hypopnea syndrome (OSAHS) and three (14%) patients with dissociative seizures had mild or moderate OSAHS. Most patients with sleep‐disordered breathing or OSAHS were overweight or obese. Time awake after sleep onset was high in both groups. There were no significant differences in sleep architecture between the groups except for a difference in average N3 sleep stage proportion. Periodic limb movements (PLMs) were common in both groups and 27% of patients with dissociative seizures had both high PLM rates and high arousal indices, suggesting a high prevalence of probable PLM disorder in that group (compared with 9% in the epilepsy group).

Conclusions

Our findings contradict the commonly reported high comorbidity of OSAHS and epilepsy, and question its purported clinical relevance. High rates of PLMs were found in patients with dissociative seizures. In both patient groups, high awake after sleep onset times were indicative of sleep disruption, which can have an epileptogenic effect and is known to increase dissociative tendencies.
Elastoplastic response and failure assessment of steel alloys: Empirical and computational analyses
Authors: Farahani Behzad V. , Belinha Jorge , Tavares Paulo J. , Moreira Pedro M.G.P.
Published: August 2018

This work aims to study material nonlinearity related to a dual‐phase Steel (DP600) specimen loaded under a tension. Experiment is performed, and then captured data are processed by 3D digital image correlation (DIC). It deals with two analyses; firstly, elastoplastic response of material due to tension up to material plastification. Then, the problem is modelled using FEM, considering an isotropic von Mises criterion/hardening behaviour. To obtain comparable numerical results, model is solved using meshless methods. Besides strain fields, load/displacement response is evaluated, and numerical formulations are validated with experimental solution. Second, failure phenomenon due to plasticity is studied since material undergoes its failure. The empirical results rely on DIC, and then, damage model is resolved using Gurson‐Tvergaard‐Needleman (GTN) criterion. As a result, the engineering stress/strain curves are reported. Comparisons are made between DIC and GTN damage model. Promising computational results are verified by DIC results implying that supportive strategy is proficient.
A global meta‐analysis of marine predator nitrogen stable isotopes: Relationships between trophic structure and environmental conditions
Authors: Pethybridge Heidi , Choy C. Anela , Logan John M. , Allain Valerie , Lorrain Anne , Bodin Nathalie , Somes Christopher J. , Young Jock , Ménard Frederic , Langlais Clothilde , Duffy Leanne , Hobday Alistair J. , Kuhnert Petra , Fry Brian , Menkes Christophe , Olson Robert J.
Published: August 2018

Aim

We examined potential environmental drivers of broad‐scale spatial patterns in the trophic structure of marine ecosystems as represented by nitrogen stable isotopes in globally distributed marine predators. Additionally, we assessed the effects of spatial scale on the predictive capabilities of environmental variables.

Location

Global oceans.

Time period

2000 to 2015.

Major taxa studied

Tunas: Thunnus albacares, Thunnus obesus, Thunnus alalunga.

Methods

We undertook a global compilation and meta‐analysis of the bulk nitrogen stable isotope ratios (δ15N values) of three tuna species (n = 4,281). After adjusting for regional variations in baseline δ15N values using a global ocean biogeochemistry model, generalized additive mixed models were employed to infer global‐scale oceanographic controls of trophic structure, using cosmopolitan tuna species as a model.

Results

For the three tuna species, variation in trophic position estimated using bulk δ15N values was largely explained by geographical location and the corresponding oxygen minimum layer depth. Tuna trophic positions declined in areas with reduced oxygen at depth. Food‐chain length, as captured by maximum trophic position, was longer in areas of the western Pacific Ocean and shorter in the northern Atlantic and eastern Pacific Oceans. Trophic adaptability of the tuna predators, as indicated by intraspecific variability, was highest in the western and central Pacific Ocean and lowest in the northern Atlantic Ocean. Our analysis demonstrated that while tunas share similar functional trophic roles, deeper‐foraging tuna species had higher trophic positions globally. The predictive capacity of environmental variables decreased at finer (regional) spatial scales.

Main conclusions

Our work suggests that habitat compression resulting from the predicted global expansion of oxygen minimum zones with ocean warming will impact the trophic structure of marine food webs and the corresponding foraging habits of marine predators. Spatial scale analyses highlighted the importance of representing differences in regional ecological dynamics in global‐scale trophic and ecosystem models.
Latitudinal variation in seagrass herbivory: Global patterns and explanatory mechanisms
Authors: Vergés Adriana , Doropoulos Christopher , Czarnik Rob , McMahon Kathryn , Llonch Nil , Poore Alistair G. B.
Published: August 2018

Aim

The aim was to quantify latitudinal patterns in seagrass–herbivore interactions in the context of a warming climate.

Location: We carried out a global meta‐analysis combined with a field experiment across 1,700 km and 12° of latitude in Western Australia.

Time period: 1984–2014.

Major taxa studied: Seagrasses.

Methods

We first synthesized the global literature on herbivore exclusion experiments in seagrasses to test whether differences in herbivore impacts are related to latitude and sea surface temperature. We then quantified leaf production and consumption rates in the field at nine meadows of the seagrass Amphibolis antarctica across 1,700 km, from tropical to temperate latitudes. Seagrass biomass and nutritional traits (nitrogen, C:N, phenolics) were also measured.

Results

Our meta‐analysis showed that herbivores had a similar net impact on seagrasses across 37° of absolute latitude, and there was little variation in herbivore exclusion effects at different temperatures. In the field, rates of both production and consumption of seagrass were greatest in the tropics and decreased with latitude. Seagrass nutritional quality was lowest in the tropics, where fish removed c. 30% of primary production. Consumption of the more nutritious temperate seagrasses was lower overall but also highly variable and dominated by invertebrates.

Main conclusions

In tropical latitudes, faster growth rates compensated for greater consumption of A. antarctica by herbivores. This resulted in similar net impacts of herbivores across latitudes, because higher latitude plants grew more slowly but also suffered less herbivory. This match between consumption and production rates might explain the global patterns derived from the literature, which show little latitudinal variation in the effects of consumers on seagrasses. As ocean temperatures continue to rise and overall herbivory levels are expected to increase in temperate regions, the survival of seagrass meadows in higher latitudes will depend on the ability of plants to increase growth at compensatory rates.
The influence of pesticide use on amphibian chytrid fungal infections varies with host life stage across broad spatial scales
Authors: Rumschlag Samantha L. , Rohr Jason R.
Published: August 2018

Aim

Widespread pesticides might influence pathogen distributions across landscapes via effects on host–pathogen interactions. Empirical research supports two hypotheses regarding effects of pesticides on amphibians and the aquatic fungal pathogen Batrachochytrium dendrobatidis (Bd): (a) pesticides can be toxic to Bd, reducing infection risk of aquatic larval amphibians; and, (b) exposure to pesticides early in amphibian development can increase disease risk after metamorphosis. The aim of this research is to evaluate whether these patterns from laboratory experiments are consistent across host species and occur in the field at broad spatial scales.

Location

Contiguous U.S.A.

Time period

1998–2009.

Major taxa studied

Amphibian hosts and Bd.

Methods

Our data included 3,946 individuals evaluated for Bd infection across 49 amphibian species, which resulted in 155 estimates of Bd prevalence in populations. We used multimodel inference to examine associations between Bd infection prevalence in amphibian populations and (a) total pesticide use, (b) pesticide use by type (herbicide, insecticide or fungicide), and (c) the most commonly used pesticide compounds across life stages, controlling for several factors documented to affect the distribution of Bd.

Results

Consistent with laboratory findings, our results indicate that use of multiple herbicide compounds is most closely associated with low infection risk in the aquatic larval stage but high risk in the terrestrial post‐metamorphic stage when controlling for insecticide and fungicide use. We caution against assuming that insecticides and fungicides do not influence Bd distributions, because use of herbicides, insecticides and fungicides are all correlated positively.

Main conclusions

The effects that pesticides can have on disease distributions are complex and should be considered strongly at broad scales and across host species, especially in environments in which use and exposure are widespread. Accurate predictions of disease distributions may lead to more effective management strategies to limit disease spread.
Cold and dark captivity: Drivers of amphibian longevity
Authors: Stark Gavin , Meiri Shai
Published: August 2018

Aim

Longevity is a critical life‐history trait of organisms. Multiple abiotic and biotic factors are thought to exert different selection pressures, resulting in a great variation in species longevity. We examined factors that, according to evolutionary theories of senescence, are thought to be related to extrinsic and intrinsic mortality rates, and thus shape the variation in longevity among amphibians.

Location

World‐wide.

Time period

Present.

Major taxa studied

Amphibia.

Methods

We collected literature data on the maximum longevities of 527 amphibian species. Correcting for phylogeny and sample size, we modelled the relationship between amphibian longevity and body size. We also examined the effects of chemical protection, activity period, microhabitat preferences and annual temperature on amphibian longevity.

Results

In general, members of larger amphibian species live longer. Body size, however, explained less of the variation in amphibian longevity than it does in mammals and birds. Nocturnal amphibians, species that use poison for defence and those inhabiting cold regions live longer, but microhabitat preferences had little effect.

Main conclusions

Our results supported predictions of evolutionary theories of senescence. Large amphibians living in colder environments probably experience slower growth and metabolic rates, reducing intrinsic drivers of mortality and increasing longevity. Moreover, species that reduce extrinsic mortality pressures via chemical protection and nocturnality have increased longevity. Sampling captive animals and sampling more individuals of a species increases the chances of finding older individuals and should be corrected for when studying maximum longevity.
Polypharmacy is associated with frailty in Japanese community‐dwelling older adults
Authors: Yuki Atsumu , Otsuka Rei , Tange Chikako , Nishita Yukiko , Tomida Makiko , Ando Fujiko , Shimokata Hiroshi
Published: August 2018

Aim

The association between polypharmacy and the development of frailty is unknown. The present study assessed the longitudinal relationship between polypharmacy and frailty risk in Japanese community‐dwelling older adults.

Methods

Participants included 299 non‐frail older Japanese adults aged 65–81 years who participated in both baseline and follow‐up examinations of a longitudinal study of aging (mean duration 6.2 years). At baseline examination, all prescribed and non‐prescribed medications used during the previous 2 weeks were confirmed and coded by physicians. Frailty was diagnosed according to frailty criteria, and included shrinking, exhaustion, low activity, low grip strength and low gait speed. The relationship between frailty and the number of medications was assessed using multiple logistic regression analysis. The logistic regression model was used to control for potential confounders, including age at baseline, sex, body fat, total physical activity, education, employment, current smoking and number of comorbidities.

Results

The percentage of participants who developed frailty during follow up was 5.1% in those taking five or fewer medications, and 22.5% in those taking six or more medications. The fully adjusted odds ratio for frailty among participants taking six or more medications was 5.55 (95% confidence interval 2.17–14.22).

Conclusions

Polypharmacy appears to be a significant risk factor for the development of frailty in older Japanese adults. Geriatr Gerontol Int 2018; 18: 1497–1500.
Higher Education institutional governance reforms in the Netherlands, Portugal and Italy: A policy translation perspective addressing the homogeneous/heterogeneous dilemma
Authors: Donina Davide , Hasanefendic Sandra
Published: August 2018

This paper addresses the homogeneous/heterogeneous dilemma regarding formal arrangements of university central governance structures. Most topical studies argue that these structures are becoming homogeneous across countries and prove it by adopting purposive sampling techniques. Yet, other scholars stress heterogeneity within countries. This paper aims to clarify this dilemma through a multi‐level analysis that simultaneously considers three levels of embeddedness (i.e., supranational, national and institutional), by employing a policy translation perspective, which can accommodate both homogeneity and heterogeneity. The national sample comprises three countries (the Netherlands, Portugal and Italy). The institutional sample is comprehensive and encompasses all public universities within each country. The study discloses heterogeneity in how countries responded to supranational policy pressures as well as heterogeneous responses at the institutional level even when unitary laws are applied. Relying on these findings, we stress the importance of adopting comprehensive (rather than purposive) sampling to infer about international and/or national homogeneity because studies that generalise results based on one/few case studies per country could be biased by the sample selection criteria. In addition, the research implications of our analysis on steering‐at‐a‐distance and on the relation between the grade of cogency of the national laws and homogeneous/heterogeneous reform outcomes are discussed.
From activism to secrecy: Contemporary experiences of living with HIV in London in people diagnosed from 1986 to 2014
Authors: Rai Tanvi , Bruton Jane , Day Sophie , Ward Helen
Published: August 2018

Background

Successes in biomedicine have transformed HIV from a debilitating and frequently fatal infection to a chronic, manageable condition.

Objective

To explore how the contemporary metanarrative of HIV as a chronic condition is understood by patients and how it varies depending on when they were diagnosed.

Design

Qualitative interviews with 52 people living with HIV who were diagnosed during different phases in the history of the epidemic.

Setting and participants

Participants were recruited from two HIV clinics in London to include four “HIV generations”: generation 1 were those who had been diagnosed pre‐1997 (pre‐ART), generation 2 from 1997 to 2005 (complex ART), generation 3 from 2006 to 2012 (simpler ART) and generation 4 diagnosed in the year before the study (2013‐2014).

Results

Participants in all HIV generations took their medication as prescribed, attended clinic appointments and were well informed about their immunological biomarkers. While the pre‐treatment generation had been engaged in community endeavours such as activism, public education and use of support groups, those more recently diagnosed had little experience of collective activities and their HIV was essentially a private matter, separate from their social identity. These strategies worked for some; however, those experiencing clinical or social problems related to HIV or wider issues often relied exclusively on their HIV clinic for wider support.

Conclusion

The loss of public conversation around HIV, the imperative for patients to take on greater individual responsibility for HIV management and the streamlining of HIV services alongside reductions in ancillary support services may expose some people to suboptimal health outcomes.
Assessment of endothelial function during the loading phase of infliximab in psoriasis: a potential predictor of its drug survival
Authors: Nakao Momoko , Nakamura Kouki , Fukasawa Takemichi , Shida Rino , Ito Arisa , Ichimura Yohei , Takahashi Takehiro , Mitsui Aya , Yoshizaki Ayumi , Shibata Sayaka , Kamata Masahiro , Araki Mayuko , Watanabe Rei , Sato Shinichi , Asano Yoshihide
Published: August 2018

Background

Tumor necrosis factor inhibitors decrease the risk of cardiovascular events in moderate to severe psoriasis, but the association between their effects on endothelial function and those on skin lesions has not been well studied. We investigated the association between infliximab effects on endothelial function during the loading phase and those on skin lesions in patients with psoriasis.

Methods

We evaluated endothelial function with reactive hyperemia‐peripheral arterial tonometry index (RHI) in 15 patients with psoriasis before the first and third infusions of infliximab. Patients were stratified into two groups; those who maintained Psoriasis Area and Severity Index (PASI) 75 response for more than 6 months (defined as responders) and the others (defined as nonresponders).

Results

Six weeks after the initiation of infliximab (before the third infusion), PASI scores were significantly improved compared with baseline, while RHI values were not altered in the whole patient group. However, when the responders and the nonresponders were analyzed separately, RHI values tended to be decreased before the third infusion compared with baseline in the nonresponders, while being unchanged in the responders. Importantly, the difference in ∆RHI reached a statistical significance between the two groups, and the cutoff value (mean − 2 standard deviation of RHI values in the responders) identified the nonresponders with 67% of sensitivity and 100% of specificity.

Conclusions

The decrease in RHI values before the third infusion may serve as a predictor for the long‐term unfavorable effect of infliximab on psoriatic skin lesions.
Model‐Assisted Regression Estimators for Longitudinal Data with Nonignorable Dropout
Authors: Wang Lei , Qi Cuicui , Shao Jun
Published: August 2018

Estimation with longitudinalYhaving nonignorable dropout is considered when the joint distribution ofYand covariateXis nonparametric and the dropout propensity conditional on (Y,X) is parametric. We apply the generalised method of moments to estimate the parameters in the nonignorable dropout propensity based on estimating equations constructed using an instrumentZ, which is part ofXrelated toYbut unrelated to the dropout propensity conditioned onYand other covariates. Population means and other parameters in the nonparametric distribution ofYcan be estimated based on inverse propensity weighting with estimated propensity. To improve efficiency, we derive a model‐assisted regression estimator making use of information provided by the covariates and previously observedY‐values in the longitudinal setting. The model‐assisted regression estimator is protected from model misspecification and is asymptotically normal and more efficient when the working models are correct and some other conditions are satisfied. The finite‐sample performance of the estimators is studied through simulation, and an application to the HIV‐CD4 data set is also presented as illustration.
Sintering of ferrous metallic compacts: Chemical reactions that involve interstitial elements
Authors: Gierl‐Mayer Christian , de Oro Calderon Raquel , Danninger Herbert
Published: August 2018

For sintering of ferrous metallic compacts, the chemical reactions with the atmosphere are of special interest. This is due to the very large specific surface of the compacts that makes them highly reactive with the atmosphere, much more than cast and wrought metals. Within this paper, the interactions of interstitial elements with the metallic matrix and the surrounding atmosphere are described. The main reaction partners are interstitial elements that may emerge from the starting powders or from the surrounding atmosphere. The oxidation/reduction and decarburization phenomena have been studied by thermoanalytical techniques both for mixed and prealloyed systems. The reaction mechanisms are discussed as well as their impacts on the sintering processes and the resulting properties. Oxygen transfer reactions (“Internal gettering”) and formation of methane are observed for systems with widely varying oxygen affinity of the components. The results presented show that controlling the interactions of the interstitial elements with the metallic components is crucial for successful sintering of advanced PM alloy steels.
High‐energy density of Pb0.97La0.02(Zr0.50Sn0.45Ti0.05)O3 antiferroelectric ceramics prepared by sol‐gel method with low‐cost dibutyltin oxide
Authors: Dan Yu , Xu Haojie , Zhang Yangyang , Zou Kailun , Zhang Qingfeng , Lu Yinmei , Chang Gang , Zhang Qi , He Yunbin
Published: August 2018

Lead lanthanum zirconate stannate titanate (PbLa(ZrSnTi)O3) antiferroelectric (AFE) ceramics are widely used in dielectric capacitors due to their superior energy‐storage capacity. Generally, these ceramics can be synthesized by solid‐state reaction and sol‐gel methods. Ceramics prepared using the sol‐gel method have a purer phase than those prepared using the solid‐state reaction method because the sol‐gel method can avoid the segregation of Sn. However, because the commonly used raw material tin acetate is very expensive, the preparation of PbLa(ZrSnTi)O3 AFE ceramics via the sol‐gel method is not cost‐effective, which prevents the use of sol‐gel method for manufacturing PbLa(ZrSnTi)O3 in a large scale. In this work, low‐cost dibutyltin oxide instead of expensive tin acetate is used to synthesize Pb0.97La0.02(Zr0.50Sn0.45Ti0.05)O3 (PLZST) nanopowders, and single‐phase powders with a perovskite structure and average grain size of 200 nm are obtained at a calcination temperature of 580°C. In addition, dense PLZST AFE ceramics with a pure perovskite structure are obtained by sintering the PLZST nanopowders at temperatures as low as 1100°C. The sintered PLZST ceramics exhibit a room‐temperature recoverable energy‐storage density as high as 1.93 J/cm3 with an efficiency of 75%, which varies only slightly in the temperature range of 20‐120°C. The high energy‐storage density (>1.9 J/cm3) over a wide temperature range illustrates that the sol‐gel‐derived PLZST ceramics with low‐cost dibutyltin oxide are quite promising for manufacturing pulse power capacitors.
Professional and family caregivers’ attitudes towards involuntary treatment in community‐dwelling people with dementia
Authors: Mengelers Angela M. H. J. , Bleijlevens Michel H. C. , Verbeek Hilde , Capezuti Elizabeth , Tan Frans E. S. , Hamers Jan P. H.
Published: August 2018

Aims

The aim of this study was to gain insight into professional and family caregivers’ attitudes towards involuntary treatment in community‐dwelling people with dementia (PwD).

Background

The number of PwD with complex care needs living at home is increasing rapidly. In some situations, caregivers provide care against the will of PwD, referred to as involuntary treatment, which includes non‐consensual care, psychotropic medication and physical restraints.

Design

A cross‐sectional study.

Methods

A total of 228 professional (nursing staff, general practitioners (GPs) and other healthcare professionals such as physical therapists and psychologists) and 77 family caregivers of PwD completed the Maastricht Attitude Questionnaire—Home Care. This questionnaire measures attitudes towards involuntary treatment and perceived restrictiveness of and experienced discomfort in using involuntary treatment. Data were collected in the Netherlands between June and November 2016.

Results

Family caregivers and GPs had more positive attitudes towards involuntary treatment than nursing staff and other healthcare professionals, indicating that they are more accepting of involuntary treatment. A more positive attitude was associated with higher perceived caregiver burden and being a family caregiver. Family caregivers and GPs found the use of involuntary treatment less restrictive and indicated feeling more comfortable when using these measures.

Conclusion

It is important to account for the differences in attitudes and foster dialogue among professional and family caregivers to find common ground about alternatives to involuntary treatment. These results will inform the development of an intervention that aims to prevent involuntary treatment in home care.
High‐power short‐duration versus standard radiofrequency ablation: Insights on lesion metrics
Authors: Bourier Felix , Duchateau Josselin , Vlachos Konstantinos , Lam Anna , Martin Claire A. , Takigawa Masateru , Kitamura Takeshi , Frontera Antonio , Cheniti Ghassen , Pambrun Thomas , Klotz Nicolas , Denis Arnaud , Derval Nicolas , Cochet Hubert , Sacher Frédéric , Hocini Mélèze , Haïssaguerre Michel , Jais Pierre
Published: August 2018

Introduction

Radiofrequency (RF) lesion metrics are influenced by underlying parameters like RF power, duration, and contact force (CF), and utilization of lesion metric indices (ablation index [AI]) is a proposed strategy to predict lesion quality. The aim of this study was to analyze the influence of underlying parameters on lesion metrics of high‐power short‐duration (HPSD) and standard RF applications using an in silico and ex vivo model.

Methods and Results

An in silico simulation study was designed to simulate HPSD and standard ablations, in which ablation parameters could systematically be varied. For each simulated ablation process (n = 5732), the corresponding AI value was calculated. HPSD and standard RF settings were then applied in a porcine ex vivo model (
n = 120 lesions). The resulting lesion metrics were compared and analyzed regarding underlying parameters. RF applications of 50 W/13 seconds, 60 W/10 seconds, 70 W/7 seconds, and 80 W/6 seconds resulted in lesion volumes not significantly different from standard RF applications (30 W/30 seconds,
P > 0.05). HPSD lesion diameters were significantly larger and lesion depths were significantly smaller (
P < 0.01) when compared with standard settings. Prolonging RF duration from 5 to 10 seconds resulted in a +27.5% increase, whereas a prolongation of RF duration from 35 to 40 seconds resulted in a +4.8% increase of AI value only. An increase of CF from 1 to 10 g resulted in a +73.0%, an increase of CF from 20 to 30 g resulted in a +10.1% increase of AI value.

Conclusion

HPSD RF applications resulted in similar lesion volumes but significantly different lesion geometries when compared with standard setting RF applications.
Developing a risk score to predict mortality in the first year after implantable cardioverter defibrillator implantation: Data from the Israeli ICD Registry
Authors: Nevzorov Roman , Goldenberg Ilan , Konstantino Yuval , Golovchiner Gregory , Strasberg Boris , Souleiman Mahmoud , Khalameizer Vladimir , Ben‐Zvi Shlomit , Sela Ron , Rosenheck Shimon , Freedberg Nahum A. , Geist Michael , Cohen Michal Einhorn , Cohen Tal , Shlomo Nir , Gabrielov‐Yusim Natalie , Geva Diklah , Glikson Michael , Haim Moti ,   On behalf of the Israeli working group of pacing and electrophysiology, the Israel Heart Society
Published: August 2018

Introduction

Life expectancy of less than 1 year is usually a contraindication for implantable cardioverter defibrillator (ICD) implantation. The aim was to identify patients at risk of death during the first year after implantation.

Methods and Results

Data were derived from a prospective Israeli ICD Registry. Two groups of patients were compared, those who died and those who were alive 1 year after ICD implantation. Factors associated with 1‐year mortality were identified on a derivation cohort. A risk score was established and validated. A total of 2617 patients have completed 1 year of follow‐up after ICD or cardiac resynchronization therapy defibrillator (CRT‐D) implantation. Age greater than 75 years (hazard ratio [HR], 2.7; 95% confidence interval [95% CI], 1.6 to 4.4), atrial fibrillation (AF; HR, 1.9; 95% CI, 1.12 to 3.17), chronic lung disease (HR, 2.0; 95% CI, 1.1 to 3.76), anemia (HR, 2.3; 95% CI, 1.3 to 3.93) and chronic renal failure (CRF; HR, 3.4; 95% CI, 1.74 to 6.6) were independent risk factors for 1‐year mortality. We propose a simple AAACC (“triple A double C”) score for prediction of 1‐year mortality after ICD implantation: Age greater than 75 years (3 points(pts)), anemia (2 pts), AF (1 pt), CRF (3 pts) and chronic lung disease (1 pt). Mortality risk increased with rising number of points (from 1% with 0 pts to 12.5% with >4 pts). The risk score was evaluated with receiver operating characteristic curve and the area under the curve of the validation curve is 0.71 (95% CI, 0.66 to 0.76).

Conclusions

Age greater than 75, AF, chronic lung disease, anemia, and CRF were independent risk factors for 1‐year mortality. AAACC risk score identifies patients at high risk of death during 1 year after ICD implantation.
Liberal Intergovernmentalism and Its Critics
Authors: Kleine Mareike , Pollack Mark
Published: August 2018

This introduction sets the stage for a special issue devoted to evaluating the contribution and continued relevance of Liberal Intergovernmentalism (LI) – a theory first formulated 25 years ago in this journal – in today's politicized and crisis‐ridden European Union (EU). We review the debates prompted by LI's three core claims about national preference formation, intergovernmental bargaining and institutional choice, as well as by the theory's three policy‐relevant corollaries relating to the EU's democratic deficit, its constitutional settlement and its role in the world. Liberal intergovernmentalism, we argue, remains highly relevant in today's EU, offering important insights and serving to structure much of the academic debate about the prospects of the Union in a time of crisis. Nevertheless, a revitalized LI faces the dual challenges of theorizing both the causes and consequences of mass politicization of EU politics, as well as the prospect of endogenous change in the direction of greater integration or disintegration.