bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium Pharmacogenetics: Where Do We Stand?
Authors: Pisanu Claudia , Melis Carla , Squassina Alessio 
Published: September 2016

ABSTRACT

Preclinical Research

Bipolar disorder (BPD) is a chronic and disabling psychiatric disorder with a prevalence of 0.8–1.2% in the general population. Although lithium is considered the first‐line treatment, a large percentage of patients do not respond sufficiently. Moreover, lithium can induce severe side effects and has poor tolerance and a narrow therapeutic index. The genetics of lithium response has been largely investigated, but findings have so far failed to identify reliable biomarkers to predict clinical response. This has been largely determined by the highly complex phenotipic and genetic architecture of lithium response. To this regard, collaborative initiatives hold the promise to provide robust and standardized methods to disantenagle this complexity, as well as the capacity to collect large samples of patietnts, a crucial requirement to study the genetics of complex phenotypes. The International Consortium on Lithium Genetics (ConLiGen) has recently published the largest study so far on lithium response reporting significant associations for two long noncoding RNAs (lncRNAs). This result provides relevant insights into the pharmacogenetics of lithium supporting the involvement of the noncoding portion of the genome in modulating clinical response. Although a vast body of research is engaged in dissecting the genetic bases of response to lithium, the several drawbacks of lithium therapy have also stimulated multiple efforts to identify new safer treatments. A drug repurposing approach identified ebselen as a potential lithium mimetic, as it shares with lithium the ability to inhibit inositol monophosphatase. Ebselen, an antioxidant glutathione peroxidase mimetic, represents a valid and promising example of new potential therapeutic interventions for BD, but the paucity of data warrant further investigation to elucidate its potential efficacy and safety in the management of BPD. Nevertheless, findings provided by the growing field of pharmacogenomic research will ultimately lead to the identification of new molecular targets and safer treatments for BPD. Drug Dev Res 77 : 368–373, 2016. © 2016 Wiley Periodicals, Inc.
Remote haemodynamic‐guided care for patients with chronic heart failure: a meta‐analysis of completed trials
Authors: Adamson Philip B. , Ginn Greg , Anker Stefan D. , Bourge Robert C. , Abraham William T. 
Published: September 2016

AbstractAimsHaemodynamic‐guided heart failure (HF) management using directly measured cardiac filling pressures in symptomatic patients is now recommended in the European Society of Cardiology (ESC) Heart Failure Guidelines [Class IIb(B)]. This meta‐analysis evaluates all data from completed clinical trials evaluating this approach in patients with HF.Methods and resultsAll trials evaluating the impact of HF management based on haemodynamic monitoring using implantable devices were reviewed using standard search engine methods. PRISMA methods were used to evaluate and screen publications that included an evaluation of an effect on HF hospitalizations. All publications meeting the inclusion criteria were included, and the outcomes data were evaluated using standard meta‐analysis methodology. Of 317 publications initially identified, five trials involving 1296 patients with chronic HF met the criteria used in this meta‐analysis. Studies included prospective controlled designs, as well as observational studies with historical control. Heterogeneity testing failed to demonstrate instability of analysis due to differences between trials. When compiled, outcomes from these trials favoured remote haemodynamic monitoring with a significant 38% reduction in HF hospitalizations (hazard ratio 0.62, 95% confidence interval 0.50–0.78, P < 0.001).ConclusionsHaemodynamic‐guided HF management using permanently implanted sensors and frequent filling pressure evaluation is superior to traditional clinical management strategies in reducing long‐term HF hospitalization risk in symptomatic patients.
Dutch Dataset Pain Rehabilitation in daily practice: Content, patient characteristics and reference data
Authors: Köke A.J.A. , Smeets R.J.E.M. , Schreurs K.M. , van Baalen B. , de Haan P. , Remerie S.C. , Schiphorst Preuper H.R. , Reneman M.F. 
Published: September 2016

AbstractBackgroundNo core set of measurement tools exists to collect data within clinical practice. Such data could be useful as reference data to guide treatment decisions and to compare patient characteristics or treatment results within specific treatment settings.MethodsThe Dutch Dataset Pain Rehabilitation was developed which included the six domains of the IMMPACT core set and three new domains relevant in the field of rehabilitation (medical consumption, patient‐specific goals and activities/participation). Between 2010 and 2013 the core set was implemented in 32 rehabilitation facilities throughout the Netherlands.ResultsA total of 8200 adult patients with chronic pain completed the core set at first consultation with the rehabilitation physician. Adult patients (18–90 years) suffering from a long history of pain (38% >5 years) were referred. Patients had high medical consumption and less than half were working. Although patients were referred with diagnosis of low back pain or neck or shoulder pain, a large group (85%) had multisite pain (39% 2–5 painful body regions; 46% >5 painful body regions). Scores on psychosocial questionnaires were high, indicating high case complexity of referred patients. Reference data for subgroups based on gender, pain severity, pain locations and on pain duration are presented.ConclusionsThe data from this clinical core set can be used to compare patient characteristics of patients of other treatment setting and/or scientific publications. As treatment success might depend on case complexity, which is high in the referred patients, the advantages of earlier referral to comprehensive multidisciplinary treatment were discussed.SignificanceA detailed description of case complexity of patients with chronic pain referred for pain rehabilitation. Insight in case complexity of patients within subgroups on the basis of gender, pain duration, pain severity and pain location. These descriptions can be used as reference data for daily practice in the field of pain rehabilitation and can be used to evaluate, monitor and improve rehabilitation care in care settings nationwide as well as internationally.
Epoxy fatty acids mediate analgesia in murine diabetic neuropathy
Authors: Wagner K. , Lee K.S.S. , Yang J. , Hammock B.D. 
Published: September 2016

AbstractBackgroundNeuropathic pain is a debilitating condition with no adequate therapy. The health benefits of omega‐3 fatty acids are established, however, the role of docosahexaenoic acid (DHA) in limiting pain has only recently been described and the mechanisms of this action remain unknown. DHA is metabolized into epoxydocosapentanoic acids (EDPs) via cytochrome P450 (CYP450) enzymes which are substrates for the soluble epoxide hydrolase (sEH) enzyme. Here, we tested several hypotheses; first, that the antinociceptive action of DHA is mediated by the EDPs. Second, based on evidence that DHA and CYP450 metabolites elicit analgesia through opioid signalling, we investigated this as a possible mechanism of action. Third, we tested whether the analgesia mediated by epoxy fatty acids had similar rewarding effects as opioid analgesics.MethodsWe tested diabetic neuropathic wild‐type and sEH null mice in a conditioned place preference assay for their response to EDPs, sEHI and antagonism of these treatments with naloxone, a mu‐opioid receptor antagonist.ResultsThe EDPs and sEH inhibitors were efficacious against chronic pain, and naloxone antagonized the action of both EDPs and sEH inhibitors. Despite this antagonism, the sEH inhibitors lacked reward side effects differing from opioids.ConclusionsThe EpFA are analgesic against chronic pain differing from opioids which have limited efficacy in chronic conditions.SignificanceEDPs and sEHI mediate analgesia in modelled chronic pain and this analgesia is blocked by naloxone. However, unlike opioids, sEHI are highly effective in neuropathic pain models and importantly lack rewarding side effects.
The interaction between NGF‐induced hyperalgesia and acid‐provoked pain in the infrapatellar fat pad and tibialis anterior muscle of healthy volunteers
Authors: Munkholm T.K. , Arendt‐Nielsen L. 
Published: September 2016

AbstractBackgroundTissue pH is lowered in inflamed tissues, and the increased proton concentration activates acid‐sensing ion channels (ASICs), contributing to pain and hyperalgesia. ASICs can be upregulated by nerve growth factor (NGF). The aim of this study was to investigate two new human experimental pain models combining NGF‐ and acid‐induced pain in a randomized, controlled, double‐blind study.MethodsIn experiment 1, volunteers (N = 16) received an injection of either NGF or isotonic saline in each infrapatellar fat pad (IFP). One day after 5 mL of phosphate‐buffered acidic saline was infused into each IFP at a rate of 20 mL/h. In experiment 2, the tibialis anterior (TA) muscle of additional volunteers (N = 16) was examined, following the same procedure except that the volume and infusion rate of acid were different (10 mL, 30 mL/h). Continuous pain ratings were recorded during and after acid infusions. In addition, soreness scores on a Likert scale and pressure pain thresholds (PPTs) were assessed.ResultsThe PPT of the IFP was significantly decreased at the NGF injection site on day 1, but acid‐provoked pain ratings and the change in PPT from pre‐ to postinfusion between the knees were similar. In the muscle pain model, local mechanical hyperalgesia developed 3 h after the NGF injection and a significant additional decrease in PPT was found after acid infusion compared to preinfusion.ConclusionsNGF sensitization in the IFP was not facilitated by acid, whereas an acid‐provoked enhancement of muscle hyperalgesia was found. NGF sensitization of adipose tissue responds differently to acid provocation compared to muscle tissue.SignificanceQuantification of two novel pain models combining NGF and acid. Hyperalgesia developed after NGF injection in the infrapatellar fat pad, but it was not facilitated by acid provocation. Contrary, NGF‐induced hyperalgesia in muscle tissue was enhanced by acid.
Efficient, Stable, Dopant‐Free Hole‐Transport Material with a Triphenylamine Core for CH3NH3PbI3 Perovskite Solar Cells
Authors: Qi Peng , Zhang Fei , Zhao Xiaoming , Liu Xicheng , Bi Xiangdong , Wei Peng , Xiao Yin , Li Xianggao , Wang Shirong 
Published: September 2016

AbstractA star‐shaped hole‐transporting material (HTM) using the triphenylamine (TPA) as the core named TP1 is designed and synthesized. The implementation of the new HTM in CH3NH3PbI3‐based perovskite solar cells exhibits an excellent overall power conversion efficiency (PCE) of 12.63 % without the use of any dopants and additives, which is comparable to the 14.93 % obtained using p‐doped spiro‐OMeTAD. Importantly, the devices based on TP1 show relatively stable device performance compared to spiro‐OMeTAD after aging in ambient air with 30 % relative humidity without encapsulation in the dark. The present results demonstrate that TPA could be an excellent building block to design dopant‐free HTMs for perovskite solar cells and holds promise to replace p‐doped spiro‐OMeTAD, which is important for the fabrication of cost‐effective and stable devices.
Germline miRNA DNA variants and the risk of colorectal cancer by subtype
Authors: Lindor Noralane M. , Larson Melissa C. , DeRycke Melissa S. , McDonnell Shannon K. , Baheti Saurabh , Fogarty Zachary C. , Win Aung Ko , Potter John D. , Buchanan Daniel D. , Clendenning Mark , Newcomb Polly A. , Casey Graham , Gallinger Steven , Le Marchand Loïc , Hopper John L. , Jenkins Mark A. , Goode Ellen L. , Thibodeau Stephen N. 
Published: September 2016

MicroRNAs (miRNAs) regulate up to one‐third of all protein‐coding genes including genes relevant to cancer. Variants within miRNAs have been reported to be associated with prognosis, survival, response to chemotherapy across cancer types, in vitro parameters of cell growth, and altered risks for development of cancer. Five miRNA variants have been reported to be associated with risk for development of colorectal cancer (CRC). In this study, we evaluated germline genetic variation in 1,123 miRNAs in 899 individuals with CRCs categorized by clinical subtypes and in 204 controls. The role of common miRNA variation in CRC was investigated using single variant and miRNA‐level association tests. Twenty‐nine miRNAs and 30 variants exhibited some marginal association with CRC in at least one subtype of CRC. Previously reported associations were not confirmed (n = 4) or could not be evaluated (n = 1). The variants noted for the CRCs with deficient mismatch repair showed little overlap with the variants noted for CRCs with proficient mismatch repair, consistent with our evolving understanding of the distinct biology underlying these two groups. © 2016 The Authors Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.
Effect of Surface Cover on NPS Pollution from Sloping Fields under Intensive Farming in Korea
Authors: Choi Joongdae , Won Chulhee , Shin Minhwan , Choi Yonghun , Park Woonji , Lee Suin , Lee Youngjoon , Jeong Wongu 
Published: September 2016

AbstractSloping fields under intensive farming have been a major source of agricultural nonpoint source (NPS) pollution in Korea. Comprehensive studies to quantify edge‐of‐field water quality and measure surface mulch effects on NPS pollution discharge have been conducted over the past several years. Edge‐of‐field water quality was seriously degraded by NPS pollutants. The range of average event mean concentrations (EMCs) was suspended solids (SS) 547 ~ 2600 mg l−1, biochemical oxygen demand (BOD) 8.7 ~ 50.7 mg l−1, total nitrogen (TN) 3.5 ~ 21.8 mg l−1, and total phosphorus (TP) 2.4 ~ 13.1 mg l−1. Experiments treated by a rice straw mat mulch (S), S with gypsum (SG), and SG with PAM (SPG) showed good results as best management practices (BMPs) in controlling NPS pollution from sloping fields. The range of reductions by the treatments was runoff 28.3 ~ 96.7%, SS 71.5 ~ 99.5%, BOD 37.5 ~ 91.9%, TN 32.4 ~ 91.0%, and TP 43.0 ~ 95.7%. The SPG showed the best reduction effect for both runoff and NPS pollution. The S also showed encouraging results as a prospective BMP. Crop yields under the treatments also increased by up to 740% (lettuce) and 6.1 ~ 39.2% (cabbage and radish). The mulch treatments were proven to be effective for the increase of farm productivity and to improve runoff quality as well. Copyright © 2016 John Wiley & Sons, Ltd.
Membrane skeleton orchestrates the platelet glycoprotein (GP) Ib‐IX complex clustering and signaling
Authors: Shang Dan , Zhang Zuping , Wang Qian , Ran Yali , Shaw Tanner S. , Van John N. , Peng Yuandong 
Published: September 2016

SummaryPlatelet glycoprotein Ib‐IX complex is affixed to the membrane skeleton through interaction with actin binding protein 280 (ABP‐280). We find that removal of the ABP‐280 binding sites in GP Ibα cytoplasmic tail has little impact on the complex clustering induced by antibody crosslinking. However, large truncation of the GP Ibα cytoplasmic tail allows the formation of larger patches of the complex, suggesting that an ABP‐280 independent force may exist. Besides, we observe that the signaling upon GP Ib‐IX clustering is elicited in both membrane lipid domain dependent and independent manner, a choice that relies on how the membrane skeleton interacts with the complex. Our findings suggest a more complex mechanism for how the membrane skeleton regulates the GP Ib‐IX function. © 2016 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 68(10):823–829, 2016
Photobiomodulation reduces abdominal adipose tissue inflammatory infiltrate of diet‐induced obese and hyperglycemic mice
Authors: Yoshimura Tania Mateus , Sabino Caetano Padial , Ribeiro Martha Simões 
Published: September 2016

Systemic inflammation is closely related to the development of insulin resistance and type‐2 diabetes, since the activation of pro‐inflammatory pathways leads to inhibition of insulin signaling. Although photobiomodulation (PBM) has proven beneficial effects on the treatment of inflammatory disorders, the phototherapeutic approach to manage the chronic inflammatory component of obesity and hyperglycemia had never been explored. In this work, obese and hyperglycemic mice are treated with PBM, and their body mass, glycemia and inflammatory infiltrate of abdominal adipose tissue are evaluated. During four weeks, irradiated animals are exposed to six irradiation sessions using an 843 nm LED (5.7 J cm–2 at 19 mW cm–2 per session). Non‐irradiated control animals display inflammatory areas almost five times greater than the treated group (p < 0.001). This result on inflammatory infiltrate may have caused impacts on the significant lower blood glucose level from irradiated animals (p = 0.04), twenty‐four hours after the last irradiation session.
PBM on obese and hyperglycemic mice reduced five times the areas of inflammatory infiltrate within abdominal adipose tissue (a, b), whereas dense inflammatory regions were a common finding amidst non‐irradiated animals (c). The asterisks on (c) correspond to the inflammatory infiltrate permeating adipocytes.magnified imagePBM on obese and hyperglycemic mice reduced five times the areas of inflammatory infiltrate within abdominal adipose tissue (a, b), whereas dense inflammatory regions were a common finding amidst non‐irradiated animals (c). The asterisks on (c) correspond to the inflammatory infiltrate permeating adipocytes.
Extracellular matrix‐derived hydrogels for dental stem cell delivery
Authors: Viswanath Aiswarya , Vanacker Julie , Germain Loïc , Leprince Julian G. , Diogenes Anibal , Shakesheff Kevin M. , White Lisa J. , des Rieux Anne 
Published: September 2016

AbstractDecellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre‐clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site‐specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site‐specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319–328, 2017.
Cost-Effectiveness of Orthogeriatric and Fracture Liaison Service Models of Care for Hip Fracture Patients: A Population-Based Study
Authors: Leal Jose , Gray Alastair M , Hawley Samuel , Prieto-Alhambra Daniel , Delmestri Antonella , Arden Nigel K , Cooper Cyrus , Javaid M Kassim , Judge Andrew ,   and the REFReSH Study Group
Published: September 2016

ABSTRACT

Fracture liaison services are recommended as a model of best practice for organizing patient care and secondary fracture prevention for hip fracture patients, although variation exists in how such services are structured. There is considerable uncertainty as to which model is most cost-effective and should therefore be mandated. This study evaluated the cost- effectiveness of orthogeriatric (OG)- and nurse-led fracture liaison service (FLS) models of post-hip fracture care compared with usual care. Analyses were conducted from a health care and personal social services payer perspective, using a Markov model to estimate the lifetime impact of the models of care. The base-case population consisted of men and women aged 83 years with a hip fracture. The risk and costs of hip and non-hip fractures were derived from large primary and hospital care data sets in the UK. Utilities were informed by a meta-regression of 32 studies. In the base-case analysis, the orthogeriatric-led service was the most effective and cost-effective model of care at a threshold of £30,000 per quality-adjusted life years gained (QALY). For women aged 83 years, the OG-led service was the most cost-effective at £22,709/QALY. If only health care costs are considered, OG-led service was cost-effective at £12,860/QALY and £14,525/QALY for women and men aged 83 years, respectively. Irrespective of how patients were stratified in terms of their age, sex, and Charlson comorbidity score at index hip fracture, our results suggest that introducing an orthogeriatrician-led or a nurse-led FLS is cost-effective when compared with usual care. Although considerable uncertainty remains concerning which of the models of care should be preferred, introducing an orthogeriatrician-led service seems to be the most cost-effective service to pursue. © 2016 American Society for Bone and Mineral Research.
The Game Saturation Number of a Graph
Authors: Carraher James M. , Kinnersley William B. , Reiniger Benjamin , West Douglas B. 
Published: September 2016

AbstractGiven a family and a host graph H, a graph is ‐saturated relative to H if no subgraph of G lies in but adding any edge from to G creates such a subgraph. In the ‐saturation game on H, players Max and Min alternately add edges of H to G, avoiding subgraphs in , until G becomes ‐saturated relative to H. They aim to maximize or minimize the length of the game, respectively; denotes the length under optimal play (when Max starts).Let denote the family of odd cycles and the family of n‐vertex trees, and write F for when . Our results include , for , for , and for . We also determine ; with , it is n when n is even, m when n is odd and m is even, and when is odd. Finally, we prove the lower bound . The results are very similar when Min plays first, except for the P4‐saturation game on .
Localized application of sewage sludge improved plant nitrogen and phosphorus uptake by rhizobox‐grown spring wheat
Authors: Wang Yaosheng , Jensen Lars Stoumann , Magid Jakob 
Published: September 2016

AbstractSewage sludge (SS) can be used as an alternative fertilizer in agriculture. It is normally broadcasted and plowed into soil, but it is not clear if it has a potential as a placement fertilizer. A rhizobox experiment was conducted to investigate the placement effect of SS and mineral nitrogen (N) fertilizer on shoot and root growth as well as nutrient uptake of spring wheat (Triticum aestivumL.). The treatments included localized SS, mixed SS, localized SS and ammonium, localized ammonium, and a control without addition of SS and ammonium to examine the effect of SS placement and, further, if ammonium co‐localization would enhance the placement effect. The results show that SS fertilization improved soil N and P availability, which significantly increased plant N and P uptake and enhanced shoot growth, while root length was significantly reduced compared to the control. Localized SS increased root proliferation in the placement region, resulting in enhanced uptake of P from the SS patch compared to homogenous application. However, co‐localized application of ammonium with SS significantly depressed plant shoot and root growth. Localized ammonium markedly restricted root proliferation in the placement region and reduced soil pH in both bulk soil and placement region, contributing to decreased nutrient uptake and plant growth.