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Clinical Research
Attentional selection predicts rapid automatized naming ability in Chinese-speaking children with ADHD
Apr 21, 2017   Scientific Reports
Wang E, Sun M, Tao Y, Gao X, Guo J, Zhao C, Li H, Qian Q, Wu Z, Wang Y, Sun L, Song Y
Attentional selection predicts rapid automatized naming ability in Chinese-speaking children with ADHD
Apr 21, 2017
Scientific Reports
Children with attention-deficit/hyperactivity disorder (ADHD) are reported to have a significantly higher risk of showing reading difficulties or disorders. Here, we aimed to identify the relationship between electroencephalographic (EEG) marker of spatial attention and reading ability in Chinese children with ADHD. First, we demonstrated that rapid automatized naming (RAN) is a strong predictor of reading ability in Chinese-speaking children. Then, EEG data of 9-to 15-year-old children with ADHD (n = 38) and typically developing (TD) controls (n = 36) were collected while the children performed a classical visual search task. Children with ADHD showed slower RAN speed than TD children. For event-related potentials (ERPs), children with ADHD showed a reduced target-evoked N2pc component, which predicted their poorer RAN performance. However, in TD children the early occipital P1 amplitude was negatively correlated with their RAN performance. The correlation between decreased N2pc and poor RAN performance in children with ADHD suggests that their reading problems may in part be due to impaired attentional selection. In contrast, in TD children, development in early visual processing co-occurs with improvements in reading ability.
Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis: An Expert Statement
Apr 21, 2017   European Heart Journal
Ruiz CE, Hahn RT, Berrebi A, Borer JS, Cutlip DE,   . . . . . .   , Weissman NJ, Zamorano JL, Serruys PW, Leon MB, of the Paravalvular Leak Academic Research Consortium
Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis: An Expert Statement
Apr 21, 2017
European Heart Journal
The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted. © 2017 American College of Cardiology Foundation and European Society of Cardiology. This article is being published concurrently in Journal of the American College of Cardiology, 10.1016/j.jacc.2017.02.038. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.
Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants
Apr 22, 2017   Human Mutation
Tio M, Wen R, Lim YL, Zukifli ZHB, Xie S, Ho P, Zhou Z, Koh TW, Zhao Y, Tan EK
Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants
Apr 22, 2017
Human Mutation
Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.182C>T, p.Thr61Ile and c.434G>A, p.Arg145Gln) and the risk (c.5C>T, p.Pro2Leu) CHCHD2 variants. All the transgenic models exhibited locomotor dysfunction which could be exacerbated by rotenone exposure, dopaminergic neuron degeneration, reduction in lifespan, mitochondrial dysfunction, oxidative stress and impairment in synaptic transmission. However, both mutants showed more severe early motor dysfunction, dopaminergic neuronal loss and higher hydrogen peroxide production compared to risk variant. p.Thr61Ile (co-segregated in three independent PD families) displayed the most severe phenotype followed by p.Arg145Gln (present only in index patient). We treated the transgenic flies with Ebselen, a mitochondrial hydrogen peroxide scavenger compound and Ebselen appears to be more effective in ameliorating motor function in the mutant than the risk variant models. We provide the first in vivo evidence of the pathological effects associated with CHCHD2 mutations. There was a difference in the pathological and drug response effects between the pathogenic and the risk variants. Ebselen may be a useful neuroprotective drug for carriers of CHCHD2 mutations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature
Apr 22, 2017   PharmacoEconomics
IJzerman MJ, Koffijberg H, Fenwick E, Krahn M
Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature
Apr 22, 2017
PharmacoEconomics
Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be "all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty". The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios.
Temporal trends of lipophilic persistent organic pollutants in serum from Danish nulliparous pregnant women 2011-2013
Apr 22, 2017   Environmental Science And Pollution Research International
Bjerregaard-Olesen C, Long M, Ghisari M, Bech BH, Nohr EA, Uldbjerg N, Henriksen TB, Olsen J, Bonefeld-Jørgensen EC
Temporal trends of lipophilic persistent organic pollutants in serum from Danish nulliparous pregnant women 2011-2013
Apr 22, 2017
Environmental Science And Pollution Research International
The use of the lipophilic persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs) and several organochlorine pesticides (OCPs) has been prohibited for more than 30 years. In this study, we present the temporal trends of the lipophilic POP serum concentrations in Danish nulliparous pregnant women between 2011 and 2013. We randomly selected 197 pregnant women (gestational age 11-13) from the Aarhus Birth Cohort. The concentrations of the lipophilic POPs in the serum samples were analyzed using gas chromatography. The concentrations were corrected for total serum lipids. The statistical analysis was performed by regression analysis with adjustment for age, BMI, gestational age at blood draw, and smoking status. The serum concentrations of PCB 118, 138, 153, 156, 170, 180, 187, and hexachlorobenzen, trans-nonachlor, β-hexachlorocyclohexane (β-HCH), and p,p'-dichlorodiphenyldichloroethylene were lower in 2013 than in 2011. However, the oxychlordane concentration was lowest in 2011. The serum levels of most lipophilic POPs followed downward trends during the study period, which was expected, as these compounds has been banned for many years. The upward trend of oxychlordane was unexpected and presumably a chance finding.
Pediatric tonsillectomy is a resource-intensive procedure: a study of Canadian health administrative data
Apr 22, 2017   Canadian Journal Of Anaesthesia = Journal Canadien D'anesthesie
Murto KTT, Katz SL, McIsaac DI, Bromwich MA, Vaillancourt R, van Walraven C
Pediatric tonsillectomy is a resource-intensive procedure: a study of Canadian health administrative data
Apr 22, 2017
Canadian Journal Of Anaesthesia = Journal Canadien D'anesthesie
The majority of pediatric surgeries are performed in a day surgery setting. The rate of adverse postoperative outcomes and the factors that influence them are poorly described in the Canadian setting. Concerns about the safety of adenotonsillectomy (AT) have been raised. The objective of this Ontario-based study was to determine the rates and risks of hospital readmission, emergency department (ED) visits, or deaths within 30 days following common pediatric surgeries, with an emphasis on AT. Inpatient and day surgery children who were < 18 yr of age and undergoing one of the ten most common surgeries in Ontario from 2002-2013 were identified by linking four provincial health administrative databases. Risk of each outcome was determined separately for all surgeries. Cox regression was used to measure the association of demographics, clinical factors, Ontario drug benefit (ODB) status, and prescribed opioids with adverse outcomes. Among 364,629 children, AT accounted for 30.5% of all surgeries. The AT patient rates of readmission and ED visits compared with the full study cohort were 2.7% vs 1.5% and 12.4% vs 9.2%, respectively. The study cohort postoperative death rate was 0.27 per 10,000 children (95% confidence interval [CI], 0.18 to 0.39). For the study cohort, an increased risk of readmission was associated with previous urgent admission (hazard ratio [HR], 2.15; 95% CI, 1.75 to 2.63), length-of-stay ≥ four days (HR, 2.04; 95% CI, 1.57 to 2.65), Charlson comorbidity score ≥ 1 (HR, 1.61; 95% CI, 1.17 to 2.22), and age ≥ 14 yr (HR, 1.15; 95% CI, 1.02 to 1.19) or ≤ 3 yr (HR, 1.16; 95% CI, 1.15 to 1.17). Similar factors were associated with an increased risk of ED visits. Patients covered by ODB (11.8%), particularly those prescribed opioids, had an increased risk for readmission and ED visit. Post-discharge readmissions and ED visits are relatively common after pediatric surgery, particularly for AT. Perioperative treatment algorithms that consider risk factors for hospital revisits are required in children.
Clinical features and long-term outcomes of pediatric spinal meningiomas
Apr 22, 2017   Journal Of Neuro-oncology
Wu L, Yang C, Liu T, Fang J, Yang J, Xu Y
Clinical features and long-term outcomes of pediatric spinal meningiomas
Apr 22, 2017
Journal Of Neuro-oncology
Pediatric spinal meningiomas are very rare. Most studies on pediatric spinal meningiomas are case reports with literature reviews. This study presented a surgical series of 14 pediatric patients with histologically proven sporadic spinal meningiomas, including 5 WHO grade II tumors. In this series, there were 9 male and 5 female patients with a mean age of 11.1 years. Seven tumors were located in the cervical spine, 5 in the thoracic spine, and 2 in the lumbar spine. Gross total resection (GTR) of the tumor with a well-demarcated dissection plane was achieved in 11 cases, subtotal resection was achieved in 2 cases, and partial resection was performed in 1 case. The symptoms were improved in 10 cases at the last follow-up and the current status of 2 patients worsened and 1 patient had no change compared to the preoperative presentation. One patient died of progressive tumor regrowth after partial resection and adjuvant radiotherapy. The postoperative follow-up magnetic resonance imaging showed tumor recurrence in one of the 11 GTR cases during the mean follow-up period of 72.5 months. Recurrence/regrowth of the residual tumors was observed in both the 2 STR cases. Although pediatric spinal meningiomas have a higher incidence of WHO grade II meningiomas, they are amenable to surgery if it is possible to achieve GTR. A good clinical outcome after GTR can be expected, even for WHO grade II meningiomas. Effect of adjuvant radiochemotherapy for controlling the tumors is still unclear and requires further investigation.
AMPK signaling in the nucleus accumbens core mediates cue-induced reinstatement of cocaine seeking
Apr 22, 2017   Scientific Reports
Gao XJ, Yuan K, Cao L, Yan W, Luo YX, Jian M, Liu JF, Fang Q, Wang JS, Han Y, Shi J, Lu L
AMPK signaling in the nucleus accumbens core mediates cue-induced reinstatement of cocaine seeking
Apr 22, 2017
Scientific Reports
Relapse to drug seeking can be caused by exposure to drug-associated cues, provoking drug craving even after prolonged abstinence. Recent studies demonstrated that AMP-activated protein kinase (AMPK) regulates neuronal morphology and membrane excitability in neurons. Here, we investigated the role of AMPK activity in the nucleus accumbens (NAc) in relapse to cocaine seeking. We found that exposure to drug-related cues reinstated cocaine-seeking behavior and increased AMPK and p70s6k phosphorylation in the NAc core but not shell. Augmenting AMPK activity by intra-NAc core infusions of the AMPK activator 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) or adenovirus expressing constitutively active subunits of AMPK decreased cue-induced reinstatement of cocaine seeking and inhibited the mammalian target of rapamycin complex 1 (mTORC1) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways. In contrast, inhibition of AMPK activity by intra-NAc core infusions of the AMPK inhibitor compound C or adenovirus expressing dominant-negative subunits of AMPK increased cue-induced reinstatement of cocaine seeking and enhanced mTORC1 and ERK1/2 activity. The regulation of AMPK activity in the NAc shell had no effect on cue-induced cocaine seeking. Altogether, these results indicate that AMPK activity in the NAc core is critical for the cue-induced reinstatement of cocaine seeking, which may be mediated by mTORC1 and ERK1/2 signaling.
Quantitative Imaging of Cerebral Thromboemboli In Vivo: The Effects of Tissue-Type Plasminogen Activator
Apr 22, 2017   Stroke
Kim DE, Kim JY, Schellingerhout D, Ryu JH, Lee SK,   . . . . . .   , Kim EJ, Kwon IC, Ahn CH, Nahrendorf M, Kim K
Quantitative Imaging of Cerebral Thromboemboli In Vivo: The Effects of Tissue-Type Plasminogen Activator
Apr 22, 2017
Stroke
Quantitative imaging for the noninvasive assessment of thrombolysis is needed to advance basic and clinical thrombosis-related research and tailor tissue-type plasminogen activator (tPA) treatment for stroke patients. We quantified the evolution of cerebral thromboemboli using fibrin-targeted glycol chitosan-coated gold nanoparticles and microcomputed tomography, with/without tPA therapy. We injected thrombi into the distal internal carotid artery in mice (n=50). Fifty-five minutes later, we injected fibrin-targeted glycol chitosan-coated gold nanoparticles, and 5 minutes after that, we treated animals with tPA or not (25 mg/kg). We acquired serial microcomputed tomography images for 24 hours posttreatment. Thrombus burden at baseline was 784×103±59×103 μm2 for the tPA group (n=42) and 655×103±103×103 μm2 for the saline group (n=8; P=0.37). Thrombus shrinkage began at 0.5 to 1 hour after tPA therapy, with a maximum initial rate of change at 4603±957 μm2/min. The rate of change lowered to ≈61% level of the initial in hours 1 to 2, followed by ≈29% and ≈1% in hours 2 to 3 and 3 to 24, respectively. Thus, 85% of total thrombolysis over 24 hours (≈500 μm2, equivalent to 64% of the baseline thrombus burden) occurred within the first 3 hours of treatment. Thrombus burden at 24 hours could be predicted at around 1.5 to 2 hours. Saline treatment was not associated with significant changes in the thrombus burden. Infarct size was smaller in the tPA group versus saline group (18.1±2.3 versus 45.8±3.3 mm2; P
Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis
Apr 22, 2017   BMC Ophthalmology
Wu MY, Wu Y, Zhang Y, Liu CY, Deng CY, Peng L, Zhou L
Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis
Apr 22, 2017
BMC Ophthalmology
Matrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk. Related studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. Overall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I2 = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I2 = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I2 = 0%). Our meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.
Validation of the Essen Stroke Risk Score in different subtypes of ischemic stroke
Apr 22, 2017   Neurological Research
Liu Y, Wang Y, Li WA, Yan A, Wang Y
Validation of the Essen Stroke Risk Score in different subtypes of ischemic stroke
Apr 22, 2017
Neurological Research
Predictive scores are important tools for stratifying patients based on their risk of future vascular events and for selecting preventive therapies. The aim of this study is to validate the Essen Stroke Risk Score (ESRS) for stratifying stroke recurrence in different subtypes of non-atrial fibrillation ischemic stroke in a large Chinese cohort. Data were derived from the Blood pressure and clinical Outcome in Stroke Survivors registry, which includes a cohort of 2204 stroke patients. All patients were further classified according to the TOAST (Trial of Org 10 172 in Acute Stroke Treatment) criteria. We stratified one-year cumulative rates for stroke and composite vascular events using the ESRS. The predictive power of the ESRS was assessed using the area under the receiver-operator curves (AUC). Among 1699 patients included in the study, the AUC of ESRS was 0.58 (95% CI: 0.52-0.64) for recurrent stroke, whereas 0.59 (95% CI: 0.53-0.64) for composite vascular events at 1 year. In patients with large-artery atherosclerosis (LAA) subtype of stroke, the AUC of ESRS was both 0.61 (95% CI: 0.54-0.68) for recurrent stroke and composite vascular events. However, no significant AUC was observed in patients with small-artery occlusion subtype of stroke. In patients with LAA subtype of non-atrial fibrillation stroke, the ESRS has moderate accuracy in stratifying the risk of both recurrent strokes and major vascular events within the first year. However, the ESRS couldn't accurately stratify the risk of recurrent strokes in patients with small-artery atherosclerosis subtype of non-atrial fibrillation stroke.
J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge
Apr 21, 2017   Europace : European Pacing, Arrhythmias, And Cardiac Electrophysiology : Journal Of The Working Groups On Cardiac Pacing, Arrhythmias, And Cardiac Cellular Electrophysiology Of The European Society Of Cardiology
Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D,   . . . . . .   , Nam GB, Sacher F, Shimizu W, Viskin S, Wilde AAM
J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge
Apr 21, 2017
Europace : European Pacing, Arrhythmias, And Cardiac Electrophysiology : Journal Of The Working Groups On Cardiac Pacing, Arrhythmias, And Cardiac Cellular Electrophysiology Of The European Society Of Cardiology
Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome
Apr 21, 2017   PloS One
Jun JE, Lee SE, Lee YB, Jee JH, Bae JC, Jin SM, Hur KY, Lee MK, Kim JH
Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome
Apr 21, 2017
PloS One
Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.
C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells
Apr 21, 2017   Scientific Reports
Wang Y, Fu D, Su J, Chen Y, Qi C, Sun Y, Niu Y, Zhang N, Yue D
C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells
Apr 21, 2017
Scientific Reports
Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein and can be upregulated or activated in a variety of malignant tumors, including those from thyroid, colon and breast, but its role remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in RCC cell influenced expression of multiple genes associated with cell adhesion, among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a reduction of C1QBP. In turn, cell adhesion and invasion abilities were significantly increased with increased metastasis to lung and liver in vivo. C1QBP may regulate RCC cell adhesion and invasion through influencing the p-GSK3/β-Catenin/L1CAM expression. Over all, our study demonstrated that C1QBP could regulate RCC metastasis by regulating the GSK3/β-Catenin/L1CAM signaling pathway.
Midkine promotes hepatocellular carcinoma metastasis by elevating anoikis resistance of circulating tumor cells
Apr 21, 2017   Oncotarget
Sun B, Hu C, Yang Z, Zhang X, Zhao L, Xiong J, Ma J, Chen L, Qian H, Luo X, Shi L, Li J, Cheng X, Yin Z
Midkine promotes hepatocellular carcinoma metastasis by elevating anoikis resistance of circulating tumor cells
Apr 21, 2017
Oncotarget
Midkine is overexpressed in hepatocellular carcinoma (HCC) and plays a role in tumor progression, but less is known about its role in resistance of circulating tumor cells (CTCs) to anoikis which leading to recurrence and metastasis. The aim of the present study was to analyze whether midkine was associated with HCC progression with anoikis resistance. We found that cultured HCC cells were more resistant to anoikis, which paralleled midkine expression, and midkine treatment significantly inhibited anoikis in a dose-dependent manner. Furthermore, in in vitro and in vivo assays, knockdown of midkine resulted in significant sensitivity to anoikis, decreased cell survival and significantly decreased tumor occurrence rate. Patients with midkine-elevated HCC had higher CTC counts and less apoptotic CTCs, as well as significantly higher recurrence rate and shorter recurrence-free interval. To understand the molecular mechanism underlying the midkine with HCC progression, we performed in vitro and in vivo studies. We found that midkine plays an important role in enhancement of HCC cell resistance to anoikis, thereby promoting subsequent metastasis. Activation of PI3K/Akt/NF-κB/TrkB signaling by midkine-activated anaplastic lymphomakinase (ALK) is responsible for anoikis resistance.
Tumor heterogeneity assessed by texture analysis on contrast-enhanced CT in lung adenocarcinoma: association with pathologic grade
Apr 21, 2017   Oncotarget
Liu Y, Liu S, Qu F, Li Q, Cheng R, Ye Z
Tumor heterogeneity assessed by texture analysis on contrast-enhanced CT in lung adenocarcinoma: association with pathologic grade
Apr 21, 2017
Oncotarget
Objectives To investigate whether texture features on contrast-enhanced computed tomography (CECT) images of lung adenocarcinoma have association with pathologic grade.Methods A cohort of 148 patients with surgically operated adenocarcinoma was retrospectively reviewed. Fifty-four CT features of the primary lung tumor were extracted from CECT images using open-source 3D Slicer software; meanwhile, enhancement homogeneity was evaluated by two radiologists using visual assessment. Multivariate logistic regression analysis was performed to determine significant image indicator of pathologic grade.Results Tumors of intermediate grade were more likely to be never smokers (P=0.020). Enhancement heterogeneity by visual assessment showed no statistical difference between intermediate grade and high grade (P=0.671). Among those 54 features, 29 of them were significantly associated with pathologic grade. Multivariate logistic regression analyses identified F33 (Homogeneity 1) (P=0.005) and F38 (Inverse Variance) (P=0.032) as unique independent image indicators of pathologic grade, and the AUC calculated from this model (AUC=0.834) was higher than clinical model (AUC=0.615) (P=0.0001).Conclusions Our study revealed that texture analysis on CECT images could be helpful in predicting pathologic grade of lung adenocarcinoma.
Enhancing Insights into Pulmonary Vascular Disease (PVD) Through a Precision Medicine Approach. A Joint NHLBI-CMREF Workshop Report
Apr 21, 2017   American Journal Of Respiratory And Critical Care Medicine
Newman JH, Rich S, Abman SH, Alexander JH, Barnard J,   . . . . . .   , Tapson VF, Lowy N, Stockbridge N, Weinmann G, Xiao L
Enhancing Insights into Pulmonary Vascular Disease (PVD) Through a Precision Medicine Approach. A Joint NHLBI-CMREF Workshop Report
Apr 21, 2017
American Journal Of Respiratory And Critical Care Medicine
The Division of Lung Diseases of the National Heart, Lung and Blood Institute, (NHLBI) and the Cardiovascular Medical Education and Research Fund (CMREF), held a workshop to discuss to leverage of the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension (PH) through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program. PVDOMICS is a protocol driven network to analyze PH patient populations to define novel pulmonary vascular disease (PVD) phenotypes. Basic, translational and clinical investigators, patient advocacy organizations, regulatory agencies, and pharmaceutical industry experts discussed the application of precision medicine to PVD clinical trials. Discussion of priorities in line with NHLBI Strategic Vision Goals included: 1. A national effort to coordinate bio-samples and bio-data from all funded programs to a web based repository so that information can be shared and correlated with other research projects. Example NHLBI programs include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative (PHBI), the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. 2. A taskforce to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: a. Adoption of smaller clinical trials that incorporate biomarker guided strategies, using adaptive and innovative statistical designs. b. Development of newer endpoints that reflect well-defined and clinically meaningful changes. 3. Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic and metabolic tests that will help precisely identify individual and shared features of PVD, and serve as the basis of novel phenotypes for therapeutic interventions.
Associations between childhood maltreatment and non-medical use of prescription drugs among Chinese adolescents
Apr 21, 2017   Addiction (Abingdon, England)
Guo L, Xu Y, Deng J, Gao X, Huang G, Huang J, Deng X, Zhang WH, Lu C
Associations between childhood maltreatment and non-medical use of prescription drugs among Chinese adolescents
Apr 21, 2017
Addiction (Abingdon, England)
To test, among Chinese adolescents: (1) whether childhood maltreatment is associated with non-medical use of prescription drugs (NMUPD), (2) whether there are interaction effects of childhood maltreatment and depressive symptoms on NMUPD. A secondary analysis of the cross-sectional data collected from 7th and 12th graders who were sampled using a multistage, stratified cluster, random sampling method in the 2015 School-based Chinese Adolescents Health Survey (SCAHS). Surveys conducted in high schools in six cities of China in 2015. There were 24,457 students who were invited to participate and 23,039 students' questionnaires were completed and qualified for our survey. The outcomes comprised self-report of NMUPD (prior 30 days); a history of childhood maltreatment was our main predictor; other covariates included depressive symptoms, smoking, drinking, and demographics. Data were analyzed using multi-level regression modeling. Our final multivariable logistic regression models demonstrated that after adjusting for other variables, physical abuse was positively associated with non-medical use of opioids (adjusted odds ratio [AOR] = 1.13, 95% confidence interval [CI] = 1.10-1.22), sedatives (AOR = 1.11, 95% CI = 1.10-1.21), and any prescription drugs (AOR = 1.13, 95% CI = 1.09-1.20); emotional abuse, sexual abuse, and emotional neglect were also associated with an increased risk of opioids misuse, sedatives misuse, and any prescription drugs misuse; students who reported that they had experienced childhood physical neglect were more likely to be involved in the non-medical use of sedatives (AOR = 1.08, 95% CI = 1.04-1.12) and any prescription drugs (AOR = 1.06, 95% CI = 1.03-1.10). Additionally, there was no evidence of interaction effects on NMUPD between depressive symptoms and each of physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect, respectively. . Maltreatment while a child is associated with an increased risk of non-medical use of prescription drugs (NMUPD) among Chinese adolescents. The interactions of maltreatment while a child and depressive symptoms do not appear to be significantly associated with NMUPD among Chinese adolescents. This article is protected by copyright. All rights reserved.
Dying in hospital: socioeconomic inequality trends in England
Apr 21, 2017   Journal Of Health Services Research & Policy
Barratt H, Asaria M, Sheringham J, Stone P, Raine R, Cookson R
Dying in hospital: socioeconomic inequality trends in England
Apr 21, 2017
Journal Of Health Services Research & Policy
Objective To describe trends in socioeconomic inequality in the proportion of deaths occurring in hospital, during a period of sustained effort by the NHS in England to improve end of life care. Methods Whole-population, small area longitudinal study involving 5,260,871 patients of all ages who died in England from 2001/2002 to 2011/2012. Our primary measure of inequality was the slope index of inequality. This represents the estimated gap between the most and least deprived neighbourhood in England, allowing for the gradient in between. Neighbourhoods were geographic Lower Layer Super Output Areas containing about 1500 people each. Results The overall proportion of patients dying in hospital decreased from 49.5% to 43.6% during the study period, after initially increasing to 52.0% in 2004/2005. There was substantial 'pro-rich' inequality, with an estimated difference of 5.95 percentage points in the proportion of people dying in hospital (confidence interval 5.26 to 6.63), comparing the most and least deprived neighbourhoods in 2011/2012. There was no significant reduction in this gap over time, either in absolute terms or relative to the mean, despite the overall reduction in the proportion of patients dying in hospital. Conclusions Efforts to reduce the proportion of patients dying in hospital in England have been successful overall but did not reduce inequality. Greater understanding of the reasons for such inequality is required before policy changes can be determined.
Are some areas more equal than others? Socioeconomic inequality in potentially avoidable emergency hospital admissions within English local authority areas
Apr 21, 2017   Journal Of Health Services Research & Policy
Sheringham J, Asaria M, Barratt H, Raine R, Cookson R
Are some areas more equal than others? Socioeconomic inequality in potentially avoidable emergency hospital admissions within English local authority areas
Apr 21, 2017
Journal Of Health Services Research & Policy
Objectives Reducing health inequalities is an explicit goal of England's health system. Our aim was to compare the performance of English local administrative areas in reducing socioeconomic inequality in emergency hospital admissions for ambulatory care sensitive chronic conditions. Methods We used local authority area as a stable proxy for health and long-term care administrative geography between 2004/5 and 2011/12. We linked inpatient hospital activity, deprivation, primary care, and population data to small area neighbourhoods (typical population 1500) within administrative areas (typical population 250,000). We measured absolute inequality gradients nationally and within each administrative area using neighbourhood-level linear models of the relationship between national deprivation and age-sex-adjusted emergency admission rates. We assessed local equity performance by comparing local inequality against national inequality to identify areas significantly more or less equal than expected; evaluated stability over time; and identified where equity performance was steadily improving or worsening. We then examined associations between change in socioeconomic inequalities and change in within-area deprivation (gentrification). Finally, we used administrative area-level random and fixed effects models to examine the contribution of primary care to inequalities in admissions. Results Data on 316 administrative areas were included in the analysis. Local inequalities were fairly stable between consecutive years, but 32 areas (10%) showed steadily improving or worsening equity. In the 21 improving areas, the gap between most and least deprived fell by 3.9 admissions per 1000 (six times the fall nationally) between 2004/5 and 2011/12, while in the 11 areas worsening, the gap widened by 2.4. There was no indication that measured improvements in local equity were an artefact of gentrification or that changes in primary care supply or quality contributed to changes in inequality. Conclusions Local equity performance in reducing inequality in emergency admissions varies both geographically and over time. Identifying this variation could provide insights into which local delivery strategies are most effective in reducing such inequalities.
A comparison of clinical characteristics of older adults treated with antidepressants in general and psychiatric hospitals in Asia
Apr 21, 2017   Psychogeriatrics : The Official Journal Of The Japanese Psychogeriatric Society
Wang YY, Xiang YT, Ungvari GS, Ng CH, Chiu HFK,   . . . . . .   , Sartorius N, Mahendran R, Teng JY, Tan CH, Shinfuku N
A comparison of clinical characteristics of older adults treated with antidepressants in general and psychiatric hospitals in Asia
Apr 21, 2017
Psychogeriatrics : The Official Journal Of The Japanese Psychogeriatric Society
This study compared the demographics, clinical characteristics, and antidepressant prescription patterns between Asian patients aged 50 years and older attending psychiatric hospitals and those attending general hospitals. In total, 955 patients (604 in general hospitals, 351 in psychiatric hospitals) aged 50 years or older treated with antidepressants in 10 Asian countries and territories were examined. Patients' demographics, clinical features, and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. Binary logistic regression revealed that high income and diagnosis of schizophrenia were independently associated with psychiatric hospital treatment, whereas outpatient care, diagnosis of anxiety disorders, and multiple major medical conditions were independently associated with general hospital treatment. In addition, tetracyclic and noradrenergic and specific serotonergic antidepressants were more likely to be prescribed in general hospitals. Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia. © 2017 Japanese Psychogeriatric Society.
Foxo1 Attenuates NaF-Induced Apoptosis of LS8 Cells through the JNK and Mitochondrial Pathways
Apr 21, 2017   Biological Trace Element Research
Li J, Zhao L, Zhao X, Wang P, Liu Y, Ruan J
Foxo1 Attenuates NaF-Induced Apoptosis of LS8 Cells through the JNK and Mitochondrial Pathways
Apr 21, 2017
Biological Trace Element Research
Fluoride-induced ameloblast apoptosis is a key event in dental fluorosis development. Forkhead box o1 (Foxo1) is a transcription factor involved in cell apoptosis. The present study aims to investigate the effect of Foxo1 on ameloblast apoptosis induced by fluoride in vitro and to explore its possible mechanism. Ameloblast-like cells (LS8 cells) were exposed to various concentrations of NaF for up to 48 h. Foxo1 activation was modulated using lentiviral vectors, and cell apoptosis was measured by flow cytometry. The expression levels of Foxo1, c-Jun N-terminal kinase (JNK), and some well-known regulators of the mitochondrial pathway of apoptosis (cytoplasmic cytochrome c, cleaved caspase-9, cleaved caspase-3, Bcl-2, and Bax) were detected by quantitative real-time PCR, western blot, and immunofluorescence assay. The results showed significantly decreased expression and increased phosphorylation of Foxo1 in NaF-treated LS8 cells. Further investigation revealed that forced Foxo1 activation with lentiviral vectors attenuated NaF-induced apoptosis of LS8 cells, markedly decreasing protein levels of cytoplasmic cytochrome c, cleaved caspase-9, and cleaved caspase-3 while increasing the Bcl-2/Bax ratio and JNK expression level. These findings suggest that Foxo1 attenuated NaF-induced apoptosis of LS8 cells via inhibiting the mitochondrial pathway and activating JNK.
TBC1D24 Mutations in a Sibship with Multifocal Polymyoclonus
Apr 21, 2017   Tremor And Other Hyperkinetic Movements (New York, N.Y.)
Ngoh A, Bras J, Guerreiro R, McTague A, Ng J, Meyer E, Chong WK, Boyd S, MacLellan L, Kirkpatrick M, Kurian MA
TBC1D24 Mutations in a Sibship with Multifocal Polymyoclonus
Apr 21, 2017
Tremor And Other Hyperkinetic Movements (New York, N.Y.)
Advances in molecular genetic technologies have improved our understanding of genetic causes of rare neurological disorders with features of myoclonus. A family with two affected siblings, presenting with multifocal polymyoclonus and neurodevelopmental delay, was recruited for whole-exome sequencing following unyielding diagnostic neurometabolic investigations. Compound heterozygous mutations in TBC1D24, a gene previously associated with various epilepsy phenotypes and hearing loss, were identified in both siblings. The mutations included a missense change c.457G>A (p.Glu157Lys), and a novel frameshift mutation c.545del (p.Thr182Serfs*6). We propose that TBC1D24-related diseases should be in the differential diagnosis for children with polymyoclonus.
CMA down-regulates p53 expression through degradation of HMGB1 protein to inhibit irradiation-triggered apoptosis in hepatocellular carcinoma
Apr 21, 2017   World Journal Of Gastroenterology
Wu JH, Guo JP, Shi J, Wang H, Li LL, Guo B, Liu DX, Cao Q, Yuan ZY
CMA down-regulates p53 expression through degradation of HMGB1 protein to inhibit irradiation-triggered apoptosis in hepatocellular carcinoma
Apr 21, 2017
World Journal Of Gastroenterology
To investigate the mechanism of chaperone-mediated autophagy (CMA)-induced resistance to irradiation-triggered apoptosis through regulation of the p53 protein in hepatocellular carcinoma (HCC). Firstly, we detected expression of lysosome-associated membrane protein 2a (Lamp-2a), which is the key protein of CMA, by western blot in HepG2 and SMMC7721 cells after irradiation. We further used shRNA Lamp-2a HCC cells to verify the radioresistance induced by CMA. Next, we detected the HMGB1 and p53 expression after irradiation by western blot, and we further used RNA interference and ethyl pyruvate (EP), as a HMGB1 inhibitor, to observe changes of p53 expression. Finally, an immunoprecipitation assay was conducted to explore the interaction between Lamp-2a and HMGB1, and the data were analyzed. We found the expression of Lamp-2a was increased on irradiation while apoptosis decreased in HepG2 and SMMC7721 cells. The apoptosis was increased markedly in the shRNA Lamp-2a HepG2 and SMMC7721 cells as detected by western blot and colony formation assay. Next, we found p53 expression was gradually reduced on irradiation but obviously increased in shRNA Lamp-2a cells. Furthermore, p53 increased the cell apoptosis on irradiation in Hep3B (p53-/-) cells. Finally, p53 levels were regulated by HMGB1 as measured through RNA interference and the EP treatment. HMGB1 was able to combine with Lamp-2a as seen by immunoprecipitation assay and was degraded via the CMA pathway. The decreased HMGB1 inhibited p53 expression induced by irradiation and further reduced the apoptosis in HCC cells. CMA pathway activation appears to down-regulate the susceptibility of HCC to irradiation by degrading HMGB1 with further impact on p53 expression. These findings have clinical relevance for radiotherapy of HCC.
Safety of Sitagliptin in Patients with Type 2 Diabetes and Chronic Kidney Disease: Outcomes from TECOS
Apr 22, 2017   Diabetes, Obesity & Metabolism
Engel SS, Suryawanshi S, Stevens SR, Josse RG, Cornel JH, Jakuboniene N, Riefflin A, Tankova T, Wainstein J, Peterson ED, Holman RR, TECOS Study Group
Safety of Sitagliptin in Patients with Type 2 Diabetes and Chronic Kidney Disease: Outcomes from TECOS
Apr 22, 2017
Diabetes, Obesity & Metabolism
To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). For participants with baseline eGFR measurements (n = 14,528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR

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