Aripiprazole for the treatment of pediatric bipolar I disorder: a 30‐week,randomized, placebo‐controlled study

Objective: To evaluate the long‐term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder. Methods: A randomized, double‐blind, 30‐week, placebo‐controlled study of aripiprazole (10 or 30 mg/day) in youths (10–17 years) with bipolar I disorder (manic or mixed) ± psychotic features (n = 296) was performed. After four weeks, acute treatment completers continued receiving ≤26 weeks of double‐blind treatment (n = 210). The primary outcome was Young Mania Rating Scale (YMRS) total score change. Results: Of the 210 subjects who entered the 26‐week extension phase, 32.4% completed the study (45.3% for aripiprazole 10 mg/day, 31.0% for aripiprazole 30 mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p < 0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol‐specified last observation carried forward analyses, but not in observed case or mixed‐model repeated measures at week 30. Overall time to all‐cause discontinuation was longer for aripiprazole 10 mg/day (15.6 weeks) and aripiprazole 30 mg/day (9.5 weeks) compared with placebo (5.3 weeks; both p < 0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children’s Global Assessment of Functioning and Clinical Global Impressions‐Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder. Conclusions: Aripiprazole 10 mg/day and 30 mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30 weeks. Despite the benefits of treatment, completion rates were low in all treatment arms.     

Biological Activity of sym-Triazines with Acetylcholine-like Substitutions as Multitarget Modulators of Alzheimer’s Disease

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Polygenic effects of common single-nucleotide polymorphisms on life span: when association meets causality

Recently we have shown that the human life span is influenced jointly by many common single-nucleotide polymorphisms (SNPs), each with a small individual effect. Here we investigate further the polygenic influence on life span and discuss its possible biological mechanisms. First we identified six sets of prolongevity SNP alleles in the Framingham Heart Study 550K SNPs data, using six different statistical procedures (normal linear, Cox, and logistic regressions; generalized estimation equation; mixed model; gene frequency method). We then estimated joint effects of these SNPs on human survival. We found that alleles in each set show significant additive influence on life span. Twenty-seven SNPs comprised the overlapping set of SNPs that influenced life span, regardless of the statistical procedure. The majority of these SNPs (74%) were within genes, compared to 40% of SNPs in the original 550K set. We then performed a review of current literature on functions of genes closest to these 27 SNPs. The review showed that the respective genes are largely involved in aging, cancer, and brain disorders. We concluded that polygenic effects can explain a substantial portion of genetic influence on life span. Composition of the set of prolongevity alleles depends on the statistical procedure used for the allele selection. At the same time, there is a core set of longevity alleles that are selected with all statistical procedures. Functional relevance of respective genes to aging and major diseases supports causal relationships between the identified SNPs and life span. The fact that genes found in our and other genetic association studies of aging/longevity have similar functions indicates high chances of true positive associations for corresponding genetic variants.     

Influence of the cathode microstructure on the stability of inverted planar perovskite solar cells

One of the main challenges for perovskite solar cells (PSC) is their environmental stability, as oxygen and water induced aging may result in mobile decomposition compounds, which can enhance the recombination rate and react with charge carrier extraction layers or the contact metallization. In this contribution the importance of the microstructure of the contact metallization on the environmental cell stability is investigated. For this purpose, the storage stability of inverted planar methylammonium lead iodide (MAPI)-based perovskite solar cells without encapsulation is tested, using the metals aluminum (Al), silver (Ag), gold (Au) and nickel (Ni) as representative cathode materials. For this study, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analysis of the different electrodes as well as the perovskite is correlated with PSC device current–voltage (J–V) and impedance measurements. Our findings substantiate that the metal microstructure has a significant influence on the PSC aging properties. While a strong perovskite decomposition and iodide diffusion to the contacts were detected for devices using Al, Ag or Au cathodes with a polycrystalline microstructure, these effects were strongly reduced when Ni metallization was employed, where a nanocrystalline microstructure was exhibited under the chosen process conditions.

The microstructure of the metal contact has a significant influence on the PSC aging properties. In this contribution we show that perovskite decomposition and iodide diffusion can be suppressed by using nanocrystalline Ni metallization.     

Disentangling breast cancer patients' perceptions and experiences with regard to endocrine therapy: Nature and relevance for non-adherence

Background & study aimsAdjuvant endocrine therapy effectively prevents recurrence and progression of estrogen-receptor positive breast cancer. However, studies reveal substantial non-adherence. The objective was therefore to identify the nature of the experiences and beliefs of women treated with endocrine therapy in an attempt to find potential determinants of non-adherence.MethodOnline Focus Groups (OFGs) and individual interviews were conducted with 37 women who were treated with endocrine therapy. Sixty-three statements derived from the OFGs and 11 belief items from the Beliefs about Medicines Questionnaire (BMQ) were used in a Q-sorting task conducted with 14 of the women. The quantitative Q-sorting data were statistically analyzed with Hierarchical Cluster Analysis.ResultsA six cluster solution was revealed that included the clusters ‘information’, ‘efficacy’, ‘tenacity’, ‘coping’, ‘side effects’ and ‘usage’. Women's own experiences and perceptions were not clearly delineated from the beliefs measured with the BMQ. However, women judged their own experiences and perceptions with regard to endocrine therapy as more relevant for adherence than the BMQ beliefs.ConclusionIn order to understand and to improve women's adherence to endocrine therapy, women's own perceptions and experiences about endocrine therapy should be targeted in addition to common beliefs that apply to a wide range of medicines.     

Health-Related Quality of Life,Treatment Efficacy,and Hemodialysis Patient Outcome

The aim of the study was to examine the influence of improved treatment of hemodialysis (HD) patients on their health-related quality of life (HrQoL) and to assess the predictive value of HrQoL dimensions on patient outcome. The prospective cohort study involved 102 HD patients, and their clinical and laboratory parameters and HD adequacy indices were followed from 2001 to 2007. HrQoL was measured using KDQOL-SF Version 1.3 in 2001, 2004, and 2007. During a six-year period, quality of HD and anemia treatment improved and resulted in significant increase of mean Kt/V (1.2–1.56) and hemoglobin levels (86.5–115.6 g/L). All four HrQoL dimensions (i.e., physical, mental health, kidney disease target issues, and patient satisfaction) remained unchanged, but significant improvement in several HrQoL physical health domains and the effects of kidney disease domain was found. Mortality rate decreased from 18.6% to 7.14% per year. Age was associated positively, but kidney disease target issue score negatively, with patient death. Improved HD adequacy and anemia treatment in HD patients were followed with maintenance of all four HrQoL dimensions unchanged over six years. Moreover, an improvement in several physical health domains and the effects of kidney disease domain was found. Age and kidney disease target issue appeared as significant predictors of patients' death.     

p21Cip restrains hippocampal neurogenesis and protects neuronal progenitors from apoptosis during acute systemic inflammation

Altered neurogenesis in adult hippocampus is implicated in cognition impairment and depression. Inflammation is a potent inhibitor of neurogenesis. The cyclin‐dependent kinase inhibitor p21^Cip1 (p21) restrains cell cycle progression and arrests the cell in the G1 phase. We recently showed that p21 is expressed in neuronal progenitors and regulates proliferation of these cells in the subgranular zone of the dentate gyrus of hippocampus where adult neurogenesis occurs. The current study suggests that p21 is induced in vivo in the hippocampus of WT mice in response to acute systemic inflammation caused by LPS injections, restrains neuronal progenitor proliferation and protects these cells from inflammation‐induced apoptosis. In intact p21^?/? hippocampus, neuronal progenitors proliferate more actively as assessed by BrdU incorporation, and give rise to increased number of DCX positive neuroblasts. However, when mice were treated with LPS, the number of neuroblasts decreased due to induced subgranular zone apoptosis. In vitro, differentiating Tuj‐1 positive neuroblasts isolated from p21^?/? hippocampus exhibited increased proliferation rate, measured by Ki‐67 staining, as compared to WT cells (p<0.05). In WT neuronal progenitors treated with IL‐6, the number of p21‐positive cells was increased (p<0.05), and this led to Tuj‐1⁺ cell proliferation restraint, whereas the number of proliferating GFAP⁺ astrocytes was increased ～ 2‐fold. Thus, when p21 is intact, inflammation might divert neuronal progenitors towards astrogliogenesis by inducing p21. At the same time, when p21 is lacking, no effects of IL‐6 on proliferation of Tuj‐1⁺ cells or GFAP⁺ cells are detected in differentiating p21^?/? neuronal progenitors. These results underscore the important role of p21 controlling hippocampal neuronal differentiation during inflammation. © 2013 Wiley Periodicals, Inc.