Patome: a database server for biological sequence annotation and analysis in issued patents and published patent applications

With the advent of automated and high-throughput techniques, the number of patent applications containing biological sequences has been increasing rapidly. However, they have attracted relatively little attention compared to other sequence resources. We have built a database server called Patome, which contains biological sequence data disclosed in patents and published applications, as well as their analysis information. The analysis is divided into two steps. The first is an annotation step in which the disclosed sequences were annotated with RefSeq database. The second is an association step where the sequences were linked to Entrez Gene, OMIM and GO databases, and their results were saved as a gene–patent table. From the analysis, we found that 55% of human genes were associated with patenting. The gene–patent table can be used to identify whether a particular gene or disease is related to patenting. Patome is available at ; the information is updated bimonthly

Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model

BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice. METHODOLOGY/PRINCIPAL FINDINGS: Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer

カンコク ノ ロウジン チョウキ リョウヨウ ホケン セイド ノ セイサク ケッテイ カテイ ニカンスル イチコウサツ

本研究は、韓国の老人長期療養保険制度の制度設計および政策決定過程における政策決定者間の相互作用が政策決定にどのような影響を及ぼしたかを明らかにするとともに、制度施行前後の政策評価や制度改善策などについて論究したものである。 研究の結果、次のようなことが明らかになった。韓国では政府主導によって老人長期療養保険制度にかかわる諸政策が決定されたが、その政策決定過程において政策への参加者の範囲が政府関係者以外に徐々に拡大した。政策決定者間の相互作用は制度設計段階では比較的良好であったが、制度の骨格が公表されたのを機に関係が急激に悪化し、対立が生じるようになった。結果的に、制度に関する知識と情報をほぼ独占していた政府関係者が主導する形で政策が決定された。一方では、制度施行までの準備期間が比較的短かったため、介護サービスの基盤整備が懸念されたが、政府主導による政策決定と制度施行が功を奏し、比較的順調に制度が運営されている。制度創設によって介護サービスの基盤整備、介護サービス利用者の拡大、利用者とその家族の満足度が向上したと評価されている反面、介護サービスの質の向上とそれに向けた制度改善は今なお大きな課題として残っている。The purpose of this study is to be used as a basic research for the whole policy process and the sustainable development of Long-term Care Insurance (LTC) by analyzing the interaction among policy making-decision participants, the impact of policy outcomes from the formation of policy agenda to the policy decision and the enforcement and evaluation contents of LTC in south Korea. The result of this study is summarized as follows. First, the policy agenda about LTC problem for the elderly was formed by the government and the number of policy participants increased by characteristics of policy process stage. Second, main policy participants have changed by the policy process stage. Third, interaction among policy participants was cooperative in early policy agenda formation stage, but it changed to be dissenting orcritical rapidly as the frame of system was announced to the people. Fourth, the characteristics of policy networks are a government-leading policy process. As a result, it influenced policy outcomes significantly because the government exclusively have knowledge and information of LTC and interact as a main policy participants. Fifth, with the improvement of quality of life for the elderly and the reduction of the economic and psychological burden of the supporter, LTC is regarded as soft-landing in a short period of time. In spite of this positive evaluation, various problems are derived from marketization of social welfare services. Finally, LTC is successful in the quantitative aspects such as the coverage,the accessibility of the LTC service users, the goals and objectives of LTC, the satisfaction survey of the elderly and their families. On the other hand in the qualitative aspects, we can find that the more fundamental and long-term improvements(reforms)in LTC are urgently needed

Interglial Crosstalk in Obesity-Induced Hypothalamic Inflammation

Glial cells have recently gained particular attention for their close involvement in neuroinflammation and metabolic disorders including obesity and diabetes. In the central nervous system (CNS), different types of resident glial cells have been documented to express several signaling molecules and related receptors, and their crosstalks have been implicated in physiology and pathology of the CNS. Emerging evidence illustrates that malfunctioning glia and their products are an important component of hypothalamic inflammation. Recent studies have suggested that glia–glia crosstalk is a pivotal mechanism of overnutrition-induced chronic hypothalamic inflammation, which might be intrinsically associated with obesity/diabetes and their pathological consequences. This review covers the recent advances in the molecular aspects of interglial crosstalk in hypothalamic inflammation, proposing a central role of such a crosstalk in the development of obesity, diabetes, and related complications. Finally, we discuss the possibilities and challenges of targeting glial cells and their crosstalk for a better understanding of hypothalamic inflammation and related metabolic dysfunctions

Vascular effects of estrogen in type II diabetic postmenopausal women

AbstractOBJECTIVESWe assessed the effects of estrogen on vascular dilatory and other homeostatic functions potentially affected by nitric oxide (NO)-potentiating properties in type II diabetic postmenopausal women.BACKGROUNDThere is a higher cardiovascular risk in diabetic women than in nondiabetic women. This would suggest that women with diabetes do not have the cardioprotection associated with estrogen.METHODSWe administered placebo or conjugated equine estrogen, 0.625 mg/day for 8 weeks, to 20 type II diabetic postmenopausal women in a randomized, double-blinded, placebo-controlled, cross-over design.RESULTSCompared with placebo, estrogen tended to lower low-density lipoprotein (LDL) cholesterol levels by 15 ± 23% (p = 0.007) and increase high-density lipoprotein (HDL) cholesterol levels by 8 ± 16% (p = 0.034). Thus, the ratio of LDL to HDL cholesterol levels significantly decreased with estrogen, by 20 ± 24%, as compared with placebo (p = 0.001). Compared with placebo, estrogen tended to increase triglyceride levels by 16 ± 48% and lower glycosylated hemoglobin levels by 3 ± 13% (p = 0.295 and p = 0.199, respectively). However, estrogen did not significantly improve the percent flow-mediated dilatory response to hyperemia (17 ± 75% vs. placebo; p = 0.501). The statistical power to accept our observation was 81.5%. Compared with placebo, estrogen did not significantly change E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 or matrix metalloproteinase-9 levels. Compared with placebo, estrogen tended to decrease tissue factor antigen and increase tissue factor activity levels by 7 ± 46% and 5 ± 34%, respectively (p = 0.321 and p = 0.117, respectively) and lower plasminogen activator inhibitor-1 levels by 16 ± 31% (p = 0.043).CONCLUSIONSThe effects of estrogen on endothelial, vascular dilatory and other homeostatic functions were less apparent in type II diabetic postmenopausal women, despite the beneficial effects of estrogen on lipoprotein levels

Efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe symptomatic hyponatremia: study protocol for a randomized controlled trial (SALSA trial)

Abstract Background Hyponatremia is the most common electrolyte imbalance encountered in clinical practice, associated with increased mortality and length of hospital stay. However, no high-quality evidence regarding whether hypertonic saline is best administered as a continuous infusion or a bolus injection has been found to date. Therefore, in the current study, we will evaluate the efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe symptomatic hyponatremia. Methods/design This is a prospective, investigator-initiated, multicenter, open-label, randomized controlled study with two experimental therapy groups. A total of 178 patients with severe symptomatic hyponatremia will be enrolled and randomly assigned to receive either rapid intermittent bolus or slow continuous infusion management with hypertonic saline. The primary outcome is the incidence of overcorrection at any given period over 2 days. The secondary outcomes will include the efficacy and safety of two other approaches to the treatment of hyponatremia with 3% hypertonic saline. Discussion This is the first clinical trial to investigate the efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe hyponatremia. Trial registration ClinicalTrials.gov, identifier number: NCT02887469 . Registered on 1 August 2016

Gray matter atrophy in multiple sclerosis despite clinical and lesion stability during natalizumab treatment

Background: Brain volume loss is an important surrogate marker for assessing disability in MS; however, contribution of gray and white matter to the whole brain volume loss needs further examination in the context of specific MS treatment.Objectives: To examine whole and segmented gray, white, thalamic, and corpus callosum volume loss in stable patients receiving natalizumab for 2-5 years.Methods: This was a retrospective study of 20 patients undergoing treatment with natalizumab for 24-68 months. Whole brain volume loss was determined with SIENA. Gray and white matter segmentation was done using FAST. Thalamic and corpus callosum volumes were determined using Freesurfer. T1 relaxation values of chronic hypointense lesions (black holes) were determined using a quantitative, in-house developed method to assess lesion evolution.Results: Over a mean of 36.6 months, median percent brain volume change (PBVC) was -2.0% (IQR 0.99-2.99). There was decline in gray (p = 0.001) but not white matter (p = 0.6), and thalamic (p = 0.01) but not corpus callosum volume (p = 0.09). Gray matter loss correlated with PBVC (Spearman's r = 0.64, p = 0.003) but not white matter (Spearman's r = 0.42, p = 0.07). Age significantly influenced whole brain volume loss (p = 0.010, multivariate regression), but disease duration and baseline T2 lesion volume did not. There was no change in T1 relaxation values of lesions or T2 lesion volume over time. All patients remained clinically stable.Conclusions: These results demonstrate that brain volume loss in MS is primarily driven by gray matter changes and may be independent of clinically effective treatment.</div