Genetic influences on prefrontal activation during a verbal fluency task in children: A twin study using near-infrared spectroscopy

Objective: The genetic and environmental influences on prefrontal function in childhood are underinvestigated due to the difficulty of measuring prefrontal function in young subjects, for which near‐infrared spectroscopy (NIRS) is a suitable functional neuroimaging technique that facilitates the easy and noninvasive measurement of blood oxygenation in the superficial cerebral cortices.Method: Using a two‐channel NIRS arrangement, we measured changes in bilateral prefrontal blood oxygenation during a category version of the verbal fluency task (VFT) in 27 monozygotic twin pairs and 12 same‐sex dizygotic twin pairs ages 5–17 years. We also assessed the participant's full‐scale intelligence quotient (FIQ) and retrieved parental socioeconomic status (SES). Classical structured equation modeling was used to estimate the heritability.Results: The heritability of VFT‐related brain activation was estimated to be 44% and 37% in the right and left prefrontal regions, respectively. We also identified a significant genetic contribution (74%) to FIQ, but did not to VFT task performance. Parental SES was not correlated with FIQ, task performance, or task‐related prefrontal activation.Conclusions: This finding provides further evidence that variance in prefrontal function has a genetic component since childhood and highlights brain function, as measured by NIRS, as a promising candidate for endophenotyping neurodevelopmental disorders

A Japanese herbal medicine (kampo), hochuekkito (TJ-41), has anti-inflammatory effects on the chronic obstructive pulmonary disease mouse model

Abstract Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway

Photosensitized Protein-Damaging Activity, Cytotoxicity, and Antitumor Effects of P(V)porphyrins Using Long-Wavelength Visible Light through Electron Transfer

Photodynamic therapy (PDT) is a less-invasive treatment for cancer through the administration of less-toxic porphyrins and visible-light irradiation. Photosensitized damage of biomacromolecules through singlet oxygen (¹O₂) generation induces cancer cell death. However, a large quantity of porphyrin photosensitizer is required, and the treatment effect is restricted under a hypoxic cellular condition. Here we report the phototoxic activity of P­(V)­porphyrins: dichloroP­(V)­tetrakis­(4-methoxyphenyl)­porphyrin (CLP­(V)­TMPP), dimethoxyP­(V)­tetrakis­(4-methoxyphenyl)­porphyrin (MEP­(V)­TMPP), and diethyleneglycoxyP­(V)­tetrakis­(4-methoxyphenyl)­porphyrin (EGP­(V)­TMPP). These P­(V)­porphyrins damaged the tryptophan residue of human serum albumin (HSA) under the irradiation of long-wavelength visible light (>630 nm). This protein photodamage was barely inhibited by sodium azide, a quencher of ¹O₂. Fluorescence lifetimes of P­(V)­porphyrins with or without HSA and their redox potentials supported the electron-transfer-mediated oxidation of protein. The photocytotoxicity of these P­(V)­porphyrins to HeLa cells was also demonstrated. CLP­(V)­TMPP did not exhibit photocytotoxicity to HaCaT, a cultured human skin cell, and MEP­(V)­TMPP and EGP­(V)­TMPP did; however, cellular DNA damage was barely observed. In addition, a significant PDT effect of these P­(V) porphyrins on a mouse tumor model comparable with the traditional photosensitizer was also demonstrated. These findings suggest the cancer selectivity of these P­(V)­porphyrins and lower carcinogenic risk to normal cells. Electron-transfer-mediated oxidation of biomacromolecules by P­(V)­porphyrins using long-wavelength visible light should be advantageous for PDT of hypoxic tumor

An Enforcement of 'Distinct Teaching Practice' at Hiroshima University (II)

本研究の目的は, 2008年度に実施された「特色ある教育実習プログラム」に関して, 「教育実習観察」の効果に焦点化して報告することである。検討の結果以下の点が明らかとなった。①「小学校教育実習観察」は, 目標とした小学校教育実習のイメージの形成, 教職に関する意識向上, 次年度の教育実習に向けた課題意識の形成の点で有効であった。しかし, 参加学生の当日の態度, 事前指導等に関して改善を要する課題も明らかになった。次年度に向けて, 参加学生の目的意識の涵養や社会人としてのマナーの向上のために事前指導の内容を改善すること, とりわけ2年次生と3年次生との事前の連絡を充実することが課題とされた。②「中・高等学校教育実習観察」は, 目標とした中・高等学校教育実習のイメージの形成, 教職に関する意識向上, 次年度の教育実習に向けた課題意識の形成の点で有効であった。しかし, 参加学生の目標の理解, 次年度実習に向けた学生の課題の解決, 成績評価の方法等に関して今後取り組むべき課題も明らかになった。今後は, 次年度の授業化に向けて観察する内容の情報伝達について事前指導を充実すると共に, 成績評価の方法を整備することが課題とされた

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo