Optogenetic Stimulation of 5-HT Neurons in the Median Raphe Nucleus Affects Anxiety and Respiration

Anxiety affects respiration, and in turn perturbs the internal environment, although the neuronal systems controlling anxiety-related respiration remain unclear. Recent reports indicate that serotonin（5-HT）neurons in the median raphe nucleus（MRN）enhance anxiety. In the present study, we aimed to clarify the contribution of 5-HT neurons in the MRN to anxiety and respiratory control using mice expressing a channelrhodopsin-2 variant-enhanced yellow fluorescent protein（ChR2 ［C128S］-EYFP; a step-function opsin）in the central 5-HT neurons. We applied an optogenetic method to bigenic mice expressing ChR2［C128S］-EYFP in 5-HT neurons and to monogenic mice without such expression. Photostimulation of free-moving mice was performed using a wireless system through an optical fiber pre-inserted above the MRN, and respiratory variables were measured using whole-body plethysmography. Anxiety was evaluated using an elevated-plus maze test. In the bigenic mice, we confirmed ChR2［C128S］-EYFP expression in tryptophan hydroxylase 2（a brain 5-HT synthase）-positive neurons in the raphe nuclei of the mesopontine, such as the MRN and the dorsal raphe nucleus. Blue light illumination to the MRN of the bigenic mice significantly increased respiratory rate and minute ventilation without affecting tidal volume, and significantly decreased the time spent in the open arms of the elevated plus maze without changing distance traveled, compared with monogenic mice. These results suggest that 5-HT neuron activity in the MRN increases anxiety-like behavior without affecting locomotor activity, enhances respiratory rhythm and minute ventilation without changing tidal volume, and can mimic anxiety-related respiratory responses in humans

TUMOR MARKERS IN BONE MARROW IN PATIENTS WITH PROSTATIC CANCER

We compared prostatic specific acid phosphatase (PAP), prostatic specific antigen (PA) and γ-seminoprotein (γ-SM) levels between bone marrow and serum for the purpose of assessing of the usefulness of these tumor markers in early detection of bone metastasis in cases with prostatic cancer. Thirty-three patients were entered into this study. Of the patients, 20 had prostatic cancer including 11 with bone metastasis, and 13 patients had benign prostatic hypertrophy (BPH) served as controls. It seemed unlikely that bone marrow PAP, PA and γ-SM are more useful than their serum levels for detection of bone metastasis of prostatic cancer. Because correlation between bone marrow and serum levels of each marker was observed not only in cases with prostate cancer accompanied by bone metastasis but also in metastasis-free prostatic cancer and BPH cases, it seems likely that PAP, PA and γ-SM in bone marrow circulate from peripheral blood rather than from bone metastasis of prostatic cancer

群馬県訪問看護事業所における医療処置及び人工呼吸療法の事故発生状況，安全対策への取組の実態調査

目的：群馬県訪問看護事業所における医療処置及び人工呼吸器装着者の事故発生状況，安全対策への取組を明らかにし，地域における安全対策の体制整備を検討する． 方法：群馬県の訪問看護事業所の管理者421人を対象に自記式質問紙調査を実施した．有効回答は67人（15.9％），記述統計量を算出し，自由記述は類似性に基づき整理した． 結果：医療処置の事故は訪問看護提供時間内に14件（n＝31），影響度はレベル3以下，人工呼吸療法に関する事故は介護者在宅時が11件（n＝25），影響度はレベル4が1件（4.0％），レベル5が3件（12.0％）であった．発生時の対応は，介護職のケア時間に発生した事故の検討47.4％，地域の多機関で話し合う30.6％であった． 結論：人工呼吸器装着者の安全対策は，介護者のみの時間の療養者・家族が行う対策が重要であり，支援チーム，地域の多機関での事故に関する情報共有・検討が課題である．Purpose: This study examined the development of local safety measure systems by clarifying the incidence of accidents in medical procedures and among users of ventilators, as well as initiatives for safety measures at home-visit nursing stations in Gunma Prefecture. Methods: A self-administered questionnaire was distributed to 421 administrators of home-visit nursing stations in Gunma Prefecture and valid responses were obtained from 67 respondents (15.9％). Each item was subject to descriptive statistics and open-ended answers were organized based on similarities. Results: The respondents reported 14 (45.2％) medical procedure accidents that occurred during home-visit nursing hours with an impact level on patients of 3 or lower, and 11 (44.0％) ventilation therapy accidents that occurred while the caregiver was home, one of which had an impact level of 4 (4.0％) and three of which had an impact level of 5 (12.0％). Measures taken to address accidents were investigations into accidents that occurred during care hours by care workers in 47.4％ of cases and discussions among various local agencies in 30.6％ of cases. Conclusions: Regarding safety measures for users of ventilators, measures carried out by the patient and their family while only the caregiver was home were important. In the future, it is necessary to address the sharing and review of information on accidents among support teams and various local agencies.報

Valence Fluctuations Revealed by Magnetic Field Scan: Comparison with Experiments in YbXCu_4 (X=In, Ag, Cd) and CeYIn_5 (Y=Ir, Rh)

The mechanism of how critical end points of the first-order valence transitions (FOVT) are controlled by a magnetic field is discussed. We demonstrate that the critical temperature is suppressed to be a quantum critical point (QCP) by a magnetic field. This results explain the field dependence of the isostructural FOVT observed in Ce metal and YbInCu_4. Magnetic field scan can lead to reenter in a critical valence fluctuation region. Even in the intermediate-valence materials, the QCP is induced by applying a magnetic field, at which the magnetic susceptibility also diverges. The driving force of the field-induced QCP is shown to be a cooperative phenomenon of the Zeeman effect and the Kondo effect, which creates a distinct energy scale from the Kondo temperature. The key concept is that the closeness to the QCP of the FOVT is capital in understanding Ce- and Yb-based heavy fermions. It explains the peculiar magnetic and transport responses in CeYIn_5 (Y=Ir, Rh) and metamagnetic transition in YbXCu_4 for X=In as well as the sharp contrast between X=Ag and Cd.Comment: 14 pages, 9 figures, OPEN SELECT in J. Phys. Soc. Jp

A Balanced Diet Is Necessary for Proper Entrainment Signals of the Mouse Liver Clock

BACKGROUND:The peripheral circadian clock in mice is entrained not only by light-dark cycles but also by daily restricted feeding schedules. Behavioral and cell culture experiments suggest an increase in glucose level as a factor in such feeding-induced entrainment. For application of feeding-induced entrainment in humans, nutrient content and dietary variations should be considered. PRINCIPAL FINDING:To elucidate the food composition necessary for dietary entrainment, we examined whether complete or partial substitution of dietary nutrients affected phase shifts in liver clocks of mice. Compared with fasting mice or ad libitum fed mice, the liver bioluminescence rhythm advanced by 3-4 h on the middle day in Per2::luciferase knock-in mice that were administered a standard mouse diet, i.e. AIN-93M formula [0.6-0.85 g/10 g mouse BW] (composition: 14% casein, 47% cornstarch, 15% gelatinized cornstarch, 10% sugar, 4% soybean oil, and 10% other [fiber, vitamins, minerals, etc.]), for 2 days. When each nutrient was tested alone (100% nutrient), an insignificant weak phase advance was found to be induced by cornstarch and soybean oil, but almost no phase advance was induced by gelatinized cornstarch, high-amylose cornstarch, glucose, sucrose, or casein. A combination of glucose and casein without oil, vitamin, or fiber caused a significant phase advance. When cornstarch in AIN-93M was substituted with glucose, sucrose, fructose, polydextrose, high-amylose cornstarch, or gelatinized cornstarch, the amplitude of phase advance paralleled the increase in blood glucose concentration. CONCLUSIONS:Our results strongly suggest the following: (1) balanced diets containing carbohydrates/sugars and proteins are good for restricted feeding-induced entrainment of the peripheral circadian clock and (2) a balanced diet that increases blood glucose, but not by sugar alone, is suitable for entrainment. These findings may assist in the development of dietary recommendations for on-board meals served to air travelers and shift workers to reduce jet lag-like symptoms

Maternal Feeding Controls Fetal Biological Clock

BACKGROUND: It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD) cycle. METHODOLOGY/PRINCIPAL FINDINGS: To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN) and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy

Aberrant expression of RAB1A in human tongue cancer

This study was designed to identify specific gene expression changes in tongue squamous cell carcinomas (TSCCs) compared with normal tissues using in-house cDNA microarray that comprised of 2304 full-length cDNAs from a cDNA library prepared from normal oral tissues, primary oral cancers, and oral cancer cell lines. The genes identified by our microarray system were further analysed at the mRNA or protein expression level in a series of clinical samples by real-time quantitative reverse transcriptase–polymerase chain reaction (qRT–PCR) analysis and imuunohositochemistry. The microarray analysis identified a total of 16 genes that were significantly upregulated in common among four TSCC specimens. Consistent with the results of the microarray, increased mRNA levels of selected genes with known molecular functions were found in the four TSCCs. Among genes identified, Rab1a, a member of the Ras oncogene family, was further analysed for its protein expression in 54 TSCCs and 13 premalignant lesions. We found a high prevalence of Rab1A-overexpression not only in TSCCs (98%) but also in premalignant lesions (93%). Thus, our results suggest that rapid characterisation of the target gene(s) for TSCCs can be accomplished using our in-house cDNA microarray analysis combined with the qRT–PCR and immunohistochemistry, and that the Rab1A is a potential biomarker of tongue carcinogenesis