Proximal Tubule Cell Hypothesis for Cardiorenal Syndrome in Diabetes

Incidence of cardiovascular disease (CVD) is remarkably high among patients with chronic kidney disease (CKD), even in the early microalbuminuric stages with normal glomerular filtration rates. Proximal tubule cells (PTCs) mediate metabolism and urinary excretion of vasculotoxic substances via apical and basolateral receptors and transporters. These cells also retrieve vasculoprotective substances from circulation or synthesize them for release into the circulation. PTCs are also involved in the uptake of sodium and phosphate, which are critical for hemodynamic regulation and maintaining the mineral balance, respectively. Dysregulation of PTC functions in CKD is likely to be associated with the development of CVD and is linked to the progression to end-stage renal disease. In particular, PTC dysfunction occurs early in diabetic nephropathy, a leading cause of CKD. It is therefore important to elucidate the mechanisms of PTC dysfunction to develop therapeutic strategies for treating cardiorenal syndrome in diabetes

Influence of Self-Efficacy on Cancer-Related Fatigue and Health-Related Quality of Life in Young Survivors of Childhood Cancer

This study aims to elucidate how self-efficacy influences cancer-related fatigue and health-related quality of life (HRQoL) in young survivors of childhood cancer. Forty-six young survivors (age range, 8-18 years) of childhood cancer who were currently in complete remission completed measures for self-efficacy (Pediatric General Self-Efficacy Scale (PedsSE)), cancer-related fatigue (Cancer-related Fatigue Score (CRFS)), and HRQoL (Pediatric Quality of Life Inventory 4.0 Generic Core Scale, Pediatric Quality of Life Inventory (PedsQL)). Structural relationships between the PedsSE and CRFS or PedsQL, including the effects of potential demographic or clinical confounders, were examined by machine learning random forest algorithms and structural equation modeling. According to the distribution of the PedsQL, six survivors with PedsQL < 70 were determined to have compromised HRQoL (referred to as low-PedsQL survivors). The random forest model identified six variables for the prediction of the CRFS, with the PedsSE being the most important, and eight variables for the distinction of low-PedsQL survivors, with the CRFS being the most and the PedsSE the third most important variable. The structural equation model indicated that a direct influence of the PedsSE on the PedsQL was less detectable (beta = -0.049), whereas an indirect influence of the PedsSE on the PedsQL via the CRFS was evident (beta = 0.333). The model explained 51% of the variation of the CRFS and 28% of the variation of the PedsQL. The PedsSE was strongly correlated with altered mood in the subclass of the CRFS (r = -0.470), and altered mood was strongly correlated with the PedsQL (r = 0.737). In conclusion, self-efficacy is a major determinant of cancer-related fatigue and influences HRQoL via cancer-related fatigue in survivors of childhood cancer. The main pathway from self-efficacy to HRQoL is thought to be via the emotional aspect of cancer-related fatigue. However, unlike adult survivors of cancer, self-efficacy for young survivors may not contribute much to self-management behaviors that maintain HRQoL

Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons

The hypothalamus plays an important role in the regulation of sleep/wakefulness states. While the ventrolateral preoptic nucleus (VLPO) plays a critical role in the initiation and maintenance of sleep, the lateral posterior part of the hypothalamus contains neuronal populations implicated in maintenance of arousal, including orexin-producing neurons (orexin neurons) in the lateral hypothalamic area (LHA) and histaminergic neurons in the tuberomammillary nucleus (TMN). During a search for neurons that make direct synaptic contact with histidine decarboxylase-positive (HDC+), histaminergic neurons (HDC neurons) in the TMN and orexin neurons in the LHA of male mice, we found that these arousal-related neurons are heavily innervated by GABAergic neurons in the preoptic area including the VLPO. We further characterized GABAergic neurons electrophysiologically in the VLPO (GABAVLPO neurons) that make direct synaptic contact with these hypothalamic arousal-related neurons. These neurons (GABAVLPO→HDC or GABAVLPO→orexin neurons) were both potently inhibited by noradrenaline and serotonin, showing typical electrophysiological characteristics of sleep-promoting neurons in the VLPO. This work provides direct evidence of monosynaptic connectivity between GABAVLPO neurons and hypothalamic arousal neurons and identifies the effects of monoamines on these neuronal pathways

Nursing students’ volunteer activities and motivating factors to continue them

本研究は看護大学生のボランティア活動の実態を把握し，ボランティア活動の継続意志と，ボランティア活動成果・継続動機との関連を明らかにすることを目的とした．調査対象者はA県B大学看護学科学生１・２・３年生の２３０名で質問紙調査を実施した．有効回答は１６２名であった．看護大学生の約８割が大学入学前にボランティア活動の経験があり，大学入学後ボランティア活動をしていない学生は全体の８割で，理由として機会がない，忙しくて時間がない，アルバイトしている等があげられた．ボランティア活動を継続したい学生ほど，人生が明るく喜びが広がるなどの意欲向上や人間関係の広がりがあるなどの成果を認識しており，ボランティアの継続動機につながっていた．しかし，多くの学生に継続意志があるにも関わらず，大学入学後にボランティア活動をしている学生は約２割であった．「機会がない」を理由にしている場合は機会があれば積極的に活動することにつながることが考えられる．ボランティアの情報提供を行い，ボランティアの活動成果が実感できるような働きかけが必要であることが示唆された．This study aimed to examine the current status of volunteer activities implemented by nursing college students and the relationship between their intention to continue volunteer work and achievements/motivation. We conducted a questionnaire survey involving ２３０ first-to third-year nursing students of University B in Prefecture A. We collected １６２ valid responses. Approximately ８０％ of the nursing students had experienced volunteering, while approximately ８０％ of the students had not participated in volunteer activities after entering the university, due to reasons such as being too busy and working part time. Volunteer activities produced positive results, such as a brightened life, shared joy, and improved enthusiasm for life, as well as a widened social circle, which motivated the students to continue their volunteer activities. Although most students had the intention of continuing their volunteer work, only approximately ２０％ were involved in such activities after entering the university. However, there were some students who cited “a lack of opportunities” as the reason. They are expected to become involved in volunteer work if they have a chance. It is important to provide students with sufficient information on volunteer work, and allow them to recognize the benefits of participating in such activities

Structural basis for high selectivity of a rice silicon channel Lsi1

Silicon (Si), the most abundant mineral element in the earth’s crust, is taken up by plant roots in the form of silicic acid through Low silicon rice 1 (Lsi1). Lsi1 belongs to the Nodulin 26-like intrinsic protein subfamily in aquaporin and shows high selectivity for silicic acid. To uncover the structural basis for this high selectivity, here we show the crystal structure of the rice Lsi1 at a resolution of 1.8 Å. The structure reveals transmembrane helical orientations different from other aquaporins, characterized by a unique, widely opened, and hydrophilic selectivity filter (SF) composed of five residues. Our structural, functional, and theoretical investigations provide a solid structural basis for the Si uptake mechanism in plants, which will contribute to secure and sustainable rice production by manipulating Lsi1 selectivity for different metalloids

Geometric Engineering of Seiberg-Witten Theories with Massive Hypermultiplets

We analyze the geometric engineering of the N=2 SU(2) gauge theories with $1\leq N_f\leq 3$ massive hypermultiplets in the vector representation. The set of partial differential equations satisfied by the periods of the Seiberg-Witten differential is obtained from the Picard-Fuchs equations of the local B-model. The differential equations and its solutions are consistent with the massless case. We show that the Yukawa coupling of the local A-model gives rise to the correct instanton expansion in the gauge theory, and propose the pattern of the distribution of the world-sheet instanton number from it. As a side result, we obtain the asymptotic form of the instanton number in the gauge theories with massless hypermultiplets.Comment: 35 pages, 3 figures, (v2) clarifying comments, additional reference

GABAergic neurons in the preoptic area send direct inhibitory projections to orexin neurons

Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly during sleep, exhibiting sleep/waking state-dependent firing patterns that are the reciprocal of those observed in the arousal system. The majority of these preoptic "sleep-active" neurons contain the inhibitory neurotransmitter GABA. On the other hand, a population of neurons in the lateral hypothalamic area (LHA) contains orexins, which play an important role in the maintenance of wakefulness, and exhibit an excitatory influence on arousal-related neurons. It is important to know the anatomical and functional interactions between the POA sleep-active neurons and orexin neurons, both of which play important, but opposite roles in regulation of sleep/wakefulness states. In this study, we confirmed that specific pharmacogenetic stimulation of GABAergic neurons in the POA leads to an increase in the amount of non-rapid eye movement (NREM) sleep. We next examined direct connectivity between POA GABAergic neurons and orexin neurons using channelrhodopsin 2 (ChR2) as an anterograde tracer as well as an optogenetic tool. We expressed ChR2-eYFP selectively in GABAergic neurons in the POA by AAV-mediated gene transfer, and examined the projection sites of ChR2-eYFP-expressing axons, and the effect of optogenetic stimulation of ChR2-eYFP on the activity of orexin neurons. We found that these neurons send widespread projections to wakefulness-related areas in the hypothalamus and brain stem, including the LHA where these fibers make close appositions to orexin neurons. Optogenetic stimulation of these fibers resulted in rapid inhibition of orexin neurons. These observations suggest direct connectivity between POA GABAergic neurons and orexin neurons. © 2013 Saito, Tsujino, Hasegawa, Akashi, Abe, Mieda, Sakimura and Sakurai

High-dose Dexamethasone Therapy as the Initial Treatment for Idiopathic Thrombocytopenic Purpura: Protocol for a Multicenter, Open-label, Single Arm Trial

Standard therapy for idiopathic thrombocytopenic purpura (ITP) has not been established. We are conducting a multicenter, prospective trial to determine the efficacy and safety of short-term, high-dose dexamethasone therapy in ITP patients aged 18-80 years with platelet counts of <20, 000 /μL, or with <50, 000/ μL and bleeding symptoms. The primary endpoints of this trial are the proportion of responses (complete plus partial response) on day 180 (day 46+180) after the completion of the 46-day high-dose dexamethasone therapy. The results of this investigation of the effectiveness and safety of this regimen will be essential for the establishment of standard therapy for ITP