地震発生時における住民の共助の意向の実態と関連する要因-地震による被災経験を持たない地域における調査-

目的：災害時における住民の共助の意向および避難行動要支援者を助けようとする意志に関する実態の調査と、それらに関連する要因を明らかにすることである。 方法：A 県 B 市 C 地区の 15 歳以上の住民 4370 人に無記名自記式質問紙調査を行い、 3651人の回答者中2861人から有効回答を得た（有効回答率78.4%）。調査内容は、基本属性、災害時における対応、災害に備える行動、災害に関する認識、地域への愛着・つながりとした。結果：災害時における共助の意向のある者は 78.1%、避難行動要支援者を助けようとする意志のある者は 79.5% であった。また、災害時における共助の意向、避難行動要支援者を助けようとする意志の両方に地域防災活動への参加の必要性、災害時に助け合える隣近所の人がいることが関連していた。考察：災害時における共助の意向を有することおよび避難行動要支援者を助けようとする意志を有することには、災害時のことを考える機会を日頃から持つこと、平常時から住民同士の交流を深める機会をつくることが必要であることが示唆された。Aim: This study was performed to investigate residents’ willingness to cooperate and help others requiring support with evacuation in the event of a disaster, and to identify factors linked to these traits. Methods: An anonymous, self-administered written survey was conducted with 4370 residents aged ≥15 in District C, City B, Prefecture A. Of the 3651 responses received, 2861 were valid (valid response rate, 78.4%). The survey covered basic attributes, coping in the event of a disaster, actions to prepare for a disaster, understanding of disasters, and attachment to and relations within the community.Results: The percentage of people who were willing to cooperate in the event of a disaster was 78.1%, and the percentage who would be willing to help others requiring support with evacuation was 79.5%. Necessity of participation in regional disaster prevention activities and having neighbors who help each other in a disaster were both found to be contributing factors to willingness to cooperate and help others requiring support with evacuation in the event of a disaster.Discussion: This study suggested that having the opportunity to think about how they would cope at the time of a disaster and to create opportunities to deepen exchanges between residents under normal conditions were necessary for willingness to cooperate and help others requiring support with evacuation in the event of a disaster

Hubs and spokes of the lateral hypothalamus: cell types, circuits and behaviour

The hypothalamus is among the most phylogenetically conserved regions in the vertebrate brain, reflecting its critical role in maintaining physiological and behavioural homeostasis. By integrating signals arising from both the brain and periphery, it governs a litany of behaviourally important functions essential for survival. In particular, the lateral hypothalamic area (LHA) is central to the orchestration of sleep–wake states, feeding, energy balance and motivated behaviour. Underlying these diverse functions is a heterogeneous assembly of cell populations typically defined by neurochemical markers, such as the well-described neuropeptides hypocretin/orexin and melanin-concentrating hormone. However, anatomical and functional evidence suggests a rich diversity of other cell populations with complex neurochemical profiles that include neuropeptides, receptors and components of fast neurotransmission. Collectively, the LHA acts as a hub for the integration of diverse central and peripheral signals and, through complex local and long-range output circuits, coordinates adaptive behavioural responses to the environment. Despite tremendous progress in our understanding of the LHA, defining the identity of functionally discrete LHA cell types, and their roles in driving complex behaviour, remain significant challenges in the field. In this review, we discuss advances in our understanding of the neurochemical and cellular heterogeneity of LHA neurons and the recent application of powerful new techniques, such as opto- and chemogenetics, in defining the role of LHA circuits in feeding, reward, arousal and stress. From pioneering work to recent developments, we review how the interrogation of LHA cells and circuits is contributing to a mechanistic understanding of how the LHA coordinates complex behaviour. (Figure presented.).SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hypothalamic tuberomammillary nucleus neurons: Electrophysiological diversity and essential role in arousal stability

Histaminergic (HA) neurons, found in the posterior hypothalamic tuberomammillary nucleus (TMN), extend fibers throughout the brain and exert modulatory influence over numerous physiological systems. Multiple lines of evidence suggest that the activity of HA neurons is important in the regulation of vigilance despite the lack of direct, causal evidence demonstrating its requirement for the maintenance of arousal during wakefulness. Given the strong correlation between HA neuron excitability and behavioral arousal, we investigated both the electrophysiological diversity of HA neurons in brain slices and the effect of their acute silencing in vivo in male mice. For this purpose, we first validated a transgenic mouse line expressing cre recombinase in histidine decarboxylase-expressing neurons (Hdc-Cre) followed by a systematic census of the membrane properties of both HA and non-HA neurons in the ventral TMN (TMNv) region. Through unsupervised hierarchical cluster analysis, we found electrophysiological diversity both between TMNv HA and non-HA neurons, and among HA neurons. To directly determine the impact of acute cessation of HA neuron activity on sleep-wake states in awake and behaving mice, we examined the effects of optogenetic silencing of TMNv HA neurons in vivo. We found that acute silencing of HA neurons during wakefulness promotes slow-wave sleep, but not rapid eye movement sleep, during a period of low sleep pressure. Together, these data suggest that the tonic firing of HA neurons is necessary for the maintenance of wakefulness, and their silencing not only impairs arousal but is sufficient to rapidly and selectively induce slow-wave sleep.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase II Study of Irinotecan plus S-1 Combination for Previously Untreated Advanced Non-Small Cell Lung Cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0601

Objective: Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC. Methods: Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m2, days 1 and 15) and oral S-1 (80 mg/m2, days 1-14). The primary endpoint was response rate, while secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 112 cycles was administered to 40 patients (median, 3 cycles; range 1-6 cycles). Twelve patients showed partial response (PR) and 17 patients exhibited stable disease (SD), representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 months and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common non-hematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055). Conclusion: The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC

Neurokinin B-Expressing Neurons of the Central Extended Amygdala Mediate Inhibitory Synaptic Input onto Melanin-Concentrating Hormone Neuron Subpopulations.

The lateral hypothalamic area (LHA) is a highly conserved brain region critical for maintaining physiological homeostasis and goal-directed behavior. LHA neurons that express melanin-concentrating hormone (MCH) are key regulators of arousal, energy balance, and motivated behavior. However, cellular and functional diversity among LHAMCH neurons is not well understood. Previous anatomic and molecular data suggest that LHAMCH neurons may be parsed into at least two distinct subpopulations, one of which is enriched in neurokinin-3 receptor (NK3R), the receptor for neurokinin B (NKB), encoded by the Tac2 gene. This tachykininergic ligand-receptor system has been implicated in reproduction, fear memory, and stress in other brain regions, but NKB interactions with LHAMCH neurons are poorly understood. We first identified how LHAMCH subpopulations may be distinguished anatomically and electrophysiologically. To dissect functional connectivity between NKB-expressing neurons and LHAMCH neurons, we used Cre-dependent retrograde and anterograde viral tracing in male Tac2-Cre mice and identified Tac2/EYFP+ neurons in the bed nucleus of the stria terminalis and central nucleus of the amygdala, the central extended amygdala, as major sources of NKB input onto LHAMCH neurons. In addition to innervating the LHA, these limbic forebrain NKB neurons also project to midbrain and brainstem targets. Finally, using a dual-virus approach, we found that optogenetic activation of these inputs in slices evokes GABA release onto a subset of LHAMCH neurons but lacked specificity for the NK3R+ subpopulation. Overall, these data define parallel tachykininergic/GABAergic limbic forebrain projections that are positioned to modulate multiple nodes of homeostatic and behavioral control.SIGNIFICANCE STATEMENT The LHA orchestrates fundamental behavioral states in the mammalian hypothalamus, including arousal, energy balance, memory, stress, and motivated behavior. The neuropeptide MCH defines one prominent population of LHA neurons, with multiple roles in the regulation of homeostatic behavior. Outstanding questions remain concerning the upstream inputs that control MCH neurons. We sought to define neurochemically distinct pathways in the mouse brain that may communicate with specific MCH neuron subpopulations using viral-based retrograde and anterograde neural pathway tracing and optogenetics in brain slices. Here, we identify a specific neuropeptide-defined forebrain circuit that makes functional synaptic connections with MCH neuron subpopulations. This work lays the foundation for further manipulating molecularly distinct neural circuits that modulate innate behavioral states

Kabuki make-up症候群(Niikawa-Kuroki症候群)

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