Active Hippocampal Networks Undergo Spontaneous Synaptic Modification

The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial) stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone

RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals

DNA double-strand breaks (DSBs) activate a canonical DNA damage response, including highly conserved cell cycle checkpoint pathways that prevent cells with DSBs from progressing through the cell cycle. In developing B cells, pre–B cell receptor (pre–BCR) signals initiate immunoglobulin light (Igl) chain gene assembly, leading to RAG-mediated DNA DSBs. The pre–BCR also promotes cell cycle entry, which could cause aberrant DSB repair and genome instability in pre–B cells. Here, we show that RAG DSBs inhibit pre–BCR signals through the ATM- and NF-κB2–dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor, resulting in suppression of pre–BCR signaling. This regulatory circuit prevents the pre–BCR from inducing additional Igl chain gene rearrangements and driving pre–B cells with RAG DSBs into cycle. We propose that pre–B cells toggle between pre–BCR signals and a RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes

在宅療養に関連する要因の分析

出雲市のT地区の20歳以上を対象に、在宅介護・療養についてのアンケート調査を行い、在宅療養に関連する要因の検討を行った。在宅療養の希望と本人の状況、家族の状況、介護への関心・知識・体験との関連を検討したところ、性別、年齢、入院経験、福祉についての知識において有意の関連がみられた

島根県立看護短期大学の地域貢献と情報ネットワークシステム

島根県立看護短期大学は平成7年4月に関学した。建学の理念は、1.人間愛、2.看護職の責務の探求、3.地域に開かれた大学である。教育、研究の成果を地域に還元し、「開かれた大学」として地域社会の発展に貢献することを一つの重要な柱とした。その目的を達成するための学内体制等を整備すると共に、地域開放事業の実施目標を設定した。本学には「情報と映像で世界と地域を結ぶ島根県立看護短期大学の2つのネットワーク」がある。これはコンピュータ情報ネットワークと音声・映像情報ネットワークの2つのシステムから構成されている。後者のシステムは出雲ケーブルピジョンにより、出雲市の家庭と結ばれている。ここでは、音声・映像情報ネットワークを用いて地域の人々に対する看護・介護支援システムを構築し地域社会に貢献する計画を述べた

島根県立看護短期大学における地域貢献 : 周辺地区の家庭訪問実習、公民館活動との連携と看護支援システム構築の歩み

島根県立看護短期大学は「開かれた大学」として、地域貢献を開学の理念の重要な柱の一つとしている。それを実現するには、周辺地区との信頼と友好関係の樹立が重要と考えた。看護学科一年次学生がおこなう基礎看護実習での家庭訪問実習は優れた教育効果をもたらすとともに、地区住民から高い評価を得ることが出来た。さらに地区住民のための在宅看護支援体制を確立するために、テレビ会議システムを導入し、公民館に設置して本学との間で双方向の音声と画像の交信実験を行い目的達成の有効な手段になると考えられた。この実験は、地域住民の教育に対する理解並びに本学との信頼と友好関係が土台となり実現したものである

イリョウ ケア カンレン ハイエン ニ カンスル マエムキ エキガク チョウサ

医療ケア関連肺炎(HCAP)は,ATS/IDSAの肺炎のガイドライン(2005年)にて提唱された概念である.当院におけるHCAPの特徴を明らかにする目的で前向き研究を行った.2010年1～12月に獨協医科大学越谷病院呼吸器内科に市中肺炎で入院した患者を対象とした.HCAPと市中肺炎(CAP)の判断にあたっては, HCAP疑い因子の有無をアンケートにより調査した.それ以外の介入は行わず,背景因子,肺炎重症度,肺炎の再燃の有無について調査した.年齢はHCAP 73±10歳,CAP 65±9歳(p<0.05)と両群間で有意差を認め,HCAP群では悪性腫瘍の合併が多く(p<0.05),自立度が低かった(p<0.05).入院時検査所見,胸部X線点数は,両群間に有意差を認めなかった.肺炎重症度は,A-DROPでは,HCAP群が,軽症30%,中等症63%,重症7%,CAP群が,軽症75%,中等症12%,重症13%で,有意差がみられた(p<0.05)が,PSIスコアでは,重症度に有意差を認めなかった.30日以内の肺炎再燃はHCAP群で21%,CAP群では0%であった.本研究より,HCAPでは,入院時の重症度に関らず,より慎重な経過観察が必要であることが示唆された.詳細にHCAP危険因子に関する病歴を聴取し,HCAPをCAPと誤認しないようにすることが重要である.Backgrounds:Healthcare associated pneumonia(HCAP) is a new concept proposed in guidelines for themanagement of adults with hospital-acquired, ventilatorassociated,and healthcare-associated pneumonia by ATS/IDSA. Several retrospective studies investigating the characteristicof HCAP in Japan have been performed. However,at present, a cohort study exploring the characteristic ofHCAP in Japan has not been published.Patients and Methods:This study was a prospectiveobservational study. Patients with pneumonia who admittedto Dokkyo Medical University Koshigaya Hospital betweenJanuary and December in 2010 were enrolled in this study.After giving informed consent, the patients were requestedto fill out a questionnaire designed to obtain informationabout risk factors of HCAP and divided into groups, HCAPor CAP, and their clinical characteristics were observed.Results:Mean age of enrolled patients were 73±10 yr inHCAP and 65±9 yr in CAP (p<0.05). The percentage ofpatients with malignant diseases were higher in HCAPgroup (p<0.05). There were no statistically significant differencesin WBC, CRP or chest X ray score on admissionbetween the groups. A-DROP score showed statistically asignificant difference between the groups while PSI scoredid not. The recurrence of pneumonia within 30 days afterdischarge of hospital was 21 % in HCAP groups but 0 % inCAP group.Conclusion:This study showed that patients withHCAP need to receive more careful care and observation toprevent recurrence even though the severity of pneumoniaon admission was not very high. It is crucial to take patients\u27history carefully to identify correctly whether a patientis with HCAP or CAP

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged &lt;20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD &lt;2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered