Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow

Chemokines arrest circulating lymphocytes within the vasculature through the rapid up-regulation of leukocyte integrin adhesive activity, promoting subsequent lymphocyte transmigration. However, the key regulatory molecules regulating this process have remained elusive. Here, we demonstrate that Rap1 plays a pivotal role in chemokine-induced integrin activation and migration. Rap1 was activated by secondary lymphoid tissue chemokine (SLC; CCL21) and stromal-derived factor 1 (CXCL4) treatment in lymphocytes within seconds. Inhibition of Rap1 by Spa1, a Rap1-specific GTPase-activating protein, abrogated chemokine-stimulated lymphocyte rapid adhesion to endothelial cells under flow via intercellular adhesion molecule 1. Expression of a dominant active Rap1V12 in lymphocytes stimulated shear-resistant adhesion, robust cell migration on immobilized intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, and transendothelial migration under flow. We also demonstrated that Rap1V12 expression in lymphocytes induced a polarized morphology, accompanied by the redistribution of CXCR4 and CD44 to the leading edge and uropod, respectively. Spa1 effectively suppressed this polarization after SLC treatment. This unique characteristic of Rap1 may control chemokine-induced lymphocyte extravasation

RNA Modification in Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by damage to the intestinal mucosa, which is caused by a combination of factors. These include genetic and epigenetic alterations, environmental influence, microorganism interactions, and immune conditions. Some populations with IBD show a cancer-prone phenotype. Recent studies have provided insight into the involvement of RNA modifications in the specific pathogenesis of IBD through regulation of RNA biology in epithelial and immune cells. Studies of several RNA modification-targeting reagents have shown preferable outcomes in patients with colitis. Here, we note a new awareness of RNA modification in the targeting of IBD and related diseases, which will contribute to early diagnosis, disease monitoring, and possible control by innovative therapeutic approaches

“Extensão Médica Acadêmica”: healthcare humanization and clinical training of medicine, nutrition and physical therapy students from the School of Medicine of University of São Paulo

A Extensão Médica Acadêmica (EMA) foi fundada em 1998 na FMUSP visando à formação de médicos que valorizam o exame clínico e o relacionamento humano. É um projeto de voluntariado atualmente organizado por estudantes de medicina, fisioterapia e nutrição da USP. O EMA é sustentado por três pilares: ensino, assistência e pesquisa. O projeto é realizado aos sábados em dois bairros carentes da cidade de São Paulo, e tem como objetivo oferecer um atendimento ambulatorial gratuito de qualidade, que priorize cuidados em saúde e humanização na relação médico-paciente. Os pacientes são atendidos por alunos e os casos são discutidos com profissionais de saúde, e durante a semana são realizadas reuniões com todos os membros do projeto, na Faculdade de Medicina da USP, contribuindo para a consolidação e aprofundamento dos conceitos em saúde. Este modelo de ensino complementa os estudos em sala de aula, pois permite o desenvolvimento de habilidades geralmente pouco exploradas durante o início da graduação tradicional. O EMA incentiva seus alunos a valorizarem a relação médico-paciente desde o primeiro ano da graduação. Assim, o projeto tem êxito em reunir pessoas dispostas a lidar com pacientes, aprender sobre saúde e ensinar outros estudantes. Como resultado, muitos de seus membros continuam a participar do projeto após o término da faculdade, tornando-se orientadores comprometidos a passar adiante o conhecimento adquirido durante sua prática profissional.The Academic Medical Extension (EMA) is a volunteer project of the School of Medicine of University of São Paulo organized by students of Medicine, Physical Therapy and Nutrition of University of São Paulo. It was founded in 1998 in order to provide a better academic developmentto students who value physical examination and human relations, besides providing to students in the beginningof graduation an early contact with patients and promotingan exchange of information between those three areas of health. EMA is sustained by three pillars: assistance, education and research, thus constituting an alternative to community-based education and assistance with a focus on humanization. The project is carried in two regions in the city of São Paulo and aims to offer these needy populations a free ambulatory care with quality, promote health and prevention. On Saturdays, undergraduate students see the patients and discuss the clinical case with a health professional;once a week, they attend a meeting with their group, which includes students of the three areas of health. During this meeting, the students report the clinical case and are assisted by other students to conduct the case and teach what they’ve learnt about the patient, collaborating with the establishment and deepening of the concepts in health. The project seeks to encourage their students since the first year of college to value the physician-patient relationship. Thus, it brings together people willing to work without the intention to earn a profit, but to learn more about health and to teach other students. As a result, members still participate in the project after graduation, as doctors committed to pass on their experience and knowledge

Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism

看護師の筋・骨格系のフィジカルアセスメントに関する実態調査

報告Reports　本研究は、看護師の筋・骨格系のフィジカルアセスメントに関する知識と実践について質問紙による実態調査を行った。対象は、総合病院勤務の看護師322 名とし、回収数は120 名（37.3％）であった。その結果、112 名（93.3％）の看護師は、フィジカルアセスメントを学んだ経験があった。必要な形態・機能の知識では、「四肢の動脈」を除くすべての項目で「まったくわからない」または「なんとなくわかる」と回答した者が４割以上を占めていた。フィジカルアセスメントの実践では、「臨床での活用の頻度」と「検査：MMT」などに関連を認めた。フィジカルアセスメントを活用している者の方が知識を持ち、実践できる傾向にあった。「実践できない」が最も多かった項目は、「検査：筋トーヌス」27.5％であった。このことから、フィジカルアセスメントに必要な形態・機能の知識を教授する研修が必要である。「臨床での活用の頻度」と関連を認めた「MMT の実践」などは、臨床場面で正確に修得できる可能性がある

ニンシン オ ケイキ ニ ジョウミャク ケッセンショウ オ ハッショウシ センテンセイ アンチトロンビンIII ケッソンショウ ト シンダン サレタ イチレイ

Congenital antithrombin III (AT III) deficiency is an inherited autosomal dominant disorder. Patients often suffer from recurrent venous thromboses that are triggered by several occasions (operation, gestation, trauma, oral contraceptive drug etc.). Moreover, 60% of them are said to be associated with pulmonary embolism. The patient of this report is 27-year-old pregnant woman in the first trimester. She felt pain in the back of her head and left auricle and presented with dyslexia and aphasia in late of March, 20XX. Getting CT brain scan, MRI brain scan, and blood sampling at the nearby hospital, she was suspected of having thrombosis of left sigmoid and transverse sinus due to AT III deficiency. Because she wanted to give birth to her first child without termination, she was referred to our hospital. We used heparin as the anticoagulant therapy because warfarin had the risk of teratogenesis. But in condition of low serum level of AT III activity, it didn’t work effectively. So we also did frequent complement of AT III. Strict anticoagulant therapy resulted in better outcome for both the patient and her baby without fatal venous thromboses or fetal complications

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe