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The aim of this study was to compare protein secretion on intact skin of extremities and verify the relationship between the marker proteins on abdominal skin and systemic factors using skin blotting. A cross‐sectional study was conducted among elderly patients aged 65 years and older (N = 73) at a long‐term medical facility in Japan. Skin blotting was performed on the right and left forearms, right and left lower legs, and abdomen. Pearson's correlations and Bland–Altman plots were utilised for comparing the protein secretion from the skin between the right or left forearms or lower legs. Multiple regression analysis was applied to determine the relationship between intensity levels of 3 proteins on the abdominal skin and the systemic factors. Bland–Altman plots demonstrated that there was no significant difference between right and left secretion levels on the forearms and lower legs among 3 proteins. Multiple regression analysis showed that age and antiplatelet use was positively associated with decreased collagen type IV and increased matrix metalloproteinase 2 levels, respectively. Our findings suggested that collecting samples from either the right or the left skin would be sufficient if skin properties between arms and legs are evaluated using skin blotting.  相似文献   
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Together with regulatory T cells (Tregs), tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte‐derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD‐L1 and chemokines by CD163+ CD206+ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD‐L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD‐L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T‐cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.  相似文献   
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Mental illness is a significant cause of disability worldwide, including here in the United States. Given the shortage of trained mental health professionals, a significant portion of patients needing care are managed in the primary care setting. Accountable Care Organizations (ACOs), for example, are seeking to improve the quality of care for this vulnerable population, but many are facing significant challenges relating to integration of new services. We sought to elucidate barriers faced by primary care practitioners (PCPs)—physicians, physician trainees and nurse practitioners—at a New York primary care clinic, which impede delivery of optimal care to those suffering from mental illness. The study was conducted with 32 PCPs in 2016–2017 at Mount Sinai Internal Medicine Associates in New York City. For the quantitative component of the study, a 54-item questionnaire was devised to assess their attitude, behavior and confidence in managing psychiatric patients. For the qualitative component, data was obtained from 3 open-ended questions. Responses were coded for salient themes. Analysis revealed a range of difficulties faced by PCPs. Overall, participants felt that the need to integrate mental health care into primary care was important, however they reported significant barriers in terms of lack of time, lack of resources, low confidence in treating more complex mental health conditions and difficulties with referring patient to mental health specialists. Despite a growing body of evidence that integration of mental health services in primary care leads to improved outcomes, addressing barriers to care will be key to ensuring feasibility of integration measures.  相似文献   
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