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Cardiovascular Drugs and Therapy - To evaluate the effectiveness of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function, as well as lipid profile, in a mouse...  相似文献   
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The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Here, using mouse genetic approaches, we found that cilia were required specifically on MC4R-expressing neurons for the control of energy homeostasis. Moreover, these cilia were critical for pharmacological activators of the MC4R to exert an anorexigenic effect. The MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus of the hypothalamus (PVN) were essential to restrict food intake. MC4R activation increased adenylyl cyclase (AC) activity. As with the removal of cilia, inhibition of AC activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, the MC4R signaled via PVN neuron cilia to control food intake and body weight. We propose that defects in ciliary localization of the MC4R cause obesity in human inherited obesity syndromes and ciliopathies.  相似文献   
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BackgroundAdjuvant chemotherapy, postoperative radiation (PORT), and prophylactic cranial irradiation (PCI) have been individually examined in limited-stage small cell lung cancer (SCLC). There is a paucity of data on the effectiveness of each adjuvant treatment modality when used in combination after surgical resection of SCLC.MethodsData were collected from 5 cancer centers on all patients with limited-stage SCLC who underwent surgical resection between 1986 and 2019. Univariate and multivariable models were conducted to identify predictors of long-term outcomes, focusing on freedom from recurrence and survival benefit of adjuvant chemotherapy, PORT, and PCI.ResultsA total of 164 patients were analyzed. Multivariable Cox regression analysis did not identify any adjuvant therapies to significantly influence recurrence in this cohort. Specifically, PORT was not associated with a significant influence on locoregional recurrence and PCI was not significantly associated with intracranial outcomes. Adjuvant chemotherapy improved survival in all stage I through III disease (hazard ratio, 0.49; 95% confidence interval, 0.29-0.81; P = .005) and even in pathologically node negative patients (hazard ratio, 0.49; 95% confidence interval, 0.27-0.91; P = .024). Although PCI was found to improve survival in univariate analysis, it was not significant in a multivariable model. PORT was not found to affect survival on either univariate or multivariable analysis.ConclusionsThis is among the largest multi-institutional studies on surgically resected limited-stage SCLC. Our results highlight survival benefit of adjuvant chemotherapy, but did not identify a statistically significant influence from mediastinal PORT or PCI in our cohort. Larger prospective studies are needed to determine the benefit of PORT or PCI in a surgically resected limited-stage SCLC population.  相似文献   
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AIDS and Behavior - Although misperceived norms often drive personal health behaviors, we do not know about this phenomenon in the context of antiretroviral therapy (ART) adherence. We conducted a...  相似文献   
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The theory of self-determination considers that both environmental issues (such as the opportunity of choice) and intra-individual factors are correlated or predictive of self-determination. With regard to within-individual factors, some studies have explored the links between intellectual functioning and self-determination in people with Down Syndrome (DS). But the links between self-determination and certain cognitive (memory and language) and motor skills have not been clearly established. In this study, we compared three groups of people with DS ranked according to their self-determination scores with a group of adult controls. The comparison covered various areas of cognitive and motor skills. The results show that the most self-determined individuals with DS have better skills in many areas such as memory, motor and language skills, compared to the least self-determined individuals. The theory of self-determination allows us to interpret our results in terms of the role of the environment (and appropriate environmental supports) in the development of self-determination and through the more frequent achievement of daily activities, in the development of cognitive and motor skills.

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