Rationale Therapeutically targeting macrophage reverse cholesterol transport is a promising approach to treat atherosclerosis. Macrophage energy metabolism can significantly influence macrophage phenotype, but how this is controlled in foam cells is not known. Bioinformatic pathway analysis predicts that miR-33 represses a cluster of genes controlling cellular energy metabolism that may be important in macrophage cholesterol efflux. Objective We hypothesized that cellular energy status can influence cholesterol efflux from macrophages, and that miR-33 reduces cholesterol efflux via repression of mitochondrial energy metabolism pathways. Methods and Results In this study, we demonstrated that macrophage cholesterol efflux is regulated by mitochondrial ATP production, and that miR-33 controls a network of genes that synchronize mitochondrial function. Inhibition of mitochondrial ATP synthase markedly reduces macrophage cholesterol efflux capacity, and anti-miR33 required fully functional mitochondria to enhance ABCA1-mediated cholesterol efflux. Specifically, anti-miR33 de-repressed the novel target genes PGC-1α, PDK4 and SLC25A25 and boosted mitochondrial respiration and production of ATP. Treatment of atherosclerotic Apoe-/- mice with anti-miR33 oligonucleotides reduced aortic sinus lesion area compared to controls, despite no changes in HDL-C or other circulating lipids. Expression of miR-33a/b was markedly increased in human carotid atherosclerotic plaques compared to normal arteries, and there was a concomitant decrease in mitochondrial regulatory genes PGC-1α, SLC25A25, NRF1 and TFAM, suggesting these genes are associated with advanced atherosclerosis in humans. Conclusions This study demonstrates that anti-miR33 therapy de-represses genes that enhance mitochondrial respiration and ATP production, which in conjunction with increased ABCA1 expression, works to promote macrophage cholesterol efflux and reduce atherosclerosis.
Recent studies have shown that women are more likely than men to use the Internet to seek health information and that the use of technology is common among perinatal women. Access to the Internet is growing through the global use of mobile phones and apps, in both developed and less developed countries. This pattern is particularly relevant for clinicians and researchers who are interested in the use of technologies to disseminate perinatal depression interventions. In a cross-sectional anonymous online survey for English and Spanish-speaking perinatal women, 509 pregnant (77.6 percent) and postpartum (22.4 percent) women provided demographic and Information and Communication Technologies data. Results indicated that the single device with greatest access was the mobile phone (47.5 percent). The majority of the sample had Internet access through mobile phones, computers, or both. Significant differences in socioeconomic status were found for Internet seeking behavior of health-related information and downloading apps between those with and without Internet access. Ninety percent of respondents (n = 267) searched for health-related information and 72.3 percent had downloaded any kind of app. More than half of respondents (57 percent, n = 188) downloaded a health-related app and 26.9 percent reported having paid for the apps. This study shows preliminary evidence to suggest the need to design, develop, and test apps that aim to disseminate prevention programs for perinatal depression.
PurposeGlobal access to adequate resources to address postpartum depression (PPD) are limited and, at times, not reflective of the needs of pregnant women and new mothers. Gathering information about the preferences and needs of women when designing and implementing Internet-based programs is warranted, especially given the diversity of experiences related to childbirth. Thus, the aim of this study was to obtain user feedback on the content, structural, and cultural factors associated with a fully automated online PPD prevention intervention that, like similar programs, suffered from poor adherence and engagement.MethodsFollowing the completion of the Mothers and Babies Internet Course (eMB), an online prevention of PPD trial, a convenience sampling method was used to invite consenting participants to return to the site. Participants provided anonymous feedback on how to improve and adapt the eMB based on screenshots and video content from the Internet intervention. Demographic information and engagement in the online trial were examined as factors influencing participant responses.ResultsOne hundred nineteen English and Spanish speaking women from 27 countries and territories provided feedback about the eMB. Content-based feedback included requesting additional detail in explanations and simplifying recommended exercises. Structure-based feedback included requests for more visual representations of the materials. In general, participants did not explicitly suggest culturally specific feedback that differed by geographic region, but instead reported similar themes related to motherhood and childrearing. An unexpected finding that only emerged among English-speaking participants was the need for the eMB to address perfectionism and introspection as factors that impact motherhood. Relative to those who did not access the eMB in the parent study, women who did thought the intervention content was acceptable (i.e., no suggested changes) and provided feedback that referenced maternal stress and pregnancy experiences. Age, education, pregnancy status and number of children were not significant factors associated with participants' use of the eMB.ConclusionsFindings from this study offer preliminary information about the needs and preferences of an international sample of childrearing women who access automated Internet interventions to manage mood changes during the perinatal period.
In response to the European financial crisis of 2008-2009, Greece reduced funding for social spending as part of its austerity program, which may have reversed past progress in Greece’s mental health system. Significant increases in depression and suicide rates coincided with the start of the crisis. A slower economic recovery may result from the combination of a less productive work force and out-migration of mental health professionals. In order to alleviate the detrimental effects of this crisis, mental health crisis training, as well as low cost community-based programs should be prioritized in Greece.
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