Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration and improve heart function. However, evidence suggests that their regenerative capacity may be limited in conditions of severe hypoxia. Elucidating the mechanisms involved in CPC protection against hypoxic stress is essential to maximize their cardioprotective and therapeutic potential. We investigated the effects of hypoxic stress on CPCs and found significant reduction in proliferation and impairment of vasculogenesis, which were associated with induction of quiescence, as indicated by accumulation of cells in the G0-phase of the cell cycle and growth recovery when cells were returned to normoxia. Induction of quiescence was associated with a decrease in the expression of c-Myc through mechanisms involving protein degradation and upregulation of p21. Inhibition of c-Myc mimicked the effects of severe hypoxia on CPC proliferation, also triggering quiescence. Surprisingly, these effects did not involve changes in p21 expression, indicating that other hypoxia-activated factors may induce p21 in CPCs. Our results suggest that hypoxic stress compromises CPC function by inducing quiescence in part through downregulation of c-Myc. In addition, we found that c-Myc is required to preserve CPC growth, suggesting that modulation of pathways downstream of it may re-activate CPC regenerative potential under ischemic conditions.
Objectives: Chronic musculoskeletal pain (CMP) causes significant health loss worldwide. Given that cultural factors may affect pain processing, it is key to have more information regarding CMP epidemiology in Latin America. In this study, we aimed to determine the prevalence of CMP and chronic widespread pain (CWP) in Chile.Methods: This was a cross-sectional survey study. We used data recollected in the 2016-2017 Chilean National Health Survey, a nationwide household survey. Our study population included subjects older than 14 years living in urban and rural Chile. We defined CMP as nontraumatic pain with a duration of longer than 3 months. Chronic widespread pain was defined by the presence of CMP in 5 body regions. The association between CMP and CWP and potential risk factors was investigated through univariate and multivariate logistic regression models. Results:After excluding subjects with missing information our final sample constituted 4045 subjects. Chronic musculoskeletal pain was present in 21.8% (95% confidence interval, 19.6%-24.1%) and CWP in 4.2% (95% confidence interval, 3.3%-5.1%). Significant risk factors in multivariate analysis were older age, female sex, lower educational level, and depressive symptoms. Factors associated with a reduced risk of CMP were not being married and moderate alcohol consumption.Conclusions: One of 5 Chilean people has chronic pain, and 1 of 20 has CWP. Data regarding alcohol and pain have been controversial in previous studies; therefore, this decreased risk in moderate consumers should be further explored. Chronic widespread pain shared risk factors and protective factors with CMP but with a higher magnitude of association.
The clinical update serves as a brief review of recently published, high-impact, and potentially practice changing journal articles summarized for our readers. Topics include menopause, sexual dysfunction, breast health, contraception, osteoporosis, and cardiovascular disease. In this clinical update, we selected recent publications relevant to osteoporosis management. We highlight articles on the safety of long-term use of denosumab and bisphosphonates, fracture risk after discontinuing menopausal hormone therapy, calcium intake and cardiovascular risk, as well as the value of repeat dual X-ray absorptiometry scanning to monitor those on osteoporosis treatment.
Background and Objective Whether and when surgical intervention is indicated for mediastinal cysts is a matter of some debate. While most mediastinal cysts are found incidentally, the anatomic location, clinical presentation, and symptoms, as well as the potential for malignancy, are important considerations that inform decisions related to whether to intervene surgically. The objective of this review is to summarize the current literature regarding the criteria for surgical excision of mediastinal cysts and provide a framework for the clinician and surgeon to arrive at a decision regarding the appropriateness of surgical intervention of mediastinal cysts. Methods A review of the published literature in the last 45 years (1977–2022) was conducted through PubMed, MeSh and Google Scholar. We included retrospective reviews, meta-analyses, and case studies published in the English language. A single author identified eligible studies, and those identified were reviewed by the team until consensus was met. Pediatric literature was excluded from this review. Key Content and Findings The current literature predominantly contains case studies, small retrospective studies, and meta-analyses describing mediastinal cysts. In the anterior mediastinum, multiloculated thymic cysts should be resected to rule out thymic malignancy. Intralesional fat, smooth borders, and a more midline location are features suggestive of a benign process, while asymmetric cystic wall thickening has been associated with malignancy. Both esophageal and bronchogenic cysts should be excised, taking into account the risk of complications (up to a 45% risk) of infection, rupture, or compression, as well as the rare risk of associated malignancy. Simple thymic and small pericardial cysts can be observed and followed with serial radiographic tools and should be resected if they increase in size, compress surrounding structures, or lead the patient to develop symptoms. Conclusions Since mediastinal cysts are rare and often asymptomatic, there are no formal guidelines outlining when surgical intervention should be undertaken. Based on our review of the literature, surgical intervention should be pursued if the patient’s symptoms correlate with radiographic findings of a mediastinal cyst, there is compression of the surrounding structures, and concern of malignancy is present.
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