Reveromycin A-Induced Apoptosis in Osteoclasts Is Not Accompanied by Necrosis.

Reveromycin A (RM-A), a small natural product isolated from Streptomyces bacteria, is a potential osteoporosis therapeutic in that it specifically induces apoptosis in osteoclasts but not osteoblasts. The purpose of the study presented here was to further elucidate the intracellular mechanisms of RM-A death effects in mature osteoclasts. A specific clone of RAW264.7 murine macrophages that was previously characterized for its ability to acquire an osteoclast nature on differentiation was differentiated in the presence of receptor activator of nuclear factor kappa B ligand (RANKL). Subsequent staining was performed for tartrate-resistant acid phosphatase to confirm their osteoclast character. These osteoclasts were treated with ten micromolar RM-A for 2, 4, 6, 24, and 48 h at a pH of 5.5. Peak apoptosis induction occurred at 4-6 h as measured by caspase 3 activity. Lactate dehydrogenase release assay revealed no significant RM-A-induced necrosis. Western blot analysis of cytoplasmic extracts demonstrated activation of caspase 9 (2.3-fold at 2 h and 2.6-fold at 4 h, each P < 0.05) and no significant changes in Bcl-XL . In nuclear extracts, NFκB levels significantly increased on differentiation with RANKL but then remained constant through RM-A treatment. Over the extended time course studied, RM-A-induced apoptosis in osteoclasts was not accompanied by necrosis, suggesting that RM-A would likely have limited effects on immediate, neighboring bone cell types. This specific cell death profile is promising for potential clinical investigations of RM-A as a bone antiresorptive.

Weight Gain and Related Comorbidities Following Antiretroviral Initiation in the 2000s: A Systematic Literature Review.

Antiretroviral therapies (ARTs) benefit millions with human immunodeficiency virus. However, concerns about subsequent weight gain and related metabolic complications have emerged. Early ARTs are associated with adipose tissue changes. While newer ARTs may have fewer adipose alterations, it is unclear whether they lead to increased weight gain. A systematic literature review was performed to describe current published literature describing the use of newer ARTs, weight gain, and related comorbidities. Titles and abstracts were screened, focusing on studies that examined ART initiation and subsequent weight gain; publications were then ranked based on publication type, methodology, and comorbidities, emphasizing US studies with large patient cohorts. This yielded a comprehensive review of the 50 publications on weight gain and a range of related comorbidities, including diabetes and hypertension. Most of the studies describing weight gain found the most significant gains during the first year after initiating ART. Overall, patients gained ∼5 kg 18-96 months after initiating ART. Many of the studies reported altered weight-related comorbidities, including increased risk of diabetes and hypertension. Despite an expectation that newer ARTs may be safer, a review of the literature suggests that contemporary ART use is associated with pronounced weight gain and related comorbidities. Future studies should define and quantify the direct role of newer ARTs in weight gain and related comorbidities, as well as clarify the role of specific drug classes in metabolic disturbance, to improve intervention strategies.

Attitudes toward teen mothers among nursing students and psychometric evaluation of Positivity Toward Teen Mothers scale.

To prepare future nurses who can deliver high quality nursing care to teen mothers, a better understanding of the nursing students' perception of teen mothers is needed. A descriptive cross-sectional study was conducted among 228 nursing students to evaluate the psychometric properties of the Positivity Toward Teen Mothers (PTTM) scale, to explore nursing students' general empathy and attitudes toward teen mothers, and to investigate the predictors of nursing students' attitudes toward teen mothers. Principal component factor analysis with varimax rotation resulted in a 19-item PTTM-Revised scale with Non-judgmental and Supportive subscales. Cronbach's alphas for the subscales were 0.84 and 0.69, respectively, and 0.87 for the total scale. Simultaneous multiple regression models showed that general empathy and having a teen mother in the family or as an acquaintance were significant predictors of positive attitudes toward teen mothers, whereas age was a significant negative predictor. The PTTM-Revised scale is a promising instrument for assessing attitudes toward teen mothers.