Efforts to search for better treatment options for cancer have been a priority, and due to these efforts, new alternative therapies have emerged. For instance, clinically relevant tumor-suppressive microRNAs that target key oncogenic drivers have been identified as potential anti-cancer therapeutics. MicroRNAs are small non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. Aberrant microRNA expression, through misexpression of microRNA target genes, can have profound cellular effects leading to a variety of diseases, including cancer. While altered microRNA expression contributes to a cancerous state, restoration of microRNA expression has therapeutic benefits. For example, ectopic expression of microRNA-34a (miR-34a), a tumor suppressor gene that is a direct transcriptional target of p53 and thus is reduced in p53 mutant tumors, has clear effects on cell proliferation and survival in murine models of cancer. MicroRNA replacement therapies have recently been tested in combination with other agents, including other microRNAs, to simultaneously target multiple pathways to improve the therapeutic response. Thus, we reasoned that other microRNA combinations could collaborate to further improve treatment. To test this hypothesis miR-34a was used in an unbiased cell-based approach to identify combinatorial microRNA pairs with enhanced efficacy over miR-34a alone. This approach identified a subset of microRNAs that was able to enhance the miR-34a antiproliferative activity. These microRNA combinatorial therapeutics could offer superior tumor-suppressive abilities to suppress oncogenic properties compared to a monotherapeutic approach. Collectively these studies aim to address an unmet need of identifying, characterizing, and therapeutically targeting microRNAs for the treatment of cancer.
BACKGROUND: Early ambulation of patients with total joint replacement (TJR) has been shown to improve outcomes while reducing length of stay and postoperative complications. Limited physical therapy (PT) resources and late-in-the-day cases may challenge day-of-surgery (POD0) ambulation. At our institution, a Mobility Technician (MT) program, composed of specially trained nurse's aides, was developed to address this issue. PURPOSE: The purpose of this study was to compare the effectiveness of the MT model with a traditional PT model in the early ambulation of patients with TJR. METHODS: Patients undergoing unilateral primary TJR at a single institution between June 1, 2014, and October 31, 2018, were included. Ambulation measures were retrospectively assessed between pre- and post-MT program groups. RESULTS: This study included 11,777 patients with TJR. Following the MT program, number of POD0 ambulations, POD0 ambulation distance, and total distance ambulated all increased while time-to-first ambulation decreased. CONCLUSION: Preliminary analyses indicate that the MT program has been successful in the early ambulation of patients with TJR.
Lifestyle interventions among breast cancer survivors with obesity have demonstrated successful short-term weight loss, but data on long-term weight maintenance are limited. We evaluated long-term weight loss maintenance in 100 breast cancer survivors with overweight/obesity in the efficacious six-month Lifestyle, Exercise, and Nutrition (LEAN) Study (intervention = 67; usual care = 33). Measured baseline and six-month weights were available for 92 women. Long-term weight data were obtained from electronic health records. We assessed weight trajectories between study completion (2012–2013) and July 2019 using growth curve analyses. Over up to eight years (mean = 5.9, SD = 1.9) of post-intervention follow-up, both the intervention (n = 60) and usual care (n = 32) groups declined in body weight. Controlling for body weight at study completion, the yearly weight loss rate in the intervention and usual care groups was –0.20 kg (−0.2%/year) (95% CI: 0.06, 0.33, p = 0.004) and −0.32 kg (−0.4%/year) (95% CI: 0.12, 0.53, p = 0.002), respectively; mean weight change did not differ between groups (p = 0.31). It was encouraging that both groups maintained their original intervention period weight loss (6% intervention, 2% usual care) and had modest weight loss during long-term follow-up. Breast cancer survivors in the LEAN Study, regardless of randomization, avoided long-term weight gain following study completion.
Despite the need for and relevance of leadership skills to the success of medical trainees and healthcare professionals, few medical schools offer formal leadership training during the preclinical years. Where such curricula exist, we have found few schools that intentionally incorporate key principles of lifestyle medicine critical to short- and long-term career development. We describe a novel relationship-centered leadership curriculum, grounded in a conceptual framework of emotional intelligence and incorporating key principles of lifestyle medicine, first piloted in 2019 and now in its fourth year of existence. In comparing pre- and post-course self-evaluations on a 5-point Likert scale, students (n = 19) reported increased competencies in Self (3.12 vs 4.20, P < .001), Teams (3.06 vs 4.00, P < .001), and System (2.55 vs 3.55, P < .001) domains. Qualitative responses demonstrated that a vital strength of the course was its direct relevance and immediate applicability to students’ personal and professional roles and goals. Results provide encouraging support for using a relationship-centered leadership framework that incorporates core elements of lifestyle medicine and emotional intelligence to facilitate medical students’ leadership development, as related to leading oneself and in dynamic relationships with others (e.g., with leaders, colleagues, patients, and within communities, teams, and systems).
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