RNA-binding motif protein 10 inactivates c-Myc by partnering with ribosomal proteins uL18 and uL5.

RNA-binding motif protein 10 (RBM10) is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). Yet, it remains unknown whether cancer-derived mutant RBM10 compromises its tumor suppression function and, if so, the molecular insight of the underlying mechanisms. Here, we show that wild-type RBM10 suppresses lung cancer cell growth and proliferation by inactivating c-Myc that is essential for cancer cell survival. RBM10 directly binds to c-Myc and promotes c-Myc's ubiquitin-dependent degradation, while RBM10 knockdown leads to the induction of c-Myc level and activity. This negative action on c-Myc is further boosted by ribosomal proteins (RPs) uL18 (RPL5) and uL5 (RPL11) via their direct binding to RBM10. Cancer-derived mutant RBM10-I316F fails to bind to uL18 and uL5 and to inactivate c-Myc, thus incapable of suppressing tumorigenesis. Our findings uncover RBM10 as a pivotal c-Myc repressor by cooperating with uL18 and uL5 in lung cancer cells, as its failure to do so upon mutation favors tumorigenesis.

Impact of Pharmacy Proximity and Delivery Services on HIV Viral Suppression Among Low Income Urban Patients.

Adherence to antiretrovirals is essential to achieve viral suppression in HIV patients. Unfortunately, numerous barriers to adherence and subsequent viral suppression still exist. This study examines the association between pharmacy location and viral suppression for low income HIV patients. We evaluated whether home delivery services or closer proximity to in-store pharmacies was associated with viral suppression. Patients utilizing delivery pharmacy had increased likelihood of sustained viral suppression compared to in-store pharmacy patients (aOR = 3.430). For patients traveling to pharmacies, there were no differences in proximity for suppressed and non-suppressed patients. Home delivery may aid adherence and improve viral suppression.

INCREASED BONE TURNOVER IN TYPE 2 DIABETES PATIENTS RANDOMIZED TO BARIATRIC SURGERY VERSUS MEDICAL THERAPY AT 5 YEARS.

OBJECTIVE: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial. METHODS: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index [BMI], 36.5 ± 3.6 kg/m2) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% [78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed. RESULTS: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB ( P<.001) and 61.1 ± 90% in SG ( P<.001) compared to 29.8 ± 93% in IMT ( P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB ( P<.001) and 71 ± 69% in SG ( P<.001) compared to 43.8 ± 121.1% in IMT ( P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients ( P<.001). Increase in CTX correlated with decreased BMI in SG patients ( P = .039). CONCLUSION: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients. ABBREVIATIONS: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione.

Estimating the causal effect of treatment with direct-acting antivirals on kidney function among individuals with hepatitis C virus infection.

BACKGROUND: Direct-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated. METHODS: We analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m2), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m2) under each intervention. For patients with baseline CKD Stages 2-4 (15

Increased Free Testosterone Levels in Men with Uncontrolled Type 2 Diabetes Five Years After Randomization to Bariatric Surgery.

Hypogonadism frequently occurs in male patients with type 2 diabetes (T2DM) and is linked to insulin resistance and inflammation. Testosterone levels rise acutely in obese patients following bariatric surgery, though long-term changes have not been investigated in a randomized controlled trial. This study evaluated obese men with T2DM randomized to either bariatric surgery or medical therapy. Testosterone, gonadotropins, body composition, insulin sensitivity, and inflammatory markers were evaluated in 32 patients at baseline and at 5 years. Surgical patients had 47.4% increase in free testosterone compared to medical therapy patients who had 2.2% decrease (P = 0.013). Increase in free testosterone correlated with reduction in body weight, high-sensitivity C-reactive protein (hsCRP), and leptin levels. Prolonged improvements in testosterone levels after bariatric surgery in T2DM are found to be related to reduction in body weight and adipogenic inflammation.