Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of hypothalamic Sirt1 in body weight and energy balance regulation is debated. The first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague-Dawley rats. Central inhibition of Sirt1 decreased body weight and food intake as a result of a forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which in turn increased phosphorylated FoxO1 via improved insulin/phosphorylated AKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-melanocyte-stimulating hormone (α-MSH) maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (triiodothyronine, thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of Sirt1 in the brain, particularly the hypothalamus, in body weight and energy balance regulation is debated. Among the first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague Dawley rats. In that study, central inhibition of Sirt1 decreased body weight and food intake as a result of a Forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which, in turn, increased phosphorylated FoxO1 via improved insulin/pAKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-MSH maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

Medical students' self-reported preparedness and attitudes in providing care to ethnic minorities.

BACKGROUND: To assess medical students' self-reported preparedness to provide care to ethnic minorities, factors that influence preparedness, and attitudes toward cultural competency training. METHODS: A cross-sectional study, which invited University of British Columbia medical students to participate in a survey on student demographics, knowledge and awareness, preparedness and willingness, and personal attitudes. Of 1024, eligible, 301 students consented to study. RESULTS: Students across all year levels felt significantly less ready to provide care for non-English speaking Chinese patients compared to "any" patients. Proficiency in working with interpreters was correlated with readiness, OR 4.447 (1.606-12.315) along with 3rd and 4th year level in medical school, OR 3.550 (1.378-9.141) and 4.424 (1.577-12.415), respectively. Over 80% of respondents reported interest in learning more about the barriers and possible ways of overcoming them. CONCLUSIONS: More opportunities for cultural competency training in the medical curriculum are warranted and would be welcomed by the students.

The impending shortage and cost of training the future plastic surgical workforce.

An expanding US population with increasing demand for aesthetic surgery, growing competition from other specialties, a constant rate of retiring plastic surgeons, and a static number of residents places increasing demands on the plastic surgical workforce in the coming years. Without certain changes, the plastic surgical workforce will be unable to meet their demand, and other specialties will increasingly encroach on aesthetic and reconstructive procedures. Given Census Bureau predictions for the US population, the numbers of residents allotted by the Balanced Budget Act of 1997, The American Board of Plastic Surgery data on the current plastic surgical workforce, and using a population-based analysis to predict future shortages in plastic surgery residents, the workforce shortage can be estimated as 800 residents in 2020 and up to 3223 residents in 2050. Based on previously reported figures, the additional cost in training these residents by 2050 is more than $1.5 billion.

Preoperative assessment of high-risk candidates to predict survival after heart transplantation.

BACKGROUND: Alternate waiting list strategies expand listing criteria for patients awaiting heart transplantation (HTx). We retrospectively analyzed clinical events and outcome of patients listed as high-risk recipients for HTx. METHODS AND RESULTS: We analyzed 822 adult patients who underwent HTx of whom 111 patients met high-risk criteria. Clinical data were collected from medical records and outcome factors calculated for 61 characteristics. Significant factors were summarized in a prognostic score. Age >65 years (67%) and amyloidosis (19%) were the most common reasons for alternate listing. High-risk recipients were older (63.2±10.2 versus 51.4±11.8 years; P<0.001), had more renal dysfunction, prior cancer, and smoking. Survival analysis revealed lower post-HTx survival in high-risk recipients (82.2% versus 87.4% at 1-year; 59.8% versus 76.3% at 5-year post-HTx; P=0.0005). Prior cerebral vascular accident, albumin <3.5 mg/dL, re-HTx, renal dysfunction (glomerular filtration rate <40 mL/min), and >2 prior sternotomies were associated with poor survival after HTx. A prognostic risk score (CARRS [CVA, albumin, re-HTx, renal dysfunction, and sternotomies]) derived from these factors stratified survival post-HTx in high-risk (3+ points) versus low-risk (0-2 points) patients (87.9% versus 52.9% at 1-year; 65.9% versus 28.4% at 5-year post-HTx; P<0.001). Low-risk alternate patients had survival comparable with regular patients (87.9% versus 87.0% at 1-year and 65.9% versus 74.5% at 5-year post-HTx; P=0.46). CONCLUSIONS: High-risk patients had reduced survival compared with regular patients post-HTx. Among patients previously accepted for alternate donor listing, application of the CARRS score identifies patients with unacceptably high mortality after HTx and those with a survival similar to regularly listed patients.

Current technology: devices available for destination therapy.

Left ventricular assist device therapy as a destination therapy for end-stage heart failure has made a large leap with continuous flow devices. Continuous flow does not seem to have a detrimental effect on end-organ function, at least in the midterm. Various expected and unexpected complications have been reported associated with this technology. More experience and research are warranted.

A minimally invasive approach is more cost-effective than a traditional sternotomy approach for mitral valve surgery.

OBJECTIVE: The aim of this study was to compare the cost and effectiveness of a minimally invasive (MI) versus traditional sternotomy (ST) approach for mitral valve surgery (MVS). METHODS: From January 1, 2003, to December 31, 2008, a total of 847 patients underwent isolated MVS at our institution. Propensity matching on 22 clinical variables was carried out to generate a study cohort of 434 patients (217 matched pairs). Direct and indirect costs from the hospital perspective were retrospectively obtained from our finance department. Total hospital costs were further stratified into 13 standardized institutional billing categories. In addition, data on morbidity, mortality, discharge location, hospital readmissions within 1 year, and freedom from reoperation were obtained. RESULTS: Compared with ST, MIMVS was associated with a $9054 ± $3302 lower mean total hospital cost (P = .006), driven largely by a reduction in direct (P = .003) versus indirect costs (P = .06). Among the 13 billing categories, MIMVS was associated with a significant reduction in costs of cardiac imaging (P = .004), laboratory tests (P = .005), boarding and nursing (P = .001), and radiology (P = .002). More patients in the ST group required intubation for more than 72 hours (P = .019); however, there were no differences in morbidity or long-term survival (P = .334). A higher proportion of MI patients were discharged home with no nursing services (P = .018), and a higher proportion of ST patients required readmission within 1 year (P = .023). There were no differences in freedom from reoperation between groups (P = .574). CONCLUSIONS: With equivalent efficacy across a range of measures and lower costs compared with ST, MIMVS represents a cost-saving strategy for MVS.