A population-based assessment of left ventricular systolic dysfunction in middle-aged and older adults: the Strong Heart Study

BACKGROUND: Although clinical congestive heart failure (CHF) is increasingly common, few data document the prevalence and correlates of underlying left ventricular (LV) systolic dysfunction (D) in population-based samples. METHODS: Echocardiography was used in the second Strong Heart Study (SHS) examination to identify mild and severe LVD (LV ejection fraction [EF] 40%-54% and <40%, respectively) in 3184 American Indians. RESULTS: Mild and severe LVD were more common in men than women (17.4% vs 7.2% and 4.7% vs 1.8%) and in diabetic than nondiabetic participants (12.7% vs 9.1% and 3.5% vs 1.6%). Stepwise increases were observed from participants with normal EF to those with mild and severe LVD in age (mean 60 vs 61 and 63 years, P <.001), prevalence of overt CHF (2% vs 6% and 28%) and definite coronary heart disease (3% vs 11% and 32%), systolic pressure (129 vs 135 and 136 mm Hg), serum creatinine level (0.98 vs 1.34 and 2.16 mg/dL), and log urinary albumin/creatinine level (3.2 vs 3.7 and 4.7); a negative relation was seen with body mass index (31.1 vs 31.0 and 28.4 kg/m(2)) (all P <.001). In multivariate analyses lower LVEFs were independently associated with clinical CHF and coronary heart disease, lower myocardial contractility, male sex, hypertension, overweight, arterial stiffening (higher pulse pressure/stroke volume) and renal dysfunction (higher serum creatinine level), higher LV mass, and lower relative wall thickness. CONCLUSIONS: LVD, present in approximately 14% of middle-aged to elderly adults, is independently associated with overt heart failure and coronary heart disease, male sex, hypertension, overweight, arterial stiffening, and renal target organ damage and, less consistently, with older age and diabetes.     

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.     

Human apolipoprotein A-IV metabolism within triglyceride-rich lipoproteins and plasma

In order to investigate the metabolism of apo A-IV within TRL and plasma, we assessed TRL and plasma apo A-IV kinetics in 19 and 4 subjects, respectively, consuming an average US diet for a 6-week period. At the end of this diet study, each subject received a primed-constant infusion of deuterated leucine over a 15 h time period with hourly feeding, and blood samples were drawn at 10 time points. TRL was separated by ultracentrifugation. Apo A-IV was isolated by immunoprecipitation and/or SDS-PAGE. Apo A-IV concentrations were determined by immunoelectrophoresis. Stable isotope tracer/tracee ratios were measured by gas chromatography/mass spectrometry, and the data were analyzed by multicompartmental modeling. The mean concentrations of plasma and TRL apo A-IV during the isotope infusion period were 21.0+/-3.2 and 0.66+/-0.25 mg/dl, respectively, and these values were 11.5 and 30.5% higher than those of fasting samples. The mean TRL and plasma apo A-IV residence times (RT) were 1.97+/-0.57 and 2.71+/-0.65 days, and transport rates (TR) were 0.17+/-0.19 and 3.90+/-1.24 mg/kg per day, respectively. There were significant correlations between TRL apo A-IV concentrations and TR (r(2)=0.79, P<0.001), and between TRL apo A-IV pool size and TRL cholesterol levels (r(2)=0.29, P=0.02). Our data indicated that; (1) TRL apo A-IV has a RT of 1.97 days which is similar to that earlier reported for HDL apo A-IV; (2) Apo A-IV recirculates between TRL and other slowly turning over pools; (3) the primary determinant of TRL apo A-IV levels is its TR; and (4) there is no correlation between TRL apo A-IV and apo B48 fractional catabolism in TRL.     

A Qualitative,Cross-Sectional Study of Positive and Negative Comments of Residency Programs Across 9 Medical and Surgical Specialties

IMPORTANCE

Residency applicants often use social media to discuss the positive and negative features of prospective training programs. An examination of the content discussed by applicants could provide guidance for how a medical education faculty can better engage with prospective trainees and adapt to meet the educational expectations of a new generation of digital-native physicians.

Persistence of urothelial carcinoma of the bladder risk among former smokers: Results from a contemporary,prospective cohort study

ObjectivesCigarette smoking is a known risk factor for urothelial carcinoma (UC) of the bladder. However, the persistence of an increased risk for UC following smoking cessation is not well established. We assessed the risk of UC among former smokers using a recent, prospective cohort with a high proportion of former smokers.Materials and methodsStudy participants were members of the VITamins And Lifestyle cohort (VITAL), a group of 77,719 men and women between the ages of 50 and 76 years from western Washington State. Smoking history and other risk factors were obtained at the time of recruitment. The primary outcome was a new diagnosis of UC (n =385), as determined through linkage to a population-based cancer registry.Results and limitationsThe cohort included 8% current and 44% former smokers, and among the UC cases, 15% were current and 60% former smokers. Both the current and former smoker had an increased risk of UC compared with never smokers (hazard ratio [HRs]: 3.81; 95% confidence intervals [CI] 2.71–5.35 and 2.0; 95% CI 1.55–2.58, respectively). Among former smokers, the risk of UC increased with the pack-years smoked and decreased with the years since quitting. When both the measures of smoking were considered together, the risk of UC was similar for long-term quitters and recent quitters for a given level of pack-years. For example, for those with pack-years of 22.5–37.5, the HR of UC was 1.91 (95% CI 1.17–3.11) for the distant quitters (≥23.5 y before baseline) and HR = 1.92 (95% CI 1.26–2.94) among the recent quitters. Limitations include the small number of cases at the extremes of smoking history and errors in self-reported smoking history.ConclusionsThe risk of bladder cancer in former smokers remains elevated>32 years after quitting, even among those with moderate smoking histories. This argues that a history of smoking confers a lifelong increased risk of UC.