Role of a plausible nuisance contributor in the declining obesity-mortality risks over time.

CONTEXT: Recent analyses of epidemiological data including the National Health and Nutrition Examination Survey (NHANES) have suggested that the harmful effects of obesity may have decreased over calendar time. The shifting BMI distribution over time coupled with the application of fixed broad BMI categories in these analyses could be a plausible nuisance contributor to this observed change in the obesity-associated mortality over calendar time. OBJECTIVE: To evaluate the extent to which observed temporal changes in the obesity-mortality association may be due to a shifting population distribution for body mass index (BMI), coupled with analyses based on static, broad BMI categories. DESIGN, SETTING, AND PARTICIPANTS: Simulations were conducted using data from NHANES I and III linked with mortality data. Data from NHANES I were used to fit a true model treating BMI as a continuous variable. Coefficients estimated from this model were used to simulate mortality for participants in NHANES III. Hence, the population-level association between BMI and mortality in NHANES III was fixed to be identical to the association estimated in NHANES I. Hazard ratios (HRs) for obesity categories based on BMI for NHANES III with simulated mortality data were compared to the corresponding estimated HRs from NHANES I. MAIN OUTCOME MEASURES: Change in hazard ratios for simulated data in NHANES III compared to observed estimates from NHANES I. RESULTS: On average, hazard ratios for NHANES III based on simulated mortality data were 29.3% lower than the estimates from NHANES I using observed mortality follow-up. This reduction accounted for roughly three-fourths of the apparent decrease in the obesity-mortality association observed in a previous analysis of these data. CONCLUSIONS: Some of the apparent diminution of the association between obesity and mortality may be an artifact of treating BMI as a categorical variable

Cool Companions to White Dwarf Stars from the Two Micron All Sky Survey All Sky Data Release

We present the culmination of our near-infrared survey of the optically spectroscopically identified white dwarf stars from the McCook and Sion catalog, conducted using photometric data from the Two Micron All Sky Survey final All Sky Data Release. The color selection technique, which identifies candidate binaries containing a white dwarf and a low-mass stellar (or substellar) companion via their distinctive locus in the near-infrared color-color diagram, is demonstrated to be simple to apply and to yield candidates with a high rate of subsequent confirmation. We recover 105 confirmed binaries, and identify 27 firm candidates (19 of which are new to this work) and 21 tentative candidates (17 of which are new to this work) from the 2MASS data. Only a small number of candidates from our survey have likely companion spectral types later than M5, none of which is an obvious L-type (i.e., potential brown dwarf) companion. Only one previously known white dwarf + brown dwarf binary is detected. This result is discussed in the context of the 2MASS detection limits, as well as other recent observational surveys that suggest a very low rate of formation (or survival) for binary stars with extreme mass ratios

Energy Cost of Slow and Normal Gait Speeds in Low and Normally Functioning Adults

Objective Slow walking speed paired with increased energy cost is a strong predictor for mortality and disability in older adults but has yet to be examined in a heterogeneous sample (ie, age, sex, disease status). The aim of this study was to examine energy cost of slow and normal walking speeds among low- and normal-functioning adults. Design Adults aged 20–90 yrs were recruited for this study. Participants completed a 10-m functional walk test at a self-selected normal walking speed and were categorized as low functioning or normal functioning based on expected age- and sex-adjusted average gait speed. Participants completed two successive 3-min walking stages, at slower than normal and normal walking speeds, respectively. Gas exchange was measured and energy cost per meter (milliliter per kilogram per meter) was calculated for both walking speeds. Results Energy cost per meter was higher (P \u3c 0.0001) in the low-functioning group (n = 76; female = 59.21%; mean ± SD age = 61.13 ± 14.68 yrs) during the slower than normal and normal (P \u3c 0.0001) walking speed bouts compared with the normal-functioning group (n = 42; female = 54.76%; mean ± SD age = 51.55 ± 19.51 yrs). Conclusions Low-functioning adults rely on greater energy cost per meter of walking at slower and normal speeds. This has implications for total daily energy expenditure in low-functioning, adult populations

Atrial GIRK Channels Mediate the Effects of Vagus Nerve Stimulation on Heart Rate Dynamics and Arrhythmogenesis

Diminished parasympathetic influence is central to the pathogenesis of cardiovascular diseases, including heart failure and hypertension. Stimulation of the vagus nerve has shown promise in treating cardiovascular disease, prompting renewed interest in understanding the signaling pathway(s) that mediate the vagal influence on cardiac physiology. Here, we evaluated the contribution of G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels to the effect of vagus nerve stimulation (VNS) on heart rate (HR), HR variability (HRV), and arrhythmogenesis in anesthetized mice. As parasympathetic fibers innervate both atria and ventricle, and GIRK channels contribute to the cholinergic impact on atrial and ventricular myocytes, we collected in vivo electrocardiogram recordings from mice lacking either atrial or ventricular GIRK channels, during VNS. VNS decreased HR and increased HRV in control mice, in a muscarinic receptor-dependent manner. This effect was preserved in mice lacking ventricular GIRK channels, but was nearly completely absent in mice lacking GIRK channels in the atria. In addition, atrial-specific ablation of GIRK channels conferred resistance to arrhythmic episodes induced by VNS. These data indicate that atrial GIRK channels are the primary mediators of the impact of VNS on HR, HRV, and arrhythmogenesis in the anesthetized mouse

Strategies to optimize the impact of nutritional surveys and epidemiological studies

The development of nutrition and health guidelines and policies requires reliable scientific information. Unfortunately, theoretical considerations and empirical evidence indicate that a large percentage of science-based claims rely on studies that fail to replicate. The session "Strategies to Optimize the Impact of Nutrition Surveys and Epidemiological Studies" focused on the elements of design, interpretation, and communication of nutritional surveys and epidemiological studies to enhance and encourage the production of reliable, objective evidence for use in developing dietary guidance for the public. The speakers called for more transparency of research, raw data, consistent data-staging techniques, and improved data analysis. New approaches to collecting data are urgently needed to increase the credibility and utility of findings from nutrition epidemiological studies. Such studies are critical for furthering our knowledge and understanding of the effects of diet on health

Primary care provider–reported involvement in breast cancer treatment decisions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149227/1/cncr31998.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149227/2/cncr31998_am.pd

Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer

Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. Thi..

Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106661/1/acel12170.pd