Cognition and brain oxygen metabolism improves after bariatric surgery-induced weight loss: A pilot study.

Objective: The primary objectives of this pilot study were to assess cognition and cerebral metabolic rate of oxygen (CMRO2) consumption in people with severe obesity before (baseline), and again, 2- and 14-weeks after sleeve gastrectomy bariatric surgery. Methods: Six people with severe/class 3 obesity (52 ± 10 years, five females, body mass index (BMI) = 41.9 ± 3.9 kg/m2), and 10 normal weight sex- and age-matched healthy controls (HC) (48 ± 6 years, eight females, 22.8 ± 1.9 kg/m2). Global CMRO2 was measured non-invasively using MRI and cognition using the Integneuro testing battery. Results: Following a sleeve gastrectomy induced weight loss of 6.4 ± 2.5 kg (% total-body-weight-lost = 5.4) over two-weeks, cognition total scores improved by 0.8 ± 0.5 T-scores (p=0.03, 15.8% improvement from baseline). Weight loss over 14-weeks post-surgery was 15.4 ± 3.6 kg (% total-body-weight-lost = 13.0%) and cognition improved by 1.1 ± 0.4 (p=0.003, 20.6% improvement from baseline). At 14-weeks, cognition was 6.4 ± 0.7, comparable to 6.0 ± 0.6 observed in the HC group. Baseline CMRO2 was significantly higher compared to the HC (230.4 ± 32.9 vs. 177.9 ± 33.9 µmol O2/100 g/min, p=0.02). Compared to baseline, CMRO2 was 234.3 ± 16.2 µmol O2/100 g/min at 2-weeks after surgery (p=0.8, 1.7% higher) and 217.3 ± 50.4 at 14-weeks (p=0.5, 5.7% lower) after surgery. 14-weeks following surgery, CMRO2 was similar to HC (p=0.17). Conclusion: Sleeve gastrectomy induced weight loss was associated with an increase in cognition and a decrease in CMRO2 observed 14-weeks after surgery. The association between weight loss, improved cognition and CMRO2 decrease should be evaluated in larger future studies.

HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol.

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERß downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

Aerobic Fitness Is Disproportionately Low in Adult Burn Survivors Years After Injury.

A maximal aerobic capacity below the 20th percentile is associated with an increased risk of all-cause mortality (Blair 1995). Adult Adult burn survivors have a lower aerobic capacity compared with nonburned adults when evaluated 38 ± 23 days postinjury (deLateur 2007). However, it is unknown whether burn survivors with well-healed skin grafts (ie, multiple years postinjury) also have low aerobic capacity. This project tested the hypothesis that aerobic fitness, as measured by maximal aerobic capacity (VO2max), is reduced in well-healed adult burn survivors when compared with normative values from nonburned individuals. Twenty-five burn survivors (36 ± 12 years old; 13 females) with well-healed split-thickness grafts (median, 16 years postinjury; range, 1-51 years) covering at least 17% of their BSA (mean, 40 ± 16%; range, 17-75%) performed a graded cycle ergometry exercise to test volitional fatigue. Expired gases and minute ventilation were measured via a metabolic cart for the determination of VO2max. Each subject's VO2max was compared with sex- and age-matched normative values from population data published by the American College of Sports Medicine, the American Heart Association, and recent epidemiological data (Aspenes 2011). Subjects had a VO2max of 29.4 ± 10.1 ml O2/kg body mass/min (median, 27.5; range, 15.9-53.3). The use of American College of Sports Medicine normative values showed that mean VO2max of the subjects was in the lower 24th percentile (median, 10th percentile). A total of 88% of the subjects had a VO2max below American Heart Association age-adjusted normative values. Similarly, 20 of the 25 subjects had a VO2max in the lower 25% percentile of recent epidemiological data. Relative to nongrafted subjects, 80 to 88% of the evaluated skin-graft subjects had a very low aerobic capacity. On the basis of these findings, adult burn survivors are disproportionally unfit relative to the general U.S. population, and this puts them at an increased risk of all-cause mortality (Blair 1995).

Carotid baroreflex control of leg vasculature in exercising and non-exercising skeletal muscle in humans.

Carotid baroreflex (CBR) function was examined in five men and three women (25 +/- 1 years) using the variable-pressure neck collar technique at rest and during dynamic, one-legged knee extension exercise at 7 W and 25 W. The CBR exhibited control of leg vascular conductance (LVC) at rest and during exercise in both an exercising leg (EL) and a non-exercising leg (NEL) across a wide range of pressures from +40 Torr neck pressure (NP) to -80 Torr neck suction (NS). Specifically, increases in LVC (% change) in response to NS were no different across -20 to -80 Torr in either EL or NEL compared to rest, P > 0.05. However, CBR-mediated decreases in percentage LVC in response to NP were attenuated in EL at both 7 W (16 +/- 1%) and 25 W (12 +/- 1%) compared to rest (40 +/- 3%; P < 0.05) as well as compared to responses in the NEL (36 +/- 6% at 7 W and 36 +/- 7% at 25 W; P < 0.05). This decrease in vascular responsiveness in EL was associated with a reduction in the gain of the percentage muscle sympathetic nerve activity (%MSNA)-%LVC relationship compared to rest (P < 0.05). Collectively, these data indicate that, despite a clear attenuation of the vascular response to MSNA in the exercising leg, CBR-mediated changes in mean arterial pressure were no different between rest and exercise.