Publications

UNLABELLED

Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. We tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end, stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%.

CONCLUSION

The data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease.

BACKGROUND

Limited data are available on the effects of air travel in patients with pulmonary hypertension (PH), despite their risk of physiologic compromise. We sought to quantify the incidence and severity of hypoxemia experienced by people with PH during commercial air travel.

METHODS

We recruited 34 participants for a prospective observational study during which cabin pressure, oxygen saturation (Sp O 2 ), heart rate, and symptoms were documented serially at multiple predefined time points throughout commercial flights. Oxygen desaturation was defined as SpO2, <85%.

RESULTS

Median flight duration was 3.6 h (range, 1.0-7.3 h). Mean ± SD cabin pressure at cruising altitude was equivalent to the pressure 1,968 ± 371 m (6,456 ± 1,218 ft) above sea level (ASL)(maximum altitude 5 2,621 m [8,600 ft] ASL). Median change in Sp O 2 from sea level to cruising altitude was 2 4.9% (range, 2.0% to 2 15.8%). Nine subjects (26% [95% CI, 12%-38%]) experienced oxygen desaturation during flight (minimum Sp O 2 5 74%). Thirteen subjects (38%) reported symptoms during flight, of whom five also experienced desaturations. Oxygen desaturation was associated with cabin pressures equivalent to . 1,829 m (6,000 ft) ASL, ambulation, and flight duration(all P values , .05).

CONCLUSIONS

Hypoxemia is common among people with PH traveling by air, occurring in one in four people studied. Hypoxemia was associated with lower cabin pressures, ambulation during flight, and longer flight duration. Patients with PH who will be traveling on flights of longer duration or who have a history of oxygen use, including nocturnal use only, should be evaluated for supplemental in-flight oxygen.

OBJECTIVE

To investigate whether time on antiretroviral therapy (ART) is associated with improvements in food security and nutritional status, and the extent to which associations are mediated by improved physical health status.

DESIGN

The Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of HIV-infected adults newly initiating ART in Mbarara, Uganda.

METHODS

Participants initiating ART underwent quarterly structured interview and blood draws. The primary explanatory variable was time on ART, constructed as a set of binary variables for each 3-month period. Outcomes were food insecurity, nutritional status, and PHS. We fit multiple regression models with cluster-correlated robust estimates of variance to account for within-person dependence of observations over time, and analyses were adjusted for clinical and sociodemographic characteristics.

RESULTS

Two hundred twenty-eight ART-naive participants were followed for up to 3 years, and 41% were severely food insecure at baseline. The mean food insecurity score progressively declined (test for linear trend P < 0.0001), beginning with the second quarter (b = -1.6; 95% confidence interval: -2.7 to -0.45) and ending with the final quarter (b = -6.4; 95% confidence interval: -10.3 to -2.5). PHS and nutritional status improved in a linear fashion over study follow-up (P < 0.001). Inclusion of PHS in the regression model attenuated the relationship between ART duration and food security.

CONCLUSIONS

Among HIV-infected individuals in Uganda, food insecurity decreased and nutritional status and PHS improved over time after initiation of ART. Changes in food insecurity were partially explained by improvements in PHS. These data support early initiation of ART in resource-poor settings before decline in functional status to prevent worsening food insecurity and its detrimental effects on HIV treatment outcomes.

OBJECTIVE

To evaluate the association between self-reported diabetes and the risk of breast cancer (BC) and its interaction with moderate-intensity physical activity in pre- and postmenopausal Mexican women.

RESEARCH DESIGN AND METHODS

A population-based case-control study was conducted using 1,000 incident case subjects and 1,074 control subjects. Blood samples and information on health, diet, physical activity, and anthropometric measurements were obtained.

RESULTS

The association between diabetes and BC risk decreased with increasing tertiles of moderate-intensity physical activity (odds ratio [OR] = 4.9 [95% CI 2.3-10.8]; 3.0 [1.3-6.9]; and 1.0 [0.1-9.2], respectively, for each tertile) (test for interaction = 0.04). Compared with the women in the lowest tertiles, increased risk was observed in those premenopausal women with the highest serum C-peptide, IGF-1, and IGF-1 binding protein 3 levels.

CONCLUSIONS

Moderate-intensity physical activity can substantially ameliorate the increased BC risk in diabetic women.

These guidelines were developed and updated by an interdisciplinary group of experts based on clinical experience and available scientific evidence. The goal of these guidelines is to help patients with cancer experience the best quality of life possible throughout the illness trajectory by providing guidance for the primary oncology team for symptom screening, assessment, palliative care interventions, reassessment, and afterdeath care. Palliative care should be initiated by the primary oncology team and augmented by collaboration with an interdisciplinary team of palliative care experts.

BACKGROUND

Cooccurring pain, mood disorders, and substance abuse are common in HIV-infected patients. Our objective was to investigate the relationship between pain, alone and in the context of mood disorders and substance abuse, on clinic utilization, antiretroviral therapy adherence, and virologic suppression.

METHODS

Pain, mood disorders, and substance abuse were assessed at the first visit. No-show and urgent visits were measured over a 1-year period. Models were adjusted for age, race, sex, insurance status, CD4(+) T-lymphocyte count, and HIV risk factor.

RESULTS

Among 1521 participants, 509 (34%) reported pain, 239 (16%) had pain alone, 189 (13%) had pain and a mood disorder, and 30 (2%) had pain and substance abuse. In univariate models, participants with pain, mood disorders, and substance abuse had higher odds of a no-show visit than those without these conditions [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-1.8; OR, 1.5; 95% CI, 1.2-1.9; OR, 2.0; 95% CI, 1.4-2.8, respectively]. In the multivariable model, pain increased the odds of a no-show visit only in participants without substance abuse (OR, 1.5; 95% CI, 1.1-1.9) and pain reduced the odds of a no-show visit in participants with substance abuse (OR, 0.5; 95% CI, 0.2-0.9; P for interaction = 0.0022).

CONCLUSIONS

In this study, pain increased the odds of no-show visits but only for participants without substance abuse. Because pain, mood disorders, and substance abuse are highly prevalent in HIV-infected patients, our findings have implications for HIV treatment success. Interventions that incorporate pain management may be important for improving health outcomes in patients living with HIV infection.