Branched-chain amino acids alter cellular redox to induce lipid oxidation and reduce de novo lipogenesis in the liver.

Metabolic and molecular interactions between branched-chain amino acid (BCAA) and lipid metabolism are evident in insulin-resistant tissues. However, it remains unclear whether insulin resistance is a prerequisite for these relationships and whether BCAAs or their metabolic intermediates can modulate hepatic lipid oxidation and synthesis. We hypothesized that BCAAs can alter hepatic oxidative function and de novo lipogenesis, independent of them being anaplerotic substrates for the mitochondria. Mice (C57BL/6NJ) were reared on a low-fat (LF), LF diet plus 1.5X BCAAs (LB), high-fat (HF) or HF diet plus 1.5X BCAAs (HB) for 12 wk. Hepatic metabolism was profiled utilizing stable isotopes coupled to mass spectrometry and nuclear magnetic resonance, together with fed-to-fasted changes in gene and protein expression. A greater induction of lipid oxidation and ketogenesis on fasting was evident in the BCAA-supplemented, insulin-sensitive livers from LB mice, whereas their rates of hepatic de novo lipogenesis remained lower than their LF counterparts. Onset of insulin resistance in HF and HB mice livers blunted these responses. Whole body turnover of BCAAs and their ketoacids, their serum concentrations, and the ketogenic flux from BCAA catabolism, all remained similar between fasted LF and LB mice. This suggested that the impact of BCAAs on lipid metabolism can occur independent of them or their degradation products fueling anaplerosis through the liver mitochondria. Furthermore, the greater induction of lipid oxidation in the LB livers accompanied higher mitochondrial NADH/NAD+ ratio and higher fed-to-fasting phosphorylation of AMPKα and ACC. Taken together, our results provide evidence that BCAA supplementation, under conditions of insulin sensitivity, improved the feeding-to-fasting induction of hepatic lipid oxidation through changes in cellular redox, thus providing a favorable biochemical environment for flux through ß-oxidation and lower de novo lipogenesis.NEW & NOTEWORTHY Branched-chain amino acids (BCAAs) have been shown to modulate lipid metabolic networks in various tissues, especially during insulin resistance. In this study we show that the dietary supplementation of BCAAs to normal, insulin-sensitive mice resulted in higher mitochondrial NADH:NAD+ ratios and AMPK activation in the liver. This change in the cellular redox status provided an optimal metabolic milieu to increase fatty acid oxidation while keeping the rates of de novo lipogenesis lower in the BCAA-supplemented mice livers.

A phenomenological understanding of residents' emotional distress of living in an environmental justice community.

Deteriorative environmental conditions in environmental justice (EJ) communities not only post direct health risks such as chronic illnesses, but also cause emotional distress such as anxiety, fear, and anger among residents, which may further exacerbate health risks. This study applies a descriptive phenomenological method to explore and describe the emotional experience of residents living in Ironbound, a known EJ community located in Newark, New Jersey. Twenty-three residents participated in the study. Four essential themes regarding the residents' emotional experiences were elicited from 43 interviews: (1) being worried about the harmful effects of the surrounding pollution; (2) being distressed by the known historical pollution sources; (3) being frustrated by the unheard voices and/or lack of responses; and (4) being angered by the ongoing pollution sources. Participants not only expressed their emotions of worry, distress, frustration, and anger in detail but also described reasons or situations that provoked such negative emotions. Such detailed depictions provide insights into potential meaningful strategies to improve residents' psychological wellbeing by alleviating negative emotions and meaningfully engaging residents in developing, implementing, and enforcing environmental laws, regulations, and policies to achieve EJ goals.

Patterns of Obesity and Lymph Fluid Level during the First Year of Breast Cancer Treatment: A Prospective Study.

Obesity is one of the risk factors for developing lymphedema following breast cancer treatment. We prospectively enrolled 140 women and followed the participants for 12 months after surgery to investigate patterns of obesity and lymph fluid level in the first year of cancer treatment. Electrical bioimpedance devices were used to measure weight, BMI, and percent of body fat as well as lymph fluid level. General instructions were given to the participants on maintaining pre-surgery weight. Among the 140 participants, 136 completed the study with 2.9% attrition. More than 60% of the participants were obese (30.8%) or overweight (32.4%), while only two participants were underweight and about 35% had normal weight. This pattern of obesity and overweight was consistent at 4-8 weeks and 12 months post-surgery. At 12 months post-surgery, the majority of the women (72.1%) maintained pre-surgery weight and 15.4% had >5% weight loss; 12.5% of the women increase >5% of their weight. Significantly more patients in the obesity group had lymphedema defined by L-Dex ratio >7.1 than those in the normal/underweight and overweight group at pre-surgery and 4-8 weeks post-surgery. There was a trend of more patients in the obesity group had L-Dex ratio >7.1 at 12 months post-surgery. Obesity and overweight remain among women at the time of cancer diagnosis and the patterns of obesity and overweight continue during the first year of treatment. General instructions on having nutrition-balanced and portion-appropriate diet and physical activities daily or weekly can be effective to maintain pre-surgery weight.

Comorbidities and Quality of Life among Breast Cancer Survivors: A Prospective Study.

Many breast cancer survivors have coexistent chronic diseases or comorbidities at the time of their cancer diagnosis. The purpose of the study was to evaluate the association of comorbidities on breast cancer survivors' quality of life. A prospective design was used to recruit 140 women before cancer surgery, 134 women completed the study. Comorbidities were assessed using self-report and verified by medical record review and the Charlson Comorbidity Index (CCI) before and 12-month after cancer surgery. Quality of life was evaluated using Short-Form Health Survey (SF-36 v2). Descriptive statistics, chi-square tests, t-tests, Fisher's exact test, and correlations were performed for data analysis. A total of 28 comorbidities were identified. Among the 134 patients, 73.8% had at least one of the comorbidities, 54.7% had 2-4, and only 7.4% had 5-8. Comorbidities did not change at 12 months after surgery. Numbers of comorbidities by patients' self-report and weighted categorization of comorbidities by CCI had a similar negative correlation with overall quality of life scores as well as domains of general health, physical functioning, bodily pain, and vitality. Comorbidities, specifically hypertension, arthritis, and diabetes, were associated with poorer quality of life in multiple domains among breast cancer survivors. Future research should consider the combined influence of comorbidity and cancer on patients' quality of life.

Electronic monitoring and counseling to improve medication adherence.

Electronic caps, pill caps that record the date and time of pill bottle opening provide an objective measure of adherence to prescribed medication. A promising intervention to improve adherence, cue-dose training, involves reviewing patients' pill cap-generated reports concerning their medication-taking and offering individualized recommendations for remembering to take medications at specific times of day. In this preliminary study, 79 patients prescribed the antihyperglycemic medication metformin had adherence assessed during a 4-week baseline period. Adherence, defined as proportion of prescribed doses taken within a predetermined 4-h window, was measured using electronic MEMS caps. Those who had less than 80% baseline adherence (n = 33) were randomly assigned to either receive 4 months of cue-dose training (n = 16) or to a control group (n = 17). Cue-dose training was associated with significantly better adherence to metformin (mean improvement of 15%). The effects of cue-dose training on adherence to other antihyperglycemic medication did not reach statistical significance. Glycosylated hemoglobin (a measure of blood sugar control) did not differ between groups. Data from nine patients who reviewed pill cap-generated data with their primary care providers suggested that both patients and providers found the discussion moderately helpful and not at all uncomfortable.

Neuropsychological correlates of suboptimal adherence to metformin.

The goal of this study was to determine if neuropsychological function is associated with adherence to prescribed medication. Altogether, 79 patients with type II diabetes at a VA primary care clinic had adherence to the antihyperglycemic drug metformin measured with MEMS caps over a 4-week period. They completed several tests of neuropsychological function: Mini-Mental Status Exam (MMSE), Trails A and B, Stroop, Digit Span, Digit Symbol, and Grooved Pegboard. In separate multivariate analyses, Stroop word score and time to complete Trails B were independently associated with adherence, as was age. Secondary analyses of the relationship between neuropsychological variables and other adherence-related measures were conducted. Low scores on the MMSE and non-Caucasian ethnicity were associated with missed appointments. None of the neuropsychological variables were associated with glycosylated hemoglobin. These results suggest that cognitive abilities should be considered when counseling patients concerning their adherence.