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The identification of ATP-binding cassette transporter A1 (ABCA1) as the defective gene in Tangier disease has contributed substantially to the understanding of its role as a key transporter of cholesterol [...], OBJECTIVE--The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low HDL cholesterol levels, obesity, and the metabolic syndrome in Mexican-Mestizos. Because a pivotal role for ABCA1 in pancreatic β-cell function was recently observed in the mouse model, we assessed the association of this variant with type 2 diabetes in this population. RESEARCH DESIGN AND METHODS--The initial group included 446 unrelated Mexican individuals: 244 with type 2 diabetes aged 20-69 years (121 with onset ≤45 years), and 202 nondiabetic control subjects aged >50 years. An independent study group included 242 type 2 diabetic case subjects and 225 control subjects with similar characteristics. RESULTS--R230C/C230C genotypes were significantly more frequent in type 2 diabetic individuals (24.6%) than in control subjects (11.4%) in the initial study group (OR 2.501; P = 0.001). After stratifying by age at diagnosis, the association was significant only in the early-onset group (age at diagnosis ≤45 years) (OR 3.776, P = 3.3 x [10.sup.-6]). Both associations remained significant after adjusting for admixture (P = 0.0008 and P = 8.1 x [10.sup.-6], respectively). Similar trends were observed in the independent study group, and the combined analysis of both populations showed a highly significant association of the R230C variant with type 2 diabetes, particularly with that of early onset (P = 7.6 x [10.sup.-6] and 9.4 x [10.sup.-8], respectively). CONCLUSIONS--The R230C ABCA1 variant is associated with type 2 diabetes, particularly of early onset, in the Mexican-Mestizo population.

Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions. [...]

•Higher residential density was associated with lower 3-year BMI increase in girls.•Nearby fast food was associated with higher BMI increase for teen girls and younger boys.•Built environment has limited impact on BMI trajectory in children and adolescents.•Independent effects are small but may accumulate over the life course.

Objective: To determine whether selected features of the built environment can predict weight gain in a large longitudinal cohort of adults. Methods: Weight trajectories over a 5-year period were obtained from electronic health records for 115,260 insured patients aged 18–64 years in the Kaiser Permanente Washington health care system. Home addresses were geocoded using ArcGIS. Built environment variables were population, residential unit, and road intersection densities captured using Euclidean-based SmartMaps at 800-m buffers. Counts of area supermarkets and fast food restaurants were obtained using network-based SmartMaps at 1600, and 5000-m buffers. Property values were a measure of socioeconomic status. Linear mixed effects models tested whether built environment variables at baseline were associated with long-term weight gain, adjusting for sex, age, race/ethnicity, Medicaid insurance, body weight, and residential property values. Results: Built environment variables at baseline were associated with differences in baseline obesity prevalence and body mass index but had limited impact on weight trajectories. Mean weight gain for the full cohort was 0.06 kg at 1 year (95% CI: 0.03, 0.10); 0.64 kg at 3 years (95% CI: 0.59, 0.68), and 0.95 kg at 5 years (95% CI: 0.90, 1.00). In adjusted regression models, the top tertile of density metrics and frequency counts were associated with lower weight gain at 5-years follow-up compared to the bottom tertiles, though the mean differences in weight change for each follow-up year (1, 3, and 5) did not exceed 0.5 kg. Conclusions: Built environment variables that were associated with higher obesity prevalence at baseline had limited independent obesogenic power with respect to weight gain over time. Residential unit density had the strongest negative association with weight gain. Future work on the influence of built environment variables on health should also examine social context, including residential segregation and residential mobility.

Background: Hospital-grade electric pumps may be useful to initiate and sustain adequate milk production for mothers who are unable to breast-feed their babies hospitalized at special care nurseries (SCN), but their cost is generally not affordable for SCN and for most mothers in developing countries. Therefore, manual breast pumps (MBPs) can be an alternative, but the best option is unknown considering clinical parameters and mothers' preference from among currently available MBPs.Objective: To compare the effectiveness of four MBPs in terms of milk volume, nutritional composition, and breast emptying in order to assist in making a choice for health care personnel and mothers in SCN settings. Duration of expression and maternal preference were also evaluated as secondary outcomes.Methods: Mothers of preterm infants used 4 MBPs in a random order, 2 with a squeeze-handle mechanism (Isis and Harmony) and 2 with a cylindrical mechanism (Little Heart and Evenflo), both at the hospital and in home settings using each pump over one 24-hour period.Results: Milk volume, nutritional composition, breast emptying, and duration of expression were not different among MBPs. Scale of maternal preference rated higher those with the squeeze-handle mechanism than the cylindrical mechanism (p< 0.05).Conclusions: There was no difference found in the effectiveness across the four pumps tested. The mothers' rating for comfort and ease of use showed a marked difference between pumps. These factors, plus cost, need to be considered when evaluating manual pumps for use in SCN settings in developing countries.

The purpose of this work was to study whether rat lactating mammary gland can synthesize PUFAs through the expression of Δ5 and Δ6 desaturases (Δ5D and Δ6D), whether these enzymes are regulated by the transcription factors sterol-regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor α (PPARα) and the coactivator peroxisome proliferator-activated receptor γ coactivator 1{szligbeta} (PGC-1{szligbeta}), and whether these desaturases are regulated by the lipid concentration in the diet. The results showed that on day 12 of lactation, ∼35% of the linoleic acid in the diet, which is the precursor of PUFAs, is transferred to the mammary gland. There was expression of Δ5D and Δ6D in mammary gland, and it was regulated by the corn oil content in the diet. The higher the corn oil content in the diet, the lower the expression of both desaturases. Induction of Δ5D and Δ6D was associated positively with similar changes in SREBP-1 and PGC-1{szligbeta}. Expression of PPARα was barely detected and was not affected by the corn oil content in the diet, whereas PGC-1{szligbeta} expression increased as the corn oil in the diet increased. These results indicate that the lactating mammary gland has the capacity to synthesize PUFAs and can be regulated by the lipid content in the diet.