Background Lesch-Nyhan disease (LND) is a rare, X-linked, neurodevelopmental metabolic disorder that results from a near-complete lack of hypoxanthine phosphoribosyl-transferase enzyme activity. LND is characterized by hyperuricemia, motor neurological abnormalities, recurrent self-injury, and cognitive impairment, but its neural substrates remain poorly understood. Methods In this cross-sectional study, we measured gray matter abnormalities in 21 persons with LND, 17 with an attenuated variant of the phenotype (LNV), and 33 healthy controls using voxel-based morphometry. We conducted an analysis of covariance to identify group differences in regional gray matter volume (GMV), followed by six pair-wise post-hoc group comparisons. Findings Patients with LND showed 20% smaller intracranial volumes (17% gray and 26% white matter) than healthy adults. The largest differences were found in basal ganglia, frontotemporal, and limbic regions, with sparing of parieto-occipital regions. The gray matter volumes of LNV participants invariably fell between those of patients with classical LND and healthy controls. Compared to healthy adults, patients with LND showed additional GMV reductions in the temporal lobe and left lateralized structures, and patients with LNV showed additional reductions in lingual and precuneus regions with sparing of right frontal and temporal regions. LND participants showed reductions in the ventral striatum and prefrontal areas relative to LNV. Interpretation This study of brain morphology reveals regional abnormalities associated with known neurological and behavioral deficits in persons with LND. It also revealed that patients with LNV show milder gray matter abnormalities in many of the same brain regions and preservation of GMV in other regions which could provide important clues to the neural substrates of differences between thephenotypes.

Methods: This study compares CAM usage between baby boomers (n ‫؍‬ 7734) and the silent generation (n ‫؍‬ 4682) through secondary analyses of the 2007 National Health Interview Survey data. The analysis also compares chronic disease and pain status. Multivariate logistic regression models were developed to identify generational differences.Results: Although the silent generation reported twice as many chronic disease (51.3% vs 26.1%; P < .001) and more painful conditions (56.1% vs 52.2%; P < .001), baby boomers were more likely to use CAM within the past year (43.1% vs 35.4%; P < .001). Adjusting for covariates, baby boomers with heart disease, cancer, and diabetes were more likely to use CAM than adults from the silent generation. Chronic pain status was independently associated with greater CAM use (adjusted odds ratio, 2.26; 95% confidence interval, 2.03-2.52).Conclusions: Baby boomers reported significantly higher rates of CAM use than the silent generation for both chronic diseases and painful conditions. Family physicians caring for the aging population must use patient-centered communication about the risks/benefits of CAM, which is necessary to promote effective coping with chronic illnesses and pain. (J Am Board Fam Med 2014;27:465-473.)

Understanding how plasma lipoproteins influence competitive displacement interactions would be valuable in helping to explain and perhaps predict pharmacokinetic parameters that may affect clinical outcome. The clinical significance of competitive displacement of drugs in patients with dyslipidemia requires further study.

Lesch-Nyhan disease (LND) is a rare, X-linked recessive neurodevelopmental disorder caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGprt), an enzyme in the purine salvage pathway. HGprt has two functions; it recycles hypoxanthine and guanine. Which of these two functions is more relevant for pathogenesis is unclear because some evidence points to hypoxanthine recycling, but other evidence points to guanine recycling. In this study, we selectively assayed hypoxanthine (Hprt) and guanine (Gprt) recycling in skin fibroblasts from 17 persons with LND, 11 with an attenuated variant of the disease (LNV), and 19 age-, sex-, and race-matched healthy controls (HC). Activity levels of both enzymes differed across groups (p< 0.0001), but only Gprt distinguished patients with LND from those with LNV (p<0.05). Gprt also showed slightly stronger correlations than Hprt with 13 of 14 measures of the clinical phenotype, including the severity of dystonia, cognitive impairment, and behavioral abnormalities. These findings suggest that loss of guanine recycling might be more closely linked to the LND/LNV phenotype than loss of hypoxanthine recycling.

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Although no change in the steady-state unbound (active) concentration of clozapine would predict no change in clinical status, it is possible that this may only apply to the individuals with a normal lipid profile. We believe clozapine's association with lipoproteins (particularly triglycerides) may actually increase clozapine's effectiveness.

Introduction: Institutions that serve on-site meals provide an unrealized opportunity to improve health on a broad scale, especially for underserved populations. Psychiatric rehabilitation programs commonly serve meals to adults with serious mental illness (SMI; schizophrenia and bipolar disorder), a population with a markedly increased prevalence of obesity and high risk of cardiovascular disease mortality. In the context of a behavioral weight-loss trial incorporating weight management counseling for persons with SMI, we delivered an environmental-level intervention, focused on the food environment. Hypothesis: We hypothesized the environmental intervention would reduce the overall calories served at the psychiatric rehabilitation program study sites. Methods: We partnered with kitchen supervisors to reduce calories and improve the nutritional quality of meals served at psychiatric rehabilitation programs. Intervention staff met with kitchen staff at the beginning and followed up quarterly to assess progress and to reinforce key nutritional messages. Environmental interventions included decreasing sugar sweetened beverages, increasing whole grains, and reducing saturated fat in meals. Breakfast and lunch menus were collected at baseline and 18 months after intervention. We calculated mean (SD) total energy and nutrient content of each meal. Results: Ten psychiatric rehabilitation programs participated. Eight sites served breakfast and all sites served lunch. Compared to baseline, average breakfast calories decreased significantly after 18-months from 568.4 to 457.1 (p=0.0048) and average lunch calories decreased from 729.4 to 623.8 (p<0.0001). Saturated fat in breakfast decreased by 1.9g (p=0.015) and 1.8g for lunch (p=0.0061). Total sugars at breakfast decreased from 53.3g to 40.1g (p=0.0008) and at lunch from 38.9g to 33.7g (p=0.004). Sodium was not significantly changed for breakfast (713.5mg to 557.3mg, p=0.148) but decreased by 412.4mg (1527.4mg to 1115.1mg, p=0.0008) for lunch. Conclusions: The environmental intervention implemented at psychiatric rehabilitation programs successfully reduced the amount of calories, saturated fat, sugars, and sodium served. This study suggests that modifying the food environment at psychiatric rehabilitation programs is feasible. Such programs can likely be applied to other institutions that serve on-site meals, and may be especially important in preventing cardiovascular disease in other underserved populations.