Money is not enough: exploring the impact of social and cultural resources on youth health

Findings on socioeconomic health differentials in youth remain fragmented with the role of cumulative and interaction effects of different forms of health resources not well understood.

Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?

Sleep-wake disturbances are frequent in patients with Parkinson's disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep-wake disturbances in Parkinson's disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson's disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson's disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin-deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson's disease. Poorer sleep quality is linked to dopamine deficiency and other disease-related factors. Despite hypocretin cell loss in Parkinson's disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients.

BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice

BOK/MTD was discovered as a protein that binds to the anti-apoptotic Bcl-2 family member MCL-1 and shares extensive amino-acid sequence similarity to BAX and BAK, which are essential for the effector phase of apoptosis. Therefore, and on the basis of its reported expression pattern, BOK is thought to function in a BAX/BAK-like pro-apoptotic manner in female reproductive tissues. In order to determine the function of BOK, we examined its expression in diverse tissues and investigated the consequences of its loss in Bok(-/-) mice. We confirmed that Bok mRNA is prominently expressed in the ovaries and uterus, but also observed that it is present at readily detectable levels in several other tissues such as the brain and myeloid cells. Bok(-/-) mice were produced at the expected Mendelian ratio, appeared outwardly normal and proved fertile. Histological examination revealed that major organs in Bok(-/-) mice displayed no morphological aberrations. Although several human cancers have somatically acquired copy number loss of the Bok gene and BOK is expressed in B lymphoid cells, we found that its deficiency did not accelerate lymphoma development in Eμ-Myc transgenic mice. Collectively, these results indicate that Bok may have a role that largely overlaps with that of other members of the Bcl-2 family, or may have a function restricted to specific stress stimuli and/or tissues.

Impact of antibiotic use on carbapenem resistance in Pseudomonas aeruginosa: is there a role for antibiotic diversity?

In this study, we aimed to evaluate the relationship between the rates of resistance of Pseudomonas aeruginosa to carbapenems and the levels and diversity of antibiotic consumption. Data were retrospectively collected from 20 acute care hospitals across 3 regions of Switzerland between 2006 and 2010. The main outcome of the present study was the rate of resistance to carbapenems among P. aeruginosa. Putative predictors included the total antibiotic consumption and carbapenem consumption in defined daily doses per 100 bed days, the proportion of very broad-spectrum antibiotics used, and the Peterson index. The present study confirmed a correlation between carbapenem use and carbapenem resistance rates at the hospital and regional levels. The impact of diversifying the range of antibiotics used against P. aeruginosa resistance was suggested by (i) a positive correlation in multivariate analysis between the above-mentioned resistance and the proportion of consumed antibiotics having a very broad spectrum of activity (coefficient = 1.77; 95% confidence interval, 0.58 to 2.96; P < 0.01) and (ii) a negative correlation between the resistance and diversity of antibiotic use as measured by the Peterson homogeneity index (coefficient = -0.52; P < 0.05). We conclude that promoting heterogeneity plus parsimony in the use of antibiotics appears to be a valuable strategy for minimizing the spread of carbapenem resistance in P. aeruginosa in hospitals.

Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood

We report on a female who is compound heterozygote for two new point mutations in the CYP19 gene. The allele inherited from her mother presented a base pair deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele inherited from her father showed a point mutation from G-->A at the splicing point (canonical GT to mutational AT) between exon and intron 3. This mutation ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase deficiency was already suspected because of the marked virilization occurring prepartum in the mother, and the diagnosis was confirmed shortly after birth. Extremely low levels of serum estrogens were found in contrast to high levels of androgens. Ultrasonographic follow-up studies revealed persistently enlarged ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day) given for 50 days at the age of 3 6/12 yr resulted in normalization of serum gonadotropin levels, regression of ovarian size, and increase of whole body and lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size returned to pretreatment levels shortly (150 days) after cessation of E2 therapy. Therefore, we recommend that affected females be treated with low-dose E2 in amounts sufficient to result in physiological prepubertal E2 concentrations using an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted throughout childhood and puberty to ensure normal skeletal maturation and adequate adolescent growth spurt, normal accretion of bone mineral density, and, at the appropriate age, female secondary sex maturation.