Use of SPARK to promote after-school physical activity.

BACKGROUND: The after-school period is potentially an important venue for increasing physical activity for youth. We sought to assess the effectiveness of the Sports, Play, and Recreation for Youth (SPARK) program to increase physical activity and improve cardiorespiratory fitness and weight status among elementary students after school. METHODS: This quasi-experimental controlled study compared change in moderate to vigorous physical activity (MVPA), body mass index (BMI) z-score, and cardiorespiratory fitness (VO(2) ) over 5 months between students in after-school programs exposed to SPARK versus controls. Participants were fifth grade students at 3 intervention schools (N = 48) and 3 control schools (N = 52). RESULTS: There was no difference between groups in mean change in MVPA, BMI z-score, or cardiorespiratory fitness. After-school time dedicated to physical activity did not increase with the implementation of SPARK. Intervention students' self-assessment of their activity levels relative to their peers significantly increased compared to control students (p = .011). CONCLUSIONS: In this 5-month study, the SPARK program did not increase MVPA in the after-school setting. Increasing the amount of time dedicated to physical activity may be as important as the curriculum used to effectively increase physical activity after school.

Validation of a hip-worn accelerometer in measuring sleep time in children.

This study compared measures of sleep from an accelerometer worn on the hip to measures obtained from an accelerometer worn on the wrist, the gold standard measure of sleep behavior in community research. The accelerometer worn on the hip provides a measure of total sleep time in 10- to 11-year-old children comparable to the wrist-worn unit. We provide an alternate method to ascertain bedtime and final wake time when diary data are missing. A hip-worn accelerometer may provide a cost-effective means of gathering physical activity and sleep data simultaneously in large samples of children with or without an accompanying sleep diary.

A microdialysis study of extracellular levels of acamprosate and naltrexone in the rat brain following acute and repeated administration.

Acamprosate and naltrexone are widely used in the treatment of alcoholism. However, numerous studies in rodents have shown differential effects of these compounds on alcohol consumption and/or relapse-like behavior following acute versus repeated administration. In order to determine if these differential behavioral effects could be attributable to changes in extracellular levels of these compounds, we used in vivo microdialysis to monitor extracellular levels of acamprosate and naltrexone in the rat medial prefrontal cortex following acute and repeated intraperitoneal administration. For acute treatment, animals received a single administration of acamprosate (100 or 300 mg/kg) or naltrexone (1 or 3 mg/kg). For repeated treatment, animals received once daily treatment with saline, acamprosate (300 mg/kg) or naltrexone (3 mg/kg) for 10 days before a subsequent challenge with the compound according to their respective pretreatment group. Dialysate levels of acamprosate and naltrexone were analyzed by liquid chromatography-tandem mass spectrometry and high performance liquid chromatography, respectively. Following acute administration, peak dialysate concentrations of each compound were dose-dependent, observed within 1 hour of administration, and were found to be in the low micromolar range for acamprosate and in the low to mid-nanomolar range for naltrexone. Pretreatment with acamprosate, but not naltrexone, for 10 days resulted in higher dialysate concentrations of the compound relative to saline-pretreated controls. Thus, repeated administration of acamprosate, but not naltrexone, results in augmented extracellular levels of the compound in the brain relative to saline-pretreated controls, which may explain the need for repeated administration of acamprosate in order to observe effects on alcohol consumption and/or relapse.

The flamenco locus controls the gypsy and ZAM retroviruses and is required for Drosophila oogenesis.

In Drosophila, the as yet uncloned heterochromatic locus flamenco (flam) controls mobilization of the endogenous retrovirus gypsy through the repeat-associated small interfering (rasi) RNA silencing pathway. Restrictive alleles (flamR) downregulate accumulation of gypsy transcripts in the somatic follicular epithelium of the ovary. In contrast, permissive alleles (flamP) are unable to repress gypsy. DIP1, the closest transcription unit to a flam-insertional mutation, was considered as a good candidate to be a gypsy regulator, since it encodes a dsRNA-binding protein. To further characterize the locus we analyzed P-induced flam mutants and generated new mutations by transposon mobilization. We show that flam is required somatically for morphogenesis of the follicular epithelium, the tissue where gypsy is repressed. This developmental activity is necessary to control gypsy and another retroelement, ZAM. We also show that flam is not DIP1, as none of the new permissive mutants affect the DIP1 coding sequence. In addition, two deletions removing DIP1 coding sequences do not affect any of the flamenco functions. Our results suggest that flamenco extends proximally to DIP1, spanning >130 kb of transposon-rich heterochromatin. We propose a model explaining the multiple functions of this large heterochromatic locus.

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes.

RATIONALE: Corticotropin-releasing factor (CRF) produces anxiety-like and aversive effects when infused directly into the various regions of the brain, including the bed nucleus of the stria terminalis (BNST). However, the CRF receptor subtypes within the BNST mediating these phenomena have not been established. OBJECTIVES: We used selective CRF receptor antagonists to determine the receptor subtypes involved in the anxiogenic-like and aversive effects CRF in the BNST. MATERIALS AND METHODS: Male Long-Evans rats were bilaterally infused with CRF (0.2 or 1.0 nmol) either alone or in combination with the CRF1 receptor antagonist CP154,526 or the CRF2 receptor antagonist anti-sauvagine 30 (AS30) before behavioral testing in the elevated plus maze or place conditioning paradigms. RESULTS: Intra-BNST administration of CRF produced a dose-dependent reduction in open arm entries and open arm time in the elevated plus maze, indicating an anxiogenic-like effect. These effects were inhibited by co-infusion of CP154,526 but not of AS30, indicating that the anxiogenic-like effects of CRF in the BNST are mediated by CRF1 receptors. Place conditioning with intra-BNST administration of CRF produced a dose-dependent aversion to the CRF-paired environment that was prevented by co-infusion of either CP154,526 or AS30, indicating that both CRF receptor subtypes mediate the aversive effects of this peptide. Intra-BNST infusions of the CRF receptor antagonists alone produced no effects in either behavioral paradigm. CONCLUSIONS: CRF1 receptors in the BNST mediate the anxiogenic-like effects of CRF in this region, whereas both CRF1 and CRF2 receptor subtypes mediate the conditioned aversive effects of this peptide within the BNST.

The mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine decreases ethanol consumption via a protein kinase C epsilon-dependent mechanism.

Glutamatergic neurotransmission plays a critical role in addictive behaviors, and recent evidence indicates that genetic or pharmacological inactivation of the type 5 metabotropic glutamate receptor (mGluR5) reduces the self-administration of cocaine, nicotine, and alcohol. Because mGluR5 is coupled to activation of protein kinase C (PKC), and targeted deletion of the epsilon isoform (PKCepsilon) in mice reduces ethanol self-administration, we investigated whether there is a functional link between mGluR5 and PKCepsilon. Here, we show that acute administration of the mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine to mice increases phosphorylation of PKCepsilon in its activation loop (T566) as well as in its C-terminal region (S729). Increases in phospho-PKCepsilon are dependent not only on mGluR5 stimulation but also on phosphatidylinositol-3 kinase (PI3K). In addition, the selective mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) reduced basal levels of phosphorylation of PKCepsilon at S729. We also show that MPEP dose dependently reduced ethanol consumption in wild-type but not in PKCepsilon-null mice, suggesting that PKCepsilon is an important signaling target for modulation of ethanol consumption by mGluR5 antagonists. Radioligand binding experiments using [(3)H]MPEP revealed that these genotypic differences in response to MPEP were not a result of altered mGluR5 levels or binding in PKCepsilon-null mice. Our data indicate that mGluR5 is coupled to PKCepsilon via a PI3K-dependent pathway and that PKCepsilon is required for the ability of the mGluR5 antagonist MPEP to reduce ethanol consumption.

Bone mineral density and urine calcium excretion among subjects with and without nephrolithiasis.

BACKGROUND: Bone mineral density (BMD) is reduced among patients with idiopathic hypercalciuria (IH) and nephrolithiasis. To disentangle effects of diet, stone formation, and physiology upon BMD, we studied vertebral and femoral neck BMD among relatives of hypercalciuric stone formers, and contrasted those with to those without stones. METHODS: Among 59 subjects from 11 families, vertebral and femoral neck BMD, diet calcium intake, urine excretions of calcium, sodium, ammonium, titratable acid, sulfate, urea nitrogen, and serum levels of calcitriol and markers of bone turnover were studied. RESULTS: Stone formers (SF) consumed less calcium than non-stone formers (NSF). Spine and femoral neck BMD z-scores varied inversely with urine calcium loss and urine ammonium excretion among SF but not NSF. No correlations of BMD z-score were found for bone markers, calcitriol, or any of the other measurements. CONCLUSION: SF consumed less calcium, presumably to prevent more stones, and displayed a bone mineral responsiveness to calcium loss and ammonium excretion not present among NSF, who ate more calcium. Lowered calcium consumption in IH, perhaps in response to stone formation, alters bone responses in a direction that can predispose to mineral loss and eventual fracture.

Influence of gender and age on calcium oxalate crystal growth inhibition by urine from relatives of stone forming patients.

PURPOSE: We define the relationships between urine inhibition of calcium oxalate crystal growth and age, gender, urine chemistries and stone formation among relatives of calcium stone forming patients. MATERIALS AND METHODS: We collected 24-hour urine samples from 366 first degree relatives of calcium stone formers. Calcium oxalate crystal growth inhibition was studied using a constant amount of dialyzed urine protein in a seeded crystallization system. Standard stone risk measurements were also performed on the urine, including supersaturation for calcium oxalate, calcium phosphate and uric acid. RESULTS: By multivariate analysis crystal growth inhibition is strongly inversely related to the amount of protein excreted per day, and the age of the subject. When corrected for protein excretion and age, urine proteins from nonstone forming male subjects inhibited crystal growth more strongly than those from corresponding female subjects. Among stone formers the sex difference was not present. CONCLUSIONS: Inhibition of calcium oxalate crystal growth is influenced by a complex combination of gender, age, stone formation and assay conditions. The effect of daily protein excretion is most likely a consequence of using a fixed amount of urine protein per assay. The influence of age is significant and unexplained, with the urine of young people (less than 20 years) demonstrating a vigorous ability to inhibit crystallization. In addition, the urine of nonstone forming male relatives appears to have a greater ability to inhibit crystallization than that of nonstone forming female relatives. Further use of this assay in clinical investigations must take age and gender into proper account.

Urinary stone risk factors in the siblings of patients with calcium renal stones.

PURPOSE: We determined which, if any, urinary stone risk factors accurately discriminate stone forming and nonstone forming siblings of patients with calcium renal stones. MATERIALS AND METHODS: A total of 252 siblings of stone formers provided 2, 24-hour urine samples, which were sent overnight and analyzed at a central laboratory. Standard stone risk factors were measured and the supersaturation of calcium oxalate, calcium phosphate and uric acid was calculated. RESULTS: Discriminant functions were derived for each gender by multivariate analysis. In stone forming sisters higher urinary calcium and pH discriminated with a success rate of 70%. In stone forming brothers higher urinary calcium, lower urinary potassium and older age discriminated with a success rate of 79%. CONCLUSIONS: Select urinary measurements as well as age classify siblings into those with and without stones with fair accuracy. Calcium excretion and urinary pH in females, and calcium excretion, urinary potassium and age in males are feasible identifiers of stone forming siblings. To determine whether these measurements can be used to predict new stone onset may require years of observation of our current cohort.