Elevated skeletal osteopontin levels contribute to the hypophosphatasia phenotype in Akp2(-/-) mice.

Increased levels of ePP(i) in mice deficient in TNALP (i.e., Akp2(-/-)) lead to elevated OPN concentrations. We examined the skeletal phenotype of mice lacking both OPN and TNALP and concluded that the increased OPN levels contribute to the hypophosphatasia phenotype characteristic of Akp2(-/-) mice. We also found that extracellular OPN regulates the PP(i) output by osteoblasts. INTRODUCTION: Akp2(-/-) display mineralization deficiencies characterized by rickets/osteomalacia. This defect has been attributed to the increased levels of extracellular inorganic pyrophosphate (ePP(i)), a substrate of tissue-nonspecific alkaline phosphatase (TNALP) and a potent inhibitor of mineral deposition. Because elevated levels of ePP(i) induce Opn gene expression, the Akp2(-/-) mice also display increased levels of osteopontin (OPN), another inhibitor of mineralization. MATERIALS AND METHODS: Akp2(-/-) mice were bred into the Opn(-/-) line. The resulting double knockout mice were analyzed for skeletal abnormalities by histology and muCT. Calvarial osteoblasts were assayed for their ability to mineralize in vitro and were probed for changes in gene expression. RESULTS: Mice lacking both Akp2 and Opn showed partial normalization at the histological level with regard to mineral deposition and BMD. However, high ePP(i) levels remained in Akp2(-/-) mice. We found that Opn(-/-) mice have themselves elevated levels of ePP(i) attributable to an increase in Enpp1 and Ank expression and a concomitant downregulation of Akp2 expression in Opn(-/-) osteoblasts, but that Opn(-/-) mice have more mineralized osteoid than wildtype (WT) controls despite their elevated ePP(i) levels. Addition of exogenous OPN to Opn(-/-) osteoblasts results in downregulation of Enpp1 and Ank gene expression and a reduction of the PP(i) output by these cells. CONCLUSIONS: Deletion of both Akp2 and Opn can partially rescue the hypomineralized phenotype of Akp2(-/-) mice. However, these double knockout mice do not display corrected ePP(i) levels, and we conclude that regulation of hydroxyapatite deposition requires the coordinated actions of both PP(i) and OPN and that the hypophosphatasia phenotype in Akp2(-/-) mice results from the combined inhibitory action of increased levels of both ePP(i) and OPN. Our data also suggest that the ePP(i)-mediated regulation of OPN and the OPN-mediated regulation of ePP(i) are linked counterregulatory mechanisms that control the concentrations of these two important mineralization inhibitors, OPN and ePP(i).     

Final-year student nurses' perceptions of role transition

Role transition can be both challenging and exciting. This study presents the findings of phase one of a two-part study conducted by Deasy et al (2011), which explored final-year student nurses' (n=116) perceptions and expectations of role transition. The students were registered on four-year BSc nursing programmes at an Irish university. Data was analyzed using SPSS (version 16). A response rate of 84% was achieved. Over half of respondents said they were adequately prepared for the post of registered nurse. Respondents generally perceived themselves to be competent across a range of domains: managing workloads; prioritizing care delivery; interpersonal skills; time management skills; ethical decision making; and providing health information and education. In contrast, not all were confident about their knowledge and many expected the transition to be problematic. Most expected to be supported and to receive constructive feedback. Recommendations include nurturing supportive work environments to reduce stress and increase confidence.     

Evaluation of between-methods agreement of extracellular water measurements in adults and children

BACKGROUND: Extracellular water (ECW), a relevant molecular level component for clinical assessment, is commonly obtained by 2 methods that rely on assumptions that may not be possible to test at the time the measurements are made. OBJECTIVE: The aim of the current study was to evaluate the degree of agreement between ECW assessment by the sodium bromide dilution (ECW(NaBr)) and total body potassium (TBK; whole-body (40)K counting) to total body water (TBW; isotope dilution) methods (ECW(TBK-TBW)) in an ethnically mixed group of children and adults. DESIGN: ECW was measured with the ECW(NaBr) and ECW(TBK-TBW) methods in 526 white and African American males and females (86 nonobese children, 193 nonobese adults, and 247 obese adults). Fat mass was assessed with dual-energy X-ray absorptiometry. Multiple regression analysis was used to examine the variables related to between-ECW method differences. RESULTS: Significant but generally small group mean (+/-SD) differences in ECW were found in the obese adults (1.28 +/- 2.54 kg) and children (-0.71 +/- 1.78 kg). The magnitude of the differences was related to mean ECW in obese adults, children, and nonobese adults, and the relations between these variables were modified by sex for nonobese adults. ECW differences were also dependent on age, weight, sex, and race or on interactions between these variables. CONCLUSIONS: Overall, although good between-method agreement was found across the 3 groups, the degree of agreement varied according to subject characteristics, particularly at the extremes of ECW and body weight. We advance a possible mechanism that may link subject characteristics with the degree of agreement between ECW measurement methods and their underlying assumptions.     

Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight

BACKGROUND: After weight loss, total energy expenditure -- in particular, energy expenditure at low levels of physical activity -- is lower than predicted by actual changes in body weight and composition. An important clinical issue is whether this reduction, which predisposes to weight regain, persists over time. OBJECTIVE: We aimed to determine whether this disproportionate reduction in energy expenditure persists in persons who have maintained a body-weight reduction of > or =10% for >1 y. DESIGN: Seven trios of sex- and weight-matched subjects were studied in an in-patient setting while receiving a weight-maintaining liquid formula diet of identical composition. Each trio consisted of a subject at usual weight (Wt(initial)), a subject maintaining a weight reduction of > or =10% after recent (5-8 wk) completion of weight loss (Wt(loss-recent)), and a subject who had maintained a documented reduction in body weight of >10% for >1 y (Wt(loss-sustained)). Twenty-four-hour total energy expenditure (TEE) was assessed by precise titration of fed calories of a liquid formula diet necessary to maintain body weight. Resting energy expenditure (REE) and the thermic effect of feeding (TEF) were measured by indirect calorimetry. Nonresting energy expenditure (NREE) was calculated as NREE = TEE - (REE +TEF). RESULTS: TEE, NREE, and (to a lesser extent) REE were significantly lower in the Wt(loss-sustained) and Wt(loss-recent) groups than in the Wt(initial) group. Differences from the Wt(initial) group in energy expenditure were qualitatively and quantitatively similar after recent and sustained weight loss. CONCLUSION: Declines in energy expenditure favoring the regain of lost weight persist well beyond the period of dynamic weight loss.     

Heterosexual experiences of secondary school pupils in Ireland: sexual coercion in context

This paper reports on data from a wider study of young people's heterosexual experiences in Ireland, but focuses in particular on issues of sexual coercion. Data were gathered from 29 focus group interviews with 102 young women and 124 young men and were analysed using a qualitative research strategy. Drawing on concepts of social coercion and interpersonal coercion, we argue that both female and male participants reported a general sense of social coercion to lose their virginity by a certain age. However, narratives of interpersonal coercion were far stronger in the case of the young women compared with their male counterparts, while the young men reported a particular type of social coercion that propelled them to subscribe to conventional heterosexual male behaviour. We argue that while the distinction between social coercion and interpersonal coercion is far from watertight, it is a useful conceptual tool in identifying broad variations in women's and men's sexually coercive experiences.