Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

The behaviour change techniques used by Australian physiotherapists to promote non-treatment physical activity to patients with musculoskeletal conditions

Objectives

To determine: (i) the behaviour change techniques used by a sample of Australian physiotherapists to promote non-treatment physical activity; and (ii) whether those behaviour change techniques are different to the techniques used to encourage adherence to rehabilitation exercises.

On estimands arising from misspecified semiparametric rate-based analysis of recurrent episodic conditions

Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration.     

Evaluating systems of care: Missing links in children's mental health research

Systems of care (SOCs) have been developed throughout the country to meet the needs of children with severe emotional disturbances (SED) and their families. In these SOCs, multiple agencies and disciplines are expected to work together with informal community supports to address families' needs (Stroul & Friedman, 1986a). A review of the literature on the impact of SOCs suggests: (a) communities' service delivery systems change; and (b) children experience modest improvements in symptomatology and functioning. At the same time, little is known about (a) which components of the SOC approach, at what levels, are necessary to impact child and family outcomes; (b) the degree to which SOCs affect other family members, beyond the target child; and (c) the impact of community contexts and supports in SOCs. Future research should improve measurement of key SOC constructs, examine the relation between specific levels of implementation and outcomes for the entire family, and investigate the impact of broader community systems and supports on families within SOCs. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 655–674, 2004.     

Measurements of Blood Pressure, Oedema and Proteinuria in a Pregnant Population of New Zealand

Summary: This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that Mood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Ffg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of >33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women. Ankle oedema was significantly associated with the development of both gestational hypertension and preeclampsia but the incidence of oedema was noted in only 11.9% of the subjects.     

Effects of laundry detergents on Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Euroglyphus maynei.

BACKGROUND: House-dust mites in clothing and bedding are the source of major allergens. Based on studies of Dermatophagoides pteronyssinus only, weekly washing in hot water is recommended to kill dust mites and remove allergens from clothing and bedding. However, in the United States, washing is most often done in warm or cold water, and other mite species are involved. OBJECTIVE: The purpose of this study was to investigate the lethal effects of various temperatures of hot water alone and hot, warm, and cold water containing detergents and chlorine bleach on Dermatophagoidesfarinae, D. pteronyssinus, and Euroglyphus maynei. METHODS: Mites were soaked in test solutions at various temperatures and for various lengths of time, allowed time to recover, and then analyzed for survival. RESULTS: D. farinae was the most temperature-sensitive and chlorine bleach-sensitive of the three species. In 50 degrees C water alone, 100% mortality for D. farinae was obtained in 10 minutes, whereas most D. pteronyssinus and E. maynei survived. However, 53 degrees C-soaks for 12 and 5 minutes were needed to kill all D. pteronyssinus and E. maynei, respectively. Laundry detergents at their recommended and doubled concentrations and chlorine bleach generally increased mite mortalities over water alone for the three species. Soaking for 4 hours in warm water containing various detergents alone induced mortalities of 19 to 50%, 2 to 35%, and 14 to 46% for D. farinae, D. pteronyssinus, and E. maynei, respectively. CONCLUSIONS: Washing bed linens weekly in warm water with a 4-hour presoak containing most detergents and bleach will kill most D. farinae and, depending on the detergent brand, moderate numbers of D. pteronyssinus. Four-hour soaks in warm water containing the recommended concentrations of various detergents alone also kills moderate numbers of D. farinae, D. pteronyssinus, and E. maynei. Therefore, the cumulative effect of weekly washing with long presoaks should significantly reduce mite levels over time in bed linens, particularly when mattresses and pillows are encased to prevent reinfestation.