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Qian Zhang Larry D. Mesner Gina M. Calabrese Naomi Dirckx Zhu Li Angela Verardo Qian Yang Robert J. Tower Marie-Claude Faugere Charles R. Farber Thomas L. Clemens 《The Journal of clinical investigation》2021,131(7)
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. 相似文献
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Angela Mauro Salvatore Mauro Roberto Rega Luigi Martemucci Rita Sottile 《Pediatric dermatology》2019,36(1):e34-e36
Henoch‐Schonlein purpura (HSP) is the most common systemic vasculitis in childhood. There is no consensus about the management for isolated cutaneous manifestations in HSP. We describe a case of HSP presenting with severe skin lesions that did not respond to standard therapy with corticosteroids. The 11‐year‐old child was treated with intravenous immunoglobulins, which induced rapid and persistent resolution of symptomatology. 相似文献
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Angela J. Jacques-Tiura Deborah A. Ellis April Idalski Carcone Sylvie Naar Kathryn Brogan Hartlieb Elizabeth K. Towner Thomas N. Templin K.-L. Catherine Jen 《The Journal of adolescent health》2019,64(3):355-361
Objective
Successful weight loss interventions for African-Americans adolescents are lacking. Cognitive-behavioral interventions seek to develop weight loss skills (e.g., counting calories, goal setting, managing one's environment). Little is known about how well adolescents implement such skills in their daily lives. Study aims were to (1) examine weight loss skills utilization at midpoint and end of a 6-month cognitive-behavioral/motivational interviewing weight loss sequential multiple assignment randomized trial (SMART), and (2) determine if greater skill utilization predicted weight loss at treatment end and 3 months post-treatment.Method
One hundred and eighty six African-Americans adolescents with obesity and their caregiver were first randomly assigned to complete 3 months of cognitive-behavioral and motivational interviewing family-based weight loss treatment in their home or in the research office (Phase 1). Nonresponders (i.e., those who lost < 3% of initial weight, n?=?161) were rerandomized to 3 months of continued skills training (n?=?83) or contingency management (n?=?78) for Phase 2; responders were allocated to 3 months of relapse prevention (n?=?20). Adolescents’ frequency of weight loss skills utilization was assessed via questionnaire at treatment midpoint and end.Results
Higher treatment attendance was associated with better skill utilization. Higher skill utilization was associated with more weight loss at treatment end, whereas higher baseline confidence was associated with more weight loss at follow-up.Conclusions
This study indicates the importance of attending weight loss intervention sessions to develop and strengthen weight loss skills in African-American adolescents with obesity, and strengthening confidence to use such skills for continued weight loss. 相似文献7.
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ABSTRACTA qualitative grounded theory approach was used to analyze 34 narratives from young men about their experience of retaining, losing, or giving away their virginity, where 7 said they were virgins, 26 said they were non-virgins, and one did not mention his virginity status. We found that virginity is a multidimensional concept, with two distinct dimensions: the experiential and the developmental. The experiential dimension refers to young men's perception and understanding of their virginity in four overlapping areas: physical, spiritual, relational, and emotional. The developmental dimension refers to young men's perception of their underlying sexual identity growth processes and the gendered and sexual double standards that influence this understanding. Clinical implications of this study are useful in education and counseling. They seek to empower young men with information relating to the multidimensional nature of virginity experience, and minimize the negative effects on romantic relationships, sexual adjustment, and self-identity development. The findings are helpful in designing interventions for young men and women who are at high risk for sexually transmitted infections and can help them negotiate mutually safe and pleasurable experiences regarding their virginity. 相似文献
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