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New Philadelphia, PA, United States

Weaver C.M.,Purdue University | Gordon C.M.,Cincinnati Childrens Hospital | Gordon C.M.,University of Cincinnati | Janz K.F.,University of Iowa | And 7 more authors.
Osteoporosis International | Year: 2016

Lifestyle choices influence 20–40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1].MacronutrientsMicronutrientsFood PatternsInfant NutritionAdolescent Special IssuesPhysical Activity and Exercise Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years—a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one’s genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach. © 2016, The Author(s). Source


McGuire J.L.,Childrens Hospital of Philadelphia | McGuire J.L.,University of Pennsylvania | Gill A.J.,University of Pennsylvania | Douglas S.D.,Childrens Hospital of Philadelphia | And 3 more authors.
Journal of NeuroVirology | Year: 2015

HIV-associated neurocognitive disorders (HAND) affect up to 50 % of HIV-infected adults, independently predict HIV morbidity/mortality, and are associated with neuronal damage and monocyte activation. Cerebrospinal fluid (CSF) neurofilament subunits (NFL, pNFH) are sensitive surrogate markers of neuronal damage in several neurodegenerative diseases. In HIV, CSF NFL is elevated in individuals with and without cognitive impairment, suggesting early/persistent neuronal injury during HIV infection. Although individuals with severe cognitive impairment (HIV-associated dementia (HAD)) express higher CSF NFL levels than cognitively normal HIV-infected individuals, the relationships between severity of cognitive impairment, monocyte activation, neurofilament expression, and systemic infection are unclear. We performed a retrospective cross-sectional study of 48 HIV-infected adults with varying levels of cognitive impairment, not receiving antiretroviral therapy (ART), enrolled in the CNS Anti-Retroviral Therapy Effects Research (CHARTER) study. We quantified NFL, pNFH, and monocyte activation markers (sCD14/sCD163) in paired CSF/plasma samples. By examining subjects off ART, these correlations are not confounded by possible effects of ART on inflammation and neurodegeneration. We found that CSF NFL levels were elevated in individuals with HAD compared to cognitively normal or mildly impaired individuals with CD4+ T-lymphocyte nadirs ≤200. In addition, CSF NFL levels were significantly positively correlated to plasma HIV-1 RNA viral load and negatively correlated to plasma CD4+ T-lymphocyte count, suggesting a link between neuronal injury and systemic HIV infection. Finally, CSF NFL was significantly positively correlated with CSF pNFH, sCD163, and sCD14, demonstrating that monocyte activation within the CNS compartment is directly associated with neuronal injury at all stages of HAND. © 2015, The Author(s). Source


Frank L.B.,Immaculata University | Schall J.I.,Childrens Hospital of Philadelphia | Samuel J.,Childrens Hospital of Philadelphia | Zemel B.S.,Childrens Hospital of Philadelphia | And 10 more authors.
Infant, Child, and Adolescent Nutrition | Year: 2014

Objective. To describe the dietary intake of HIV-infected urban children and young adults and to evaluate their diet quality. Methods. Participants were children and youth with both perinatally and behaviorally acquired HIV infection participating in a study of vitamin D supplementation. Data collected included dietary intake, anthropometrics, and HIV status, with medical history abstracted from participants’ medical records. Results. Of 55 participants, 38 were male, 46 were African American, with a mean age of 20.7 ± 3.8 years. Growth and nutritional status were comparable to reference norms. Only 22% either met or exceeded their estimated energy requirement at low-active and 40% at sedentary activity levels. Fiber, potassium, and intakes of vitamins D and E were <50% of recommended dietary allowance/adequate intake (RDA/AI), whereas vitamins A and K, choline, potassium, calcium, and magnesium were ≤75% of RDA/AI. Sodium intake exceeded the dietary reference intake upper limit in 92%. Vitamin D intake was significantly and positively associated with CD4% HIV status indicator. Conclusion. Dietary intake was inadequate for multiple micronutrients, particularly vitamin D, calcium, and potassium. Overall poor dietary quality was observed (in terms of intake of sodium, sugar, saturated fat, cholesterol, and fiber). Participants had high rates of overweight and obesity. These dietary and body weight concerns were similar to those seen in healthy American peers. The vitamin D intake and immunological status correlation deserves further investigation. HIV-infected individuals may benefit from routine dietary assessment and counseling. © 2014 The Author(s). Source


Di Sante G.,Thomas Jefferson University | Wang L.,Thomas Jefferson University | Wang C.,Thomas Jefferson University | Jiao X.,Thomas Jefferson University | And 11 more authors.
Molecular Endocrinology | Year: 2015

Hypogonadatropic hypogonadism (HH) can be acquired through energy restriction or may be inherited as congenital hypogonadotropic hypogonadism and its anosmia-associated form, Kallmann’s syndrome. Congenital hypogonadotropic hypogonadism is associated with mutations in a group of genes that impact fibroblast growth factor 8 (FGF8) function. The Sirt1 gene encodes a nicotinamide adenine dinucleotide-dependent histone deacetylase that links intracellular metabolic stress to gene expression. Herein Sirt1_/_mice are shown to have HH due to failed GnRH neuronal migration. Sirtuin-1 (Sirt1) catalytic function induces GnRH neuronal migration via binding and deacetylating cortactin. Sirt1 colocalized with cortactin in GnRH neurons in vitro. Sirt1 colocalization with cortactin was regulated in an FGF8/fibroblast growth factor receptor-1 dependent manner. The profound effect of Sirt1 on the hormonal status of Sirt1_/_ mice, mediated via defective GnRH neuronal migration, links energy metabolism directly to the hypogonadal state. Sirt1-cortactin may serve as the distal transducer of neuronal migration mediated by the FGF8 synexpression group of genes that govern HH. © 2015 by the Endocrine Societ. Source


Kim J.,Pohang University of Science and Technology | Park T.-J.,The Childrens Hospital Of Philadelphia Research Institute | Kwon N.,Pohang University of Science and Technology | Lee D.,Pohang University of Science and Technology | And 6 more authors.
Brain Structure and Function | Year: 2015

The dendritic planarity of Purkinje cells is critical for cerebellar circuit formation. In the absence of Crk and CrkL, the Reelin pathway does not function resulting in partial Purkinje cell migration and defective dendritogenesis. However, the relationships among Purkinje cell migration, dendritic development and Reelin signaling have not been clearly delineated. Here, we use synchrotron X-ray microscopy to obtain 3-D images of Golgi-stained Purkinje cell dendrites. Purkinje cells that failed to migrate completely exhibited conical dendrites with abnormal 3-D arborization and reduced dendritic complexity. Furthermore, their spines were fewer in number with a distorted morphology. In contrast, Purkinje cells that migrated successfully displayed planar dendritic and spine morphologies similar to normal cells, despite reduced dendritic complexity. These results indicate that, during cerebellar formation, Purkinje cells migrate into an environment that supports development of dendritic planarity and spine formation. While Reelin signaling is important for the migration process, it does not make a direct major contribution to dendrite formation. © 2014, The Author(s). Source

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