The discovery of leptin changed the view of adipose tissue from that of a passive vessel that stores fat to that of a dynamic endocrine organ that actively regulates behaviour and metabolism. ...Secreted by adipose tissue, leptin functions as an afferent signal in a negative feedback loop, acting primarily on neurons in the hypothalamus and regulating feeding and many other functions. The leptin endocrine system serves a critical evolutionary function by maintaining the relative constancy of adipose tissue mass, thereby protecting individuals from the risks associated with being too thin (starvation and infertility) or too obese (predation). In this Review, the biology of leptin is summarized, and a conceptual framework is established for studying the pathogenesis of obesity, which, analogously to diabetes, can result from either leptin hyposecretion or leptin resistance. Herein, these two states are distinguished with the terms 'type 1 obesity' and 'type 2 obesity': type 1 obesity describes a subset of obese individuals with low endogenous plasma leptin levels who respond to leptin therapy, whereas type 2 obesity describes most obese individuals, who are leptin resistant but might respond to leptin therapy in combination with other drugs, such as leptin sensitizers.
This book addresses the fundamentals of randomized control clinical trials, devoting a chapter to each of the critical areas of a protocol. The new edition is revised and expanded, with the number of ...examples illustrating the fundamentals considerably increased.
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Harm reduction refers to interventions aimed at reducing the negative effects of health behaviors without necessarily extinguishing the problematic health behaviors completely. The vast majority of ...the harm reduction literature focuses on the harms of drug use and on specific harm reduction strategies, such as syringe exchange, rather than on the harm reduction philosophy as a whole. Given that a harm reduction approach can address other risk behaviors that often occur alongside drug use and that harm reduction principles have been applied to harms such as sex work, eating disorders, and tobacco use, a natural evolution of the harm reduction philosophy is to extend it to other health risk behaviors and to a broader healthcare audience.
Building on the extant literature, we used data from in-depth qualitative interviews with 23 patients and 17 staff members from an HIV clinic in the USA to describe harm reduction principles for use in healthcare settings.
We defined six principles of harm reduction and generalized them for use in healthcare settings with patients beyond those who use illicit substances. The principles include humanism, pragmatism, individualism, autonomy, incrementalism, and accountability without termination. For each of these principles, we present a definition, a description of how healthcare providers can deliver interventions informed by the principle, and examples of how each principle may be applied in the healthcare setting.
This paper is one of the firsts to provide a comprehensive set of principles for universal harm reduction as a conceptual approach for healthcare provision. Applying harm reduction principles in healthcare settings may improve clinical care outcomes given that the quality of the provider-patient relationship is known to impact health outcomes and treatment adherence. Harm reduction can be a universal precaution applied to all individuals regardless of their disclosure of negative health behaviors, given that health behaviors are not binary or linear but operate along a continuum based on a variety of individual and social determinants.
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Sleep duration is associated with cardiovascular disease and diabetes risk factors, depression, automobile and workplace accidents, and prospective mortality. Little is known, however, about sleep ...patterns in the US population. The 2004–2007 National Health Interview Survey-Sample Adult Files provide nationally representative data for 110,441 noninstitutionalized US adults aged 18 years or older, and multinomial logistic regression examines whether variables in 5 domains—demographic, family structure, socioeconomic, health behavior, and health status—are associated with long or short sleep duration. Being older, non-Hispanic black, or a current or former smoker; having low levels of education, income, or few income sources; consuming few or numerous drinks in a week; or reporting cardiovascular disease, diabetes, depression, underweight, or activity limitations is associated with increased odds of both long and short sleep duration. Other variables are associated with shorter (e.g., living with young children, being unmarried, working long hours, more frequent binge drinking) or longer (e.g., being younger, Mexican American, pregnant, or having low levels of physical activity) sleep hours. The authors identify numerous risk factors for long and short sleep; many of those variables are potential confounders of the relation between sleep hours and other health outcomes.
Inside the castle Grossman, Joanna L; Friedman, Lawrence M
2011., 20110718, 2011, 2011-07-18
eBook
Inside the Castle is a comprehensive social history of twentieth-century family law in the United States. Joanna Grossman and Lawrence Friedman show how vast, oceanic changes in society have reshaped ...and reconstituted the American family. Women and children have gained rights and powers, and novel forms of family life have emerged. The family has more or less dissolved into a collection of independent individuals with their own wants, desires, and goals. Modern family law, as always, reflects the brute social and cultural facts of family life.
Neurofibromatosis 1 is an autosomal dominant disorder characterized by multiple café-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. Learning ...disabilities are present in at least 50% of individuals with neurofibromatosis 1. Less common but potentially more serious manifestations include plexiform neurofibromas, optic nerve and other central nervous system gliomas, malignant peripheral nerve sheath tumors, scoliosis, tibial dysplasia, and vasculopathy. The diagnosis of neurofibromatosis 1 is usually based on clinical findings. Neurofibromatosis 1, one of the most common Mendelian disorders, is caused by heterozygous mutations of the NF1 gene. Almost one half of all affected individuals have de novo mutations. Molecular genetic testing is available clinically but is infrequently needed for diagnosis. Disease management includes referral to specialists for treatment of complications involving the eye, central or peripheral nervous system, cardiovascular system, spine, or long bones. Surgery to remove both benign and malignant tumors or to correct skeletal manifestations is sometimes warranted. Annual physical examination by a physician familiar with the disorder is recommended. Other recommendations include ophthalmologic examinations annually in children and less frequently in adults, regular developmental assessment in children, regular blood pressure monitoring, and magnetic resonance imaging for follow-up of clinically suspected intracranial and other internal tumors.
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Leptin is a hormone produced by the adipose tissue that acts in the brain, stimulating white fat breakdown. We find that the lipolytic effect of leptin is mediated through the action of sympathetic ...nerve fibers that innervate the adipose tissue. Using intravital two-photon microscopy, we observe that sympathetic nerve fibers establish neuro-adipose junctions, directly “enveloping” adipocytes. Local optogenetic stimulation of sympathetic inputs induces a local lipolytic response and depletion of white adipose mass. Conversely, genetic ablation of sympathetic inputs onto fat pads blocks leptin-stimulated phosphorylation of hormone-sensitive lipase and consequent lipolysis, as do knockouts of dopamine β-hydroxylase, an enzyme required for catecholamine synthesis. Thus, neuro-adipose junctions are necessary and sufficient for the induction of lipolysis in white adipose tissue and are an efferent effector of leptin action. Direct activation of sympathetic inputs to adipose tissues may represent an alternative approach to induce fat loss, circumventing central leptin resistance.
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•The neuro-adipose junction in white adipose tissue is visualized in vivo•Adipocyte-projecting neurons can completely envelop an adipocyte•Leptin stimulates lipolysis via sympathetic neurons in fat•Optogenetic activation of sympathetic fibers in fat drives lipolysis and fat mass reduction
The lipolytic effect of leptin is mediated by sympathetic neurons that innervate adipocytes, forming neuro-adipose junctions that directly mediate fat breakdown. Anti-obesity strategies targeting the sympathetic neurons in fat have the potential to circumvent central leptin resistance.
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Studies of resting-state activity in the brain have provoked critical questions about the brain’s functional organization, but the biological basis of this activity is not clear. Specifically, the ...relationships between interregional correlations in resting-state measures of activity, neuronal functional connectivity and anatomical connectivity are much debated. To investigate these relationships, we have examined both anatomical and steady-state functional connectivity within the hand representation of primary somatosensory cortex (areas 3b and 1) in anesthetized squirrel monkeys. The comparison of three data sets (fMRI, electrophysiological, and anatomical) indicate two primary axes of information flow within the SI: prominent interdigit interactions within area 3b and predominantly homotopic interactions between area 3b and area 1. These data support a strikingly close relationship between baseline functional connectivity and anatomical connections. This study extends findings derived from large-scale cortical networks to the realm of local millimeter-scale networks.
•Anatomical, neural, and resting-state connectivity patterns are very similar in SI•Intra-areal connections are cross-digit; interareal connections are same-digit•Resting-state patterns reveal functional connectivity at the local millimeter scale
Wang et al. present the novel finding that when the brain is at rest, spatial coactivation patterns in fMRI signal correspond to anatomical and neural connectivity patterns at a local spatial scale. Thus, resting-state connectivity reflects neural connection patterns.
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The increased white adipose tissue (WAT) mass associated with obesity is the result of both hyperplasia and hypertrophy of adipocytes. However, the mechanisms controlling adipocyte number are unknown ...in part because the identity of the physiological adipocyte progenitor cells has not been defined in vivo. In this report, we employ a variety of approaches, including a noninvasive assay for following fat mass reconstitution in vivo, to identify a subpopulation of early adipocyte progenitor cells (Lin
−:CD29
+:CD34
+:Sca-1
+:CD24
+) resident in adult WAT. When injected into the residual fat pads of A-Zip lipodystrophic mice, these cells reconstitute a normal WAT depot and rescue the diabetic phenotype that develops in these animals. This report provides the identification of an undifferentiated adipocyte precursor subpopulation resident within the adipose tissue stroma that is capable of proliferating and differentiating into an adipose depot in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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