A Necessary Sin : An Ethnographic Study Of Sex Selection In Western India

This dissertation analyzes sex-selective abortion in western India as a lived process with profound cultural, ethical, and demographic implications. Over the past three decades, selective elimination of female fetuses has emerged as a disturbing form of family planning across parts of Europe and Asia. In India, the practice remains widespread despite extensive efforts to combat it, with drastically skewed girl-to-boy ratios resulting in many locales. Drawing on eighteen months of ethnographic fieldwork with families and clinicians practicing sex selection, as well as with government officials and activists attempting to regulate it, this dissertation examines how prenatal sex determination marks fetuses with gender and incorporates them into local systems of kinship, biomedicine, and governance. Elucidating a kinship logic that renders daughters threatening and sons indispensable, I follow prospective parents and clinicians as they imagine divergent futures for children-to-be, navigate a clandestine black market, and employ specific biomedical techniques to produce and act on gendered fetuses. In the process of sex selection, fetuses become subject to complex ethical deliberations, familial struggles over reproductive decision-making, herbal and religious modalities of son production, and a host of public interventions aimed at saving daughters-to-be. I argue that the diverse actions around prenatal sex determination presuppose, shape, and intervene on a “gendered fetal subject”—an imagined or potential person whose liminal status (between human and non-human, between alive and un-alive) makes it a point of connection among households, clinics, and governance institutions. Tracing the production, transformation, and elimination of gendered fetal subjects reveals how kinship extends prenatally, as well as how fetuses become incorporated into social life. Furthermore, as suggested by prospective parents’ fraught reflections on the notion of a “necessary sin” (profoundly unethical but nonetheless unavoidable), understanding gendered fetal subjects provides an entry point for untangling the moral complexities of sex selection as a liminal form of violence—a gendered violation at the very threshold of human social existence

Genetically altering organismal metabolism by leptin-deficiency benefits a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease that causes death of motor neurons. ALS patients and mouse models of familial ALS display organismal level metabolic dysfunction, which includes increased energy expenditure despite decreased lean mass. The pathophysiological relevance of abnormal energy homeostasis to motor neuron disease remains unclear. Leptin is an adipocyte-derived hormone that regulates whole-animal energy expenditure. Here, we report that placing mutant superoxide dismutase 1 (SOD1) mice in a leptin-deficient background improves energy homeostasis and slows disease progression. Leptin-deficient mutant SOD1 mice possess increased bodyweight and fat mass, as well as decreased energy expenditure. These observations coincide with enhanced survival, improved strength and decreased motor neuron loss. These results suggest that altering whole-body energy metabolism in mutant SOD1 mice can mitigate disease progression. We propose that manipulations that increase fat mass and reduce energy expenditure will be beneficial in the setting of motor neuron diseas

The Intersection of Diabetes and Cardiovascular Disease—A Focus on New Therapies

Diabetes is a leading cause of cardiovascular disease and its associated morbidity. While the medical community has had access to numerous glucose lowering therapies over the last decades, it was not until recently that newer agents demonstrated improvement in cardiovascular outcomes. In particular, diabetes care and management of its attendant cardiovascular risk is now being revolutionized with the development and provision of the SGLT-2 inhibitors and GLP1-receptor agonists. Given the exciting data with these new classes of diabetes therapeutics, there is a clear need to improve education and utilization of these evidence-based medications across a wide spectrum of clinicians, including cardiologists. The aim of this review is to familiarize the cardiovascular specialist with the benefits and harms of the most commonly used oral anti- hyperglycemic medications, with an emphasis on SGLT-2 inhibitors and GLP-1 receptor agonists

Everything in Moderation: Investigating the U-Shaped Link Between HDL Cholesterol and Adverse Outcomes

Despite historical evidence suggesting an inverse association between HDL cholesterol (HDL-C) and adverse cardiovascular events, pharmacological efforts to increase HDL-C and improve outcomes have not been successful. Recently, a U-shaped association between HDL-C and adverse events has been demonstrated in several population cohorts, further complicating our understanding of the clinical significance of HDL. Potential explanations for this finding include genetic mutations linked to very high HDL-C, impaired HDL function at high HDL-C levels, and residual confounding. However, our understanding of this association remains premature and needs further investigation

The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals

Age-related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high- and low-functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low-functioning elderly (LFE) participants when compared to young and high-functioning elderly participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in cytochrome c oxidase activity. Levels of key metabolic regulators, SIRT3 and PGC-1\u3b1, were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects; however, no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population. \ua9 2012 The Authors. Aging Cell \ua9 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland

Life's simple 7 approach to atrial fibrillation prevention

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice. It constitutes a major public health problem, with total related annual expenses estimated at $6.65 billion. The American Heart Association developed Life's Simple 7 (LS7) to define and monitor ideal cardiovascular health (CVH). In this review, we examine the role of individual components of LS7 to provide further insight regarding potential influence of achieving AHA's strategic goal on AF prevention. While significant advances have been made in the secondary prevention of AF, little progress has been made to prevent the first occurrence of this arrhythmia in at-risk patients. Improvement of overall cardiovascular health as defined by LS7 may substantially reduce AF risk

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Genetically altering organismal metabolism by leptin-deficiency benefits a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease that causes death of motor neurons. ALS patients and mouse models of familial ALS display organismal level metabolic dysfunction, which includes increased energy expenditure despite decreased lean mass. The pathophysiological relevance of abnormal energy homeostasis to motor neuron disease remains unclear. Leptin is an adipocyte-derived hormone that regulates whole-animal energy expenditure. Here, we report that placing mutant superoxide dismutase 1 (SOD1) mice in a leptin-deficient background improves energy homeostasis and slows disease progression. Leptin-deficient mutant SOD1 mice possess increased bodyweight and fat mass, as well as decreased energy expenditure. These observations coincide with enhanced survival, improved strength and decreased motor neuron loss. These results suggest that altering whole-body energy metabolism in mutant SOD1 mice can mitigate disease progression. We propose that manipulations that increase fat mass and reduce energy expenditure will be beneficial in the setting of motor neuron disease

Primary Prevention of Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of death worldwide. This article focuses on current guidelines for the primary prevention of CVD and addresses management of key risk factors. Dietary modification, weight loss, exercise, and tobacco use cessation are specific areas where focused efforts can successfully reduce CVD risk on both an individual and a societal level. Specific areas requiring management include dyslipidemia, hypertension, physical activity, diabetes, aspirin use, and alcohol intake. These preventive efforts have major public health implications. As the global population continues to grow, health care expenditures will also rise, with the potential to eventually overwhelm the health care system. Therefore it is imperative to apply our collective efforts on CVD prevention to improve the cardiovascular health of individuals, communities, and nations