Association between secondhand smoke and obesity and glucose abnormalities: data from the National Health and Nutrition Examination Survey (NHANES 1999-2010).

ObjectiveThe objective of this study is to investigate the relationship between cotinine level-confirmed secondhand smoke (SHS) exposure and glycemic parameters and obesity.Research design and methodsWe examined a cohort of 6472 adults from the National Health and Nutrition Examination Surveys, 1999-2010. Serum cotinine levels and self-reported data on smoking were used to determine smoking status. The outcome variables were body mass index (BMI) and glycemic status (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and fasting plasma glucose (FPG). Descriptive, bivariate, and multivariate analyses were conducted.ResultsUsing cotinine level-confirmed smoking status, 1794 (27.4%) of the sample were current smokers, 1681 (25.0%) were former smokers, 1158 (17.8%) were secondhand smokers, and 1839 (29.8%) were non-smokers. In a generalized linear model after controlling for potential confounding variables, secondhand smokers had higher adjusted levels of HOMA-IR, FPG, and BMI compared with non-smokers (p<0.05). Adjustment for BMI demonstrated that some, but not all, of the detrimental effects of SHS on glycemic parameters are mediated by the increased body weight of secondhand smokers.ConclusionsWe conclude that SHS is associated with obesity and worsening glycemic parameters. More studies are needed to show a causal relationship between SHS and glycemic parameters and to understand the mechanisms involved in the association

Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III

ObjectiveTo determine the association between diabetes mellitus (DM) and marijuana use.DesignCross-sectional study.SettingData from the National Health and Nutrition Examination Survey (NHANES III, 1988-1994) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention.ParticipantsThe study included participants of the NHANES III, a nationally representative sample of the US population. The total analytic sample was 10 896 adults. The study included four groups (n=10 896): non-marijuana users (61.0%), past marijuana users (30.7%), light (one to four times/month) (5.0%) and heavy (more than five times/month) current marijuana users (3.3%). DM was defined based on self-report or abnormal glycaemic parameters. We analysed data related to demographics, body mass index, smoking status, alcohol use, total serum cholesterol, high-density lipoprotein, triglyceride, serum 25-hydroxy vitamin D, plasma haemoglobin A1c, fasting plasma glucose level and the serum levels of C reactive protein and four additional inflammatory markers as related to marijuana use.Main outcome measuresOR for DM associated with marijuana use adjusted for potential confounding variables (ie, odds of DM in marijuana users compared with non-marijuana users).ResultsMarijuana users had a lower age-adjusted prevalence of DM compared to non-marijuana users (OR 0.42, 95% CI 0.33 to 0.55; p<0.0001). The prevalence of elevated C reactive protein (>0.5 mg/dl) was significantly higher (p<0.0001) among non-marijuana users (18.9%) than among past (12.7%) or current light (15.8%) or heavy (9.2%) users. In a robust multivariate model controlling for socio-demographic factors, laboratory values and comorbidity, the lower odds of DM among marijuana users was significant (adjusted OR 0.36, 95% CI 0.24 to 0.55; p<0.0001).ConclusionsMarijuana use was independently associated with a lower prevalence of DM. Further studies are needed to show a direct effect of marijuana on DM

Alterations in Phosphorylated CREB Expression in Different Brain Regions following Short- and Long-Term Morphine Exposure: Relationship to Food Intake

Background. Activation of the cyclic adenosine monophosphate (cAMP)/phosphorylated CREB (P-CREB) system in different brain regions has been implicated in mediating opioid tolerance and dependence, while alteration of this system in the lateral hypothalamus (LH) has been suggested to have a role in food intake and body weight. Methods. Given that opioids regulate food intake, we measured P-CREB in different brain regions in mice exposed to morphine treatments designed to induce different degrees of tolerance and dependence. Results. We found that a single morphine injection or daily morphine injections for 8 days did not influence P-CREB levels, while the escalating dose of morphine regimen raised P-CREB levels only in the ventral tegmental area (VTA). Chronic morphine pellet implantation for 7 days raised P-CREB levels in the LH, VTA, and dorsomedial nucleus of the hypothalamus (DM) but not in the nucleus accumbens and amygdala. Increased P-CREB levels in LH, VTA, and DM following 7-day treatment with morphine pellets and increased P-CREB levels in the VTA following escalating doses of morphine were associated with decreased food intake and body weight. Conclusion. The morphine regulation of P-CREB may explain some of the physiological sequelae of opioid exposure including altered food intake and body weight

The role of Neurochemicals, Stress Hormones and Immune System in the Positive Feedback Loops between Diabetes, Obesity and Depression

Type 2 diabetes mellitus (T2DM) and depression are significant public health and socioeconomic issues. They commonly co-occur, with T2DM occurring in 11.3% of the US population, while depression has a prevalence of about 9%, with higher rates among youths. Approximately 31% of patients with T2DM suffer from depressive symptoms, with 11.4% having major depressive disorders, which is twice as high as the prevalence of depression in patients without T2DM. Additionally, over 80% of people with T2DM are overweight or obese. This review describes how T2DM and depression can enhance one another, using the same molecular pathways, by synergistically altering the brain’s structure and function and reducing the reward obtained from eating. In this article, we reviewed the evidence that eating, especially high-caloric foods, stimulates the limbic system, initiating Reward Deficiency Syndrome. Analogous to other addictive behaviors, neurochemical changes in those with depression and/or T2DM are thought to cause individuals to increase their food intake to obtain the same reward leading to binge eating, weight gain and obesity. Treating the symptoms of T2DM, such as lowering HbA1c, without addressing the underlying pathways has little chance of eliminating the disease. Targeting the immune system, stress circuit, melatonin, and other alterations may be more effective

Molecular Hydrogen in the FUSE Translucent Lines of Sight: The Full Sample

We report total abundances and related parameters for the full sample of the FUSE survey of molecular hydrogen in 38 translucent lines of sight. New results are presented for the "second half" of the survey involving 15 lines of sight to supplement data for the first 23 lines of sight already published. We assess the correlations between molecular hydrogen and various extinction parameters in the full sample, which covers a broader range of conditions than the initial sample. In particular, we are now able to confirm that many, but not all, lines of sight with shallow far-UV extinction curves and large values of the total-to-selective extinction ratio, $R_V$ = $A_V$ / $E(B-V)$ -- characteristic of larger than average dust grains -- are associated with particularly low hydrogen molecular fractions ($f_{\rm H2}$). In the lines of sight with large $R_V$, there is in fact a wide range in molecular fractions, despite the expectation that the larger grains should lead to less H$_2$ formation. However, we see specific evidence that the molecular fractions in this sub-sample are inversely related to the estimated strength of the UV radiation field and thus the latter factor is more important in this regime. We have provided an update to previous values of the gas-to-dust ratio, $N$(H$_{\rm tot}$)/$E(B-V)$, based on direct measurements of $N$(H$_2$) and $N$(H I). Although our value is nearly identical to that found with Copernicus data, it extends the relationship by a factor of 2 in reddening. Finally, as the new lines of sight generally show low to moderate molecular fractions, we still find little evidence for single monolithic "translucent clouds" with $f_{\rm H2}$ $\sim$ 1.Comment: 35 pages, 5 tables, 7 figures, accepted for publication in The Astrophysical Journal Supplements Serie

Recent Advances in Combined Modality Therapy

This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy

Increased Glycogen Synthase Kinase-3β and Hexose-6-Phosphate Dehydrogenase Expression in Adipose Tissue May Contribute to Glucocorticoid-Induced Mouse Visceral Adiposity

BACKGROUND Increased adiposity in visceral depots is a crucial feature associated with glucocorticoid (GC) excess. The action of GCs in target tissue is regulated by GC receptor (GR) and 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6pdh). Glycogen synthase kinase-3β (GSK3β) is known to be a crucial mediator of ligand-dependent gene transcription. We hypothesized that the major effects of corticosteroids on adipose fat accumulation are in part medicated by changes in GSK3β and H6pdh. METHODS We characterized the alterations of GSK3β and GC metabolic enzymes, and determined the impact of GR antagonist mifepristone on obesity-related genes and the expression of H6pdh and 11ß-HSD1 in adipose tissue of mice exposed to excess GC as well as in in vitro studies using 3T3-L1 adipocytes treated with GCs. RESULTS Corticosterone (CORT) exposure increased abdominal fat mass and induced expression of lipid synthase ACC and ACL with activation of GSK3β phosphorylation in abdominal adipose tissue of C57BL/6J mice. Increased pSer9 GSK3β was correlated with induction of H6pdh and 11ß-HSD1. Additionally, mifepristone treatment reversed the production of H6pdh and attenuated CORT-mediated production of 11ß-HSD1 and lipogenic gene expression with reduction of pSer9 GSK3β, thereby leading to improvement of phenotype of adiposity within adipose tissue in mice treated with excess GCs. Suppression of pSer9 GSK3β by mifepristone was accompanied by activation of pThr308 Akt and blockade of CORT-induced adipogenic transcriptor C/EBPα and PPARγ. In addition, mifepristone also attenuated CORT-mediated activation of IRE1α/XBP1. Additionally, reduction of H6pdh by shRNA showed comparable effects to mifepristone on attenuating CORT-induced expression of GC metabolic enzymes and improved lipid accumulation in vitro in 3T3-L1 adipocytes. CONCLUSION These findings suggest that elevated adipose GSK3β and H6pdh expression contribute to 11ß-HSD1 mediating hypercortisolism associated with visceral adiposity

Bureaucracy as a Lens for Analyzing and Designing Algorithmic Systems

Scholarship on algorithms has drawn on the analogy between algorithmic systems and bureaucracies to diagnose shortcomings in algorithmic decision-making. We extend the analogy further by drawing on Michel Crozier’s theory of bureaucratic organizations to analyze the relationship between algorithmic and human decision-making power. We present algorithms as analogous to impartial bureaucratic rules for controlling action, and argue that discretionary decision-making power in algorithmic systems accumulates at locations where uncertainty about the operation of algorithms persists. This key point of our essay connects with Alkhatib and Bernstein’s theory of ’street-level algorithms’, and highlights that the role of human discretion in algorithmic systems is to accommodate uncertain situations which inflexible algorithms cannot handle. We conclude by discussing how the analysis and design of algorithmic systems could seek to identify and cultivate important sources of uncertainty, to enable the human discretionary work that enhances systemic resilience in the face of algorithmic errors.Peer reviewe

Genotypes and haplotypes of the methyl-CpG-binding domain 2 modify breast cancer risk dependent upon menopausal status

INTRODUCTION: MBD2, the gene encoding methyl-CpG-binding domain (MBD)2, is a major methylation related gene and functions as a transcriptional repressor that can specifically bind to the methylated regions of other genes. MBD2 may also mediate gene activation because of its potential DNA demethylase activity. The present case-control study investigated associations between two single nucleotide polymorphisms (SNPs) in the MBD2 gene and breast cancer risk. METHODS: DNA samples from 393 Caucasian patients with breast cancer (cases) and 436 matched control individuals, collected in a recently completed breast cancer case–control study conducted in Connecticut, were included in the study. Because no coding SNPs were found in the MBD2 gene, one SNP in the noncoding exon (rs1259938) and another in the intron 3 (rs609791) were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate cancer risk associated with the variant genotypes and the reconstructed haplotypes. RESULTS: The variant genotypes at both SNP loci were significantly associated with reduced risk among premenopausal women (OR = 0.41 for rs1259938; OR = 0.54 for rs609791). Further haplotype analyses showed that the two rare haplotypes (A-C and A-G) were significantly associated with reduced breast cancer risk (OR = 0.40, 95% CI = 0.20–0.83 for A-C; OR = 0.47, 95% CI = 0.26–0.84 for A-G) in premenopausal women. No significant associations were detected in the postmenopausal women and the whole population. CONCLUSION: Our results demonstrate a role for the MBD2 gene in breast carcinogenesis in premenopausal women. These findings suggest that genetic variations in methylation related genes may potentially serve as a biomarker in risk estimates for breast cancer