Despite generally lower socioeconomic status and worse access to healthcare, Latinos have better overall health outcomes and longer life expectancy than non-Latino Whites. This “Latino Health Paradox” has been partially attributed to healthier cardiovascular (CV) behaviors among Latinos. However, as Latinos become more acculturated, differences in some CV behaviors disappear. This study aimed to explore how associations between acculturation and CV behaviors among Latinos vary by country of origin. Combined weighted data from the 2005 and 2007 California Health Interview Survey (CHIS) were used to investigate associations between acculturation level and CV behaviors among Latinos by country of origin. Among all Latinos, increased acculturation was associated with more smoking, increased leisure-time physical activity, and greater consumption of fast foods, but no change in fruit/vegetable and less soda intake. These trends varied, however, by Latino sub-groups from different countries of origin. Country of origin appears to impact associations between acculturation and CV behaviors among Latinos in complex ways.
Acculturation Cardiovascular behaviors Latinos Country of origin
Aged rhesus monkeys exhibit deficits in hippocampus-dependent memory, similar to aging humans. Here we explored the basis of cognitive decline by first testing young adult and aged monkeys on a standard recognition memory test (delayed nonmatching-to-sample test; DNMS). Next we quantified synaptic density and morphology in the hippocampal dentate gyrus (DG) outer (OML) and inner molecular layer (IML). Consistent with previous findings, aged monkeys were slow to learn DNMS initially, and they performed significantly worse than young subjects when challenged with longer retention intervals. Although OML and IML synaptic parameters failed to differ across the young and aged groups, the density of perforated synapses in the OML was coupled with recognition memory accuracy. Independent of chronological age, monkeys classified on the basis of menses data as peri/post-menopausal scored worse on DNMS, and displayed lower OML perforated synapse density, than pre-menopausal monkeys. These results suggest that naturally occurring reproductive senescence potently influences synaptic connectivity in the DG OML, contributing to individual differences in the course of normal cognitive aging.
delayed nonmatching-to-sample; disector method; estrogen; hippocampus; menopause; outer molecular layer; perforated synapse; post-synaptic density; recognition memory
Itaconic acid, or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR based metabolomics and 13C-labeling, we have detected itaconic acid in both macrophage-like VM-M3 and RAW 264.7 tumor cell lines as well as stimulated and unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide and IFN-γ markedly increased itaconic acid production and secretion. Crude cell extracts synthesize itaconic acid via decarboxylation of cis-aconitate, indicative of a novel mammalian cis-aconitic decarboxylase activity. Our results highlight a previously unidentified biosynthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.
metabolomics; NMR; LC-MS; itaconic acid; tumor cells; macrophages
Unplanned pregnancies and sexually transmitted infections (STIs) are important and costly public health problems in the United States resulting from unprotected sexual intercourse. Risk factors for unplanned pregnancies and STIs (poverty, low educational attainment, homelessness, substance abuse, lack of health insurance, history of an abusive environment, and practice of commercial sex work) are especially high among women with a history of incarceration. Project CARE (Contraceptive Awareness and Reproductive Education) is designed to evaluate an innovative intervention, Motivational Interviewing with Computer Assistance (MICA), aimed at enhancing contraceptive initiation and maintenance among incarcerated women who do not want a pregnancy within the next year and who are anticipated to be released back to the community. This study aims to: (1) increase the initiation of highly effective contraceptives while incarcerated; (2) increase the continuation of highly effective contraceptive use at 3, 6, 9, and 12 months after release; and (3) decrease unsafe sexual activity.
This randomized controlled trial will recruit 400 women from the Rhode Island Department of Corrections (RI DOC) women’s jail at risk for an unplanned pregnancy (that is, sexually active with men and not planning/wanting to become pregnant in the next year). They will be randomized to two interventions: a control group who receive two educational videos (on contraception, STIs, and pre-conception counseling) or a treatment group who receive two sessions of personalized MICA. MICA is based on the principles of the Transtheoretical Model (TTM) and on Motivational Interviewing (MI), an empirically supported counseling technique designed to enhance readiness to change targeted behaviors. Women will be followed at 3, 6, 9, and 12 months post release and assessed for STIs, pregnancy, and reported condom use.
Results from this study are expected to enhance our understanding of the efficacy of MICA to enhance contraceptive initiation and maintenance and reduce sexual risk-taking behaviors among incarcerated women who have re-entered the community.
Social isolation confers increased risk for coronary heart disease (CHD) events and mortality. In two recent studies, low levels of social integration among older adults were related to higher levels of C-reactive protein (CRP), a marker of inflammation, suggesting a possible biological link between social isolation and CHD. The current study examined relationships among social isolation, CRP, and 15-year CHD death in a community sample of US adults aged 40 years and older without a prior history of myocardial infarction. A nested case-cohort study was conducted from a parent cohort of community-dwelling adults from the southeastern New England region of the United States (N = 2,321) who were interviewed in 1989 and 1990. CRP levels were measured from stored sera provided by the nested case-cohort (n = 370), which included all cases of CHD death observed through 2005 (n = 48), and a random sample of non-cases. We found that the most socially isolated individuals had two-and-a-half times the odds of elevated CRP levels compared to the most socially integrated. In separate logistic regression models, both social isolation and CRP predicted later CHD death. The most socially isolated continued to have more than twice the odds of CHD death compared to the most socially integrated in a model adjusting for CRP and more traditional CHD risk factors. The current findings support social isolation as an independent risk factor of both high levels of CRP and CHD death in middle-aged adults without a prior history of myocardial infarction. Prospective study of inflammatory pathways related to social isolation and mortality are needed to fully delineate whether and how CRP or other inflammatory markers contribute to mechanisms linking social isolation to CVD health.
USA; social isolation; social integration; social support; inflammation; C-reactive protein; coronary heart disease; mortality
Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI] ≥ 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcohol were 4 times more likely to be obese (OR 4.11, CI 2.04–9.76) than children not exposed to either drug. No increase in obesity prevalence was found in children exposed to alcohol but not cocaine (OR 1.08, CI .59–1.93) or both (OR 1.21, CI 0.66–2.22). Alcohol exposure may attenuate the effect of cocaine exposure on obesity. Increased obesity associated with cocaine but not alcohol exposure was first observed at 7 years. BMI was also elevated from 3 to 9 years in children exposed to cocaine but not alcohol, due to increasing weight but normal height. Prenatal exposure to cocaine may alter the neuroendocrine system and metabolic processes resulting in increased weight gain and childhood obesity.
Prenatal cocaine exposure; prenatal alcohol exposure; childhood obesity; growth; fetal origins
One of the goals of the 2011 International Year of Chemistry is to celebrate the contributions of women to science. A question that has been frequently asked in this regard is... Why is it necessary to highlight women in the "age of equality"? The reasons are varied but the facts are that many women scientists worked in obscurity throughout the 19th and even well into the 20th century, sometimes publishing anonymously to be heard. This celebration of Women in Science is one way to recognize both the resiliency and passion of these women. As part of this celebration, Chemistry Central Journal's Thematic Series of "Women in Chemistry" includes this article describing the path several women took as they pursued chemistry careers spanning the latter part of the 20th century and into the early 21st century. Sharon Haynie, Nancy Jones, Cheryl Martin, Paula Olsiewski, Mary Roberts and Amber Hinkle each have unique story of their personal journey from childhood to adulthood. As you read these stories, listen generously, and feel free to share your own stories, comments and thoughts.
PTEN is an important control element of PI3K/AKT signaling involved in controlling the processes of embryonic development, cell migration and apoptosis. While its dysfunction is implicated in a large fraction of cancers, PTEN activity in the same pathway may also contribute to metabolic syndromes such as diabetes. In those cases, selective inhibitors of PTEN may be useful. A new class of chiral PTEN inhibitors based on the 3-deoxy-phosphatidylinositol derivatives was recently identified [Wang et al. (2008) J. Am. Chem. Soc. 130, 7746]. However, lack of detailed understanding of protein-ligand interactions has hampered efforts to develop effective agonists or antagonists of PTEN. Here, we use computational modeling to characterize the interactions of the diverse 3-deoxyphosphatidylinositol inhibitors with the PTEN protein. We show that, while each of the compounds binds with the inositol headgroup inserting into the proposed active site of the PTEN phosphatase domain, hydrogen bonding restrictions lead to distinct binding geometries for ligand pairs of opposite chirality. We furthermore demonstrate that the binding modes differ primarily in the orientation of acyl tails of the ligands and that the activity of the compounds is primarily controlled by the effectiveness of tail-protein contacts. These findings are confirmed by binding affinity calculations which are in good agreement with experiment. Finally, we show that while more potent D-series ligands bind in a manner similar to that of the native substrate, an alternate hydrophobic pocket suitable for binding the opposite chirality L-series inhibitors exists, offering the possibility of designing highly selective PTEN- targeting compounds.
PTEN; apoptosis; PI3K/AKT; molecular dynamics; cancer; phosphatidylinositol
We sought to determine the association between small for gestational age (SGA), birth weight, and childhood obesity within preterm polysubstance exposed children. We sampled 312 preterm children with 11-year body mass index (BMI; age- and sex-specific) data from the Maternal Lifestyle Study (51% girls, 21.5% SGA, 46% prenatal cocaine, and 55% tobacco exposed). Multinomial regression analyzed the association between 11-year obesity (OBE) and overweight (OW) and SGA, birth weight, first-year growth velocity, diet, and physical activity variables. Overall, 24% were OBE (BMI for age ≥95th percentile) and 16.7% were OW (BMI ≥85th and <95th percentiles). In adjusted analyses, SGA was associated with OW (odds ratio [OR]=3.4, confidence interval [CI] 1.5 to 7.5). Higher birth weight was associated with OBE (OR = 1.8, CI 1.3 to 2.4) and OW (OR=1.4, CI 1.1 to 2.0). Growth velocity was associated with OBE (OR=2.7, CI 1.8 to 4.0) and OW (OR=1.6, CI 1.1 to 2.4). Low exercise was associated with OBE (OR=2.1, CI 1.0 to 4.4) and OW (OR=2.1, CI 1.0 to 4.5). There was no effect of substance exposure on obesity outcomes. Many (41%) of these high-risk preterm 11-year-olds were obese/overweight. Multiple growth-related processes may be involved in obesity risk for preterm children, including fetal programming as indicated by the SGA effect.
Childhood obesity; premature birth; infant SGA; birth weight; exercise; prenatal drug exposure
Maximal oxygen uptake (VO2max), the gold standard for measurement of cardiorespiratory fitness, is frequently difficult to assess in overweight individuals due to physical limitations. Reactance and resistance measures obtained from bioelectrical impedance analysis (BIA) have been suggested as easily obtainable predictors of cardiorespiratory fitness, but the accuracy with which ht2/Z can predict VO2max has not previously been examined in overweight adolescents.
The impedance index was used as a predictor of VO2max in 87 overweight girls and 47 overweight boys ages 12 to 17 with mean BMI of 38.6 ± 7.3 and 42.5 ± 8.2 in girls and boys respectively. The Bland Altman procedure assessed agreement between predicted and actual VO2max.
Predicted VO2max was significantly correlated with measured VO2max (r2=0.48, p<0.0001). Using the Bland Altman procedure, there was significant magnitude bias (r2=0.10; p<0.002). The limits of agreement for predicted relative to actual VO2max were −589 to 574 mL O2/min.
The impedance index was highly correlated with VO2max in overweight adolescents. However, using BIA data to predict maximal oxygen uptake over-predicted VO2max at low levels of oxygen consumption and under-predicted VO2max at high levels of oxygen consumption. This magnitude bias, along with the large limits of agreement of BIA-derived predicted VO2max, limit its usefulness in the clinical setting for overweight adolescents.
Cycle ergometry; Obesity; Pediatrics; Physical Fitness; VO2max
A family history of later-onset breast cancer (FHLBC) may suggest multi-factorial inheritance of breast cancer risk, including unhealthy lifestyle behaviors that may be shared within families. We assessed whether adherence to lifestyle behaviors recommended for breast cancer prevention--including maintaining a healthful body weight, being physically active and limiting alcohol intake--modifies breast cancer risk attributed to FHLBC in postmenopausal women.
Breast cancer outcomes through August 2003 were analyzed in relationship to lifestyle and risk factors collected by questionnaire during enrollment (between 1993 and 1998) of 85,644 postmenopausal women into the Women's Health Initiative Observational Study.
During a mean follow-up of 5.4 years, 1997 women were diagnosed with invasive breast cancer. The rate of invasive breast cancer among women with an FHLBC who participated in all three behaviors was 5.94 per 1,000 woman-years, compared with 6.97 per 1,000 woman-years among women who participated in none of the behaviors. The rate among women with no FHLBC who participated in all three behavioral conditions was 3.51 per 1,000 woman-years compared to 4.67 per 1,000 woman-years for those who participated in none. We did not observe a clinically important departure from additive effects (Interaction Contrast: 0.00014; 95% CI: -0.00359, 0.00388).
Participating in breast healthy behaviors was beneficial to postmenopausal women and the degree of this benefit was the same for women with and without an FHLBC.
More optimistic perceptions of cardiovascular disease risk are associated with substantively lower rates of cardiovascular death among men. It remains unknown whether this association represents causality (i.e. perception leads to actions/conditions that influence cardiovascular disease occurrence) or residual confounding by unmeasured factors that associate with risk perceptions and with physiological processes that promote cardiovascular disease (i.e. inflammation or endothelial dysfunction).
To evaluate whether previously unmeasured biological markers of inflammation or endothelial dysregulation confound the observed association between cardiovascular disease risk perceptions and cardiovascular disease outcomes;
We conducted a nested case-cohort study among community-dwelling men from Southeastern New England (USA) who were interviewed between 1989 and 1990 as part of the Pawtucket Heart Health Program. We measured C-reactive protein (CRP) and Vascular Endothelial Growth Factor (VEGF) levels from stored sera for a random sample of the parent cohort (control sample, n = 127) and all cases of cardiovascular death observed through 2005 (case sample, n = 44). We evaluated potential confounding using stratified analyses and logistic regression modeling.
Optimistic ratings of risk associated with lower odds of dying from cardiovascular causes among men (OR = 0.39, 95% CI = 0.17, 0.91). Neither CRP nor VEGF confounded these findings.
The strong cardio-protective association between optimistic ratings of cardiovascular disease risk and lower rates of cardiovascular mortality among men is not confounded by baseline biomarkers of systemic inflammation or endothelial dysfunction.
31P NMR relaxation studies from 0.005 to 11.7 T are used to monitor water-soluble inositol 1,2-(cyclic)-phosphate (cIP) binding to phosphatidylinositol-specific phospholipase C spin-labeled at H82C, a position near the active site of the enzyme, and to determine how activating phosphatidylcholine (PC) molecules affect this interaction. We show that, in the absence of an interface, cIP binding to the protein is not rate-limiting, and that lower activation by PC vesicles as opposed to micelles is likely due to hindered product release. The methodology is general and could be used for determining distances in other weakly binding small molecule ligand/protein interactions.
Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes simultaneously interact with the substrate, PI, and with non-substrate lipids such as phosphatidylcholine (PC). For Bacillus thuringiensis PI-PLC these interactions are synergistic with maximal catalytic activity observed at low to moderate mole fractions of PC (XPC) and maximal binding occurring at low mole fractions of anionic lipids. It has been proposed that residues in α helix B help modulate membrane binding and that dimerization on the membrane surface both increases affinity for PC and activates PI-PLC yielding the observed PI/PC synergy. Vesicle binding and activity measurements using a variety of PI-PLC mutants support many aspects of this model and reveal that while single mutations can disrupt anionic lipid binding and the anionic lipid/PC synergy, the residues important for PC binding are less localized. Interestingly, at high XPC mutations can both decrease membrane affinity and increase activity, supporting a model where reductions in wildtype activity at XPC>0.6 results from both dilution of the substrate and tight membrane binding of PI-PLC limiting enzyme hopping or scooting to the next substrate molecule. These results provide a direct analysis of vesicle binding and catalytic activity and shed light on how occupation of the activator site enhances enzymatic activity.
peripheral membrane protein; interfacial activation; mixed phospholipid vesicles; fluorescence correlation spectroscopy
The Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (PI-PLC), an interfacial enzyme associated with prokaryotic infectivity, is activated by binding to zwitterionic surfaces, particularly phosphatidycholine (PC). Two tryptophan residues (Trp47 in the two-turn helix B and Trp242 in a disordered loop) at the rim of the barrel structure are critical for this interaction. The helix B region (Ile43 to Gly48) in wild-type PI-PLC orients the side chains of Ile43 and Trp47 so that they pack together and form a hydrophobic protrusion from the protein surface that likely facilitates initial membrane binding. In previous studies we reported that in the crystal structure of the dimeric W47A/W242A mutant, which is unable to bind to PC, the helix B region has been reorganized by the mutation into an extended loop. Here we report the construction and characterization (catalytic activity, fluorescence and NMR studies) of a series of PI-PLC mutants targeting helix B residues and surrounding regions to explore what is needed to stabilize the ‘membrane active’ conformation of the helix B region. Results strongly suggest that, while hydrophobic groups and presumably an intact helix B are critical for the initial binding of PI-PLC to membranes, disruption of helix B to allow enzyme dimerization is what leads to the activated PI-PLC conformation.
To evaluate via a research literature survey the anterior neurological significance of decreased olfactory functioning following traumatic brain injuries.
Materials and Methods:
A computer literature review was performed to locate all functional neuro-imaging studies on patients with post-traumatic anosmia and other olfactory deficits.
A convergence of findings from nine functional neuro-imaging studies indicating evidence for reduced metabolic activity at rest or relative hypo-perfusion during olfactory activations. Hypo-activation of the prefrontal regions was apparent in all nine post-traumatic samples, with three samples yielding evidence of reduced activity in the temporal regions as well.
The practical ramifications include the reasonable hypothesis that a total anosmic head trauma patient likely has frontal lobe involvement.
Anosmia; functional neuro-imaging; olfaction; traumatic brain injury
d-3-Deoxy-phosphatidylinositol derivatives have cytotoxic activity against various human cancer cell lines. These phosphatidylinositols have a potentially wide array of targets in the phosphatidylinositol-3-kinase (PI3K)/Akt signaling network. To explore the specificity of these types of molecules, we have synthesized d-3-deoxy-dioctanoylphosphatidylinositol (d-3-deoxy-diC8PI), d-3,5-dideoxy-diC8PI and d-3-deoxy-dioctanoylphosphatidylinositol-5-phosphate and their enantiomers, characterized their aggregate formation by novel high resolution field cycling 31P NMR, and examined their susceptibility to phospholipase C (PLC) and their effects on the catalytic activity of PI3K and PTEN against diC8PI and dioctanoylphosphatidylinositol-3-phosphate substrates, respectively, as well as their ability to induce the death of the U937 human leukemic monocyte lymphoma cells. Of these molecules, only d-3-deoxy-diC8PI was able to promote cell death; it did so with an IC50 of 40 μM, well below the CMC of 0.4 mM. Under these conditions, there was little inhibition of PI3K or PTEN observed in assays of recombinant enzymes (although the complete series of deoxy-PI compounds did provide insights into ligand binding by PTEN). The d-3-deoxy-diC8PI was a poor substrate and not an inhibitor of the PLC enzymes. The in vivo results are consistent with the current thought that the PI analogue acts on Akt1 since the transcription initiation factor eIF4e, which is a downstream signaling target of the PI3K/Akt pathway, exhibited reduced phosphorylation on Ser209. Phosphorylation of Akt1 on Ser473, but not Thr308, was reduced. Since the potent cytotoxicity for U937 cells is completely lost with the l-3-deoxy-diC8PI as well as with modification of the hydroxyl group at the inositol C5 (either replacing the –OH with a hydrogen or phosphorylating it) in d-3-deoxy-diC8PI, both chirality of the phosphoinositol moiety and the hydroxyl group at C5 are major determinants of 3-deoxy-PI binding to its target in cells.
3-deoxyphosphatidylinositol; PTEN; field cycling NMR; short-chain phospholipids; U937 cells
The phosphatidylinositol-specific phospholipase C from Listeria monocytogenes forms aggregates with anionic lipids leading to low activity. The specific activity of the enzyme can be enhanced by dilution of the protein, addition of both zwitterionic / neutral amphiphiles (e.g., diheptanoylphosphatidylcholine or Triton X-100) or 0.1–0.2 M inorganic salts. Activation by amphiphiles occurs with both micellar (phosphatidylinositol dispersed in detergents) and monomeric (dibutroylphosphatidylinositol, diC4PI) phosphotransferase substrates and inositol 1,2-(cyclic)-phosphate (cIP), the phosphodiesterase substrate. The presence of zwitterionic / neutral amphiphiles (to which the protein binds weakly) dilutes the surface concentration of the interfacial anionic substrate and thereby reduces enzyme/phospholipid particle aggregation. Zwitterionic amphiphiles also can bind directly to the protein and enhance catalysis since they enhance both diC4PI and cIP hydrolysis. In contrast to activation by amphiphiles, the rate enhancement by salt only occurs for the phosphotransferase step of the reaction. Added salt has a synergistic effect with zwitterionic phospholipids, leading to high specific activities for PI cleavage with only moderate dilution of the anionic substrate in the interface. This kinetic activation correlates with weakening of strong PI-PLC hydrophobic interactions with the interface as monitored by a decrease in the maximum monolayer surface pressure for insertion of the protein. Several point mutations of surface hydrophobic residues (W49A, L151A, L235A, and F237W) can dramatically alter the unusual kinetics of this secreted enzyme. The high affinity of PI-PLC for anionic phospholipids along with a strong hydrophobic interaction, which gives rise to the unusual kinetic behavior, is considered in terms of how it might contribute to the role of this phospholipase in L. monocytogenes infectivity.
asymmetric catalysis; phosphorylation; inositol; peptide; extremophile
High resolution 13C NMR field cycling (covering 11.7 down to 0.002 T) relaxation studies of the sn-2 carbonyl of phosphatidylcholines in vesicles provide a detailed look at the dynamics of this position of the phospholipid in vesicles. The spin-lattice relaxation rate, R1, observed down to 0.05 T is the result of dipolar and CSA relaxation components characterized by a single correlation time τc, with a small contribution from a faster motion contributing CSA relaxation. At lower fields, R1 increases further with a correlation time consistent with vesicle tumbling. The τc is particularly interesting since it is 2-3 times slower than what is observed for 31P of the same phospholipid. However, cholesterol increases the τc for both 31P and 13C sites to the same value, ~25 ns. These observations suggest faster local motion dominates the dipolar relaxation of the 31P while a slower rotation or wobble dominates the relaxation of the carbonyl carbon by the α-CH2 group. The faster motion must be damped with the sterol present. As a general methodology, high resolution 13C field cycling may be useful for quantifying dynamics in other complex systems as long as a 13C label (without attached protons) can be introduced.
There is a universal requirement for post-translational regulatory mechanisms in circadian clock systems. Previous work in Drosophila has identified several kinases, phosphatases and an E3 ligase that are critical for determining the nuclear translocation and/or stability of clock proteins. The present study evaluated the function of p90 ribosomal S6 kinase (RSK) in the Drosophila circadian system. In mammals, RSK1 is a light- and clock-regulated kinase known to be activated by the MAPK pathway, but there is no direct evidence that it functions as a component of the circadian system. Here, we show that Drosophila S6KII RNA displays rhythms in abundance, indicative of circadian control. Importantly, an S6KII null mutant exhibits a short-period circadian phenotype that can be rescued by expression of the wild-type gene in clock neurons, indicating a role for S6KII in the molecular oscillator. Peak PER clock protein expression is elevated in the mutant, indicative of enhanced stability, whereas per mRNA level is decreased, consistent with enhanced feedback repression. Gene reporter assays show that decreased S6KII is associated with increased PER repression. Surprisingly, we demonstrate a physical interaction between S6KII and the Casein Kinase 2 regulatory subunit (CK2β), suggesting a functional relationship between the two kinases. In support of such a relationship, there are genetic interactions between S6KII and CK2 mutations, in vivo, which indicate that CK2 activity is required for S6KII action. We propose that the two kinases cooperate within clock neurons to fine-tune circadian period, improving the precision of the clock mechanism.
Circadian; Post-transcriptional; p90 ribosomal S6 Kinase; RSK1; Casein Kinase 2; MAP Kinase
Language barriers among some Latinos may contribute to the lower rates of colorectal cancer (CRC) screening between Latinos and non-Latino Whites. The purpose of this study was to examine the relationship between language and receipt of colorectal cancer screening tests among Latinos and non-Latinos using a geographically diverse, population-based sample of adults.
Cross-sectional analysis of the Behavioral Risk Factor Surveillance System (BRFSS) survey. Analysis included adults 50 years of age and older, who completed the 2006 BRFSS in a state that recorded data from English and Spanish-speaking participants.
The primary outcome measure was receipt of colorectal screening tests (fecal occult blood testing within prior 12 months and/or lower endoscopy within 10 years). Of the 99,895 respondents included in the study populations, 33% of Latinos responding-in-Spanish reported having had CRC testing, while 51% of Latinos responding-in-English and 62% of English-speaking non-Latinos reported test receipt. In multivariable analysis, compared to non-Latinos, Latinos responding-in-English were 16% less likely (OR,0.84, 95 % CI, 0.73-0.98), and Latinos responding-in-Spanish were 43% less likely to have received colorectal cancer testing (OR,0.57, 95% CI, 0.44-0.74). Additionally, compared to Latinos responding-in-English, Latinos responding-in-Spanish were 36% less likely to have received CRC testing (OR, 0.64; 95% CI, 0.48-0.84)
Latinos responding to the 2006 BRFSS survey in Spanish had a significantly lower likelihood of receiving CRC screening tests compared to non-Latinos and to Latinos responding-in-English. Based on this analysis, Spanish language use is negatively associated with CRC screening and may contribute to disparities in CRC screening.
Colorectal cancer; Screening; Latino/Hispanic; Language; BRFSS
To examine the relationship between energy intake during a buffet meal and indices of insulin dynamics in overweight children.
95 non-diabetic, overweight (BMI ≥95th percentile) children (age 10.3±1.4y) selected lunch from a 9,835kcal buffet eaten ad libitum after an overnight fast. The associations between energy intake and measures of insulin dynamics, in the post-absorptive state and during a 2h-hyperglycemic clamp, were determined. Covariates in the statistical model included race, sex, skeletal age, fat-free mass, fat mass, socioeconomic status, and number of foods in the buffet rated as acceptable.
Energy intake was positively associated with the fasting homeostasis model assessment for insulin resistance index (HOMA-IR; β=0.24, p=0.042), fasting insulin/glucose ratio (β=0.24, p=0.044), 1st-phase insulin (β=0.23, p=0.032), and 1st-phase C-peptide (β=0.21, p=0.046); energy intake was negatively associated with clamp-derived insulin sensitivity (SIclamp; β= -0.29, p=0.042). Each 10% decrease in SIclamp predicted 27 kcal greater energy intake.
Insulin resistance and hyperinsulinemia are associated with greater energy intake after an overnight fast in overweight children. These associations suggest mechanisms whereby insulin resistance may contribute to excessive weight gain in children.
Glucose homeostasis; obesity; food intake; hyperglycemic clamp; insulin dynamics
This study examined gender differences in a range of lifetime psychiatric disorders in a sample of 272 offenders newly admitted to a prison substance abuse program. Although these men and women did not differ in severity of substance use in the six months prior to incarceration, women were significantly more likely than men to report a lifetime psychiatric disorder and a lifetime severe disorder. Furthermore, gender differences emerged in the pattern of lifetime psychiatric comorbidity. Women reported greater lifetime major depression, posttraumatic stress disorder, eating disorder, and borderline personality disorder; men were more likely than women to meet criteria for antisocial personality disorder. Additionally, female offenders were found to have a higher degree of internalizing disorders than male offenders, but there were no gender differences in degree of externalizing disorders. The study concluded that women offenders newly admitted to a prison substance abuse program present with a greater psychiatric vulnerability and a different pattern of psychiatric comorbidity than their male counterparts.