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Objective Fetuses measuring below the 10th percentile for gestational age may be either constitutionally small for gestational age (SGA) or have pathologic fetal growth restriction (FGR). FGR is associated with adverse outcomes; however, identification of low-risk SGA cases is difficult. We performed a pilot study evaluating maternal markers of pathologic FGR, hypothesizing there are distinct amino acid signatures that might be used for diagnosis and development of new interventions. Study Design This was a cohort study of healthy women with sonographic fetal estimated fetal weight Results Among 14 women included, five had abnormal UmA, and three had abnormal UtA Doppler results. Those with abnormal UmA showed elevated ornithine. Those with abnormal UtA had lower dimethylglycine, isoleucine, methionine, phenylalanine, and 1-methylhistidine. Conclusion We found several amino acids that might identify pregnancies affected by pathologic FGR. These findings support the feasibility of future larger studies to identify maternal metabolic approaches to accurately stratify risk for small fetuses.

Background: The role of vitamin D in population subgroups throughout the world continues to be a topic of interest among researchers. Current evidence demonstrates that treating vitamin D deficiency plays a significant role in improving mortality in hospitalized patients, reducing hospital length of stay, and boosting innate immune system. Vitamin D levels vary with age, gender, body mass index (BMI) and geographical area. The purpose of this study is to evaluate vitamin D levels in a cohort of patients in Northeast Tennessee. Study: This institutional review board-approved, retrospective study evaluated vitamin D levels of patients obtained from Mcleod Cancer and Blood Center. Vitamin D levels were collected over a 2-year period and classified as deficient (30 ng/mL). Data were then stratified based on patient characteristics (age, gender, body mass index (BMI), race, seasons, and place of residence) and compounds of vitamin D (D2 and D3). Results: There were 2011 individuals included, with only 44.3% having replete levels and 21.4% with levels less than 20 ng/mL. Females with vitamin D deficiency are more likely to have levels below 20 ng/ml compared to males (18.6% vs. 23%, respectively, p = 0.003). Regarding BMI, the highest levels were reported in normal weight and overweight. With regards to age, advanced age (≥70) was associated with the highest levels and most replete patients. Winter months were associated with the lowest levels of vitamin D. Higher vitamin D levels were found in individuals over 70 years, normal weight and overweight category. Conclusion: Testing vitamin D levels in high-risk groups becomes of utmost importance in areas with longer winter months, obese and underweight patients. Vitamin D levels should be routinely tested and treated in vulnerable populations.

OBJECTIVES: Colorado’s relatively high altitudes have been reported to lower birth weight but the most recent studies were conducted 20 years ago. Since then, the accuracy for assigning altitude of residence has been improved with the use of geocoding, and recommendations for pregnancy weight gain have changed. We therefore sought to determine whether currently, residence at high altitude (≥ 2500 m, 8250 ft) lowers birth weight in Colorado. METHODS: Birth certificate data for all live births (n = 670,017) to Colorado residents from 2007 to 2016 were obtained from the Colorado Department of Public Health and Environment. Geocoded altitude of maternal residence for the current birth was assigned to each birth record. Linear and logistic regression models were used to examine the effects of altitude on birth weight or low birth weight (< 2500 g) while controlling for other factors affecting birth weight, including pregnancy weight gain. RESULTS: Compared to low altitude, infants born at high altitude weighed 118 g less and were more often low birth weight (8.8% vs. 11.7%, p < 0.05). After accounting for other factors influencing birth weight, high altitude reduced birth weight by 101 g and increased the risk of low birth weight by 27%. The only factors with larger impacts on birth weight were hypertensive disorders of pregnancy and cigarette use during pregnancy. CONCLUSIONS FOR PRACTICE: High altitude remains an important determinant of elevated LBW rates in Colorado, and likely contributes to Colorado’s comparative resistance towards meeting the Healthy People 2010/2020 nationwide goal to reduce the low birth weight rate to 7.2% by 2020.

Introduction Psychosocial well-being variables from the Tennessee Intervention for Pregnant Smokers (TIPS) study, a longitudinal smoking cessation study in South-Central Appalachia, were investigated as potential predictors of smoking status. Methods A sample of 1031 pregnant women participated in an expanded 5A's (Ask, Advise, Assess, Assist, Arrange) program, from 2008 to 2011. Measures of stress, self-esteem, depressive symptoms, and disordered eating collected by interview during the first trimester, or during the third trimester in a combined interview if participants began prenatal care late, were hypothesized to differ among three groups of participants: pregnant women who never smoked, pregnant women who smoked but quit prior to birth, and pregnant women who smoked and did not quit prior to birth. Smoking status was measured throughout the study. Whether or not a participant quit smoking was assessed at delivery. Results Non-smokers were lowest in stress F(2,1027) = 46.38, p, Highlights • Low stress and high self-esteem predicted smoking cessation in pregnancy. • Disordered eating did not predict smoking cessation in pregnancy. • Depressive symptoms were highest in pregnant smokers who did not quit smoking. • Non-smokers had higher psychosocial well-being scores than smokers and quitters.

Objective: Social support and religious commitment were examined in relation to antenatal and postpartum depressive symptoms in a prospective, longitudinal study to determine whether religious commitment explained variance in depression scores beyond that accounted for by social support. Background: Social support and religiosity are positively related to good mental/physical health, and depression is related to poor health outcomes in pregnancy and postpartum. It was hypothesised that social support and religious commitment would be inversely related to depressive symptoms, and that religious commitment would predict variance in depression scores over and above social support. Methods: In 106 mostly low SES Appalachian pregnant women, social support and religious commitment were measured during the first trimester. First and third trimester (Center for Epidemiological Studies Depression Scale – 10 item version), and 6 weeks and 6 months postpartum (Edinburgh Postnatal Depression Scale) depression...

Gestational diabetes (GDM) occurs in up to 9% of pregnancies. Perinatal depression affects up to 20% of women during pregnancy, and can extend into the postpartum period. A number of studies have linked depression and diabetes, however, whether this applies to GDM or which might come first is less understood. The purpose of this study was to examine the potential relationship between depression identified in the first trimester of pregnancy and the subsequent development of GDM. Women without pre-existing Type I/II diabetes (n = 1021) were evaluated for depression during the first trimester of pregnancy, and medical records were reviewed to identify a positive history of diabetes. Women identified as depressed during the first trimester were more likely to have GDM compared to those not depressed. After controlling for demographic factors and weight-related variables level of depression in the first trimester still predicted later GDM development. Depression identified in early pregnancy may predict increased risk of subsequent GDM development. Due to the numerous maternal, fetal and neonatal complications associated with GDM, early recognition is essential to promote the best possible outcomes for mother and infant. Recognizing depression as a possible risk factor for GDM development could lead to earlier screening and preventative measures.

Little attention has been given to differences in obesity risk factors by racial/ethnic groups. Using data from the 2011-2012 California Health Interview Survey, we examined differences in risk factors for obesity among Whites, Latinos, Asians, and African Americans among 42,935 adults (24.8% obese). Estimates were weighted to ensure an unbiased representation of the Californian population. Multiple logistic and linear regression analyses were used to examine the differences in risk factors for obesity. Large ethnic disparities were found in obesity prevalence: Whites (22.0%), Latinos (33.6%), African Americans (36.1%), and Asians (9.8%). Differences in risk factors for obesity were also observed: Whites (gender, age, physical activity, smoking, arthritis, and diabetes medicine intake), Latinos (age, arthritis, and diabetes medicine intake), Asians (age, binge drinking, arthritis, and diabetes medicine intake), and African Americans (gender, physical activity, smoking, binge drinking, and diabetes medicine intake). Females were more likely to be obese among African Americans (odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.05–1.94), but less likely among Whites (OR = 0.80, 95% CI = 0.74–0.87). Race/ethnicity should be considered in developing obesity prevention strategies.

The purpose of this study was to investigate the relative contributions of previously identified Polycystic ovary syndrome (PCOS) manifestations (infertility, hirsutism, obesity, menstrual problems) to multiple psychological symptoms. Participants were 126 female endocrinology patient volunteers diagnosed with PCOS who completed a cross-sectional study of PCOS manifestations and psychological symptoms. Participants had significantly elevated scores on nine subscales of psychological symptoms. Menstrual problems were significantly associated with all symptom subscales as well as the global indicator, while hirsutism and obesity were significantly related to five or more subscales. After controlling for demographic factors, menstrual problems were the strongest predictor of psychological symptoms. Findings suggest features of excess body hair, obesity, and menstrual abnormalities carry unique risks for adverse psychologic symptoms, but menstrual problems may be the most salient of these features and deserve particular attention as a marker for psychological risk among women with PCOS.

Although physical abuse during pregnancy has been linked to poor birth outcomes, the role of psychological abuse is less well understood. Associations between birth outcomes and types of psychological abuse during pregnancy (being threatened, screamed at, or insulted) were examined in 489 women with no history of physical abuse. Being threatened was significantly associated with adverse birth outcomes, with women reporting any instance during pregnancy twice as likely to deliver a low birth weight baby. These results remained after controlling for background factors. Finally, most of the variance between threats and birth weight was accounted for by mediating health behaviors (specifically prenatal care utilization and pregnancy weight gain), suggesting pathways for the negative effects of being threatened by an intimate partner during pregnancy.

Objective To examine the relationship between pre-pregnancy weight and body image concerns and smoking status in late pregnancy. Methods Participants included 172 pregnant smokers. Pre-pregnancy weight and body image concerns were assessed during first trimester via the Weight Concern Scale and Body Image Concern Inventory. Smoking status was evaluated at third trimester via self-report. Results Logistic regression analyses revealed that weight concerns played a significant role in smoking continuation in late pregnancy. Conclusions Beliefs about weight control properties of cigarettes may play an important role in smoking continuation among pregnant women. These findings suggest assessing weight concerns with pregnant women who smoke in an effort to facilitate successful cessation.

Objectives: Veterans of the armed forces, like most population groups, have a high prevalence of vitamin D deficiency, which may be associated with adverse outcomes in several types of cancer. Ultraviolet irradiation is inversely linked with the risk of bladder cancer, presumably through enhanced vitamin D synthesis. We hypothesized that variations in vitamin D status and monitoring predict adverse outcomes in bladder cancer among veterans. Methods: A retrospective analysis of data in the Veterans Integrated Service Network-9 (southeastern United States) was performed for patients diagnosed between October 1, 1999 and February 29, 2008. Age, tobacco exposure, body mass index, and latitude and seasonality of sampling were included as variables in addition to serum vitamin 25(OH)D levels. Results: Monitoring of vitamin D and vitamin D levels and status were closely linked to survival in bladder cancer. Both the chances of survival and longevity improved with enhanced vitamin D status and monitoring. Veterans with bladder cancer had better outcomes if the initial vitamin D level was higher and had more monitoring of the vitamin. Initial vitamin D levels were more strongly related to outcomes than follow-up levels. The link between vitamin D and outcomes remained after adjusting for background variables such as age, body mass index, latitude, seasonality, and tobacco exposure. Conclusions: Findings suggest that adequate vitamin D levels early in the course of the disease provide the best opportunity to improve outcomes. Ensuring that veterans with bladder cancer have adequate vitamin D reserves with appropriate monitoring may play a role in improving outcomes in bladder cancer.

Short interpregnancy interval (IPI),18 months between pregnancies, is a potential cause of adverse delivery and birth outcomes, and may be a particular issue among those with other risks. Our goal was to examine IPI and delivery/infant complications in Tennessee.Birth certificate/vital records data included 101,912 women with a previous delivery. IPI groups (6, 6-12, 12-18, 18-60 months) were compared on outcomes.Thirty-nine percent of the deliveries had IPI18 months, 9% were6 months, rates 11% and 27% higher than nationally. Women with IPI18 months were younger, lower educated with lower income, had higher BMIs, and were more likely to be unmarried, smokers, and have begun prenatal care later (p .001). In adjusted analyses, IPI18 months predicted elevated risk for precipitous labor, low-birth weight, preterm delivery, NICU admission, and infant mortality, with effects strongest for IPI6 months. Finally, risks related to IPI6 months were substantially higher for the lowest income women.Rates of less than optimal IPI were high in this population already experiencing significant maternal-child health disparities, with short IPI a particular risk factor for poor outcomes for the most disadvantaged women, suggesting yet another precursor for adverse birth outcomes in those already most at risk.

Background The pleckstrin and Sec7 domain-containing 3 ( PSD3 ) gene has been linked to immune diseases. We examined whether the genetic variants within the PSD3 gene are associated with obesity, type 2 diabetes (T2D), and high-density lipoprotein (HDL) cholesterol level. Methods Multiple logistic regression model and linear regression model were used to examine the associations of 259 single nucleotide polymorphisms (SNPs) within the PSD3 gene with obesity and T2D as binary traits, and HDL level as a continuous trait using the Marshfield data, respectively. A replication study of obesity was conducted using the Health Aging and Body Composition (Health ABC) sample. Results 23SNPs were associated with obesity ( p p =3.97×10 −6 ). Of the 23SNPs, 20 were significantly associated with obesity in the meta-analysis of two samples ( p p =3.05×10 −3 ); while two SNPs (rs6983992 and rs7843239) were associated with both obesity and T2D ( p =0.0188 and 0.023 for obesity and p =8.47×10 −3 and 0.0128 for T2D, respectively). Furthermore, 11SNPs revealed associations with HDL level (top SNP rs13254772 with p =2.79×10 −3 ) in the Marshfield data; meanwhile rs7009615 was associated with both T2D ( p =0.038) and HDL level ( p =4.44×10 −3 ). In addition, haplotype analyses further supported the results of single SNP analysis. Conclusions Common variants in PSD3 were associated with obesity, T2D and HDL level. These findings add important new insights into the pathogenesis of obesity, T2D and HDL cholesterol.

This “Controversies in Cardiovascular Research” article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good.

Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking were significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African American sample. Some drinking measures averaged across pregnancy may have underestimated consumption and overestimated risk of SAb, but others risk-drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk-level alcohol consumption and protect from pregnancy loss.

Purpose: Living in a rural region is associated with significant health disparities and increased medical costs. Vitamin D deficiency, which is increasingly common, is also associated with many adverse health outcomes. The purpose of this study was to determine whether rural-urban residence status of veterans was related to vitamin D levels, and to determine if this factor also influenced medical costs/service utilization. Additionally explored was whether vitamin D differences accounted for part of the association between area of residence and medical costs/service utilization. Methods: Medical records of 9,396 veterans from 6 Veterans Administration Medical Centers were reviewed for variables of interest including county of residence, vitamin D level, medical costs and service utilization, and background variables. Rurality status was classified as large metropolitan, urban, and rural. Findings: The 3 rurality status groups differed significantly in vitamin D levels, with the highest levels observed for urban residents, followed by rural residents, and the lowest for large metro residents. Compared with urban residents, large metro residents were 49% more likely, while rural residents were 20% more likely, to be vitamin D deficient. Both rural and large metro residents had higher medical costs, and they were significantly more likely to be hospitalized. Vitamin D levels explained a statistically significant amount of the relationship between rurality status and medical costs/service utilization. Conclusions: Vitamin D deficiency may be an additional health disparity experienced by both rural and inner-city veterans, and patients residing in these locations should be considered at increased risk for deficiency and routinely tested.

Aim: Vitamin D deficiency is a global health issue associated with increased health-care costs, and could play a role in the pathogenesis and management of inflammatory bowel disease. Prior studies show a high prevalence of vitamin D deficiency in veterans with inflammatory bowel disease. We aimed to examine the outcome differences in patients with inflammatory bowel disease, comparing treatment with ergocalciferol to cholecalciferol. Methods: A retrospective review of electronic medical records of patients with inflammatory bowel disease at a Veterans Affairs Medical Facility in the Southeastern United States was carried out. Those with at least one serum 25(OH) vitamin D level were included. Initial and follow-up vitamin D values were recorded. The type of vitamin D supplementation, whether cholecalciferol or ergocalciferol, was documented. Costs in the year after measurement of vitamin D were divided into separate inpatient and outpatient categories. Results: Veterans (n = 108) with ulcerative colitis or Crohn’s disease and an available 25(OH) vitamin D level were studied. There were differences in follow-up vitamin D levels; those who received weekly ergocalciferol had higher subsequent levels than those who received cholecalciferol, especially at a second follow up, although differences did not achieve statistical significance. However, those who received vitamin D3 were less likely to use laboratory, pharmacy, radiology and fee-based services, and had lower laboratory and pharmacy costs. Conclusions: Our data suggest that cholecalciferol replacement might improve outcomes to a greater extent than ergocalciferol, and might be better in limiting health-care costs and expenses in patients with inflammatory bowel disease. Geriatr Gerontol Int 2012; 12: 475‐480.

Introduction: Restless legs syndrome (RLS) is a common neurological disorder affecting 10% of the population. Most antidepressants exacerbate symptoms; however, correlational studies have noted symptom improvement with bupropion. The purpose of the current study was to examine whether, in a controlled study, bupropion would improve the symptoms of RLS, or at least not exacerbate them. Methods: This was a double-blinded, randomized controlled trial. Twenty-nine participants with moderate to severe RLS received 150 mg sustained-release bupropion once daily, and 31 control participants received a placebo. Participants were followed for 6 weeks and completed standardized tools, including the International Restless Legs Syndrome Study Group (IRLSSG) severity scale. Results: The primary outcome was change from baseline in IRLSSG severity score; lower scores were associated with improved symptoms. At 3 weeks, IRLSSG scores were 10.8 points lower in the bupropion group and 6.0 points lower in the placebo group (P .016). At 6 weeks, IRLSSG scores were10.4 points lower in the bupropion group and 7.6 points lower in the placebo group (P .108). Bupropion was more effective than placebo in the treatment of RLS at 3 weeks; however, this difference was not statistically significant at 6 weeks. Conclusions: The data from our study suggest that bupropion does not exacerbate the symptoms of RLS and may be a reasonable choice if an antidepressant is needed in individuals with RLS. Larger studies that include titration of bupropion should be considered to determine if bupropion is appropriate for primary treatment of RLS, particularly considering the lower cost and favorable side effect profile compared with currently recommended first-line dopamine agonists. (J Am Board Fam Med 2011;24: 422‐428.)

Methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) infections are frequently associated with hospitalization and increased healthcare costs. Vitamin D deficiency may contribute to increased costs for patients with these infections and there is evidence that vitamin D may have an antimicrobial role. To evaluate the role of vitamin D deficiency in the costs incurred with these infections, we studied the relationship of serum 25(OH)D levels to healthcare costs in veterans in the southeastern United States. Patients with both infections were vitamin D deficient to a similar extent and so were combined for further analysis. Vitamin D deficient patients had higher costs and service utilization than those who were not vitamin D deficient. Those with vitamin D deficiency had higher inpatient costs compared to the non-deficient group, and this difference was across most categories except for the number of inpatient hospitalizations or total number of days as an inpatient. Vitamin D deficiency was not significantly related to outpatient cost or service utilization parameters. We conclude that vitamin D deficiency is intimately linked to adverse healthcare costs in veterans with MRSA and P. aeruginosa infections. Vitamin D status should be assayed in patients with these infections.

Objectives Peripheral arterial disease (PAD) is a common and often overlooked entity responsible for considerable morbidity and mortality. Recent evidence suggests that nontraditional risk factors such as vitamin D may contribute to atherosclerosis. We hypothesized that vitamin D status was associated with cardiovascular risk factors and that vitamin D deficiency (25(OH)D Design We reviewed medical records of 1435 veterans between 2000 and 2008 in Tennessee via retrospective chart analysis using correlations, logistic regressions, t tests, and χ 2 analyses. Results Vitamin D status was significantly and inversely correlated with body mass index (BMI), glucose, and triglyceride values. Hypertension and diabetes but not smoking also emerged as significantly associated. Of the sample population, 5.2% (n = 75) had an amputation performed. Those individuals who were vitamin D deficient had a significantly higher amputation rate (6.7%) compared with patients who were nondeficient (4.2%). BMI, triglyceride, total cholesterol, hypertension, and diabetes were found to account for 5.7% of the variation in amputation status. Vitamin D concentration and deficiency status accounted for a nonsignificant amount of additional variance. Conclusions We conclude that vitamin D deficiency is closely linked to increased adiposity, triglyceride, and glucose measurements. Vitamin D deficiency was associated with an increased amputation risk in veterans with PAD and appears to mediate its effects through traditional risk factors.

Vitamin D insufficiency remains a costly pandemic in veterans. Treatment requires achievement of desired 25-hydroxyvitamin D [25(OH)D] concentrations. The frequency with which 25(OH)D should be measured following treatment remains speculative. A retrospective analysis of veterans with vitamin D insufficiency was conducted. The group was stratified on the basis of initial 25(OH)D and assessed for frequency of follow-up 25(OH)D concentrations. Over 3 years, 278 patients with insufficient 25(OH)D concentrations were identified. Of these, 87 (31%) patients had subsequent levels assessed in the year following initial documentation of vitamin D insufficiency. The likelihood of follow-up testing was unrelated to the initial vitamin D level. In the patients with follow-up 25(OH)D levels, 90% eventually achieved a serum level of 30 ng/mL or greater. Veterans with vitamin D insufficiency have inadequate serial monitoring of 25(OH)D concentrations.

Background: In 2000, the American College of Obstetricians/Gynecologists (ACOG) established the 5 A's method of brief smoking cessation counseling (ask, advise, assess, assist, arrange) as a standard component of prenatal care. The purpose of this study was to describe use of the 5 A's in prenatal care in Northeast Tennessee, where pregnancy smoking rates are three times the national average, and to evaluate provider attitudes toward addressing pregnancy smoking. Method: Surveys were distributed to all obstetric practices in a 6-county area. Results: One-quarter of respondents indicated they always asked pregnant patients about smoking, with two-thirds always giving their pregnant smokers advice to quit. Over half reported always assessing willingness to quit, while one-quarter or fewer always provided quit assistance, or arranged follow up. Over half believed addressing smoking was of significant value. Secondhand smoke was infrequently addressed. Demographics, efficacy, and outcome beliefs predicted use of the 5 A's. Conclusions: Most obstetric providers in Northeast Tennessee are not following ACOG recommendations for pregnancy smoking. Efforts to address pregnancy smoking and associated adverse pregnancy outcomes in the region should include facilitation of smoking cessation interventions in prenatal care.

Context: Rates of preterm birth (PTB) and low birth weight (LBW) vary by region, with disparities particularly evident in the Appalachian region of the South. Community conditions related to rurality likely contribute to adverse birth outcomes in this region. Purpose: This study examined associations between rurality and related community conditions, and newborn outcomes in southern Appalachia, and explored whether pregnancy smoking explained such associations. Methods: Data for all births in a southern Appalachian county over a 2-year period were extracted from hospital records. Findings: Data were available for 4,144 births, with 45 different counties of residence. Babies born to women from completely rural counties, on average, weighed 700 g less, were 1.5 inches shorter, and were born over 3 weeks earlier than less rural infants. In addition, these babies were 4.5 times more likely to be LBW, 4 times more likely to be PTB, and 5 times more likely to be admitted to the neonatal intensive care unit (NICU). Effects were also found for per capita income, poverty rate, and unemployment rate, all of which were associated with rurality. Some, but not all of the association was explained by elevated rates of pregnancy smoking. Conclusions: Babies born to women residing in rural and economically depressed counties in southern Appalachia are at substantially increased risk for poor birth outcomes. Improving these outcomes in the rural South will likely require addressing access to health services and information, health care provider retention, transportation services, employment opportunities, and availability of public health services including smoking cessation assistance.

Vitamin D deficiency is often unrecognized and has been linked to many chronic diseases. Vitamin D supplementation has been shown to ameliorate these chronic diseases and may reduce the prevalence of some cancers. We analyzed the health care costs associated with vitamin D deficiency in Veterans in Northeast Tennessee. A retrospective electronic chart analysis of the relationship of 25-hydroxyvitamin D [25(OH)D] status to health care costs, services, and utilization was done in 886 veterans. The overall costs were higher by 39% in the vitamin D-deficient group. Vitamin D deficiency was associated with increased service utilization in many areas including more frequent emergency room and clinic visits as well as increased inpatient stay and inpatient services. The serum level of vitamin D was also related to health care costs, although to a lesser extent. Vitamin D deficiency is closely linked to increased health care costs in veterans.

Pregnancy alcohol consumption has been linked to poor birth outcomes and long-term developmental problems. Despite this, a significant number of women drink during pregnancy. Although most prenatal care providers are asking women about alcohol use, validated screening tools are infrequently employed. Research has demonstrated that currently available screening methods and intervention techniques are effective in identifying and reducing pregnancy drinking. Implementing universal screening and appropriate intervention for pregnancy alcohol use should be a priority for prenatal care providers, as these efforts could substantially improve pregnancy, birth, and longer term developmental outcomes for those affected.

Since fetal alcohol syndrome was first reported, studies have demonstrated a range of perinatal/developmental abnormalities that fall under the umbrella term fetal alcohol spectrum disorders. Of these, low birth weight in exposed children is among the most commonly observed and widely accepted. However, in the past, assertion of an association between prenatal alcohol exposure and preterm birth was controversial. Methodological difficulties may have contributed to failure to consistently detect such a relationship. However, new evidence suggests that pregnancy drinking may be a major contributor to extreme, but not mild prematurity. Extreme prematurity is a major cause of severe perinatal morbidity and mortality. If recent findings are confirmed, it suggests that extreme prematurity might be reduced by eliminating prenatal alcohol exposure.

Objectives: The purpose of the present study was to examine background and modifiable pregnancy health behavior factors predicting infant birthweight in an economically and educationally disadvantaged sample with low medical risk. Methods: Participants were recruited from a family practice center in rural Appalachia. Participants: Over 220, predominantly Caucasian and lower SES women with low risk pregnancies were included in the sample. Data were collected through systematic chart review. Half of the women smoked during pregnancy and over 10% gave birth to low birth weight (LBW; < 2500 g) babies. Results: Compared with those who gave birth to normal weight newborns, women with LBW babies had more miscarriages, but did not differ significantly on other background factors. Women who delivered LBW babies gained less weight during pregnancy and were more likely to smoke than remaining women. After control for background factors, modifiable pregnancy health behavior factors (weight gain, prenatal care, smoking, alcohol and substance use) accounted for over 11% of birth weight variance, with nearly 7% attributable solely to smoking. Conclusions: Pregnancy smoking was the strongest behavioral predictor of LBW in this economically and educationally disadvantaged rural sample, suggesting that efforts to reduce LBW in similar populations should include targeting pregnancy smoking.

Background and Objectives: Restless legs syndrome (RLS) is a common, underdiagnosed neurological movement disorder of undetermined etiology. The primary treatments for restless legs syndrome are pharmacological. To date, no randomized controlled trials have examined the effectiveness of an exercise program on the symptoms of RLS. Methods: Study participants (N = 41) were randomized to either exercise or control groups. 28 participants (average age 53.7; 39% males) were available and willing to begin the 12-week trial. The exercise group was prescribed a conditioning program of aerobic and lower-body resistance training 3 days per week. Restless legs symptoms were assessed by the International RLS Study Group (IRLSSG) severity scale and an ordinal scale of RLS severity at the beginning of the trial, and at 3, 6, 9, and 12 weeks. Results: Twenty-three participants completed the trial. At the end of the 12 weeks, the exercise group (N = 11) had a significant improvement in symptoms compared with the control group (N = 12) (P = .001 for the IRLSSG severity scale and P Conclusions: The prescribed exercise program was effective in improving the symptoms of RLS.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) offer unique, noninvasive methods of measuring, respectively, in vivo quantitative neuroanatomy and neurochemistry. The main purpose of the present study was to identify and compare the neuroanatomical and neurochemical abnormalities that are associated with prenatal exposure to alcohol in both fetal alcohol syndrome (FAS)-diagnosed children and those diagnosed with fetal alcohol effects (FAE). MR data of three age-, gender- and race-balanced groups of children, FAS-diagnosed, FAE-diagnosed and non-exposed controls, were compared. Effects of prenatal alcohol exposure, regardless of diagnosis, were found in the caudate nucleus. Specifically, a significantly smaller caudate nucleus was found for the FAS and FAE participants compared to the controls. In addition, the metabolite ratio of N-acetyl-aspartate to creatine (NAA/Cr), an indicator of neuronal function, in left caudate nucleus of both the FAS and FAE participants was elevated compared to the control group. Analysis of absolute concentrations revealed that the increase in the ratio of NAA/Cr was due to an increase in NAA alone. Although its exact function in the CNS is unknown, NAA is believed to be a neuronal marker due to its exclusive localization to neurons. Some also speculate a role for NAA in myelination. Elevated NAA in the prenatal alcohol-exposed participants could indicate a lack of normal program cell death, dendritic pruning and/or myelination during development. The present study demonstrates that prenatal alcohol-exposed children, with or without facial dysmorphology, have abnormal brain anatomy and chemistry.

This article focuses on a systems biology approach to studying the pathophysiology of cigarette smoking during pregnancy. Particular emphasis is given to the damaging role of oxidative stress. Cigarette smoking exerts multiple adverse affects but abundant evidence, mostly in adults, suggests that oxidative stress and free radical damage is a major pathophysiological factor. Smoking during pregnancy is known to contribute to numerous poor birth outcomes, such as low birth weight, preterm birth as well as life-long health and developmental problems. It is clinically important to know the separate contributions that cigarette derived-nicotine and smoking-induced free oxidative stress make to these poor outcomes. Surprisingly, the extent to which smoking dependent oxidative stress contributes to these poor outcomes is not well studied but the application of redox proteomics should be useful. Considerable biochemical evidence suggests that antioxidants, such as tocopherols and ascorbate, could be useful in minimizing oxidative stress induced pathology to the developing fetus in those women who, despite medical advice, continue to smoke. Nevertheless, this suggestion has yet to be tested in well-designed clinical studies.

Background Pregnancy substance use is linked to low birth weight. However, less is known about relative contributions of various substances and whether effects are due to decreased gestational duration, restriction of fetal growth, or both. The study goal was to use causal modeling to evaluate the individual impact of alcohol, tobacco, cocaine, and marijuana on gestational duration and fetal growth. Methods Participants were 3164 urban black women recruited at entry to prenatal care and followed to delivery, with all gestational dating ultrasound supported. Pregnancy substance use was assessed via self-report (alcohol, tobacco, cocaine, and marijuana). Results Alcohol, cigarette, and cocaine use were all individually and negatively related to gestational age at delivery. However, only alcohol, cigarette, and marijuana use predicted fetal growth, with effects for alcohol and cigarette greater and more discrepant for older women. Overall, heavy cigarette smoking had the greatest individual impact on birth weight (up to 431 g). Heavy levels of use of all 4 substances by older women decreased birth weight by 26% (806 g). Conclusions For perhaps the first time, reduced birth weight is apportioned both by type of substance and mechanism of effect. The use of alcohol and/or cigarettes was clearly more harmful to fetal growth than cocaine use. Findings demonstrate the need for continued emphasis on intervention efforts to address legal and illicit pregnancy substance use.

Prostate cancer remains the second most commonly diagnosed cancer among the male population worldwide. Vitamin D deficiency has been linked to prostate cancer and its aggressiveness. Herein, we initiated a retrospective study to evaluate vitamin D status and monitoring in veterans with prostate cancer, and to examine the potential link between vitamin D and survival status and length of survival in this population. We found that veterans who were initially vitamin D deficient were significantly less likely to survive than those who were not initially deficient, and that both initial and follow-up vitamin D deficiency were associated with decreased likelihood of survival after prostate cancer diagnosis. We recommend that vitamin D deficiency be replaced in veterans with prostate cancer.

The objective of this study was to further explore the cellular basis of the reduced rate and magnitude of contraction of feline left ventricular myocytes with severe hypertrophy induced by slow progressive pressure overload. A 3.0 mm internal diameter band was placed around the ascending aorta of 12 young (8–10 weeks old) cats, and sham operations were performed in 13 others. This caused no major pressure overload initially, but 15 weeks later there was a significant pressure gradient across the band (56±14 mmHg) and the heart weight to body weight ratio had increased from 4.2–7 gm/kg. Contraction rates and magnitudes of myocytes isolated from the hearts with hypertrophy (LVH) were significantly slower and smaller, respectively, than those from control (C) animals. Indo-1 fluorescence transients in LVH myocytes were significantly smaller in magnitude and longer in duration than in C, suggesting that contractile defects result from Ca 2 + derangements. Elevation of bath Ca 2 + increased the peak Indo-1 fluorescence and the rate and magnitude of contraction in all myocytes. At the bath Ca 2 + which had maximal inotropic effects there were no differences in the peak Indo-1 fluorescence in LVH and C myocytes, but contraction magnitude remained significantly smaller in LVH. This suggests that there are Ca 2 +-independent contractile derangements in LVH. In support of this hypothesis, the relationship between contraction magnitude and the peak Indo-1 fluorescence (index of myofibrillar Ca 2 + sensitivity) was significantly shifted in LVH myocytes, suggesting that myofibrillar Ca 2 + sensitivity was reduced. There was also a significant shift of the terminal portions of hysteresis loops of cell length v indo-1 fluorescence ratio, providing additional support for this idea. Experiments with isoproterenol suggest that it can reduce myofibrillar Ca 2 + sensitivity in C, but not LVH myocytes. The idea that increased internal resistance to shortening (internal load) is responsible for the contractile defects of LVH myocytes was examined by defining the relationship between the rate of relengthening and the magnitude of shortening. There was no significant difference in this relation between C and LVH myocytes. In addition, colchicine (which depolymerizes microtubular tubulin) had no significant effect on contraction magnitude in either C or LVH myocytes. These results suggest that the contractile properties of feline LVH myocytes result from changes in cellular Ca 2 + regulation and myofibrillar Ca 2 + sensitivity, but not from changes in the internal loading.

Alcohol consumption during pregnancy remains a common occurrence and is associated with a multitude of adverse birth and long-term outcomes. Binge drinking in particular is shown to be particularly harmful to the developing fetus. Effects include full fetal alcohol syndrome, with characteristic facial dysmorphology, growth restriction, and developmental to delays. Exposed children may also have partial fetal alcohol syndrome, alcohol-related birth defects, and alcohol-related neurodevelopmental disorders. These effects are preventable, and efforts must begin with accurate identification of women who consume alcohol during pregnancy. Several screening tools have been developed and validated for use in prenatal care settings, and the most recently proposed brief and easy to use T-ACER3 has demonstrated high sensitivity and specificity in both identifying risk drinking during pregnancy and predicting long-term neurobehavioral outcomes in exposed children. Once identified, effective interventions are available for use with pregnant women consuming alcohol. Brief interventions, which can be delivered by a health professional and involve motivational interviewing, have been demonstrated to significantly reduce alcohol consumption during pregnancy. These approaches, recommended by American College of Obstetricians and Gynecologist (ACOG), help move patients toward increased readiness to positively change their drinking behavior. Ultimately, all prenatal care providers should routinely screen all patients for alcohol use using validated tools, and where appropriate, should offer intervention.

Background Measurement of carbon monoxide in expired air samples (ECO) is a non-invasive, cost-effective biochemical marker for smoking. Cut points of 6 ppm–10 ppm have been established, though appropriate cut-points for pregnant woman have been debated due to metabolic changes. This study assessed whether an ECO cut-point identifying at least 90% of pregnant smokers, and misidentifying fewer than 10% of non-smokers, could be established. Methods Pregnant women (N = 167) completed a validated self-report smoking assessment, a urine drug screen for cotinine (UDS), and provided an expired air sample twice during pregnancy. Results Half of women reported non-smoking status early (51%) and late (53%) in pregnancy, confirmed by UDS. Using a traditional 8 ppm + cut-point for the early pregnancy reading, only 1% of non-smokers were incorrectly identified as smokers, but only 56% of all smokers, and 67% who smoked 5 + cigarettes in the previous 24 h, were identified. However, at 4 ppm +, only 8% of non-smokers were misclassified as smokers, and 90% of all smokers and 96% who smoked 5 + cigarettes in the previous 24 h were identified. False positives were explained by heavy second hand smoke exposure and marijuana use. Results were similar for late pregnancy ECO, with ROC analysis revealing an area under the curve of .95 for early pregnancy, and .94 for late pregnancy readings. Conclusions A lower 4 ppm ECO cut-point may be necessary to identify pregnant smokers using expired air samples, and this cut-point appears valid throughout pregnancy. Work is ongoing to validate findings in larger samples, but it appears if an appropriate cut-point is used, ECO is a valid method for determining smoking status in pregnancy.

Objectives: Vitamin D deficiency has reached epidemic levels and has been frequently found in United States veterans. This deficiency has been linked to cardiovascular disease; however few studies have examined the relationship of vitamin D status to cardiac sonography. The purpose of the current study was to examine the relationship between vitamin D and echocardiography findings. Design: Retrospective chart review. Setting: Veterans administration hospital in the Southeastern United States. Participants: Thirty two eligible patients were included. Measurements: Charts were reviewed for key variables of interest, and patients with coronary artery disease and without vitamin D testing were excluded. Results: Several of the echocardiogram parameters were significantly associated with vitamin D level and status. Those with mitral regurgitation were more than twice as likely as remaining patients to be vitamin D deficient, as were those with pulmonary hypertension. In addition, patients with aortic sclerosis were almost twice as likely to be vitamin D deficient compared with patients who were negative. Conclusion: Pending additional studies to confirm the cardiac benefits of a vitamin D repletes state, we urge clinicians to monitor and appropriately treat vitamin D deficiency. The benefits of maintaining adequate vitamin D reserves combined with the low potential for toxicity with modest vitamin D supplementation provides clinicians with a door to improving wellbeing and possibly ameliorating cardiac valvular disease.

Vitamin D deficiency has reached pandemic proportions and has been closely linked to coronary and peripheral vascular disease. Moreover, vitamin D replacement may play a role in improving ejection fraction with the potential to influence cardiac valvular function. To investigate this relationship further we studied 32 veterans without a diagnosis of coronary artery disease. A retrospective study evaluated veterans with both a 25(OH) D determination and an echocardiogram. The echocardioraphic parameters were identified through chart review. Vitamin D deficiency was significantly “(P< 0.05)” associated with mitral insufficiency, aortic sclerosis and pulmonary hypertension as shown in the table below. Mitral Regurgitation % Vitamin D deficient Absent 23 Present * 56 Aortic Sclerosis % Vitamin D deficient Absent 32 Present * 61 Pulmonary Hypertension % Vitamin D deficient Absent 32 Present * 67 * is P

Relationship of Vitamin D status to cardiac arrhythmias in Veterans Islam T. MD MPH, Bailey B. PhD, Ferdous C. MD, Finton C. MD, Manning T. and Peiris A.N. MD PhD Introduction. Vitamin D deficiency is widespread and is associated with coronary artery disease. However, few studies have examined the link between Vitamin D status and cardiac arrhythmias. The present study was undertaken to explore this relationship. Method. We studied 34580 veterans in the southeastern USA and evaluated the relationship of Vitamin D status to both atrial and ventricular arrhythmias by retrospective chart review. Approximately 34.8 % (12030) patient were Vitamin D deficient (25(OH)D < 20 ng/ml). This group was more likely to be younger, have a significantly greater body mass index, more likely to be female and belong to a racial minority when compared to the Vitamin D replete group. The Vitamin D deficient group was also more likely to have hyperlipidemia, diabetes, hypertension and be tobacco users. Result. The presence of arrhythmias varied between 0.3 % (ventricular) to 25 % (Any arrhythmia plus heart block). Atrial and ventricular arrhythmias were significantly greater in the vitamin D deficient group. Vitamin D deficiency remained significantly associated with atrial and ventricular arrhythmias after adjusting for other variables through multivariate logistic regression analysis. Conclusion. To our knowledge, this is the first report indicating a significant link between vitamin D status and cardiac arrhythmias in Veterans. Vitamin D remained a significant predictor of this relationship even after adjusting for other variables. Emerging evidence suggest that Vitamin D replacement can improve cardiac ejection fraction. The potential for Vitamin D replacement to reduce an underlying arrythmogenic propensity is an exciting area for future research. Adjusted logistic regression model predicting atrial and ventricular arrhythmia by vitamin D level. Atrial Arrhythmia Present Absent p-value Vitamin D treated as Continuous variable, beta estimate -0.006 0 (ref.) 0.001 Categorical (low versus replete), odds ratio 1.18 1.00 (ref.) Ventricular Arrhythmia Present Absent p-value Vitamin D treated as Continuous variable, beta estimate -0.020 0 (ref.) 0.042 Categorical (low versus replete), odds ratio 1.48 1.00 (ref.) 0.055

OBJECTIVES Vitamin D deficiency is highly prevalent and has been linked to increased morbidity and mortality. There has been an increase in testing for vitamin D with a concomitant increase in costs. While individual factors are significantly linked to vitamin D status, prior studies have not yielded a model predictive of vitamin D status or 25(OH)D levels. The purpose of this investigation was to determine if a prediction model of vitamin D could be developed using extensive demographic data and laboratory parameters. METHODS Patient data from 6 Veterans Administration Medical Centers were extracted from medical charts. RESULTS For the 14,920 available patients, several factors including triglyceride level, race, total cholesterol, body mass index, calcium level, and number of missed appointments were significantly linked to vitamin D status. However, these variables accounted for less than 15% of the variance in vitamin D levels. While the variables correctly classified vitamin D deficiency status for 71% of patients, only 33% of those who were actually deficient were correctly identified as deficient. CONCLUSION Given the failure to find a sufficiently predictive model for vitamin D deficiency, we propose that there is no substitute for laboratory testing of 25(OH)D levels. A baseline vitamin D 3 daily replacement of 1000-2000 IU initially with further modification based on biannual testing appears to factor in the wide variation in dose response observed with vitamin D replacement and is especially important in high-risk groups such as ethnic minorities.

African Americans have lower vitamin D levels and reduced health outcomes compared to white Americans. Vitamin D deficiency may contribute to adverse health outcomes in African Americans. We hypothesized that race would be associated with vitamin D status and testing in African Americans veterans, and that vitamin D status is a major contributor to health care costs in African American veterans compared to white veterans. A retrospective analysis of the medical data in the Veterans Integrated Service Network 9 (southeastern United States) was performed, and 14148 male veterans were identified. Race was designated by the patient and its relationship to vitamin D levels/status and costs was assessed. Vitamin D levels were significantly lower and the percent of patients with vitamin D deficiency was significantly higher in African American veterans. This difference was independent of latitude and seasonality. Vitamin D testing was done significantly more in white veterans compared to African American veterans (5.4 % vs 3.8 %). While follow-up testing was 42% more likely if a patient was found to be vitamin D deficient, white veterans were 34% more likely than African American veterans to have at least 1 follow-up 25-hydroxyvitamin D performed. African American veterans had significantly higher health care costs, which were linked to lower vitamin D levels; however, the cost differential persisted even after adjusting for vitamin D status. Vitamin D deficiency is highly prevalent in African American veterans and needs improved management within the Veteran Administration system. Vitamin D status appears not to be the sole contributor to increased health care costs in African American veterans.

Vitamin D deficiency is a global pandemic associated with increased health care costs and could play a role in the pathogenesis and management of inflammatory bowel disease. This study examined vitamin D status in veterans with ulcerative colitis (UC) and Crohn's disease (CD) and assessed its relationship to health care costs and service utilization. Veteran patients (n = 125) with UC or CD and with an available 25-hydroxyvitamin D level were studied. CD patients were more likely to be vitamin D insufficient than the UC group. Despite the higher vitamin D levels among UC patients, they were significantly more likely to utilize laboratory and pharmacy services compared with CD patients, whereas patients with CD had significantly higher radiology and pharmacy costs. Thus, it is likely that disease-specific characteristics rather than vitamin D status determine the costs of health care services in veterans with established inflammatory bowel disease.

Poor birth outcomes are associated with illicit drug use during pregnancy. While prenatal cigarette exposure has similar effects, cessation of illicit drug use during pregnancy is often prioritized over cessation of smoking. The study goal was to examine the impact of pregnancy tobacco use, relative to use of illicit drugs, on birth outcomes. Women were recruited at entry to prenatal care, with background and substance use information collected during pregnancy. Urine drug screens were performed during pregnancy, and the final sample (n = 265) was restricted to infants who also had biologic drug testing at delivery. Participants were classified by pregnancy drug use: no drugs/no cigarettes, no drugs/cigarette use, illicit drugs/no cigarettes, and illicit drugs/cigarette use. Groups differed significantly on infant birthweight, but not gestational age at delivery after control for confounders including background and medical factors. Among women who smoked, the adjusted mean birthweight gain was 163 g for those not using hard illicit drugs, while marijuana use had no effect on birth weight beyond the effect of smoking cigarettes. Women who used hard illicit drugs and did not smoke had an adjusted mean birthweight gain of 317 g over smokers. Finally, women who refrained from hard illicit drugs and smoking had a birthweight gain of 352 g. Among substance using pregnant women, smoking cessation may have a greater impact on birthweight than eliminating illicit drug use. Intervention efforts should stress that smoking cessation is at least as important to improving pregnancy outcomes as abstaining from illicit drug use.

Serial echocardiography and Doppler were used to monitor the progression of pressure-overload produced by banding the ascending aortas of young cats. The peak Doppler gradient across the band increased (as the animals grew in size) from 42 +/- 4.2 mmHg at 1 wk to 78 +/- 4.5 mmHg at 2-3 mos. Echocardiographic measurements of septal wall thickness increased significantly at 1 wk. Global ventricular function was unaltered in banded cats versus shams at each time point. However, in the subgroup of animals with an aortic-constricted area of < 0.025 cm2 at 1 wk, fractional shortening decreased by 40% at 2-3 mos. Contractile abnormalities were present in isolated myocytes from hypertrophied hearts. Mechanical function was more profoundly depressed in cells from hearts with echocardiographic evidence of ventricular decompensation. Echocardiographic and Doppler studies assessed cardiac size and function and identified indexes predictive of global and cellular myocardial dysfunction. The use of noninvasive techniques as a predictor of failure makes the feline model of progressive left ventricular pressure-overload useful for studies of cellular and molecular factors regulating not only the development of cardiac hypertrophy but also the transition from compensated hypertrophy to myocardial failure.