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1.  Maternal Sleep Duration and Complaints of Vital Exhaustion during Pregnancy is Associated with Placental Abruption 
Sleep disorders are associated with cardiovascular complications and preterm delivery (PTD). Insufficient sleep results in metabolic alterations and increased inflammation, both known to contribute to placental abruption (abruption), a determinant of PTD. We examined associations of abruption with sleep duration and complaints of vital exhaustion.
The study included 164 abruption cases and 160 controls in a multicenter study in Peru. Data on habitual sleep duration and vital exhaustion during the first 6 months of pregnancy were elicited during interviews conducted following delivery. Women were categorized according to short, normal and long sleep duration (≤6, 7-8 and ≥9 h); and frequency of feeling exhausted. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.
Short and long sleep durations were associated with increased odds of abruption. The ORs of abruption in relation to short (≤6 h) and long (≥9 h) sleep duration were 2.0 (95%CI 1.1-3.7) and 2.1 (95%CI 1.1-4.1), compared with normal sleep duration (7-8 h). Complaints of vital exhaustion were also associated with abruption (OR=2.37; 95%CI 1.46-3.85), and were independent of sleep duration.
We extend the existing literature and support the thesis that maternal sleep habits and disorders should be assessed among pregnant women.
PMCID: PMC4241173  PMID: 24749793
sleep duration; exhaustion; placental abruption; pregnancy
2.  Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus 
Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods.
Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05.
Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling.
Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-015-0125-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4331385
Cardiovascular magnetic resonance; Myocardial blood flow; Fermi modeling; Distributed parameter modeling; Fractional flow reserve; Invasive coronary angiography
3.  Association of Childhood Physical and Sexual Abuse with Intimate Partner Violence, Poor General Health and Depressive Symptoms among Pregnant Women 
PLoS ONE  2015;10(1):e0116609.
We examined associations of childhood physical and sexual abuse with risk of intimate partner violence (IPV). We also evaluated the extent to which childhood abuse was associated with self-reported general health status and symptoms of antepartum depression in a cohort of pregnant Peruvian women.
In-person interviews were conducted to collect information regarding history of childhood abuse and IPV from 1,521 women during early pregnancy. Antepartum depressive symptomatology was evaluated using the Patient Health Questionnaire-9. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI).
Any childhood abuse was associated with 2.2-fold increased odds of lifetime IPV (95%CI: 1.72–2.83). Compared with women who reported no childhood abuse, those who reported both, childhood physical and sexual abuse had a 7.14-fold lifetime risk of physical and sexual IPV (95%CI: 4.15–12.26). The odds of experiencing physical and sexual abuse by an intimate partner in the past year was 3.33-fold higher among women with a history of childhood physical and sexual abuse as compared to women who were not abused as children (95%CI 1.60–6.89). Childhood abuse was associated with higher odds of self-reported poor health status during early pregnancy (aOR = 1.32, 95%CI: 1.04–1.68) and with symptoms of antepartum depression (aOR = 2.07, 95%CI: 1.58–2.71).
These data indicate that childhood sexual and physical abuse is associated with IPV, poor general health and depressive symptoms in early pregnancy. The high prevalence of childhood trauma and its enduring effects of on women’s health warrant concerted global health efforts in preventing violence.
PMCID: PMC4312043  PMID: 25635902
4.  Vitamin D Deficiency Treatment Patterns in Academic Urban Medical Center 
Assess racial/ethnic and sex differences in treatment of vitamin D deficiency with high dose ergocalciferol (‘vitamin D2’) or other forms of vitamin D in a northeastern U.S. ambulatory clinic of an academic urban medical center.
Cross-sectional observational review of electronic medication prescribing records of patients with 25-hydroxyvitamin D (25OHD) deficiency (25OHD < 20 ng/ml) from 2004–2008.
Using multivariable logistic regression adjusting for patients’ demographics, and Elixhauser comorbidity score, we examined the association of sex and race/ethnicity with prescription for at least one dose of vitamin D.
Among 2,140 patients without renal disease and tested for 25OHD deficiency (25OHD < 20 ng/ml), 66.2% received no vitamin D prescription for vitamin D deficiency. Blacks and Hispanics received vitamin D prescriptions at a higher frequency than whites, 37.8% 38.4% and 30.9%, respectively, p=0.003. The vitamin D prescription rate for women versus men was 26.3% and 7.5%, respectively, p=0.04. In a fully adjusted model, no difference in prescription likelihood for blacks and whites [OR=1.18 95% CI, 0.88–1.58; p=0.29] or Hispanics and whites was noted [OR=1.01 95% CI, 0.70–1.45;p=0.73]. Similarly, fully adjusted model showed no difference in prescription likelihood for females and males [OR=1.23 95% CI, 0.93–1.63; p=0.12].
Among primary care patients with vitamin D deficiency, vitamin D supplementation was low and white patients were less likely to receive vitamin D treatment than blacks or Hispanics. Interventions to correct the high prevalence of vitamin D deficiency should address the markedly low rate of vitamin D prescribing when 25OHD levels are measured.
PMCID: PMC4199332  PMID: 25328637
Vitamin D; electronic prescribing; ambulatory
5.  Construct Validity and Factor Structure of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale in a Multi-National Study of African, South East Asian and South American College Students 
PLoS ONE  2014;9(12):e116383.
The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) are questionnaires used to assess sleep quality and excessive daytime sleepiness in clinical and population-based studies. The present study aimed to evaluate the construct validity and factor structure of the PSQI and ESS questionnaires among young adults in four countries (Chile, Ethiopia, Peru and Thailand).
A cross-sectional study was conducted among 8,481 undergraduate students. Students were invited to complete a self-administered questionnaire that collected information about lifestyle, demographic, and sleep characteristics. In each country, the construct validity and factorial structures of PSQI and ESS questionnaires were tested through exploratory and confirmatory factor analyses (EFA and CFA).
The largest component-total correlation coefficient for sleep quality as assessed using PSQI was noted in Chile (r = 0.71) while the smallest component-total correlation coefficient was noted for sleep medication use in Peru (r = 0.28). The largest component-total correlation coefficient for excessive daytime sleepiness as assessed using ESS was found for item 1 (sitting/reading) in Chile (r = 0.65) while the lowest item-total correlation was observed for item 6 (sitting and talking to someone) in Thailand (r = 0.35). Using both EFA and CFA a two-factor model was found for PSQI questionnaire in Chile, Ethiopia and Thailand while a three-factor model was found for Peru. For the ESS questionnaire, we noted two factors for all four countries
Overall, we documented cross-cultural comparability of sleep quality and excessive daytime sleepiness measures using the PSQI and ESS questionnaires among Asian, South American and African young adults. Although both the PSQI and ESS were originally developed as single-factor questionnaires, the results of our EFA and CFA revealed the multi- dimensionality of the scales suggesting limited usefulness of the global PSQI and ESS scores to assess sleep quality and excessive daytime sleepiness.
PMCID: PMC4281247  PMID: 25551586
6.  Placental Genome and Maternal-Placental Genetic Interactions: A Genome-Wide and Candidate Gene Association Study of Placental Abruption 
PLoS ONE  2014;9(12):e116346.
While available evidence supports the role of genetics in the pathogenesis of placental abruption (PA), PA-related placental genome variations and maternal-placental genetic interactions have not been investigated. Maternal blood and placental samples collected from participants in the Peruvian Abruptio Placentae Epidemiology study were genotyped using Illumina’s Cardio-Metabochip platform. We examined 118,782 genome-wide SNPs and 333 SNPs in 32 candidate genes from mitochondrial biogenesis and oxidative phosphorylation pathways in placental DNA from 280 PA cases and 244 controls. We assessed maternal-placental interactions in the candidate gene SNPS and two imprinted regions (IGF2/H19 and C19MC). Univariate and penalized logistic regression models were fit to estimate odds ratios. We examined the combined effect of multiple SNPs on PA risk using weighted genetic risk scores (WGRS) with repeated ten-fold cross-validations. A multinomial model was used to investigate maternal-placental genetic interactions. In placental genome-wide and candidate gene analyses, no SNP was significant after false discovery rate correction. The top genome-wide association study (GWAS) hits were rs544201, rs1484464 (CTNNA2), rs4149570 (TNFRSF1A) and rs13055470 (ZNRF3) (p-values: 1.11e-05 to 3.54e-05). The top 200 SNPs of the GWAS overrepresented genes involved in cell cycle, growth and proliferation. The top candidate gene hits were rs16949118 (COX10) and rs7609948 (THRB) (p-values: 6.00e-03 and 8.19e-03). Participants in the highest quartile of WGRS based on cross-validations using SNPs selected from the GWAS and candidate gene analyses had a 8.40-fold (95% CI: 5.8–12.56) and a 4.46-fold (95% CI: 2.94–6.72) higher odds of PA compared to participants in the lowest quartile. We found maternal-placental genetic interactions on PA risk for two SNPs in PPARG (chr3∶12313450 and chr3∶12412978) and maternal imprinting effects for multiple SNPs in the C19MC and IGF2/H19 regions. Variations in the placental genome and interactions between maternal-placental genetic variations may contribute to PA risk. Larger studies may help advance our understanding of PA pathogenesis.
PMCID: PMC4280220  PMID: 25549360
7.  Obstructive Sleep Apnea and Multiple Anthropometric Indices of General Obesity and Abdominal Obesity among Young Adults 
This study aimed to examine the association between obstructive sleep apnea (OSA) and obesity among young adults. A total of 2911 college students in Thailand participated in the study. Anthropometric measurements and blood pressure were taken by trained research staff. Overall, 6.3% of college students had OSA determined by the Berlin Questionnaire, 9.6% were overweight (BMI: 25–29 kg/m2), 4.5% were obese (BMI≥30 kg/m2); 12.4% had abdominal obesity (men: waist circumference≥90 cm; women: waist circumference≥80 cm). There were significant associations between OSA and overweight (odds ratio (OR)=1.72; 95% confidence interval (CI)=1.04–1.85) and obesity (OR=24.23; 95% CI=15.20–38.61), independent of demographic and lifestyle factors, blood pressure, and psychological distress. Students with OSA were more likely to have abdominal obesity than those without OSA (OR=2.09; 95% CI=1.19–3.67). OSA was significantly related to joint effects of general and abdominal obesity. The OSA-obesity associations were robust and evident for both genders, individuals with normal and elevated blood pressure, and those with and without psychological distress. This study shows independent associations of OSA with general and abdominal obesity among young adults. OSA could be a risk factor for obesity and consequent cardiovascular morbidities. OSA screening and treatment might be important for young adults.
PMCID: PMC4270013  PMID: 25530977
obstructive sleep apnea; obesity; abdominal obesity; college student; Asia; Thailand
8.  Validity of the Patient Health Questionnaire-9 for Depression Screening and Diagnosis in East Africa 
Psychiatry research  2013;210(2):10.1016/j.psychres.2013.07.015.
Depression is often underdiagnosed and undertreated in primary care settings, particularly in developing countries. This is, in part, due to challenges resulting from a lack of skilled mental health workers, stigma associated with mental illness, and lack of cross-culturally validated screening instruments. We conducted this study to evaluate the reliability and validity of the Patient Health Questionnaire-9 (PHQ-9) questionnaire as a screen for diagnosing major depressive disorder among adults in Ethiopia, the second most populous country in sub-Saharan Africa. A total of 926 adults attending outpatient departments in a major referral hospital in Ethiopia participated in this study. We assessed criterion validity and performance characteristics against an independent, blinded, and psychiatrist administered semi-structured Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview. Overall, the PHQ-9 items showed good internal (Cronbach's alpha=0.85) and test re-test reliability (intraclass correlation coefficient=0.92). A factor analysis confirmed a 1-factor structure. Receiver Operating Characteristics (ROC) analysis showed that a PHQ-9 threshold score of 10 offered optimal discriminatory power with respect to diagnosis of MDD via the clinical interview (sensitivity=86% and specificity=67%). The PHQ-9 appears to be a reliable and valid instrument that may be used to diagnose major depressive disorders among Ethiopian adults.
PMCID: PMC3818385  PMID: 23972787
PHQ-9; Validation; Africa; Ethiopia; Depression
9.  The Sinonasal Tract: Another Potential “Hot Spot” for Carcinomas with Transcriptionally-Active Human Papillomavirus 
Head and Neck Pathology  2013;8(3):241-249.
While high risk human papillomavirus (HPV) is well established as causative and clinically important for squamous cell carcinoma (SCC) of the oropharynx, its role in non-oropharyngeal head and neck SCC is much less clearly elucidated. In the sinonasal region, in particular, although it is a relatively uncommon site for SCC, as many as 20 % of SCC harbor transcriptionally-active high risk HPV. These tumors almost always have a nonkeratinizing morphology and may have a better prognosis. In addition, specific variants of SCC as well as other rare carcinoma types, when arising in the sinonasal tract, can harbor transcriptionally-active HPV. This article reviews the current literature on HPV in sinonasal carcinomas, attempts to more clearly demonstrate what tumors have it and how this relates to possible precursor lesions like inverted papilloma, and discusses the possible clinical ramifications of the presence of the virus.
PMCID: PMC4126925  PMID: 24338611
Human papillomavirus; Sinonasal; Nonkeratinizing; Squamous cell carcinoma; p16
10.  Correlates of Cortisol in Human Hair: Implications for Epidemiologic Studies on Health Effects of Chronic Stress 
Annals of epidemiology  2013;23(12):797-811.e2.
Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, “cortisol” “hair” “confounders” “chronic” “stress” and “correlates.” Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., PTSD), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing´s syndrome) and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear to not be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies.
PMCID: PMC3963409  PMID: 24184029
hair; cortisol; chronic stress; correlates; assessment; analysis; determinants; psychiatric disorders
11.  Blood vessel segmentation and width estimation in ultra-wide field scanning laser ophthalmoscopy 
Biomedical Optics Express  2014;5(12):4329-4337.
Features of the retinal vasculature, such as vessel widths, are considered biomarkers for systemic disease. The aim of this work is to present a supervised approach to vessel segmentation in ultra-wide field of view scanning laser ophthalmoscope (UWFoV SLO) images and to evaluate its performance in terms of segmentation and vessel width estimation accuracy. The results of the proposed method are compared with ground truth measurements from human observers and with existing state-of-the-art techniques developed for fundus camera images that we optimized for UWFoV SLO images. Our algorithm is based on multi-scale matched filters, a neural network classifier and hysteresis thresholding. After spline-based refinement of the detected vessel contours, the vessel widths are estimated from the binary maps. Such analysis is performed on SLO images for the first time. The proposed method achieves the best results, both in vessel segmentation and in width estimation, in comparison to other automatic techniques.
PMCID: PMC4285608  PMID: 25574441
(100.2960) Image analysis; (100.3008) Image recognition, algorithms and filters; (100.4996) Pattern recognition, neural networks; (170.4470) Ophthalmology
12.  Racial Disparities in Short Sleep Duration by Occupation and Industry 
American Journal of Epidemiology  2013;178(9):1442-1451.
Short sleep duration, which is associated with increased morbidity and mortality, has been shown to vary by occupation and industry, but few studies have investigated differences between black and white populations. By using data from a nationally representative sample of US adult short sleepers (n = 41,088) in the National Health Interview Survey in 2004–2011, we estimated prevalence ratios for short sleep duration in blacks compared with whites for each of 8 industry categories by using adjusted Poisson regression models with robust variance. Participants' mean age was 47 years; 50% were women and 13% were black. Blacks were more likely to report short sleep duration than whites (37% vs. 28%), and the black-white disparity was widest among those who held professional occupations. Adjusted short sleep duration was more prevalent in blacks than whites in the following industry categories: finance/information/real estate (prevalence ratio (PR) = 1.44, 95% confidence interval (CI): 1.30, 1.59); professional/administrative/management (PR = 1.30, 95% CI: 1.18, 1.44); educational services (PR = 1.39, 95% CI: 1.25, 1.54); public administration/arts/other services (PR = 1.30, 95% CI: 1.21, 1.41); health care/social assistance (PR = 1.23, 95% CI: 1.14, 1.32); and manufacturing/construction (PR = 1.14, 95% CI: 1.07, 1.20). Short sleep generally increased with increasing professional responsibility within a given industry among blacks but decreased with increasing professional roles among whites. Our results suggest the need for further investigation of racial/ethnic differences in the work-sleep relationship.
PMCID: PMC3888251  PMID: 24018914
industry; occupation; race; sleep; work
13.  Daytime Sleepiness, Circadian Preference, Caffeine Consumption and Use of Other Stimulants among Thai College Students 
We conducted this study to evaluate the prevalence of daytime sleepiness and evening chronotype, and to assess the extent to which both are associated with the use of caffeinated stimulants among 3,000 Thai college students. Demographic and behavioral characteristics were collected using a self-administered questionnaire. The Epworth Sleepiness Scale and the Horne and Ostberg Morningness-Eveningness Questionnaire were used to evaluate prevalence of daytime sleepiness and circadian preference. Multivariable logistic regression models were used to evaluate the association between sleep disorders and consumption of caffeinated beverages. Overall, the prevalence of daytime sleepiness was 27.9 % (95% CI: 26.2–29.5%) while the prevalence of evening chronotype was 13% (95% CI: 11.8–14.2%). Students who use energy drinks were more likely to be evening types. For instance, the use of M100/M150 energy drinks was associated with a more than 3-fold increased odds of evening chronotype (OR 3.50; 95% CI 1.90–6.44), while Red Bull users were more than twice as likely to have evening chronotype (OR 2.39; 95% CI 1.02–5.58). Additionally, those who consumed any energy drinks were more likely to be daytime sleepers. For example, Red Bull (OR 1.72; 95% CI 1.08–2.75) or M100/M150 (OR 1.52; 95% CI 1.10–2.11) consumption was associated with increased odds of daytime sleepiness. Our findings emphasize the importance of implementing educational and prevention programs targeted toward improving sleep hygiene and reducing the consumption of energy drinks among young adults
PMCID: PMC4209847  PMID: 25356368
14.  History of Infertility and Risk of Gestational Diabetes Mellitus: A Prospective Analysis of 40,773 Pregnancies 
American Journal of Epidemiology  2013;178(8):1219-1225.
Studies of delayed conception and risk of gestational diabetes (GDM) are sparse, although common underlying mechanisms are plausible, including insulin resistance and inflammation. The association between a history of infertility and GDM was assessed prospectively among 40,773 eligible pregnancies in the US Nurses' Health Study II cohort (1989–2001). Biennial questionnaires provided updated information on infertility and several lifestyle and health-related characteristics. Multivariable log-binomial models with generalized estimating equations were used to compute risk ratios and 95% confidence intervals, adjusting for age, prepregnancy body mass index (weight (kg)/height (m)2), and additional potential confounders. GDM occurred among 1,405 (5.2%) women. A prepregnancy history of infertility was reported by 5,497 (20.5%) participants and was significantly associated with a 39% greater risk of GDM (risk ratio (RR) = 1.39, 95% confidence interval (CI): 1.24, 1.57; P < 0.001). Underlying reasons for infertility associated with GDM included ovulation disorders (RR = 1.52, 95% CI: 1.23, 1.87; P < 0.001) and tubal blockage (RR = 1.83, 95% CI: 1.20, 2.77; P = 0.005). The association of cervical mucus disorder with GDM was of borderline significance (RR = 1.70, 95% CI: 0.88, 3.30; P = 0.11). Endometriosis (RR = 1.27, 95% CI: 0.70, 2.31; P = 0.43) and male factor infertility (RR = 1.12, 95% CI: 0.78, 1.61; P = 0.55) were not associated with GDM risk. These novel findings suggest that infertility, particularly from ovulation disorders and tubal blockage, is associated with an increased GDM risk. Further research is needed to identify mechanisms or common underlying metabolic dysfunction explaining these observations.
PMCID: PMC3792729  PMID: 23956097
cohort studies; gestational diabetes mellitus; infertility
15.  Association of Age at Menarche and Menstrual Characteristics with Adult Onset Asthma among Reproductive Age Women 
Observations of increasing asthma incidence, decreasing age at menarche, and common risk factors have led investigators to hypothesize potential associations of age at menarche or menstrual characteristics with incidence of adult onset asthma. We evaluated these associations among reproductive age women.
Study participants were selected from among women enrolled in a pregnancy cohort study. Information on age at menarche, menstrual characteristics, and history of asthma was collected using interviewer-administered questionnaires. Adult onset asthma was defined as asthma first diagnosed after onset of menarche. Women who had no information on asthma and menstrual history and those who were diagnosed with asthma before menarche were excluded. A total of 3,461 women comprised the analytic population. Logistic regression was used to estimate adjusted relative risk (aRR) and 95% confidence intervals (95% CI) relating age at menarche and menstrual characteristics with adult onset asthma.
Mean age at menarche was 12.8 years (standard deviation=1.46). Among study participants, 7.5% were diagnosed with asthma after the onset of menarche. After controlling for potential confounders (age, race, body mass index, and socio-economic status), women who had early menarche (<12 years old) had 60% higher risk of being diagnosed with adult onset asthma as compared with women who did not have early menarche (≥ 12 years old) (aRR= 1.59, 95% CI 1.19 – 2.13). Menstrual irregularities or abnormal (short or long) cycle length were not associated with risk of adult onset asthma. In addition, no significant interaction was observed between age at menarche or menstrual characteristics with body mass index or physical activity (in adolescence) in relation to adult onset asthma.
Early menarche is associated with a higher risk of developing adult onset asthma among reproductive age women. Mechanisms for this association are potential areas of future research.
PMCID: PMC4192656  PMID: 25309820
16.  Sleep Disturbances and Common Mental Disorders in College Students 
To estimate the prevalence of common mental disorders (CMDs) and examine the association of sleep disorders with presence of CMDs.
A self-administered questionnaire was used to ascertain demographic information and behavioral characteristics among 2,645 undergraduate students in Ethiopia. Standard questionnaires were used to assess CMDs, evening chronotype, sleep quality and daytime sleepiness.
A total of 716 students (26.6%) were characterized as having CMDs. Female students had higher prevalence of CMDs (30.6%) compared to male students (25.4%). After adjusting for potential confounders, daytime sleepiness (OR=2.02; 95% CI 1.64-2.49) and poor sleep quality (OR=2.36; 95% CI 1.91-2.93) were associated with increased odds of CMDs.
There is a high prevalence of CMDs comorbid with sleep disorders among college students.
PMCID: PMC4190836  PMID: 25309939
sleep; mental disorders; college; Ethiopia; Africa
17.  Episodic migraine and obesity and the influence of age, race, and sex 
Neurology  2013;81(15):1314-1321.
To evaluate the episodic migraine (EM)-obesity association and the influence of age, race, and sex on this relationship.
We examined the EM-obesity association and the influence of age, race, and sex in 3,862 adult participants of both black and white race interviewed in the National Comorbidity Survey Replication. EM diagnostic criteria were based on the International Classification of Headache Disorders. Body mass index was classified as underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), or obese (≥30 kg/m2). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for EM were estimated using logistic regression. Models were stratified by age (<50/≥50 years), race (white/black), and sex (male/female).
A total of 188 participants fulfilled criteria for EM. In all participants, the adjusted odds of EM were 81% greater in individuals who were obese compared with those of normal weight (OR 1.81; 95% CI: 1.27–2.57; p = 0.001), with a significant trend of increasing odds of EM with increasing obesity status from normal weight to overweight to obese (p = 0.001). In addition, stratified analyses demonstrated that the odds of EM were greater in obese as compared with normal-weight individuals who were 1) younger than 50 years of age (OR 1.86; 95% CI: 1.20–2.89; p for trend = 0.008), 2) white (OR 2.06; 95% CI: 1.41–3.01; p for trend ≤0.001), or 3) female (OR 1.95; 95% CI: 1.38–2.76; p for trend ≤0.001).
The odds of EM are increased in those with obesity, with the strongest relationships among those younger than 50 years, white individuals, and women.
PMCID: PMC3806922  PMID: 24027060
18.  Clinical Responses to Vemurafenib in Patients with Metastatic Papillary Thyroid Cancer Harboring BRAFV600E Mutation 
Thyroid  2013;23(10):1277-1283.
Clinical benefit from cytotoxic chemotherapy for metastatic papillary thyroid carcinoma (PTC) is disappointing, and effective therapeutic approaches for these patients are urgently needed. Because kinase-activating mutations in the BRAF proto-oncogene commonly occur in advanced PTC, and inhibition of BRAFV600E has shown promising clinical activity in melanoma, BRAF inhibitor therapy may be an effective strategy to treat metastatic PTC.
The dose escalation portion of a first-in-human, phase I study of vemurafenib, a selective RAF inhibitor, included three patients with metastatic PTC harboring the BRAFV600E mutation. Vemurafenib was initially dosed at 240–360 mg twice a day, later escalated to 720 mg twice a day. Response evaluation was performed every 8 weeks per Response Evaluation Criteria in Solid Tumors (RECIST).
Among the three patients, one had a confirmed partial response with reduction of pulmonary target lesions by 31%, and the duration of response was 7.6 months before the disease progressed in the lungs and the bones. The time to progression was 11.7 months. The other two patients had stable disease, and the time to progression was 13.2 and 11.4 months, respectively.
Vemurafenib appears to have a promising clinical activity in patients with metastatic PTC, and our data suggest that the BRAFV600E mutant kinase is a relevant target for therapy in this patient population. Further investigation of inhibitors of mutated BRAF kinase in patients with PTC in a phase II study is warranted.
PMCID: PMC3967415  PMID: 23489023
19.  Sleep-Disordered Breathing and Gestational Diabetes Mellitus 
Diabetes Care  2013;36(10):3353-3360.
Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM.
We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed.
Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89–4.96).
These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy.
PMCID: PMC3781575  PMID: 24065843
20.  Attitudes, beliefs, and perceptions of caregivers and rehabilitation providers about disabled children’s sleep health: a qualitative study 
BMC Pediatrics  2014;14(1):245.
Children with disabilities are more likely to have sleep disturbances than children without disabilities. Identifying attitudes, beliefs, knowledge, and perceptions of caregivers and health professionals is essential in developing effective intervention programs to improve disabled children’s sleep health. However, no such qualitative data about adults who have key roles in the life and daytime activities of children with disabilities are available. This qualitative study aimed to understand attitudes, beliefs, knowledge, and perceptions about disabled children’s sleep hygiene among caregivers and rehabilitation providers of children with disabilities.
Twenty seven adults, including nine primary caregivers and eighteen rehabilitation providers, participated in five focus group discussions between September and December 2012 at the Rehabilitation Center in Punta Arenas, Chile. A trained facilitator guided focus group discussions using a semi-structured script. Audiotapes and transcripts of focus group discussions were reviewed and analyzed for recurrent themes.
Participants identified seven themes related to children’s sleep hygiene: lifestyle behaviors, family factors, children’s disabilities and/or comorbidities, environmental factors, adults’ responsibilities for children’s sleep, perception of good sleep, and parental distress about children’s sleep problems. While both caregivers and rehabilitation providers recognized the importance of sleep for children’s health and functioning, they differed in their understanding of how sleep hygiene practices influence sleep. Rehabilitation providers recognized the negative influence of electronics on sleep and the positive influence of sleep routines. In contrast, caregivers reported use of television/movie watching and stimulants as coping strategies for managing children’s sleep problems.
Caregivers may benefit from better understanding the influence of electronics and stimulant use on child sleep health. Rehabilitation providers are well positioned to provide educational messages to both children and caregivers in order to change their attitudes, perceptions, and practices surrounding sleep. These qualitative data are valuable in developing intervention programs aimed at improving sleep health among children with disabilities.
PMCID: PMC4194412  PMID: 25273034
Child; Disability; Sleep hygiene; Parent; Health care provider; Focus group
21.  Sleep duration, vital exhaustion, and odds of spontaneous preterm birth: a case–control study 
Preterm birth is a leading cause of perinatal morbidity and mortality worldwide, resulting in a pressing need to identify risk factors leading to effective interventions. Limited evidence suggests potential relationships between maternal sleep or vital exhaustion and preterm birth, yet the literature is generally inconclusive.
We examined the relationship between maternal sleep duration and vital exhaustion in the first six months of pregnancy and spontaneous (non-medically indicated) preterm birth among 479 Peruvian women who delivered a preterm singleton infant (<37 weeks gestation) and 480 term controls who delivered a singleton infant at term (≥37 weeks gestation). Maternal nightly sleep and reports of vital exhaustion were ascertained through in-person interviews. Spontaneous preterm birth cases were further categorized as those following either spontaneous preterm labor or preterm premature rupture of membranes. In addition, cases were categorized as very (<32 weeks), moderate (32–33 weeks), and late (34- <37 weeks) preterm birth for additional analyses. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).
After adjusting for confounders, we found that short sleep duration (≤6 hours) was significantly associated with preterm birth (aOR = 1.56; 95% CI 1.11-2.19) compared to 7–8 hours of sleep. Vital exhaustion was also associated with increased odds of preterm birth (aOR = 2.41; 95% CI 1.79-3.23) compared to no exhaustion (Ptrend <0.001). These associations remained significant for spontaneous preterm labor and preterm premature rupture of membranes. We also found evidence of joint effects of sleep duration and vital exhaustion on the odds of spontaneous preterm birth.
The results of this case–control study suggest maternal sleep duration, particularly short sleep duration, and vital exhaustion may be risk factors for spontaneous preterm birth. These findings call for increased clinical attention to maternal sleep and the study of potential intervention strategies to improve sleep in early pregnancy with the aim of decreasing risk of preterm birth.
PMCID: PMC4190429  PMID: 25261975
Sleep duration; Exhaustion; Preterm birth; Pregnancy
22.  Sleep Quality, Sleep Patterns and Consumption of Energy Drinks and Other Caffeinated Beverages among Peruvian College Students 
Health  2013;5(8B):26-35.
To evaluate sleep quality in relation to lifestyle characteristics including consumption of energy drinks and other caffeinated beverages among Peruvian college students.
A total of 2,458 college students were invited to complete a self-administered questionnaire that collected information about a variety of behaviors including consumption of energy drinks, caffeinated and alcoholic beverages. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for poor sleep quality in relation to lifestyle characteristics.
A total of 965 males and 1,493 female students were enrolled in the study. 52.0% of males and 58.4% of females experienced poor sleep quality (p=0.002). Females (OR=1.28; 95% CI 1.08–1.51) and those who reported consuming ≥ 3 stimulant beverages per week (OR=1.88; 95% CI 1.42–2.50) had higher odds of poor sleep quality. Students who consumed 1–19 alcoholic beverages monthly (OR=1.90; 95% CI 1.46–2.49) had a higher odds of long sleep latency. Consumption of ≥ 3 stimulant beverages per week was associated with daytime dysfunction due to sleep loss (OR=1.45; 95% CI 1.10–1.90), short sleep duration (OR= 1.49; 95% CI 1.14–1.94), and use of sleep medication (OR= 2.10; 95% CI 1.35–3.28).
Consumption of energy drinks, other caffeinated beverages and alcoholic beverages are risk factors of poor sleep quality. Increased awareness of these associations should promote interventions to improve students’ lifestyle habits, including consumption of alcoholic and caffeinated beverages, and overall health.
PMCID: PMC4169115  PMID: 25243056
23.  Pre-Adolescent Cardio-Metabolic Associations and Correlates: PACMAC methodology and study protocol 
BMJ Open  2014;4(9):e005815.
Although cardiovascular disease is typically associated with middle or old age, the atherosclerotic process often initiates early in childhood. The process of atherosclerosis appears to be occurring at an increasing rate, even in pre-adolescents, and has been linked to the childhood obesity epidemic. This study will investigate the relationships between obesity, lifestyle behaviours and cardiometabolic health in pre-pubescent children aged 8–10 years, and investigates whether there are differences in the correlates of cardiometabolic health between Māori and Caucasian children. Details of the methodological aspects of recruitment, inclusion/exclusion criteria, assessments, statistical analyses, dissemination of findings and anticipated impact are described.
Methods and analysis
Phase 1: a cross-sectional study design will be used to investigate relationships between obesity, lifestyle behaviours (nutrition, physical activity/fitness, sleep behaviour, psychosocial influences) and cardiometabolic health in a sample of 400 pre-pubescent (8–10 years old) children. Phase 2: in a subgroup (50 Caucasian, 50 Māori children), additional measurements of cardiometabolic health and lifestyle behaviours will be obtained to provide objective and detailed data. General linear models and logistic regression will be used to investigate the strongest correlate of (1) fatness; (2) physical activity; (3) nutritional behaviours and (4) cardiometabolic health.
Ethics and dissemination
Ethical approval will be obtained from the New Zealand Health and Disabilities Ethics Committee. The findings from this study will elucidate targets for decreasing obesity and improving cardiometabolic health among preadolescent children in New Zealand. The aim is to ensure an immediate impact by disseminating these findings in an applicable manner via popular media and traditional academic forums. Most importantly, results from the study will be disseminated to participating schools and relevant Māori health entities.
PMCID: PMC4170204  PMID: 25234509
24.  Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance 
Salivary duct carcinoma over-expresses epidermal growth factor receptor (EGFR) and HER-2 though underlying mechanisms remain undefined. Because of potential utilization of these markers as treatment targets, we evaluated protein and gene status by several techniques to determine complementary value.
Experimental Design
A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquanititively evaluated into a 3-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status. Sequencing of Exons 18, 19 and 21 of the EGFR gene for mutations was performed.
EGFR Forty-six (69.7%) of the 66 tumors showed some form of EGFR expression (17,3+; 17,2+; 12,1+) but none gene amplification. Five (9.4%) of 53 tumors showed mutations in exon 18 (3) and exon 19 (2). Polysomy of chromosome 7(average >2.5 copies per cell) was detected in 15 (25.0%) of 60 tumors (6,3+; 5,2+; 2,1+; 2,0+ expression) and correlated with poor 3-year survival (p=0.015). HER-2: Seventeen (25.8%) of 66 tumors expressed HER-2 (10,3+; 3,2+; 4,1+). Eight tumors showed HER-2 gene amplification (6,3+; 1,1+; 1,0+ protein expression). Chromosome 17 polysomy was found in eight (15.7%) of 51 tumors; two with HER-2 expression (3+; 1+).
Our study shows that salivary duct carcinomas: 1) harbor EGFR gene mutations in a subset of tumors which may guide therapy, 2) pursue aggressive clinical course in cases with Chromosome 7 polysomy and high EGFR expression, and 3) with HER-2 gene amplification and protein high-expression maybe selected for targeted therapy.
PMCID: PMC4152860  PMID: 20371674
Salivary duct carcinoma; epidermal growth factor receptor; HER-2; Fluorescence in situ hybridization; polysomy; mutation
25.  Sleep Quality and Sleep Patterns in Relation to Consumption of Energy Drinks, Caffeinated Beverages and Other Stimulants among Thai College Students 
Sleep & breathing = Schlaf & Atmung  2012;17(3):1017-1028.
Poor sleep and heavy use of caffeinated beverages have been implicated as risk factors for a number of adverse health outcomes. Caffeine consumption and use of other stimulants are common among college students globally. However, to our knowledge, no studies have examined the influence of caffeinated beverages on sleep quality of college students in Southeast Asian populations. We conducted this study to evaluate the patterns of sleep quality; and to examine the extent to which poor sleep quality is associated with consumption of energy drinks, caffeinated beverages and other stimulants among 2,854 Thai college students.
A questionnaire was administered to ascertain demographic and behavioral characteristics. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep habits and quality. Chi-square tests and multivariate logistic regression models were used to identify statistically significant associations.
Overall, the prevalence of poor sleep quality was found to be 48.1%. A significant percent of students used stimulant beverages (58.0%). Stimulant use (OR 1.50; 95%CI 1.28-1.77) was found to be statistically significant and positively associated with poor sleep quality. Alcohol consumption (OR 3.10; 95% CI 1.72-5.59) and cigarette smoking (OR 1.43; 95% CI 1.02-1.98) also had statistically significant association with increased daytime dysfunction. In conclusion, stimulant use is common among Thai college students and is associated with several indices of poor sleep quality.
Our findings underscore the need to educate students on the importance of sleep and the influences of dietary and lifestyle choices on their sleep quality and overall health.
PMCID: PMC3621002  PMID: 23239460
Sleep; Energy Drinks; Alcohol; Caffeine; Students; Cigarettes

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