To analyze the association of hemoglobin A1c (HbA1c) at gestational diabetes mellitus (GDM) diagnosis with postpartum abnormal glucose in a cohort of women with GDM.
Women with singleton pregnancies managed for GDM at a large diabetes and pregnancy program located in Charlotte, North Carolina who completed a postpartum 2-hour oral glucose tolerance test were eligible for inclusion in this retrospective cohort study. Clinical information, including maternal HbA1c at diagnosis was abstracted from medical records. A parametric survival model was used to assess the association of HbA1c at GDM diagnosis with postpartum maternal abnormal glucose including impaired fasting glucose, impaired glucose tolerance, and any postpartum abnormal glucose.
Of the 277 postpartum women with GDM 75 (32%) had impaired fasting glucose, 61 (28%) had impaired glucose tolerance, and 15 (9%) were diagnosed with type 2 diabetes after delivery. After adjustment for clinic, maternal age, parity, prepregnancy BMI 25 kg/m2 or higher, non-white race or ethnicity, and gestational week at first HbA1c we detected a trend of increased risk for impaired fasting glucose (p=0.01), impaired glucose tolerance (p=0.002), and any glucose abnormality (p <0.001) associated with increased quartile of HbA1c at GDM diagnosis.
HbA1c measured at GDM diagnosis may be a useful tool for identifying GDM patients at highest risk of developing postpartum abnormal glucose.
Sleep is an important physiological process for humans. University students in most resource limited countries often report poor sleep quality due to changing social opportunities and increasing academic demands. However, sleep quality among university students has not been studied in Ethiopia. Thus, this study assessed sleep quality and its demographic and psychological correlates among university students.
A cross-sectional survey was conducted in two universities in Ethiopia. Multistage sampling procedures were used to enroll 2,817 students into the study. A self-administered structured questionnaire including the Pittsburgh Sleep Quality Index (PSQI), the Depression Anxiety Stress Scale-21, the Perceived Stress Scale (PSS) and selected modules of the World Health Organization STEPS instrument was used for the study. This research included 2,551 students. Frequency, median, mean with standard deviation and 95% confidence interval were used to characterize sleep quality and other variables. Analysis of variance and binary logistic regression procedures were also used.
The prevalence of poor sleep quality (total PSQI score > 5) was 55.8% (1,424). Female students (adjusted odds ratio (AOR) 1.23; 95% CI: 1.00, 1.57), second year (AOR 2.91; 95% CI: 2.1, 4.02) and third year students (AOR 2.25; 95% CI 1.62, 3.12) had statistically significant higher odds of poor sleep quality. Perceived stress level and symptoms of depression and anxiety were strongly associated with sleep quality.
A substantial proportion of university students are affected by poor sleep quality. If our results are confirmed in prospective studies, health promotion and educational programs for students should emphasize the importance of sleep and mental health.
Pittsburgh sleep quality index; Perceived stress; Anxiety; Depression; Students; Ethiopia
Vaginal injuries are common outside of obstetric practice. Post coital posterior fornix perforation and intra-abdominal bleeding is however an uncommon cause for laparotomy.
PRESENTATION OF CASE
We present two cases of posterior fornix perforation with hypovolemic shock after sexual intercourse in two young women. In both cases there was a delay in the diagnosis because there was illicit sex. Both women however eventually had laparotomy and uneventful post-operative outcomes.
This is an uncommon condition but it is important to suspect it in sexually active women. Previous reports that it was only found in females with vaginal thinning (children and postmenopausal women) are refuted by these two cases and the importance of interviewing women without a chaperone to get the true story is highlighted for prompt treatment.
Acute post-coital vaginal injuries should be suspected in women who present to hospital with vaginal bleeding and abdominal pain.
Post coital; Posterior fornix perforation; Peritonitis
Accumulating evidence suggests that placental abruption has a complex multifactorial pathogenesis that involves cardiovascular risk and metabolic dysfunction. However, comprehensive assessment of variations in genes involved in cardiometabolic traits associated with the risk of placental abruption is lacking. We conducted a case-control study investigating associations of variations in maternal cardiometabolic genes (characterized using 217,697 SNPs on the Illumina Cardio-Metabo Chip) with risk of placental abruption. A total of 253 abruption cases and 258 controls were selected from among participants enrolled in the Peruvian Abruptio Placentae Epidemiology Study in Lima, Peru. In the genome-wide association analyses, top hits did not surpass genome-wide significance. However, we observed suggestive associations of placental abruption with several SNPs, including SNPs in SMAD2 (P-value=1.88e-6), MIR17HG (P-value=7.8e-6], and DGKB (P-value=8.35e-6] loci. In candidate gene analyses, we observed associations of variations in a priori selected genes involved in coagulation, rennin-angiotensin, angiogenesis, inflammation, and B-vitamin metabolism with the risk of abruption. Our study suggests that variations in maternal cardiovascular and metabolic genes may be associated with risk of placental abruption. Future studies with large sample sizes are warranted.
Placental abruption; pregnancy complications; Cardio-Metabo chip; genetic association; single nucleotide polymorphism; genome-wide association study
Heme oxygenase-1 (HO-1) concentrations have been recently reported to be elevated in impaired glucose tolerance and type 2 diabetes mellitus (T2DM). However, no study has examined the association between HO-1 concentrations and gestational diabetes mellitus (GDM).
In a case-control study, nested within a prospective cohort of pregnant women (186 GDM cases and 191 women who remained eu-glycemic through pregnancy), we assessed the association of maternal serum HO-1 concentrations, measured in samples collected at 16 weeks gestation, on average, with subsequent risk of GDM. Maternal serum HO-1 concentrations were determined using ELISA. We fitted multivariate logistic regression models to derive estimates of odds ratios (ORs) and 95% confidence intervals (CIs).
Median serum HO-1 concentrations in early pregnancy were lower in women who subsequently developed GDM compared with those who did not (1.60 vs. 1.80 ng/mL, p-value = 0.002). After adjusting for maternal age, race, family history of T2DM and pre-pregnancy body mass index, women with HO-1≥3.05 ng/mL (highest decile) experienced a 74% reduction of GDM risk (95% CI; 0.09–0.77) compared with women whose concentrations were<1.23 ng/mL (lowest quartile).
Serum HO-1 concentrations were inversely associated with subsequent GDM risk. These findings underscore the role of oxidative stress in the pathogenesis of GDM. Additional studies are warranted to confirm the clinical utility of serum HO-1 in diagnosis of GDM, particularly in the early pregnancy.
To evaluate the prevalence of mental distress and its correlates among working Ethiopian adults.
This cross-sectional study of 2,180 individuals (1,316 men and 864 women) was conducted among working adults in Addis Ababa, Ethiopia. A structured questionnaire was used to collect information on socio-demographic and lifestyle characteristics of participants. Mental distress was assessed using the self-reporting questionnaire (SRQ). Logistic regression was employed to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).
The prevalence of mental distress in the study sample was 17.7% (25.9% in women and 12.4% in men). Younger participants (age ≤24 years) had the highest prevalence of mental distress (35.5% in women and 16.7% in men). The odds of mental distress was 2.47-fold higher among women as compared with men (OR=2.47, 95% CI 1.97-3.09). Participants reporting excellent health status had a 50% reduced odds of mental distress (OR=0.47; 95%CI: 0.38-0.59); and moderate alcohol consumption was associated with a slight increased odds of mental distress (OR=1.26; 95%CI: 1.00-1.67).
A high prevalence of mental distress was observed among working adults in Ethiopia. Our findings suggest that the workforce institutions should provide targeted prevention and intervention programs to improve the mental health state of their employees. National mental health policy that clearly outlines and addresses mental distress among working adults is also warranted.
Mental Distress; Ethiopia; Mental Health; Working Adults; SRQ.
We evaluated the influence of physician-diagnosed migraine on blood pressure levels and the risk of hypertensive disorders of pregnancy in a clinic-based prospective cohort study of 3,373 healthy pregnant women.
The relationship between migraine and blood pressure is controversial with results from several studies suggesting positive associations, while others suggest null or inverse associations. To our knowledge, no previous study has investigated blood pressure profiles among pregnant migraineurs.
We abstracted blood pressure values and delivery information from medical records of women presenting to prenatal clinics in Washington State. Mean blood pressure differences for pregnant migraineurs and non-migraineurs were estimated in regression models, using generalized estimating equations. We calculated, odds ratios (OR) and 95% confidence intervals (95%CIs) for gestational hypertension and preeclampsia in relation migraine status.
Mean first, second and third trimester systolic blood pressure (SBP) were elevated among pregnant migraineurs as compared with non-migraineurs. Migraineurs had higher mean third trimester SBP (4.08 mm Hg) than non-migraineurs. Trimester-specific diastolic blood pressure (DBP) values were variably related with migraine status. Mean first (0.82 mm Hg) and third(2.39 mm Hg) trimester DBP were higher, and second trimester DBP values were lower (−0.24) among migraineurs as compared with non-migraineurs. Migraineurs had a 1.53-fold increased odds of preeclampsia (95%CI 1.09 to 2.16). Additionally, migraineurs who were overweight or obese had a 6.10-fold increased odds of preeclampsia (95%CI 3.83 to 9.75) as compared with lean non-migraineurs.
Pregnant migraineurs had elevated blood pressures, particularly SBP measured in the third trimester, and a higher risk of preeclampsia than pregnant women without migraine. Observed associations were more pronounced among overweight or obese migraineurs. Our findings add to the accumulating evidence of adverse pregnancy outcomes among migraineurs.
Migraine; Blood Pressure; Hypertension; Preeclampsia; Pregnancy
Psychiatric disorders have been associated with sleep disorders in men and non-pregnant women, but little is known about sleep complaints and disorders among pregnant women with psychiatric disorders.
A cohort of 1,332 women was interviewed during early pregnancy. We ascertained psychiatric diagnosis status and collect information about sleep duration, daytime sleepiness, vital exhaustion and perceived stress. Logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Approximately 5.1% of the cohort (n=68) reported having a physician-diagnosis of mood or anxiety disorder before interview. Compared with women without a psychiatric diagnosis, the multivariable-adjusted OR (95% CI) for short sleep duration in early pregnancy (≤6 hours) were 1.95 (1.03-3.69). The corresponding OR (95%CI) for long sleep duration (≥9 hours) during early pregnancy was 1.13 (0.63-2.03). Women with psychiatric disorders had an increased risk of vital exhaustion (OR=2.41; 95%CI 1.46-4.00) and elevated perceived stress (OR=3.33; 95%CI 1.89-5.88). Observed associations were more pronounced among overweight/obese women.
Women with a psychiatric disorder were more likely to report short sleep durations, vital exhaustion and elevated perceived stress. Prospective studies are needed to more thoroughly explore factors that mediate the apparent mood/anxiety-sleep comorbidity among pregnant women.
c-Src inhibition in cancer cells leads to an abrogation of invasion but a variable effect on apoptosis. The pathways downstream of c-Src promoting survival are not well-characterized. Because cancer therapy that both decreases invasion and induces significant apoptosis would be ideal, we sought to characterize the mechanisms of resistance to c-Src inhibition.
c-Src was inhibited in a panel of oral cancer cell lines and subsequent survival and signaling measured. The interactions between c-Src and c-Met were evaluated using immunoprecitation and an in vitro kinase assay. Cytotoxicity was measured and the Chou-Talalay combination index calculated. An orthotopic model of oral cancer was used to assess the effects of c-Met and c-Src inhibitors.
Inhibition of c-Src resulted in c-Met inhibition in sensitive cells lines, but not in resistant cell lines. Isolated c-Met was a c-Src substrate in both sensitive and resistant cells, but there was no interaction of c-Src and c-Met in intact resistant cells. To examine the biological consequences of this mechanism, we demonstrated synergistic cytotoxicity, enhanced apoptosis, and decreased tumor size with the combination of c-Src and c-Met inhibitors.
Sustained c-Met activation can mediate resistance to c-Src inhibition. These data suggest that the differences between c-Met and c-Src signaling in sensitive and resistant cells are due to distinct factors promoting or inhibiting interactions, respectively, rather than to intrinsic structural changes in c-Src or c-Met. The synergistic cytotoxic effects of c-Src and c-Met inhibition may be important for the treatment of head and neck cancers.
c-Src; c-Met; head and neck cancer
The classification of follicular thyroid neoplasms requires surgical resection for histologic evaluation of malignancy. As variable clinical behavior exists, genomic expression profiling may lead to the identification of novel markers that facilitate better biological classification. We performed for the first time gene expression analysis on clinically aggressive and non-aggressive follicular carcinomas (FCs) from patients for whom long-term follow-up data were available. We examined matched fresh/frozen tissue from 15 histopathologically diagnosed FCs (7 patients with documented distant metastasis and/or death from disease and 8 patients without recurrence). For categorical comparison, we analyzed 4 follicular adenomas (FAs). The biological control comprised 11 normal thyroid tissue specimens. High-quality RNA was extracted from the tissues, labeled, and hybridized to an Affymetrix oligonucleotide microarray (HG-U133A). With the exceptions of 1 FA and 1 FC, unsupervised hierarchical cluster analysis revealed 2 distinct groups—one containing normal thyroid tissue and FAs and another containing FCs. We identified 421 genes that were differentially expressed between histologically normal thyroid tissues and all follicular neoplasms (P < 0.01; fold-change >2), 94 genes that distinguished FCs from FAs (including PBP and CKS2), and 4 genes that distinguished aggressive FCs from non-aggressive FCs (NID2, TM7SF2, TRIM2 and GLTSCR2). Comparative genomic groupings identified differentially expressed genes that may lead to better classification of follicular thyroid neoplasms. Such genes may be used in future prospective validation studies to establish clinically useful and complementary diagnostic markers.
Follicular neoplasms; follicular carcinoma; gene expression; Affymetrix
To evaluate the cross-sectional relationship between asthma and pre-gravid body mass index (BMI); and to assess the risk of adult weight change among women with history asthma diagnosed in childhood or adulthood, respectively.
Study participants were 3,737 pregnant women enrolled in a cohort study. Information on history of asthma, pre-gravid BMI, adult weight change (difference between BMI at age 18 and pre-gravid BMI) and other socio demographic characteristics was collected using interviewer-administered questionnaires. Pre-gravid BMI was categorized into lean (BMI <18.5 kg/m2), overweight (BMI 25–24.9 kg/m2) and obese (BMI ≥30 kg/m2). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).
Approximately 13.1% of study participants reported history of asthma. Compared with the reference group (BMI 18.5–24.9 kg/m2), the odds of asthma was higher among overweight (OR=1.51; 95%CI 1.18–1.93) and obese (OR=1.47; 95% CI 1.06–2.03) women while it was lower among lean women (OR=0.42; 95% CI 0.21–0.84) (trend p-value <0.001). Women who gained ≥20 kg, compared with those who maintained their weight (±2.5 kg) had a 2.7-fold increased odds of asthma (95% CI 1.02–7.00).
Overweight and obese women were more likely to have history of asthma. Adult weight gain was positively associated with asthma diagnosis. Longitudinal studies designed to prospectively assess patterns of adult weight change in relation to asthma are warranted.
Asthma; Pediatric Asthma; Body Mass Index; Obesity; Adult Weight Change
A growing body of evidence suggests that mitochondrial dysfunction is associated with oxidative stress and impaired differentiation and invasion of trophoblasts, both of which have been related to preeclampsia pathogenesis. However, studies that examined circulating mitochondrial DNA (mtDNA) copy number in relation to preeclampsia are limited. Therefore, we examined association of maternal whole blood mtDNA copy number (a novel biomarker of systemic mitochondrial dysfunction) with the odds of preeclampsia. This case-control study was comprised of 144 preeclampsia cases and 407 normotensive controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in maternal whole blood samples collected at delivery. Logistic regression procedures were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Median mtDNA copy number was significantly higher among preeclamptic women compared with controls (271.5 vs. 239.3, Mann-Whitney U test p-value <0.001). There was evidence of a linear trend in higher odds of preeclampsia with increasing quartiles of mtDNA copy number (P for trend=0.03) after controlling for confounders. The adjusted ORs for the successive quartiles of mtDNA copy number, compared with the referent (first quartile) were 1.30 (95%CI 0.66-2.56), 1.93 (95%CI 1.02-3.67) and 1.86 (95%CI 1.00-3.48). Our findings suggest that maternal mitochondrial dysfunction may contribute to the pathogenesis of preeclampsia. However, replication in prospective studies is needed to further investigate this relationship.
Mitochondria; DNA; mitochondrial DNA; preeclampsia; pregnancy
Background. To evaluate the association of migraine and asthma and to estimate the risk of hypertensive disorders of pregnancy in relation to maternal comorbid migraine and asthma. Methods. Reproductive age women (N = 3.731) were interviewed during early pregnancy. At the time of interview, we ascertained participants' migraine and asthma status. From medical records, we collected information to allow the diagnosis of pregnancy-induced hypertension (PIH) and preeclampsia. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression procedures. Results. After adjusting for confounders, migraineurs had 1.38-fold increased odds of asthma as compared with nonmigraineurs (95% CI 1.09–1.38). The odds of hypertensive disorders of pregnancy were highest among women with comorbid migraine-asthma. The ORs for PIH preeclampsia and the two disorders combined were 2.53 (95% CI 1.39–4.61), 3.53 (95% CI 1.51–8.24), and 2.64 (95% CI 1.56–4.47), respectively, for women with comorbid migraine-asthma as compared with those who had neither disorder. Conclusion. These findings confirm prior reports and extend the literature by documenting particularly high odds of pregnancy-induced hypertension and preeclampsia among women with comorbid migraine-asthma. Increased knowledge about the prevalence and sequelae of comorbidities during pregnancy may lead to improved symptom management and perinatal outcomes.
It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic β-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM.
RESEARCH DESIGN AND METHODS
A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses’ Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors.
Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87–1.43), 1.31 (1.03–1.68), 1.51 (1.17–1.93), and 1.58 (1.21–2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10–1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk.
These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.
Higher heme iron intake is associated with increased type 2 diabetes risk. However, no previous study has evaluated gestational diabetes mellitus (GDM) risk in relation to heme iron intake during pregnancy. We investigated associations of maternal preconceptional and early pregnancy heme and nonheme iron intake with subsequent GDM risk.
RESEARCH DESIGN AND METHODS
We conducted a prospective cohort study of 3,158 pregnant women. A food frequency questionnaire was used to assess maternal diet. Multivariable generalized linear regression models were used to derive estimates of relative risks (RRs) and 95% CIs.
Approximately 5.0% of the cohort developed GDM (n = 158). Heme iron intake was positively and significantly associated with GDM risk (Ptrend = 0.04). After adjusting for confounders, women reporting the highest heme iron intake levels (≥1.52 vs. <0.48 mg per day) experienced a 3.31-fold–increased GDM risk (95% CI 1.02–10.72). In fully adjusted models, we noted that a 1-mg per day increase in heme iron was associated with a 51% increased GDM risk (RR 1.51 [95% CI 0.99–2.36]). Nonheme iron was inversely, though not statistically significantly, associated with GDM risk, and the corresponding RRs were 1.00, 0.83, 0.62, and 0.61 across quartiles of nonheme iron intake (Ptrend = 0.08).
High levels of dietary heme iron intake during the preconceptional and early pregnancy period may be associated with increased GDM risk. Associations of GDM risk with dietary nonheme iron intake are less clear. Confirmation of these findings by future studies is warranted.
Biomarkers of cancer can indicate the presence of disease and serve as therapeutic targets. Our goal is to develop an optical imaging approach using molecularly targeted contrast agents to assess several centimeters of mucosal surface for mapping expression of multiple biomarkers simultaneously with high spatial resolution. The ability to image biomarker expression level and heterogeneity in vivo would be extremely useful for clinical cancer research, patient selection of personalized medicine, and monitoring therapy. In this proof-of-concept ex vivo study, we examined correlation of neoplasia with two clinically relevant biomarkers: epidermal growth factor receptor (EGFR) and metabolic activity. Two hundred eighty-six unique locations in nine samples of freshly resected oral mucosa were imaged after topically applying optical imaging agents EGF-Alexa 647 (to target EGFR) and 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (to target metabolic activity). Quantitative features were calculated from resulting fluorescence images and compared with tissue histopathology maps. The EGF-Alexa 647 signal correlated well with EGFR expression as indicated by immunohistochemistry. A classification algorithm for presence of neoplasia based on the signal from both contrast agents resulted in an area under the curve of 0.83. Regions with a posterior probability from 0.80 to 1.00 contained more than 50% neoplasia 99% (84/85) of the time. This study demonstrates a proof-of-concept of how noninvasive optical imaging can be used as a tool to study expression levels of multiple biomarkers and their heterogeneity across a large mucosal surface and how biomarker characteristics correlate with presence of neoplasia. Applications of this approach include predicting regions with the highest likelihood of disease, elucidating the role of biomarker heterogeneity in cancer biology, and identifying patients who will respond to targeted therapy.
Little is known about the influence of psychiatric factors on the etiology of placental abruption (PA), an obstetrical condition that complicates 1-2% of pregnancies. We examined the risk of AP in relation to maternal psychiatric symptoms during pregnancy.
This case-control study included 373 AP cases and 368 controls delivered at five medical centers in Lima, Peru. Depressive, anxiety and stress symptoms were assessed using the Patient Health Questionnaire (PHQ-9) and the Depression Anxiety Stress Scales (DASS-21). Multivariable logistic regression models were fit to calculate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for confounders.
Depressive symptoms of increasing severity (using the DASS depression subscale) was associated with AP (p for trend=0.02). Compared with women with no depressive symptoms, the aOR (95%CI) for AP associated with each level of severity of depression symptoms based on the DASS assessment were as follows: mild 1.84 (0.91-3.74); moderate 1.25 (0.67-2.33); and severe 4.68 (0.98-22.4). The corresponding ORs for mild, moderate, and moderately severe depressive symptoms based on the PHQ assessment were 1.10 (0.79-1.54), 3.31 (1.45-7.57), and 5.01 (1.06-23.6), respectively. A positive gradient was observed for the odds of AP with severity of anxiety (p for trend=0.002) and stress symptoms (p for trend=0.002).
These cross-sectionally collected data may be subject to recall bias.
Maternal psychiatric disorders may be associated with an increased occurrence of AP. Larger studies that allow for more precise evaluations of maternal psychiatric health in relation to AP risk are warranted.
placental abruption; epidemiology; pregnancy; depression; anxiety; risk factors
Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes.
Archival HNSCC tumor specimens (n = 89) were assembled onto a tissue microarray and stained with antibodies raised against 38 biomarkers. The biomarker set was enriched for proteins involved in DSB repair, in addition to established mechanistic markers of radioresistance. Staining was correlated with treatment response and survival alongside established clinical and pathologic covariates. Results were validated in an independent intramural cohort (n = 34).
Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy (P < 0.01). The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a 9-fold greater risk of death at 2 years.
Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment.
To evaluate the cross-sectional relationship between migraine and pre-gravid obesity; and to assess the risk of adult weight gain among women with history of a pediatric diagnosis of migraine.
Obesity, comorbid with pain disorders including migraine, shares common pathophysiological characteristics including systemic inflammation, and derangements in adipose-tissue derived cytokines. Despite biochemical and epidemiological commonalities, obesity-migraine associations have been inconsistently observed.
A cohort of 3,733 women was interviewed during early pregnancy. We ascertained participants’ self-reported history of physician-diagnosed migraine and collected self-reported information about pre-gravid weight, adult height and net weight change from age 18 to the 3-monthsperiodpriorto pregnancy. Using pre-gravid body mass index, we categorized participants as follows: lean (<18.5 kg/m2); normal (18.5–24.9 kg/m2); overweight (25–29.9 kg/m2), obese (30–34.9 kg/m2), severely obese (35–39.9 kg/m2), and morbidly obese (≥ 40 kg/m2). Logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
After adjusting for confounders, relative to normal weight women, obese women had a 1.48-fold increased odds of migraine(OR=1.48; 95%CI 1.12–1.96). Severely obese (OR=2.07; 95%CI 1.27–3.39) and morbidly obese (OR=2.75; 95%CI 1.60–4.70) had the highest odds of migraines. Women with a history of diagnosed pediatric migraine had a 1.67-fold higher odds of gaining ≥10.0 kg above their weight at age 18, as compared with non-migraineurs (OR=1.67; 95%CI 1.13–2.47).
These data support earlier observations of migraine-obesity association among women, and extend the literature to include evidence of adult weight gain among women with a history of pediatric migraine.
Migraine; Obesity; Adult Weight Gain; Pediatric Migraine; Body Mass Index
Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus. However, their association with gestational diabetes mellitus (GDM) has not been evaluated. The authors assessed such associations in both a prospective cohort study (1996–2008; 3,158 participants) and a case-control study (1998–2002; 185 cases, 411 controls). A food frequency questionnaire was used to assess maternal diet. Multivariable models were used to derive relative risks and 95% confidence intervals. Compared with no egg consumption, adjusted relative risks for GDM were 0.94, 1.01, 1.12, 1.54, and 2.52 for consumption of ≤1, 2–3, 4–6, 7–9, and ≥10 eggs/week, respectively (P for trend = 0.008). Women with high egg consumption (≥7/week) had a 1.77-fold increased risk compared with women with lower consumption (95% confidence interval (CI): 1.19, 2.63). The relative risk for the highest quartile of cholesterol intake (≥294 mg/day) versus the lowest (<151 mg/day) was 2.35 (95% CI: 1.35, 4.09). In the case-control study, the adjusted odds ratio for consuming ≥7 eggs/week versus <7 eggs/week was 2.65 (95% CI: 1.48, 4.72), and the odds of GDM increased with increasing cholesterol intake (P for trend = 0.021). In conclusion, high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM.
cholesterol; diabetes, gestational; eggs
Primary lingual adenocarcinomas are rare and typically of salivary or seromucinous glands origin. Similarly, metastatic adenocarcinoma from distant primary sites to the tongue is an uncommon event, with only three cases from a colonic primary site reported. We present, for the first time, two primary colonic-type adenocarcinomas of the base of the tongue and discuss their putative origin and the clinicopathologic characteristics.
Base of tongue; Primary adenocarcinoma; Intestinal-type; Metastatic carcinoma
Obstructive sleep apnea (OSA) or habitual snoring and asthma are known comorbid conditions in men and non-pregnant women. This comorbidity has not been evaluated among pregnant women. We assessed the habitual snoring-asthma relationship among pregnant women.
A cohort of women (N=1,335) were interviewed during pregnancy, and we ascertained participants’ asthma status and collected information about habitual snoring, before and during pregnancy. Logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Compared with non-asthmatics, the adjusted OR among asthmatics for snoring before pregnancy was 2.13 (95%CI 1.10–4.12). The odds of snoring during early pregnancy was 1.79-fold (OR=1.79; 95%CI 1.07–3.01). Associations were more pronounced among overweight (≥25 kg/m2) asthmatics (OR=5.39; 95%CI 2.27–12.75).
We report a cross-sectional association of habitual snoring and asthma among pregnant women. If confirmed, pregnant asthmatics may benefit from more vigilant screening and management of OSA or habitual snoring during pregnancy.
Asthma; Obstructive Sleep Apnea; Sleep Disordered Breathing; Habitual Snoring; Obesity; Pregnancy
The role of post-transcription regulation in preeclampsia is largely unknown. We investigated preeclampsia related placental microRNA (miRNA) expression using microarray and confirmatory qRT-PCR experiments.
Placental expressions of characterized and novel miRNAs (1,295 probes) were measured in samples collected from 20 preeclampsia cases and 20 controls. Differential expression was evaluated using Students T-test and fold change analyses. In pathway analysis, we examined functions/functional relationships of targets of differentially expressed miRNAs.
Eight miRNAs were differentially expressed (1 up- and 7 down-regulated) among preeclampsia cases compared with controls. These included previously identified candidates (miR-210, miR-1 and a miRNA in the 14q32.31 cluster region) and others that are novel (miR- 584 and miR-34c-5p). These miRNAs target genes that participate in organ/system development (cardiovascular and reproductive system), immunologic dysfunction, cell adhesion, cell cycle and signaling.
Expression of microRNAs that target genes in diverse pathophysiological processes is altered in the setting of preeclampsia.
expression; microRNA; placenta; preeclampsia
To investigate the association of high sensitivity C-reactive protein (hsCRP) concentrations and metabolic syndrome among Thai adults.
This cross-sectional study is comprised of 467 Thai participants (209 men and 258 women) receiving annual health check-up. Spearman’s rank correlation coefficients were used to assess associations of metabolic parameters (age, waist circumference, blood pressure, triglycerides, HDL-C, fasting plasma glucose, fasting insulin and uric acid) with hsCRP concentrations for men and women, respectively. Multivariable logistic regression procedures were used to estimate the risk (odds ratios [OR] and 95% confidence intervals [95% CI]) of metabolic syndrome according to low, moderate and high hsCRP concentrations (<1.0, 1.0–3.0 and >3.0 mg/l, respectively).
Measures of adiposity and fasting insulin were positively and significantly correlated with hsCRP concentrations among women with and without metabolic syndrome. Similar associations were observed among men without metabolic syndrome. After controlling for confounders, moderately elevated hsCRP concentrations were associated with a 2.38-fold increased risk of metabolic syndrome (OR=2.38, 95% CI: 1.20–4.72) among men. Men with high hsCRP concentrations had a 5.45-fold increased risk of metabolic syndrome (OR=5.45, 95% CI: 2.24–13.27) when compared with those who had low hsCRP concentrations. The corresponding odds ratios for women with moderately elevated and high hsCRP concentrations were 4.92 (OR=4.92, 95% CI: 2.34–10.35) and 11.93 (OR=11.93, 95% CI: 5.54–25.72), respectively.
These findings are consistent with the literature suggesting a role of hsCRP as a biomarker for metabolic syndrome.
C-Reactive Protein; Inflammation; Obesity; Metabolic Syndrome
We examined associations of age at menarche and menstrual characteristics with the risk of preeclampsia among participants (n = 3,365) of a pregnancy cohort study. Data were collected using in-person interviews and medical record abstraction. Logistic regression was used to estimate adjusted odds ratio (OR) and 95% confidence interval (95% CI). There was a significant inverse association between age at menarche and risk of preeclampsia (P value for trend < 0.05). Association of long cycle length (>36 days) with higher risk of preeclampsia was present only among women who had prepregnancy body mass index <25 kg/m2 (interaction P value = 0.04). Early menarche is associated with higher risk of preeclampsia. Prepregnancy weight may modify associations of long menstrual cycles with risk of preeclampsia.