Comparing SF-36 scores across three groups of women with different health profiles

Background: The widespread use of the Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) facilitates the comparison of health-related quality of life (HRQL) across independent studies. Objectives : To compare the scores of eight scales and two summary scales of the SF-36 across participants in the Women’s Healthy Eating and Living (WHEL) trial, the Women’s Health Initiative-Dietary Modification trial (WHI-DM), and the MOS, and to illustrate the use of effect sizes for interpreting the importance of group differences. Methods : WHEL and WHI-DM are both multi-center dietary interventions; only data from the UC Davis sites were used in our study. WHEL participants had a recent history of breast cancer, WHI-DM participants were healthy, postmenopausal women, and women in the MOS had a history of hypertension, diabetes, heart disease, or depression. General linear models were used to identify statistically significant differences in scale scores. Meaningful differences were determined by effect sizes computed using a common within-group standard deviation (SD) and SDs from normative data. Results : After adjusting for age and marital status, SF-36 scores for the WHI-DM and WHEL samples were similar and both had statistically significantly higher scores than the MOS sample. Relative to the WHEL or WHI-DM studies, MOS scores for scales related to the physical domain were clearly meaningfully lower whereas scale scores related to the mental health domain were potentially meaningfully lower. Conclusions : The HRQL of breast cancer survivors is comparable to that of healthy women and better than that of women with chronic health conditions, particularly with respect to physical health. This study illustrated the use of ranges of effects sizes for aiding the interpretation of SF-36 scores differences across independent studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43569/1/11136_2004_Article_6673.pd

Computational modeling of threat learning reveals links with anxiety and neuroanatomy in humans

Influential theories implicate variations in the mechanisms supporting threat learning in the severity of anxiety symptoms. We use computational models of associative learning in conjunction with structural imaging to explicate links among the mechanisms underlying threat learning, their neuroanatomical substrates, and anxiety severity in humans. We recorded skin-conductance data during a threat-learning task from individuals with and without anxiety disorders (N=251; 8-50 years; 116 females). Reinforcement-learning model variants quantified processes hypothesized to relate to anxiety: threat conditioning, threat generalization, safety learning, and threat extinction. We identified the best-fitting models for these processes and tested associations among latent learning parameters, whole-brain anatomy, and anxiety severity. Results indicate that greater anxiety severity related specifically to slower safety learning and slower extinction of response to safe stimuli. Nucleus accumbens gray-matter volume moderated learning-anxiety associations. Using a modeling approach, we identify computational mechanisms linking threat learning and anxiety severity and their neuroanatomical substrates

Duration of menopausal vasomotor symptoms over the menopause transition

IMPORTANCE: The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES: To determine total duration of frequent VMS ( \u3e /= 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS: The Study of Women\u27s Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES: Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS: The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, \u3e 11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE: Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women

Sex steroid metabolism polymorphisms and mammographic density in pre- and early peri-menopausal women

Abstract Introduction We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17β-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women. Methods The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI). Results After multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01). Conclusions SNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density.http://deepblue.lib.umich.edu/bitstream/2027.42/78273/1/bcr2340.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78273/2/bcr2340.pdfPeer Reviewe

Prenatal Exposure to Wood Fuel Smoke and Low Birth Weight

Background: Maternal exposure to wood fuel smoke may lead to impaired fetal growth due to hypoxia and or oxidative stress from smoke constituents such as carbon monoxide and particulate matter. Objectives: We studied the risk of low birth weight (LBW) and reduced mean birth weight in relation to reported use of wood for cooking during the prenatal period, compared with natural gas (NG).Methods: We studied a historical cohort of women who had a singleton live birth in the years 2000-2002, from a semirural area of Pakistan. Infant\u27s birth weight was obtained from records, and prenatal records had data for maternal body mass index and parity. Cooking habits, daytime sleep habits, and type of fuel used during the pregnancies in 2000-2002 were ascertained by a survey done in 2004-2005. We performed multiple linear and logistic regression modeling using propensity scores to adjust for confounding variables.Results: Unadjusted mean (+/- SD) birth weight was 2.78 +/- 0.45 kg in wood users, and 2.84 +/- 0.43 kg (p \u3c 0.06) in NG users. Infants born to wood users averaged 82 g lighter than infants born to NG users when weight was adjusted for confounders (p \u3c 0.07). The rate of LBW (\u3c 2,500 g) was 22.7% among wood users compared with 15.0% in NG users (p \u3c 0.01), for an adjusted relative risk of 1.64 (95% confidence interval, 1.10-2-34). The population attributable risk for LBW explained by wood use was estimated to be 24%.Conclusion: Cooking with wood fuel during pregnancy, a potentially modifiable exposure, was associated with LBW and marginally lower mean birth weight compared with using NG

The InterLACE study: design, data harmonization and characteristics across 20 studies on women's health

The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE

Blood-Brain Barrier Permeability of Normal Appearing White Matter in Relapsing-Remitting Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS). METHODOLOGY/PRINCIPAL FINDINGS: Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046). CONCLUSIONS/SIGNIFICANCE: We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS

Reactivity of Biarylazacyclooctynones in Copper-Free Click Chemistry

The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Here we performed a systematic analysis of the effects of strain and electronics on the reactivity of cyclooctynes with azides through both experimental measurements and computational studies using a density functional theory (DFT) distortion/interaction transition state model. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Drawing on these results, we analyzed the relationship between alkyne bond angles, which we determined using X-ray crystallography, and reactivity, quantified by experimental second-order rate constants, for a range of cyclooctynes. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry