Adherence to healthy food choices during the COVID-19 pandemic in a U.S. population attempting to lose weight.

BACKGROUND AND AIMS: Food preferences are often modified in populations during stressful, unanticipated events. We examined how a U.S. population's food choices changed during the beginning of the COVID-19 stay-at-home orders, specifically during the spring of 2020. METHODS AND RESULTS: Daily dietary intake data from a digital behavior change weight loss program, which includes an interface for logging meals, beverages, and snacks, were analyzed to assess self-reported food choices from March 5-March 11, 2020 ("Start-COVID") and during the first week of the COVID-19 lockdown (March 12-March 18, 2020; "during-COVID"). The final sample consisted of 381,564 participants: 318,076 (83.4%) females, the majority who were aged 45-65 years (45.2%). Results indicate that self-reported servings of fresh fruit and vegetable intake decreased from start-to during-COVID, while intake of red meat and starchy vegetables increased. More men than women increased their intake of red meat and processed meat. Less overall change in fruit and vegetable consumption was seen in those 66 and older, compared to aged 18-35. Lean meat and starchy vegetable intake increased in older participants, but the change was negligible in younger subjects. More subjects aged 18-35 years reduced their intake of caffeine, desserts, lean meat, and salads compared to older participants. No changes were observed in snack or alcohol intake logged. CONCLUSION: This study revealed that particular food groups were altered according to age and gender during the first weeks of COVID lockdown. Understanding changes in food choices during a crisis may be useful for preparing supply chains and public health responses.

Obesity, smoking, and risk of vasomotor menopausal symptoms: a pooled analysis of eight cohort studies.

BACKGROUND: Frequent and severe vasomotor symptoms during menopause are linked with adverse health outcomes. Understanding modifiable lifestyle factors for the risk of vasomotor menopausal symptoms is important to guide preventive strategies. OBJECTIVE: We investigated the associations between body mass index and smoking, their joint effects with the risk of vasomotor symptoms, and whether the associations differed by menopausal stage. STUDY DESIGN: The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events pooled data on 21,460 midlife women from 8 studies (median age, 50 years; interquartile range, 49-51 years) for the cross-sectional analysis. Four studies provided data for the prospective analysis (n=11,986). Multinomial logistic regression models with 4 categories of frequency/severity for the outcome of vasomotor symptoms were used to estimate relative risk ratios and 95% confidence intervals that were adjusted for within-study correlation and covariates. RESULTS: At baseline, nearly 60% of the women experienced vasomotor symptoms. One-half of them were overweight (30%) or obese (21%), and 17% were current smokers. Cross-sectional analyses showed that a higher body mass index and smoking more cigarettes with longer duration and earlier initiation were all associated with more frequent or severe vasomotor symptoms. Never smokers who were obese had a 1.5-fold (relative risk ratio, 1.52; 95% confidence interval, 1.35-1.73) higher risk of often/severe vasomotor symptoms, compared with never smokers who were of normal-weight. Smoking strengthened the association because the risk of often/severe vasomotor symptoms was much greater among smokers who were obese (relative risk ratio, 3.02; 95% confidence interval, 2.41-3.78). However, smokers who quit at <40 years of age were at similar levels of risk as never smokers. Prospective analyses showed a similar pattern, but the association attenuated markedly after adjustment for baseline vasomotor symptoms. Furthermore, we found that the association between body mass index and vasomotor symptoms differed by menopausal status. Higher body mass index was associated with increased risk of vasomotor symptoms in pre- and perimenopause but with reduced risk in postmenopause. CONCLUSION: High body mass index (≥25 kg/m2) and cigarette smoking substantially increased women's risk for experiencing frequent or severe vasomotor symptoms in a dose-response manner, and smoking intensified the effect of obesity. However, the effect of body mass index on the risk of vasomotor symptoms was opposite among postmenopausal women. Maintaining a normal weight before the menopausal transition and quitting smoking at <40 years of age may mitigate the excess risk of vasomotor symptoms in midlife.

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BACKGROUND: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. METHODS AND FINDINGS: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40-44 (early), 45-49, 50-51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. CONCLUSIONS: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

The role of sleep difficulties in the vasomotor menopausal symptoms and depressed mood relationships: an international pooled analysis of eight studies in the InterLACE consortium.

BACKGROUND: Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions. METHODS: A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49-51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation. RESULTS: At baseline, the prevalence of VMS (40%, range 13-62%) and depressed mood (26%, 8-41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27-1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47-2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90-1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38-2.34). CONCLUSIONS: Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.

Body mass index and age at natural menopause: an international pooled analysis of 11 prospective studies.

Current evidence on the association between body mass index (BMI) and age at menopause remains unclear. We investigated the relationship between BMI and age at menopause using data from 11 prospective studies. A total of 24,196 women who experienced menopause after recruitment was included. Baseline BMI was categorised according to the WHO criteria. Age at menopause, confirmed by natural cessation of menses for ≥ 12 months, was categorised as < 45 years (early menopause), 45-49, 50-51 (reference category), 52-53, 54-55, and ≥ 56 years (late age at menopause). We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CI) for the associations between BMI and age at menopause. The mean (standard deviation) age at menopause was 51.4 (3.3) years, with 2.5% of the women having early and 8.1% late menopause. Compared with those with normal BMI (18.5-24.9 kg/m2), underweight women were at a higher risk of early menopause (RRR 2.15, 95% CI 1.50-3.06), while overweight (1.52, 1.31-1.77) and obese women (1.54, 1.18-2.01) were at increased risk of late menopause. Overweight and obesity were also significantly associated with around 20% increased risk of menopause at ages 52-53 and 54-55 years. We observed no association between underweight and late menopause. The risk of early menopause was higher among obese women albeit not significant (1.23, 0.89-1.71). Underweight women had over twice the risk of experiencing early menopause, while overweight and obese women had over 50% higher risk of experiencing late menopause.

Self-Reported Nutritional Factors Are Associated with Weight Loss at 18 Months in a Self-Managed Commercial Program with Food Categorization System: Observational Study.

Little is known about nutritional factors during weight loss on digital commercial weight loss programs. We examined how nutritional factors relate to weight loss for individuals after 4 and 18 months on a mobile commercial program with a food categorization system based on energy density (Noom). This is a two-part (retrospective and cross-sectional) cohort study. Two time points were used for analysis: 4 months and 18 months. For 4-month analyses, current Noom users who met inclusion criteria (n = 9880) were split into 5% or more body weight loss and stable weight loss (0 ± 1%) groups. Individuals who fell into one of these groups were analyzed at 4 months (n = 3261). For 18-month analyses, individuals from 4-month analyses who were still on Noom 18 months later were invited to take a one-time survey (n = 803). At 18 months 148 participants were analyzed. Noom has a system categorizing foods as low-, medium-, and high-energy-dense. Measures were self-reported proportions of low-, medium-, and high-energy-dense foods, and self-reported nutritional factors (fruit and vegetable intake, dietary quality, nutrition knowledge, and food choice). Nutritional factors were derived from validated survey measures, and food choice from a novel validated computerized task in which participants chose a food they would want to eat right now. ANOVAs compared participants with 5% or more body weight loss and participants with stable weight (0 ± 1%) at 4 months on energy density proportions. Analyses at 18 months compared nutritional factors across participants with >10% (high weight loss), 5-10% (moderate weight loss), and less than 5% body weight loss (low weight loss), and then assessed associations between nutritional factors and weight loss. Individuals with greater weight loss reported consuming higher proportions of low-energy-dense foods and lower proportions of high-energy-dense foods than individuals with less weight loss at 4 months and 18 months (all ps < 0.02). Individuals with greater weight loss had higher fruit and vegetable intake (p = 0.03), dietary quality (p = 0.02), nutrition knowledge (p < 0.001), and healthier food choice (p = 0.003) at 18 months. Only nutrition knowledge and food choice were associated with weight loss at 18 months (B = -19.44, 95% CI: -33.19 to -5.69, p = 0.006; B = -5.49, 95% CI: -8.87 to -2.11, p = 0.002, respectively). Our results highlight the potential influence of nutrition knowledge and food choice in weight loss on a self-managed commercial program. We also found for the first time that in-the-moment inclination towards food even when just depicted is associated with long-term weight loss.

Psychosocial Characteristics by Weight Loss and Engagement in a Digital Intervention Supporting Self-Management of Weight.

There is substantial variability in weight loss outcomes. Psychosocial characteristics underlying outcomes require better understanding, particularly on self-managed digital programs. This cross-sectional study examines differences in psychosocial characteristics by weight loss and engagement outcome, and which characteristics are most associated with weight loss, on a self-managed digital weight loss program. Some underexplored psychosocial characteristics are included, such as flourishing, or a sense of meaning and purpose in life. A questionnaire was emailed to a random sample of 10,000 current users at week 5 in the program and 10,000 current users at week 17. The questionnaire was completed by 2225 users, and their self-reported weight and recorded program engagement data were extracted from the program's database. Multiple comparison tests indicated that mental health quality of life, depression, anxiety, work-life balance, and flourishing differed by weight loss outcome at program end (week 17; ≥5%, 2-5%, below 2%) and by engagement tertile at program beginning and end (weeks 5 and 17). Only anxiety was associated with weight loss in a backward stepwise regression controlling for engagement and sociodemographic characteristics. Flourishing did not predict weight loss overall but predicted the weight loss outcome group. Our findings have implications for creating more effective interventions for individuals based on psychosocial characteristics and highlight the potential importance of anxiety in underexplored self-managed digital programs.

Contribution of 100% Fruit Juice to Micronutrient Intakes in the United States, United Kingdom and Brazil.

The contribution of 100% fruit juice (FJ) to the total daily intakes of energy, sugars, and select vitamins and minerals and to the recommended dietary allowances (RDAs) or adequate intake (AI) of these micronutrients was assessed in individuals reporting the consumption of 100% FJ in the national dietary intake surveys of the United States (U.S.; n = 8661), the United Kingdom (UK; n = 2546) and Brazil (n = 34,003). Associations of 100% FJ intake with the odds of being overweight or obese also were assessed. Data from the U.S. National Health and Nutrition Examination Survey (2013-2014), the UK National Diet and Nutrition Survey (2012-2014), and Brazil's Pesquisa de Orçamentos Familiares (2008-2009) were used, and all analyses were limited to individuals reporting consumption of 100% FJ on at least one day of the dietary intake survey. Approximately 34%, 37%, and 42% of individuals surveyed reported the consumption of 100% FJ on at least one day of the dietary intake survey in the U.S., UK, and Brazil, respectively, and the average daily intakes of 100% FJ were 184 g, 130 g, and 249 g, respectively. Across the 3 countries, 100% FJ contributed to 3-6% of total energy intakes, 12-31% of total sugar intakes, 21-54% of total vitamin C intakes, 1-12% of total vitamin A intakes, 4-15% of total folate intakes, 7-17% of total potassium intakes, 2-7% of total calcium intakes, and 4-12% of total magnesium intakes. In a multivariate logistic regression model, juice intake was associated with a significant reduction in the odds of being overweight or obese in UK adults (OR = 0.79; 0.63, 0.99), and significant increases in the odds of being overweight or obese in UK children (OR = 1.16; 1.01, 1.33) and Brazilian adults (OR = 1.04; 1.00, 1.09). Nutrient contributions of 100% FJ vary according to regional intake levels. In all three countries studied, 100% FJ contributed to more than 5% of the RDAs for vitamin C and folate. In the U.S. and Brazil, 100% FJ contributed to more than 5% of the RDA for magnesium and more than 5% of the AI for potassium.

Adaptations in 5-HT receptor expression and function: implications for treatment of cognitive impairment in aging.

Malfunction of the serotonin system may contribute to memory deficits during aging. We evaluated the 5-HT(6) antagonist RO4368554 in two models of learning and memory in aged rats. Male rats (18 months) were assigned to two groups of equal cognitive performance. After 2 weeks of 5-HT(6) antagonist RO4368554 (5 mg/kg, i.p.) treatment, rats showed significant improvement in object recognition and social discrimination compared with rats given chronic vehicle. Brains from these animals were examined for changes in plasticity-associated proteins Ki-67 and PCNA. No differences were seen between groups in any of these markers. We also measured mRNA expression of 5-HT(6), along with 5-HT(1A), 5-HT(1B), and tryptophan hydroxylase-2 mRNAs in 4-month-old and 24-month-old F344 rats. Decreases in 5-HT(1B) expression were observed in several forebrain regions in the old rats. These results demonstrate that 5-HT(6) and 5-HT(1B) receptors are potential targets for treatment of age-related memory disorders.

More than just caffeine: psychopharmacology of methylxanthine interactions with plant-derived phytochemicals.

In general, preparations of coffee, teas, and cocoa containing high levels of polyphenols, L-theanine and other bioactive compounds selectively enhance mood and cognition effects of caffeine. This review summarizes the bioactive components of commonly consumed natural caffeine sources (e.g. guayusa, mate and camellia teas, coffee and cocoa) and analyzes the psychopharmacology of constituent phytochemicals: methylxanthines, polyphenols, and L-theanine. Acute and chronic synergistic effects of these compounds on mood and cognition are compared and discussed. Specific sets of constituent compounds such as polyphenols, theobromine and L-theanine appear to enhance mood and cognition effects of caffeine and alleviate negative psychophysiological effects of caffeine. However, more research is needed to identify optimal combinations and ratios of caffeine and phytochemicals for enhancement of cognitive performance.

Abdominal pain during the menopause transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: To assess the relationship between abdominal pain severity during the menopausal transition (MT) and age, MT stage, reproductive biomarkers, stress biomarkers, and stress perceptions. METHODS: Women ages 35-55 were recruited from multiethnic neighborhoods in the greater Seattle area from 1990 to 1992, for an original study cohort of 508. From 1990 to 2013, a subset of this cohort consented to ongoing annual data collection by annual health questionnaire, health diary, and daily menstrual calendar. Beginning in 1997, a portion of these women also provided a first morning voided urine specimen to be assayed for levels of estrone glucuronide (E1G), follicle stimulating hormone (FSH), testosterone, cortisol, norepinephrine, and epinephrine. To identify how changes in abdominal pain severity changed over time in relation to age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions, mixed effects modeling was used. RESULTS: In a univariate model, E1G (p = 0.02) and testosterone (p = 0.02) were significantly and negatively related to abdominal pain severity, while perceived stress (p = 0.06), tension (p <  0.001), and anxiety (p <  0.001) were significantly and positively associated. In a multivariate model, increasing age (p = 0.001) and E1G (p = 0.04) were negatively associated with abdominal pain severity, and anxiety (p = 0.00) positively associated. Testosterone did not improve the fit to the final model, nor did tension or perceived stress. CONCLUSIONS: These results suggest that age, anxiety, and E1G each show a significant association with abdominal pain severity in the MT. In contrast, stress perception, tension, testosterone, stress biomarkers, and MT stage do not. These factors should be evaluated further in research on abdominal pain experienced during the MT and early postmenopause years.

Soy intake and vasomotor menopausal symptoms among midlife women: a pooled analysis of five studies from the InterLACE consortium.

BACKGROUND/OBJECTIVES: Phytoestrogen rich-foods such as soy may be associated with less frequent/severe vasomotor menopausal symptoms (VMS), although evidence is limited. We thus investigated the associations between the consumption of soy products and soy milk and the frequency/severity of VMS. SUBJECTS/METHODS: We pooled data from 19,351 middle-aged women from five observational studies in Australia, UK, USA, and Japan that contribute to the International Collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on soy consumption, VMS and covariates were collected by self-report. We included 11,006 women who had complete data on soy consumption, VMS and covariates at baseline for the cross-sectional analysis. For the prospective analysis, 4522 women who were free of VMS at baseline and had complete data on VMS at follow-up were considered. Multinomial logistic regression and binary logistic regression models were used. RESULTS: No statistically significant evidence of an association was found between soy products (relative risk ratio (RRR): 0.92, 95% CI: 0.76-1.11) or soy milk (RRR: 1.24, 95% CI: 0.93-1.65) and the likelihood of reporting frequent or severe VMS cross-sectionally. Prospective results indicated that frequent consumption of soy products (odds ratio (OR): 0.63, 95% CI: 0.45-0.89) but not soy milk (OR: 1.11, 95% CI: 0.85-1.45) was associated with lower likelihood of reporting subsequent VMS, after adjustment for socio-demographic and reproductive factors. CONCLUSIONS: These are the first ever findings from pooled observational data of association between consumption of soy products and VMS.

Association of estrogen-related polymorphisms with age at menarche, age at final menstrual period, and stages of the menopausal transition.

OBJECTIVE: To explore the association of estrogen-related polymorphisms with age at menarche, age at onset and duration of stages of the menopausal transition, and age at final menstrual period (FMP). DESIGN: A total of 152 white women were genotyped for CYP17, CYP19 3-untranslated region, CYP19 TTTA7-13, HSDB1, CYP1A1, CYP1B1, and ESR1 polymorphisms. Analysis of variance was used to test a nonspecific model for differences among genotypes associated with each polymorphism. RESULTS: Five of the 84 associations tested were significant at P < 0.05, which could be expected by chance. Women with two CYP19 7r alleles had menarche earlier (11.5 y) than those with one 7r allele (13.1 y). Women with two 11r alleles were 2 years older at onset of late stage than those with one 11r allele (50.7 y vs 48.6 y). Those with two 7r(-3) alleles were 2 years older at FMP than those without this allele (53.9 y vs 51.3 y). Women with the homozygous wild-type allele for HSDB1 (rs2830) were younger at FMP by 2 years than those with the heterozygous allele (50.8 y vs 52.9 y). Women with the heterozygous allele for CYP1B1*2 had a later age at menarche compared with women with the homozygous wild type (13 y vs 12.5 y). CONCLUSIONS: Age at onset of late stage and FMP and age at menarche are associated with specific genetic polymorphisms in the estrogen biosynthesis and metabolism genes. However, because of the number of comparisons, these associations may be false positives. These findings should be confirmed with a larger sample of white women.

5-HT6 receptor antagonist reversal of emotional learning and prepulse inhibition deficits induced by apomorphine or scopolamine.

5-HT6 receptors have been implicated in consolidation of visuospatial and reward-based learning tasks. Since 5-HT6 receptors may be important in modulation of sensory gating which is often affected in schizophrenic patients, we tested whether Ro 4368554, a 5-HT6 selective antagonist at a dose of 10 mg/kg, could reverse the loss of prepulse inhibition from apomorphine or scopolamine. In addition, we also tested whether Ro 4368554 altered fear conditioning using fear potentiated startle, a model for emotional learning. Prepulse inhibition of startle was disrupted by apomorphine (0.5 mg/kg) when prepulse emissions were 5 dB above background but not above 15 dB, while scopolamine (0.5 mg/kg) caused disruption at both prepulse levels. Scopolamine-mediated disruption was not reversed by Ro 4368854 but apomorphine-mediated disruption was significantly ameliorated by 5-HT6 inhibition. For fear potentiated startle, scopolamine and/or Ro 4368554 were administered before two daily fear conditioning sessions; rats were tested on the following day. Rats that received scopolamine displayed no fear potentiated startle but Ro 4368554 reversed this scopolamine deficit. Additionally, we mapped Fos induction in rats treated with scopolamine and/or Ro 4368554; scopolamine increased Fos expression in the central nucleus of the amygdala and this was attenuated by Ro 4368554. In summary, we have demonstrated the efficacy of 5-HT6 antagonists in modulating sensory gating and fear conditioning, and thus may be of therapeutic use for schizophrenia-related disorders.

Constipation and diarrhea during the menopause transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: To assess the relationship of constipation and diarrhea severity during the menopause transition (MT) with age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions. METHODS: From 1990 to 1992, women aged 35 to 55 years were recruited from the greater Seattle area; 291 of them consented to ongoing (1990-2013) annual data collection by daily menstrual calendar, health diary, and annual health questionnaire. A subset (n = 131) provided a first morning voided urine specimen (1997-2013). These were assayed for levels of E1G, follicle-stimulating hormone, testosterone, cortisol, norepinephrine, and epinephrine. Mixed-effects modeling was used to identify how changes in constipation and diarrhea severity over time related to age, MT stage, reproductive biomarkers, stress-related biomarkers, and stress-related perceptions. RESULTS: In a univariate model, age, late reproductive (LR) stage, tension, and anxiety were all significantly and positively related to constipation severity, whereas cortisol was significantly and negatively associated. In a multivariate model, only tension and cortisol remained significant predictors of constipation severity (P < 0.05). In a univariate model, age, LR stage, and estrone glucuronide were significantly and negatively associated with diarrhea severity, whereas tension, anxiety, and perceived stress were significantly and positively related. In a multivariate model, only tension and age remained significant predictors of diarrhea severity. CONCLUSIONS: Key reproductive hormones do not play a significant role in constipation or diarrhea severity in the MT. In contrast, stress perception, tension, anxiety, and cortisol do. These factors should be evaluated in further research involving constipation and diarrhea.

Water intake reverses dehydration associated impaired executive function in healthy young women.

INTRODUCTION: Healthy women do not always consume Recommended Daily Levels of fluid intake ad libitum. We hypothesized that 1) women lose≥1.0% BW during daily activities, 2) that mild body water loss impairs memory and executive function, 3) water intake to recommended daily levels will improve cognitive function. METHODS: We tested 12 women (26±5yr, 22.5±2.6kg/m2 BMI). Session 1 was a control (CON) session, during which subjects monitored their food and fluid intake (diary) and activity (Fitbit®). The next two sessions were applied in balanced order: dehydration (DEH) session, where subjects minimized drinking, and a euhydration (EUH) session, where subjects drank Recommended Daily Levels of fluid for their age and sex, or 2500ml/24h. We compared emotion, sensory perception and cognition with computer based visual analog tests and computer based cognitive tasks (Cogstate) at 5PM, i.e. baseline (BL) on the evening prior to the session, and at 7AM, 12PM, and 5PM during the session. RESULTS: Urine specific gravity (USG) was similar at BL across conditions (CON 1.013±0.002, DEH 1.015±0.002, EUH 1.014±0.002) and increased with dehydration (CON 1.011±0.003, DEH 1.021±0.002, EUH 1.010±0.002, P<0.05) by 5PM of the session. Uncontrolled fluid intake and physical activity were similar across sessions. The water challenges did not impact Detection, Identification, One-Card Learning, but EUH improved visual and working memory (Groton Maze Learning Test) errors: CON 40.1±11.1, DEH 40.5±10.1, EUH 33.9±10.9, P<0.05. Executive function [Set Shifting (SETS)] also improved under EUH, errors: BL 22.5±12.7 vs. 5PM 17.8±6.2, P<0.05. CONCLUSIONS: Mild dehydration caused deficits in visual and working memory and executive function in healthy young women. These deficits were reversed by drinking water to the European Food Safety Authority and Institute of Medicine requirements of 2.5l/day for adult women.

Increased expression of 5-HT6 receptors in the rat dorsomedial striatum impairs instrumental learning.

A number of studies have shown that systemic 5-HT(6) receptor antagonists can improve learning and memory, but the mechanism for these observations is not known. As striatum normally expresses 5-HT(6) receptors abundantly and is important in consolidating stimulus-response learning, we used targeted gene delivery to further increase the expression of 5-HT(6) receptors in rat striatum and then examined learning. Increased 5-HT(6) expression had no effect on performance in the Morris water maze, a hippocampal-dependent learning paradigm, and did not alter the latency to approach or consume sucrose tablets. However, rats with increased 5-HT(6) expression failed to acquire a reward-based instrumental learning task, a striatum-dependent learning model, during 3 days of successive sessions as compared to sham surgery or GFP-expressing control rats. This behavioral deficit was observed in rats overexpressing 5-HT(6) receptors in the dorsomedial striatum, but not in rats with increased dorsocentral striatal expression. The 5-HT(6) receptor-associated deficit was reversed by administration of a 5-HT(6) antagonist, SB-258585, before each training session. When animals learned the instrumental learning task before gene transfer, increased 5-HT(6) receptor expression had no effect on long-term recall or performance of the task or on extinction of operant responding. Thus, 5-HT(6) receptor activity in rat striatum disrupts acquisition of new instrumental learning but does not impair memory or performance of reward-motivated behavior once established.

The value of follicle-stimulating hormone concentration and clinical findings as markers of the late menopausal transition.

CONTEXT: The Stages of Reproductive Aging Workshop proposed bleeding and hormonal criteria for the menopausal transition, but operational definitions of hormone parameters were not specified. OBJECTIVE: This paper investigates the longitudinal relationship of annual serum FSH levels with four proposed bleeding criteria for the late menopausal transition in two cohort studies. The goal is to provide empirically based guidance regarding application of hormonal criteria that may be optimal for widespread application in clinical and research settings for assessing menopausal stage. DESIGN/SETTING: Prospective menstrual calendar and annual serum FSH data were collected from two population-based cohort studies: the Melbourne Women's Midlife Health Project and the Study of Women's Health Across the Nation. PARTICIPANTS: Participants in the study were 193 Melbourne Women's Midlife Health Project and 2223 Study of Women's Health Across the Nation women aged 42-57 yr at baseline who contributed 10 or more menstrual cycles and at least one annual serum FSH value. MAIN OUTCOME MEASURE(S): Association between bleeding criteria for the late menopausal transition and FSH was a main outcome measure. Associations of bleeding criteria, FSH, and hot flashes with the final menstrual period were also measured. RESULTS: A single FSH measure is an independent marker of the late menopausal transition, but FSH concentrations are less predictive of menopausal stage than any of four proposed bleeding criteria. Criterion FSH values for the late transition are similar across both studies. Experience of hot flashes adds no information in the presence of hormonal and bleeding criteria. CONCLUSIONS: An annual serum FSH concentration of 40 IU/liter could be incorporated, in conjunction with bleeding markers, into the Stages of Reproductive Aging Workshop paradigm for markers of the late menopausal transition.

Evaluation of four proposed bleeding criteria for the onset of late menopausal transition.

CONTEXT: The current criterion for onset of late menopausal transition is amenorrhea of 90 d or more. The Stages of Reproductive Aging Workshop proposed alternative criteria based on a shorter period of amenorrhea. Empirical data comparing proposed criteria are not available. OBJECTIVE: This paper evaluates the several bleeding criteria that served as the basis of these recommendations. The goal was to provide empirically based guidance regarding which bleeding criterion may be optimal for widespread application in clinical and research settings. DESIGN/SETTING: The study used prospective menstrual calendar data from four community and population-based cohort studies: TREMIN, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, and Study of Women's Health Across the Nation. PARTICIPANTS: The study included 735 TREMIN, 279 Seattle Midlife Women's Health Study, 216 Melbourne Women's Midlife Health Project, and 2270 Study of Women's Health Across the Nation women aged 35-57 yr at baseline who contributed 10 menstrual cycles or more. MAIN OUTCOME MEASURE(S): The main measures were the frequency of and median age at occurrence and time from occurrence to final menstrual period (FMP) for four criteria: skipped segment, 10-segment running range, 60- and 90-d amenorrhea. RESULTS: A skipped segment, 10-segment running range greater than 42 d and 60-d amenorrhea identify a similar time in women's reproductive lives. The latter two identify the exact same date in two thirds of women. All three criteria occur in a greater proportion of women than the 90-d criterion and are equally predictive of the FMP, although they occur 1-2 yr earlier. CONCLUSIONS: These findings support the recommendation of the Stages of Reproductive Aging Workshop that 60 d of amenorrhea be used to define onset of the late menopausal transition.

5-HT6 receptors: a novel target for cognitive enhancement.

Over the past decade, there has been increasing interest in the role of serotonin 6 (5-HT6) receptors in higher cognitive processes such as memory. Polymorphisms of the 5-HT6 receptor have been implicated in syndromes that affect cognition, such as schizophrenia and dementia. Manipulation of 5-HT6 receptor activity alters the transmission of several neurotransmitters important in memory: acetylcholine and glutamate, as well as dopamine, ã-aminobutyric acid (GABA), epinephrine (E), and norepinephrine (NE). Several 5-HT6 antagonists have been developed, advancing the understanding of the relationship between 5-HT6 blockade and memory consolidation in diverse learning paradigms. There is also evidence that 5-HT6 receptor activity affects anxiety behaviors and may be involved in the pathophysiology of schizophrenia. Several clinically useful atypical antipsychotics and antidepressants have 5-HT6 affinity, but recently developed selective 5-HT6 receptor antagonists may present attractive, new therapeutic options for several types of disease states.