Embryonic Caffeine Exposure Acts via A1 Adenosine Receptors to Alter Adult Cardiac Function and DNA Methylation in Mice

Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2–4 cups of coffee in humans. After dams gave birth, offspring were examined at 8–10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation

What do older people do when sitting and why? Implications for decreasing sedentary behaviour

Background and Objectives: Sitting less can reduce older adults’ risk of ill health and disability. Effective sedentary behavior interventions require greater understanding of what older adults do when sitting (and not sitting), and why. This study compares the types, context, and role of sitting activities in the daily lives of older men and women who sit more or less than average. Research Design and Methods: Semistructured interviews with 44 older men and women of different ages, socioeconomic status, and objectively measured sedentary behavior were analyzed using social practice theory to explore the multifactorial, inter-relational influences on their sedentary behavior. Thematic frameworks facilitated between-group comparisons. Results: Older adults described many different leisure time, household, transport, and occupational sitting and non-sitting activities. Leisure-time sitting in the home (e.g., watching TV) was most common, but many non-sitting activities, including “pottering” doing household chores, also took place at home. Other people and access to leisure facilities were associated with lower sedentary behavior. The distinction between being busy/not busy was more important to most participants than sitting/not sitting, and informed their judgments about high-value “purposeful” (social, cognitively active, restorative) sitting and low-value “passive” sitting. Declining physical function contributed to temporal sitting patterns that did not vary much from day-to-day. Discussion and Implications: Sitting is associated with cognitive, social, and/or restorative benefits, embedded within older adults’ daily routines, and therefore difficult to change. Useful strategies include supporting older adults to engage with other people and local facilities outside the home, and break up periods of passive sitting at home

Poor Potential Coverage for 7-Valent Pneumococcal Conjugate Vaccine, Malawi

Streptococcus pneumoniae infections can be prevented by using new conjugate vaccines, but these vaccines have limited serogroup coverage. We report the first serogrouping data from carried and invasive isolates obtained from children and adults in Malawi. The 7-valent vaccine would cover 41% of invasive isolates from children and 25% from adults. A 9-valent vaccine, including types 1 and 5, would cover 66% of invasive isolates from children and 55% from adults

Sitting time, fidgeting and all-cause mortality in the UK Women's Cohort Study

Introduction: Sedentary behaviours (including sitting) may increase risk of mortality independently of physical activity level. Little is known about how fidgeting behaviours might modify the association. Methods: Data were drawn from the UK Women’s Cohort Study. In 1999/2002, 12,778 women (age 37 to 78) provided data on average daily sitting time, overall fidgeting (irrespective of posture), and a range of relevant covariates including physical activity, diet, smoking status and alcohol consumption. Participants were followed for mortality over a mean of 12 years. Proportional hazards Cox regression models were used to estimate the relative risk of mortality in the high (vs. low) and medium (vs. low) sitting time groups. Results: Fidgeting modified the risk associated with sitting time (p value for interaction = 0.04), leading us to separate groups for analysis. Adjusting for a range of covariates, sitting for 7+ hours/day (vs. <5 hours/day) was associated with 30% increased risk of all-cause mortality (HR = 1.30, 95% CI 1.02, 1.66) only among women in the low fidgeting group. Among women in the high fidgeting group, sitting for 5/6 (vs. <5 hrs/day) was associated with decreased risk of mortality (HR = 0.63, 95% CI 0.43, 0.91), adjusting for a range of covariates. There was no increased risk of mortality from longer sitting time in the middle and high fidgeting groups. Conclusions: Fidgeting may reduce the risk of all-cause mortality associated with excessive sitting time. More detailed and better validated measures of fidgeting should be identified in other studies in order to replicate these findings and identity mechanisms, particularly measures that distinguish fidgeting in a seated from standing posture

Early Menarche, Nulliparity, and the Risk for Premature and Early Natural Menopause

Study question: How the timing of menarche and parity link with premature and early natural 42 menopause? Summary answer: Early menarche (≤11 years) is a risk factor for both premature menopause (final 44 menstrual period, FMP <40 years) and early menopause (FMP 40-44 years), a risk that is amplified for nulliparous women. What is known already: Women with either premature or early menopause face increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, adjustment for confounding factors, and statistical power. Study design, size, duration: This pooled study comprises 51,450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia, and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Participants/materials, setting, methods: Age at menarche (categorised as ≤11, 12, 13, 14, and 15 56 or more years) and parity (categorised as no children, one child, and two or more children) were exposure of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorised as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years, and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% confidence intervals (95%CI) for associations between menarche, parity and age at FMP adjusting for within-study correlation. Main results and the role of chance: The median age at FMP was 50 years (interquartile range 48 to 53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53 to 2.12) and early menopause (1.31, 1.19 to 1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84 to 2.77) and early menopause (1.32, 1.09 to 1.59). Women having early menarche and nulliparity were at over five folds increased risk of premature menopause (5.64, 4.04 to 7.87) and two folds increased risk of early menopause (2.16, 1.48 to 3.15) compared with women who had menarche at ≥12 years and two or more children. Limitations, reasons for caution: Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche which may have led to some degree of recall bias. Wider implications of the findings: Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause

Development of a Patient-Report Measure of Psychotherapy for Depression

Despite clear indications of need to improve depression treatment, practical tools that efficiently measure psychotherapy are not available. We developed a patient-report measure of psychotherapy for depression that assesses Cognitive Behavioral (CBT), Interpersonal (IPT), and Psychodynamic therapies. 420 patients with depression from a large managed behavioral health care organization completed the measure. The three subscales measuring CBT, IPT, and Psychodynamic Therapy showed good internal consistency, appropriate item-total correlations, and were supported by a 3-factor structure. Our results suggest that a patient questionnaire is a promising approach for assessing psychotherapy in quality improvement interventions

Signatures of the post-hydration heating of highly aqueously altered CM carbonaceous chondrites and implications for interpreting asteroid sample returns

The CM carbonaceous chondrites have all been aqueously altered, and some of them were subsequently heated in a parent body environment. Here we have sought to understand the impact of short duration heating on a highly aqueously altered CM through laboratory experiments on Allan Hills (ALH) 83100. Unheated ALH 83100 contains 83 volume per cent serpentine within the fine-grained matrix and altered chondrules. The matrix also hosts grains of calcite and dolomite, which are often intergrown with tochilinite, Fe(Ni) sulphides (pyrrhotite, pentlandite), magnetite and organic matter. Some of the magnetite formed by replacement of Fe(Ni) sulphides that were accreted from the nebula. Laboratory heating to 400 °C has caused partial dehydroxylation of serpentine and loss of isotopically light oxygen leading to an increase in bulk δ18O and fall in Δ17O. Tochilinite has decomposed to magnetite, whereas carbonates have remained unaltered. With regards to infrared spectroscopy (4000–400 cm-1; 2.5–25 µm), heating to 400 °C has resulted in decreased emissivity (increased reflectance), a sharper and more symmetric OH band at 3684 cm-1 (2.71 µm), a broadening of the Si—O stretching band together with movement of its minimum to longer wavenumbers, and a decreasing depth of the Mg—OH band (625 cm-1; 16 µm). The Si—O bending band is unmodified by mild heating. With heating to 800 °C the serpentine has fully dehydroxylated and recrystallized to ∼Fo60/70 olivine. Bulk δ18O has further increased and Δ17O decreased. Troilite and pyrrhotite have formed, and recrystallization of pentlandite has produced Fe,Ni metal. Calcite and dolomite were calcined at ∼700 °C and in their place is an un-named Ca-Fe oxysulphide. Heating changes the structural order of organic matter so that Raman spectroscopy of carbon in the 800 °C sample shows an increased (D1 + D4) proportional area parameter. The infrared spectrum of the 800 °C sample confirms the abundance of Fe-bearing olivine and is very similar to the spectrum of naturally heated stage IV CM Pecora Escarpment 02010. The temperature-related mineralogical, chemical, isotopic and spectroscopic signatures defined in ALH 83100 will help to track the post-hydration thermal histories of carbonaceous chondrite meteorites, and samples returned from the primitive asteroids Ryugu and Bennu