Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

Techniques for direct experimental evaluation of structure-transport relationships in disordered porous solids

Determining structure-transport relationships is critical to optimising the activity and selectivity performance of porous pellets acting as heterogeneous catalysts for diffusion-limited reactions. For amorphous porous systems determining the impact of particular aspects of the void space on mass transport often requires complex characterization and modelling steps to deconvolve the specific influence of the feature in question. These characterization and modelling steps often have limited accuracy and precision. It is the purpose of this work to present a case-study demonstrating the use of a more direct experimental evaluation of the impact of pore network features on mass transport. The case study evaluated the efficacy of the macropores of a bidisperse porous foam structure on improving mass transport over a purely mesoporous system. The method presented involved extending the novel integrated gas sorption and mercury porosimetry method to include uptake kinetics. Results for the new method were compared with those obtained by the alternative NMR cryodiffusometry technique, and found to lead to similar conclusions. It was found that the experimentally-determined degree of influence of the foam macropores was in line with expectations from a simple resistance model for a disconnected macropore network

Bedside Interactions from the Other Side of the Bedrail

To assess the importance to patients of various aspects of bedside interactions with physician teams. Design : Cross-sectional survey. Setting : VA hospital. Patients : Ninety-seven medical inpatients. Intervention : Survey of 44 questions including short answer, multiple choice, and Likert-type questions. Measurements and Main Results : Data analysis included descriptive statistics. The sample was predominantly male, with a mean age of 62. Overall satisfaction with the hospital experience and with the team of doctors were both high (95% and 96% reported being very or mostly satisfied, respectively). Patients reported learning about several issues during their interactions with the teams; the 3 most highly rated areas were new problems, tests that will be done, and treatments that will be done. Most patients (76%) felt that their teams cared about them very much. Patients were made comfortable when the team showed that they cared, listened, and appeared relaxed (reported by 63%, 57%, and 54%, respectively). Patients were made uncomfortable by the team using language they did not understand (22%) and when several people examined them at once (13%). Many (58%) patients felt personally involved in teaching. The majority of patients liked having medical students and residents involved in their care (69% and 64%, respectively). Conclusions : Patients have much to teach about what is important about interacting with physician teams. Although patients' reactions to team interactions are generally positive, patients are different with respect to what makes them comfortable and uncomfortable. Taking their preferences into account could improve the experience of being in a teaching hospital.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75456/1/j.1525-1497.2005.40192.x.pd

Can depression be a menopause-associated risk?

There is little doubt that women experience a heightened psychiatric morbidity compared to men. A growing body of evidence suggests that, for some women, the menopausal transition and early postmenopausal years may represent a period of vulnerability associated with an increased risk of experiencing symptoms of depression, or for the development of an episode of major depressive disorder. Recent research has begun to shed some light on potential mechanisms that influence this vulnerability. At the same time, a number of studies and clinical trials conducted over the past decade have provided important data regarding efficacy and safety of preventative measures and treatment strategies for midlife women; some of these studies have caused a shift in the current thinking of how menopausal symptoms should be appropriately managed

Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies

Importance: Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated. Objective: To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia. Design, Setting, and Participants: Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors. Exposures: Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed. Outcomes: Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death. Results: There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (-2.8 points; 95% CI, -4.5 to -1.0; P < .001). Cognitive decline attributable to delirium was -0.37 MMSE points per year (95% CI, -0.60 to -0.13; P < .001). Decline attributable to the pathologic processes of dementia was -0.39 MMSE points per year (95% CI, -0.57 to -0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional -0.16 MMSE points per year (95% CI, -0.29 to -0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level-matched controls. Conclusions and Relevance: Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia.The Cambridge Brain Bank Laboratory (which processed all the CC75C and some of the CFAS cases) is supported by the National Institute for Health Research Cambridge BioMedical Research Centre. The original Epidemiological Clinicopathological Studies in Europe (EClipSE) harmonization project was established through grant RHAG/094 from the Bupa UK Foundation and a European Union Marie Curie International Incoming Fellowship (Dr Keage). Dr Fleming is supported by grant RHAG/058 from the Bupa UK Foundation, which included the latest CC75C fieldwork funding. Dr Davis is supported by grants 090661/Z/09/Z and 107467/Z/15/Z from the Wellcome Trust. Drs Davis and MacLullich are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative funded by grant G0700704/84698. Funding from the Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, and the Medical Research Council is gratefully acknowledged. Dr Keage is supported by Australian National Health and Medical Research Council Fellowship grant 568890. Dr Cunningham is supported by grant 09/09/07 from the Wellcome Trust Senior Research Fellowship

Fluid Mechanics in Dentinal Microtubules Provides Mechanistic Insights into the Difference between Hot and Cold Dental Pain

Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not “equally sensitive” to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices

Identification of Antifreeze Proteins and Their Functional Residues by Support Vector Machine and Genetic Algorithms based on n-Peptide Compositions

For the first time, multiple sets of n-peptide compositions from antifreeze protein (AFP) sequences of various cold-adapted fish and insects were analyzed using support vector machine and genetic algorithms. The identification of AFPs is difficult because they exist as evolutionarily divergent types, and because their sequences and structures are present in limited numbers in currently available databases. Our results reveal that it is feasible to identify the shared sequential features among the various structural types of AFPs. Moreover, we were able to identify residues involved in ice binding without requiring knowledge of the three-dimensional structures of these AFPs. This approach should be useful for genomic and proteomic studies involving cold-adapted organisms