Ovarian Hormones, Aging and Stress on Hippocampal Synaptic Plasticity

The ovarian steroid hormones estradiol and progesterone regulate a wide variety of non-reproductive functions in the central nervous system by interacting with molecular and cellular processes. A growing literature from studies using rodent models suggests that 17β-estradiol, the most potent of the biologically relevant estrogens, enhances synaptic transmission and the magnitude of long-term potentiation recorded from in vitro hippocampal slices. In contrast, progesterone has been shown to decrease synaptic transmission and reduce hippocampal long-term potentiation in this model system. Hippocampal long-term depression, another form of synaptic plasticity, occurs more prominently in slices from aged rats. A decrease in long-term potentiation magnitude has been recorded in hippocampal slices from both adult and aged rats behaviorally stressed just prior to hippocampal slice tissue preparation and electrophysiological recording. 17β-estradiol modifies synaptic plasticity in both adult and aged rats, whether behaviorally stressed or not by enhancing long-term potentiation and attenuating long-term depression. The studies discussed in this review provide an understanding of new approaches used to investigate the protective effects of ovarian hormones against aging and stress, and how these hormones impact age and stress-related learning and memory dysfunction

Estrogen and Hippocampal Synaptic Plasticity

During the past several years, there has been increasing interest in the effects of estrogen on neural function. This enthusiasm is driven, in part, by the results of early clinical studies suggesting that estrogen therapy given after menopause may prevent, or at least delay, the onset of Alzheimer\u27s disease in older women. However, later clinical trials of women with probable Alzheimer\u27s disease had contrary results. Much of the current research related to estrogen and brain function is focused in two directions. One involves clinical studies that examine the potential of estrogen in protecting against cognitive decline during normal aging and against Alzheimer\u27s disease (neuroprotection). The other direction, which is the primary focus of this review, involves laboratory studies that examine the mechanisms by which estrogen can modify the structure of nerve cells and alter the way neurons communicate with other cells in the brain (neuroplasticity). In this review, we examine recent evidence from experimental and clinical research on the rapid effects of estrogen on several mechanisms that involve synaptic plasticity in the nervous system, including hippocampal excitability, long-term potentiation and depression related to sex and aging differences, cellular neuroprotection and probable molecular mechanisms of the action of estrogen in brain tissue

Wide-field Magnetic Field and Temperature Imaging using Nanoscale Quantum Sensors

The simultaneous imaging of magnetic fields and temperature (MT) is important in a range of applications, including studies of carrier transport, solid-state material dynamics, and semiconductor device characterization. Techniques exist for separately measuring temperature (e.g., infrared (IR) microscopy, micro-Raman spectroscopy, and thermo-reflectance microscopy) and magnetic fields (e.g., scanning probe magnetic force microscopy and superconducting quantum interference devices). However, these techniques cannot measure magnetic fields and temperature simultaneously. Here, we use the exceptional temperature and magnetic field sensitivity of nitrogen vacancy (NV) spins in conformally-coated nanodiamonds to realize simultaneous wide-field MT imaging. Our "quantum conformally-attached thermo-magnetic" (Q-CAT) imaging enables (i) wide-field, high-frame-rate imaging (100 - 1000 Hz); (ii) high sensitivity; and (iii) compatibility with standard microscopes. We apply this technique to study the industrially important problem of characterizing multifinger gallium nitride high-electron-mobility transistors (GaN HEMTs). We spatially and temporally resolve the electric current distribution and resulting temperature rise, elucidating functional device behavior at the microscopic level. The general applicability of Q-CAT imaging serves as an important tool for understanding complex MT phenomena in material science, device physics, and related fields

Estrogen and Hippocampal Plasticity in Rodent Models

Accumulating evidence indicates that ovarian hormones regulate a wide variety of non-reproductive functions in the central nervous system by interacting with several molecular and cellular processes. A growing animal literature using both adult and aged rodent models indicates that 17β-estradiol, the most potent of the biologically relevant estrogens, facilitates some forms of learning and memory, in particular those that involve hippocampal-dependent tasks. A recently developed triple-transgenic mouse (3xTg-AD) has been widely used as an animal model of Alzheimer\u27s disease, as this mouse exhibits an age-related and progressive neuropathological phenotype that includes both plaque and tangle pathology mainly restricted to hippocampus, amygdala and cerebral cortex. In this report, we examine recent studies that compare the effects of ovarian hormones on synaptic transmission and synaptic plasticity in adult and aged rodents. A better understanding of the non-reproductive functions of ovarian hormones has far-reaching implications for hormone therapy to maintain health and function within the nervous system throughout aging

Exploring Relations between Teachers’ Beliefs, Instructional Practices, and Students’ Beliefs in Statistics

We examined the epistemic climate of statistics classrooms across two different classrooms by measuring teachers’ espoused beliefs about teaching statistics and observing their teaching practices. We then explored whether students’ beliefs became more aligned with the epistemic climate of the classroom over time. Post-secondary students’ beliefs were measured at the beginning and end of the semester. To measure the epistemic climate, teachers completed self-reports of their beliefs about teaching and learning, and participated in two semi-structured interviews at the beginning and end of the semester. Moreover, several classroom observations were conducted over the course of the semester. Analyses of the data revealed that for one group of students in one class, their beliefs were well aligned with the classroom climate and remained stable over time whereas for the other group of students, their beliefs shifted over time to align with the classroom climate

Keck Laser Guide Star Adaptive Optics Monitoring of 2MASS J1534-2952AB: First Dynamical Mass Determination of a Binary T Dwarf

(Abridged) We present multi-epoch imaging of the T5.0+T5.5 binary 2MASS J1534-2952AB obtained with the Keck laser guide star adaptive optics system. Combined with an extensive (re-)analysis of archival HST imaging, we find a total mass of 0.056+/-0.003 Msun (59+/-3 Mjup). This is the first field binary for which both components are directly confirmed to be substellar. This is also the coolest and lowest mass binary with a dynamical mass determination to date. Using evolutionary models, we derive an age of 0.78+/-0.09 Gyr for the system, and we find Teff = 1028+/-17 K and 978+/-17 K and masses of 0.0287+/-0.0016 Msun (30.1+/-1.7 Mjup) and 0.0269+/-0.0016 Msun (28.2+/-1.7 Mjup) for the individual components. These precise measurements generally agree with previous studies of T dwarfs and affirm the current theoretical models. However, (1) the temperatures are about 100 K cooler than derived for similar objects and suggest that the ages of field brown dwarfs may be overestimated. Also, (2) the H-R diagram positions are discrepant with current predictions. While this may arise from large errors in the evolutionary models, the likely cause is a modest (~100 K) overestimate in temperatures determined from model atmospheres. We discuss future tests of theory as the sample of substellar dynamical masses increases. In particular, we suggest that low-mass field binaries with dynamical masses ("mass benchmarks") can serve as reference points for Teff and log(g) and thereby constrain ultracool atmosphere models, as good as or even better than single brown dwarfs with age estimates ("age benchmarks").Comment: ApJ, in press. Typo in Eqn. 6 corrected in v

Explaining variable effects of an adaptable implementation package to promote evidence-based practice in primary care : a longitudinal process evaluation

This study is funded by the National Institute for Health Research (NIHR) [Programme Grants for Applied Research (Grant Reference Number RP-PG-1209-10040)] (https://www.nihr.ac.uk/).Background Implementing evidence-based recommendations is challenging in UK primary care, especially given system pressures and multiple guideline recommendations competing for attention. Implementation packages that can be adapted and hence applied to target multiple guideline recommendations could offer efficiencies for recommendations with common barriers to achievement. We developed and evaluated a package of evidence-based interventions (audit and feedback, educational outreach and reminders) incorporating behaviour change techniques to target common barriers, in two pragmatic trials for four “high impact” indicators: risky prescribing; diabetes control; blood pressure control; and anticoagulation in atrial fibrillation. We observed a significant, cost-effective reduction in risky prescribing but there was insufficient evidence of effect on the other outcomes. We explored the impact of the implementation package on both social processes (Normalisation Process Theory; NPT) and hypothesised determinants of behaviour (Theoretical Domains Framework; TDF). Methods We conducted a prospective multi-method process evaluation. Observational, administrative and interview data collection and analyses in eight primary care practices were guided by NPT and TDF. Survey data from trial and process evaluation practices explored fidelity. Results We observed three main patterns of variation in how practices responded to the implementation package. First, in integration and achievement, the package “worked” when it was considered distinctive and feasible. Timely feedback directed at specific behaviours enabled continuous goal setting, action and review, which reinforced motivation and collective action. Second, impacts on team-based determinants were limited, particularly when the complexity of clinical actions impeded progress. Third, there were delivery delays and unintended consequences. Delays in scheduling outreach further reduced ownership and time for improvement. Repeated stagnant or declining feedback that did not reflect effort undermined engagement. Conclusions Variable integration within practice routines and organisation of care, variable impacts on behavioural determinants, and delays in delivery and unintended consequences help explain the partial success of an adaptable package in primary care.Publisher PDFPeer reviewe

A pragmatic cluster randomised controlled trial of a tailored intervention to improve the initial management of suspected encephalitis

Objective To determine whether a tailored multifaceted implementation strategy improves the initial management of patients with suspected encephalitis. Design Pragmatic two arm cluster randomised controlled trial. Setting Hospitals within the United Kingdom. Participants Twenty-four hospitals nested within 12 postgraduate deaneries. Patients were identified retrospectively by searching discharge, microbiology, radiology and pharmacy records and included if they met clinical criteria or had a recorded suspicion of encephalitis. Intervention An implementation strategy designed to overcome barriers to change, comprising local action planning, education and training, feedback on performance, a lumbar puncture pack and a range of optional components. Outcomes The primary outcome was the proportion of patients with suspected encephalitis undergoing diagnostic lumbar puncture within 12 hours of admission and starting aciclovir treatment within six hours. Secondary outcomes included the proportions of adults and children who had a lumbar puncture, who had appropriate cerebrospinal fluid investigations, and who had appropriate radiological imaging within 24 hours of admission. Data were collected from patient records for 12 months before and 12 months during the intervention period, and analysed blind to allocation. Results 13 hospitals were randomised to intervention and 11 to control (no intervention), with 266 and 223 patients with suspected encephalitis identified respectively. There was no significant difference in primary outcome between intervention and control hospitals (13.5% and 14.8% respectively, p = 0.619; treatment effect -0.188, 95% confidence interval -0.927 to 0.552), but both had improved compared to pre-intervention (8.5%). Conclusion The improvement in both intervention and control arms may reflect overall progress in management of encephalitis through wider awareness and educatio

A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

OBJECTIVES: To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. METHODS: The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. RESULTS: Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. CONCLUSIONS: This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis

Progesterone Receptors: Form and Function in Brain

Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and/or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging