Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse.

BackgroundExposure to interpersonal violence, namely verbal and physical abuse, is a highly prevalent threat to women's health and well-being. Among older, post-menopausal women, several researchers have characterized a possible bi-directional relationship of abuse exposure and diminished physical functioning. However, studies that prospectively examine the relationship between interpersonal abuse exposure and physical functioning across multiple years of observation are lacking. To address this literature gap, we prospectively evaluate the association between abuse exposure and physical functioning in a large, national cohort of post-menopausal women across 12 years of follow-up observation.MethodsMultivariable logistic regression was used to measure the adjusted association between experiencing abuse and physical function score at baseline in 154,902 Women's Health Initiative (WHI) participants. Multilevel modeling, where the trajectories of decline in physical function were modeled as a function of time-varying abuse exposure, was used to evaluate the contribution of abuse to trajectories of physical function scores over time.ResultAbuse was prevalent among WHI participants, with 11 % of our study population reporting baseline exposure. Verbal abuse was the most commonly reported abuse type (10 %), followed by combined physical and verbal abuse (1 %), followed by physical abuse in the absence of verbal abuse (0.2 %). Abuse exposure (all types) was associated with diminished physical functioning, with women exposed to combined physical and verbal abuse presenting baseline physical functioning scores consistent with non-abused women 20 years senior. Results did not reveal a differential rate of decline over time in physical functioning based on abuse exposure.ConclusionsTaken together, our findings suggest a need for increased awareness of the prevalence of abuse exposure among postmenopausal women; they also underscore the importance of clinician's vigilance in their efforts toward the prevention, early detection and effective intervention with abuse exposure, including verbal abuse exposure, in post-menopausal women. Given our findings related to abuse exposure and women's diminished physical functioning at WHI baseline, our work illuminates a need for further study, particularly the investigation of this association in younger, pre-menopausal women so that the temporal ordering if this relationship may be better understood

Calcineurin, Synaptic Plasticity, and Memory

A long-held hypothesis in neuroscience holds that learning and memory mechanisms involve lasting changes in synaptic weights. Multiple mechanisms for producing such changes exist, of which NMDA-receptor-dependent long-term potentiation (LTP) is the most widely studied. Curiously, the relatively simple hypothesis that LTP plays a role in learning and memory has proven difficult to test. A current experimental strategy is to generate genetically altered mice with mutations in genes thought to be involved in LTP and assess the effects of these mutations both on LTP and animal behavior Phosphorylation/dephosphorylation plays a critical role in the induction of LTP, and pharmacological and genetic approaches have begun to tease out the various roles played by specific kinases. Until recently though, little emphasis has been placed upon phosphatases. However, two key sets of pharmacological studies, two by Mulkey and Malenk

Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) trial: Study design and sample characteristics

Background Pain is the most common presenting somatic symptom in medical outpatients, and depression and anxiety are the two most common mental disorders. They frequently co-occur, are under-treated, and result in substantial disability and reduced health-related quality of life. Objectives The Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) study is a randomized comparative effectiveness trial designed to test the relative effectiveness of a lower-resource vs. a higher-resource technology-assisted intervention for the management of patients suffering from pain plus anxiety and/or depression. Methods/design CAMMPS has enrolled 294 primary care patients with chronic pain plus comorbid anxiety and/or depression and randomized them to either: 1) Assisted Symptom Management (ASM) consisting of automated symptom monitoring by interactive voice recording or Internet and prompted pain and mood self-management; or 2) Comprehensive Symptom Management (CSM) which combines ASM with optimized medication management delivered by a nurse-physician specialist team and facilitated mental health care. Outcomes are assessed at baseline, 1, 3, 6, and 12 months. The primary outcome is a composite pain-anxiety-depression (PAD) severity score. Secondary outcomes include individual pain, anxiety, and depression scores, health-related quality of life, disability, healthcare utilization, and treatment satisfaction. Discussion CAMMPS provides an integrated approach to PAD symptoms rather than fragmented care of single symptoms; coordinated symptom management in partnership with primary care clinicians and psychologists embedded in primary care; efficient use of health information technology; attention to physical and psychological symptom comorbidity; and the coupling of self-management with optimized medication management and facilitated mental health care

Cognitive State Measurement from Eye Gaze Analysis in an Intelligent Virtual Reality Driving System for Autism Intervention

Abstract-Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disabilities with a high prevalence rate. While much research has focused on improving social communication deficits in ASD populations, less emphasis has been devoted to improving skills relevant for adult independent living, such as driving. In this paper, a novel virtual reality (VR)-based driving system with different difficulty levels of tasks is presented to train and improve driving skills of teenagers with ASD. The goal of this paper is to measure the cognitive load experienced by an individual with ASD while he is driving in the VR-based driving system. Several eye gaze features are identified that varied with cognitive load in an experiment participated by 12 teenagers with ASD. Several machine learning methods were compared and the ability of these methods to accurately measure cognitive load was validated with respect to the subjective rating of a therapist. Results will be used to build models in an intelligent VR-based driving system that can sense a participant's real-time cognitive load and offer driving tasks at an appropriate difficulty level in order to maximize the participant's long-term performance

Oviductal and endometrial mRNA expression of implantation candidate biomarkers during early pregnancy in rabbit

[EN] Prenatal losses are a complex problem. Pregnancy requires orchestrated communication between the embryo and the uterus that includes secretions from the embryo to signal pregnancy recognition and secretion and remodelling from the uterine epithelium. Most of these losses are characterized by asynchronization between embryo and uterus. To better understand possible causes, an analysis was conducted of gene expression of a set of transcripts related to maternal recognition and establishment of rabbit pregnancy (uteroglobin, SCGB1A1; integrin 1, ITGA1; interferon- , IFNG; vascular endothelial growth factor, VEGF) in oviduct and uterine tissue at 16, 72 or 144 h post-ovulation and insemination. In the oviduct tissue, a significant decrease in the level of SCGB1A1 mRNA expression was observed from 144 h post-ovulation. In the case of ITGA1, the transcript abundance was initially lower, but mRNA expression increased significantly at 72 and 144 h post-ovulation. For IFNG, a huge decrease was observed from 16 to 72 h post-ovulation. Finally, no significant differences were observed in the VEGF transcript. For the endometrium, the results showed a significant decline in the level of SCGB1A1 mRNA expression from 16 to 144 h post-ovulation induction. The highest levels of ITGA1 transcript were detected at 144 h, followed by the 16 h group and lower at 72 h post-ovulation. For IFNG there were no significant differences among post-ovulation induction times. Finally, it was possible to observe that VEGF mRNA abundance was present at low levels at 16 h post-ovulation and remained low at 72 h,but increased at 144 h. The functional significance of these observations may provide new insights into the maternal role in prenatal losses.This work was supported by the Spanish Research Projects (CICYT AGL2011-29831-C03-01). M.D. Saenz-de-Juano was supported by a research grant from Generalitat Valenciana (Programa VALI+d, ACIF/2011/254).Saeed, AM.; Saenz De Juano Ribes, MDLD.; Marco Jiménez, F.; Vicente Antón, JS. (2015). Oviductal and endometrial mRNA expression of implantation candidate biomarkers during early pregnancy in rabbit. Zygote. 23(2):288-296. https://doi.org/10.1017/S0967199413000555S28829623

Cognitive vulnerability to depression: A comparison of the weakest link, keystone and additive models

Multiple theories of cognitive vulnerability to depression have been proposed, each focusing on different aspects of negative cognition and utilising different measures of risk. Various methods of integrating such multiple indices of risk have been examined in the literature, and each demonstrates some promise. Yet little is known about the interrelations among these methods, or their incremental validity in predicting changes in depression. The present study compared three integrative models of cognitive vulnerability: the additive, weakest link, and keystone models. Support was found for each model as predictive of depression over time, but only the weakest link model demonstrated incremental utility in predicting changes in depression over the other models. We also explore the correlation between these models and each model’s unique contribution to predicting onset of depressive symptoms

Developmental pathways to autism: a review of prospective studies of infants at risk

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social interaction and communication, and the presence of restrictive and repetitive behaviors. Symptoms of ASD likely emerge from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the child's environment, modified by compensatory skills and protective factors. Prospective studies of infants at high familial risk for ASD (who have an older sibling with a diagnosis) are beginning to characterize these developmental pathways to the emergence of clinical symptoms. Here, we review the range of behavioral and neurocognitive markers for later ASD that have been identified in high-risk infants in the first years of life. We discuss theoretical implications of emerging patterns, and identify key directions for future work, including potential resolutions to several methodological challenges for the field. Mapping how ASD unfolds from birth is critical to our understanding of the developmental mechanisms underlying this disorder. A more nuanced understanding of developmental pathways to ASD will help us not only to identify children who need early intervention, but also to improve the range of interventions available to them

Serum estradiol/progesterone ratio on day of embryo transfer may predict reproductive outcome following controlled ovarian hyperstimulation and in vitro fertilization

BACKGROUND: To determine whether estradiol-to-progesterone (E(2)/P) ratios at the time of embryo transfer (ET) have an effect on implantation and pregnancy in IVF cycles. METHODS: 239 women consecutively treated by IVF or ICSI were retrospectively analyzed and early luteal serum E(2 )and P were measured on the day of ET. Transfer occurred after a variable in vitro culture period ranging from 4–7 days after ovulation induction (OI). Following ET, serum E(2)/P ratios were calculated for clinical pregnancies, preclinical abortions and non-coneption cycles. RESULTS: Receiver-operator curve analysis demonstrated that the E(2)/P ratio could differentiate between clinical pregnancies and non-pregnant cycles (area under the curve on OI +4 days = 0.70; 95% CI = 0.60–0.80; p = 0.003, on OI +5 days = 0.76; 95% CI = 0.64–0.88; p = 0.001, OI +7 days = 0.85; 95% CI = 0.75–0.96; p < 0.0001). CONCLUSION: These retrospective data may hold prognostic value regarding endometrial receptivity as reflected by E(2)/P measurements and may help improve IVF treatment outcome. Further prospective studies should be undertaken to confirm these obersveration

In developing hippocampal neurons, NR2B-containing N-methyl-d-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death

It has been suggested that NR2B-containing NMDA receptors have a selective tendency to promote pro-death signalling and synaptic depression, compared to the survival promoting, synapse potentiating properties of NR2A-containing NMDA receptors. A preferential localization of NR2A-containing NMDA receptors at the synapse in maturing neurons could thus explain differences in synaptic vs. extrasynaptic NMDA receptor signalling. We have investigated whether NMDA receptors can mediate signalling to survival, death, and synaptic potentiation, in neurons at a developmental stage prior to significant NR2A expression and subunit-specific differences between synaptic and extrasynaptic NMDA receptors. We show that in developing hippocampal neurons, the progressive reduction in sensitivity of NMDA receptor currents to the NR2B antagonist ifenprodil applies to both synaptic and extrasynaptic locations. However, the reduction is less acute in extrasynaptic currents, indicating that NR2A does partition preferentially, but not exclusively, into synaptic locations at DIV>12. We then studied NMDA receptor signalling at DIV10, when both synaptic and extrasynaptic NMDA receptors are both overwhelmingly and equally NR2B-dominated. To analyse pro-survival signalling we studied the influence of synaptic NMDA receptor activity on staurosporine-induced apoptosis. Blockade of spontaneous NMDAR activity with MK-801, or ifenprodil exacerbated the apoptotic insult. Furthermore, MK-801 and ifenprodil both antagonized neuroprotection promoted by enhancing synaptic activity. Pro-death signalling induced by a toxic dose of NMDA is also blocked by NR2B-specific antagonists. Using a cell culture model of synaptic NMDA receptor-dependent synaptic potentiation, we find that this is mediated exclusively by NR2B-containing NMDARs, as implicated by NR2B-specific antagonists and the use of selective vs. non-selective doses of the NR2A-preferring antagonist NVP-AAM077. Therefore, within a single neuron, NR2B-NMDA receptors are able to mediate both survival and death signalling, as well as model of NMDA receptor-dependent synaptic potentiation. In this instance, subunit differences cannot account for the dichotomous nature of NMDA receptor signalling