Inhibitory control as a mediator of bidirectional effects between early oppositional behavior and maternal depression.

Maternal depression is an established risk factor for child conduct problems, but relatively few studies have tested whether children's behavioral problems exacerbate mothers' depression or whether other child behavioral characteristics (e.g., self-regulation) may mediate bidirectional effects between maternal depression and child disruptive behavior. This longitudinal study examined the parallel growth of maternal depressive symptoms and child oppositional behavior from ages 2 to 5; the magnitude and timing of their bidirectional effects; and whether child inhibitory control, a temperament-based self-regulatory mechanism, mediated effects between maternal depression and child oppositionality. A randomized control trial of 731 at-risk families assessed children annually from ages 2 to 5. Transactional models demonstrated positive and bidirectional associations between mothers' depressive symptoms and children's oppositional behavior from ages 2 to 3, with a less consistent pattern of reciprocal relations up to age 5. Mediation of indirect mother-child effects and child evocative effects depended on the rater of children's inhibitory control. Findings are discussed in regard to how child evocative effects and self-regulatory mechanisms may clarify the transmission of psychopathology within families

Global Gene Expression Profiling of Individual Human Oocytes and Embryos Demonstrates Heterogeneity in Early Development

Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted

Global gene expression profiling of individual human oocytes and embryos demonstrates heterogeneity in early development

Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted

It's all in the past:Temporal-context effects modulate subjective evaluations of emotional visual stimuli, regardless of presentation sequence

The aim of this study was to investigate if and how temporal context influences subjective affective responses to emotional images. To do so, we examined whether the subjective evaluation of a target image is influenced by the valence of its preceding image, and/or its overall position in a sequence of images. Furthermore, we assessed if these potentially confounding contextual effects can be moderated by a common procedural control: randomized stimulus presentation. Four groups of participants evaluated the same set of 120 pictures from the International Affective System (IAPS) presented in four different sequences. Our data reveal strong effects of both aspects of temporal context in all presentation sequences, modified only slightly in their nature and magnitude. Furthermore, this was true for both valence and arousal ratings. Subjective ratings of negative target images were influenced by temporal context most strongly across all sequences. We also observed important gender differences: females expressed greater sensitivity to temporal-context effects and design manipulations relative to males, especially for negative images. Our results have important implications for future emotion research that employs normative picture stimuli, and contributes to our understanding of context effects in general

Clinical Influences in the Multidisciplinary Management of Small Renal Masses at a Tertiary Referral Center

Introduction We designed a multidisciplinary Small Renal Mass Center to help patients decide among treatment options and individualize therapy for small renal masses. In this model physicians and support staff from multiple specialties work as a team to evaluate and devise a treatment plan for patients at the same organized visit. Methods We retrospectively reviewed the records of 263 patients seen from 2009 to 2014. Monitored patient characteristics included age, Charlson comorbidity index, body mass index, nephrometry score, tumor size and estimated glomerular filtration rate. Univariate and multivariate analyses were performed to identify patient characteristics associated with each treatment choice. Results Of the cohort 88 patients elected active surveillance, 64 underwent ablation and 111 were treated with surgery, including partial and radical nephrectomy in 74 and 37, respectively. There were significant associations between treatment modality and age, Charlson comorbidity index, tumor size and estimated glomerular filtration rate. Mean patient age at presentation was 61.1 years. Patients with a high Charlson comorbidity index score (greater than 5) or a decreased estimated glomerular filtration rate (less than 60 ml/minute/1.73 m2) were more likely to undergo active surveillance (41.6% and 35%) and ablative therapy (29.6% and 34%) vs partial nephrectomy (10.6% and 9%, respectively, each p \u3c0.001). On multivariable analysis age, tumor size and estimated glomerular filtration rate remained significantly associated with modality after adjustment for all other factors (each p \u3c0.001). Conclusions The Small Renal Mass Center enables patients to assess the various treatment modalities for a small renal mass in a single setting. By providing simultaneous access to the various specialists it provides an invaluable opportunity for informed patient decision making. © 2016 American Urological Association Education and Research, Inc

The relationship between antihypertensive medications and mood disorders: analysis of linked healthcare data for 1.8 million patients

Background: Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists (AAs) and calcium channel blockers, were associated with reduced risk of new-onset major depressive disorder (MDD) or bipolar disorder (BD). Method: Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009–2016) and hospital admission (1981–2016) records. Eligibility for cohort membership was determined by a receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n = 538 730) included patients with no previous history of mood disorder, whereas the other (n = 262 278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression. Results: For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For AA monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95% CI 1.04–1.31). Beta blockers' association was stronger (HR 2.68; 95% CI 2.45–2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against BD, particularly AAs (HR 0.46; 95% CI 0.30–0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD. Conclusions: There was no evidence that antihypertensive medications prevented new episodes of MDD but AAs may represent a novel treatment avenue for BD

Interactome comparison of human embryonic stem cell lines with the inner cell mass and trophectoderm

Networks of interacting co-regulated genes distinguish the inner cell mass (ICM) from the differentiated trophectoderm (TE) in the preimplantation blastocyst, in a species specific manner. In mouse the ground state pluripotency of the ICM appears to be maintained in murine embryonic stem cells (ESCs) derived from the ICM. This is not the case for human ESCs. In order to gain insight into this phenomenon, we have used quantitative network analysis to identify how similar human (h)ESCs are to the human ICM. Using the hESC lines MAN1, HUES3 and HUES7 we have shown that all have only a limited overlap with ICM specific gene expression, but that this overlap is enriched for network properties that correspond to key aspects of function including transcription factor activity and the hierarchy of network modules. These analyses provide an important framework which highlights the developmental origins of hESCs

High frequency oscillations in epileptic and non-epileptic human hippocampus during a cognitive task

Hippocampal high-frequency electrographic activity (HFOs) represents one of the major discoveries not only in epilepsy research but also in cognitive science over the past few decades. A fundamental challenge, however, has been the fact that physiological HFOs associated with normal brain function overlap in frequency with pathological HFOs. We investigated the impact of a cognitive task on HFOs with the aim of improving differentiation between epileptic and non-epileptic hippocampi in humans. Hippocampal activity was recorded with depth electrodes in 15 patients with focal epilepsy during a resting period and subsequently during a cognitive task. HFOs in ripple and fast ripple frequency ranges were evaluated in both conditions, and their rate, spectral entropy, relative amplitude and duration were compared in epileptic and non-epileptic hippocampi. The similarity of HFOs properties recorded at rest in epileptic and non-epileptic hippocampi suggests that they cannot be used alone to distinguish between hippocampi. However, both ripples and fast ripples were observed with higher rates, higher relative amplitudes and longer durations at rest as well as during a cognitive task in epileptic compared with non-epileptic hippocampi. Moreover, during a cognitive task, significant reductions of HFOs rates were found in epileptic hippocampi. These reductions were not observed in non-epileptic hippocampi. Our results indicate that although both hippocampi generate HFOs with similar features that probably reflect non-pathological phenomena, it is possible to differentiate between epileptic and non-epileptic hippocampi using a simple odd-ball task

Potential implications of coronary artery calcium testing for guiding aspirin use among asymptomatic individuals with diabetes.

ObjectiveIt is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.Research design and methodsOf 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.ResultsThere were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50-59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.ConclusionsCAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention

Development of functional connectivity during adolescence:A longitudinal study using an action-observation paradigm

Successful interpersonal interactions rely on an ability to read the emotional states of others and to modulate one's own behavior in response. The actions of others serve as valuable social stimuli in this respect, offering the observer an insight into the actor's emotional state. Social cognition continues to mature throughout adolescence. Here we assess longitudinally the development of functional connectivity during early adolescence within two neural networks implicated in social cognition: one network of brain regions consistently engaged during action observation and another one associated with mentalizing. Using fMRI, we reveal a greater recruitment of the social-emotional network during the observation of angry hand actions in male relative to female adolescents. These findings are discussed in terms of known sex differences in adolescent social behavior