Longitudinal associations between paternal mental health and child behavior and cognition in middle childhood

IntroductionPaternal mental health has been associated with adverse consequences on offspring psychosocial development, and family environmental factors may partly explain those associations. To clarify this, we need comprehensive prospective studies, particularly in middle-childhood when the child enters school and is expected to make use of behavioral and cognitive skills as part of their interactions and learning.MethodUsing data from a sub-sample of the prospective 3D birth cohort study comprised of mother-father-child triads, and a follow-up of the parents and the children at 6–8 years of age (n = 61; 36 boys, 25 girls), we examined whether paternal anxious and depressive symptoms measured during the pregnancy period (i.e., prenatally) or concurrently when the child was assessed at 6–8 years old were associated with children's cognition/behavior.ResultsIn contrast to our hypotheses, we found that greater prenatal paternal depressive symptoms predicted fewer child behavioral difficulties; and that greater concurrent childhood paternal depression or anxiety symptoms were associated with higher child full-scale IQ, controlling for the equivalent maternal mental health assessment and parental education. Father parenting perception did not mediate these associations, nor were they moderated by maternal mental health at the concurrent assessment, or paternal ratings of marital relationship quality.DiscussionThese findings suggest that higher symptoms of paternal mental health symptoms are associated with fewer child behavioral difficulties and higher cognitive performance in middle childhood. Potential clinical implications and future research directions are discussed

Wnt4 Enhances Murine Hematopoietic Progenitor Cell Expansion Through a Planar Cell Polarity-Like Pathway

Background: While the role of canonical (b-catenin-mediated) Wnt signaling in hematolymphopoiesis has been studied extensively, little is known of the potential importance of non-canonical Wnt signals in hematopoietic cells. Wnt4 is one of the Wnt proteins that can elicit non-canonical pathways. We have previously shown that retroviral overexpression of Wnt4 by hematopoietic cells increased thymic cellularity as well as the frequency of early thymic progenitors and bone marrow hematopoietic progenitor cells (HPCs). However, the molecular pathways responsible for its effect in HPCs are not known. Methodology/Principal Findings: Here we report that Wnt4 stimulation resulted in the activation of the small GTPase Rac1 as well as Jnk kinases in an HPC cell line. Jnk activity was necessary, while b-catenin was dispensable, for the Wnt4-mediated expansion of primary fetal liver HPCs in culture. Furthermore, Jnk2-deficient and Wnt4 hemizygous mice presented lower numbers of HPCs in their bone marrow, and Jnk2-deficient HPCs showed increased rates of apoptosis. Wnt4 also improved HPC activity in a competitive reconstitution model in a cell-autonomous, Jnk2-dependent manner. Lastly, we identified Fz6 as a receptor for Wnt4 in immature HPCs and showed that the absence of Wnt4 led to a decreased expression of four polarity complex genes. Conclusions/Significance: Our results establish a functional role for non-canonical Wnt signaling in hematopoiesis throug

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Rethinking place-making: aligning placeness factors with perceived urban design qualities (PUDQs) to improve the built environment in historical district

Understanding the concept of place is critically important for urban design and place-making practice, and this research attempted to investigate the pathways by which perceived urban design qualities (PUDQs) influence placeness factors in the Chinese context. Twelve hypotheses were developed and combined in a structural equation model for validation. The Tanhualin historical district in Wuhan, China was selected for the analysis. As a result, place attachment was verified as a critical bridge factor that mediated the influence of PUDQs on place satisfaction. Among the five selected PUDQs, walkability and space quality were revealed as the most influential factors associated with place attachment and place satisfaction. Accessibility was actually indirectly beneficial to place-making via the mediation of walkability. Corresponding implications and strategies were discussed to maintain the sense of place for historic districts

Contribution of Microglia and Müller Cells to Retinal Degeneration Due to MerTk Deficiency

AbstractDeborah S. LewB.S, Paris XI University, FranceM.S, Lyon I University, FranceContribution of Microglia and Müller cells to Retinal Degeneration due to MerTK deficiencyDissertation directed by Silvia C. Finnemann, PhDRetinitis Pigmentosa (RP) is a group of inherited retinal degenerative diseases that lead patients to progressively lose peripheral photoreceptors resulting in total blindness usually at about 40 years of age. One of the most severe forms of RP is due to mutations in the gene MERTK, encoding a receptor tyrosine kinase. Patients with MERTK mutations experience symptoms already in early childhood and progress to complete blindness by about 15 years of age. It was the goal of my thesis research to determine the cellular–physiological mechanisms that underlie the early onset and rapid progression of retinal degeneration in MerTK related RP.In the eye, MerTK receptors of the RPE are required for the daily renewal of photoreceptor outer segments allowing the life-long maintenance of a healthy, functional retina. This process is essential for vision and involves many other genes and their protein products in addition to MerTK. However, only mutations in MERTK lead to early onset RP. Although its role in photoreceptor renewal is well understood, it is still unknown whymutations in this gene cause such devastating blinding disease, which unfortunately has no cure or therapy available to date.In my studies, I focused on approaches to delay the retinal degeneration. I found that inflammation through the activation of microglia, and potentially Müller cells are aggravating the retinal degeneration. By reducing microglia activity, I was able to successfully delay the retinal degeneration and improve visual acuity in models animals.Additionally, I showed that galectin-3 plays an important neuroprotective role in the degenerating retina. Lack of galectin-3 worsens retinal degeneration in both a model of inherited degeneration and a model of chemically induced degeneration. While underlying mechanisms still need unravelling, my results suggest that galectin-3 likely acts by modulating the activation/proliferation and potentially phagocytic activities of retinal inflammatory cells such as microglia and Müller cells.Interestingly, I found that Müller cells like RPE cells express MerTK receptors. Moreover, I have shown that Müller cells were able to use Protein S and galectin-3 as ligands for MerTK receptor to mediate clearance phagocytosis. These results suggest that the loss of MerTK-dependent phagocytosis by Müller cells could also contribute to the rapid onset of retinal degeneration due to MerTK deficiency.Altogether, my results reveal that both microglia and Müller cells are important players whose activities in part via galectin-3 affect the outcome of Retinitis Pigmentosa and other forms of retinal degeneration. Therefore, these cells should strongly be considered as potential targets for future therapy aiming at delaying retinal degeneration

Optimal BV estimates for a discontinuous Galerkin method for linear elasticity

We analyze a discontinuous Galerkin method for linear elasticity. The discrete formulation derives from the Hellinger-Reissner variational principle with the addition of stabilization terms analogous to those previously considered by others for the Navier-Stokes equations and a scalar Poisson equation. For our formulation, we first obtain convergence in a mesh-dependent norm and in the natural mesh-independent BD norm. We then prove a generalization of Korn's second inequality which allows us to strengthen our results to an optimal, mesh-independent BV estimate for the error