Promoting Father Involvement for Child and Family Health

Paternal involvement in children's lives is associated with a variety of child outcomes, including improved cognition, improved mental health, reduced obesity rates, and asthma exacerbation. Given this evidence, the American Academy of Pediatrics has promoted actions by pediatricians to engage fathers in pediatric care. Despite these recommendations, the mother–child dyad, rather than the mother–father–child triad, remains a frequent focus of care. Furthermore, pediatric care is often leveraged to improve maternal health, such as screening for maternal depression, but paternal health is infrequently addressed even as men tend to exhibit riskier behaviors, poorer primary care utilization, and lower life expectancy. Therefore, increasing efforts by pediatric clinicians to engage fathers may affect the health of both father and child. These efforts to engage fathers are informed by currently used definitions and measures of father involvement, which are discussed here. Factors described in the literature that affect father involvement are also summarized, including culture and context; interpersonal factors; logistics; knowledge and self-efficacy; and attitudes, beliefs, and incentives. Innovative ways to reach fathers both in the clinic and in other settings are currently under investigation, including use of behavior change models, motivational interviewing, mobile technologies, peer support groups, and policy advocacy efforts. These modalities show promise in effectively engaging fathers and improving family health.     

Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction

Probing a wide range of cellular phenotypes in neurodevelopmental disorders using patient-derived neural progenitor cells (NPCs) can be facilitated by 3D assays, as 2D systems cannot entirely recapitulate the arrangement of cells in the brain. Here, we developed a previously unidentified 3D migration and differentiation assay in layered hydrogels to examine how these processes are affected in neurodevelopmental disorders, such as Rett syndrome. Our soft 3D system mimics the brain environment and accelerates maturation of neurons from human induced pluripotent stem cell (iPSC)-derived NPCs, yielding electrophysiologically active neurons within just 3 wk. Using this platform, we revealed a genotype-specific effect of methyl-CpG-binding protein-2 (MeCP2) dysfunction on iPSC-derived neuronal migration and maturation (reduced neurite outgrowth and fewer synapses) in 3D layered hydrogels. Thus, this 3D system expands the range of neural phenotypes that can be studied in vitro to include those influenced by physical and mechanical stimuli or requiring specific arrangements of multiple cell types.Neuronal migration and maturation is a key step in brain development. Defects in this process have been implicated in many disorders, including autism (1) and schizophrenia (2). Thoroughly understanding how neural progenitor cell (NPC) migration is affected in neurodevelopmental disorders requires a means of dissecting the process using cells with genetic alterations matching those in patients. Existing in vitro assays of migration generally involve measurement of cell movement across a scratch or gap or through a membrane toward a chemoattractant in 2D culture systems. Although widely used, such assays may not accurately reveal in vivo differences, as neuronal migration is tightly regulated by physical and chemical cues in the extracellular matrix (ECM) that NPCs encounter as they migrate.In vitro 3D culture systems offer a solution to these limitations (3–7). Compared with 2D culture, a 3D arrangement allows neuronal cells to interact with many more cells (4); this similarity to the in vivo setting has been shown to lengthen viability, enhance survival, and allow formation of longer neurites and more dense networks in primary neurons in uniform matrices or aggregate culture (8, 9). Indeed, 3D culture systems have been used to study nerve regeneration, neuronal and glial development (10–12), and amyloid-β and tau pathology (13). Thus, measuring neuronal migration through a soft 3D matrix would continue this trend toward using 3D systems to study neuronal development and pathology.We sought to develop a 3D assay to examine potential migration and neuronal maturation defects in Rett syndrome (RTT), a genetic neurodevelopmental disorder that affects 1 in 10,000 children in the United States and is caused by mutations in the X-linked methyl-CpG-binding protein-2 (MECP2) gene (14). Studies using induced pluripotent stem cells (iPSCs) from RTT patients in traditional 2D adherent culture have revealed reduced neurite outgrowth and synapse number, as well as altered calcium transients and spontaneous postsynaptic currents (1). However, 2D migration assays seemed unlikely to reveal inherent defects in this developmental process, which could be affected because MeCP2 regulates multiple developmental related genes (15). Migration of RTT iPSC-derived NPCs has not previously been studied.Using a previously unidentified 3D tissue culture system that allows creation of layered architectures, we studied differences in migration of MeCP2-mutant iPSC-derived versus control iPSC-derived NPCs. This approach revealed a defect in migration of MeCP2-mutant iPSC-derived NPCs induced by either astrocytes or neurons. Further, this 3D system accelerated maturation of neurons from human iPSC-derived NPCs, yielding electrophysiologically active neurons within just 3 wk. With mature neurons derived from RTT patients and controls, we further confirmed defective neurite outgrowth and synaptogenesis in MeCP2-mutant neurons. Thus, this 3D system enables study of morphological features accessible in 2D system as well as previously unexamined phenotypes.     

Annular and subvalvular dynamics after extracellular matrix mitral tube graft implantation in pigs

 Open in a separate windowOBJECTIVESEntire mitral valve reconstruction with an extracellular matrix tube graft is a potential candidate to overcome the current limitations of mechanical and bioprosthetic valves. However, clinical data have raised concern with respect to patch failure. The aim of our study was to evaluate the impact of extracellular matrix mitral tube graft implantation on mitral annular and subvalvular regional dynamics in pigs.METHODSA modified tube graft design made of 2-ply extracellular matrix was used (CorMatrix^®; Cardiovascular Inc., Alpharetta, GA, USA). The reconstructions were performed in an acute 80-kg porcine model (N = 8), where each pig acted as its own control. Haemodynamics were assessed with Mikro-Tip pressure catheters and mitral annular and subvalvular geometry and dynamics with sonomicrometry.RESULTSCatheter-based peak left atrial pressure and pressure difference across the mitral and aortic valves in the reconstructions were comparable to the values seen in the native mitral valves. Also comparable were maximum mitral annular area (755 ± 100 mm²), maximum septal-lateral distance (29.7 ± 1.7 mm), maximum commissure–commissure distance (35.0 ± 3.4 mm), end-systolic annular height-to-commissural width ratio (10.2 ± 1.0%) and end-diastolic interpapillary muscle distance (27.7 ± 3.3 mm). Systolic expansion of the mitral annulus was, however, observed after reconstruction.CONCLUSIONSThe reconstructed mitral valves were fully functional without regurgitation, obstruction or stenosis. The reconstructed mitral annular and subvalvular geometry and subvalvular dynamics were found in the same range to those in the native mitral valve. A regional annular ballooning effect occurred that might predispose to patch failure. However, the greatest risk was found at the papillary muscle attachments.     

Targeted BRCA1/2 population screening among Ashkenazi Jewish individuals using a web-enabled medical model: An observational cohort study

PurposeThis study aimed to evaluate uptake and follow-up using internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs).MethodsAcross 4 cities in the United States, from December 2017 to March 2020, individuals aged ≥25 years with ≥1 Ashkenazi Jewish grandparent were offered enrollment. Participants consented and enrolled online with chatbot and video education, underwent BRCA1/2 AJPV GT, and chose to receive results from their primary care provider (PCP) or study staff. Surveys were conducted at baseline, at 12 weeks, and annually for 5 years.ResultsA total of 5193 participants enrolled and 4109 (79.1%) were tested (median age = 54, female = 77.1%). Upon enrollment, 35.1% of participants selected a PCP to disclose results, and 40.5% of PCPs agreed. Of those tested, 138 (3.4%) were AJPV heterozygotes of whom 21 (15.2%) had no significant family history of cancer, whereas 86 (62.3%) had a known familial pathogenic variant. At 12 weeks, 85.5% of participants with AJPVs planned increased cancer screening; only 3.7% with negative results and a significant family history reported further testing.ConclusionAlthough continued follow-up is needed, internet-enabled outreach can expand access to targeted GT using a medical model. Observed challenges for population genetic screening efforts include recruitment barriers, improving PCP engagement, and increasing uptake of additional testing when indicated.     

Early placenta previa and delivery outcome

Ultrasound scan showed some degree of placenta previa in 503 patients. Of this group, 5.6% (28) had clinically significant bleeding or documented placenta previa at delivery. A scoring system based on placental localization was not successful in predicting who was at high risk for bleeding. However, the likelihood of clinically excessive bleeding did significantly increase if the placenta previa was noted after 30 weeks' gestation. The study did not find a greater incidence of small-for-gestational-age babies in women with low-lying placentas.     

Maximal aerobic power, lactate threshold, and running performance in master athletes

PURPOSE: This study sought to determine how lactate threshold (LT) is related to running performance in older male and female runners, if LT changes significantly with age, and if gender alters the relationship between LT and performance in older runners. METHODS: Subjects were 168 master runners (111 men, 57 women) selected from a longitudinal study, who ran at least 10 miles x wk(-1) for 5 yr or more. VO2max was measured on a treadmill and body composition by hydrostatic weighing. Blood samples taken each minute of exercise were analyzed for lactate concentration and LT determined as the breakpoint in lactate accumulation. Performance times and training histories were self-reported by questionnaire. RESULTS: Men had significantly greater body mass, fat-free mass (FFM), and VO2max (L x min(-1); mL x kg(-1) x min(-1)) than women. FFM and VO2max (L x min(-1); mL x kg(-1) x min(-1)) declined with age in both men and women. Running performance was significantly different between men and women and declined with age in both. LT (L x min(-1); mL x kg(-1) x min(-1)) was significantly different between men and women, and declined significantly with age in men, whereas LT (%VO2max) did not differ between men and women and increased significantly with age in both. VO2max (mL x kg(-1) x min(-1)) was the most significant predictor of performance in both men and women, whereas LT (L x min(-1)) added to the prediction of 5-km and 10-km performance in women. CONCLUSION: The results of this study demonstrate that VO2max (mL x kg(-1) x min(-1)) is a better predictor of performance than LT in older male and female runners. Additionally, LT as a percentage of VO2max increases significantly with age.