A multilevel approach to understanding the determinants of maternal harsh parenting: the importance of maternal age and perceived partner support

Determinants of parenting are most often considered using one child per family within a cross-sectional design. In 182 families, the current study included two siblings and sought to predict maternal harsh parenting measured prospectively when each child was age 2 years from child gender, infant temperament, maternal age, maternal educational attainment, maternal depression and anxiety and maternal perceptions of partner support. Multilevel modeling was used to examine between- and within-family variance simultaneously. Mothers reported levels of harsh parenting that were similar towards both children (intraclass correlation = 0.69). Thus, the majority of variance in maternal perceptions of their harsh parenting resided between rather than within families and was accounted for in part by maternal age and maternal perceptions of partner support. Results are discussed in relation to family-wide determinants of harsh parenting, previous literature pertaining to parenting siblings and the potential avenues for future research and practice

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

peer reviewedBackground: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non–oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non–OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction. © 202

3D self-organized human Blood-Brain Barrier in a microfluidic chip

A preclinical blood-brain barrier (BBB) model is important for the study of fundamental transport mechanisms and in accessing the delivery of small molecules and antibodies that target brain. Transwell assays for BBB models are easy to create and use but lack the true 3D anatomy of the brain microvasculature and also often the cell-cell and cell-matrix interactions that are important in ensuring a tight BBB. Here we describe the formation of a BBB that expresses neurovascular membrane transporters, tight junction and extracellular matrix proteins using the co-culture of human induced pluripotent stem cell-derived endothelial cells (iPSC-EC), brain pericytes (PC) and astrocytes (AC) in a microfluidic device. The BBB model recapitulates human brain vascular permeability with values that are lower than conventional in vitro models and are comparable to in vivo measurements in rat brain. This in vitro BBB model can therefore be used to screen for brain-targeting drugs or to study neurovascular functions