Parental resilience: A neglected construct in resilience research

The substantial focus of resilience research on childhood well‐being has resulted in limited knowledge regarding other aspects of resilience in families, such as that of parents. Informed by literature in childhood and family resilience, in this review, we progress conceptual understanding by focusing on parental resilience. The definition of parental resilience, as the capacity of parents to deliver a competent and quality level of parenting to children despite the presence of risk factors, is offered here as a worthwhile framework through which to explore variables thought to contribute to resilience among parents. A conceptual model is proposed whereby parental psychological well‐being and self‐efficacy, family functioning, and social connectedness are specifically addressed, with each posited as playing an important role in parents’ ability to deliver high‐quality parenting. In addition to these factors, how parents accommodate adversity and find meaning in their everyday lives within their families is hypothesised to be an important process in understanding parental resilience.     

Optimized isolation and expansion of human airway epithelial basal cells from endobronchial biopsy samples

Autologous airway epithelial cells have been used in clinical tissue‐engineered airway transplantation procedures with a view to assisting mucosal regeneration and restoring mucociliary escalator function. However, limited time is available for epithelial cell expansion due to the urgent nature of these interventions and slow epithelial regeneration has been observed in patients. Human airway epithelial cells can be expanded from small biopsies or brushings taken during bronchoscopy procedures, but the optimal mode of tissue acquisition from patients has not been investigated. Here, we compared endobronchial brushing and endobronchial biopsy samples in terms of their cell number and their ability to initiate basal epithelial stem cell cultures. We found that direct co‐culture of samples with 3T3‐J2 feeder cells in culture medium containing a Rho‐associated protein kinase inhibitor, Y‐27632, led to the selective expansion of greater numbers of basal epithelial stem cells during the critical early stages of culture than traditional techniques. Additionally, we established the benefit of initiating cell cultures from cell suspensions, either using brushing samples or through enzymatic digestion of biopsies, over explant culture. Primary epithelial cell cultures were initiated from endobronchial biopsy samples that had been cryopreserved before the initiation of cell cultures, suggesting that cryopreservation could eliminate the requirement for close proximity between the clinical facility in which biopsy samples are taken and the specialist laboratory in which epithelial cells are cultured. Overall, our results suggest ways to expedite epithelial cell preparation in future airway cell therapy or bioengineered airway transplantation procedures.     

Emerging Treatments in Episodic Migraine

Purpose of Review

The purpose of this review is to evaluate and describe recent and emerging treatment options for episodic migraine.

Recent Findings

Recent advances have been made in better understanding the pathophysiology of migraine, which has led to further investigation of potential new pharmacologic and non-pharmacologic treatment options.

Summary

A number of new medications are emerging for the acute and preventive treatment of migraine, including CGRP monoclonal antibodies, CGRP receptor antagonists, serotonin 5-HT_1F agonists, and PACAP receptor monoclonal antibodies. Additionally, newer studies on existing non-invasive neuromodulation devices including transcranial magnetic stimulation, supraorbital transcutaneous nerve stimulation, and transcutaneous vagus nerve stimulation have recently received FDA approval for use in migraine. Neuromodulation devices including percutaneous mastoid electrical stimulation, non-painful remote electrical stimulation, and caloric vestibular stimulation are undergoing further investigation and have shown promising results thus far. These new developments are expected to contribute to better treatment and decreased disability in migraine.

     

Acute morphine affects the rat circadian clock via rhythms of phosphorylated ERK1/2 and GSK3β kinases and Per1 expression in the rat suprachiasmatic nucleus

Background and Purpose

Opioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling.

Experimental Approach

A time-dependent effect of morphine (1 mg·kg⁻¹, i.p.) applied either during the day or during the early night was followed, and the levels of phosphorylated ERK1/2, GSK3β, c-Fos and Per genes were assessed by immunohistochemistry and in situ hybridization. The effect of morphine pretreatment on light-induced pERK and c-Fos was examined, and day/night difference in activity of opioid receptors was evaluated by [³⁵S]-GTPγS binding assay.

Key Results

Morphine stimulated a rise in pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus (SCN) when applied during the day but significantly reduced both kinases when applied during the night. Morphine at night transiently induced Period1 but not Period2 in the SCN and did not attenuate the light-induced level of pERK1/2 and c-Fos in the SCN. The activity of all three principal opioid receptors was high during the day but decreased significantly at night, except for the δ receptor. Finally, we demonstrated daily profiles of pERK1/2 and pGSK3β levels in the rat ventrolateral and dorsomedial SCN.

Conclusions and Implications

Our data suggest that the phase-shifting effect of opioids may be mediated via post-translational modification of clock proteins by means of activated ERK1/2 and GSK3β.Tables of Links

Potential of biofluid components to modify silver nanoparticle toxicity

Establishing realistic exposure scenarios is critical for cytotoxic investigation of silver nanoparticles (AgNP) in the gastrointestinal tract. This study investigated the potential interaction with and effect of biofluid components, namely cholic acid, deoxycholic acid and ursodeoxycholic acid, on AgNP toxicity. Two cell lines corresponding to organs related to the biofluid components were employed. These were HepG‐2 a hepatocellular carcinoma derived from liver tissue and Hep2 an epithelial cell line. Physiochemical and cytotoxic screening was performed and the ability of biofluid components to modify AgNP cytotoxicity was explored. No alteration to the physiochemical characteristics of AgNP by biofluid components was demonstrated. However, biofluid component addition resulted in alteration of AgNP toxicity. Greater reactive oxygen species induction was noted in the presence of cholic acid and deoxycholic acid. Ursodeoxycholic acid demonstrated no modification of toxicity in HepG‐2 cells; however, significant modification was noted in Hep2 cells. It is concluded that biofluid components can modify AgNP toxicity but this is dependent on the biofluid component itself and the location where it acts. Copyright © 2015 John Wiley & Sons, Ltd.     

CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects

Aims

Ketamine analgesia is limited by low intrinsic efficacy compounded by large interindividual variability in drug responses, possibly due to the heterogeneity in drug concentration. The CYP2B6*6 allele is associated with substantially reduced ketamine metabolism in vitro and, therefore, may affect ketamine clearance. Our aims were to examine the impact of the CYP2B6*6 allele on ketamine plasma clearance and on adverse effects in chronic pain patients.

Methods

CYP2B6 genotypes were identified in 49 chronic pain patients who received 24 h continuous subcutaneous infusions of ketamine. Steady-state plasma concentrations of ketamine (C_ss,k) and norketamine (C_ss,nk) were determined using HPLC.

Results

The median plasma clearance of ketamine after 100 mg 24 h^–1 dose was significantly lower in patients with the CYP2B6*6/*6 (21.6 l h^–1) and CYP2B6*1/*6 (40.6 l h^–1) genotypes compared with patients with the CYP2B6*1/*1 genotype (68.1 l h^–1, P < 0.001). The ketamine : norketamine plasma metabolic ratio was significantly higher in patients with the CYP2B6*6/*6 genotype than in those with the CYP2B6*1/*6 and the CYP2B6*1/*1 genotypes (P < 0.001). Patients who experienced adverse effects had lower plasma clearance (45.6 l h^-1) than those who did not (52.6 l h^-1, P = 0.04). The CYP2B6*6 genotype and age, and their combined impact explained 40%, 30% and 60% of the variation in C_ss,k, respectively. Similar results were observed after higher doses.

Conclusions

The CYP2B6*6 allele is associated with a substantial decrease in steady-state ketamine plasma clearance in chronic pain patients. The decreased clearance and resultant higher plasma concentrations may be associated with a higher incidence of ketamine adverse effects.