Parenting in a time of COVID-19 Cluver, Lucie; Lachman, Jamie M; Sherr, Lorraine ...
The Lancet (British edition),
04/2020, Letnik:
395, Številka:
10231
Journal Article
Epithelial-mesenchymal transition (EMT) occurs during embryonic development and may also be associated with the metastatic spread of epithelial tumors. During EMT, E-cadherin is down-regulated and ...this correlates with increased motility and invasion of cells. We show that differentiation of human embryonic stem (ES) cells in monolayer culture is associated with an E- to N-cadherin switch, increased vimentin expression, up-regulation of E-cadherin repressor molecules (Snail and Slug proteins), and increased gelatinase (matrix metalloproteinases; MMP-2 and MMP-9) activity and cellular motility, all characteristic EMT events. The 5T4 oncofetal antigen, previously shown to be associated with early human ES cell differentiation, is also part of this process. Abrogation of E-cadherin-mediated cell-cell contact in undifferentiated ES cells using neutralizing antibody (nAb) SHE78.7 resulted in increased cellular motility, altered actin cytoskeleton arrangement and a mesenchymal phenotype together with presentation of the 5T4 antigen at the cell surface. nAb-treated ES cells remained in an undifferentiated state, as assessed by OCT-4 protein expression, and did not express EMT-associated transcripts. Removal of nAb from ES cells resulted in the restoration of cell-cell contact, absence of cell surface 5T4, decreased mesenchymal cellular morphology and motility, and enabled the differentiation of the cells to the three germ layers upon their removal from the fibroblast feeder layer. We conclude that E-cadherin functions in human ES cells to stabilize the cortical actin cyoskeletal arrangement and this prevents cell surface localization of the 5T4 antigen. Furthermore, human ES cells represent a useful model system with which to study EMT events relevant to embryonic development and tumor cell metastasis.
We aimed to complete a nationally representative study of sexual violence against children in South Africa, and its correlates, since we could identify no other such study.
For this nationally ...representative, cross-sectional study in South Africa, households were selected by use of a multistage sampling frame, stratified by province, urban or rural setting, and race group, and schools were selected on the basis that they were closest to the area in which households were selected. Interviews and self-administered questionnaires in each location inquired into lifetime and last-year prevalence of sexual abuse, and its correlates among children aged 15–17 years, whose parents gave informed consent and they themselves gave informed assent.
The final household sample was 5631 (94·6% participation rate). 9·99% (95% CI 8·65–11·47) of boys and 14·61% (95% CI 12·83–16·56) of girls reported some lifetime sexual victimisation. Physical abuse, emotional abuse, neglect, family violence, and other victimisations were all strongly associated with sexual victimisation. The following were associated with greater risk of sexual abuse (adjusted odds ratio OR); school enrolment (OR 2·12, 95% CI 1·29–3·48); rural dwelling (0·59; 0·43–0·80); having a flush toilet (1·43, 1·04–1·96); parental substance misuse (2·37, 1·67–3·36); being disabled (1·42, 1·10–1·82); female (but not male) caregivers' poor knowledge of the child's whereabouts, friends, and activities (1·07, 0·75–1·53) and poor quality of the relationship with the child (ie, poor acceptance; 1·20, 0·55–2·60). The child's own substance misuse (4·72, 3·73–5·98) and high-risk sexual behaviour (3·71, 2·99–4·61) were the behaviours most frequently associated with sexual abuse, with mental health conditions found to be less prevalent than these factors but still strongly associated with sexual victimisation (post-traumatic stress disorder 2·81, 1·65–4·78; depression 3·43, 2·26–5·19; anxiety 2·48, 1·61–3·81).
Sexual violence is widespread among both girls and boys, and is associated with serious health problems. Associated factors require multisectoral responses to prevent sexual violence or mitigate consequences.
UBS Optimus Foundation.
Many children across the world are exposed to school violence, which undermines their right to education and adversely affects their development. Studies of interventions for school violence suggest ...that it can be prevented. However, this evidence base is challenging to navigate. We completed a systematic review of interventions to reduce four types of school violence: (a) peer violence; (b) corporal punishment; (c) student-on-teacher violence and (d) teacher-on-student violence. Reviewers independently searched databases and journals. Included studies were published between 2005 and 2015; in English; considered school-based interventions for children and measured violence as an outcome. Many systematic reviews were found, thus we completed a systematic review of systematic reviews. Only systematic reviews on interventions for intimate partner violence (IPV) and peer aggression were found. These reviews were generally of moderate quality. Research on both types of violence was largely completed in North America. Only a handful of programmes demonstrate promise in preventing IPV. Cognitive behavioral, social-emotional and peer mentoring/mediation programmes showed promise in reducing the levels of perpetration of peer aggression. Further research needs to determine the long-term effects of interventions, potential moderators and mediators of program effects, program effects across different contexts and key intervention components.
Training in non-violent discipline is important to prevent violence against children and ensure that their caregivers remain a safe base for them. This paper aims to deepen understanding of ...non-violent discipline by exploring attunement as a mechanism in the effectiveness of non-violent discipline tools. Attunement describes the sensitive responsiveness of caregivers towards their children and has been found to be central to the formation of secure attachment bonds and development of self-regulation. It includes understanding or being "in tune with" the child's needs and signals, matching these with appropriate responses. The objective of this paper is to explore attunement in relation to non-violent discipline. Peer-reviewed systematic reviews previously included in a systematic overview of evidence on non-violent discipline options were screened for information relevant to attunement. All reviews were published in English between 1999 and 2018 and offered evidence on at least one non-violent discipline tool. Although no reviews explicitly addressed attunement, evidence was found suggesting its importance in the use and effectiveness of discipline methods. Research directly investigating attunement in discipline is needed.
We have recently shown that loss of E-cadherin in mouse embryonic stem cells (mESCs) results in significant alterations to both the transcriptome and hierarchy of pluripotency-associated signaling ...pathways. Here, we show that E-cadherin promotes kruppel-like factor 4 (Klf4) and Nanog transcript and protein expression in mESCs via STAT3 phosphorylation and that β-catenin, and its binding region in E-cadherin, is required for this function. To further investigate the role of E-cadherin in leukemia inhibitory factor (LIF)-dependent pluripotency, E-cadherin null (Ecad(-/-)) mESCs were cultured in LIF/bone morphogenetic protein supplemented medium. Under these conditions, Ecad(-/-) mESCs exhibited partial restoration of cell-cell contact and STAT3 phosphorylation and upregulated Klf4, Nanog, and N-cadherin transcripts and protein. Abrogation of N-cadherin using an inhibitory peptide caused loss of phospho STAT3, Klf4, and Nanog in these cells, demonstrating that N-cadherin supports LIF-dependent pluripotency in this context. We therefore identify a novel molecular mechanism linking E- and N-cadherin to the core circuitry of pluripotency in mESCs. This mechanism may explain the recently documented role of E-cadherin in efficient induced pluripotent stem cell reprogramming.
Background
Parenting programs suitable for delivery at scale in low‐resource contexts are urgently needed. We conducted a randomized trial of Parenting for Lifelong Health (PLH) for Young Children, a ...low‐cost 12‐session program designed to increase positive parenting and reduce harsh parenting and conduct problems in children aged 2–9.
Methods
Two hundred and ninety‐six caregivers, whose children showed clinical levels of conduct problems (Eyberg Child Behavior Inventory Problem Score, >15), were randomly assigned using a 1:1 ratio to intervention or control groups. At t0, and at 4–5 months (t1) and 17 months (t2) after randomization, research assistants blind to group assignment assessed (through caregiver self‐report and structured observation) 11 primary outcomes: positive parenting, harsh parenting, and child behavior; four secondary outcomes: parenting stress, caregiver depression, poor monitoring/supervision, and social support. Trial registration: ClinicalTrials.gov (NCT02165371); Pan African Clinical Trial Registry (PACTR201402000755243); Violence Prevention Trials Register (http://www.preventviolence.info/Trials?ID=24).
Results
Caregivers attended on average 8.4 sessions. After adjustment for 30 comparisons, strongest results were as follows: at t1, frequency of self‐reported positive parenting strategies (10% higher in the intervention group, p = .003), observed positive parenting (39% higher in the intervention group, p = .003), and observed positive child behavior (11% higher in the intervention group, p = .003); at t2, both observed positive parenting and observed positive child behavior were higher in the intervention group (24%, p = .003; and 17%, p = .003, respectively). Results with p‐values < .05 prior to adjustment were as follows: At t1, the intervention group self‐reported 11% fewer child problem behaviors, 20% fewer problems with implementing positive parenting strategies, and less physical and psychological discipline (28% and 14% less, respectively). There were indications that caregivers reported 20% less depression but 7% more parenting stress at t1. Group differences were nonsignificant for observed negative child behavior, and caregiver‐reported child behavior, poor monitoring or supervision, and caregiver social support.
Conclusions
PLH for Young Children shows promise for increasing positive parenting and reducing harsh parenting.
Read the Commentary on this article at doi: 10.1111/jcpp.13172
Volumetric muscle loss (VML) injuries are prevalent in civilian and military trauma patients and are known to impart chronic functional deficits. The frank loss of muscle tissue that defines VML ...injuries is beyond the robust reparative and regenerative capacities of mammalian skeletal muscle. Given the nature of VML injuries, there is a clear need to develop therapies that promote de novo regeneration of skeletal muscle fibers, which can integrate with the remaining musculature and restore muscle strength. However, the pathophysiology of VML injuries is not completely defined, and, therefore, there may be other opportunities to improve functional outcomes other than de novo regeneration. Herein, clinical and preclinical studies of VML were reviewed to ascertain salient manifestations of VML injury that can impair limb function and muscle strength. The limited clinical data available highlighted proliferative fibrosis secondary to VML injury as a viable target to improve limb range of motion. Selected preclinical studies that used standardized neuromuscular functional assessments broadly identified that the muscle mass remaining after VML injury is performing suboptimally, and, therefore, percent VML strength deficits are significantly worse than can be explained by the initial frank loss of contractile machinery. Potential mechanisms of suboptimal strength of the remaining muscle mass suggested within the literature include intramuscular nerve damage, muscle architectural perturbations, and diminished transmission of force. Collectively, both clinical and preclinical data indicate a complex pathophysiology after VML that presents multiple therapeutic targets. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel.
Volumetric muscle loss (VML) is a traumatic and functionally debilitating muscle injury with limited treatment options. Developmental regenerative therapies for the repair of VML typically comprise ...an ECM scaffold. In this study, we tested if the complete reliance on host cell migration to a devitalized muscle scaffold without myogenic cells is sufficient for de novo muscle fiber regeneration. Devitalized (muscle ECM with no living cells) and, as a positive control, vital minced muscle grafts were transplanted to a VML defect in the tibialis anterior muscle of Lewis rats. Eight weeks post-injury, devitalized grafts did not appreciably promote de novo muscle fiber regeneration within the defect area, and instead remodeled into a fibrotic tissue mass. In contrast, transplantation of vital minced muscle grafts promoted de novo muscle fiber regeneration. Notably, pax7+ cells were absent in remote regions of the defect site repaired with devitalized scaffolds. At 2 weeks post-injury, the devitalized grafts were unable to promote an anti-inflammatory phenotype, while vital grafts appeared to progress to a pro-regenerative inflammatory response. The putative macrophage phenotypes observed in vivo were supported in vitro, in which soluble factors released from vital grafts promoted an M2-like macrophage polarization, whereas devitalized grafts failed to do so. These observations indicate that although the remaining muscle mass serves as a source of myogenic cells in close proximity to the defect site, a devitalized scaffold without myogenic cells is inadequate to appreciably promote de novo muscle fiber regeneration throughout the VML defect.
Child abuse prevention research has been hampered by a lack of validated multi-dimensional non-proprietary instruments, sensitive enough to measure change in abuse victimization or behavior. This ...study aimed to adapt the ICAST child abuse self-report measure (parent and child) for use in intervention studies and to investigate the psychometric properties of this substantially modified tool in a South African sample. First, cross-cultural and sensitivity adaptation of the original ICAST tools resulted in two preliminary measures (ICAST-Trial adolescents: 27 items, ICAST-Trial caregivers: 19 items). Second, ICAST-Trial data from a cluster randomized trial of a parenting intervention for families with adolescents (N = 1104, 552 caregiver-adolescent dyads) was analyzed. Confirmatory factor analysis established the hypothesized 6-factor (adolescents) and 4-factor (caregivers) structure. Removal of two items for adolescents and five for caregivers resulted in adequate model fit. Concurrent criterion validity analysis confirmed hypothesized relationships between child abuse and adolescent and caregiver mental health, adolescent behavior, discipline techniques and caregiver childhood abuse history. The resulting ICAST-Trial measures have 25 (adolescent) and 14 (caregiver) items respectively and measure physical, emotional and contact sexual abuse, neglect (both versions), and witnessing intimate partner violence and sexual harassment (adolescent version). The study established that both tools are sensitive to measuring change over time in response to a parenting intervention. The ICAST-Trial should have utility for evaluating the effectiveness of child abuse prevention efforts in similar socioeconomic contexts. Further research is needed to replicate these findings and examine cultural appropriateness, barriers for disclosure, and willingness to engage in child abuse research.
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