Role of self-compassion in psychological well-being among perinatal women.

Self-compassion is associated with depression and anxiety in general samples. Although recent research indicates that dysfunctional maternal attitudes predict the development of perinatal depression and anxiety symptoms, no research to date has examined the construct of self-compassion and its relationship with psychological well-being in perinatal women. Pregnant and postpartum women (N = 189) completed self-report measures of depression and anxiety history, current depression and anxiety symptom severity, and self-compassion. Women with higher depression and anxiety symptom severity had significantly lower self-compassion. Additionally, women with self-reported prior history of depression or anxiety had significantly lower self-compassion even while controlling for current depression or anxiety symptom severity, respectively. Our results suggest that self-compassion warrants further attention in the study of the development, maintenance, and treatment of perinatal mood and anxiety disorders.

Nanoscale Mapping of the Magnetic Properties of (111)-Oriented La(0.67)Sr(0.33)MnO3.

Spatially resolved analysis of magnetic properties on the nanoscale remains challenging, yet strain and defects on this length-scale can profoundly affect a material's bulk performance. We present a detailed investigation of the magnetic properties of La0.67Sr0.33MnO3 thin films in both free-standing and nanowire form and assess the role of strain and local defects in modifying the films' magnetic properties. Lorentz transmission electron microscopy is used to measure the magnetocrystalline anisotropy and to map the Curie temperature and saturation magnetization with nanometric spatial resolution. Atomic-scale defects are identified as pinning sites for magnetic domain wall propagation. Measurement of domain wall widths and crystalline strain are used to identify a strong magnetoelastic contribution to the magnetic anisotropy. Together, these results provide unique insight into the relationship between the nanostructure and magnetic functionality of a ferromagnetic complex oxide film.

Medical Cannabis in Canadian Schools: A Scoping Review of Existing Policies.

Objective: An increasing number of children and youth in Canada are taking medical cannabis for complex medical conditions. While they deserve safe and consistent access to pharmacotherapy throughout the day, administrative policies on cannabis use in schools are inconsistent. A scoping review identified policies and publications associated with medical cannabis in Canadian schools. Methods: Five databases (Scopus, PubMed, CINAHL, EMBASE, and Web of Science) were searched to identify scientific literature. Legislation in each province and territory and Ministry of Education webpages were reviewed for pertinent laws and policies regarding cannabis use in schools. Results: The scientific search resulted in 1289 articles. The five included articles pertain to implications for school nurses in the United States, which are not relevant to the Canadian context. A search of Ministry of Education websites identified only one policy with information regarding medical cannabis in schools (from Ontario). Federal legislation (the Cannabis Act) does not specifically address medical cannabis in schools, and there is a lack of consistency in terminology and clarity within provincial and territorial laws. All provinces and territories prohibit smoking and vaping of cannabis on school property and some provinces prohibit any method of cannabis consumption. Conclusions: In Canada, there is a lack of guidance for medical cannabis administration, storage, and disposal in schools, with some policies explicitly prohibiting this type of treatment. This shifts the burden to families to individually create plans school by school. A federally harmonized approach to supporting children who take cannabis for medical purposes ought to be explored.

Self-guided behavioral skills training: A public health approach to promoting nurturing care environments.

The World Health Organization identified the promotion of "Nurturing Care Environments" as a global health priority. Responsive caregiving, 1 of 5 domains describing nurturing care, is critical for healthy child development. Relatively little research has evaluated population-level interventions aimed to increase responsive caregiving during the first 1,000 days of an infant's life. In this pilot study, we evaluated an intervention designed for population-level dissemination that targeted responsive caregiving. The self-guided behavioral skills training aimed to teach mothers to imitate infant vocalizations. The intervention was delivered within an on-line asynchronous training. All 3 mothers increased vocal imitative behavior following training without receiving coaching or behavior-specific feedback from an implementer. The results offer a preliminary proof of concept with implications for population-level intervention design and evaluation.

A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF.

Hepatocyte growth factor (HGF) is associated with tumour progression and increases the invasiveness of prostate carcinoma cells. Cell migration and invasion requires reorganisation of the actin cytoskeleton; processes mediated by the Rho family GTPases. p21 activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is activated downstream of HGF. We report here the novel finding that in prostate cancer cells PAK4 binds to and phosphorylates LIM kinase 1 (LIMK1) in an HGF-dependent manner. We show for the first time that variations in the level of PAK4 expression change the level of cofilin phosphorylation in cells, a change we correlate with LIMK1 activity, cell morphology and migratory behaviour. We identify for the first time a direct and localised interaction between PAK4 and LIMK1 within cells using FRET: FLIM. Moreover we show here that HGF mediates this interaction which is concentrated in small foci at the cell periphery. PAK4 and LIMK1 act synergistically to increase cell migration speed, whilst a reduction in PAK4 expression decreases cell speed. It is well established that unphosphorylated (active) cofilin is a required to drive cell migration. Our results support a model whereby HGF-stimulated cell migration also requires a cofilin phosphorylation step that is mediated by PAK4.

An assay to measure poly(ADP ribose) glycohydrolase (PARG) activity in cells.

After a DNA damage signal multiple polymers of ADP ribose attached to poly(ADP) ribose (PAR) polymerases (PARPs) are broken down by the enzyme poly(ADP) ribose glycohydrolase (PARG). Inhibition of PARG leads to a failure of DNA repair and small molecule inhibition of PARG has been a goal for many years. To determine whether biochemical inhibitors of PARG are active in cells we have designed an immunofluorescence assay to detect nuclear PAR after DNA damage. This 384-well assay is suitable for medium throughput high-content screening and can detect cell-permeable inhibitors of PARG from nM to µM potency. In addition, the assay has been shown to work in murine cells and in a variety of human cancer cells. Furthermore, the assay is suitable for detecting the DNA damage response induced by treatment with temozolomide and methylmethane sulfonate (MMS). Lastly, the assay has been shown to be robust over a period of several years.

ROCK1 and LIMK2 interact in spread but not blebbing cancer cells.

Cancer cells migrating within a 3D microenvironment are able to adopt either a mesenchymal or amoeboid mode of migration. Amoeboid migration is characterised by membrane blebbing that is dependent on the Rho effectors, ROCK1/2. We identify LIMK2 as the preferred substrate for ROCK1 but find that LIMK2 did not induce membrane blebbing, suggesting that a LIMK2 pathway is not involved in amoeboid-mode migration. In support of this hypothesis, novel FRET data demonstrate a direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells. Our results point to a specific role for the ROCK1:LIMK2 pathway in mesenchymal-mode migration.

Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport.

Charcot-Marie-Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system, and mutations in neurofilaments have been linked to some forms of CMT. Neurofilaments are the major intermediate filaments of neurones, but the mechanisms by which the CMT mutations induce disease are not known. Here, we demonstrate that CMT mutant neurofilaments disrupt both neurofilament assembly and axonal transport of neurofilaments in cultured mammalian cells and neurones. We also show that CMT mutant neurofilaments perturb the localization of mitochondria in neurones. Accumulations of neurofilaments are a pathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and diabetic neuropathy. Our results demonstrate that aberrant neurofilament assembly and transport can induce neurological disease, and further implicate defective neurofilament metabolism in the pathogenesis of human neurodegenerative diseases.