Predictors of Therapists Use of Homework in Community Mental Health: Session and Therapist Characteristics

Assigning and reviewing homework as a strategy to help clients gain therapeutic skills is a common technique used across a variety of evidence-based practices (EBPs) and has been shown to improve therapy outcomes for children and youth. However, in studies characterizing routine psychotherapy delivered in community mental health settings, homework is rarely used in sessions. While some therapist and client level predictors of EBP strategy use have been identified in routine psychotherapy (e.g. client stressors, therapists’ attitudes towards EBPs) it is unknown what is associated with community mental health therapists using homework in the increasingly common context of system-driven implementation of multiple EBPs. To identify predictors of therapists’ use of homework, 680 videos of sessions with 274 clients were collected from 103 therapists (of which 55% were Hispanic) providing children’s mental health services through the Los Angeles County Department of Mental Health (LACDMH). The current study uses a multilevel logistic regression analysis model to identify which factors are associated with therapist use of homework in therapy sessions when there is system-driven implementation support for the use of multiple EBPs in community mental health settings. After controlling for the EBP delivered in session and the number of EBPs therapists were trained in, having a caregiver present in the therapy session, older child age, and being an unlicensed therapist were associated with a higher likelihood of therapists assigning and reviewing homework during a specific session. Therapist race/ethnicity, perceptions of the EBP being delivered, their report of emotional exhaustion, and direct hours with clients, as well as emergent unexpected stressful client life events within a session were not significantly associated with therapists’ delivery of homework. These findings underscore the need to provide explicit attention during therapist training on the use of homework with younger clients when caregivers are absent from sessions and the need to facilitate the use of homework among licensed therapists

Feminization of male mouse liver by continuous growth hormone infusion or loss of EZH1/2: activation of sex-biased transcriptional networks and dynamic changes in chromatin states

The sex-dependent pituitary growth hormone (GH) secretory profiles, pulsatile in males and persistent in females, regulate sex-biased expression of hundreds of genes in mammalian liver, contributing to sex differences in hepatic metabolism and disease. The sex-biased GH actions in the liver are mediated by STAT5b and enhanced by a network of transcription factors including the male-biased BCL6 and the female-specific CUX2, acting in the context of sex-biased chromatin states. First, the transcriptional and epigenomic changes induced by continuous-GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity, were examined. RNA-seq analysis determined that cGH repressed the majority of male-biased genes and induced most female-biased genes within 4-days; however, several highly female-specific genes showed partial feminization. Female-biased genes already in an active chromatin state in male liver were induced early; genes in an inactive chromatin state often responded late. Early cGH-responsive genes included Cux2 and Bcl6 and their targets. DNase-seq and ChIP-seq were used to identify changes in sex-specific chromatin accessibility and histone modifications accompanying these cGH-induced gene expression changes. H3-K27me3 is a key sex-biased repressive mark found preferentially at highly female-biased genes in male mouse liver. Consistently, induction of female-biased genes by cGH was associated with loss of H3-K27me3 at their gene bodies. H3K27 methylation is catalyzed by Polycomb Repressive Complex-2 (PRC2) through its homologous catalytic subunits EZH1 and EZH2. An Ezh1-knockout mouse model with a hepatocyte-specific knockout of Ezh2 (DKO) was used to further investigate the role of H3-K27me3 in repressing sex-biased genes in mouse liver. Loss of Ezh1/Ezh2 led to a significant decrease in sex-specific gene expression, with many female-biased genes induced and male-biased genes repressed. These gene responses were more extensive in male than female liver, as was the loss of H3K27me3 sites and the reciprocal increases in active histone marks. There was substantial up-regulation of liver cancer and liver fibrosis-related genes in male and female DKO-mouse liver, with a subset of genes preferentially up-regulated in females. Thus, GH regulated sex-biased liver physiology is dictated by transcription factors arranged in a hierarchical network and by dynamic sex-biased epigenetic states.2020-06-12T00:00:00

In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction

Background: A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R) was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown. Methods. We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's horn and in premotor cortex in rats. Results: Patient's CSF increased the concentrations of glutamate in the extracellular space. The increase was dose-dependent and was dramatic with purified IgG. Patients' CSF impaired both the NMDA- and the AMPA-mediated synaptic regulation of glutamate, and did not affect the glial transport of glutamate. Blockade of GABA-A receptors was associated with a marked elevation of extra-cellular levels of glutamate following a pretreatment with patients' CSF. Conclusion: These results support a direct role of NMDA-R antibodies upon altering glutamatergic transmission. Furthermore, we provide additional evidence in vivo that NMDA-R antibodies deregulate the glutamatergic pathways and that the encephalitis associated with these antibodies is an auto-immune synaptic disorder. © 2010 Manto et al; licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cellular Senescence in Livers from Children with End Stage Liver Disease

Senescent cells occur in adults with cirrhotic livers independent of the etiology. Aim: Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease. staining occurred in the areas of ductular transformation and in the interlobular bile ducts.Cellular senescence in livers of children with end stage disease is associated with damage rather than corresponding to an age dependent phenomenon. Further studies are needed to support the hypothesis that these senescence markers correlate with disease progression

Adaptation of High-Throughput Screening in Drug Discovery—Toxicological Screening Tests

High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound’s toxicity having only 1–3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study

Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice

Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrPC, efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrPC selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrPSc and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories

Neuromuscular changes and the rapid adaptation following a bout of damaging eccentric exercise

An initial bout of eccentric exercise is known to protect against muscle damage following a repeated bout of the same exercise, however, the neuromuscular adaptions owing to this phenomenon are unknown. Aim: To determine if neuromuscular disturbances are modulated following a repeated bout of eccentric exercise. Methods: Following eccentric exercise performed with the elbow-flexors, we measured maximal voluntary force, resting twitch force, muscle soreness, creatine kinase and voluntary activation using motor point and motor cortex stimulation at baseline, immediately post and at 1, 2, 3, 4 and 7 days post-exercise on two occasions, separated by 3 weeks. Results: Significant muscle damage and fatigue was evident following the first exercise bout; maximal voluntary contraction was reduced immediately by 32% and remained depressed at 7 days post-exercise. Soreness and creatine kinase release peaked at 3 and 4 days post-exercise, respectively. Resting twitch force remained significantly reduced at 7 days (−48%) whilst voluntary activation measured with motor point and motor cortex stimulation was reduced until 2 and 3 days, respectively. A repeated bout effect was observed with attenuated soreness and creatine kinase release and a quicker recovery of maximal voluntary contraction and resting twitch force. A similar decrement in voluntary activation was observed following both bouts; however, following the repeated bout there was a significantly smaller reduction in, and a faster recovery of voluntary activation measured using motor cortical stimulation. Conclusion: Our data suggest that the repeated bout effect may be explained, partly, by a modification in motor corticospinal drive

Nutrition for the ageing brain: towards evidence for an optimal diet

As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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