Teaching Psychotherapy to Psychiatric/Mental Health Nurse Practitioner Students in the Virtual Classroom.

The aim of this quality improvement project was to evaluate student satisfaction and achievement of select core competencies in psychotherapy by Psychiatric Mental Health Nurse Practitioner (PMHNP) students enrolled in a newly developed, and virtually delivered psychotherapy course. Both qualitative and quantitative data were collected to assess students' competencies in five domains (i.e. professionalism, cultural diversity, ethical/legal standards of care, reflective practices, and application of knowledge and skills) and satisfaction with content and delivery using simulation and virtual sessions. Using pre- and post-training surveys, we found that competencies in the five domains increased from an average score of 3.1 to 4.5. Integrating a virtual psychotherapy course in advanced nursing education, bringing PMHNP students together to learn about interviewing clients, applying various psychotherapeutic modalities and techniques across diverse cultures, and maintaining ethical and legal standards of care is a challenging but achievable endeavor. We found that using a version of an APA self-assessment tool that was used in psychiatric residency training programs was an effective way to assess PMHNP students' knowledge, skills, and attitudes on these core competencies. Although this training course proved to be effective in imparting appropriate skills, there is a need to develop sophisticated methods to evaluate how students use complex psychotherapy skills in the clinical setting.

Well-Defined Star-Shaped Polyglutamates with Improved Pharmacokinetic Profiles As Excellent Candidates for Biomedical Applications.

There is a need to develop new and innovative polymer carriers to be used as drug delivery systems and/or imaging agents owing to the fact that there is no universal polymeric system that can be used in the treatment of all diseases. Additionally, limitations with existing systems, such as a lack of biodegradability and biocompatibility, inevitably lead to side effects and poor patient compliance. New polymer therapeutics based on amino acids are excellent candidates for drug delivery, as they do not suffer from these limitations. This article reports on a simple yet powerful methodology for the synthesis of 3-arm star-shaped polyglutamic acid with well-defined structures, precise molecular weights (MW), and low polydispersity (D = <1.3). These were synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCA) in a divergent method from novel multifunctional initiators. Herein, their exhaustive physicochemical characterization is presented. Furthermore, preliminary in vitro evaluation in selected cell models, and exhaustive in vivo biodistribution and pharmacokinetics, highlighted the advantages of these branched systems when compared with their linear counterparts in terms of cell uptake enhancement and prolonged plasma half-life.

Mineralization dynamics in soil fertilized with seaweed-fish waste compost.

BACKGROUND: Seaweed and fish waste can be composted together to obtain fertilizer with high organic matter and nutrient contents. The nutrients, however, are mostly in organic form and must be mineralized to make them available to plants. The objective of this work was to establish a usage guideline for the compost by studying its mineralization dynamics. Also, the release of inorganic N and C from soil fertilized with the compost was monitored and modelled. RESULTS: C and N were released throughout the assay, to an extent significantly dependent on fertilizer rate. Mineralization of both elements fitted a first-order exponential model, and each fertilizer rate required using a specific fitting model. An increased rate favoured mineralization (especially of carbon). After 90 days, 2.3% of C and 7.7% of N were mineralized (and 23.3% of total nitrogen made plant available) with the higher rate. CONCLUSION: C mineralization was slow because organic matter in the compost was very stable. On the other hand, the relatively high initial content in mineral N of the compost increased gradually by the effect of mineralization. The amount of N available would suffice to meet the requirements of moderately demanding crops at the lower fertilizer rate, and even those of more demanding crops at the higher rate.

Clinical Interprofessional Education in Inpatient Pharmacy: Findings From a Secondary Analysis of a Scoping Review.

OBJECTIVES: Clinical interprofessional education (IPE) is defined as learning that occurs within clinical learning environments such as hospitals, primary care clinics, and long-term care facilities where learners collaborate to deliver care to real patients. The objective of this secondary analysis of a scoping review is to identify, characterize, and summarize evidence from the published literature regarding clinical IPE for pharmacy learners in the inpatient setting. FINDINGS: PubMed, CINAHL, and Scopus databases were searched for clinical IPE articles that met the following inclusion criteria: ≥ 2 health professions, ≥ 2 learner groups, and involvement of real patients/patient care. For this secondary analysis, 12 articles involving pharmacy learners in an inpatient setting were included. The most common interprofessional partner was medicine (66%), and the median number of student participants involved in the activity was 19 (range, 10-525). Five studies conducted clinical IPE in the context of advanced pharmacy practice experiences. Clinical IPE activities were described primarily as inpatient rounding with the medical team, but were often outside the normal clinical workflow (66%). Incorporation of Interprofessional Education Collaborative competencies was limited, as was the use of validated IPE assessment tools to measure outcomes. SUMMARY: Current literature is limited in reports of pharmacy learner involvement in inpatient clinical IPE. Expansion of pharmacy partnerships and alignment of team outcomes with the Interprofessional Education Collaborative competencies are needed to demonstrate the relationship between clinical IPE and patient care outcomes within established workflows.

Metronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells.

In this article, the effectiveness of a multi-targeted chemo-switch (C-S) schedule that combines metronomic chemotherapy (MET) after treatment with the maximum tolerated dose (MTD) is reported. This schedule was tested with gemcitabine in two distinct human pancreatic adenocarcinoma orthotopic models and with cyclophosphamide in an orthotopic ovarian cancer model. In both models, the C-S schedule had the most favourable effect, achieving at least 80% tumour growth inhibition without increased toxicity. Moreover, in the pancreatic cancer model, although peritoneal metastases were observed in control and MTD groups, no dissemination was observed in the MET and C-S groups. C-S treatment caused a decrease in angiogenesis, and its effect on tumour growth was similar to that produced by the MTD followed by anti-angiogenic DC101 treatment. C-S treatment combined an increase in thrombospondin-1 expression with a decrease in the number of CD133+ cancer cells and triple-positive CD133+/CD44+/CD24+ cancer stem cells (CSCs). These findings confirm that the C-S schedule is a challenging clinical strategy with demonstrable inhibitory effects on tumour dissemination, angiogenesis and CSCs.

The long-term effects of adolescent Δ9-tetrahydrocannabinol on brain structure and function assessed through neuroimaging techniques in male and female rats.

Several studies performed on human subjects have examined the effects of adolescent cannabis consumption on brain structure or function using brain imaging techniques. However, the evidence from these studies is usually heterogenous and affected by several confounding variables. Animal models of adolescent cannabinoid exposure may help to overcome these difficulties. In this exploratory study, we aim to increase our understanding of the protracted effects of adolescent Δ9-tetrahydrocannabinol (THC) in rats of both sexes using magnetic resonance (MR) to obtain volumetric data, assess grey and white matter microstructure with diffusion tensor imaging (DTI) and measure brain metabolites with 1H-MR spectroscopy (MRS); in addition, we studied brain function using positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose as the tracer. THC-exposed rats exhibited volumetric and microstructural alterations in the striatum, globus pallidus, lateral ventricles, thalamus, and septal nuclei in a sex-specific manner. THC administration also reduced fractional anisotropy in several white matter tracts, prominently in rostral sections, while in vivo MRS identified lower levels of cortical choline compounds. THC-treated males had increased metabolism in the cerebellum and olfactory bulb and decreased metabolism in the cingulate cortex. By contrast, THC-treated females showed hypermetabolism in a cluster of voxels comprising the entorhinal piriform cortices and in the cingulate cortex. These results indicate that mild THC exposure during adolescence leaves a lingering mark on brain structure and function in a sex-dependant manner. Some of the changes found here resemble those observed in human studies and highlight the importance of studying sex-specific effects in cannabinoid research.

Interaction between maternal immune activation and peripubertal stress in rats: impact on cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome.

Substance use disorders are more prevalent in schizophrenia, but the causal links between both conditions remain unclear. Maternal immune activation (MIA) is associated with schizophrenia which may be triggered by stressful experiences during adolescence. Therefore, we used a double-hit rat model, combining MIA and peripubertal stress (PUS), to study cocaine addiction and the underlying neurobehavioural alterations. We injected lipopolysaccharide or saline on gestational days 15 and 16 to Sprague-Dawley dams. Their male offspring underwent five episodes of unpredictable stress every other day from postnatal day 28 to 38. When animals reached adulthood, we studied cocaine addiction-like behaviour, impulsivity, Pavlovian and instrumental conditioning, and several aspects of brain structure and function by MRI, PET and RNAseq. MIA facilitated the acquisition of cocaine self-administration and increased the motivation for the drug; however, PUS reduced cocaine intake, an effect that was reversed in MIA + PUS rats. We found concomitant brain alterations: MIA + PUS altered the structure and function of the dorsal striatum, increasing its volume and interfering with glutamatergic dynamics (PUS decreased the levels of NAA + NAAG but only in LPS animals) and modulated specific genes that could account for the restoration of cocaine intake such as the pentraxin family. On its own, PUS reduced hippocampal volume and hyperactivated the dorsal subiculum, also having a profound effect on the dorsal striatal transcriptome. However, these effects were obliterated when PUS occurred in animals with MIA experience. Our results describe an unprecedented interplay between MIA and stress on neurodevelopment and the susceptibility to cocaine addiction.

Clinical interprofessional education in the health professions: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to identify, characterize, and summarize evidence from the published literature on clinical interprofessional education. INTRODUCTION: Clinical interprofessional education refers to learning within clinical learning environments, such as hospitals, primary care clinics, and long-term care facilities. The learning involves direct interaction with real patients, where learners collaborate to deliver care and improve health outcomes. INCLUSION CRITERIA: This scoping review will consider clinical interprofessional education activities in the context of patient care. Criteria include two or more health professions, two or more learner groups, and involvement of real patients/patient care. METHODS: This review will be conducted in accordance with the JBI methodology for scoping reviews. Databases searched will include PubMed, CINAHL, and Scopus. Results will be limited to English language publications from 2015 to the present. Extracted data will include the different types of clinical learning environments, the professions involved, the targeted learning/competency outcomes, and the measurement tools used by the authors. Titles/abstracts and full texts of articles will be screened by two reviewers for potential inclusion, with discrepancies resolved by a third reviewer if necessary. Extracted data will be presented in diagrammatic or tabular format. A narrative summary will accompany the tabulated and/or charted results, describing how the results relate to the review objective and research questions, and how the results might inform future clinical interprofessional education in health professions education.

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

BACKGROUND: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. METHODS: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). RESULTS: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. CONCLUSIONS: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.

Using methylome data to inform exposome-health association studies: An application to the identification of environmental drivers of child body mass index.

BACKGROUND: The exposome is defined as encompassing all environmental exposures one undergoes from conception onwards. Challenges of the application of this concept to environmental-health association studies include a possibly high false-positive rate. OBJECTIVES: We aimed to reduce the dimension of the exposome using information from DNA methylation as a way to more efficiently characterize the relation between exposome and child body mass index (BMI). METHODS: Among 1,173 mother-child pairs from HELIX cohort, 216 exposures ("whole exposome") were characterized. BMI and DNA methylation from immune cells of peripheral blood were assessed in children at age 6-10 years. A priori reduction of the methylome to preselect BMI-relevant CpGs was performed using biological pathways. We then implemented a tailored Meet-in-the-Middle approach to identify from these CpGs candidate mediators in the exposome-BMI association, using univariate linear regression models corrected for multiple testing: this allowed to point out exposures most likely to be associated with BMI ("reduced exposome"). Associations of this reduced exposome with BMI were finally tested. The approach was compared to an agnostic exposome-wide association study (ExWAS) ignoring the methylome. RESULTS: Among the 2284 preselected CpGs (0.6% of the assessed CpGs), 62 were associated with BMI. Four factors (3 postnatal and 1 prenatal) of the exposome were associated with at least one of these CpGs, among which postnatal blood level of copper and PFOS were directly associated with BMI, with respectively positive and negative estimated effects. The agnostic ExWAS identified 18 additional postnatal exposures, including many persistent pollutants, generally unexpectedly associated with decreased BMI. DISCUSSION: Our approach incorporating a priori information identified fewer significant associations than an agnostic approach. We hypothesize that this smaller number corresponds to a higher specificity (and possibly lower sensitivity), compared to the agnostic approach. Indeed, the latter cannot distinguish causal relations from reverse causation, e.g. for persistent compounds stored in fat, whose circulating level is influenced by BMI.

Leaching techniques for saline wastes composts used as growing media in organic agriculture: assessment and modelling.

The purpose of this work was to examine solute release by the effect of leaching of a saline compost with two main objectives: (1) to identify the most efficient method for this purpose, in order to minimize the environmental impact of this process in terms of water consumption and (2) to study the composition of the leachates to manage them properly and avoid possible contamination. A laboratory method involving column leaching with distilled water (CL) and two field methods involving saturation leaching (SL) and drip leaching (DL) were compared to this end. In order to more accurately assess nutrient release and compare the three leaching techniques, the cumulative amounts of ions leached were processed by using an exponential growth model. All target ions fitted properly, and so did the curve for the ions as a whole. Salts were removed mainly by effect of the leaching of major ions in the substrate (Na(+), Cl(-), inorganic N, SO4 (2-) and K(+)). SL and CL proved similarly efficient and reduced the salt content of the substrate to an electrical conductivity below 2 dS m(-1) in the saturation extract, which is the optimum level for nursery crops. By contrast, the DL method provided poor results: salt contents were reduced to an electrical conductivity of only 8 dS m(-1) in the saturation extract, so the resulting substrate can only be useful to grow highly salt-tolerant crops.

Polymer-doxycycline conjugates as fibril disrupters: an approach towards the treatment of a rare amyloidotic disease.

The term amyloidosis describes neurological diseases where an abnormal protein is misfolded and accumulated as deposits in organs and tissues, known as amyloid, disrupting their normal function. In the most common familial amyloid polyneuropathy (FAP), transthyretin (TTR) displays this role primarily affecting the peripheral nervous system (PNS). Advanced stages of this inherited rare amyloidosis, present as fibril deposits that are responsible for disease progression. In order to stop disease progression, herein we designed an efficient family of nanoconjugates as fibril disrupters. These polymer conjugates are based on doxycycline (doxy), already in phase II trials for Alzheimer's disease, covalently linked to poly-l-glutamic acid (PGA). The conjugates were rationally designed, looking at drug loading and drug release rate by adequate linker design, always considering the physiological conditions at the molecular target site. Conjugation of doxycycline exhibited greater potential towards TTR fibril disaggregation in vitro compared to the parent drug. Exhaustive physico-chemical evaluation of these polymer-drug conjugates concluded that drug release was unnecessary for activity, highlighting the importance of an appropriate linker. Furthermore, biodistribution studies through optical imaging (OI) and the use of radiolabelled polymer-drug conjugates demonstrated conjugate safety profile and renal clearance route of the selected PGA-doxy candidate, settling the adequacy of our conjugate for future in vivo evaluation. Furthermore, preliminary studies in an FAP in vivo model at early stages of disease development showed non-organ toxicity evidences. This nanosized-system raises a promising treatment for advanced stages of this rare amyloidotic disease, and also presents a starting point for possible application within other amyloidosis-related diseases, such as Alzheimer's disease.