The Impact of Patients and Student Mental Health Nurses Sharing Time Together in Forensic Units.

ABSTRACT: Student mental health nurses have greater patient contact than registered nurses, and this is appreciated by patients. This phenomenological study explored the impact of patients and student mental health nurses' time shared on forensic units for men carrying a personality disorder diagnosis. Phenomenology was the underpinning philosophy of this research. Patients and student mental health nurses in forensic hospitals participated in unstructured hermeneutic interviews. The time students and patients shared together was considered a gift, enabling them to feel that they were "just people" and valued, strongly impacting on their sense of person. The impact the students have on patients' quality of life is meaningful. When the students and patients connected, it had powerful implications for their sense of humanness and value, highlighting the reciprocal impact they each have on another and the importance of having student nurse clinical placements in forensic wards and facilities.Implications for Clinical Forensic Nursing Practice: This article offers a unique contribution to forensic practice by exploring the experiences of the time patients and students share together in forensic units. Students, who often have the greatest contact with patients, represent the present and future of nursing, and their time is appreciated by patients. Previous research focuses on attitudes and therapeutic relationships, rather than the impact of shared contact. In addition to this, patients in forensic services with personality disorder diagnoses can be the most stigmatized group in mental health care, and exploration of their experiences is lacking. These experiences must be shared.

Clinical utility of DNA methylation profiling for choroid plexus tumors.

Background: Choroid plexus tumors (CPTs) are rare, potentially aggressive CNS tumors with defined histologic criteria for grading. In recent years, several patients within our practice have demonstrated discordance between the histologic diagnosis and clinical behavior. DNA methylation profiling has emerged as a potential diagnostic adjunct for aiding the clinical approach. Methods: We reviewed the clinical and pathologic data of all CPTs diagnosed at Boston Children's Hospital from 1995 to 2023. All cases with available material (38/48) underwent DNA methylation profiling at NIH/NCI, and the classifier results were correlated with the WHO histologic grade and patient outcomes. Survival information was analyzed using Kaplan-Meier curves. Results: There was good correlation (11/12, 92%) between methylation class and WHO histologic grade for choroid plexus carcinomas (CPC); one histologic CPC grouped with choroid plexus papilloma (CPP) group pediatric (P). Five CPPs grouped with methylation class CPC (5/17, 29%). In the group of atypical CPPs (n = 9), there were two that grouped with methylation class CPC. Survival analysis showed utility of methylation classes in the prediction of biologic behavior. Conclusions: Results indicated that methylation profiling may serve as a valuable tool in the clinical decision-making process for patients with CPTs, providing additional prognostic information compared to WHO histologic grade alone. The value of methylation array analysis is particularly important given the lack of consensus on treatment regimens for CPTs.

Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer.

To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children's Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.

A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients.

BACKGROUND: The frequency and significance of IDH mutations in glioma across age groups is incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes. METHODS: Clinical, histologic, and sequencing data from patients with IDH-mutant, grade 2-4 gliomas, were collected from collaborating institutions between 2013-2019. Patients were categorized as pediatric (<19y), YA (19-39y) or older adult (≥40y). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine association of age and other covariates with overall (OS) and progression-free survival (PFS). RESULTS: We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS. CONCLUSIONS: IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approach varied significantly by patient age and warrant further study as addressable age-associated outcome drivers.

Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ.

Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1ß (IL-1ß), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1ß concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.

Heat and desiccation tolerances predict bee abundance under climate change.

Climate change could pose an urgent threat to pollinators, with critical ecological and economic consequences. However, for most insect pollinator species, we lack the long-term data and mechanistic evidence that are necessary to identify climate-driven declines and predict future trends. Here we document 16 years of abundance patterns for a hyper-diverse bee assemblage1 in a warming and drying region2, link bee declines with experimentally determined heat and desiccation tolerances, and use climate sensitivity models to project bee communities into the future. Aridity strongly predicted bee abundance for 71% of 665 bee populations (species × ecosystem combinations). Bee taxa that best tolerated heat and desiccation increased the most over time. Models forecasted declines for 46% of species and predicted more homogeneous communities dominated by drought-tolerant taxa, even while total bee abundance may remain unchanged. Such community reordering could reduce pollination services, because diverse bee assemblages typically maximize pollination for plant communities3. Larger-bodied bees also dominated under intermediate to high aridity, identifying body size as a valuable trait for understanding how climate-driven shifts in bee communities influence pollination4. We provide evidence that climate change directly threatens bee diversity, indicating that bee conservation efforts should account for the stress of aridity on bee physiology.

Clicked BODIPY-Fullerene-Peptide Assemblies: Studies of Electron Transfer Processes in Self-Assembled Monolayers on Gold Surfaces.

Two BODIPY-C60-peptide assemblies were synthesized by CuAAC reactions of BODIPY-C60 dyads and a helical peptide functionalized with a terminal alkyne group and an azide group, respectively. The helical peptide within these assemblies was functionalized at its other end by a disulfide group, allowing formation of self-assembled monolayers (SAMs) on gold surfaces. Characterizations of these SAMs, as well as those of reference molecules (BODIPY-C60-alkyl, C60-peptide and BODIPY-peptide), were carried out by PM-IRRAS and cyclic voltammetry. BODIPY-C60-peptide SAMs are more densely packed than BODIPY-C60-alkyl and BODIPY-peptide based SAMs. These findings were attributed to the rigid peptide helical conformation along with peptide-peptide and C60-C60 interactions within the monolayers. However, less dense monolayers were obtained with the target assemblies compared to the C60-peptide, as the BODIPY entity likely disrupts organization within the monolayers. Finally, electron transfer kinetics measurements by ultra-fast electrochemistry experiments demonstrated that the helical peptide is a better electron mediator in comparison to alkyl chains. This property was exploited along with those of the BODIPY-C60 dyads in a photo-current generation experiment by converting the resulting excited and/or charge separated states from photo-illumination of the dyad into electrical energy.

Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma.

PURPOSE: There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population. EXPERIMENTAL DESIGN: In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting. RESULTS: 5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA. CONCLUSIONS: These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.

Care giving and receiving for people with complex emotional needs within a crisis resolution/home treatment setting: A qualitative evidence synthesis.

WHAT IS KNOWN ON THE SUBJECT?: The term 'complex emotional needs' (CEN) is used here to describe people with difficulties and needs that are often associated with the diagnostic label of 'personality disorder'. People with CEN might use out of hours services such as emergency departments and Crisis Resolution/Home Treatment (CRHT) teams more often when experiencing a mental health crisis. Very little is understood about the experiences of both those receiving, and those delivering care, for people with CEN within CRHT settings. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: There are differences between priorities for those delivering and those receiving care within CRHT settings. CRHT staff members are likely to focus more upon those aspects of their role relating to risk issues. managing resources, anxieties and the expectations of others. Service users, meanwhile, focus upon the caring relationship, wanting staff to listen to them, and to feel supported and reassured. In the papers reviewed, service users experiencing CEN did not always feel 'listened to' or 'taken seriously' especially in relation to risk issues and decision-making. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Relating the findings to mental health nursing and CEN within the context of CRHT, to better understand the person experiencing a mental health crisis, mental health nurses need to focus more upon the person and when making decisions around their care and must be aware of the potential for power imbalances. Collaborative 'sense-making' in relation to a person's risk behaviours may help. ABSTRACT: Background A growing body of qualitative evidence focusing upon the experiences of care within Crisis Resolution/Home Treatment (CRHT) is emerging; however, a firm evidence base regarding both the giving and receiving of care for those with complex emotional needs (CEN) in this context is yet to be established. Objective A qualitative evidence synthesis was used to develop a comprehensive understanding of how crisis care for people with CEN is experienced by both those giving and receiving care, within the context of CRHT. Method Findings from 19 research papers considering both clinician and service users' experiential accounts of CRHT were synthesised using meta-ethnography. Findings Both the giving and receiving of care within a CRHT context was experienced across four related meta-themes: 'contextual', 'functional', 'relational' and 'decisional'. Discussion Service user accounts focused upon relational aspects, highlighting a significance to their experience of care. Meanwhile, clinicians focused more upon contextual issues linked to the management of organisational anxieties and resources. For those with CEN, a clinician's focus upon risk alone highlighted power differentials in the caring relationship. Conclusions There is a need for nurses to connect with the experience of the person in crisis, ensuring a better balance between contextual issues and relational working.

The Enrichment of Whey Protein Isolate Hydrogels with Poly-γ-Glutamic Acid Promotes the Proliferation and Osteogenic Differentiation of Preosteoblasts.

Osseous disease accounts for over half of chronic pathologies, but there is a limited supply of autografts, the gold standard; hence, there is a demand for new synthetic biomaterials. Herein, we present the use of a promising, new dairy-derived biomaterial: whey protein isolate (WPI) in the form of hydrogels, modified with the addition of different concentrations of the biotechnologically produced protein-like polymeric substance poly-γ-glutamic acid (γ-PGA) as a potential scaffold for tissue regeneration. Raman spectroscopic analysis demonstrated the successful creation of WPI-γ-PGA hydrogels. A cytotoxicity assessment using preosteoblastic cells demonstrated that the hydrogels were noncytotoxic and supported cell proliferation from day 3 to 14. All γ-PGA-containing scaffold compositions strongly promoted cell attachment and the formation of dense interconnected cell layers. Cell viability was significantly increased on γ-PGA-containing scaffolds on day 14 compared to WPI control scaffolds. Significantly, the cells showed markers of osteogenic differentiation; they synthesised increasing amounts of collagen over time, and cells showed significantly enhanced alkaline phosphatase activity at day 7 and higher levels of calcium for matrix mineralization at days 14 and 21 on the γ-PGA-containing scaffolds. These results demonstrated the potential of WPI-γ-PGA hydrogels as scaffolds for bone regeneration.