Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas.

Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.

New Technologies in Diagnosis and Prognosis of Melanocytic Lesions.

Analysis of morphological characteristics for the diagnosis of melanoma remains a challenge. New technologies for the diagnosis and prognosis of melanocytic lesions have been emerging to ensure earlier and more accurate detection. In this article, we review multiple technologies that improve melanoma diagnostic accuracy such as electrical impedance spectroscopy, pigmented lesion assay, reflectance confocal microscopy, and gene expression profile tests.

School performance in youth after a concussion.

Objective: This study aimed to identify school problems and levels of cognitive activity in youths aged 5-18 years with a concussion during the recovery stages of return to school (RTS). Study Design: In a prospective cohort, participants completed in-person assessments at three time points: First Visit Post-injury, Symptom Resolution Visit, and Follow-Up Visit. These time points varied based on the participants' recovery progress. The post-concussion symptom scale (PCSS) and a cognitive activity scale were completed every 2 days until symptom resolution was achieved. Participants and their parents completed a school questionnaire detailing how their concussion had impacted their school learning/performance and their level of concern about their injury as well as the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). Results: Sixty-three percent (N = 44/70) of participants returned to school by the First Visit Post-injury (average 7.7 days following injury), and of these, 50% (N = 22) were experiencing school problems. Sixty-five participants (out of 70) returned to school at the Follow-Up Visit, and of these, 18% reported school problems. There was a significant difference in the school problems reported by parents and youth. At the First Visit Post-injury, the youth reported more problems (p = 0.02), and the In-Person Symptom Resolution Visit with parents reported more problems (p = 0.01). The cognitive activity score increased, while the PCSS score decreased from RTS Stage 1 to Stage 5. Conclusions: This study identified that 50% of youth experienced school problems at the First Visit Post-injury, whereas only 18% reported school problems at the Follow-Up Visit. There is a significant difference in the perception of school problems reported by youth and their parents at different stages of recovery. The amount and complexity of cognitive activity increased with decreasing symptoms and increasing RTS stage. Findings can guide youth with a concussion and their parents in supporting a cautious return to school with accommodations. Healthcare providers and researchers can use this knowledge to better support youth in their return to school and understand the importance of gathering information from youth and their parents to gain the best insight into recovery.

Examining the development and utilization of infection control policies to safely support adults with intellectual and developmental disabilities in congregate living settings during COVID-19.

OBJECTIVE: Congregate living settings supporting individuals with intellectual and developmental disabilities (IDD) have experienced unprecedented challenges during the COVID-19 pandemic. This study aimed to explore the development and utilization of infection control policies in congregate living settings supporting individuals with IDD during the COVID-19 pandemic. METHODS: This qualitative study employed an interpretive description using semi-structured interviews involving administrative personnel from agencies assisting those with IDD residing in Developmental Services congregate living settings in Ontario, Canada. RESULTS: Twenty-two semi-structured interviews were conducted with individuals from 22 agencies. Thematic analysis revealed three categories: Development of infection control policies, Implementation of infection control policies, and Impact of infection control policies. Each category yielded subsequent themes. Themes from the Development of infection control policies category included New responsibilities and interpreting the grey areas, and Feeling disconnected and forgotten. Four themes within the Implementation of infection control policies category included, "It's their home" (i.e. difficulty balancing public health guidance and organizational values), Finding equipment and resources (e.g. supports and barriers), Information overload (i.e. challenges agencies faced when implementing policies), and Emerging vaccination (i.e. perspective of agencies as they navigate vaccination for clients and staff). The category of Impact of infection control policies had one theme-Fatigue and burnout, capturing the impact of policies on stakeholders in congregate living settings. CONCLUSION: Agencies experienced difficulties developing and implementing infection control policies, impacting the clients they serve and their families and staff. Public health guidance should be tailored to each congregate living setting rather than generally applied.

RéSUMé: OBJECTIF: Les lieux d'hébergement collectif pour les personnes ayant une déficience intellectuelle ou de développement (DID) ont affronté des défis sans précédent durant la pandémie de la COVID-19. La présente étude vise à explorer l'élaboration et l'utilisation des politiques de prévention des infections dans les lieux d'hébergement collectif pour les personnes ayant une DID durant la pandémie de la COVID-19. MéTHODES: Cette étude qualitative repose sur la description interprétative lors d'entrevues semi-structurées auprès du personnel administratif des organismes qui viennent en aide aux personnes ayant une DID et résidant dans des lieux d'hébergement collectif en Ontario, au Canada. RéSULTATS: Au total, 22 entrevues semi-structurées ont été effectuées auprès de personnes provenant de 22 organismes. L'analyse thématique a révélé trois catégories : Élaboration des politiques de prévention des infections, mise en œuvre des politiques de prévention des infections, et impacts des politiques de prévention des infections. Chaque catégorie a généré des thèmes subséquents. Les thèmes liés à l'élaboration des politiques de prévention des infections comprenaient les nouvelles responsabilités et l'interprétation des zones grises, et le sentiment de détachement et d'avoir été oublié. Quatre thèmes découlant de la mise en œuvre des politiques de prévention des infections comprenaient « c'est leur maison ¼ (c'est-à-dire difficulté d'équilibrer les mesures de santé publique et les valeurs organisationnelles), trouver de l'équipement et des ressources (p. ex., mesures de soutien et obstacles), surcharge d'information (c'est-à-dire les défis qu'ont dû affronter les organismes lors de la mise en œuvre des politiques) et la vaccination émergente (notamment la perspective des organismes lorsqu'ils ont dû composer avec le processus de vaccination pour la clientèle et le personnel). La catégorie des impacts des politiques de prévention des infections avait un thème : la fatigue et l'épuisement professionnel, saisissant les impacts des politiques de prévention des infections dans les lieux d'hébergement collectif sur ses intervenants. CONCLUSION: Les organismes ont éprouvé des difficultés lors de l'élaboration et la mise en œuvre de politiques de prévention des infections, touchant ainsi leurs clients, leurs familles et leurs employés. Les mesures de santé publique devraient plutôt être adaptées à chaque lieu d'hébergement collectif, et non pas appliquées de façon générale.

Review on Novel Oral Therapies for Psoriasis.

Currently, several classes of oral therapies for psoriasis are in use, in development, or in investigative stages. Standard non-biologic treatments for psoriasis, such as methotrexate, cyclosporine, and acitretin, have generally unfavorable safety profiles and are not ideal for long-term use. This review will address the safety and efficacy of existing and novel oral therapies for psoriasis that target inflammatory pathways via modulation of phosphodiesterase 4 (PDE4), Janus kinases (JAKs), sphingosine 1-phosphate (S1P), A3 adenosine receptors, and rho-associated kinase 2 (ROCK2), with an emphasis on JAK inhibitors.