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The sexual agency of youth with physical disabilities is often unacknowledged and underdeveloped. Concerned adults often make decisions about sexual and reproductive care for youth with physical disabilities to protect them from adverse outcomes, such as sexual abuse. Additionally, sexuality resources available to youth with physical disabilities are often not specific to their disability, which may limit their ability to foster positive sexuality. We conducted a systematic review to understand the knowledge created through qualitative inquiry on the sexuality of youth with physical disabilities. We considered qualitative or mixed-method studies published between 1999 and 2021. The electronic databases MEDLINE, PsycINFO, CINAHL, Dissertations and Theses Global were searched, as well as the DuckDuckGo search engine for grey literature. Nineteen peer-reviewed studies and 10 grey literature sources were included. Six themes were identified: (1) Sexuality resources did not adequately support the sexual rights of youth with physical disabilities, (2) Parents of youth with disabilities feared their child was sexually vulnerable, (3) Many healthcare providers felt unprepared to discuss sexuality with youth with disabilities, (4) Youth with physical disabilities experienced discrimination related to their sexuality, (5) The sexual agency of youth with physical disabilities was often unrecognized, and (6) Youth with physical disabilities had diverse sexual experiences and identities. This review revealed the complex, intersecting, and diverse experiences of youth with physical disabilities when it comes to their sexuality. Recommendations call on parents/caregivers, healthcare providers, researchers, and society at large, to combat systemic misconceptions and recognize the sexual agency of youth with physical disabilities.

Background: Children with disabilities are twice as likely to have overweight/obesity than their typically developing peers. Higher weights in these individuals may compound challenges already experienced with their disability, including mobility and activities of daily living. However, children with disabilities often find it challenging accessing weight management care. It is therefore important to understand the experiences and needs of the health care professionals (HCPs) who work in specialized pediatric weight management clinics about providing weight-related care to children with disabilities. Methods: Employing an interpretive description approach, purposeful sampling was used to recruit 17 HCP participants working in pediatric weight management settings in Canada. Qualitative semistructured interviews were conducted online or via telephone. All interview recordings were transcribed and a reflexive thematic analysis approach was used to develop themes from the data. Results: Four themes were developed: (1) infrequent referrals leads to a lack of experience with children with disabilities; (2) adapting group-based clinics can be challenging; (3) perceived lack of disability-specific knowledge causes moral distress; and (4) disability-specific training and greater interdisciplinary collaboration are desired. Conclusions: This work identifies the urgent need for more evidence-based, specialized, weight-related treatment options for children with disabilities, as well as more support for HCPs working in existing programs.

Disease-modifying antirheumatic drugs (DMARDs) have greatly improved the treatment of rheumatoid arthritis (RA), but strategies to prevent disease onset and recurring flares remain limited. While abatacept (CTLA-4 IgG) can delay RA onset and corticosteroids are used for flare control, the benefit is temporary. We report that combining standard-of-care treatments with a locally administered immunomodulatory agent, termed Agg-CLNP, enhances both disease prevention and flare mitigation. Agg-CLNP consists of polymer nanoparticles conjugated with an immunodominant aggrecan peptide and encapsulate calcitriol. These nanoparticles are optimized for uptake by dendritic cells (DC) in lymph nodes proximal to arthritic joints. In vitro, Agg-CLNP suppressed costimulatory molecules and HLA class II (HLA-2) expression and upregulated CTLA-4 in human monocyte-derived DC from healthy and RA donors. In SKG mice, a T cell-driven RA model, Agg-CLNP combined with CTLA-4 IgG synergistically delayed disease onset and reduced severity. In a dexamethasone (Dex) withdrawal flare model, post-Dex Agg-CLNP treatment reduced flare severity and preserved a regulatory phenotype in DC, while suppressing local pathogenic TH17 cells. Next generation RNA sequencing of lymph node DC revealed Ctla4 upregulation and changes in other immunomodulatory genes linked to flare prevention. These findings highlight Agg-CLNP as a potential therapeutic strategy to address critical unmet needs in RA management.

Cancer patients have high mortality from COVID-19, and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 cancer patients hospitalized for COVID-19, patients with hematologic cancers had higher mortality relative to solid cancers. In two additional cohorts, flow cytometric and serologic analyses demonstrated that solid cancer and non-cancer patients had a similar immune phenotype during acute COVID-19 whereas hematologic cancer patients had impairment of B cells and SARS-CoV-2-specific antibody responses. Despite the impaired humoral immunity and high mortality in hematologic cancer patients with COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Further, 77% of hematologic cancer patients had detectable SARS-CoV-2 specific T-cell responses. Thus, CD8 T cells may influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in hematologic cancer patients even in the setting of limited humoral responses.

Synapse loss correlates with cognitive decline in Alzheimer’s disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human AD remains to be established. Here we observe astrocytes and microglia from human brains contain greater amounts of synaptic protein in AD compared to non-disease controls, and that proximity to amyloid-β plaques and the APOE4 risk gene exacerbate this effect. In culture, mouse and human astrocytes and primary mouse and human microglia phagocytose AD patient-derived synapses more than synapses from controls. Inhibiting MFG-E8 function rescued the elevated engulfment of AD synapses by astrocytes and microglia without affecting control synapse uptake. Thus, AD promotes increased synapse ingestion by human glial cells via an MFG-E8 opsonophagocytic mechanism with potential for targeted therapeutic manipulation. Glial cells ingest synapses in Alzheimer’s disease and antibody treatment reduces this ingestion in cultured human cells.