Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease.

Protein aggregation in brainstem nuclei is thought to occur in the early stages of Alzheimer's disease (AD), but its specific role in driving prodromal symptoms and disease progression is largely unknown. The dorsal raphe nucleus (DRN) contains a large population of serotonin (5-hydroxytryptamine; 5-HT) neurons that regulate mood, reward-related behavior, and sleep, which are all disrupted in AD. We report here that tau pathology is present in the DRN of individuals 25-80 years old without a known history of dementia, and its prevalence was comparable to the locus coeruleus (LC). By comparison, fewer cases were positive for other pathological proteins including α-synuclein, ß-amyloid, and TDP-43. To evaluate how early tau pathology impacts behavior, we overexpressed human P301L-tau in the DRN of mice and observed depressive-like behaviors and hyperactivity without deficits in spatial memory. Tau pathology was predominantly found in neurons relative to glia and colocalized with a significant proportion of Tph2-expressing neurons in the DRN. 5-HT neurons were also hyperexcitable in P301L-tauDRN mice, and there was an increase in the amplitude of excitatory post-synaptic currents (EPSCs). Moreover, astrocytic density was elevated in the DRN and accompanied by an increase in IL-1α and Frk expression, which suggests increased inflammatory signaling. Additionally, tau pathology was detected in axonal processes in the thalamus, hypothalamus, amygdala, and caudate putamen. A significant proportion of this tau pathology colocalized with the serotonin reuptake transporter (SERT), suggesting that tau may spread in an anterograde manner to regions outside the DRN. Together these results indicate that tau pathology accumulates in the DRN in a subset of individuals over 50 years and may lead to behavioral dysregulation, 5-HT neuronal dysfunction, and activation of local astrocytes which may be prodromal indicators of AD.

Clade I-Associated Mpox Cases Associated with Sexual Contact, the Democratic Republic of the Congo.

We report a cluster of clade I monkeypox virus infections linked to sexual contact in the Democratic Republic of the Congo. Case investigations resulted in 5 reverse transcription PCR-confirmed infections; genome sequencing suggest they belonged to the same transmission chain. This finding demonstrates that mpox transmission through sexual contact extends beyond clade IIb.

Lifting the curtain on the emergency department crisis: a multi-method reception study of Larry Saves the Canadian Healthcare System.

BACKGROUND: Despite growing evidence of the potential of arts-based modalities to translate knowledge and spark discussion on complex issues, applications to health policy are rare. This study explored the potential of a research-based theatrical video to increase public capacity and motivation to engage with the complex issues that make Emergency Department wait times such an intractable problem. METHODS: Larry Saves the Canadian Healthcare System is a digital musical micro-series developed from extensive research examining system-level causes of Emergency crowding and the ineffectiveness of prevailing approaches. We released individual episodes and a revised full-length version on YouTube, using organic promotion strategies and paid advertising. We used YouTube Analytics to track views, engagement and viewer demographics, and content-analyzed viewer comments. We also conducted five university-based screenings; 92 students completed questionnaires, rating Larry on 16 descriptors using a 7-point Likert scale. RESULTS: From June 2022 through May 2023, Larry garnered over 100,000 views (76,752 of the full-length version, 35,535 of episodes), 1329 likes, 2780 shares, and 139 comments. Views and watch time were higher among women and positively associated with age. Among YouTube comments, the predominating themes were praise for the video and criticism of the healthcare system. Many commenters applauded the show's accuracy, humor, and/or resonance with their experience; several shared healthcare horror stories. Students overwhelmingly agreed with all positive and disagreed with all negative descriptors, and nearly unanimously deemed the video informative, thought-provoking, and entertaining. Most also affirmed that it had increased their knowledge, interest, and confidence to participate in discussions about healthcare issues. Neither gender, primary language, nor employment in healthcare predicted ratings, but graduate students and those 25+ years old evaluated the video most positively. DISCUSSION: These findings highlight the promise of research-informed musical satire to inform and invigorate discourse on an urgent health policy problem. Larry has reached tens of thousands of viewers, garnered excellent feedback, and received high student ratings. Further research should directly assess educational and behavioural outcomes and explore what facilitative strategies could maximize this knowledge translation product's potential to foster informed, impactful policy dialogue.

Gender Harmony: A Case for Nursing Informatics.

The design of digital health information systems around a conflated gender/sex binary contributes to health inequities. Lack of specific information that supports affirming communication lead to inappropriate care, disrespectful encounters with healthcare staff, and avoidance of health services by clients who have been harmed by misgendering, deadnaming and being outed. The HL7 International Gender Harmony Model (HL7 GHM) supports the design, implementation and use of DHIS that enable affirming clinical interactions and care. This case study will demonstrate how applying the HL7 GHM can address the harms reported in a recently published account of one patient in Canada.

Mapping gender and sexual minority representation in cancer research: a scoping review protocol.

BACKGROUND: Addressing the risk of people from gender and sexual minority (GSM) groups experiencing inequities throughout the cancer continuum requires a robust evidence base. In this scoping review, we aim to map the literature on cancer outcomes among adults from GSM groups and the factors that influence them along the cancer continuum. METHODS: This mixed-methods scoping review will follow the approach outlined by JBI. We will systematically search electronic databases for literature in collaboration with a health sciences librarian. Two reviewers will screen titles and abstracts to determine eligibility based on inclusion criteria, and then retrieve full text articles for data extraction. Results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Quantitative data will be qualitized through a narrative interpretation and pooled with qualitative data. We will use meta-aggregation to synthesize findings. This protocol was developed in collaboration with GSM patient and public advisors. We will engage people from GSM groups, community organizations and knowledge users in disseminating results. INTERPRETATION: This review will direct future research efforts by expanding the wider body of research examining cancer disparities across the cancer continuum that GSM groups experience, identifying literature gaps and limitations, and highlighting relevant social determinants of health that influence cancer outcomes for adults from GSM groups.