Partnering with First Nations in Northern British Columbia Canada to Reduce Inequity in Access to Genomic Research.

Indigenous-led, culturally safe health research and infrastructure are essential to address existing inequities and disparities for Indigenous Peoples globally. Biobanking, genomic research, and self-governance could reduce the existing divide and increase Indigenous participation in health research. While genomic research advances medicine, barriers persist for Indigenous patients to benefit. In northern BC, Canada, the Northern Biobank Initiative (NBI), with guidance from a Northern First Nations Biobank Advisory Committee (NFNBAC), has engaged in consultations with First Nations on biobanking and genomic research. Key informant interviews and focus groups conducted with First Nations leaders, Elders, Knowledge Keepers, and community members established culturally safe ways of biobanking and exploring genomic research. Strong support for a Northern British Columbia First Nations Biobank (NBCFNB) that will promote choice, inclusion, and access to health research opportunities emerged. The acceptance and enthusiasm for the development of this NBCFNB and its governance table highlight the shift towards Indigenous ownership and support of health research and its benefits. With engagement and partnership, community awareness, multigenerational involvement, and support from diverse and experienced healthcare leaders, the NBCFNB will establish this culturally safe, locally driven, and critically important research priority that may serve as an example for diverse Indigenous groups when designing their unique biobanking or genomic research opportunities.

Primary Cutaneous Secretory Carcinoma: A Case Report and Literature Review.

Cutaneous secretory carcinomas (CSCs) are primary neoplasms of the skin that have been just recently described in the literature through case reports and series. In this case, a cutaneous lesion was found on the left temporal region of an 83-year-old male. He was referred to plastic surgery for complete excision, with negative margins confirmed by pathology. Histology, immunostaining, and genetic testing showed characteristics confirming the diagnosis of CSC and were supported by the information present in the current literature. Our patient showed no evidence of nodal disease or recurrence during regular follow-ups. Given the rarity of CSCs, we aim to present our experience regarding the diagnosis, pathological analysis, and management of our patient as well as summarize the present literature to further open avenues of research.

Technique for Reconstruction of Midcarpal Instability Associated with Lunotriquetral Coalition.

Carpal coalition is a rare congenital presentation of 2 or more fused carpal bones due to a failure of apoptotic segmentation during development. The most common subtype is lunotriquetral coalition (LTC). Most cases are asymptomatic and found incidentally on imaging; however, a few symptomatic cases requiring treatment have been reported. Surgical intervention of arthrodesis and proximal row carpectomy in adults have been reported where conservative management of splinting, physiotherapy, anti-inflammatory medication, or steroid injections have failed. We report a unique case of Minnaar type 2 LTC in a 20-year-old man with a 6-year history of daily right wrist pain and symptomatic wrist instability whose previous conservative therapies failed. Midcarpal instability and volar intercalated segment instability-volar flexion of the lunate-were present. A novel technique using the palmaris longus tendon to reconstruct the triquetrohamate, triquetrocapitate, and dorsal radiolunate ligaments was performed. The graft was secured dorsally to the hamate, triquetrum, and capitate. An additional graft from the lunate to distal radius acted as a biomechanical checkrein. There were no complications. Temporary Kirschner wires were removed 2 months postoperatively, followed by occupational hand therapy. At 1-year follow-up, the patient no longer reported pain or lunotriquetral tenderness. Midcarpal instability and volar intercalated segment instability resolved. Postoperative right wrist flexion and extension were 40 and 75 degrees, respectively. We discuss the successful outcome of this novel technique as an alternative to arthrodesis in the surgical management of LTC.

Microglia dynamics in sleep/wake states and in response to sleep loss.

Sleep has an essential role for optimal brain function, but the cellular substrates for sleep regulation are not fully understood. Microglia, the immune cells of the brain, have gained increasingly more attention over the last two decades for their important roles in various brain functions that extend beyond their well-known immune function, including brain development, neuronal protection, and synaptic plasticity. Here we review recent advances in understanding: i) morphological and phenotypic dynamics of microglia including process motility/growth and gene/protein expression, and ii) microglia-neuron interactions including phagocytosis and contact at synapses which alters neuronal circuit activity, both under physiological state in the adult brain. We discuss how the microglia-neuron interactions particularly at synapses could influence microglia and neuronal activities across circadian cycles and sleep/wake states. We also review recent findings on how microglia respond to sleep loss. We conclude by pointing out key questions and proposing suggestions for future research to better understand the role of microglia in sleep regulation, sleep homeostasis, and the function of sleep.

Homeostatic state of microglia in a rat model of chronic sleep restriction.

Chronic sleep restriction (CSR) negatively impacts brain functions. Whether microglia, the brain's resident immune cells, play any role is unknown. We studied microglia responses to CSR using a rat model featuring slowly rotating wheels (3 h on/1 h off), which was previously shown to induce both homeostatic and adaptive responses in sleep and attention. Adult male rats were sleep restricted for 27 or 99 h. Control rats were housed in locked wheels. After 27 and/or 99 h of CSR, the number of cells immunoreactive for the microglia marker ionized calcium-binding adaptor molecule-1 (Iba1) and the density of Iba1 immunoreactivity were increased in 4/10 brain regions involved in sleep/wake regulation and cognition, including the prelimbic cortex, central amygdala, perifornical lateral hypothalamic area, and dorsal raphe nucleus. CSR neither induced mitosis in microglia (assessed with bromodeoxyuridine) nor impaired blood-brain barrier permeability (assessed with Evans Blue). Microglia appeared ramified in all treatment groups and, when examined quantitatively in the prelimbic cortex, their morphology was not affected by CSR. After 27 h, but not 99 h, of CSR, mRNA levels of the anti-inflammatory cytokine interleukin-10 were increased in the frontal cortex. Pro-inflammatory cytokine mRNA levels (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) were unchanged. Furthermore, cortical microglia were not immunoreactive for several pro- and anti-inflammatory markers tested, but were immunoreactive for the purinergic P2Y12 receptor. These results suggest that microglia respond to CSR while remaining in a physiological state and may contribute to the previously reported homeostatic and adaptive responses to CSR.