Social determinants of self-reported health for Canada's indigenous peoples: a public health approach.

OBJECTIVE: In Canada, indigenous peoples suffer from a multitude of health disparities. To better understand these disparities, this study aims to examine the social determinants of self-reported health for indigenous peoples in Canada. STUDY DESIGN: This study uses data from Statistics Canada's Aboriginal Peoples Survey 2012. METHODS: Multinomial logistic regression models were used to examine how selected social determinants of health are associated with self-reported health among off-reserve First Nations and Métis peoples in Canada. RESULTS: Our analysis shows that being older, female, and living in urban settings were significantly associated with negative ratings of self-reported health status among the indigenous respondents. Additionally, we found that higher income and levels of education were strongly and significantly associated with positive ratings of self-reported health status. Compared with indigenous peoples with an education level of grade 8 or lower, respondents with higher education were 10 times (5.35-22.48) more likely to report 'excellent' and 'very good' health. Respondents who earned more than $40,000 annually were three times (2.17-4.72) more likely to report 'excellent' and 'very good' health compared with those who earned less than $20,000 annually. When interacted with income, we also found that volunteering in the community is associated with better self-reported health. CONCLUSIONS: There are known protective determinants (income and education) and risk determinants (location of residence, gender, and age) which are associated with self-reported health status among off-reserve First Nations and Métis peoples. For indigenous-specific determinants, volunteering in the community appears to be associated with self-perceived health status. Thus, addressing these determinants will be necessary to achieve better health outcomes for indigenous peoples in Canada. Next steps include developing indigenous-specific social determinants of health indicators that adequately measure culture, connection, and community.

Cell cycle control of Schwann cell proliferation: role of cyclin-dependent kinase-2.

Schwann cell proliferation is regulated by multiple growth factors and axonal signals. However, the molecules that control growth arrest of Schwann cells are not well defined. Here we describe regulation of the cyclin-dependent kinase-2 (CDK2) protein, an enzyme that is necessary for the transition from G1 to S phase. Levels of CDK2 protein were elevated in proliferating Schwann cells cultured in serum and forskolin. However, when cells were grown with either serum-free media or at high densities, CDK2 levels declined to low levels. The decrease in CDK2 levels was associated with growth arrest of Schwann cells. The modulation of CDK2 appears to be regulated at the transcriptional level, because CDK2 mRNA levels and its promoter activity both decline during cell cycle arrest. Furthermore, analysis of the CDK2 promoter suggests that Sp1 DNA binding sites are essential for maximal activation in Schwann cells. Together, these data suggest that CDK2 may represent a significant target of developmental signals that regulate Schwann cell proliferation and that this regulation is mediated, in part, through regulation of Sp1 transcriptional activity.

Ectopic expression of p27Kip1 in oligodendrocyte progenitor cells results in cell-cycle growth arrest.

Oligodendrocyte differentiation is a complex process believed to be controlled by an intrinsic mechanism associated with cell-cycle arrest. Recently, the cell-cycle inhibitor protein p27 Kip1 has been proposed as a key element in causing growth arrest of oligodendrocyte precursor cells. To investigate the effects of p27 upon oligodendrocyte cell development, we have introduced the p27 cDNA in oligodendrocyte progenitor cells using an adenovirus vector. Progenitor cells normally express low levels of p27. After adenoviral infection and p27 overexpression, progenitor cells were able to undergo cell-cycle arrest, even in the presence of strong mitogens. The effects of p27 were shown to be directly upon cyclin-dependent kinase-2 (CDK2), the protein kinase complex responsible for G1/S transition, as immunodepletion of oligodendrocyte extracts of p27 protein resulted in the activation of CDK2 activity. However, cells that became growth arrested owing to infection with p27 adenovirus did not display conventional oligodendrocyte differentiation markers, such as O4 or O1. Taken together, these data provide mechanistic evidence indicating that p27 is primarily involved in oligodendroglial progenitor proliferation by inhibiting CDK2 activity and inducing oligodendrocyte cell-cycle arrest.

Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1.

During development of the central nervous system, oligodendrocyte progenitor cells (O-2A) undergo an orderly pattern of cell proliferation and differentiation, culminating in the ability of oligodendrocytes to myelinate axons. Here we report that p27(Kip1), a cyclin-dependent kinase inhibitor, is an important component of the decision of O-2A cells to withdraw from the cell cycle. In vitro, accumulation of p27 correlates with differentiation of oligodendrocytes. Furthermore, only a fraction of O-2A cells derived from p27-knockout mice differentiate successfully compared to controls. Inability to differentiate correlates with continued proliferation, suggesting that p27 is an important component of the machinery required for the G1/G0 transition in O-2A cells. In vivo, expansion of O-2A precursors before withdrawal, in part, leads to a greater number of oligodendrocytes. Together these data indicate a role for p27 during the decision to withdraw from the cell cycle in the oligodendrocyte lineage.

Changes in cyclin-dependent kinase 2 and p27kip1 accompany glial cell differentiation of central glia-4 cells.

The generation of different glial cell types in the central nervous system depends upon a wide variety of proliferative and differentiative signals. Here we report that changes in the levels of cyclin-dependent kinase 2 (CDK2) and the cell cycle inhibitor p27kip1 accompany the differentiation of central glia-4 (CG-4) progenitor cells to an astrocytic cell phenotype in the presence of fetal calf serum. Although a decrease in CDK2 levels was observed in both oligodendrocyte and astrocyte cells derived from CG-4 cells, a striking increase in the levels of p27 was observed during the differentiation of astrocyte cells. In astrocyte cell extracts, inhibition of CDK2 activity could be overcome with exogenously added cyclin E. Furthermore, depletion of p27 from astrocyte extracts lowered the amount of cyclin E required for CDK2 activation. Taken together, these results suggest that the inhibitory action of p27 upon cyclin E-CDK2 may prevent entry of cells into the S phase and regulate the progression of CG-4 cells toward an astrocytic lineage.

Predictive value of intraoperative brainstem auditory evoked responses in surgery for conductive hearing losses.

OBJECTIVE: To assess the efficacy of intraoperative brainstem auditory evoked responses (BAER) in predicting postoperative hearing improvement in surgery for conductive hearing loss. STUDY DESIGN: A prospective study of consecutive patients undergoing surgery for conductive hearing loss under general anesthesia by a single surgeon. SETTING: A tertiary care university affiliated medical center. PATIENTS: All patients undergoing surgery for conductive hearing loss by the senior author between June 25, 1993 and March 20, 1995. INTERVENTIONS: Pre- and postreconstruction intraoperative BAERs; pre- and postoperative pure tone and speech audiometry. MAIN OUTCOME MEASURES: Changes in audiometric pure tone air-conduction thresholds, bone-air gaps (BAG), and speech reception thresholds (SRT), compared with changes in BAER wave five (V) latencies. RESULTS: A decrease in the wave V latency on the intraoperative BAER correlates significantly with improvement in postoperative pure-tone air-conduction, BAG, and SRT using chi 2 and linear regression analyses. CONCLUSIONS: Improvement in intraoperative BAER correlates with postoperative hearing improvement in surgery for conductive hearing loss done under general anesthesia in our population.

Discontinuous distribution of senile plaques within striate cortex hypercolumns in Alzheimer's disease.

Tangential sections of the primary visual (striate) cerebral cortex from five patients with histopathologically verified Alzheimer's disease were used to study the laminar and tangential disposition of senile plaques. These lesions were visualized with thioflavin S or the modified Bielschowsky method, and classified into four different, purely morphological types: "classical", (predominantly) "neuritic", (primarily amyloid) "core" and "diffuse", which were charted and analyzed using computer-assisted three- and two-dimensional reconstruction and mapping methods. These analyses reveal a tendency for a selective laminar disposition of the lesions (preferentially in layers II/III and V) which is generally consistent with previous reports performed at lower resolution, yet the specific pattern is highly variable among patients, and among plaque subtypes within individual patients. In addition, we observed a clustering of senile plaques in the tangential domain (i.e. parallel to the pial surface) in layers II/III, that suggests a selective involvement of iterated circuits within the "units", "modules", or "hypercolumns" that some believe compose this region of the cortex. These findings also imply an intriguing relative sparing of immediately adjacent components of the modular circuitry of the cerebral cortex, in the same cytoarchitectonic layers. Taken together, these findings indicate that: (1) senile plaques may arise in functionally and anatomically distinct subsets of iterated neuronal circuits that cannot be reduced to schemes based on traditional cytoarchitectonic layers; and (2) that individual variability in the patterns of striate cortex involvement and clinical manifestations must be taken into consideration when addressing the specific mechanisms underlying visual dysfunction in Alzheimer's disease.

Alz-50 immunoreactivity in the thalamic reticular nucleus in Alzheimer's disease.

Examination of the thalamic reticular nucleus (Rt) with the monoclonal antibody Alz-50 in brains of Alzheimer's disease patients reveals dense extracellular and terminal-like immunoreactivity in the absence of neurofibrillary tangles or neuritic plaques. Similar terminal-like immunoreactivity is not present in other thalamic nuclei of AD brains or in the brains of controls. Based on (1) an immunocytochemical and histopathological analysis of areas known to project to the Rt, (2) that Alz-50 immunocytochemistry reveals immunoreactive neurons, neurofibrillary tangles and neuritic plaques, and (3) evidence that Alz-50 immunoreactivity can be demonstrated in the terminal fields of immunoreactive neurons, the terminal-like immunoreactivity in the Rt probably corresponds to altered preterminal axons and terminals from degenerating basal forebrain neurons. Given the presumed physiological role of the Rt, these selective lesions could alter thalamocortical processing and contribute to the cognitive impairment in Alzheimer's disease.