A Framework for Enhancing Access to Equitable Home Care for 2SLGBTQ+ Communities.

Canadian, US, and UK public health and clinical research has identified barriers to health service access for Two-Spirit, lesbian, gay, bisexual, transgender, queer, non-binary, and intersex (2SLGBTQ+) communities. While offering important insight into the health service experiences of 2SLGBTQ+ communities, this body of research only recently, and still only minimally, reports on home care access experiences. Drawing on key findings from the 2SLGBTQ+ Home Care Access Project, a mixed-methods, Ontario-wide study, this paper animates an Access and Equity Framework, using participant stories and perspectives to underscore the relevance and effectiveness of the Framework as a tool to support systematic organizational assessment, evaluation, and implementation of access and equity strategies. Home care organizations can use this tool to assess their programs and services along a continuum of intentionally inviting, unintentionally inviting, unintentionally disinviting, and intentionally disinviting care for 2SLGBTQ+ people. To support this process, the framework includes six indicators of access to care: community engagement, leadership, environment, policies and processes, education and training, and programs and services.

Lesbian disclosure and health care seeking in the United States: A replication study.

The current study explored factors associated with lesbian disclosure to health care providers (HCPs) and engagement in preventative health behaviors by replicating and extending a Canadian path analysis study with a sample of U.S. lesbians. Both patient (education, feminism, global outness, and internalized homophobia) and HCP-related (lesbian-friendly HCPs and patient comfort) factors were either directly or indirectly associated with disclosure and engagement in preventative health behaviors, including avoidance of health-compromising behaviors (e.g., smoking) and health care seeking. Importantly, findings suggest that HCPs-particularly those who are inclusive of lesbian patients-may play a role in assuaging their patients' experiences of minority stress. Overall, the findings were similar to those originally reported in the Canadian study, with the exception of internalized homophobia playing a more visible role in the current study.

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production.

Human airway epithelial cells express pannexin 1 (Panx1) channels to release ATP, which regulates mucociliary clearance. Airway inflammation causes mucociliary dysfunction. Exposure of primary human airway epithelial cell cultures to IFN-γ for 48 h did not alter Panx1 protein expression but significantly decreased ATP release in response to hypotonic stress. The IFN-γ-induced functional down-regulation of Panx1 was due to the up-regulation of dual oxidase 2 (Duox2). Duox2 suppression by siRNA led to an increase in ATP release in control cells and restoration of ATP release in cells treated with IFN-γ. Both effects were reduced by the pannexin inhibitor probenecid. Duox2 up-regulation stoichiometrically increases H2O2 and proton production. H2O2 inhibited Panx1 function temporarily by formation of disulfide bonds at the thiol group of its terminal cysteine. Long-term exposure to H2O2, however, had no inhibitory effect. To assess the role of cellular acidification upon IFN-γ treatment, fully differentiated airway epithelial cells were exposed to ammonium chloride to alkalinize the cytosol. This led to a 2-fold increase in ATP release in cells treated with IFN-γ that was also inhibited by probenecid. Duox2 knockdown also partially corrected IFN-γ-mediated acidification. The direct correlation between intracellular pH and Panx1 open probability was shown in oocytes. Therefore, airway epithelial cells release less ATP in response to hypotonic stress in an inflammatory environment (IFN-γ exposure). Decreased Panx1 function is a response to cell acidification mediated by IFN-γ-induced up-regulation of Duox2, representing a novel mechanism for mucociliary dysfunction in inflammatory airway diseases.

Under what conditions do lesbians disclose their sexual orientation to primary healthcare providers? A review of the literature.

Under what conditions do lesbians disclose their sexual orientation to primary healthcare providers? A review of the literature was undertaken to answer this question and to provide insight into the ways healthcare professionals can play an active role assisting their lesbian patients in "coming out." Thirty empirical studies met the inclusion criteria and were reviewed. Collectively, these separate studies have found that a myriad of internal (patient attributes) and external (healthcare context, patient-provider relationship) factors influence disclosure. The discussion highlights the critical role of healthcare professionals in supporting disclosure.

Variations in women's help seeking in response to intimate partner violence: findings from a Canadian population-based study.

This study examined the role of sociodemographic factors and violence characteristics in influencing women's use of informal and formal supports in response to intimate partner violence (IPV) in a national survey of Canadian households. A subset of female respondents in the 1999 Canadian General Social Survey who experienced at least one incident of physical or sexual IPV by a male current or former intimate partner was used for this analysis. Findings suggest that although there are significant sociodemographic variations in women's help seeking, the largest independent predictor of women's use of supports is fear that one's life is in danger.

External barriers to help-seeking encountered by Canadian gay and lesbian victims of intimate partner abuse: an application of the barriers model.

While understanding of intimate partner abuse (IPA) in gay and lesbian relationships has increased within the past decade, there remain several gaps in the help-seeking research. In particular, research examining the external barriers to help-seeking encountered by gay and lesbian victims of IPA has been largely atheoretical. To address this gap, an application of The Barriers Model was undertaken. This mixed-methods study surveyed 280 gay, lesbian, and/or queer participants living in Canada. Findings revealed that victims encountered external barriers in the environment (i.e., Layer 1 of the model), such as lack of availability of gay and lesbian specific services. Results also suggested that barriers due to family/socialization/role expectations (i.e., Layer 2 of the model), such as concealment of sexual orientation, had an impact on help-seeking.

A novel neural substrate for the transformation of olfactory inputs into motor output.

It is widely recognized that animals respond to odors by generating or modulating specific motor behaviors. These reactions are important for daily activities, reproduction, and survival. In the sea lamprey, mating occurs after ovulated females are attracted to spawning sites by male sex pheromones. The ubiquity and reliability of olfactory-motor behavioral responses in vertebrates suggest tight coupling between the olfactory system and brain areas controlling movements. However, the circuitry and the underlying cellular neural mechanisms remain largely unknown. Using lamprey brain preparations, and electrophysiology, calcium imaging, and tract tracing experiments, we describe the neural substrate responsible for transforming an olfactory input into a locomotor output. We found that olfactory stimulation with naturally occurring odors and pheromones induced large excitatory responses in reticulospinal cells, the command neurons for locomotion. We have also identified the anatomy and physiology of this circuit. The olfactory input was relayed in the medial part of the olfactory bulb, in the posterior tuberculum, in the mesencephalic locomotor region, to finally reach reticulospinal cells in the hindbrain. Activation of this olfactory-motor pathway generated rhythmic ventral root discharges and swimming movements. Our study bridges the gap between behavior and cellular neural mechanisms in vertebrates, identifying a specific subsystem within the CNS, dedicated to producing motor responses to olfactory inputs.

Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature.

This study aims to demonstrate the role of stress-induced senescence in aged-related neointimal formation. We demonstrated that aging increases senescence-associated beta-galactosidase activity (SA-beta-Gal) after vascular injury and the subsequent neointimal formation (neointima-to-media ratio: 0.8 +/- 0.2 vs. 0.54 +/- 0.15) in rats. We found that senescent cells (SA-beta-Gal(+) p21(+)) were scattered throughout the media and adventitia of the vascular wall at day 7 after injury and reached their maximum number at day 14. However, senescent cells only persisted in the injured arteries of aged animals until day 30. No senescent cells were observed in the noninjured, contralateral artery. Interestingly, vascular senescent cells accumulated genomic 8-oxo-7,8-dihydrodeoxyguanine, indicating that these cells were under intense oxidative stress. To demonstrate whether senescence worsens intimal hyperplasia after injury, we seeded matrigel-embedded senescent and nonsenescent vascular smooth muscle cells around injured vessels. The neointima was thicker in arteries treated with senescent cells with respect to those that received normal cells (neointima-to-media ratio: 0.41 +/- 0.105 vs. 0.26 +/- 0.04). In conclusion, these results demonstrate that vascular senescence is not only a consequence of postinjury oxidative stress but is also a worsening factor for neointimal development in the aging vasculature.

A novel mouse model of in-stent restenosis.

BACKGROUND AND AIMS: In-stent restenosis (ISR) is the major complication that occurs after percutaneous coronary interventions to facilitate coronary revascularization. Herein we described a simple and cost-effective model, which reproduces important features of ISR in the mouse. METHODS AND RESULTS: Microvascular bare metal stents were successfully implanted in the abdominal aorta of atherosclerotic ApoE-null mice. Patency of implanted stents was interrogated using ultrasound biomicroscopy. Aortas were harvested at different time points after implantation and processed for histopathological analysis. Thrombus formation was histologically detected after 1 day. Leukocyte adherence and infiltration were evident after 7 days and decreased thereafter. Neointimal formation, neointimal thickness and luminal stenosis simultaneously increased up to 28 days after stent implantation. Using multichannel fluorescence molecular tomography (FMT) for spatiotemporal resolution of MMP activities, we observed that MMP activity in the stented aorta of Apo-E null mice was 2-fold higher than that of wild-type mice. Finally, we compared neointimal formation in response to stenting in two genetically different mouse strains. In-stent neointimas in FVB/NJ mice were 2-fold thicker than in C57BL/6J mice (p=0.002). CONCLUSION: We have developed a model that can take advantage of the multiple genetic resources available for the mouse to study the mechanisms of in-stent restenosis.

Aging increases p16 INK4a expression in vascular smooth-muscle cells.

Alteration of VSMC (vascular smooth-muscle cell) physiology is associated with the development of atherosclerosis and restenosis. We hypothesize that aging up-regulates the expression of p16 INK4a in VSMCs, which may increase the susceptibility of blood vessels to vascular occlusive diseases. Aortic VSMCs were obtained from young and aged mice. Cells from aged mice grew more slowly than those from their younger counterparts. Progression of cell cycle in response to serum stimulation was significantly inhibited in those cells with aging, as determined by FACS after propidium iodide staining. A significant up-regulation of p16 INK4a (2.5-fold, P=0.0012) was found in VSMC from aged animals using gene arrays. The up-regulation of this gene was further confirmed by quantitative RT-PCR (reverse transcription-PCR) and Western-blot experiments. Immunostaining for p16 INK4a confirmed that aortas from aged mice contained more p16 INK4a+ SMA (smooth-muscle cell actin)+ cells than aortas from young animals (26.79+/-2.45 versus 7.06+/-1.44, P=0.00027, n=4). In conclusion, we have shown that aging up-regulates the expression of p16 INK4a in VSMC in both cultures and arteries. The increase in p16 INK4a in the vasculature with aging may modify VSMC's response to post-injury stress and therefore accelerate the development of age-related cardiovascular diseases.

The origin of post-injury neointimal cells in the rat balloon injury model.

AIMS: The origin of post-injury neointimal cells is still a matter of debate. This study aims to determine the anatomic source of neointimal cells in one of the most important animal models for the study of vascular stenosis in response to injury, the rat balloon injury model. METHODS AND RESULTS: Chimeric rats were generated by rescuing lethally irradiated animals with green fluorescent protein (GFP)(+) bone marrow (BM) cells from transgenic rats. Neointimal formation was induced in the right iliac artery of these animals using a balloon angioplasty catheter. Injured and non-injured contra-lateral arteries were harvested at 7, 14, and 30 days post-surgery. BM-derived monocytes/macrophages (CD68(+) GFP(+)) were abundant in the media and adventitia of injured vessels harvested at 7 days as determined by immunofluorescence and confocal microscopy. The number of GFP(+) cells declined in the vascular wall with time. Post-injury neointimal cells were mostly GFP(-)/smooth muscle actin (SMA)(+), which indicated that those cells originated in the recipient. Only a few neointimal cells seemed to come from circulating progenitors (GFP(+) SMA(+), 2.34% +/- 1.61). The vascular origin of cells in the neointima was further confirmed by transplanting injured GFP arteries into wild-type recipients. In these grafts, 94.23 +/- 0.44% of medial and 92.95 +/- 19.34% of neointimal cells were GFP(+) SMA(+). Finally, we tested the capacity of vascular smooth muscle cells (VSMC) to migrate through the vascular wall using a novel in vivo assay. As expected, VSMC migrated and populated the neointima only in response to injury. CONCLUSION: Our results suggest that neointimal cells in the rat balloon injury model mostly derive from pre-existing vascular cells and that only a small population of those cells come from BM-derived progenitors.

Initiation of locomotion in lampreys.

The spinal circuitry underlying the generation of basic locomotor synergies has been described in substantial detail in lampreys and the cellular mechanisms have been identified. The initiation of locomotion, on the other hand, relies on supraspinal networks and the cellular mechanisms involved are only beginning to be understood. This review examines some of the findings relative to the neural mechanisms involved in the initiation of locomotion of lampreys. Locomotion can be elicited by sensory stimulation or by internal cues associated with fundamental needs of the animal such as food seeking, exploration, and mating. We have described mechanisms by which escape swimming is elicited in lampreys in response to mechanical skin stimulation. A rather simple neural connectivity is involved, including sensory and relay neurons, as well as the brainstem rhombencephalic reticulospinal cells, which act as command neurons. We have shown that reticulospinal cells have intrinsic membrane properties that allow them to transform a short duration sensory input into a long-lasting excitatory command that activates the spinal locomotor networks. These mechanisms constitute an important feature for the activation of escape swimming. Other sensory inputs can also elicit locomotion in lampreys. For instance, we have recently shown that olfactory signals evoke sustained depolarizations in reticulospinal neurons and chemical activation of the olfactory bulbs with local injections of glutamate induces fictive locomotion. The mechanisms by which internal cues initiate locomotion are less understood. Our research has focused on one particular locomotor center in the brainstem, the mesencephalic locomotor region (MLR). The MLR is believed to channel inputs from many brain regions to generate goal-directed locomotion. It activates reticulospinal cells to elicit locomotor output in a graded fashion contrary to escape locomotor bouts, which are all-or-none. MLR inputs to reticulospinal cells use both glutamatergic and cholinergic transmission; nicotinic receptors on reticulospinal cells are involved. MLR excitatory inputs to reticulospinal cells in the middle (MRRN) are larger than those in the posterior rhombencephalic reticular nucleus (PRRN). Moreover at low stimulation strength, reticulospinal cells in the MRRN are activated first, whereas those in the PRRN require stronger stimulation strengths. The output from the MLR on one side activates reticulospinal neurons on both sides in a highly symmetrical fashion. This could account for the symmetrical bilateral locomotor output evoked during unilateral stimulation of the MLR in all animal species tested to date. Interestingly, muscarinic receptor activation reduces sensory inputs to reticulospinal neurons and, under natural conditions, the activation of MLR cholinergic neurons will likely reduce sensory inflow. Moreover, exposing the brainstem to muscarinic agonists generates sustained recurring depolarizations in reticulospinal neurons through pre-reticular effects. Cells in the caudal half of the rhombencephalon appear to be involved and we propose that the activation of these muscarinoceptive cells could provide additional excitation to reticulospinal cells when the MLR is activated under natural conditions. One important question relates to sources of inputs to the MLR. We found that substance P excites the MLR, whereas GABA inputs tonically maintain the MLR inhibited and removal of this inhibition initiates locomotion. Other locomotor centers exist such as a region in the ventral thalamus projecting directly to reticulospinal cells. This region, referred to as the diencephalic locomotor region, receives inputs from several areas in the forebrain and is likely important for goal-directed locomotion. In summary, this review focuses on the most recent findings relative to initiation of lamprey locomotion in response to sensory and internal cues in lampreys.