"I'm still not over feeling so isolated": Métis women, Two-Spirit, and gender-diverse people's experiences of the COVID-19 pandemic.

OBJECTIVES: The aim of this study was to explore and learn from the experiences of Métis women, Two-Spirit, and gender-diverse people accessing health and social services in Victoria, British Columbia, during the COVID-19 pandemic. METHODS: This paper comes from a larger study exploring Métis women, Two-Spirit, and gender-diverse people's experiences accessing health and social services in Victoria. Using a by-and-for Métis approach that employed a conversational interview method, we conducted interviews with Métis women, Two-Spirit, and gender-diverse people who lived in and/or accessed services in Victoria in December 2020 and January 2021. This paper focuses specifically on data addressing how COVID-19 impacted these participants. RESULTS: A total of 24 Métis women, Two-Spirit, and gender-diverse people participated in the study. Overall, three themes specific to COVID-19 were identified. First, participants described the detrimental impacts of COVID-19 on their ability to connect with their Métis community and practice their culture, as well as their overall feelings of isolation. Second, participants highlighted some of the ways that COVID-19 has exacerbated existing barriers to culturally safe healthcare. Last, participants spoke about the mixed economic impacts that COVID-19 has had for them, sharing insight into the ways in which gender, in particular, has shaped their financial instability. CONCLUSION: Improving access to culturally safe health and social services by incorporating the experiences and expertise of Métis women, Two-Spirit, and gender-diverse people is crucial to mitigating the disproportional negative impacts of the pandemic and improving overall health outcomes within Métis communities across Canada.

RéSUMé: OBJECTIFS: Explorer les expériences de femmes métisses et de personnes métisses bispirituelles et de diverses identités de genre ayant accédé aux services sociaux et de santé à Victoria (Colombie-Britannique) pendant la pandémie de COVID-19, et en tirer des leçons. MéTHODE: Cet article vient d'une vaste étude sur les expériences de femmes métisses et de personnes métisses bispirituelles et de diverses identités de genre ayant accédé aux services sociaux et de santé à Victoria. À l'aide d'une démarche par et pour les personnes métisses qui a fait appel à une méthode d'entrevue directe, nous avons mené des entrevues avec des femmes métisses et des personnes bispirituelles et de diverses identités de genre ayant vécu à Victoria en décembre 2020 et janvier 2021 et/ou accédé à des services dans cette ville durant cette période. Le présent article porte spécifiquement sur les données liées aux incidences de la COVID-19 chez ces personnes. RéSULTATS: En tout, 24 femmes et personnes métisses bispirituelles et de diverses identités de genre ont participé à l'étude. Dans l'ensemble, trois aspects relatifs à la COVID-19 sont ressortis des données. Premièrement, les personnes participantes ont décrit les effets préjudiciables de la COVID-19 sur leur capacité de rester en lien avec leur communauté métisse et de pratiquer leur culture, ainsi que leurs sentiments d'isolement en général. Deuxièmement, elles ont souligné certaines des façons dont la COVID-19 a exacerbé les barrières existantes à l'accès aux soins de santé culturellement sûrs. Enfin, les personnes participantes ont parlé des retombées économiques mitigées de la COVID-19 dans leur cas, et elles ont partagé leurs idées sur le rôle du genre, en particulier, dans leur instabilité financière. CONCLUSION: Pour atténuer les effets préjudiciables disproportionnés de la pandémie et améliorer les résultats cliniques globaux au sein des communautés métisses du Canada, il est essentiel d'améliorer l'accès aux services sociaux et de santé culturellement sûrs en y intégrant les expériences et le savoir-faire de femmes métisses et de personnes métisses bispirituelles et de diverses identités de genre.

'By identifying myself as Métis, I didn't feel safe ': Experiences of navigating racism and discrimination among Métis women, Two-Spirit and gender diverse community members in Victoria, Canada.

OBJECTIVE: Racism acts as a major barrier to accessing health services for Indigenous communities in Canada, often leading to delayed, avoided or lack of treatment altogether. The Métis population is uniquely positioned in urban settings, as they experience discrimination from both Indigenous and mainstream health and social services due to Canada's long colonial history that is ongoing. Yet, Métis are often left out of discussions regarding racism and health service access. This study explores the experiences of racism and health service access among Métis peoples in Victoria, British Columbia. METHODS: We allied a conversational interview method to explore and understand experiences of self-identifying Métis women, Two-Spirit and gender diverse people (n = 24) who access health and social services in Victoria. Data analysis followed Flicker and Nixon's six-stage DEPICT model. RESULTS: In this paper, we share the experiences of racism and discrimination of those who accessed health and social services in Victoria, British Columbia Such experiences include passing as White, experiencing racism following Métis identity disclosure and witnessing racism. Passing as White was viewed as a protective factor against discrimination as well as harming participants' sense of identity. Experiences of racism took the form of discriminatory comments, harassment and mistreatment, which influenced the willingness of disclosing Métis identity. Witnessing racism occurred in participants, personal and professional lives, negatively impacting them in indirect ways. Each experience of racism had a negative influence on participants' wellbeing and shaped their experience of accessing health and social services. CONCLUSIONS: Métis people confront racism and discrimination when attempting to access health and social services through first-hand experiences, witnessing and/or avoidance. While this study contributes to the all too often unacknowledged voices of Métis in Canada, there is a continued need for Métis-specific research to accurately inform policy and practice.

T1Gd is reduced in bone marrow lesions overlying cartilage in the hip.

OBJECTIVE: Bone Marrow Lesions (BMLs) are areas in bone with high fluid signal on MRI associated with painful and progressive OA. While cartilage near BMLs in the knee has been shown to be degenerated, this relationship has not been investigated in the hip. RESEARCH QUESTION: is T1Gd lower in areas of cartilage overlying BMLs in the hip? DESIGN: 128 participants were recruited from a population-based study of hip pain in 20-49-year-olds. Proton-density weighted fat-suppressed and delayed Gadolinium Enhanced MR Imaging of Cartilage (dGEMRIC) images were acquired to locate BMLs and quantify hip cartilage health. BML and cartilage images were registered and cartilage was separated into BML overlying and surrounding regions. Mean T1Gd was measured in 32 participants with BMLs in both cartilage regions and in matched regions in 32 age- and sex-matched controls. Mean T1Gd in the overlying cartilage was compared using linear mixed-effects models between BML and control groups for acetabular and femoral BMLs, and between cystic and non-cystic BML groups. RESULTS: Mean T1Gd of overlying cartilage was lower in the BML group compared to the control group (acetabular: -105 ms; 95% CI: -175, -35; femoral: -8 ms; 95% CI: -141, 124). Mean T1Gd in overlying cartilage was lower in cystic compared to non-cystic BML subjects, but the confidence interval is too large to provide certainty in this difference (-3 [95% CI: -126, 121]). CONCLUSIONS: T1Gd is reduced in overlying cartilage in hips from a population-based sample of adults aged 20-49, which suggests BMLs are associated with local cartilage degeneration in hips.

New directions in cancer and aging: State of the science and recommendations to improve the quality of evidence on the intersection of aging with cancer control.

BACKGROUND: The global population of older cancer survivors is growing. However, the intersections of aging-related health risks across the cancer control continuum are poorly understood, limiting the integration of aging into cancer control research and practice. The objective of this study was to review the state of science and provide future directions to improve the quality of evidence in 6 priority research areas in cancer and aging. METHODS: The authors identified priority research areas in cancer and aging through an evidence-based Research Jam process involving 32 investigators and trainees from multiple disciplines and research centers in aging and cancer; then, they conducted a narrative review of the state of the science and future directions to improve the quality of evidence in these research areas. Priority research areas were defined as those in which gaps in scientific evidence or clinical practice limit the health and well-being of older adults with cancer. RESULTS: Six priority research areas were identified: cognitive and physical functional outcomes of older cancer survivors, sampling issues in studies of older cancer survivors, risk and resilience across the lifespan, caregiver support and well-being, quality of care for older patients with cancer, and health disparities. Evidence in these areas could be improved through the incorporation of bias reduction techniques into longitudinal studies of older cancer survivors, novel data linkage, and improved representation of older adults in cancer research. CONCLUSIONS: The priority research areas and methodologies identified here may be used to guide interdisciplinary research and improve the quality of evidence on cancer and aging.

Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage Values in Hips With Bone Marrow Lesions.

OBJECTIVE: Bone marrow lesions (BMLs) are associated with painful and progressive osteoarthritis (OA). Quantitative magnetic resonance imaging (MRI) has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) relaxation values (T1Gd) in hips with BML to hips without BML in a population-based study. Reduced T1Gd suggests depleted glycosaminoglycan. Our hypothesis was that mean T1Gd is lower in hips with BML compared to hips without BML. METHODS: Study participants (n = 128) were recruited from a cross-sectional population-based study of people ages 20-49 years with and without hip pain. dGEMRIC and proton density (PD)-weighted MRI scans of 1 hip from each participant were used for this analysis. BMLs were identified from PD-weighted fat-suppressed images. We applied a sampling-weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T1Gd (significance: P < 0.05). The model was adjusted for age, sex, body mass index (BMI), hip pain, cam/pincer deformity, and physical activity. RESULTS: Thirty-two (25%) of the 128 participants had at least 1 BML. Subjects with at least 1 BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T1Gd was 75.25 msec lower (95% confidence interval -149.69, -0.81; P = 0.048) (9%) in the BML compared to the no-BML group. CONCLUSION: Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process.

Effect of posture and femoral neck osteochondroplasty on femur-acetabulum clearance in patients with cam-type femoroacetabular impingement.

It is not clear whether femoral neck osteochondroplasty achieves its objective of increasing femoroacetabular clearance. We used an upright open magnetic resonance imaging scanner to image the hip joint in multiple postures to explore the effect of posture and femoral neck osteochondroplasty on femur-acetabulum clearance in patients with cam-type femoroacetabular impingement. We recruited 13 consecutive patients scheduled to undergo arthroscopic femoral neck osteochondroplasty and completed assessments on 10 patients. We scanned each subject before surgery and at 6 months post-op in supine and 3 other physiological postures: supine 90° flexion with adduction and internal rotation (FADIR), sitting deep (maximal flexion with internal rotation and adduction), and sitting crossed leg (maximal adduction with flexion and internal rotation). We measured the alpha angle, which describes the severity of cam deformity, and the beta angle, which defines joint clearance. We also evaluated hip flexion, internal rotation, and adduction before and after surgery. Femoral neck osteochondroplasty significantly decreased alpha angle by 23.9° ± 4.6° (p = 0.001) and increased beta angle across all postures by 28.1° ± 6.3° (p = 0.002). An increase in beta angle represented a decreased chance of impingement. Femoral neck osteochondroplasty significantly increased flexion by an average of 8.6° in the sitting deep posture after surgery (p = 0.007) which might indicate an improvement of joint function. These findings lend support to the hypothesis that arthroscopic osteochondroplasty accomplishes its stated goals of increasing bone-bone clearance in the hip joint and improving joint mechanics for the static postures assessed.

Effect of positioning error on the Hilgenreiner epiphyseal angle and the head-shaft angle compared to the femoral neck-shaft angle in children with cerebral palsy.

Children with cerebral palsy (CP) often have changes in proximal femoral geometry. Neck-shaft angle (NSA), Hilgenreiner epiphyseal angle (HEA) and head-shaft angle (HSA) are used to measure these changes. The impact of femoral rotation on HEA/HSA and of ab/adduction on HEA/HSA/NSA is not well known. This study aimed to determine and compare the effect of rotation, ab/adduction and flexion/extension on HEA/HSA/NSA. Radiographic measurements from 384 patients with Gross Motor Function Classification System (GMFCS) levels I-V were utilized. NSA/HSA for affected hips were used with femoral anteversion averages to create three-dimensional models of 694 hips in children with CP. Each hip was rotated, ab/adducted and flexed/extended to simulate malpositioning. HEA/HSA/NSA of each model were measured in each joint position, and differences from correct positioning were determined. Mean HEA error at 20° of internal/external rotations were -0.60°/3.17°, respectively, with the NSA error of -6.56°/9.94° and the HSA error of -3.69°/1.21°. Each degree of ab/adduction added 1° of the HEA error, with no NSA/HSA error. NSA was most sensitive to flexion. Error for all measures increased with increasing GMFCS level. HEA/HSA were minimally impacted by rotation. NSA error was much higher than HEA/HSA in internal rotation and flexion whereas HEA was sensitive to changes in ab/adduction. Given abduction is more easily detectable on imaging than rotation, HEA may be less affected by positioning errors that are common with children with CP than NSA. HSA was least affected by position changes. HEA/HSA could be robust, complementary measures of hip deformities in children with CP.

T1ρ and T2 MRI show hip cartilage damage in adolescents with healed Legg-Calvé-Perthes disease.

Legg-Calvé-Perthes disease (LCPD) is a juvenile hip disorder associated with residual femoral head deformity, cartilage degeneration and a high risk of early onset hip osteoarthritis. Assessing management of LCPD in the healed phase requires an understanding of when and where hip cartilage damage happens. While it has been shown that cartilage is degenerated in healed LCPD hips in adults, it is not clear when this degeneration begins. Our research question was: Are the MR markers of cartilage degeneration T1ρ and T2 increased in healed LCPD hips in adolescents? Twelve adolescents [10-17 years old (mean 14); 3 female 9 male] with healed LCPD (Stulberg 2-5; 8 unilateral and 4 bilateral) and 15 age- and sex-matched controls were imaged in a 3T MRI using a T1ρ and a T2 sequence. We applied a mixed-effects model adjusted for age and nested by subject to determine the effect of Stulberg grade on overall and regional mean T1ρ and T2 values. T1ρ was significantly higher overall and in the medial region of Stulberg ≥3 hips, and in the medial region of Stulberg 2 hips than in the control group. T2 was significantly higher in the medial region of Stulberg ≥3 hips than in the control group. Our results suggest that cartilage damage in LCPD has begun by adolescence and that T1ρ can detect early changes in cartilage associated with LCPD.

A novel secreted-cAMP pathway inhibits pulmonary hypertension via a feed-forward mechanism.

AIMS: Cyclic adenosine monophosphate (cAMP) is the predominant intracellular second messenger that transduces signals from Gs-coupled receptors. Intriguingly, there is evidence from various cell types that an extracellular cAMP pathway is active in the extracellular space. Herein, we investigated the role of extracellular cAMP in the lung and examined whether it may act on pulmonary vascular cell proliferation and pulmonary vasculature remodelling in the pathogenesis of pulmonary hypertension (PH). METHODS AND RESULTS: The expression of cyclic AMP-metabolizing enzymes was increased in lungs from patients with PH as well as in rats treated with monocrotaline and mice exposed to Sugen/hypoxia. We report that inhibition of the endogenous extracellular cAMP pathway exacerbated Sugen/hypoxia-induced lung remodelling. We found that application of extracellular cAMP induced an increase in intracellular cAMP levels and inhibited proliferation and migration of pulmonary vascular cells in vitro. Extracellular cAMP infusion in two in vivo PH models prevented and reversed pulmonary and cardiac remodelling associated with PH. Using protein expression analysis along with luciferase assays, we found that extracellular cAMP acts via the A2R/PKA/CREB/p53/Cyclin D1 pathway. CONCLUSIONS: Taken together, our data reveal the presence of an extracellular cAMP pathway in pulmonary arteries that attempts to protect the lung during PH, and suggest targeting of the extracellular cAMP signalling pathway to limit pulmonary vascular remodelling and PH.

AAV1.SERCA2a Gene Therapy Reverses Pulmonary Fibrosis by Blocking the STAT3/FOXM1 Pathway and Promoting the SNON/SKI Axis.

Inhibition of pulmonary fibrosis (PF) by restoring sarco/endoplasmic reticulum calcium ATPase 2a isoform (SERCA2a) expression using targeted gene therapy may be a potentially powerful new treatment approach for PF. Here, we found that SERCA2a expression was significantly decreased in lung samples from patients with PF and in the bleomycin (BLM) mouse model of PF. In the BLM-induced PF model, intratracheal aerosolized adeno-associated virus serotype 1 (AAV1) encoding for human SERCA2a (AAV1.hSERCA2a) reduces lung fibrosis and associated vascular remodeling. SERCA2a gene therapy also decreases right ventricular pressure and hypertrophy in both prevention and curative protocols. In vitro, we observed that SERCA2a overexpression inhibits fibroblast proliferation, migration, and fibroblast-to-myofibroblast transition induced by transforming growth factor ß (TGF-ß1). Thus, pro-fibrotic gene expression is prevented by blocking nuclear factor κB (NF-κB)/interleukin-6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) activation. This effect is signaled toward an inhibitory mechanism of small mother against decapentaplegic (SMAD)/TGF-ß signaling through the repression of OTU deubiquitinase, ubiquitin aldehyde binding 1 (OTUB1) and Forkhead box M1 (FOXM1). Interestingly, this cross-inhibition leads to an increase of SKI and SnoN expression, an auto-inhibitory feedback loop of TGF-ß signaling. Collectively, our results demonstrate that SERCA2a gene transfer attenuates bleomycin (BLM)-induced PF by blocking the STAT3/FOXM1 pathway and promoting the SNON/SKI Axis. Thus, SERCA2a gene therapy may be a potential therapeutic target for PF.

Southwick angle measurements and SCFE slip severity classifications are affected by frog-lateral positioning.

OBJECTIVE: Slipped capital femoral epiphysis (SCFE) is a hip disorder where the femoral head slips relative to the neck at the physis. Appropriate treatment of SCFE depends on the severity of the slip, commonly categorised using the Southwick (SW) angle. The SW angle is measured in the frog-lateral leg position, which can be painful and potentially unattainable for patients. The purpose of this study is to determine how errors in frog-lateral radiograph positioning affect measured SW angles and slip classifications. METHODS: Models of SCFE hips were produced from one CT scan of a normal hip; 360 deformities were created. SW angles were measured from a simulated frog-lateral position. Femoral lateral head-neck angles (LHNA; equivalent to SW in incorrect frog-lateral plane) were measured over a range of 837 incorrect frog-lateral leg positions with positioning errors in flexion and/or internal/external rotation. RESULTS: Seventy-six per cent of all imaging position-deformity combinations had error in the reported angle (>1° difference between LHNA and SW). Of those, 70% had <5°, 24% had 5° to 10°, and 6% had >10° of error from the actual SW angle. Three per cent of LHNAs that had >10° error resulted from <10° of positioning error. CONCLUSIONS: If the patient is limited in flexion or external rotation, more diagnostic testing should be considered if error in the reported slip measurement would affect treatment decisions or if accurate severity classification is needed for research. Small positioning errors in moderate and severe slips can cause a > 10° LHNA error; additional three-dimensional imaging should be considered.

Relationships Between Severity of Deformity and Impingement in Slipped Capital Femoral Epiphysis.

BACKGROUND: In situ pinning, a low-risk treatment for slipped capital femoral epiphysis (SCFE), leaves the slipped femoral head in place and may reduce range of motion (ROM) and cause impingement. It is unclear when a more complex surgery should be considered, because the relationships between severity, slip stability, remodeling, impingement, and ROM are unknown. RESEARCH QUESTIONS: (1) Do more severe acute SCFE deformities (no bony remodeling) result in a greater loss of flexion ROM?(2) Does the presence or location of impingement on the pelvis vary with severity of acute SCFE deformity? METHODS: We developed a 3D geometric model of acute SCFE deformity from 1 computed tomography scan of a normal adolescent hip. Ethics board approval was obtained from our institution. Bone models were created from the segmented pelvis, epiphysis, and subphyseal femur.In total, 3721 SCFE deformities were simulated by combining posterior and inferior slips in the axial and coronal planes, respectively. Southwick angles were estimated from a frog-leg lateral projection. Deformities were divided into mild (0 to 30 degrees), moderate (30 to 60 degrees), and severe (≥60 degrees) Southwick groups. Each joint was flexed in combination with internal/external rotation until contact occurred. A total of 121 ROM trials, with different degrees of internal/external rotation (0 to 90 degrees at 1.5-degree steps) were performed for each deformity. RESULTS: In total, 3355 simulated SCFE deformities (363 could not be rotated out of impingement) were analyzed.Increasing slip severity reduced flexion ROM across the range of internal/external rotation. Contact occurred for most mild deformities, and for all moderate and severe deformities in at least 1 ROM trial. Impingement was observed mainly on the anterosuperior aspect of the acetabulum. CONCLUSIONS: Increasing slip severity in acute SCFE reduced flexion and increased incidence of impingement, primarily occurring on the anterosuperior aspect of the acetabulum. The impingement patterns observed are consistent with damaged cartilage locations seen in clinical literature. CLINICAL RELEVANCE: In this experimental model, moderate and severe acute slips in SCFE lead to reduced ROM and impingement with the acetabulum. This suggests that in situ pinning may result in impingement of moderate and severe acute SCFE slips.

MRI-detectable changes in mouse brain structure induced by voluntary exercise.

Physical exercise, besides improving cognitive and mental health, is known to cause structural changes in the brain. Understanding the structural changes that occur with exercise as well as the neuroanatomical correlates of a predisposition for exercise is important for understanding human health. This study used high-resolution 3D MR imaging, in combination with deformation-based morphometry, to investigate the macroscopic changes in brain structure that occur in healthy adult mice following four weeks of voluntary exercise. We found that exercise induced changes in multiple brain structures that are involved in motor function and learning and memory including the hippocampus, dentate gyrus, stratum granulosum of the dentate gyrus, cingulate cortex, olivary complex, inferior cerebellar peduncle and regions of the cerebellum. In addition, a number of brain structures, including the hippocampus, striatum and pons, when measured on MRI prior to the start of exercise were highly predictive of subsequent exercise activity. Exercise tended to normalize these pre-existing differences between mice.