Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat encoding a polyglutamine tract in ATXN7, a component of the SAGA histone acetyltransferase (HAT) complex. Previous studies provided conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here, we report that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing wild-type (wt) Atxn7, however, causes only mild ataxia and does not lead to the early lethality observed in SCA7 mice. Reduced Gcn5 expression strongly enhances retinopathy in SCA7 mice, but does not affect the known transcriptional targets of Atxn7, as expression of these genes is not further altered by Gcn5 depletion. These findings demonstrate that loss of Gcn5 functions can contribute to the time of onset and severity of SCA7 phenotypes, and suggest that non-transcriptional functions of SAGA may play a role in neurodegeneration in this disease.
Objectives. To compare health care coverage and utilization between men who have sex with men (MSM) in Medicaid expansion versus nonexpansion states. Methods. We used cross-sectional weighted data from the National HIV Behavioral Surveillance system, which used venue-based methods to interview and test MSM in 22 US cities from June through December, 2017 (n = 8857). We compared MSM in Medicaid expansion versus nonexpansion states by using the Rao-Scott χ2 test stratified by HIV status. We used multivariable logistic regression to model the relationship between Medicaid expansion, coverage, and preexposure prophylaxis (PrEP) use. Results. MSM in expansion states were more likely to have insurance (87.9% vs 71.6%), have Medicaid (21.3% vs 3.8%), discuss PrEP with a provider (58.8% vs 44.3%), or use PrEP (31.1% vs 17.5%). Conclusions. Medicaid expansion is associated with higher coverage and care, including PrEP. Public Health Implications. States may consider expanding Medicaid to help end the HIV epidemic. (Am J Public Health. Published online ahead of print January 21, 2021: e1–e9. https://doi.org/10.2105/AJPH.2020.306035 )
Objectives:
This study describes the hormone profiles for gonadal late effects after alkylator-based hematopoietic stem cell transplant (HSCT) regimens used for sickle-cell disease (SCD).
Methods:
This is a retrospective chart review of subjects followed in the post-HSCT clinic for sickle-cell disease. Patient demographics, pubertal development, characteristics of pre-HSCT disease severity, treatment before HSCT, conditioning regimens, presence of graft versus host disease and follicle-stimulating hormone, anti-Müllerian hormone (AMH), luteinizing hormone and testosterone were abstracted from the medical record.
Results:
Forty subjects (24 female individuals) with SCD were 9 (±4.3) years old at HSCT and 7.9 years (±5.6) from HSCT. At the time of transplant, 8% of female individuals and no male individuals were pubertal and 58% of female individuals and 38% of male individuals had been treated with hydroxyurea. Post-HSCT, all of the female individuals had diminished ovarian reserve on the basis of low AMH values and 10 of the pubertal female individuals (71%) had premature ovarian insufficiency defined as follicle-stimulating hormone >40 mIU/mL ×2. There was no ovarian recovery and AMH remained very low or undetectable up to 13 years post-HSCT. In male individuals, luteinizing hormone and testosterone levels were normal for age.
Conclusions:
Post-HSCT for SCD, all female individuals had diminished ovarian reserve and most female individuals had POI, whereas male individuals had normal testosterone hormone production.
To examine the association between HIV laws, perceived community stigma, and behaviors and to compare differences between and within Black and White men who have sex with men (MSM).Design/Methods: National HIV Behavioral Surveillance conducted interviews and HIV testing with MSM in 23 U.S. cities in 2017 using venue-based sampling methods. We used weighted cross-sectional data to compare MSM living in states with versus without HIV laws using Rao-Scott chi-square tests. We modeled the association between stigma and state HIV laws within racial groups to obtain adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs).Results: Among 7392 MSM, 56% lived in a state with HIV laws. In law states, Black MSM were more likely than White MSM to report their community would discriminate against persons with HIV (PWH) (59 versus 34%), not support the rights of PWH (20 versus 9%), not be friends with PWH (19 versus 10%), believe PWH 'got what they deserved' (27 versus 16%), and be intolerant of MSM (14 versus 5%). Adjusted for confounders, Black MSM in HIV law states were more likely to think their community would discriminate against PWH (aPR, 1.14; 95% CI, 1.02-1.29; P ¼ 0.02) and be intolerant toward MSM (aPR, 2.02; 95% CI, 1.43-2.86; P < 0.001) than Black MSM in states without such laws.Conclusions: HIV laws were related to higher stigma, but only for Black MSM. Future research regarding HIV-related laws should account for racial/ethnic disparities. Modernizing laws can delegitimize stigma and promote focusing on effective HIV prevention strategies.
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