Hippocampal Reduction of α-Synuclein via RNA Interference Improves Neuropathology in Alzheimer's Disease Mice.

BACKGROUND: Alzheimer's disease (AD) cases are often characterized by the pathological accumulation of α-synuclein (α-syn) in addition to amyloid-ß (Aß) and tau hallmarks. The role of α-syn has been extensively studied in synucleinopathy disorders, but less so in AD. Recent studies have shown that α-syn may also play a role in AD and its downregulation may be protective against the toxic effects of Aß accumulation. OBJECTIVE: We hypothesized that selectively knocking down α-syn via RNA interference improves the neuropathological and biochemical findings in AD mice. METHODS: Here we used amyloid precursor protein transgenic (APP-Tg) mice to model AD and explore pathologic and behavioral phenotypes with knockdown of α-syn using RNA interference. We selectively reduced α-syn levels by stereotaxic bilateral injection of either LV-shRNA α-syn or LV-shRNA-luc (control) into the hippocampus of AD mice. RESULTS: We found that downregulation of α-syn results in significant reduction in the number of Aß plaques. In addition, mice treated with LV-shRNA α-syn had amelioration of abnormal microglial activation (Iba1) and astrocytosis (GFAP) phenotypes in AD mice. CONCLUSION: Our data suggests a novel link between Aß and α-syn pathology as well as a new therapeutic angle for targeting AD.

Ethics of a Mandatory Waiting Period for Female Sterilization.

Due to a history of coerced sterilization, a federal Medicaid sterilization policy mandates that a specific consent form be signed by a patient at least thirty days prior to when the patient undergoes sterilization. However, in contemporary obstetrical practice, the Medicaid sterilization policy serves as a policy-level barrier to autonomously desired care. We review the clinical and ethical implications of the current Medicaid sterilization policy. After discussing the utility and impact of waiting periods for other surgical procedures, we explore the psychology of time required for decision-making and consider scientific understanding of regret. We argue that the current Medicaid sterilization waiting period is clinically and ethically unjustifiable and that the policy ought to be revised in light of the goals, preferences, and concerns of the people most affected by it. While the need for continued protection against coercion remains, the current mandated waiting period does little to enforce the high-quality shared decision-making that is desired for sterilization counseling.

Association of race and ethnicity with postpartum contraceptive method choice, receipt, and subsequent pregnancy.

BACKGROUND: We sought to assess racial/ethnic differences in choice of postpartum contraceptive method after accounting for clinical and demographic correlates of contraceptive use. METHODS: This is a secondary analysis of a single-center retrospective cohort study examining postpartum women from 2012 to 2014. We determined the association between self-identified race/ethnicity and desired postpartum contraception, receipt, time to receipt, postpartum visit attendance, and subsequent pregnancy within 365 days of delivery. RESULTS: Of the 8649 deliveries in this study, 46% were by Black women, 36% White women, 12% Hispanic, and 6% by women of other races. Compared with White women, Black and Hispanic women were more likely to have a postpartum contraception plan for all methods. After multivariable analysis, Hispanic women (relative to White women) were less likely to receive their chosen method (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.64-0.87). Women of races other than Black or Hispanic were less likely to experience a delay in receipt of their desired highly-effective method compared to White women (hazard ratio [HR] = 0.70, 95% CI 0.52-0.94). There were no differences between racial/ethnic groups in terms of postpartum visit adherence. Black women were more likely to be diagnosed with a subsequent pregnancy compared to White women (OR 1.17, 95% CI 1.04-1.32). CONCLUSION: Racial/ethnic variation in postpartum contraceptive outcomes persists after accounting for clinical and demographic differences. While intrinsic patient-level differences in contraceptive preferences should be better understood and respected, clinicians should take steps to ensure that the observed differences in postpartum contraceptive plan methods between racial/ethnic groups are not due to biased counseling.