Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling.

The Disrupted in Schizophrenia 1 (DISC1) gene is disrupted by a balanced chromosomal translocation (1; 11) (q42; q14.3) in a Scottish family with a high incidence of major depression, schizophrenia, and bipolar disorder. Subsequent studies provided indications that DISC1 plays a role in brain development. Here, we demonstrate that suppression of DISC1 expression reduces neural progenitor proliferation, leading to premature cell cycle exit and differentiation. Several lines of evidence suggest that DISC1 mediates this function by regulating GSK3beta. First, DISC1 inhibits GSK3beta activity through direct physical interaction, which reduces beta-catenin phosphorylation and stabilizes beta-catenin. Importantly, expression of stabilized beta-catenin overrides the impairment of progenitor proliferation caused by DISC1 loss of function. Furthermore, GSK3 inhibitors normalize progenitor proliferation and behavioral defects caused by DISC1 loss of function. Together, these results implicate DISC1 in GSK3beta/beta-catenin signaling pathways and provide a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders.

Pharmacists' knowledge, perspectives, and experiences with mifepristone dispensing for medication abortion.

BACKGROUND: The U.S. Food and Drug Administration (FDA) restricts dispensing of mifepristone for medication abortion to certified health care providers at clinical facilities, thus prohibiting pharmacist dispensing. Allowing mifepristone dispensing by pharmacists could improve access to medication abortion. OBJECTIVE: To assess the feasibility of pharmacists dispensing mifepristone to patients who have undergone evaluation for eligibility and counseling for medication abortion by a clinician. METHODS: Before providing a study training on medication abortion, we administered baseline surveys to pharmacists who participated in a multisite mifepristone-dispensing intervention. The survey assessed medication abortion knowledge-using a 15-item score-and perceptions about the benefits and challenges of the model. We administered follow-up surveys in the study's final month that also assessed the pharmacists' satisfaction and experiences with mifepristone dispensing. To investigate the association of the study intervention with the pharmacists' knowledge, perceptions, and experiences dispensing mifepristone, we conducted multivariable linear regression analyses using generalized estimating equation models, accounting for clustering by individual. RESULTS: Among the 72 pharmacists invited from 6 pharmacies, 47 (65%) completed the baseline surveys, and 56 (78%) received training. At the study's end (mean 18 months later), 43 of the 56 pharmacists who received training (77%) completed the follow-up surveys. At follow-up, 36 (83%) respondents were very or somewhat satisfied with mifepristone dispensing, and 24 (56%) reported experiencing no challenges dispensing mifepristone. Four (6%) of the 72 pharmacists invited objected to participating in mifepristone dispensing. In regression analyses, average knowledge scores, perceived ease of implementation, and level of support for the pharmacist-dispensing model were higher at follow-up (P < 0.001). CONCLUSION: Most pharmacists were willing to be trained, dispensed mifepristone with few challenges when given the opportunity, were satisfied with the model, and had higher knowledge levels at follow-up. Our findings support removal of FDA's restriction on pharmacist dispensing of mifepristone.

Abortion Trends in Georgia Following Enactment of the 22-Week Gestational Age Limit, 2007-2017.

Objectives. To measure trends before, during, and after implementation of Georgia House Bill 954, a limit on abortion at 22 or more weeks of gestation passed in 2012, in total abortions and abortions by gestational age and state residence.Methods. We analyzed aggregate year-level induced termination of pregnancy data from the Georgia Department of Public Health from 2007 to 2017. We used linear regression to describe annual trends in the number of abortions and χ2 analyses to describe changes in proportions of abortions by gestational age (< 20 weeks, 20-21 weeks, and > 21 weeks) across policy implementation periods (before, partial, and full implementation) for Georgia residents and nonresidents.Results. Although the total number of abortions and abortions at 21 weeks or less remained stable from 2007 to 2017, the number of abortions at more than 21 weeks declined (P = .02). The decline in number of abortions at more than 21 weeks was steeper for nonresidents (31/year; Β = -31.3; P = .02) compared with Georgia residents (14/year; Β = -13.9; P = .06).Conclusions. Findings suggest that implementation of Georgia's 22-week gestational age limit has effectively limited access to needed abortion services in Georgia and beyond. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e5. doi:10.2105/AJPH.2020.305653).

Self-Determination of Eligibility for Medication Abortion Without Ultrasonography Using a History-Based Tool: LMP-SURE.

OBJECTIVE: To evaluate a self-screening eligibility tool for medication abortion without an ultrasonogram. METHODS: We designed a patient-administered, five-question screening tool (LMP-SURE) that assesses gestational age plus factors associated with misdating or ectopic pregnancy. We recruited participants without prior ultrasonograms from family planning clinics in Alaska, Hawai'i, Idaho, and Utah to complete a brief survey including LMP-SURE and then obtained ultrasound dating by chart review. We compared eligibility for medication abortion by ultrasonogram with eligibility by the LMP-SURE screening tool. RESULTS: We consented 1,026 participants; 781 met eligibility requirements and completed the tool. Using the LMP-SURE tool, we identified 493 participants (65.1%) eligible for medication abortion without an ultrasonogram. The LMP-SURE tool sensitivity (ability to correctly identify a patient ineligible for medication abortion) was 83.8% (95% CI, 73.1-90.8), specificity (ability to correctly identify a patient eligible for medication abortion) was 70.0% (95% CI, 66.4-73.3), likelihood ratio (-) (probability of someone eligible by LMP-SURE to be ineligible by ultrasonogram vs eligible by ultrasonogram) was 0.23 (95% CI, 0.13-0.40), and percentage of false-negatives was 1.5%. Only 11 patients (1.5%) who met eligibility for medication abortion without an ultrasonogram by the LMP-SURE tool were found ineligible for medication abortion by their ultrasonogram. Of those with conflicts, six (0.8%) had a gestational age beyond 77 days. The two participants (0.3%) diagnosed with ectopic pregnancies both required ultrasonograms by LMP-SURE. CONCLUSION: This patient-facing, brief, history-based screening tool can safely minimize the need for ultrasonogram before medication abortion.

Identifying Patients at Risk for Alcohol-Exposed Pregnancies: The Importance of Addressing Multiple Risk Factors.

BACKGROUND: The increasing prevalence of fetal alcohol spectrum disorders is a critical public health issue. Two behaviors, consuming alcohol and using less effective pregnancy prevention, may result in alcohol-exposed pregnancies (AEPs) in individuals who can become pregnant. In the context of alcohol screening and brief intervention (SBI) services, cutoff scores on widely used alcohol risk assessments (eg, Alcohol Use Disorders Identification Test, U.S. version [USAUDIT]) may fail to identify individuals whose relatively low alcohol consumption may still put them at risk for an AEP due to their pregnancy prevention method. METHODS: To identify this gap in alcohol SBI service delivery, we examined data from 2 reproductive healthcare systems implementing alcohol SBI, to explore the prevalence of individuals who met both of the following risk conditions: reported any alcohol use on the USAUDIT and a pregnancy prevention method less than 88% effective. Electronic health records for individuals aged 18 to 49 presenting for preventive care in 2021 were analyzed. RESULTS: Of 11 567 screened, 7638 reported some alcohol use, but screened at a lower-risk level and were not flagged to receive an alcohol-focused brief intervention (BI). Of these, 1477 were using a method of pregnancy prevention that was less than 88% effective. In addition, 118 of the 1676 who screened positive on the USAUDIT were using less effective contraception and did not receive a BI. In summary, the number of individuals at risk of an AEP who did not receive an alcohol BI was 1595 (13.8%) of the total patients screened for at-risk alcohol use. CONCLUSIONS: There is a need for system modifications to assess multiple behaviors simultaneously and alert providers when a combination of behaviors increases a specific health risk, such as an AEP. Tailored alcohol BIs that include the risks/benefits of various pregnancy prevention methods to reduce AEPs provide opportunities to enhance the reach of standard alcohol SBI services.

"No Big Deal": A Qualitative Study of Pharmacists' Perspectives on Dispensing Mifepristone for Medication Abortion.

INTRODUCTION: Until December 2021, the United States Food and Drug Administration impeded abortion access by restricting pharmacists from dispensing mifepristone, one of two drugs used in medication abortion. This study aimed to explore pharmacists' perspectives on dispensing mifepristone. METHODS: We conducted semistructured interviews with pharmacists before and after participating in a pilot project where mifepristone was dispensed from their pharmacies. We thematically coded all interview transcripts, then summarized emergent themes related to pharmacists' support, comfort, experiences, and concerns around dispensing mifepristone. RESULTS: Between May 2018 and July 2020, we interviewed 29 pharmacists (22 at baseline and 15 at follow-up, with 8 completing both interviews) from 5 pharmacies. At both baseline and follow-up, interviewees strongly supported pharmacists dispensing mifepristone, feeling it would improve quality of care by providing more convenient medication abortion access and streamlined service delivery and take advantage of pharmacists' expertise and availability. All pharmacists interviewed at follow-up reported dispensing mifepristone except two who were willing but did not have the opportunity. Pharmacists experienced few challenges dispensing mifepristone. Their main concern was perceived discomfort that other pharmacists and pharmacy staff may experience, particularly in conservative areas or small pharmacies where pharmacists' refusal to dispense mifepristone could impede abortion access. CONCLUSIONS: Most pharmacists supported dispensing mifepristone and were comfortable doing so after education on mifepristone and medication abortion. They dispensed mifepristone without difficulty, in a similar process as dispensing other medications. With the recent removal of U.S. Food and Drug Administration restrictions prohibiting it, our findings support the feasibility of pharmacists dispensing mifepristone.

Racial and Ethnic Abortion Disparities Following Georgia's 22-Week Gestational Age Limit.

INTRODUCTION: Georgia's 2012 House Bill 954 (HB954) prohibiting abortions after 22 weeks from last menstrual period (LMP) has been associated with a significant decrease in abortions after 22 weeks. However, the policy's effects by race or ethnicity remain unexplored. We investigated whether changes in abortion numbers and ratios (per 1,000 live births) in Georgia after HB954 varied by race or ethnicity. METHODS: Using Georgia Department of Public Health induced terminations of pregnancy data from 2007 to 2017, we examined changes in number of abortions and abortion ratios (per 1,000 live births) by race and ethnicity following HB954 implementation. RESULTS: After full implementation of HB954 in 2015, the number of abortions and abortion ratios at or after 22 weeks (from last menstrual period) decreased among White (bNumber = -261.83, p < .001; bRatio = -3.31, p < .001), Black (bNumber = -416.17, p < .001; bRatio = -8.84, p < .001), non-Hispanic (bNumber = -667.00, p = .001; bRatio = -5.82, p < .001), and Hispanic (bNumber = -56.25, p = .002; bRatio = -2.44, p = .002) people. However, the ratio of abortions before 22 weeks increased for Black people (bLessThan22Weeks = 44.06, p = .028) and remained stable for White (bLessThan22Weeks = -6.78, p = .433), Hispanic (bLessThan22Weeks = 21.27, p = .212), and non-Hispanic people (bLessThan22Weeks = 26.93, p = .172). CONCLUSION: The full implementation of HB954 had differential effects by race/ethnicity and gestational age. Although abortion at 22 weeks or more decreased for all groups, abortion at less than 22 weeks increased among Black people. Additional research should elucidate the possible causes, consequences, and reactions to differential effects of abortion restrictions by race and ethnicity.

Medication Abortion With Pharmacist Dispensing of Mifepristone.

OBJECTIVE: To estimate effectiveness and acceptability of medication abortion with mifepristone dispensed by pharmacists. METHODS: We conducted a prospective cohort study at eight clinical sites and pharmacies in California and Washington State from July 2018 to March 2020. Pharmacists at participating pharmacies underwent a 1-hour training on medication abortion. We approached patients who had already been evaluated, counseled, and consented for medication abortion per standard of care. Patients interested in study participation gave consent, and the clinician electronically sent a prescription to the pharmacy for mifepristone 200 mg orally, followed 24-48 hours later by misoprostol 800 micrograms buccally. Participants were sent web-based surveys about their experience and outcomes on days 2 and 14 after enrollment and had routine follow-up with study sites. We extracted demographic and clinical data, including abortion outcome and adverse events, from medical records. We performed multivariable logistic regression to assess the association of pharmacy experience and other covariates with satisfaction. RESULTS: We enrolled 266 participants and obtained clinical outcome information for 262 (98.5%), of whom two reported not taking either medication. Of the 260 participants with abortion outcome information, 252 (96.9%) and 237 (91.2%) completed day 2 and 14 surveys, respectively. Complete medication abortion (primary outcome) occurred for 243 participants (93.5%, 95% CI 89.7-96.1%). Four participants (1.5%, 95% CI 0.4-3.9%) had an adverse event, none of which was serious or related to pharmacist dispensing. In the day 2 survey, 91.3% (95% CI 87.1-94.4%) of participants reported satisfaction with the pharmacy experience. In the day 14 survey, 84.4% (95% CI 79.1-88.8%) reported satisfaction with the medication abortion experience. Those reporting being very satisfied with the pharmacy experience had higher odds of reporting overall satisfaction with medication abortion (adjusted odds ratio 2.96, 95% CI 1.38-6.32). CONCLUSION: Pharmacist dispensing of mifepristone for medication abortion is effective and acceptable to patients, with a low prevalence of adverse events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03320057.

Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning.

Neurotrophins were initially identified as critical regulators of neuronal survival. However, these factors have many additional functions. In the developing cerebellum the roles of the neurotrophins BDNF and NT3 include a surprising effect on patterning, as revealed by changes in foliation in neurotrophin-deficient mice. Here we examine the potential role of p75NTR in cerebellar development and patterning. We show that p75NTR is expressed at highest levels in the region of the cerebellum where foliation is altered in BDNF and NT3 mutants. Although the cerebellar phenotype of p75NTR mutant animals is indistinguishable from wild type, mutation of p75NTR in BDNF heterozygotes results in defects in foliation and in Purkinje cell morphologic development. Taken together, these data suggest that p75NTR activity is critical for cerebellar development under pathologic circumstances where neurotrophin levels are reduced.