GM1-gangliosidosis: The caregivers' assessments of symptom impact and most important symptoms to treat.

GM1-gangliosidosis (GM1) is a rare neurodegenerative disorder leading to early mortality and causing progressive decline of physical skills and cerebral functioning. No approved treatment for GM1 exists. In this study-the first to explore priorities of parents of subjects with pediatric onset forms of GM1-we address a crucial gap by characterizing symptoms most critical to caregivers of children with GM1 to treat. Our two-part, mixed-methods approach began with focus groups, followed by interviews with a distinct set of parents. Interviews included a prioritization activity that used best-worst scaling. Quantitative data were analyzed descriptively. Qualitative data were analyzed using thematic analysis and rapid analysis process. Parents prioritized the symptoms they believed would increase their child's lifespan and improve their perceived quality of life (QoL); these symptoms focused on communicating wants/needs, preventing pain/discomfort, getting around and moving one's body, and enhancing eating/feeding. Although lifespan was highly valued, almost all parents would not desire a longer lifespan without acceptable child QoL. Parents indicated high caregiver burden and progressive reduction in QoL for children with GM1. This novel study of caregiver priorities identified important symptoms for endpoints' selection in patient-focused drug development in the context of high disease impact and unmet treatment needs.

A qualitative exploration of unintentional versus intentional exposure to fentanyl among people who use drugs in Austin, TX.

BACKGROUND: The prevalence of deaths involving synthetic opioids has historically been lower in Texas than most U.S. states but more than quadrupled from January 2020 to January 2022. This paper explores the emergence of fentanyl in a drug supply where black tar heroin predominates, a factor considered protective against fentanyl adulteration, through the perspectives of people who use drugs (PWUD). OBJECTIVES: We describe experiences of unintentional exposure to fentanyl, illustrate how some people identify fentanyl in their supply, and present harm reduction strategies that PWUD use to avoid overdose. METHODS: Thirty rapid assessment interviews were conducted in July 2021 at 2 mobile outreach sites of a harm reduction organization in Austin, Texas. The brief semistructured interviews were designed to assess participant fentanyl exposure experiences. RESULTS: Participants were clients who reported using heroin or fentanyl in the past week and had lived in Texas for at least 6 months. Seventeen participants identified as male, 10 as female, and 3 as nonbinary. Half identified as white; other participants were Latinx (6), black (2), American Indian (1), and mixed race (6). Two-thirds were unhoused or in transitional housing. The drug supply in Texas has evolved; most participants reported that the heroin and other drugs they obtained contain fentanyl. Participants detected differences by observing changes in the physical characteristics of the drug, experiencing unexpected effects, and using fentanyl test strips. Many had been unintentionally exposed to fentanyl and expressed concerns about fentanyl's presence. The presence of fentanyl had negative unintended consequences for participants, including adverse effects and developing a dependence on opioids. CONCLUSION: PWUD in Austin, Texas, report increasing prevalence of unintentional fentanyl exposure, despite the predominance of black tar heroin. Pharmacists can provide crucial supplies and education to safeguard the health of this vulnerable population.

Health Disparities in the Neurosurgical Care of Patients with Trigeminal Neuralgia.

BACKGROUND: There has been limited investigation into how social determinants of health impact treatment outcomes in patients with trigeminal neuralgia (TN). We aimed to investigate how social determinants of health may alter the course of clinical care for patients with TN. METHODS: The electronic medical record was queried for patients with a diagnosis of TN comanaged by neurosurgeons and other facial pain specialists at our medical center. Area Deprivation Index served as a proxy for socioeconomic status (SES). Multivariable linear regression models were performed using RStudio to assess the impact of social determinants on the time to neurosurgical referral and surgical intervention. RESULTS: A total of 229 patients (mean age 50 years, 74% female) were included. Of these, 135 (60%) patients underwent a neurosurgical procedure after referral, the most common being microvascular decompression (n = 84, 62%) (Table 1). Most of the patients were white (76.3%) and insured by Medicare (51.8%), followed by private insurance (38.6%). Age and sex were significant predictors of time to neurosurgical referral after symptom onset, as older patients (P < 0.01, Figure 3) and females (P = 0.02) tended to have a greater delay between symptom onset and specialist referral. Race, SES, and insurance status were not significantly associated with time-to-referral or time-to-treatment. CONCLUSION: This study found that older and female patients with TN had a longer time from symptom onset to specialist referral. Based on these data, there is no association between race, SES, and insurance status with time-to-referral or time-to-treatment in patients with TN.

"Nothing is ever going to change if we don't start advocating for our child.": Community-level disclosure and stigma management strategies among parents of internationally adopted children living with PHIV.

Background: The number of internationally adopted children living with perinatally-acquired HIV (IACP) in the U.S. is increasing, yet little is known about their families' experiences navigating HIV disclosure within a community context. This paper examines the lived experiences of adoptive parents as they navigate HIV disclosure and manage stigma toward their adopted children within their broader communities. Methods: A purposive sample of parents of IACP was recruited at two pediatric infectious disease clinics and via closed Facebook groups. Parents completed two semi-structured interviews approximately one year apart. Interview questions included strategies parents used to reduce the impact of community level stigma that their child is likely to encounter as they mature. Interviews were analyzed using Sort and Sift, Think and Shift analytic approach. All parents (n = 24) identified as white and most (n = 17) had interracial families, with children adopted from 11 different countries (range: age at adoption 1-15 years; range: age at first interview 2-19 years). Results: Analyses revealed that parents serve as advocates for their child by both supporting more public HIV disclosure at times, but also applying indirect strategies such as working to improve outdated sex education material. Knowledge of HIV disclosure laws empowered parents to make informed decisions about who, if anyone, in the community needed to know their child's HIV status. Conclusion: Families with IACP would benefit from HIV disclosure support/training and community-based HIV stigma reduction interventions.

Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation.

Glutamate dysregulation occurs in multiple sclerosis (MS), but whether excitotoxic mechanisms in mature oligodendrocytes contribute to demyelination and axonal injury is unexplored. Although current treatments modulate the immune system, long-term disability ensues, highlighting the need for neuroprotection. Glutamate is elevated before T2-visible white matter lesions appear in MS. We previously reported that myelin-reactive T cells provoke microglia to release glutamate from the system xc - transporter promoting myelin degradation in experimental autoimmune encephalomyelitis (EAE). Here, we explore the target for glutamate in mature oligodendrocytes. Most glutamate-stimulated calcium influx into oligodendrocyte somas is AMPA receptor (AMPAR)-mediated, and genetic deletion of AMPAR subunit GluA4 decreased intracellular calcium responses. Inducible deletion of GluA4 on mature oligodendrocytes attenuated EAE and loss of myelinated axons was selectively reduced compared to unmyelinated axons. These data link AMPAR signaling in mature oligodendrocytes to the pathophysiology of myelinated axons, demonstrating glutamate regulation as a potential neuroprotective strategy in MS.