Ubiquitination of stalled ribosomes enables mRNA decay via HBS-1 and NONU-1 in vivo.

As ribosomes translate the genetic code, they can encounter a variety of obstacles that hinder their progress. If ribosomes stall for prolonged times, cells suffer due to the loss of translating ribosomes and the accumulation of aberrant protein products. Thus to protect cells, stalled ribosomes experience a series of reactions to relieve the stall and degrade the offending mRNA, a process known as No-Go mRNA Decay (NGD). While much of the machinery for NGD is known, the precise ordering of events and factors along this pathway has not been tested. Here, we deploy C. elegans to unravel the coordinated events comprising NGD. Utilizing a novel reporter and forward and reverse genetics, we identify the machinery required for NGD. Our subsequent molecular analyses define a functional requirement for ubiquitination on at least two ribosomal proteins (eS10 and uS10), and we show that ribosomes lacking ubiquitination sites on eS10 and uS10 fail to perform NGD in vivo. We show that the nuclease NONU-1 acts after the ubiquitin ligase ZNF-598, and discover a novel requirement for the ribosome rescue factors HBS-1/PELO-1 in mRNA decay via NONU-1. Taken together, our work demonstrates mechanisms by which ribosomes signal to effectors of mRNA repression, and we delineate links between repressive factors working toward a well-defined NGD pathway.

Preexposure Prophylaxis (PrEP) for HIV Prevention at Outpatient Substance Use Treatment Facilities, United States, 2021.

Objectives. To determine the percentage of US outpatient substance use treatment facilities that offer HIV preexposure prophylaxis (PrEP). Methods. We used a retrospective cross-sectional design with data from the National Substance Use and Mental Health Services Survey, which was administered to directors of US outpatient substance use treatment facilities in 2021. We evaluated the percentage of outpatient substance use treatment facilities offering PrEP and factors associated with the likelihood of offering PrEP. Results. We included 12 182 outpatient substance use treatment facilities. Of these, 637 (5.2%) offered PrEP. Offering HIV treatment (adjusted odds ratio [AOR] = 45.3; 95% confidence interval [CI] = 36.0, 56.9) and offering programs for LGBTQ (lesbian, gay, bisexual, transgender, and queer or questioning) people (AOR = 1.3; 95% CI = 1.0, 1.6) were associated with higher likelihoods of offering PrEP. Conclusions. PrEP is highly effective and recommended for patients at risk for HIV from injection drug use. Nearly 95% of US outpatient substance use treatment facilities did not offer PrEP-a missed opportunity for harm reduction through primary HIV prevention. Public Health Implications. Diversification of the array of available HIV PrEP options and the ongoing HIV and opioid use epidemics require outpatient substance use treatment facilities to expand PrEP availability. (Am J Public Health. 2024;114(8):833-837. https://doi.org/10.2105/AJPH.2024.307699).

Parallel Application to U.S. Psychiatry Residency Programs: Trends in Frequency and Differences by Applicant Group, 2009-2021.

OBJECTIVE: The present study examines trends of percent of applicants, number of specialties, and specialty combinations for psychiatry residency applicants applying to multiple specialties (parallel application). METHODS: The authors conducted a retrospective analysis of data captured by the Association of American Medical Colleges Electronic Residency Application System for applicants to psychiatry residency between 2009 and 2021. The percent parallel-applying, the mean number of specialties, mean application counts, and frequency of specialty combinations with psychiatry residency were determined. RESULTS: The dataset described 67,261 applicants. The percentage parallel-applying decreased from 73.7% in 2009 to 60.0% in 2021. International Medical Graduates and U.S. International Medical Graduate parallel-applied at the greatest rate in each year. Applicants who were parallel-applying submitted larger numbers of applications compared to those who were single-specialty applying. CONCLUSIONS: Parallel application to psychiatry residency appears to be a common practice, but has decreased in frequency. However, the mean numbers of applications submitted to each specialty in parallel application combination and among single-specialty applicants have increased. This practice appears to have a disproportionate impact on international and osteopathic applicants. Additional efforts are needed to develop evidence-based advising tools to reduce the number of residency applications submitted to psychiatry programs.

Availability of Long-Acting Injectable Buprenorphine at Substance Use Treatment Facilities in 2021.

This study assesses the proportion of US substance use and mental health care facilities that offered any medications for opioid use disorder and, specifically, long-acting injectable buprenorphine in 2021.

Psychiatry and Family Medicine Residents' Likelihood of Prescribing HIV Pre-exposure Prophylaxis to Patients With Mental Illness and HIV Vulnerability.

BACKGROUND: People living with mental illness (PLMI) experience disproportionately high incidence of and vulnerability to HIV. Pre-exposure prophylaxis (PrEP) is an effective and safe HIV prevention method, but data regarding prescription to PLMI are lacking. Psychiatrists may serve as important points of access for PrEP prescription for PLMI. METHODS: We conducted a vignette-based study of residents in psychiatry and family medicine (FM) to assess likelihood of prescribing PrEP and assumptions about the fictional patient. Participants were randomized to one of five vignettes in which the patients' psychiatric diagnosis was varied (schizophrenia on long-acting injectable or oral antipsychotic, bipolar disorder, major depression) or a control vignette without a psychiatric diagnosis. RESULTS: A total of 439 residents participated. We found that high percentages of psychiatry (96.8%) and FM (97.4%) residents were aware of PrEP. High percentages of psychiatry (92.0%-98.1%) and FM (80.8%-100%) residents reported that PrEP was indicated for all patient conditions. Family medicine residents were more likely to prescribe PrEP to all experimental conditions than psychiatry residents. There was no difference in likelihood of prescribing to the control condition without a psychiatric diagnosis. The belief that PrEP prescription was out of scope of practice was greater among psychiatry residents. CONCLUSIONS: A majority of psychiatry residents responded that PrEP was indicated for an array of patients with psychiatric diagnoses. However, psychiatry residents were broadly less likely to prescribe PrEP to patients with these diagnoses. The high percentage of psychiatry residents who reported that PrEP was indicated for all patients suggests that additional training is needed to facilitate PrEP prescription by psychiatrists.

Application in Parallel to U.S. Residency Training Programs in Multiple Specialties: Trends and Differences by Applicant Educational Background, 2009-2021.

PURPOSE: The medical education community is pursuing reforms addressing unsustainable growth in the number of residency applications per applicant and application costs. Little research has examined the prevalence or contributions of parallel applications (application to residency in multiple specialties) to this growth. METHOD: A retrospective analysis of Electronic Residency Application Service® data provided by the Association of American Medical Colleges was conducted. The percentage of applicants applying to ≥1 specialty, mean number of specialties applied, number of submitted applications, and percentage of applicants to each specialty who were parallel applying were determined. MD, DO, and international (U.S. international medical graduate [IMG] and IMG) applicants were included. RESULTS: The sample contained 586,246 applicant records from 459,704 unique applicants. The percentage of applicants who parallel applied decreased from 41.3% to 35.4% between 2009 and 2021. DO applicants were the only group for whom the percentage parallel applying increased (30.6% vs. 32.1%). IMG (60.4% vs. 49.1%) or USIMG applicants (69.6% vs. 63.1%) were groups with the greatest percentage of applicants parallel applying each year (2009-2021). The mean number of specialties applied to when parallel applying also decreased from 2.96 in 2009 to 2.79 in 2021, overall. Between 2009 and 2021, mean number of applications increased for all applicant types amongst both single-specialty applicant and parallel-applying applicants. Among applicants who were single-specialty applying, mean number of applications grew from 38.6 in 2009 to 74.6 in 2021 and from 95.2 to 149.8 for parallel-applying applicants. CONCLUSIONS: All applicant groups experienced decreases in percentages parallel applying except for DO applicants. Parallel application appears to be common and slowly declining, and does not appear to significantly contribute to increasing numbers of applications per candidate. Efforts to control the growth of applications per applicant should continue to focus on applicants' numbers of applications submitted to each specialty.