Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

Allergens TRP a swITCH to Initiate Type 2 Immunity.

Allergens induce type-2 immunity, but unresolved questions remain about initiation of this response. In this issue, Perner et al. propose that cutaneous activation of TRPV1+ sensory neurons by protease allergens stimulates release of substance P to induce migration of Th2-skewing CD301b+ DC to draining lymph nodes.

Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts.

Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, two from the US (All of Us, n = 82,474; the Million Veteran Program, n = 622,497) and one from the UK (UK Biobank, n = 380,899). Our results from a mixed-effect meta-analysis demonstrate an overall trend of decreasing autozygosity over generational time (meta-analyzed slope = -0.029, SE = 0.009, p = 6.03e-4). On the basis of our estimates, we would predict FROH to decline 0.29% for every 20-year increase in birth year. We determined that a model including an ancestry-by-country interaction term fit the data best, indicating that ancestry differences in this trend differ by country. We found further evidence to suggest a difference between the US and UK cohorts by meta-analyzing within country, observing a significant negative estimate in the US cohorts (meta-analyzed slope = -0.058, SE = 0.015, p = 1.50e-4) but a non-significant estimate in the UK (meta-analyzed slope = -0.001, SE = 0.008, p = 0.945). The association between autozygosity and birth year was substantially attenuated when accounting for educational attainment and income (meta-analyzed slope = -0.011, SE = 0.008, p = 0.167), suggesting they may partially account for decreasing autozygosity over time. Overall, we demonstrate decreasing autozygosity over time in a large, modern sample and speculate that this trend can be attributed to increases in urbanization and panmixia and differences in sociodemographic processes lead to country-specific differences in the rate of decline.

DUF2285 is a novel helix-turn-helix domain variant that orchestrates both activation and antiactivation of conjugative element transfer in proteobacteria.

Horizontal gene transfer is tightly regulated in bacteria. Often only a fraction of cells become donors even when regulation of horizontal transfer is coordinated at the cell population level by quorum sensing. Here, we reveal the widespread 'domain of unknown function' DUF2285 represents an 'extended-turn' variant of the helix-turn-helix domain that participates in both transcriptional activation and antiactivation to initiate or inhibit horizontal gene transfer. Transfer of the integrative and conjugative element ICEMlSymR7A is controlled by the DUF2285-containing transcriptional activator FseA. One side of the DUF2285 domain of FseA has a positively charged surface which is required for DNA binding, while the opposite side makes critical interdomain contacts with the N-terminal FseA DUF6499 domain. The QseM protein is an antiactivator of FseA and is composed of a DUF2285 domain with a negative surface charge. While QseM lacks the DUF6499 domain, it can bind the FseA DUF6499 domain and prevent transcriptional activation by FseA. DUF2285-domain proteins are encoded on mobile elements throughout the proteobacteria, suggesting regulation of gene transfer by DUF2285 domains is a widespread phenomenon. These findings provide a striking example of how antagonistic domain paralogues have evolved to provide robust molecular control over the initiation of horizontal gene transfer.

Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

Sexual and Gender Minorities' Vaccine Uptake and Behavioral Change in Response to the Mpox Outbreak in the United States: August 2022 Through November 2022.

BACKGROUND: In the summer of 2022, the United States faced a nationwide outbreak of mpox, with cases concentrated in sexual and gender minorities who have sex with men. Understanding rates of mpox vaccine uptake and concomitant behavioral change is essential to guide the implementation of targeted public health responses to the potential reemergence of mpox. METHODS: Between August 2022 and November 2022, 8551 individuals recruited via geosocial networking apps completed a brief survey that assessed mpox vaccine uptake, intentions to get a mpox vaccine, and behavioral change. RESULTS: In August, 17.4% of participants reported having received at least 1 dose of the mpox vaccine. By November, this prevalence estimate was 35.0%. Black participants were significantly less likely to be vaccinated, and vaccine hesitancy increased among Black participants over time. Among those who had not yet received a vaccination, the intention to get vaccinated decreased over time. We observed trends that coincided with the evolving outbreak, such as decreased worry about mpox and less engagement in risk reduction behaviors over time. CONCLUSIONS: Despite a 2-fold increase in mpox vaccine uptake between August 2022 and November 2022 in sexual and gender minorities who have sex with men, disparities in vaccine uptake were observed among Black participants. Findings will guide the implementation of public health responses to the potential reemergence of mpox and other viral infectious diseases (eg, meningitis) with a specific focus on optimizing vaccine uptake in Black communities.

Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program.

BACKGROUND: The Million Veteran Program (MVP) participants represent 100 years of US history, including significant social and demographic changes over time. Our study assessed two aspects of the MVP: (i) longitudinal changes in population diversity and (ii) how these changes can be accounted for in genome-wide association studies (GWAS). To investigate these aspects, we divided MVP participants into five birth cohorts (N-range = 123,888 [born from 1943 to 1947] to 136,699 [born from 1948 to 1953]). RESULTS: Ancestry groups were defined by (i) HARE (harmonized ancestry and race/ethnicity) and (ii) a random-forest clustering approach using the 1000 Genomes Project and the Human Genome Diversity Project (1kGP + HGDP) reference panels (77 world populations representing six continental groups). In these groups, we performed GWASs of height, a trait potentially affected by population stratification. Birth cohorts demonstrate important trends in ancestry diversity over time. More recent HARE-assigned Europeans, Africans, and Hispanics had lower European ancestry proportions than older birth cohorts (0.010 < Cohen's d < 0.259, p < 7.80 × 10-4). Conversely, HARE-assigned East Asians showed an increase in European ancestry proportion over time. In GWAS of height using HARE assignments, genomic inflation due to population stratification was prevalent across all birth cohorts (linkage disequilibrium score regression intercept = 1.08 ± 0.042). The 1kGP + HGDP-based ancestry assignment significantly reduced the population stratification (mean intercept reduction = 0.045 ± 0.007, p < 0.05) confounding in the GWAS statistics. CONCLUSIONS: This study provides a characterization of ancestry diversity of the MVP cohort over time and compares two strategies to infer genetically defined ancestry groups by assessing differences in controlling population stratification in genome-wide association studies.

MRI-based radiomic features of the urinary bladder wall identify patients with moderate-to-severe international prostate symptom score.

BACKGROUND: The International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder outlet obstruction induces molecular and morphological alterations in the urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, and nerves. We sought to analyze MRI-based radiomics features of the urinary bladder wall and their association with IPSS. METHOD: In this retrospective study, 87 patients who had pelvic MRI scans were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features of the bladder wall from MR images, including morphological, intensity-based, and texture-based features, along with clinical variables. Mathematical models were created using subsets of features and evaluated based on their ability to discriminate between low and moderate-to-severe IPSS (less than 8 vs. equal to or greater than 8). RESULTS: Of the 7,666 features per patient, four highest-ranking optimal features were derived (all texture-based features), which provided a classification accuracy of 0.80 with a sensitivity, specificity, and area under the receiver operating characteristic curve of 0.81, 0.81, and 0.87, respectively. CONCLUSION: A highly independent set of urinary bladder wall features derived from MRI scans were able to discriminate between patients with low vs. moderate-to-severe IPSS with accuracy of 80%. Such differences in MRI-based properties of the bladder wall in patients with varying IPSS's might reflect differences in underlying molecular and morphological alterations that occur in the setting of chronic bladder outlet obstruction.

Perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP) as an STI-prevention strategy among gay and bisexual men (GBM) in the United States: Results from a qualitative study.

OBJECTIVE: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.S., nor how best to engage those most vulnerable to STIs in taking up this nascent prevention strategy. METHOD: Between July and September of 2023, 24 GBM from across the U.S. completed qualitative interviews about their perceptions regarding Doxy-PEP. Interviews were analyzed using a codebook approach to thematic analysis. RESULTS: Participants were generally interested in using Doxy-PEP, but were concerned about the potential for antibiotic resistance, side-effects, medication interactions to occur, along with stigmatizing discourse around its use. Meanwhile, participants were motivated by the simplicity of Doxy-PEP and the protection it could confer on both an individual and community-level- as well as its potential to reduce STI-related anxiety. Finally, participants desired additional information on Doxy-PEP to address their concerns. CONCLUSIONS: There is a need for clear guidelines and expanded public health messaging on Doxy-PEP in the U.S.

Exploration of bromodomain ligand-linker conjugation sites for efficient CBP/p300 heterobifunctional degrader activity.

Synthesis of proteolysis targeting chimeras (PROTACs) involves conjugation of an E3 ligase binding ligand to a ligand targeting a protein of interest via a rigid or flexible chemical linker. The choice of linker conjugation site on these ligands can be informed by structural analysis of ligand-target binding modes, the feasibility of synthetic procedures to access specific sites, and computational modeling of predicted ternary complex formations. Small molecules that target bromodomains - epigenetic readers of lysine acetylation - typically offer several potential options for linker conjugation sites. Here we describe how varying the linker attachment site (exit vector) on a CBP/p300 bromodomain ligand along with linker length affects PROTAC degradation activity and ternary complex formation. Using kinetic live cell assays of endogenous CBP and p300 protein abundance and bead-based proximity assays for ternary complexes, we describe the structure-activity relationships of a diverse library of CBP/p300 degraders (dCBPs).

PrEP Uptake and Methamphetamine Use Patterns in a 4-Year U.S. National Prospective Cohort Study of Sexual and Gender Minority People, 2017-2022.

Methamphetamine use is on the rise among sexual and gender minority people who have sex with men (SGMSM), escalating their HIV risk. Despite pre-exposure prophylaxis (PrEP) being an effective biomedical HIV prevention tool, its uptake in relation to methamphetamine use patterns in SGMSM has not been studied. In a U.S. cohort study from 2017 to 2022, 6,253 HIV-negative SGMSM indicated for but not using PrEP were followed for four years. Methamphetamine use was categorized (i.e., newly initiated, persistently used, never used, used but quit), and PrEP uptake assessed using generalized estimating equation (GEE), adjusted for attrition. Participants had a median age of 29, with 51.9% White, 11.1% Black, 24.5% Latinx, and 12.5% other races/ethnicities. Over the four years, PrEP use increased from 16.3 to 27.2%. GEE models identified risk factors including housing instability and food insecurity. In contrast, older age, health insurance, clinical indications, and prior PrEP use increased uptake. Notably, Latinx participants were more likely to use PrEP than Whites. Regarding methamphetamine use, those who newly initiated it were more likely to use PrEP compared to non-users. However, those who quit methamphetamine and those who persistently used it had PrEP usage rates comparable to those of non-users. Though PrEP uptake increased, it remained low in SGMSM. Methamphetamine use was associated with PrEP uptake. Healthcare providers should assess methamphetamine use for harm reduction. Prioritizing younger, uninsured SGMSM and addressing basic needs can enhance PrEP uptake and reduce HIV vulnerabilities.

Use of antithymocyte globulin (rabbit) in a patient with known alpha-gal syndrome undergoing allogenic stem cell transplantation.

INTRODUCTION: Alpha-gal syndrome (AGS) is a hypersensitivity disorder in which tick bites-most commonly from the lone star tick (Ambylomma americanum)-trigger immunoglobulin E-mediated hypersensitivity reaction upon exposure to oligosaccharide galactosse-alpha-1,3-galactose (α-gal). α-gal is most notorious for being found in "red meat" products but is present in mammalian meats such as beef, pork, lamb, rabbit, and others. Manifestations of AGS hypersensitivity are variable. There is currently no in vivo data describing allergic reactions against rabbit products in patients with AGS. CASE REPORT: Here, we describe a case of a 44-year-old male with myelodysplastic syndrome and a known history of AGS undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) with the use of rabbit antithymocyte globulin (rATG) for graft-versus-host disease (GVHD) prophylaxis. MANAGEMENT AND OUTCOME: The risk of cross-reactivity against rATG in our patient with AGS could not be ruled out and, therefore, a test dose was administered. The patient tolerated the test dose with no signs of anaphylaxis. After demonstrating tolerance to the test dose, rATG was utilized for GVHD prophylaxis. DISCUSSION: Due to the heterogeneity of AGS manifestations in patients, the use of rATG in patients with known AGS should be considered on a case-by-case basis. The administration of a test dose may help predict the occurrence of severe hypersensitivity reactions. The limited data surrounding the risk of AGS with rabbit-containing products and the various indications for the use of rATG warrants more in-depth study of the reactivity of this medication in this population.

Veteran Beliefs About the Causes of Gulf War Illness and Expectations for Improvement.

BACKGROUND: Individuals' beliefs about the etiology of persistent physical symptoms (PPS) are linked to differences in coping style. However, it is unclear which attributions are related to greater expectations for improvement. METHOD AND RESULTS: A cross-sectional regression analysis (N = 262) indicated that Veterans with Gulf War Illness (GWI) who attributed their GWI to behavior, (e.g., diet and exercise), had greater expectations for improvement (p = .001) than those who attributed their GWI to deployment, physical, or psychological causes (p values > .05). CONCLUSIONS: Findings support the possible clinical utility of exploring perceived contributing factors of PPS, which may increase perceptions that improvement of PPS is possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02161133.

Degenerative medial and lateral menisci root tears: demographics, clinical presentation, imaging features, and associated findings.

PURPOSE: (I) Characterize the demographics and clinical features of patients with meniscal root tears (MRT); (II) analyze the morphology, extent, and grade of MRT on MRI; (III) evaluate associated abnormalities on imaging; and (IV) evaluate the associations between imaging findings, demographics, clinical features, and joint structural abnormalities. MATERIAL AND METHODS: A search was performed to identify meniscal root tears. Age, sex, BMI, and pain were recorded. Knee radiographs and MRI were reviewed. Presence, grade and morphology of MRT, meniscal extrusion, insufficiency fractures, as well as joint structural abnormalities were scored. For goals (I), (II), and (III), tabulations for categorical variables and mean for continuous variables were computed. MRT findings variables were described using percentages. For goal (IV), adjusted linear and logistic regression were employed. RESULTS: Ninety-six patients with a mean age of 56.6 years (69 females) and mean BMI of 28.9 kg/m2 were included; 88 of the MRT were located at the posterior horn of the medial meniscus (PHMM), and 82% were radial tear. The mean tear diameter was 3.8 mm, and 78/96 tears presented with meniscal extrusion. Nineteen patients presented with subchondral insufficiency fracture (SIF), which was significantly associated with the gap of the tear (p = 0.001) and grade of the meniscal root lesion (p = 0.005). CONCLUSION: MRT typically found in middle-aged to older overweight and obese women. Lesions were mostly radial tears and located at PHMM and were frequently associated with meniscal extrusion and SIF. Moreover, the presence of SIF was significantly associated with the gap width and grade of root tear.

Increasing Hip Arthroscopy Case Volume Is Associated With Increased Risk for Revision Surgery but Not Conversion to Total Hip Arthroplasty or 90-Day Hospitalizations: A Cross-Sectional Analysis of 468 Surgeons.

PURPOSE: To analyze the effects of surgeon-specific factors, including case volume, career duration, fellowship training, practice type, and region of practice, on rates of 2-year revision surgery, conversion to total hip arthroplasty (THA), and 90-day hospitalizations following hip arthroscopy. METHODS: The PearlDiver Mariner Database was used to query patients undergoing hip arthroscopy between 2015 and 2018. Surgeons performing these procedures were identified, and surgeon-specific demographics and variables were collected from publicly available data. Patients were followed for 2 years to assess for reoperations, including revision hip arthroscopy and conversion to THA, as well as 90-day hospitalizations, including emergency department visits and hospital readmissions. International Classification of Diseases, Tenth Revision codes were used to track the laterality of revision hip procedures. Associations between surgeon-specific factors and postoperative outcomes were assessed through univariate and multivariate analyses. RESULTS: In total, 20,834 patients underwent hip arthroscopy procedures by 468 surgeons. Multivariate analysis with logistic regression adjusted for patient-related factors (age, sex, obesity, Charlson Comorbidity Index, and smoking status) identified increasing surgeon case volume to be associated with increased risk for 2-year revision hip arthroscopy (P < .001), but not 2-year conversion to THA or 90-day hospitalizations. Nonsports medicine fellowship-trained surgeons were associated with greater risk for 2-year THA conversion (P < .001) and 90-day hospital readmissions (P < .01). Surgeons practicing in an academic setting demonstrated greater risk for 90-day hospital readmissions (P < .001). Surgeons practicing in the West region of the United States were more likely to incur 2-year revision hip arthroscopy procedures compared to surgeons in the South, Midwest or Northeast (P < .001). CONCLUSIONS: Increasing surgeon hip arthroscopy case volume is associated with an increased risk for 2-year revision hip arthroscopy but not conversion to THA or 90-day hospitalizations. Further, non-sports medicine fellowship-trained surgeons were associated with higher risk for 2-year THA conversion after hip arthroscopy. LEVEL OF EVIDENCE: Level III, retrospective cohort analysis.

No Differences in 2-Year Reoperation Rates for Meniscus Allograft Transplant With Concomitant Cartilage Restoration or Osteotomy: A National Database Study.

PURPOSE: To investigate reoperation rates after meniscus allograft transplant (MAT), comparing rates with and without concomitant articular cartilage and osteotomy procedures using a national insurance claims database. METHODS: We performed a retrospective cohort study of patients who underwent MAT from 2010 to 2021 with minimum 2 year follow-up using the PearlDiver database. Using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) codes, we identified patients who underwent concomitant procedures including chondroplasty or microfracture, cartilage restoration defined as osteochondral graft or autologous chondrocyte implantation (ACI), or osteotomy. Univariate logistic regressions identified risk factors for reoperation. Reoperations were classified as knee arthroplasty, interventional procedures, or diagnostic or debridement procedures. RESULTS: 750 patients were included with an average age of 29.6 years (interquartile range 21.0-36.8) and average follow-up time was 5.41 years (SD: 2.51). 90-day, 2-year, and all-time reoperation rates were 1.33%, 14.4%, and 27.6% respectively. MAT with cartilage restoration was associated with increased reoperation rate at 90 days (OR: 4.88; 95% CI: 1.38-19.27; p=.015), however there was no significant difference in reoperation rates at 2 years or to the end of follow-up. ACI had increased reoperation rates at 90 days (OR: 6.95; 95% CI: 1.45-25.96; p=.006), with no difference in reoperation rates 2 years post-operatively or to the end of follow-up. Osteochondral autograft and allograft were not associated with increased reoperation rates. CONCLUSION: 14.4% of patients in our cohort had a reoperation within 2 years of MAT. Nearly one in four patients undergoing MAT had concomitant cartilage restoration, showing that it is commonly performed on patients with articular cartilage damage. Concomitant osteochondral autograft, osteochondral allograft, chondroplasty, microfracture and osteotomy were not associated with any significant difference in reoperation rates. ACI was associated with increased reoperation rates at 90 days, but not later.

Concomitant Medial Collateral Ligament Injury Increases the Risk of Revision Anterior Cruciate Ligament Reconstruction.

PURPOSE: To compare rates of revisions between patients with isolated ACL reconstruction to those who had concomitant MCL injuries managed either operatively or non-operatively at time of index ACL reconstruction (ACLR). METHODS: The PearlDiver-Mariner Database was queried for all patients who underwent ACLR between 2016-2020 using laterality-specific International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes. Patients were included if they were ages 15 or higher and had a minimum of 2 years follow-up after index ACLR. Patients were then divided into cohorts by presence or absence of concomitant MCL injury. The cohort of concomitant MCL injuries was further subdivided into those with MCL injuries managed non-operatively, with MCL repair, or with MCL reconstruction at time of index ACLR. Multivariate regression was performed between cohorts to evaluate for factors associated with revision ACLR. RESULTS: We identified 47,306 patients with isolated ACL injuries and 10,846 with concomitant MCL and ACL injuries. 93% of patients with concomitant MCL injuries had their MCL treated non-operatively; however, the annual proportion of patients being surgically managed for their MCL injury increased by 70% from 2016-2020. Concomitant MCL injury patients had higher odds of undergoing revision ACLR compared to patients with isolated ACL injuries (OR:1.50, 95%CI: 1.36-1.66, p<0.001). Amongst patients with concomitant MCL injuries, surgically managed patients had higher risk of revision ACLR compared to non-operatively managed MCL injuries (OR:1.39, 95%CI:1.01-1.86, p=0.034). CONCLUSIONS: Despite an increase in operatively managed concomitant MCL injuries, the majority of concomitant MCL injuries are still managed non-operatively at time of ACLR. Patients with concomitant MCL injury, particularly those managed operatively, at the time of ACLR are at increased risk of requiring revision ACLR compared to those with isolated ACL injuries.

Incidence, risk factors, and complications of acromial stress fractures after reverse total shoulder arthroplasty.

BACKGROUND: An acromial stress fracture (ASF) is an uncommon complication after reverse total shoulder arthroplasty (RTSA) that can have severe clinical consequences on shoulder function. Although patient-specific factors have been identified to influence the risk of ASF, it is unclear whether modifying these factors can minimize risk. Moreover, there is limited information on the treatment outcomes of these fractures. Therefore, the purpose of this study was to determine modifiable risk factors for ASFs and the complication and revision rates of conservatively and operatively managed ASFs. METHODS: The PearlDiver database was queried to identify a cohort of patients who underwent RTSA with minimum 2-year follow-up. Current Procedural Terminology and International Classification of Diseases codes were used to compare the demographic characteristics, comorbidities, and medication use of patients with and without ASFs. Surgical complication and revision rates were compared between operatively and conservatively treated fractures. RESULTS: The overall incidence of ASFs was 1.4%. Patient-specific factors that were independently associated with the occurrence of an ASF included osteoporosis, rheumatologic disease, shoulder corticosteroid injection within 3 months before surgery, and chronic oral corticosteroid use. Among patients with osteoporosis, the initiation of physical therapy within 6 weeks after surgery also increased the risk of ASF. Patients who underwent surgical treatment of ASFs had a revision arthroplasty rate of 7.0% compared to a rate of 3.2% among those with conservatively managed fractures. CONCLUSION: ASFs are infrequent complications that can occur after RTSA. Preoperative factors that affect the quality of bone independently increase the fracture risk. Moreover, this risk can be minimized by avoiding shoulder corticosteroid injections 3 months before surgery and delaying physical therapy exercises among patients with osteoporosis. Surgical fixation of these fractures should be reserved for instances when conservative management has failed given high rates of infection, instability, and revision shoulder arthroplasty.

Psychosocial Distress Among Young Men Who Have Sex With Men: A Scoping Review.

PURPOSE: Psychosocial distress negatively impacts coping and adaptation among young men (aged 18 to 44 years) who have sex with men (YMSM) with, or at risk of acquiring, HIV. However, the stressors and risky behaviors associated with psychosocial distress that impair viral suppression have not been clearly explicated. The current scoping review was conducted to explore the extant literature and identify research gaps. METHOD: PubMed and CINAHL were searched for peer-reviewed publications, with a total of eight articles meeting inclusion criteria. RESULTS: Stressors that contributed to psychosocial distress included HIV+ status, stigma, discrimination, insufficient resources, exposure to community violence, and incarceration. Risky behaviors impacting viral suppression were condomless anal sex, drug use, and medication nonadherence. CONCLUSION: Understanding and addressing psychosocial distress is imperative for providing holistic care tailored to the unique health care needs of YMSM. A better understanding of stressors and associated risky behaviors will aid efforts to mitigate psychosocial distress and reduce viral load among YMSM. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

Methadone-Induced Hypoglycemia in a Hospitalized Patient.

Methadone is used as an agent for chronic pain and management of opioid use disorder. While similar pharmacologically to other opioids, methadone does have unique characteristics, including long half-life, low cost, and high oral bioavailability. While advantageous in some ways, methadone is associated with unique adverse effects not seen with other opioids (ie, hypoglycemia). In this case, we describe a patient in his late-60s with opioid use disorder on chronic methadone who presents with symptoms of generalized weakness, fatigue, and decreased appetite for 2 days. The hospital course was complicated by hypoglycemia, without obvious cause other than methadone-induced hypoglycemia. The patient was managed with supportive care to maintain normoglycemia. He was continued on methadone and instructed to follow-up with his opioid treatment program to assess for dose de-escalation to minimize future hypoglycemia risk. While other case reports of methadone-induced hypoglycemia highlight the risk of this adverse effect, our case highlights the importance of assessing methadone as a cause of hypoglycemia and provides discussion around the legality of dose de-escalation at discharge from an acute care setting.