Faculty Bibliography

RESEARCH QUESTION/OBJECTIVE:What are the overall, singleton and twin live birth rates (LBR) after a double embryo transfer (DET) involving mosaic embryos? DESIGN/METHODS:This was a retrospective cohort study of DET with at least one mosaic embryo between 1 December 2016 and 1 December 2024. Each DET was assigned a prognostic score (A-F) based on the ploidy of both embryos. The primary outcome was the overall, singleton and twin LBR of good-prognosis (A and B), moderate-prognosis (C and D) and poor-prognosis (E and F) DET. Secondary outcomes were the LBR for mosaic/mosaic compared with euploid/mosaic transfers. Comparisons were also made with previously published data on euploid/euploid transfers. RESULTS:In total, there were 38 DET: 22 mosaic/mosaic and 16 euploid/mosaic. Twenty-nine (76.3%) patients had prior failed euploid transfers, and 19 (86.4%) mosaic/mosaic patients did not have any euploid embryos. The differences in overall LBR between the prognostic groups did not reach significance [65.0% (13/20) good-prognosis group versus 71.4% (5/7) moderate-prognosis group versus 45.5% (5/11) poor-prognosis group; P = 0.5]. The twin LBR was higher in the good-prognosis group (46.2%) compared with the moderate- and poor-prognosis groups (0% for both; P = 0.04). Overall [72.7% (16/22) versus 43.8% (7/16); P = 0.07], singleton [54.5% (12/22) versus 31.3% (5/11); P = 0.20] and twin [18.2% (4/22) versus 12.5% (2/16); P = 0.6] LBR were similar between mosaic/mosaic and euploid/mosaic DET. While the multiple LBR was high in both groups, it was lower for mosaic/mosaic and euploid/mosaic DET compared with euploid/euploid DET [26.1% (6/23) versus 49.8% (113/227, previously published data); P = 0.04]. CONCLUSIONS:Caution must be exercised with mosaic embryos as they can behave like euploid embryos, and DET can result in twins. DET with moderate- or poor-prognosis mosaic embryos had lower twin rates and may be reasonably considered. Larger studies are needed.

INTRODUCTION/UNASSIGNED:The potential buffering role of benefit finding, a cognitive and behavior adaptation process, in the relationship between financial concerns and psychological distress is not well understood among Asian American populations. Our study examined how financial concerns impacted Asian Americans' mental health, specifically in the presence of benefit finding and received pay during the COVID-19 pandemic. METHODS/UNASSIGNED:Survey-weighted data from the 2021 Asian American and Native Hawaiian/Pacific Islander COVID-19 Needs Assessment Project was analyzed to test the associations between financial concerns and psychological distress among Asian American adults 18 years or older (unweighted N = 3,152). Multivariable linear regression models included an interaction term for benefit finding, financial concerns, and received pay to test the moderation effect of benefit finding on psychological distress. RESULTS/UNASSIGNED:: 1.24, 95% CI: 0.91, 1.56). Asian Americans who reported greater levels of benefit finding had lower psychological distress, but benefit finding alone did not moderate the relationship between financial concerns and psychological distress. However, having both greater levels of benefit finding and received pay protected Asian American participants the most from psychological distress when experiencing financial concerns. DISCUSSION/UNASSIGNED:Our findings suggest that benefit finding and received pay combined may have important implications for interventions and policy-level changes targeting financial concerns among Asian Americans. Future research should explore the relationships between benefit finding and health outcomes over the life course, other protective coping responses for Asian Americans, and potential differences by Asian ethnicity or specific subgroups.

Cardiolipin (CL) is a mitochondria-specific phospholipid that forms heterotypic interactions with membrane-shaping proteins and regulates the dynamic remodeling and function of mitochondria. However, the precise mechanisms through which CL influences mitochondrial morphology are not well understood. In this study, employing molecular dynamics (MD) simulations, we determined that CL molecules extensively engage with the paddle domain (PD) of mitochondrial fusion protein Optic Atrophy 1 (OPA1), which controls membrane-shaping mechanisms. Structure-function analysis confirmed the interactions between CL and two conserved motifs of OPA1 at the membrane-binding sites. We further developed a bromine-labeled CL probe to enhance cryoEM contrast and characterized the structure of OPA1 assemblies bound to the CL-brominated lipid bilayers. Our images provide direct evidence of CL enrichment within the OPA1-binding leaflet. Last, we observed a decrease in membrane remodeling activity for OPA1 in lipid compositions with increasing concentrations of monolyso-cardiolipin (MLCL). This suggests that the partial replacement of CL by MLCL, as observed in Barth syndrome-associated mutations of the tafazzin phospholipid transacylase, alters the malleability of the membrane and compromises proper remodeling. Together, these data provide insights into how biological membranes regulate the mechanisms governing mitochondrial homeostasis.

Brown adipose tissue (BAT) is an evolutionary innovation that enables placental mammals to regulate body temperature through adaptive thermogenesis. Brown adipocytes are embedded within an intricate network of blood vessels and sympathetic nerves that support their development and thermogenic function. Cold exposure activates BAT thermogenesis through the coordinated induction of brown adipogenesis, angiogenesis, and sympathetic innervation. However, how these distinct processes are coordinated remains unclear. Here, we show that fragments of Slit guidance ligand 3 (Slit3) drive crosstalk among adipocyte progenitors, endothelial cells, and sympathetic nerves. We demonstrate that adipocyte progenitors secrete Slit3, which regulates both angiogenesis and sympathetic innervation in BAT and is essential for BAT thermogenesis in vivo. Proteolytic cleavage of Slit3 generates secreted Slit3-N and Slit3-C fragments, which bind distinct receptors to stimulate angiogenesis and sympathetic innervation, respectively. We identify Plxna1 as a previously unrecognized receptor for Slit3-C and show that it is essential for sympathetic innervation and cold-induced neurite expansion in BAT. Moreover, we introduce bone morphogenetic protein 1 (Bmp1) as the first Slit protease identified in vertebrates. In summary, this work establishes a mechanistic framework for the coordinated regulation of sympathetic innervation and angiogenesis to enhance thermogenic function. The co-regulation of neurovascular expansion by distinct Slit3 fragments offers a bifurcated yet harmonized mechanism to ensure a synchronized BAT response to environmental challenges. Finally, this study provides the first evidence that adipocyte progenitors regulate tissue innervation, revealing a previously unrecognized dimension of cellular interaction within adipose tissue.

Cardiolipin is a mitochondria-specific phospholipid that forms heterotypic interactions with membrane-shaping proteins and regulates the dynamic remodeling and function of mitochondria. However, the precise mechanisms through which cardiolipin influences mitochondrial morphology are not well understood. In this study, employing molecular dynamics simulations, we determined that cardiolipin molecules extensively engage with the paddle domain of mitochondrial fusion protein OPA1, which controls membrane-shaping mechanisms. Structure-function analysis confirmed the interactions between cardiolipin and two conserved motifs of OPA1 at the membrane-binding sites. We further developed a bromine-labeled cardiolipin probe to enhance cryoEM contrast and characterized the structure of OPA1 assemblies bound to the cardiolipin brominated lipid bilayers. Our images provide direct evidence of cardiolipin enrichment within the OPA1-binding leaflet. Last, we observed a decrease in membrane remodeling activity for OPA1 in lipid compositions with increasing concentrations of monolyso-cardiolipin. This suggests that the partial replacement of cardiolipin by monolyso-cardiolipin, as observed in Barth syndrome, alters the malleability of the membrane and compromises proper remodeling. Together, these data provide insights into how biological membranes regulate the mechanisms governing mitochondrial homeostasis.

In oxygenic photosynthetic organisms, light energy is converted to chemical energy to drive CO₂ fixation reactions and sustain life on Earth. Cyanobacteria contain phycobilisome (PBS) complexes that play critical roles in light harvesting and directing light energy to the photosystem I and II reaction centers. The proper assembly of PBS components is an intricate process that is required for their activity and association with photosystem I and II. To understand the complex mechanisms regulating the PBS assembly, we knocked out the terminal emitter apcE, which forms the structural scaffold for the PBS core. ApcE knockout led to growth and pigment defects, including elevated levels of photosystem II and abnormal emission spectra. Light microscopy experiments revealed the accumulation of highly fluorescent puncta localized to the pole of apcE knockout cells. Further investigation using electron cryoto-mography identified highly repetitive crystalline arrays of densely packed PBS cylinders. Together, these data indicate that cyanobacteria may accumulate PBS components in the form of highly organized crystalline bodies as intermediates during PBS assembly.

Acromion and scapular spine fractures (ASFs) pose significant challenges in the management of patients undergoing reverse total shoulder arthroplasty and there is a pressing need for effective preventive measures. Current predictive factors for ASF include female sex, osteoporosis, older age, and anatomical considerations such as glenoid medialization and acromial morphology. However, surgical options to mitigate ASF risk are limited. In this study, we propose a novel technique: incorporation of distal acromial tip fusion (DATF) during primary reverse total shoulder arthroplasty procedures. DATF involves bony fusion between the undersurface of the anterolateral acromion and the region where the superior rim of the glenoid meets the lateral base of the coracoid using a strut graft. The primary objective is to reinforce the anterior acromion process, thereby enhancing shoulder suspensory complex rigidity and theoretically reducing ASF risk. The technique involves precise positioning and exposure, graft preparation, and fixation. While DATF shows promise in ASF prevention, further biomechanical and clinical data are needed to validate its efficacy and safety. Nevertheless, in patients with a high risk of ASF, DATF may offer a viable prophylactic intervention alongside existing management strategies.

PURPOSE OF REVIEW/UNASSIGNED:Tusi, also known as "pink cocaine," has emerged across nightlife scenes in Latin America, Europe, Australia, and the United States (US). Tusi is typically a drug mixture containing ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Due to tusi's inconsistent chemical makeup, surveillance and harm reduction efforts have proven difficult for researchers and consumers alike. This review synthesizes evidence from peer-reviewed literature, drug checking programs, toxicology reports, and law enforcement data published between 2020 and 2025 to characterize tusi's composition, epidemiology, and associated risks. RECENT FINDINGS/UNASSIGNED:Drug checking services in various countries have identified ketamine and MDMA as the main components of tusi with additional substances often added (e.g., synthetic cathinones, cocaine, methamphetamine) in varying combinations. Laboratory data from Spain show that ketamine concentrations in tusi have increased over time. Surveys in Spain and Colombia highlight increases in initiation, polysubstance use involving tusi, and misclassification of its contents. Toxicology and case series reports indicate that harms associated with use stem largely from polysubstance mixtures rather than any single component, yet morbidity and mortality data typically focus on individual drugs detected. SUMMARY/UNASSIGNED:Tusi exemplifies a novel trend in emerging drugs: it is a blend of substances rather than a single compound, with its identity shaped by its distinctive color and association with nightlife. Its inconsistent composition and frequent co-use with stimulants and dissociatives elevate risk while complicating surveillance. Standardized survey items, expanded drug checking, and improved toxicological monitoring are needed to track and respond to this evolving mixture in the global drug supply.

PURPOSE/UNASSIGNED:To evaluate short-term clinical and patient reported outcomes after gluteus maximus/tensor fascia lata (GM/TFL) transfer for abductor insufficiency. METHODS/UNASSIGNED:This was a retrospective case series. Inclusion criteria were patients who underwent GM/TFL for chronic abductor insufficiency from 2017 to 2024 at a single institution with a minimum follow-up of 6 months and at least 1 recorded postoperative visit. Demographic, clinical, and outcome data were collected, including hip range of motion, abduction strength, presence of Trendelenburg gait, postoperative rehabilitation details, complications, and patient-reported outcomes. Statistical comparisons of pre- and postoperative objective measures were performed using the Wilcoxon signed-rank test. RESULTS/UNASSIGNED:> .05), and Trendelenburg gait persisted in 80% of patients. However, patient-reported outcome scores were strong, with a mean postoperative modified Harris Hip Score of 76.5 ± 22.4 and Non-Arthritic Hip Score of 74.1 ± 21.7. Patient satisfaction was high, with 100% of patients indicating they would undergo the procedure again. Three patients experienced complications (30%), including 2 patients who had persistent pain and seroma formation, and a patient who had a recurrent hematoma. CONCLUSIONS/UNASSIGNED:GM/TFL transfer does not consistently improve hip strength or gait mechanics; however, it provides pain relief and improved quality of life, as evidenced by high patient satisfaction and favorable modified Harris Hip Score outcomes. Three patients experienced complications (30%), including two patients who had persistent pain and seroma formation, and a patient who had a recurrent hematoma. LEVEL OF EVIDENCE/UNASSIGNED:Level IV, retrospective therapeutic case series.

OBJECTIVE/UNASSIGNED:Chronic non-specific lower back pain (cNSLBP) is a prevalent and disabling condition, imposing a substantial socioeconomic burden due to high healthcare costs and productivity losses, with limited accessible and effective long-term treatment options. Automated Thermo-mechanical Therapy (ATT) is a promising, non-drug intervention that leverages innovative technical advances to provide multimodal pain relief, offering accessibility and low-cost delivery. This study tested ATT for immediate pain relief in individuals with cNSLBP in a single-session, double-blind, randomized controlled trial. METHODS/UNASSIGNED:= 20) in a 40-min session with urn randomization. The active device applied heated cylindrical rollers along the spine, using far-infrared heat and mechanical tissue stimulation tailored to spinal alignment. In the control condition, the device used minimal mechanical therapy intensity without heat, targeting only the cervical area to avoid lower back therapeutic effects. Pre- and post-intervention assessments measured changes in pain intensity (primary outcome) via a 100-mm Visual Analog Scale for Pain (VAS-P100), alongside secondary outcomes assessing pain characteristics, anxiety, and functional mobility. RESULTS/UNASSIGNED:= 0.0031). No adverse events were reported, and all participants tolerated the intervention well. CONCLUSIONS/UNASSIGNED:A single session of ATT provides immediate, significant pain relief in individuals with cNSLBP, supporting its potential as a safe, non-invasive option for managing chronic back pain. Future studies should examine the long-term benefits of repeated ATT sessions and explore mechanistic insights into thermo-mechanical stimulation's effects on pain and function. CLINICAL TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov, identifier: NCT06769321.