Effects of Vancomycin/Tobramycin-Doped Ceramic Composite (PVA-VAN/TOB-PDCPD) in a Rat Femur Model Implanted with Contaminated Porous Titanium Cylinders.

INTRODUCTION: Periprosthetic joint infection (PJI) remains common and problematic. We hypothesized that using a bioceramic that has rapid release of an antibiotic (vancomycin [VAN] or vancomycin/tobramycin [VAN/TOB]) from a polyvinyl alcohol composite (PVA) combined with a delayed and sustained antibiotic release from polymeric dicalcium phosphate dihydrate (P-DCPD) ceramic would inhibit S. aureus-associated implant infection. METHODS: A total of fifty male Sprague Dawley rats were randomly divided into 5 experimental groups: I-negative control; II-bacteria only; III-bacteria+saline wash; IV-bacteria+PVA-VAN-PDCPD, and V-bacteria+PVA-VAN-TOB-PDCPD. A porous titanium (Ti) implant was press-fit into the rat knee. S. aureus-containing broth was added into the joint space to create a PJI. After one week, the joints from groups III to V were washed with saline and the fluid collected for bacterial quantification. This was followed by saline irrigation treatment (groups III to V) and application of the antibiotic-loaded PVA-PDCPD bioceramic (groups IV and V). On day 21, joint fluid was collected, and the implants were harvested for bacterial quantification. RESULTS: No bacteria were isolated from the negative control (group I). The positive control (group II) was positive on both days 7 and 21. Bacteria were still present on day 21 in the fluid and implant in Group III. Groups (IV and V) showed a decrease in the bacterial burden in the fluid and implant on day 21. There were significant differences in bacteria levels in the collected wash fluid and on the implant at day 21 between the saline wash (Group III) and treatment groups (IV and V). CONCLUSIONS: In this rat model of acute periprosthetic infection, treatment with PVA-VAN-PDCPD and PVA-VAN/TOB-PDCPD reduced the bacterial load in the infected joint and the infected Ti implant. Application of PVA-VAN-PDCPD and/or PVA-VAN/TOB-PDCPD after saline irrigation could be used as an addition to the treatment of PJI.

Trafficking of Connexin36 (Cx36) in the early secretory pathway.

Gap junctions formed by the major neuronal connexin Cx36 function as electrical synapses in the nervous system and provide unique functions such as synchronizing activities or network oscillations. Although the physiological significance of electrical synapses for neuronal networks is well established, little is known about the pathways that regulate the transport of its main component: Cx36. Here we have used HEK293T cells as an expression system in combination with siRNA and BioID screens to study the transition of Cx36 from the ER to the cis Golgi. Our data indicate that the C-terminal tip of Cx36 is a key factor in this process, mediating binding interactions with two distinct components in the early secretory pathway: the COPII complex and the Golgi stacking protein Grasp55. The C-terminal amino acid valine serves as an ER export signal to recruit COPII cargo receptors Sec24A/B/C at ER exit sites, whereas the PDZ binding motif "SAYV" mediates an interaction with Grasp55. These two interactions have opposing effects in their respective compartments. While Sec24 subunits carry Cx36 out of the ER, Grasp55 stabilizes Cx36 in the Golgi as shown in over expression experiments. These early regulatory steps of Cx36 are expected to be essential for the formation, function, regulation and plasticity of electrical synapses in the developing and mature nervous system.

Automated surgical step recognition in transurethral bladder tumor resection using artificial intelligence: transfer learning across surgical modalities.

Objective: Automated surgical step recognition (SSR) using AI has been a catalyst in the "digitization" of surgery. However, progress has been limited to laparoscopy, with relatively few SSR tools in endoscopic surgery. This study aimed to create a SSR model for transurethral resection of bladder tumors (TURBT), leveraging a novel application of transfer learning to reduce video dataset requirements. Materials and methods: Retrospective surgical videos of TURBT were manually annotated with the following steps of surgery: primary endoscopic evaluation, resection of bladder tumor, and surface coagulation. Manually annotated videos were then utilized to train a novel AI computer vision algorithm to perform automated video annotation of TURBT surgical video, utilizing a transfer-learning technique to pre-train on laparoscopic procedures. Accuracy of AI SSR was determined by comparison to human annotations as the reference standard. Results: A total of 300 full-length TURBT videos (median 23.96 min; IQR 14.13-41.31 min) were manually annotated with sequential steps of surgery. One hundred and seventy-nine videos served as a training dataset for algorithm development, 44 for internal validation, and 77 as a separate test cohort for evaluating algorithm accuracy. Overall accuracy of AI video analysis was 89.6%. Model accuracy was highest for the primary endoscopic evaluation step (98.2%) and lowest for the surface coagulation step (82.7%). Conclusion: We developed a fully automated computer vision algorithm for high-accuracy annotation of TURBT surgical videos. This represents the first application of transfer-learning from laparoscopy-based computer vision models into surgical endoscopy, demonstrating the promise of this approach in adapting to new procedure types.

Cementless versus Cemented Total Knee Arthroplasty Using the Same Implant Design: A Mean 5-Year Follow-up Study.

Cementless implant use continues to increase primarily due to increased numbers of younger and obese patients opting for primary total knee arthroplasty (TKA). Given the increased use of cementless implants, the purpose of this study was to evaluate the midterm clinical performance of cementless TKA using a highly porous tibial baseplate compared with its cemented counterpart of the same system. We conducted a retrospective case-control study of 400 patients undergoing primary TKA that included 200 patients with cementless components matched for age and body mass index (BMI) to 200 patients with cemented implants of the same implant design with a 5-year follow-up. We evaluated clinical results, complications, revisions, and overall survivorship between the cohorts. Statistical analysis was performed using student t-test and chi-square analysis. There was no statistical difference in age (64.3 vs. 64.3 p = 0.81), BMI (34 vs. 33.1 p = 0.19), preoperative Knee Society Score (KSS) function (41 vs. 32.3 p = 0.22), and preoperative KSS knee score (39.2 vs. 38.3 p = 0.54) between the cementless and cemented cohorts, respectively. The cementless group had seven revisions, while the cemented group had nine revisions (p = 0.609). The cementless group had one revision due to aseptic loosening versus five in the cemented group (p = 0.09). Postoperative 5-year KSS knee scores were 92.84 versus 91.75 (p = 0.386) and function scores were 81.81 versus 69.65 (p = 0.00004) in the cementless and cemented groups, respectively. The cementless group had survivorship of 96.5% for all-cause revision compared with 95.5% in the cemented group at 5-year follow-up (p = 0.60). Cementless TKA using a highly porous tibial baseplate showed excellent midterm results with one case of aseptic loosening at 5-year follow-up and with similar Knee Society outcome scores and survivorship compared with the cemented group. Cementless TKA demonstrated noninferiority to cemented TKA and could be used as an alternative mode of fixation in patients opting for primary TKA. Additional long-term follow-up is needed to determine if cementless TKA can demonstrate improved survivorship over cemented TKA.

Cephalopod Sex Determination and its Ancient Evolutionary Origin Revealed by Chromosome-level Assembly of the California Two-Spot Octopus.

Sex chromosomes are critical elements of sexual reproduction in many animal and plant taxa, however they show incredible diversity and rapid turnover even within clades. Here, using a chromosome-level assembly generated with long read sequencing, we report the first evidence for genetic sex determination in cephalopods. We have uncovered a sex chromosome in California two-spot octopus (Octopus bimaculoides) in which males/females show ZZ/ZO karyotypes respectively. We show that the octopus Z chromosome is an evolutionary outlier with respect to divergence and repetitive element content as compared to other chromosomes and that it is present in all coleoid cephalopods that we have examined. Our results suggest that the cephalopod Z chromosome originated between 455 and 248 million years ago and has been conserved to the present, making it the among the oldest conserved animal sex chromosomes known.

Brain network connectivity during peer evaluation in adolescent females: Associations with age, pubertal hormones, timing, and status.

Despite copious data linking brain function with changes to social behavior and mental health, little is known about how puberty relates to brain functioning. We investigated the specificity of brain network connectivity associations with pubertal indices and age to inform neurodevelopmental models of adolescence. We examined how brain network connectivity during a peer evaluation fMRI task related to pubertal hormones (dehydroepiandrosterone and testosterone), pubertal timing and status, and age. Participants were 99 adolescents assigned female at birth aged 9-15 (M = 12.38, SD = 1.81) enriched for the presence of internalizing symptoms. Multivariate analysis revealed that within Salience, between Frontoparietal - Reward and Cinguloopercular - Reward network connectivity were associated with all measures of pubertal development and age. Specifically, Salience connectivity linked with age, pubertal hormones, and status, but not timing. In contrast, Frontoparietal - Reward connectivity was only associated with hormones. Finally, Cinguloopercular - Reward connectivity related to age and pubertal status, but not hormones or timing. These results provide evidence that the salience processing underlying peer evaluation is jointly influenced by various indices of puberty and age, while coordination between cognitive control and reward circuitry is related to pubertal hormones, pubertal status, and age in unique ways.

The α-crystallin Chaperones Undergo a Quasi-ordered Co-aggregation Process in Response to Saturating Client Interaction.

Small heat shock proteins (sHSPs) are ATP-independent chaperones vital to cellular proteostasis, preventing protein aggregation events linked to various human diseases including cataract. The α-crystallins, αA-crystallin (αAc) and αB-crystallin (αBc), represent archetypal sHSPs that exhibit complex polydispersed oligomeric assemblies and rapid subunit exchange dynamics. Yet, our understanding of how this plasticity contributes to chaperone function remains poorly understood. Using biochemical and biophysical analyses combined with single-particle electron microscopy (EM), we examined structural changes in αAc, αBc and native heteromeric lens α-crystallins (αLc) in their apo-states and at varying degree of chaperone saturation leading to co-aggregation, using lysozyme and insulin as model clients. Quantitative single-particle analysis unveiled a continuous spectrum of oligomeric states formed during the co-aggregation process, marked by significant client-triggered expansion and quasi-ordered elongation of the sHSP oligomeric scaffold, whereby the native cage-like sHSP assembly displays a directional growth to accommodate saturating conditions of client sequestration. These structural modifications culminated in an apparent amorphous collapse of chaperone-client complexes, resulting in the creation of co-aggregates capable of scattering visible light. Intriguingly, these co-aggregates maintain internal morphological features of highly elongated sHSP oligomers with striking resemblance to polymeric α-crystallin species isolated from aged lens tissue. This mechanism appears consistent across αAc, αBc and αLc, albeit with varying degrees of susceptibility to client-induced co-aggregation. Importantly, our findings suggest that client-induced co-aggregation follows a distinctive mechanistic and quasi-ordered trajectory, distinct from a purely amorphous process. These insights reshape our understanding of the physiological and pathophysiological co-aggregation processes of α-crystallins, carrying potential implications for a pathway toward cataract formation.

A 12.4-day periodicity in a close binary system after a supernova.

Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.

Fracture Risk Among Living Kidney Donors 25 Years After Donation.

Importance: Living kidney donors may have an increased risk of fractures due to reductions in kidney mass, lower concentrations of serum 1,25-dihydroxyvitamin D, and secondary increases in serum parathyroid hormone. Objective: To compare the overall and site-specific risk of fractures among living kidney donors with strictly matched controls from the general population who would have been eligible to donate a kidney but did not do so. Design, Setting, and Participants: This survey study was conducted between December 1, 2021, and July 31, 2023. A total of 5065 living kidney donors from 3 large transplant centers in Minnesota were invited to complete a survey about their bone health and history of fractures, and 16 156 population-based nondonor controls without a history of comorbidities that would have precluded kidney donation were identified from the Rochester Epidemiology Project and completed the same survey. A total of 2132 living kidney donors and 2014 nondonor controls responded to the survey. Statistical analyses were performed from May to August 2023. Exposure: Living kidney donation. Main Outcomes and Measures: The rates of overall and site-specific fractures were compared between living kidney donors and controls using standardized incidence ratios (SIRs). Results: At the time of survey, the 2132 living kidney donors had a mean (SD) age of 67.1 (8.9) years and included 1245 women (58.4%), and the 2014 controls had a mean (SD) age of 68.6 (7.9) years and included 1140 women (56.6%). The mean (SD) time between donation or index date and survey date was 24.2 (10.4) years for donors and 27.6 (10.7) years for controls. The overall rate of fractures among living kidney donors was significantly lower than among controls (SIR, 0.89; 95% CI, 0.81-0.97). However, there were significantly more vertebral fractures among living kidney donors than among controls (SIR, 1.42; 95% CI, 1.05-1.83). Conclusions and Relevance: This survey study found a reduced rate of overall fractures but an excess of vertebral fractures among living kidney donors compared with controls after a mean follow-up of 25 years. Treatment of excess vertebral fractures with dietary supplements such as vitamin D3 may reduce the numbers of vertebral fractures and patient morbidity.

Neural Correlates of the p Factor in Adolescence: Cognitive Control With and Without Enhanced Positive Affective Demands.

BACKGROUND: Recent research has aimed to characterize processes underlying general liability toward psychopathology, termed the p factor. Given previous research linking the p factor with difficulties in both executive functioning and affective regulation, the present study investigated nonaffective and positive affective inhibition in the context of a sustained attention/inhibition paradigm in adolescents exhibiting mild to severe psychopathology. METHODS: Functional magnetic resonance imaging data were collected during an integrated reward conditioning and go/no-go task in 138 adolescents assigned female at birth. We modeled the p factor using hierarchical confirmatory factor analysis. Positive affective inhibition was measured by examining responses to no-go stimuli with a history of reward conditioning. We examined associations between p factor scores and neural function and behavioral performance. RESULTS: Consistent with nonaffective executive function as a primary risk factor, p factor scores were associated with worse behavioral performance and hypoactivation in the left superior frontal gyrus and middle frontal gyrus during response initiation (go trials). The p factor scores were additionally associated with increased error-related signaling in the temporal cortex during incorrect no-go trials. CONCLUSIONS: During adolescence, a period characterized by heightened risk for emergent psychopathology, we observed unique associations between p factor scores and neural and behavioral indices of response initiation, which relies primarily on sustained attention. These findings suggest that shared variation in mental disorder categories is characterized in part by sustained attention deficits. While we did not find evidence that the p factor was associated with inhibition in this study, this observation is consistent with our hypothesis that the p factor would be related to nonaffective control processes.

Threat exposure moderates associations between neural and physiological indices of emotion reactivity in adolescent females.

Early life adversity (ELA) characterized by threat (e.g., abuse, witnessing violence) impacts neural and physiologic systems involved in emotion reactivity; however, research on how threat exposure impacts the interplay between these systems is limited. This study investigates ELA characterized by threat as a potential moderator of the association between (a) neural activity during a negative image processing fMRI task and (b) cortisol production following a modified Trier Social Stress Test (TSST). The sample is comprised of 117 young adolescent females (Mage = 11.90 years, SD = 1.69) at elevated risk for internalizing problems. Whole-brain analyses revealed a positive association between cortisol production and increased right lateral orbitofrontal cortex activity during the emotion reactivity task. In moderation models, threat exposure interacted with bilateral amygdala activation (b = -3.34, p = 0.021) and bilateral hippocampal activation (b = -4.14, p = 0.047) to predict cortisol response to the TSST. Specifically, participants with low, but not high, levels of threat exposure demonstrated a positive association between cortisol production and neural activity in these regions, while no significant association emerged for participants with high threat exposure. Findings contribute to the growing field of research connecting physiological and neural emotion processing and response systems, suggesting that dimensions of ELA may uniquely disrupt associations between neural activation and cortisol production.

Genomic analyses indicate resilience of a commercially and culturally important marine gastropod snail to climate change.

Genomic vulnerability analyses are being increasingly used to assess the adaptability of species to climate change and provide an opportunity for proactive management of harvested marine species in changing oceans. Southeastern Australia is a climate change hotspot where many marine species are shifting poleward. The turban snail, Turbo militaris is a commercially and culturally harvested marine gastropod snail from eastern Australia. The species has exhibited a climate-driven poleward range shift over the last two decades presenting an ongoing challenge for sustainable fisheries management. We investigate the impact of future climate change on T. militaris using genotype-by-sequencing to project patterns of gene flow and local adaptation across its range under climate change scenarios. A single admixed, and potentially panmictic, demographic unit was revealed with no evidence of genetic subdivision across the species range. Significant genotype associations with heterogeneous habitat features were observed, including associations with sea surface temperature, ocean currents, and nutrients, indicating possible adaptive genetic differentiation. These findings suggest that standing genetic variation may be available for selection to counter future environmental change, assisted by widespread gene flow, high fecundity and short generation time in this species. We discuss the findings of this study in the content of future fisheries management and conservation.

Electrical synapse structure requires distinct isoforms of a postsynaptic scaffold.

Electrical synapses are neuronal gap junction (GJ) channels associated with a macromolecular complex called the electrical synapse density (ESD), which regulates development and dynamically modifies electrical transmission. However, the proteomic makeup and molecular mechanisms utilized by the ESD that direct electrical synapse formation are not well understood. Using the Mauthner cell of zebrafish as a model, we previously found that the intracellular scaffolding protein ZO1b is a member of the ESD, localizing postsynaptically, where it is required for GJ channel localization, electrical communication, neural network function, and behavior. Here, we show that the complexity of the ESD is further diversified by the genomic structure of the ZO1b gene locus. The ZO1b gene is alternatively initiated at three transcriptional start sites resulting in isoforms with unique N-termini that we call ZO1b-Alpha, -Beta, and -Gamma. We demonstrate that ZO1b-Beta and ZO1b-Gamma are broadly expressed throughout the nervous system and localize to electrical synapses. By contrast, ZO1b-Alpha is expressed mainly non-neuronally and is not found at synapses. We generate mutants in all individual isoforms, as well as double mutant combinations in cis on individual chromosomes, and find that ZO1b-Beta is necessary and sufficient for robust GJ channel localization. ZO1b-Gamma, despite its localization to the synapse, plays an auxiliary role in channel localization. This study expands the notion of molecular complexity at the ESD, revealing that an individual genomic locus can contribute distinct isoforms to the macromolecular complex at electrical synapses. Further, independent scaffold isoforms have differential contributions to developmental assembly of the interneuronal GJ channels. We propose that ESD molecular complexity arises both from the diversity of unique genes and from distinct isoforms encoded by single genes. Overall, ESD proteomic diversity is expected to have critical impacts on the development, structure, function, and plasticity of electrical transmission.

Exploring whether mental health crisis text conversations that include discussion of firearms differ from those without firearms.

BACKGROUND: Firearm violence represents a public health crisis in the United States. Yet, there is limited knowledge about how firearms are discussed in the context of mental health emergencies representing a major gap in the current research literature. This study addresses this gap by examining whether the content of mental health crisis text conversations that mention firearms differ from those that do not mention firearms in a large, unique dataset from a national crisis text line. METHODS: We examined data from over 3.2 million conversations between texters to Crisis Text Line and volunteer crisis counselors between September 2018 and July 2022. We used a study developed text classification machine learning algorithm that builds on natural language processing to identify and label whether crisis conversations mentioned firearms. We compared the frequency of psychosocial factors between conversations that mention firearms with those that did not. RESULTS: Results from a generalized linear mixed-effects model demonstrated that. conversations mentioning firearms more frequently were associated with suicide, racism, physical, sexual, emotional, and unspecified abuse, grief, concerns about a third party, substance use, bullying, gender and sexual identity, relationships, depression, and loneliness. Further, conversations mentioning firearms were less likely to be related to self-harm and eating/body image. CONCLUSIONS: These results offer an initial glimpse of how firearms are mentioned in the context of acute mental health emergencies, which has been completely absent in prior literature. Our results are preliminary and help sharpen our understanding of contextual factors surrounding mental health emergencies where a firearm is mentioned.

Neural Markers of Emotion Reactivity and Regulation Before and After a Targeted Social Rejection: Differences Among Girls With and Without Suicidal Ideation and Behavior Histories.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are common among adolescent girls and increase risk for suicide death. Emotion regulation difficulties are linked with STBs, particularly in response to targeted social rejection. However, neural correlates of this link have not been investigated and may identify novel targets for interventions. Here, we examined neural correlates of emotion regulation before and after an experimentally delivered targeted social rejection in adolescent girls with STBs and girls without STBs (i.e., control participants). METHODS: Girls (N = 138; age range, 9-15 years; mean [SD] age = 11.6 [1.79] years) completed a functional neuroimaging emotion regulation task. In the middle of the task, participants were socially rejected by an unfamiliar confederate whom the participants had elected to meet. Participants also completed a multimethod STB assessment. RESULTS: Before rejection, girls with a history of STBs, compared with control participants, showed greater activation in the right superior frontal gyrus when passively viewing negative stimuli, and girls with suicidal behavior (SB) versus those without SB showed less activation in the right frontal pole during emotion regulation attempts. Following the rejection, girls with STBs, compared with control participants, showed greater activation in the right inferior frontal gyrus during emotion regulation. CONCLUSIONS: Before social rejection, girls with SB versus without SB may not activate brain regions implicated in emotion regulation, suggesting a vulnerability to poor regulation at their baseline emotional state. After social rejection, girls with any history of STBs showed altered activation in a brain region strongly associated with inhibition and emotion regulation success, possibly reflecting increased effort at inhibiting emotional responses during regulation following stress exposure.

Campylobacter jejuni Outbreak Linked to Raw Oysters in Rhode Island, 2021.

Oysters and other shellfish are not a food that is commonly highlighted as high risk for Campylobacter contamination. The Rhode Island Department of Health (RIDOH) conducted a multiagency investigation of a Campylobacter jejuni outbreak that was linked to the consumption of raw oysters; the first such outbreak was detected in Rhode Island. The environmental investigation identified birds as the likely source of contamination of the aquacultured oysters. As a result of this outbreak response, several investigative processes and best practice recommendations are offered. 1) RIDOH will be including exposure to raw shellfish as a question on their case report forms to better identify future oyster-related Campylobacter clusters. 2) It is important that shellfish aquaculture farms be aware of the risks of using floating gear to hold oyster cages and of the importance of using bird abatement to keep birds off floating aquaculture gear to prevent contamination of oysters from bird feces. 3) It should be recognized that fecal coliform water samples collected near an oyster aquaculture farm may not act as an adequate indicator for the presence of Campylobacter. 4) For the first time, Rhode Island has developed guidelines for the closure and reopening of oyster harvest areas due to contamination with Campylobacter. It is hoped that increased awareness and mitigation of the described risk factors will help prevent future similar outbreaks of illness.

Untargeted metabolomic profiles reveal widespread metabolic perturbations and identify candidate biomarkers in aminoaciduric canine hypoaminoacidemic hepatopathy syndrome.

OBJECTIVE: To identify metabolites and metabolic pathways affected in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) compared to healthy control (CON) dogs of similar ages and breeds. To improve our understanding of ACHES pathophysiology and identify novel candidate biomarkers associated with ACHES. ANIMALS: A prospective case-control study. Privately owned dogs with ACHES (n = 19) and healthy (CON) dogs (n = 9) were recruited between February 18, 2015, and April 18, 2018. METHODS: A prospective case-control study. Plasma and urine were collected from ACHES and CON dogs. The Cornell University Proteomics and Metabolomics Core Facility conducted an untargeted metabolomic analysis. RESULTS: After controlling for age, sex, and weight, 111 plasma and 207 urine metabolites significantly differed between ACHES and CON dogs. Data reduction and cluster analysis revealed robust segregation between ACHES and CON dogs. Enrichment analysis of significant compounds in plasma or urine identified altered metabolic pathways, including those related to AA metabolism, cellular energetics, and lipid metabolism. Biomarker analysis identified metabolites that best-distinguished ACHES from CON dogs, including pyruvic acid isomer and glycerol-3-phosphate in the plasma and an alanine isomer and choline in the urine. CLINICAL RELEVANCE: Our findings provide an in-depth analysis of metabolic perturbations associated with ACHES. Several affected metabolic pathways (eg, lipid metabolism) offer a new understanding of ACHES pathophysiology. Novel candidate biomarkers warrant further evaluation to determine their potential to aid in ACHES diagnosis, prognosis, and treatment monitoring.

Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky.

Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.

A Single-Center Retrospective Evaluation of Decision-Making and Factors Motivating Hand Transplant Candidates.

INTRODUCTION: Advancements in vascularized composite allotransplantation have made hand transplants possible for persons living with upper limb loss. Hand transplantation is not a life-saving procedure, but rather a quality-of-life enhancing procedure; hence the risk of morbidity and mortality must be weighed against improvements in function and appearance. This study explored the decision-making process of patients evaluated for hand transplantation. METHODS/APPROACH: A qualitative case series study using retrospective chart data of evaluations was conducted between January 1, 2011 and February 28, 2020. Notes were extracted and read by three reviewers. Each case was summarized noting similarities and differences. FINDINGS: Nine patients underwent evaluation. Eight were no longer under evaluation and did not receive transplant; one was still undergoing evaluation. Patient motivations for evaluation were dissatisfaction with prostheses or self-image, chronic pain, performing activities of daily living, occupation, burden placed on caregivers, and concerns about overuse of non-affected limbs. Patients chose not to pursue transplantation due to rehabilitation time, immunosuppression, alternative treatments, and social and financial challenges. The clinical team discontinued evaluations due to unmet evaluation requirements, medical contraindications, or treatment alternatives. Different modes of shared decision-making were present depending on the party most heavily featured in the charts as driving decisions. DISCUSSION: This was an examination of shared decision-making with hand transplant candidates who did not proceed to transplant. Reasons for choosing alternative strategies for management were multifactorial. Lessons learned regarding patient motivations and shared decision-making can inform future interventions to better support patients.