Predicting the Future Caretakers of Traumatic Vascular Injury Management via Operative Exposure among Surgical Trainees.

BACKGROUND: The management of vascular trauma requires specialized training and expertise. While traumatic vascular injury is currently treated by both vascular and trauma surgeons in modern practice, it remains unclear who will inherit the role of managing vascular trauma in the coming decades. In this study, we examined disparities in operative experience in vascular trauma among surgical trainees across different surgical specialties. METHODS: Accreditation Council for Graduate Medical Education national operative log reports were collected for graduating vascular surgery residents (VSR), vascular surgery fellows (VSF), and general surgery residents (GSR) from 2012 to 2022. Total operative volume for traumatic vascular injury was examined, as were the five major contributing operative domains (neck, thoracic, abdominal, peripheral, and fasciotomy). RESULTS: A total of 22,052 GSR, 334 VSR, and 1,672 VSF graduated over the ten-year study period. VSR had the highest vascular trauma case volume (24.9 ± 3.9 cases/five yrs), followed by VSF (22.1 ± 1.5 cases/two yrs) then GSR (2.4 ± 0.3 cases/five yrs, p<0.001). Thoracic vessel exploration/repair (0.7 vs 0.6 vs 0.0 cases), abdominal vessel exploration/repair (1.0 vs 0.9 vs 0.0 cases), neck vessel exploration/repair (4.0 vs 3.4 vs 0.2 cases), peripheral vessel exploration/repair (12.1 vs 9.5 vs 1.1 cases), and lower extremity fasciotomy for trauma (7.2 vs 7.6 vs 1.1 cases) were most frequent among VSR and VSF groups (p<0.001 each). On linear regression analysis, both VSF (+0.5 cases/yr, R2=0.81, p<0.001) and GSR (+0.1 cases/yr, R2=0.75, p=0.001) groups experienced a growth in vascular trauma volume. Contrariwise, vascular trauma volume did not change among graduating VSR (R2=0.13, p=0.31). CONCLUSIONS: Dedicated vascular surgical training provides the highest operative exposure to civilian vascular trauma in the United States.

Update of newly-recognized salivary gland neoplasms: molecular and immunohistochemical findings and clinical importance.

With the advancement of molecular testing and the routine use of immunohistochemical stains, salivary gland tumours previously categorized as adenoma or adenocarcinoma, not otherwise specified, are being reclassified with distinct diagnoses. Newly recognized benign entities include: sclerosing polycystic adenoma, keratocystoma, intercalated duct hyperplasia and adenoma, and striated duct adenoma. Newly recognized malignant salivary gland tumours include: microsecretory adenocarcinoma, sclerosing microcytic adenocarcinoma, and mucinous adenocarcinoma. Additionally, rare subtypes of mucoepidermoid carcinoma have been described, including Warthin-like and oncocytic. Understanding of intraductal carcinoma continues to evolve. Correctly distinguishing these lesions from mimickers can be crucial for appropriate patient care and prognostication, as well as future conceptualization of salivary disease.

BRCA1/BRC-1 and SMC-5/6 regulate DNA repair pathway engagement during C. elegans meiosis.

The preservation of genome integrity during sperm and egg development is vital for reproductive success. During meiosis, the tumor suppressor BRCA1/BRC-1 and structural maintenance of chromosomes 5/6 (SMC-5/6) complex genetically interact to promote high fidelity DNA double strand break (DSB) repair, but the specific DSB repair outcomes these proteins regulate remain unknown. Using genetic and cytological methods to monitor resolution of DSBs with different repair partners in Caenorhabditis elegans, we demonstrate that both BRC-1 and SMC-5 repress intersister crossover recombination events. Sequencing analysis of conversion tracts from homolog-independent DSB repair events further indicates that BRC-1 regulates intersister/intrachromatid noncrossover conversion tract length. Moreover, we find that BRC-1 specifically inhibits error prone repair of DSBs induced at mid-pachytene. Finally, we reveal functional interactions of BRC-1 and SMC-5/6 in regulating repair pathway engagement: BRC-1 is required for localization of recombinase proteins to DSBs in smc-5 mutants and enhances DSB repair defects in smc-5 mutants by repressing theta-mediated end joining (TMEJ). These results are consistent with a model in which some functions of BRC-1 act upstream of SMC-5/6 to promote recombination and inhibit error-prone DSB repair, while SMC-5/6 acts downstream of BRC-1 to regulate the formation or resolution of recombination intermediates. Taken together, our study illuminates the coordinate interplay of BRC-1 and SMC-5/6 to regulate DSB repair outcomes in the germline.

Risk factors underlying racial and ethnic disparities in tuberculosis diagnosis and treatment outcomes, 2011-19: a multiple mediation analysis of national surveillance data.

BACKGROUND: Despite an overall decline in tuberculosis incidence and mortality in the USA in the past two decades, racial and ethnic disparities in tuberculosis outcomes persist. We aimed to examine the extent to which inequalities in health and neighbourhood-level social vulnerability mediate these disparities. METHODS: We extracted data from the US National Tuberculosis Surveillance System on individuals with tuberculosis during 2011-19. Individuals with multidrug-resistant tuberculosis or missing data on race and ethnicity were excluded. We examined potential disparities in tuberculosis outcomes among US-born and non-US-born individuals and conducted a mediation analysis for groups with a higher risk of treatment incompletion (a summary outcome comprising diagnosis after death, treatment discontinuation, or death during treatment). We used sequential multiple mediation to evaluate eight potential mediators: three comorbid conditions (HIV, end-stage renal disease, and diabetes), homelessness, and four census tract-level measures (poverty, unemployment, insurance coverage, and racialised economic segregation [measured by Index of Concentration at the ExtremesRace-Income]). We estimated the marginal contribution of each mediator using Shapley values. FINDINGS: During 2011-19, 27 788 US-born individuals and 57 225 non-US-born individuals were diagnosed with active tuberculosis, of whom 27 605 and 56 253 individuals, respectively, met eligibility criteria for our analyses. We did not observe evidence of disparities in tuberculosis outcomes for non-US-born individuals by race and ethnicity. Therefore, subsequent analyses were restricted to US-born individuals. Relative to White individuals, Black and Hispanic individuals had a higher risk of not completing tuberculosis treatment (adjusted relative risk 1·27, 95% CI 1·19-1·35; 1·22, 1·11-1·33, respectively). In multiple mediator analysis, the eight measured mediators explained 67% of the disparity for Black individuals and 65% for Hispanic individuals. The biggest contributors to these disparities for Black individuals and Hispanic individuals were concomitant end-stage renal disease, concomitant HIV, census tract-level racialised economic segregation, and census tract-level poverty. INTERPRETATION: Our findings underscore the need for initiatives to reduce disparities in tuberculosis outcomes among US-born individuals, particularly in highly racially and economically polarised neighbourhoods. Mitigating the structural and environmental factors that lead to disparities in the prevalence of comorbidities and their case management should be a priority. FUNDING: US Centers for Disease Control and Prevention National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention Epidemiologic and Economic Modeling Agreement.

The long-term effects of domestic and international tuberculosis service improvements on tuberculosis trends within the USA: a mathematical modelling study.

BACKGROUND: For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023. METHODS: Using a mathematical modelling framework, we simulated how US tuberculosis incidence could be affected by changes in tuberculosis services in the countries of origin for future migrants to the USA, as well as changes in tuberculosis services inside the USA. To do so, we used a linked set of transmission dynamic models, calibrated to demographic and epidemiological data for each setting. We constructed intervention scenarios representing improvements in tuberculosis services internationally and within the USA, individually and in combination, plus a base-case scenario representing continuation of current services. We simulated health and economic outcomes until 2100, using a Bayesian approach to quantify uncertainty in these outcomes. FINDINGS: Under the base-case scenario, US tuberculosis incidence was projected to decline to 1·8 cases per 100 000 (95% uncertainty interval [UI] 1·5-2·1) in the total population by 2050. Intervention scenarios produced substantial reductions in tuberculosis incidence, with the combination of all domestic and international interventions projected to achieve pre-elimination by 2033 (95% UI 2031-2037). Compared with the base-case scenario, this combination of interventions could avert 101 000 tuberculosis cases (95% UI 84 000-120 000) and 13 300 tuberculosis deaths (95% UI 10 500-16 300) in the USA from 2025 to 2050. Tuberculosis elimination was not projected before 2100. INTERPRETATION: Strengthening tuberculosis services domestically, promoting the development of more effective technologies and interventions, and supporting tuberculosis programmes in countries with a high tuberculosis burden are key strategies for accelerating progress towards tuberculosis elimination in the USA. FUNDING: US Centers for Disease Control and Prevention.

Bright New Resources for Syphilis Research: Genetically Encoded Fluorescent Tags for Treponema pallidum and Sf1Ep Cells.

The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. pallidum (T. pallidum) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance of controlled studies to assess differential treponemal gene expression, and generation of loss-of-function mutants to evaluate the contribution of specific genetic loci to T. pallidum virulence. Building on this progress, we engineered the T. pallidum SS14 strain to express a red-shifted green fluorescent protein (GFP) and Sf1Ep cells to express mCherry and blue fluorescent protein (BFP) for enhanced visualization. These new resources improve microscopy- and cell sorting-based applications for T. pallidum, better capturing the physical interaction between the host and pathogen, among other possibilities. Continued efforts to develop and share new tools and resources are required to help our overall knowledge of T. pallidum biology and syphilis pathogenesis reach that of other bacterial pathogens, including spirochetes.

Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes.

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and emerging therapeutic target that is overexpressed in most castration-resistant prostate cancers and implicated as a driver of disease progression and resistance to hormonal therapies. Here we define the lineage-specific action and differential activity of EZH2 in both prostate adenocarcinoma and neuroendocrine prostate cancer (NEPC) subtypes of advanced prostate cancer to better understand the role of EZH2 in modulating differentiation, lineage plasticity, and to identify mediators of response and resistance to EZH2 inhibitor therapy. Mechanistically, EZH2 modulates bivalent genes that results in upregulation of NEPC-associated transcriptional drivers (e.g., ASCL1) and neuronal gene programs in NEPC, and leads to forward differentiation after targeting EZH2 in NEPC. Subtype-specific downstream effects of EZH2 inhibition on cell cycle genes support the potential rationale for co-targeting cyclin/CDK to overcome resistance to EZH2 inhibition.

Lacosamide and Levetiracetam Are Not Toxic to the Developing Mouse Brain.

Many antiseizure medications cause apoptotic cell death in developing brains. The newer antiseizure medication lacosamide is increasingly used in neonates and infants. Neurotoxicity of lacosamide and its combination with levetiracetam was studied in neonatal mice. Animals received single or repeat injections of saline, phenobarbital (75mg/kg), lacosamide (20-40mg/kg), levetiracetam (100mg/kg), lacosamide (40mg/kg) + levetiracetam (100mg/kg) and euthanized at 6 to 30 hours. Cells undergoing apoptosis were increased in the brains of phenobarbital-treated animals. Densities of apoptotic profiles following lacosamide and levetiracetam treatment did not differ from saline-treated controls. Findings suggest that lacosamide, levetiracetam and their combination do not cause apoptosis in developing mouse brains. ANN NEUROL 2024.

Initial promise of child-parent psychotherapy in reducing stress and postpartum depression among mothers experiencing homelessness: a feasibility and pilot study.

PURPOSE: Mothers experiencing homelessness undergo significant stressors in addition to parenting stress, yet the rate and treatment of postpartum depression (PPD) within this population has yet to be explored. We assessed the risk for PPD and examined the changes in PDD and parenting stress following engagement in treatment. METHODS: Participants included 182 mothers with infants 7 months of age or younger in a shelter setting. After initial assessment of PPD and parenting stress, families participated in Child-Parent Psychotherapy (CPP). Post assessment was then conducted after 16 weeks. RESULTS: CPP was successfully implemented with high levels of procedural and content fidelity (M = 0.99, SD = 0.04; M = 0.95, SD = 0.09, respectively), treatment satisfaction (94%; M = 4.83, SD = 0.52), and relatively moderate levels of intervention completion (53.8%). Following participation in CPP, mothers reported decreases in parenting stress (d = 0.51) and continuous PPD symptom severity (d = 0.43). The proportion of mothers with clinically elevated self-report PPD symptoms also decreased from 15.3 to 6.7% (p = .013). Lastly, improvements in total parenting stress predicted improvements in PPD symptom severity (B = 0.12, p < .001). CONCLUSIONS: The findings highlight the relevance of screening for PPD among mothers experiencing homelessness. Most importantly, relationship-based interventions like CPP demonstrate promise in indirectly treating PPD for at-risk populations and within a shelter setting.

The independent and combined effects of aerobic exercise intensity and dose differentially increase post-exercise cerebral shear stress and blood flow.

This research examined the impact of aerobic exercise intensity and dose on acute post-exercise cerebral shear stress and blood flow. Fourteen young adults (27 ± 5 years of age, eight females) completed a maximal oxygen uptake ( V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ ) treadmill test followed by three randomized study visits: treadmill exercise at 30% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min, 70% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min and 70% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for a duration that resulted in caloric expenditure equal to that in the 30% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ visit (EqEE). A venous blood draw and internal carotid artery (ICA) ultrasound were collected before and immediately following exercise. ICA diameter and blood velocity were determined using automated edge detection software, and blood flow was calculated. Using measures of blood viscosity, shear stress was calculated. Aerobic exercise increased ICA shear stress (time: P = 0.005, condition: P = 0.012) and the increase was greater following exercise at 70% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆4.1 ± 3.5 dyn/cm2) compared with 30% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆1.1 ± 1.9 dyn/cm2; P = 0.041). ICA blood flow remained elevated following exercise (time: P = 0.002, condition: P = 0.010) with greater increases after 70% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (Δ268 ± 150 mL/min) compared with 30% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆125 ± 149 mL/min; P = 0.041) or 70% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ EqEE (∆127 ± 177 mL/min; P = 0.004). Therefore, aerobic exercise resulted in both intensity- and dose-dependent effects on acute post-exercise ICA blood flow whereby vigorous intensity exercise provoked a larger increase in ICA blood flow compared to light intensity exercise when performed at a higher dose.

Research with women sexual assault survivors presenting for emergency care is safe: Results from a multi-site, prospective observational cohort study.

A barrier to research with sexual assault survivors is the concern that research participation might be a negative experience for participants. We report the experiences with research of adult women sexual assault survivors participating in a large-scale, multi-site, prospective observational study that enrolled participants at the time of presentation for emergency care. Participants (n = 706, M = 28 years of age; 57% white, 15% Black) self-reported their experience with research 1 week, 6 weeks, 6 months, and 1 year post-assault. The vast majority rated the research experience as positive (95-97%), reported no drawbacks (84-89%), and felt that participating was worth it (93-95%). Positive experiences with research remained stable across the year, were generally consistent across demographic and clinical groups, and were reflected in qualitative comments. Given the tremendous morbidity experienced by sexual assault survivors and lack of progress in developing improved treatments for this population, ethically-conducted research with sexual assault survivors receiving emergency care should be encouraged.

Loss of RREB1 reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes.

There are multiple independent genetic signals at the Ras-responsive element binding protein 1 (RREB1) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of RREB1 in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss in vivo remains unknown. Here, we show that male and female global heterozygous knockout (Rreb1 +/-) mice have reduced body length, weight, and fat mass on high-fat diet. Rreb1+/- mice have sex- and diet-specific decreases in adipose tissue and adipocyte size; male mice on high-fat diet had larger gonadal adipocytes, while males on standard chow and females on high-fat diet had smaller, more insulin sensitive subcutaneous adipocytes. Mouse and human precursor cells lacking RREB1 have decreased adipogenic gene expression and activated transcription of genes associated with osteoblast differentiation, which was associated with Rreb1 +/- mice having increased bone mineral density in vivo. Finally, human carriers of RREB1 T2D protective alleles have smaller adipocytes, consistent with RREB1 loss-of-function reducing diabetes risk.

The chlamydial transcriptional regulator Euo is a key switch in cell form developmental progression but is not involved in the committed step to the formation of the infectious form.

Bacteria in the genus Chlamydia are a significant health burden worldwide. They infect a wide range of vertebrate animals, including humans and domesticated animals. In humans, C. psittaci can cause zoonotic pneumonia, while C. pneumoniae causes a variety of respiratory infections. Infections with C. trachomatis cause ocular or genital infections. All chlamydial species are obligate intracellular bacteria that replicate exclusively inside of eukaryotic host cells. Chlamydial infections are dependent on a complex infection cycle that depends on transitions between specific cell forms. This cycle consists of cell forms specialized for host cell invasion, the elementary body (EB), and a form specialized for intracellular replication, the reticulate body (RB). In addition to the EB and RB, there is a transitionary cell form that mediates the transformation between the RB and the EB, the intermediate body (IB). In this study, we ectopically expressed the regulatory protein Euo and showed that high levels of expression resulted in reversible arrest of the development cycle. The arrested chlamydial cells were trapped phenotypically at an early IB stage of the cycle. These cells had exited the cell cycle but had not shifted gene expression from RB like to IB/EB like. This arrested state was dependent on continued expression of Euo. When ectopic expression was reversed, Euo levels dropped in the arrested cells which led to the repression of native Euo expression and the resumption of the developmental cycle. Our data are consistent with a model where Euo expression levels impact IB maturation to the infectious EB but not the production of the IB form. IMPORTANCE: Bacterial species in the Chlamydiales order infect a variety of vertebrate animals and are a global health concern. They cause various diseases in humans, including genital and respiratory infections. The bacteria are obligate intracellular parasites that rely on a complex infectious cycle involving multiple cell forms. All species share the same life cycle, transitioning through different states to form the infectious elementary body (EB) to spread infections to new hosts. The Euo gene, encoding a DNA-binding protein, is involved in regulating this cycle. This study showed that ectopic expression of Euo halted the cycle at an early stage. This arrest depended on continued Euo expression. When Euo expression was reversed, the developmental cycle resumed. Additionally, this study suggests that high levels of Euo expression affect the formation of the infectious EB but not the production of the cell form committed to EB formation.

Engineered transcription activator-like effector dimer proteins confer DNA loop-dependent gene repression comparable to Lac repressor.

Natural prokaryotic gene repression systems often exploit DNA looping to increase the local concentration of gene repressor proteins at a regulated promoter via contributions from repressor proteins bound at distant sites. Using principles from the Escherichia coli lac operon we design analogous repression systems based on target sequence-programmable Transcription Activator-Like Effector dimer (TALED) proteins. Such engineered switches may be valuable for synthetic biology and therapeutic applications. Previous TALEDs with inducible non-covalent dimerization showed detectable, but limited, DNA loop-based repression due to the repressor protein dimerization equilibrium. Here, we show robust DNA loop-dependent bacterial promoter repression by covalent TALEDs and verify that DNA looping dramatically enhances promoter repression in E. coli. We characterize repression using a thermodynamic model that quantitates this favorable contribution of DNA looping. This analysis unequivocally and quantitatively demonstrates that optimized TALED proteins can drive loop-dependent promoter repression in E. coli comparable to the natural LacI repressor system. This work elucidates key design principles that set the stage for wide application of TALED-dependent DNA loop-based repression of target genes.

CDK12 is a promising therapeutic target for the transcription cycle and DNA damage response in metastatic osteosarcoma.

Osteosarcoma (OS) is a bone malignant tumor affecting children, adolescents and young adults. Currently, osteosarcoma is treated with chemotherapy regimens established over 40 years ago. The investigation of novel therapeutic strategies for the treatment of osteosarcoma remains an important clinical need. Cyclin-dependent kinases (CDKs) have been considered promising molecular targets in cancer therapy. Among these, CDK12 has been shown to play a crucial role in the pathogenesis of malignancies, but its clinical significance and biological mechanisms in osteosarcoma remain unclear. In the present study, we aim to determine the expression and function of CDK12, and evaluate its prognostic and therapeutic value in metastatic osteosarcoma. We found that overexpression of CDK12 was associated with high tumor grade, tumor progression and reduced patient survival. Underlying mechanism revealed that knockdown of CDK12 expression with siRNA or functional inhibition with the CDK12-targeting agent THZ531 effectively exhibited time- and dose-dependent cytotoxicity. Downregulation of CDK12 paused transcription by reducing RNAP II phosphorylation, interfered with DNA damage repair with increased γH2AX, and decreased cell proliferation through the PI3K-AKT pathway. This was accompanied by the promotion of apoptosis, as evidenced by enhanced Bax expression and reduced Bcl-xL expression. Furthermore, the CDK12 selective inhibitor THZ531 also hindered ex vivo 3D spheroid formation, growth of in vitro 2D cell colony, and prevented cell mobility. Our findings highlight the clinical importance of CDK12 as a potentially valuable prognostic biomarker and therapeutic target in metastatic osteosarcoma.

Innovative drug discovery strategies in epilepsy: integrating next-generation syndrome-specific mouse models to address pharmacoresistance and epileptogenesis.

INTRODUCTION: Although there are numerous treatment options already available for epilepsy, over 30% of patients remain resistant to these antiseizure medications (ASMs). Historically, ASM discovery has relied on the demonstration of efficacy through the use of 'traditional' acute in vivo seizure models (e.g. maximal electroshock, subcutaneous pentylenetetrazol, and kindling). However, advances in genetic sequencing technologies and remaining medical needs for people with treatment-resistant epilepsy or special patient populations have encouraged recent efforts to identify novel compounds in syndrome-specific models of epilepsy. Syndrome-specific models, including Scn1a variant models of Dravet syndrome and APP/PS1 mice associated with familial early-onset Alzheimer's disease, have already led to the discovery of two mechanistically novel treatments for developmental and epileptic encephalopathies (DEEs), namely cannabidiol and soticlestat, respectively. AREAS COVERED: In this review, the authors discuss how it is likely that next-generation drug discovery efforts for epilepsy will more comprehensively integrate syndrome-specific epilepsy models into early drug discovery providing the reader with their expert perspectives. EXPERT OPINION: The percentage of patients with pharmacoresistant epilepsy has remained unchanged despite over 30 marketed ASMs. Consequently, there is a high unmet need to reinvent and revise discovery strategies to more effectively address the remaining needs of patients with specific epilepsy syndromes, including drug-resistant epilepsy and DEEs.

Digital Ink and Surgical Dreams: Perceptions of Artificial Intelligence-Generated Essays in Residency Applications.

INTRODUCTION: Large language models like Chat Generative Pre-Trained Transformer (ChatGPT) are increasingly used in academic writing. Faculty may consider use of artificial intelligence (AI)-generated responses a form of cheating. We sought to determine whether general surgery residency faculty could detect AI versus human-written responses to a text prompt; hypothesizing that faculty would not be able to reliably differentiate AI versus human-written responses. METHODS: Ten essays were generated using a text prompt, "Tell us in 1-2 paragraphs why you are considering the University of Rochester for General Surgery residency" (Current trainees: n = 5, ChatGPT: n = 5). Ten blinded faculty reviewers rated essays (ten-point Likert scale) on the following criteria: desire to interview, relevance to the general surgery residency, overall impression, and AI- or human-generated; with scores and identification error rates compared between the groups. RESULTS: There were no differences between groups for %total points (ChatGPT 66.0 ± 13.5%, human 70.0 ± 23.0%, P = 0.508) or identification error rates (ChatGPT 40.0 ± 35.0%, human 20.0 ± 30.0%, P = 0.175). Except for one, all essays were identified incorrectly by at least two reviewers. Essays identified as human-generated received higher overall impression scores (area under the curve: 0.82 ± 0.04, P < 0.01). CONCLUSIONS: Whether use of AI tools for academic purposes should constitute academic dishonesty is controversial. We demonstrate that human and AI-generated essays are similar in quality, but there is bias against presumed AI-generated essays. Faculty are not able to reliably differentiate human from AI-generated essays, thus bias may be misdirected. AI-tools are becoming ubiquitous and their use is not easily detected. Faculty must expect these tools to play increasing roles in medical education.

Development and application of a multi-sugar assay to assess intestinal permeability.

Aim: Bioanalytical assays to measure rhamnose, erythritol, lactulose and sucralose in human urine and plasma were developed to support an indomethacin challenge study for intestinal permeability assessment in healthy participants. Methods: The multi-sugar assays utilized 5-µl sample matrix and a simple chemical derivatization with acetic anhydride, followed by RPLC-MS/MS detection. Results: Rhamnose and erythritol quantification was established between 1.00-1,000 µg/ml in urine and 250-250,000 ng/ml in plasma. For lactulose and sucralose, dynamic ranges of 0.1-100 µg/ml (urine) and 25-25,000 ng/ml (plasma) were applied for biological measurements. Conclusion: This work helped overcome some of the common analytical challenges associated with the bioanalysis of mono- and disaccharides and achieved improved limits of quantification.

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