Structure and Spectroscopic Insights for CH3PCO Isomers: A High-Level Quantum Chemical Study.

The exploration of phosphorus-bearing species stands as a prolific field in current astrochemical research, particularly within the context of prebiotic chemistry. Herein, we have employed high-level quantum chemistry methodologies to predict the structure and spectroscopic properties of isomers composed of a methyl group and three P, C, and O atoms. We have computed relative and dissociation energies, as well as rotational, rovibrational, and torsional parameters using the B2PLYPD3 functional and the explicitly correlated coupled cluster CCSD(T)-F12b method. Based upon our study, all the isomers exhibit a bent heavy atom skeleton with CH3PCO being the most stable structure, regardless of the level theory employed. Following in energy, we found four high-energy isomers, namely, CH3OCP, CH3CPO, CH3COP, and CH3OPC. The computed adiabatic dissociation energies support the stability of all [CH3, P, C, O] isomers against fragmentation into CH3 and [P, C, O]. Torsional barrier heights associated with the methyl internal rotation for each structure have been computed to evaluate the occurrence of possible A-E splittings in the rotational spectra. For the most stable isomer, CH3PCO, we found a V3 barrier of 82 cm-1, which is slightly larger than that obtained experimentally for the N-counterpart, CH3NCO, yet still very low. Therefore, the analysis of its rotational spectrum can be anticipated as a challenging task owing to the effect of the CH3 internal rotation. The complete set of spectroscopic constants and transition frequencies reported here for the most stable isomer, CH3PCO, is intended to facilitate eventual laboratory searches.

The Utility of Prevena Negative Pressure Wound Therapy on Groin Incisions for Critical Limb-Threatening Ischemia: A Single Institution Experience.

BACKGROUND: Incisional negative pressure wound therapy (iNPWT) is an adjunctive treatment that uses constant negative pressure suction to facilitate healing. The utility of this treatment modality on vascular operations for critical limb-threatening ischemia (CLTI) has yet to be elucidated. This study compares the incidence of postoperative wound complications between the Prevena Incision Management System, a type of iNPWT, and standard wound dressings for vascular patients who also underwent plastic surgery closure of groin incisions for CLTI. METHOD: We performed a retrospective cohort study of 40 patients with CLTI who underwent 53 open vascular surgeries with subsequent sartorius muscle flap closure. Patient demographics, intraoperative details, and wound complications were measured from 2015 to 2018 at the University of California San Francisco. Two cohorts were generated based on the modality of postoperative wound management and compared on wound healing outcomes. RESULTS: Of the 53 groin incisions, 29 were managed with standard dressings, and 24 received iNPWT. Patient demographics, comorbidities, and operative characteristics were similar between the 2 groups. Patients who received iNPWT had a significantly lower rate of infection (8.33% vs 31.0%, P = 0.04) and dehiscence (0% vs 41.3%, P < 0.01). Furthermore, the iNPWT group had a significantly lower rate of reoperation (0% vs 17.2%, P = 0.03) for wound complications within 30 days compared with the control group and a moderately reduced rate of readmission (4.17% vs 20.7%, P = 0.08). CONCLUSIONS: Rates of infection, reoperation, and dehiscence were significantly reduced in patients whose groin incisions were managed with iNPWT compared with standard wound care. Readmission rates were also decreased, but this difference was not statistically significant. Our results suggest that implementing iNPWT for the management of groin incisions, particularly in patients undergoing vascular operations for CLTI, may significantly improve clinical outcomes.

Nodule detection and generation on chest X-rays: NODE21 Challenge.

Pulmonary nodules may be an early manifestation of lung cancer, the leading cause of cancer-related deaths among both men and women. Numerous studies have established that deep learning methods can yield high-performance levels in the detection of lung nodules in chest X-rays. However, the lack of gold-standard public datasets slows down the progression of the research and prevents benchmarking of methods for this task. To address this, we organized a public research challenge, NODE21, aimed at the detection and generation of lung nodules in chest X-rays. While the detection track assesses state-of-the-art nodule detection systems, the generation track determines the utility of nodule generation algorithms to augment training data and hence improve the performance of the detection systems. This paper summarizes the results of the NODE21 challenge and performs extensive additional experiments to examine the impact of the synthetically generated nodule training images on the detection algorithm performance.

Dietary fatty acid composition drives neuroinflammation and impaired behavior in obesity.

Nutrient composition in obesogenic diets may influence the severity of disorders associated with obesity such as insulin-resistance and chronic inflammation. Here we hypothesized that obesogenic diets rich in fat and varying in fatty acid composition, particularly in omega 6 (ω6) to omega 3 (ω3) ratio, have various effects on energy metabolism, neuroinflammation and behavior. Mice were fed either a control diet or a high fat diet (HFD) containing either low (LO), medium (ME) or high (HI) ω6/ω3 ratio. Mice from the HFD-LO group consumed less calories and exhibited less body weight gain compared to other HFD groups. Both HFD-ME and HFD-HI impaired glucose metabolism while HFD-LO partly prevented insulin intolerance and was associated with normal leptin levels despite higher subcutaneous and perigonadal adiposity. Only HFD-HI increased anxiety and impaired spatial memory, together with increased inflammation in the hypothalamus and hippocampus. Our results show that impaired glucose metabolism and neuroinflammation are uncoupled, and support that diets with a high ω6/ω3 ratio are associated with neuroinflammation and the behavioral deterioration coupled with the consumption of diets rich in fat.

Neurobehavioral Precursors of Compulsive Cocaine Seeking in Dual Frontostriatal Circuits.

Background: Only some individuals who use drugs recreationally eventually develop a substance use disorder, characterized in part by the rigid engagement in drug foraging behavior (drug seeking), which is often maintained in the face of adverse consequences (i.e., is compulsive). The neurobehavioral determinants of this individual vulnerability have not been fully elucidated. Methods: Using a prospective longitudinal study involving 39 male rats, we combined multidimensional characterization of behavioral traits of vulnerability to stimulant use disorder (impulsivity and stickiness) and resilience (sign tracking and sensation seeking/locomotor reactivity to novelty) with magnetic resonance imaging to identify the structural and functional brain correlates of the later emergence of compulsive drug seeking in drug-naïve subjects. We developed a novel behavioral procedure to investigate the individual tendency to persist in drug-seeking behavior in the face of punishment in a drug-free state in subjects with a prolonged history of cocaine seeking under the control of the conditioned reinforcing properties of a drug-paired Pavlovian conditioned stimulus. Results: In drug-naïve rats, the tendency to develop compulsive cocaine seeking was characterized by behavioral stickiness-related functional hypoconnectivity between the prefrontal cortex and posterior dorsomedial striatum in combination with impulsivity-related structural alterations in the infralimbic cortex, anterior insula, and nucleus accumbens. Conclusions: These findings show that the vulnerability to developing compulsive cocaine-seeking behavior stems from preexisting structural or functional changes in two distinct corticostriatal systems that underlie deficits in impulse control and goal-directed behavior.

Study on Miscibility, Thermomechanical Behavior, and Thermoregulation Performance of Paraffin Wax/Bituminous Blends for Solar Thermal Energy Storage Applications.

The goal of this work was to study the miscibility, thermal stability, thermomechanical properties, and temperature regulation performance of paraffin wax/bitumen blends for their potential use in solar thermal energy storage applications. Results indicated that these blends present a suitable thermal stability, and their thermomechanical properties are strongly dependent on composition, developed microstructure, and temperature. Among all paraffin wax concentrations studied, the blend containing 40 wt % paraffin wax displays enhanced binder elastic properties together with lower thermal susceptibility compared to base bitumen. In addition, this binder also presents improved thermal properties (thermal conductivity and specific heat capacity) and still maintains a high crystallinity, thereby retaining a large enough latent heat to be used for thermal energy storage. Thus, results from the temperature regulation test, which was conducted by subjecting the sample to simulated solar irradiation at a constant radiant flux density, provide a higher latent heat thermoregulation index value than other microencapsulated phase change materials systems. Therefore, it can be stated that paraffin wax/bitumen blends are promising base materials to formulate form-stable products for thermal energy storage applications for thermoregulation purposes.

On retrospective k-space subsampling schemes for deep MRI reconstruction.

Acquiring fully-sampled MRI k-space data is time-consuming, and collecting accelerated data can reduce the acquisition time. Employing 2D Cartesian-rectilinear subsampling schemes is a conventional approach for accelerated acquisitions; however, this often results in imprecise reconstructions, even with the use of Deep Learning (DL), especially at high acceleration factors. Non-rectilinear or non-Cartesian trajectories can be implemented in MRI scanners as alternative subsampling options. This work investigates the impact of the k-space subsampling scheme on the quality of reconstructed accelerated MRI measurements produced by trained DL models. The Recurrent Variational Network (RecurrentVarNet) was used as the DL-based MRI-reconstruction architecture. Cartesian, fully-sampled multi-coil k-space measurements from three datasets were retrospectively subsampled with different accelerations using eight distinct subsampling schemes: four Cartesian-rectilinear, two Cartesian non-rectilinear, and two non-Cartesian. Experiments were conducted in two frameworks: scheme-specific, where a distinct model was trained and evaluated for each dataset-subsampling scheme pair, and multi-scheme, where for each dataset a single model was trained on data randomly subsampled by any of the eight schemes and evaluated on data subsampled by all schemes. In both frameworks, RecurrentVarNets trained and evaluated on non-rectilinearly subsampled data demonstrated superior performance, particularly for high accelerations. In the multi-scheme setting, reconstruction performance on rectilinearly subsampled data improved when compared to the scheme-specific experiments. Our findings demonstrate the potential for using DL-based methods, trained on non-rectilinearly subsampled measurements, to optimize scan time and image quality.

Acid-sensing ion channel 3 mediates pain hypersensitivity associated with high-fat diet consumption in mice.

ABSTRACT: Lipid-rich diet is the major cause of obesity, affecting 13% of the worldwide adult population. Obesity is a major risk factor for metabolic syndrome that includes hyperlipidemia and diabetes mellitus. The early phases of metabolic syndrome are often associated with hyperexcitability of peripheral small diameter sensory fibers and painful diabetic neuropathy. Here, we investigated the effect of high-fat diet-induced obesity on the activity of dorsal root ganglion (DRG) sensory neurons and pain perception. We deciphered the underlying cellular mechanisms involving the acid-sensing ion channel 3 (ASIC3). We show that mice made obese through consuming high-fat diet developed the metabolic syndrome and prediabetes that was associated with heat pain hypersensitivity, whereas mechanical sensitivity was not affected. Concurrently, the slow conducting C fibers in the skin of obese mice showed increased activity on heating, whereas their mechanosensitivity was not altered. Although ASIC3 knockout mice fed with high-fat diet became obese, and showed signs of metabolic syndrome and prediabetes, genetic deletion, and in vivo pharmacological inhibition of ASIC3, protected mice from obesity-induced thermal hypersensitivity. We then deciphered the mechanisms involved in the heat hypersensitivity of mice and found that serum from high-fat diet-fed mice was enriched in lysophosphatidylcholine (LPC16:0, LPC18:0, and LPC18:1). These enriched lipid species directly increased the activity of DRG neurons through activating the lipid sensitive ASIC3 channel. Our results identify ASIC3 channel in DRG neurons and circulating lipid species as a mechanism contributing to the hyperexcitability of nociceptive neurons that can cause pain associated with lipid-rich diet consumption and obesity.

AIROGS: Artificial Intelligence for Robust Glaucoma Screening Challenge.

The early detection of glaucoma is essential in preventing visual impairment. Artificial intelligence (AI) can be used to analyze color fundus photographs (CFPs) in a cost-effective manner, making glaucoma screening more accessible. While AI models for glaucoma screening from CFPs have shown promising results in laboratory settings, their performance decreases significantly in real-world scenarios due to the presence of out-of-distribution and low-quality images. To address this issue, we propose the Artificial Intelligence for Robust Glaucoma Screening (AIROGS) challenge. This challenge includes a large dataset of around 113,000 images from about 60,000 patients and 500 different screening centers, and encourages the development of algorithms that are robust to ungradable and unexpected input data. We evaluated solutions from 14 teams in this paper and found that the best teams performed similarly to a set of 20 expert ophthalmologists and optometrists. The highest-scoring team achieved an area under the receiver operating characteristic curve of 0.99 (95% CI: 0.98-0.99) for detecting ungradable images on-the-fly. Additionally, many of the algorithms showed robust performance when tested on three other publicly available datasets. These results demonstrate the feasibility of robust AI-enabled glaucoma screening.

Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a.

Phosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacological inhibition of PDE2A has been associated to its pro-cognitive role in normal animals and in models of ID and ASD, homozygous PDE2A mutations have been identified in patients affected by ID, ASD and epilepsy. To clarify this apparent paradox about the role of PDE2A in brain development, we characterized here Pde2a+/- mice (homozygote animals being not viable) at the behavioral, cellular, molecular and electrophysiological levels. Pde2a+/- females display a milder form of the disorder with reduced cognitive performance in adulthood, conversely males show severe socio-cognitive deficits throughout their life. In males, these phenotypes are associated with microglia activation, elevated glutathione levels and increased externalization of Glutamate receptor (GluR1) in CA1, producing reduced mGluR-dependent Long-term Depression. Overall, our results reveal molecular targets of the PDE2A-dependent pathway underlying socio-cognitive performance. These results clarify the mechanism of action of pro-cognitive drugs based on PDE2A inactivation, which have been shown to be promising therapeutic approaches for Alzheimer's disease, schizophrenia, FXS as well as other forms of ASD.

BabyNet＋＋: Fetal birth weight prediction using biometry multimodal data acquired less than 24 hours before delivery.

Accurate prediction of fetal weight at birth is essential for effective perinatal care, particularly in the context of antenatal management, which involves determining the timing and mode of delivery. The current standard of care involves performing a prenatal ultrasound 24 hours prior to delivery. However, this task presents challenges as it requires acquiring high-quality images, which becomes difficult during advanced pregnancy due to the lack of amniotic fluid. In this paper, we present a novel method that automatically predicts fetal birth weight by using fetal ultrasound video scans and clinical data. Our proposed method is based on a Transformer-based approach that combines a Residual Transformer Module with a Dynamic Affine Feature Map Transform. This method leverages tabular clinical data to evaluate 2D+t spatio-temporal features in fetal ultrasound video scans. Development and evaluation were carried out on a clinical set comprising 582 2D fetal ultrasound videos and clinical records of pregnancies from 194 patients performed less than 24 hours before delivery. Our results show that our method outperforms several state-of-the-art automatic methods and estimates fetal birth weight with an accuracy comparable to human experts. Hence, automatic measurements obtained by our method can reduce the risk of errors inherent in manual measurements. Observer studies suggest that our approach may be used as an aid for less experienced clinicians to predict fetal birth weight before delivery, optimizing perinatal care regardless of the available expertise.

Deep learning for estimation of fetal weight throughout the pregnancy from fetal abdominal ultrasound.

BACKGROUND: Fetal weight is currently estimated from fetal biometry parameters using heuristic mathematical formulas. Fetal biometry requires measurements of the fetal head, abdomen, and femur. However, this examination is prone to inter- and intraobserver variability because of factors, such as the experience of the operator, image quality, maternal characteristics, or fetal movements. Our study tested the hypothesis that a deep learning method can estimate fetal weight based on a video scan of the fetal abdomen and gestational age with similar performance to the full biometry-based estimations provided by clinical experts. OBJECTIVE: This study aimed to develop and test a deep learning method to automatically estimate fetal weight from fetal abdominal ultrasound video scans. STUDY DESIGN: A dataset of 900 routine fetal ultrasound examinations was used. Among those examinations, 800 retrospective ultrasound video scans of the fetal abdomen from 700 pregnant women between 15 6/7 and 41 0/7 weeks of gestation were used to train the deep learning model. After the training phase, the model was evaluated on an external prospectively acquired test set of 100 scans from 100 pregnant women between 16 2/7 and 38 0/7 weeks of gestation. The deep learning model was trained to directly estimate fetal weight from ultrasound video scans of the fetal abdomen. The deep learning estimations were compared with manual measurements on the test set made by 6 human readers with varying levels of expertise. Human readers used standard 3 measurements made on the standard planes of the head, abdomen, and femur and heuristic formula to estimate fetal weight. The Bland-Altman analysis, mean absolute percentage error, and intraclass correlation coefficient were used to evaluate the performance and robustness of the deep learning method and were compared with human readers. RESULTS: Bland-Altman analysis did not show systematic deviations between readers and deep learning. The mean and standard deviation of the mean absolute percentage error between 6 human readers and the deep learning approach was 3.75%±2.00%. Excluding junior readers (residents), the mean absolute percentage error between 4 experts and the deep learning approach was 2.59%±1.11%. The intraclass correlation coefficients reflected excellent reliability and varied between 0.9761 and 0.9865. CONCLUSION: This study reports the use of deep learning to estimate fetal weight using only ultrasound video of the fetal abdomen from fetal biometry scans. Our experiments demonstrated similar performance of human measurements and deep learning on prospectively acquired test data. Deep learning is a promising approach to directly estimate fetal weight using ultrasound video scans of the fetal abdomen.

Automatic Segmentation of Retinal Layers in Multiple Neurodegenerative Disorder Scenarios.

Retinal Optical Coherence Tomography (OCT) allows the non-invasive direct observation of the central nervous system, enabling the measurement and extraction of biomarkers from neural tissue that can be helpful in the assessment of ocular, systemic and Neurological Disorders (ND). Deep learning models can be trained to segment the retinal layers for biomarker extraction. However, the onset of ND can have an impact on the neural tissue, which can lead to the degraded performance of models not exposed to images displaying signs of disease during training. We present a fully automatic approach for the retinal layer segmentation in multiple neurodegenerative disorder scenarios, using an annotated dataset of patients of the most prevalent NDs: Alzheimer's disease, Parkinson's disease, multiple sclerosis and essential tremor, along with healthy control patients. Furthermore, we present a two-part, comprehensive study on the effects of ND on the performance of these models. The results show that images of healthy patients may not be sufficient for the robust training of automated segmentation models intended for the analysis of ND patients, and that using images representative of different NDs can increase the model performance. These results indicate that the presence or absence of patients of ND in datasets should be taken into account when training deep learning models for retinal layer segmentation, and that the proposed approach can provide a valuable tool for the robust and reliable diagnosis in multiple scenarios of ND.

Thermal optimality and physiological parameters inferred from experimental studies scale latitudinally with marine species occurrences.

Ocean warming is expected to occur due to anthropogenic climate change bringing a spatial shift of marine communities. Experimental data that characterize the aerobic power budget via an aerobic scope, thermal metabolic scope, or thermal preferences have been proposed as tools that can describe species distribution since they characterize species fitness or performance under different temperatures. This study tested the potential relationship between observed occurrences and different physiological studies in the Americas for 11 commercially important species in Mexico. Projections were also developed for Mexico's exclusive economic zone under different climate warming scenarios. The physiological data were fitted from optimum up to pejus temperatures and projected to sea surface temperatures for present (2003-2014) and Representative Concentration Pathway (RCP) scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5) for the period 2040-2050 and 2090-2100. For species with wide distributions in the Americas, the number of occurrences reported decreases at higher latitudes related to the decrease in species performance calculated from laboratory experiments. In addition, higher species occurrences are usually reported around optimum temperatures. Overall, the results suggest that pejus temperatures likely restrict latitudinal distribution, at least for widely distributed taxons. Regarding Mexican projections, the results varied widely by species. For example, in the Atlantic Ocean, Octopus maya and Panulirus argus are vulnerable to warming scenarios, while Centropomus undecimalis is not. Interestingly, northern Campeche Bank, the Gulf of California, and Western Baja California may act as thermal refugia for marine species indicating they could be assigned as protected areas to support fisheries throughout the Mexican exclusive economic zone. This research adds to the increasing evidence of the relationship between thermal niche and wild population distribution.

Case planning and execution of inframalleolar bypass for chronic limb-threatening ischemia.

Chronic limb-threatening ischemia is challenging to treat because of the complex patient population, heterogeneity of limb presentations, and complicated arterial pathology. To meet this challenge, vascular surgeons need a broad range of skills to appropriately tailor interventions to each patient's specific needs. One tool in the armamentarium for patients with extensive arterial occlusive disease below the knee is an inframalleolar bypass. However, these procedures require a systematic approach to surgical planning and a high degree of technical competence. We describe our approach to inframalleolar bypass for limb preservation in suitable patients with advanced tibial artery disease.

Reliability and validity of the Spanish adaptation of the Functional Independence Measure + Functional Assessment Measure.

BACKGROUND: The Functional Independence Measure + Functional Assessment Measure (FIM+FAM) Scale is one of the most widely used instruments to measure functional independence post-stroke, and features many cultural adaptations to various languages. AIM: The aim of this study was to determine the psychometric properties of a Spanish cross-cultural adaptation of the FIM+FAM for use in the stroke population. DESIGN: Observational study. SETTING: Outpatient long-term service of a neurorehabilitation unit. POPULATION: One hundred and twenty-two individuals with stroke. METHODS: The functional independence of the participants was assessed with the adapted version of the FIM+FAM. Additionally, the functional, motor and cognitive condition of the participants was assessed with a battery of standardized clinical instruments. Finally, a group of 31 participants out of the total were evaluated a second time with the FIM+FAM by a different evaluator than the one who performed the first evaluation. Internal consistency, inter-rater reliability and convergent validity with other clinical instruments of the adapted version of the FIM+FAM were determined. RESULTS: The internal consistency of the adapted version of the FIM+FAM was excellent, as evidenced by Cronbach's α values that exceeded 0.973. The inter-rater reliability was likewise excellent, with correlations above 0.990 in all domains and subscales. Additionally, the convergent validity of the scale adaptation with clinical instruments was variable, with values ranging from 0.264 to 0.983, but consistent with the construct assessed in the different instruments examined. CONCLUSIONS: The internal consistency, inter-rater reliability and convergent validity of the Spanish-adapted version of the FIM+FAM Scale showed excellent reliability and validity of the adaptation, which supports its use to assess functional independence after stroke. CLINICAL REHABILITATION IMPACT: Availability of a valid adaptation for the evaluation of functional independence after stroke in Spanish population.

Characteristics of a Large, Labeled Data Set for the Training of Artificial Intelligence for Glaucoma Screening with Fundus Photographs.

Purpose: Significant visual impairment due to glaucoma is largely caused by the disease being detected too late. Objective: To build a labeled data set for training artificial intelligence (AI) algorithms for glaucoma screening by fundus photography, to assess the accuracy of the graders, and to characterize the features of all eyes with referable glaucoma (RG). Design: Cross-sectional study. Subjects: Color fundus photographs (CFPs) of 113 893 eyes of 60 357 individuals were obtained from EyePACS, California, United States, from a population screening program for diabetic retinopathy. Methods: Carefully selected graders (ophthalmologists and optometrists) graded the images. To qualify, they had to pass the European Optic Disc Assessment Trial optic disc assessment with ≥ 85% accuracy and 92% specificity. Of 90 candidates, 30 passed. Each image of the EyePACS set was then scored by varying random pairs of graders as "RG," "no referable glaucoma (NRG)," or "ungradable (UG)." In case of disagreement, a glaucoma specialist made the final grading. Referable glaucoma was scored if visual field damage was expected. In case of RG, graders were instructed to mark up to 10 relevant glaucomatous features. Main Outcome Measures: Qualitative features in eyes with RG. Results: The performance of each grader was monitored; if the sensitivity and specificity dropped below 80% and 95%, respectively (the final grade served as reference), they exited the study and their gradings were redone by other graders. In all, 20 graders qualified; their mean sensitivity and specificity (standard deviation [SD]) were 85.6% (5.7) and 96.1% (2.8), respectively. The 2 graders agreed in 92.45% of the images (Gwet's AC2, expressing the inter-rater reliability, was 0.917). Of all gradings, the sensitivity and specificity (95% confidence interval) were 86.0 (85.2-86.7)% and 96.4 (96.3-96.5)%, respectively. Of all gradable eyes (n = 111 183; 97.62%) the prevalence of RG was 4.38%. The most common features of RG were the appearance of the neuroretinal rim (NRR) inferiorly and superiorly. Conclusions: A large data set of CFPs was put together of sufficient quality to develop AI screening solutions for glaucoma. The most common features of RG were the appearance of the NRR inferiorly and superiorly. Disc hemorrhages were a rare feature of RG. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Defining sources and ramifications of mistreatment among female vascular surgery trainees.

OBJECTIVE: Mistreatment among vascular surgery trainees is a known risk factor for physician burnout. This study aims to characterize forms of and identify sources of mistreatment. METHODS: This is a cross-sectional study of United States vascular surgery trainees who voluntarily participated in an anonymous survey administered after the 2021 Vascular Surgery In-Training Examination. The primary outcome measures were self-reported mistreatment and sources of mistreatment between genders. Logistic regression was used for multivariable analysis. RESULTS: Representing all 125 vascular surgery training programs, 510 trainees (66.9% male) participated in the survey (83.6% response rate). Mistreatment was reported by 54.8% of trainees, with twice as many women reporting as men (82.3% vs 41.0%; P < .001). Women reported higher rates of being shouted at (44.1% vs 21.1%; P < .001); repeatedly reminded of errors (24.3% vs 16.1%; P = .04); ignored/treated hostilely (28.9% vs 10.5%; P < .001); subjected to crude/sexually demeaning remarks, stories, jokes (19.2% vs 2.1%; P < .001); evaluated by different standards (29.3% vs 2.1%; P < .001); and mistaken for a non-physician (75.2% vs 3.5%; P < .001). Among trainees reporting bullying, attendings were the most common source (68.5%). Patients and their families were the most common source of sexual harassment (66.7%), gender discrimination (90.4%), and racial discrimination (74.4%). Compared with men, women identified more patients and families as the source of bullying (50.0% vs 29.7%; P = .005), gender discrimination (97.2% vs 50.0%; P < .001), and sexual harassment (78.4% vs 27.3%; P = .003). Compared with men, women more frequently felt unprepared to respond to the behavior in the moment (10.4% vs 4.6%; P = .002), did not know how to report mistreatment at their institution (7.6% vs 3.2%; P = .04), and did not believe that their institution would take their mistreatment report seriously (9.0% vs 3.9%; P = .002). On multivariable analysis, female gender was an independent risk factor for both gender discrimination (odds ratio, 56.62; 95% confidence interval, 27.89-115) and sexual harassment (odds ratio, 26.2; 95% confidence interval, 3.34-14.8) when adjusting for children, training year, relationship status, and training program location. CONCLUSIONS: A majority of vascular surgery trainees experience mistreatment during training. Sources and forms of abuse are varied. Understanding the sources of mistreatment is critical to guide intervention strategies such as faculty remediation and/or sanctions; allyship training for staff, residents, and faculty; and institutional procedures for patient-initiated abuse.

The development of compulsive coping behaviour is associated with a downregulation of Arc in a Locus Coeruleus neuronal ensemble.

Some compulsive disorders have been considered to stem from the loss of control over coping strategies, such as displacement. However, the cellular mechanisms involved in the acquisition of coping behaviours and their subsequent compulsive manifestation in vulnerable individuals have not been elucidated. Considering the role of the locus coeruleus (LC) noradrenaline-dependent system in stress and related excessive behaviours, we hypothesised that neuroplastic changes in the LC may be associated with the acquisition of an adjunctive polydipsic water drinking, a prototypical displacement behaviour, and the ensuing development of compulsion in vulnerable individuals. Thus, male Sprague Dawley rats were characterised for their tendency, or not, to develop compulsive polydipsic drinking in a schedule-induced polydipsia (SIP) procedure before their fresh brains were harvested. A new quantification tool for RNAscope assays revealed that the development of compulsive adjunctive behaviour was associated with a low mRNA copy number of the plasticity marker Arc in the LC which appeared to be driven by specific adaptations in an ensemble of tyrosine hydroxylase (TH)+, zif268- neurons. This ensemble was specifically engaged by the expression of compulsive adjunctive behaviour, not by stress, because its functional recruitment was not observed in individuals that no longer had access to the water bottle before sacrifice, while it consistently correlated with the levels of polydipsic water drinking only when it had become compulsive. Together these findings suggest that downregulation of Arc mRNA levels in a population of a TH+/zif268- LC neurons represents a signature of the tendency to develop compulsive coping behaviours.

Open revascularization approach is associated with healing and ambulation after transmetatarsal amputation in patients with chronic limb threatening ischemia.

BACKGROUND: Transmetatarsal amputation (TMA) allows for maintenance of ambulatory function for patients with significant forefoot tissue loss. Effective revascularization is key to optimizing limb salvage for patients with chronic limb threatening ischemia (CLTI). We hypothesized that CLTI patients requiring TMA will have better healing and functional outcomes with open bypass than with endovascular revascularization. METHODS: Consecutive TMAs performed at three affiliated centers between 2008 and 2020 were retrospectively reviewed. The baseline characteristics, including WIfI (wound, ischemia, foot infection) stage, noninvasive vascular studies, healing, and ambulatory outcomes, were collected. Catheter-based angiographic images were evaluated using the GLASS (global limb anatomic staging system). The primary outcomes were TMA healing and community ambulation. The secondary outcomes were TMA that had healed at study end, any ambulatory function postoperatively, major amputation, and mortality. Descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses were performed. RESULTS: A total of 346 TMAs had been performed in 318 patients, 209 of whom had had peripheral artery disease (PAD). The median follow-up was 2.5 years. Patients with PAD had had significantly lower rates of healing compared with those without PAD (64% vs 77%; P = .007). Revascularization was performed in 185 limbs, with 102 treated endovascularly and 83 with open surgery. The patients who had undergone endovascular surgery were significantly less likely to have had the TMA healed at any point (55% vs 76%; P = .003) and less likely to have remained healed at study end (49% vs 66%; P = .02). Patients with GLASS stage 3 anatomy were significantly more likely to have healed after open surgery (75% vs 45%; P = .003). Long-term ambulation data were available for 72% of the revascularized patients. Endovascular surgery was associated with a lower likelihood of community ambulation after TMA (34% vs 57%; P = .002). On multivariable analysis, open surgery was significantly associated with TMA healing (odds ratio, 2.8; P = .007) and ambulation (odds ratio, 2.9; P = .001). CONCLUSIONS: For patients with CLTI and significant tissue loss requiring TMA, an initial open approach to revascularization was associated with improved healing and higher rates of ambulation compared with endovascular interventions. The metabolic requirement for healing of a TMA in patients with CLTI might be better met by open revascularization.