Drosophila are hosts to the first described parasitoid wasp of adult flies.

Parasitoid wasps are exceptionally diverse and use specialized adaptations capable of manipulating the physiology and behaviour of host organisms1. In more than two centuries since the first records of Drosophila-parasitizing wasps, nearly 200 described and provisional parasitoid species of drosophilids have been identified2. These include endoparasitoids and ectoparasitoids, as well as species attacking larval and pupal hosts3. Despite a deep history of research attention and remarkable biodiversity, a wasp species that attacks and develops inside the adult stage of a fly host has not been described previously. Here we report the discovery of a wasp species that infects the adult stage of fruit flies in the genus Drosophila, including one of the most deeply studied model organisms in biology, Drosophila melanogaster. Notably, this wasp can be easily collected from backyard fly baits and has a broad geographic distribution throughout the eastern USA. We document its life history and unique host interactions, including egg-laying into and larval emergence from adult flies, and provide protocols to raise wasps from wild-caught host flies. Our results emphasize the need for ongoing research investment in insect biodiversity and systematics. As parasitoid research continues to uncover unusual biology and supports fundamental mechanistic insights into immunity4, metabolism5, ecology6, evolution7-9 and behaviour10-12, we anticipate that this wasp's association with the laboratory model organism, D. melanogaster, will provide new research opportunities across the life sciences.

Laser-Induced Thermal Decomposition of Uranium Coordination Compounds with Non-oxidic Ligands to Produce Nitride and Carbide Materials.

The production of ceramics from uranium coordination compounds can be achieved through thermal processing if an excess amount of the desired atoms (i.e., C or N), or reactive gaseous products (e.g., methane or nitrogen oxide) is made available to the reactive uranium metal core via decomposition/fragmentation of the surrounding ligand groups. Here, computational thermodynamic approaches were utilized to identify the temperatures necessary to produce uranium metal from some starting compounds─UI4(TMEDA)2, UCl4(TMEDA)2, UCl3(pyridine)x, and UI3(pyridine)4. Experimentally, precursors were irradiated by a laser under various gaseous environments (argon, nitrogen, and methane) creating extreme reaction conditions (i.e., fast heating, high temperature profile >2000 °C, and rapid cooling). Despite the fast dynamics associated with laser irradiation, the central uranium atom reacted with the thermal decomposition products of the ligands yielding uranium ceramics. Residual gas analysis identified vaporized products from the laser irradiation, and the final ceramic products were characterized by powder X-ray diffraction. The composition of the uranium precursor as well as the gaseous environment had a direct impact on the production of the final phases.

Sleep and seizure risk in epilepsy: bed and wake times are more important than sleep duration.

Sleep duration, sleep deprivation and the sleep-wake cycle are thought to play an important role in the generation of epileptic activity and may also influence seizure risk. Hence, people diagnosed with epilepsy are commonly asked to maintain consistent sleep routines. However, emerging evidence paints a more nuanced picture of the relationship between seizures and sleep, with bidirectional effects between changes in sleep and seizure risk in addition to modulation by sleep stages and transitions between stages. We conducted a longitudinal study investigating sleep parameters and self-reported seizure occurrence in an ambulatory at-home setting using mobile and wearable monitoring. Sixty subjects wore a Fitbit smartwatch for at least 28 days while reporting their seizure activity in a mobile app. Multiple sleep features were investigated, including duration, oversleep and undersleep, and sleep onset and offset times. Sleep features in participants with epilepsy were compared to a large (n = 37 921) representative population of Fitbit users, each with 28 days of data. For participants with at least 10 seizure days (n = 34), sleep features were analysed for significant changes prior to seizure days. A total of 4956 reported seizures (mean = 83, standard deviation = 130) and 30 485 recorded sleep nights (mean = 508, standard deviation = 445) were included in the study. There was a trend for participants with epilepsy to sleep longer than the general population, although this difference was not significant. Just 5 of 34 participants showed a significant difference in sleep duration the night before seizure days compared to seizure-free days. However, 14 of 34 subjects showed significant differences between their sleep onset (bed) and/or offset (wake) times before seizure occurrence. In contrast to previous studies, the current study found undersleeping was associated with a marginal 2% decrease in seizure risk in the following 48 h (P < 0.01). Nocturnal seizures were associated with both significantly longer sleep durations and increased risk of a seizure occurring in the following 48 h. Overall, the presented results demonstrated that day-to-day changes in sleep duration had a minimal effect on reported seizures, while patient-specific changes in bed and wake times were more important for identifying seizure risk the following day. Nocturnal seizures were the only factor that significantly increased the risk of seizures in the following 48 h on a group level. Wearables can be used to identify these sleep-seizure relationships and guide clinical recommendations or improve seizure forecasting algorithms.

Transcriptional signatures of fentanyl use in the mouse ventral tegmental area.

Synthetic opioids such as fentanyl contribute to the vast majority of opioid-related overdose deaths, but fentanyl use remains broadly understudied. Like other substances with misuse potential, opioids cause lasting molecular adaptations to brain reward circuits, including neurons in the ventral tegmental area (VTA). The VTA contains numerous cell types that play diverse roles in opioid use and relapse; however, it is unknown how fentanyl experience alters the transcriptional landscape in specific subtypes. Here, we performed single nuclei RNA sequencing to study transcriptional programs in fentanyl-experienced mice. Male and female C57/BL6 mice self-administered intravenous fentanyl (1.5 µg/kg/infusion) or saline for 10 days. After 24 h abstinence, VTA nuclei were isolated and prepared for sequencing on the 10× platform. We identified different patterns of gene expression across cell types. In dopamine neurons, we found enrichment of genes involved in growth hormone signalling. In dopamine-glutamate-GABA combinatorial neurons, and some GABA neurons, we found enrichment of genes involved in Pi3k-Akt signalling. In glutamate neurons, we found enrichment of genes involved in cholinergic signalling. We identified transcriptional regulators for the differentially expressed genes in each neuron cluster, including downregulated transcriptional repressor Bcl6, and upregulated transcription factor Tcf4. We also compared the fentanyl-induced gene expression changes identified in mouse VTA with a published rat dataset in bulk VTA, and found overlap in genes related to GABAergic signalling and extracellular matrix interaction. Together, we provide a comprehensive picture of how fentanyl self-administration alters the transcriptional landscape of the mouse VTA that serves as the foundation for future mechanistic studies.

A high throughput microphysiological model of prosthetic valve endocarditis for investigating factors that influence bacterial adhesion under fluid shear stress.

Prosthetic heart valves are associated with almost one quarter of cases of infective endocarditis, a rare but serious condition with a staggering 25 % mortality rate. Without the endothelium of native valves, the risk of infection is exacerbated for implanted devices exposed to blood. There are currently no physiologically relevant in vitro or animal models of prosthetic valve endocarditis (PVE). Of particular importance, Staphylococcus aureus, a common agent of PVE, has demonstrated enhanced binding to blood plasma proteins (e.g., fibrinogen) and exposed matrix under fluid shear stress (FSS). An in vitro platform that mimics the multiple physiological determinants for S. aureus adhesion to prosthetic valve materials would facilitate the discovery of new treatments to minimize PVE. To this end, we developed a first-of-its-kind microphysiological model of PVE to study the effects of several key variables (endothelial cell coverage, fibrinogen deposition, surface treatments, and FSS) on S. aureus adhesion to bioprosthetic material surfaces. Our model demonstrated that viable endothelial monolayers diminished the deposition of fibrinogen and that fibrinogen was required for the subsequent adhesion of S. aureus to the bioprosthetic surface model. Next, we examined factors that affected endothelial cell coverage, such as FSS and glutaraldehyde, a common chemical treatment for bioprosthetic materials. In particular, glutaraldehyde treatment obstructed endothelialization of otherwise biocompatible collagen-coated surfaces, further enabling fibrinogen and S. aureus deposition. In future work, this model could impact multiple research areas, such as screening candidate bioprosthetic valve materials and new surface treatments to prevent PVE and further understanding host-pathogen interactions.

Electronic Patient Portal Use After Kidney Transplant: A Single-Center Retrospective Study.

INTRODUCTION: Online patient portals have become a core component of patient-centered care. Limited research exists on such portal use in patients after kidney transplantation. The aim of this study was to examine preoperative, perioperative, and postoperative factors associated with post-transplantation portal use. METHODS: This cross-sectional study included all patients who underwent kidney transplantation from April 2016 to May 2019 at the University of Toledo Medical Center. Exclusion criteria included international travel for transplantation and those without available postoperative lab or follow-up records. Data were collected for 2 y post-transplantation. Univariable and multivariable linear regression was performed to determine associations with portal use. RESULTS: Two hundred and forty-seven kidney transplant recipients were included in the study; 35.6% (n = 88) used the portal versus 64.4% (n = 159) did not. Preoperative factors associated with increased use included income >$40,000 (odds ratio [OR], 2.95; P = 0.006) and cancer history (OR, 2.46; P = 0.007), whereas diabetes history had reduced use (OR, 0.51; P = 0.021). The Black race had the least use. Perioperatively, reduced use was associated with dialysis before transplant (OR, 0.25; P < 0.001) and hospital stay ≥4 d (OR, 0.49; P = 0.009). Postoperatively, associations with increased use included average eGFR >30 (P = 0.04) and hospital readmissions (n = 102), whereas those with ER (n = 138) visits had decreased use. Multivariable analysis revealed increased use with income >$40,000 (OR, 2.51; P = 0.033). CONCLUSIONS: There was no observed difference in clinical outcomes for portal users and nonusers undergoing kidney transplantation, although portal use may decrease the likelihood of ER visits. Socioeconomic status and ethnicity may play a role on who utilizes the patient portals.

Base-Catalyzed Phenol-Mannich Condensation of Preformed Cesium Iminodiacetate. The Direct Synthesis of Calcein Blue AM and Related Acyloxymethyl Esters.

A rapid and highly practical one-flask procedure for the positionally selective preparation of (acyloxy)methyl N-(2-hydroxybenzyl)iminodiacetate and related diesters from iminodiacetic acid and phenols is described. The key to this multicomponent phenol-Mannich condensation resides in the use of cesium iminodiacetate as the reaction partner. This protocol has been applied in an unusually direct synthesis of the intracellular fluorescent dye Calcein blue AM, for which scant experimental and spectroscopic data are presently available.

The Telemedicine Experience in Primary Care Practices in the United States: Insights From Practice Leaders.

PURPOSE: The need to rapidly implement telemedicine in primary care during the coronavirus disease 2019 (COVID-19) pandemic was addressed differently by various practices. Using qualitative data from semistructured interviews with primary care practice leaders, we aimed to report commonly shared experiences and unique perspectives regarding telemedicine implementation and evolution/maturation since March 2020. METHODS: We administered a semistructured, 25-minute, virtual interview with 25 primary care practice leaders from 2 health systems in 2 states (New York and Florida) included in PCORnet, the Patient-Centered Outcomes Research Institute clinical research network. Questions were guided by 3 frameworks (health information technology evaluation, access to care, and health information technology life cycle) and involved practice leaders' perspectives on the process of telemedicine implementation in their practice, with a specific focus on the process of maturation and facilitators/barriers. Two researchers conducted inductive coding of qualitative data open-ended questions to identify common themes. Transcripts were electronically generated by virtual platform software. RESULTS: Twenty-five interviews were administered for practice leaders representing 87 primary care practices in 2 states. We identified the following 4 major themes: (1) the ease of telemedicine adoption depended on both patients' and clinicians' prior experience using virtual health platforms, (2) regulation of telemedicine varied across states and differentially affected the rollout processes, (3) visit triage rules were unclear, and (4) there were positive and negative effects of telemedicine on clinicians and patients. CONCLUSIONS: Practice leaders identified several challenges to telemedicine implementation and highlighted 2 areas, including telemedicine visit triage guidelines and telemedicine-specific staffing and scheduling protocols, for improvement.

Sentiment Analysis of Online Patient-Written Reviews of Vascular Surgeons.

BACKGROUND: Online patient reviews influence a patient's choice of a vascular surgeon. The aim of this study is to examine underlying factors that contribute to positive and negative patient reviews by leveraging sentiment analysis and machine learning methods. METHODS: The Society of Vascular Surgeons publicly accessible member directory was queried and cross-referenced with a popular patient-maintained physician review website, healthgrades.com. Sentiment analysis and machine learning methods were used to analyze several parameters. Demographics (gender, age, and state of practice), star rating (of 5 stars), and written reviews were obtained for corresponding vascular surgeons. A sentiment analysis model was applied to patient-written reviews and validated against the star ratings. Student's t-test or one-way analysis of variance assessed demographic relationships with reviews. Word frequency assessments and multivariable logistic regression analyses were conducted to identify common and determinative components of written reviews. RESULTS: A total of 1,799 vascular surgeons had public profiles with reviews. Female gender of surgeon was associated with lower star ratings (male = 4.19, female = 3.95, P < 0.01) and average sentiment score (male = 0.50, female = 0.40, P < 0.01). Younger physician age was associated with higher star rating (P = 0.02) but not average sentiment score (P = 0.12). In the Best reviews, the most commonly used one-words were Care (N = 999), Caring (N = 767), and Kind (N = 479), while the most commonly used two-word pairs were Saved/Life (N = 189), Feel/Comfortable (N = 106), and Kind/Caring (N = 104). For the Worst reviews, the most commonly used one-words were Pain (N = 254) and Rude (N = 148), while the most commonly used two-word pairs were No/One (N = 27), Waste/Time (N = 25), and Severe/Pain (N = 18). In a multiple logistic regression, satisfactory reviews were associated with words such as Confident (odds ratio [OR] = 8.93), Pain-free (OR = 4.72), Listens (OR = 2.55), and Bedside Manner (OR = 1.70), while unsatisfactory reviews were associated with words such as Rude (OR = 0.01), Arrogant (OR = 0.09), Infection (OR = 0.20), and Wait (OR = 0.48). CONCLUSIONS: Female surgeons received significantly worse reviews and younger surgeons tended to receive better reviews. The positivity and negativity of reviews were largely related to words associated with the patient-doctor experience and pain. Vascular surgeons should focus on these 2 areas to improve patient experiences and their own reviews.

Comparison of Frailty Indices and the Charlson Comorbidity Index in Traumatic Brain Injury.

BACKGROUND: Comorbidity scales for outcome prediction in traumatic brain injury (TBI) include the 5-component modified Frailty Index (mFI-5), the 11-component modified Frailty Index (mFI-11), and the Charlson Comorbidity Index (CCI). OBJECTIVE: To compare the accuracy in predicting clinical outcomes in TBI of mFI-5, mFI-11, and CCI. METHODS: The National Trauma Data Bank (NTDB) of the American College of Surgeons (ACS) was utilized to study patients with isolated TBI for the years of 2017 and 2018. After controlling for age and injury severity, individual multivariable logistic regressions were conducted with each of the 3 scales (mFI-5, mFI-11, and CCI) against predefined outcomes, including any complication, home discharge, facility discharge, and mortality. RESULTS: All 3 scales demonstrated adequate internal consistency throughout their individual components (0.63 for mFI-5, 0.60 for CCI, and 0.56 for mFI-11). Almost all studied complications were significantly more likely in frail patients. mFI-5 and mFI-11 had similar areas under the curve (AUC) for all outcomes, while CCI had lower AUCs (0.62-0.61-0.53 for any complication, 0.72-0.72-0.52 for home discharge, 0.78-0.78-0.53 for facility discharge, and 0.71-0.70-0.52 for mortality, respectively). CONCLUSION: mFI-5 and mFI-11 demonstrated similar accuracy in predicting any complication, home discharge, facility discharge, and mortality in TBI patients across the NTDB. In addition, CCI's performance was poor for the aforementioned metrics. Since mFI-5 is simpler, yet as accurate as the 2 other scales, it may be the most practical both for clinical practice and for future studies with the NTDB.

Development of a novel instrument to characterize telemedicine programs in primary care.

BACKGROUND: Given the rapid deployment of telemedicine at the onset of the COVID - 19 pandemic, updated assessment methods are needed to study and characterize telemedicine programs. We developed a novel semi - structured survey instrument to systematically describe the characteristics and implementation processes of telemedicine programs in primary care. METHODS: In the context of a larger study aiming to describe telemedicine programs in primary care, a survey was developed in 3 iterative steps: 1) literature review to obtain a list of telemedicine features, facilitators, and barriers; 2) application of three evaluation frameworks; and 3) stakeholder engagement through a 2-stage feedback process. During survey refinement, items were tested against the evaluation frameworks while ensuring it could be completed within 20-25 min. Data reduction techniques were applied to explore opportunity for condensed variables/items. RESULTS: Sixty initially identified telemedicine features were reduced to 32 items / questions after stakeholder feedback. Per the life cycle framework, respondents are asked to report a month in which their telemedicine program reached a steady state, i.e., "maturation". Subsequent questions on telemedicine features are then stratified by telemedicine services offered at the pandemic onset and the reported point of maturation. Several open - ended questions allow for additional telemedicine experiences to be captured. Data reduction techniques revealed no indication for data reduction. CONCLUSION: This 32-item semi-structured survey standardizes the description of primary care telemedicine programs in terms of features as well as maturation process. This tool will facilitate evaluation of and comparisons between telemedicine programs across the United States, particularly those that were deployed at the pandemic onset.

The relationship between lower extremity amputation and body mass index.

OBJECTIVES: Non-traumatic lower extremity amputation (LEA) is associated with significant morbidity and mortality. Diabetes mellitus (DM) and peripheral vascular disease (PVD) are associated with increased risk for LEA. As such, DM and PVD account for 54% of all LEA's, performed in the United States annually. As obesity is highly associated with both DM and PVD, our study sought to explore the relationship between LEA and obesity defined by BMI. METHODS: Using the National Inpatient Sample (NIS) database, a retrospective review of patients who underwent non-traumatic LEA (LEA) between 2008 and 2014 was performed. The International Classification of Diseases 9th edition (ICD-9) codes were utilized to determine the diagnoses, comorbidities, and procedures. Patient BMIs were classified as follows: Non-obese [BMI <30], Obesity class I [BMI 30-34.9], Obesity class II [BMI 35-39.9], and Obesity class III [BMI ≥40]. Predictors for LEA were compared between groups using chi-square test and binary logistic regression to identify possible underlying factors associated with LEA. We also conducted a multivariate analysis to measure the effect of multiple variables on LEA. RESULTS: We identified 16,259 patients with non-traumatic LEA and a mean age of 59.9 years. Rate of amputation in females was lower than males at 0.35% vs 0.87% respectively (p < 0.001). Of patients that underwent amputation there was a V-shape trend based on BMI, with 30.4% in non-obese patients, 18.2% in obesity class I, 17.3% in obesity class II, and 34.1% in obesity class III. The incidence of diabetes increased with obesity class, while the incidence of PVD decreased. Interestingly, of those with DM there was an inverse relationship between amputation rate and BMI class, with LEA rates in non-obese versus obesity class III patients were 1.63% vs 0.98% respectively (p < 0.001). Similarly, patients who had both diabetes and PVD showed a downward trend in LEA rate as obesity class increased; non-obese patients had a LEA rate of 8.01%, while obesity class III had 4.65% (p < 0.001). Patients in higher income bracket have lower odds of LEA (OR 0.77, p < 0.001) compared to the lowest income patients. Also, patients with comorbidities such as PVD (OR 10.78), diabetes (OR 5.02), renal failure (OR 1.41), and hypertension (OR 1.36) had higher odds to get an LEA (p < 0.001). Individuals with obesity class III are almost at half the odds (OR 0.52) to get an LEA compared to non-obese (p < 0.001). CONCLUSIONS: Higher BMI and female gender are protective factors against lower extremity amputation. Factors that predisposing to LEA include lower household income and certain comorbidities such as PVD, diabetes, renal failure, and hypertension. These findings warrant further research to identify patients at high risk for LEA and help develop management guidelines for targeted populations.

Anatomy of Protein Electrospray Ionization Mass Spectra by Superconducting Tunnel Junction Mass and Energy Spectrometry.

Cryogenic superconducting tunnel junction (STJ) detectors have the advantage of single-particle sensitivity, high quantum efficiency, low noise, and the ability to detect the time and relative impact energy of deposited ions. This makes them attractive for use in mass spectrometry (MS) and as a form of energy spectrometry. STJ cryodetectors have been coupled to time-of-flight (TOF) mass spectrometers equipped with a matrix-assisted laser desorption ionization (MALDI) source and to an electrospray ionization (ESI) TOF mass spectrometer. Here, a lab-made linear quadrupole ion trap (LIT) mass spectrometer system was coupled to an ESI source and a 16-channel Nb-STJ array with improved readout electronics. The goal was to investigate fundamentals of ESI-generated protein ions by further exploiting the advantage of resolving these ions in a third dimension of the relative energy deposited into the STJs. The proteins equine cytochrome c, bovine carbonic anhydrase, bovine serum albumin, and murine immunoglobulin G were studied using this ESI-LIT-STJ-MS instrument. Multiply charged monomers, multimers, and fragments from metastable ions were resolved from monomer peaks by differences in ion deposition energy even when these ions have the same mass-to-charge ratio as the corresponding monomer. The determination of a fragment mass from metastable decomposition is accomplished without knowing the charge state of the fragment. The average charge state of the multimers is reduced with each addition of a protein which is presumed to be a direct reflection of the surface area available for charging. Multiply charged in-source fragments have also been observed and distinguished in the mass spectrum of carbonic anhydrase by using the differences in the energy deposited in the STJs.

Diketoenamine-Based Vitrimers via Thiol-ene Photopolymerization.

Likened to both thermosets and thermoplastics, vitrimers are a unique class of materials that combine remarkable stability, healability, and reprocessability. Herein, this work describes a photopolymerized thiol-ene-based vitrimer that undergoes dynamic covalent exchanges through uncatalyzed transamination of enamines derived from cyclic ß-triketones, whereby the low energy barrier for exchange facilitates reprocessing and enables rapid depolymerization. Accordingly, an alkene-functionalized ß-triketone, 5,5-dimethyl-2-(pent-4-enoyl)cyclohexane-1,3-dione, is devised which is then reacted with 1,6-diaminohexane in a stoichiometrically imbalanced fashion (≈1:0.85 primary amine:triketone). The resulting networks exhibit subambient glass transition temperature (Tg = 5.66 °C) by differential scanning calorimetry. Using a Maxwell stress-relaxation fit, the topology-freezing temperature (Tv ) is calculated to be -32 °C. Small-amplitude oscillatory shear rheological analysis enables to identify a practical critical temperature above which the vitrimer can be successfully reprocessed (Tv,eff ). Via the introduction of excess primary amines, this work can readily degrade the networks into monomeric precursors, which are in turn reacted with diamines to regenerate reprocessable networks. Photopolymerization provides unique spatiotemporal control over the network topology, thereby opening the path for further investigation of vitrimer properties. As such, this work expands the toolbox of chemical upcycling of networks and enables their wider implementation.

Compression Stocking Compliance Does Not Impact Reintervention or Symptom Change after Iliac Vein Stenting in Patients with Moderate to Severe Lower Extremity Edema.

BACKGROUND: Medical compression stocking (MCS) therapy remains a core treatment for chronic venous disease, particularly in patients with lower extremity edema. This study investigated the impact of postoperative MCS adherence on patients with moderate to severe edema who underwent iliac vein stenting (IVS). METHODS: Patients at a large tertiary care center who underwent IVS from August 2011 to June 2021 were analyzed. Symptoms were quantified using the venous clinical severity score (VCSS) and clinical assessment score (CAS). The criterion for inclusion was moderate or severe lower extremity edema at the time of IVS. Patients were stratified into two cohorts: complete postoperative compression therapy compliance (MCS+) and no postoperative compression therapy use (MCS-). RESULTS: Among 376 patients fitting our study criteria, we identified 168 MCS+ and 208 MCS- patients. The VCSS edema score did not significantly differ between groups (P = 0.179). Postoperatively, the mean changes in VCSS edema at the first postoperative visit, the one-year follow-up, and the two-year follow-up were not significantly different between the MCS+ and MCS- cohorts (P = 0.123, 0.296, and 0.534, respectively). An analysis of CAS for edema revealed that the MCS+ cohort had a modestly better improvement in edema at the 90-day follow-up visit versus the MCS- cohort (P = 0.018), but this difference was not observed in the 30-day (P = 0.834) or six-month follow-up visit (P = 0.755). A multivariate analysis revealed no difference in the need for major intervention (OR 0.93, 95% CI 0.44 to 1.50, P = 0.504). A Kaplan-Meier analysis via log-rank test revealed no difference in reintervention-free survival between groups (P = 0.77). CONCLUSIONS: Many patients with moderate to severe lower extremity edema experience a reduction in their edema after IVS. In our study, compression stocking compliance after surgery had a little impact on edema relief in this population.

Symptom Relief and Reintervention after Iliac Vein Stenting Stratified by CEAP Clinical Classification.

BACKGROUND: This study sought to evaluate long-term symptom relief and reintervention rates after iliac vein stenting (IVS) in patients with chronic venous outflow obstruction. METHODS: A single-institution database of patients undergoing IVS from August 2011 to June 2021 was analyzed. Patients were stratified into three cohorts based on the clinical component of the clinical, etiology, anatomical, and pathophysiology (CEAP) classification: C3, C4, and C5/6. Symptoms were quantified using the venous clinical severity score (VCSS). Reintervention was defined as any procedure using venography. Edema, pigmentation, and ulceration progression-free survival as well as reintervention-free survival were assessed with Kaplan Meier analysis. RESULTS: Among 737 total patients, there were 435 C3, 206 C4, and 96 C5/6 patients. The C5/6 cohort had the highest percentage of patients undergo reoperation (36.4%). C5/6 patients yielded the poorest ulceration progression-free survival (P < 0.001) while C3 patients had the poorest skin pigmentation progression-free survival (P = 0.009). On adjusted analysis there was no significant difference in odds of reintervention between study cohorts. Mean composite VCSS scores were significantly different at each yearly post-operative follow-up visit up to 6 years. CONCLUSIONS: The present study is one of the largest investigations of long-term outcomes in IVS patients. Most patients with long-term follow-up experienced an improvement in their composite VCSS. CEAP clinical classification at the time of IVS had a significant influence on the likelihood and quantity of reintervention.

A mechanistic examination of salting out in protein-polymer membrane interactions.

Developing a mechanistic understanding of protein dynamics and conformational changes at polymer interfaces is critical for a range of processes including industrial protein separations. Salting out is one example of a procedure that is ubiquitous in protein separations yet is optimized empirically because there is no mechanistic description of the underlying interactions that would allow predictive modeling. Here, we investigate peak narrowing in a model transferrin-nylon system under salting out conditions using a combination of single-molecule tracking and ensemble separations. Distinct surface transport modes and protein conformational changes at the negatively charged nylon interface are quantified as a function of salt concentration. Single-molecule kinetics relate macroscale improvements in chromatographic peak broadening with microscale distributions of surface interaction mechanisms such as continuous-time random walks and simple adsorption-desorption. Monte Carlo simulations underpinned by the stochastic theory of chromatography are performed using kinetic data extracted from single-molecule observations. Simulations agree with experiment, revealing a decrease in peak broadening as the salt concentration increases. The results suggest that chemical modifications to membranes that decrease the probability of surface random walks could reduce peak broadening in full-scale protein separations. More broadly, this work represents a proof of concept for combining single-molecule experiments and a mechanistic theory to improve costly and time-consuming empirical methods of optimization.

Race differences in iliofemoral vein stenting for chronic venous insufficiency.

INTRODUCTION: Major disparities in outcomes by race are present throughout vascular surgery, yet little has been published on iliac vein stent outcomes by race. This retrospective study assessed iliac vein stent outcomes by patient race. METHODS: Patients who underwent iliac vein stenting at a single institution for chronic venous insufficiency (CVI) from 2011 to 2021 were reviewed. Demographic, preoperative, perioperative, and postoperative data were collected. Self-reported race groups included Asian, Black, Hispanic, and White. Univariate differences were analyzed using χ2 tests for categorical variables and 1-way ANOVA for continuous variables. Outcomes included change in Venous Clinical Severity Score (VCSS) at interval timepoints relative to a preoperative baseline and reinterventions. Logistic regression models were used to determine the unadjusted and adjusted odds ratio (OR) of any minor and major reintervention. Multivariate regression models controlled for demographic and comorbidity characteristics. RESULTS: A total of 827 patients were included. Asian patients were younger and had a greater proportion of male patients, lower Body mass index (BMI), less smoking history, and fewer comorbidities. White patients were more likely to have a history of deep vein thrombosis (DVT). White patients presented with the most severe CVI symptoms as defined by both Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification and preoperative VCSS composite scores. There were no differences in acute DVT, number of stents deployed, and bilateral versus unilateral stent placement. Black patients had the longest average days of follow-up, followed sequentially by Hispanic, White, and Asian. Black patients had the most reinterventions, while Asian patients had the fewest. Asian patients were less likely to have a major reintervention. No differences in VCSS composite or change in VCSS were observed. CONCLUSIONS: In patients with CVI, Asian patients presented younger and healthier, while White patients presented with the most severe symptoms. No differences were observed in VCSS outcomes, though Black patients had the most reinterventions.

Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence, Severity, and Treatment Response.

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea−hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.

Single-Molecule Dynamics Reflect IgG Conformational Changes Associated with Ion-Exchange Chromatography.

Conformational changes of antibodies and other biologics can decrease the effectiveness of pharmaceutical separations. Hence, a detailed mechanistic picture of antibody-stationary phase interactions that occur during ion-exchange chromatography (IEX) can provide critical insights. This work examines antibody conformational changes and how they perturb antibody motion and affect ensemble elution profiles. We combine IEX, three-dimensional single-protein tracking, and circular dichroism spectroscopy to investigate conformational changes of a model antibody, immunoglobulin G (IgG), as it interacts with the stationary phase as a function of salt conditions. The results indicate that the absence of salt enhances electrostatic attraction between IgG and the stationary phase, promotes surface-induced unfolding, slows IgG motion, and decreases elution from the column. Our results reveal previously unreported details of antibody structural changes and their influence on macroscale elution profiles.