Decreasing prevalence of centers meeting the Society for Vascular Surgery abdominal aortic aneurysm guidelines in the United States.

OBJECTIVE: Based on data supporting a volume-outcome relationship in elective aortic aneurysm repair, the Society of Vascular Surgery (SVS) guidelines recommend that endovascular aortic repair (EVAR) be localized to centers that perform ≥10 operations annually and have a perioperative mortality and conversion-to-open rate of ≤2% and that open aortic repair (OAR) be localized to centers that perform ≥10 open aortic operations annually and have a perioperative mortality ≤5%. However, the number and distribution of centers meeting the SVS criteria remains unclear. This study aimed to estimate the temporal trends and geographic distribution of Centers Meeting the SVS Aortic Guidelines (CMAG) in the United States. METHODS: The SVS Vascular Quality Initiative was queried for all OAR, aortic bypasses, and EVAR from 2011 to 2019. Annual OAR and EVAR volume, 30-day elective operative mortality for OAR or EVAR, and EVAR conversion-to-open rate for all centers were calculated. The SVS guidelines for OAR and EVAR, individually and combined, were applied to each institution leading to a CMAG designation. The proportion of CMAGs by region (West, Midwest, South, and Northeast) were compared by year using a χ2 test. Temporal trends were estimated using a multivariable logistic regression for CMAG, adjusting by region. RESULTS: Overall, 67,865 patients (49,264 EVAR; 11,010 OAR; 7591 aortic bypasses) at 336 institutions were examined. The proportion of EVAR CMAGs increased nationally by 1.7% annually from 51.6% (n = 33/64) in 2011 to 67.1% (n = 190/283) in 2019 (ß = .05; 95% confidence interval [CI], 0.01-0.09; P = .02). The proportion of EVAR CMAGs across regions ranged from 27.3% to 66.7% in 2011 to 63.9% to 72.9% in 2019. In contrast, the proportion of OAR CMAGs has decreased nationally by 1.8% annually from 32.8% (n = 21/64) in 2011 to 16.3% (n = 46/283) in 2019 (ß = -.14; 95% CI, -0.19 to -0.10; P < .01). Combined EVAR and OAR CMAGs were even less frequent and decreased by 1.5% annually from 26.6% (n = 17/64) in 2011 to 13.1% (n = 37/283) in 2019 (ß = -.12; 95% CI, -0.17 to -0.07; P < .01). In 2019, there was no significant difference in regional variation of the proportion of combined EVAR and OAR CMAGs (P = .82). CONCLUSIONS: Although an increasing proportion of institutions nationally meet the SVS guidelines for EVAR, a smaller proportion meet them for OAR, with a concerning downward trend. These data question whether we can safely offer OAR at most institutions, have important implications about sufficient OAR exposure for trainees, and support regionalization of OAR.

Linkage Transformations in a Three-Dimensional Covalent Organic Framework for High-Capacity Adsorption of Perfluoroalkyl Substances.

Despite their many advantages, covalent organic frameworks (COFs) built from three-dimensional monomers are synthetically difficult to functionalize. Herein, we provide a new synthetic approach to the functionalization of a three-dimensional covalent organic framework (COF-300) by using a series of solid-state linkage transformations. By reducing the imine linkages of the framework to amine linkages, we produced a more hydrolytically stable material and liberated a nucleophilic amino group, poised for further functionalization. We then treated the amine-linked COF with diverse electrophiles to generate a library of functionalized materials, which we tested for their ability to adsorb perfluoroalkyl substances (PFAS) from water. The framework functionalized with dimethylammonium groups, COF-300-dimethyl, adsorbed more than 250 mg of perfluorooctanoic acid (PFOA) per 1 g of COF, which represents an approximately 14,500-fold improvement over that of COF-300 and underscores the importance of electrostatic interactions to PFAS adsorption performance. This work provides a conceptually new approach to the design and synthesis of functional three-dimensional COFs.

Pragmatic design and inclusion of patient-partner representatives improves participant experience in clinical research.

Objectives: Patient engagement in the design and implementation of clinical trials is necessary to ensure that the research is relevant and responsive to patients. The PREP-IT trials, which include 2 pragmatic trials that evaluate different surgical preparation solutions in orthopaedic trauma patients, followed the patient-centered outcomes research (PCOR) methodology throughout the design, implementation, and conduct. We conducted a substudy within the PREP-IT trials to explore participants' experiences with trial participation. Methods: At the final follow-up visit (12 months after their fracture), patients participating in the PREP-IT trials were invited to participate in the substudy. After providing informed consent, participants completed a questionnaire that asked about their experience and satisfaction with participating in the PREP-IT trials. Descriptive statistics are used to report the findings. Results: Four hundred two participants participated in the substudy. Most participants (394 [98%]) reported a positive experience, and 376 (94%) participants felt their contributions were appreciated. The primary reasons for participation were helping future patients with fracture (279 [69%]) and to contribute to science (223 [56%]). Two hundred seventeen (46%) participants indicated that their decision to participate was influenced by the minimal time commitment. Conclusions: Most participants reported a positive experience with participating in the PREP-IT trials. Altruism was the largest motivator for participating in this research. Approximately half of the participants indicated that the pragmatic, low-participant burden design of the trial influenced their decision to participate. Meaningful patient engagement, a pragmatic, and low-burden protocol led to high levels of participant satisfaction.

Age-specific reproduction in female Steller sea lions in Southeast Alaska.

Age-, region-, and year-specific estimates of reproduction are needed for monitoring wildlife populations during periods of ecosystem change. Population dynamics of Steller sea lions (Eumetopias jubatus) in Southeast Alaska varied regionally (with high population growth and survival in the north vs. the south) and annually (with reduced adult female survival observed following a severe marine heatwave event), but reproductive performance is currently unknown. We used mark-resighting data from 1006 Steller sea lion females marked as pups at ~3 weeks of age from 1994 to 1995 and from 2001 to 2005 and resighted from 2002 to 2019 (to a maximum age of 25) to examine age-, region-, and year-specific reproduction. In the north versus the south, age of first reproduction was earlier (beginning at age 4 vs. age 5, respectively) but annual birth probabilities of parous females were reduced by 0.05. In an average year pre-heatwave, the proportion of females with pup at the end of the pupping season peaked at ages 12-13 with ~0.60/0.65 (north/south) with pup, ~0.30/0.25 with juvenile, and ~0.10 (both regions) without a dependent. In both regions, reproductive senescence was gradual after age 12: ~0.40, 0.40, and 0.20 of females were in these reproductive states, respectively, by age 20. Correcting for neonatal mortality, true birth probabilities at peak ages were 0.66/0.72 (north/south). No cost of reproduction on female survival was detected, but pup production remained lower (-0.06) after the heatwave event, which if sustained could result in population decline in the south. Reduced pup production and greater retention of juveniles during periods of poor prey conditions may be an important strategy for Steller sea lions in Southeast Alaska, where fine-tuning reproduction based on nutritional status may improve the lifetime probability of producing pups under good conditions in a variable and less productive environment.

Identification of optimal conditions for human placental explant culture and extracellular vesicle release.

Extracellular vesicles (EVs) can mediate intercellular communication, including signaling between the placenta and maternal tissues. Human placental explant culture is a versatile in vitro model system to investigate placental function. We performed systematic studies in different tissue culture media types and oxygen tensions to identify a defined serum-free culture condition that supports high trophoblast viability and metabolism, as well as the release of similar populations of EVs, compared to traditional undefined conditions that contain media additives potentially contaminated with exogenous EVs. We also determined the time frame in which trophoblast viability and functionality remain optimal. Multiplex vesicle flow cytometry with classical EV and placenta-specific markers revealed three separate populations of explant-derived EVs: small CD63+ EVs; large PLAP+ EVs; and CD63-/PLAP- EVs. These culture and analytical approaches will enable in vitro modeling of short-term effects of environmental perturbations associated with pregnancy complications on placental function and EV release.

Socioeconomic status fails to account for worse outcomes in non-Hispanic black patients undergoing carotid revascularization.

OBJECTIVE: Previous studies have reported an association of Black race with worse carotid revascularization outcomes, but rarely include socioeconomic status as a confounding covariate. We aimed to assess the association of race and ethnicity with in-hospital and long-term outcomes following carotid revascularization before and after accounting for socioeconomic status. METHODS: We identified non-Hispanic Black and non-Hispanic white patients who underwent carotid endarterectomy, transfemoral carotid stenting, or transcarotid artery revascularization between 2003 and 2022 in the Vascular Quality Initiative. Primary outcomes were in-hospital stroke/death and long-term stroke/death. Multivariable logistic regression and Cox proportional hazards models were used to assess the association of race with perioperative and long-term outcomes after adjusting for baseline characteristics using a sequential model approach without and with consideration of Area Deprivation Index (ADI), a validated composite marker of socioeconomic status. RESULTS: Of 201,395 patients, 5.1% (n = 10,195) were non-Hispanic Black, and 94.9% (n = 191,200) were non-Hispanic white. Mean follow-up time was 3.4±0.01 years. A disproportionately high percentage of Black patients were living in more socioeconomically deprived neighborhoods relative to their white counterparts (67.5% vs 54.2%; P < .001). After adjusting for demographic, comorbidity, and disease characteristics, Black race was associated with greater odds of in-hospital (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.10-1.40) and long-term stroke/death (adjusted hazard ratio [aHR], 1.13; 95% CI, 1.04-1.23). These associations did not substantially change after additionally adjusting for ADI; Black race was persistently associated with greater odds of in-hospital (aOR, 1.23; 95% CI, 1.09-1.39) and long-term stroke/death (aHR, 1.12; 95% CI, 1.03-1.21). Patients living in the most deprived neighborhoods were at greater risk of long-term stroke/death compared with patients living in the least deprived neighborhoods (aHR, 1.19; 95% CI, 1.05-1.35). CONCLUSIONS: Non-Hispanic Black race is associated with worse in-hospital and long-term outcomes following carotid revascularization despite accounting for neighborhood socioeconomic deprivation. There appears to be unrecognized gaps in care that prevent Black patients from experiencing equitable outcomes following carotid artery revascularization.

Proximal Instructions for Use Violations in Elective Endovascular Aneurysm Repair in the Vascular Quality Initiative: Retrospective Analysis.

BACKGROUND: Endovascular aneurysm repair (EVAR) is often attempted in patients with marginal anatomy. These patients' midterm outcomes are available in the Vascular Quality Initiative for analysis. STUDY DESIGN: Retrospective analysis of prospectively collected data in the Vascular Quality Initiative from patients who underwent elective infrarenal EVAR between 2011 and 2018. Each EVAR was identified as either on- or off-instructions for use (IFU) based on aortic neck criteria. Multivariable logistic regression models were used to assess associations between aneurysm sac enlargement, reintervention, and type Ia endoleak with IFU status. Kaplan-Meier time-to-event models estimated reintervention, aneurysm sac enlargement, and overall survival. RESULTS: We identified 5,488 patients with at least 1 follow-up recorded. Those treated off-IFU included 1,236 patients ([23%] mean follow-up 401 days) compared with 4,252 (77%) treated on-IFU (mean follow-up 406 days). There was no evidence of significant differences in crude 30-day survival (96% vs 97%; p = 0.28) or estimated 2-year survival (97% vs 97%; log-rank p = 0.28). Crude type Ia endoleak frequency was greater in patients treated off IFU (2% vs 1%; p = 0.03). Off-IFU EVAR was associated with type Ia endoleak on multivariable regression model (odds ratio 1.84 [95% CI 1.23 to 2.76]; p = 0.003). Patients treated off IFU vs on IFU experienced had increased risk of reintervention within 2 years (7% vs 5%; log-rank p = 0.02), a finding consistent with results from the Cox modeling (hazard ratio 1.38 [95% CI 1.06 to 1.81]; p = 0.02). CONCLUSIONS: Patients treated off IFU were at greater risk for type Ia endoleak and reintervention, although they had similar 2-year survival compared with those treated on IFU. Patients with anatomy outside IFU should be considered for open surgery or complex endovascular repair to reduce the probability for revision.

Stabilizing large pores in a flexible metal-organic framework via chemical cross-linking.

A barrier to the isoreticular expansion of flexible metal-organic frameworks is their complex breathing behavior, which can lead to pore closure upon solvent exchange and removal. Here we show that chemical cross-linking stabilizes the open form of a flexible aluminum framework with large 17 Å pores.

Increased Regional Market Competition is Associated with a Lower Threshold for Revascularization in Asymptomatic Carotid Artery Stenosis.

BACKGROUND: Revascularization practices with respect to asymptomatic carotid stenosis (ACAS) are known to vary widely among proceduralists. In addition, regional market competition has been previously shown to drive more aggressive practices in a number of surgical procedures. The aim of our study was to examine the association of regional market competition with revascularization thresholds for ACAS. METHODS: All patients undergoing carotid revascularization in the Vascular Quality Initiative carotid endarterectomy and stenting databases (2016-2020) were included. High-grade carotid stenosis was defined as ≥80%. We calculated the Herfindahl-Hirschman Index (HHI; a measure of physician market competition) for each U.S region as defined by the U.S Department of Health and Human Services. Logistic regression was used to examine the association of degree of carotid stenosis at revascularization with HHI stratified by symptomatology, adjusting for age, sex, race, insurance, and revascularization modality. RESULTS: Of 92,243 carotid interventions, 57,094 (61.9%) were performed for ACAS and 35,149 (38.1%) were performed for symptomatic carotid stenosis (SCAS). ACAS patients undergoing revascularization for moderate-grade stenosis were significantly less likely to be aspirin (85.6% vs. 86.3%), clopidogrel (41.3% vs. 45.1%), dual anti-platelet therapy (35.9% vs. 39.2%) and systemic anticoagulants (10.9 vs. 11.7%) compared to high-grade stenosis (all P < 0.05). Multivariable analysis demonstrated that decreased local market competition was independently associated with a lower odds of revascularization for moderate versus high-grade ACAS (odds ratio OR: 0.99 per 10 point increase in HHI, 95% confidence interval CI: 0.98-0.99). There was no association of local market competition with degree of carotid stenosis at time of revascularization among patients with SCAS (OR: 1.00 per 10 point increase in HHI, 95% CI: 0.99-1.00). Among ACAS patients, patients with moderate-grade stenosis had a higher odds ratio of in-hospital stroke or death compared to patients with high-grade stenosis (OR: 1.22, 95% CI 1.03-1.45). This association was not redemonstrated in the SCAS group (OR: 0.92, 95% CI: 0.80-1.06). CONCLUSIONS: Increased local market competition is associated with a lower threshold for revascularization of ACAS. There is no association between regional market competition and revascularization threshold for SCAS. These findings, combined with the significantly increased risk of perioperative stroke/death among moderate-grade ACAS patients, suggest that competition among proceduralists may result in a higher tolerance for increased operative risk in patients who might otherwise be reasonable candidates for surveillance.

Cadaver Simulation is Associated with Increased Comfort in Performing Open Vascular Surgery Among Integrated Vascular Surgery (0+5) Residents and Recent Graduates.

BACKGROUND: With the evolution in vascular surgery toward increased endovascular therapy and decreased open surgical training, comfort with open procedures by current trainees is declining. A proposed method to improve this discomfort is simulator training. We hypothesized that open, cadaver, and endovascular surgery simulation would be associated with increased self-perceived comfort in performing corresponding procedures. METHODS: Integrated (0 + 5) vascular surgery residents and recent graduates in the United States were asked to complete a survey quantifying comfort via a Likert scale with procedures and experience with simulation training. Simulation groups were then matched using coarsened exact matching. Ordinal logistic regression assessed the association between simulation experience and comfort in performing procedures. RESULTS: Surveys were completed by 68 trainees and 20 attending surgeons in their first 5 years of practice. On unmatched analyses, there were no significant differences in comfort in performing any open or endovascular aorto-mesenteric or peripheral vascular procedures between respondents who reported experience with open or endovascular simulation, respectively. However, respondents who reported cadaver simulation experience (58%, 51/88) had a significantly higher reported comfort score performing open juxtarenal aortic repair (2.4 vs. 1.7), superior mesenteric artery thrombectomy or bypass (2.5 vs. 1.9), inferior vena cava or iliac vein repair (2.2 vs. 1.7), axillary-femoral artery bypass (3.4 vs. 2.5), femoral-popliteal artery bypass (3.7 vs. 2.8), and inframalleolar artery bypass (2.8 vs. 2.1; all P < 0.05). After matching on training level, number of abdominal cases completed, and number of open vascular cases completed, ordinal logistic regression demonstrated that previous cadaver simulation was significantly associated with increased comfort in performing open aortic repairs, venous repair, visceral revascularization, and peripheral bypasses. CONCLUSIONS: In this nationally representative sample, cadaver, but not open or endovascular, simulation was associated with increased comfort in performing open vascular surgery. Providing cadaver simulation to trainees may help to improve comfort levels in performing open surgery. Integrated vascular surgery training programs should consider implementing these experiences into their curriculum.

Selective Upregulation of SIRT1 Expression in Retinal Ganglion Cells by AAV-Mediated Gene Delivery Increases Neuronal Cell Survival and Alleviates Axon Demyelination Associated with Optic Neuritis.

Optic neuritis (ON), the most common ocular manifestation of multiple sclerosis, is an autoimmune inflammatory demyelinating disease also characterized by degeneration of retinal ganglion cells (RGCs) and their axons, which commonly leads to visual impairment despite attempted treatments. Although ON disease etiology is not known, changes in the redox system and exacerbated optic nerve inflammation play a major role in the pathogenesis of the disease. Silent information regulator 1 (sirtuin-1/SIRT1) is a ubiquitously expressed NAD+-dependent deacetylase, which functions to reduce/prevent both oxidative stress and inflammation in various tissues. Non-specific upregulation of SIRT1 by pharmacologic and genetic approaches attenuates RGC loss in experimental ON. Herein, we hypothesized that targeted expression of SIRT1 selectively in RGCs using an adeno-associated virus (AAV) vector as a delivery vehicle is an effective approach to reducing neurodegeneration and preserving vision in ON. We tested this hypothesis through intravitreal injection of AAV7m8.SNCG.SIRT1, an AAV2-derived vector optimized for highly efficient SIRT1 transgene transfer and protein expression into RGCs in mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis that recapitulates optic neuritis RGC loss and axon demyelination. Our data show that EAE mice injected with a control vehicle exhibit progressive alteration of visual function reflected by decreasing optokinetic response (OKR) scores, whereas comparatively, AAV7m8.SNCG.SIRT1-injected EAE mice maintain higher OKR scores, suggesting that SIRT1 reduces the visual deficit imparted by EAE. Consistent with this, RGC survival determined by immunolabeling is increased and axon demyelination is decreased in the AAV7m8.SNCG.SIRT1 RGC-injected group of EAE mice compared to the mouse EAE counterpart injected with a vehicle or with control vector AAV7m8.SNCG.eGFP. However, immune cell infiltration of the optic nerve is not significantly different among all EAE groups of mice injected with either vehicle or AAV7m8.SNCG.SIRT1. We conclude that despite minimally affecting the inflammatory response in the optic nerve, AAV7m8-mediated SIRT1 transfer into RGCs has a neuroprotective potential against RGC loss, axon demyelination and vison deficits associated with EAE. Together, these data suggest that SIRT1 exerts direct effects on RGC survival and function.

Transcarotid artery revascularization is associated with similar outcomes to carotid endarterectomy regardless of patient risk status.

BACKGROUND: Carotid artery stenting (CAS), including both transfemoral carotid artery stenting (TFCAS) and transcarotid artery revascularization (TCAR), reimbursement has been limited to high-risk patients by the Centers for Medicare & Medicaid Services (CMS) since 2005. We aimed to assess the association of CMS high-risk status with perioperative outcomes for carotid endarterectomy (CEA), TFCAS, and TCAR. METHODS: We performed a retrospective review of all Vascular Quality Initiative patients who underwent carotid revascularization between 2015 and 2020. Patients were stratified by whether they met CMS CAS criteria, and univariable and multivariable logistic regression analyses were performed to assess the association of procedure type (CEA, TFCAS, TCAR) with perioperative outcomes. RESULTS: Of 124,531 individuals who underwent carotid revascularization procedures, 91,687 (73.6%) underwent CEA, 17,247 (13.9%) underwent TFCAS, and 15,597 (12.5%) underwent TCAR. Among patients who met the CMS CAS criteria (ie, high-risk patients), the incidence of perioperative stroke was 2.7% for CEA, 3.4% for TFCAS, and 2.4% for TCAR (P < .001). Among standard-risk patients, the incidence of perioperative stroke was 1.7% for CEA, 2.7% for TFCAS, and 1.8% for TCAR (P < .001). After adjusting for baseline demographic and clinical characteristics, the odds of perioperative stroke were lower for TCAR versus CEA in high-risk patients (adjusted odds ratio [aOR], 0.82; 95% confidence interval [CI], 0.68-0.99) and similar in standard-risk patients (aOR, 1.05; 95% CI, 0.84, 1.31). In contrast, the adjusted odds of perioperative stroke were higher for TFCAS versus CEA in high-risk patients (aOR, 1.23; 95% CI, 1.03-1.46) and standard-risk patients (aOR, 1.60; 95% CI, 1.37-1.86). In both populations, TFCAS and TCAR patients had significantly lower odds of myocardial infarction than CEA patients (both P < .001). CONCLUSIONS: The perioperative risks associated with CEA, TFCAS, and TCAR in high-risk patients support the current CMS criteria, although the risks associated with each revascularization approach in standard-risk patients suggest that distinguishing TCAR from TFCAS may be warranted.

The Nonmonotonic Dose Dependence of Protein Expression in Cells Transfected with Self-Amplifying RNA.

Self-amplifying (sa) RNA molecules-"replicons"-derived from the genomes of positive-sense RNA viruses are receiving increasing attention as gene and vaccine delivery vehicles. This is because mRNA forms of genes of interest can be incorporated into them and strongly amplified, thereby enhancing target protein expression. In this report, we demonstrate a nonmonotonic dependence of protein expression on the mass of transfected replicon, in contrast to the usual, monotonic case of non-saRNA transfections. We lipotransfected a variety of cell lines with increasing masses of enhanced yellow fluorescent protein (eYFP) as a reporter gene in sa form and found that there is a "sweet spot" at which protein expression and cell viability are optimum. To control the varying mass of transfected replicon RNA for a given mass of Lipofectamine, the replicons were mixed with a "carrier" RNA that is neither replicated nor translated; the total mass of transfected RNA was kept constant while increasing the fraction of the replicon from zero to one. Fluorescence microscopy studies showed that the optimum protein expression and cell viability are achieved for replicon fractions as small as 1/10 of the total transfected RNA, and these results were quantified by a systematic series of flow cytometry measurements. IMPORTANCE Positive-sense RNA viruses often have a cytotoxic effect on their host cell because of the strength of their RNA replicase proteins, even though only one copy of their genome begins the viral life cycle in each cell. Noninfectious forms of them-replicons-which include just their RNA replication-related genes, are also strongly self-amplifying and cytotoxic. Accordingly, when replicons fused with nonviral genes of interest are transfected into cells to amplify expression of proteins of interest, one needs to keep the replicon "dose" sufficiently low. We demonstrate how to control the number of RNA replicons getting into transfected cells and that there is a sweet spot for the replicon dose that optimizes protein expression and cell viability. Examples are given for the case of Nodamura viral replicons with fluorescent protein reporter genes in a variety of mammalian cell lines, quantified by flow cytometry and live/dead cell assays.

Association between Race and Perioperative Outcomes after Carotid Endarterectomy for Asymptomatic Carotid Artery Stenosis in NSQIP.

BACKGROUND: Previous studies have documented that Black patients have worse outcomes after lower extremity revascularization procedures compared with White patients. However, the association of race on carotid endarterectomy (CEA) outcomes is not well described. The aim of this study was to compare perioperative outcomes of CEA for Black vs White patients with asymptomatic carotid artery stenosis. STUDY DESIGN: All patients who underwent CEA for asymptomatic carotid stenosis in the ACS-NSQIP targeted vascular database (2011-2019) were included. Perioperative (30-day) outcomes were compared for Black vs White patients using multivariable logistic regression adjusting for age/sex, comorbidities, and disease characteristics. RESULTS: Of 16,764 asymptomatic CEA patients, 95.2% (N = 15,960) were White and 4.8% (N = 804) were Black. Black patients were slightly younger (mean age 71.4 ± 0.1 vs 69.9 ± 0.3 years, P < 0.001) and more frequently had high-grade carotid artery stenosis compared to White patients (79.5% vs 74.0%, p = 0.001). Comorbidities including hypertension, diabetes, kidney disease, congestive heart failure, and coronary artery disease were all more prevalent among Black patients (p ≤ 0.01). Crude perioperative stroke (2.4% vs 1.3%, p = 0.007) and stroke/death (2.6% vs 1.4%, p = 0.003) were higher for Black patients, but myocardial infarction (1.7% vs 1.5%, p = 0.67) and death (0.4% vs 0.2%, p = 0.12) were similar. After adjusting for baseline differences between groups, the risk of perioperative stroke (odds ratio 1.66, 95% CI 1.01 to 2.73) and stroke/death (odds ratio 1.75, 95% CI 1.10 to 2.81) remained significantly higher for Black patients compared with White patients. CONCLUSIONS: Black patients undergoing CEA for asymptomatic carotid artery stenosis had more severe stenosis, more comorbidities, and worse perioperative outcomes compared to White patients. Overall, our data suggest substantial differences in the treatment and outcomes of asymptomatic carotid artery stenosis based on race.

Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro.

The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 µM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus.

Kinetic characterization and thermostability of C. elegans cytoplasmic and mitochondrial malate dehydrogenases.

Malate dehydrogenase (MDH) catalyzes the conversion of NAD+ and malate to NADH and oxaloacetate in the citric acid cycle. Eukaryotes have one MDH isozyme that is imported into the mitochondria and one in the cytoplasm. We overexpressed and purified Caenorhabditis elegans cytoplasmic MDH-1 and mitochondrial MDH-2 in E. coli. Our goal was to compare the kinetic and structural properties of these enzymes because C. elegans can survive adverse environmental conditions, such as lack of food and elevated temperatures. In steady-state enzyme kinetics assays, we measured KM values for oxaloacetate of 54 and 52 µM and KM values for NADH of 61 and 107 µM for MDH-1 and MDH-2, respectively. We partially purified endogenous MDH-1 and MDH-2 from a mixed population of worms and separated them using anion exchange chromatography. Both endogenous enzymes had a KM for oxaloacetate similar to that of the corresponding recombinant enzyme. Recombinant MDH-1 and MDH-2 had maximum activity at 40 °C and 35 °C, respectively. In a thermotolerance assay, MDH-1 was much more thermostable than MDH-2. Protein homology modeling predicted that MDH-1 had more intersubunit salt-bridges than mammalian MDH1 enzymes, and these ionic interactions may contribute to its thermostability. In contrast, the MDH-2 homology model predicted fewer intersubunit ionic interactions compared to mammalian MDH2 enzymes. These results suggest that the increased stability of MDH-1 may facilitate its ability to remain active in adverse environmental conditions. In contrast, MDH-2 may use other strategies, such as protein binding partners, to function under similar conditions.

Expedient Endovascular Hemorrhage Control During Anterior Lumbar Spinal Exposure Allows Procedural Completion in Rescued Patients.

OBJECTIVES: To propose a contemporary management strategy for venous injury during anterior lumbar spinal exposure that incorporates endovascular treatment. METHODS: Vein injuries suffered by patients treated in a single practice were reviewed. A treatment algorithm based on these experiences was formulated. RESULTS: Between 2015 and 2018, 914 patients received anterior access procedures for indicated lumbar interbody fusions. Of these patients, 15 (1.6%) suffered minor vascular injuries treated with manual pressure or suture repair. Four (0.4%) patients undergoing anterior lumbar spine surgery suffered major venous injuries, all of whom received the indicated spinal hardware following endovascular rescue. Primary repair was attempted in three patients before endovascular control and not at all in one. Vascular access was obtained via the bilateral femoral veins in 2 patients, unilateral femoral in one, and bilateral femoral plus right internal jugular vein in one. Stent choice included both uncovered (5, 63%) and covered stents (3, 38%). Deep venous thrombosis occurred in 2 patient's post-treatment. 1 DVT was encountered in the setting of a covered stent and 1 uncovered stent thrombosis was treated with catheter-directed lysis 4 weeks post-operatively. Ultimately, 3 patients were therapeutically anticoagulated. Mean follow-up is 13 months (range 1-36) with duplex ultrasounds available at 6 months or later in 3 of 4 patients. There is no evidence of post-thrombotic syndrome in the 2 patients that developed DVT's or in-stent stenosis in the 3 patients with available follow-up imaging. CONCLUSIONS: Endovascular techniques are important adjuncts when controlling large-volume hemorrhage associated with venous tears during anterior spinal exposure. Adequate direct compression allowing occlusion balloon inflation are key steps to reduce blood loss. Covered and uncovered stents are both appropriate choices to treat injuries. Patients must be anticoagulated post-operatively and surveilled for the sequelae of venous insufficiency. With expedient hemostasis, the indicated spinal surgery may be safely completed.

In-hospital and one-year outcomes are similar for women and men following transcarotid artery revascularization in symptomatic and asymptomatic patients.

OBJECTIVE: In randomized controlled trials and retrospective series, women have higher rates of periprocedural stroke and death following carotid endarterectomy and transfemoral carotid artery stenting compared with men. We sought to compare outcomes by sex following transcarotid artery revascularization (TCAR) among patients in the Vascular Quality Initiative (VQI). METHODS: We reviewed all patients in the VQI who underwent TCAR from 2017 to 2020. We stratified the analysis by symptom status. The primary outcome was in-hospital stroke/death, and secondary outcomes were in-hospital stroke and death and 1-year stroke/death, stroke, and death. We used multivariable logistic and Cox regression models to assess the association of sex with in-hospital and 1-year outcomes after adjusting for preoperative and intraoperative characteristics. RESULTS: We identified 15,851 patients who underwent TCAR, of whom 7391 (47%) were symptomatic (2708 or 37% female) and 8460 (53%) were asymptomatic (3097 or 37% female). Women were less frequently considered anatomic high risk than men in both groups (symptomatic: 43% vs 46%; P = .004; asymptomatic: 44% vs 48%; P = .004). Among symptomatic patients, women more often had severe ≥70% stenosis (89% vs 87%; P = .02). There were no differences in in-hospital death, stroke, or stroke/death for women vs men following TCAR among symptomatic or asymptomatic patients (all P > .05). After adjusting for baseline differences between groups, female sex was not associated with in-hospital stroke/death in either symptomatic (odds ratio, 1.05; 95% confidence interval, 0.72-1.56) or asymptomatic (odds ratio, 0.93; 95% confidence interval, 0.53-1.63) patients undergoing TCAR. There were also no differences in 1-year stroke, death, or stroke/death risk for women compared with men with and without symptoms on unadjusted or adjusted analyses (P > .05). CONCLUSIONS: We found no sex differences in in-hospital or 1-year stroke/death following TCAR, regardless of symptom status. TCAR appears to be as safe of a surgical procedure for women as for men in patients with both symptomatic and asymptomatic carotid artery disease.

An integrated path for spatial capture-recapture and animal movement modeling.

Ecologists and conservation biologists increasingly rely on spatial capture-recapture (SCR) and movement modeling to study animal populations. Historically, SCR has focused on population-level processes (e.g., vital rates, abundance, density, and distribution), whereas animal movement modeling has focused on the behavior of individuals (e.g., activity budgets, resource selection, migration). Even though animal movement is clearly a driver of population-level patterns and dynamics, technical and conceptual developments to date have not forged a firm link between the two fields. Instead, movement modeling has typically focused on the individual level without providing a coherent scaling from individual- to population-level processes, whereas SCR has typically focused on the population level while greatly simplifying the movement processes that give rise to the observations underlying these models. In our view, the integration of SCR and animal movement modeling has tremendous potential for allowing ecologists to scale up from individuals to populations and advancing the types of inferences that can be made at the intersection of population, movement, and landscape ecology. Properly accounting for complex animal movement processes can also potentially reduce bias in estimators of population-level parameters, thereby improving inferences that are critical for species conservation and management. This introductory article to the Special Feature reviews recent advances in SCR and animal movement modeling, establishes a common notation, highlights potential advantages of linking individual-level (Lagrangian) movements to population-level (Eulerian) processes, and outlines a general conceptual framework for the integration of movement and SCR models. We then identify important avenues for future research, including key challenges and potential pitfalls in the developments and applications that lie ahead.

Templated synthesis enhances the cobalt adsorption capacity of a porous organic polymer.

Divalent transition metals such as Co(II) are important targets for removal from water sources, due to their potential toxicity as well as their high value. In this study, we found that a series of porous organic polymers based on amide-linked tetraphenylmethane units are effective Co(II) ion adsorbents in aqueous solution. To increase the density of Co(II) binding sites, we then developed a templated synthesis in which the branched, rigid monomers are pre-assembled around Co(II) ions prior to polymerization. After polymer formation, the Co(II) template ions are removed to yield a material rich in Co(II) binding sites. Ion adsorption isotherms show that the Co(II)-templated material has an ion adsorption capacity significantly greater than those of the non-templated materials, highlighting the utility of a templated synthetic route. SEM and TEM images show the morphology of the templated polymer to be dramatically different from the non-templated polymers and to be similar in size and shape to the Co(II)-monomer precursors, emphasizing the role of the template ions in directing the formation of the resulting polymer. This guest-templated approach requires no functionalization of the generic monomer and represents a promising synthetic route to high-capacity ion adsorbents for water purification and aqueous separations.