Management of renal artery aneurysms: A retrospective study.

BACKGROUND: Although renal artery aneurysms (RAAs) are rare and often asymptomatic with slow growth, their natural progression and optimal management are not well understood. Treatment recommendations for RAAs do exist; however, they are supported by limited data. METHODS: A retrospective cohort study was conducted to explore the management of patients diagnosed with an RAA at our institution from January 1st, 2013, to December 31st, 2020. Patients were identified through a search of our radiological database, followed by a comprehensive chart review for further assessment. Data collection encompassed patient and aneurysm characteristics, the rationale for initial imaging, treatment, surveillance, and all-cause mortality. RESULTS: One hundred eighty-five patients were diagnosed with or treated for RAAs at our center during this timeframe, with most aneurysms having been discovered incidentally. Average aneurysm size was 1.40 cm (±0.05). Of those treated, the mean size was 2.38 cm (±0.24). Among aneurysms larger than 3 cm in size, comprising 3.24% of the total cases, 83.3% underwent treatment procedures. Only 20% of women of childbearing age received treatment for their aneurysms. There was one instance of aneurysm rupture, with no associated mortality or significant morbidity. CONCLUSIONS: Our institution's management of RAAs over the period of the study generally aligned with guidelines. One potential area of improvement is more proactive intervention for women of childbearing age.

NEXUS Arch: A Multicenter Study Evaluating the Initial Experience With a Novel Aortic Arch Stent Graft System.

OBJECTIVE: To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. SUMMARY BACKGROUND DATA: The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. METHODS: Patients underwent transcatheter aortic arch repair with a single branch, 2 stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the 2 stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk, and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid-carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through 1 year. Survival analysis used the Kaplan-Meier method. RESULTS: Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients, while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5 (17.8%) had combined or other pathologies. At 1 month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all nondisabling), and combined mortality/stroke rate was 10.7%. One-year mortality was 10.7%, without device or aneurysm-related death. Two patients (7.1%) reported stroke or transient ischemic attack at 1 year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were 3 patients (10.7%) that had device-related unplanned reinterventions through 1 year. CONCLUSIONS: The NEXUS Aortic Arch Stent Graft System, a novel single branch, 2 stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent 1 year safety and performance.

Vascular Closure Devices For Axillary Artery Access: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the technical success and complication rates of vascular closure devices (VCDs) in the axillary artery. MATERIALS AND METHODS: MEDLINE and Embase were searched independently by two reviewers to identify observational studies from inception through October 2021. The following outcomes were meta-analyzed: technical success, hematoma, dissection, pseudoaneurysm, infection, and local neurological complications. Complications were also graded as mild, moderate, and severe. A logistic regression evaluating the influence of sheath size for the outcome of technical success rate was performed using individual patient-level data. RESULTS: Of 1496 unique records, 20 observational studies were included, totaling 915 unique arterial access sites. Pooled estimates were as follows: technical success 84.8% (95% confidence interval [CI]: 78%-89.7%, I2=60.4%), hematoma 7.9% (95% CI: 5.8%-10.6%, I2=0%), dissection 3.1% (95% CI: 1.3%-7.3%, I2=0%), pseudoaneurysm 2.7% (95% CI: 1.3%-5.7%, I2=0%), infection <1% (95% CI: 0%-5.7%, I2=20.5%), and local neurological complications 2.7% (95% CI: 1.7%-4.4%, I2=0%). There was a significant negative association between sheath size and technical success rate (odds ratio [OR]: 0.87 per 1 French (Fr) increase in sheath size, 95% CI: 0.80-0.94, p=0.0005). Larger sheath sizes were associated with a greater number of access-site complications (adjusted odds ratio [aOR]: 1.21 per 1 Fr increase sheath size, 95% CI: 1.04-1.40, p=0.013). CONCLUSIONS: Off-label use of VCDs in the axillary artery provides an 85% successful closure rate and variable complication rate, depending on the primary procedure and sheath size. Larger sheaths were associated with a lower technical success and greater rate of access-related complications. CLINICAL IMPACT: Safe arterial access is the foundation for arterial intervention. While the common femoral artery is a well established access site, alternative arterial access sites capable of larger sheath sizes are needed in the modern endovascular era. This article provides the largest synthesis to date on the use of vascular closure devices for percutaneous axillary artery access in endovascular intervention. It should serve clinicians with added confidence around this approach in terms of providing a reference for technical success and complications. Clinically, this data is relevant for patient consent purposes as well as for practice quality improvement in setting safety standards for this access site.

The Use of Vascular Closure Devices for Brachial Artery Access: A Systematic Review and Meta-Analysis.

PURPOSE: To estimate the rates of technical success and adverse events of vascular closure devices (VCDs) in the brachial artery and compare the rates of adverse events with manual compression. MATERIALS AND METHODS: MEDLINE and Embase were searched for observational studies examining VCDs in the brachial artery. Meta-analyses were performed using random effects for the following outcomes: (a) technical success, (b) hematoma at the access site, (c) pseudoaneurysm, (d) local neurological adverse events, and (e) total number of adverse events. A pairwise meta-analysis compared VCD with manual compression for the outcomes of hematoma and the total number of adverse events. RESULTS: Of 1,761 eligible records, 16 studies including 510 access sites were included. Primary procedures performed were peripheral arterial disease interventions, percutaneous coronary intervention, and endovascular thrombectomy for ischemic stroke. The technical success rate was 93% (95% CI, 87%-96%; I2 = 47%). Data on the following adverse events were obtained via meta-analysis: (a) hematoma, 9% (5%-15%; I2 = 54%); (b) stenosis or occlusion at access site, 3% (1%-14%; I2 = 51%); (c) infection, 0% (0%-5%; I2 = 0%); (d) pseudoaneurysm, 4% (1%-13%; I2 = 61%); (e) local neurological adverse events, 5% (2%-13%; I2 = 54%); and (f) total number of adverse events, 15% (10%-22%; I2 = 51%). Angio-Seal success rate was 96% (93%-98%; I2 = 0%), whereas the ExoSeal success rate was 93% (69%-99%; I2 = 61%). When comparing VCD and manual compression, there was no difference in hematoma formation (relative risk, 0.75; 95% CI, 0.35-1.63; I2 = 0%; P = .47) or the total number of adverse events (relative risk, 0.75; 95% CI, 0.35-1.58; I2 = 76%; P = .45). CONCLUSIONS: Despite being off-label, studies suggest that VCDs in the brachial artery have a high technical success rate. There was no significant difference in adverse events between VCDs and manual compression in the brachial artery.

Silicon nanowire FET biosensor and its application in acute myocardial infarction.

Over the last two decades, silicon nanowire field-effect transistors (SiNW-FETs) with prominent merits of high surface-to-volume ratio, excellent biocompatibility and mature fabrication with standard silicon technology, have been widely studied as ultrahigh sensitive biosensors for the detection of target biomolecules, such as proteins, nucleic acids, cells and viruses so on. Herein we present a comprehensive review of the fundamental aspects of SiNW-FET biosensors, involving the working principle and the device fabrication, surface functionalization, and system integration with fluid exchange and electrical detection. Futhermore, we emphatically discuss the electrical detection of cardiac-specific biomarkers related to acute myocardial infarction disease. SiNW-FET biosensors are being increasingly exploited as promising diagnostic devices, which provide high sensitivity, high integration density, high speed sampling, strong specificity, and real-time and label-free detection for simple and cheap clinical testing.

Effect of vertebral compression fractures on aortic neck angulation after endovascular aneurysm repair.

OBJECTIVE: Aortic neck angulation (ANA) prior to endovascular aneurysm repair (EVAR) and its changes after EVAR are considered important predictors of postoperative complications. We sought to assess the effects of vertebral body height loss on ANA in patients post-EVAR. METHODS: All patients who had undergone EVAR for infrarenal aortic aneurysms in our institution between August 2010 and December 2018 were assessed. Anterior and posterior vertebral body heights were measured in all patients on preoperative, early postoperative, and follow-up computed tomography scans (T12-L5 vertebral bodies). Patients who had significant height loss in their follow-up period were designated as the Study group. These were matched to a Control group of the same size using propensity-score matching based on age, gender, and duration between follow-up scans. Aortic neck morphology indices including ANA and its changes were measured, and information related to postoperative endoleaks and aneurysm sac size were extracted in the Study and Control groups. RESULTS: During the follow-up period, 10 of 185 patients had a radiologically significant vertebral body compression fracture. There was no significant difference between the Study (n = 10) and Control groups in age (77.6 ± 6.9 vs 77.2 ± 7.5 years; P = .64), gender (seven males and three females in each group; P = 1.0), duration between postoperative scans (1830 ± 665 vs 1800 ± 670 days; P = .25), preoperative ANA (36.0° ± 15.6° vs 42.4° ± 18.6°; P = .41), and early postoperative ANA (21.9° ± 11.7° vs 20.9° ± 16.3°; P = .72). Changes in ANA in the postoperative period (7.2° ± 11.1° vs -4.7° ± 6.7°; P = .009; power = .838) were significantly higher in the Study group. CONCLUSIONS: Post-EVAR vertebral body compression fractures exacerbate ANA. Awareness of this can guide both preoperative assessment and postoperative management and follow-up.

Arteries of the Lower Limb-Embryology, Variations, and Clinical Significance.

OBJECTIVES: The purpose of this article is to review the embryology of the lower limb arterial anatomy along with common variants and their clinical relevance. DESIGN: Embryologic variations of the lower limb arterial system may be explained by i.) persistence of primordial arterial segments, ii.) abnormal fusion, iii.) segmental hypoplasia/absence, or a combination of both. Persistent sciatic artery, corona mortis, and popliteal entrapment syndrome will also be discussed with associated symptoms, and potential complications. CONCLUSION: Knowledge of these variations is essential for surgical and endovascular management as failure to recognize them can result in complications.

[Chinesization of the quality of life scale and its reliability and validity tests for non-alcoholic fatty liver disease].

Objective: To translate the English version of the non-alcoholic fatty liver disease quality of life scale (CLDQ-NAFLD) into the Chinese version in order to test its reliability and validity. Methods: The English version of the CLDQ-NAFLD was translated according to the cross-cultural research tool debugging and validation guidelines to form the Chinese version of the CLDQ-NAFLD. A questionnaire survey was conducted on 515 NAFLD cases in a tertiary hospital in Hangzhou from September 2021 to April 2022 to evaluate the reliability and validity of the scale. Results: The Chinese version of the CLDQ-NAFLD contained six domains with a total of thirty-six items (X2/DF=3.105, RMSEA=0.064, TLI=0.905, CFI=0.912, and IFI=0.913). I-CVI, S-CVI/UA, and S-CVI/Ave was 0.83 to 1.00, 0.86 and 0.98, respectively. The 12-item Short-Form Health Survey (SF-12) was used as the calibration standard, and the correlation validity of the calibration standard was 0.704 (P<0.001). The Cronbach's alpha coefficient of the total scale and each dimension of the scale was 0.964 and 0.807-0.956, respectively. The test-retest reliability was 0.839. Conclusion: The Chinese version of the CLDQ-NAFLD has good reliability and validity. Thus, it can be used to evaluate the quality of life for NAFLD patients with a Chinese cultural background.

Multimodal small-molecule screening for human prion protein binders.

Prion disease is a rapidly progressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), and there are currently no therapeutic options. PrP ligands could theoretically antagonize prion formation by protecting the native protein from misfolding or by targeting it for degradation, but no validated small-molecule binders have been discovered to date. We deployed a variety of screening methods in an effort to discover binders of PrP, including 19F-observed and saturation transfer difference (STD) NMR spectroscopy, differential scanning fluorimetry (DSF), DNA-encoded library selection, and in silico screening. A single benzimidazole compound was confirmed in concentration-response, but affinity was very weak (Kd > 1 mm), and it could not be advanced further. The exceptionally low hit rate observed here suggests that PrP is a difficult target for small-molecule binders. Whereas orthogonal binder discovery methods could yield high-affinity compounds, non-small-molecule modalities may offer independent paths forward against prion disease.

Toronto PowerWire fenestration technique to access false lumen branches in fenestrated endovascular aneurysm repair for chronic type B dissection.

Chronic type B aortic dissection with aneurysmal degeneration requiring intervention presents significant therapeutic challenges. Thoracic endovascular aortic repair with a fenestrated endograft is a feasible option, but false lumen branches without an adjacent re-entry or perforation in the septum can pose a significant challenge. We present two cases of fenestrated endovascular aneurysm repair for chronic type B aortic dissection in which a renal artery from the false lumen was cannulated by creating a "neofenestration" through the dissection flap using a radiofrequency PowerWire (Baylis Medical Inc, Montreal, Quebec, Canada) technique (Toronto PowerWire fenestration technique).

Outcomes at a single center after subintimal arterial flossing with antegrade-retrograde intervention for critical limb ischemia.

OBJECTIVE: The subintimal arterial flossing with antegrade-retrograde intervention technique has been used to overcome antegrade recanalization failures for peripheral lower limb arterial occlusive disease. There are few outcomes published for this technique and we sought to evaluate outcomes at our institution over a 7-year period. METHODS: A retrospective review was performed of all subintimal arterial flossing with antegrade-retrograde intervention procedures of infrainguinal occlusive disease from 2009 to 2016. Retrograde and antegrade accesses were combined when occlusions could not be crossed from the antegrade direction. Baseline patient characteristics, procedures, procedure time, fluoroscopy time, contrast used, and radiation dose were collected. Posterior tibial waveforms, ankle-brachial index, limb salvage, vessel patency, and the presence of symptoms were assessed at follow-up. RESULTS: Treatment was performed in 52 limbs in 52 patients (35 men and 17 women; mean age, 77.62 ± 11.61 years) with critical limb ischemia and no appropriate venous conduit for surgical bypass. Among the cohort, 63.5% were diabetics, 98% had hypertension, 53.8% had a prior myocardial infarction, and 36.5% end-stage renal disease. The average Rutherford Category before the intervention was 5.08 ± 1.01. Retrograde pedal access was most commonly obtained in the anterior tibial artery/dorsalis pedis (55.7%), followed by the posterior tibial artery (40.3%). The technical success rate was 63.5% (33/52); adjunctive stenting was needed in 19 (36.5%) to optimize results. Preprocedural ankle-brachial index score was 0.54 ± 0.25, which improved after the procedure to an ankle-brachial index score of 0.77 ± 0.25. The primary patency rates at 3 and 6 months were 65% and 60%, respectively. The limb salvage rate at a mean follow-up of 5.4 months was 78.8%. There were 5 complications; 4 were hematomas managed conservatively and 1 was a major retroperitoneal bleed resulting in patient death. CONCLUSIONS: Retrograde pedal access is a viable revascularization technique for achieving limb salvage in patients with critical limb ischemia with acceptable patency for limb-threatening ischemia. This technique expands revascularization options after failed conventional endovascular antegrade approaches.

Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits.

To predict the orbifloxacin concentrations in rabbits after multiple routes of administration, a flow-limited multiroute physiologically based pharmacokinetic (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were incorporated into this model. Physiological parameters including tissue weights and blood flows through different tissues were obtained from the literature. The tissue/plasma partition coefficients (PX s) for noneliminating tissues were calculated according to the area method, while the PX s for kidney and the rest of the body compartment, together with other parameters for absorption and elimination, were optimized based on the published concentrations. The comparisons between predicted and observed orbifloxacin concentrations proved its validity, and the present model predicted available concentration data well, including those in liver, kidney, muscle, lung, heart, and plasma after oral, intravenous, or intramuscular administration. A local sensitivity analysis was also performed, which showed that the parameters for oral absorption were most influential on the orbifloxacin concentrations. This model was used to predict plasma and tissue concentrations after multiple oral or intramuscular administration. This study demonstrated the feasibility of predicting drug residues in minor species after multiple routes of administration in the extra-label manner using the PBPK modeling.

Pharmacokinetics of orbifloxacin in crucian carp (Carassius auratus) after intravenous and intramuscular administration.

The pharmacokinetics of orbifloxacin was studied after a single dose (7.5 mg/kg) of intravenous or intramuscular administration to crucian carp (Carassius auratus) reared in freshwater at 25°C. Plasma samples were collected from six fish per sampling point. Orbifloxacin concentrations were determined by high-performance liquid chromatography with a 0.02 µg/ml limit of detection, then were subjected to noncompartmental analysis. After intravenous injection, initial concentration of 5.83 µg/ml, apparent elimination rate constant (λz ) of 0.039 hr-1 , apparent elimination half-life (T1/2λz ) of 17.90 hr, systemic total body clearance (Cl) of 75.47 ml hr-1  kg-1 , volume of distribution (Vz) of 1,948.76 ml/kg, and volume of distribution at steady-state (Vss) of 1,863.97 ml/kg were determined, respectively. While after intramuscular administration, the λz , T1/2λz , mean absorption time (MAT), absorption half-life (T1/2ka ), and bioavailability were determined as 0.027 hr-1 , 25.69, 10.26, 7.11 hr, and 96.46%, respectively, while the peak concentration was observed as 3.11 ± 0.06 µg/ml at 2.0 hr. It was shown that orbifloxacin was completely but relatively slowly absorbed, extensively distributed, and slowly eliminated in crucian carp, and an orbifloxacin dosage of 10 mg/kg administered intravenously or intramuscularly would be expected to successfully treat crucian carp infected by strains with MIC values ≤0.5 µg/ml.

Intraarterial Lidocaine for Pain Control in Uterine Artery Embolization: A Prospective, Randomized Study.

PURPOSE: To assess efficacy of two different techniques of lidocaine injection in the uterine arteries to reduce pain following uterine artery embolization (UAE) for leiomyomas. MATERIALS AND METHODS: This prospective randomized single-blinded study was performed with 60 patients enrolled between November 2014 and December 2015 equally randomized to 3 arms. Group A received 10 mL lidocaine 1% (100 mg) mixed with polyvinyl alcohol particles (355-500 µm). Group B received the same dose of lidocaine injected after embolization. Group C was a control group. Pain was assessed on a 100-point visual analog scale at 4, 7, and 24 hours after the procedure. Narcotic agent dose to 24 hours was recorded. Outcomes were examined by analysis of variance and pairwise comparison. Leiomyoma infarction was assessed with magnetic resonance imaging 3 months after the procedure. RESULTS: Technical success rate of UAE was 100%. Mean pain score at 4 hours was significantly lower in the lidocaine groups (group A, 28.6; group B, 35.8) compared with the control group (59.4; P = .001). Pain scores at 7 and 24 hours were not statistically different among the 3 arms. The mean in-hospital narcotic agent dose was significantly lower in both lidocaine groups than in the control group (group A, 8.5 mg [P = .002]; group B, 11.1 mg [P = .03]; group C, 17.4 mg). There were no adverse events related to the use of lidocaine. The number of patients with complete infarction of leiomyomas at 3 months was significantly lower in group A at 38.9% (group B, 77.8%; group C, 75%; P = .0451). CONCLUSIONS: Lidocaine injected in the uterine arteries reduced postprocedural pain and narcotic agent dose after UAE. There were more cases of incomplete necrosis when lidocaine was mixed with the particles.

Combined Coil Embolization and Foam Sclerotherapy for the Management of Varicose Veins.

BACKGROUND: We propose a novel technique for endovenous treatment of varicose veins (VVs) using combined coil embolization and foam sclerotherapy of the great saphenous vein (GSV). METHODS: A retrospective case-series analysis on patients undergoing fluoroscopically guided coil embolization of the GSV and foam sclerotherapy of the GSV and below-knee varices at a single Canadian center. RESULTS: Twenty-two patients underwent the procedure on 23 legs. Most patients (78.3%) presented for follow-up 57.2 ± 21.9 days postoperatively. Doppler studies demonstrated complete GSV occlusion in all patients. While 3 patients (13.6%) noted skin discoloration overlying the treated VVs, none complained of pain on follow-up or developed leg numbness, deep vein thrombosis, or pulmonary emboli. CONCLUSIONS: Coil embolization and foam sclerotherapy are a novel and effective treatment for VVs that uses existing and readily available angiographic equipment.

Direct sac puncture versus transarterial embolization of type II endoleaks: An evaluation and comparison of outcomes.

Purpose To determine the outcomes of type II endoleak embolization with aneurysm sac obliteration and whether the approach - direct sac puncture or transarterial - affects outcome. Methods A retrospective review of patients who underwent endovascular aneurysm repairs and subsequent type II endoleak embolization over 10 years was performed. Twenty-three patients (median age: 73 years, range: 40-88 years) underwent 35 embolizations. Embolization was performed with the goal of obliterating both the endoleak sac and feeding vessels. Embolization agents used include cyanoacrylate glue only (48%), glue and coils (36%), coils only (13%), and other (3%). Results Mean follow-up was 21.8 months. Patients underwent an average of 1.5 embolizations, with 35% requiring more than one. Technical success rate was 89%. Freedom from aneurysm sac expansion was achieved in 91%. Freedom from type II endoleak was accomplished in 70%. There were no ruptured aneurysms during the follow-up period. Direct sac puncture and transarterial approaches had similar incidences of aneurysm sac growth ( p = 0.74), persistent type II endoleak ( p = 0.32), and complications ( p = 0.64). However, direct sac puncture had significantly shorter fluoroscopy ( p < 0.001) and total procedure times ( p < 0.001) than transarterial embolizations. Conclusion Direct sac puncture and transarterial embolization of type II endoleak with aneurysm sac obliteration are similarly effective for the prevention of aneurysm sac growth. However, direct sac puncture is our preferred approach given its significantly shorter fluoroscopic and procedural times.

[Genetic Polymorphisms of 30 InDel Loci in Ewenki Ethnic Group from Inner Mongolia].

OBJECTIVES: To study the genetic polymorphisms of 30 insertion/deletion （InDel） loci and evaluate their forensic application in Ewenki ethnic group from Inner Mongolia. METHODS: Peripheral blood samples were collected from 87 unrelated healthy individuals in Ewenki ethnic group. Genomic DNA were extracted, and 30 InDel loci of the samples were multiplex amplified and genotyped. Hardy-Weinberg balance tests were preformed for all loci and genetic parameters were calculated by modified PowerStats v1.2 software. The linkage disequilibrium between loci were tested by SNPAnalyzer v2.0 software. Based on the allele frequencies of 30 InDel loci, the genetic relationships between Ewenki ethnic group and other populations were evaluated by analysis of molecular variance, principal component analysis and phylogenetic reconstruction. RESULTS: After correction, 30 InDel loci conformed to Hardy-Weinberg equilibrium. It was found that the pairwise InDel loci were in linkage equilibrium after Bonferroni correction. The results of population genetics indicated that Ewenki ethnic group had close genetic relationships with Henan Han and Beijing Han populations; whereas it was significantly different from several populations in Europe and Mexico. CONCLUSIONS: There are relatively high genetic polymorphisms on 30 InDel loci of Ewenki ethnic group from Inner Mongolia, which can be used as a helpful supplement application for STR detection system.

Structural diversity of the epigenetics pocketome.

Protein families involved in chromatin-templated events are emerging as novel target classes in oncology and other disease areas. The ability to discover selective inhibitors against chromatin factors depends on the presence of structural features that are unique to the targeted sites. To evaluate challenges and opportunities toward the development of selective inhibitors, we calculated all pair wise structural distances between 575 structures from the protein databank representing 163 unique binding pockets found in protein domains that write, read or erase post-translational modifications on histones, DNA, and RNA. We find that the structural similarity of binding sites does not always follow the sequence similarity of protein domains. Our analysis reveals increased risks of activity across target-class for compounds competing with the cofactor of protein arginine methyltransferases, lysine acetyltransferases, and sirtuins, while exploiting the conformational plasticity of a protein target is a path toward selective inhibition. The structural diversity landscape of the epigenetics pocketome can be explored via an open-access graphic user interface at thesgc.org/epigenetics_pocketome.

The in-hospital costs of treating high-risk patients with fenestrated and branched endografts.

OBJECTIVE: This study determined the 30-day morbidity and mortality and in-hospital costs of elective fenestrated (fEVAR) and branched (bEVAR) endovascular aneurysm repairs at a single academic institution and determined factors that influence them. METHODS: All elective fEVAR or bEVAR patients treated between November 2007 and March 2014 in a Canadian academic hospital were included. Procedural details, 30-day morbidity and mortality rates, and cost of hospitalization were analyzed. Nonparametric bootstrap analysis was used to compare means between groups and calculate confidence intervals (CIs). RESULTS: There were 84 consecutive fEVAR (n = 61) and bEVAR (n = 23) procedures. The 30-day mortality was 3.3% for fEVAR and 4.3% for bEVAR. Mean hospital stay was 7.2 ± 0.8 days for fEVAR and 12.6 ± 2.2 days for bEVAR. The mean cost of the index hospitalization was $57,000 for fEVAR and $91,000 for bEVAR. Device-related costs accounted for 55% of the total costs. The occurrence of intraoperative or postoperative events were used to further divide each of the fEVAR and bEVAR groups into "complicated hospitalization" (fEVAR, n = 10; bEVAR, n = 13) and "uncomplicated hospitalization" (fEVAR, n = 51; bEVAR, n = 10) groups. Device-related costs were not significantly different between the complicated and uncomplicated hospitalization groups (mean difference [95% CI] fEVAR: $3383 [-$3405 to $9809], P = .3; and bEVAR: $1930 [-$7892 to $11,288], P = .68). However, there were significant differences between the complicated and uncomplicated hospitalization groups in hospital length of stay (mean difference [95% CI] fEVAR: 8.1 [3.0-13.2] days, P = .001; and bEVAR: 10.8 [5.9-19.9] days, P = .002) and nondevice-related costs (mean difference [95% CI,] fEVAR: $25,843 [$11,689-$43,247], P = .001; and bEVAR; $20,326 [$9362-$36,615], P = .002). CONCLUSIONS: bEVAR and fEVAR are expensive interventions. Intraoperative adverse events and postoperative systemic complications dramatically increase costs and length of stay. Measures to minimize complications will reduce hospitalization costs and improve patient outcomes.

Linear magnetoresistance caused by mobility fluctuations in n-doped Cd(3)As(2).

Cd(3)As(2) is a candidate three-dimensional Dirac semimetal which has exceedingly high mobility and nonsaturating linear magnetoresistance that may be relevant for future practical applications. We report magnetotransport and tunnel diode oscillation measurements on Cd(3)As(2), in magnetic fields up to 65 T and temperatures between 1.5 and 300 K. We find that the nonsaturating linear magnetoresistance persists up to 65 T and it is likely caused by disorder effects, as it scales with the high mobility rather than directly linked to Fermi surface changes even when approaching the quantum limit. From the observed quantum oscillations, we determine the bulk three-dimensional Fermi surface having signatures of Dirac behavior with a nontrivial Berry phase shift, very light effective quasiparticle masses, and clear deviations from the band-structure predictions. In very high fields we also detect signatures of large Zeeman spin splitting (g∼16).