Pediatric epileptologist from Latin America.

Experience of how to become a pediatric epileptologist in Colombia.

Median raphe cysts: A clinico-pathologic and immunohistochemical study of 52 cases.

BACKGROUND: Median raphe cysts (MRC) are epithelial-lined cystic lesions of the genital area that do not communicate with the urethra or the overlying epidermis. Immunohistochemically, MRC show positivity for cytokeratin (CK) 5-6, CK 7, carcinoembryonic antigen, p63 and uroplakin III (URO III). GATA3 and human milk fat globulin 1 (HMFG1) are immunohistochemical markers that have been not previously studied in MRC. METHODS: We conducted a study of 52 patients diagnosed with MRC in the Pathology Departments of eight hospitals between 1990 and 2016. The monoclonal antibodies used were CK5-6, CK7, CK20, URO III, p63, GATA3, and HMFG1. HMFG1 was studied in five cases of apocrine hidrocystomas and compared with five cases of MRC from our series. RESULTS: CK 5-6, CK7, and p63 expression showed strong positivity in the urothelial epithelium of 48 cases. CK20 was focally positive in areas of mucinous differentiation in three cases. GATA3 showed intense nuclear staining in 30 cases. HMFG1 was positive in three cases of MRC and in three cases of apocrine hidrocystoma. CONCLUSION: Positivity of GATA3 and CK7 in MRC supports the urothelial origin of these cysts. We found no differences in HMFG1 expression between MRC and apocrine hidrocystomas.

Exclusionary discipline practices and their relation to Chilean students' perception of school climate practices.

One of the challenges of school climate policies has been to promote dialogical conflict resolution by reducing punitive practices and encouraging student participation. However, exclusionary punitive practices are still being used, and in Chile, they are considered acceptable forms of conflict resolution. In this study, we analyzed the association between students' reports of punitive and democratic school climate in a sample of 2459 eighth graders (mean age = 13.56, SD = 0.84) from 128 Chilean schools. Multilevel analyses showed that a higher perception of punitive practices and higher academic performance were associated with a higher perception of an inclusive, democratic, and peaceful school climate. The perception of a higher school-level frequency of punishment was associated with a higher perception of an inclusive and democratic school climate. We discuss the implications of these findings for an authoritarian school culture.

Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma.

The absence of standardized molecular profiling to differentiate uterine leiomyosarcomas versus leiomyomas represents a current diagnostic challenge. In this study, we aimed to search for a differential molecular signature for these myometrial tumors based on artificial intelligence. For this purpose, differential exome and transcriptome-wide research was performed on histologically confirmed leiomyomas (n = 52) and leiomyosarcomas (n = 44) to elucidate differences between and within these two entities. We identified a significantly higher tumor mutation burden in leiomyosarcomas vs. leiomyomas in terms of somatic single-nucleotide variants (171,863 vs. 81,152), indels (9491 vs. 4098), and copy number variants (8390 vs. 5376). Further, we discovered alterations in specific copy number variant regions that affect the expression of some tumor suppressor genes. A transcriptomic analysis revealed 489 differentially expressed genes between these two conditions, as well as structural rearrangements targeting ATRX and RAD51B. These results allowed us to develop a machine learning approach based on 19 differentially expressed genes that differentiate both tumor types with high sensitivity and specificity. Our findings provide a novel molecular signature for the diagnosis of leiomyoma and leiomyosarcoma, which could be helpful to complement the current morphological and immunohistochemical diagnosis and may lay the foundation for the future evaluation of malignancy risk.

Brick-CFCMC: Open Source Software for Monte Carlo Simulations of Phase and Reaction Equilibria Using the Continuous Fractional Component Method.

We present a new molecular simulation code, Brick-CFCMC, for performing Monte Carlo simulations using state-of-the-art simulation techniques. The Continuous Fractional Component (CFC) method is implemented for simulations in the NVT/NPT ensembles, the Gibbs Ensemble, the Grand-Canonical Ensemble, and the Reaction Ensemble. Molecule transfers are facilitated by the use of fractional molecules which significantly improve the efficiency of the simulations. With the CFC method, one can obtain phase equilibria and properties such as chemical potentials and partial molar enthalpies/volumes directly from a single simulation. It is possible to combine trial moves from different ensembles. This enables simulations of phase equilibria in a system where also a chemical reaction takes place. We demonstrate the applicability of our software by investigating the esterification of methanol with acetic acid in a two-phase system.

Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening.

Vascular stiffening and its sequelae are major causes of morbidity and mortality in the elderly. The increasingly accepted concept of "smooth muscle cell (SMC) stiffness syndrome" along with matrix deposition has emerged in vascular biology to account for the mechanical phenotype of arterial aging, but the molecular targets remain elusive. In this study, using an unbiased proteomic analysis, we identified lysyl oxidase-like 2 (LOXL2) as a critical SMC mediator for age-associated vascular stiffening. We tested the hypothesis that loss of LOXL2 function is protective in aging-associated vascular stiffening. We determined that exogenous and endogenous nitric oxide markedly decreased LOXL2 abundance and activity in the extracellular matrix of isolated SMCs and LOXL2 endothelial cells suppress LOXL2 abundance in the aorta. In a longitudinal study, LOXL2+/- mice were protected from age-associated increase in pulse-wave velocity, an index of vascular stiffening, as occurred in littermate wild-type mice. Using isolated aortic segments, we found that LOXL2 mediates vascular stiffening in aging by promoting SMC stiffness, augmented SMC contractility, and vascular matrix deposition. Together, these studies establish LOXL2 as a nodal point for a new therapeutic approach to treat age-associated vascular stiffening. NEW & NOTEWORTHY Increased central vascular stiffness augments risk of major adverse cardiovascular events. Despite significant advances in understanding the genetic and molecular underpinnings of vascular stiffening, targeted therapy has remained elusive. Here, we show that lysyl oxidase-like 2 (LOXL2) drives vascular stiffening during aging by promoting matrix remodeling and vascular smooth muscle cell stiffening. Reduced LOXL2 expression protects mice from age-associated vascular stiffening and delays the onset of isolated systolic hypertension, a major consequence of stiffening.

Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition.

We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the nonvisual G protein-coupled receptor melanopsin (Opsin 4; Opn4). Here we tested the hypothesis that nonvisual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G protein-coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2, as demonstrated with a proximity ligation assay. Light elicited an intensity-dependent relaxation of PAs preconstricted with phenylephrine (PE), with a maximum response between 400 and 460 nm (blue light). Wavelength-specific photorelaxation was attenuated in PAs from Opn4-/- mice and further reduced following shRNA-mediated knockdown of Opn3. Inhibition of GRK2 amplified the response and prevented physiological desensitization to repeated light exposure. Blue light also prevented PE-induced constriction in isolated PAs, decreased basal tone, ablated PE-induced single-cell contraction of PASMCs, and reversed PE-induced depolarization in PASMCs when GRK2 was inhibited. The photorelaxation response was modulated by soluble guanylyl cyclase but not by protein kinase G or nitric oxide. Most importantly, blue light induced significant vasorelaxation of PAs from rats with chronic pulmonary hypertension and effectively lowered pulmonary arterial pressure in isolated intact perfused rat lungs subjected to acute hypoxia. These findings show that functional Opn3 and Opn4 in PAs represent an endogenous "optogenetic system" that mediates photorelaxation in the pulmonary vasculature. Phototherapy in conjunction with GRK2 inhibition could therefore provide an alternative treatment strategy for pulmonary vasoconstrictive disorders.

Prognostic factors of weight loss after sleeve gastrectomy: Multi centre study in Spain and Portugal. / Factores predictivos de pérdida ponderal tras la gastrectomía vertical. Estudio multicéntrico hispano-portugués.

INTRODUCTION: Sleeve gastrectomy (SG) has become a technique in its own right although a selective or global indication remains controversial. The weight loss data at 5 years are heterogeneous. The aim of the study is to identify possible prognostic factors of insufficient weight loss after SG. METHODS: A SG retrospective multicenter study of more than one year follow-up was performed. Failure is considered if EWL>50%. Univariate and multivariate study of Cox regression were performed to identify prognostic factors of failure of weight loss at 1, 2 and 3 years of follow up. RESULTS: A total of 1,565 patients treated in 29 hospitals are included. PSP per year: 70.58±24.7; 3 years 69.39±29.2; 5 years 68.46±23.1. Patients with EWL<50 (considered failure): 17.1% in the first year, 20.1% at 3 years, 20.8% at 5 years. Variables with influence on the weight loss failure in univariate analysis were: BMI>50kg/m2, age>50years, DM2, hypertension, OSA, heart disease, multiple comorbidities, distance to pylorus> 4cm, bougie>40F, treatment with antiplatelet agents. The reinforcement of the suture improved results. In multivariate study DM2 and BMI are independent factors of failure. CONCLUSION: The SG associates a satisfactory weight loss in 79% of patients in the first 5 years; however, some variables such as BMI>50, age>50, the presence of several comorbidities, more than 5cm section of the pylorus or bougie>40F can increase the risk of weight loss failure.

Fabrication of 3-dimensional multicellular microvascular structures.

Despite current advances in engineering blood vessels over 1 mm in diameter and the existing wealth of knowledge regarding capillary bed formation, studies for the development of microvasculature, the connecting bridge between them, have been extremely limited so far. Here, we evaluate the use of 3-dimensional (3D) microfibers fabricated by hydrogel electrospinning as templates for microvascular structure formation. We hypothesize that 3D microfibers improve extracellular matrix (ECM) deposition from vascular cells, enabling the formation of freestanding luminal multicellular microvasculature. Compared to 2-dimensional cultures, we demonstrate with confocal microscopy and RT-PCR that fibrin microfibers induce an increased ECM protein deposition by vascular cells, specifically endothelial colony-forming cells, pericytes, and vascular smooth muscle cells. These ECM proteins comprise different layers of the vascular wall including collagen types I, III, and IV, as well as elastin, fibronectin, and laminin. We further demonstrate the achievement of multicellular microvascular structures with an organized endothelium and a robust multicellular perivascular tunica media. This, along with the increased ECM deposition, allowed for the creation of self-supporting multilayered microvasculature with a distinct circular lumen following fibrin microfiber core removal. This approach presents an advancement toward the development of human microvasculature for basic and translational studies.

PyF2F: a robust and simplified fluorophore-to-fluorophore distance measurement tool for Protein interactions from Imaging Complexes after Translocation experiments.

Structural knowledge of protein assemblies in their physiological environment is paramount to understand cellular functions at the molecular level. Protein interactions from Imaging Complexes after Translocation (PICT) is a live-cell imaging technique for the structural characterization of macromolecular assemblies in living cells. PICT relies on the measurement of the separation between labelled molecules using fluorescence microscopy and cell engineering. Unfortunately, the required computational tools to extract molecular distances involve a variety of sophisticated software programs that challenge reproducibility and limit their implementation to highly specialized researchers. Here we introduce PyF2F, a Python-based software that provides a workflow for measuring molecular distances from PICT data, with minimal user programming expertise. We used a published dataset to validate PyF2F's performance.

Textbook outcome in gastric surgery, what implications does it have on survival?

INTRODUCTION: The textbook outcome (TO) is a multidimensional measure to assess the quality of healthcare practice. This is reflected as the "ideal" surgical result, attending to a series of indicators or established reference points that are adapted depending on the surgical disease that we want to analyze. There are few references and series published about TO, all of them very recent. OBJECTIVE: We present a series of gastric surgery from the TO perspective and we analyze its impact on survival. METHOD: Retrospective observational study of all gastric neoplasms operated on in our center. PERIOD: January 2015-December 2020. The criteria for TO were: margins R0, >15 lymph nodes in the histological study, no Clavien-Dindo complications > IIIa, hospital stay < 21 days, no mortality or readmission in the 30 postoperative days. A comparative analysis was performed between the TO group versus the non-TO group. RESULTS: 91 patients were operated on. We reached the TO in 34.1% of the patients. The variable >15 lymph nodes was the one that most affected to achieve a TO. When performing the survival analysis, we obtained that the group in which the TO was obtained had a greater survival (p < 0.008). CONCLUSION: In our series, obtaining the TO has an impact on survival which 34,1% of degree of compliance.

Textbook Outcome in Bariatric Surgery: Evolution During 15 Years in a Referral Center.

BACKGROUND: Textbook outcome (TO) is a multidimensional measure used to assess the quality of care. It is the "ideal" surgical result, based on a series of established indicators. In the field of bariatric surgery (BS), only one publication on TO is available. OBJECTIVES: To determine TO in our BS unit and identify the factors linked to TO. SETTING: University public hospital in Alicante (Spain). METHODS: Retrospective observational study of all primary BS was performed. TO for BS was defined in relation to the following features: no major postoperative complications (Clavien-Dindo >II), hospital stay <75th percentile, and no mortality or readmissions within 30 days of surgery. Comparative analysis of the characteristics of the TO and non-TO groups was performed, as well as univariate and multivariate logistic regressions, to identify the independent factors associated with obtaining TO. RESULTS: In 970 patients, TO was achieved in 71.5%. The hospital stay was the one that most affected achievement of TO. Analysis according to the type of procedure (sleeve gastrectomy and gastric bypass) did not reveal any differences between both procedures in terms of obtaining TO (71.5 vs 71.26%). Logistic regression identified smoking, heart disease, operative time, and upper gastrointestinal bleeding as independent factors associated with obtaining TO (p<0.05). Analysis of the annual evolution of TO reveals a progressive increase in its achievement (7.7-86.4%). CONCLUSION: In our series, TO was obtained in 71.5% of patients. The standardization of the technique and the experience gained over the years has improved our TO results.

Improving the Physical Health of Psychiatric Hospital Residents: An Evaluation of an Obesity Education Program for Mental Health Professionals.

BACKGROUND: People living with mental health disorders are at increased risk for developing obesity due to poor diet, physical inactivity, and antipsychotic medications. In the United States, the obesity rate is 36% in the general population and more than 50% for people living with mental health disorders. Although mental health clinicians concentrate on managing psychiatric disorders, they seldom recognize the gradual increase in body mass index of their patients. The result is a disconnection between the clinical management of psychiatric disorders and the medical management of obesity. PURPOSE: This study assessed the effectiveness of an evidence-based education program for improving the obesity management practices of mental health clinicians caring for residents at a state psychiatric hospital. METHODS: This was a quasi-experimental study design with a pretest and posttest evaluation. Convenience sampling was used to recruit mental health professionals, or clinicians, at a large psychiatric hospital in the Southern region of the United States. Data was collected with the Advising and Treating Overweight and Obese Patient questionnaire (17 items). Data analysis included descriptive and inferential statistics. The findings were reported in accordance with the TREND and GREET guidelines. RESULTS: The education program was completed by 50 MHCs. The pretest indicated that 76% of MHCs were not involved in helping obese residents manage their weight, but the posttest indicated 90% were involved. There was a significant increase in MHC knowledge about obesity management and reported actions 90-days after the program. MHCs were unable to arrange follow-up visits for residents, a task not directly within their control. CONCLUSIONS: Mental health clinicians reported increased knowledge and improved clinical practice after an education program. Because the outcomes were reported at 90-days after the program, further research needs to evaluate the longitudinal impact of this type of program, where the reported behaviors are correlated to process and clinical outcome measures for obesity.

Dorsal Vascular Complex Nonligation Method and Preservation of Puboprostatic Ligaments and Endopelvic Fascia During Laparoscopic Radical Prostatectomy: Effect on Continence.

OBJECTIVE: To evaluate the impact on continence rate during 1-year follow-up of a preservation technique that included nonligation of the dorsal vascular complex and sparing of the puboprostatic ligaments and the endopelvic fascia during laparoscopic radical prostatectomy. MATERIAL AND METHODS: Information from 30 patients who underwent the preservation technique was prospectively collected and compared with data from 60 patients who underwent the nonpreservation traditional technique. A single surgeon performed all procedures. RESULTS: Demographic and preoperative characteristics were similar. The mean patient age was 59 years in both groups. All patients were stage cT1c or cT2. Operative time was significantly lower in the preservation technique group (229.6 vs. 262.7 minutes, P < .001). There were no significant differences in intraoperative bleeding, discharge hemoglobin level, blood transfusion rate, length of hospitalization, and drop in the hemoglobin level. The probability of continence recovery was significantly higher in the preservation technique group than in the traditional technique group (hazard ratio = 0.50, 95% CI = 0.31-0.81). The continence rate (0 pads/day) for the preservation technique group versus the traditional technique group at 1, 3, 6, and 12 months was, respectively, 53.3% versus 30% (P = .031), 90% versus 45% (P < .001), 90% versus 63.3% (P = .008), and 96.6% versus 78.3% (P = .024). There were no significant differences between the groups regarding potency and oncologic outcomes. CONCLUSION: Nonligation of the dorsal vascular complex and preservation of the puboprostatic ligaments and the endopelvic fascia improved urinary continence compared with the traditional nonpreservation technique, with no impact in terms of bleeding and oncologic outcomes.

Early postoperative complications after gastric bypass revisional surgery in patients with previous sleeve gastrectomy versus primary gastric bypass.

BACKGROUND: Revisional bariatric surgery (RS) is indicated if there is weight regain or insufficient weight loss, no improvement or reappearance of co-morbidities, or previous bariatric surgery complications. It has been associated with higher postoperative morbidity. OBJECTIVE: To evaluate the early postoperative complications (<30 d) of Roux-en-Y gastric bypass RS (RYGB-RS) after primary sleeve gastrectomy (SG-1) compared with primary RYGB (RYGB-1) at a bariatric surgery referral center. SETTING: Department of General and Digestive Surgery of General Universitary Hospital of Alicante, Spain. METHODS: Retrospective cohort study comparing RYGB-RS after SG-1 and RYGB-1 between January 2008 and March 2021. Postoperative complications, hospital stay, mortality, and readmissions were analyzed. RESULTS: Six hundred and twenty-eight RYGB surgeries (48 RYGB-RS, 580 RYGB-1) were studied. The mean age of patients undergoing RYGB-RS was 50 years, compared with 46 years in the RYGB-1 group (P = .017). Mean initial body mass index was 44.2 kg/m2 (RYGB-RS) versus 47.6 kg/m2 (RYGB-1; P = .004). Cardiovascular risk factors were higher in the RYGB-1 group (P < .05). Indications for RS were weight regain or insufficient weight loss (72.9%), weight regain or insufficient weight loss plus gastroesophageal reflux disease (14.6%), and gastroesophageal reflux disease (12.5%). There were no differences in the frequency of complications (RYGB-RS 22.9% vs RYGB-1 20.5%) or in their severity (Clavien-Dindo ≥IIIa; RYGB-RS 10.4% vs RYGB-1 6.4%; P > .05). There were no differences in emergency room visits (RYGB-RS at 12.5% vs RYGB-1 at 14.9%) or in readmissions (RYGB-RS at 12.5% vs RYGB-1 at 9.4%). CONCLUSION: No differences were observed between primary RYGB and revisional RYGB in early morbidity, mortality, emergencies, or readmissions. Revisional bariatric surgery is a safe procedure at referral centers and must be done by expert hands.

Higher Adherence to ERAS Society® Recommendations is Associated with Shorter Hospital Stay Without an Increase in Postoperative Complications or Readmissions in Bariatric Surgery: the Association Between Use of Enhanced Recovery After Surgery Protocols and Postoperative Complications after Bariatric Surgery (POWER 3) Multicenter Observational Study.

PURPOSE: The effectiveness of enhanced recovery after surgery (ERAS) pathways in patients undergoing bariatric surgery remains unclear. Our objective was to determine the effect of the ERAS elements on patient outcomes following elective bariatric surgery. MATERIALS AND METHODS: Prospective cohort study in adult patients undergoing elective bariatric surgery. Each participating center selected a single 3-month data collection period between October 2019 and September 2020. We assessed the 24 individual components of the ERAS pathways in all patients. We used a multivariable and multilevel logistic regression model to adjust for baseline risk factors, ERAS elements, and center differences RESULTS: We included 1419 patients. One hundred and fourteen patients (8%) developed postoperative complications. There were no differences in the incidence of overall postoperative complications between the self-designated ERAS and non-ERAS groups (54 (8.7%) vs. 60 (7.6%); OR, 1.14; 95% CI, 0.73-1.79; P = .56), neither for moderate-to-severe complications, readmissions, re-interventions, mortality, or hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 0.85; 95% CI, 0.62-1.17; P = .33) Adherence to the ERAS elements in the highest adherence quartile (Q1) was greater than 72.2%, while in the lowest adherence quartile (Q4) it was less than 55%. Patients with the highest adherence rates had shorter hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 1.54; 95% CI, 1.09-2.17; P = .015), while there were no differences in the other outcomes CONCLUSIONS: Higher adherence to ERAS Society® recommendations was associated with a shorter hospital stay without an increase in postoperative complications or readmissions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03864861.

Contributions of Individual, Family, and School Characteristics to Chilean Students' Social Well-Being at School.

Schools are an essential part of students' lives and can promote and facilitate their well-being. Although research on well-being among school-aged children and adolescents has distinguished subjective well-being from social well-being, very few studies examined student's social well-being at school (SWS). SWS is understood as students' valuation of the circumstances and functioning of their school. This framework posits that the context of the schools can shape students' perception of feeling integrated and making significant contributions to their schools. However, not much is known regarding the joint contribution of individual, family, and school characteristics to students' SWS. This study analyzed these joint contributions in a nationally representative sample of 6,389 children and adolescents enrolled in 5th-11th grades. Findings show that being female and younger were individual predictors of SWS. Students' satisfaction with their family and fewer changes of schools were also significant contributors. When students' perceptions of their schools were incorporated, the individual and family characteristics decreased or lost significance. In the full model, the highest contribution to SWS was explained by the school-level aggregated perception of school climate. These findings call for integrated policies and practices to foster students' sense of belonging, feeling integrated, and contribution to their schools, with a focus on school-level interventions to improve SWS through positive and engaging school climates that foster students' sense of agency.

A Bayesian approach to extracting free-energy profiles from cryo-electron microscopy experiments.

Cryo-electron microscopy (cryo-EM) extracts single-particle density projections of individual biomolecules. Although cryo-EM is widely used for 3D reconstruction, due to its single-particle nature it has the potential to provide information about a biomolecule's conformational variability and underlying free-energy landscape. However, treating cryo-EM as a single-molecule technique is challenging because of the low signal-to-noise ratio (SNR) in individual particles. In this work, we propose the cryo-BIFE method (cryo-EM Bayesian Inference of Free-Energy profiles), which uses a path collective variable to extract free-energy profiles and their uncertainties from cryo-EM images. We test the framework on several synthetic systems where the imaging parameters and conditions were controlled. We found that for realistic cryo-EM environments and relevant biomolecular systems, it is possible to recover the underlying free energy, with the pose accuracy and SNR as crucial determinants. We then use the method to study the conformational transitions of a calcium-activated channel with real cryo-EM particles. Interestingly, we recover not only the most probable conformation (used to generate a high-resolution reconstruction of the calcium-bound state) but also a metastable state that corresponds to the calcium-unbound conformation. As expected for turnover transitions within the same sample, the activation barriers are on the order of [Formula: see text]. We expect our tool for extracting free-energy profiles from cryo-EM images to enable more complete characterization of the thermodynamic ensemble of biomolecules.

Competitive Adsorption of Xylenes at Chemical Equilibrium in Zeolites.

The separation of xylenes is one of the most important processes in the petrochemical industry. In this article, the competitive adsorption from a fluid-phase mixture of xylenes in zeolites is studied. Adsorption from both vapor and liquid phases is considered. Computations of adsorption of pure xylenes and a mixture of xylenes at chemical equilibrium in several zeolite types at 250 °C are performed by Monte Carlo simulations. It is observed that shape and size selectivity entropic effects are predominant for small one-dimensional systems. Entropic effects due to the efficient arrangement of xylenes become relevant for large one-dimensional systems. For zeolites with two intersecting channels, the selectivity is determined by a competition between enthalpic and entropic effects. Such effects are related to the orientation of the methyl groups of the xylenes. m-Xylene is preferentially adsorbed if xylenes fit tightly in the intersection of the channels. If the intersection is much larger than the adsorbed molecules, p-xylene is preferentially adsorbed. This study provides insight into how the zeolite topology can influence the competitive adsorption and selectivity of xylenes at reaction conditions. Different selectivities are observed when a vapor phase is adsorbed compared to the adsorption from a liquid phase. These insight have a direct impact on the design criteria for future applications of zeolites in the industry. MRE-type and AFI-type zeolites exclusively adsorb p-xylene and o-xylene from the mixture of xylenes in the liquid phase, respectively. These zeolite types show potential to be used as high-performing molecular sieves for xylene separation and catalysis.

Probing tissue transglutaminase mediated vascular smooth muscle cell aging using a novel transamidation-deficient Tgm2-C277S mouse model.

Tissue transglutaminase (TG2), a multifunctional protein of the transglutaminase family, has putative transamidation-independent functions in aging-associated vascular stiffening and dysfunction. Developing preclinical models will be critical to fully understand the physiologic relevance of TG2's transamidation-independent activity and to identify the specific function of TG2 for therapeutic targeting. Therefore, in this study, we harnessed CRISPR-Cas9 gene editing technology to introduce a mutation at cysteine 277 in the active site of the mouse Tgm2 gene. Heterozygous and homozygous Tgm2-C277S mice were phenotypically normal and were born at the expected Mendelian frequency. TG2 protein was ubiquitously expressed in the Tgm2-C277S mice at levels similar to those of wild-type (WT) mice. In the Tgm2-C277S mice, TG2 transglutaminase function was successfully obliterated, but the transamidation-independent functions ascribed to GTP, fibronectin, and integrin binding were preserved. In vitro, a remodeling stimulus led to the significant loss of vascular compliance in WT mice, but not in the Tgm2-C277S or TG2-/- mice. Vascular stiffness increased with age in WT mice, as measured by pulse-wave velocity and tensile testing. Tgm2-C277S mice were protected from age-associated vascular stiffening, and TG2 knockout yielded further protection. Together, these studies show that TG2 contributes significantly to overall vascular modulus and vasoreactivity independent of its transamidation function, but that transamidation activity is a significant cause of vascular matrix stiffening during aging. Finally, the Tgm2-C277S mice can be used for in vivo studies to explore the transamidation-independent roles of TG2 in physiology and pathophysiology.