Genome-Wide DNA Methylation in Early-Onset-Dementia Patients Brain Tissue and Lymphoblastoid Cell Lines.

Epigenetics, a potential underlying pathogenic mechanism of neurodegenerative diseases, has been in the scope of several studies performed so far. However, there is a gap in regard to analyzing different forms of early-onset dementia and the use of Lymphoblastoid cell lines (LCLs). We performed a genome-wide DNA methylation analysis on sixty-four samples (from the prefrontal cortex and LCLs) including those taken from patients with early-onset forms of Alzheimer's disease (AD) and frontotemporal dementia (FTD) and healthy controls. A beta regression model and adjusted p-values were used to obtain differentially methylated positions (DMPs) via pairwise comparisons. A correlation analysis of DMP levels with Clariom D array gene expression data from the same cohort was also performed. The results showed hypermethylation as the most frequent finding in both tissues studied in the patient groups. Biological significance analysis revealed common pathways altered in AD and FTD patients, affecting neuron development, metabolism, signal transduction, and immune system pathways. These alterations were also found in LCL samples, suggesting the epigenetic changes might not be limited to the central nervous system. In the brain, CpG methylation presented an inverse correlation with gene expression, while in LCLs, we observed mainly a positive correlation. This study enhances our understanding of the biological pathways that are associated with neurodegeneration, describes differential methylation patterns, and suggests LCLs are a potential cell model for studying neurodegenerative diseases in earlier clinical phases than brain tissue.

Identification of epigenetic silencing of the SFRP2 gene in colorectal cancer as a clinical biomarker and molecular significance.

BACKGROUND: Several studies have suggested secreted frizzled-related protein 2 (SFRP2) gene as a potential clinical biomarker in colorectal cancer (CRC). However, its diagnostic role remains unclear. In this study, we aimed to investigate the significance of SFRP2 methylation levels in a large cohort of biological specimens (including blood, adipose and colonic tissues) from patients with CRC, thereby potentially identifying new biomarker utility. METHODS: We examined the expression (by qPCR) and methylation status (by 450 K DNA array and DNA pyrosequencing) of the SFRP2 gene in healthy participants (N = 110, aged as 53.7 (14.2), 48/62 males/females) and patients with CRC (N = 85, aged 67.7 (10.5), 61/24 males/females), across different biological tissues, and assessing its potential as a biomarker for CRC. Additionally, we investigated the effect of recombinant human SFRP2 (rhSFRP2) as a therapeutic target, on cell proliferation, migration, and the expression of key genes related to carcinogenesis and the Wnt pathway. RESULTS: Our findings revealed that SFRP2 promoter methylation in whole blood could predict cancer stage (I + II vs. III + IV) (AUC = 0.653), lymph node invasion (AUC = 0.692), and CRC recurrence (AUC = 0.699) in patients with CRC (all with p < 0.05). Furthermore, we observed a global hypomethylation of SFRP2 in tumors compared to the adjacent area (p < 0.001). This observation was validated in the TCGA-COAD and TCGA-READ cohorts, demonstrating overall hypermethylation (both with p < 0.001) and low expression (p < 0.001), as shown in publicly available scRNA-Seq data. Notably, neoadjuvant-treated CRC patients exhibited lower SFRP2 methylation levels compared to untreated patients (p < 0.05) and low promoter SFRP2 methylation in untreated patients was associated with poor overall survival (p < 0.05), when compared to high methylation. Finally, treatment with 5 µg of rhSFRP2 treatment in CRC cells (HCT116 cells) inhibited cell proliferation (p < 0.001) and migration (p < 0.05), and downregulated the expression of AXIN2 (p < 0.01), a gene involved in Wnt signaling pathway. CONCLUSIONS: These findings establish promoter methylation of the SFRP2 gene as a prognostic candidate in CRC when assessed in blood, and as a therapeutic prognostic candidate in tumors, potentially valuable in clinical practice. SFRP2 also emerges as a therapeutic option, providing new clinical and therapeutical avenues.

Unraveling Drug Delivery from Cyclodextrin Polymer-Coated Breast Implants: Integrating a Unidirectional Diffusion Mathematical Model with COMSOL Simulations.

Breast cancer ranks among the most commonly diagnosed cancers worldwide and bears the highest mortality rate. As an integral component of cancer treatment, mastectomy entails the complete removal of the affected breast. Typically, breast reconstruction, involving the use of silicone implants (augmentation mammaplasty), is employed to address the aftermath of mastectomy. To mitigate postoperative risks associated with mammaplasty, such as capsular contracture or bacterial infections, the functionalization of breast implants with coatings of cyclodextrin polymers as drug delivery systems represents an excellent alternative. In this context, our work focuses on the application of a mathematical model for simulating drug release from breast implants coated with cyclodextrin polymers. The proposed model considers a unidirectional diffusion process following Fick's second law, which was solved using the orthogonal collocation method, a numerical technique employed to approximate solutions for ordinary and partial differential equations. We conducted simulations to obtain release profiles for three therapeutic molecules: pirfenidone, used for preventing capsular contracture; rose Bengal, an anticancer agent; and the antimicrobial peptide KR-12. Furthermore, we calculated the diffusion profiles of these drugs through the cyclodextrin polymers, determining parameters related to diffusivity, solute solid-liquid partition coefficients, and the Sherwood number. Finally, integrating these parameters in COMSOL multiphysics simulations, the unidirectional diffusion mathematical model was validated.

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Efecto de la "ley de residentes" sobre el bienestar laboral en cirugía: resultados de un estudio nacional de métodos mixtos en Colombia / Effect of the "residents' law" on occupational well-being in surgery: Results of a national mixed methods study in Colombia

Introducción. El efecto de las políticas para el mejoramiento del bienestar de los residentes, en términos de desgaste profesional y compromiso laboral, es controversial y su resultado tras la implementación de la "ley de residentes" (1917/2018) en Colombia es desconocido. Este estudio explora el efecto de esta ley en médicos residentes de cirugía colombianos. Métodos. Estudio de métodos mixtos secuencial explicativo. Inicialmente, se invitó a todos los residentes de cirugía del país a autodiligenciar los cuestionarios UWES-17 y MBI-HSS para evaluar el compromiso laboral (vigor, dedicación y absorción) y desgaste profesional (agotamiento emocional, despersonalización y baja realización personal) antes (2019) y después (2022) de la implementación de la ley. Se probaron diferentes hipótesis mediante modelos de ecuaciones estructurales. Los resultados fueron explorados con cirujanos mediante grupos focales. La información cualitativa fue analizada manualmente y por inteligencia artificial, y reportada en temas principales. Resultados. Participaron en el estudio 400 residentes. La tasa de desgaste profesional fue de 24,8 % antes y 15,8 % después (p=0,032). El análisis de ecuaciones estructurales confirmó que el agotamiento emocional sobre el desgaste profesional fue menor en 2022 (p=0,022). No se identificaron cambios significativos en el compromiso laboral. La principal explicación fue atribuida a los beneficios económicos de la ley. Conclusión. La tasa de desgaste profesional en médicos residentes de cirugía colombianos se redujo significativamente tras la implementación de la "ley de residentes". Estos hallazgos tienen implicaciones para la practica y el mejoramiento de la calidad de la educación.

Introduction. The effect of policies to improve residents' well-being, in terms of professional burnout and work commitment is controversial, and its result after the implementation of the "residents' law" (1917/2018) in Colombia is unknown. This study explores the effect of this law on Colombian surgical residents. Methods. Explanatory sequential mixed methods study. Initially, all surgical residents in the country were invited to self-complete the UWES-17 and MBI-HSS questionnaires to evaluate work commitment (vigor, dedication, and absorption) and professional burnout (emotional exhaustion, depersonalization, and low personal accomplishment) before (2019) and after (2022) the implementation of the law. Different hypotheses were tested using structural equation models. The results were explored with surgeons through focus groups. Qualitative information was analyzed manually and by artificial intelligence, and reported into main themes. Results. 400 residents participated in the study. Burnout rates were 24.8% before and 15.8% after (p=0.032). The structural equations analysis confirmed that emotional exhaustion over professional burnout was lower in 2022 (p=0.022). No significant changes in work commitment were identified. The main explanation was attributed to the economic benefits of the law. Conclusion. The burnout rate in Colombian surgical residents was significantly reduced after the implementation of the "residents' law". These findings have implications for practice and improving the quality of education

Impact of sex differences on the feasibility and safety of distal radial access for coronary procedures: a multicenter prospective observational study.

BACKGROUND: Conventional transradial access in women is associated with a lower success rate and a higher incidence of spasm compared to men. To date, the effect of sex on the performance of distal radial access (DRA) has not been fully elucidated. The aim of this study was to assess the impact of sex on catheterization success and other performance parameters of DRA procedures. METHODS: This is a prospective three-center observational study. From August 2020 to September 2022, data from all consecutive patients who underwent DRA for coronary procedures were collected. RESULTS: A total of 868 procedures were registered and stratified into two groups according to sex: women (n = 258) and men (n = 610). Female patients had less favorable baseline characteristics than male patients in terms of absent or weak pulse (29% vs. 17%; P < 0.001), distal radial diameter (2.2 ±â€…0.3 vs. 2.4 ±â€…0.4 mm; P < 0.001) and proximal radial diameter (2.5 ±â€…0.7 vs. 2.7 ±â€…0.7 mm; P = 0.001). No differences in success rates were found in women compared to men (94.2% vs. 96.6%; P = 0.135), with a higher presence of arterial spasm in women (5.8% vs. 3.0%; P = 0.044). The preprocedural ultrasound evaluation was the only predictor of DRA success [odds ratio = 20.0 (4.739-83.333); P < 0.001]. CONCLUSION: In patients undergoing coronary procedures, the success rate of DRA was high regardless of sex, with a higher incidence of arterial spasm in women.

Additive manufactured gyroid-based cell structures under compression: design, testing and simulation for biomedical applications.

The mechanical behaviour of a DMLS Ti-6Al-4V gyroid-based cellular structure (CS), with potential application in the fabrication of implants, was studied under compressive conditions. The influence of the CS volumetric fraction on the elastic modulus was experimentally evaluated in cubic and cylindrical samples. The experimental results showed that the selected parameters allowed approximating the mechanical behaviour of the CS to that of trabecular bone. Finite element analysis was employed to study the mechanical behaviour of the CS. The model presented a good approximation of the experimental results, being useful to predict the mechanical behaviour of the CS.

Soft-metal(loid)s induce protein aggregation in Escherichia coli.

Metal(loid) salts were used to treat infectious diseases in the past due to their exceptional biocidal properties at low concentrations. However, the mechanism of their toxicity has yet to be fully elucidated. The production of reactive oxygen species (ROS) has been linked to the toxicity of soft metal(loid)s such as Ag(I), Au(III), As(III), Cd(II), Hg(II), and Te(IV). Nevertheless, few reports have described the direct, or ROS-independent, effects of some of these soft-metal(loid)s on bacteria, including the dismantling of iron-sulfur clusters [4Fe-4S] and the accumulation of porphyrin IX. Here, we used genome-wide genetic, proteomic, and biochemical approaches under anaerobic conditions to evaluate the direct mechanisms of toxicity of these metal(loid)s in Escherichia coli. We found that certain soft-metal(loid)s promote protein aggregation in a ROS-independent manner. This aggregation occurs during translation in the presence of Ag(I), Au(III), Hg(II), or Te(IV) and post-translationally in cells exposed to Cd(II) or As(III). We determined that aggregated proteins were involved in several essential biological processes that could lead to cell death. For instance, several enzymes involved in amino acid biosynthesis were aggregated after soft-metal(loid) exposure, disrupting intracellular amino acid concentration. We also propose a possible mechanism to explain how soft-metal(loid)s act as proteotoxic agents.

Oral Pyogenic Granuloma: A Narrative Review.

Pyogenic granuloma (PG) is a benign vascular lesion found predominantly in the oral cavity. Characterized by rapid growth and propensity to bleed, PG presents diagnostic challenges due to its similarity and alarming proliferation. This narrative review synthesizes current knowledge on the epidemiology, etiopathogenesis, clinical manifestations, and management of oral PG, with emphasis on recent advances in diagnostic and therapeutic approaches. The epidemiology of the injury is meticulously analyzed, revealing a higher incidence in women and a wide range of ages of onset. It delves into the etiopathogenesis, highlighting the uncertainty surrounding the exact causal factors, although historical attributions suggest an infectious origin. It exhaustively analyzes the clinical and histopathological aspects of oral PG, offering information on its various presentations and the importance of an accurate diagnosis to guide effective treatment. It details treatment strategies, emphasizing the personalized approach based on individual patient characteristics. This comprehensive review consolidates current knowledge on oral PG, highlighting the need for further research to clarify its pathogenesis and optimize treatment protocols.

Analysis of immortal-time effect in post-infarction ventricular septal defect.

Introduction: Time-fixed analyses have traditionally been utilized to examine outcomes in post-infarction ventricular septal defect (VSD). The aims of this study were to: (1) analyze the relationship between VSD closure/non-closure and mortality; (2) assess the presence of immortal-time bias. Material and methods: In this retrospective cohort study, patients with ST-elevation myocardial infarction (STEMI) complicated by VSD. Time-fixed and time-dependent Cox regression methodologies were employed. Results: The study included 80 patients: surgical closure (n = 26), transcatheter closure (n = 20), or conservative management alone (n = 34). At presentation, patients without VSD closure exhibited high-risk clinical characteristics, had the shortest median time intervals from STEMI onset to VSD development (4.0, 4.0, and 2.0 days, respectively; P = 0.03) and from STEMI symptom onset to hospital arrival (6.0, 5.0, and 0.8 days, respectively; P < 0.0001). The median time from STEMI onset to closure was 22.0 days (P = 0.14). In-hospital mortality rate was higher among patients who did not undergo defect closure (50%, 35%, and 88.2%, respectively; P < 0.0001). Closure of the defect using a fixed-time method was associated with lower in-hospital mortality (HR = 0.13, 95% CI 0.05-0.31, P < 0.0001, and HR 0.13, 95% CI 0.04-0.36, P < 0.0001, for surgery and transcatheter closure, respectively). However, when employing a time-varying method, this association was not observed (HR = 0.95, 95% CI 0.45-1.98, P = 0.90, and HR 0.88, 95% CI 0.41-1.87, P = 0.74, for surgery and transcatheter closure, respectively). These findings suggest the presence of an immortal-time bias. Conclusions: This study highlights that using a fixed-time analytic approach in post-infarction VSD can result in immortal-time bias. Researchers should consider employing time-dependent methodologies.

Very long-term efficacy and safety of paclitaxel-eluting balloon after a bare-metal stent for the treatment of ST-elevation myocardial infarction: 8-year results of a randomized clinical trial (PEBSI study).

Background: Drug-eluting stents (DES) are considered the therapy of choice in ST-segment elevation myocardial infarction (STEMI); however, a low persistent rate of revascularizations and stent thrombosis exist over the time. We have previously shown that a paclitaxel (PTX)-drug-coated balloon (DCB) after a bare-metal stent (BMS) implantation (DCB-combined strategy) yields superior angiographic and clinical results compared to BMS in the short term. However, the long-term safety and efficacy of this approach remain uncertain. Methods: An 8-year clinical follow-up was conducted on patients enrolled in the randomized PEBSI-1 trial (NCT01839890). The original trial included patients who suffered a STEMI, patients were randomly assigned to receive a DCB-combined strategy or BMS only and the primary endpoint was in-stent late luminal loss (LLL) at 9-month follow-up. After the completion of this study, death, myocardial re-infarction, ischemia-driven repeated revascularizations included target lesion revascularization (TLR) and target vessel revascularization (TVR), and stent thrombosis, were assessed by yearly contact by a clinical visit, telephone or by electronic records. These outcomes were adhered to ARC-2 criteria. Results: The rate of incomplete follow-up was very low, with only 3 out of 111 patients (2.7%) in the DCB-combined strategy group and 1 out of 112 patients (0.9%) in the BMS group. At 8 years there were a lower rate of TVR [3.7% vs. 14.3%; hazard ratio (HR): 0.243; 95% confidence interval (CI): 0.081-0.727; P=0.006], and a trend towards lower TLR (2.8% vs. 8.9%; HR: 0.300; 95% CI: 0.083-1.090; P=0.052) in the DCB-combined strategy group. No statistical difference between the DCB-combined strategy and BMS groups were found for all causes of death, deaths from cardiovascular disease, reinfarctions or stent thrombosis. Notably in the DCB-combined strategy group, no episode of stent thrombosis occurred after the first year. Similarly, there were no cardiovascular deaths, TVR and TLR in the DCB-combined strategy group after 5 years. In contrast, during the period from year 5 to 8, the BMS group experienced an additional cardiovascular death, as well as one case of TVR, one case of TLR, and one case of stent thrombosis. Conclusions: In STEMI patients, the DCB-combined strategy maintains its safety and clinical efficacy over time. Our rates of TVR, TLR, and very late stent thrombosis (VLST) at very long-term are the lowest ever found in a STEMI trial. Further studies are warranted to assess the potential superiority of this novel strategy as compared with new-generation DES to prevent very late events in these patients. Trial Registration: ClinicalTrials.gov; identifier: NCT01839890.

Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

The Best Models of Bodipy's Electronic Excited State: Comparing Predictions from Various DFT Functionals with Measurements from Femtosecond Stimulated Raman Spectroscopy.

Density functional theory (DFT) and time-dependent DFT (TD-DFT) are pivotal approaches for modeling electronically excited states of molecules. However, choosing a DFT exchange-correlation functional (XCF) among the myriad of alternatives is an overwhelming task that can affect the interpretation of results and lead to erroneous conclusions. The performance of these XCFs to describe the excited-state properties is often addressed by comparing them with high-level wave function methods or experimentally available vertical excitation energies; however, this is a limited analysis that relies on evaluation of a single point in the excited-state potential energy surface (PES). Different strategies have been proposed but are limited by the difficulty of experimentally accessing the electronic excited-state properties. In this work, we have tested the performance of 12 different XCFs and TD-DFT to describe the excited-state potential energy surface of Bodipy (2,6-diethyl-1,3,5,7-tetramethyl-8-phenyldipyrromethene difluoroborate). We compare those results with resonance Raman spectra collected by using femtosecond stimulated Raman spectroscopy (FSRS). By simultaneously fitting the absorption spectrum, fluorescence spectrum, and all of the resonance Raman excitation profiles within the independent mode displaced harmonic oscillator (IMDHO) formalism, we can describe the PES at the Franck-Condon (FC) region and determine the solvent and intramolecular reorganization energy after relaxation. This allows a direct comparison of the TD-DFT output with experimental observables. Our analysis reveals that using vertical absorption energies might not be a good criterion to determine the best XCF for a given molecular system and that FSRS opens up a new way to benchmark the excited-state performance of XCFs of fluorescent dyes.

Stimulated Resonance Raman and Excited-State Dynamics in an Excitonically Coupled Bodipy Dimer: A Test for TD-DFT and the Polarizable Continuum Model.

Bodipy is one of the most versatile and studied functional dyes due to its myriad applications and tunable spectral properties. One of the strategies to adjust their properties is the formation of Bodipy dimers and oligomers whose properties differ significantly from the corresponding monomer. Recently, we have developed a novel strategy for synthesizing α,α-ethylene-bridged Bodipy dimers; however, their excited-state dynamics was heretofore unknown. This work presents the ultrafast excited-state dynamics of a novel α,α-ethylene-bridge Bodipy dimer and its monomeric parent. The dimer's steady-state absorption and fluorescence suggest a Coulombic interaction between the monomeric units' transition dipole moments (TDMs), forming what is often termed a "J-dimer". The excited-state properties of the dimer were studied using molecular excitonic theory and time-dependent density functional theory (TD-DFT). We chose the M06 exchange-correlation functional (XCF) based on its ability to reproduce the experimental oscillator strength and resonance Raman spectra. Ultrafast laser spectroscopy reveals symmetry-breaking charge separation (SB-CS) in the dimer in polar solvents and the subsequent population of the charge-separated ion-pair state. The charge separation rate falls into the normal regime, while the charge recombination is in the inverted regime. Conversely, in nonpolar solvents, the charge separation is thermodynamically not feasible. In contrast, the monomer's excited-state dynamics shows no dependence on the solvent polarity. Furthermore, we found no evidence of significant structural rearrangement upon photoexcitation, regardless of the deactivation pathway. After an extensive analysis of the electronic transitions, we concluded that the solvent fluctuations in the local environment around the dimer create an asymmetry that drives and stabilizes the charge separation. This work sheds light on the charge-transfer process in this new set of molecular systems and how excited-state dynamics can be modeled by combining the experiment and theory.

Pulmonary arterial hypertension in children with congenital heart disease: a deeper look into the role of endothelial progenitor cells and circulating endothelial cells to assess disease severity.

Endothelial progenitor cells and circulating endothelial cells have been proposed as useful markers of severity and disease progression in certain vascular diseases, including pulmonary arterial hypertension. Our study focused on evaluating the levels of circulating endothelial progenitor cells and circulating endothelial cells in patients with congenital left-to-right shunts and pulmonary hypertension undergoing definitive repair. Endothelial progenitor cells (identified by simultaneous co-expression of CD45dim, CD34 + and KDR2 + surface antibodies) and circulating endothelial cells (identified by simultaneous co-expression of inherent antibodies CD45-, CD31+, CD146 + and CD105+) were prospectively measured in seventy-four children (including children with Down syndrome), median age six years (2.75-10), with clinically significant left-to-right shunts undergoing transcatheter or surgical repair and compared to thirty healthy controls. Endothelial progenitor cells and, particularly, circulating endothelial cells were significantly higher in children with heart disease and pulmonary arterial hypertension when compared to controls. Endothelial progenitor cells showed significant correlation with pulmonary vascular resistance index when measured both systemically (r = 0.259; p = 0.026) and in the superior vena cava (r = 0.302; p = 0.009). Children with Down syndrome showed a stronger correlation between systemic cellularity and pulmonary vascular resistance index (r = 0.829; p = 0.002). Endothelial progenitor cells were reduced along their transit through the lung, whereas circulating endothelial cells did not suffer any modification across the pulmonary circulation. In children with yet to be repaired left-to-right shunts, endothelial progenitor cells and circulating endothelial cell counts are increased compared to healthy subjects.

Sinus node dysfunction during transcatheter assessment and stent correction of sinus venosus atrial septal defects.

Covered stent correction of a superior sinus venosus atrial septal defect is increasingly performed as an alternative to surgical repair. While sinus node dysfunction requiring pacemaker implantation may be required after surgical repair, this has not been previously reported after covered stent implantation. We reviewed the experience in two interventional centers. Balloon inflation in the superior vena cava was used to confirm the anomalous pulmonary vein drainage would be unobstructed after stent implantation. During balloon testing in 62 consecutive patients, we assessed gradients across the pulmonary vein to left atrium while monitoring the rhythm. We observed the outcomes after covered stent correction in 51 patients. In a single patient, significant bradycardia and pauses developed on repeat balloon testing and the procedure was abandoned without stent implantation. In another patient, there was no sign of sinus node dysfunction during balloon testing but several hours after stent implantation, the patient became symptomatic from sinus bradycardia and pauses and had a pacemaker implanted 3 days later. Over a year later there are some signs of improvement in sinus node function. While sinus node dysfunction has not been described previously during balloon testing or after stent implantation, this report demonstrates for the first time that it may occur. Larger registries are therefore required to monitor for this uncommon complication.

The effects of emotions on the disposition to normative and non-normative political action in the context of the Chilean post-social outburst.

This article analyzes the role of Chileans' emotions as predictors of normative and non-normative political action in the context of the post-social outbreak and the constituent process. We carried out three descriptive studies: first, a study conducted 1 year after the social outburst (n = 607), a second one carried out before the constitutional referendum (n = 320), and a third study conducted after the constitutional referendum (n = 210). The results indicated that participants present a higher disposition to normative over non-normative political action, although both lose strength as the studies temporally move away from the social outburst. Also, our research established that emotions directed towards different events related to the Chilean political process play a conspicuous role in predicting the disposition to mobilize in a normative and non-normative way.

Unusual clinical presentation of oral pyogenic granuloma with severe alveolar bone loss: A case report and review of literature.

BACKGROUND: Pyogenic granuloma (PG) is a localized, reddish and vascularized hyperplastic lesion of the connective tissue which occurs in the oral cavity. In most cases, the presence of this lesion does not show alveolar bone resorption. The pathology is diagnosed clinically with some caution. However, the diagnosis and treatment are usually corroborated with histopathological evidence. CASE SUMMARY: Three clinical cases of PG associated with bone loss were described in this study. The three patients presented tumor-like growth which bled on touch, and were associated with local irritant factors. Radiographs showed bone loss. All cases were treated with conservative surgical excision. The scarring was satisfactory, and there was no case of recurrence. The diagnoses were based on clinical findings, and were confirmed histopathologically. CONCLUSION: The occurrence of oral PG with bone loss is unusual. Therefore, clinical and radiographic evaluations are important for the diagnosis.

Pulmonary Hypertension in Congenital Heart Disease: A Scientific Statement From the American Heart Association.

Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring with them added complexity because of underlying anatomical and hemodynamic abnormalities. Currently, no consensus recommendations are available on how to best manage this group of patients for either the primary cardiologist or pulmonary hypertension subspecialist, including timing of referral. The purposes of this document are (1) to describe the various pulmonary hypertension groups and subgroups associated with congenital heart disease, (2) to describe imaging modalities used in patient evaluation, (3) to elucidate medical and surgical management considerations, (4) to highlight disparities within this population, and (5) to identify gaps and future research needs of patients with pulmonary hypertension associated with congenital heart disease.