PARP-1 : interaction du domaine de liaison à l'adn avec des oligonucléotides simple brin

La PARP-1 est une enzyme modulaire très conservée, dont la structure comprend: 1) un domaine amino-terminal de liaison à l'ADN (DBD), contenant un signal de localisation nucléaire et trois doigts de zinc Znl, Zn2 et le Zn3 récemment découverts, ces trois doigts agissent comme détecteur moléculaire de cassures dans l'ADN; 2) un domaine régulateur central contenant un motif BRCT et des sites accepteurs de poly (ADP-ribose) permettant d'inactiver la PARP-1 (réaction d'automodification) ; et 3) un domaine carboxy-terminal catalytique renfermant le site actif. Dans notre étude, après avoir clone différentes protéines recombinantes par PCR, nous avons fait des essais de poly (ADP) ribosylation sur des extraits crus des cellules. En outre, nous avons fait des essais de retardement sur gel (EMSA) avec des oligonucleotides pour évaluer les interactions des peptides, correspondants aux fragments du domaine DBD, avec ces oligonucleotides afin d'essayer d'expliquer le mode d'activation de l'enzyme

Benefits of Metaverse Application in Education: A Systematic Review

The COVID-19 pandemic has brought about significant changes in people’s lifestyles, with the educational sector being one of the most reliant on technology to facilitate the teaching and learning process. In this literature review, a search for articles related to the metaverse in education, published in 2022 and 2023, has been conducted across six databases: Scopus, EBSCO Host, ScienceDirect, Taylor & Francis Online, IEEE Xplore, and Springer. The PRISMA methodology was used to analyze and systematize the manuscripts found. The aim of this research was to examine how integrating the metaverse into education can enhance educational accessibility and equity by enabling students to utilize virtual learning resources and opportunities. In addition, they can engage in interactions with others to learn and create interactive content during the teaching and learning process. This requires a commitment from the student because a connection between the student and the machine will be established through the use of emerging technologies. These technologies offer unique opportunities to enhance teaching quality, broaden access to education, and prepare individuals for an increasingly digital and evolving world. The analysis identified 14 emerging technologies: artificial intelligence, cloud computing, big data, Internet of Things, blockchain, augmented reality, extended reality, virtual reality, 5G, EON-XR, digital twins, 3D virtual reality, and immersive virtual reality. These technologies offer immersion (simulation of a real world in a virtual world), interactivity (interaction with different people), improvement of the educational environment (innovative presentation of content), and motivation for learning (capturing attention). When it comes to the different types of learning, there are six categories: experiential (based on experience), collaborative (involving a guide to lead the process), cooperative (involving teamwork), significant (building on existing knowledge), explicit (self-directed learning), and emotional (involving the regulation of emotions)

Cine colombiano 1977-1987: dos opiniones

Hablar de lo acontecido en el cine colombiano durante el último decenio es posible, a condición de que no se olvide lo relativo que resulta este tipo de análisis. Significa que no pueden mirarse las cosas con independencia de lo sucedido hasta 1977 , y el conocimiento de la situación con que arrancó este período es fundamental para una consideración más vasta y comprensiva. Por eso, antes de emprender la presentación de los cinco puntos en que hemos decidido resumir la década 77-87, haremos una referencia sintética al panorama de lo vivido en los cinco años anteriores a 1977

Deep sternal infections after in situ bilateral internal thoracic artery grafting for left ventricular myocardial revascularization: predictors and influence on 20-year outcomes

Background: The incidence and potential factors influencing deep sternal wound infection (DSWI) in a cohort of patients undergoing coronary artery bypass grafting (CABG) using skeletonized bilateral internal thoracic artery (BITA) was explored. Furthermore, we studied influence of DSWI on long-term survival, major adverse cardiac events (MACEs) and repeat coronary revascularization (RCR).Methods: The study cohort consisted of 1,325 consecutive patients who were divided in two groups: patients experiencing DSWI (n=33, group 1) and those who did not have sternal infection (n=1,292, group 2). A logistic regression model was employed to find predictors of DSWI whereas Cox regression and a competing risk models were carried out to test predictors of late death, MACE and RCR, respectively. Follow up was 100% complete and ranged from 1 to 245 months. Median follow-up was 103 months (IQR, 61 to 189 months). Cumulative follow-up was 16,430 patient years.Results: The incidence of DSWI was 2.4%. Multivariable logistic regression analysis found any single independent predictor of DSWI. However, the association of peripheral vascular disease (PVD) and diabetes increased the risk by 1.4 and 1.6 times. When DM was associated with obesity the risk increased by 2.1 and 2.6 times compared to the single factors, respectively. Obese female patients were at a 1.6-fold higher risk when compared to the association of DM with obesity. DSWI was not an independent predictor of long-term survival (HR, 2.31; 95% CI: 0.59–9.12), RCR (SHR, 2.89; 95% CI: 0.65–10.12), or MACE (SHR, 1.98; 95% CI: 0.44–8.56).Conclusions: With an accurate patient selection (i.e., exclusion of obese diabetic females) and strict DM control BITA represents a first choice for most of CABG patients, even at high risk for DSWI. The occurrence of DSWI does not influence long-term survival and late outcomes. Our findings should be confirmed by further larger research.</br

Comparison between three different equations for the estimation of glomerular filtration rate in predicting mortality after coronary artery bypass

Background This study was undertaken to compare the accuracy of chronic kidney disease-epidemiology collaboration (eGFRCKD-EPI) to modification of diet in renal disease (eGFRMDRD) and the Cockcroft-Gault formulas of Creatinine clearance (CCG) equations in predicting post coronary artery bypass grafting (CABG) mortality. Methods Data from 4408 patients who underwent isolated CABG over a 11-year period were retrieved from one institutional database. Discriminatory power was assessed using the c-index and comparison between the scores’ performance was performed with DeLong, bootstrap, and Venkatraman methods. Calibration was evaluated with calibration curves and associated statistics. Results The discriminatory power was higher in eGFRCKD-EPI than eGFRMDRD and CCG (Area under Curve [AUC]:0.77, 0.55 and 0.52, respectively). Furthermore, eGFRCKD-EPI performed worse in patients with an eGFR ≤29 ml/min/1.73m2 (AUC: 0.53) while it was not influenced by higher eGFRs, age, and body size. In contrast, the MDRD equation was accurate only in women (calibration statistics p = 0.72), elderly patients (p = 0.53) and subjects with severe impairment of renal function (p = 0.06) whereas CCG was not significantly biased only in patients between 40 and 59 years (p = 0.6) and with eGFR 45–59 ml/min/1.73m2 (p = 0.32) or ≥ 60 ml/min/1.73m2 (p = 0.48). Conclusions In general, CKD-EPI gives the best prediction of death after CABG with unsatisfactory accuracy and calibration only in patients with severe kidney disease. In contrast, the CG and MDRD equations were inaccurate in a clinically significant proportion of patients

The Role of Obesity in Early and Long-Term Outcomes after Surgical Excision of Lung Oligometastases from Colorectal Cancer

Obesity correlates with better outcomes in many neoplastic conditions. The aim of this study was to assess its role in the prognosis and morbidity of patients submitted to resection of lung oligometastases from colorectal cancer. Seventy-six patients undergoing a first pulmonary metastasectomy were retrospectively included in the study. Seventeen (22.3%) were obese (body mass index (BMI) >30 kg/m(2)). Assessed outcomes were overall survival, time to recurrence, and incidence of post-operative complications. Median follow-up was 33 months (IQR 16-53). At follow-up, 37 patients (48.6%) died, whereas 39 (51.4%) were alive. A significant difference was found in the 3-year overall survival (obese 80% vs. non-obese 56.8%, p = 0.035). Competing risk analysis shows that the cumulative incidence of recurrence was not different between the two groups. Multivariate analysis reveals that the number of metastases (p = 0.028), post-operative pneumonia (p = 0.042), and DFS (p = 0.007) were significant predictors of death. Competing risk regression shows that no independent risk factor for recurrence has been identified. The complication rate was not different between the two groups (17.6% vs. 13.6%, p = 0.70). Obesity is a positive prognostic factor for survival after pulmonary metastasectomy for colorectal cancer. Overweight patients do not experience more post-operative complications. Our results need to be confirmed by large multicenter studies

Lymphadenectomy during pulmonary metastasectomy: Impact on survival and recurrence

Background and Objectives: Lymphadenectomy during pulmonary metastasectomy (PM) is widely carried out. We assessed the potential benefit on patient survival and tumor recurrence of this practice. Methods: One hundred eighty‐one patients undergoing a first PM were studied. Eighty‐six patients (47.5%) underwent lymphadenectomy (L+ group) whereas 95 (52.5%) did not undergo nodal harvesting (L−group). Main outcomes were overall survival (OS) and disease‐free survival (DFS). Median follow‐up was 25 months (interquartile range [IQR], 13‐49). Results: At follow‐up 84 patients (46.4%) died, whereas 97 (53.6%) were still alive with recurrence in 78 patients (43%). There was no difference in 5‐year survival (L+ 30.0% vs L− 43.2%; P = .87) or in the 5‐year cumulative incidence of recurrence (L + 63.2% vs L−80%; P = .07) between the two groups. Multivariable analysis indicated that disease‐free interval (DFI) less than 29 months (P P = .003) were significant predictors of death. Metastases from non‐small–cell lung cancer increased the risk of lung comorbidities by a factor of 19.8, whereas the risk of DFI less than 29 months was increased nearly 11‐fold. Competing risk regression identified multiple metastases (P = .004), head/neck primary tumor (P = .009), and age less than 67 years (P = .024) as independent risk factors for recurrence. Conclusion: Associated lymphadenectomy showed not to give any additional advantage in terms of survival and recurrence after PM

Papillary muscle intervention vs mitral ring annuloplasty in ischemic mitral regurgitation

Background and Aims The main pathophysiological factor of chronic ischemic mitral regurgitation (MR) is the outward displacement of the papillary muscles (PMs) leading to leaflet tethering. For this reason, papillary muscle intervention (PMI) in combination with mitral ring annuloplasty (MRA) has recently been introduced into clinical practice to correct this displacement, and to reduce the recurrence of regurgitation. Methods A meta‐analysis was conducted comparing the outcomes of PMI and MRA performed in combination vs MRA performed alone, in terms of MR recurrence and left ventricular reverse remodeling (LVRR). A meta‐regression was carried out to investigate the impact of the type of PMI procedure on the outcomes. Results MR recurrence in patients undergoing both PMI and MRA was lower than in those who only had MRA (log incidence rate ratio, −0.66; lower‐upper limits, −1.13 to 0.20; I2 = 0.0%; p = .44; Egger's test: intercept 0.35 [−0.78 to 1.51]; p = .42). The group with both PMI and MRA and that with only MRA showed a slightly higher reduction in left ventricular diameters (−5.94%; −8.75% to 3.13%,). However, in both groups, LVRR was p = .33). Conclusions Using PMI and MRA together has a lower MR recurrence than using MRA alone. No significant LVRR was observed between the two groups nor between the PMI techniques employed

Pharmacological Management of Atrial Fibrillation: One, None, One Hundred Thousand

Abstract atrial fibrillation (AF) is associated with a significant burden of morbidity and increased risk of mortality. Antiarrhythmic drug therapy remains a cornerstone to restore and maintain sinus rhythm for patients with paroxysmal and persistent AF based on current guidelines. However, conventional drugs have limited efficacy, present problematic risks of proarrhythmia and cause significant noncardiac organ toxicity. Thus, inadequacies in current therapies for atrial fibrillation have made new drug development crucial. New antiarrhythmic drugs and new anticoagulant agents have changed the current management of AF. This paper summarizes the available evidence regarding the efficacy of medications used for acute management of AF, rhythm and ventricular rate control, and stroke prevention in patients with atrial fibrillation and focuses on the current pharmacological agents

Surgical Risk Factors for Ischemic Stroke Following Coronary Artery Bypass Grafting. A Multi-Factor Multimodel Analysis

Background: Ischemic stroke after coronary artery bypass (CABG) has been often linked to aortic manipulation during surgery. Objectives: The objective of the study was to estimate the rate of postoperative ischemic stroke within 30 days from CABG by surgical risk factors alone or in combination. Methods: The multinomial propensity score for multiple treatments was used to create six models with a total of 16,255 consecutive patients undergoing isolated CABG. For each model, a different classification variable was used to stratify patients. Results: Balance achieved in all models was substantial, enabling unbiased estimation of the treatment estimand. Both off-pump techniques with (0.009; 95% CI 0.006–0.011) or without proximal anastomoses (0.005; 0.005–0.003), and surgery performed on the beating heart using cardiopulmonary bypass with (0.009; 0.006–0.011) or without proximal anastomoses (0.024; 0.021–0.029) showed a mean stroke estimate significantly lower than the other techniques. Off-pump surgery and on-pump surgery without an aortic cross-clamp yielded nearly equal incidences of stroke (0.012; 0.008–0.015 and 0.018; 0.012–0.023, respectively). Using an aortic cross-clamp significantly increased the stroke estimate (0.075; 0.061–0.088), whereas using a side-biting clamp did not (0.039; 0.033–0.044). The number of aortic touches (0.029; 0.026–0.031) and the number of proximal anastomoses (0.044; 0.035–0.047) did not significantly increase the incidence of stroke. Conclusions: Aortic cross-clamping was found to be the primary cause of post-CABG ischemic stroke. Instead, additional aortic manipulation from a side-biting clamp, on-pump surgery, multiple aortic touches, number of proximal anastomoses, and aortic cannulation were found not to increase the estimate of stroke significantly. Further research on this topic is warranted