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Spliced leader trans-splicing is essential for gene expression in many eukaryotes. To elucidate the molecular mechanism of this process, we characterise the molecules associated with the Caenorhabditis elegans major spliced leader snRNP (SL1 snRNP), which donates the spliced leader that replaces the 5′ untranslated region of most pre-mRNAs. Using a GFP-tagged version of the SL1 snRNP protein SNA-1 created by CRISPR-mediated genome engineering, we immunoprecipitate and identify RNAs and protein components by RIP-Seq and mass spectrometry. This reveals the composition of the SL1 snRNP and identifies associations with spliceosome components PRP-8 and PRP-19. Significantly, we identify a novel, nematode-specific protein required for SL1 trans-splicing, which we designate SNA-3. SNA-3 is an essential, nuclear protein with three NADAR domains whose function is unknown. Mutation of key residues in NADAR domains inactivates the protein, indicating that domain function is required for activity. SNA-3 interacts with the CBC-ARS2 complex and other factors involved in RNA metabolism, including SUT-1 protein, through RNA or protein-mediated contacts revealed by yeast two-hybrid assays, localisation studies and immunoprecipitations. Our data are compatible with a role for SNA-3 in coordinating trans-splicing with target pre-mRNA transcription or in the processing of the Y-branch product of the trans-splicing reaction.

Funding Acknowledgements Type of funding sources: None. Introduction Electrical cardioversion (ECV) is an effective therapeutic alternative for atrial fibrillation (AF) and atrial flutter (AFL); however, in the medium-long term, the recurrence rate is significant and the evidence is limited. Methods Retrospective, observational, single-center, retrospective registry of 154 consecutive cases of patients undergoing electrical cardioversion for AF or AF flutter of more than 48 hours of evolution. Recurrence, emergency visits, readmissions and new ECV were recorded during a mean follow-up of 34±11 months. Results The median time from diagnosis to ECV was 60 days. The success rate of ECV was 91.7%. The immediate recurrence rate (< 2 hours) was 3.9%. The incidence of recurrence during follow-up is shown in Table 1. Of the total number of recurrences, 12.7% were detected on Holter-ECG. During follow-up, 5.8% of the patients died, none due to cardiovascular causes, 33.1% of the patients were readmitted, 25.3% due to cardiovascular causes and 15.6% as a consequence of AF/AFL. A total of 17.5% of patients attended the emergency department for episodes of AF/AFL with rapid ventricular response. Up to 18.8% of patients underwent repeat ECV and 16.2% underwent pulmonary vein ablation; in contrast, 35.3% of patients opted for a rate control strategy. Previous ECV and atrial dilatation were associated with a higher (76.9% vs 52.6% p=0.02; 64.9% vs 24% p Conclusion ECV is an effective therapy against AF and AFL, however, the recurrence rate in the medium-long term is high. Previous ECV and atrial dilatation are associated with a higher and earlier recurrence. Antiarrhythmic treatment had a neutral impact on the maintenance of sinus rhythm in the medium to long term.

Funding Acknowledgements Type of funding sources: None. Introduction Electrical cardioversion is an effective therapy for the restoration of sinus rhythm. The success of cardioversion has been related to different clinical and echocardiographic variables, although the available evidence is scarce and heterogeneous. Methods Ambispective, observational, single-center registry that consecutively included 271 patients scheduled for elective electrical cardioversion (ECV) on the inpatient ward for atrial fibrilation (AF) or flutter fibrilation (AFL) >48 hours of onset during the years 2018-2021. All patients scheduled for CVE that were ultimately discontinued on the day of the procedure were excluded, finally analyzing 244 patients. Results The baseline characteristics are shown in Picture 1. No statistically significant differences were observed in the main comorbidities, cardiovascular risk factors, CHAD2S2-VASc scale, the position of the paddles, or days to ECV between patients with successful ECV and those with a failed procedure. Neither were they observed in terms of pharmacological treatment, including the presence of previous antiarrhythmic treatment as part of a facilitated ECV strategy (Picture 2). Moderately-severely depressed systolic function and the presence of moderate-severe mitral regurgitation were associated with a higher rate of cardioversion failure (3% vs 2.6% p= 0.002; 3.3% vs 1.3% p=0.001), higher number of biphasic electric shocks (1.3 vs 1.6 p Conclusion Patients with moderate-severe systolic dysfunction and significant mitral and tricuspid regurgitation have a lower success rate of ECV. Previous antiarrhythmic therapy presents a neutral effect on sinus rhythm restoration and immediate recurrence.

Funding Acknowledgements Type of funding sources: None. Introduction and objectives The prevalence of left atrial (LA) thrombus in patients with atrial fibrillation (AF) or atrial flutter (AFL) on guideline-directed anticoagulation is nor well known, moreover, evidence on the presence of left atrial thrombus with different anticoagulation therapies provides heterogeneous results. Methods Ambispective, observational, single-center study that consecutively included 271 patients undergoing elective electrical cardioversion (ECV) for AF or AFL >48 hours of onset. A transoesophageal echocardiogram (TOE) was performed in all patients within 24 hours prior to ECV. Patients with Results The main baseline characteristics are shown in Picture 1. A total of 66.5% of the patients were receiving treatment with direct oral anticoagulants (NOAC) dabigatran (15.9%); rivaroxaban (28.3%); apixaban (31.2%) and edoxaban (23.9%). The remaining 33.5% were anticoagulated with vitamin K antagonists (VKA). Eight thrombi were detected in the left atrial appendage (prevalence 4.7%), and on 2 occasions the presence of thrombus could not be ruled out, and CVE was also suspended. No statistically significant differences were observed between the prevalence of thrombus and the type of anticoagulant (NOAC vs VKA 4.5% vs 4.9%; p= 0.56) or between the different NOACs (p=0.61). Of the 8 patients with left atrial thrombus, anticoagulant treatment was modified in 3 of them. Control TOE was performed (median until new TOE 64 days), and resolution was verified in 3 cases (all under treatment with NOAC), of which 2 patients had maintained their previous anticoagulant treatment. Conclusions Anticoagulated patients scheduled for elective ECV present a prevalence of left atrial thrombus close to 5%. No differences were observed with respect to the anticoagulation treatment received.

Nursing Home Placement (NHP) can prove to be the only solution to some dead-end situations in Alzheimer's disease (AD). The predictors of NHP are known and can be related to either the person with dementia or his/her caregiver. We aimed to identify predictors of NHP among people with AD over a 2-year follow-up period, with a particular interest in the modifiable predictors, notably those involving caregivers.We studied data from the THERAD study, a French monocentric randomized controlled trial, involving 196 community-dwelling dyads, primarily assessing an educational intervention in AD. We performed a bivariate analysis followed by a multivariate Cox model, with a backward stepwise procedure.The mean age of the patients was 82 years old, 67.7% were women and 56.9% were living with a partner. The mean age of the caregivers was 65.8 years old, 64.6% were women and half were spouses of the patients with a moderate burden. During the follow-up, 23 patients died and 49 were institutionalized. The majority of NHPs occurred during the first year (35 NHP). The mean time to NHP was 27.77 months after the diagnosis. Five independent predictors of NHP were found: a higher patient education level (aHR 6.31; CI95% = 1.88-21.22), a high caregiver Burden (aHR 3.97; CI95% = 1.33-11.85), the caregiver being the offspring of the patient (aHR 2.92; CI95% = 1.43-5.95), loss of autonomy (aHR 2.75; CI95% = 1.13-6.65) and disinhibition as a behavioural and psychological symptoms of dementia (BPSD) (aHR 2.38; CI95% = 1.26-4.47).Our data are in accordance with the literature in identifying loss of autonomy, burden and BPSD (disinhibition) as risk factors of NHP. We also found high patient education level and status of offspring caregiver as additional factors. It is essential to take into account the caregiver status when designing psychoeducational trials aiming to delay NHP. Further studies need to take into account both the modifiable risk factors related to the patient (productive BPSD) and the needs of offspring caregivers (work-life balance, mental load).

Funding Acknowledgements Type of funding sources: None. Introduction Despite the undoubted relationship between retinopathy and cardiovascular pathology, its role as a predictor in the development of myocardial ischemia has not been sufficiently studied. Methodology Prospective study of a Spanish cohort of 107 patients who underwent diagnostic-therapeutic coronary angiography by medical indication. A fundus examination was also performed, determining the existence of retinopathy of vascular etiology (diabetic, hypertensive or atherosclerotic) and classifying it according to its degree. During follow-up, the appearance of myocardial perfusion defects was recorded by gated-SPECT. Results The median age was 67 years. 60.7% were men. The mean follow-up time was 111±19.7 months. Of the patients, 91.6% had some cardiovascular risk factor: 32.7% were diabetic, 78.5% had hypertension and 57% had dyslipidemia. 91.6% of the patients had some cardiovascular risk factor: 32.7% were diabetic, 78.5% had hypertension and 57% had dyslipidemia. 84.1% of the patients, had retinopathy of vascular etiology, 43.6% of whom had high-grade retinopathy. Significant coronary artery disease was present in 44.9%, with a mean SYNTAX score of 3.99±7.5 and 39.3% required percutaneous intervention. During follow-up, 15% presented inducible ischemia assessed by gated-SPECT. Subsequent coronary angiography was performed in 68.8% of these cases. Advanced vascular retinopathy, male sex, SYNTAX score and previous percutaneous coronary intervention were associated with a higher risk of myocardial perfusion defects. In logistic regression adjusted for these variables, vascular retinopathy presented an OR of 5.3 (95%CI 0.9-30.6; p=0.063) for the development of myocardial ischemia. Conclusion The presence of high-grade vascular retinopathy is an independent risk marker for the development of myocardial ischemia assessed by SPECT. Performing a funduscopic examination as part of the stratification of the cardiovascular patient could allow us to identify patients at higher risk.

Funding Acknowledgements Type of funding sources: None. Introduction Although the effects of SARS-CoV-2 infection on the cardiovascular system are well known in the acute phase, the cardiovascular impact in the elderly population surviving respiratory COVID-19 infection after 1-year follow-up has not been sufficiently studied. Methods Observational registry of 240 elderly patients (75 years or older) consecutively admitted for and surviving COVID-19 respiratory infection between March 1 and April 30, 2020. The incidence of major cardiovascular events [MACE] (cardiovascular death [CD], acute coronary syndrome [ACS], cerebrovascular disease [CVD], venous thromboembolic disease [VTE], and heart failure [HF]) was prospectively analyzed. Results The mean age was 83.8 ± 5.6 years (range 75-103 years). A total of 54.2% were women. Most patients had a personal history of cardiovascular risk factors: hypertension (83.3%), diabetes mellitus (27.9%), dyslipidemia (43.8%). Among the main cardiological comorbidities, a history of atrial fibrillation was the most frequent (18.8%). Of note was the high percentage of institutionalized patients (37.1%) and those with moderate-severe dementia (16.7%). After a mean follow-up of 352.2±70.4 days, 13.8% of patients died and 9.6% had MACE, the most frequent being heart failure (7.5%), with no differences in the severity or overall evolution of the acute disease. Of the 33 patients who developed HF, only 3 died of cardiovascular causes. Only 2 patients suffered a stroke, in both cases without a history of AF or anticoagulants. Only 2 patients had a thromboembolic event (0.8%). The low incidence of thrombotic events may be due in part to the high rate of anticoagulation and chronic antiplatelet therapy and the high percentage of prophylactic heparin prescription at discharge, as well as the fact that only cases with clinical repercussions. COPD, CKD, institutionalization and moderate-severe dementia are associated with an increased risk of MACE, although only COPD and prescription of loop diuretics were identified as independent risk markers in the multivariate analysis. Conclusions In elderly COVID-19 survivors, the incidence of MACE after one year of follow-up is high, the main manifestation being heart failure. COPD and the prescription of loop diuretics were identified as independent risk markers for the development of MACE in the multivariate analysis.

Funding Acknowledgements Type of funding sources: None. Introduction The management of antihypertensive drugs and especially ACEI/ARA2 during the first wave of the SARS-CoV-2 pandemic was a matter of debate. The change in antihypertensive treatment during the pandemic and its repercussions have not been sufficiently studied. Methods Observational and prospective study that analyzed consecutive patients admitted for respiratory infection and positive polymerase chain reaction (PCR) between March 1 and April 30, 2020. During the period analyzed, 921 patients were registered, of whom 673 patients were discharged; among them 359 were patients with a diagnosis of arterial hypertension and pharmacological treatment. These patients were followed up in days, from the time of discharge to data analysis, with a mean of 352±70.4 days. Results The mean age was 74.4±12.9 years, and 50.7% were male. A total of 28.7% were diabetic patients, 49% were dyslipidemic, 17.8% were smokers, and 19.8% were obese. Of the patients analyzed, 13.4% had a previous diagnosis of ischemic heart disease, a similar percentage, 13.1% had heart failure, and 13.6% had atrial fibrillation. The antihypertensive drugs analyzed were ACE inhibitors (angiotensin-converting enzyme inhibitors), ARA-2 (angiotensin II receptor antagonists), calcium antagonists, thiazide diuretics, loop diuretics, aldosterone antagonists, beta-blockers and alpha-blockers. At discharge, 75.8% of the patients maintained their antihypertensive treatment, and the remaining 24.2% were modified. Prior to admission, 77.2% were taking ACE inhibitors or ARA-2; however, in 16.4% of the patients they were discontinued after admission. In contrast, treatment with calcium antagonists increased from 27.6% to 34.1% after hospitalization. In both cases there were statistically significant differences in the bivariate analysis in the McNemar test (p < 0.05 in both cases), with no differences in the other antihypertensive drugs analyzed. After follow-up, the combined event occurred in 28 patients, with the most frequent event being the development of HF; in contrast, only 0.8% presented ACS. Overall mortality was 8.9%. Picture 1 shows the events recorded according to the change in antihypertensive treatment and the maintenance or discontinuation of ACEI/ARA-2 in those patients who were already taking it on admission. Similarly, a survival analysis was performed in which no differences were observed in terms of all-cause mortality or major cardiovascular events between patients who maintained their antihypertensive treatment and those who modified it. Conclusions In the population surviving SARS-CoV-2 respiratory infection, maintaining or discontinuing treatment with ACEI/ARA-2 did not influence mortality or the appearance of major cardiovascular events after the first year of follow-up.

Funding Acknowledgements Type of funding sources: None. Introduction Although an association between some forms of vascular retinopathy and cardiovascular disease has been described, its predictive role in ischemic heart disease has not been sufficiently clarified. Methods Prospective cohort of 107 patients with medical indication for coronary angiography who underwent funduscopic examination to assess the presence of retinopathy. We recorded the occurrence of new acute coronary syndromes, the detection of perfusion defects in ischemia tests, the need for new catheterization and revascularization, and hospital readmission for cardiovascular causes with a median follow-up of 10 years. Results The median age was 67 years. A total of 39.3% were women, and 91.2% presented some cardiovascular risk factor, the most frequent being arterial hypertension in 78.5%, followed by dyslipidemia in 57% and diabetes in 32.7%. At the start of follow-up, 84.1% had some type of vascular retinopathy, with 46.3% of patients having high-grade retinopathy. In coronary angiography, up to 55% presented significant coronary artery disease, and angioplasty was performed in 39% of cases. During follow-up, only 2.9% of patients suffered ACS, 15% presented pathological myocardial SPECT, up to 14% underwent a new coronary angiography and 6.5% required new myocardial revascularization. The presence of advanced vascular retinopathy was associated with a higher rate of defects on Tc99 perfusion scintigraphy (p=0.002); a higher rate of coronary angiography (p=0.001) and myocardial revascularization (p=0.045). In addition, in the survival analysis, ischemia development was observed in earlier SPECT (103.13±4 vs 116.3±1.9 p=0.01), as well as earlier myocardial revascularization (109.72±3.5 vs 118.8±0.1 p=0.03) than in the rest of patients. Conclusions High-grade vascular retinopathy is associated with more and earlier inducible ischemia as well as more need for revascularization. The performance of fundus imaging in patients with suspected ischemic heart disease may be useful for long-term stratification.

En la presente investigación se estudia Determinar de qué manera se relaciona las estrategias metacognitivas con las habilidades del pensamiento crítico en los estudiantes de la Facultad de Psicología de la Universidad Nacional Mayor de San Marcos. La muestra estuvo constituida por 187 estudiantes, los cuales fueron seleccionados de manera probabilística. Los resultados fueron analizados en el nivel descriptivo, en donde se encontró que las estrategias metacognitivas se perciben en un nivel medio o regulas, asimismo, las habilidades del pensamiento crítico se perciben en un nivel medio, en el nivel inferencial se ha hecho uso de la estadística no paramétrica y como tal se ha utilizado Rho de Spearman a un nivel de 0,05, dado que los datos no presentan distribución normal. Los resultados indican que existe relación alta, directa y significativa entre las estrategias metacognitivas y las habilidades del pensamiento crítico. In this research we study to determine how metacognitive strategies are related to critical thinking skills in students of the Faculty of Psychology of the Universidad Nacional Mayor de San Marcos. The sample consisted of 187 students, who were selected in a probabilistic way. The results were analyzed at the descriptive level, where it was found that metacognitive strategies are perceived at a medium or regular level, likewise, critical thinking skills are perceived at a medium level, at the inferential level, use has been made of the Nonparametric statistics and as such Spearman's Rho has been used at a level of 0.05, since the data do not present a normal distribution. The results indicate that there is a high, direct and significant relationship between metacognitive strategies and critical thinking skill.

The lack of pharmacological treatment leads nonpharmacological therapies at the forefront of therapeutic strategies in Neurodegenerative diseases such as Alzheimer's disease (AD). Among them psychoeducational interventions are efficient. We hypothesized that a Therapeutic Patient Education (TPE) programme, using a dyadic approach, could have a positive impact on the patient's quality of life (QOL) and conducted a trial to test it. Our objectives were to assess the efficacy of a TPE programme adressed to the dyad (caregiver/patient) on the AD patient's QOL proxy-reported by caregiver, its impact on the caregiver's well-being (QOL, burden), and to better characterize subgroups of caregivers and, lastly, identify predictors of nursing home placement (NHP) among dyads. THERAD is a monocentric, randomized, controlled trial assessing the effect of a 2-month educational programme in AD patients (MMSE 11-26) among 196 dyads on patient's QOL caregiver-reported at 2 months. The intervention was a TPE programme (validated tools, format and methods. The primary outcome was the patient's QOL caregiver reported at 2 months. Secondary outcomes were : self-reported patient QOL (same scale), autonomy, behavioural and psychological symptoms (NPI), and caregiver QOL (NHP) and burden (Zarit) were secondary outcomes at 6 months. We performed an intention to treat analysis and sensitivity analysis in the THERAD per protocol population. Sub-group analysis were made (on gender, status, burden) on every outcomes (primary and secondary). A descriptive analysis of 153 caregivers (> 65 years) was made in a cohort of 1711 older adults from an ambulatory unit. We identified predictors of NHP in THERAD at 24 months by a multivariate analysis. We did not report any significant difference in caregiver-reported patients' QOL at 2 months but a significant one in self-reported patients' QOL at 2 and 6 months. No significant results on secondary outcomes(art1). In the sub-group of exhausted caregivers (burden>40vs 65) the mean age, level of comorbidities and frailty scores were the same in caregivers and non-caregivers. Men were most represented among caregivers. Caregivers were more independent, with greater physical performance, cognitive and nutritional. A higher alcohol consumption was found among caregivers (art2). Five independent predictors of NHP from multivariate analysis: a higher patient education level, a high caregiver burden, being a child as caregiver status, loss of autonomy and disinhibition. No effect of the intervention. Some modifiable factors could be the target of future interventions (Burden), including TPE, or criteria to define sub-groups of interest (art3). The caregiver did not report any improvement in the patient's QOL after a dyadic TPE, however the patient perceived one. This contrasted result underlines the interest of a double perspective and the need of methodological strains to limit bias. [...], Les stratégies non pharmacologiques sont au devant de la prise en charge de la maladie d'Alzheimer (MA) et parmi elles, les interventions psychoeducationnelles. Nous avons émis l'hypothèse qu'une intervention d'Education Thérapeutique (ETP) adressée à la dyade pourrait avoir un impact positif sur la qualité de vie du patient et mené un essai pour la tester. Les objectifs généraux étaient d'évaluer l'efficacité d'une ETP adressée à la dyade sur la qualité de vie du patient atteint de MA et sur le bien-être de l'aidant (fardeau et qualité de vie) mais aussi de mieux caractériser les sous populations cibles et les particularités des dyades pour concevoir de futures interventions. Nous avons aussi souhaité identifier des facteurs associés à l'entrée en EHPAD, chez chaque membre de la dyade. THERAD est un essai monocentrique, randomisé et contrôlé évaluant l'impact de l'ETP sur la qualité de vie du patient atteint de MA à domicile, chez 196 dyades. L'intervention était un programme d'ETP. Le critère de jugement principal était la qualité de vie du patient heteroevaluée par l'aidant, à 2 mois sur l'échelle de qualité de vie QOL (Quality of life) de Logsdon. Les critères de jugement secondaires étaient la qualité de vie du patient autoévaluée, les troubles du comportement (NPI), le fardeau de l'aidant (Zarit), la qualité de vie de l'aidant (échelle NHP) à 6 mois. Nous avons réalisé une analyse en intention de traiter et per protocole dans THERAD. Des analyses en sous-groupes ont été faites pour cibler les sous-populations d'aidants d'intérêt (genre, statut, fardeau). Nous avons aussi caractérisé 153 aidants dans une cohorte de 1711 sujets âgés (> 65 ans) et identifié des facteurs associés à l'entrée en EHPAD dans THERAD à 24 mois, par une analyse multivariée. Nous ne mettons pas en évidence de différence significative sur la qualité de vie du patient rapportée par l'aidant à 2 mois mais une différence significative sur la qualité de vie autodéclarée à 2 mois et 6 mois, sans autres résultats significatifs (art1). Nous retrouvons un effet significatif de l'intervention sur la qualité de vie du patient évaluée par l'aidant à 6 et 12 mois dans le sous-groupes de fardeau élevé > 40 (vs < = 20) et sur la qualité de vie du patient évaluée par l'aidant à 2 mois dans le sous-groupe de fardeau modéré 20-40 (vs < = 20). Il n'y a pas d'autre résultat significatif dans les sous-groupes étudiés (art1). Chez 153 aidants parmi 1711 sujets âgés, l'âge moyen, les comorbidités et le score de fragilité ne sont pas signitifcativement différents entre aidants et non aidants Les hommes sont plus représentés chez les aidants, plus autonomes, avec de meilleures performances physiques, cognitives et nutritionnelles. Une plus importante consommation d'alcool est trouvée chez les aidants (art2). Dans ces dyades, 5 facteurs prédictifs d'entrée en EHPAD ont été trouvés : un haut niveau socio culturel du patient, un fardeau élevé de l'aidant, le statut d'aidant " enfant " et pour le patient, le fait d'être dépendant et une desinhinbition. L'intervention n'est identifiée comme un facteur prédictif. Certains facteurs modifiables pourraient être la cible d'interventions d'ETP ou permettre d'identifier des sous-groupes (aidants enfants) (art3). La qualité de vie du patient n'est pas améliorée par l'ETP, lorsqu'elle est évaluée par l'aidant mais significativement améliorée quand autoévaluée par le patient. Ce résultat souligne l'intérêt d'une double perspective et la nécessité d'efforts méthodologiques limitant les biais.[...]