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Abstract Background Loneliness is considered a public health problem, particularly among older adults. Although risk factors for loneliness have been studied extensively, fewer studies have focused on the protected and risk groups that these factors configure. Our objective is to analyze the variables and latent factors that predict loneliness in older adults and that enable risk and protected groups to be configured. Methods We employed an epidemiological, cross-sectional survey that was carried out on a random sample of 2060 people over 65 years extracted from the census. A structured telephone interview was used to assess mental and physical health, habits, quality of life, and loneliness, applying the COOP-Wonca, Goldberg General Health (GHQ-12), and Barber Questionnaires. Results Predictors of loneliness were: mental health, living alone, quality of life, depressive symptoms, low educational level, and some deficiency situations such as having no one to turn to for help. The factors extracted (Factorial Analysis) were: a subjective experience of poor health, objective isolation, and psychological isolation. We established at risk and protected groups (“Decision Tree” procedure), and loneliness was referred to by 73.2% of the people living alone and with poor mental health and quality of life (risk group). By contrast, only 0.8% of people living with others, with good mental health and good quality of life felt loneliness (protected group). Conclusion In a well-developed city, subjective and objective factors are associated with loneliness. These factors, especially those associated with at risk or protected groups, must be considered to develop strategies that address loneliness.

Abstract The challenge of three‐dimensional (3D) printing by polymeric extrusion in tissue bioengineering is to control with precision the microarchitecture and porous interconnectivity of scaffolds, as well as search for models that allow and facilitate the development of personalized constructs that meet optimal characteristics for the regeneration of significant bone defects. In this study, anatomically accurate scaffolds were designed and printed to a critical size defect from a microtomography image of the rat calvaria. Different software is used to design a scaffold with exact anatomy. With Ultimaker Cura software, distinct printing parameters were standardized, permitting the printing of different types of pores and graded porosity scaffolds, with exact adaptation to the bone defect, utilizing a commercial 3D printer with a fused deposition modeling technique and compensating for the limitations of the method. The scaffolds were characterized by evaluating their mechanical properties and surface characteristics (pore size and porosity), employing scanning electron microscopy images, verifying that the size and shape of the pores were controlled, and evaluating cell viability and cell distribution on the 3D printed scaffold. Therefore, this work proves that by standardizing the printing parameters, it was possible to print a unique customized scaffold, controlling the shape and size of pores.

Introduction and Objectives: : C-reactive protein (CRP) and D-dimer have been shown to be predictors of severity in patients with COVID-19. The FIB-4 and APRI scoring systems are tools calculated using routine laboratory parameters that allow non-invasive evaluation of liver fibrosis. Some studies have demonstrated that the parameters comprising these scores predict mortality in COVID-19. The objective of this study was to determine the role of various liver injury biomarkers in stratifying the severity of hospitalized patients with COVID-19. Materials and Patients: Analytical and retrospective study. Patients with COVID-19 were included, while those with liver disease were excluded. A receiver operating characteristic (ROC) analysis with 95% confidence intervals (CI) was performed to determine the predictive performance of FIB-4, APRI, D-dimer, and CRP in terms of the need for invasive mechanical ventilation (IMV) and mortality. Results: A total of 448 hospitalized patients with COVID-19 were included in the study. 68.2% were male, with a mean age of 56.27 ± 14.7 years. 35.1% had systemic arterial hypertension, 29.2% had diabetes mellitus, 6% had cancer, 5% had chronic obstructive pulmonary disease, and 3.3% had chronic kidney disease. 21.4% required nasal cannula support, 29.4% required mask with reservoir, 35.5% required high-flow oxygen therapy, and 13.1% required IMV. 48% had severe disease, and 28.1% died. ROC analysis with 95% CI revealed that the best predictor of the need for IMV was the FIB-4 index, with an AUC of 0.637 (95% CI 0.545 - 0.732, p= 0.003), followed by APRI with an AUC of 0.596 (95% CI 0.504-0.687, p=0.04). The best predictor of mortality was FIB-4 with an AUC of 0.689 (95% CI 0.620 - 0.785, p=

Introduction and Objectives: It is estimated that 71 million people live with chronic hepatitis C viral infection (HCV). Part of the comorbidities associated with cirrhosis is frailty. Remarkably, diet is highly important in the management of cirrhosis and liver diseases. Therefore, it is necessary to evaluate the quality of the diet in this population. In this context, we evaluated the frailty and quality of the diet in patients with chronic HCV infection with or without cirrhosis, as well as the association between demographic, clinical, and anthropometric variables. Materials and Patients: A cross-sectional study was conducted in the hepatitis clinic of the Civil Hospital of Guadalajara Fray Antonio Alcalde. Each participant was required to complete the Liver Frailty index (LFI) which include hand grip strength, chair stand test and balance test. Additionally, the mini survey was applied to evaluate the quality of food consumption (Mini-ECCA v.2). This questionnaire includes 14 questions, each with 3 or 4 response options on a Likert scale. The outcome yields three classifications: “healthy food intake, habit to be improved, and unhealthy food intake.'' Finally, upper arm anthropometry was performed. P< 0.05 was considered statistically significant. Results: A preliminary sample of 20 patients was assessed. Of them, 60% (n=12) had only chronic HCV infection, 85% (n=17) of LFI were considered pre-fragile, while the rest of the participants were classified as fragile. The quality of the diet, 65% (n=13), was considered “a habit to be improved.” A relationship was found between the quality of the diet and LFI. Likewise, a negative correlation was also found between the mean arm muscle circumference (MAMC) and the LFI score (r=-0.577; p=0.008) as well as MAMC and time in chair supports (r=-0.504;p=0.023). In addition, we found a positive correlation between the MAMC and hand grip strength (r=-0.624; p=0.003). Conclusions: Some degree of frailty was found in the participants, and the quality of the diet was found to be “a habit to be improved” in most of the population sample.

POPDC2 encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due in part to its cAMP-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia and morpholino knockdown of popdc2 in zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in POPDC2 in 4 families that presented with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects and hypertrophic cardiomyopathy. Using homology modelling we show that the identified POPDC2 variants are predicted to diminish the ability of POPDC2 to bind cAMP. In in vitro electrophysiological studies we demonstrated that, while co-expression of wild-type POPDC2 with TREK-1 increased TREK-1 current density, POPDC2 variants found in the patients failed to increase TREK-1 current density. While patient muscle biopsy did not show clear myopathic disease, it showed significant reduction of the expression of both POPDC1 and POPDC2, suggesting that stability and/or membrane trafficking of the POPDC1-POPDC2 complex is impaired by pathogenic variants in any of the two proteins. Single-cell RNA sequencing from human hearts demonstrated that co-expression of POPDC1 and 2 was most prevalent in AV node, AV node pacemaker and AV bundle cells. Sinoatrial node cells expressed POPDC2 abundantly, but expression of POPDC1 was sparse. Together, these results concur with predisposition to AV node disease in humans with loss-of-function variants in POPDC1 and POPDC2 and presence of sinus node disease in POPDC2, but not in POPDC1 related disease in human. Using population-level genetic data of more than 1 million individuals we showed that none of the familial variants were associated with clinical outcomes in heterozygous state, suggesting that heterozygous family members are unlikely to develop clinical manifestations and therefore might not necessitate clinical follow-up. Our findings provide evidence for POPDC2 as the cause of a novel Mendelian autosomal recessive cardiac syndrome, consistent with previous work showing that mice and zebrafish deficient in functional POPDC2 display sinus and AV node dysfunction.

Aims: To conduct a contemporary cost-effectiveness analysis examining the use of implantable cardioverter defibrillators (ICDs) for primary prevention in patients with hypertrophic cardiomyopathy (HCM)., Methods: A discrete-time Markov model was used to determine the cost-effectiveness of different ICD decision-making rules for implantation. Several scenarios were investigated, including the reference scenario of implantation rates according to observed real-world practice. A 12-year time horizon with an annual cycle length was used. Transition probabilities used in the model were obtained using Bayesian analysis. The study has been reported according to the Consolidated Health Economic Evaluation Reporting Standards checklist., Results: Using a 5-year SCD risk threshold of 6% was cheaper than current practice and has marginally better total quality adjusted life years (QALYs). This is the most cost-effective of the options considered, with an incremental cost-effectiveness ratio of £834 per QALY. Sensitivity analyses highlighted that this decision is largely driven by what health-related quality of life (HRQL) is attributed to ICD patients and time horizon., Conclusion: We present a timely new perspective on HCM-ICD cost-effectiveness, using methods reflecting real-world practice. While we have shown that a 6% 5-year SCD risk cut-off provides the best cohort stratification to aid ICD decision-making, this will also be influenced by the particular values of costs and HRQL for subgroups or at a local level. The process of explicitly demonstrating the main factors, which drive conclusions from such an analysis will help to inform shared decision-making in this complex area for all stakeholders concerned., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cardiomyopathies (CMs), one of the main causes of sudden death among the young population, are a heterogeneous group of myocardial diseases, usually with a genetic cause. Next-Generation Sequencing (NGS) has expanded the genes studied for CMs; however, the yield is still around 50%. The systematic study of Copy Number Variants (CNVs) could contribute to improving our diagnostic capacity. These alterations have already been described as responsible for cardiomyopathies in some cases; however, their impact has been rarely assessed. We analyzed the clinical significance of CNVs in cardiomyopathies by studying 11,647 affected patients, many more than those considered in previously published studies. We evaluated the yield of the systematic study of CNVs in a production context using NGS and a novel CNV detection software tool v2.0 that has demonstrated great efficacy, maximizing sensitivity and avoiding false positives. We obtained a CNV analysis yield of 0.8% that fluctuated depending on the type of cardiomyopathy studied (0.29% HCM, 1.41% DCM, 1.88% ARVC, 1.8% LVNC, 1.45% RCM), and we present the frequency of occurrence for 18 genes that agglutinate the 95 pathogenic/likely pathogenic CNVs detected. We conclude the importance of including in diagnostic tests a systematic study of these genetic alterations for the different cardiomyopathies.

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)