Mitochondrial mutation in adult patient with Hypertrophic Cardiomyopathy and renal failure

Background: Mitochondrial diseases (MDs) (1:5000-10000) represents a wide group of human disorders associated with mitochondrial DNA (mtDNA) variations causing defect of oxidative phosphorylation system, whereas nuclear genome mutations are somewhat rare. The extremely heterogeneous clinical phenotype, extending from oligosymptomatic condition to complex syndromes involving neurological, ophtalmological, gastroenterological and endocrine features, depends to the involved tissue well as to the specific mtDNA mutations and their heteroplasmic level. Diabetes and deafness are common features of mitochondrial diseases, while renal alterations are rarely reported, especially in adults, probably because of lack of association to mitochondrial conventional phenotypes. Case Presentation: We investigated a 62 years old male affected by hypertrophic cardiomyopathy (HCM) and renal failure that caused already a bilateral transplantation. Pathological anamnesis revealed also diabetes, deafness and Crohn disease. Family history of cardiomyopathy showed a strong mitochondrial involvement. The proband's mother, three brothers (one of which died of renal failure at 26 years), the sister and her child were affected. Materials and Methods: Genomic DNA from peripheral blood and buccal cells was extracted with the Kit-Nucleon-BACC2 (Illustra DNA-Extraction Kit-BACC2-GE Healthcare, UK) and the whole mitochondrial genome was amplified by two pair of primers designed in our laboratory to generate two overlapping fragments. The PCR products were then sequenced and compared to mitochondrial reference sequence (rCRS NC_012920). Results and Discussion: In both biological samples the mtDNA analysis showed the heteroplasmic A3243G mutation in the tRNALeu (UUR), frequently associated with MDs. A cardiological involvement leading to hypertrophic remodelling, caused to mitochondria intermyofibrillar proliferation, occurs up to 40% of patients with mtDNA disease. Molecular backgrounds of mitochondrial cardiomyopathy of adult age are still quite poorly known and the A3243G mutation in tRNA Leu(UUR) of mtDNA has been reported in 40-60% of patients with HCM. The interesting finding presented here support the knowledge that mitochondrial gene altertation represents a possible etiology in cardiological patients with unexplained renal failure. This is particularly true, as in this case, when other associated symtoms linked with dysfunctional oxidative phosphorylation are present. The case presented in this report further suggests that a differential diagnosis in presence of HCM should be solved by a multidisciplinary approach together with mutation analysis of mitochondrial DNA

The impact of the COVID-19 pandemic on perinatal loss among Italian couples: A mixed-method study

Background: Perinatal bereavement is an event that greatly impacts the emotional, psychological, and psychosocial aspects of those who want to have a child. Objectives: Since there are few studies on the psychological impact of the COVID-19 pandemic on couples grieving for perinatal loss, this research aimed to survey this experience. Participants: Between 2020 and 2021, in Italian provinces highly affected by the COVID-19 pandemic, 21 parents participated: 16 mothers (76%; mean age 36.2; SD: 3.1) and 5 fathers (24%; mean age 40.2; SD: 3.4), among which there were 4 couples. Methods: A mixed-method design was used through self-report questionnaires and in-depth interviews. Accompanied by a sociodemographic form, the following questionnaires were administered: Prolonged Grief-13, the Parental Assessment of Paternal Affectivity (PAPA) (to fathers), the Parental Assessment of Maternal Affectivity (PAMA) (to mothers), the Dyadic Adjustment Scale short version, the Daily Spiritual Experiences Scale, and the Impact of Event Scale-Revised. The texts obtained through the in-depth interviews underwent thematic analysis. Results: Fifty per cent of participants suffered from Post-Traumatic Stress Disorders (PTSD) symptoms and 20% suffered from relational dyadic stress. Four areas of thematic prevalence emerged: psychological complexity of bereavement, the impact of the COVID-19, disenfranchisement vs. support, and spirituality and contact with the lost child. Participants interpreted their distress as related to inadequate access to healthcare services, and perceiving the pandemic restrictions to be responsible for less support and lower quality of care. Furthermore, they needed psychological help, and most of them were unable to access this service. Spirituality/religiosity did not help, while contact with the fetus and burial did. Conclusion: It is important to implement psychological services in obstetrics departments to offer adequate support, even in pandemic situations

Molecular Epidemiology of Mitochondrial Cardiomyopathy: A Search Among Mitochondrial and Nuclear Genes

Mitochondrial Cardiomyopathy (MCM) is a common manifestation of multi-organ Mitochondrial Diseases (MDs), occasionally present in non-syndromic cases. Diagnosis of MCM is complex because of wide clinical and genetic heterogeneity and requires medical, laboratory, and neuroimaging investigations. Currently, the molecular screening for MCM is fundamental part of MDs management and allows achieving the definitive diagnosis. In this article, we review the current genetic knowledge associated with MDs, focusing on diagnosis of MCM and MDs showing cardiac involvement. We searched for publications on mitochondrial and nuclear genes involved in MCM, mainly focusing on genetic screening based on targeted gene panels for the molecular diagnosis of the MCM, by using Next Generation Sequencing. Here we report twelve case reports, four case-control studies, eleven retrospective studies, and two prospective studies, for a total of twenty-nine papers concerning the evaluation of cardiac manifestations in mitochondrial diseases. From the analysis of published causal mutations, we identified 130 genes to be associated with mitochondrial heart diseases. A large proportion of these genes (34.3%) encode for key proteins involved in the oxidative phosphorylation system (OXPHOS), either as directly OXPHOS subunits (22.8%), and as OXPHOS assembly factors (11.5%). Mutations in several mitochondrial tRNA genes have been also reported in multi-organ or isolated MCM (15.3%). This review highlights the main disease-genes, identified by extensive genetic analysis, which could be included as target genes in next generation panels for the molecular diagnosis of patients with clinical suspect of mitochondrial cardiomyopathies

Genetic pre-participation screening in selected athletes: a new tool for the prevention of sudden cardiac death?

Sudden cardiac death (SCD) of athletes is a topical issue. “Borderline cardiac abnormalities”, which occur in ~2% of elite male athletes, may result in SCD, which may have a genetic base. Genetic analysis may help identify pathological cardiac abnormalities. We performed phenotype-guided genetic analysis in athletes who, pre-participation, showed ECG and/or echo “borderline” abnormalities, to discriminate subjects at a greater risk of SCD. Methods: We studied 24 elite athletes referred by the National Federation of Olympic sports; and 25 subjects seeking eligibility to practice agonistic sport referred by the Osservatorio Epidemiologico della Medicina dello Sport della Regione Campania. Inclusion criteria: a) ECG repolarization borderline abnormalities; b) benign ventricular arrhythmias; c) left ventricular wall thickness in the grey zone of physiology versus pathology (max wall thickness 12-15 mm in females; 13-16 mm in males). Based on the suspected phenotype, we screened subjects for the LMNA gene, for 8 sarcomeric genes, 5 desmosomal genes, and cardiac calcium, sodium and potassium channel disease genes. Results: Genetic analysis was completed in 37/49 athletes, 22 competitive and 27 non-competitive athletes, showing “borderline” clinical markers suggestive of hypertrophic cardiomyopathy (HCM,n. 24), dilated cardiomyopathy (n. 4), arrhythmogenic right ventricular dysplasia/cathecholaminergic polymorphic ventricular tachycardia (ARVD/CPVT, n. 11), long QT syndrome (LQTS, n. 4), sick sinus syndrome (SSS, n. 5), Brugada syndrome (BrS, n. 1). We identifyed 11 mutations in 9 athletes (an ARVD athlete was compound heterozygote for the PKP2 gene and an HCM athlete was double heterozygote for the MYBPC3 and TNNT2 genes): 3 known mutations related to LQTS, HCM and ARVD, respectively, and 8 novel mutations, located in the SCN5A, RyR2, PKP2, MYBPC3 and ACTC1 genes. The new mutations were absent in ~800 normal chromosomes and were predicted “probably damaging” by in silico analysis. Patch clamp analysis in channelopathies indicated for some mutation abnormal biophysical behavior of the corresponding mutant protein. Conclusion: Genetic analysis may help distinguish between physiology and pathology in athletes with clinically suspected heart disease

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves.tThe 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts

A module for adaptive course configuration and assessment in moodle

Personalization and Adaptation are among the main challenges in the field of e-learning, where currently just few Learning Management Systems, mostly experimental ones, support such features. In this work we present an architecture that allows moodle to interact with the Lecomps system, an adaptive learning system developed earlier by our research group, that has been working in a stand-alone modality so far. In particular, the Lecomps responsibilities are circumscribed to the sole production of personalized learning objects sequences and to the management of the student model, leaving to moodle all the rest of the activities for course delivery. The Lecomps system supports the "dynamic" adaptation of learning objects sequences, basing on the student model, i.e., learner's Cognitive State and Learning Style. Basically, this work integrates two main Lecomps tasks into moodle, to be directly managed by it: Authentication and Quizzes. All in all, and so far, the advantage of the presented integration is in the real possibility to deliver and take personalized courses, residing and basically remaining into the moodle environment. © 2010 Springer-Verlag

Automated and flexible comparison of course sequencing algorithms in the LS-Lab framework

Curriculum Sequencing is one of the most interesting challenges in learning environments, such as Intelligent Tutoring Systems and e-learning. The goal is to automatically produce personalized sequences of didactic materials or activities, on the basis of each individual student's model. In this paper we present the extension of the LS-Lab framework, supporting an automated and flexible comparison of the outputs coming from a variety of Curriculum Sequencing algorithms over the same student models. The main aim of LS-Lab is to provide researchers or teachers with a ready-to-use and possibly extensible environment, supporting a reasonably low-cost experimentation of several sequencing algorithms. The system accepts a student model as input, together with the selection of the algorithms to be used and a given learning material; then the algorithms are applied, the resulting courses are shown to the user, and some metrics computed over the selected characteristics are presented, for the user's appraisal. © 2010 Springer-Verlag