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This article reports the first detection of Grapevine pararetrovirus (GPRV) infecting grapevines in Greece. Leaf samples from a commercial vineyard in the Messinia region were collected and analyzed using high-throughput sequencing (HTS) and PCR. GPRV was confirmed in two of the samples, and their sequences were submitted to GenBank. The presence of GPRV in Greece suggests that its distribution may be wider than previously thought, emphasizing the need for further surveillance. The study was supported by grants and funding from the University of Crete and the European Union's Horizon 2020 program. [Extracted from the article]

We give sufficient conditions for the existence of complex ℓ 2 solutions of a non-homogeneous system of linear difference equations and of two general classes of delay systems of linear difference equations. In some cases, bounds of the established solutions are also given. As a consequence of the space ℓ 2 where we work, information can be obtained about the asymptotic behavior of the established solutions and, the asymptotic stability of the zero equilibrium point of the systems under consideration. The method we use is a functional-analytic one. [ABSTRACT FROM AUTHOR]

A discrete equivalent and not analogue of the well-known logistic differential equation is proposed. This discrete equivalent logistic equation is of the Volterra convolution type, is obtained by use of a functional-analytic method, and is explicitly solved using the -transform method. The connection of the solution of the discrete equivalent logistic equation with the solution of the logistic differential equation is discussed. Also, some differences of the discrete equivalent logistic equation and the well-known discrete analogue of the logistic equation are mentioned. It is hoped that this discrete equivalent of the logistic equation could be a better choice for the modelling of various problems, where different versions of known discrete logistic equations are used until nowadays.

We will give the generalization of a recently developed functional-analytic method for studying linear and nonlinear, ordinary and partial, difference equations in the and spaces, p∈ℕ, . The method will be illustrated by use of two examples concerning a nonlinear ordinary difference equation known as the Putnam equation, and a linear partial difference equation of three variables describing the discrete Newton law of cooling in three dimensions.

Introduction: Phenylketonuria (PKU), an inborn error of metabolism, when inadequately treated, may lead to nutritional deficits, which could affect bone health. This remains a controversial issue, given that in the majority of PKU cases, bone mineral density is within normal limits. On the other hand, WNT1 mutations are detrimental for bone, as they lead to primary osteoporosis., Case Presentation: We present an eleven-year-old girl under a very strict diet for PKU (i.e., with low phenylalanine levels) and severe osteoporosis, signified by the presence of multiple vertebral fractures, which could not be attributed to her inborn error of metabolism. Family screening, including bone densitometry, revealed unexplained osteoporosis in her father and brother. Further genetic workup revealed a new WNT1, disease-causing mutation. The patient's dietary plan was modified, in order to achieve better metabolic control, and she was given vitamin D and calcium supplements. These measures led to great clinical and radiological improvement, without the use of bisphosphonates., Conclusion: In a patient with a chronic disorder known to affect the skeleton, the presence of disproportionally severe osteoporosis should prompt further diagnostic workup, in order to explain the severe bone phenotype, thus enabling more efficient and targeted therapeutic interventions., (© 2024 S. Karger AG, Basel.)

Background: Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor TBX5 (T-box transcription factor 5) and no SCN5A variant., Methods: We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals)., Results: TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced "late" cardiac sodium current (I Na ), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct SCN5A down-regulation caused decreased peak I Na , and that reduced PDGF receptor ( PDGFRA [platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late I Na . Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval ( P <0.001)., Conclusions: These results not only establish decreased SCN5A transcription by the TBX5 variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor-mediated PI3K signaling.

The significance of the right ventricle (RV) as a predictor of outcomes in a series of cardiac conditions has recently been recognized. Consequently, more studies are now focusing on improving the assessment of the RV. Its primary function is to support adequate pulmonary perfusion pressure in different circulatory and loading situations and to ensure that there is a low systemic venous pressure. Echocardiography is the first-line method of choice due to its accuracy when assessing RV structure and function, as well as its wide availability. The geometry of the RV is complex and its evaluation can be difficult. Integrating and combining multiple parameters may be a more reliable way to determine normal or abnormal function. Novel techniques are increasingly being performed more routinely in clinical practice and are facilitating diagnosis and treatment choices., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © The Author(s), 2022. Published by Radcliffe Group Ltd.)

Sarcopenia is a progressive clinical syndrome characterized by general loss of skeletal muscle mass and impaired muscle function. Due to the general progressive aging of population, sarcopenia has gradually grown into a global health problem, with great negative impact on the quality of life of the affected patients as well as an adverse societal impact. In this review, we discuss the pathophysiology, diagnosis, and determination of severity of sarcopenia. Special attention is given to the rehabilitative treatment against sarcopenia, pointing out that a thorough evaluation and intervention of nutritional deficits and exercise capacity as well as treatment with medical agents are needed in order to personalize the treatment according to the patient's needs. By targeting goals to improve musculoskeletal and functional disorders associated with chronic conditions, clinicians could apply a therapeutic plan focusing on how to prevent/delay the development of sarcopenia and improve the quality of the patients' lives.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Familial dilated cardiomyopathy (DCM) is characterized by ventricular dilation and depressed myocardial performance. It is a genetically heterogeneous disorder associated with mutations in over 60 genes. We carried out whole exome sequencing in combination with cardiomyopathy-related gene-filtering on two affected family members to identify the possible causative mutation in a consanguineous Iranian family with DCM. Two novel variants in cardiomyopathy-related genes were identified: c.247 A > C; p.N83H in the Troponin T Type 2 gene (TNNT2) and c.2863G > A; p.D955N in the Myosin Heavy Polypeptide 7 gene (MYH7). Sanger sequencing and co-segregation analysis in the remaining family members supported the coexistence of these digenic mutations in affected members of the family. Carriers of either variant alone were asymptomatic. In summary, we find that digenic inheritance of two novel variants in DCM related genes is associated with a severe form of DCM. Exome sequencing has been shown to be very useful in identifying pathogenic mutations in cardiomyopathy families, and this report emphasizes the importance of comprehensive screening of DCM related genes, even after the identification of a single disease-causing mutation., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Providers of supported living services to adults with intellectual disabilities (IDs) in the United Kingdom have procedures in place to monitor injuries; this provides opportunity to learn about the injuries being reported and recorded. The aim was to determine the incidence, causes and types of injuries experienced by 593 adults with intellectual disabilities who live with paid support in a 12-month period., Method: Injury data, collected via a standard electronic injury monitoring system, were compared with data collected for a matched sample of the general population in the same year., Results: The adults with intellectual disabilities experienced a higher rate of injury. Falls were the commonest cause of injury for both samples, but significantly more so for the adults with intellectual disabilities., Conclusions: The higher rate of injuries, particularly minor injuries, being reported suggests a culture of injury reporting and recording within these supported living services. Electronic injury monitoring is recommended for organizations providing supported living services for adults with intellectual disabilities., (© 2016 John Wiley & Sons Ltd.)

Objectives: Coagulopathy and mesenteric thrombosis are common in premature neonates with necrotizing enterocolitis (NEC). This pilot study aimed to investigate the hypothesis that there are changes in the gene expression related to the coagulation and anticoagulation systems in NEC., Methods: Consecutive neonates (n = 11) with NEC (Bell stages 2-3) were recruited. Two comparison groups, matched for birth weight and corrected gestational age, were selected based on the absence of inflammation and coagulopathy (healthy control, n = 10), or the presence of a confirmed blood infection (sepsis control, n = 12). A pathway-specific quantitative polymerase chain reaction array was used to determine the expression of 94 genes involved in human blood coagulation and anticoagulation cascade., Results: Twelve genes of the coagulation and anticoagulation systems were significantly altered in the patients with NEC compared with healthy controls. In particular, neutrophil elastase, CD63, PROS1, HGF, and F12 were significantly upregulated (mean fold changes [FCs] +2.74, P < 0.05) with an overall procoagulant effect; MFGE8, factor II (thrombin) receptor-like 1 (F2RL1), FGL2, PLAT, PROCR, SERPIND1, and HNF4A were significantly downregulated (mean FCs -2.45, P < 0.05) with a reduction in fibrinolysis and endothelial regeneration. In the comparison between NEC and sepsis, we did observe a significant difference in expression of F2RL1 (FC -2.50, P = 0.01)., Conclusions: We have identified potential biomarkers associated with coagulopathy and disease progression in NEC. In particular, the overall procoagulant status, at the transcriptional level, should be further investigated to unveil molecular mechanisms leading to intestinal necrosis, multiorgan failure, and death.

Aims: Brugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration., Methods and Results: A multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN, CASQ2, TKT, TBX3, and TBX5) in 156 Caucasian SCN5A mutation-negative BrS patients (80% male; mean age 48) with symptoms (64%) and/or a family history of sudden death (47%) or BrS (18%). Forty-nine variants were identified: 18 were rare (MAF <1%) and non-synonymous; and 11/18 (61.1%), mostly in SCN10A, were predicted as pathogenic using multiple bioinformatics tools. Allele frequencies were compared with the Exome Sequencing and UK10K Projects. SKAT methods tested rare variation in SCN10A finding no statistically significant difference between cases and controls. Co-segregation analysis was possible for four of seven probands carrying a novel pathogenic variant. Only one pedigree (I671V/G1299A in SCN10A) showed co-segregation. The SCN10A SNP V1073 was, however, associated strongly with BrS [66.9 vs. 40.1% (UK10K) OR (95% CI) = 3.02 (2.35-3.87), P = 8.07 × 10-19]. Voltage-clamp experiments for NaV1.8 were performed for SCN10A common variants V1073, A1073, and rare variants of interest: A200V and I671V. V1073, A200V and I671V, demonstrated significant reductions in peak INa compared with ancestral allele A1073 (rs6795970)., Conclusion: Rare variants in the screened QRS-associated genes (including SCN10A) are not responsible for a significant proportion of SCN5A mutation negative BrS. The common SNP SCN10A V1073 was strongly associated with BrS and demonstrated loss of NaV1.8 function, as did rare variants in isolated patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Ventricular arrhythmia induced by drugs (pro-arrythmia) is an uncommon event, whose occurrence is unpredictable but potentially fatal. The ability of a variety of medications to induce these arrhythmias is a significant problem facing the pharmaceutical industry. Genetic variants have been shown to play a role in adverse events and are also known to influence an individual's optimal drug dose. This review provides an overview of the current understanding of the role of genetic variants in modulating the risk of drug induced arrhythmias., (© 2013 The British Pharmacological Society.)

Background: Tetralogy of Fallot (ToF) patients face an increased risk of sudden cardiac death late after repair. Heart rate turbulence (HRT) indices are well-known predictors of sudden cardiac death. We aimed to estimate whether HRT is impaired in repaired ToF patients compared to healthy controls and relate those HRT parameters to already recognized prognostic markers., Methods: Continuous ECG recordings were performed in 19 patients late after ToF repair (36.3+/-12.4 years, 26.6+/-7.1 years after repair) and 20 age-matched healthy controls (40.8+/-8.1 years). Turbulence slope (TS) and onset (TO), frequency and time domain heart rate variability parameters and QRS duration were estimated. Volumes of the right (RV) and left ventricle (LV) and ejection fraction (EF) were assessed by cardiovascular magnetic resonance imaging. Cardiopulmonary exercise testing was used to estimate peak oxygen consumption (VO(2)) and VE/VCO(2) slope., Results: TS (15.95+/-9.41 vs 28.73+/-12.24 ms/RRI, p=0.0007) and TO (-0.98+/-2.06% vs -3.45+/-3.25%, p=0.007) were found to be significantly different between ToF patients and controls. TO correlated with LVEF (r=0.47, p<0.05), LVSVi (r=0.50, p=0.03), RVEF (r=0.53, p=0.02), peak VO(2) (r=0.50, p=0.05), VE/VCO(2) slope (r=-0.55, p=0.03) and with heart rate variability frequency domain indices (log LF, r=0.47, p=0.04, log HF, r=0.56, p=0.01)., Conclusion: HRT indices are impaired in ToF patients late after surgical repair compared to healthy controls and relate to coexisting haemodynamic, ventilatory and autonomic impairment. A clinical prognostic role of HRT may be speculated, which warrants further investigation.

Objectives: This study was performed to evaluate the feasibility of quantitative analysis of exercise echocardiography using pulsed wave Doppler myocardial imaging (DMI) and to examine the relation between age and DMI parameters at rest and during graded exercise in normal subjects., Methods and Results: Seventy-two healthy volunteers were divided into three age groups (group I, age < or = 40 years, group II, age 41 - 59 years and group III, age > or = 60 years), and underwent a semi-supine exercise echocardiogram. Peak systolic velocity (SV), time to peak SV (TPV), systolic velocity time integral (VTI) and peak diastolic velocities (VE and VA) were measured off-line. There was a heterogeneity in DMI parameters between different myocardial walls and a gradient was found between basal and mid segments. Both persisted during exercise. Group I had significantly higher TPV than groups II and III. Increase in workload was accompanied by an increase in velocities, while TPV decreased. Differences between groups persisted throughout exercise., Conclusions: Off-line measurements of DMI parameters are feasible during exercise. SV and E decline as age increases while A increases. SV already increases at low charge exercise and may serve as a quantitative marker for the detection of myocardial viability. Change of the absolute DMI velocity values during exercise may provide a better indicator of ischaemia or viability than the absolute values themselves.

Following thrombolysis and primary percutaneous transluminal coronary angioplasty (PTCA) for acute ST segment elevation myocardial infarction, basal flow in the culprit artery is known to influence prognosis. The purpose of this study was to determine if differences exist in basal flow in culprit and nonculprit coronary arteries in patients with acute ST segment elevation myocardial infarction who were treated with thrombolysis or primary PTCA with stent implantation. Twenty patients were randomized to thrombolysis (with recombinant tissue plasminogen activator) and 24 to primary PTCA with stent implantation within 3 hours of onset of acute ST segment elevation myocardial infarction. Coronary angiography was performed 90-120 minutes after thrombolysis or immediately after PTCA with stent implantation and again at 18-36 hours after intervention in both groups. Patients who failed to achieve thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow were excluded. The corrected TIMI frame count was used as the index of basal coronary artery flow. Early after intervention the mean corrected TIMI frame count in the culprit coronary artery was significantly lower in the primary PTCA with stent group (27.4 +/- 7.7 frames) than in the thrombolysis group (39.8 +/- 10 frames, p < 0.001). Eight thrombolysis patients (40%) and 20 primary PTCA patients (83%, p < 0.01) achieved TIMI grade 3 flow early after intervention. By 18-36 hours after intervention there were no significant differences in the mean correct TIMI frame count between the thrombolysis and primary PTCA with stent groups. There were no significant differences in the mean corrected TIMI frame count between these two groups in the nonculprit coronary artery, either early after intervention or at 18-36 hours. In successfully reperfused coronary arteries following acute ST segment elevation myocardial infarction, primary angioplasty with stent implantation reestablished TIMI grade 2 or 3 flow faster and more effectively than thrombolysis did.

A 42-year-old man presented with effort angina pectoris of 20 minutes' duration. Hypertrophic obstructive cardiomyopathy, severe myocardial bridging involving the midleft anterior descending coronary artery, and apical hypokinesis were identified. Regional wall motion normalized following the initiation of beta blockade.

Several previous studies have shown that endothelin-1 (ET 1) plasma levels are raised in cases of endothelial abnormality and microvascular dysfunction. Syndrome-X constitutes an important clinical entity characterized by angina-like pain and normal coronary arteries which is believed to reflect microvascular dysfunction. The aim of the present study was to investigate the role of ET 1 in the pathophysiology of the above syndrome. For that purpose the plasma ET 1 concentrations, measured by radioimmunoassay, between 28 X-syndrome patients (group A) and 10 age-matched normal control subjects (group B) at rest and at the peak of the exercise testing were compared. We specify that all individuals of group A were referred to our Department for effort angina and were found to have normal coronary arteriograms, negative ergonovine and hyperventilation test and positive exercise test. Our results showed that while at rest ET 1 plasma concentrations did not differ significantly between the two groups, at the peak of the exercise test its levels were found to be significantly higher in syndrome-X patients as compared with those of normal subjects (p< 0.001). In addition, in healthy control subjects ET 1 levels decreased during exercise as compared with the baseline values and that difference was found to be statistically significant (p approximately 0.01). The above finding suggests opposite kinetics during exercise of ET 1 between the two groups studied, which could explain effort angina onset in patients with syndrome-X.