Application of next generation sequencing in cardiology: current and future precision medicine implications.

Inherited cardiovascular diseases are highly heterogeneous conditions with multiple genetic loci involved. The application of advanced molecular tools, such as Next Generation Sequencing, has facilitated the genetic analysis of these disorders. Accurate analysis and variant identification are required to maximize the quality of the sequencing data. Therefore, the application of NGS for clinical purposes should be limited to laboratories with a high level of technological expertise and resources. In addition, appropriate gene selection and variant interpretation can result in the highest possible diagnostic yield. Implementation of genetics in cardiology is imperative for the accurate diagnosis, prognosis and management of several inherited disorders and could eventually lead to the realization of precision medicine in this field. However, genetic testing should also be accompanied by an appropriate genetic counseling procedure that clarifies the significance of the genetic analysis results for the proband and his family. In this regard, a multidisciplinary collaboration among physicians, geneticists, and bioinformaticians is imperative. In the present review, we address the current state of knowledge regarding genetic analysis strategies employed in the field of cardiogenetics. Variant interpretation and reporting guidelines are explored. Additionally, gene selection procedures are accessed, with a particular emphasis on information concerning gene-disease associations collected from international alliances such as the Gene Curation Coalition (GenCC). In this context, a novel approach to gene categorization is proposed. Moreover, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, focusing on cardiology-related genes. Finally, the most recent information on genetic analysis's clinical utility is reviewed.

Markedly elevated troponin and NT-proBNP and myocardial dysfunction in an adolescent with severe diabetic ketoacidosis: A case report.

Severe diabetic ketoacidosis (DKA), rarely, may be associated with elevated troponin and proBNP levels in adults with a history of diabetes. However, few cases have reported this association in children with severe and complicated DKA. We describe a case of severe DKA (pH: 6.89, HCO3: 6.5) in a 14-yr-old female adolescent in which the symptoms of DKA were presented days before the diagnosis. The patient was under the effect of acidosis (Kussmaul respiration) for 12 h before admission to our hospital, where she was admitted in a critical clinical condition. After successful treatment with DKA with intensive intravenous fluid and regular insulin, the patient presented with abnormal cardiac rhythm, disturbance of interventricular septum motility, a mild decrease in left ventricular systolic function, negative T waves in leads III and aVF, and a marked increase in troponin and brain natriuretic peptide (NT-proBNP) levels. All abnormal findings completely resolved within 8 days after the initiation of DKA treatment. The phenomenon in our case was transient, and the patient had a good long-term outcome. However, it represents a challenge for clinicians; therefore, emphasis should be given to cardiac monitoring during the course of severe and prolonged DKA in children and adolescents.

Incentives and limitations of Greek blood donors: Application of the Health Belief Model in the design of recruiting strategies.

BACKGROUND: Studies of the behavior of blood donors suggest that the examination of their incentives and reported barriers could be utilized in designing targeted recruiting strategies and awareness-raising campaigns. METHODOLOGY: Data was collected via a questionnaire based on the Health Belief Model (HBM), aimed to examine reported incentives, limitations, benefits, and self-efficacy of 261 blood donors at Thriasio General Hospital from January 1 to March 1, 2020, after required permission provided. The analysis was performed by the use of the SPSS statistical software. In addition, a Greek translation of the K6+ distress scale was provided. RESULTS: Our sample consisted of 261 blood donors, the majority of which were men (88.5%), 40-50 years old (36.4%), high school graduates (49.4%), and married (53.3%). Heightened awareness of increased blood needs and blood shortages was mentioned. 92.8% of respondents believe that blood donation is an act of contribution to society or beneficial for their health (86.6%). The limited working hours of blood donation services are the main obstacle mentioned by the participants (32.8%), while 80.7% emphasized the need for public information campaigns. Based on the K6 scale answers score, most participants are classified in the intermediate-risk category for Serious Mental Illness (SMI). CONCLUSION: The study of beliefs and incentives of blood donors is a critical factor in developing an effective recruiting strategy in a volunteering frame. Public information campaigns regarding the blood donation process and reminders aiming at the return of blood donors after the necessary time interval could facilitate this effort.

Recent Advances in Ruthenium-Catalyzed Hydrogenation Reactions of Renewable Biomass-Derived Levulinic Acid in Aqueous Media.

Levulinic acid (LA) is classified as a key platform chemical for the development of future biorefineries, owing to its broad spectrum of potential applications and because it is simply available from lignocellulosic biomass through inexpensive and high-yield production routes. Catalytic hydrogenation reactions of LA into the pivotal intermediate compound γ-valerolactone (GVL), and beyond GVL to yield valeric acid (VA), 1,4-pentanediol (1,4-PDO), and 2-methyltetrahydrofuran (2-MTHF) have gained considerable attention in the last decade. Among the various transition metals used as catalysts in LA hydrogenation reactions, ruthenium-based catalytic systems have been the most extensively applied by far, due to the inherent ability of ruthenium under mild conditions to hydrogenate the keto functionality of LA selectively into an alcohol group to form 4-hydroxyvaleric acid intermediate, which yields GVL spontaneously after dehydration and cyclization. This review focuses on recent advances in the field of aqueous-phase ruthenium-catalyzed hydrogenation reactions of LA toward GVL, VA, 1,4-PDO, 2-MTHF, 2-pentanol, and 2-butanol. It employs heterogeneous catalysts on solid supports, and heterogeneous water-dispersible catalytic nanoparticles or homogeneous water-soluble catalytic complexes with biphasic catalyst separation, for the inter alia production of advanced biofuels such as valeric biofuels and other classes of liquid transportation biofuels, value-added fine chemicals, solvents, additives to gasoline, and to food as well. The significance of the aqueous solvent to carry out catalytic hydrogenations of LA has been highlighted because the presence of water combines several advantages: (i) it is highly polar and thus an ideal medium to convert polar and hydrophilic substrates such as LA; (ii) water is involved as a byproduct; (iii) the presence of the aqueous solvent has a beneficial effect and enormously boosts hydrogenation rates. In sharp contrast, the use of various organic solvents gives rise to a dramatic drop in catalytic activities. The promotional effect of water was proven by numerous experimental investigations and several theoretical studies employing various types of catalytic systems; (iv) the large heat capacity of water renders it an excellent medium to perform large scale exothermic hydrogenations more safely and selectively; and (v) water is a non-toxic, safe, non-inflammable, abundantly available, ubiquitous, inexpensive, and green/sustainable solvent.

Association between blood pressure and risk of cancer development: a systematic review and meta-analysis of observational studies.

With the exception of renal cell carcinoma, studies assessing the association between hypertension and other cancers are inconsistent. We conducted a meta-analysis to assess this evidence. We included observational studies investigating the association between any definition of hypertension or systolic and diastolic blood pressure and risk of any cancer, after searching PubMed until November 2017. We calculated summary relative risks (RR) and 95% confidence intervals (CI) using inverse-variance weighted random effects methods. A total of 148 eligible publications were identified out of 39,891 initially screened citations. Considering only evidence from 85 prospective studies, positive associations were observed between hypertension and kidney, colorectal and breast cancer. Positive associations between hypertension and risk of oesophageal adenocarcinoma and squamous cell carcinoma, liver and endometrial cancer were also observed, but the majority of studies did not perform comprehensive multivariable adjustments. Systolic and diastolic blood pressure were positively associated with risk of kidney cancer but not with other cancers. In addition to the previously well-described association between hypertension and risk of kidney cancer, the current meta-analysis suggested that hypertensive individuals may also be at higher risk of colorectal and breast cancer. However, careful interpretation is required as most meta-analyses included relatively small number of studies, several relative risks had weak or moderate magnitude and maybe affected by residual confounding.

The contribution of the medial retinaculum as a restraining factor to the patella dislocation.

The objective of this study was to evaluate the contribution of the medial retinaculum to the stability of the patella, for several angles of knee flexion. For six cadaveric knees, the patella and patella retinaculum were exposed, and the force required to dislocate the patella laterally by 5 mm was measured, in 0, 45 and 90 degrees of knee flexion, preserving and dissecting the medial retinaculum. Wilcoxon singed rank test (SPSS, version 23, Chicago, USA) was used for data analysis. A p value of < 0.05 was considered as statistically significant. The force required to displace the patella laterally is smaller with the medial retinaculum dissected than intact, in 0, 45 and 90 degrees (p = 0.028, p = 0.046, p = 0.027 respectively). The lateral displacement force is greater as the flexion angle increases, with medial retinaculum intact or dissected (p = 0.028). Thus, an intact medial retinaculum provides more stability against lateral displacement forces to the patella, especially in lower flexion angles. Consequently, surgical methods reinforcing the medial retinaculum combined or not with lateral retinaculum release, are of great importance in the plan of the orthopedic surgeons. The engagement of the bones during flexion of the knee contributes significantly to the stability of the patella.

Mapping the expanded often inappropriate use of the Framingham Risk Score in the medical literature.

OBJECTIVES: To systematically evaluate the use of Framingham Risk Score (FRS) in the medical literature and specifically examine the use of FRS in different populations and settings and for different outcomes than the ones originally developed for. STUDY DESIGN AND SETTING: We identified all the citations to the article by Wilson et al. (1998), in which FRS was originally described through ISI Web of Science until April 2011. We selected studies that stated in their abstract that they calculated or used the FRS for any reason and extracted information on publication date, population studied, outcome, or disease risk factor with which FRS was associated and study design. RESULTS: We identified 375 eligible articles corresponding to 471 analyses using the FRS in cohort (n = 141), case-control (n = 16), or cross-sectional (n = 314) settings. Only a minority of the cohort studies had as a primary aim to externally validate the FRS (n = 45). The studied population was different (from general or healthy) in 35 (25%) and 133 (42%) of the cohort and cross-sectional analyses, respectively. All case-control studies examined healthy controls. The studied outcome was different (from coronary heart disease) in 79 (56%) of the cohort analyses and 10 (63%) of the case-control studies. Overall, only 46 (33%) of the 141 cohort analyses examined the same outcome and population as FRS was originally developed for. CONCLUSION: A large number of studies use FRS in populations and for outcomes other than the ones it has been developed for and therefore for which its performance is unknown and nonvalidated.