Epigenetic and Coping Mechanisms of Stress in Affective Disorders: A Scoping Review.

This review aims to explore the intricate relationship among epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorder occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes, such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay among genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Elderly Individuals Residing in Nursing Homes in Western Romania Who Have Been Diagnosed with Hearing Loss are at a Higher Risk of Experiencing Cognitive Impairment.

Purpose: The objective of this research was to determine if there is any correlation between the severity of neurocognitive disorder and hearing impairment in the elderly. Patients and Methods: This is a population-based observational study that included subjects aged ≥ 65 years. They were evaluated for the existence of cardiovascular risk factors, diabetes, stroke, alcohol abuse, and smoking. Hearing impairment was diagnosed by an audiologist, using behavioral audiometric examination. These evaluations might have been performed in response to concerns about hearing loss, or they could have been a routine component of yearly comprehensive health screenings that included a Mini-Mental State Examination 2nd Edition (MMSE-2) test. According to the results of the MMSE-2 scale, we divided the individuals into two groups, Group I for those who had cognitive impairment and severe neurocognitive disorder, and Group II for those who did not have cognitive impairment. Results: The study enrolled 203 patients with a mean age of 77 ± 7.5 years (range 65-98), 99 (48%) were males. When comparing the two groups, group I patients presented more often cardiovascular risk factors, stroke, diabetes, and impaired hearing. The univariable logistic regression found that cognitive impairment was significantly more frequent in the elderly with cardiovascular disease, diabetes, and stroke (p<0.0001). The multivariate regression analysis found that stroke (p<0.0001) diabetes (p=0.0008), cardiovascular disease (p=0.0004), and impaired hearing (p=0.0011) were significantly linked to cognitive impairment. The occurrence of hearing impairment in the elderly was related to having an MMSE-2 score of 14 or below. Conclusion: According to the findings of this research, the elderly who have trouble hearing in addition to other conditions might have an increased risk for severe neurocognitive disorder.

Subtle Changes in Myocardial Work Indices Assessed by 2D-Speckle Tracking Echocardiography Are Linked with Pathological LV Remodeling and MACEs Following an Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

The goal of this study was to assess whether subtle changes in myocardial work indices may predict left ventricular (LV) remodeling and major cardiac events (MACEs) in patients with a first ST-elevation acute myocardial infarction (STEMI) and preserved LVEF after successful myocardial revascularization with PCI. Methods. Consecutive STEMI patients in sinus rhythm and with an LV ejection fraction ≥ 50% following a successful PCI were recruited. Conventional and two-dimensional speckle tracking echocardiography (2D-STE) was conducted within 36 h of the PCI and 3 months later. Patients having an increase of more than 20% in LV diastolic volume were included in the LV remodeling group. MACEs were noted throughout a four-year period of follow-up. Results: The study comprised 246 STEMI patients with a mean age of 66; 72% of whom were men. In 24% (58) of the patients, LV remodeling developed. These patients were older, more frequently hypertensive, and had a smoking history. They also exhibited significantly lower baseline and 3-month values for the myocardial global index (GWI), global constructive work (GCW), and global myocardial efficiency (GWE). The cut-off values of 1670 mmHg% for GWI and 83% for GWE were predictive of LV remodeling (p < 0.0001). During the four-year follow-up period, 19% of STEMI patients experienced a MACE, involving 15% from non-LV remodelers and 34% from LV remodelers (p = 0.01). The cut-off values for baseline GWI of 1680 mmHg% and baseline GWE of 84% had the best accuracy in predicting MACEs. In conclusion, non-invasive myocardial work indices offered a reproducible and accurate method to predict post-MI LV remodeling and MACEs.

Increased Left Atrial Stiffness is Significantly Associated with Paroxysmal Atrial Fibrillation in Diabetic Patients.

Purpose: Atrial fibrillation (AF) and diabetes mellitus (DM) are common pathogenic diseases. Diabetes is an independent risk factor for AF, and coexisting AF is a risk factor for the diabetic pa-tient's progression. The purpose of this study was to see if two-dimensional-speckle tracking echocardiography (2D-STE) might provide valuable criteria for determining the risk of AF in diabetic patients. Patients and Methods: This retrospective study compared 30 adult diabetic patients with documented paroxysmal atrial fibrillation (PAF) with 30 age- and sex-matched diabetic patients without PAF. Inclusion criteria were: age ≥18 years, sinus rhythm, diabetes mellitus type 2, and the ability to sign the informed consent. Exclusion criteria included: moderate or severe valvular disease, previous myocardial infarction, left ventricular ejection fraction (LVEF) <50%, congenital heart disease, a history of cardiac surgery, paced atrial or ventricular rhythm, inadequate echocardiography imaging. The medical history, clinical, biochemical data and the results of the transthoracic cardiac ultrasound examination were registered during their evaluation at the outpatients cardiology clinics. Results: The mean age of the patients was 62.5±1.7 years, 60% were men. Diabetic patients who experienced PAF episodes demonstrated significantly impaired left atrial (LA) deformation patterns, with decreased LA strains and increased LA stiffness (p < 0.05). Conclusion: The present study demonstrates that LA strains and LA stiffness are significantly associated with the occurrence of PAF in diabetic patients. As 2D-STE of the LA is more sensitive than routine echocardiographic examination, it should be performed in patients suspected of being suffering from PAF.

Myocardial Work Evaluation-A Useful Non-Invasive Method to Predict Coronary Artery Sub-Occlusion in a Patient with Unstable Angina and Multiple Myocardial Revascularization Interventions.

BACKGROUND: While lifestyle changes, management of coronary artery disease (CAD) risk factors, myocardial revascularization procedures, and medication can improve a patient's prognosis, de novo native coronary lesions and in-stent restenosis (ISR) remain significant clinical concerns. ISR is more frequent with a bare-metal stent than with a drug-eluting stent and has been documented in around 12% of DES patients. Acute coronary syndrome (ACS) manifests as unstable angina in about 30% to 60% of ISR patients. Myocardial work imaging is a modern, non-invasive technique able to identify individuals with critical coronary artery lesions with high sensitivity and specificity. CASE REPORT: We present the case of a 72-year-old Caucasian gentleman with multiple cardiovascular risk factors, admitted to the Cardiology Clinic of Timișoara Municipal Hospital with unstable angina. From 1999 to 2021, the patient experienced two myocardial infarctions, a double aortocoronary bypass graft, and multiple percutaneous coronary interventions with 11 stent implantations, including 6 for ISR. Using two-dimensional speckle-tracking echocardiography and myocardial work assessment, we detected that the lateral wall of the left ventricle had a severely impaired deformation pattern. Angio-coronarography was performed, and sub-occlusion of the posterolateral branch of the right coronary artery was found. Angioplasty was performed and a DES was inserted, with a good final angiographic result and complete release of symptoms. CONCLUSION: In patients with a history of multiple myocardial revascularization interventions and ISR, it is challenging to identify the critical ischemia region by non-invasive methods. Myocardial work imaging was beneficial in the detection of the altered deformation patterns indicating significant ischemia, its accuracy being superior to that of LV strain, as proven by coronary angiography. Urgent coronary angiography followed by angioplasty and stent implantation resolved the issue.

Fall Risk in Elderly with Insomnia in Western Romania-A Retrospective Cross-Sectional Study.

Background and Objectives: Falls are frequent among the elderly, imply large social and economic costs, and have serious outcomes. The purpose of this study was to investigate the links between insomnia, comorbidities, multisite pain, physical activity, and fall risk in the elderly. Materials and Methods: This retrospective cross-sectional study included persons recruited from nursing homes for the elderly in Timisoara. We separated the participants into two groups by the absence (group I) or presence of fractures (group II) starting with the age of 65 years. Participants were asked how they feel about their sleep using one item on a 4-point scale from the Assessment of Quality of Life questionnaire. The risk of fall was evaluated using the Falls Risk Assessment Tool. Results: The study enrolled 140 patients with a mean age of 78.4 ± 2.4 years (range 65-98 years), 55 of them being males (39%). By comparing the two groups, we found that the elderly with a history of fractures had a greater number of comorbidities, a higher risk of fall, and more severe sleep disturbances. When using univariate logistic regression, the occurrence of fractures in the elderly was significantly associated with the number of comorbidities, the risk of fall, and the presence of sleep disturbances (p < 0.0001). The multivariate regression analysis selected four independent parameters significantly linked to fractures, and these were the number of comorbidities (p < 0.03), the risk of fall score (p < 0.006), and the sleep disturbances of type 3 (p < 0.003) and 4 (p = 0.001). Conclusions: A fall-risk score over 14 and a number of comorbidities over 2 were notably associated with the occurrence of fractures. We also found strong positive correlations between the type of sleep disturbance and the risk of fall score, the number of comorbidities, and the number of fractures in the elderly.

Significant Association between Subclinical Left Cardiac Dysfunction and Liver Stiffness in Metabolic Syndrome Patients with Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.

Background and Objectives: Diabetes mellitus (DM) is connected to both cardiovascular disease and non-alcoholic fatty liver disease (NAFLD), and is an important component of metabolic syndrome (MetS). NAFLD can be detected and quantified using the vibration controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), whereas traditional and two-dimensional speckle tracking echocardiography (2D-STE) can reveal subclinical abnormalities in heart function. We sought to see if there was a link between left cardiac dysfunction and different levels of hepatic fibrosis in MetS patients with DM and NAFLD. Patients and Methods: We recruited successive adult subjects with MetS and a normal left ventricular ejection fraction, who were divided into two groups according to the presence or absence of DM. The presence of NAFLD was established by CAP and VCTE, while conventional and 2D-STE were used to assess left heart's systolic and diastolic function. The mean age of the MetS subjects was 62 ± 10 years, 82 (55%) were men. The distribution of liver steatosis severity was similar among diabetics and non-diabetics, while liver fibrosis grade 2 and 3 was significantly more frequent in diabetics (p = 0.02, respectively p = 0.001). LV diastolic dysfunction was found in 52% of diabetic and in 36% of non-diabetic MetS patients (p = 0.04). 2D-STE identified in the diabetic subjects increased LA stiffness (40% versus 24%, p = 0.03) and reduced global left ventricular longitudinal strain (47% versus 16%, p < 0.0001). Liver fibrosis grade ≥ 2 was identified as an independent predictor of both subclinical LV systolic dysfunction and of LA dysfunction in MetS patients with DM (p < 0.0001). Conclusions: The current investigation confirms the link between liver stiffness and subclinical cardiac dysfunction as detected by 2D-STE in MetS patients with DM. The novel parameters derived from LA and LV 2D-STE have demonstrated greater sensitivity compared to the older measurements, and a substantial connection with hepatic fibrosis.

Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells.

Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata, has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen's eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved.

Left Ventricular Remodeling and Heart Failure Predictors in Acute Myocardial Infarction Patients with Preserved Left Ventricular Ejection Fraction after Successful Percutaneous Intervention in Western Romania.

(1) Acute myocardial infarction (AMI) patients are at risk of left ventricular (LV) remodeling and heart failure (HF), even after successful revascularization by percutaneous coronary intervention (PCI). We wanted to assess the independent predictors of these outcomes in AMI patients. (2) Methods: The study enrolled patients with a LVEF ≥50% after a successful PCI for their first AMI. After 24 months, patients were separated into two groups based on whether their LVEF remained ≥50% (group I), or decreased to <50% (group II). (3) Outcomes: 26% of the patients experienced a decrease in LVEF below 50%, 41% showed LV remodeling, and 8% had experienced HF hospitalizations. HF hospitalizations were significantly more frequent in group II patients (p < 0.0001). The Killip class at admission >2, infarct-related longitudinal strain ≤−12.5%, and the presence of LV remodeling were identified as independent predictors of HF hospitalizations. (4) Conclusions: About 26% of AMI patients with normal LV function after a successful PCI developed HF. More sensitive techniques are required that allow for a more efficient risk-stratification and preventive therapy to reduce LV remodeling and HF in AMI patients with LVEF ≥50% after a successful PCI. The detection of abnormal ventricular deformation patterns after PCI by speckle-tracking echocardiography might be a valuable method in this approach.

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells.

Background and Objectives: The consumption of dietary supplements has increased over the last decades among pregnant women, becoming an efficient resource of micronutrients able to satisfy their nutritional needs during pregnancy. Furthermore, gestational drug administration might be necessary to treat several pregnancy complications such as hypertension. Folic acid (FA) and folate (FT) supplementation is highly recommended by clinicians during pregnancy, especially for preventing neural tube birth defects, while labetalol (LB) is a ß-blocker commonly administered as a safe option for the treatment of pregnancy-related hypertension. Currently, the possible toxicity resulting from the co-administration of FA/FT and LB has not been fully evaluated. In light of these considerations, the current study was aimed at investigating the possible in vitro cardio- and hepato-toxicity of LB-FA and LB-FT associations. Materials and Methods: Five different concentrations of LB, FA, FT, and their combination were used in myoblasts and hepatocytes in order to assess cell viability, cell morphology, and wound regeneration. Results: The results indicate no significant alterations in terms of cell viability and morphology in myoblasts (H9c2(2-1)) and hepatocytes (HepaRG) following a 72-h treatment, apart from a decrease in the percentage of viable H9c2(2-1) cells (~67%) treated with LB 150 nM−FT 50 nM. Additionally, LB (50 and 150 nM)−FA (0.2 nM) exerted an efficient wound regenerating potential in H9c2(2-1) myoblasts (wound healing rates were >80%, compared to the control at 66%), while LB-FT (at all tested concentrations) induced no significant impairment to their migration. Conclusions: Overall, our findings indicate that LB-FA and LB-FT combinations lack cytotoxicity in vitro. Moreover, beneficial effects were noticed on H9c2(2-1) cell viability and migration from LB-FA/FT administration, which should be further explored.

Fibrosis Predictive Score in Caucasian Patients with Metabolic Syndrome.

Introduction: Many of the patients presenting with metabolic syndrome (MetS) also have liver steatosis (NAFLD) and some of them could develop liver fibrosis. Purpose: To develop a simple score that could rule out fibrosis, especially significant fibrosis (F≥2) and could be used in daily practice in patients with MetS, in order to identify patients at risk. Patients and Methods: A total of 204 patients with MetS were prospectively enrolled. Evaluation of liver fibrosis was made using Vibration Controlled Transient Elastography while evaluation of steatosis was achieved using ultrasound (US). Results: Out of 204 patients with MetS, 179 patients (87.7%) had reliable liver stiffness measurements and 22.9% (41/179) had F ≥2. To formulate the fibrosis predicting score, all clinical variables associated with F ≥2 in the univariate analysis were considered in a multivariate regression model. According to the power of correlation, by consensus, we attributed 1 point for BMI >31.4 kg/m2, 1 point for female gender, 1 point for HDLc <47mg/dL, 1 point for mild steatosis at US, 1.5 point for moderate and 2 points for severe steatosis. Conclusion: At an optimal cut-off value of <3.5, our score could be used to rule-out the risk for developing at least significant fibrosis with a high negative predictive value (NPV 89.2%) in patients with MetS.

Left Atrial Strain Helps Identifying the Cardioembolic Risk in Transient Ischemic Attacks Patients with Silent Paroxysmal Atrial Fibrillation.

Purpose: Patients with transient ischemic attacks often present asymptomatic and paroxysmal atrial fibrillation. Since atrial fibrillation initiates in the atria, we aimed to identify whether the abnormalities in left atrial structure and function could identify the cardioembolic etiology of the transient ischemic attacks in patients at sinus rhythm. Patients and Methods: A total of 190 patients over 50 years old with sinus rhythm discharged after a transient ischemic attack were included in the study and divided into two groups according to the presence (group I) or absence (group II) of documented paroxysmal atrial fibrillation. The documentation of paroxysmal atrial fibrillation was based on the examination of medical registers. Cardiac ultrasound assessment was performed at a minimum of 14 days after the onset of the transient ischemic attack, to avoid assessment of atrial stunning. Results: The group I patients were older, more frequent women, with a history of stroke or transient ischemic attack and a higher CHA2DS2-VASc score. They also presented larger left atrial volumes, lower left atrial emptying fraction, and significantly impaired left atrial deformation patterns. Multivariate logistic regression identified three variables that were independently associated with paroxysmal atrial fibrillation: age, left atrial reservoir strain, and left atrial emptying fraction (P < 0.0001). The cut-off levels for the variables were age > 55 years, reservoir strain < -17%, and emptying fraction < 51%. Conclusion: The present study demonstrates that the LA strain is independently associated with paroxysmal atrial fibrillation in transient ischemic attack patients and might be of great help in identifying their cardioembolic etiology and preventing subsequent strokes by the initiation of anticoagulant therapy.

Clinical characteristics and outcomes in acute myocardial infarction patients aged ≥65 years in Western Romania.

Older age is known as a negative prognostic parameter in patients with acute myocardial infarction (AMI). In this study, we aimed to investigate age-related differences in treatment protocols, in-hospital and 1-year mortality. This retrospective observational single-center study enrolled consecutive AMI patients with an urgent percutaneous coronary intervention (PCI) as the main method of myocardial revascularization. The patients divided were divided by age into group I (≥65 years) and group II (<65 years). The primary endpoint was in-hospital mortality, the secondary endpoints were 1-year mortality and rehospitalization rates. Of the 522 admitted with AMI, 476 were enrolled in the study. The mean age was 67 ± 13 years; 62% were men. Group I patients had a significantly lower rate of performed PCI (65% vs. 79%, P < 0.001). 53 patients (12.3%) died during hospitalization, and this proportion was notably higher in the older population (20% vs. 6%, P < 0.0001). The cardiac causes of death were more frequent in group I patients (12% vs. 5.6%, P = 0.016). The multivariate logistic regression selected two variables as independent predictors for the risk of in-hospital death: age ≥65 years (P = 0.0170), and Killip class at admission (P < 0.0001). The 1-year mortality was 3.3%, slightly higher in group I patients (4.8% vs. 1.5%, P = 0.05). In conclusion, patients aged ≥65 years have three times higher in-hospital mortality, but similar 1-year mortality and readmission rates when compared with the younger patients. It is obvious that there is a large potential for improvement of the AMI care in this age group of patients.

Independent predictors of in-hospital and 1-year mortality rates in octogenarians with acute myocardial infarction.

Older age is known as a negative prognostic parameter in acute myocardial infarction (AMI) patients. In this study, we aimed to explore age-associated differences in treatment protocols, in-hospital and 1-year mortality. This cohort observational study included 277 consecutive AMI patients, separated into 2 groups according to whether their age was ≥80 years or not. We found that group I patients (aged ≥80 years) had a notably lower rate of percutaneous coronary intervention (PCI) performed (P < 0.0001) and a notably higher in-hospital death rate (P < 0.003). The multivariate logistic regression analysis found that three variables were independent predictors of in-hospital mortality: age ≥80 years (P < 0.0001), LVEF <40% (P < 0.0001), and Killip class ≥3 (P < 0.0001). The 1-year death rate was again significantly higher in group I patients (P < 0.001) and was independently predicted by the triple-vessel coronary artery disease (P = 0.004) and an LVEF <40% at admission (P = 0.001). The 1-year readmission rate was superior in group I (P < 0.01) and independently predicted by an age ≥80 years (P < 0.001), and an history of congestive heart failure (P < 0.0001) or permanent atrial fibrillation (P < 0.001). We concluded that patients aged ≥80 benefit less often from a PCI and have higher rates of in-hospital mortality, as well as of 1-year readmission and mortality rates.

Left Ventricular Remodeling Risk Predicted by Two-Dimensional Speckle Tracking Echocardiography in Acute Myocardial Infarction Patients with Midrange or Preserved Ejection Fraction in Western Romania.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at high risk for left ventricular (LV) remodeling and heart failure. We aimed to study whether LV strains (S) and strain rates (SR) could predict cardiac remodeling in patients with AMI having a midrange or preserved LV ejection fraction (EF) following a percutaneous coronary intervention (PCI) within the first 12 hours from the onset of symptoms. PATIENTS AND METHODS: This is a case-control observational study including patients admitted for their first AMI, either with ST-segment elevation (STEMI) or without ST elevation (NSTEMI), with an LVEF > 40% after a successful PCI. Echocardiography was repeated after 6 months, and the patients were divided into two groups, according to whether LV remodeling was determined on echocardiography. RESULTS: Of the 253 AMI patients (mean 66 aged ± 13 years), including 185 males (73%), 61 (24%) presented signs of LV remodeling. In univariate logistic regression analysis, age, male sex, smoking history, hypertension, hypercholesterolemia, Killip class, renal function, peak creatine phosphokinase - MB level, 2- and 3-vessel coronary artery disease (CAD), and several echocardiographic parameters were significantly associated with LV remodeling (P<0.05). In multivariate logistic regression analysis harmed (H) LS and SR, Killip class, 3-vessel CAD, and LV end-diastolic volume were outlined as independent predictors for LV remodeling. Receiver operating characteristic curve analyses showed that HLS and HLSR were the most powerful independent predictors for LV remodeling (P<0.001), with an area under the curve (AUC) of 0.85 (sensitivity 83%; specificity 84%; p <0.001) and 0.77 (sensitivity 93; specificity 61%; p <0.001), respectively. The identified cut-off values for predictor variables were HLS< -11%, and HLSR< -0.65s-1. CONCLUSION: We concluded that 2D-STE was the best method to evaluate LV remodeling in patients with AMI and midrange or preserved LVEF following myocardial revascularization by a PCI.

Significant Association Between Left Ventricular Diastolic Dysfunction, Left Atrial Performance and Liver Stiffness in Patients with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease.

PURPOSE: The constitutive elements of the metabolic syndrome (MetS) are linked with both non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. Controlled attenuation parameter (CAP), and vibration controlled transient elastography (VCTE), are able to detect and quantify NAFLD, while conventional and two-dimensional speckle tracking echocardiography (2D-STE) is capable to identify subclinical changes in cardiac function. We wanted to evaluate whether there is any correspondence between left ventricular (LV) diastolic dysfunction and different degrees of liver steatosis and fibrosis in MetS subjects with NAFLD. PATIENTS AND METHODS: A total of 150 adult subjects having MetS and a normal left ventricular (LV) systolic function were recorded in the study, while 150 age- and sex- matched adults without MetS were enrolled as controls. NAFLD was established by VCTE and CAP. The left heart systolic and diastolic function was evaluated by conventional and 2D-ST echocardiography. Left atrial (LA) stiffness was calculated as the ratio between the E/A ratio and the LA reservoir-strain. RESULTS: In univariate regression analysis, the variables associated with LV diastolic dysfunction in MetS patients were: liver steatosis grade ≥2, liver fibrosis grade ≥2, the longitudinal LA peak strain during the reservoir phase, the LA strain rate during ventricular contraction and the LA stiffness. In multivariate logistic regression, two variables were selected as independent predictors of LV diastolic dysfunction, namely the liver stiffness (P=0.0003) and the LA stiffness (P<0.0001). LA stiffness predicted subclinical LV diastolic dysfunction in MetS patients with a sensitivity of 45% and a specificity of 96% when using a cut-off value >0.38, and was significantly correlated with liver steatosis stage ≥2 and liver fibrosis stage ≥2. CONCLUSION: The present study confirms the association between liver stiffness, LA stiffness and LV diastolic dysfunction in MetS patients. Our study suggests that liver elastography and 2D-STE should become habitual assessments in MetS patients.

Association Between Subclinical Left Ventricular Myocardial Systolic Dysfunction Detected by Strain and Strain­Rate Imaging and Liver Steatosis and Fibrosis Detected by Elastography and Controlled Attenuation Parameter in Patients with Metabolic Syndrome.

PURPOSE: The components of metabolic syndrome (MS) are risk factors for developing both cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Strain (SI) and strain­rate imaging (SRI) are able to recognize early changes in cardiac function. Vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) detect and quantify liver fibrosis and steatosis. We aimed to assess whether there is any correlation between liver fibrosis and steatosis and left ventricular (LV) dysfunction in MS patients. PATIENTS AND METHODS: A total of 150 adults with MS were registered in the study. They were compared with a control group of 150 age- and sex-matched adults without MS. After the classic echocardiographic assessment of LV function, two-dimensional speckle echocardiography (2D-STE) was used to evaluate LV peak systolic strain (S) and peak systolic strain rate (SR), while liver steatosis and fibrosis were evaluated by VCTE and CAP. RESULTS: LV diastolic dysfunction was significantly more frequent among the patients with MS. We found significant differences between the two groups regarding the presence of subtle LV systolic dysfunction, detected by reduced values of S and SR. The risk for LV diastolic dysfunction was 3.6 times higher in MS with severe steatosis and 8 times higher in patients with severe fibrosis, P<0.0001. The risk for LV systolic dysfunction was double in MS with severe steatosis and 1.7 times higher in MS with severe fibrosis, P<0.0001. CONCLUSION: In MS patients with normal LV ejection fraction, conventional echocardiography parameters identified diastolic LV dysfunction, while SI and SRI identified subtle impairment of systolic LV dysfunction. The presence of hepatic steatosis and fibrosis increases significantly the risk for cardiac dysfunction in MS patients (P<0.0001).

Toll-like receptor 4 (TLR4) expression is correlated with T2* iron deposition in response to doxorubicin treatment: cardiotoxicity risk assessment.

Although doxorubicin (Dox) is an effective antitumor antibiotic in the anthracycline class, it often induces the undesirable side effect of cardiomyopathy leading to congestive heart failure, which limits its clinical use. The primary goal of this study is to evaluate a reliable translational method for Dox-induced cardiotoxicity (CTX) screening, aiming to identify a high-risk population and to discover new strategies to predict and investigate this phenomenon. Early identification of the presence of iron deposits and genetic and environmental triggers that predispose individuals to increased risk of Dox-induced CTX (e.g., overexpression of Toll-like receptor 4 (TLR4)) will enable the early implementation of countermeasure therapy, which will improve the patient's chance of survival. Our cohort consisted of 25 consecutive patients with pathologically confirmed cancer undergoing Dox chemotherapy and 12 control patients. The following parameters were measured: serum TLR4 (baseline), serum transferrin (baseline and 6-week follow-up) and iron deposition (baseline and 6-week follow-up). The average number of gene expression units was 0.121 for TLR4 (range 0.051-0.801). We subsequently correlated serum TLR4 levels in our cohort with myocardial iron overload using the cardiac magnetic resonance (CMR) T2* technique, the ventricular function (% ejection fraction, %EF) and serum transferrin levels. There is a strong negative linear relationship between serum TLR4 and CMR T2* values (r = - 0.9106, ****P < 0.0001). There is also a linear correlation (either positive or negative) with EF and transferrin; no established relationship related to the sex of the patients was found. Patients with elevated serum TLR4 at baseline also exhibited an increase in serum transferrin levels and Dox-induced left ventricular dysfunction with a decreased EF (< 50%); this phenomenon was observed in 7 of 25 patients (28%) at the 6-week follow-up. There were no significant differences or correlations based on sex. We concluded that there is a direct relationship between Dox-induced CTX (indicated by elevated serum TLR4) and the times (ms) for T2* (decreases in which correspond to immediate and rapid iron overload).

Obtaining and Characterization of a Polydisperse System Used as a Transmembrane Carrier for Isosorbide Derivatives.

Due to their effect of vasodilatation, isosorbide nitrates represent one of the most important and most used solutions for angina pectoris. Unfortunately, these compounds have multiple dose-related adverse drug reactions such as headache, weakness, mild dizziness, and occasionally heart rate changes, nausea, vomiting, and sweating. The main aims of this research were to obtain and to evaluate new polyurethane (PU) structures that can be used as a proper transmembrane carrier with an improved release kinetic. Chitosan-based PU structures were obtained by a polyaddition process between hexamethylene diisocyanate and a mixture of chitosan, butanediol, and polyethylene glycol in the presence of caffeine as a synthesis catalyst. The obtained samples (with and without isosorbide nitrates) were characterized regarding the encapsulation and release rate (UV-Vis spectra), chemical composition (FTIR), thermal stability (thermal analysis), morphology changes (SEM and SANS), and in vivo irritation tests. These methods revealed no significant differences between the two sample structures. Multipopulational structures with sizes between 73 and 310 nm, with an increased tendency to form clusters and a high resistance to heat (up to 280°C), were obtained. This study presents an alternative administration of isosorbide derivatives based on a PU carrier with a high biocompatibility and a prolonged release.

The Predictive Value of Endothelial Inflammatory Markers in the Onset of Schizophrenia.

PURPOSE: This study aimed to assess the serum levels of intracellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1), in the first psychotic episode schizophrenia (SZ) patients, before and after six months of antipsychotic treatment. PATIENTS AND METHODS: The study included 50 patients with a first hospitalization for SZ and 50 healthy control subjects that were patient-matched regarding age, gender, body mass index and smoking status. The evaluation included the presence of cardiovascular risk factors, measurements of systolic and diastolic blood pressure, body mass index, smoking status, ankle-brachial index, carotid intima-media thickness, and echocardiography. The Brief Psychiatric Rating Scale (BPRS) score was calculated for the patients. The plasma levels of fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, sICAM-1 and sVCAM-1 were determined at baseline in all subjects and after six months of antipsychotic treatment. Thirty patients (60%) were treated with olanzapine and 20 (40%) with risperidone. RESULTS: The average age of patients experiencing their first episode of SZ was 29.7±6.6 years, and 23 (46%) were men. The initial sICAM-1 levels of the patients were lower than those of the control group (P<0.0001), and increased after treatment (P=0.02), but remained lower than in the healthy controls (P=0.026). The initial levels of sVCAM-1 levels were higher in the patients (P<0.0001) and decreased after treatment (P<0.0001) to values that were similar to those of the control group (P=0.39). The only independent predictor of a baseline BPRS over 120 was the baseline sVCAM-1 level (P<0.0001). Antipsychotic treatment induced significant decreases in BPRS score (P<0.0001), in systolic (P=0.005) and diastolic (P<0.0001) blood pressure, in HDL-c (P=0.02), as well as significant increases in blood glucose (P<0.01) and LDL-c (P<0.001), with no differences between olanzapine and risperidone. CONCLUSION: In the patients experiencing an FEP of SZ, the levels of sICAM-1 were lower, while the levels of sVCAM-1 were higher than in the healthy control subjects. The antipsychotics used in the treatment of schizophrenia increased sICAM-1 and decreased sVCAM. The baseline level of sVCAM-1 was an independent predictor of a BPRS score >120 at baseline.