The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma.

Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.

Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP. MATERIALS AND METHODS: systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022. RESULTS: a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.

Bioactive Compounds in Moringa oleifera: Mechanisms of Action, Focus on Their Anti-Inflammatory Properties.

Moringa oleifera (M. oleifera) is a tropical tree native to Pakistan, India, Bangladesh, and Afghanistan; it is cultivated for its nutritious leaves, pods, and seeds. This scientific study was conducted to outline the anti-inflammatory properties and mechanisms of action of bioactive compounds from M. oleifera. The existing research has found that the plant is used in traditional medicine due to its bioactive compounds, including phytochemicals: flavonoids and polyphenols. The compounds are thought to exert their anti-inflammatory effects due to: (1) inhibition of pro-inflammatory enzymes: quercetin and kaempferol inhibit the pro-inflammatory enzymes (cyclooxygenase and lipoxygenase); (2) regulation of cytokine production: isothiocyanates modulate signaling pathways involved in inflammation, such as the nuclear factor-kappa B (NF-kappa B) pathway; isothiocyanates inhibit the production of pro-inflammatory cytokines such as TNF-α (tumor necrosis factor α) and IL-1ß (interleukin-1ß); and (3) antioxidant activity: M. oleifera contains flavonoids, polyphenols, known to reduce oxidative stress and inflammation. The review includes M. oleifera's effects on cardiovascular protection, anti-hypertensive activities, type 2 diabetes, inflammatory bowel disease, and non-alcoholic fatty liver disease (NAFLD). This research could prove valuable for exploring the pharmacological potential of M. oleifera and contributing to the prospects of developing effective medicines for the benefit of human health.

Particularities of Catheter Ablation in Women with Atrial Fibrillation and Associated Ischemic Heart Disease.

BACKGROUND: Atrial fibrillation is more common in men, but in the presence of ischemic heart disease, this arrhythmia is more frequent in women. However, like in coronary heart disease, women with atrial fibrillation are suboptimally treated. METHODS: To identify particularities of ablation, in women with atrial fibrillation and ischemic heart disease. RESULTS: 29 women and 26 men, with documented ischemic heart disease and atrial fibrillation, who underwent catheter ablation, were admitted in the study. No significant differences were registered regarding the heart rate control treatment. Electrical cardioversion was significantly higher in men, while pharmacological cardioversion was predominantly recommended in women. The ablation was performed later in women, after 2.55 ± 1.84 years versus 1.80 ± 1.05 in men (p = 0.05). The time elapsed until the ablation was performed was statistically correlated with atypical symptomatology and with the number of antiarrhythmics used prior to the ablation. There were no significant differences for the relapse of atrial fibrillation at 3 months. Quality of life at 3 months after ablation was increased in both groups. CONCLUSION: Catheter ablation is performed much later in women, and the causes responsible for this delay would be more atypical symptoms and a greater number of antiarrhythmics tried before the ablation.

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review.

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.

One Molecule for Mental Nourishment and More: Glucose Transporter Type 1-Biology and Deficiency Syndrome.

Glucose transporter type 1 (Glut1) is the main transporter involved in the cellular uptake of glucose into many tissues, and is highly expressed in the brain and in erythrocytes. Glut1 deficiency syndrome is caused mainly by mutations of the SLC2A1 gene, impairing passive glucose transport across the blood-brain barrier. All age groups, from infants to adults, may be affected, with age-specific symptoms. In its classic form, the syndrome presents as an early-onset drug-resistant metabolic epileptic encephalopathy with a complex movement disorder and developmental delay. In later-onset forms, complex motor disorder predominates, with dystonia, ataxia, chorea or spasticity, often triggered by fasting. Diagnosis is confirmed by hypoglycorrhachia (below 45 mg/dL) with normal blood glucose, 18F-fluorodeoxyglucose positron emission tomography, and genetic analysis showing pathogenic SLC2A1 variants. There are also ongoing positive studies on erythrocytes' Glut1 surface expression using flow cytometry. The standard treatment still consists of ketogenic therapies supplying ketones as alternative brain fuel. Anaplerotic substances may provide alternative energy sources. Understanding the complex interactions of Glut1 with other tissues, its signaling function for brain angiogenesis and gliosis, and the complex regulation of glucose transportation, including compensatory mechanisms in different tissues, will hopefully advance therapy. Ongoing research for future interventions is focusing on small molecules to restore Glut1, metabolic stimulation, and SLC2A1 transfer strategies. Newborn screening, early identification and treatment could minimize the neurodevelopmental disease consequences. Furthermore, understanding Glut1 relative deficiency or inhibition in inflammation, neurodegenerative disorders, and viral infections including COVID-19 and other settings could provide clues for future therapeutic approaches.

The role of matrix metalloproteinases in patients with pulmonary hypertension: data from a prospective study.

BACKGROUND: Despite several therapies, pulmonary hypertension (PH) is still a severe disease which can lead to right heart failure. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cardiac and vascular remodeling in PH. Therefore, these biomarkers play an important role in PH patients. This study investigated whether TIMP-4, MMP-2, and N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) plasma levels are useful in assessing the severity of PH and other clinical or echocardiographic parameters. METHODS: The concentrations of MMP-2, TIMP-4, and NT-proBNP in 68 PH patients were compared with those of 12 controls without PH. All patients underwent a physical examination, echocardiography, and were checked for the presence of cardiovascular risk factors; also, plasma concentrations of MMP-2, TIMP-4, NT-proBNP, total cholesterol, and triglycerides were determined. RESULTS: In PH patients, significantly elevated plasma levels of TIMP-4 (PH: 2877.99 ± 1363.78 pg/ml, control: 2028.38 ± 762.67 pg/ml, p = 0.0068) and NT-proBNP ( PH: 2405.00 pg/ml-5423.47 ± 6703.38 pg/ml, control: 411.0000 pg/ml-421.75 ± 315.37 pg/ml, p = 0.01) were detected. We also observed that MMP-2 and NT-proBNP were significantly increased in patients with higher WHO functional class (p = 0.001 for MMP-2, p = 0.008 for NT-proBNP), higher pressure in the pulmonary artery (p = 0.002 for MMP-2, p = 0.001 for NT-proBNP), and more severe tricuspid regurgitation (p = 0.001 for MMP-2, p = 0.009 for NT-proBNP). TIMP-4 was elevated in patients with more severe pressure in the pulmonary artery (p = 0.006). CONCLUSIONS: The plasma levels of TIMP-4 and NT-proBNP are higher in PH patients. MMP-2 and NT-proBNP correlates with different PH parameters severity (WHO functional class, sPAP severity, TV regurgitation severity). Therefore, plasmatic levels of MMP-2 and NT-proBNP at this kind of patients reflect disease severity and may have a prognostic role. MMP-2 can help assess the beneficial effects of PH pharmacotherapy on tissue remodeling. These remodeling biomarkers may not have a diagnostic value but they have the potential to predict survival. Nevertheless, a greater understanding of the involvement of MMPs in PH is mandatory to further explore the prognostic role and the possibilities of therapeutic MMP inhibition in PH.

The Role of IL-6 and ET-1 in the Diagnosis of Coronary MicroVascular Disease in Women.

BACKGROUND: Microvascular angina is a common clinical entity, with about a three-fold higher frequency in women. The pathogenesis of microvascular angina has not been much studied, but inflammation and endothelial dysfunction have been incriminated as the main mechanisms of this disease. Methoss: Our purpose was to analyze whether certain inflammatory markers, i.e., interleukin 6 (IL-6) and endothelin 1 (ET-1), can play a role in the diagnosis of microvascular angina in women. RESULTS: Ninety women with ischemic heart disease were divided into two groups, based on their affliction with either microvascular or macrovascular disease. In general, the levels of IL6 and ET1 were similar between the two groups. Analyzing these marker levels according to the number of coronary lesions, we obtained an increased IL6 value that was similar for patients with microvascular angina, one-vessel, and two-vessel coronary disease, but significantly lower than in women with three-vessel coronary lesions. Also, in microvascular angina, IL6 level was correlated with the NYHA IV functional class. Unexpectedly, the level of ET1 was correlated with left ventricular systolic dysfunction. CONCLUSIONS: In women with an increased suspicion of microvascular angina, in whom microvascular dysfunction cannot be tested invasively, IL-6 level, unlike the ET-1 level, might be considered a diagnostic marker of this disease.

Endothelial Dysfunction, Inflammation, and Oxidative Stress in COVID-19-Mechanisms and Therapeutic Targets.

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.

Leptin, Galectin-3 and Angiotensin II Type 1 Receptor Polymorphism in Overweight and Obese Patients with Heart Failure - Role and Functional Interplay.

BACKGROUND AND AIMS: Leptin, one of the best-known adipocytes, together with the renin-angiotensin-aldosterone system and galectin-3 are important players in inflammation, arterial hypertension and heart failure pathophysiology. Moreover, uninucleotide A1166C polymorphism is associated with hypertension and poor prognosis in heart failure. The aim of the study was to investigate a possible relationship between leptin serum values, specific heart failure biomarkers and the presence of AT1 receptor A1166C polymorphism in overweight and obese heart failure patients. METHODS: The study included 88 consecutive overweight and obese patients admitted for decompensated heart failure. NT-proBNP, MR-proANP, galectin-3 and leptin levels were determined on the arrival day. Genotyping of the A1166C allele - AT1 receptor gene was performed in all patients in order to find variants. RESULTS: We found a strong positive correlation (r = 0.347, p = 0.001) between leptin serum concentrations and BMI. Leptin levels were not correlated with heart failure biomarkers (NT-proBNP, MR-proANP and galectin-3). All homozygote CC variants were hypertensive, but we registered no significant difference in genetic AC and AA variants distribution between hypertensive and normotensive. Leptin was not significantly modified by the presence of potentially pathogenic A1166C-AT 1 receptor genotypes (AC + CC). But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations. CONCLUSION: Overweight and obese patients with heart failure display high leptin serum levels. Leptin does not offer incremental prognostic value in heart failure overweight and obese patients. But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations, suggesting a worse prognosis probably due to more advanced cardiac fibrosis.

Assessment of subclinical diabetic cardiomyopathy by speckle-tracking imaging.

BACKGROUND: Diastolic dysfunction is traditionally believed to be the first subclinical manifestation of diabetic cardiomyopathy (DCM), leading to systolic dysfunction and then overt heart failure. However, in the last few years, several studies suggested that systolic subclinical dysfunction measured by speckle-tracking echocardiography (STE) may appear ahead of diastolic dysfunction. In this review, the main endpoint is to show whether subclinical myocardial systolic dysfunction appears ahead of diastolic dysfunction and the implication this may have on the evolution and management of DCM. MATERIALS AND METHODS: We performed a search in PubMed for all relevant publications on the assessment of DCM by STE from 1 June 2015 to 1 June 2020. RESULTS AND CONCLUSIONS: The results illustrate that subclinical systolic dysfunction assessed by STE is present in early DCM stages, with or without the association of diastolic dysfunction. This could be a promising perspective for the early management of patients with DCM leading to the prevention of the overt form of disease.

The Impact of Obesity on Left Ventricular Hypertrophy and Diastolic Function in Caucasian Children.

Background: Left ventricular hypertrophy (LVH) and diastolic dysfunction are correlated with obesity and hypertension in adult patients, but few studies have investigated the association between obesity itself and left ventricular function in children. The aim of this study was to evaluate the effect of obesity and LVH on left ventricular diastolic function in pediatric subjects compared with children without obesity. Methods: A number of 454 patients from an outpatient cardiology service were enrolled in a prospective study, 33 children with obesity, 20 overweight children, and 401 children without obesity. The subjects were assigned to three groups according to age and school grade. A standardized two-dimensional echocardiography analysis was performed in all children. The evaluated echocardiographic parameters included thickness of the interventricular septum (IVS), thickness of the posterior wall of the left ventricle, and left atrium size. The left ventricular diastolic function was analyzed by the classic pulsed-wave Doppler technique, tissue Doppler technique, and continuous Doppler technique. Results: The number of children with obesity was higher in the school and adolescent groups. The median age of children with obesity was 9 years. The subjects were classified according to blood pressure values in hypertensive, with high-normal blood pressure/prehypertension and with normal blood pressure values. Standard echocardiography showed that children with obesity had significantly increased thickness of the IVS and of the posterior wall compared with nonobesity subjects (P < 0.001). Left ventricular systolic function was preserved in both groups. Diastolic function was normal in the obesity group and in the non-obesity group, respectively. Conclusions: The results of this study demonstrate that childhood obesity is associated with significant changes in the myocardial structure consisting of LVH, but we did not find an early alteration in the left ventricular diastolic function of the subjects with obesity compared with patients with a normal weight.

Diabetes and Obesity-Cumulative or Complementary Effects On Adipokines, Inflammation, and Insulin Resistance.

BACKGROUND: Diabetes and obesity are increasingly significant public health issues. The aim of this study was to evaluate the relationship between adipocytokines (leptin, ghrelin, and chemerin), inflammation (sVCAM1-soluble vascular adhesion molecule 1, sICAM1-soluble intercellular adhesion molecule 1), and insulin resistance in the presence of obesity and diabetes mellitus. METHODS: 88 subjects, with a mean age of 61.96 ± 10.15 years, 75% of whom were women, were evaluated (in order to consider different associations between obesity and diabetes, subjects were categorized into four groups). RESULTS: Overall, we found significant correlations between sICAM1-sVCAM1 rho = 0.426 and ghrelin-chemerin rho = -0.224. In the obesity + diabetes group, leptin correlated with sICAM1 rho = 0.786, and sVCAM1 negatively with glycemia/insulin rho = -0.85. Significant differences were found between the groups regarding sVCAM1 (p = 0.0134), leptin (p = 0.0265) and all insulin resistance scores, with differences influenced by the subjects' gender. In conclusion, although there are currently many unknown aspects of the release and the role of various adipokines, in particular chemerin, its implication in early glucose metabolism dysregulation disorders seems very likely.

Influence of pesticides on respiratory pathology - a literature review.

INTRODUCTION: Pesticides are widely employed in agriculture, and the food industry is forced to combat the pests and diseases they cause. Respiratory pathology is related to occupational exposure to pesticides. Impairment of pulmonary function was observed among people professionally exposed to pesticides. Because of the marked use of pesticides in agriculture during the last 20 years, there has been a significant increase in respiratory problems within the population, not only among people who come in direct contact with them, but even in the case of manipulators. OBJECTIVE: The aim is a review of the literature of the past 10 years on the correlation between occupational exposure to pesticides and respiratory pathology. MATERIAL AND METHODS: Electronic search in 'Pub Med' and 'Web of Science' was performed in September 2019 to find papers regarding the above-investigated aspects. Abstracts and full-text articles containing the targeted subject were included. Reviews and studies about the influence of pesticides on other pathologies than respiratory were excluded. After applying the inclusion and exclusion criteria, eligible full-text articles were identified. CONCLUSIONS: Exposure to pesticides is highly correlated with respiratory pathologies (asthma, COPD, lung cancer). Contact with these substances can occur at any time in the production, transport, preparation or application of the treatments. Numerous studies documented the association between exposure to pesticides, and therefore the increased incidence of respiratory, cardiovascular and renal diseases, as well as the aging phenomenon.

Profile of Obesity and Comorbidities in Elderly Patients with Heart Failure.

BACKGROUND AND PURPOSE: In Romania, robust data about the prevalence of obesity and heart failure are lacking, especially in the elderly; therefore, this study aims to analyze the profile of overweight and obese patients aged >65 years admitted to a Romanian hospital for worsening heart failure, and also their risk in the presence of comorbidities. PATIENTS AND METHODS: This cross-sectional study was conducted in 126 consecutive elderly patients with overweight and obesity admitted to a Romanian hospital for worsening heart failure. They were divided into three groups: with reduced (<40%) - HFrEF, mid-range (40-49%) - HFmrEF and preserved (≥50%) ejection fraction - HFpEF. Obesity was defined according to the body mass index (BMI) status: obesity, ≥30 kg/m2; overweight, 25-29.9 kg/m2. The Charlson Comorbidity Index (CCI) was calculated to evaluate the severity of comorbidity, with a score ranging from 2 (only heart failure present and age >65 years) to 30 (extensive comorbidity). RESULTS: NT-proBNP values are negatively correlated with BMI only in patients with HFpEF. Creatinine clearance (p=0.0166), the presence of atrial fibrillation (p=0.0095) and NYHA functional class were independent predictors of increased NT-proBNP values. CCI score is negatively correlated with NT-proBNP values in patients with HFmrEF (r= -0.448, p=0.009) and HFpEF (r= -0.273, p=0.043). The CCI risk was not significantly different between the three groups. CONCLUSION: Elderly heart failure patients with overweight or obesity have particular characteristics in terms of NT-proBNP values and presence of comorbidities. In the studied population, NT-proBNP levels were strongly influenced by renal function, NYHA functional class, the presence of atrial fibrillation and left ventricular ejection fraction.

Effect of Liposomal Curcumin on Acetaminophen Hepatotoxicity by Down-regulation of Oxidative Stress and Matrix Metalloproteinases.

BACKGROUND/AIM: The hepatoprotective role of various molecules in drug-induced hepatotoxicity arouses great interest. We investigated the effect of liposomal curcumin (LCC) on experimental acetaminophen (APAP)-induced hepatotoxicity. MATERIALS AND METHODS: Rats were randomly allocated into 5 groups, and the effect of two LCC concentrations was studied: group 1 - 1 ml intraperitoneal (i.p.) saline, group 2 - APAP pretreatment, group 3 - APAP+silymarin (extract of the silybum marianum with anti-inflammatory, anti-oxidant, and anti-fibrotic properties), group 4 - APAP+LCC1, group 5 - APAP+LCC2. The biomarkers of oxidative stress (nitric oxide and malondialdehyde) and antioxidant status of plasma (thiols and catalase), TNF-α, MMP-2 and MMP-9 serum levels were evaluated. RESULTS: An improvement in oxidative stress, antioxidant status, and TNF-α, MMP-2 and MMP-9 levels was obtained in groups pretreated with LCC compared to silymarin treatment, in a dose-dependent manner. Histopathological examination reinforced the results. CONCLUSION: Liposomal curcumin improves the oxidative stress/antioxidant balance and alleviates inflammation in experimental APAP-induced hepatotoxicity.

Hemodialysis Patients with Pruritus and Insomnia Have Increased Risk of Death.

BACKGROUND: Pruritus and insomnia are common disorders in hemodialysis (HD) patients, with a major clinical impact as they are associated with poor quality of life and increased mortality. Their coexistence and impact on survival in HD patients have rarely been investigated. Our aim is to investigate the survival of HD patients presenting either none, one, or both disorders and to compare certain features between these groups. METHODS: After the inclusion/exclusion criteria, 170 patients treated by HD or online hemodiafiltration were assigned in 4 study groups depending on the presence of either, neither, or both pruritus and insomnia. We analyzed the survival difference between groups after 20 months, and we searched if there were significant differences in terms of clinical and laboratory features. RESULTS: Survival at 20 months was lower in patients with both pruritus and insomnia. Patients with pruritus alone had a lower Kt/V than those with no complaints or insomnia alone. Those with no complaints had lower C-reactive protein and higher albumin levels than patients with insomnia alone or both conditions. CONCLUSION: Pruritus and insomnia should be actively investigated and correlated with some clinical and laboratory features as they have a significant impact on survival in HD patients.

The Effect of Mofettes on Oxidative Stress/Antioxidant Balance in Experimental Myocardial Ischemia.

BACKGROUND/AIM: Natural mofettes are gases resulting from post-volcanic emanations. This study aimed to examine the effect of mofette therapy on plasma oxidative stress and antioxidant parameters in rats after experimental induction of myocardial ischemia, as well as on structural changes in myocardial tissue. MATERIALS AND METHODS: White Wistar-Bratislava rats were divided into three groups. In groups 2 and 3, myocardial ischemia was induced by isoproterenol. Rats in group 3 were additionally exposed to high levels mofettes. Oxidative stress and antioxidant parameters were determined in plasma. The structural changes of the myocardium were observed in paraffin embedded slices contrasted using Goldner's trichrome staining. RESULTS: A statistically significant change in serum oxidative stress biomarkers, including nitric oxide, malondialdehyde, total oxidant status, as well as in the tested antioxidant molecules and total antioxidant capacity were observed in group 3 compared to group 2. Also, rats of group 3 showed an obvious improvement in inflammatory infiltration and repair of necrotic areas through collagen proliferation (proliferation of fibrous connective tissue) compared to group 2. CONCLUSION: Mofette had a beneficial effect on the balance between oxidative stress and antioxidant status following experimentally induced myocardial ischemia.

DNA Methylation and Micro-RNAs: The Most Recent and Relevant Biomarkers in the Early Diagnosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a frequently encountered cancer type, and its alarming incidence is explained by genetic and epigenetic alterations. Epigenetic changes may represent diagnostic and prognostic biomarkers of HCC. In this review we discussed deoxyribonucleic acid (DNA) hypomethylation, DNA hypermethylation, and aberrant expression of small non-coding ribonucleic acid (RNA), which could be useful new biomarkers in the early diagnosis of HCC. We selected the articles on human subjects published in English over the past two years involving diagnostic markers detected in body fluids, cancer diagnosis made on histopathological exam, and a control group of those with benign liver disease or without liver disease. These biomarkers need further investigation in clinical trials to develop clinical applications for early diagnosis and management of HCC.

Clinical and genetic predictors of diabetes drug's response.

Diabetes is a major health problem worldwide. Glycemic control is the main goal in the management of type 2 diabetes. While many anti-diabetic drugs and guidelines are available, almost half of diabetic patients do not reach their treatment goal and develop complications. The glucose-lowering response to anti-diabetic drug differs significantly between individuals. Relatively little is known about the factors that might underlie this response. The identification of predictors of response to anti-diabetic drugs is essential for treatment personalization. Unfortunately, the evidence on predictors of drugs response in type 2 diabetes is scarce. Only a few trials were designed for specific groups of patients (e.g. patients with renal impairment or older patients), while subgroup analyses of larger trials are frequently unreported. Physicians need help in picking the drug which provides the maximal benefit, with minimal side effects, in the right dose, for a specific patient, using an omics-based approach besides the phenotypic characteristics.