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BACKGROUND/OBJECTIVES Religious fasting (RF) is practiced annually by millions of Christian and Muslim followers worldwide. Scarce data exist on the impact of RF on the metabolic and hematological profile of individuals with or without dyslipidemia. SUBJECTS/METHODS The present study included: (i) 60 Greek Orthodox participants, 30 with dyslipidemia and 30 without dyslipidemia, who abstained from meat, fish and dairy products for seven consecutive weeks, and (ii) 15 young, non-dyslipidemic Muslim participants abstaining totally from food and liquid from dawn till sunset during 30 days. Biochemical (iron, ferritin, vitamin B12, calcium, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglyceride and fasting glucose) and hematological (hemoglobin, hematocrit) serum blood test results of study participants were measured pre- and post- RF (at weeks 0 and 7 for Orthodox participants and at weeks 0 and 4 for Muslim participants). RESULTS In dyslipidemic and non-dyslipidemic Orthodox participants, a significant reduction of fasting glucose, HDL, LDL and TC levels was found post-RF. Hemoglobin, hematocrit, iron and ferritin levels were significantly increased, while post-RF vitamin B12 and calcium levels were substantially decreased. Subanalysis between dyslipidemic and non-dyslipidemic Orthodox participants revealed a greater decrease of cholesterol levels in the former. In Muslim participants, triglyceride, LDL and total cholesterol levels were increased post-RF (all p values < 0.05). CONCLUSIONS Our study adds to the existing literature evidence about the significant impact of RF on metabolic and hematological profiles of Orthodox and Muslim followers. The prevention of calcium and B12 deficiency during Orthodox RF by supplement consumption as well as the protection from dehydration and dysregulation of lipid metabolism during Ramadan RF should concern both clinicians and dietician nutritionists. Nevertheless, studies with larger sample size and/or long-term follow-up are warranted before reaching definite conclusions about the effects of RF on human health.

Background Coronary artery disease (CAD) remains one of the leading causes of mortality and morbidity worldwide. As oxygen and nutrient supply to the myocardium significantly decrease during ischemic periods, important changes occur regarding myocardial intermediary energy metabolism. Metabolomics is an emerging field in systems biology, which quantifies metabolic changes in response to disease progression. This study aims to evaluate the diagnostic utility of plasma metabolomics-based biomarkers for determining the complexity and severity of CAD, as it is assessed via the SYNTAX score. Methods Corlipid is a prospective, non-interventional cohort trial empowered to enroll 1065 patients with no previous coronary intervention history, who undergo coronary angiography in University Hospital AHEPA, Thessaloniki. Venous blood samples are collected before coronary angiography. State-of the-art analytical methods are performed to calculate the serum levels of novel biomarkers: ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and the ratio of apolipoprotein B/apolipoprotein A1. Furthermore, all patients will be categorized based on the indication for coronary angiography (acute coronary syndrome, chronic coronary syndrome, preoperative coronary angiography) and on the severity of CAD using the SYNTAX score. Follow-up of 12 months after enrollment will be performed to record the occurrence of major adverse cardiovascular events. A risk prediction algorithm will be developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD based on their metabolite signatures. The first patient was enrolled in July 2019 and completion of enrollment is expected until May 2021. Discussion CorLipid is an ongoing trial aiming to investigate the correlation between metabolic profile and complexity of coronary artery disease in a cohort of patients undergoing coronary angiography with the potential to suggest a decision-making tool with high discriminative power for patients with CAD. To our knowledge, Corlipid is the first study aspiring to create an integrative metabolomic biomarkers-based algorithm by combining metabolites from multiple classes, involved in a wide range of pathways with well-established biochemical markers. Trial registration CorLipid trial registration: ClinicalTrials.gov number: NCT04580173. Registered 8 October 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04580173.

Recent studies support that acylcarnitines exert a significant role in cardiovascular disease development and progression. The aim of this metabolomics-based study was to investigate the association of serum acylcarnitine levels with coronary artery disease (CAD) severity, as assessed via SYNTAX Score. Within the context of the prospective CorLipid trial (NCT04580173), the levels of 13 circulating acylcarnitines were accurately determined through a newly developed HILIC-MS/MS method in 958 patients undergoing coronary angiography in the AHEPA University Hospital of Thessaloniki, Greece. Patients presenting with acute coronary syndrome had significantly lower median acylcarnitine C8, C10, C16, C18:1 and C18:2 values, compared to patients with chronic coronary syndrome (p = 0.012, 0.007, 0.018, 0.011 and 22 (p = 0.002, 0.024, 0.044 and 0.012, respectively), indicating a potential prognostic capability of those metabolites and of the ratio C4/C18:2 for the prediction of CAD severity. In conclusion, serum acylcarnitines could serve as clinically useful biomarkers leading to a more individualized management of patients with CAD, once further clinically oriented metabolomics-based studies provide similar evidence.

Micro-computed tomography (micro-CT) is a promising novel medical imaging modality that allows for non-destructive volumetric imaging of surgical tissue specimens at high spatial resolution. The aim of this study is to provide a comprehensive assessment of the clinical applications of micro-CT for the tissue-based diagnosis of lung diseases. This scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews, aiming to include every clinical study reporting on micro-CT imaging of human lung tissues. A literature search yielded 570 candidate articles, out of which 37 were finally included in the review. Of the selected studies, 9 studies explored via micro-CT imaging the morphology and anatomy of normal human lung tissue; 21 studies investigated microanatomic pulmonary alterations due to obstructive or restrictive lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis; and 7 studies examined the utility of micro-CT imaging in assessing lung cancer lesions (n = 4) or in transplantation-related pulmonary alterations (n = 3). The selected studies reported that micro-CT could successfully detect several lung diseases providing three-dimensional images of greater detail and resolution than routine optical slide microscopy, and could additionally provide valuable volumetric insight in both restrictive and obstructive lung diseases. In conclusion, micro-CT-based volumetric measurements and qualitative evaluations of pulmonary tissue structures can be utilized for the clinical management of a variety of lung diseases. With micro-CT devices becoming more accessible, the technology has the potential to establish itself as a core diagnostic imaging modality in pathology and to enable integrated histopathologic and radiologic assessment of lung cancer and other lung diseases.

The GRACE score constitutes a useful tool for risk stratification in patients with acute coronary syndrome (ACS), while the SYNTAX score determines the complexity of coronary artery disease (CAD). This study sought to correlate these scores and assess the accuracy of the GRACE score in predicting the extent of CAD. A total of 539 patients with ACS undergoing coronary angiography were included in this analysis. The patients were classified into those with a SYNTAX score &lt, 33 and a SYNTAX score ≥ 33. Spearman’s correlation and receiver operator characteristic analysis were conducted to investigate the role of the GRACE score as a predictor of the SYNTAX score. There was a significantly positive correlation between the SYNTAX and the GRACE scores (r = 0.32, p &lt, 0.001). The GRACE score predicted severe CAD (SYNTAX ≥ 33) moderately well (the area under the curve was 0.595 (0.522–0.667)). A GRACE score of 126 was documented as the optimal cut-off for the prediction of a SYNTAX score ≥ 33 (sensitivity = 53.5% and specificity = 66%). Therefore, our study reports a significantly positive correlation between the GRACE and the SYNTAX score in patients with ACS. Notably, NSTEMI patients with a high-risk coronary anatomy have higher calculated GRACE scores. A multidisciplinary approach by a heart team could possibly alter the therapeutic approach and management in patients presenting with ACS and a high calculated GRACE score.

Background and Aims Peritoneal dialysis (PD) are the main renal replacement treatment for children and adolescents with end stage kidney disease (ESRD). Peritoneal fibrosis is a major complication in long-term PD patients. Aim of the present study is to record the metabolic "fingerprint" of children on PD and to investigate its correlation with PD history and dialysis adequacy as well as the emergence of potential biomarkers that could detect early or predict peritoneal dysfunction. Method Samples of serum, urine and peritoneal effluent collected from 15 children with ESRD on PD. At the same time and 6 months later was performed PET-test as well as assessment of KT/V and creatinine clearance. Samples were subjected to targeted metabolomic analysis of amino acids and derivatives. Regarding metabolic technologies used, all samples (peritoneal fluid, urine, blood) were analyzed by a hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC-MS / MS) method previously developed and validated in our laboratory for the simultaneous determination of amino acids and their derivatives in biological fluids. Αalso, high flow analysis was carried out (LC-q-tof analysis – HPLC /MS ). Results Using (HILIC-MS / MS) method, we found out that peritoneal dialysis duration, presence or absence of diuresis and PD creatinine clearance values are associated with significant differences in the levels of several metabolites, including glycine, creatinine, proline and 4-hydroxyproline, leucine, valine, glutamine and glutamic acid. Using (LC-q-tof analysis – HPLC /MS) approximately 200 metabolites were analyzed in the aforementioned samples. Figure 1 illustrates the number of metabolites detected in each matrix, as well as the common metabolites between the three matrices. These metabolites were associated with peritoneal dialysis duration, creatine clearance and presence or absence of diuresis. Several metabolites showed statistical difference between the examined groups. In detail, regarding serum analysis, five metabolites, including hydroxy phenyl acetic acid, glutathione ox, glucosamine-6-P, indole acetic acid and riboflavin showed statistical difference between the examined groups based on PD vintage. Based on urine excretion four metabolites named histidine, shikimic acid, thiamine and methionine were statistically different. Concerning urine analysis, two metabolites namely uridine and itaconic acid showed statistical difference when patients sub grouped based on PD vintage. Peritoneal fluid analysis highlighted one metabolite, uridine, that levels are significantly lower in patients on PD therapy for more than 4 years while based on creatinine clearance levels subgroups, two metabolites, lactate and pantothenic acid present statistically significant difference. Conclusion Metabolomics may be a tool in the evaluation of patients with ESRD on PD as it appears to reflect the clinical phenotype of the patient and the functional phenotype of the peritoneal membrane. Our results are the preliminary results of an ongoing prospective study. Limitation of the study is the small sample of patients, which does not allow safe clinical interpretation.

Background Micro-computed tomography (micro-CT) constitutes an emerging imaging technique, which can be utilized in cardiovascular medicine to study in-detail the microstructure of heart and vessels. This paper aims to systematically review the clinical utility of micro-CT in cardiovascular imaging and propose future applications of micro-CT imaging in cardiovascular research. Methods A systematic scoping review was conducted by searching for original studies written in English according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Medline, Scopus, ClinicalTrials.gov , and the Cochrane library were systematically searched through December 11, 2020 to identify publications concerning micro-CT applications in cardiovascular imaging. Preclinical-animal studies and case reports were excluded. The Newcastle-Ottawa assessment scale for observational studies was used to evaluate study quality. Results In total, the search strategy identified 30 studies that report on micro-CT–based cardiovascular imaging and satisfy our eligibility criteria. Across all included studies, the total number of micro-CT scanned specimens was 1,227. Six studies involved postmortem 3D-reconstruction of congenital heart defects, while eleven studies described atherosclerotic vessel (coronary or carotid) characteristics. Thirteen other studies employed micro-CT for the assessment of medical devices (mainly stents or prosthetic valves). Conclusion Micro-CT is a novel imaging modality, effectively adapted for the 3D visualization and analysis of cardiac soft tissues and devices at high spatial resolution. Its increasing use could make significant contributions to our improved understanding of the histopathophysiology of cardiovascular diseases, and thus has the potential to optimize interventional procedures and technologies and improving patient outcomes.

ST-elevation myocardial infarction (STEMI) remains one of the leading causes of mortality worldwide. The identification of novel metabolic and imaging biomarkers could unveil key pathophysiological mechanisms at the molecular level and promote personalized care in patients with acute coronary syndromes. We studied 38 patients with STEMI who underwent primary percutaneous coronary intervention and thrombus aspiration. We sought to correlate serum ceramide levels with micro-CT quantified aspirated thrombus volume and relevant angiographic outcomes, including modified TIMI thrombus grade and pre- or post-procedural TIMI flow. Higher ceramide C16:0 levels were significantly but weakly correlated with larger aspirated thrombus volume (Spearman r = 0.326, p = 0.046), larger intracoronary thrombus burden (TB; p = 0.030) and worse pre- and post-procedural TIMI flow (p = 0.049 and p = 0.039, respectively). Ceramides C24:0 and C24:1 were also significantly associated with larger intracoronary TB (p = 0.008 and p = 0.001, respectively). Receiver operating characteristic analysis demonstrated that ceramides C24:0 and C24:1 could significantly predict higher intracoronary TB (area under the curve: 0.788, 95% CI: 0.629–0.946 and 0.846, 95% CI: 0.706–0.985, respectively). In conclusion, serum ceramide levels were higher among patients with larger intracoronary and aspirated TB. This suggests that quantification of serum ceramides might improve risk-stratification of patients with STEMI and facilitate an individualized approach in clinical practice.

Background: Angiographic detection of thrombus in STEMI is associated with adverse outcomes. However, routine thrombus aspiration failed to demonstrate the anticipated benefit. Hence, management of high coronary thrombus burden remains challenging. We sought to assess for the first time extracted thrombotic material characteristics utilizing micro-computed tomography (micro-CT).Methods: One hundred thirteen STEMI patients undergoing thrombus aspiration were enrolled. Micro-CT was undertaken to quantify retrieved thrombus volume, surface, and density. Correlation of these indices with angiographic and electrocardiographic outcomes was performed.Results: Mean aspirated thrombus volume, surface, and density (±standard deviation) were 15.71 ± 20.10 mm3, 302.89 ± 692.54 mm2, and 3139.04 ± 901.88 Hounsfield units, respectively. Aspirated volume and surface were significantly higher (p < 0.001) in patients with higher angiographic thrombus burden. After multivariable analysis, independent predictors for thrombus volume were reference vessel diameter (RVD) (p = 0.011), right coronary artery (RCA) (p = 0.039), and smoking (p = 0.027), whereas RVD (p = 0.018) and RCA (p = 0.019) were predictive for thrombus surface. Thrombus volume and surface were independently associated with distal embolization (p = 0.007 and p = 0.028, respectively), no-reflow phenomenon (p = 0.002 and p = 0.006, respectively), and angiographically evident residual thrombus (p = 0.007 and p = 0.002, respectively). Higher thrombus density was correlated with worse pre-procedural TIMI flow (p < 0.001). Patients with higher aspirated volume and surface developed less ST resolution (p = 0.042 and p = 0.023, respectively).Conclusions: Angiographic outcomes linked with worse prognosis were more frequent among patients with larger extracted thrombus. Despite retrieving larger thrombus load in these patients, current thrombectomy devices fail to deal with thrombotic material adequately. Further studies of novel thrombus aspiration technologies are warranted to improve patient outcomes.Clinical Trial Registration: QUEST-STEMI trial ClinicalTrials.gov number: NCT03429608 Date of registration: February 12, 2018. The study was prospectively registered.

Background/aim Tumour budding (TB), i.e. the presence of groups of ≤5 tumour cells ahead of the invasive tumour front, is a pathological feature associated with an aggressive outcome in several cancer types. The aim of this study was to assess the value of TB as an independent prognostic factor of cutaneous squamous cell carcinomas (cSCC). Materials and methods We studied 25 cases of aggressive cSCC (defined as tumours that developed local recurrences and/or metastases after adequate excision) and 27 cases of non-aggressive cSCC. TB was expressed as the mean number of tumour buds in 5 adjacent high-power fields (HPF). Results Statistical analysis showed that TB is an independent predictive factor of cSCC aggressiveness. When the cut-off value of 0.8 buds/HPF was considered, the positive and negative predictive values for cSCC aggressiveness reached 77.3% and 75.0%, respectively. Conclusion As with other cancer types, TB appears to be a new independent pathological factor of aggressiveness of cSCC, providing a new tool to predict cSCC outcome, similar to other already established features associated with an adverse outcome (such as tumour size).

To evaluate different methods of defining fetal nasal bone hypoplasia in the second trimester for the detection of trisomy 21.Prospective study in Greek women undergoing anomaly scan between 18 + 0 and 23 + 6 weeks. The following methods of defining nasal bone hypoplasia were evaluated, either as a single marker or in combination with others: (1) BPD to nasal bone length (NBL) ratio; (2) multiples of the median (MoM) of NBL, according to normal curves from a Greek population; (3-4) NBL 2.5 percentile according to normal curves (3) commonly used internationally curves and (4) curves from a Greek population.In total, 1301 singleton fetuses were evaluated - 10 with trisomy 21. The best detection rate of trisomy 21 was achieved when the applied method was nasal bone percentiles adjusted to maternal ethnicity, in combination with other markers (2.5 percentile according to normal curves from a Greek population; p 0.001; sensitivity 50%; specificity 94.8%; false-positive rate 5.2%; positive likelihood ratio 9.6).Screening performance of fetal nasal bone hypoplasia in detecting trisomy 21 varies according to the method applied. The best screening performance is achieved by using percentiles adjusted to maternal ethnicity in combination with other markers of aneuploidy.

To compare two-dimensional with three-dimensional ultrasound evaluation of the fetal nasal bone in the second trimester.A prospective, non-interventional study was conducted, in 55 singleton fetuses, between 18 and 24 weeks' gestation. Fetal nasal bone length was measured in the midsagittal plane by two-dimensional imaging and in the midsagittal and coronal plane with three-dimensional ultrasound. All three measurements were compared with one another using one-way repeated samples-measures ANOVA and paired samples t-test.The average fetal nasal bone length (mean ± SD) as determined by the three methods was 7.01 ± 0.94 mm for the two-dimensional midsagittal, 6.96 ± 1.34 mm for the three-dimensional midsagittal, and 6.98 ± 1.32 mm for the three-dimensional coronal plane; comparisons between one another were not statistically significant. Unilateral hypoplasia and bifid shape of the fetal nasal bone were detected in 8.2% and 20.4% of cases, respectively, by three-dimensional ultrasound, whereas all cases evaded detection with two-dimensional ultrasound (p 0.001 and p = 0.001, respectively).Fetal nasal bone length measured with two-dimensional ultrasound does not differ significantly from three-dimensional measurements. However, three-dimensional ultrasound is superior in detecting unilateral nasal bone hypoplasia or absence and in assessing fetal nasal bone shape. Hence, fetal nasal bone examination in the second trimester should include three-dimensional ultrasound evaluation.

BACKGROUND Neuroendocrine (NE) cells are present in both normal prostate and prostate cancer. In addition, NE differentiation can be induced by various factors, such as IL-6, in vitro and in vivo. However, the mechanism of this differentiation and the role of NE cells in prostate cancer are not well understood. In this study, we evaluated the gene expression and analyzed the pathways in prostate cancer cells exposed to various NE differentiation inducing factors in vitro. METHODS Gene expression signatures between control LNCaP cells and each treatment induced NE cell line were compared using Affymetrix GeneChip with network and pathway analysis. RESULTS All treatments were able to transdifferentiate LNCaP cells into NE phenotype as shown by morphology changes and NE marker measurements. Of the 54,675 oligonucleotide-based probe sets in microarray, 44,975 were mapped into the Ingenuity Pathway Analysis database and were filtered according to the t-test P value. At P

High-throughput technologies such as DNA microarray are in the process of revolutionising the way modern biological research is being done. Bioinformatics tools are becoming increasingly important to assist biomedical scientists in their quest in understanding complex biological processes. Gene expression analysis has attracted a large amount of attention over the last few years mostly in the form of algorithms, exploring cluster and regulatory relationships among genes of interest, and programs that try to display the multidimensional microarray data in appropriate formats so that they make biological sense. To reduce the dimensionality of microarray data and make the corresponding analysis more biologically relevant, in this paper we propose a biologically-led approach to biochemical pathway analysis using microarray data and relevant biological knowledge. The method selects a subset of genes for each pathway that describes the behaviour of the pathway at a given experimental condition, and transforms them into pathway signatures. The metabolic pathways of Escherichia coli are used as a case study.

To compare normal ranges of ultrasonographically measured fetal nasal bone length in the second trimester between different ethnic groups.A prospective, non-interventional study in order to establish normal ranges of fetal nasal bone length in the second trimester in a Greek population was conducted in 1220 singleton fetuses between 18 completed weeks and 23 weeks and 6 days of gestation. A literature search followed in order to identify similar studies in different population groups. Fetal nasal bone length mean values and percentiles from different population groups were compared.Analysis of measurements in the Greek population showed a linear association, i.e., increasing nasal bone length with increasing gestational age from 5.73 mm at 18 weeks to 7.63 mm at 23 weeks. Eleven studies establishing normal ranges of fetal nasal bone length in the second trimester were identified. Comparison of fetal nasal bone length mean values between the 12 population groups showed statistically significant differences (PNormal ranges of fetal nasal bone length in the second trimester vary significantly between different ethnic groups. Hence, distinct ethnic nomograms of fetal nasal bone length in the second trimester should be used in a given population rather than an international model.

Neuroendocrine (NE) cells are present in both normal prostate and prostate cancer. In addition, NE differentiation can be induced by various factors, such as IL-6, in vitro and in vivo. However, the mechanism of this differentiation and the role of NE cells in prostate cancer are not well understood. In this study, we evaluated the gene expression and analyzed the pathways in prostate cancer cells exposed to various NE differentiation inducing factors in vitro.Gene expression signatures between control LNCaP cells and each treatment induced NE cell line were compared using Affymetrix GeneChip with network and pathway analysis.All treatments were able to transdifferentiate LNCaP cells into NE phenotype as shown by morphology changes and NE marker measurements. Of the 54,675 oligonucleotide-based probe sets in microarray, 44,975 were mapped into the Ingenuity Pathway Analysis database and were filtered according to the t-test P value. At P0.002, the number of genes that were differentially expressed included 302 of the IL-6 treated cells, 201 of genistein, 233 of epinephrine, and 191 of the charcoal stripped serum ones. A pooled data approach also showed 346 differentially expressed genes at the same P value. Gene ontology analysis showed that cancer-related function had the highest significance.Despite some overlap, each NE transdifferentiation inducing treatment was associated with a changed expression of a unique set of genes, and such gene profiling may help to elucidate the molecular mechanisms involved in NE transdifferentiation of prostate cancer cells.

Biology has been revolutionised by microarrays and bioinformatics is now a powerful tool in the hands of biologists. Gene expression analysis is at the centre of attention over the last few years mostly in the form of algorithms, exploring cluster relationships and dynamic interactions between gene variables, and programs that try to display the multidimensional microarray data in appropriate formats so that they make biological sense. In this paper we propose a simple yet effective approach to biochemical pathway analysis based on biological knowledge. This approach, based on the concept of signature and heuristic search methods such as hill climbing and simulated annealing, is developed to select a subset of genes for each pathway that fully describes the behaviour of the pathway at a given experimental condition in a bid to reduce the dimensionality of microarray data and make the analysis more biologically relevant.