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The authors evaluated the lipid profile of children with a positive family history of coronary heart disease (CHD), cerebrovascular disease (CVD), or hyperlipidemia and compared them with controls in order to identify risk indicators for atherosclerosis. A group of 315 children (group A) aged more than 2 years old with a positive family history were evaluated for serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein B100 (ApoB100), apolipoprotein A1 (Apo A1), and lipoprotein (a) (Lp[a]). These values were compared with the levels of a control group of 214 children of comparable age (group B). The median age of children in groups A and B was 10.6 (range 2.3-16) and 9.8 (range 3-13.7) years of age, respectively. Among these children, 196 (52%), 47 (12.5%), and 72 (19.1%) had a positive family history of CHD (group A1), cerebrovascular disease (CVD) (group A2), and hypercholesterolemia (group A3), respectively. We identified 8 children with genetically determined dyslipidemia: 2 children with homozygous and 6 with heterozygous familial hypercholesterolemia. Children in group A3 had significantly higher concentrations of TC, TG, LDL-C, and ApoB100 and lower concentrations of Apo A1 compared with controls, while no significant differences were found in concentrations of lipid variables among children of group A1, A2, and A3. Significant differences were also noted in the concentrations of TC, LDL-C, and Lp(a) between children of group A1 and controls. Screening the progeny of young patients with CHD or familial hypercholesterolemia can identify children at excessive risk for future vascular disease. [ABSTRACT FROM AUTHOR]

Background: L-asparaginase is valuable in treating pediatric acute lymphoblastic leukemia (ALL), yet its use has been associated with lipid profile disturbances. Methods: We compared the lipid profile [high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, apolipoprotein-α1 (Apo-A1), apolipoprotein-B100 (Apo-B100), lipoprotein-α (Lp-α), glucose, amylase, and lipase] between newly diagnosed ALL patients, ALL survivors, and healthy controls. We also assessed alterations of the parameters mentioned earlier during induction and consolidation treatment. Results: We recorded significant differences in the lipid profile at diagnosis of children with ALL compared to controls (HDL cholesterol, triglycerides, Apo-A1, and Apo-B100 levels). HDL cholesterol, total cholesterol, and Apo-A1 levels increased significantly during induction at most time points. Levels of Apo-B100, triglycerides, and Lp-α exhibited a downward trend. During re-induction, no change was observed. During the treatment of high-risk patients, we found no statistically significant difference for any of the examined variables. Conclusion: To confirm our preliminary results, the role of the administration of L-asparaginase and other medications in the variations in the lipid profile at diagnosis of children with ALL needs to be further elucidated with larger multicentre studies, including more patients from diverse ethnic backgrounds. [ABSTRACT FROM AUTHOR]

Background/Objectives : Lipid dysmetabolism seems to contribute to the development and progression of nonalcoholic fatty liver disease (NAFLD). Our aim was to compare serum lipidomic profile between patients with NAFLD having received monotherapy with vitamin E (400 IU/d) and those having received combination therapy with vitamin E (400 IU/d) and low-dose spironolactone (25 mg/d) for 52 weeks. Methods : This was a post hoc study of a randomized controlled trial (NCT01147523). Serum lipidomic analysis was performed in vitamin E monotherapy group ( n = 15) and spironolactone plus vitamin E combination therapy group ( n = 12). We employed an untargeted liquid chromatography-mass spectrometry lipid profiling approach in positive and negative ionization mode. Results : Univariate analysis revealed 36 lipid molecules statistically different between groups in positive mode and seven molecules in negative mode. Multivariate analysis in negative mode identified six lipid molecules that remained robustly different between groups. After adjustment for potential confounders, including gender, omega-3 supplementation, leptin concentration and homeostasis model assessment-insulin resistance (HOMA-IR), four lipid molecules remained significant between groups: FA 20:5, SM 34:2;O2, SM 42:3;O2 and CE 22:6, all being higher in the combination treatment group. Conclusions : The combination of spironolactone with vitamin E led to higher circulating levels of four lipid molecules than vitamin E monotherapy, after adjustment for potential confounders. Owing to very limited relevant data, we could not support that these changes in lipid molecules may be beneficial or not for the progression of NAFLD. Thus, mechanistic studies are warranted to clarify the potential clinical significance of these findings.

The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The cytotoxic effect on malignant cells has been attributed mainly to biologically active plasma-generated compounds, namely, reactive oxygen and nitrogen species. The intracellular accumulation of reactive oxygen and nitrogen species interferes strongly with the antioxidant defense system of malignant cells, activating multiple signaling cascades and inevitably leading to oxidative stress-induced cell death. This study aims to determine whether plasma-induced cancer cell death operates through a universal molecular mechanism that is independent of the cancer cell type. Using whole transcriptome data, we sought to investigate the activation mechanism of plasma-treated samples in patient-derived prostate cell cultures, melanoma, breast, lymphoma, and lung cancer cells. The results from the standardized single-cohort gene expression analysis and parallel multi-cohort meta-analysis strongly indicate that plasma treatment globally induces cancer cell death through immune-mediated mechanisms, such as interleukin signaling, Toll-like receptor cascades, and MyD88 activation leading to pro-inflammatory cytokine release and tumor antigen presentation.

Introduction: The Oxfordshire Community Stroke Project denotes four subtypes of ischemic stroke (total and partial anterior infarct, posterior, and lacunar). Hyperglycemia has been associated with a larger infarct size and poor prognosis., Aim: The purpose of the study was to investigate the correlation of glucose fluctuations with the Oxford sub-categories and patient outcomes using a blinded continuous glucose monitoring system., Methods: This is a non-interventional prospective observational study. Stroke patients with symptoms onset in the last 24h, participated in the study. A glucose sensor was placed for 72 hours. Disability was assessed using the modified Rankin Scale. Stroke subtypes were compared with total mean glucose and time in range using ANOVA analysis. Multiple ordinal logistic regression was employed to analyze outcomes and survival., Results: The sample consisted of 105 diabetic and non-diabetic patients. The overall mean glucose was 127.06 mg/dL and the time in range (70-140 mg/dL) was 70.98%. There was no significant difference between the stroke sub-categories and the total mean glucose. For every one-point increase in the time in range, we expect a 1.5% reduction in the odds of having a worse outcome. Patients with total anterior infarct are 2.31 times more likely to have a worse outcome than lacunar patients., Conclusion: The utilization of the Oxford classification may not be necessary for managing acute ischemic stroke glucose levels. Achieving glucose regulation and an increase in time in range can be attained through meticulous control, potentially extending life expectancy. Continuous glucose monitors may aid in achieving this objective., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Aristotle's University Ethics Committee issued approval 6.261. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fountouki et al.)

Nesfatin concentrations are positively correlated with beta cell function. However, it is unclear whether diet composition mediates this relationship. We recruited 27 overweight individuals who practiced Orthodox fasting (OF), a subset of the Mediterranean diet (MedDiet), for 7 weeks. Fourteen overweight people who practiced 16:8 time-restricted eating served as control group. Anthropometric parameters, biochemical data and adipokine levels were evaluated at baseline and after the end of the diet period (7 weeks from baseline). Subsequently, participants were asked to return to their usual eating plans, and an additional evaluation was performed 5 weeks after the end of the research diets (12 weeks from baseline). We observed a significant and negative correlation between HOMA-B and nesfatin values at 12 weeks, only in the OF group ( r = -0.455, p  = 0.01). In conclusion, returning to normal eating habits after 7 weeks of strict adherence to MedDiet affects the homeostatic balance between insulin secretion and nesfatin.

Background: Medications used to treat acute lymphoblastic leukemia (ALL), such as L-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes., Procedure: We aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls., Results: The only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence)., Conclusions: Lipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings., (© 2024. The Author(s).)

Athonian Orthodox fasting (AOF) is characterized by energy- and time-restricted eating (TRE) and is based on the Mediterranean diet. We aimed to investigate the impact of AOF compared to another TRE model on vaspin, omentin, nesfatin, and visfatin levels. We included 25 individuals (mean age 50.3 ± 8.6 years, 24% men) who practiced AOF and abstained from animal products, with the exception of seafood and fish. This group adopted a 12 h eating interval (08.00 to 20.00). In total, 12 participants (mean age 47.7 ± 8.7 years, 33.3% men) who practiced 16:8 TRE (eating from 09:00 to 17:00) and were allowed to consume meat served as the controls. Anthropometric and dietary data and adipokine levels were prospectively collected at three time points: at baseline, after the end of the diets (7 weeks), and 5 weeks after the participants returned to their typical eating habits (12 weeks from baseline). Vaspin levels decreased [795.8 (422.1-1299.4) (baseline) vs. 402.7 (203.8-818.9) (7 weeks) pg/mL, p = 0.002] and omentin levels increased [568.5 (437.7-1196.5) (baseline) vs. 659.0 (555.7-1810.8) (12 weeks) pg/mL, p = 0.001] in the AOF group, while none of the analyzed adipokines changed significantly in the TRE group. The variations observed in vaspin and omentin concentrations in the AOF group were independent of age, sex, changes in anthropometry and fat intake. In conclusion, AOF can significantly reduce vaspin and increase omentin, whose levels are known to increase and decrease, respectively, in obesity and type 2 diabetes. The implications of these findings for cardiometabolic health warrant further investigation.

Background: Acute pyelonephritis (APN) in pediatric patients may lead to kidney scarring and is one of the main causes of permanent kidney damage. The incidence of kidney scarring after one febrile urinary tract infection (UTI) is reported to range from 2.8 to 15%, with the percentage rising to 28.6% after ≥ 3 febrile UTIs. Corticosteroids may have a role in the reduction of kidney scar formation and urine cytokine levels. The possible benefit of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN has been recently examined in randomized controlled trials (RCTs)., Objectives: The aim of this meta-analysis was to provide a summary of the current literature about the efficacy and safety of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN., Data Sources: An extensive literature search through major databases (PubMed/MEDLINE and Scopus) was carried out for RCTs from inception until October 12, 2022, investigating the efficacy and safety of adjuvant corticosteroids in preventing kidney scarring in children with APN. A risk ratio with 95% CI was used for dichotomous outcomes., Results: In total, 5 RCTs with 918 pediatric patients with APN were included in the study. Adjuvant corticosteroid treatment revealed a statistically significant reduction in kidney scarring (95% CI 0.42-0.95, p = 0.03), without increasing the risk of adverse events like bacteremia, prolonged hospitalization, or recurrence of UTI., Limitations: There were limitations regarding sample size (n = 498 children), different classes of corticosteroids (methylprednisolone or dexamethasone), different routes of corticosteroid administration (intravenous or oral), and different day courses (3-day or 4-day course)., Conclusions: Adjuvant corticosteroid administration seems to have a beneficial effect on kidney scar reduction in children with APN. Future studies should focus on the evaluation of the efficacy and safety of corticosteroids in kidney scarring reduction after APN to strengthen the results of our study. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s).)

Background: Acute myocardial infarction (AMI) remains a major cause of death worldwide. Survivors of AMI are particularly at high risk for additional cardiovascular events. Consequently, a comprehensive approach to secondary prevention is necessary to mitigate the occurrence of downstream complications. This may be achieved through a multiparametric tailored risk stratification by incorporating clinical, laboratory and echocardiographic parameters., Methods: The ''CLEAR-AMI Study'' (ClinicalTrials.gov Identifier: NCT05791916) is a non-interventional, prospective study including consecutive patients with AMI without a known history of coronary artery disease. All patients satisfying these inclusion criteria are enrolled in the present study. The rationale of this study is to refine risk stratification by using clinical, laboratory and novel echocardiographic biomarkers. All the patients undergo a comprehensive transthoracic echocardiographic assessment, including strain and myocardial work analysis of the left and right heart chambers, within 48 h of admission after coronary angiography. Their laboratory profile focusing on systemic inflammation is captured during the first 24 h upon admission, and their demographic characteristics, past medical history, and therapeutic management are recorded. The angioplasty details are documented, the non-culprit coronary lesions are archived, and the SYNTAX score is employed to evaluate the complexity of coronary artery disease. A 24-month follow-up period will be recorded for all patients recruited., Conclusion: The ''CLEAR-AMI" study is an ongoing prospective registry endeavoring to refine risk assessment in patients with AMI without a known history of coronary artery disease, by incorporating echocardiographic parameters, biochemical indices, and clinical and coronary characteristics in the acute phase of AMI.

Introduction: Fibroblast growth factor 23 (FGF23) belongs structurally to the endocrine FGF protein family, which also includes FGF19 and FGF21. In the past decade, FGF23 has emerged as a possible diagnostic, prognostic biomarker, and therapeutic target in several conditions. Data about COVID-19 and FGF23 is still limited, yet they suggest interesting interactions., Objective: In the present study, the levels of FGF23 were investigated in COVID-19 patients. These levels were also correlated with other inflammatory markers., Materials and Methods: In our prospective observational study, blood samples were collected from 81 patients admitted with COVID-19 (31 males and 50 females). We analyzed the relation of serum FGF23 levels with biochemistry, total blood count, coagulation parameters, and demographic data., Results: The distribution of FGF23 serum levels according to sex and age (n 28-40 =8, n 41-60 =28, n 65-75= 25, n 75+ =20) was similar. No significant correlation between FGF23 and any other biochemistry, total blood count, and coagulation parameter was revealed in the whole sample. Nevertheless, there was a variation in the results among different age groups., Conclusion: FGF23 levels seem to vary in symptomatic COVID-19 infection, but well-organized studies with larger numbers of patients in each group are needed to determine any reliable correlation between FGF23 and other laboratory parameters., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Myrou et al.)

During the COVID-19 pandemic, different SARS-CoV-2 variants of concern (VOC) with specific characteristics have emerged and spread worldwide. At the same time, clinicians routinely evaluate the results of certain blood tests upon patient admission as well as during hospitalization to assess disease severity and the overall patient status. In the present study, we searched for significant cell blood count and biomarker differences among patients affected with the Alpha, Delta and Omicron VOCs at admission. Data from 330 patients were retrieved regarding age, gender, VOC, cell blood count results (WBC, Neut%, Lymph%, Ig%, PLT), common biomarkers (D-dimers, urea, creatinine, SGOT, SGPT, CRP, IL-6, suPAR), ICU admission and death. Statistical analyses were performed using ANOVA, the Kruskal-Wallis test, two-way ANOVA, Chi-square, T-test, the Mann-Whitney test and logistic regression was performed where appropriate using SPSS v.28 and STATA 14. Age and VOC were significantly associated with hospitalization, whereas significant differences among VOC groups were found for WBC, PLT, Neut%, IL-6, creatinine, CRP, D-dimers and suPAR. Our analyses showed that throughout the current pandemic, not only the SARS-CoV-2 VOCs but also the laboratory parameters that are used to evaluate the patient's status at admission are subject to changes.

Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular carcinoma. It affects almost 30% of adults in the general population and up to 70% of people with type 2 diabetes (T2DM), sharing common pathogenetic pathways with the latter. In addition, NAFLD is closely related to obesity, which acts in synergy with other predisposing conditions, including alcohol consumption, provoking progressive and insidious liver damage. Among the most potent risk factors for accelerating the progression of NAFLD to fibrosis or cirrhosis, diabetes stands out. Despite the rapid rise in NAFLD rates, identifying the optimal treatment remains a challenge. Interestingly, NAFLD amelioration or remission appears to be associated with a lower risk of T2DM, indicating that liver-centric therapies could reduce the risk of developing T2DM and vice versa. Consequently, assessing NAFLD requires a multidisciplinary approach to identify and manage this multisystemic clinical entity early. With the continuously emerging new evidence, innovative therapeutic strategies are being developed for the treatment of NAFLD, prioritizing a combination of lifestyle changes and glucose-lowering medications. Based on recent evidence, this review scrutinizes all practical and sustainable interventions to achieve a resolution of NAFLD through a multimodal approach.

Background: Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide. The majority of patients who suffer an AMI have a history of at least one of the standard modifiable risk factors (SMuRFs): smoking, hypertension, dyslipidemia, and diabetes mellitus. However, emerging scientific evidence recognizes a clinically significant and increasing proportion of patients presenting with AMI without any SMuRF (SMuRF-less patients). To date, there are no adequate data to define specific risk factors or biomarkers associated with the development of AMIs in these patients., Methods: The ''Beyond-SMuRFs Study'' is a prospective, non-interventional cohort trial designed to enroll patients with AMI and no previous coronary intervention history, who undergo coronary angiography in two academic hospitals in Thessaloniki, Greece. The rationale of the study is to investigate potential relations between SMuRF-less AMIs and the clinical, laboratory and imaging profile of patients, by comparing parameters between patients with and without SMuRFs. Complete demographic and comprehensive clinical data will be recorded, Venous blood samples will be collected before coronary angiography and the following parameters will be measured: total blood count, standard biochemistry parameters, coagulation tests, hormone levels, glycosylated hemoglobin, N- terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels- as well as serum levels of novel atherosclerosis indicators and pro-inflammatory biomarkers. Furthermore, all participants will undergo a complete and comprehensive transthoracic echocardiographic assessment according to a pre-specified protocol within 24 h from admission. Among others, 2D-speckle-tracking echocardiographic analysis of cardiac chambers and non-invasive calculation of myocardial work indices for the left ventricle will be performed. Moreover, all patients will be assessed for angiographic parameters and the complexity of coronary artery disease using the SYNTAX score. Multivariable linear and logistic regression models will be used to phenotypically characterize SMuRF-less patients and investigate independent clinical, laboratory, echocardiographic and angiographic biomarkers-predictors of SMuRF-less status in AMI.The first patient was enrolled in March 2022 and completion of enrollment is expected until December 2023., Discussion: The ''Beyond-SmuRFs'' study is an ongoing prospective trial aiming to investigate potential clinical, laboratory and imaging biomarkers associated with the occurrence of AMIs in SMuRF-less patients. The configuration of these patients' profiles could lead to the development of personalized risk-stratification models predicting the occurrence of cardiovascular events in SΜuRF-less individuals., Trial Registration: ClinicalTrials.gov Identifier: NCT05535582 / September 10, 2022., (© 2023. The Author(s).)

Background: Despite ongoing treatment advancements in chronic heart failure (HF), mortality and readmission rates remain high for patients hospitalized for decompensated acute HF. These patients represent a distinct HF group, which requires emergent echocardiographic evaluation in an attempt to provide optimal and individualized acute care. The role of serial advanced echocardiographic assessment in acute HF for risk stratification and treatment guidance has not been thoroughly explored., Methods: The "Beyond Myo-HF Study" is a prospective, non-interventional cohort trial designed to enroll acutely admitted patients with symptoms and/or signs of HF. The aim of this study is to investigate whether intrahospital changes of conventional and novel echocardiographic indices of myocardial function and congestion-related markers can predict early mortality, late mortality, and HF rehospitalization. As per the protocol, all patients undergo a pair of state-of-the-art echocardiographic assessments, with a rigorous protocol including speckle tracking analysis of all cardiac chambers and myocardial work analysis for the left and right ventricle, upon admission and pre-discharge. Their laboratory profile is captured at those two time-points, and their therapeutic management is recorded. Patients will be followed-up for a median period of 12 months after enrollment., Conclusions: The "Beyond Myo-HF" study is an ongoing, prospective trial aspiring to provide deep insight into the pathophysiology of acute HF, to enlighten the reverse cardiac functional and anatomical remodeling during hospitalization, and to recognize echocardiographic patterns capable of predicting adverse outcomes during and post decompensation of acute HF.

We prospectively assessed changes in free 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (VDBP) among overweight adults who followed a pescatarian Orthodox intermittent fasting regimen ( n  = 59) and controls who followed a low-fat 12:12 diet ( n  = 46). Total and free 25(OH)D, parathyroid hormone, VDBP, anthropometric data, and amino acid intake were evaluated in both groups at three time points: at baseline, 7 weeks after diet implementation, and 5 weeks after participants returned to their usual eating habits (12 weeks from baseline). An increase in amino acid intake between baseline and 12 weeks was independently correlated with higher free 25(OH)D values at 12 weeks for both groups. Our findings suggest that diet can affect free 25(OH)D concentrations, through variations in amino acid intake, independently of exposure to sunlight, providing novel mechanistic insights into the future planning of vitamin D supplementation strategies. However, this hypothesis needs to be tested in larger studies.

Introduction: Investigations of biofeedback (BF) and neurofeedback (NF) training for nicotine addiction have been long documented to lead to positive gains in smoking status, behavior and to changes in brain activity. We aimed to: (a) evaluate a multi-visit combined BF/NF intervention as an alternative smoking cessation approach, (b) validate training-induced feedback learning, and (c) document effects on resting-state functional connectivity networks (rsFCN); considering gender and degree of nicotine dependence in a longitudinal design. Methods: We analyzed clinical, behavioral, and electrophysiological data from 17 smokers who completed five BF and 20 NF sessions and three evaluation stages. Possible neuroplastic effects were explored comparing whole-brain rsFCN by phase-lag index (PLI) for different brain rhythms. PLI connections with significant change across time were investigated according to different resting-state networks (RSNs). Results: Improvements in smoking status were observed as exhaled carbon monoxide levels, Total Oxidative Stress, and Fageström scores decreased while Vitamin E levels increased across time. BF/NF promoted gains in anxiety, self-esteem, and several aspects of cognitive performance. BF learning in temperature enhancement was observed within sessions. NF learning in theta/alpha ratio increase was achieved across baselines and within sessions. PLI network connections significantly changed across time mainly between or within visual, default mode and frontoparietal networks in theta and alpha rhythms, while beta band RSNs mostly changed significantly after BF sessions. Discussion: Combined BF/NF training positively affects the clinical and behavioral status of smokers, displays benefit in smoking harm reduction, plays a neuroprotective role, leads to learning effects and to positive reorganization of RSNs across time. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02991781., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pandria, Athanasiou, Styliadis, Terzopoulos, Mitsopoulos, Paraskevopoulos, Karagianni, Pataka, Kourtidou-Papadeli, Makedou, Iliadis, Lymperaki, Nimatoudis, Argyropoulou-Pataka and Bamidis.)

Background: Clinical classification of autistic patients based on current WHO criteria provides a valuable but simplified depiction of the true nature of the disorder. Our goal is to determine the biology of the disorder and the ASD-associated genes that lead to differences in the severity and variability of clinical features, which can enhance the ability to predict clinical outcomes., Method: Novel Whole Exome Sequencing data from children (n = 33) with ASD were collected along with extended cognitive and linguistic assessments. A machine learning methodology and a literature-based approach took into consideration known effects of genetic variation on the translated proteins, linking them with specific ASD clinical manifestations, namely non-verbal IQ, memory, attention and oral language deficits., Results: Linear regression polygenic risk score results included the classification of severe and mild ASD samples with a 81.81% prediction accuracy. The literature-based approach revealed 14 genes present in all sub-phenotypes (independent of severity) and others which seem to impair individual ones, highlighting genetic profiles specific to mild and severe ASD, which concern non-verbal IQ, memory, attention and oral language skills., Conclusions: These genes can potentially contribute toward a diagnostic gene-set for determining ASD severity. However, due to the limited number of patients in this study, our classification approach is mostly centered on the prediction and verification of these genes and does not hold a diagnostic nature per se. Substantial further experimentation is required to validate their role as diagnostic markers. The use of these genes as input for functional analysis highlights important biological processes and bridges the gap between genotype and phenotype in ASD., (© 2022. The Author(s).)

The global vaccination against SARS-CoV-2 has highlighted the need of assessing vaccines' immunogenicity against COVID-19. To evaluate humoral immunity induced by the BNT162b2 vaccine, we enrolled health care workers at AHEPA University Hospital of Thessaloniki, Greece to measure Anti-S SARS-CoV-2, anti-RBD SARS-CoV-2 and neutralizing antibodies. A total of 955 individuals with a median age of 50 years, were included in the study. Median values of antibodies were 1947.27 BAU/mL (Abbott SARS-CoV-2 IgG II Quant), 2064.98 BAU/mL (MAGLUMI SARS-CoV-2 S-RBD IgG) and 2464.63 IU/mL (MAGLUMI SARS-CoV-2 Neutralizing Antibodies). Individuals previously infected had greater antibody responses than infection naive ones and a 7-fold higher neutralizing antibodies titre. Antibodies degreased by age but not sex. Spearman's correlation coefficient among the three assays ranged from 0.903 to 0.969. The BNT162b2 vaccine was highly immunogenic in our cohort. Further research is needed to evaluate the vaccine's immunogenicity through time as well as in different populations., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

The exact mechanisms mediating the metabolic effects of Orthodox fasting remain unclear. Plasma adiponectin, biochemical and anthropometrical data were evaluated in 55 Orthodox fasters (OF) and 42 time-restricted eating controls (all women, mean age 47.8 years) at three time points: baseline, end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). In the OF group, there was an increase in adiponectin values at 12 weeks compared with baseline (9815.99 vs 8983.52 mg/ml, p  = 0.02) and a reduction in body fat mass between baseline and 12 weeks (35.44 vs 32.17%, p  = 0.004) and between 7 and 12 weeks (35.33 vs 32.17%, p  = 0.003). In the same group, an inverse correlation between adiponectin and waist circumference values was observed over the entire study period. Our results provide novel evidence that Orthodox fasting has favourable metabolic effects related to improved adiponectin concentrations.

Background: We sought to assess the interplay between right ventricle (RV) fibrosis, biventricular dysfunction based on global longitudinal strain (GLS) analysis, and biomarkers such as Galectin-3 (Gal-3), procollagen type III (PCIII), and NTproBNP., Methods: We studied 35 adult patients with rToF. All patients underwent a cardiac magnetic resonance (CMR) scan including feature tracking for deformation imaging. Blood biomarkers were measured., Results: LGE RV was detected in all patients, mainly at surgical sites. Patients with the highest RV LGE scoring had greater RV dilatation and dysfunction whereas left ventricular (LV) function was preserved. LV GLS correlated with RV total fibrosis score ( p = 0.007). A LV GLS value of -15.9% predicted LGE RV score > 8 (AUC 0.754 ( p = 0.02)). Neither RV GLS nor biomarker levels were correlated with the extent of RV fibrosis. A cut-off value for NTproBNP of 145.25 pg/mL predicted LGE RV score > 8 points (AUC 0.729, ( p = 0.03)). A cut-off value for Gal-3 of 7.42 ng/mL predicted PR Fraction > 20% [AUC 0.704, ( p = 0.05)]., Conclusions: A significant extent of RV fibrosis was mainly detected at surgical sites of RV, affecting RV performance. CMR-FT reveals subtle LV dysfunction in rToF patients, due to decreased performance of the fibrotic RV. Impaired LV function and elevated NTproBNP in rToF reflect a dysfunctional fibrotic RV.

Continuous glucose monitoring (CGM) facilitates the assessment of short-term glucose variability and identification of acute excursions of hyper- and hypo-glycemia. Among 37 diabetic hemodialysis patients who underwent 7-day CGM with the iPRO2 device (Medtronic Diabetes, Northridge, CA, USA), we explored the accuracy of glycated albumin (GA) and hemoglobin A1c (HbA1c) in assessing glycemic control, using CGM-derived metrics as the reference standard. In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) in diagnosing a time in the target glucose range of 70-180 mg/dL (TIR 70-180 ) in <50% of readings was higher for GA (AUC: 0.878; 95% confidence interval (CI): 0.728-0.962) as compared to HbA1c (AUC: 0.682; 95% CI: 0.508-0.825) ( p < 0.01). The accuracy of GA (AUC: 0.939; 95% CI: 0.808-0.991) in detecting a time above the target glucose range > 250 mg/dL (TAR >250 ) in >10% of readings did not differ from that of HbA1c (AUC: 0.854; 95% CI: 0.699-0.948) ( p = 0.16). GA (AUC: 0.712; 95% CI: 0.539-0.848) and HbA1c (AUC: 0.740; 95% CI: 0.570-0.870) had a similarly lower efficiency in detecting a time below target glucose range < 70 mg/dL (TBR <70 ) in >1% of readings ( p = 0.71). Although the mean glucose levels were similar, the coefficient of variation of glucose recordings (39.2 ± 17.3% vs. 32.0 ± 7.8%, p < 0.001) and TBR <70 (median (range): 5.6% (0, 25.8) vs. 2.8% (0, 17.9)) were higher during the dialysis-on than during the dialysis-off day. In conclusion, the present study shows that among diabetic hemodialysis patients, GA had higher accuracy than HbA1c in detecting a 7-day CGM-derived TIR 70-180 < 50%. However, both biomarkers provided an imprecise reflection of acute excursions of hypoglycemia and inter-day glucose variability.

We aimed to evaluate sex differences in changes of lipid profiles in a cohort of metabolically healthy adults following Orthodox fasting (OF), as well as to assess a potential role of vitamin D status in mediating these variations. 45 individuals (24 premenopausal females, 53.3 %) with mean age 48.3 ± 9.1 years and mean Body Mass Index 28.7 ± 5.8 kg/m 2 were prospectively followed for 12 weeks. Anthropometry, dietary and biochemical data regarding serum lipids, and vitamin D status were collected at baseline, 7 weeks after the implementation of OF, and 5 weeks after fasters returned to their standard dietary habits (12 weeks from baseline). According to 25-hydroxy-vitamin D [25(OH)D] measurements, participants were divided into two groups: those with concentrations above and below the median of values. Females with 25(OH)D concentrations below the median manifested a non-significant reduction by approximately 15 % in total and low-density lipoprotein cholesterol during the fasting period, followed by a significant increase 5 weeks after OF cessation (170.7 vs. 197.5 and 99.6 vs. 121.0 mg/dl respectively, p < 0.001). In contrast, males with 25(OH)D levels below the median demonstrated an inverse, non-significant trend of increase in lipid concentrations during the whole study period. Our findings suggest strikingly different inter-gender lipid responses to a dietary model of low-fat, mediated by vitamin D status. Further studies are necessary to reveal the underlying mechanisms and assess the importance of these differences with respect to cardiovascular health and the benefit of vitamin D supplementation strategies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Irisin has been recently identified as an adipomyokine produced during physical activity and involved in the browning of adipose tissue. Despite the emerging evidence suggesting an inverse relationship between irisin plasma concentrations and adverse metabolic outcomes, the exact impact of diet on irisin levels remains obscure. Thus, we aimed to assess the effects of two dietary patterns, Christian Orthodox fasting (OF) and 16:8 time-restricted eating (TRE), on circulating irisin levels among overweight, metabolically healthy, adults. Plasma irisin, glucose and lipid parameters, calcium homeostasis, and anthropometry were evaluated in 29 Orthodox fasters and 14 age and body mass index (BMI)-matched TRE controls (mean age and BMI, 48.8 years and 28.7 kg/m 2 , respectively) at three, distinct time points-before the implementation of the energy-restricted diets (baseline), at the end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). Repeated measures analysis was applied to assess differences between the two groups and the effect of several indices on irisin levels at all three time points. At 12 weeks, the OF group manifested higher irisin concentrations compared with both its baseline values (64.3 ± 54.4 vs. 43.6 ± 42.2 ng/mL, p = 0.01) and those of the TRE group at the same time point (64.3 ± 54.4 vs. 44.2 ± 26.6 ng/mL, p = 0.04). Glycemic, lipid, and anthropometric parameters were not found to correlate with irisin levels. In contrast, parathyroid hormone (PTH) concentrations at 12 weeks correlated with irisin concentrations ( p = 0.04), indicating that lower values of irisin are expected for higher PTH measurements. The findings of this pilot study suggest favorable long-term effects of OF on irisin levels. The interplay between irisin, PTH, and diet warrants further investigation.