Publications by authors named "George P Chrousos"

582 Publications

Inherited/Genetically-Associated Pheochromocytoma/ Paraganglioma Syndromes and COVID-19.

Medicina (Kaunas) 2021 Sep 28;57(10). Epub 2021 Sep 28.

University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, GR-11527 Athens, Greece.

In some subjects with inherited pheochromocytoma/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1α) stabilization/activation could lead to an increase in angiotensin converting enzymes (ACE). This would result in the stimulation of angiotensin (AT) II production and, hence, reduce the availability of ACE 2. The latter would provide decreased numbers of binding sites for the spike protein of SARS-CoV-2 and, therefore, result in less points of viral entry into cells. Thus, subjects with HIF1α-associated PPG syndromes may benefit from an inherent protective effect against COVID-19. Such an implication of HIF1α vis-à-vis COVID-19 could open ways of therapeutic interventions.
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http://dx.doi.org/10.3390/medicina57101033DOI Listing
September 2021

lncRNA is consistently detected in breastmilk exosomes and its expression is downregulated in mothers of preterm infants.

Int J Mol Med 2021 Dec 15;48(6). Epub 2021 Oct 15.

Laboratory of Gene Expression, Molecular Diagnostics and Modern Therapeutics, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece.

Breast milk is the ideal food for infants and undoubtedly has immediate and long‑term benefits. Breast milk contains extracellular vesicles (EVs) i.e., exosomes secreted by maternal breast cells. Exosomes carry genetic material, such as long non‑coding RNAs (lncRNAs), which possibly participate in cell‑to‑cell communications, as they are known to regulate critical gene pathways. The aim of the present study was to screen human breastmilk exosomes for their lncRNA cargo and to examine exosomal lncRNA levels associated with milk obtained from mothers that gave birth at term or prematurely (<37 weeks of gestation). Samples were collected at 3 weeks postpartum from 20 healthy, breastfeeding mothers; 10 mothers had given birth at full‑term and 10 mothers preterm. Exosomal RNA was extracted from all samples and the expression of 88 distinct lncRNAs was determined using reverse transcription‑quantitative PCR. A total of 13 lncRNAs were detected in ≥85% of the samples, while 31 were detected in ≥50% of the samples. Differential expression analysis of the lncRNAs between the two groups revealed ≥2‑fold differences, with generally higher lncRNA concentrations found in the milk of the mothers that gave birth at term compared with those that gave birth preterm. Among these, the non‑coding RNA activated at DNA damage () was prominently detected in both groups, and its expression was significantly downregulated in the breast milk exosomes of mothers who delivered preterm. On the whole, the present study demonstrates that breast milk lncRNAs may be important factors of normal early human development. Collectively, the presence of lncRNAs in human breast milk may explain the consistent inability of researchers to fully 'humanize' animal milk.
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http://dx.doi.org/10.3892/ijmm.2021.5049DOI Listing
December 2021

Validation of the Cosmetic Procedure Screening (COPS) Questionnaire in the Greek language.

EMBnet J 2021 23;26. Epub 2021 Aug 23.

Postgraduate Course of Science of Stress and Health Promotion, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Practitioners in cosmetic and aesthetic treatment practices are likely to unknowingly work with patients with Body Dysmorphic Disorder (BDD). Screening questionnaires to identify the disorder in Greece are lacking. The purpose of this study was to validate a Greek version of the Cosmetic Procedure Screening (COPS) questionnaire, a self-report measure of how the respondents feel about their appearance, before an aesthetic intervention. The COPS was translated into Greek and was completed by 216 adult females from several areas of Attica (four private beauty centers, three dermatology clinics, five plastic surgery clinics, and Thriasio General Hospital of Elefsina) who pursued a cosmetic procedure. Participants also completed the Perceived Stress Scale (PSS-14). The Greek version of the COPS questionnaire demonstrated high internal consistency (Cronbach's α of 0.856) with corrected item's total range 0.468 to 0.687. Two of the factors explained 58.98% of total variance. Twenty (9.26%) women had a possible diagnosis of BDD (80% were unmarried, 95% had no children, 80% had university education). An increase in perceived stress levels was associated with an increase in the likelihood of being diagnosed with BDD (Pearson's r=0.726). The Greek version of the COPS questionnaire is a valid instrument that can be used by professionals to screen adult women for BDD.
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http://dx.doi.org/10.14806/ej.26.1.971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494448PMC
August 2021

Reliability and validity of the Peer Relation Questionnaire in a sample of Greek school children and adolescents.

EMBnet J 2021 23;26. Epub 2021 Aug 23.

Postgraduate Course of Science of Stress and Health Promotion, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Bullying among children and adolescents can have detrimental effects on their physical and mental health. The first step in the identification of bullying is the detection of relevant signs and behaviours, with the use of appropriate instruments. The widely used Peer Relation Questionnaire (PRQ)has been developed to measure bullying behaviour in children and adolescents. The aim of this study was to translate and validate this instrument in the Greek language in a school sample of children and adolescents. A sample of 193 students (mean age ± SD 11.44 ± 1.26 years, girls 49.7%), was recruited from elementary and junior high schools of the public and private sector, in the capital of Athens, Greece. Along with the Peer Relation Questionnaire, the Stress in Children questionnaire and a structured inquiry regarding satisfaction from various aspects of life were used to assess the criterion validity of the Peer Relation Questionnaire. Results revealed good psychometric properties of the questionnaire in the Greek language. The principal component analysis resulted in two subscales that demonstrated an adequate internal consistency and a significant correlation with stress and satisfaction parameters, suggesting satisfying criterion validity. Meaningful associations between demographic characteristics and the subscales were also found. The Greek version of the Peer Relation Questionnaire-short form can be used as a valid tool to measure bullying behaviour in children and adolescents.
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http://dx.doi.org/10.14806/ej.26.1.974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494435PMC
August 2021

Validation of the Instagram Addiction Scale in Greek Youth.

EMBnet J 2021 23;26. Epub 2021 Aug 23.

Postgraduate Course of Science of Stress and Health Promotion, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Instagram is one of the fastest growing social networking platforms. A body of evidence suggests that Instagram problematic use and addiction have negative effects on the psychological well-being of young people. The Instagram Addiction Scale, a self-report tool assessing Instagram problematic use and addiction, has been developed recently. The aim of the present study was to validate the Instagram Addiction Scale in the Greek language and to assess its psychometric properties. An online and on-print self-report survey was conducted among Greek youth, aged between 18 and 24 years. The survey included the Instagram Addiction Scale, the Rosenberg Self-esteem Scale, the Perceived Stress Scale, and the Big Five Inventory. A total of 967 respondents participated in the study. The analysis suggested that the Greek version of the Instagram Addiction Scale has good psychometric properties. The principal component factor analysis for construct validity generated two subscales as the original instrument: social effect and impulsion. Internal consistency for the two subscales and the scale's total score was satisfactory, with Cronbach's α at 0.76, 0.85 and 0.88, respectively. Correlation analyses revealed positive associations between the perceived stress scale and social effect, and the Instagram Addiction Scale's total score (p<0.0001 and p=0.002 respectively). This is the first study validating the Instagram Addiction Scale in Greek youth, which can be used by researchers and practitioners for the evaluation of youth problematic use of Instagram.
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http://dx.doi.org/10.14806/ej.26.1.973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494434PMC
August 2021

Pythagorean Self Awareness Intervention in Caregivers of Patients with Motor Disabilities.

EMBnet J 2021 23;26. Epub 2021 Aug 23.

Postgraduate Course of Science of Stress and Health Promotion, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Caregiving for disabled people is a strenuous task often provided by family members, with adverse repercussions on the caregivers' health. The aim of this study was to evaluate, for the first time, the effects of a novel cognitive-based stress management technique, the Pythagorean Self-Awareness Intervention (PSAI) on the stress levels and other cognitive and psychological characteristics of non-paid caregivers of patients with motor disability. In this quasi-experimental study, 59 caregivers of first-degree relatives with motor disabilities due to chronic neurological diseases, inpatients at a Rehabilitation Center, in Athens, Greece, were assigned to an intervention (PSAI, n=28) and a control group (received unstructured consultation, n=31). Psychological, cognitive, and sleep-related measurements (Zarit Burden Interview tool, Pittsburgh Sleep Quality Index, Self-Efficacy Scale, Depression, Anxiety and Stress Scale, Symbol Digit Modalities Test, California Verbal Learning Test-II, Brief Visuospatial Memory Test-Revised) were held at baseline and after 8 weeks (at completion of PSAI) in both groups. PSAI was found to decrease caregivers' stress, depressive symptoms and anxiety and improve their sleep quality, visual memory, self-efficacy, and cognitive speed processing. Future randomized controlled studies are needed to investigate the effects of this novel intervention in larger samples of caregivers.
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http://dx.doi.org/10.14806/ej.26.1.970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494422PMC
August 2021

Stress Management in Elementary School Students: a Pilot Randomised Controlled Trial.

EMBnet J 2021 23;26. Epub 2021 Aug 23.

Postgraduate Course of Science of Stress and Health Promotion, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Research has shown that stress experiences begin in early stages of life. Stress management techniques have appeared to be beneficial for the development or enhancement of stress coping skills. The aim of this pilot randomised controlled trial was to assess the effect of a 12-week intervention, comprising training in diaphragmatic breathing and progressive muscular relaxation, on elementary school students' stress levels. Outcomes on the quality of life and behavioural aspects of the students were also assessed. Standardised questionnaires were administered at baseline and after the 12-week intervention program. Fifty-two children aged 10 to 11 years were randomly assigned to intervention (n=24) and control groups (n=28). Children of the intervention group demonstrated lower levels of stress (in all three subscales of lack of well-being, distress, and lack of social support) and improved aspects of quality of life (physical, emotional, and school functioning). No significant differences were observed regarding the examined behavioural dimensions, in the intervention group. Larger randomised controlled trials with follow-up evaluations are needed to ascertain the positive outcomes of such programs on elementary school children.
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http://dx.doi.org/10.14806/ej.26.1.976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494420PMC
August 2021

Validation of the Greek version of the Problematic Internet Use Questionnaire - Short Form (PIUQ-SF-6).

EMBnet J 2021 23;26. Epub 2021 Aug 23.

University Research Institute of Maternal and Child Health & Precision Medicine and UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.

Internet is a necessary tool of everyday routine, however, concerns about the development of abnormal behaviours in relation to its use by adolescents are constantly growing. The need of brief screening tools for problematic internet use in teenagers in Greece is imperative. The purpose of this study was to validate the 6-item short form of the Problematic Internet Use Questionnaire (PIUQ-SF-6) in a Greek sample of adolescents. The sample consisted of 200 adolescents (55.0% males, 61.6% high school students, 38.4% junior high school students) who completed the study's questionnaires i.e., a demographic questionnaire, the PIUQ-SF-6, the Young's Diagnostic Questionnaire (YDQ) and the Adolescent Computer Addiction Test (ACAT). The internal consistency of the Greek version of PIUQ-SF-6 was sufficient and acceptable (Cronbach's alpha coefficient a = 0.80). Confirmatory Factor Analysis was significant, and goodness-of-fit was adequate. For establishing convergent validity, Pearson's and Spearman's correlation coefficients were calculated between the PIUQ-SF-6 and ACAT scales and Receiver Operating Characteristic (ROC) analysis (between PIUQ-SF-6 and YDQ) indicated an excellent accuracy. The Greek version of the PIUQ-SF-6 demonstrated satisfactory psychometric properties (reliability and validity) and is recommended as a reliable screening tool for problematic internet use in Greek adolescents.
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http://dx.doi.org/10.14806/ej.26.1.978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494242PMC
August 2021

Human‑made electromagnetic fields: Ion forced‑oscillation and voltage‑gated ion channel dysfunction, oxidative stress and DNA damage (Review).

Int J Oncol 2021 Nov 7;59(5). Epub 2021 Oct 7.

Choremeion Research Laboratory, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Exposure of animals/biological samples to human‑made electromagnetic fields (EMFs), especially in the extremely low frequency (ELF) band, and the microwave/radio frequency (RF) band which is always combined with ELF, may lead to DNA damage. DNA damage is connected with cell death, infertility and other pathologies, including cancer. ELF exposure from high‑voltage power lines and complex RF exposure from wireless communication antennas/devices are linked to increased cancer risk. Almost all human‑made RF EMFs include ELF components in the form of modulation, pulsing and random variability. Thus, in addition to polarization and coherence, the existence of ELFs is a common feature of almost all human‑made EMFs. The present study reviews the DNA damage and related effects induced by human‑made EMFs. The ion forced‑oscillation mechanism for irregular gating of voltage‑gated ion channels on cell membranes by polarized/coherent EMFs is extensively described. Dysfunction of ion channels disrupts intracellular ionic concentrations, which determine the cell's electrochemical balance and homeostasis. The present study shows how this can result in DNA damage through reactive oxygen species/free radical overproduction. Thus, a complete picture is provided of how human‑made EMF exposure may indeed lead to DNA damage and related pathologies, including cancer. Moreover, it is suggested that the non‑thermal biological effects attributed to RF EMFs are actually due to their ELF components.
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http://dx.doi.org/10.3892/ijo.2021.5272DOI Listing
November 2021

Fingolimod as a first- or second-line treatment in a mini-series of young Hellenic patients with adolescent-onset multiple sclerosis: focus on immunological data.

Neurol Sci 2021 Oct 1. Epub 2021 Oct 1.

Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece.

Background: Pediatric onset multiple sclerosis(POMS) is characterized by a highly active profile, often warranting treatment with high efficacy disease-modulating therapies (DMTs). Fingolimod, an oral sphingosine-1-phosphate receptor modulator, is the first Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved DMT for the treatment of POMS.

Object: Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece.

Methods: Clinical and imaging/laboratory data from 7 Hellenic patients fulfilling the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for POMS diagnosis, who have received fingolimod treatment, were selected. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques.

Results: Three patients were treatment-naïve adolescents who received fingolimod as first-line treatment. Two experienced ongoing clinical and radiological disease activity and have been switched to natalizumab. The remaining cases were post-adolescent adults with POMS, where the vast majority experienced total/near-total disease remission. Fingolimod was generally well-tolerated. Two patients with high disease activity carried the HLA-DRB1*03 allele, while five patients were carriers of at least one of the HLA-DRB1*04, HLA-DRB1*13, and HLA-DRB1*14 alleles, which when not combined with HLA-DRB1*03 showed a trend towards a more favorable clinical course. Fingolimod responders showed a trend towards increased CD(16-56)NK cell counts in immunophenotyping assays.

Conclusions: Our preliminary results support that response of POMS patients to fingolimod may be partially dependent on age and previous DMT, with younger and treatment-naïve patients presenting worse outcomes. The role of immunogenetics and immunophenotyping in personalized treatment warrants investigation in larger and more diverse populations.
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http://dx.doi.org/10.1007/s10072-021-05623-2DOI Listing
October 2021

Correction: From warrior genes to translational solutions: novel insights into monoamine oxidases (MAOs) and aggression.

Transl Psychiatry 2021 Sep 22;11(1):488. Epub 2021 Sep 22.

University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Medical School, Aghia Sophia Children's Hospital, Livadias 8, 115 27, Athens, Greece.

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http://dx.doi.org/10.1038/s41398-021-01611-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458303PMC
September 2021

A novel variant in DYNC1H1 could contribute to human amyotrophic lateral sclerosis-frontotemporal dementia spectrum.

Cold Spring Harb Mol Case Stud 2021 Sep 17. Epub 2021 Sep 17.

Laboratory of Neurogenetics, Department of Neurology, School of Medicine, University Hospital of Larissa, University of Thessaly, Larissa, Greece.

Amyotrophic lateral sclerosis (ALS) belongs to the ALS-frontotemporal dementia (FTD) spectrum and is hallmarked by upper and lower motor neuron degeneration. Here, we present a patient with a cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) pathogenic variant who fulfilled the ALS El Escorial criteria, and we review relevant literature. Using whole-exome sequencing, we identified a deleterious point variant in DYNC1H1 [c.4106A>G (p. Q1369R))] as a likely contributor to the ALS phenotype. In silico structural analysis, molecular dynamics simulation, and protein stability analysis predicted that this variant may increase DYNC1H1 protein stability. Moreover, this variant may disrupt binding of the transcription factor TFAP4, thus potentially acting as duon. Since a) DYNC1H1 forms part of a ubiquitous eukaryotic motor protein complex, and b) disruption of dynein function by perturbation of the dynein-dynactin protein complex is implicated in other motor neuron degenerative conditions, this variant could disrupt processes like retrograde axonal transport, neuronal migration, and protein recycling. Our findings expand the heterogenous spectrum of DYNC1H1 pathogenic variants-associated phenotype and prompt further investigations of the role of this gene in ALS.
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http://dx.doi.org/10.1101/mcs.a006096DOI Listing
September 2021

Diagnostic significance of IgG and albumin indices versus oligoclonal band types in demyelinating disorders.

J Clin Pathol 2021 Sep 15. Epub 2021 Sep 15.

University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Aims: The laboratory diagnosis of demyelinating inflammatory disorders (DIDs) relies on both intrathecal oligoclonal band (OCB) positivity and IgG index. Although OCB typing remains the gold-standard test for DIDs, it can be laborious and ambiguous, complicating diagnostics, and unduly increasing diagnostic time. We examined whether serum or cerebrospinal fluid (CSF) parameters can classify OCB types and, thus, be used as a replacement test to standard OCB typing.

Methods: We retrospectively analysed >1000 prospectively collected samples of patients with DIDs and quantified albumin and IgG levels in the CSF and serum. We determined OCB types by isoelectric focusing combined with immunofixation and evaluated the diagnostic accuracies of IgG and albumin indices in discriminating OCB types by receiver operating characteristic curves and multinomial regression.

Results: An IgG index cut-off of 0.589 differentiated types 2/3 from types 1/4 (area under the curve 0.780, 95% CI 0.761 to 0.812, p<0.001; specificity: 71.10%, sensitivity: 73.45%). Albumin quotient cut-off values of 6.625 and of 6.707 discriminated type 1 from type 4 and type 2 from type 3, respectively (specificity: <55%, sensitivity: <75%). Female sex, age, IgG index, CSF IgG and serum albumin were associated with different OCB types.

Conclusions: Our study reveals that IgG and albumin index can differentiate OCB types with adequate accuracy, especially if refined by age and gender.
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http://dx.doi.org/10.1136/jclinpath-2021-207766DOI Listing
September 2021

Dietary Sugar Intake and Its Association with Obesity in Children and Adolescents.

Children (Basel) 2021 Aug 3;8(8). Epub 2021 Aug 3.

Department of Food Science and Human Nutrition, Agricultural University of Athens, Iera Odos 75, 118 55 Athens, Greece.

Sugar intake has been associated with increased prevalence of childhood overweight/obesity; however, results remain controversial. The aim of this study was to examine the probability of overweight/obesity with higher sugar intakes, accounting for other dietary intakes. Data from 1165 children and adolescents aged ≥2-18 years (66.8% males) enrolled in the Hellenic National Nutrition and Health Survey (HNNHS) were used; specifically, 781 children aged 2-11 years and 384 adolescents 12-18 years. Total and added sugar intake were assessed using two 24 h recalls (24 hR). Foods were categorized into specific food groups to evaluate the main foods contributing to intakes. A significant proportion of children (18.7%) and adolescents (24.5%) exceeded the recommended cut-off of 10% of total energy intake from added sugars. Sweets (29.8%) and processed/refined grains and cereals (19.1%) were the main sources of added sugars in both age groups, while in adolescents, the third main contributor was sugar-sweetened beverages (20.6%). Being overweight or obese was 2.57 ( = 0.002) and 1.77 ( = 0.047) times more likely for intakes ≥10% of total energy from added sugars compared to less <10%, when accounting for food groups and macronutrient intakes, respectively. The predicted probability of becoming obese was also significant with higher total and added-sugar consumption. We conclude that high consumption of added sugars increased the probability for overweight/obesity among youth, irrespectively of other dietary or macronutrient intakes.
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http://dx.doi.org/10.3390/children8080676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391470PMC
August 2021

Stress Management as an Effective Complementary Therapeutic Strategy for Weight Loss in Children and Adolescents with Obesity: A Systematic Review of Randomized Controlled Trials.

Children (Basel) 2021 Jul 31;8(8). Epub 2021 Jul 31.

University Research Institute of Maternal and Child Health & Precision Medicine and UNESCO Chair in Adolescent Health Care, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Lifestyle intervention programs, including mindfulness and stress management/emotional control training techniques have been infrequently studied in children. The aim of this systematic review was to assess whether implementing stress management/emotional control training strategies in the context of a body weight loss program in children and adolescents is associated with improved body weight outcome in this age group. A systematic literature search was conducted to identify relevant studies published before 31 December 2020 in the following databases: Medline (PubMed), Scopus, and Cochrane Central Registry of Controlled Trials. Only randomized clinical trials (RCTs) on mindfulness or stress management in children and adolescents with obesity were included in this systematic review. Six RCTs fulfilled the study inclusion criteria and included intervention (112 subjects) and control (137 subjects) groups. The interventions used were Mindfulness-Based Stress Reduction therapy for 8 weeks (three studies), a mindfulness-based group program for adolescents (one study), and Mindful Eating Intervention for 6 weeks (one study) and 10 weeks (one study). The intervention group demonstrated reduced adiposity markers as compared to controls in four of the six included studies. The presented studies support the hypothesis that a structured, mindfulness-based intervention program may lead to a decrease in the biomarkers of obesity.
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http://dx.doi.org/10.3390/children8080670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391124PMC
July 2021

Interactions Networks for Primary Heart Sarcomas.

Cancers (Basel) 2021 Aug 1;13(15). Epub 2021 Aug 1.

Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, 4, Soranou Ephessiou Str., 11527 Athens, Greece.

Personalized medicine incorporates genetic information into medical practice so as to optimize the management of chronic diseases. In rare diseases, such as heart cancer (incidence 0.0017-0.33%), this may be elusive. Ninety-five percent of the cases are due to secondary involvementwith the neoplasm originating in the lungs, breasts, kidney, blood, or skin. The clinical manifestations of heart tumors (benign or malignant) include heart failure, hypertension, and cardiac arrhythmias of varying severity, frequently resulting in blood vessel emboli, including strokes. This study aims to explain the pathophysiology and contribute to a P4 medicine model for use by cardiologists, pathologists, and oncologists. We created six gene/protein heart-related and tumor-related targets high-confidence interactomes, which unfold the main pathways that may lead to cardiac diseases (heart failure, hypertension, coronary artery disease, arrhythmias), i.e., the sympathetic nervous system, the renin-angiotensin-aldosterone axis and the endothelin pathway, and excludes others, such as the K oxidase or cytochrome P450 pathways. We concluded that heart cancer patients could be affected by beta-adrenergic blockers, ACE inhibitors, QT-prolonging antiarrhythmic drugs, antibiotics, and antipsychotics. Interactomes may elucidate unknown pathways, adding to patient/survivor wellness during/after chemo- and/or radio-therapy.
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http://dx.doi.org/10.3390/cancers13153882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345524PMC
August 2021

Clinical Application of the Novel Cell-Based Biosensor for the Ultra-Rapid Detection of the SARS-CoV-2 S1 Spike Protein Antigen: A Practical Approach.

Biosensors (Basel) 2021 Jul 6;11(7). Epub 2021 Jul 6.

Laboratory of Cell Technology, Department of Biotechnology, Agricultural University of Athens, EU-CONEXUS European University, 11855 Athens, Greece.

The availability of antigen tests for SARS-CoV-2 represents a major step for the mass surveillance of the incidence of infection, especially regarding COVID-19 asymptomatic and/or early-stage patients. Recently, we reported the development of a Bioelectric Recognition Assay-based biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus in just three minutes, with high sensitivity and selectivity. The working principle was established by measuring the change of the electric potential of membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody after attachment of the respective viral protein. In the present study, we applied the novel biosensor to patient-derived nasopharyngeal samples in a clinical set-up, with absolutely no sample pretreatment. More importantly, membrane-engineered cells were pre-immobilized in a proprietary biomatrix, thus enabling their long-term preservation prior to use as well as significantly increasing their ease-of-handle as test consumables. The plug-and-apply novel biosensor was able to detect the virus in positive samples with a 92.8% success rate compared to RT-PCR. No false negative results were recorded. These findings demonstrate the potential applicability of the biosensor for the early, routine mass screening of SARS-CoV-2 on a scale not yet realized.
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http://dx.doi.org/10.3390/bios11070224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301797PMC
July 2021

Age at sampling and sex distribution of AChRAb vs. MuSKAb myasthenia gravis in a large Greek population.

Clin Neurol Neurosurg 2021 Sep 27;208:106847. Epub 2021 Jul 27.

University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Levadias, Athens, Greece.

Objective: Myasthenia gravis (MG) is a typical B-cell-mediated neuromuscular junction disease that can be classified into seropositive and seronegative subtypes. Association of patients' age at sampling and sex with the two major seropositive MG subcategories, i.e., MGs linked to antibodies directed against the acetylcholine receptor (AChRAb) and against the muscle-specific kinase (MuSKAb), has not been compared in a large population.

Methods: We performed a retrospective analysis of samples from patients with MG in Greece who underwent neurochemical diagnostic evaluation between January 2, 2013, and August 31, 2016.

Results: Overall, 1620 adult (623 male and 997 female patients; male-to-female ratio = 0.62) and 51 pediatric patients were found to be seropositive for MG. The distributions in both male and female patients were bimodal in the total and AChRAb MG cases but not in the total MuSKAb MG cases. Significant differences in the age at sampling distribution between the male and female adult patients were observed only in the AChRAb MG subtype. Significant differences between the AChRAb and MuSKAb MG categories were noted in the mean age values (60.10 and 51.49 years, respectively, for female and 65.69 and 56.19 years, respectively, for male adult patients).

Conclusion: Our findings confirm an uneven profile of age at sampling and sex between the AChRAb and MuSKAb MG cases in a large population. Future mechanistic studies can elucidate the cause of these differences. Moreover, clinical studies can explore how such differences can affect MG treatment and prognosis.
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http://dx.doi.org/10.1016/j.clineuro.2021.106847DOI Listing
September 2021

The neuroendocrinology of stress: the stress-related continuum of chronic disease development.

Mol Psychiatry 2021 Jul 21. Epub 2021 Jul 21.

University Research Institute of Maternal and Child Health and Precision Medicine and UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Medical School, Aghia Sophia Children's Hospital, Athens, Greece.

Stress is defined as a state of threatened homeodynamic balance by a wide range of intrinsic or extrinsic, real or perceived challenges or stimuli, defined as stressors. To preserve this optimal homeodynamic state within a physiologic range, organisms have developed a highly sophisticated system, the stress system, which serves self-regulation and adaptability of the organism by energy redirection according to the current needs. Repeated, ephemeral, and motivating stress states lead to adaptive responses and response habituations, being fairly beneficial; in contrast, inadequate, aversive, excessive, or prolonged stress may surpass the regulatory capacity and adjustive resources of the organism and produce maladaptive responses and a chronically altered homeodynamic state associated with compromised mental and physical health and life expectancy. Neuroendocrine responses to stress depend on developmental timing, duration, time of day and nature of stressors leading to a vulnerable phenotype with disrupted stress reactivity (i.e., hyper- or hypoactivation of the stress system), impaired glucocorticoid signaling, and accumulated cacostatic load with cumulatively elevated long-term risk of mental and physical morbidity. This article offers a brief overview on the organization and physiology of the human stress system and its (re)activity, refreshes the plethora of somatic effects of acute and chronic stress and discusses a conceptual model of acute and chronic stress pathophysiology as a continuum in chronic disease development.
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http://dx.doi.org/10.1038/s41380-021-01224-9DOI Listing
July 2021

Tubarial Salivary Glands in Sjogren Syndrome: Are They Just a Potential Missing Link With No Broader Implications?

Front Immunol 2021 29;12:684490. Epub 2021 Jun 29.

University Research Institute of Maternal and Child Health and Precision Medicine, and UNESCO Chair on Adolescent Health Care, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

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http://dx.doi.org/10.3389/fimmu.2021.684490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276103PMC
June 2021

Metabolic Profiling Indicates Diversity in the Metabolic Physiologies Associated With Maternal Postpartum Depressive Symptoms.

Front Psychiatry 2021 25;12:685656. Epub 2021 Jun 25.

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Postpartum depression (PPD) is a devastating disease requiring improvements in diagnosis and prevention. Blood metabolomics identifies biological markers discriminatory between women with and those without antenatal depressive symptoms. Whether this cutting-edge method can be applied to postpartum depressive symptoms merits further investigation. As a substudy within the Biology, Affect, Stress, Imagine and Cognition Study, 24 women with PPD symptom (PPDS) assessment at 6 weeks postpartum were included. Controls were selected as having a score of ≤ 6 and PPDS cases as ≥12 on the Edinburgh Postnatal Depression Scale. Blood plasma was collected at 10 weeks postpartum and analyzed with gas chromatography-mass spectrometry metabolomics. Variations of metabolomic profiles within the PPDS samples were identified. One cluster showed altered kidney function, whereas the other, a metabolic syndrome profile, both previously associated with depression. Five metabolites (glycerol, threonine, 2-hydroxybutanoic acid, erythritol, and phenylalanine) showed higher abundance among women with PPDSs, indicating perturbations in the serine/threonine and glycerol lipid metabolism, suggesting oxidative stress conditions. Alterations in certain metabolites were associated with depressive pathophysiology postpartum, whereas diversity in PPDS physiologies was revealed. Hence, plasma metabolic profiling could be considered in diagnosis and pathophysiological investigation of PPD toward providing clues for treatment. Future studies require standardization of various subgroups with respect to symptom onset, lifestyle, and comorbidities.
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http://dx.doi.org/10.3389/fpsyt.2021.685656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267859PMC
June 2021

Lamotrigine Reduces Stress Symptoms of Chronic Anxiety in the Times of the Covid-19 Natural Catastrophe-A Case Report.

Front Psychiatry 2021 21;12:655079. Epub 2021 Jun 21.

Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Leipzig, Leipzig, Germany.

The SARS-CoV-2 pandemic has been a worldwide chronic, stress-inducing natural catastrophe associated with increased emotional challenging. Patients with Post-traumatic stress disorder (PTSD), self-injury behavior, and obesity are predisposed to aggravation of their symptoms at this time, requiring new therapeutic approaches to balance their disrupted neuro-hormonal stress axis. Here we present our observations of an off-label treatment with lamotrigine in an adolescent girl with PTSD, self-injury behavior, and obesity. Lamotrigine was an efficacious pharmaceutical intervention that helped the patient deal with chronic stress and associated anxiety. The results are discussed based on our previous basic research outcomes in animals and humans that focused on the glutamate-cortisol circuits within the limbic brain.
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http://dx.doi.org/10.3389/fpsyt.2021.655079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255466PMC
June 2021

Clinical Genomic, phenotype and epigenetic insights into the pathology, autoimmunity and weight management of patients with Myasthenia Gravis (Review).

Mol Med Rep 2021 07 5;24(1). Epub 2021 Jul 5.

Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 11855 Athens, Greece.

Myasthenia Gravis (MG) is an autoimmune disease that affects neuromuscular junctions and is characterized by muscle weakness as a result of autoantibodies against certain proteins. As a heterogeneous disorder, MG presents with different types, including neonatal, ocular and generalized in both juveniles and adults. Different types of antibodies serve a role in how MG presents. The main biological characteristic of MG is the production of antibodies against the muscular acetylcholine receptor; however, other types of antibody have been associated with the disorder. The role of the thymus gland has been established and thymectomy is a possible treatment of the disease, along with traditional medication such as pyridostigmine bromide (Mestinon) and immunosuppresants. In recent years, steps have been made towards developing more sensitive diagnostic methods. Additionally, novel treatments have demonstrated promising results. Developing new assays may lead to an increased understanding of the disease and to unravelling the genetic pathway that leads to the development of neuromuscular diseases.
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http://dx.doi.org/10.3892/mmr.2021.12151DOI Listing
July 2021

Significant improvement of stress and aging biomarkers using a novel stress management program with the cognitive restructuring method "Pythagorean Self-Awareness Intervention" in patients with type 2 diabetes mellitus and healthy adults.

Mech Ageing Dev 2021 Sep 1;198:111538. Epub 2021 Jul 1.

Institute of Chemical Biology, National Hellenic Research Foundation (NHRF), Athens, 11635, Greece. Electronic address:

Stress accelerates aging by affecting relevant cellular pathways including, among others, leucocyte telomere length (LTL) and proteasome levels. Their impaired function underlies several age-related and non-communicable conditions, such as type 2 diabetes mellitus. The aim of the present study was to investigate, for the first time, the dynamics of stress-related aging factors in the frame of a novel stress-management technique, the Pythagorean Self Awareness Intervention (PSAI), in healthy volunteers and adults with type 2 diabetes. To this end a cohort of 311 healthy volunteers was initially studied and LTL and proteasome levels were analysed in a subgroup of healthy volunteers and adults with type 2 diabetes who were enrolled in the PSAI, with regards to specific physio- and psychometric characteristics of the participants (baseline and post-intervention). We have found a significant improvement of aging biomarkers and of psycho-/bio-factors in all participants. More specifically, post-intervention, both healthy adults and patients with type 2 diabetes demonstrated improved LTL and proteasome levels. Significant improvements were also observed in psychometric, anthropometric and key metabolic features as well as in hair cortisol. In conclusion our results highlighted potential key targets of such interventions and prognostic tools for the assessment of aging pace in clinical practice.
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http://dx.doi.org/10.1016/j.mad.2021.111538DOI Listing
September 2021

Increased Serum Concentrations of High Mobility Group Box 1 (HMGB1) Protein in Children with Autism Spectrum Disorder.

Children (Basel) 2021 Jun 5;8(6). Epub 2021 Jun 5.

Laboratory of Developmental Psychophysiology and Stress Research, Unit of Developmental and Behavioral Pediatrics, First Department of Pediatrics, "Aghia Sophia" Children's Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.

High mobility group box 1 protein (HMGB1) has been suggested to be involved in the immune dysfunction and inflammation reported in autism spectrum disorder (ASD). We aimed to assess HMGB1 serum concentrations (SCs) in high-functioning ASD children compared to typically developing (TD) controls and to explore their associations with the autism spectrum quotient (AQ), the empathy quotient (EQ), and the systemizing quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged between 6.1 and 13.3 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay (ELISA). Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth. ASD children showed significantly higher HMGB1 SCs compared to TD children (1.25 ± 0.84 ng/mL versus 1.13 ± 0.79 ng/mL, respectively, = 0.039). The Spearman's rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale (rs = 0.46, = 0.045) and with the SQ total score (rs = 0.42, = 0.04) in the ASD group. These results show that HMGB1 serum concentrations are altered in ASD children, and suggest that inflammatory processes mediated by HMGB1 may be associated with specific cognitive features observed in ASD.
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http://dx.doi.org/10.3390/children8060478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228126PMC
June 2021

From Brain Organoids to Networking Assembloids: Implications for Neuroendocrinology and Stress Medicine.

Front Physiol 2021 10;12:621970. Epub 2021 Jun 10.

University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Brain organoids are three-dimensional cultures that contain multiple types of cells and cytoarchitectures, and resemble fetal human brain structurally and functionally. These organoids are being used increasingly to model brain development and disorders, however, they only partially recapitulate such processes, because of several limitations, including inability to mimic the distinct cortical layers, lack of functional neuronal circuitry as well as non-neural cells and gyrification, and increased cellular stress. Efforts to create improved brain organoid culture systems have led to region-specific organoids, vascularized organoids, glia-containing organoids, assembloids, sliced organoids and polarized organoids. Assembloids are fused region-specific organoids, which attempt to recapitulate inter-regional and inter-cellular interactions as well as neural circuitry development by combining multiple brain regions and/or cell lineages. As a result, assembloids can be used to model subtle functional aberrations that reflect complex neurodevelopmental, neuropsychiatric and neurodegenerative disorders. Mammalian organisms possess a highly complex neuroendocrine system, the stress system, whose main task is the preservation of systemic homeostasis, when the latter is threatened by adverse forces, the stressors. The main central parts of the stress system are the paraventricular nucleus of the hypothalamus and the locus caeruleus/norepinephrine-autonomic nervous system nuclei in the brainstem; these centers innervate each other and interact reciprocally as well as with various other CNS structures. Chronic dysregulation of the stress system has been implicated in major pathologies, the so-called chronic non-communicable diseases, including neuropsychiatric, neurodegenerative, cardiometabolic and autoimmune disorders, which lead to significant population morbidity and mortality. We speculate that brain organoids and/or assembloids could be used to model the development, regulation and dysregulation of the stress system and to better understand stress-related disorders. Novel brain organoid technologies, combined with high-throughput single-cell omics and gene editing, could, thus, have major implications for precision medicine.
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http://dx.doi.org/10.3389/fphys.2021.621970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222922PMC
June 2021

Diverse patterns of vulnerability to visual illusions in children with neurodevelopmental disorders.

Cogn Process 2021 Jun 21. Epub 2021 Jun 21.

First Department of Psychiatry, School of Medicine, National and Kapodistrian University of Athens, "Eginition" University Hospital, Vasilissis Sophias 72-74, 11528, Athens, Greece.

Research on how children with neurodevelopmental disorders perceive, process, and interpret visual illusions (VIs) has been extensively focused on children with autism spectrum disorder providing controversial findings. In this study, we investigated the patterns of vulnerability to a wide set of VIs comprising 23 standard text book VIs and their variations in a clinical sample of children with neurodevelopmental disorders compared to typically developing children (TD). A total of 176 children, aged between 4.6 and 13.8 years old, were distributed into four groups: high-functioning autism (HFA; N = 23), attention-deficit/hyperactivity disorder (ADHD; N = 42), specific learning disorder (SLD; N = 70), and TD (N = 41). Regression models, adjusted for sex, age, and non-verbal IQ, showed that HFA was associated with greater responses accuracy than TD children to the full battery of VIs, to the cognitive illusions, to the distortions, and to both geometrical illusions of size/shape (cognitive distortions) and lightness contrast effects (physical distortions). The susceptibility of ADHD children was found attenuated for illusory contours and greater for paradoxical illusions in comparison with TD children. No significant differences were shown between the SLD group and the TD children. Our findings, which were adjusted for the same duration of visual working memory across groups, showed that there is a potential specific tendency of HFA children to failure of processing visual information in context. Contrarily, children with ADHD showed in general normal global processing such as children diagnosed with SLD.
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http://dx.doi.org/10.1007/s10339-021-01041-6DOI Listing
June 2021

Pythagorean Self-Awareness Intervention for Multiple Sclerosis Patients: A Quasi-Experimental Pragmatic Trial.

Arch Clin Neuropsychol 2021 Jun 15. Epub 2021 Jun 15.

1st Department of Neurology, Aeginition Hospital, Medical School, National Kapodistrian University of Athens, Athens, Greece.

Objective: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system affecting patients' well-being and quality of life. Pythagorean Self-Awareness Intervention (PSAI) is a novel non-pharmaceutical intervention with significant benefits both in MS and other chronic diseases. In this study, the longstanding effectiveness of PSAI was investigated.

Method: This was a two-arm quasi-experimental pragmatic trial in relapsing-remitting MS patients (23 in the PSAI and 21 in the control group). PSAI patients received an 8-week training period and then they performed PSAI at home for another 16 weeks. Assessments took place at baseline, 8 weeks, and 24 weeks. These included cognition, fatigue, perceived stress, and hair cortisol.

Results: Significant group × time interactions favoring PSAI were found during the first 8-week period for information processing speed, fatigue, and perceived stress. However, only verbal memory was found to be significantly improved in the PSAI group during the 24-week follow-up period. There were no significant group × time differences with respect to hair cortisol. No side effects were noted and compliance was excellent.

Conclusions: PSAI was mostly effective during the first 8-week training period. Its benefits worn out during the non-training period, albeit we observed a delayed significant improvement of verbal memory. Our findings will help to further refine the technique, either by extending the training period and/or by including booster sessions, throughout the PSAI treatment. This study provided Class III evidence for PSAI.
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http://dx.doi.org/10.1093/arclin/acab044DOI Listing
June 2021

Adrenocortical dysfunction in rheumatoid arthritis: Α narrative review and future directions.

Eur J Clin Invest 2021 Jun 7:e13635. Epub 2021 Jun 7.

1st Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Background: Iatrogenic adrenal insufficiency (AI) secondary to long-term treatment with exogenous glucocorticoids (GC) is common in patients with systematic rheumatic diseases, including rheumatoid arthritis (RA). Moreover, a proportion of these patients is always in need of even small doses of glucocorticoids to maintain clinical remission, despite concomitant treatment with conventional and biologic disease-modifying drugs.

Methods: We conducted a literature review up to December 2020 on (a) the incidence of AI in both long-term GC-treated and GC-treatment naïve RA patients; (b) the potential effects of increased levels of circulating proinflammatory cytokines, as well as of chronic stress, in adrenocortical function in RA; (c) the circadian cortisol rhythm in RA; and (d) established and evolving methods of assessment of adrenocortical function.

Results: Up to 48% of RA patients develop glucocorticoid-induced AI; however, predictors are not established, while adrenocortical dysfunction may also occur in GC-treatment naïve RA patients. Experimental and clinical data have suggested that inadequate production of endogenous cortisol relative to enhanced clinical needs associated with the systemic inflammatory response, coined as the 'disproportion principle', may operate in RA. Although the underlying mechanisms are unknown, both proinflammatory cytokines and chronic stress may contribute the most in the adrenals hyporesponsiveness and the target tissue glucocorticoid resistance that have been described, but not systematically studied. A precise longitudinal assessment of endogenous cortisol production may be needed for optimal RA management.

Conclusion: Apart from iatrogenic AI, an intrinsically compromised adrenal reserve in RA may have a pathogenetic role and interfere with effective management, thus deserving further research.
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http://dx.doi.org/10.1111/eci.13635DOI Listing
June 2021

European Childhood Obesity Risk Evaluation (CORE) index based on perinatal factors and maternal sociodemographic characteristics: the Feel4Diabetes-study.

Eur J Pediatr 2021 Aug 14;180(8):2549-2561. Epub 2021 May 14.

Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 70 El Venizelou Ave, 176 71 Kallithea, Athens, Greece.

The aim of this study was to develop and examine the predictive accuracy of an index that estimates obesity risk in childhood based on perinatal factors and maternal sociodemographic characteristics. Analysis was conducted by using cross-sectional and retrospective data collected from a European cohort of 2775 schoolchildren and their families participating in the Feel4Diabetes-study. The cohort was randomly divided by using two-thirds of the sample for the development of the index and the remaining one third for assessing its predictive accuracy. Logistic regression analyses determined a prediction model for childhood obesity. The area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated. Cut-off analysis was applied to identify the optimal value of the index score that predicts obesity with the highest possible sensitivity and specificity. Eight factors were found to be significantly associated with obesity and were included as components in the European "Childhood Obesity Risk Evaluation" (CORE) index: region of residence, maternal education, maternal pre-pregnancy weight status, gestational weight gain, maternal smoking during pregnancy, birth weight for gestational age, infant growth velocity, and exclusive breastfeeding during the first 6 months. Risk score ranged from 0 to 22 corresponding to a risk from 0.9 to 54.6%. The AUC-ROC was 0.725 with optimal cut-off ≥9 (sensitivity = 74.1%, specificity = 61.0%, PPV = 11.3%, NPV = 97.2%).Conclusion: The European CORE index can be used as a screening tool for the identification of infants at high-risk for becoming obese at 6-9 years. This tool could assist healthcare professionals in initiating preventive measures from the early life.Trial registration: The Feel4Diabetes-intervention is registered at https://clinicaltrials.gov/ ; number, CT02393872; date, March 20, 2015. What is Known: • As prevention of obesity should start early in life, there is a compelling rationale for the early identification of high-risk children to facilitate targeted intervention. What is New: • This study developed and assessed the predictive accuracy of an index for the Childhood Obesity Risk Evaluation (CORE), combining certain perinatal factors and maternal sociodemographic characteristics in a large European cohort. • The European CORE index can be used as a screening tool for identifying infants at high-risk for becoming obese at 6-9 years and assist health professionals in initiating early prevention strategies.
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http://dx.doi.org/10.1007/s00431-021-04090-3DOI Listing
August 2021
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