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Abstract Background The aim of this study was to determine the genotype distribution and allelic frequencies of ACE (I/D), AGTR1 (A +1166 C), BDKRB2 (+9/−9) and LEP (G–2548A) genomic variations in 175 Greek athletes who excelled at a national and/or international level and 169 healthy Greek adults to identify whether some particular combinations of these loci might serve as predictive markers for superior physical condition. Results The D/D genotype of the ACE gene (p = 0.034) combined with the simultaneous existence of BDKRB2 (+9/−9) (p = 0.001) or LEP (G/A) (p = 0.021) genotypes was the most prevalent among female athletes compared to female controls. A statistical trend was also observed in BDKRB2 (+9/−9) and LEP (G–2548A) heterozygous genotypes among male and female Greek athletes, and in ACE (I/D) only in male athletes. Finally, both male and female athletes showed the highest rates in the AGTR1 (A/A) genotype. Conclusions Our results suggest that the co-existence of ACE (D/D), BDKRB2 (+9/−9) or LEP (G/A) genotypes in female athletes might be correlated with a superior level of physical performance.

Introduction: Female hormones and obesity have an impact on women with asthma. We aimed to describe how these components affect asthma inflammatory processes. Methods: Sex hormones [FSH, LH, estradiol (E2), estrone (E1), testosterone and Δ4 androstenedione (A4)] and serum IL1β, IL13, IL17a, IL-5, IL6, TNF-a were measured from 11 to18 pre- and postmenopausal women with asthma. Results: Premenopausal normal weight women revealed higher levels of IL5 and IL17a than obese women on both days of the menstrual cycle (IL5: D1: 6.4 vs 1.4 pg/ml, p =.036 and D14: 3 vs 1.4 pg/ml, p =.045 and IL17a: D1: 13.7 pg/ml vs 10.6 pg/ml and D14: 12.4 pg/ml vs 10.6 pg/ml, p =.009, respectively). In premenopausal women on D1, Δ4 Androstenedione was positively correlated with IL1β (p =.016, r = 0.733), whereas on D14, Estradiol with IL1β (p =.009, r = −.768) and TNF-a with Testosterone (p =.004, r = −0.816), and Δ4 Androstenedione (p =.002, r = −0.841) negatively. In postmenopausal women, TNF-a was negatively associated with FSH (p =.004, r = −0.638), but positively with Testosterone (p =.025, r = 0.526) and IL10 also positively with Estradiol (p =.007, r = 0.610). Conclusion: Obesity shows a protective role in asthma through the suppression of IL5 and IL17. Estrogens seem to inhibit Th1 and Th2 inflammation, while androgens have a dual role with negative and positive correlations with neutrophilic biomarkers. [ABSTRACT FROM AUTHOR]

Abstract Introduction The identification of pregnant women with Gestational Diabetes Mellitus (GDM) who will require insulin therapy, may modify their management to closer monitoring and probable early interventions. The aim of the study was to develop a predictive model for the necessity of insulin treatment in women with GDM. Materials and methods This was a prospective cohort study. Data from 775 women diagnosed with GDM per the IADPSG criteria were analyzed using logistic regression and a machine learning algorithm, the Classification and Regression Trees (CART). Potential predictors routinely recorded at follow-up visits were tested and used for the development of the model. The resultant model was externally validated using the data from two different perinatology clinics. Results Preconceptional maternal BMI and morning fasting blood glucose levels at baseline and at 1 h during an Oral Glucose Tolerance Test (OGTT) were independent significant predictors for the treatment modality of GDM. Baseline blood glucose greater than 98 mg/dl and preconceptional maternal Body Mass Index (BMI) between 26 and 31 kg/height2 increased substantially the probability of insulin therapy (odds ratio [OR] 4.04, 95% confidence interval [CI] CI 2.65–6.17 and 2.21, 95%CI 1.42–3.43, respectively). The area under the curve (AUC) for the internal and external validation of the predictive model was 0.74 and 0.77, respectively. Conclusions A simple model based on maternal characteristics and the values of an OGTT can predict the need for insulin treatment with accuracy. Overweight women with an abnormal baseline blood glucose at OGTT are at high likelihood for insulin treatment. Key message Fifteen to 30% of women with Gestational Diabetes Mellitus (GDM) require insulin therapy. Overweight women with baseline blood glucose greater than 98 mg/dl at OGTT are at increased risk for insulin treatment and close monitoring and increased physical exercise are required.

Acne diagnosis, severity assessment and treatment follow‐up rely primarily on clinical examination. In vivo reflectance confocal microscopy (RCM) provides non‐invasively, real‐time images of skin lesions with a level of detail close to histopathology. This systematic literature review aims to provide an overview of RCM utility in acne and a summary of specific features with clinical application that may increase objectivity in evaluating this condition. We used the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines for reporting our results. We systematically searched three databases: PubMed, Clarivate and Google Scholar (January 2022). All included studies used RCM to investigate acne in human patients and reported the investigated skin area and type (acne lesions or clinically uninvolved skin), the substance used in the case of treatment. Our search identified 2184 records in the three databases investigated. After duplicate removal, 1608 records were screened, 35 were selected for full‐text assessment, and 14 were included in this review. We used the QUADAS‐2 tool to evaluate the risk of bias and applicability concerns. RCM was selected as the index test and clinical examination as the reference standard. The total number of patients from all studies was 291, with 216 acne patients and 60 healthy participants aged between 13 and 45 years. The 14 considered studies analysed 456 follicles from healthy participants, 1445 follicles from uninvolved skin in acne patients and 1472 acne lesions. Consistent RCM findings concerning follicles of acne patients reported across studies were increased follicular infundibulum size, thick, bright border, intrafollicular content and inflammation. Our analysis indicates that RCM is a promising tool for acne evaluation. Nevertheless, standardization, a unified terminology, consistent research methods and unitary reporting of RCM findings are necessary. PROSPERO registration number CRD42021266547. [ABSTRACT FROM AUTHOR]

Static balancing assessment is often complemented with dynamic balancing tasks. Numerous dynamic balancing assessment methods have been developed in recent decades with their corresponding balancing devices and tasks.The aim of this systematic literature review is to identify and categorize existing objective methods of standing dynamic balancing ability assessment with an emphasis on the balancing devices and tasks being used.Three major scientific literature databases (Science Direct, Web of Science, PLoS ONE) and additional sources were used.Studies had to use a dynamic balancing device and a task described in detail. Evaluation had to be based on objectively measureable parameters. Functional tests without instrumentation evaluated exclusively by a clinician were excluded. A total of 63 articles were included.The data extracted during full-text assessment were: author and date; the balancing device with the balancing task and the measured parameters; the health conditions, size, age and sex of participant groups; and follow-up measurements.A variety of dynamic balancing assessment devices were identified and categorized as 1) Solid ground, 2) Balance board, 3) Rotating platform, 4) Horizontal translational platform, 5) Treadmill, 6) Computerized Dynamic Posturography, and 7) Other devices. The group discrimination ability of the methods was explored and the conclusions of the studies were briefly summarized.Due to the wide scope of this search, it provides an overview of balancing devices and do not represent the state-of-the-art of any single method.The identified dynamic balancing assessment methods are offered as a catalogue of candidate methods to complement static assessments used in studies involving postural control.

Introduction: The purpose of this study was to investigate the analgesic effect of 3 different regimens of combination analgesics administered to patients undergoing thyroidectomy. Material and methods: A total of 152 patients undergoing total or subtotal thyroidectomy were enrolled. Patients allocated to group A received a combination of intravenous (IV) paracetamol and intramuscular (IM) pethidine, patients in group B received a combination of IV paracetamol and IV parecoxib, while patients in group C received IV paracetamol monotherapy. Results: The analgesic regimens of groups A and B were found to be of equivalent efficacy (p-value = 1.000). In contrast, patients in group C (paracetamol monotherapy) had higher numerical rating scale scores, compared to both patients in groups A (p-value < 0.001) and B (p-value < 0.001). Conclusions: The combinations of IV paracetamol with either IM pethidine or IV parecoxib are superior to IV paracetamol monotherapy in achieving pain control in patients undergoing thyroid surgery. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies exhibit a remarkable phenotypic diversity in terms of disease severity, while individual genetic background plays a key role in differential response to drug treatment. In the last decade, genomic variants in genes located within, as well as outside the human β-globin cluster have been shown to be significantly associated with Hb F increase, in relation to hydroxyurea (HU) therapy in patients with these diseases. Here, we aim to determine the effect of genomic variants located in genes, such as MAP3K5, ASS1, NOS2A, TOX, PDE7B, NOS1, FLT1 and ARG2, previously shown to modulate fetal hemoglobin (Hb F) levels in patients with β type hemoglobinopathies and reflecting disease severity and response to HU therapy in an independent cohort of Greek patients with these diseases. We recruited and genotyped 45 β-thalassemia patients (β-thal), either transfusion-dependent (TDT) or non transfusion-dependent (NTDT), 42 Hb S (HBB: c.20A>T)-β-thal compound heterozygotes, who were treated with HU, as well as 53 healthy individuals, all of Hellenic origin. Our study showed that genomic variants of the MAP3K5, NOS2A and ARG2 gene are associated with HU therapy efficacy in Hb S-β-thal compound heterozygotes. We have also shown that FLT1 and ARG2 genomic variants are associated with the mild phenotype of NTDT patients. Our findings provide evidence that MAP3K5, NOS2A, ARG2 and FLT1 genomic variants could be considered as genomic biomarkers to predict HU therapy efficacy in Hb S-β-thal compound heterozygotes and also to describe disease severity in patients with β type hemoglobinopathies. [ABSTRACT FROM AUTHOR]

Background: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. Results: From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its gene expression characteristics. Selected VEGFA genomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in β-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent β-thalassemia patients, β-thalassemia major patients, compound heterozygous sickle cell disease/β-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFA genomic variants were associated with disease severity in β-thalassemia patients and hydroxyurea treatment efficacy in SCD/β-thalassemia compound heterozygous patients. Conclusions: Our findings suggest that VEGFA may act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in β-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: Static balancing assessment is often complemented with dynamic balancing tasks. Numerous dynamic balancing assessment methods have been developed in recent decades with their corresponding balancing devices and tasks. Objective: The aim of this systematic literature review is to identify and categorize existing objective methods of standing dynamic balancing ability assessment with an emphasis on the balancing devices and tasks being used. Data Sources: Three major scientific literature databases (Science Direct, Web of Science, PLoS ONE) and additional sources were used. Study selection: Studies had to use a dynamic balancing device and a task described in detail. Evaluation had to be based on objectively measureable parameters. Functional tests without instrumentation evaluated exclusively by a clinician were excluded. A total of 63 articles were included. Data extraction: The data extracted during full-text assessment were: author and date; the balancing device with the balancing task and the measured parameters; the health conditions, size, age and sex of participant groups; and follow-up measurements. Data synthesis: A variety of dynamic balancing assessment devices were identified and categorized as 1) Solid ground, 2) Balance board, 3) Rotating platform, 4) Horizontal translational platform, 5) Treadmill, 6) Computerized Dynamic Posturography, and 7) Other devices. The group discrimination ability of the methods was explored and the conclusions of the studies were briefly summarized. Limitations: Due to the wide scope of this search, it provides an overview of balancing devices and do not represent the state-of-the-art of any single method. Conclusions: The identified dynamic balancing assessment methods are offered as a catalogue of candidate methods to complement static assessments used in studies involving postural control. [ABSTRACT FROM AUTHOR]

The rs2071348 (g.5264146A>C) polymorphism on the HBB pseudogene, namely HBBP1, previously emerged as a variant significantly associated with a milder disease phenotype in Asian β0-thalassemia/hemoglobin (Hb) E (β0-thal/Hb E [β26(B8)Glu→Lys, GAG> AAG]) patients. In this study, we aimed to explore the possible association of rs2071348 with β-thalassemia (β-thal) disease severity in a group of β-thal major (β-TM) patients (severe phenotype) and β-thal intermedia (β-TI) patients (mild phenotype) of Hellenic origin and compare the results with normal (non thalassemic) individuals of the same origin. In addition, we explored whether this single nucleotide polymorphism (SNP) can be exploited as a pharmacogenomic marker to predict the outcome of Hb F-augmenting therapy in β-thal patients receiving hydroxyurea (HU). Our data suggest that the rs2071348 polymorphism is associated with higher Hb F levels and a milder β-thal disease phenotype. However, the rs2071348 polymorphism in the HBBP1 gene does not correlate with response to HU treatment. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the genotype distribution and allelic frequencies of ACE (I/D), AGTR1 (A +1166 C), BDKRB2 (+9/−9) and LEP (G–2548A) genomic variations in 175 Greek athletes who excelled at a national and/or international level and 169 healthy Greek adults to identify whether some particular combinations of these loci might serve as predictive markers for superior physical condition. Results: The D/D genotype of the ACE gene (p = 0.034) combined with the simultaneous existence of BDKRB2 (+9/−9) (p = 0.001) or LEP (G/A) (p = 0.021) genotypes was the most prevalent among female athletes compared to female controls. A statistical trend was also observed in BDKRB2 (+9/−9) and LEP (G–2548A) heterozygous genotypes among male and female Greek athletes, and in ACE (I/D) only in male athletes. Finally, both male and female athletes showed the highest rates in the AGTR1 (A/A) genotype. Conclusions: Our results suggest that the co-existence of ACE (D/D), BDKRB2 (+9/−9) or LEP (G/A) genotypes in female athletes might be correlated with a superior level of physical performance. [ABSTRACT FROM AUTHOR]

The human fetal globin genes are highly similar at the DNA sequence level, resulting in a single amino acid difference between the Gγγ- and Aγγ-globin chains. A large proportion of hemoglobin (Hb) variants of the Gγγ- and Aγγ-globin chains result from an identical mutation in the HBG2 and HBG1 genes, respectively, while the same is true for a fraction of mutations leading to nondeletional hereditary persistence of fetal Hb (HPFH). In particular, 11 different Hb variants result from identical mutations on either one of the two human γγ-globin paralogous genes, while seven other promoter substitutions result either in nondeletional HPFH or are benign polymorphisms. In the former case, the percentage of the Hb variants due to an HBG2 gene mutation was significantly higher than the percentage of Hb variants due to the same HBG1 gene mutation, following the Gγγ//Aγγ-globin chain ratio seen in wild-type individuals. These γγ-globin chain variants have most likely occurred via recurrent mutations, gene conversion events or both and, contrary to the situation observed in the human αα-globin genes, these mutations lead to distinct variant Hb molecules. [ABSTRACT FROM AUTHOR]

We report the first heterozygous case of Hb A2-NYU (HBD:c.39T>A) in the Hellenic population. The proband, an adult female from the island of Crete, Greece, was identified during routine family screening. DEAE chromatography of the index case revealed a minor hemoglobin (Hb) fraction preceding the elution of the wild-type Hb A2. DNA sequencing of the entire HBD gene coding regions indicated that the index case was heterozygous for the rare variant Hb A2-NYU. Family studies indicated that this Hb variant was inherited from the mother. This finding underlines the vast genetic heterogeneity of the HBD gene in the Hellenic population. [ABSTRACT FROM AUTHOR]

β-Thalassemia (β-thal), is caused by reduced or absent synthesis of β-globin chains resulting in impaired erythropoiesis. It is the most common single gene defect disease in Greece, with heterozygous rates reaching, on average, 8% in the general population. Here, we performed molecular analyses on 199 unrelated β-thal and compound β-thal/sickle cell disease patients, of whom 157 originated from three prefectures of South-Western Greece, namely Achaia, Ilia and Etoloakarnania. Our results indicate that the frequency of specific HBB gene mutations, namely the HBB:c.118C>T (codon 39, C>T), HBB:c.92+6T>C (IVS-I-6, T>C), and HBB:c.20A>T [Hb S, β6(A3)Glu→Val, G AG>G TG], present distinct distribution patterns in the Achaia and Ilia prefectures ( p < 0.001, p < 0.003 and p < 0.002, respectively). This detailed analysis of the distribution of the HBB gene mutations is useful for genetic counseling in the region, and illustrates that the identification of the HBB gene mutation spectrum in this region is necessary for population carrier screening and for efficient provision of prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Pheromones are water-soluble chemicals that elicit neuroendocrine and physiological changes, while they also provide information about gender within individuals of the same species. VN1R1is the only functional pheromone receptor in humans. We have undertaken a large mutation screening approach in 425 adult individuals from the Hellenic population to investigate whether the allelic differences, namely alleles 1a and 1b present in the human VN1R1gene, are gender specific. Here we show that both VN1R11a and 1b alleles are found in chromosomes of both male and female subjects at frequency of 26.35 and 73.65, respectively. Given the fact that those allelic differences potentially cause minor changes in the protein conformation and its transmembrane domains, as simulated by the TMHMM software, our data suggest that the allelic differences in the human VN1R1gene are unlikely to be associated with gender and hence to contribute to distinct gender-specific behavior. [ABSTRACT FROM AUTHOR]

The mechanisms by which mutations within the 5′ untranslated region (UTR) of the human β-globin gene ( HBB) cause thalassaemia are currently not well understood. We present here the first comprehensive comparative functional analysis of four ‘silent’ mutations in the human β-globin 5′UTR, namely: +10(−T), +22(G → A), +33(C → G) and +(40–43)(−AAAC), which are present in patients with β-thalassaemia intermedia. Expression of these genes under the control of the β-globin locus control region in stable transfected murine erythroleukaemia cells showed that all four mutations decreased steady state levels of mRNA to 61·6%, 68%, 85·2% and 70·6%, respectively, compared with the wildtype gene. These mutations did not interfere with either mRNA transport from the nucleus to the cytoplasm, 3′ end processing or mRNA stability. Nuclear run-on experiments demonstrated that mutations +10(−T) and +33(C → G) reduced the rate of transcription to a degree that fully accounted for the observed lower level of mRNA accumulation, suggesting a disruption of downstream promoter sequences. Interestingly, mutation +22(G → A) decreased the rate of transcription to a low degree, indicating the existence of a mechanism that acts post-transcriptionally. Generally, our data demonstrated the significance of functionally analysing mutants of this type in the presence of a full complement of transcriptional regulatory elements within a stably integrated chromatin context in an erythroid cell environment. [ABSTRACT FROM AUTHOR]