Contact allergy caused by acrylates in nail cosmetics: A pilot study from Greece.

BACKGROUND: The growing popularity of nail techniques based on acrylates has led to a higher frequency of sensitization in both nail technicians and users. OBJECTIVES: The study aimed to assess cases of allergic contact dermatitis (ACD) caused by acrylates in individuals with occupational or non-occupational exposure to nail techniques. METHODS: A preliminary study was conducted on 30 patients with ACD caused by acrylates in nail techniques, who were patch tested from September 2022 to March 2023 at the First Department of Dermatology and Venereology of Andreas Syggros Hospital, Athens, Greece. RESULTS: Thirty female patients with ACD to acrylates were documented (15 users and 15 nail technicians and users). The most common allergens were: 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl methacrylate (HPMA) and ethyleneglycol dimethacrylate (EGDMA), which tested positive in all 30 patients (100.0%). Twenty patients (66.7%) had been exposed to dental procedures involving acrylates, before the onset of ACD. Nail technicians exhibited extensive skin lesions, 40.0% experienced ACD within the first year of work and 13.3% during their professional practice. Three of them (20.0%) had to discontinue their work. CONCLUSION: Acrylates have been identified as potent allergens, necessitating the implementation of safety measures for the use of these chemicals in nail techniques.

Octenidine Versus Dispase Gels for Wound Healing After Cryosurgery Treatment in Patients with Basal Cell Carcinoma.

For a specific group of patients with basal cell carcinoma (small, low risk), cryosurgery could be the suggested treatment, which results in the formation of an ulcer in the lesion area. The proteolytic enzymes' contribution to the wound healing is an ongoing research goal. Preclinical animal experiments in the Laboratory of the Pharmaceutical Technology Department of the National and Kapodistrian University of Athens have showed that a dose of 5 U/mL of dispase gel after the formation of tissue rashes, significantly promoted wound healing. Herein, a feasibility study in 16 patients enrolled by the First Department of Dermatology of Andreas Syggros Hospital was designed: 5 U/mL of dispase gel (once every 3 days) versus a drug reference containing octenidine (daily administration). The evaluation of the healing effect, safety, and tolerance was done on days 1 (cryosurgery), 2, 7, 21, and 60. The study end point was considered either the ulcer complete healing or the eighth week since treatment initiation. Wound healing was faster with dispase gel and hemoglobin reduced rapidly after the seventh day. Yet, hydration was higher in the control group. Our non-parametric analysis provides evidence that the dispase gel shows faster healing compared to the reference drug, in humans, meriting further investigation in larger human sample sizes before massive production of the product.

Polycystic οvary syndrome revisited: An interactions network approach.

BACKGROUND: The polycystic ovary syndrome (PCOS) has genetic, epigenetic, metabolic and reproductive aspects, while its complex pathophysiology has not been conclusively deciphered. AIM: The goal of this research was to screen the gene/gene products associated with PCOS and to predict any possible interactions with the highest possible fidelity. MATERIALS AND METHODS: STRING v10.5 database and a confidence level of 0.7 were used. RESULTS: A highly interconnected network of 48 nodes was created, where insulin (INS) appears to be the major hub. INS upstream and downstream defects were analysed and revealed that only the kisspeptin- and glucagon-coding genes were upstream of INS. CONCLUSION: A metabolic dominance was inferred and discussed herein with its implications in puberty, obesity, infertility and cardiovascular function. This study, thus, may contribute to the resolution of a scientific conflict between the USA and EU definitions of the syndrome and/or provide a new P4 medicine approach.

Adults' Stress Response to Unexpected Oral and Arithmetic Tasks in Supine Position.

To study the autonomic nervous system (ANS) and hypothalamus pituitary adrenal axis (HPA) response before and after mental stress test in healthy adolescents and adults, is the aim of this study. Twenty healthy adults (aged 23-46 years) entered the Trier Social Stress Test (TSST), after informed consent signing. The procedure was modified: (a) the participants' position was supine as ANS system changes were to be assessed, (b) the interviewers were entering and departing from the session room. Salivary cortisol (marker of HPA axis response) samples were collected at the end of the baseline and 20 min after TSST. ANS of the heart was measured with CNS Task Force Monitor in supine position and was recorded during relaxation (15 min) and after TSST. The sympathovagal balance (LF/HF ratio) for each phase was computed. Evaluations were conducted with R. The HPA axis disturbance between baseline and 20 min after TSST was significant (g = 0.545 [0.092, 0.999]) and in adolescents (whereas, the mean intervals of the sinus rhythm RR parameter were found largely changed (g = 0.834 [0.340, 1.327]). The sympathovagal balance component of heart rate variability LF/HF ratio was founded unchanged (g = 0.215 [-0.211, 0.641]). RR changes were not correlated to salivary cortisol concentrations at any phase. Mean RRIs and salivary cortisol levels were significantly increased, although HPA axis showed medium size effect. However, the systems effectively counterbalance the perturbation, since the LF/HF ratio does not change. Our findings suggest further research in stress effect on HPA and ANS cross-talk and dynamics.

Adiponectin and Its Effects on Acute Leukemia Cells: An Experimental and Bioinformatics Approach.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. It is known that deregulation of adipokine pathways is probably implicated in the ontogenesis of ALL. The present work aims at investigating the role of adiponectin and its effects on an ALL cell line. The CCRF-CEM cells were used as a model. Cells have been treated with adiponectin, with different concentrations up to 72 h. Cytotoxicity and cell cycle distribution were investigated for all concentrations using flow cytometry. Selected concentrations were also used for additional microarray analysis, using a small gene set of cancer-related genes. Lower and higher adiponectin concentrations did not produce an inhibition of proliferation, as well as an increase in cell death. It was found that adiponectin regulated differentially genes, such as CD22, CDH1, IFNG, LCK, MSH2, SPINT2, and others. At the same time, it appeared that adiponectin-related gene expression was more active on chromosomes 18 and 1. Machine learning classification algorithms showed that several genes were grouped together indicating common regulatory mechanisms. The present study showed that adiponectin is able to induce gene differential expression in leukemic cells in vitro, suggesting a possible role in the progression of leukemia. It is also an indication that more studies are required in order to further understand the role of adiponectin and adipokines in general in the role of human neoplasms.

Early and Very Early GRIM19 and MCL1 Expression Are Correlated to Late Acquired Prednisolone Effects in a T-Cell Acute Leukemia Cell Line.

Glucocorticoids (GCs) are still first-line drugs for the treatment of childhood acute lymphoblastic leukemia (ALL). Prednisolone is a corticosteroid and one of the most important agents in the treatment of ALL. We report here a study of Prednisolone treatment using as a model a leukemia cell line with subsequent investigation of resistance-related gene expression. Gene silencing has been used in order to identify significant targets of resistance to GC-induced apoptosis in ALL cells. We analyzed effects of increasing doses of Prednisolone on ALL cell survival and growth, and we monitored immediate effects on gene expression through gene expression assays. We determined Prednisolone cytotoxicity and cell cycle distribution as well as DNA content. Upon treatment with escalating Prednisolone concentration, we observed a gradual decline in cell survival. MCL1 and GRIM19 were investigated as possible genes for the intrinsic capacity of this cell line to respond to corticosteroid and a snapshot of early changes was examined. Early MCL1 and GRIM19 expression correlated significantly to late GC-induced apoptosis. Prednisolone competitively induces MCL1 expression. Consistently with previous studies on primary leukemia blasts, cells are sensitive to proteasome inhibitor MG132; no interference of Prednisolone with MG132 effects on this cell line was noted. The inherent plasticity of clinically evolving cancer justifies approaches to characterize and prevent undesirable activation of early oncogenic pathways. Study of the pattern of intracellular signal pathway activation by anticancer drugs can lead to development of efficient treatment strategies by reducing detrimental secondary effects.

Systems Approaches in the Common Metabolomics in Acute Lymphoblastic Leukemia and Rhabdomyosarcoma Cells: A Computational Approach.

Acute lymphoblastic leukemia is the most common childhood malignancy. Rhabdomyosarcoma, on the other hand, is a rare type of malignancy which belongs to the primitive neuroectodermal family of tumors. The aim of the present study was to use computational methods in order to examine the similarities and differences of the two different tumors using two cell lines as a model, the T-cell acute lymphoblastic leukemia CCRF-CEM and rhabdomyosarcoma TE-671, and, in particular, similarities of the metabolic pathways utilized by two different cell types in vitro. Both cell lines were studied using microarray technology. Differential expression profile has revealed genes with similar expression, suggesting that there are common mechanisms between the two cell types, where some of these mechanisms are preserved from their ancestor embryonic cells. Expression of identified species was modeled using known functions, in order to find common patterns in metabolism-related mechanisms. Species expression manifested very interesting dynamics, and we were able to model the system with elliptical/helical functions. We discuss the results of our analysis in the context of the commonly occurring genes between the two cell lines and the respective participating pathways as far as extracellular signaling and cell cycle regulation/proliferation are concerned. In the present study, we have developed a methodology, which was able to unravel some of the underlying dynamics of the metabolism-related species of two different cell types. Such approaches could prove useful in understanding the mechanisms of tumor ontogenesis, progression, and proliferation.

Bioinformatics Analyses of Spatial Peripheral Circadian Clock-Mediated Gene Expression of Glucocorticoid Receptor-Related Genes.

Glucocorticoids are ubiquitous, pleotropic steroid hormones secreted from the cortices of the adrenal glands in a circadian fashion under the strong influence of the central Clock center located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In previous work, we reported that the circadian transcription factor CLOCK and its heterodimer partner BMAL1 suppress the transcriptional activity of the glucocorticoid receptor (GR) by acetylating a lysine cluster located in its hinge region between the DNA- and ligand-binding domains. This regulation of GR transcriptional activity by CLOCK/BMAL1 functions as a counter-regulatory loop against the diurnally fluctuating circulating glucocorticoids. Here, we have performed further analyses of our data using bioinformatics and computational methods. Gene expression data were analyzed using unsupervised machine learning methods, such as hierarchical clustering, k-means, Naïve Bayes classification, and polynomial regression analyses. We determined expression patterns of Clock-related genes, unraveled the dynamics of spatial data, and defined the temporal function of Clock-mediated GR-regulated genes. Gene expressions manifested nonlinear dynamics, possibly because we obtained dynamic results from stationary measurements. The mechanics of the circadian rhythms are still obscure, and more studies are required to understand how such rhythms influence mammalian physiology.

Genotypic and Clinical Analysis of a Thalassemia Major Cohort: An Observational Study.

Thalassemia major (TM) is a hereditary disease caused by defective globin synthesis. Because of the significant increase in life expectancy, these patients are suffering from various health conditions, including endocrinopathies and low bone mineral density. The aim of the present study was to investigate the correlation between clinical and biochemical parameters as well as to identify possible relations in a genotype to phenotype pattern. Sixty-four patients with TM (32 men and 32 women) participated in a cross-sectional study design. The patients were recruited from "Aghia Sofia" Children's Hospital. Clinical and biochemical parameters were evaluated as well as specific mutations were identified. We have found significant correlations between biochemical parameters and iron chelation, hormone replacement treatment as well as TM genotype and hematocrit and T-score. To conclude, the current study showed that clinical parameters of TM patients correlate significantly with both biochemical factors and genotypical patient parameters. Our present study showed that there is a connection between genotype and phenotype as, for example, the identified relation between hematocrit and T-scores and TM-specific mutations. This connection indicates that there is still much more to learn about the role of mutations not only in the disease itself but also in the underlying comorbidities.

Urticaria from the Neurodermatological Perspective: A Temporal Analysis of Urticaria and Cognition.

Chronic spontaneous urticaria (CSU, or CU) is a disease that significantly affects the quality of life of patients. The connection between the cognitive state of an individual and dermatological diseases has been previously reported, and it is known, although not thoroughly investigated, that there is a cognitive and quality of life relation to dermal pathologies. Urticaria is a chronic disease that requires a specialized approach to diagnosis and treatment but also a holistic approach with respect to the consideration of both the pathophysiology of the disease and the cognition status of the patient. The present study aims at analyzing CU score and cognitive indexes with respect to time, as a time series and their subsequent interactions. We have attempted to model the investigated time series in order to unravel possible causative relationships between cognitive/quality of life factors and urticaria. One hundred and eleven patients (29 males/82 females) admitted to our department were diagnosed with CU. CU was estimated on UAS7 score basis, which was used in order to define disease severity. Indexes used for assessing the cognitive and quality of life of patients' status included the Urticaria Control Test (UCT) and Dermatology Life Quality Index (DLQI). Significant correlations were found between UAS7 score and the UCT and DLQI scores, respectively. Interestingly, each score time series was modelled by different sets of equations, indicating the unique effect each one has on the disease, as well as that each score probably is manifested by a different pathophysiological mechanism.

Cellular Phone User's Age or the Duration of Calls Moderate Autonomic Nervous System? A Meta-Analysis.

BACKGROUND: The European Health Risk Assessment Network on Electromagnetic Fields Exposure (EFHRAN) reported in 2012: "Children and adolescents represent the first generation of Europeans to be exposed to diffuse EMF since their conception and birth, thus, they are expected to be more sensitive to these fields." On the other hand, the body's physiologic processes are regulated by the autonomic nervous system (ANS) in a way that warrants further elucidation. OBJECTIVE: Age and duration of exposure are investigated for modifying the variance of the reported effects of mobile/cellular phone call (CPC) on ANS indexed, herein, by the heart rate variability (HRV). METHOD: Five studies targeted to 124 healthy subjects (aged 15.3-28.4 years (24.3 ± 5.2), who have been recorded in supine position before and/or sham versus real exposure (to a CPC lasting 5-32 minutes), are included in this meta-analysis. Age and duration of a CPC are evaluated as predictors in two separate meta-regressions. RESULTS: The meta-analysis identified a heterogeneity I2 = 63.2% for all outcomes and I2 = 65.2% for sympathovagal balance. Thus, we performed meta-regressions: for the sympathovagal balance rather than the combined parameters effect, the goodness of fit model presents significance only for age - the residual sum of squares compared to chi-square distribution (QR) is 4.24 for age (p = 0.12) - while, for minutes of exposure, QR = 8.2805 (p = 0.016). CONCLUSIONS: The sympathovagal balance - indispensible for health/homeostasis maintenance - is strongly predicted by age. Minutes of exposure did not affect overall HRV or sympathovagal balance. The results endorse/validate the EFHRAN 2012 suggestion for future research targeting to youngsters.

SSEv: A New Small Samples Evaluator Based on Modified Survival Curves.

Rare diseases, either of genetic or epigenetic origin, either proliferative or degenerative, are hard to be studied credibly, because of sparse prevalence, thus, small sampling. In addition, biological or translational experimentation either with animal models, or in vitro studies share small sampling-often due to lack of financial support or due to mannered and costly techniques. Pilot or feasibility studies been performed, before expensive clinical trials are decided, focus on small samples. Small Samples Evaluator (SSEv) is a useful tool based on a modification of survival curves. The technique can be applied to repeated measures, as well as to case-control or cross-sectional designed studies. A web-based application of SSEv is created and presented herein. The application is freely accessible at: https://ssev.eu .

Bioimpedance Measurements in Adolescents with Polycystic Ovary Syndrome: A Pilot Study.

Limited data are available on the body composition of adolescent women with polycystic ovary syndrome (PCOS). The aim of this study was to examine differences in body composition indices of metabolism, homeostasis and inflammation, between Greek adolescent females suffering from PCOS and age- and body mass index (BMI)-matched non-PCOS controls. Thirteen PCOS patients and nine non-PCOS controls, aged 13-24 years participated in this cross-sectional study. Study participants underwent assessment by a novel dual frequency bioimpedance device (BIA-ACC). The following body composition indices were measured in each adolescent: extra cellular water (ECW) as inflammation marker, total body water (TBW) as homeostasis marker, extracellular mass to body cell mass ratio (ECM/BCM), fat mass (FM), fat-free mass (FFM) and intracellular water (ICW) as markers of body mass composition and metabolism. Non-linear analysis showed no statistically significant differences in the body composition characteristics between PCOS patients and controls. Further studies with larger sample sizes are needed to confirm whether adolescents with PCOS actually have similar body composition profile with their non-PCOS peers.

Evaluating the Homeostasis Assessment Model Insulin Resistance and the Cardiac Autonomic System in Bariatric Surgery Patients: A Meta-Analysis.

Morbid obesity is a severe chronic disease and subject to surgical methods for losing weight. This intervention is expected to drive to better quality of life and health status. Other important aspects which may be influenced are: HOMA-IR (as insulin resistance marker) and heart rate variability (as cardiac function and autonomic nervous system marker), which are independent and valid predictors of future cardiac, neurological, metabolic health. We pooled 4 studies (646 subjects) resulting to HOMA-IR and nine HRV components-grouped in those undergone to gastric bypass (RYGP) and those operated with vertical sleeve gastrectomy (SG) method. We performed a meta-analysis in patients for HOMA-IR and HRV, using Hedge's g correction of Cohen d for small samples. We concluded that RYGP favors insulin resistance decrease, whereas SG increases the vagal tone, improving cardiac function. The severity of cardiovascular diseases history suggests the selection of the surgery method: SG for the most severe cardiovascular cases and RYGP for those with higher HOMA-IR.

Interactome of Obesity: Obesidome : Genetic Obesity, Stress Induced Obesity, Pathogenic Obesity Interaction.

Obesity is a chronic disease of increasing prevalence reaching epidemic proportions. Genetic defects as well as epigenetic effects contribute to the obesity phenotype. Investigating gene (e.g. MC4R defects)-environment (behavior, infectious agents, stress) interactions is a relative new field of great research interest. In this study, we have made an effort to create an interactome (henceforth referred to as "obesidome"), where extrinsic stressors response, intrinsic predisposition, immunity response to inflammation and autonomous nervous system implications are integrated. These pathways are presented in one interactome network for the first time. In our study, obesity-related genes/gene products were found to form a complex interactions network.

Diet and metabolism are back: The oldest known Islamic medical manuscript bridges the gap from ancient to modern gout management.

Gout is a chronic disease frequently associated with lifestyle; its prevalence is increasing in Western societies, as well as in the Middle East. Apart from its partial genetic features, diet accounts for 12% of the causality of the disease, while purine-rich foods contribute decisively to its development and evaluation. The influential Persian physician of the medieval ages, Abu Bakr Muhammad Ibn Zakariya al-Razi (or by his Latin name Rhazes; 860-925 AD), wrote a short book (20 chapters) entitled 'Treatise on gout'. Rhazes adopted the Hippocratic humoralism, and suggested that the disease results from metabolic excess in the peripheral blood, presenting sex dimorphism and age-dependence. His therapeutic guidelines include a diet prescribed by a physician, the use of laxatives and emetics, counter-balancing excess or deficiency of bile or phlegm and analgesics, bloodletting, foot and steam baths, as well as salves and poultices as preventive measures. He appends differential dietary restrictions/suggestions for phlegmatic or choleric patients: Small rations and intake of good quality foods low in purine by 20% for phlegmatic and 28% for choleric patients, as well as the restriction of foods high in purine by 27% for phlegmatic and 22% for the choleric patients. Finally, the acidic to alkaloid food intake ratio suggested is 2/5 for choleric and 3/7 for phlegmatic patients. His suggested foods and drugs are vitamin C and B-rich complexes, thereby inhibiting the accumulation of tophi.

Neuroendocrine System Adaptation during Consecutive Extrinsic Stimuli: A Pilot Dynamic Study.

This pilot repeated measures study aims to evaluate the dynamics of the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis, and/or their interplay with low-level inflammation in healthy schoolchildren during consecutive extrinsic stimuli. Twenty healthy schoolchildren and adolescents aged 11-14 years (12.5 ± 1.5) were consecutively exposed to an oral task (#2) and an arithmetic task (#3) (Trier Social Stress Test for Children (TSST-C)), lasting 5 min each, and a three-minute cellular phone call (#4). Salivary cortisol (SC) was sampled at baseline (#1) and immediately after each exposure (#2, 3, and 4). Baseline serum high-sensitivity C-reactive protein (hsCRP) and cortisol levels were also assessed. ANS dynamics and complexity were measured using Sample Entropy (SampEn) at each experimental time period (#1-4). Baseline serum hCRP and cortisol correlated negatively to each other, while the ANS and HPA axis acute reactions to the three consecutive stimuli differed over time. The ANS adaptation to these stimuli included complexity modulation, which was not dependent on baseline hsCRP or cortisol, and weakened during the third stimulation. However, baseline hsCRP and cortisol had a weakening and an increasing effect on the HPA axis over time, respectively. We conclude that low-level inflammation and baseline morning cortisol level have no effect on ANS dynamics but influence the HPA axis response to consecutive external stimuli.

Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.

Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.

Tissue and Serum Biomarkers in Degenerative Aortic Stenosis-Insights into Pathogenesis, Prevention and Therapy.

BACKGROUND AND AIM: Degenerative Aortic Stenosis (DAS) is a common disease that causes substantial morbidity and mortality worldwide, especially in the older population. Our aim was to further investigate novel serum and tissue biomarkers to elucidate biological processes involved in this entity. MATERIAL AND METHODS: We evaluated the expression of six biomarkers significantly involved in cardiovascular pathology, i.e., irisin, periostin, osteoglycin, interleukin 18, high mobility group box 1 and proprotein convertase subtilisin/kexin type 9 in the serum at the protein level, and in the tissue at both the protein and mRNA levels of patients with AS (N = 60). Five normal valves obtained after transplantation from hearts of patients with idiopathic dilated cardiomyopathy were also studied. Serum measurements were also performed in 22 individuals without valvular disease who served as controls (C). RESULTS: Higher levels of all factors were found in DAS patients' serum than in normal C. IHC and PCR mRNA tissue analysis showed the presence of all biomarkers in the aortic valve cusps with DAS, but no trace of PCR mRNA was found in the five transplantation valves. Moreover, periostin serum levels correlated significantly with IHC and mRNA tissue levels in AS patients. CONCLUSION: We showed that six widely prevalent biomarkers affecting the atherosclerotic process were also involved in DAS, suggesting a strong osteogenic and pro-inflammatory profile, indicating that aortic valve calcification is a multifactorial biological process.