Biological and contextual determinants of early development in marginalized Roma communities: A research protocol of the RomaREACH study.

BACKGROUND: The period of early childhood bears significant importance from the lifespan perspective. Children from marginalized Roma communities face several risk factors that endanger their early development. Based on the gaps in available evidence, the aim of the RomaREACH research project (Research on Early Childhood in marginalized Roma communities) is, therefore, to explore the complex mechanisms influencing psychomotor development in the first 3 years of a child's life in marginalized Roma communities, and to translate and adapt instruments for measuring development and parenting in marginalized Roma communities and assess their psychometric qualities and suitability METHODS: The project comprises two parts. The first part is a validation study of the translated Caregiver-Reported Early Development Instrument (CREDI) and the Comprehensive Early Childhood Parenting Questionnaire (CECPAQ), tools for the assessment of early development and of parenting strategies and practices. The second part is a longitudinal cohort study, in which the relationships of risk and protective factors with development are explored. DISCUSSION: The RomaREACH project is a multicomponent study of social determinants of health and development in early childhood that can provide new evidence on the relationship of risk and protective factors with early development. Such young children from difficult-to-reach marginalized Roma communities are rarely included in research, and information about the scope and the extent of inequities in health and development in the period of early childhood is scarce. The expected results of the RomaREACH project have the potential to influence policy and practice by providing validated tools and evidence-based insights that can help mitigate the developmental risks faced by children in marginalized Roma communities and contribute to improving developmental outcomes and equity.

Flavonoids as Promising Natural Compounds in the Prevention and Treatment of Selected Skin Diseases.

Phytochemicals represent a large and diverse group of naturally occurring compounds, bioactive nutrients, or phytonutrients produced by plants, widely found in fruits, vegetables, whole grains products, legumes, beans, herbs, seeds, nuts, tea, and dark chocolate. They are classified according to their chemical structures and functional properties. Flavonoids belong to the phenolic class of phytochemicals with potential solid pharmacological effects as modulators of multiple signal transduction pathways. Their beneficial effect on the human body is associated with their antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic properties. Flavonoids are also widely used in various nutritional, pharmaceutical, medical, and cosmetic applications. In our review, we discuss the positive effect of flavonoids on chronic skin diseases such as vitiligo, psoriasis, acne, and atopic dermatitis.

The Effect of Oestrogen Supplementation on Antioxidant Enzymes and Mitochondrial Respiratory Function After Myocardial Infarction of Ovariectomized Rats.

ABSTRACT: Acute myocardial infarction (MI) is the leading cause of mortality worldwide with premenopausal women showing a lower incidence of cardiovascular disease compared with men of the same age. After menopause, this advantage disappears, suggesting that sex hormones play a cardioprotective role. This study was aimed to assess on the activity of antioxidant enzymes in plasma and the respiratory function of isolated heart mitochondria after the induction of MI in rats after ovariectomy and estradiol benzoate supplementation. Sprague-Dawley female rats were ovariectomized 3 months before the induction of MI and supplemented/not supplemented with oestrogen 3 months before/7 days after the induction of MI. No significant differences in glutathione peroxidase activities were found in any group. Differences between values were only significant in the ovariectomized not supplemented group (P < 0.01) for the glutathione reductase activity and glutathione concentrations. In isolated mitochondria (7 days after MI), the decline in respiration was observed comparing the ovariectomized and nonovariectomized group. Respiratory functions did not show significant differences between animals supplemented with oestrogen before MI or treated with oestrogen after MI. Ovariectomy worsened mitochondrial dysfunction after MI, and oestrogen supplementation before or after the induction of MI did not improve mitochondrial function.

Tryptophan: Its Metabolism along the Kynurenine, Serotonin, and Indole Pathway in Malignant Melanoma.

(1) Background: Tryptophan metabolism is known to be one of the important mechanisms used by cancer to evade immune surveillance. Altered tryptophan metabolism was studied in patients with pigmented malignant melanoma confirmed histologically by the anatomic stage grouping for cutaneous melanoma using clinical staging on the basis of the Breslow thickness of the melanoma, the degree of spread to regional lymph nodes, and by the presence of distant metastasis. (2) Methods: Urinary tryptophan metabolites were detected by RP-HPLC method. (3) Results: In the present work, we provided evidence of altered metabolism of all tryptophan pathways in melanoma patients. (4) Conclusions: Knowledge of the shifted serotonin pathway toward DHICA formation and kynurenine pathway shifted toward NAD+ production could serve in the early detection of the disease and the initiation of early treatment of malignant melanoma.

Salivary Redox Homeostasis in Human Health and Disease.

Homeostasis is a self-regulatory dynamic process that maintains a stable internal environment in the human body. These regulations are essential for the optimal functioning of enzymes necessary for human health. Homeostasis elucidates disrupted mechanisms leading to the development of various pathological conditions caused by oxidative stress. In our work, we discuss redox homeostasis and salivary antioxidant activity during healthy periods and in periods of disease: dental carries, oral cavity cancer, periodontal diseases, cardiovascular diseases, diabetes mellitus, systemic sclerosis, and pancreatitis. The composition of saliva reflects dynamic changes in the organism, which makes it an excellent tool for determining clinically valuable biomarkers. The oral cavity and saliva may form the first line of defense against oxidative stress. Analysis of salivary antioxidants may be helpful as a diagnostic, prognostic, and therapeutic marker of not only oral, but also systemic health.

Current View on the Mechanisms of Alcohol-Mediated Toxicity.

Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic pathological conditions. Some of the effects are very well described and explained, but there are still gaps in the explanation of empirically co-founded dysfunction in many alcohol-related conditions. This work focuses on reviewing actual knowledge about the toxic effects of ethanol and its degradation products.

Strong Dependence between Tryptophan-Related Fluorescence of Urine and Malignant Melanoma.

Urine autofluorescence at 295 nm is significantly higher in patients with malignant melanoma at each clinical stage compared to the healthy group. The largest difference is in the early-stages and without metastases. With increasing stage, the autofluorescence at 295 nm decreases. There is also a significant negative correlation between autofluorescence and Clark classification. Based on our results, it is assumed that the way malignant melanoma grows also affects urinary autofluorescence.

Specific Urinary Metabolites in Malignant Melanoma.

Background and objectives: Melanin, which has a confirmed role in melanoma cell behaviour, is formed in the process of melanogenesis and is synthesized from tryptophan, L-tyrosine and their metabolites. All these metabolites are easily detectable by chromatography in urine. Materials and Methods: Urine samples of 133 individuals (82 malignant melanoma patients and 51 healthy controls) were analysed by reversed-phase high-performance liquid chromatography (RP-HPLC). The diagnosis of malignant melanoma was confirmed histologically. Results: Chromatograms of melanoma patients showed increased levels of 5,6-dihydroxyindole-2-carboxylic acid, vanilmandelic acid, homovanilic acid, tryptophan, 5-hydroxyindole-3-acetic acid, and indoxyl sulphate compared to healthy controls. Concentration of indoxyl sulphate, homovanilic acid and tryptophan were significantly increased even in the low clinical stage 0 of the disease (indoxyl sulphate, homovanilic acid and tryptophan in patients with clinical stage 0 vs. controls expressed as medium/ interquartile range in µmol/mmol creatinine: 28.37/15.30 vs. 5.00/6.91; 47.97/33.08 vs. 7.33/21.25; and 16.38/15.98 vs. 3.46/6.22, respectively). Conclusions: HPLC detection of metabolites of L-tyrosine and tryptophan in the urine of melanoma patients may play a significant role in diagnostics as well as a therapeutic strategy of melanoma cancer.

Assessment of clinical biochemical parameters in Roma minority residing in eastern Slovakia compared with the majority population.

Roma constitute the largest ethnic minority in Europe and the second largest minority in Slovakia. Their health problems originate mainly from their low socioeconomic status, certain cultural aspects and their health-threatening lifestyle as well as the psycho-social burden arising from poverty and frequent migration. Evaluation of glucose, albumin, triacylglycerol (TAG) and low density lipoprotein cholesterol (LDL-C) concentrations did not reveal any clue about the presumed deteriorated health of the Roma population. Higher proportions of subjects with elevated serum total cholesterol were found in Roma women as compared to both control groups of women (p = 0.027, p = 0.006) and in Roma men as compared to the male control group living in standard conditions. Only the low level of HDL-cholesterol gives a glimpse of their deteriorated health. Significantly lower levels of serum HDL-C were reported in Roma men and women compared to the respondents in both control groups with a p value of p < 0.001. Comparing the ratio of LDL-C/HDL-C yielded significant differences between the number of physiological values in Roma men and men from the control group 1 (p = 0.022) in favour of the control group. When comparing the number of people with physiological values of cholesterols and with worsening TAG parameters at the same time, the increased risk of Roma men compared with men from the control group 1 became evident, with a level of significance of p = 0.023. Evaluation of urine samples pointed to significantly higher concentrations of urinary protein in Roma women compared with women in the control group 1 (p = 0.012).

A Multi-Biomarker Approach to Increase the Accuracy of Diagnosis and Management of Coronary Artery Disease.

Non-invasive possibilities of predicting cardiovascular risk and monitoring the treatment and progression of coronary artery disease (CAD) are important subjects of cardiovascular research. Various inflammatory markers have been identified as potential biomarkers of CAD, including interleukin-6 (IL-6), lipocalin-2 (LCN-2), growth differentiation factor 15 (GDF-15), and T cell immunoglobulin and mucin domain-3 (TIM-3). This research aims to identify their utility in the investigation of CAD severity and progression. The basic anthropometric parameters, as well as the levels of urea, creatinine, CRP, leukocytes, fibrinogen, and biomarkers of inflammation, were measured in 130 patients who underwent coronary angiography. In male patients, divided according to findings on coronary angiography, we observed an increasing expression of GDF-15 with increasing stenosis (with worsening findings). In females, we observed increasing fibrinogen expression with increasing stenosis, i.e., findings on coronary angiography. Correlation analysis did not confirm the relationship between TIM-3, LCN and 2, IL-6 and the severity of findings obtained by coronary angiography; however, the correlation of TIM-3 and LCN-2 expression was positive with the finding, and the correlation of IL-6 with the finding was surprisingly negative. Understanding the role of these inflammatory markers in CAD can be helpful in risk stratification, guiding therapeutic strategies, and monitoring treatment responses in patients with CAD.

Mothers in stress: Hair cortisol of mothers living in marginalised Roma communities and the role of socioeconomic disadvantage.

Roma living in marginalised communities are among the most disadvantaged groups in Slovakia. Socioeconomic disadvantage is associated with higher hair cortisol concentrations (HCC), including in parents. The aim of this study is therefore to assess differences in HCC, reflecting the levels of stress, between mothers living in MRCs and from the majority population, to assess the association of socioeconomic disadvantage with HCC, and whether disadvantage mediates the MRC/majority differences in HCC. Participants were mothers of children aged 15-18 months old living in MRCs (N=61) and from the Slovak majority population (N=90). During preventive paediatric visits, visits at community centres and home visits, hair samples and data by questionnaire were collected. HCC differed significantly between mothers living in MRCs and mothers from the majority population, with the mean HCC value being twice as high in mothers living in MRCs (22.98 (95% confidence interval, CI, 15.70-30.30) vs. 11.76 (8.34-15.20), p<0.05). HCC was significantly associated with education, household equipment and household overcrowding, but not with billing, socioeconomic stress and social support. The difference in HCC between mothers living in MRCs and mothers from the majority population was partially mediated by poor house equipment, such as no access to running water, no flushing toilet or no bathroom (the indirect effect of B=7.63 (95% CI: 2.12-13.92)). Practitioners and policymakers should be aware of high stress levels among mothers living in MRCs and aim at enhancing their living and housing conditions.

Serum Oxidative Status in People with Obesity: Relation to Tissue Losses, Glucose Levels, and Weight Reduction.

BACKGROUND: This work aims to study the effect of reductions in various body mass components on the oxidative, glycemic, and lipid parameters of people with obesity (PWO). METHODS: A total of 53 PWO underwent a six-month individualized low-calorie diet combined with moderate exercise, during which anthropometric, biochemical, and oxidative parameters were measured. Probands were divided into groups based on weight, visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses. RESULTS: Weight reduction normalizes glycemia, but VFA reduction is less pronounced, while SMM and TBW reductions are more pronounced in patients with higher initial concentrations of glucose and fructosamine. Moreover, changes in oxidative parameters correlate with changes in glucose. CONCLUSIONS: Weight loss, regardless of the reduced tissue, decreases cardiovascular risk. We observed a significant change in almost all parameters related to the redox state. In general, parameters responsible for antioxidant action improved, and markers of oxidative damage decreased. Malondialdehyde, lipid peroxides, and total oxidative status levels can be considered biomarkers reflecting only the current severity of reactive oxygen species genesis processes. When considering the glycemic state, the results are not as clear due to the substantial differences between normoglycemic and hyperglycemic patients. Glycemic status is a factor playing a crucial role in weight reduction.

Age dependency on some physiological and biochemical parameters of male Wistar rats in controlled environment.

The aim of the study was to assess the age dependence on some physiological and serum chemistry parameters of male Wistar rats for the estimation of reference values in controlled environment. We are presenting values obtained from a large number of animals such as survival, average life span, body mass, food and water intake, serum chemistry parameters as total protein, albumin, transferrin and ferritin in serum. One part of this work compares the relationship between rat and human age. The maximal life span of our rats was determined to be about 4.4 years. The average life span was 3.75 years. The body weight quickly rose to the 85th week of life and then remained in the range of about 640-660 g up to the 163rd week when it began to decline. Food intake rose from the beginning to the maximum of about 39 g in the 33rd week and then decreased to about 20 g in the 163rd week. The water intake had a similar dynamics (about 43 mL in the 33rd week and 33 mL in the 163rd week). Levels of total protein in serum increased with age, in contrast, albumin levels decreased. Transferrin and ferritin decreased to approximately the 160th week of life and then increased.

Loss of Skeletal Muscle Mass and Intracellular Water as Undesired Outcomes of Weight Reduction in Obese Hyperglycemic Women: A Short-Term Longitudinal Study.

The current study is focused on the influence of hyperglycemia on weight loss in obese premenopausal women. Specifically, the study evaluated the impact of a six-month individualized low-calorie diet combined with moderate exercise on weight reduction and glucose metabolism in obese women with normoglycemia compared to obese women with moderate hyperglycemia. The results indicated that patients with normoglycemia achieved a successful weight loss, which was connected to a decrease in adipose tissue and reflected by diminished content of visceral fat area (VFA) and percent body fat. In contrast, weight reduction in patients with hyperglycemia was connected not only to the loss of VFA but also to undesired decrease in skeletal muscle mass as well as intracellular and total body water. These unfavorable outcomes were observed despite normalization of glucose metabolism reflected by statistically significant lowering glucose, fructosamine, advanced glycation end-products, and HOMA-IR levels. Overall, the obtained results indicate the importance of the measurement of the carbohydrate profile in obese women and the need for an early introduction of weight reduction strategies before the development of hyperglycemia.

Successful correction of hyperglycemia is critical for weight loss and a decrease in cardiovascular risk in obese patients.

Weight loss is recommended for obese patients with cardiovascular risk; however, it remains questionable how hyperglycemia affects this process. To address this problem, we aimed to determine the association between weight loss, lipid profile, and body mass parameters in obese normoglycemic and hyperglycemic patients. Obese (body mass index30 kg/m2) normoglycemic and hyperglycemic volunteers were placed on a weight reduction program that included a balanced, low-calorie diet and moderate exercise for 6 months. Participants were assessed for serum glucose, ß-cell functions, insulin resistance, lipid metabolism, lipoprotein profile, and body mass parameters. This weight reduction program fully normalized serum glucose levels only in a subpopulation of patients. These individuals also exhibited a significant reduction in body weight, and significant improvement in serum lipid profile and insulin resistance. In contrast, the patients that remained hyperglycemic were characterized by persistent insulin resistance, increased levels of atherogenic fractions of LDL and HDL lipoproteins, and elevated values of a modified Atherogenic Index of Plasma. Correlation analysis indicated a strong positive association between the modified Atherogenic Index of Plasma with atherogenic lipid profile, insulin resistance, and body mass parameters, indicating its usefulness in clinical studies in obese patients. Overall, our data indicate that successful treatment of hyperglycemia facilitates weight loss and improves the composition of blood lipids, while persisting hyperglycemia negatively affects the weight loss process and maintains an atherogenic lipid profile. Because hyperglycemia predisposes to cardiovascular disorders, its correction should be the primary goal during weight reduction therapy.

Urinary bisphenol A in women with polycystic ovary syndrome - a possible suppressive effect on steroidogenesis?

OBJECTIVES: There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. METHODS: Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. RESULTS: PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. CONCLUSIONS: PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

Toluene abuse markers in marginalized populations.

Toluene abuse is one of the most common addictions among marginalized Roma. The aim of the study was the comparison of urinary toluene metabolite levels in marginalized population of Eastern Slovakia as compared to the majority population, and to verify the validity of the answers, given in the questionnaires, regarding toluene abuse. The study was carried out as part of the HEPA-META project aiming to map the prevalence of health problems in marginalized Roma. The majority of people living outside the area of the segregated Roma communities comprised the control group. The total number of study participants was 770. Statistically significant differences in the levels of hippuric acid and o-cresol were found between Roma and the majority population. Variations in urinary hippuric acid levels in addition to toluene abuse can be caused also by dietary factors, medical treatment as well as alcohol consumption, which is frequent (not only) in marginalized communities.

Lipoprotein-Cholesterol Fractions in Marginalized Roma versus Majority Population.

The trend of modern clinical biochemistry is to emphasize the composition and the quality of lipoproteins over their quantity. The serum lipoprotein fractions and subfractions were analyzed by the Lipoprint Lipoprotein Subfractions Testing System, the parameters of lipid profile, as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triacylglycerides (TAG) were determined by an automated selective biochemical analyzer. Our results showed a significantly lower concentration of cholesterol in the LDL fractions 1 and 2 and in the HDL fractions 8 to 10 in Roma compared to the majority population. The most significant differences between Roma and the majority population when considering body mass index (BMI), waist-to-hip ratio and the index of central obesity were in very low-density lipoproteins (VLDL), intermediate-density lipoproteins, fraction A (IDL-A) and LDL-2. The last two listed were significantly higher in the majority population. VLDL was significantly higher in overweight or obese Roma men and in Roma men with central obesity compared to men from the majority population, as well as in Roma women with normal weight and physiological waist-to-hip ratio compared to the women from majority population. Our study is among the first describing the distribution of lipoprotein subfractions in different ethnic groups.

Prognostic Value of the Modified Atherogenic Index of Plasma during Body Mass Reduction in Polish Obese/Overweight People.

Although weight loss is recommended for obese patients, it remains questionable how much weight loss is optimal. A novel index that accurately determines the risk of cardiovascular diseases (CVDs) in terms of weight loss is needed. The modified Atherogenic Index of Plasma (AIP), presented here is unique in the literature. It is calculated based on data for anti-atherogenic, high-density lipoprotein cholesterol (HDL-C) fractions, instead of the total HDL-C. This study investigates whether weight loss correlates with CVD risk, and whether the modified AIP allows more accurate diagnostics in obese/overweight people. According to the increase or decrease of AIP during weight loss, 52 Polish patients were subdivided into two groups: group I (increased AIP; n = 16) and group II (decreased AIP; n = 36). The patients' body mass composition and fasting serum lipid parameters (total cholesterol, triglycerides, HDL-C, and LDL-C (low-density lipoprotein cholesterol)), and cholesterol in 21 lipoprotein sub-fractions were determined. Over six months, all patients reduced their body mass by about 10%. There were no significant differences in anthropometric measures between groups. Increases in large and intermediate HDL-C fractions 1 to 6 and decreases in smaller fractions 7 to 10 were observed in group II. In group I, HDL-C fractions 1 and 10 decreased, while cholesterol in other fractions increased. Increases were observed in the antiatherogenic HDL-C of 52% of group II and 4% of group I. As for atherogenic HDL-C, a decrease of 24% was observed in group II and an increase of 9% in group I. In group I, increases of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and large LDL fractions were noticed, and the reverse in group II. The results show that the modified AIP is a more accurate indicator of CVD risk than existing indices, and that uncontrolled weight reduction does not necessarily have a beneficial influence, and may adversely affect the cardiovascular system.

The effect of R-(-)-deprenyl administration on reproductive parameters of rat males.

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the reproductive parameters of rat males. After 30 days of intraperitoneal administration of saline or 0.0025mg/kg (10(-5)mol/l) of R-(-)-deprenyl dissolved in saline, males were mated with females of the same strain. Subsequently, animals were killed by thiopental, and their blood and sperm were collected. We found that epididymis of males exposed to R-(-)-deprenyl had higher sperm count (P<0.05), and females who mated with these males gave birth to a greater number of offspring (P<0.05) compared to control. The blood of experimental animals contained higher levels of testosterone (P<0.05), FSH (P<0.01), and total antioxidants (P<0.01). We did not detect sperm DNA fragmentation in control or in experimental males. Interestingly, round spermatids were often observed inside seminiferous tubules of experimental animals, but obviously without any negative consequences on male fertility. Our findings could be verified on a sample of human male volunteers treated for infertility, because human organism tolerate higher doses of R-(-)-deprenyl, which is a selective inhibitor of monoamine oxidase B employed in our experiment and used in the therapy of Parkinson׳s disease, rather well.