Selective screening for inborn errors of metabolism using tandem mass spectrometry in West Kazakhstan children: study protocol.

Data on the prevalence of most inborn errors of metabolism are still unavailable in Kazakhstan. The study aims to perform selective screening for hereditary metabolic diseases among patients aged from 1 day to 18 years in western Kazakhstan using the LC-MS/MS method, with establishing the reference values for the content of amino acids, acylcarnitines, and succinylacetone in blood samples of healthy children. Tasks: 1. To assess the burden of metabolic disorders detected by LC-MS/MS in western Kazakhstan by examination of children at clinical risk in pediatric clinics throughout the region; https://www.frontiersin.org/register?returnUrl=https://loop.frontiersin.org 2. To set the reference values of metabolites in the child population; 3. To analyze the age distribution, prevalence, and age of onset for each identified IEM, further comparing the obtained findings with those from previously published reports in other populations. METHODS: To set the reference values of 51 metabolites in the child population, 750 healthy children will be included. The selective screening will be performed among 1,500 patients aged 1 day to 18 years with suspected hereditary metabolic disorders. ANTICIPATED RESULTS: The results of selective screening will be interpreted by comparison with the reference values established. Diagnosis will be based on clinical signs, blood levels of amino acids, acylcarnitines, succinylacetone, and urine levels of organic acids and tests for gene mutations. An assessment of 37 inborn errors of metabolism frequencies in high-risk children will be performed. The research will further develop the national as selective as expanded newborn screening programs. The study was registered in clinicaltrials. gov (https://www. CLINICALTRIALS: gov/study/NCT05910151) on 16 June 2023.

Chromium as a Risk Factor for Breast Cancer: A Meta-Analysis.

BACKGROUND: Chromium (Cr) is a transition metal, natural element. Chromium is the 21st most abundant element in Earth's crust. Cr is found in soil, rocks and living organisms. It may have various oxidation states, from -2 to +6, but most of these states are too unstable to exist in any significant quantities. The purpose of this review and meta-analysis is to critically assess the scientific evidence on the carcinogenic effects of chromium (Cr) and to determine whether there is currently sufficient evidence to suggest that that there is a link between chromium levels in hair and blood serum and breast cancer in women. MATERIAL AND METHODS: Research on the relationship between heavy metal chromium and the risk of developing breast cancer has been searched in PubMed, EMBASE, Web of Science, Scopus among papers published between January 2000 and September 2020. The search used the following terms (MeSH): breast cancer, women, trace elements, metals, chromium, chemically-induced, hair, serum using additional terms. RESULTS: In the second group of comparisons of women from "ecologically clean" districts of Aktobe Region, there were significantly lower indicators of the microelements in tumor tissue. The amount of Fe ranges from 38.46 to 65.39 ug/g (average 49.56±5.81 ug/g), Cu from 2.8 to 6.69 ug/g (average 5.06±1.01 ug/g), Zn from 1.89 to 5.38 ug/g (average 3.88±0.89 ug/g), Cr from zero to 6,1 ug/g (average 2.13±1.29 ug/g), Ni from 0.11 to 0.42 ug/g (average 0.28±0.067 ug/g) и Pb from zero to 0.19 ug/g (average 0.098±0.06 ug/g). CONCLUSION: The article established that women who live or work in ecologically polluted areas or have problems with micronutrient exchange need in-depth screening and more frequent screening for early detection of pre- and breast cancer.

Comparison of the Effect of Endurance, Strength and Endurance-Strength Training on Glucose and Insulin Homeostasis and the Lipid Profile of Overweight and Obese Subjects: A Systematic Review and Meta-Analysis.

The most effective type of training to improve cardiometabolic parameters in overweight subjects is unknown. This meta-analysis compared the effect of endurance, strength and combined training on glucose, insulin metabolism and the lipid profile of overweight and obese adults. The Cochrane, PubMed, Scopus and Web of Science databases were searched to identify randomised trials assessing the effect of training intervention on fasting and 2 h glucose and insulin levels, glycated haemoglobin (HbA1c), homeostatic model assessment of insulin resistance (HOMA), C-peptide, total cholesterol (TC), low- (LDL-C) and high-density lipoprotein cholesterol and triglycerides (TG). Forty-six studies were included showing that endurance training more favourably reduced HbA1c (p = 0.044), and LDL-C (p = 0.021) than strength training. Endurance-strength training more effectively decreased glucose (p = 0.002), HbA1c (p = 0.032), HOMA (p = 0.002), TC (p = 0.039), LDL-C (p = 0.046), HDL (p = 0.036) and TG levels (p = 0.025) than strength training. Combined training significantly reduced the HOMA index (p = 0.009) and TG levels (p = 0.039) compared with endurance training. Endurance and endurance-strength training have a more favourable effect on glucose and insulin homeostasis and lipid profile than strength training in overweight and obese adults. However, the results from this meta-analysis should be interpreted cautiously due to significant heterogeneity among included studies.

Content of Essential Trace Elements in the Hair of Residents of the Caspian Region of the Republic of Kazakhstan Who Recovered from COVID-19.

This study aimed to investigate the content of essential elements in the hair of unvaccinated residents of the Caspian region who recovered from COVID-19. This cross-sectional study involved 260 unvaccinated permanent residents of Mangistau oblast aged 18−60. The diagnosis and severity of COVID-19 were based on clinical signs and symptoms, laboratory data, R-graph results, and oxygen saturation by the Clinical Protocol of the Ministry of Health of the Republic of Kazakhstan. Inductively coupled plasma mass spectrometry determined the content of trace elements cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), iodine (I), manganese (Mn), selenium (Se), and zinc (Zn). The content of Cr (p < 0.05), Cu (p < 0.05), Fe (p < 0.001), I (p < 0.05), Mn (p < 0.001), and Zn (p < 0.05) in the hair of individuals who had a coronavirus infection was lower than those who did not have this infection. There were significantly higher levels of Cu (p < 0.05) in the hair of participants who had moderate or severe COVID-19 compared to those with mild forms. The results of multiple regression analysis showed that in the presence of a COVID-19 infection in a subject's history, the content of Cr (0.871 (95% CI: 0.811; 0.936)), Cu (0.875 (95% CI: 0.803; 0.955)), Fe (0.745 (95% CI: 0.636; 0.873)), and Mn (0.642 (95%CI: 00.518; 0.795)) decreased in the hair. The data obtained indicate that past COVID-19 infections affect the trace element status of the inhabitants of the Caspian region of Kazakhstan.

Hair Toxic Trace Elements of Residents across the Caspian Oil and Gas Region of Kazakhstan: Cross-Sectional Study.

This study aimed to assess the relationship between the content of toxic trace elements, such as aluminum (Al), arsenic (As), beryllium (Be), cadmium (Cd), mercury (Hg), and lead (Pb), in the hair of the adult population of western Kazakhstan and the distance of their residence from oil and gas fields. The cross-sectional study included 850 adults aged 18-60 years. Inductively coupled plasma mass spectrometry was used to measure the level of Al, As, Be, Cd, Hg, and Pb in hair. The relationship between the concentration of toxic trace elements in the hair and the distance from oil and gas fields was assessed in three groups (<16 km, 16-110 km, and >110 km), using multiple linear regression analysis. The highest concentration of Hg = 0.338 µg/g was determined in the group living near oil and gas fields (0-16 km), whereas the lowest concentration of Al = 3.127 µg/g and As = 0.028 µg/g was determined in participants living at a long distance (more than 110 km) (p < 0.001). The concentration of Al (-0.126 (CI: -0.174; -0.077)), Hg (-0.065 (CI: -0.129; -0.001)), and Pb (0.111 (CI: 0.045; 0.177)) is associated with the distance to oil and gas fields. The obtained data indicate a change in the toxic trace element content in the hair of residents in the Caspian region of western Kazakhstan, a change that is most pronounced in residents living in the zone of oil and gas pollution. The distance to the oil and gas fields affects the content of toxic elements in scalp hair. In particular, the concentration of Al and Hg is associated with a decrease in the distance to oil and gas fields, while the concentration of Pb is associated with an increase in the distance to these fields. The lowest content of Al and As was determined in the hair of study participants living in the most remote areas (more than 110 km from oil and gas fields). Our results demonstrate the need for the biomonitoring of toxic elements to determine long-term temporal trends in the impact of chemicals on public health in western Kazakhstan.

Essential Trace Elements in Scalp Hair of Residents across the Caspian Oil and Gas Region of Kazakhstan.

Most of the country's oil and gas fields are situated in West Kazakhstan, mainly on the Caspian Sea coast, causing significant damage to the local environment and contributing to an imbalance in the trace element composition of the human body. The study is aimed to evaluate the relationship between the concentration of essential trace elements in scalp hair of the western Kazakhstan adult population and the remoteness of their residence from oil and gas fields. The concentration of essential trace elements (Co, Cu, Fe, I, Mn, Se, Zn) in the hair of 850 individuals aged 18−60 years was determined by inductively coupled plasma mass spectrometry. In residents of settlements located at a distance of >110 km from oil and gas fields, the concentration of Cu and I in hair was significantly higher than in those closer to 110 km (p < 0.001). The content of Cu and I were associated with the distance to oil and gas fields (0.072 (95% CI: 0.050; 0.094)) and (0.121 (95% CI: 0.058; 0.185)), respectively. We detected a significant imbalance in the distribution of some essential trace elements in residents' scalp hair from the Caspian region of western Kazakhstan, living near oil and gas fields. The concentrations of Cu and I were significantly interrelated with the distance to oil and gas fields. The level of copper in the hair of both inhabitants of the area most remote from oil and gas facilities and the entire population of western Kazakhstan as a whole remains significantly low. The data obtained provide evidence of the possible impact of pollutants generated by the oil and gas facilities on a shortage of essential trace elements and associated subsequent health risks.

Preclinical atherosclerosis in cystic fibrosis: Two distinct presentations are related to pancreatic status.

BACKGROUND: Patients with cystic fibrosis (CF) are exposed to overlapping cardiovascular risk factors. We hypothesized that CF is characterized by increased arterial stiffness and greater intima-media thickness (IMT). METHODS: This cross-sectional study assessed the digital volume pulse arterial stiffness index (SIDVP) using photopletysmography, measured intima-media complex thickness (IMT) at the common carotid artery, and obtained an extended set of clinical and atherosclerosis-related laboratory parameters. RESULTS: Fifty-five patients with moderate-to-severe CF (mean age 26.3±8.6 years, BMI 20.3±3.1 kg/m2, FEV1 62±26%) and 51 healthy controls (25.1±4.4 years, BMI 21.7±3.0 kg/m2) entered the study. SIDVP was greater in pancreatic insufficient (PI), but not pancreatic sufficient (PS) CF patients compared with control (7.3±1.8 m/s vs 6.0±1.2 m/s; p=7.1 × 10-5). IMT was increased in PS (but not PI) participants relative to control (552±69 µm vs 456±95 µm, p=0.0011). SIDVP was also greater in PI than in PS patients (7.3±1.8 m/s vs 6.3±1.7 m/s, p=0.0232) and IMT was higher in PS compared with PI (552±69 µm vs 453±82 µm, p=0.0002). SIDVP independently associated with age, PI, the lack of liver cirrhosis, and with Pseudomonas aeruginosa colonization. PS was the only independent correlate of IMT in CF. CONCLUSIONS: PI patients are at risk of developing general arterial stiffness. PS may relate to carotid IMT thickening, which underscores the need for further study that could lead to reconsideration of dietary guidance in PS CF.

Ileal Lactase Expression Associates with Lactase Persistence Genotypes.

(1) Background: Lactose digestion depends on persistence genotypes (including rs4988235), the frequency of which exhibits broad geographical variability. However, little is known about the relationship between lactase (LCT) genotypes and intestinal expression of LCT. We aimed to investigate ileal expression of LCT depending on main genetic polymorphisms (rs4988235, rs3754689, rs3739022), age, sex, smoking status, body mass index (BMI), and the expression of other genes; (2) Methods: phenotype, array-based genotype, and ileal mucosal biopsy expression data were obtained from the CEDAR study; (3) Results: analyses included 196 healthy Europeans (53.6% women) aged 53.0 ± 13.6 years with a mean BMI of 25.6 ± 4.2 kg/m2, of whom 17.4% were smoking. Ileal LCT expression was mostly independent of age, sex, BMI, or smoking. Rs4988235 homozygous minor allele (GG) associated with lower LCT expression (vs. AG p = 2.2 × 10-6, vs. AA p = 1.1 × 10-7). Homozygous major allele of rs3754689 (GG) was related to higher LCT expression (vs. AG p = 1.7 × 10-5, vs. AA p = 0.0074). Rs3754689 genotype did not modify LCT expression (GG vs. AG p = 0.051) in rs4988235-heterozygous subgroup. Interestingly, CD14, which is a marker of monocytes and macrophages, was the strongest negative transcriptomic correlate of LCT expression (r = -0.57, pFDR = 1.1 × 10-14); (4) Conclusions: both rs4988235 and rs3754689 associated with ileal LCT expression, which did not seem related to age, sex, smoking, or BMI. The inverse correlation between LCT and CD14 expression in the ileum is striking and requires further investigation.

Severe Genotype, Pancreatic Insufficiency and Low Dose of Pancreatic Enzymes Associate with Abnormal Serum Sterol Profile in Cystic Fibrosis.

BACKGROUND: Several factors could lead to lipid disturbances observed in cystic fibrosis (CF). This study aimed to assess sterol homeostasis in CF and define potential exogenous and endogenous determinants of lipid dysregulation. METHODS: The study involved 55 CF patients and 45 healthy subjects (HS). Sterol concentrations (µg/dL) were measured by gas chromatography/mass spectrometry. CF was characterised by lung function, pancreatic status, liver disease and diabetes coexistence, Pseudomonas aeruginosa colonisation and BMI. CFTR genotypes were classified as severe or other. RESULTS: Campesterol and ß-sitosterol concentrations were lower (p = 0.0028 and p < 0.0001, respectively) and lathosterol levels (reflecting endogenous cholesterol biosynthesis) were higher (p = 0.0016) in CF patients than in HS. Campesterol and ß-sitosterol concentrations were lower in patients with a severe CFTR genotype, pancreatic insufficiency and lower pancreatic enzyme dose (lipase units/gram of fat). In multiple regression analyses, ß-sitosterol and campesterol concentrations were predicted by genotype and pancreatic insufficiency, whereas cholesterol and its fractions were predicted by phytosterol concentrations, age, dose of pancreatic enzymes, nutritional status and genotype. CONCLUSIONS: Independent determinants of lipid status suggest that malabsorption and pancreatic enzyme supplementation play a significant role in sterol abnormalities. The measurement of campesterol and ß-sitosterol concentrations in CF patients may serve for the assessment of the effectiveness of pancreatic enzyme replacement therapy and/or compliance, but further research is required.