Prevalence and associated factors of iron deficiency in Spanish children aged 1 to 11 years.

Iron deficiency (ID) is the most common nutritional deficiency affecting children worldwide. Most traditional laboratory parameters to assess ID can be altered by infections or other inflammatory states, including obesity. The aims of this study were to determine the prevalence of ID in healthy children and to analyse associated factors, avoiding potential confounding factors through the use of serum transferrin receptor (sTfR), reticulocyte haemoglobin content and sTfR/log ferritin index. A cross-sectional population-based study was conducted on 951 children aged 1 to 11 years in Almería (Spain). ID was detected in 7.7% of children and iron deficiency anaemia in 0.9%. Multivariate analysis identified the following as independent risk factors: age under 5 years (OR: 2.2, 95% CI: 1.35-3.6); excessive consumption of cow's milk and dairy products (OR: 1.87, 95% CI: 1.13-3.1); and insufficient consumption of vegetables (OR: 2.7, 95% CI: 1.2-6.1).Conclusions: Using a combination of iron status parameters with greater discriminatory power than classical measures, this study detected a considerable iron deficiency prevalence in Spanish children. Younger children and specific dietary habits exhibit a particular risk for ID, so special attention should be paid to this population. What is Known: • Iron deficiency remains the most prevalent nutritional deficit worldwide, and children aged under 3 years are the most vulnerable to this condition. • Accurate assessment of iron status, based on a combination of biochemical indicators, can often be complicated. What is New: • Iron deficiency continues to present a health problem in Spanish children aged 1 to 11 years, considering the serum transferrin receptor and reticulocyte haemoglobin content for diagnosis. • Excessive consumption of dairy products and low consumption of vegetables are independent risk factors for iron deficiency.

Monitoring the incidence, duration and distribution of hyperglycaemia in very-low-birth-weight newborns and identifying associated factors.

Objectives Hyperglycaemia is a common metabolic disorder in very-low-birth-weight (VLBW) infants and is associated with increased morbidity and mortality. The objective is to describe the incidence, duration, episodes and distribution of hyperglycaemia during the first 7 days of life of VLBW infants. Methods This is a prospective cohort study of 60 newborns weighing <1,500 g. Blood glucose levels were monitored with a continuous glucose monitoring system (CGMS) during the first 7 days of life. Hyperglycaemia was defined as glucose ≥180 mg/dL (≥10 mmol/L). Results Incidence of hyperglycaemia recorded with the CGMS was 36.6% (95%CI: 24.6-50.1). In almost 74.6±5.48% of these cases the duration of the episode exceeded 30 min and in 45.25% (95%CI: 2.26-57.82) it exceeded 2 h. The condition occurred most frequently during the first 72 h of life. One-fifth of cases were not detected with scheduled capillary tests and 84.6% of these had hyperglycaemic episode durations of 30 min or more. Agreement between the two techniques was very good (r=0.90, p<0.001) and the CGMS proved to be reliable, accurate and safe. Hyperglycaemia detected by a CGMS is associated with lower gestational age (OR: 0.66, p=0.002), lower birth weight (OR: 0.99, p=0.003), the use of ionotropic drugs (OR: 11.07, p=0.005) and death (OR: 10.59, p=0.03), and is more frequent in preterm infants with sepsis (OR: 2.73, p=0.1). No other association was observed. Conclusions A CGMS could be useful during the first week of life in VLBW infants due to the high incidence and significant duration of hyperglycaemia and the high proportion of cases that remain undetected. The advantage of the CGMS is that it is able to detect hyperglycaemic episodes that the capillary test does not.

The usefulness of reticulocyte haemoglobin content, serum transferrin receptor and the sTfR-ferritin index to identify iron deficiency in healthy children aged 1-16 years.

This cross-sectional study, conducted on a population-based representative sample, evaluates the usefulness of reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) to recognise iron deficiency (ID) without anaemia, provides specific cut-off points for age and gender, and proposes a new definition of ID. A total of 1239 healthy children and adolescents aged 1-16 years were included. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, CHr, sTfR, and sTfR-F index were determined. ROC curves were obtained and sensitivity, specificity, predictive values, likelihood ratios, and accuracy for each specific cut-off points were calculated. Seventy-three had ID without anaemia. Area under the curve for sTfR-F index, sTfR and CHr were 0.97 (CI95% 0.95-0.99), 0.87 (CI95% 0.82-0.92) and 0.68 (CI95% 0.61-0.74), respectively. The following cut-off points defined ID: sTfR-F Index > 1.5 (1-5 years and 12-16 years boys) and > 1.4 (6-11 years and 12-16 years girls); sTfR (mg/L) > 1.9 (1-5 years), > 1.8 (6-11 years), > 1.75 (12-16 years girls) and > 1.95 (12-16 years boys); and CHr (pg) < 27 (1-5 years) and < 28.5 (6-16 years).Conclusions: CHr, sTfR and the sTfR-F index are useful parameters to discriminate ID without anaemia in children and adolescents, and specific cut-off values have been established. The combination of these new markers offers an alternative definition of ID with suitable discriminatory power. What is Known: • In adults, reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) have been evaluated and recognised as reliable indicators of iron deficiency (ID). • Clinical manifestations of ID may be present in stages prior to anaemia, and the diagnosis of ID without anaemia continues to pose problems. What is New: • CHr, sTfR and the sTfR-F index are useful parameters in diagnosis of ID in childhood and adolescence when anaemia is not present. • We propose a new strategy for the diagnosis of ID in childhood and adolescence, based on the combination of these measures, which offer greater discriminatory power than the classical parameters.

Genetic 3'UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight.

Sunlight exposure induces signalling pathways leading to the activation of melanin synthesis and tanning response. MicroRNAs (miRNAs) can regulate the expression of genes involved in pigmentation pathways by binding to the complementary sequence in their 3'untranslated regions (3'UTRs). Therefore, 3'UTR SNPs are predicted to modify the ability of miRNAs to target genes, resulting in differential gene expression. In this study, we investigated the role in pigmentation and sun-sensitivity traits, as well as in melanoma susceptibility, of 38 different 3'UTR SNPs from 38 pigmentation-related genes. A total of 869 individuals of Spanish origin (526 melanoma cases and 343 controls) were analysed. The association of genotypic data with pigmentation traits was analysed via logistic regression. Web-based tools for predicting the effect of genetic variants in microRNA-binding sites in 3'UTR gene regions were also used. Seven 3'UTR SNPs showed a potential implication in melanoma risk phenotypes. This association is especially noticeable for two of them, rs2325813 in the MLPH gene and rs752107 in the WNT3A gene. These two SNPs were predicted to disrupt a miRNA-binding site and to impact on miRNA-mRNA interaction. To our knowledge, this is the first time that these two 3'UTR SNPs have been associated with sun-sensitivity traits. We state the potential implication of these SNPs in human pigmentation and sensitivity to sunlight, possibly as a result of changes in the level of gene expression through the disruption of putative miRNA-binding sites.

Reference Values of Reticulocyte Hemoglobin Content and Their Relation With Other Indicators of Iron Status in Healthy Children.

Reticulocyte hemoglobin content (CHr) is considered an indicator of functional iron deficiency, but is understudied in children. The goals of this study are to determine the reference intervals for CHr in healthy children, and their relation with iron parameters, erythropoiesis, and individual conditions. A total of 902 children without iron deficiency, aged 1 to 11 years were analyzed in a cross-sectional study. Besides a physical examination of the subjects and a questionnaire completed by their parents, the complete blood count, serum transferrin receptor, ferritin, transferrin saturation, erythrocyte protoporphyrin, serum erythropoietin, C-reactive protein, and CHr levels were measured. Changes in CHr, iron status, and erythropoiesis at different age intervals were analyzed and linear multiple regression was used to identify the factors that determine CHr variability. Mean value obtained for CHr was 30.9±1.8 pg (P2.5-P97.5: 26.9 to 34.3 pg), but the influence of age on CHr (the values increased with age) and on the iron parameters justified the establishment of different reference ranges. In addition to age, nutritional status, hematologic measurements, reticulocytes, transferrin saturation, and erythrocyte protoporphyrin accounted for 39% of CHr variability.

Reference values of serum transferrin receptor (sTfR) and sTfR/log ferritin index in healthy children.

ABSTARCT The aims of this study were to determine appropriate reference ranges for serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) in healthy children and their relationship with iron parameters, erythropoiesis, and other conditions presented by the subject. A total of 902 children with normal iron status, aged 1-11 years, were included in a cross-sectional study. A physical examination was conducted and z-score of body mass index (zBMI) obtained. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, sTfR, and sTfR/log ferritin were determined. Linear multiple regression was applied to identify the factors that determined sTfR and sTfR-F index variability. Mean values for sTfR and sTfR-F index were 1.22 ± 0.28 mg/L (95% confidence interval [CI]: 1.2-1.23) and 0.87 ± 0.25 (95% CI: 0.85-0.88). The reference intervals (2.5th to 97.5th percentiles [P2.5-P97.5]) were 0.78-1.9 mg/L and 0.49-1.46, respectively. sTfR and sTfR-F values decreased with age (P <.03 and P <.0001, respectively). No changes were observed with sex. Changes in sTfR and sTfR-F index were consistent with ferritin and erythropoietin variations. Iron biomarkers, erythropoietin, and zBMI predicted 19% and 18.1% of the sTfR and sTfR-F index variability. The results provide reference ranges for sTfR and sTfR-F index in healthy children for clinical use in the assessment of body iron status. Both biomarkers are predicted by iron parameters, erythropoietin, and zBMI.

Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition.

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high-risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta-analysis (3940 melanoma cases and 3620 controls) with two-side p values of 0.002, (OR = 0.86) and 4.07 × 10(-10) (OR = 0.80), respectively. Exome sequencing revealed a non-synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma.

Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population.

BACKGROUND: Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case-control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. METHODS: We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. RESULTS: We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10(-4)). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10(-4)). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. CONCLUSIONS: To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that pigmentation characteristics correlated with eye color are potential mediators between PARP1 and MM protection.

Cutaneous nodules as a diagnostic clue in multiple myeloma.

Cutaneous plasmacytomas are monoclonal proliferations of plasma cells which can be classified into primary (with no other concomitant bony or extramedullary disease) or secondary (generally associated with multiple myeloma (MM), extramedullary plasmacytoma, or plasma cell leukemia). Cutaneous plasmacytomas can appear in some patients with MM and, rarely, the skin lesions suppose the first clinical manifestation of the disease. Their development is considered as a poor prognostic sign, associated with a life expectancy of less than 12 months after diagnosis. An unusual case of MM is described, in which the histopathological study of a skin nodule provided invaluable information for diagnosis.

Osteopathic Manual Therapy for Infant Colic: A Randomised Clinical Trial.

BACKGROUND: Infant colic is a multifactorial syndrome for which various therapeutic strategies have been proposed. In this study, we evaluate the effectiveness of osteopathic manual therapy in treating symptoms related to infant colic. METHOD: A prospective, randomised, blinded clinical trial was conducted of patients diagnosed with infant colic. The treatment group were given osteopathic manual therapy, and their parents received two sessions of counselling. The control group received no such therapy, but their parents attended the same counselling sessions. The non-parametric Mann-Whitney U test was applied to determine whether there were significant differences between the groups for the numerical variables considered. For the qualitative variables, Fisher's exact test was used. The threshold assumed for statistical significance was 0.05. RESULTS: A total of 42 babies were assigned to each group. Those in the experimental group presented less severe infant colic with a trend towards statistical significance after the first session (p = 0.09). In sucking, excretion, eructation and gas there were no significant differences between the groups. Crying was a statistically significant dimension both after the first intervention (p = 0.03) and two weeks after (p = 0.04). Regurgitation values were significantly lower in the experimental group during the three weeks of follow-up (p = 0.05). Values for sleep were lower in the experimental group, but the differences were not statistically significant. In both groups, colic severity decreased over time, with no side effects. CONCLUSIONS: Treatment with osteopathic manual therapy alleviates the symptoms of infant colic and could be recommended for this purpose from the onset of the condition.

Worldwide research trends on bronchiolitis in pediatrics.

BACKGROUND: The COVID-19 pandemic has led to a significant increase in cases of bronchiolitis among children. As a result, there has been a corresponding increase in the number of publications on this topic. It is essential to examine the main areas of focus within the scientific literature to understand the current trends in research on pediatric bronchiolitis. This research aims to analyze the types of scientific advances related to pediatric bronchiolitis, the research trends being pursued, and the countries and research institutions leading these efforts. By understanding these aspects of bronchiolitis research, we can better understand the current state of knowledge and identify areas where further research is needed. METHODS: To conduct a bibliometric analysis of the scientific literature on pediatric bronchiolitis, all relevant publications were retrieved from the Scopus database. The Scopus API and the SW VosViewer software with optimized modularity functions were used. This analysis was intended to provide a comprehensive overview of the current state of research on this topic, including the types of scientific advances being developed, the research trends being pursued, and the countries and research institutions leading these efforts. RESULTS: A total of 3810 publications were reviewed. We observed an increasing number of publications, particularly in recent years. Of these, 73.7% were articles, 95% were written in English, and 29.4% were from the United States. The main keywords used in these publications included: human, bronchiolitis, child, preschool, preschool child, major clinical study, controlled study, pneumonia, asthma, adolescent, hospitalization, infant, and newborn. These keywords were grouped into six clusters: outpatient management, long-term consequences, etiology, intensive care management, diagnostic methods, and the main cluster, which focused on hospital treatment and clinical studies. CONCLUSIONS: The bibliometric analysis of bronchiolitis research in pediatrics reveals that there has been a significant increase in the number of publications on this topic, particularly in recent years. Most of these publications are articles written in English and published in the United States. The main keywords used in these studies relate to various aspects of bronchiolitis, including diagnosis, treatment, and long-term consequences. The results of this analysis suggest that bronchiolitis is a topic of significant interest and concern for researchers and practitioners in the field of pediatrics and that further research is needed to improve our understanding and management of this condition.

Comparison of Easy-to-Use Bronchiolitis Scores in the Post-COVID-19 Era-An Observational Study.

In the post-restrictions COVID-19 period, the incidence of bronchiolitis in infants has increased considerably. Several scores determine the degree of severity of the bronchiolitis episode, but few are clinician-friendly. The main aim of this research was to find the easy-to-use score that most accurately estimated the severity of patients' infections according to their clinical situations and most accurately predicted the need for hospital admission. An observational cross-sectional study was performed in a reference pediatric hospital during the post-restrictions period of the COVID-19 pandemic (2021 and 2022). A comparison was made between the severity estimate provided by five international acute bronchiolitis scales and the clinical severity of the acute bronchiolitis episode. Three hundred and seventy-seven patients participated in the investigation, with a mean age of 5.68 months; 68.7% of the participants had a mild episode of bronchiolitis, 24.5% had a moderate episode, and 6.9% had a severe episode. The severity estimated by the Tal scale modified by McCallum showed a statistically significant correlation with the clinical severity established by clinical criteria (0.836; p < 0.001). It showed a high correlation with other international scores, such as the Wang score (0.820; p < 0.05) and the Wood-Downes-Ferrés score (0.936; p < 0.001). In the multivariate analysis, the constituent variables of the modified Tal score appeared in the final model that predicts the need for hospital admission. In the context of increased incidence after COVID-19, the Tal score modified by McCallum is an easy-to-use measuring instrument that presents an excellent concordance with the clinical severity estimated at first care contact. It also offers a more significant prediction of the need for hospital admission.

Efficacy of a Deep Learning Convolutional Neural Network System for Melanoma Diagnosis in a Hospital Population.

(1) Background: The purpose of this study was to evaluate the efficacy in terms of sensitivity, specificity, and accuracy of the quantusSKIN system, a new clinical tool based on deep learning, to distinguish between benign skin lesions and melanoma in a hospital population. (2) Methods: A retrospective study was performed using 232 dermoscopic images from the clinical database of the Ramón y Cajal University Hospital (Madrid, Spain). The skin lesions images, previously diagnosed as nevus (n = 177) or melanoma (n = 55), were analyzed by the quantusSKIN system, which offers a probabilistic percentage (diagnostic threshold) for melanoma diagnosis. The optimum diagnostic threshold, sensitivity, specificity, and accuracy of the quantusSKIN system to diagnose melanoma were quantified. (3) Results: The mean diagnostic threshold was statistically lower (p < 0.001) in the nevus group (27.12 ± 35.44%) compared with the melanoma group (72.50 ± 34.03%). The area under the ROC curve was 0.813. For a diagnostic threshold of 67.33%, a sensitivity of 0.691, a specificity of 0.802, and an accuracy of 0.776 were obtained. (4) Conclusions: The quantusSKIN system is proposed as a useful screening tool for melanoma detection to be incorporated in primary health care systems.

Using a 31-Gene Expression Profile Test to Stratify Patients with Stage I-II Cutaneous Melanoma According to Recurrence Risk: Update to a Prospective, Multicenter Study.

BACKGROUND: Fifteen to forty percent of patients with localized cutaneous melanoma (CM) (stages I-II) will experience disease relapse. The 31-gene expression profile (31-GEP) uses gene expression data from the primary tumor in conjunction with clinicopathologic features to refine patient prognosis. The study's objective was to evaluate 31-GEP risk stratification for disease-free survival (DFS) in a previously published cohort with longer follow-up. METHODS: Patients with stage IB-II CM (n = 86) were prospectively tested with the 31-GEP. Follow-up time increased from 2.2 to 3.9 years. Patient outcomes were compared using Kaplan-Meier and Cox regression analysis. RESULTS: A Class 2B result was a significant predictor of 3-year DFS (hazard ratio (HR) 8.4, p = 0.008) in univariate analysis. The 31-GEP significantly stratified patients by risk of relapse (p = 0.005). A Class 2B result was associated with a lower 3-year DFS (75.0%) than a Class 1A result (100%). The 31-GEP had a high sensitivity (77.8%) and negative predictive value (95.0%). CONCLUSIONS: The 31-GEP is a significant predictor of disease relapse in patients with stage IB-II melanoma and accurately stratified patients by risk of relapse.

Blood Lead Level in a Paediatric Population of South-Eastern Spain and Associated Risk Factors.

OBJECTIVE: To determine blood lead levels (BLL) in a healthy paediatric population and to analyse related sociodemographic, dietary and haematological factors. METHODS: A cross-sectional study was made of 1427 healthy subjects aged 1-16 years from the city of Almería (south-eastern Spain). BLL, iron parameters and erythropoietin were determined, and sociodemographic and dietary data obtained. The study paramateters was analyses in BLL toxic and BLL no toxic group by multiple logistic regression. RESULTS: The mean BLL was 1.98 ± 1.1 µg/dL (95% CI:1.91-2.04). For 5.7% of the population, mean BLL was 2-5 µg/dL, for 2.1% it was >5 µg/dL and for 0.15% it was >10 µg/dL. Multivariate analysis showed that immigrant origin (OR:11.9; p < 0.0001), low level of parental education (OR:4.6; p < 0.02) and low dietary iron bioavailability (OR: 3.2; p < 0.02) were all risk factors for toxic BLL. Subjects with toxic and non-toxic BLL presented similar iron and erythropoiesis-related parameters, except erythrocyte protoporphyrin, which was significantly higher in the BLL >5 µg/dL group. CONCLUSIONS: BLL and the prevalence of toxic BLL in healthy subjects aged 1-16 years living in south-eastern Spain are low and similar to those found in other developed countries. The factors associated with toxic BLL are immigrant origin, low level of parental education and dietary iron deficiency. The toxicity of BLL was not related to changes in the analytical parameters studied.

Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2.

The CDKN2A gene is regarded as the major familial malignant melanoma (MM) susceptibility gene. Human pigmentation is one of the main modulators of individual risk of developing MM. Therefore, the genes involved in the determination of skin colour and tanning response are potentially implicated in MM predisposition and may be useful predictors of MM risk in the general population. The human melanocortin-1 receptor gene (MC1R) plays a crucial role in pigmentation and also appears to be important in MM. The OCA2 gene has emerged as a new and significant determinant of human iris colour variation. We present a case-control study in Spanish population including 390 consecutive patients with melanoma and 254 control subjects. Sequence analysis of the entire coding region and genotyping of 5 tag-SNPs in the genomic region of MC1R was performed. We identified 27 variants, two reaching statistical significance [R160W (OR: 4.18, 95% CI: 1.24-14.04, P = 0.02) and D294H (OR: 3.10, 95% CI: 1.37-7.01, P = 0.01)] and we detected two novel non-synonymous changes: V92L and T308M. Odds ratio for carrying two functional variants was 4.25 (95% CI: 2.30-7.84, P = 3.63 x 10(-6)). Haplotypes of the entire MC1R region have been established, and we observed an enrichment of a rare European haplotype similar to African values carrying variants V92M and I155T. In addition, three potentially functional SNPs were selected in p16/CDKN2A and in the promoter region of OCA2/HERC2. Our data for CDKN2A gene did not reach statistically significant results for any of the two studied alleles. We found that the variant allele A > G of OCA2/HERC2 (rs12913832) was associated with pigmentation features: eye, hair and skin colour; P-values = 1.8 x 10(-29), 9.2 x 10(-16), 1.1 x 10(-3), respectively, validating previous results.

Relationship between Obesity and Iron Deficiency in Healthy Adolescents.

The relationship between overweight/obesity (excess of weight [EW]) and iron deficiency (ID) is not well defined. Objective: To analyze the relationship between EW and ID in healthy adolescents, assessing the contribution of new diagnostic measures of iron status and erythropoietic activity. Method: A cross-sectional study was made of 405 healthy adolescents, 12-16 years of age. A total of 289 were normal weight (NW) and 116 were otherwise healthy EW. Epidemiological, socioeconomic, diet, BMI Z-score, CRP (C-reactive protein), hematological, iron status, and erythropoietic activity parameters were measured. Statistical tests were Student's, analysis of variance (ANOVA), Chi-square, Pearson's correlation, and odds ratio. Results: ID prevalence in the EW group was 22.6% vs. 29.5% in the NW group (p: 0.3). Greater body weight was associated with lower reticulocyte hemoglobin content (CHr) (NW: 31.3 ± 1.7 pg vs. OW: 30.2 ± 1.7 pg, p: 0.007) and greater CRP (NW: 0.1 ± 0.2 mg/dL vs. OW: 0.2 ± 0.18 mg/dL, p < 0.001), leukocytes (NW: 6.69 ± 1.57 × 103/L vs. OW: 7.43 ± 1.63 × 103/L, p < 0.02), platelets (NW: 265.6 ± 58.9 × 103/L vs. OW: 291.8 ± 54.4 × 103/L, p < 0.002), ferritin (NW: 32.1 ± 17.9 ng/mL vs. OW: 42.8 ± 20.3 ng/mL, p: 0.01), serum transferrin receptor (sTfR) (NW: 1.39 ± 0.4 mg/L vs. OW: 1.73 ± 0.45 mg/L, p: 0.008), sTfR-F index (sTfR/log Ferritin) (NW: 1.06 ± 0.7 vs. OW: 1.33 ± 0.85, p: 0.036) and reticulocyte count (NW: 54.2 ± 18 × 103/L vs. OW: 65.4 ± 24.2 × 103/L, p: 0.003). A positive correlation was observed between the BMI Z-score and CRP, ferritin, sTfR, leukocytes, platelets, and reticulocyte count, and a negative one between the BMI Z-score and CHr and medium corpuscular volume. Conclusions: The prevalence of ID in otherwise healthy EW adolescents was no higher than in NW. The effect of obesity on iron status was low. The findings reveal the concomitant low-grade inflammation, and probably the effect of adiposity on erythropoietic activity. Specific cutoff values for ID in adolescents with OW need to be defined.

Pigmentation-related genes and their implication in malignant melanoma susceptibility.

Human pigmentation appears to be one of the main modulators of individual risk of developing malignant melanoma (MM). A large number of genes are known to be involved in rare pigmentary disorders and explain most of the variation in pigmentation phenotypes seen in human populations. This Spanish case-control study included 205 patients with melanoma and 245 control subjects. Thirty-one single nucleotide polymorphisms (SNPs) in genes that had been mainly associated with congenital pigmentation syndromes (ADTB3A, ATRN, CHS1, EDNRB, HPS, KIT, MGRN1, MITF, MLANA, MYO5A, MYO7A, OA1, OCA2, PAX3 and SOX10) were selected. We found that the variant allele of OCA2 R419Q (rs1800407) was associated with increased risk of MM (OR 1.55, 95% CI 1.04-2.31, P = 0.03). This effect on melanoma risk appeared to be stronger among individuals with solar lentigines, or at least 50 nevi. We also describe, for the first time, an association with the variant S1666C (rs2276288) in the MYO7A gene (OR 1.35; 95% CI 1.04-1.76; P = 0.03). Again, this association appeared to be stronger in several phenotypic groups such as individuals with fair skin and those with childhood sunburns. We also found that several variants in the pigmentation genes considered were associated with intermediate phenotypic characteristics. Our findings highlight the potential importance of pigmentation genes in sporadic MM susceptibility.