The Oncopig as an Emerging Model to Investigate Copper Regulation in Cancer.

Emerging evidence points to several fundamental contributions that copper (Cu) has to promote the development of human pathologies such as cancer. These recent and increasing identification of the roles of Cu in cancer biology highlights a promising field in the development of novel strategies against cancer. Cu and its network of regulatory proteins are involved in many different contextual aspects of cancer from driving cell signaling, modulating cell cycle progression, establishing the epithelial-mesenchymal transition, and promoting tumor growth and metastasis. Human cancer research in general requires refined models to bridge the gap between basic science research and meaningful clinical trials. Classic studies in cultured cancer cell lines and animal models such as mice and rats often present caveats when extended to humans due to inherent genetic and physiological differences. However, larger animal models such as pigs are emerging as more appropriate tools for translational research as they present more similarities with humans in terms of genetics, anatomical structures, organ sizes, and pathological manifestations of diseases like cancer. These similarities make porcine models well-suited for addressing long standing questions in cancer biology as well as in the arena of novel drug and therapeutic development against human cancers. With the emergent roles of Cu in human health and pathology, the pig presents an emerging and valuable model to further investigate the contributions of this metal to human cancers. The Oncopig Cancer Model is a transgenic swine model that recapitulates human cancer through development of site and cell specific tumors. In this review, we briefly outline the relationship between Cu and cancer, and how the novel Oncopig Cancer Model may be used to provide a better understanding of the mechanisms and causal relationships between Cu and molecular targets involved in cancer.

Mutations in XLF/NHEJ1/Cernunnos gene results in downregulation of telomerase genes expression and telomere shortening.

NHEJ1-patients develop severe progressive lymphocytopenia and premature aging of hematopoietic stem cells (HSCs) at a young age. Here we show a patient with a homozygous-NHEJ1 mutation identified by whole exome-sequencing that developed severe pancytopenia and bone marrow aplasia correlating with the presence of short telomeres. The mutation resulted in a truncated protein. In an attempt to identify the mechanism behind the short telomere phenotype found in the NHEJ1-patient we downregulated NHEJ1 expression in 293T and CD34+cells. This downregulation resulted in reduced telomerase activity and decreased expression of several telomerase/shelterin genes. Interestingly, cell lines derived from two other NHEJ1-deficient patients with different mutations also showed increased p21 expression, inhibition in expression of several telomerase complex genes and shortened telomeres. Decrease in expression of telomerase/shelterin genes did not occur when we inhibited expression of other NHEJ genes mutated in SCID patients: DNA-PK, Artemis or LigaseIV. Because premature aging of HSCs is observed only in NHEJ1 patients, we propose that is the result of senescence induced by decreased expression of telomerase/shelterin genes that lead to an inhibition of telomerase activity. Previous reports failed to find this connection because of the use of patient´s cells immortalized by TERT expression or recombined telomeres by ALT pathway. In summary, defective regulation of telomere biology together with defective V(D)J recombination can negatively impact on the evolution of the disease in these patients. Identification of telomere shortening is important since it may open new therapeutic interventions for these patients by treatments aimed to recover the expression of telomerase genes.

Cysteine Rich Intestinal Protein 2 is a copper-responsive regulator of skeletal muscle differentiation.

Copper (Cu) is an essential trace element required for respiration, neurotransmitter synthesis, oxidative stress response, and transcriptional regulation. Imbalance in Cu homeostasis can lead to several pathological conditions, affecting neuronal, cognitive, and muscular development. Mechanistically, Cu and Cu-binding proteins (Cu-BPs) have an important but underappreciated role in transcription regulation in mammalian cells. In this context, our lab investigates the contributions of novel Cu-BPs in skeletal muscle differentiation using murine primary myoblasts. Through an unbiased synchrotron X-ray fluorescence-mass spectrometry (XRF/MS) metalloproteomic approach, we identified the murine cysteine rich intestinal protein 2 (mCrip2) in a sample that showed enriched Cu signal, which was isolated from differentiating primary myoblasts derived from mouse satellite cells. Immunolocalization analyses showed that mCrip2 is abundant in both nuclear and cytosolic fractions. Thus, we hypothesized that mCrip2 might have differential roles depending on its cellular localization in the skeletal muscle lineage. mCrip2 is a LIM-family protein with 4 conserved Zn2+-binding sites. Homology and phylogenetic analyses showed that mammalian Crip2 possesses histidine residues near two of the Zn2+-binding sites (CX2C-HX2C) which are potentially implicated in Cu+-binding and competition with Zn2+. Biochemical characterization of recombinant human hsCRIP2 revealed a high Cu+-binding affinity for two and four Cu+ ions and limited redox potential. Functional characterization using CRISPR/Cas9-mediated deletion of mCrip2 in primary myoblasts did not impact proliferation, but impaired myogenesis by decreasing the expression of differentiation markers, possibly attributed to Cu accumulation. Transcriptome analyses of proliferating and differentiating mCrip2 KO myoblasts showed alterations in mRNA processing, protein translation, ribosome synthesis, and chromatin organization. CUT&RUN analyses showed that mCrip2 associates with a select set of gene promoters, including MyoD1 and metallothioneins, acting as a novel Cu-responsive or Cu-regulating protein. Our work demonstrates novel regulatory functions of mCrip2 that mediate skeletal muscle differentiation, presenting new features of the Cu-network in myoblasts.

Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells.

Cancer treatment typically involves multiple strategies, such as surgery, radiotherapy, and chemotherapy, to remove tumors. However, chemotherapy often causes side effects, and there is a constant search for new drugs to alleviate them. Natural compounds are a promising alternative to this problem. Indole-3-carbinol (I3C) is a natural antioxidant agent that has been studied as a potential cancer treatment. I3C is an agonist of the aryl hydrocarbon receptor (AhR), a transcription factor that plays a role in the expression of genes related to development, immunity, circadian rhythm, and cancer. In this study, we investigated the effect of I3C on cell viability, migration, invasion properties, as well as mitochondrial integrity in hepatoma, breast, and cervical cancer cell lines. We found that all tested cell lines showed impaired carcinogenic properties and alterations in mitochondrial membrane potential after treatment with I3C. These results support the potential use of I3C as a supplementary treatment for various types of cancer.

Real-life disease monitoring in follicular lymphoma patients using liquid biopsy ultra-deep sequencing and PET/CT.

In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we used an ultra-deep sequencing approach with 2 · 10-4 sensitivity (LiqBio-MRD) to track those mutations on 151 follow-up liquid biopsy samples from 54 treated patients. Positive LiqBio-MRD at first-line therapy correlated with a higher risk of progression both at the interim evaluation (HRINT 11.0, 95% CI 2.10-57.7, p = 0.005) and at the end of treatment (HREOT, HR 19.1, 95% CI 4.10-89.4, p < 0.001). Similar results were observed by PET/CT Deauville score, with a median PFS of 19 months vs. NR (p < 0.001) at the interim and 13 months vs. NR (p < 0.001) at EOT. LiqBio-MRD and PET/CT combined identified the patients that progressed in less than two years with 88% sensitivity and 100% specificity. Our results demonstrate that LiqBio-MRD is a robust and non-invasive approach, complementary to metabolic imaging, for identifying FL patients at high risk of failure during the treatment and should be considered in future response-adapted clinical trials.

Physical activity habits and their relationship with sociodemographic factors in Chilean adolescents.

Physical activity plays an important role in the well-being and development of adolescents. Physical activity habits expressed in terms of frequency and duration are consistently associated with sociodemographic factors such as age, gender, and socioeconomic status. However, there is less evidence of the relationship between the type and context of physical activity in adolescents. The aim of this article is to analyze physical activity habits and their relationship with sociodemographic factors in Chilean adolescents. The cross-sectional study consisted of 7,263 adolescents aged between 10 and 20 years old, students from both public and private schools in all regions of Chile. Physical activity habits were examined by means of a self-report questionnaire. The age groups were classified according to the three stages of adolescence (early: 10 to 13, middle: 14 to 16, and late: 17 to 20 years old). Socioeconomic level was established based on the school vulnerability index (SVI) of the school attended by each adolescent. In the study it was obvious to the level of physical activity for the adolescents was below the international recommendations. A statistically significant association can also be found between the sociodemographic factors studied and the physical activity habits reported by the young people. The multivariate regression analysis established that the risk of not achieving the physical activity recommendations was 2.8 times higher in females than in males, 2.4 times higher in the older age groups (14-16 and 17-20 years old) compared to the 10-13-year age range and 1.1 times in the medium and high vulnerability groups than in the low socioeconomic vulnerability group. These findings highlight the importance of considering all these factors holistically whenever designing programs or public policies that promote the development of healthy physical activity habits in adolescents.

Brain-lung interaction: a vicious cycle in traumatic brain injury.

The brain-lung interaction can seriously affect patients with traumatic brain injury, triggering a vicious cycle that worsens patient prognosis. Although the mechanisms of the interaction are not fully elucidated, several hypotheses, notably the "blast injury" theory or "double hit" model, have been proposed and constitute the basis of its development and progression. The brain and lungs strongly interact via complex pathways from the brain to the lungs but also from the lungs to the brain. The main pulmonary disorders that occur after brain injuries are neurogenic pulmonary edema, acute respiratory distress syndrome, and ventilator-associated pneumonia, and the principal brain disorders after lung injuries include brain hypoxia and intracranial hypertension. All of these conditions are key considerations for management therapies after traumatic brain injury and need exceptional case-by-case monitoring to avoid neurological or pulmonary complications. This review aims to describe the history, pathophysiology, risk factors, characteristics, and complications of brain-lung and lung-brain interactions and the impact of different old and recent modalities of treatment in the context of traumatic brain injury.

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA.

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E-4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E-4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.

Devazepide, a nonpeptide antagonist of CCK receptors, induces apoptosis and inhibits Ewing tumor growth.

The Ewing family of tumors is a group of highly malignant tumors that mainly arise in bone and most often affect children and young adults in the first two decades of life. Despite the use of multimodal therapy, the long-term disease-free survival rate of patients with Ewing tumors is still disappointingly low, making the discovery of innovative therapeutic strategies all the more necessary. We have recently shown that cholecystokinin (CCK), a neuroendocrine peptide, involved in many biological functions, including cell growth and proliferation, is a relevant target of the EWS/FLI1 oncoprotein characteristic of Ewing tumors. CCK silencing inhibits cell proliferation and tumor growth in vivo, suggesting that CCK acts as an autocrine growth factor for Ewing cells. Here, we analyzed the impact of two CCK receptor antagonists, devazepide (a CCK1-R antagonist) and L365 260 (a CCK2-R antagonist), on the growth of Ewing tumor cells. Devazepide (10 micromol/l) inhibited cell growth of four different Ewing tumor cells in vitro (range 85-88%), whereas the effect of the CCK2-R antagonist on cell growth was negligible. In a mouse tumor xenograft model, devazepide reduced tumor growth by 40%. Flow cytometry experiments showed that devazepide, but not L365 260, induced apoptosis of Ewing tumor cells. In summary, devazepide induces cell death of Ewing tumor cells, suggesting that it could represent a new therapeutic approach in the management of Ewing's tumor patients.

Assessment of sleep disorders and proposed percentiles for adolescents. / Evaluación de los trastornos del sueño y propuesta de percentiles para los adolescentes.

OBJECTIVES: The objectives of this study included: a) to develop a valid and reliable self-reporting instrument to assess sleep disorders among Chilean adolescent students and b) to develop percentiles for age and sex. METHODOLOGY: This was a descriptive, crosssectional study in 2310 adolescent students conducted in the Maule Region, Chile. The sleep disorder self-report was developed considering five categories: duration, alterations, breathing problems, fatigue, and stimulant use. The instrument was validated using a confirmatory factor analysis. Reliability was assessed based on internal consistency. Percentiles were developed using the LMS method (L: lambda, asymmetry; M: mu, median; S: sigma, coefficient of variation). RESULTS: Questions 3, 9, and 12 showed saturation values below 0.40, while the rest had saturation values above 0.41. The Kaiser-Meyer-Olkin measure of adequacy was 0.749 and the test of sphericity X2 was 4790.09; the percentage of variance accounted for 62.1 %. Cronbach's alpha ranged between 0.71 and 0.76. CONCLUSION: The self-report developed to measure sleep disorders in adolescents is valid and reliable for its use in health, education, and sports science programs. Percentiles should be used to identify normal patterns and/or sleep disorders by sex and age.

Objetivos. Los objetivos del estudio fueron los siguientes: a) construir un instrumento válido y confiable que evaluara, por autoinforme, los trastornos del sueño en adolescentes escolares chilenos y b) desarrollar valores percentílicos según la edad y el sexo. Metodología. Se efectuó un estudio de tipo descriptivo de corte transversal en 2310 adolescentes escolares de la Región del Maule, Chile. Se construyó el autoinforme de trastornos del sueño considerando cinco categorías (duración, alteraciones, problemas en la respiración, fatiga y uso de estimulantes). Se validó por medio del análisis factorial confirmatorio. La fiabilidad se evaluó por la consistencia interna. Se crearon percentiles a través del método LMS (L: asimetría, M: mediana y S: coeficiente de variación). Resultados. Las preguntas 3, 9 y 12 presentaron saturaciones inferiores a 0,40, y las demás preguntas reflejaron saturaciones superiores a 0,41. El valor de adecuación Kaiser-Meyer-Olkin fue 0,749 y la prueba de esfericidad de X2= 4790,09; el porcentaje de la varianza explicó el 62,1 %. El alfa de Cronbach mostró valores entre 0,71 y 0,76. Conclusión. El autoinforme desarrollado para medir los trastornos del sueño en los adolescentes puede ser aplicado de forma válida y confiable en programas de ciencias de la salud, de la educación y del deporte. Se sugiere el uso de percentiles para identificar los patrones normales y/o trastornos del sueño por edad y género.

GSE4 peptide suppresses oxidative and telomere deficiencies in ataxia telangiectasia patient cells.

Ataxia telangiectasia (AT) is a genetic disease caused by mutations in the ATM gene but the mechanisms underlying AT are not completely understood. Key functions of the ATM protein are to sense and regulate cellular redox status and to transduce DNA double-strand break signals to downstream effectors. ATM-deficient cells show increased ROS accumulation, activation of p38 protein kinase, and increased levels of DNA damage. GSE24.2 peptide and a short derivative GSE4 peptide corresponding to an internal domain of Dyskerin have proved to induce telomerase activity, decrease oxidative stress, and protect from DNA damage in dyskeratosis congenita (DC) cells. We have found that expression of GSE24.2 and GSE4 in human AT fibroblast is able to decrease DNA damage, detected by γ-H2A.X and 53BP1 foci. However, GSE24.2/GSE4 expression does not improve double-strand break signaling and repair caused by the lack of ATM activity. In contrast, they cause a decrease in 8-oxoguanine and OGG1-derived lesions, particularly at telomeres and mitochondrial DNA, as well as in reactive oxygen species, in parallel with increased expression of SOD1. These cells also showed lower levels of IL6 and decreased p38 phosphorylation, decreased senescence and increased ability to divide for longer times. Additionally, these cells are more resistant to treatment with H202 and the radiomimetic-drug bleomycin. Finally, we found shorter telomere length (TL) in AT cells, lower levels of TERT expression, and telomerase activity that were also partially reverted by GSE4. These observations suggest that GSE4 may be considered as a new therapy for the treatment of AT that counteracts the cellular effects of high ROS levels generated in AT cells and in addition increases telomerase activity contributing to increased cell proliferation.

Physical Growth and Body Adiposity Curves in Students of the Maule Region (Chile).

Objectives: Physical growth and body adiposity patterns provide relevant information to infer the nutritional and health status of students. Our objectives were (a) to compare the variables of body adiposity and physical growth of Chilean children and adolescents with data from the CDC-2012 and international studies, and (b) to develop regional reference curves to evaluate growth and body adiposity. Methods: 8,261 children and adolescents were studied. We evaluated the weight, height, and waist circumference (WC). The Body Mass Index (BMI) was calculated. Their physical growth and body adiposity were compared with the CDC-2012 references as well as with other international references. Percentile curves for weight, height, BMI, and WC were constructed with the LMS method. Results: The Chilean students showed reduced weight and height during adolescence when compared with the CDC-2012 reference. During early ages, the BMI for the Chilean sample was lower while at advanced ages, the WC values were greater in comparison to the CDC-2012 reference. Graphic comparisons with international studies indicated that Chilean students weighed more at all ages. However, height was slightly greater until age 14 for males and age 11 for females. Body adiposity (BMI and WC) for the Chilean students was slightly higher at early ages while at later ages, adiposity values were relatively similar for both sexes. Conclusions: Discrepancies were observed between the physical growth and body adiposity trajectories and the American CDC-2012 references and the international studies. The proposed percentiles for weight, height, BMI, and WC for each age and sex may be useful for health sciences professionals and researchers.

Muscle Mass in Children and Adolescents: Proposed Equations and Reference Values for Assessment.

Objectives: The goal of this study was to develop regression equations to estimate LM with anthropometric variables and to propose percentiles for evaluating by age and sex. Methods: A cross sectional study was conducted with 2,182 Chilean students (1,347 males and 835 females). Ages ranged from 5.0 to 17.9 years old. A total body scan was carried out with the double energy X-ray anthropometry (DXA) to examine and measure lean muscle mass of the entire body. Weight, height, and the circumference of the relaxed right arm were also measured. Results: Four anthropometric equations were generated to predict lean mass for both sexes (R 2 = 83-88%, SEE = 3.7-5.0%, precision = 0.90-0.93, and accuracy = 0.99). The Lambda-mu-sigma method was used to obtain the sex-specific and age-specific percentile curves of lean mass (p3, p5, p10, p15, p25, p50, p75, p85, p90, p95, and p97). Conclusion: The four proposed equations were acceptable in terms of precision and accuracy to estimate lean mass in children and adolescents. The percentiles were created by means of anthropometric equations and real values for DXA. These are fundamental tools for monitoring LM in Chilean children and adolescents of both sexes.

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes.

BACKGROUND: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. METHODS: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes. RESULTS: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening. CONCLUSION: Novel variants in telomere, DNA repair and replication genes are described that might indicate the contribution of variants in these genes to the development of telomeropathies. Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed.

Cholecystokinin down-regulation by RNA interference impairs Ewing tumor growth.

PURPOSE: Tumors of the Ewing family are characterized by chromosomal translocations that yield chimeric transcription factors, such as EWS/FLI1, which regulate the expression of specific genes that contribute to the malignant phenotype. In the present study, we show that cholecystokinin (CCK) is a new target of the EWS/FLI1 oncoprotein and assess its functional role in Ewing tumor pathogenesis. EXPERIMENTAL DESIGN: Relevant EWS/FLI1 targets were identified using a combination of cell systems with inducible EWS/FLI1 expression, Ewing tumors and cell lines, microarrays, and RNA interference with doxycycline-inducible small hairpin RNA (shRNA) vectors. A doxycycline-inducible CCK-shRNA vector was stably transfected in A673 and SK-PN-DW Ewing cell lines to assess the role of CCK in cell proliferation and tumor growth. RESULTS: Microarray analysis revealed that CCK was up-regulated by EWS/FLI1 in HeLa cells. CCK was overexpressed in Ewing tumors as compared with other pediatric malignancies such as rhabdomyosarcoma and neuroblastoma, with levels close to those detected in normal tissues expressing the highest levels of CCK. Furthermore, EWS/FLI1 knockdown in A673 and SK-PN-DW Ewing cells using two different doxycycline-inducible EWS/FLI1-specific shRNA vectors down-regulated CCK mRNA expression and diminished the levels of secreted CCK, showing that CCK is a EWS/FLI1 specific target gene in Ewing cells. A doxycycline-inducible CCK-specific shRNA vector successfully down-regulated CCK expression, reduced the levels of secreted CCK in Ewing cell lines, and inhibited cell growth and proliferation in vitro and in vivo. Finally, we show that Ewing cell lines and tumors express CCK receptors and that the growth inhibition produced by CCK silencing can be rescued by culturing the cells with medium containing CCK. CONCLUSIONS: Our data support the hypothesis that CCK acts as an autocrine growth factor stimulating the proliferation of Ewing cells and suggest that therapies targeting CCK could be promising in the treatment of Ewing tumors.

Weight, height and body mass index of children and adolescents living at moderate altitude in Colombia. / Peso, estatura e índice de masa corporal de niños y adolescentes de moderada altitud de Colombia.

INTRODUCTION: There is increasing concern over the study of physical growth in different regions of the world, although altitude is not considered an adjustment factor. OBJECTIVES: Compare physical growth variables and body mass index (BMI) patterns with the Centers for Disease Control and Prevention (CDC) 2012 reference data and develop percentiles for children and adolescents. METHODOLOGY: School children living at moderate altitude in Bogotá (Colombia) were studied. Their weight and height were evaluated and their BMI was calculated. Anthropometric variables were compared against reference data of the CDC-2012, Brazil, Peru and Argentina. Curves were constructed using the least mean square (LMS) method. RESULTS: A total of 2241 school children (1159 girls) aged 6.0 to 17.9 years were included. There were no significant differences in weight and BMI in 6 to 8 year-olds relative to CDC-2012 reference data; in 9 to 17 year-old children, however, this sample evidenced lower values in terms of weight and BMI as compared to those of the CDC-2012. As far as height is concerned, in both sexes, values were lower than those of the CDC-2012. Comparisons against the regional curves of Argentina, Peru and Brazil yielded relatively similar results, with the exception of girls' BMI, as 13 to 17 year-old girls exhibited lower values. CONCLUSION: Growth variables of school children were lower relative to the CDC-2012 reference data. There were slight discrepancies in physical growth and BMI in relation to the curves of Argentina, Peru and Brazil. Curves were constructed to evaluate growth in school children living at moderate altitude in Colombia.

INTRODUCCIÓN: Existe preocupación progresiva por estudiar el crecimiento físico de diversas regiones del mundo, aunque no se considera la altitud como factor de ajuste. OBJETIVOS: Comparar variables de crecimiento físico y patrones de índice de masa corporal (IMC) con la referencia del Centro para el Control y Prevención de Enfermedades 2012 (CDC según siglas en inglés) y desarrollar percentiles para niños y adolescentes. METODOLOGÍA: Se investigaron escolares de moderada altitud de Bogotá (Colombia). Se evaluó el peso, la estatura y se calculó el IMC. Las variables antropométricas fueron comparadas con referencia al CDC-2012, Brasil, Perú y Argentina. Se construyeron curvas por el método LMS (least-mean-square algorithm). RESULTADOS: Se estudió a 2241 escolares (1159 mujeres), entre 6,0 y 17,9 años. No hubo diferencias significativas en el peso e IMC entre 6 y 8 años con relación al CDC-2012; sin embargo, desde los 9 a 17 años, esta muestra evidenció valores inferiores de peso e IMC en relación con el CDC-2012. En la estatura, en ambos sexos, se mostraron valores inferiores del CDC-2012. Las comparaciones con las curvas regionales de Argentina, Perú y Brasil fueron relativamente similares, excepto en el IMC en mujeres, que presentron valores inferiores desde 13 a 17 años. CONCLUSIÓN: Las variables de crecimiento de los escolares fueron inferiores con referencia al CDC-2012. Hubo ligeras discrepancias en el crecimiento físico y en el IMC con las curvas de Argentina, Brasil y Perú. Se construyeron curvas para evaluar el crecimiento y el IMC de escolares de moderada altitud de Colombia.

Validation of equations and proposed reference values to estimate fat mass in Chilean university students. / Validación de ecuaciones y propuesta de valores referenciales para estimar la masa grasa de jóvenes universitarios chilenos.

OBJECTIVES: (i) To propose regression equations based on anthropometric measures to estimate fat mass (FM) using dual energy X-ray absorptiometry (DXA) as reference method, and (ii)to establish population reference standards for equation-derived FM. MATERIAL AND METHODS: A cross-sectional study on 6,713 university students (3,354 males and 3,359 females) from Chile aged 17.0 to 27.0years. Anthropometric measures (weight, height, waist circumference) were taken in all participants. Whole body DXA was performed in 683 subjects. A total of 478 subjects were selected to develop regression equations, and 205 for their cross-validation. Data from 6,030 participants were used to develop reference standards for FM. Equations were generated using stepwise multiple regression analysis. Percentiles were developed using the LMS method. RESULTS: Equations for men were: (i) FM=-35,997.486 +232.285 *Weight +432.216 *CC (R2=0.73, SEE=4.1); (ii)FM=-37,671.303 +309.539 *Weight +66,028.109 *ICE (R2=0.76, SEE=3.8), while equations for women were: (iii)FM=-13,216.917 +461,302 *Weight+91.898 *CC (R2=0.70, SEE=4.6), and (iv) FM=-14,144.220 +464.061 *Weight +16,189.297 *ICE (R2=0.70, SEE=4.6). Percentiles proposed included p10, p50, p85, and p95. CONCLUSION: The developed equations provide valid and accurate estimation of FM in both sexes. The values obtained using the equations may be analyzed from percentiles that allow for categorizing body fat levels by age and sex.

Normative data for handgrip strength in children and adolescents in the Maule Region, Chile: Evaluation based on chronological and biological age.

BACKGROUND: Hand grip strength (HGS) is associated with a number of causes resulting in cardiovascular death, in addition to bone fragility, and the presence of sarcopenia. The goal of our study was to analyze HGS of students based on chronological and biological age and propose normative standards for children and adolescents from Chile. METHODS: We studied 4604 school children of both sexes between the ages of 6.0 and 17.9 years of age. Weight, standing height, sitting height, and hand grip strength (HGS- right and left) were measured. The Body Mass Index (BMI) was calculated, and the biological age was calculated by using age at peak height velocity (APHV). RESULTS: When arranged by chronological age, no significant differences occurred in HGS between both sexes of school children from age 6 to 12 years of age. However, from ages 13 to 17, males showed greater HGS than females. Significant differences also emerged between both sexes and at all levels for biological age (APHV). For males, chronological age explained the HGS occurring between 0.74 to 0.75% and for females between 0.54 to 0.59%. For males, biological age explained the HGS for the range of 0.79 to 0.80% and 0.62 to 0.67% for females. The normative data for HGS for both sexes is expressed in percentiles. CONCLUSIONS: HGS during childhood and adolescence needs be analyzed and interpreted in terms of biological age rather than chronological age. The normative data to evaluate the HGS are a tool that can help professionals working in clinical and epidemiological contexts.

Reference norms for evaluating maximum expiratory flow of children and adolescents of the Maule Region in Chile.

BACKGROUND: The norms for evaluating the maximum expiratory flow (MEF) usually are developed according to chronological age and height. However, to date, little research has been conducted using reference values that take into account the temporal changes of biological maturation. The objectives of this study were to (a) compare the MEF with those of other international studies, (b) align the MEF values with chronological and biological age, and (c) propose reference standards for children and adolescents. METHODS: The sample studied consisted of 3,566 students of both sexes (1,933 males and 1,633 females) ranging in age from 5.0 to 17.9 years old. Weight, standing height, and sitting height were measured. Body mass index was calculated. Biological maturation was predicted by using age of peak height velocity growth (APHV). MEF (L/min) was obtained by using a forced expiratory manoeuvre. Percentiles were calculated using the LMS method. RESULTS AND DISCUSSION: Predicted APHV was at age 14.77 ± 0.78 years for males and for females at age 12.74 ± 1.0 years. Biological age was more useful than chronological age for assessing MEF in both sexes. Based on these findings, regional percentiles were created to diagnose and monitor the risk of asthma and the general expiratory status of paediatric populations.