Medical research at the Mexican Institute of Social Security: Seven decades of work, achievements, and challenges.

Since its foundation, more than 75 years ago, the Mexican Institute of Social Security (IMSS) has carried out multidisciplinary research -biomedical, clinical and epidemiological- focused on understanding and solving the medical problems that afflict its beneficiaries (more than 50% of the Mexican population). Initially, research was the result of individual and isolated efforts. In the 1960s, a small number of researchers formed the first research groups. Currently, 240 full-time scientists work at five centers and 40 research units located in different states of Mexico. In addition, approximately 270 doctors carry out clinical research at different primary, secondary and tertiary care units. During these seven decades, IMSS scientists have made relevant contributions to medicine, which have not only helped increase knowledge on the etiopathogenesis of numerous diseases, but also their diagnosis, prognosis and treatment. This article presents an overview of medical research carried out at IMSS, based on a historical approach and a review of some of the most relevant contributions in different fields of research.

Desde su fundación, hace más de 75 años, el Instituto Mexicano del Seguro Social (IMSS) realiza investigación multidisciplinaria ­biomédica, clínica y epidemiológica­ enfocada a entender y resolver los problemas médicos que aquejan a sus derechohabientes (más de 50 % de la población mexicana). En un inicio, la investigación fue resultado de esfuerzos individuales y aislados. En la década de 1960, un número reducido de investigadores conformó los primeros grupos de investigación. Actualmente, 240 científicos de tiempo completo trabajan en cinco centros y 40 unidades de investigación ubicados en distintos estados de México. Además, aproximadamente 270 médicos efectúan investigación clínica en las distintas unidades de primer, segundo y tercer nivel de atención. Durante estas siete décadas, los científicos del IMSS han realizado aportaciones relevante para la medicina, las cuales no solo han ayudado a incrementar el conocimiento acerca de la etiopatogenia de numerosas enfermedades, sino también al diagnóstico, pronóstico y tratamiento de ellas. En este artículo se presenta un panorama general sobre la investigación médica que se desarrolla en el IMSS, a partir de un enfoque histórico y de la revisión de algunas de las contribuciones más relevantes en los distintos campos de la investigación.

Reconstructing Native American population history.

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

Maíz nixtamalizado suplementado con un concentrado de proteínas de sardina para mejorar el valor biológico de las tortillas.

INTRODUCCIÓN: La mayor parte de la población rural en México adquiere casi la mitad de su energía de la tortilla de maíz y sus fuentes de proteína son principalmente de origen vegetal. OBJETIVO: Obtener un concentrado de proteína de sardina para adicionar harina de maíz e identificar la concentración que proporcione la mejor calidad biológica de las tortillas sin modificar sus características físicas y sensoriales. MÉTODO: Obtención de un concentrado de proteína de sardina y elaboración de tortillas con harina de maíz suplementada con diferentes concentraciones de proteína. Las características físicas y sensoriales de las tortillas fueron evaluadas por panelistas no entrenados. La calidad biológica de las tortillas se analizó en un modelo murino (crecimiento y la relación de eficiencia de proteína, PER). Para el análisis se utilizó estadística paramétrica. RESULTADOS: Se obtuvo un concentrado de proteína con 70.48 g/100 g. La suavidad, inflado, doblado y calidad de las tortillas preparadas con las mezclas con 0.63-3.75 % de proteínas de sardina fueron comparables con los de las tortillas elaboradas con harina no adicionada. El crecimiento de las ratas alimentadas con tortillas adicionadas fue mayor que el de las alimentadas con harina no adicionada; la diferencia fue significativa a partir de la concentración de 3.75 % (p < 0.05). El PER de las tortillas con 3.75 % de proteínas de sardina fue de 2.41, comparable al de la proteína de referencia (caseína). CONCLUSIÓN: La harina de maíz adicionada con proteínas de sardina en una proporción de 96.25:3.75 % mejora el valor biológico de las tortillas sin alterar sus características físicas y sensoriales. INTRODUCTION: Most part of the rural population in Mexico obtains almost half its energy from corn tortilla, and its sources of protein are mainly of vegetal origin. OBJECTIVE: To obtain a concentrate of sardine protein (SP) to supplement corn flour, and to identify which concentration provides corn tortillas with a better biological value, without modifying its physical and sensorial characteristics. METHOD: Obtainment of the SP concentrate, preparation of tortillas with corn flour and different SP concentrations, assessment of tortillas physical and sensorial characteristics by untrained panelists, assessment of biological quality in a murine model (growth and protein efficiency ratio [PER]). Parametric statistics was used. RESULTS: A protein concentrate of 70.48 g/100 g was obtained. Smoothness, blistering, foldability and quality of the tortillas prepared with mixtures containing 0.63-3.75% of SP were comparable to those of tortillas prepared with non-supplemented flour. The growth of rats fed supplemented tortillas was superior; the difference was significant with ≥ 3.75% concentrations (p < 0.05). The PER of tortillas with 3.75% of SP was 2.41, which was comparable to that of the reference protein (casein). CONCLUSION: SP-supplemented corn flour at a 96.25:3.75% ratio improves the biological value of tortillas without modifying their physical and sensorial characteristics.

Adipokines, insulin resistance, and adiposity as a predictors of metabolic syndrome in child survivors of lymphoma and acute lymphoblastic leukemia of a developing country.

BACKGROUND: There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. METHODS: Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study. Testing included fasting insulin, glucose, adipokines and lipids; body fat mass was measured by DXA. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. Comparisons between continuous variables were performed according to the data distribution. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. With the purpose of assessing the risk of a present MS diagnosis, odds ratios (OR) with a 95% confidence interval (95% IC) were obtained using logistic regression analysis according to the various metabolic markers. RESULTS: The median children age was 12.1 years, and the interval time from the completion of therapy to study enrollment was 4 years. Among the MS components, the prevalence of HDL-C low was most common (42%), followed by central obesity (29%). The HOMA-IR (OR 9.0, 95% CI 2.0; 41.1), body fat (OR 5.5, 95% CI 1.6; 19.3), leptin level (OR 5.7, 95% CI 1.6; 20.2) and leptin/adiponectin ratio (OR 9.4, 95% CI 2.0; 49.8) in the highest tertile, were predictive factors of developing MS; whereas the lowest tertile of adiponectin was associated with a protective effect but not significant. CONCLUSIONS: Biomarkers such as HOMA-IR, leptin and leptin/adiponectin are associated with each of the components of the MS and with a heightened risk of suffering MS among children survivors of cancer. Given the close relationship between MS with risk of developing type 2 diabetes and cardiovascular disease, it is imperative to implement prevention measures in this population and especially in developing countries where these pathologies have become the leading cause of death.

Subtle metabolic alterations in adolescents with obesity and polycystic ovarian syndrome. / Alteraciones metabólicas sutiles en adolescentes con obesidad y síndrome de ovario poliquístico.

Objective: To evaluate the frequency of some subtle metabolic alterations in a group of adolescents with obesity and polycystic ovary syndrome (PCOS). Materials and Methods: A cross-sectional, comparative study was conducted in a group of adolescents with obesity, and characterized as with or without PCOS according with the Rotterdam Consensus. Medical history, anthropometry, gynecologic pelvic ultrasound (to evaluate ovarian volumes, number of antral follicles and endometrial width), as well as serum glucose, insulin, lipoproteins, interleukin-6, tumor necrosis factor alpha, total testosterone, dehydroepiandrosterone, sexual hormones binding globulin, leptin, adiponectin and insulin-like growth factor 1, the free-androgen index, free and available testosterone, and homeostatic model assessment index were calculated. For statistics, mean and standard deviation, or median and ranges were used for description as appropriate. Likewise, Student t-test or Mann-Whitney test were used for comparisons. Results: From a sample of 180 adolescents, 47 attached to selection criteria. Mean age was 13.5 year and Z-score 2.5. Eighty percent of adolescents presented central distribution of body fat and 95% hyperinsulinemia. The more frequent dyslipidemias were hypertriglyceridemia in 57% and hypercholesterolemia in 12.8%; 25.5% of adolescents presented two out of three criteria for polycystic ovary syndrome (PCOS). Body mass index and insulin were correlated with free testosterone, but the multivariate analysis demonstrated that the magnitude of the association was significantly higher in SOP patients. Conclusions: The metabolic alterations detected in obese adolescents with SOP suggest that the clinical manifestations that accompany the syndrome characterize the PCOS as a metabolic disease, which carry important health risks at short, medium and long term. Therefore, they merit intervening actions to prevent, diagnose and provide timing treatment in order to limit the damage in the course of the natural history of PCOS.

Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study.

BACKGROUND: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. METHODS: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. RESULTS: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1ß+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1ß+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. CONCLUSIONS: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

BACKGROUND: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. METHODS: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. RESULTS: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 µg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (ß = -27 µg/kg, p = 0.028; R2 model = 0.90) for shorter duration (ß = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. CONCLUSIONS: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.

[Interactions between markers of endothelial damage (homocysteine and asymmetric dimethylarginine) and antioxidants and B-vitamins in preeclamptic women]. / Interacción entre los marcadores de daño endotelial (homocisteóna y dimetilarginina asimétrica) con las vitaminas antioxidantes y del grupo B en pacientes con preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-related pathological condition triggered by an abnormal placentation which produces endothelial dysfunction (ED). ED, in turn, is associated with an increase in homocysteine (hcy) and asymmetric dimethylarginine (ADMA); these molecules are also increased when some of the B-vitamins are deficient. It is unclear whether increases in hcy and ADMA during preeclampsia are the result of ED, or the consequence of a B-vitamin deficiency. OBJECTIVE: To evaluate hcy, ADMA, folic acid (FA), vitamin B6 and B2 concentrations in patients with preeclampsia. METHODS: In a cross-sectional design 19 patients with severe preeclamp- sia (preeclampsia) and 57 with normal pregnancy (no-preeclampsia), paired by gestational age and body mass index, were studied. Plasma hcy, ADMA, FA and vitamins B6 and B12 were determined. Non-parametric statistics was used for between-groups comparisons and regression analyses to evaluate interactions among molecules. RESULTS: 72% of women were vitamin B deficient, 40% were deficient of B12 and 4% of FA. Preeclamptic patients presented hcy and ADMA concentrations higher than no-preeclamptic ones. Inferential analyses demonstrated that: hcy and ADMA are increased during preeclampsia independently from vitamins blood concentration; that the risk for pre- eclampsia is associated with high hcy but not with vitamins deficiency; and that the ratio L-arginine:ADMA decreases the preeclampsia risk. CONCLUSION: In patients with preeclampsia, increases of hcy and ADMA are associated with ED, but not with deficiency of the vitamins involved in their metabolism.

Excessive refined carbohydrates and scarce micronutrients intakes increase inflammatory mediators and insulin resistance in prepubertal and pubertal obese children independently of obesity.

BACKGROUND: Low-grade inflammation is the link between obesity and insulin resistance. Because physiologic insulin resistance occurs at puberty, obese pubertal children are at higher risk for insulin resistance. Excessive diets in refined carbohydrates and saturated fats are risk factors for insulin resistance, but calcium, magnesium, vitamin-D, and the omega-3 fatty acids likely protect against inflammation and insulin resistance. OBJECTIVE: To analyze interactions among dietary saturated fat, refined carbohydrates, calcium, magnesium, vitamin D, and omega-3 fatty acids on the risk of inflammation and insulin resistance in a sample of prepubertal and pubertal children. METHODS: A sample of 229 children from Mexico City was analyzed in a cross-sectional design. Anthropometric measurements, 24 h recall questionnaires, and blood samples were obtained. Serum insulin, glucose, calcium, magnesium, 25-OHD3, C-reactive protein, leptin, adiponectin, and erythrocytes fatty acids were measured. Parametric and nonparametric statistics were used for analysis. RESULTS: While mean macronutrients intake was excessive, micronutrients intake was deficient (P < 0.01). Inflammation determinants were central obesity and magnesium-deficient diets. Determinants of insulin resistance were carbohydrates intake and circulating magnesium and adiponectin. CONCLUSIONS: Magnesium-deficient diets are determinants of inflammation, while high intake of refined carbohydrates is a risk factor for insulin resistance, independently of central adiposity.

Obesity and Hyperandrogenemia in Polycystic Ovary Syndrome: Clinical Implications.

Polycystic ovary syndrome (PCOS) is often accompanied with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is usually not investigated. Ninety-nine women with PCOS and forty-one without PCOS were evaluated. The clinical biomarkers of alterations related to glucose (glucose, insulin, and clamp-derived glucose disposal - M), liver (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase), and endothelium (arginine, asymmetric dymethylarginine, carotid intima-media thickness, and flow-mediated dilation) metabolism were measured; participants were categorized into four groups according to their obesity (OB) and hyperandrogenemia (HA) status as follows: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were very frequent in women with PCOS (≈70%). BMI correlated with all biomarkers, whereas free testosterone (FT) correlated with only glucose- and liver-related indicators. Although insulin sensitivity and liver enzymes were associated with FT, women with obesity showed lower M (coef = 8.56 - 0.080(FT) - 3.71(Ob); p < 0.001) and higher aspartate aminotransferase (coef = 26.27 + 0.532 (FT) + 8.08 (Ob); p = 0.015) than lean women with the same level of FT. Women with obesity showed a higher risk of metabolic disorders than lean women, independent of hyperandrogenemia. Clinicians are compelled to look for metabolic alterations in women with PCOS. Obesity should be treated in all cases, but hyperandrogenemia should also be monitored in those with glucose-or liver-related disturbances.

Pilot study on the effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on body composition in children with acute lymphoblastic leukemia: randomized clinical trial.

BACKGROUND: N-3 polyunsaturated fatty acids (LCPUFA-ω3), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) might have beneficial effects on lean mass and fat mass synthesis. OBJECTIVE: To investigate the effect of LCPUFA-ω3 supplementation on body composition changes in children with acute lymphoblastic leukemia (ALL) at remission and three months (3 mo) after supplementation. METHODS: This randomized controlled trial enrolled 72 children (3-13 y) with newly diagnosed ALL (placebo group [500 mg sunflower oil]: 36 patients; LCPUFA-ω3 group [225 mg DHA, 45 mg EPA]: 36 patients). LCPUFA-ω3 was administered at 0.100 g/kg of body weight/day for 3 mo. Both groups were provided with an oral milkshake supplement. MAIN OUTCOMES AND MEASURES: Body composition was measured at diagnosis, remission, and 3 months after supplementation by dual-energy X-ray absorptiometry (DXA). Red blood cell fatty acid analyses were performed with gas chromatography. Student's t test compared the percentage changes in body weight, total body fat percentage (TBFP), and lean body mass (LBM) between the groups. The Mann-Whitney U test was used to compare the groups, and the Friedman range test and Wilcoxon signed rank test were used for intratreatment comparisons. Spearman correlation coefficients were calculated for LBM and erythrocyte LCPUFA-ω3 content. RESULTS: LBM decreased significantly in both groups. This loss was greater in the placebo group than in the LCPUFA-ω3 group at remission (p = 0.044) and at 3 months of supplementation (p = 0.039). There were significant and progressive increases in DHA and EPA concentrations in the LCPUFA-ω3 group (p < 0.001). LBM at remission was directly correlated with increased DHA (r = 0.487, p = 0.034) and EPA (r = 0.499, p = 0.030) erythrocytes in the LCPUFA-ω3 group. CONCLUSION: At ALL diagnosis and during the first three months of treatment, 100 mg/kg of body weight/d DHA and EPA decreased LBM loss and allowed the incorporation of fatty acids into cell membranes (clinicaltriasl.gov #: NCT01051154).

Effect of long-chain omega-3 polyunsaturated fatty acids on cardiometabolic factors in children with acute lymphoblastic leukemia undergoing treatment: a secondary analysis of a randomized controlled trial.

Introduction: Increased triglycerides (TGs) are a major risk factor for cardiovascular disease. Furthermore, hypertriglyceridemia is commonly associated with a reduction of high-density lipoprotein cholesterol (HDL-C) and an increase in atherogenic small-dense low-density lipoprotein (LDL-C) levels. Studies provide support that polyunsaturated omega-3 fatty acids (ω3-LCPUFAs) are cardioprotective and have antithrombotic and anti-inflammatory effects. The potential effects of ω3-LCPUFAs on cardiometabolic factors and anti-inflammatory actions in children with acute lymphoblastic leukemia (ALL) are limited. This is a secondary analysis of a previous clinical trial registered at clinical trials.gov (# NCT01051154) that was conducted to analyze the effect of ω3-LCPUFAs in pediatric patients with ALL who were receiving treatment.Objective: To examine the effect of supplementation with ω3-LCPUFAs on cardiometabolic factors in children with ALL undergoing treatment. Methods: Thirty-four children (placebo group: 20 patients; ω3-LCPUFAs group: 14 patients) aged 6.7 ± 2.7 years who were newly diagnosed with ALL were evaluated. Children were randomized to receive either ω3-LCPUFAs or placebo capsules (sunflower oil). ω3-LCPUFAs were administered in the form of 500-mg soft capsules. The ω3-LCPUFA capsules contained 225 mg of DHA, 45 mg of EPA, and 20 mg of another ω3-LCPUFAs. The omega-3 dose was administered at a rate of 0.100 g/kg of body weight/day for three months. Main outcomes: Fasting cholesterol, HDL-C, very-low-density lipoprotein (VLDL-C), TGs, atherogenic index of plasma (AIP), android/gynoid ratio (A/GR), IL-6, TNF-α, and percentage of fat mass (DXA) were measured in all patients. Fatty acid analyses in red blood cells were performed with gas chromatography. Results: We found significantly lower levels of TGs (p=0.043), VLDL-C (p=0.039), IL-6 (p=0.025), and AIP (p=0.042) in the ω3-LCPUFAs group than in the placebo group at three months. In contrast, the total cholesterol concentration was higher at 3 months in the ω3-LCPUFAs group than in the placebo group (155 mg/dl vs. 129 mg/dl, p=0.009). The number of children with hypertriglyceridemia (85% vs. 50%; p=0.054) tended to be lower between the time of diagnosis and after 3 months of supplementation with ω3-LCPUFAs. Conclusion: These findings support the use of ω3-LCPUFAs to reduce some adverse cardiometabolic and inflammatory risk factors in children with ALL. Clinical trial registration: ClinicalTrials.gov, identifier NCT01051154.

Participation of mammary gland in long-chain polyunsaturated fatty acid synthesis during pregnancy and lactation in rats.

Metabolic adaptations are triggered in the maternal organism to synthesize milk with an adequate concentration of long-chain polyunsaturated fatty acids (LC-PUFAs) required to the newborn. They may be a high uptake of dietary linoleic acid and its conversion to LC-PUFAs by desaturases of fatty acids (FADS) 1 and 2 in the mammary gland (MG). It is unknown if they also occur from onset of pregnancy. The aim of this study was to explore the participation of the MG as a mechanism involved in LC-PUFAs synthesis to support their demand during pregnancy and lactation in rats. The expression of desaturases in MG was significantly (P<0.05) higher (12.3-fold for FADS1 and 41.2-fold for FADS2) during the late pregnancy and throughout lactation (31.7-fold for FADS1 and 67.1-fold higher for FADS2) than in nonpregnant rats. SREBF-1c showed a similar pattern of increase during pregnancy but remained higher only during the early lactation (11.7-fold, P<0.005). Transcript of ELOVL6 and FASN increased throughout pregnancy and lactation, respectively. ELOVL5 mRNA increased in MG only during lactation (2.8 to 5.3-fold, P<0.005). Accordingly, a higher content of LC-PUFAs was found in lactating MG than in nonpregnant rats. Results suggest that MG participates from late pregnancy and throughout lactation by expressing desaturases and elongases as a mechanism involved in LC-PUFAs synthesis, probably by SREBF-1c. Because desaturases and ELOVL5 were expressed in cultured lactocytes and such expression was downregulated by linoleic and arachidonic acid, these cells may be a useful model for understanding the regulatory mechanisms for LC-PUFAs synthesis in MG.

Effectiveness of four manual breast pumps for mothers after preterm delivery in a developing country.

BACKGROUND: Hospital-grade electric pumps may be useful to initiate and sustain adequate milk production for mothers who are unable to breast-feed their babies hospitalized at special care nurseries (SCN), but their cost is generally not affordable for SCN and for most mothers in developing countries. Therefore, manual breast pumps (MBPs) can be an alternative, but the best option is unknown considering clinical parameters and mothers' preference from among currently available MBPs. OBJECTIVE: To compare the effectiveness of four MBPs in terms of milk volume, nutritional composition, and breast emptying in order to assist in making a choice for health care personnel and mothers in SCN settings. Duration of expression and maternal preference were also evaluated as secondary outcomes. METHODS: Mothers of preterm infants used 4 MBPs in a random order, 2 with a squeeze-handle mechanism (Isis and Harmony) and 2 with a cylindrical mechanism (Little Heart and Evenflo), both at the hospital and in home settings using each pump over one 24-hour period. RESULTS: Milk volume, nutritional composition, breast emptying, and duration of expression were not different among MBPs. Scale of maternal preference rated higher those with the squeeze-handle mechanism than the cylindrical mechanism (p < 0.05). CONCLUSIONS: There was no difference found in the effectiveness across the four pumps tested. The mothers' rating for comfort and ease of use showed a marked difference between pumps. These factors, plus cost, need to be considered when evaluating manual pumps for use in SCN settings in developing countries.

[Management of obesity in schoolchildren and adolescents]. / Manejo de la obesidad en niños y adolescentes.

Pediatric obesity is a pathological process explained by genetic susceptibility, inappropriate diet, sedentary life patterns, and other environmental factors. It is related with psychological disturbances and chronic diseases in childhood or later in adulthood. Obesity prevention must start early in life and requires lifestyle multicomponent intervention (diet, physical activity and behavior), include children, family, and community, and offered in the primary health care service by the healthcare staff (physicians, nurses, dietists, and psychologists). Obesity treatment may include in addition other treatment alternatives. It must be provided by physicians, to simultaneously treat obesity and the associated morbidity. Pediatric obesity is a global problem, and its management has not been effective. Therefore, scientific research must be involved to identify new management options.

La obesidad pediátrica es un proceso patológico que se puede explicar por la predisposición genética, la dieta inadecuada, el sedentarismo y otros factores ambientales. Se asocia a trastornos psicológicos y enfermedades crónicas en la niñez o más tarde, en la edad adulta. La prevención de la obesidad debe iniciar desde etapas tempranas de la vida y requiere cambios integrales en el estilo de vida (dieta, ejercicio y conductual) involucrando al niño, la familia y la comunidad; se debe realizar por todo el equipo de salud en el primer nivel de atención (médicos, enfermeras, nutriólogos y psicólogos). El tratamiento de la obesidad puede incluir otras alternativas de tratamiento y debe ser otorgado por el médico (apoyado por el equipo de salud) para atender simultáneamente la obesidad y la morbilidad asociada. El problema de la obesidad pediátrica es mundial y su manejo ha sido poco eficiente hasta ahora, por lo que se requiere la participación de la investigación científica para identificar nuevas estrategias de manejo.

Efficacy and safety of vitamin D supplementation in hospitalized COVID-19 pediatric patients: A randomized controlled trial.

Background: Some studies suggested that adequate levels of vitamin D (VD) decrease the risk of severe COVID-19. Information about the effectiveness of VD supplementation in children is scarce. Objective: To assess the efficacy and safety of VD supplementation compared to the standard of care in hospitalized children with COVID-19. Patients and methods: An open-label randomized controlled single-blind clinical trial was carried out. We included patients from 1 month to 17 years, with moderate COVID-19, who required hospitalization and supplemental oxygen. They were randomized into two groups: the VD group, which received doses of 1,000 (children < 1 year) or 2,000 IU/day (from 1 to 17 years) and the group without VD (control). The outcome variables were the progression of oxygen requirement, the development of complications, and death. Statistical analysis: For comparison between groups, we used the chi-squared test or Fisher's exact test and the Mann-Whitney U test. Absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated. p ≤ 0.05 was considered statistically significant. Results: From 24 March 2020 to 31 March 2021, 87 patients were eligible to participate in the trial; 45 patients were randomized: 20 to the VD group and 25 to the control group. There was no difference in general characteristics at baseline, including serum VD levels (median 13.8 ng/ml in the VD group and 11.4 ng/ml in the control group). Outcomes: 2/20 (10%) in the VD group vs. 9/25 (36%) in the control group progressed to a superior ventilation modality (p = 0.10); one patient in the VD group died (5%) compared to 6 (24%) patients in the control group (p = 0.23). ARR was 26% (95% CI 8.8 to 60.2%) and NNT was 3 (2 to 11) for progression and ARR was 19% (95% CI -3.9 to 42.8%) and NNT was 6 (2 to 26) for death. None of the patients receiving VD had adverse effects. The trial was stopped for ethical reasons; since after receiving the results of the basal VD values, none of the patients had normal levels. Conclusion: In this trial, VD supplementation in pediatric patients seems to decrease the risk of COVID-19 progression and death. More studies are needed to confirm these findings. Clinical Trial Registration: This protocol was registered on ClinicalTrials.gov with the registration number NCT04502667.

Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial.

BACKGROUND: Associations between vitamin D (VD) deficiency and the risk of SARS-CoV-2 infection have been documented in cross-sectional population studies. Intervention studies in patients with moderate to severe COVID-19 have failed to consistently document a beneficial effect. OBJECTIVE: To determine the efficacy and safety of VD-supplementation in the prevention of SARS-CoV-2 infection in highly exposed individuals. METHODS: A double-blind, parallel, randomized trial was conducted. Frontline healthcare workers from four hospitals in Mexico City, who tested negative for SARS-CoV-2 infection, were enrolled between July 15 and December 30, 2020. Participants were randomly assigned to receive 4,000 IU VD (VDG) or placebo (PG) daily for 30 d. RT-PCR tests were taken at baseline and repeated if COVID-19 manifestations appeared during follow-up. Serum 25-hydroxyvitamin D3 and antibody tests were measured at baseline and at day 45. Per-protocol and intention-to-treat analysis were conducted. RESULTS: Of 321 recruited subjects, 94 VDG and 98 PG completed follow-up. SARS-CoV-2 infection rate was lower in VDG than in PG (6.4 vs. 24.5%, p <0.001). The risk of acquiring SARS-CoV-2 infection was lower in the VDG than in the PG (RR: 0.23; 95% CI: 0.09-0.55) and was associated with an increment in serum levels of 25-hydroxyvitamin D3 (RR: 0.87; 95% CI: 0.82-0.93), independently of VD deficiency. No significant adverse events were identified. CONCLUSIONS: Our results suggest that VD-supplementation in highly exposed individuals prevents SARS-CoV-2 infection without serious AEs and regardless of VD status.

Randomized placebo-controlled trial of guava juice as a source of ascorbic acid to reduce iron deficiency in Tarahumara indigenous schoolchildren of northern Mexico.

OBJECTIVE: Assess the efficacy of a 10-week consumption of guava juice on the iron status of children with mild iron deficiency anemia. METHODS: Ninety-five boarding school children aged 6-9 years identified as anemic were randomly allocated to receive 300 mL of natural guava juice containing ∼200 mg of ascorbic acid (AA) or placebo (guava-flavored juice free of AA) with the main meal (5 d/wk). Information about dietary intake was collected at weeks 3, 5, and 7 at school and household levels. Changes in hemoglobin (Hb) and plasma ferritin (PF) among the subsample iron deficient at baseline (n = 33) were the main outcomes. RESULTS: Iron and phytic acid intakes at school and at home did not differ between groups. Baseline Hb and PF were 11.9 ± 0.5 g/dL and 8.2 ± 3.6 ng/mL for the guava, and 11.4 ± 1.1 g/dL and 7.4 ± 4.6 ng/mL for the placebo group (Hb: p = 0.08; PF: p = 0.31); at week 10 of the study, corresponding values were 13.1 ± 0.9 g/dL and 17.9 ± 10.3 ng/mL (n = 16), and 12.3 ± 1.3 g/dL and 15.4 ± 5.8 ng/mL (n = 12) (Hb: p = 0.05; PF: p = 0.21). With analysis of variance (ANOVA) for repeated measures, the guava group had 0.64 g/dL higher Hb (CI(95), 0.18-1.11; p = 0.01) and 2.47 ng/mL higher PF (CI(95), -1.04 to 5.98; p = 0.12) compared with the placebo group. CONCLUSION: Guava juice providing 200 mg AA at one meal on each school day had a marginal effect on Hb and PF concentrations in children consuming high-phytate diets fortified with iron.

The role of LCPUFA-ω3 on the obesity-associated hyperandrogenemia of pubertal girls: secondary analysis of a randomized clinical trial.

Introduction Hyperandrogenism (HA), either clinical or biochemical, is associated with obesity in adolescent girls. Long chain polyunsaturated fatty acids ω3 (LCPUFA-ω3) play protective roles in some obesity-associated morbidities, but their contribution to preventing HA is unclear. Our aim was to examine the potential positive relationships between erythrocyte LCPUFA-ω3, with or without supplementation, and hyperandrogenemia. Methods Secondary analysis of a clinical trial that was conducted previously to analyze the effect of LCPUFA-ω3 on insulin resistance and body weight. Here, we present a cross-sectional analysis of 180 girls with obesity, and a longitudinal analysis of 117 girls who completed a 3-month supplementation period (57 LCPUFA-ω3 [DO3] and 60 placebo [DP)]). Dehydroepiandrosterone sulfate (DHEAS), total testosterone (TT) and steroid hormone binding globulin (SHBG) were measured with chemiluminescence; free testosterone (FT) was calculated. Erythrocyte fatty acids were determined by gas chromatography. Non-parametric statistics was used for analysis. Results In cross-sectional analysis, age (odds ratio [OR] = 1.35; 95% confidence interval [CI] = 1.03, 1.78; p = 0.027), insulin (OR = 1.05; 95% CI: 1.00, 1.10; p = 0.018), and erythrocytes eicosapentaenoic acid (EPA) (OR = 0.04; 95% CI: 0.01, 0.65; p = 0.012) were predictors of hyperandrogenemia (FT >0.63 ng/mL). In longitudinal analysis, EPA, adiponectin and SHBG increased, while FT decreased, in the DO3 group (p < 0.05). The risk of hyperandrogenemia at the end of follow-up was predicted by basal hyperandrogenemia (OR = 18.16, 95% CI: 5.37, 61.4; p < 0.001) and by increases in EPA (OR = 0.40; 95% CI: 0.01, 0.65; p = 0.06 marginal significance). Conclusions Our results suggest a preventive role of EPA on the risk for hyperandrogenemia in girls with obesity, but further studies are needed to demonstrate a benefit.

Effect of a Nutritional Support System (Diet and Supplements) for Improving Gross Motor Function in Cerebral Palsy: An Exploratory Randomized Controlled Clinical Trial.

BACKGROUND: Most patients with cerebral palsy (CP) do not respond to physical therapy due to deterioration in their nutritional status, secondary to gastrointestinal disorders and the catabolic state of the disease itself. However, basic treatments only contemplate the energy requirements and do not consider supplementation with glutamine, zinc, selenium, colecalciferol, spirulina, omega 3 or even vegetal proteins. OBJECTIVE: In this study, we determined the effect of using a nutritional support system (NSS): diet and supplements, on the gross motor function in children with CP with spastic diparesic and Gross Motor Function Classification System III (GMFCS III). METHODS: An exploratory study was performed. Thirty patients (from 4 to 12 years old) were randomly assigned to: (1) dietary surveillance (FG), (2) deworming and WHO diet (CG), or (3) deworming and the NSS (IG). Gross motor function was evaluated using the gross motor function measure (GMFM) scale. RESULTS: The IG-treated group presented a significant improvement in standing and walking parameters analyzed in the GMFM compared with FG and CG groups. Fifty percent of the IG-treated patients managed to walk, while in the other groups, no patients were able to walk. CONCLUSIONS: The NSS used in the present work improves gross motor function and promotes walking in patients with CP.