Bias correction of nutritional status estimates when reported age is used for calculating WHO indicators in children under five years of age

Objective.To assess the performance of a simple correction method for nutritional status estimates in children under five years of age when exact age is not available from the data. Materials and methods. The proposed method was ba- sed on the assumption of symmetry of age distributions within a given month of age and validated in a large population-based survey sample of Mexican preschool children. Results. The main distributional assumption was consistent with the data. All prevalence estimates derived from the correction method showed no statistically significant bias. In contrast, failing to correct attained age resulted in an underestimation of stunting in general and an overestimation of overweight or obesity among the youngest. Conclusions. The proposed method performed remarkably well in terms of bias correction of estimates and could be easily applied in situations in which either birth or interview dates are not available from the data

Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study

Mitokines (Humanin (HN), GDF15 and FGF21) are produced as a result of mitochondrial dysfunction and may have major roles in chronic inflammation, malnutrition and exercise capacity in people with COPD. Except for GDF15, studies on this subject are lacking. A total of 165 patients with stable COPD and 49 smokers without COPD were enrolled. We assessed their serum mitokine levels and clinical characteristics at baseline. We recorded moderate and severe exacerbation for the next 12 months. Baseline serum HN (p = 0.037) and GDF-15 (p = 0.013) levels were higher in the COPD group. High HN levels were independently associated with a high risk of exacerbation (HRE) (OR 2.798, 95% CI 1.266-6.187, p = 0.011), malnutrition (OR 6.645, 95% CI 1.859-23.749, p = 0.004), and 6MWD (OR 0.995, 95% CI 0.991-0.999, p = 0.008), and future moderate (HR 1.826, 95% CI 1.181-2.822, p = 0.007) and severe exacerbations (HR 3.445, 95% CI 1.357-8.740, p = 0.009). High GDF15 levels were associated with HRE (OR 3.028, 95% CI 1.134-8.083, p = 0.027), 6MWD (OR 0.995, 95% CI 0.990-0.999, p = 0.017) and predicted desaturation in 6MWT (OR 3.999, 95% CI 1.487-10.757, p = 0.006). High FGF21 levels were associated with HRE (OR 2.144, 95% CI 1.000-4.600, p = 0.05), and predicted future severe exacerbation (HR 4.217, 95% CI 1.459-12.193, p = 0.008). The mitokine levels were higher in patients with COPD than smokers without COPD, and were associated with important clinical outcomes such as exercise capacity and COPD exacerbation. Among the mitokines, HN showed the strongest association with COPD and may serve as a future risk biomarker in this disease.Trial registation NCT04449419.Funding: This study was funded by Instituto de investigación sanitaria of Cantabria (IDIVAL): NextVAL grant: NVAL19/01 and GSK (NCT04449419)

An Iterative Process for Training Design and Implementation Increased Health Workers\u27 Knowledge for Taking Nutrition Behavior Change to Scale

The shortage of skilled, motivated, and well-supported health workers is a major barrier to scaling up nutrition interventions and services. Objective: The objective of this study is to describe the process for developing and implementing a training of health personnel for the delivery of the Integrated Strategy for Attention to Nutrition (EsIAN), an evidence-based strategy for promoting infant and young child feeding through primary health care in Mexico. The specific objective is to provide a case study and highlight challenges, as well as elements to successfully mitigate these, and discuss potential applications of findings beyond the Mexican context. Methods: The design and implementation of training followed a 5-phase process: situation analysis, formative research, large-scale feasibility study, redesign and scale up, and evaluation. We conducted document reviews, surveys, and focus groups during the first phases to inform and refine the training, as well as a pre- and posttraining telephone survey to evaluate change in knowledge. Results: The initial phases of the design provided a clear understanding of the opportunities and challenges for promoting infant and young child feeding, as well as health workers\u27 routines and practices, which informed training design. The feasibility study allowed tailoring and refinement of training. The vertical coherence and coordination between the federal and state levels during redesign and scale up facilitated compliance with training timeline and process. Evaluation results showed significant improvement in knowledge posttraining of up to 19 percentage points. Conclusions: The EsIAN training component for health providers was developed using a systematic approach to consolidate and generate relevant evidence, following an iterative process to test, learn, and improve both design and implementation. This process allowed for flexibility to take advantage of new opportunities and respond to findings from iterations. Garnering and ensuring political support allowed for continuity and sustainability of actions

Effect of hemodialysis session on acute changes in inflammatory and cardiovascular risk biomarkers

Background: Inflammation is associated with enhanced cardiovascular risk profile and increased cardiovascular mortality in end-stage kidney disease patients undergoing hemodialysis. Mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. As successful treatment of the inflammatory condition in these patients may improve long-term survival, we studied potential changes in different inflammatory biomarkers of cardiovascular risk in end-stage kidney disease patients after a mid-week hemodialysis session. Methods: Inflammatory biomarkers of cardiovascular risk (cystatin-C, homocysteine, C-reactive protein, procalcitonin, pentraxin-3, serum amyloid-A) and atherogenic plasma lipoproteins (Lipoprotein(a), cholesterol low and high density lipoproteins) were studied in 21 end-stage kidney disease patients previously and after a mid-week hemodialysis session. Results: We found a significant reduction in serum levels of low molecular weight molecules: cystatin-C (5.56 to 1.85 mg/L, 66.73%, p < 0.001), homocysteine (22.85 to 13.25 µmol/L, 42.01%, p < 0.001) and procalcitonin (0.788 to 0.457 ng/mL, 42.01%, p < 0.001). Large molecules as C-reactive protein (9.70 to 9.90 mg/L, 2.06%, p = 0.022) and pentraxin-3 (1.67 to 4.28 ng/mL, 156%, p < 0.001) increased, but serum amyloid-A decreased (15.90 to 12.70 mg/L, 20.13%, p < 0.05). There was no change in Lipoprotein (a) levels. Conclusion: Pentraxin-3 was a more specific inflammatory vascular marker than C-reactive protein, and the best inflammatory marker associated with hemodialysis. Homocysteine, procalcitonin and the other small proteins could be released and removed during hemodialysis session. Further studies are needed to understand the behavior and significance of these markers after successive hemodialysis

Sex hormones and the total testosterone: estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men

Background: The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. Objectives: To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. Materials and methods: This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. Results: We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111 ± 89 vs. 191 ± 143 ng/dL; p < 0.001), dehydroepiandrosterone (1.69 ± 1.26 vs. 2.96 ± 2.64 ng/mL; p < 0.001), and dehydroepiandrosterone sulfate (91.72 ± 76.20 vs. 134.28 ± 98.261 μg/dL; p = 0.009), significantly higher levels of estradiol (64.61 ± 59.35 vs. 33.78 ± 13.78 pg/mL; p = 0.001), and significantly lower total testosterone:estradiol ratio (0.28 ± 0.31 vs. 0.70 ± 0.75; p < 0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p = 0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p < 0.001). Discussion and conclusion: Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.This project was funded with aid from the innovation project INN-VAL 20/15 (Instituto de Investigación Marqués de Valdecilla—IDIVAL). ACKNOWLEDGMENTS: The authors thank Fernando Rico-Villademoros (COCIENTE S.L., Madrid, Spain) for his editorial assistance; this assistance has been funded by Instituto de Investigación Marqués de Valdecilla (IDIVAL; Santander, Spain)

Alterations in circulating mitochondrial signals at hospital admission for COPD exacerbation

Background: Chronic obstructive pulmonary disease (COPD) exacerbation (ECOPD) alters the natural course of the disease. To date, only C-reactive protein has been used as a biomarker in ECOPD, but it has important limitations. The mitochondria release peptides (Humanin (HN), FGF-21, GDF-15, MOTS-c and Romo1) under certain metabolic conditions. Here, we aimed to evaluate the pathophysiologic, diagnostic and prognostic value of measuring serum mitochondrial peptides at hospital admission in patients with ECOPD. Methods: A total of 51 consecutive patients admitted to our hospital for ECOPD were included and followed for 1 year; in addition, 160 participants with stable COPD from our out-patient clinic were recruited as controls. Results: Serum FGF-21 (p < .001), MOTS-c (p < .001) and Romo1 (p = .002) levels were lower, and GDF-15 (p < .001) levels were higher, in patients with ECOPD than stable COPD, but no differences were found in HN. In receiver operating characteristic analysis, MOTS-c (AUC 0.744, 95% CI 0.679-0.802, p < .001) and GDF-15 (AUC 0.735, 95% CI 0.670-0.793, p < .001) had the best diagnostic power for ECOPD, with a diagnostic accuracy similar to that of C-RP (AUC 0.796 95% IC 0.735-0.848, p < .001). FGF-21 (AUC 0.700, 95% CI 0.633-0.761, p < .001) and Romo1 (AUC 0.645 95% CI 0.573-0.712, p = .001) had lower diagnostic accuracy. HN levels did not differentiate patients with ECOPD versus stable COPD (p = .557). In Cox regression analysis, HN (HR 2.661, CI95% 1.009-7.016, p = .048) and MOTS-c (HR 3.441, CI95% 1.252-9.297, p = .016) levels exceeding mean levels were independent risk factors for re-admission. Conclusions: Most mitochondrial peptides are altered in ECOPD, as compared with stable COPD. MOTS-c and GDF15 levels have a diagnostic accuracy similar to C-RP for ECOPD. HN and MOTS-c independently predict future re-hospitalization.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Instituto de investigación sanitaria of Cantabria (IDIVAL): NextVAL grant: NVAL19/01 and GSK (NCT04449419). GSK was provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation

Specific NOTCH1 antibody targets DLL4-induced proliferation, migration, and angiogenesis in NOTCH1-mutated CLL cells

Targeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), particularly in NOTCH1-mutated patients. We provide first evidence that the Notch ligand DLL4 is a potent stimulator of Notch signaling in NOTCH1-mutated CLL cells while increases cell proliferation. Importantly, DLL4 is expressed in histiocytes from the lymph node, both in NOTCH1-mutated and -unmutated cases. We also show that the DLL4-induced activation of the Notch signaling pathway can be efficiently blocked with the specific anti-Notch1 antibody OMP-52M51. Accordingly, OMP-52M51 also reverses Notch-induced MYC, CCND1, and NPM1 gene expression as well as cell proliferation in NOTCH1-mutated CLL cells. In addition, DLL4 stimulation triggers the expression of protumor target genes, such as CXCR4, NRARP, and VEGFA, together with an increase in cell migration and angiogenesis. All these events can be antagonized by OMP-52M51. Collectively, our results emphasize the role of DLL4 stimulation in NOTCH1-mutated CLL and confirm the specific therapeutic targeting of Notch1 as a promising approach for this group of poor prognosis CLL patients

Narrar, exponer y argumentar: secuencias didácticas para la comprensión y producción de textos

Narrar, exponer y argumentar es el resultado de 10 años de investigación, de la Maestría en Educación, de la Universidad Tecnológica de Pereira. En esta obra se da cuenta de "nueve experiencias de intervención con secuencias didácticas, orientadas hacia la comprensión o producción de textos narrativos, expositivos y argumentativos. Estos procesos, que hacen parte de los propósitos nacionales por transformar la educación, logran, entre muchas otras cosas: visibilizar la persona del estudiante en la construcción de su propio conocimiento, empoderar al maestro y re-considerar su papel en la cimentación de una nueva sociedad y, algo de vital interés, demostrar que desde el aula, profesores y estudiantes, pueden alcanzar grandes metas cognitivas, procedimentales y actitudinales si se democratiza el saber, se modifican las metodologías y se abren las puertas a una verdadera participación. En el inicio de las investigaciones aquí evidenciadas, los maestros investigadores pudieron constatar que sus propias prácticas de enseñanza asumían el lenguaje como algo estático, abordado, primordialmente, desde una perspectiva gramatical. La realidad indicaba que los significativos avances teóricos en didáctica no habían transformado las prácticas educativas, las cuales seguían perpetuando modelos tradicionales, en los cuales los problemas están ubicados, de manera reiterativa, en los estudiantes y no en la manera como se enseña. Por esta razón, las iniciativas deben partir de la buena disposición del profesor y de su deseo de hacer las cosas de manera distinta, algo que aún tiene un carácter de osadía, de profanación y rebeldía. En este orden de ideas, esta obra es, a la vez, un ejemplo de la potencia del cambio, representado en una determinación altruista del profesor y un indicio de todo aquello que se ha dejado de hacer en educación, por falta de esa determinación y por haber olvidado, bajo el embrujo de la conformidad, que educar tiene que ver con soñar, descubrir y ser felices.Contenido Prólogo 13 Introducción 15 CAPÍTULO UNO 19 1.1 Lenguaje 21 El lenguaje en la educación 21 1.2 Lenguaje escrito 23 1.3 Los géneros discursivos 25 1.3.1 El texto narrativo 27 1.3.2 El texto expositivo 28 1.3.3 El texto argumentativo 29 Bibliografía 31 CAPÍTULO DOS 35 La enseñanza de la comprensión en la escuela: miradas y retos 37 Bibliografía 47 CAPÍTULO TRES 51 3.1 Presentación 53 La enseñanza de la producción escrita 53 3.2 Creencias sobre los textos escritos 55 3.3 El proceso de producción: ¿qué enseñar en el momento 56 de escribir un texto? 56 Bibliografía 60 CAPÍTULO CUATRO 61 Secuencias didácticas para la producción y comprensión de textos, a través de prácticas discursivas, orales y escritas 63 4.1 Planeación de la práctica pedagógica 63 4.2 Secuencias didácticas mediadas por las TIC 66 4.3 Fases para la implementación de una secuencia didáctica 68 4.3.1 La fase de preparación o planeación 68 4.3.2 Fase de desarrollo o ejecución 70 4.3.3 Fase de cierre 74 Bibliografía 77 CAPÍTULO CINCO 81 Telenovelas, un pretexto para leer textos: secuencia didáctica de enfoque socio-cultural, para mejorar la comprensión lectora de textos narrativos, en estudiantes de grado noveno 83 5.1 Enfoque teórico 84 5.2 Fases de la secuencia didáctica 85 5.3 Conclusiones 98 Bibliografía 99 CAPÍTULO SEIS 101 Conservación y medio ambiente: una secuencia didáctica para la comprensión de textos expositivos, con estudiantes de grado noveno 103 6.1 Contextualización 104 6.1.1 Justificación 104 6.2 Sustentación teórica 105 6.3 Secuencia didáctica 107 6.4 Conclusiones 117 Bibliografía 119 CAPÍTULO SIETE 121 Los reality shows y los medios de comunicación: una secuencia didáctica para la comprensión de textos argumentativos, con estudiantes de grado octavo 123 7.1 Enfoque teórico 124 7.1.1 Contextualización 124 7.1.2 Fundamento teórico 124 7.2 Fases de la secuencia didáctica 125 7.3 Conclusiones 133 Bibliografía 134 CAPÍTULO OCHO 135 Bebés animales en peligro: una secuencia didáctica para la producción de textos narrativos, a través de la creación de un libro-álbum 137 8.1 Enfoque teórico 138 8.1.1 Contextualización 138 8.1.2 El libro-álbum 139 8.2 Fases de la secuencia didáctica 140 8.2.1 Objetivos de la secuencia didáctica 140 8.2.2 Descripción de la secuencia 140 8.3 Conclusiones 145 Bibliografía 146 CAPÍTULO NUEVE 147 Los superhéroes: una secuencia didáctica mediada por las TIC para la producción de textos narrativos 149 9.1 Enfoque teórico 150 9.1.1 Contexto general 150 9.1.2 El cómic y su trabajo desde un enfoque comunicativo 152 9.2 Fases de la secuencia didáctica 153 9.2.1 Objetivos 153 9.2.2 Descripción de la secuencia 154 9.2.3 Procedimiento 154 9.3 Conclusiones 158 Bibliografía 160 CAPÍTULO DIEZ 163 De la bombilla al lápiz. El cómic, input para la producción de textos narrativos 165 10.1 Enfoque teórico 165 10.2 Fases de la secuencia didáctica 167 10.3 Conclusiones 176 Bibliografía 178 CAPÍTULO ONCE 179 El rey del ocaso: una secuencia didáctica de enfoque comunicativo, para la producción de textos expositivo-descriptivos en inglés, con estudiantes de grado cuarto y quinto de la Institución Educativa Ciudadela del Sur 181 11.1 Enfoque teórico 182 11.1.1 Contextualización 182 11.2 Fases de la secuencia didáctica 182 11.2.1 Objetivo general de la secuencia didáctica 182 11.2.2 Realización de la secuencia didáctica 183 11.3 Conclusiones 191 Bibliografía 193 CAPÍTULO DOCE 195 El deporte opina: producción colaborativa de textos argumentativos, con estudiantes universitarios 197 12.1 Enfoque teórico 198 12.1.1 El porqué de la secuencia 198 12.1.2 El texto argumentativo 199 12.1.3 El contexto de la secuencia 201 12.2 Fases de la secuencia didáctica 201 12.3 Conclusiones 209 Bibliografía 211 CAPÍTULO TRECE 215 13.1 Enfoque teórico 217 13.1.1 Justificación 217 No pensemos para hablar, hablemos para pensar: Una secuencia didáctica para la producción de textos argumentativos, a través de la conversación 217 13.1.2 ¿Por qué el texto argumentativo? 219 13.2 Fases de la secuencia didáctica 220 13.3 Conclusiones 232 Bibliografía 233 A MANERA DE CIERRE 23

Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway

Objectives: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc. Methods: This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method. Results: Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis (p=3.08×10−13, OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals (p=2.28×10−3, OR=0.80; p=1.27×10−3, OR=0.59; p=2.63×10−5, OR=0.83, respectively). Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants. Conclusions: We report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology