Pharmacogenetics of trough serum anti-TNF levels in paediatric inflammatory bowel disease.

AIMS: Identifying DNA variants associated with trough serum anti-tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti-TNF levels and whether these variants are differential markers for infliximab and adalimumab. METHODS: We included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty-one polymorphisms were genotyped using real-time PCR. Trough serum anti-TNF levels were measured using enzyme-linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti-TNF drugs was analysed by Fisher exact test, student's t-test and logistic regression. RESULTS: The variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05). CONCLUSION: Genotyping of these DNA variants before starting treatment may help to select the best anti-TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti-TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti-TNF levels.

Genetic Predictors of Long-term Response to Antitumor Necrosis Factor Agents in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Inflammatory bowel disease (IBD) is more complex in children and they will have to live with the disease for much longer. For this reason, it is necessary to optimize treatment. The polymorphisms associated with the response to anti-tumor necrosis factor (TNF) drugs in adults with IBD have not been analyzed in children. The aim of the study was to identify genetic variants associated with the long-term response to anti-TNF drugs in children with IBD. METHODS: An observational, longitudinal, ambispective cohort's study was conducted. We recruited 209 anti-TNF-treated children diagnosed with IBD and genotyped 21 polymorphisms previously studied in adults with Crohn disease (CD) using real-time PCR. The association between single-nucleotide polymorphisms (SNPs) and time-to-failure was analyzed using the log-rank test. RESULTS: After multivariate analysis, 3 SNPs in IL10, IL17A and IL6 were significantly associated with response to anti-TNF treatment among patients diagnosed with CD (rs1800872-HR, 4.749 (95% confidence interval [CI] 1.156-19.517), P value < 0.05; rs2275913-HR, 0.320 [95% CI 0.111-0.920], P value  < 0.05; and rs10499563-HR, 0.210 [95% CI 0.047-0.947], P value 0.05, respectively). None of these SNPs were associated with response to infliximab in adults diagnosed with CD. Among patients diagnosed with ulcerative colitis (UC), 1 SNP in LY96 was significantly associated with response to anti-TNF treatment (rs-11465996-HR, 10.220 [95% CI 1.849-56.504] P value < 0.05). CONCLUSIONS: Genotyping of these DNA variants before starting treatment may help to identify children who are long-term responders to anti-TNF drugs, and thus tailor treatment of pediatric IBD.

Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease.

Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2-∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.

Protein supplement consumption prevalence, habits and complications in adolescents.

INTRODUCTION: The consumption of nutritional and protein supplements by adolescents may have important consequences for their health. METHODS: Prospective observational study based on a survey of adolescents enrolled in 6 schools selected at random in the city of Seville. Our primary objective was to determine the actual consumption of dietary supplements in the adolescent population and quantifying their protein content. RESULTS: We obtained a total of 263 valid responses that showed a prevalence of consumption of nutritional supplements of any kind of 19.01%, of which 56.0% (10.64% of the total) corresponded to adolescents that consumed protein supplements for a mean protein intake of 0.26 g/kg/day (SD, 0.18). The profile of consumers of any type of supplements differed from that of nonconsumers in age, use of long-term medication and weight loss or high-protein diets. The comparison of adolescents who consumed protein supplements versus nonprotein supplements only evinced a significant difference in the control of supplement consumption. Although most of these adolescents were not subject to external control, 25.92% of those who consumed protein supplements were monitored by a professional, compared to 7.38% of consumers of nonprotein supplements. In the group that consumed protein supplements, 85.18% of adolescents achieved the desired effect and 18.51% reported some form of negative effect. CONCLUSIONS: The prevalence of protein supplement consumption among adolescents in our area is 10.64%, with consumption of amounts corresponding to 25% of the recommended daily allowance of protein. The profile of protein supplement consumers is very similar to that of nonprotein supplement consumers.

Confinement, Comfort and Health: Analysis of the Real Influence of Lockdown on University Students during the COVID-19 Pandemic.

The COVID-19 pandemic forced the population worldwide into lockdown. The purpose of this study was to assess the impact of this measure on the health and comfort of university students and the role that the characteristics of the home may have played. It is essential to differentiate between the terms comfort and health both from the medical and architectural perspectives, as there are differences between the two concepts that are, nonetheless, shared by both disciplines. An online survey was fulfilled by 188 medicine and architecture undergraduate students at the University of Seville, Spain. In terms of health, 89% suffered neuropsychiatric disorders (56% anxiety and 49% depression), 38% gained weight and 59% reported alcohol consumption. In relation to comfort, the majority rated their home positively, comfortable in terms of room temperature and noise at night, and they had a good relationship with cohabitants. However, those who did not have a balcony or terrace would have liked to have open spaces They would have also liked to increase the size of their bedroom, where they spent most of their time and where they studied. A built-up environment gave them a sense of being imprisoned, while those who enjoyed open spaces found a sense of peace. The absence of open spaces in the house, the environment and the impossibility of making the most frequently used spaces more flexible may have had negative impacts on the health and comfort of university students during confinement.

Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease.

BACKGROUND: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. METHODS: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. RESULTS: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <-0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). CONCLUSION: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.

Health and Habitability in the Solar Decathlon University Competitions: Statistical Quantification and Real Influence on Comfort Conditions.

Medicine and architecture are disciplines with the main objectives of satisfying the fundamental needs of human beings: health, comfort, well-being, safety, and ensuring an acceptable quality of life in a sustainable habitat. In both areas of knowledge, the advances and the most innovative proposals in the fields of research and teaching are focused on transversal knowledge and the use of learning methods through problem solving (learning by doing). The student competitions called "Solar Decathlon" are focused on the development of these concepts, in which prototypes of sustainable and, as far as possible, healthy social housing are tested. In these university competitions, the design of energy-efficient and comfortable living environments that contribute to the health of the occupants are encouraged; however, the methodology for evaluating the "comfort conditions" stipulated in the competition rules considers only parameters that can be monitored by sensors. For this article, the prototypes presented by the "Solar Decathlon Team of the University of Seville" to the editions of said competition held in Latin America and Europe (in 2015 and 2019, respectively) are being studied. The present research starts from the fact that the unique consideration of measurable indices (such as temperature, humidity, etc.), is clearly insufficient when it comes to evaluating the real conditions of habitability and comfort that a domestic architectural space presents. For this reason, a theoretical-practical analysis is carried out by means of surveys, with the final objective of determining a methodology for evaluating comfort-complementary to that of the competition-which assesses other relevant issues and which, in short, takes into account the repercussion on people's health. From our analysis, we conclude that at least these two methodologies should be used to evaluate comfort because they are individually considered incomplete in terms of the data provided by each one of them. The survey-based methodology provides complementary information on comfort and health that could be taken into account in future editions of Solar Decathlon.