Long-term follow-up of IPEX syndrome patients after different therapeutic strategies : an international multicenter retrospective study

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n 5 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term.disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen

Understanding Zea mays genetic influence on the structure and function of the rhizosphere microbiome

Assembly of the plant rhizosphere microbiome is driven by plant genetic and evolutionary history. Plant microbiomes play a major role in altering plant resilience, fitness, nutrition, and productivity. Plant hosts selectively filter microorganisms that colonize their rhizosphere. This selective process is heritable across plant cultivars, yet the implication of heritability on rhizosphere microbiome function has been relatively unexplored. This dissertation attempts to characterize the N-cycling functions associated with heritable recruitment to the rhizosphere microbiome. The following dissertation aims to address these specific objectives: examine whether the contemporary agricultural practices that maize has experienced over the past 50 years of breeding has altered the rhizosphere N-cycling microbiome assembly, determine how domestication altered modern maize rhizosphere microbiome assembly from its ancestral progenitor teosinte, assess whether these genotype driven microbiome assembly processes persist in the field setting and influence N-cycling ecosystem function and finally attempt to determine the underlying genetic regions and mechanisms contributing to differential microbial community assembly and function in the rhizosphere. The findings of these specific objectives suggest that the maize microbiome has been unintentionally altered through the process of contemporary breeding and domestication, resulting in the microbiome interaction to be less agriculturally sustainable. These anthropogenic driven changes to the maize microbiome can be characterized by changes in nitrifying and denitrifying microbiome recruitment that consequently alter the rates of nitrification and denitrification of a soil. Furthermore, wild genetic diversity appears to house more sustainable N-cycling microbiome interactions compared to modern maize. The dissertation closes by showing how “rewilding” the plant microbiome interaction could be a potential solution to improve our agricultural system. Modern agricultural practices have resulted in the unprecedented degradation of our global nitrogen cycle. This N-cycle disruption by agriculture has been primarily driven by the over-application of synthetic N fertilizers. On average only about half of this applied synthetic N is taken up by our focal crop, while the remainder is lost through microbiome activities such as nitrification and denitrification. Broadly, the work in this dissertation shows that genotype-driven rhizosphere microbiome assembly can have a considerable effect on N-cycling functional groups that carry out nitrification and denitrification. Additionally, this dissertation suggests that at least in maize, a global staple crop, it appears that breeding has disrupted N-cycling functional group control in the rhizosphere especially when compared to its wild progenitor teosinte. Finally, we show that modern maize can regain the ability to influence N-cycling microbes in the rhizosphere with genetic introgressions from teosinte. Overall, this dissertation uses a combination of microbial ecology and plant genetics to provide some explanations for why our contemporary agricultural system is so unsustainable (via N-pollution) and provides some potential solutions to improve it (via rewilding).U of I OnlyAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD syste

Factores personales y creencias relacionados con el consumo de alcohol en mujeres embarazadas

The purpose was to determine the consumption of alcohol before and during the gestation in connection with personal characteristics and to identify its beliefs on the consumption of low alcohol the theory of the social representations of Serge Moscovici. The desing, descriptive-correlational. The sample, 165 pregnant women. The questionnaire TWEAK was applied to measure the alcohol consumption of previous alcohol to the pregnancy of 62.4% (95% IC, 0,55-0,70) and during the pregnancy 14.5% (95% IC, 0,15-0,32). Found significant difference of the consumption of alcohol before the pregnancy with the age of the women (H=11.15, p<0.05). The main belief of the women on the consumption of alcohol before the gestation was to socialize and during the pregnancy to have addiction to the alcohol.El propósito fue determinar el consumo de alcohol antes y durante la gestación en relación con las características personales e identificar sus creencias sobre el consumo de alcohol bajo la teoría de las respresentaciones sociales de Serge Moscovici. El diseño, descriptivo-correlacional. La muestra, 165 mujeres embarazadas. Se aplicó el cuestionario TWEAK, para medir el consumo de alcohol. Los resultados mostraron una prevalencia de consumo de alcohol previo al embarazo de 62,4% (95% IC, 0,55 - 0,70) y durante el embarazo 14,5% (95% IC, 0,15 - 0,32). Se encontró una diferencia significativa del consumo de alcohol antes del embarazo con la edad de las mujeres (H= 11,15; p < 0,05). La creencia principal de las mujeres sobre el consumo de alcohol antes de la gestación fue para socializar y durante el embarazo por tener adicción al alcohol. ABSTRACTThe purpose was to determine the consumption of alcohol before and during the gestation in connection with personal characteristics and to identify its beliefs on the consumption of low alcohol the theory of the social representations of Serge Moscovici. The desing, descriptive-correlational. The sample, 165 pregnant women. The questionnaire TWEAK was applied to measure the alcohol consumption of previous alcohol to the pregnancy of 62.4% (95% IC, 0,55-0,70) and during the pregnancy 14.5% (95% IC, 0,15-0,32). Found significant difference of the consumption of alcohol before the pregnancy with the age of the women (H=11.15, p<0.05). The main belief of the women on the consumption of alcohol before the gestation was to socialize and during the pregnancy to have addiction to the alcohol

Factores personales y creencias relacionados con el consumo de alcohol en mujeres embarazadas

The purpose was to determine the consumption of alcohol before and during the gestation in connection with personal characteristics and to identify its beliefs on the consumption of low alcohol the theory of the social representations of Serge Moscovici. The desing, descriptive-correlational. The sample, 165 pregnant women. The questionnaire TWEAK was applied to measure the alcohol consumption of previous alcohol to the pregnancy of 62.4% (95% IC, 0,55-0,70) and during the pregnancy 14.5% (95% IC, 0,15-0,32). Found significant difference of the consumption of alcohol before the pregnancy with the age of the women (H=11.15, p<0.05). The main belief of the women on the consumption of alcohol before the gestation was to socialize and during the pregnancy to have addiction to the alcohol.El propósito fue determinar el consumo de alcohol antes y durante la gestación en relación con las características personales e identificar sus creencias sobre el consumo de alcohol bajo la teoría de las respresentaciones sociales de Serge Moscovici. El diseño, descriptivo-correlacional. La muestra, 165 mujeres embarazadas. Se aplicó el cuestionario TWEAK, para medir el consumo de alcohol. Los resultados mostraron una prevalencia de consumo de alcohol previo al embarazo de 62,4% (95% IC, 0,55 - 0,70) y durante el embarazo 14,5% (95% IC, 0,15 - 0,32). Se encontró una diferencia significativa del consumo de alcohol antes del embarazo con la edad de las mujeres (H= 11,15; p < 0,05). La creencia principal de las mujeres sobre el consumo de alcohol antes de la gestación fue para socializar y durante el embarazo por tener adicción al alcohol. ABSTRACTThe purpose was to determine the consumption of alcohol before and during the gestation in connection with personal characteristics and to identify its beliefs on the consumption of low alcohol the theory of the social representations of Serge Moscovici. The desing, descriptive-correlational. The sample, 165 pregnant women. The questionnaire TWEAK was applied to measure the alcohol consumption of previous alcohol to the pregnancy of 62.4% (95% IC, 0,55-0,70) and during the pregnancy 14.5% (95% IC, 0,15-0,32). Found significant difference of the consumption of alcohol before the pregnancy with the age of the women (H=11.15, p<0.05). The main belief of the women on the consumption of alcohol before the gestation was to socialize and during the pregnancy to have addiction to the alcohol

Forensic parameters and admixture in seven geographical regions of the Guerrero state (South, Mexico) based on STRs of the Globalfiler® kit

Background: New commercial STR kits have emerged with greater numbers of markers, which allows for obtaining stronger conclusions in forensic casework, which has been poorly studied in Mexico. Aim: To obtain forensic parameters and to analyse the genetic relationships, structure and admixture in seven geographic regions of Guerrero state (South, Mexico) based on the Globalfiler® kit. Subjects and methods: A total of 245 unrelated Mexican individuals from seven regions of the state of Guerrero were analysed with the Globalfiler® kit. Forensic parameters, pairwise comparisons, genetic distances, structure analysis and admixture levels were estimated. Results: Allele frequencies and forensic parameters of 22 STRs were estimated in this Mexican population sample. The combined power of exclusion and power of discrimination values were > 99.9999% and >99.99999999%, respectively. The Native American, European and African ancestries estimated in the Guerrero state population were 70.9%, 25.9% and 3.2%, respectively. Conclusion: Forensic validation of the Globalfiler® kit was performed in the Guerrero state population. The geographic isolation level seems to be the principal factor in defining genetic relationships and admixture among the Guerrero sub-populations. Despite the intrinsic limitations of STRs for admixture analysis, these results are very close to previous values based on AIMs and genome-wide SNPs

Analysis of the TSER and G>C variants in the TYMS gene: a high frequency of low expression genotypes predicted in the Mexican population

Background In the TYMS gene promoter, there is a repeat polymorphism (TSER) that affects the expression level of the thymidylate synthetase (TS) enzyme involved in the response to some anticancer drugs. The G>C transversion located in the TSER*3R allele decreases the expression level of the TS enzyme avoiding the upstream stimulatory factor (USF-1) binding site. Despite the biomedical impact of the SNP G>C, only TSER has been reported in most worldwide populations. Thus, we studied both TSER and SNP G>C variants in the Mexican population. Subjects and methods A population sample (n = 156) was genotyped for the TSER and G>C variants by PCR and PCR-RFLPs, respectively, followed by PAGE and silver staining. Results For TSER, the most frequent allele was 2 R (52.56%), as well as the genotype 2 R/3R (42.3%). Comparison with Latin American, European, and American (USA) populations suggest a heterogeneous worldwide distribution (FST-value = 0.01564; p-value = 0.0000). When the G>C variant was included (2RG, 3RG, and 3RC), a high frequency of low expression genotypes was observed: 2RG/2RG, 2RG/3RC, and 3RC/3RC (84.6%). Conclusion The high frequency of genotypes associated with low TS enzyme expression justifies obtaining the TYMS gene variant profile in Mexican patient’s candidates to pharmaceutical treatments like 5’-Fluoracil, methotrexate, and pemetrex

Education in the Anthropocene: Assessing planetary health science standards in the US

The environmental crises defining the Anthropocene demand ubiquitous mitigation efforts, met with collective support. Yet, disengagement and disbelief surrounding planetary health threats are pervasive, especially in the United States (US). This skepticism may be influenced by inadequate education addressing the scope and urgency of the planetary health crisis. We analyzed current K-12 science standards related to planetary health throughout the US, assessing their quality and potential predictors of variation. While planetary health education varies widely across the US with respect to the presence and depth of terms, most science standards neglected to convey these concepts with a sense of urgency. Furthermore, state/territory political affiliation and primary GDP contributor were each predictive of the quality of planetary health education. We propose that a nation-wide science standard could fully address the urgency of the planetary health crisis and prevent political bias from influencing the breadth and depth of concepts covered

Education in the Anthropocene: Assessing planetary health science standards in the US

The environmental crises defining the Anthropocene demand ubiquitous mitigation efforts, met with collective support. Yet, disengagement and disbelief surrounding planetary health threats are pervasive, especially in the United States (US). This skepticism may be influenced by inadequate education addressing the scope and urgency of the planetary health crisis. We analyzed current K-12 science standards related to planetary health throughout the US, assessing their quality and potential predictors of variation. While planetary health education varies widely across the US with respect to the presence and depth of terms, most science standards neglected to convey these concepts with a sense of urgency. Furthermore, state/territory political affiliation and primary GDP contributor were each predictive of the quality of planetary health education. We propose that a nation-wide science standard could fully address the urgency of the planetary health crisis and prevent political bias from influencing the breadth and depth of concepts covered