Impact of gastroesophageal reflux disease on work absenteeism, presenteeism and productivity in daily life: a European observational study

<p>Abstract</p> <p>Background</p> <p>The RANGE (<it>R</it>etrospective <it>AN</it>alysis of <it>G</it>astro<it>E</it>sophageal reflux disease [GERD]) study assessed differences among patients consulting a primary care physician due to GERD-related reasons in terms of: symptoms, diagnosis and management, response to treatment, and effects on productivity, costs and health-related quality of life. This subanalysis of RANGE determined the impact of GERD on productivity in work and daily life.</p> <p>Methods</p> <p>RANGE was conducted at 134 primary care sites across six European countries (Germany, Greece, Norway, Spain, Sweden and the UK). All subjects (aged ≥18 years) who consulted with their primary care physician over a 4-month identification period were screened retrospectively, and those consulting at least once for GERD-related reasons were identified (index visit). From this population, a random sample was selected to enter the study and attended a follow-up appointment, during which the impact of GERD on productivity while working (absenteeism and presenteeism) and in daily life was evaluated using the self-reported Work Productivity and Activity Impairment Questionnaire for patients with GERD (WPAI-GERD).</p> <p>Results</p> <p>Overall, 373,610 subjects consulted with their primary care physician over the 4-month identification period, 12,815 for GERD-related reasons (3.4%); 2678 randomly selected patients attended the follow-up appointment. Average absenteeism due to GERD was highest in Germany (3.2 hours/week) and lowest in the UK (0.4 hours/week), with an average of up to 6.7 additional hours/week lost due to presenteeism in Norway. The average monetary impact of GERD-related work absenteeism and presenteeism were substantial in all countries (from €55/week per employed patient in the UK to €273/patient in Sweden). Reductions in productivity in daily life of up to 26% were observed across the European countries.</p> <p>Conclusion</p> <p>GERD places a significant burden on primary care patients, in terms of work absenteeism and presenteeism and in daily life. The resulting costs to the local economy may be substantial. Improved management of GERD could be expected to lessen the impact of GERD on productivity and reduce costs.</p

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

Resequencing

[ES] La revolución que supone la secuenciación de próxima generación está permitiendo la resecuenciación del genoma completo (WGRS) de cientos o incluso miles de ejemplares de cultivos básicos y especies modelo. Con el lanzamiento de su genoma de referencia, progresivamente se están emprendiendo proyectos WGRS también para otras especies de plantas en una amplia variedad de estudios. En berenjena común (Solanum melongena L.), aunque se ha publicado un primer borrador de la secuencia del genoma de referencia, hasta el momento no se han realizado estudios de resecuenciación. En este capítulo presentamos los primeros resultados de la resecuenciación de ocho accesiones, siete de berenjena común y una del pariente silvestre S. incanum L., que corresponden a los progenitores de un cruce multiparental de generación avanzada (MAGIC) población que se encuentra actualmente en desarrollo utilizando la secuencia del genoma de la berenjena recién desarrollada que se presenta en el Cap. 7 de este libro. Se identificaron más de diez millones de polimorfismos entre las accesiones, el 90% de ellos en el S. incanum silvestre relacionado, lo que confirma la erosión genética de la berenjena común cultivada. Entre los progenitores de la población MAGIC, el patrón de distribución de polimorfismos comunes a lo largo de los cromosomas ha revelado posibles huellas de introgresión ancestral de cruces interespecíficos. El conjunto de polimorfismos se ha anotado extensamente y actualmente se está utilizando para análisis adicionales con el fin de genotipar eficientemente la población MAGIC en curso y diseccionar rasgos agronómicos y morfológicos importantes. La información proporcionada en este primer estudio de resecuenciación en berenjena será extremadamente útil para ayudar al fitomejoramiento a desarrollar nuevas variedades mejoradas y resistentes para enfrentar futuras amenazas y desafíos.[EN] The next-generation sequencing revolution is allowing the whole-genome resequencing (WGRS) of hundreds or even thousands of accessions for staple crops and model species. With the release of their reference genome, progressively also other plants, species are undertaking WGRS projects for a broad variety of studies. In common eggplant (Solanum melongena L.), although a first draft of the reference genome sequence has been published, no resequencing studies have been performed so far. In this chapter, we present the first results of the resequencing of eight accessions, seven of common eggplant and one of the wild relative S. incanum L., that correspond to the parents of a multi-parent advanced generation inter-cross (MAGIC) population that is currently under develop- ment using the newly developed eggplant genome sequence presented in Chap. 7 of this book. Over ten million polymorphisms were identified among the accessions, 90% of them in the wild related S. incanum, confirming the genetic erosion of the cultivated common eggplant. Among the MAGIC population parents, the common polymorphism distribu- tion pattern along the chromosomes has revealed possible footprints of ancestral intro- gression from interspecific crosses. The set of polymorphisms has been extensively anno- tated and currently is being used for further analyses in order to efficiently genotype the ongoing MAGIC population and to dissect important agronomic and morphological traits. The information provided in this first resequencing study in eggplant will be extremely helpful to assist plant breeding to develop new improved and resilient varieties to face future threats and challenges.This work has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 677379 (G2P-SOL project: Linking genetic resources, genomes and phenotypes of Solanaceous crops) and from Spanish Ministerio de Economía, Industria y Competitividad and Fondo Europeo de Desarrollo Regional (grant AGL2015-64755-R from MINECO/FEDER).Prohens Tomás, J.; Vilanova Navarro, S.; Gramazio, P. (2019). Resequencing. En The Eggplant Genome. Springer. 81-89. http://hdl.handle.net/10251/181875S818

Two Brothers with Skewed Thiopurine Metabolism in Ulcerative Colitis Treated Successfully with Allopurinol and Mercaptopurine Dose Reduction

Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism. We discuss two brothers who were both diagnosed with ulcerative colitis (UC). Their disease remained active despite oral and topical mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully introduced for both patients and both were found to have high 6-MMP and low 6-TGN levels, despite normal TMPT enzyme activity, accompanied by transaminitis. Allopurinol was introduced in combination with MP dose reduction. For both brothers addition of allopurinol was associated with successful remission and optimized MP metabolites. These siblings with active UC illustrate that skewed thiopurine metabolism may occur despite normal TPMT enzyme activity and can lead to adverse events in the absence of disease control. We confirm previous data showing that addition of allopurinol can reverse this skewed metabolism, and reduce both hepatotoxicity and disease activity, but we now also introduce the concept of a family history of preferential MP metabolism as a clue to effective management for other family members

Predicting olfactory receptor neuron responses from odorant structure

Background Olfactory receptors work at the interface between the chemical world of volatile molecules and the perception of scent in the brain. Their main purpose is to translate chemical space into information that can be processed by neural circuits. Assuming that these receptors have evolved to cope with this task, the analysis of their coding strategy promises to yield valuable insight in how to encode chemical information in an efficient way. Results We mimicked olfactory coding by modeling responses of primary olfactory neurons to small molecules using a large set of physicochemical molecular descriptors and artificial neural networks. We then tested these models by recording in vivo receptor neuron responses to a new set of odorants and successfully predicted the responses of five out of seven receptor neurons. Correlation coefficients ranged from 0.66 to 0.85, demonstrating the applicability of our approach for the analysis of olfactory receptor activation data. The molecular descriptors that are best-suited for response prediction vary for different receptor neurons, implying that each receptor neuron detects a different aspect of chemical space. Finally, we demonstrate that receptor responses themselves can be used as descriptors in a predictive model of neuron activation. Conclusions The chemical meaning of molecular descriptors helps understand structure-response relationships for olfactory receptors and their 'receptive fields'. Moreover, it is possible to predict receptor neuron activation from chemical structure using machine-learning techniques, although this is still complicated by a lack of training data

The Plasmodium Export Element Revisited

We performed a bioinformatical analysis of protein export elements (PEXEL) in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide

An insertional mutagenesis programme with an enhancer trap for the identification and tagging of genes involved in abiotic stress tolerance in the tomato wild-related species Solanum pennellii

Salinity and drought have a huge impact on agriculture since there are few areas free of these abiotic stresses and the problem continues to increase. In tomato, the most important horticultural crop worldwide, there are accessions of wild-related species with a high degree of tolerance to salinity and drought. Thus, the finding of insertional mutants with other tolerance levels could lead to the identification and tagging of key genes responsible for abiotic stress tolerance. To this end, we are performing an insertional mutagenesis programme with an enhancer trap in the tomato wild-related species Solanum pennellii. First, we developed an efficient transformation method which has allowed us to generate more than 2,000 T-DNA lines. Next, the collection of S. pennelli T0 lines has been screened in saline or drought conditions and several presumptive mutants have been selected for their salt and drought sensitivity. Moreover, T-DNA lines with expression of the reporter uidA gene in specific organs, such as vascular bundles, trichomes and stomata, which may play key roles in processes related to abiotic stress tolerance, have been identified. Finally, the growth of T-DNA lines in control conditions allowed us the identification of different development mutants. Taking into account that progenies from the lines are being obtained and that the collection of T-DNA lines is going to enlarge progressively due to the high transformation efficiency achieved, there are great possibilities for identifying key genes involved in different tolerance mechanisms to salinity and drought

The α1-adrenergic receptors: diversity of signaling networks and regulation

The α1-adrenergic receptor (AR) subtypes (α1a, α1b, and α1d) mediate several physiological effects of epinephrineand norepinephrine. Despite several studies in recombinant systems and insightfrom genetically modified mice, our understanding of the physiological relevance and specificity of the α1-AR subtypes is still limited. Constitutive activity and receptor oligomerization have emerged as potential features regulating receptor function. Another recent paradigm is that βarrestins and G protein-coupled receptors themselves can act as scaffolds binding a variety of proteins and this can result in growing complexity of the receptor-mediated cellular effects. The aim of this review is to summarize our current knowledge on some recently identified functional paradigms and signaling networks that might help to elucidate the functional diversity of the α1-AR subtypes in various organs