The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis

[Background] The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. [Methodology and Results] We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5′ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01–0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = −0.27 [−0.56– −0.01], p = 0.042; TT genotype = −0.68 [−1.64– −0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. [Conclusions] Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.This work was partially supported by the RETICS (Redes Tematicas de Investigación Cooperativa, Cooperative Research Thematic Networks) Program, RD08/0075 (RIER) and FIS (Fondo de Investigación en Salud) Health Research Fund grant FIS 08/0754 to IG-A from Instituto de Salud Carlos III (ISCIII; www.isciii.es) and by grants from the European Innovative Medicines Initiative and BTCure Program (http://www.life-sciences-europe.com/orga​nisation/btcure-project-imi-efpia-201103​-innovative-medicines-initiative-2001-28​657.html). The work of IG-A was in part supported by a Research Intensification Grant from the National Health Care System (Instituto Carlos III; www.isciii.es), Madrid, Spain

From the bacterial citrus microbiome to the selection of potentially host-beneficial microbes

Citrus is the most cultivated fruit crop worldwide. The modern citrus industry needs new bioproducts to overcome phytopathological threats, tolerate stresses and increase yield and quality. Mutualistic microbes from roots significantly impact host physiology and health and are a potentially beneficial resource. The bacterial microbiome can be surveyed to select potentially host-beneficial microbes. To achieve this goal, a prevalent “core-citrus” bacterial microbiome was obtained by picking those operational taxonomic units (OTUs) shared among samples within and across two Citrus rootstock genotypes grown in the same soil for more than 20 years. A sub-selection of main OTUs from the defined "core-citrus" microbiome was made based on abundance, host-enriched versus bulk soil, and rhizosphere-indicator species. In parallel, an extensive census of the cultivable microbiota was performed to collect a large number of bacterial citrus isolates. Metataxonomic data were linked to cultured microbes, matching 16S rRNA gene sequences from bacterial isolates with those counterpart OTU reference sequences from the selected bacterial "core-citrus" microbiome. This approach allowed selection of potentially host-beneficial bacteria to mine for agricultural probiotics in future biotechnological applications required for the citrus industry

Enfermedad de Kawasaki en pediatría: caso clínico

ntroducción: La enfermedad de Kawasaki (EK) es una vasculitis multisistémica que se presenta en la infancia, por lo general es una enfermedad aguda, febril, autolimitada, de etiología desconocida, puede desarrollar alteraciones cardiovasculares; su expresión clínica es variable al presentar inflamación de los vasos de mediano calibre y de múltiples tejidos: pulmonar, meníngeo, cardiaco, urinario, gastrointestinal, musculoesquelético, neurológico o linfático; el diagnóstico es clínico y el tratamiento busca disminuir la duración de los síntomas clínicos y prevenir la presencia de aneurismas coronarios. Objetivo: Describir el caso clínico de un paciente lactante con enfermedad de Kawasaki, donde se identificó criterios clínicos característicos de esta patología. Caso clínico: Paciente masculino de 22 meses de edad, ingresa a urgencias con cuadro clínico evolutivo de 14 días consistente en fiebre, episodios eméticos y dolor abdominal, sin respuesta a acetaminofén, más episodios diarreicos, a los dos días manifiesta exantema generalizado en la región inguinal que se distribuye a testículo derecho, espalda y tórax, posteriormente presenta conjuntivitis bilateral no purulenta durante 3 días, recibió tratamiento con esteroides tópicos y antihistamínicos orales, mejoría parcial con posterior evolución edema testicular derecho, descamación bilateral en manos y pies, se sospecha la EK se envía ecocardiograma transtorácico sin dilataciones aneurismáticas coronarias y se inicia tratamiento con ASA, sin indicación dado tiempo de evolución de inmunoglobulina. Conclusiones: La EK es infrecuente en la infancia y se debe sospechar en pacientes que cursan con cuadro febril prolongado sin respuesta a tratamientos convencionales y en quienes se descarta presencia de otras patologías

Searching for glycosylated natural products in actinomycetes and identification of novel macrolactams and angucyclines

Many bioactive natural products are glycosylated compounds in which the sugar components usually participate in interaction and molecular recognition of the cellular target. Therefore, the presence of sugar moieties is important, in some cases essential, for bioactivity. Searching for novel glycosylated bioactive compounds is an important aim in the field of the research for natural products from actinomycetes. A great majority of these sugar moieties belong to the 6-deoxyhexoses and share two common biosynthetic steps catalyzed by a NDP-D-glucose synthase (GS) and a NDP-D-glucose 4,6-dehydratase (DH). Based on this fact, seventy one Streptomyces strains isolated from the integument of ants of the Tribe Attini were screened for the presence of biosynthetic gene clusters (BGCs) for glycosylated compounds. Total DNAs were analyzed by PCR amplification using oligo primers for GSs and DHs and also for a NDP-D-glucose-2,3-dehydratases. Amplicons were used in gene disruption experiments to generate non-producing mutants in the corresponding clusters. Eleven mutants were obtained and comparative dereplication analyses between the wild type strains and the corresponding mutants allowed in some cases the identification of the compound coded by the corresponding cluster (lobophorins, vicenistatin, chromomycins and benzanthrins) and that of two novel macrolactams (sipanmycin A and B). Several strains did not show UPLC differential peaks between the wild type strain and mutant profiles. However, after genome sequencing of these strains, the activation of the expression of two clusters was achieved by using nutritional and genetic approaches leading to the identification of compounds of the cervimycins family and two novel members of the warkmycins family. Our work defines a useful strategy for the identification new glycosylated compounds by a combination of genome mining, gene inactivation experiments and the activation of silent biosynthetic clusters in Streptomyces strains

Development of Photonic Multi-Sensing Systems Based on Molecular Gates Biorecognition and Plasmonic Sensors: The PHOTONGATE Project

[EN] This paper presents the concept of a novel adaptable sensing solution currently being developed under the EU Commission-founded PHOTONGATE project. This concept will allow for the quantification of multiple analytes of the same or different nature (chemicals, metals, bacteria, etc.) in a single test with levels of sensitivity and selectivity at/or over those offered by current solutions. PHOTONGATE relies on two core technologies: a biochemical technology (molecular gates), which will confer the specificity and, therefore, the capability to be adaptable to the analyte of interest, and which, combined with porous substrates, will increase the sensitivity, and a photonic technology based on localized surface plasmonic resonance (LSPR) structures that serve as transducers for light interaction. Both technologies are in the micron range, facilitating the integration of multiple sensors within a small area (mm2). The concept will be developed for its application in health diagnosis and food safety sectors. It is thought of as an easy-to-use modular concept, which will consist of the sensing module, mainly of a microfluidics cartridge that will house the photonic sensor, and a platform for fluidic handling, optical interrogation, and signal processing. The platform will include a new optical concept, which is fully European Union Made, avoiding optical fibers and expensive optical components.The micro-nanofabrication capabilities required in the PHOTONGATE project- 101093042 are funded by the Pluri-Regional FEDER funding Plan 2014-2020 European Commission. This research project has received funding from the European Union¿s HORIZON-CL4-2022 research and innovation programme under grant agreement ID 101093042, PHOTONGATE projectNieves-Paniagua, Ó.; Ortiz De Zárate-Díaz, D.; Aznar, E.; Caballos-Gómez, MI.; Garrido-García, EM.; Martínez-Máñez, R.; Dortu, F.... (2023). Development of Photonic Multi-Sensing Systems Based on Molecular Gates Biorecognition and Plasmonic Sensors: The PHOTONGATE Project. Sensors. 23(20):1-13. https://doi.org/10.3390/s23208548113232

Medios de comunicación y derecho a la información en Jalisco 2013

En el primer apartado, dedicado al sistema de medios en general, se presentan tres artículos: “Nuevos medios de comunicación en Jalisco”, “c7 ¿medio público o vocero del gobierno?” y “Réquiem por un ombudsman”. El segundo apartado está dedicado al tema de la libertad de expresión; se presentan aquí dos textos: “La vulnerabilidad en un ambiente de cambio. Los ataques a los medios de comunicación en Jalisco durante el año” y “Violaciones a la libertad de expresión de periodistas y trabajadores de medios en Jalisco, 1995-2013”. En el apartado “Derecho a la información, comunicación y política” se ofrecen cuatro textos de índole muy diversa: “La estrategia de comunicación del Gobierno del Estado”, “Diálogos públicos: la discusión de una nueva ley de transparencia para Jalisco”, “Cuando un niño desaparece, el peor enemigo es el tiempo…”, sobre la alerta Amber, y “2013: un año marcado por despidos en diversos periódicos de Guadalajara”. En la sección “Los que se fueron” se presenta la semblanza de Felipe Vicencio. Y en el apartado de “La investigación del observatorio de medios” se comparten los resultados de un trabajo sobre los columnistas de opinión jaliscienses que escriben en la prensa local.ITESO, A.C

Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep.

Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and forested osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis

Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica

Introduction: the aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). Methods: data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. Results: the incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. Conclusions: the risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection

Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA