Fungal and Bacterial Loads: Noninvasive Inflammatory Bowel Disease Biomarkers for the Clinical Setting

Malaltia inflamatòria intestinal; Càrrega microbiana; PrediccióEnfermedad inflamatoria intestinal; Carga microbiana; PredicciónInflammatory bowel disease; Microbial load; PredictionMicrobiome sequence data have been used to characterize Crohn's disease (CD) and ulcerative colitis (UC). Based on these data, we have previously identified microbiomarkers at the genus level to predict CD and CD relapse. However, microbial load was underexplored as a potential biomarker in inflammatory bowel disease (IBD). Here, we sought to study the use of fungal and bacterial loads as biomarkers to detect both CD and UC and CD and UC relapse. We analyzed the fecal fungal and bacterial loads of 294 stool samples obtained from 206 participants using real-time PCR amplification of the ITS2 region and the 16S rRNA gene, respectively. We combined the microbial data with demographic and standard laboratory data to diagnose ileal or ileocolonic CD and UC and predict disease relapse using the random forest algorithm. Fungal and bacterial loads were significantly different between healthy relatives of IBD patients and nonrelated healthy controls, between CD and UC patients in endoscopic remission, and between UC patients in relapse and non-UC individuals. Microbial load data combined with demographic and standard laboratory data improved the performance of the random forest models by 18%, reaching an average area under the receiver operating characteristic curve (AUC) of 0.842 (95% confidence interval [CI], 0.65 to 0.98), for IBD diagnosis and enhanced CD and UC discrimination and CD and UC relapse prediction. Our findings show that fecal fungal and bacterial loads could provide physicians with a noninvasive tool to discriminate disease subtypes or to predict disease flare in the clinical setting. IMPORTANCE Next-generation sequence data analysis has allowed a better understanding of the pathophysiology of IBD, relating microbiome composition and functions to the disease. Microbiome composition profiling may provide efficient diagnosis and prognosis tools in IBD. However, the bacterial and fungal loads of the fecal microbiota are underexplored as potential biomarkers of IBD. Ulcerative colitis (UC) patients have higher fecal fungal and bacterial loads than patients with ileal or ileocolonic CD. CD patients who relapsed harbor more-unstable fungal and bacterial loads than those of relapsed UC patients. Fecal fungal and bacterial load data improved prediction performance by 18% for IBD diagnosis based solely on clinical data and enhanced CD and UC discrimination and prediction of CD and UC relapse. Combined with existing laboratory biomarkers such as fecal calprotectin and C-reactive protein (CRP), microbial loads may improve the diagnostic accuracy of IBD and of ileal CD and UC disease activity and prediction of UC and ileal CD clinical relapse.This work was funded by Instituto de Salud Carlos III, grant PI17/00614, cofinanced by the European Regional Development Fund (ERDF) and by the PERIS (SLT002/16). F. Casellas has received research funding from AbbVie, Ferring, MSD, Shire, and Zambon and speaker fees from AbbVie, Chiesi, Ferring, Gebro, MSD, Shire, Takeda, and Zambon. S. Vermeire has received grant support from AbbVie, MSD, Pfizer, J&J, and Takeda; received speaker fees from AbbVie, MSD, Takeda, Ferring, Dr. Falk Pharma, Hospira, Pfizer Inc., and Tillots; and served as a consultant for AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Robarts clinical trials, Gilead, Celgene, Prometheus, Avaxia, Prodigest, Shire, Pfizer Inc, Galapagos, Mundipharma, Hospira, Celgene, Second Genome, and Janssen. C. Manichanh has received financial support for research from Danone

New lithostratigraphy for the Cantabrian Mountains: A common tectono-stratigraphic evolution for the onset of the Alpine cycle in the W Pyrenean realm, N Spain

The Pyrenean-Cantabrian Orogen arose through the collision of the Iberian and Eurasian plates, mostly in Cenozoic times. This orogen comprises two main mountain ranges, the Pyrenees to the east, and the Cantabrian Mountains to the west. To date, the early Alpine tectono-sedimentary phases preserved in the Cantabrian Mountains, of Permian and Triassic age, have been considered independently from the same phases in neighbouring basins of SW Europe, and even from the eastern part of the same orogeny (the Pyrenean orogeny). In consequence, the beginning of the Alpine cycle in the Cantabrian Mountains has been interpreted within a specific geodynamic context, far from the general evolutionary phases of the western Peri-Tethys basins. Through detailed field work, including geological mapping, sedimentology, lithostratigraphy and petrology of volcanic rocks, and new palaeontological data, here we define several new lithostratigraphical formations and five new tectono-sedimentary cycles (TS I-V) for the initial phases of evolution of the Mesozoic Basque-Cantabrian Basin, interrupted by periods of tectonic stability. To complete this information, we include data from an onshore borehole (Villabona Mine) and two offshore boreholes constrained by 2D reflection seismic profiles acquired in the North Iberian continental platform. The main tectono-sedimentary cycles, related to the deposition of five major identified lithostratigraphic units, can be described as follows: TS I (late Gzelian-early Asselian), relating to the late Variscan deformation and preserved in a single outcrop in all the Cantabrian Mountains (San Tirso Formation). This formation is constituted by medium-distal alluvial fan deposits in which humid intervals predominate, forming some thin coal beds. TS II (Asselian-Sakmarian), a post-Variscan extensional phase with associated calc-alkaline magmatism, represented by profuse volcanic and volcanosedimentary intercalations in the early Permian sedimentary basins (Acebal Formation) and small plutons in surrounding areas. TS III (Kungurian), or reactivation of the post-Variscan extension leading to alluvial and lacustrine carbonate sedimentation in arid climate conditions, which do not change during the rest of the Permian and Triassic periods (Sotres Formation). A generalized karstification in the basin represents the end of Permian deposition, followed by an interruption in sedimentation longer than 30 Myr. The Permian tectono-sedimentary cycles (TS II and TS III) are contemporary with Variscan belt collapse and the basins are controlled by extensional reactivation of NE-SW and E-W Variscan structures, and NW-SE late Variscan structures. TS IV (late Anisian–middle Carnian), renewed sedimentation in more extensive basins, precursors of the great Mesozoic Basque-Cantabrian Basin. This cycle is represented by fluvial deposits (Cicera Formation, or Buntsandstein facies), which are interrupted by the first Mesozoic marine ingression (Rueda Formation, or Muschelkalk facies). TS V (Norian-Rhaetian), or shallow marine carbonate deposits (Transición Formation) related to increasingly compartmentalized sub-basins, controlled by normal faults. This final TS is broadly connected with different basins of the western Peri-Tethys domain. The identification of units TS I-V in the Cantabrian Mountains along with the volcanic character of TS II, all indicate the development of a common post-Variscan to early Alpine tectono-sedimentary evolution for the whole Pyrenean-Cantabrian realm

Bifidobacterium infantis strains with and without a combination of Oligofructose and Inulin (OFI) attenuate inflammation in DSS-induced colitis in rats

BACKGROUND: Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. METHODS: Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1β, TNF-α, IL-10 and TGF-β) and malondialdehyde (MDA). RESULTS: OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1β decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. CONCLUSION: Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations

Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies

Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.This work was supported by Novartis Pharmaceuticals Spain

Polysulfone-modified epoxy networks prepared by reaction induced phase separation

The effect of epoxy/hydrogen-amine ratio and thermoplastic molecular weight on the curing process and final morphology of epoxy thermoset-polysulfone blend is presented. The cure kinetics was followed by differential scanning calorimetry, the beginning of phase separation by was determined by visual inspection and final morphology was analyzed by SEM

Polysulfone-modified epoxy networks prepared by reaction induced phase separation

The effect of epoxy/hydrogen-amine ratio and thermoplastic molecular weight on the curing process and final morphology of epoxy thermoset-polysulfone blend is presented. The cure kinetics was followed by differential scanning calorimetry, the beginning of phase separation by was determined by visual inspection and final morphology was analyzed by SEM

The opinion of patients with inflammatory bowel disease on healthcare received Opinión de los pacientes con enfermedad inflamatoria intestinal sobre la atención sanitaria recibida

Backgrounds and aim: an item to consider in analyzing a healthcare model for a population group suffering from chronic disease is necessary health-care resources, their use, and their rating by endusers. Regarding inflammatory bowel disease (IBD), healthcare resources used by patients are numerous and varied, and yet they have been never assessed. Design: an anonymous self-rated questionnaire has been developed with 24 basic questions on overall disease, who is monitoring the patient, how are visits scheduled, need for urgent care, patient view on how control may be improved, etc. This questionnaire was sent to 393 patients who were asked to fill it out and then return it by mail. Results: two hundred and thirty-seven patients returned a filled-out questionnaire. Most patients were followed up in a hospital, and only 8.8% were being monitored by a general practitioner or area specialist. Ninety-two percent of patients reported visits were routinely scheduled irrespective of clinical status, and 79.6% of patients reported having occasionally presented to an emergency department, because of not knowing what to do or due to having no other resources available in 25.2% of times. This entails that 38% of visits to an emergency unit may be prevented with a better understanding of disease or by means of a phone call. Thirty percent of patients reported that current healthcare is inadequate in terms of contents, form, or waiting time. In all, 97.8% of patients feel that information and knowledge on their disease would help in its control, and 69.6% consider that adequate information would allow them to initiate a proper treatment before visiting their doctor. Family care is another poorly lookedafter aspect that 74.6% of subjects believe would be of help in controlling their disease. Conclusions: overall, the opinion of patients with IBD on healthcare received is good; however, a number of deficiencies were detected, as is the case with insufficient information, care of family members, and healthcare resources accessibility/agility.<br>Fundamento: un elemento a tener en cuenta al analizar un modelo de atención sanitaria dirigido a un grupo de población afecta de una enfermedad crónica es el de los recursos sanitarios necesarios, su utilización y la valoración que tienen los usuarios de ellos. En la enfermedad inflamatoria intestinal (EII) los recursos sanitarios utilizados por los enfermos son numerosos y variados, pero no han sido evaluados. Diseño: se ha realizado una encuesta autorrellenable anónima de 24 preguntas básicas a cerca de datos generales de la enfermedad, quién les controla, cómo se programan las visitas, necesidad de atención urgente, cómo creen que se puede mejorar su control, etc. La encuesta se remitió al domicilio de 393 pacientes para su contestación y se les pidió que la devolvieran por correo. Resultados: doscientos treinta y siete pacientes devolvieron la encuesta cumplimentada. La mayoría de los pacientes eran controlados en un hospital, y sólo el 8,8% lo eran por el médico de cabecera o especialista de zona. El 92% de pacientes refieren que las visitas se programan de forma rutinaria, independientemente del estado clínico. El 79,6% de pacientes refiere haber acudido alguna vez a urgencias, siendo el motivo en el 25,2% de las ocasiones no saber qué hacer o no tener otro recurso disponible. Ello explica que el 38% de visitas al servicio de urgencias se podrían haber evitado con un mejor conocimiento de la enfermedad o una consulta telefónica. El 30% de pacientes refiere que la actual atención sanitaria es inadecuada, ya sea por su contenido, la forma o el tiempo de espera. El 97,8% de pacientes cree que la información y conocimiento de la enfermedad ayudarían a su control, de forma que el 69,6% considera que con la información adecuada podrían iniciar el tratamiento ya antes de la visita médica. Otro aspecto poco atendido, y que el 74,6% de pacientes opina que ayudaría al control de la enfermedad, es la atención a su entorno familiar. Conclusiones: la opinión general de los pacientes con EII sobre la atención sanitaria recibida es, en general buena, sin embargo se detectan carencias como la información insuficiente, el cuidado al entorno familiar y la accesibilidad-agilidad de los recursos sanitarios

Imaging of spontaneous emission from 980 nm tapered lasers with windowed N-contacts

Experimental measurements of the spatial distribution of the spontaneous emission produced inside the cavity of a 4° 980 nm tapered laser are presented and compared with the results of a 2.5 D half-space, hot-cavity simulation. A custom device with a windowed n-contact was designed and fabricated for this work. The effectiveness of this windowed contact was investigated and appears to be satisfactory. The measurement system for photo- and electroluminescence microscopy imaging was quantitatively calibrated with an error of < ±15%. Good agreement between the experimental and simulated results are presented, with an error of ~ 6% in the carrier density at the output facet