Effect of various dietary regimens on oral challenge with Mycobacterium avium subsp. paratuberculosis in a rabbit model

Rabbits are susceptible to infection by Mycobacterium avium subspecies paratuberculosis (MAP) in both wildlife and experimental conditions. Under the hypotheses that nutrient balance might influence the establishment of infection, we designed an experiment where MAP intestinal colonization was assessed under three dietary regimens: high fiber, high protein, and regular diet in New Zealand white rabbits submitted to oral challenge with MAP.Lowest weight gain (F=5.17, p=0.024), higher tissue culture positivity rates (X2=7.43, p=0.024) and especially extended MAP-compatible lesions (F=5.78, p=0.017) were detected in the regular diet.Taken altogether, results indicate that paratuberculosis infection was achieved affecting mostly regular diet animals and showing that dietary changes may modulate the course of the infection

Azure A embedded in carbon dots as NADH electrocatalyst: Development of a glutamate electrochemical biosensor

Carbon nanodots modified with azure A (AA-CDs) have been synthesized and applied as redox mediator of bioelectrocatalytic reactions. A deep characterization of AA-CDs nanomaterial has been carried out, proving the covalent attachment of azure A molecules into the carbon dots nanostructure. Disposable screen-printed carbon electrodes (SPCE) have been modified with AA-CDs, through the action of chitosan polymer (Chit-AA-CDs/SPCE). The Chit-AA-CDs/SPCE electrocatalytic activity towards the oxidation of NADH has been proved, obtaining excellent results regarding the low oxidation potential achieved (−0.15 V vs. Ag) and low detection and quantification limits (LOD and LOQ) for NADH, 16 and 53 µM, respectively. The developed electrochemical platform has been applied for the construction of a glutamate biosensor by immobilizing L-glutamic dehydrogenase (GLDH/Chit-AA-CDs/SPCE). The morphology of GLDH/Chit-AA-CDs/SPCE platform was analysed by AFM at each different step of the electrode modification process. The resulting biosensing platform is capable of detect NADH enzymatically generated by GLDH in the presence of glutamate and NAD+. Good analytical parameters were obtained for glutamate analysis using GLDH/Chit-AA-CDs/SPCE, as LOD and LOQ of 3.3 and 11 µM, respectively. The biosensor has been successfully applied to the analysis of food and biological samplesThis work has been supported by the Spanish Ministerio de Ciencia e Innovacion (PID2020–116728RB-I00) and Comunidad Autonoma de Madrid (SI3/PJI/2021–00341, P2018/NMT-4349 TRANSNANOAVANSENS Program

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence. © 2024, The Author(s)

A Cross-National Investigation of Hallucination-Like Experiences in 10 Countries: The E-CLECTIC Study

Hallucination-like experiences (HLEs) are typically defined as sensory perceptions in the absence of external stimuli. Multidimensional tools, able to assess different facets of HLEs, are helpful for a better characterization of hallucination proneness and to investigate the cross-national variation in the frequencies of HLEs. The current study set out to establish the validity, factor structure, and measurement invariance of the Launay-Slade Hallucinations Scale-Extended (LSHS-E), a tool to assess HLEs. A total of 4419 respondents from 10 countries were enrolled. Network analyses between the LSHS-E and the 3 dimensions of the Community Assessment of Psychic Experiences (CAPE) were performed to assess convergent and divergent validity of the LSHS-E. Confirmatory factor analysis was used to test its measurement invariance. The best fit was a 4-factor model, which proved invariant by country and clinical status, indicating cross-national stability of the hallucination-proneness construct. Among the different components of hallucination-proneness, auditory-visual HLEs had the strongest association with the positive dimension of the CAPE, compared with the depression and negative dimensions. Participants who reported a diagnosis of a mental disorder scored higher on the 4 LSHS-E factors. Small effect size differences by country were found in the scores of the 4 LSHS-E factors even after taking into account the role of socio-demographic and clinical variables. Due to its good psychometric properties, the LSHS-E is a strong candidate tool for large investigations of HLEs

Enteritis secundaria a nivolumab, una causa creciente de diarrea

La inmunoterapia es una herramienta cada vez más utilizada en el campo de la oncología. Conviene conocerla debido a sus crecientes usos, entre los que se incluye el tratamiento de tumores del aparato digestivo (hepatocarcinoma1, adenocarcinoma colorrectal con alta inestabilidad en microsatelites2) así como por las reacciones adversas que con elevada frecuencia afectan al tubo digestivo. Presentamos el caso de un varón de 74 años, con antecedentes personales de enfermedad pulmonar obstructiva crónica (EPOC) y melanoma con metástasis pulmonares. Debido a estas patologías tomaba de manera habitual inhaladores de salbutamol y había estado en tratamiento con nivolumab, suspendido hacía cuatro meses tras conseguir una respuesta radiológica completa de las metástasis pulmonares. El paciente refería cuadro diarreico de un mes de evolución, consistente en tres a cuadro deposiciones (Bristol 5-6) sin productos patológicos, que afectaban el descanso nocturno, asociaban molestias centroabdominales intermitentes y pérdida de peso de unos 3-4 kg. No había ingerido alimentos crudos, antibióticos o nuevas medicaciones. Tampoco había convivientes con la misma sintomatología ni había realizado viajes al extranjero. Negaba cualquier otra sintomatología y antecedentes familiares de interés. La exploración física era anodina a excepción de unas ligeras molestias a la palpación profunda en mesogastrio..

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: Part 1 (diagnosis)

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-fac

Aproximación al manejo de la disección del tronco celíaco

El dolor abdominal constituye uno de los motivos de consulta más frecuentes en los servicios de Urgencias y de Aparato Digestivo. Además, el diagnóstico diferencial supone un importante reto, dado el amplio abanico de entidades clínicas que pueden provocarlo, algunas de ellas con un pronóstico desfavorable. En este sentido, en algunas cohortes no se ha llegado a un diagnóstico específico en más de un 30% de los casos1, 2. Se presenta el caso de un varón de 40 años, fumador activo desde hace más de 20 años, sin otros antecedentes personales ni familiares de interés, excepto traumatismo cerrado abdominal hace cuatro años, que no seguía tratamiento farmacológico habitual. Presentaba dolor abdominal epigástrico continuo e irradiado hacia ambos hipocondrios, de ocho horas de evolución. No asociaba ictericia mucocutánea ni coluria o acolia, tampoco náuseas ni vómitos ni alteraciones en el ritmo y características de las deposiciones. No presentaba fiebre, síndrome constitucional ni otra sintomatología asociada. A la exploración física destacaba dolor a la palpación de epigastrio, sin signos de irritación peritoneal, con peristaltismo y pulsos distales conservados. Asimismo, no presentaba signos de colagenopatía. Para una primera aproximación diagnóstica se realizó analítica de sangre, destacando como únicos hallazgos ligera alteración del perfil hepático (AST 66 U/L, ALT 58 U/L, GGT 106 U/L, FA 76 U/L) con amilasemia, ..

A Crystalline 1D Dynamic Covalent Polymer

The synthesis of crystalline one-dimensional polymers provides a fundamental understanding about the structure-property relationship in polymeric materials and allows the preparation of materials with enhanced thermal, mechanical, and conducting properties. However, the synthesis of crystalline one-dimensional polymers remains a challenge because polymers tend to adopt amorphous or semicrystalline phases. Herein, we report the synthesis of a crystalline one-dimensional polymer in solution by dynamic covalent chemistry. The structure of the polymer has been unambiguously confirmed by microcrystal electron diffraction that together with charge transport studies and theoretical calculations show how the ?-stacked chains of the polymer generate optimal channels for charge transport

Spoken term detection ALBAYZIN 2014 evaluation: overview, systems, results, and discussion

The electronic version of this article is the complete one and can be found online at: http://dx.doi.org/10.1186/s13636-015-0063-8Spoken term detection (STD) aims at retrieving data from a speech repository given a textual representation of the search term. Nowadays, it is receiving much interest due to the large volume of multimedia information. STD differs from automatic speech recognition (ASR) in that ASR is interested in all the terms/words that appear in the speech data, whereas STD focuses on a selected list of search terms that must be detected within the speech data. This paper presents the systems submitted to the STD ALBAYZIN 2014 evaluation, held as a part of the ALBAYZIN 2014 evaluation campaign within the context of the IberSPEECH 2014 conference. This is the first STD evaluation that deals with Spanish language. The evaluation consists of retrieving the speech files that contain the search terms, indicating their start and end times within the appropriate speech file, along with a score value that reflects the confidence given to the detection of the search term. The evaluation is conducted on a Spanish spontaneous speech database, which comprises a set of talks from workshops and amounts to about 7 h of speech. We present the database, the evaluation metrics, the systems submitted to the evaluation, the results, and a detailed discussion. Four different research groups took part in the evaluation. Evaluation results show reasonable performance for moderate out-of-vocabulary term rate. This paper compares the systems submitted to the evaluation and makes a deep analysis based on some search term properties (term length, in-vocabulary/out-of-vocabulary terms, single-word/multi-word terms, and in-language/foreign terms).This work has been partly supported by project CMC-V2 (TEC2012-37585-C02-01) from the Spanish Ministry of Economy and Competitiveness. This research was also funded by the European Regional Development Fund, the Galician Regional Government (GRC2014/024, “Consolidation of Research Units: AtlantTIC Project” CN2012/160)

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research