Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor

The World Health Organization’s tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RTqPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT.Spanish Ministry of Science and Innovation (PID2021-126111OB-I00)Junta de Andalucía (PIGE-0213-2020, PI-0203-2022)University of Granada (B-CTS-480-UGR20)The Fundaci on Científica Asociaci on Española Contra el Cáncer (LAB-AECC-2018)FPU17/01258 fellowshipPrograma Operativo de Empleo Juvenil y de la Iniciativa de Empleo Juvenil (#04/2022-05)Grant from the Scientific Foundation of the Spanish Association Against Cancer in Granada (#PRDGR21428SAN

Changes in foot posture during pregnancy and their relation with musculoskeletal pain: A longitudinal cohort study

Aim: To examine foot posture changes during the three trimesters of pregnancy and to determine whether there is a relationship between these changes and the pain experienced in this period. Methods: The study sample consisted of 62 pregnant women who attended the Gynaecology Service at Hospital Santa María del Puerto (Cádiz, Spain), between January 2013 and May 2014. In their first visit, the following sociodemographic and anthropometric data were recorded: age, weight, height and foot size. In addition, information was obtained regarding pain in the lower back, knees, ankles and feet. In this first visit, too, the Foot Posture Index (FPI) was assessed, and three subsequent controls were performed during the first, second and third months of pregnancy (termed Stages 1, 2 and 3, respectively). Results: In Stage 1, the average foot size (i.e., shoe size) was 38.3 (SD 1.5). This size did not change between Stages 1, 2 and 3. However, body weight and BMI did present statistically significant changes during this period (p < 0.0001). The FPI varied during pregnancy but no relation was observed between these changes and the onset of pain. Conclusions: During pregnancy, pronation increases but this does not appear to influence the onset of pain in the lower limb

Portable flow multiplexing device for continuous, in situ biodetection of environmental contaminants

A compact, low-cost and low-powered device was developed and arranged for multiplexed biodetection of sea water contaminants from continuous flow mode. Electronics, mechanics and fluidics were designed to guarantee identical functional liquid flow through eight parallel sensor microchambers during a predetermined time period providing 8 values at the same time. The accuracy and repeatability of the device was tested in-lab, achieving a deviation of less than 10% when measuring the same analyte in all the chambers. The experimental results obtained with our device were finally compared with those measured in continuous flux by a commercial potentiostat SP150 (Bio-Logic Science Instruments), obtaining identical results, which validated the proposed device

Redox imbalance is associated to lung damage triggered by silver nanoparticles exposure

Along with the AgNP applications development, the concern about their possible toxicity has increasingly gained attention. As the respiratory system is one of the main exposure routes, the aim of this study was to evaluate the harmful effects developed in the lung after an acute AgNP exposure. In vivo studies using Balb/c mice intranasally instilled with 0.1 mg AgNP/kg b.w, were performed. 99mTc-AgNP showed the lung as the main organ of deposition, where, in turn, AgNP may exert barrier injury observed by increased protein content and total cell count in BAL samples. In vivo acute exposure showed altered lung tissue O2 consumption due to increased mitochondrial active respiration and NOX activity. Both O2 consumption processes release ROS triggering the antioxidant system as observed by the increased SOD, catalase and GPx activities and a decreased GSH/GSSG ratio. In addition, increased protein oxidation was observed after AgNP exposure. In A549 cells, exposure to 2.5 μg/mL AgNP during 1 h resulted in augment NOX activity, decreased mitochondrial ATP associated respiration and higher H2O2 production rate. Lung 3D tissue model showed AgNP-initiated barrier alterations as TEER values decreased and morphological alterations. Taken together, these results show that AgNP exposure alters O2 metabolism leading to alterations in oxygen metabolism lung toxicity. AgNP-triggered oxidative damage may be responsible for the impaired lung function observed due to alveolar epithelial injury.Fil: Garces, Mariana Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Pecorelli, Alessandra. Università di Ferrara; ItaliaFil: Calabró López, María Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Caceres, Lourdes Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Pambianchi, Erika. Università di Ferrara; ItaliaFil: Galdopórpora, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Vico, Tamara Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Salgueiro, María Jimena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Zubillaga, Marcela Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moretton, Marcela Analía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Alvarez, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Valacchi, Giuseppe. Università di Ferrara; ItaliaFil: Evelson, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentin

Quality of Life in Cohabitants of Patients Suffering Inflammatory Bowel Disease: A Cross-Sectional Study

(1) Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition with a significant impact on patients&rsquo; general health perception. No studies have considered consequences of IBD on cohabitants. (2) Aims: The aims of this study were to address the influence of IBD on cohabitants&rsquo; quality of life (QoL) and the factors potentially conditioning this impact. (3) Methods: We conducted a cross-sectional study in which IBD patients and their cohabitants were invited to participate. Validated questionnaires were used to measure QoL in patients and cohabitants. Main clinical and sociodemographic variables were collected. (4) Results: A total of 56 patients and 82 cohabitants with significant QoL impairment were included. A direct association was found between Inflammatory Bowel Disease Questionnaire (IBDQ32) score in patients and the Household Members Quality of Life&mdash;Inflammatory Bowel Disease (HHMQoL-IBD). IBDQ32 was related to the number of flares in the last 12 months, number of hospital admissions and Mayo Score. (5) Conclusions: HHMQoL-IBD score was related to patients IBDQ32 score and the presence of extraintestinal disease. We identified CRP, a marker of disease activity, as a factor related to cohabitants&rsquo; quality of life, pointing to a direct relationship of patients&rsquo; disease activity and their cohabitants&rsquo; quality of life

Quality of Life in Cohabitants of Patients Suffering Inflammatory Bowel Disease: A Cross-Sectional Study.

(1) Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition with a significant impact on patients' general health perception. No studies have considered consequences of IBD on cohabitants. (2) Aims: The aims of this study were to address the influence of IBD on cohabitants' quality of life (QoL) and the factors potentially conditioning this impact. (3) Methods: We conducted a cross-sectional study in which IBD patients and their cohabitants were invited to participate. Validated questionnaires were used to measure QoL in patients and cohabitants. Main clinical and sociodemographic variables were collected. (4) Results: A total of 56 patients and 82 cohabitants with significant QoL impairment were included. A direct association was found between Inflammatory Bowel Disease Questionnaire (IBDQ32) score in patients and the Household Members Quality of Life-Inflammatory Bowel Disease (HHMQoL-IBD). IBDQ32 was related to the number of flares in the last 12 months, number of hospital admissions and Mayo Score. (5) Conclusions: HHMQoL-IBD score was related to patients IBDQ32 score and the presence of extraintestinal disease. We identified CRP, a marker of disease activity, as a factor related to cohabitants' quality of life, pointing to a direct relationship of patients' disease activity and their cohabitants' quality of life

Performance of the New ABC and MAP(ASH) Scores in the Prediction of Relevant Outcomes in Upper Gastrointestinal Bleeding

Background & Aims: Several risk scores have been proposed for risk-stratification of patients with upper gastrointestinal bleeding. ABC score was found more accurate predicting mortality than AIMS65. MAP(ASH) is a simple, pre-endoscopy score with a great ability to predict intervention and mortality. The aim of this study was to compare ABC and MAP(ASH) discriminative ability for the prediction of mortality and intervention in UGIB. As a secondary aim we compared both scores with Glasgow-Blatchford score and AIMS65. Methods: Our study included patients admitted to the emergency room of Virgen de las Nieves University Hospital with UGIB (2017-2020). Information regarding clinical, biochemical tests and procedures was collected. Main outcomes were in-hospital mortality and a composite endpoint for intervention. Results: MAP(ASH) and ABC had similar AUROCs for mortality (0.79 vs. 0.80). For intervention, MAP(ASH) (AUROC = 0.75) and ABC (AUROC = 0.72) were also similar. Regarding rebleeding, AUROCs of MAP(ASH) and ABC were 0.67 and 0.61 respectively. No statistically differences were found in these outcomes. With a low threshold for MAP(ASH) <= 2, ABC and MAP(ASH) classified a similar proportion of patients as being at low risk of death (42% vs. 45.2%), with virtually no mortality under these thresholds. Conclusions: MAP(ASH) and ABC were similar for the prediction of relevant outcomes for UGIB, such as intervention, rebleeding and in-hospital mortality, with an accurate selection of low-risk patients. MAP(ASH) has the advantage of being easier to calculate even without the aid of electronic tools

Devices and methods for multiplexing liquid in biosensor micro-chambers

A biosensors device for simultaneous multiple-analyte analysis by a plurality of biosensors dipped in single biosensor micro-chamber flooded with a functional liquid flowing to the biosensor micro-chambers from a fluidic circuit with no symmetry prerequisite comprises micro-valves operably associated to biosensor micro-chambers for selectively allowing the crossing of a functional liquid to the biosensor micro-chambers, a biosensor micro-chamber at a time, according to a pulsating flow mode so that the total flow rate can be greatly reduced and a predetermined amount of a pressured functional liquid is multiplexed to biosensor micro-chambers. Companion methods are defined for such a biosensors device.Dispositivo de biosensores para análisis simultáneo de múltiples analitos por una pluralidad de biosensores sumergidos en una microcámara biosensora inundada con un líquido funcional que fluye a las microcámaras biosensoras a partir de un circuito fluídico sin ningún prerequisito de simetría que comprende microválvulas asociadas operativamente a las microcámaras biosensoras para permitir selectivamente el cruce de un líquido funcional a las microcámaras biosensoras, una microcámara biosensora cada vez, de acuerdo con un modo de flujo pulsante, de manera que el caudal total puede ser reducido en gran medida y una cantidad predeterminada de un líquido funcional presurizado es multiplexado hacia las microcámaras biosensoras. Se definen métodos asociados para dicho dispositivo de biosensores