563 research outputs found
Language therapy effects on the treated and untreated languages of a multilingual person with aphasia
We administered language treatment in the first language of a multilingual person with aphasia and tested his skills pre- and post-treatment in his additional languages. We report improvement in object and action naming in the treated language (Catalan, the participantâs L1). Small cross-language generalization was found for Spanish, his highly-proficient, early-acquired, L2 as well as for English, his least-proficient language. Improvement was noted not only in items that were translation-equivalents of trained items but also of untrained items. Cognate status did not seem to influence the results
The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles
Tissue factor (TF) is critical for the activation of blood coagulation. TF function is regulated by the amount of externalised phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the surface of the cell in which it is expressed. We investigated the role PS and PE in fibroblast TF function. Fibroblasts expressed 6â9 x 104 TF molecules/cell but had low specific activity for FXa generation. We confirmed that this was associated with minimal externalized PS and PE and characterised for the first time the molecular species of PS/PE demonstrating that these differed from those found in platelets. Mechanical damage of fibroblasts, used to simulate vascular injury, increased externalized PS/PE and led to a 7-fold increase in FXa generation that was inhibited by annexin V and an anti-TF antibody. Platelet-derived extracellular vesicles (EVs), that did not express TF, supported minimal FVIIa-dependent FXa generation but substantially increased fibroblast TF activity. This enhancement in fibroblast TF activity could also be achieved using synthetic liposomes comprising 10% PS without TF. In conclusion, despite high levels of surface TF expression, healthy fibroblasts express low levels of external-facing PS and PE limiting their ability to generate FXa. Addition of platelet-derived TF-negative EVs or artificial liposomes enhanced fibroblast TF activity in a PS dependent manner. These findings contribute information about the mechanisms that control TF function in the fibroblast membrane
Polyamines Drive Myeloid Cell Survival by Buffering Intracellular pH to Promote Immunosuppression in Glioblastoma
Glioblastoma is characterized by the robust infiltration of immunosuppressive tumor-associated myeloid cells (TAMCs). It is not fully understood how TAMCs survive in the acidic tumor microenvironment to cause immunosuppression in glioblastoma. Metabolic and RNA-seq analysis of TAMCs revealed that the arginine-ornithine-polyamine axis is up-regulated in glioblastoma TAMCs but not in tumor-infiltrating CD8+ T cells. Active de novo synthesis of highly basic polyamines within TAMCs efficiently buffered low intracellular pH to support the survival of these immunosuppressive cells in the harsh acidic environment of solid tumors. Administration of difluoromethylornithine (DFMO), a clinically approved inhibitor of polyamine generation, enhanced animal survival in immunocompetent mice by causing a tumor-specific reduction of polyamines and decreased intracellular pH in TAMCs. DFMO combination with immunotherapy or radiotherapy further enhanced animal survival. These findings indicate that polyamines are used by glioblastoma TAMCs to maintain normal intracellular pH and cell survival and thus promote immunosuppression during tumor evolution
Reprint: Learning With a Strategic Management Simulation Q2 Game: A Case Study
The use of simulation games as a pedagogic method is well established though its effective
use is context-driven. This study adds to the increasing growing body of empirical evidence
of the effectiveness of simulation games but more importantly emphasises why by
explaining the instructional design implemented reflecting best practices. This multimethod
study finds evidence that student learning was enhanced through the use of
simulation games, reflected in the two key themes; simulation games as a catalyst for
learning and simulation games as a vehicle for learning. In so doing the research provides
one of the few empirically based studies that support simulation games in enhancing
learning and, more importantly, contextualizes the enhancement in terms of the
instructional design of the curriculum. This research should prove valuable for those with
an academic interest in the use of simulation games and management educators who use,
or are considering its use. Further, the findings contribute to the academic debate concerning
the effective implementation of simulation game-based training in business and
management education
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Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation
Background: Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Methods and Findings: Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (â„3,200 copies/”l plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6â15.8, p = 1Ă10â7) and ME ARDS (OR 8.4, 95% CI 2.9â24.2, p = 9Ă10â5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1Ă10â4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Conclusions: Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors' Summar
Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players.
Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability
Cuerpo extraño inusual en recto como causa de obstrucción intestinal, Reporte de un caso.
The rectum, the penultimate portion of the large intestine, tends to be of special interest due to so-called anorectal emergencies, which are defined as âa wide variety of conditions that share common symptoms, such as anorectal pain or bleeding, which may require immediate management." These emergencies are considered a public health problem that result in a large economic expense, time, medications, days of working life and culmination of quality of life. The presence of a foreign body in the rectum constitutes a challenge for the surgeon. This pathology shows a wide predisposition for the male gender with a peak in its presentation between 20 and 40 years, being the main etiology of a sexual nature, which is why patients often tend to avoid seeking help for fear of being judged.
We present the case of a 33-year-old man, with a history of chronic alcoholism, in the process of rehabilitation admitted to a clinic, where he was referred for presenting abdominal pain, vomiting on numerous occasions, and inability to evacuate for 3 days. , in addition to transanal bleeding in a mild to moderate amount, fetid, dark liquid, a simple and contrast-enhanced tomography is performed, showing the presence of impaction at the level of the rectal ampulla of apparent "bird bones", which is corroborated after directed questioning and rectal exploration with extraction of some pieces. He is admitted to the operating room where the foreign body is extracted under regional anesthesia and instrumentation, he is hospitalized and managed with laxatives, he is discharged after 4 days due to improvement.El recto, la penĂșltima porciĂłn del intestino grueso, tiende a ser de especial interĂ©s debido a las denominadas urgencias anorrectales, las cuales se definen como âuna amplia variedad de enfermedades que comparten sĂntomas en comĂșn, como son dolor anorrectal o sangrado, las cuales pueden requerir de manejo inmediatoâ. Estas urgencias, son consideradas un problema de salud pĂșblica que derivan en un gran gasto econĂłmico, tiempo, medicamentos, dĂas de vida laboral y afectan la calidad de vida. La presencia de un cuerpo extraño en el recto constituye un reto para el cirujano. Esta patologĂa muestra una amplia predisposiciĂłn por el gĂ©nero masculino con un pico en su presentaciĂłn entre los 20 y 40 años, siendo la principal etiologĂa de Ăndole sexual por lo que muchas veces los pacientes tienden a evitar el buscar ayuda por miedo a ser juzgados.
Se presenta el caso de un hombre de 33 años de edad, con antecedente de alcoholismo crĂłnico, en proceso de rehabilitaciĂłn internado en una clĂnica, de donde es referido por presentar dolor abdminal, vĂČmito en numerosas ocasiones e incapacidad para evacuar de 3 dĂas de evoluciĂłn, ademĂĄs de sangrado transanal en cantidad leve a moderada, fĂ©tida, lĂquida oscura, se realiza tomografĂa simple y contrastada que muestra la presencia de impactaciĂłn a nivel de ĂĄmpula rectal de aparentes âhuesos de polloâ, el cual se corrobora tras el interrogatorio dirigido y la exploraciĂłn rectal con extracciĂłn de algunas piezas. Es ingresado a sala de quirĂłfano donde se extrae bajo bloqueo regional y con instrumentaciĂłn el cuerpo extraño, es hospitalizado y manejado con laxantes, se egresa a los 4 dĂas por mejorĂa
Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases
BackgroundPro-inflammatory fibroblasts are critical for pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögrenâs syndrome and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited our understanding of which pathways are shared by multiple diseases.MethodsWe profiled fibroblasts derived from inflamed and non-inflamed synovium, intestine, lungs, and salivary glands from affected individuals with single-cell RNA sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes.FindingsTwo shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts, were expanded in all inflamed tissues and mapped to dermal analogs in a public atopic dermatitis atlas. We confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation.ConclusionsThis work represents a thorough investigation into fibroblasts across organ systems, individual donors, and disease states that reveals shared pathogenic activation states across four chronic inflammatory diseases.FundingGrant from F. Hoffmann-La Roche (Roche) AG
Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases
BackgroundPro-inflammatory fibroblasts are critical for pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögrenâs syndrome and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited our understanding of which pathways are shared by multiple diseases.MethodsWe profiled fibroblasts derived from inflamed and non-inflamed synovium, intestine, lungs, and salivary glands from affected individuals with single-cell RNA sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes.FindingsTwo shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts, were expanded in all inflamed tissues and mapped to dermal analogs in a public atopic dermatitis atlas. We confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation.ConclusionsThis work represents a thorough investigation into fibroblasts across organ systems, individual donors, and disease states that reveals shared pathogenic activation states across four chronic inflammatory diseases.FundingGrant from F. Hoffmann-La Roche (Roche) AG
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