Miracle-dz/UniFAR-FTUs huggingface dataset:
Interferon‐gamma‐expressing cells are a major source of interleukin‐21 in inflammatory bowel diseases

Background: We previously demonstrated that in inflammatory bowel disease (IBD) there is enhanced production of interleukin (IL)‐21, a cytokine that activates multiple pathways that sustain mucosal inflammation. However, the phenotype of IL‐21‐producing cells in IBD, and the cytokine(s) they coproduce, is not known. We here characterized the cell source of IL‐21 and determined which factors regulate IL‐21 in the human gut. Methods: Cytokines were analyzed in CD4+ T intestinal lamina propria lymphocytes (T‐LPL) isolated from IBD patients and controls by flow cytometry. Moreover, IL‐21 was evaluated in mucosal T follicular cells (TFH). To assess the involvement of IL‐12 and IL‐23 in the production of IL‐21, T‐LPL were activated in the presence or absence of IL‐12 or IL‐23. Results: The proportion of IL‐21‐producing CD4+ T‐LPL was increased in IBD compared to controls. The majority of IL‐21‐producing T‐LPL coexpressed interferon (IFN)‐&ggr;, and to a lesser extent IL‐4 or IL‐17A. Activation of CD4+ T‐LPL with IL‐12 but not IL‐23 enhanced the fraction of cells coexpressing IL‐21 and IFN‐&ggr;. TFH cells in LPL were identified by CXCR5 expression and expressed IL‐21 both in IBD and controls; however, the fraction of IL‐21‐positive TFH cells was higher in Crohn's disease than in ulcerative colitis and controls. Treatment of CD4+ T‐LPL with IL‐12 enhanced the frequency of CXCR5+ IL‐21‐producing TFH cells. Conclusions: These findings indicate that in IBD IL‐21 is mostly produced by CD4+ T‐LPL coexpressing IFN‐&ggr;, reinforcing the concept that distinct subsets of T cells can produce IL‐21. Inflamm Bowel Dis 2010
Aspectos genéticos da obesidade

A obesidade definida como a acumulacao excessiva de gordura corporal deriva de um desequilibrio cronico entre a energia ingerida e a energia gasta. Neste desequilibrio podem estar implicados diversos fatores relacionados com o estilo de vida (dieta e exercicio fisico), alteracoes neuro-endocrinas, juntamente com um componente hereditario. O componente genetico constitui um fator determinante de algumas doencas congenitas e um elemento de risco para diversas doencas cronicas como diabetes, osteoporose, hipertensao, câncer, obesidade, entre outras. O aumento da prevalencia da obesidade em quase todos os paises durante os ultimos anos, parece indicar que existe uma predisposicao ou susceptibilidade genetica para a obesidade, sobre a qual atuam os fatores ambientais relacionados com os estilos de vida, em que se incluem principalmente os habitos alimentares e a atividade fisica. A utilizacao de modelos animais de obesidade, a transferencia genica e os estudos de associacao e ligamento, permitiram a identificacao de varios genes implicados na obesidade.
Probiotic and prebiotic use in patients with inflammatory bowel disease: A case‐control study†

Background: The use of complementary and alternative medicine in inflammatory bowel disease (IBD) has been extensively studied. However, the use of probiotics and prebiotics is poorly documented, despite evidence of efficacy of particular probiotic strains in specific forms of IBD. Methods: A case‐control study comprising interviewer‐administered questionnaires was conducted in IBD patients and healthy controls. Data regarding use and knowledge of probiotics and prebiotics, demographic, and clinical information were collected. Results: In total, 334 participants (234 IBD, 100 controls) were interviewed. Significantly more IBD patients than controls had ever used probiotics to manage their health (Crohn's disease [CD] 43%, ulcerative colitis [UC] 51%, controls 21%, P < 0.001). Prebiotic use was negligible. On logistic regression analysis, having UC (odds ratio [OR] 4.30, 95% confidence interval [CI] 2.27–8.12) or CD (OR 3.05, 95% CI 1.66–5.60) were the strongest predictors of probiotic use. Within IBD patients the strongest predictor of probiotic use was current steroid use (OR 2.4, 95% CI 1.11–5.18). IBD patients had greater probiotic knowledge scores than controls (P = 0.003), although 20% of IBD probiotic users could not provide a definition of a probiotic. Less than half of IBD probiotic users discussed probiotic use with healthcare professionals, with commercial advertising being the primary source of information. Conclusions: Patients with IBD use probiotics to manage their health but frequently choose strains without evidence of efficacy in IBD. Patients rely on nonclinical sources of information and often do not disclose probiotic use to healthcare professionals. Conventional healthcare providers should inquire about probiotic use among their patients and offer evidence‐based advice. (Inflamm Bowel Dis 2010)
Immunosuppressive effects of tacrolimus on macrophages ameliorate experimental colitis

Background: Tacrolimus is a novel immunomodulator for inflammatory bowel diseases. Immunosuppressive effects of tacrolimus on T cells are well known; however, the effects of tacrolimus on macrophages remain unclear. The aim of this study was to investigate the effects of tacrolimus on activated macrophages and to examine its efficacy in murine colitis models. Methods: Proinflammatory cytokine production from lipopolysaccharide (LPS)–stimulated peritoneal macrophages of IL‐10‐knockout (KO) mice with and without tacrolimus was measured. We investigated the effects of tacrolimus on nuclear factor‐&kgr;B (NF‐&kgr;B), mitogen‐activated protein kinase (MAPK), and caspase activation in macrophages and the induction of apoptosis in macrophages in vitro and examined the in vivo apoptotic effect of tacrolimus on colonic macrophages in IL‐10‐KO mice. We evaluated the effect of the rectal administration of tacrolimus on colonic inflammation in IL‐10‐KO mice and dextran sulfate sodium (DSS)–induced colitis in CB.17/SCID mice. Results: Proinflammatory cytokine production from tacrolimus‐treated macrophages was significantly lower than that from untreated cells. Tacrolimus suppressed LPS‐induced activation of both NF‐&kgr;B and MAPK in macrophages and induced apoptosis of macrophages via activation of caspases 3 and 9. Rectal administration of tacrolimus evoked apoptosis of colonic macrophages in IL‐10‐KO mice. Moreover, the rectal administration of tacrolimus ameliorated colitis in IL‐10‐KO mice and DSS‐induced colitis in CB.17/SCID mice. Gene expression of inflammatory cytokines in colonic mucosa was significantly lower in tacrolimus‐treated mice than in untreated mice. Conclusions: Tacrolimus suppresses the function of activated macrophages and promotes their apoptosis, which may lead to the amelioration of colonic inflammation. Inflamm Bowel Dis 2010
Enabling devices, empowering people: The design and evaluation of Trackball EdgeWrite

Purpose. To describe the research and development that led to Trackball EdgeWrite, a gestural text entry method that improves desktop input for some people with motor impairments. To compare the character-level version of this technique with a new word-level version. Further, to compare the technique with competitor techniques that use on-screen keyboards. Method. A rapid and iterative design-and-test approach was used to generate working prototypes and elicit quantitative and qualitative feedback from a veteran trackball user. In addition, theoretical modelling based on the Steering law was used to compare competing designs. Results. One result is a refined software artifact, Trackball EdgeWrite, which represents the outcome of this investigation. A theoretical result shows the speed benefit of word-level stroking compared to character-level stroking, which resulted in a 45.0% improvement. Empirical results of a trackball user with a spinal cord injury indicate a peak performance of 8.25 wpm with the character-level version of Trackball EdgeWrite and 12.09 wpm with the word-level version, a 46.5% improvement. Log file analysis of extended real-world text entry shows stroke savings of 43.9% with the word-level version. Both versions of Trackball EdgeWrite were better than on-screen keyboards, particularly regarding user preferences. Follow-up correspondence shows that the veteran trackball user with a spinal cord injury still uses Trackball EdgeWrite on a daily basis 2 years after his initial exposure to the software. Conclusions. Trackball EdgeWrite is a successful new method for desktop text entry and may have further implications for able-bodied users of mobile technologies. Theoretical modelling is useful in combination with empirical testing to explore design alternatives. Single-user lab and field studies can be useful for driving a rapid iterative cycle of innovation and development.
Imaging of Osteochondritis Dissecans of the Knee

The imaging goals in patients with osteochondritis dissecans are lesion identification, characterization, staging, and follow-up. The macroscopic features visible by imaging reflect the microscopic histology of the abnormality. Osteochondritis dissecans involves subchondral bone with possible resultant effect on the overlying articular cartilage. Unresolved, degenerative arthritis, effusion, and loose bodies may occur. In this article, features of the disorder as they appear on plain film, bone scintigraphy, and magnetic resonance imaging are reviewed.
Cognitive design in action: developing assistive technology for situational awareness for persons who are blind

Cognitive design constitutes a cognitively-informed engineering method for developing assistive technologies. The approach is challenging in that it involves matching key cognitive principles for a given problem domain to engineering principles, and that an independent validation procedure is required for the cognitive component. In addition, we argue for a broad set of evaluation criteria and adapt a participatory design framework, one that involves the client population throughout the design process. After laying out the main precepts of the approach, we illustrate these via a particular design process, seeking to provide situational awareness and navigational assistance to persons who are blind. The problem domain is described in some detail. A solution is then presented that involves matching the need for configural knowledge about the person's surroundings with a hierarchical organisation in the spatial database so that information may be presented to the user at different levels of detail. The process involved to implement this solution is then outlined, and appropriate validation experiments described. It is noted that the cognitive design process as presented here is in use now in a number of initiatives, and that it involves a high degree of collaboration between experts from different disciplines.
Neurochemistry and Plasticity of the Median Eminence and Neural Pituitary Lobe in Relation to Background Adaptation of Xenopus laevis

Using immunocytochemistry and morphometry we have supported our hypothesis that magnocellular neurons in the preoptic area of the brain of Xenopus laevis release identical sets of neuropeptides containing not only the previously identified vasotocin, mesotocin, corticotropin‐releasing factor, thyrotropin‐releasing hormone, brain‐derived neurotrophic factor, urocortin 1, and pituitary adenylate cyclase‐activating peptide but also mesotocin and met‐enkephalin from both neurohemal areas in the pituitary neural lobe and in the median eminence. We also show that the external zone of the median eminence is plastic, depending in size on the state of background illumination.
Deformable Contour-Based Maneuvering Flying Vehicle Tracking in Color Video Sequences

This paper presents a new method for the tracking of maneuvering flying vehicles using a deformable contour model in color video sequences. The proposed approach concentrates on targets with maneuvering motion in sky, which involves fundamental aspect change stemmed from 3D rotation of the target or video camera. In order to segment and track the aircraft in a video, at first, the target contour is initialized manually in a key frame, and then it is matched and tracked automatically in the subsequent frames. Generally active contour models employ a set of energy functions based on edge, texture, color, and shape features. Afterwards, objective function is minimized iteratively to track the target contour. In the proposed algorithm, we employ game of life cellular automaton to manage snake pixels’ (snaxels’) deformation in each epoch of minimization procedure. Furthermore, to cope with the large aspect change of aircraft, a Gaussian model has been taken into account to represent the target color in RGB space. To compensate for changes in luminance and chrominance ingredients of the target, the prior distribution function is dynamically updated during tracking. The proposed algorithm is evaluated using the collected dataset, and the expected probability of tracking error is calculated. Experimental results show positive results for the proposed algorithm.
Two-dimensional speckle tracking imaging detects impaired myocardial performance in children with septic shock, not recognized by conventional echocardiography*

Objective: Sepsis is common in children and often results in cardiac dysfunction. Assessment of patients with sepsis-associated myocardial depression using ejection fraction and fractional shortening with conventional echocardiography is load dependent and often reveals cardiac dysfunction only after clinical deterioration has occurred. Speckle tracking imaging is a novel technology that can assess deformation and strain by tracking displacement of acoustic markers in the myocardium. We hypothesize that speckle tracking imaging will detect cardiac impairments during sepsis that are not appreciated by conventional echocardiography. Design: Retrospective, observational study. Setting: A large, tertiary-care pediatric intensive care unit. Patients: Fifteen pediatric patients with septic shock, and 30 age- and gender-matched healthy controls. Interventions: Transthoracic echocardiograms from subjects with septic shock (by American College of Chest Physicians/Society of Critical Care Medicine consensus criteria) and controls were evaluated. Speckle tracking imaging was used to obtain tissue displacement, velocity, strain, and strain rate in radial, longitudinal, and circumferential planes. Ejection fraction and fractional shortening were determined by conventional methods. Comparisons between groups were made using a paired t test. Measurements and Main Results: Compared to control subjects, children with septic shock demonstrated impaired myocardial performance as quantified by speckle tracking imaging. Significant differences were seen in circumferential and longitudinal strain (p < .001), strain rate (p < .05), radial displacement (p < .001), and rotational velocity and displacement (p < .01). There was no significant difference in ejection fraction and fractional shortening between septic patients and controls. Conclusions: Speckle tracking imaging detected a number of significantly impaired measures of ventricular performance in children with sepsis, not appreciated by conventional echocardiography. This technology may improve our understanding and identification of myocardial depression in the critically ill septic child.
Impulsive Testing of Semicircular‐Canal Function Using Video‐oculography

The head impulse test (HIT) is a safe, quick way of assessing horizontal semicircular‐canal function in patients with peripheral vestibular loss. At the bedside, the clinician identifies “overt” catch‐up saccades back to the target after brisk passive head rotation as an indirect sign of canal paresis. However, saccades during head rotation (“covert” saccades) may not be detectable by the naked eye, and so lead to incorrect diagnosis. Up to now, the scleral search coil technique has been the standard for HIT measurement, but that technique is not practical for routine diagnostic use. A new lightweight, nonslip, high‐speed video‐oculography system (vHIT) that measures eye velocity during horizontal head impulses has been developed. This system is easy to use in a clinical setting, provides an objective measure of the vestibulo‐ocular reflex (VOR), and detects both overt and covert catch‐up saccades in patients with vestibular loss.
Microstructural optimization of MFI-type zeolite membranes for ethanol–water separation

High quality pure-silica MFI-type zeolite membranes are successfully prepared by simply controlling the amount of structure directing agent (SDA), i.e., tetrapropylammonium (TPA+) in the synthesis solution for seeded growth. The effects of several synthesis parameters such as alkalinity (OH−/Si), TPA+ concentration (TPA+/Si), and crystallization time on the membrane pervaporation performance are investigated in detail. The synthesized MFI-type zeolite membranes are thoroughly characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, the water contact angle test, X-ray diffraction (XRD), the pervaporation test and gas permeation. The membrane microstructure is very sensitive to the TPA+/Si ratio of the synthesis solution. At a high TPA+/Si ratio (typically 0.17), parasitic twin crystals are intergrown in the zeolite layer, thus resulting in the formation of membrane defects during SDA removal treatment (calcination at 500 °C). When the membrane is prepared with a low TPA+/Si ratio (≤0.05), the appearance of twin crystals can be significantly suppressed and the synthesized dense MFI-type zeolite membranes exhibit pervaporation separation factors higher than 85 for 5 wt% ethanol–water mixtures at 60 °C. We demonstrate for the first time that controlling the SDA concentration in the precursor solution is beneficial to the elimination of membrane microstructural defects, showing a pathway to high quality MFI-type zeolite membranes.
Investigations into the Inhibitory Effects of Relaxin on Renal Myofibroblast Differentiation

Derived from fibroblasts, myofibroblasts are the principal cells that are responsible for the synthesis and reorganization of excess matrix in renal interstitial fibrosis. Recognized from their de novo expression of α‐smooth muscle actin, myofibroblast differentiation and activity can be influenced by several factors, including a combination of growth factors and other soluble mediators, extracellular matrix components, and mechanical stress. Relaxin has previously been shown to inhibit renal myofibroblast differentiation in vitro, an effect partly mediated through its ability to interfere with the transforming growth factor‐β1 (TGF‐β1) pathway via inhibition of Smad2 phosphorylation and translocation. Furthermore, endogenous relaxin has been shown to protect the kidney from a myofibroblast‐mediated model of injury in vivo. However, the pathways involved in the interaction between relaxin and TGF‐β1 remain unknown. In this report, the inhibitory actions of relaxin on TGF‐β1‐induced renal myofibroblast differentiation are summarized to date, and the potential signaling pathways that are implicated in relaxin's inhibitory actions are discussed.
Acceptability of methods and measures used to determine quality of general practice consultations: results of a focus group study and an acceptability questionnaire

General practitioner activity is increasingly under pressure to monitor its performance. The involvement of service users in the development and assessment of services is said to be a key feature of this process. This article reports on the acceptability among general practitioners of a patient-completed post-consultation measure of outcome (the Patient Enablement Instrument; PEI), and its use in conjunction with two further indicators of quality, namely time spent in consultation and patients reporting knowing the doctor well. The survey was conducted using focus groups and the administration of a postal questionnaire among a group of general practices that had participated and received feedback from a large quantitative study testing these measures. The focus group study provided useful insights into general practitioners' perceptions of patient assessment of their performance and their concerns surrounding the measurement of general practice activity. The general practitioners' perceptions of the measures under the study were enmeshed within these concerns overall. The PEI was seen as being generally acceptable as a measure of patient assessment of care, and the methods of data collection were acceptable for routine use in general practice. General practitioners who performed better in terms of their feedback scores generally approved more of the proposed measures. However, these general practitioners were not comfortable with the concept of assessment of the clinical interaction by patients, and were anxious to link such assessment explicitly with clinical (disease-related) outcome. Doctors who performed ‘better’ were no more likely than those who performed less well to advocate more use of patient assessment, or to believe that patient assessment of consultations is a reliable quality indicator. These concerns need to be addressed if patients' assessments of their care are to be taken seriously.
„Apical ballooning” des linken Ventrikels

HISTORY: A 40-year-old woman and a 50-year-old man were admitted with acute chest pain indicative of an acute coronary syndrome. INVESTIGATIONS: In addition to ECG changes suggestive of acute ischemia and a minor increase in the serum concentration of troponin-I both patients had a severely reduced left ventricular function with extensive apical akinesis on echocardiography (LV- ejection fraction 20, respectively 40%). Stenotic coronary artery disease was excluded by coronary angiography, however left ventriculography showed a "ballooned" apex resembling an aneurysm. DIAGNOSIS, TREATMENT AND COURSE: Both patients were observed and treated symptomatically in the intensive care unit. Within four weeks the LV-function had completely recovered in both patients. Both patients had an atypical acute coronary syndrome as indicated by electrocardiographic signs of ischemia and serological markers. After perusal of the relevant literature the diagnosis of "apical ballooning" based on the finding of a "ballooned" akinesis of the left ventricular apex in the absence of coronary artery stenosis or a reasonable alternative cause of myocardial ischemia was made. The aneurysm-like left ventricular dysfunction is fully reversible without specific treatment. CONCLUSION: Left apical ballooning is a rare, but increasingly recognized diagnosis in patients presenting with the clinical picture of cardiac ischemia in the absence of coronary artery disease. The pathogenesis of the LV-dysfunction, which is reversible, is not known and the prognosis is good in patients who survive the initial period of severe ventricular dysfunction.
Avanafil - a further step to tailoring patient needs and expectations

ABSTRACT Introduction: Phosphodiesterase type 5 inhibitors (PDE5Is) represent the first-line treatment for erectile dysfunction (ED). Almost one in two patients, however, show some level of treatment dissatisfaction and up to 30% fail to respond to any of the currently available PDE5Is. Recently, the second-generation PDE5I avanafil was launched for the treatment of ED. Areas covered: Pivotal studies of clinical development along with placebo-controlled randomized clinical trials (RCTs) of avanafil in patients with ED were reviewed. Studies concerning the pharmacokinetics and pharmacodynamic of the drug were also analysed. A systematic literature search for English-language studies published up to May 2016 using the Medline database was performed. The search included the terms avanafil and ED. Expert commentary: Avanafil is a potent, highly selective PDE5I whose efficacy is comparable to that of currently available PDE5Is in both naïve and previous PDE5I users. Avanafil is effective within approximately 15 minutes of dosing, thus representing the only PDE5I approved for as-needed use, 15 to 30 minutes before sexual activity. Avanafil has high selectivity for the PDE5 isoenzyme, thus resulting in a lower incidence of drug-related side effects compared to other PDE5Is.