Miracle-dz/UniFAR-FTUs huggingface dataset:
Pregnane X Receptor Activation Attenuates Inflammation-Associated Intestinal Epithelial Barrier Dysfunction by Inhibiting Cytokine-Induced Myosin Light-Chain Kinase Expression and c-Jun N-Terminal Kinase 1/2 Activation

The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex etiology. IBD is thought to arise in genetically susceptible individuals in the context of aberrant interactions with the intestinal microbiota and other environmental risk factors. Recently, the pregnane X receptor (PXR) was identified as a sensor for microbial metabolites, whose activation can regulate the intestinal epithelial barrier. Mutations in NR1I2, the gene that encodes the PXR, have been linked to IBD, and in animal models, PXR deletion leads to barrier dysfunction. In the current study, we sought to assess the mechanism(s) through which the PXR regulates barrier function during inflammation. In Caco-2 intestinal epithelial cell monolayers, tumor necrosis factor-α/interferon-γ exposure disrupted the barrier and triggered zonula occludens-1 relocalization, increased expression of myosin light-chain kinase (MLCK), and activation of c-Jun N-terminal kinase 1/2 (JNK1/2). Activation of the PXR [rifaximin and [[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]ethenylidene]bis-phosphonic acid tetraethyl ester (SR12813); 10 μM] protected the barrier, an effect that was associated with attenuated MLCK expression and JNK1/2 activation. In vivo, activation of the PXR [pregnenolone 16α-carbonitrile (PCN)] attenuated barrier disruption induced by toll-like receptor 4 activation in wild-type, but not Pxr−/−, mice. Furthermore, PCN treatment protected the barrier in the dextran-sulfate sodium model of experimental colitis, an effect that was associated with reduced expression of mucosal MLCK and phosphorylated JNK1/2. Together, our data suggest that the PXR regulates the intestinal epithelial barrier during inflammation by modulating cytokine-induced MLCK expression and JNK1/2 activation. Thus, targeting the PXR may prove beneficial for the treatment of inflammation-associated barrier disruption in the context of IBD.
The Integration of Clinical and Managerial Supervision: A Critical Literature Review

The introduction of a new development review process, the Knowledge and Skills Framework (KSF), has placed a greater demand on occupational therapists within the health service to be more accountable for practice. It has been proposed that the KSF may provide a useful structure for supervision in order to ensure continual development. Therefore, this literature review looked at the appropriateness of addressing both clinical and managerial issues within the supervisory process. The results indicate that despite many professions being unsure of how best to deliver supervision, there is a common understanding that a structure combining clinical and managerial supervision, such as the KSF, may be useful. It is, however, recommended that the roles of appraiser and supervisor remain separate, because many researchers found conflict within this duality of role as having an impact upon the effectiveness of supervision. It is also recommended that further research be undertaken in order to evaluate formally the effectiveness of integrating the KSF into supervision.
Causas múltiplas de morte relacionadas à tuberculose no Estado do Rio de Janeiro entre 1999 e 2001

OBJETIVO: Avaliar a mortalidade relacionada a tuberculose por meio de causas multiplas. METODOS: Foram estudados todos os obitos de residentes no Estado do Rio de Janeiro entre 1999 e 2001 nos quais havia mencao de tuberculose na declaracao de obito. As disposicoes da Organizacao Mundial da Saude foram usadas para caracterizar causa basica e causas associadas (nao basicas) de morte. RESULTADOS: Nas mortes por tuberculose as afeccoes relacionadas a sua historia natural foram as principais causas associadas, alem do alcoolismo e diabetes. A sindrome da imunodeficiencia adquirida foi a principal causa basica em cerca de tres quintos das mortes em que a tuberculose foi informada como associada. A elevada percentagem de obitos por causas mal definidas, e os baixos numeros de causas informadas por declaracao de obito e de tuberculose como causa associada levam a pressupor certa subestimacao de mortes relacionadas a tuberculose. CONCLUSAO: O estudo mostra que os coeficientes de mortalidade relacionados a tuberculose, calculados pelo numero de causas basicas bem como pelo total de suas mencoes nas declaracoes de obito, sao os maiores do pais. A vigilância epidemiologica das mortes ocorridas, preconizada como medida para orientar as atividades do programa de controle da tuberculose, deve ser efetivada.
Biliary Elimination of Pemetrexed Is Dependent on Mrp2 in Rats: Potential Mechanism of Variable Response in Nonalcoholic Steatohepatitis

Hepatic multidrug resistance–associated protein 2 (MRP2) provides the biliary elimination pathway for many xenobiotics. Disruption of this pathway contributes to retention of these compounds and may ultimately lead to adverse drug reactions. MRP2 mislocalization from the canalicular membrane has been observed in nonalcoholic steatohepatitis (NASH), the late stage of nonalcoholic fatty liver disease, which is characterized by fat accumulation, oxidative stress, inflammation, and fibrosis. MRP2/Mrp2 mislocalization is observed in both human NASH and the rodent methionine and choline–deficient (MCD) diet model, but the extent to which it impacts overall transport capacity of MRP2 is unknown. Pemetrexed is an antifolate chemotherapeutic indicated for non–small cell lung cancer, yet its hepatobiliary elimination pathway has yet to be determined. The purpose of this study was to quantify the loss of Mrp2 function in NASH using an obligate Mrp2 transport substrate. To determine whether pemetrexed is an obligate Mrp2 substrate, its cumulative biliary elimination was compared between wild-type and Mrp2−/− rats. No pemetrexed was detected in the bile of Mrp2−/− rats, indicating pemetrexed is completely reliant on Mrp2 function for biliary elimination. Comparing the biliary elimination of pemetrexed between MCD and control animals identified a transporter-dependent decrease in biliary excretion of 60% in NASH. This study identifies Mrp2 as the exclusive biliary elimination mechanism for pemetrexed, making it a useful in vivo probe substrate for Mrp2 function, and quantifying the loss of function in NASH. This mechanistic feature may provide useful insight into the impact of NASH on interindividual variability in response to pemetrexed.
Volumetric analysis of lung nodules in computed tomography (CT): comparison of two different segmentation algorithm softwares and two different reconstruction filters on automated volume calculation

Background A precise detection of volume change allows for better estimating the biological behavior of the lung nodules. Postprocessing tools with automated detection, segmentation, and volumetric analysis of lung nodules may expedite radiological processes and give additional confidence to the radiologists. Purpose To compare two different postprocessing software algorithms (LMS Lung, Median Technologies; LungCARE®, Siemens) in CT volumetric measurement and to analyze the effect of soft (B30) and hard reconstruction filter (B70) on automated volume measurement. Material and Methods Between January 2010 and April 2010, 45 patients with a total of 113 pulmonary nodules were included. The CT exam was performed on a 64-row multidetector CT scanner (Somatom Sensation, Siemens, Erlangen, Germany) with the following parameters: collimation, 24x1.2 mm; pitch, 1.15; voltage, 120 kVp; reference tube current-time, 100 mAs. Automated volumetric measurement of each lung nodule was performed with the two different postprocessing algorithms based on two reconstruction filters (B30 and B70). The average relative volume measurement difference (VME%) and the limits of agreement between two methods were used for comparison. Results At soft reconstruction filters the LMS system produced mean nodule volumes that were 34.1% (P < 0.0001) larger than those by LungCARE® system. The VME% was 42.2% with a limit of agreement between −53.9% and 138.4%. The volume measurement with soft filters (B30) was significantly larger than with hard filters (B70); 11.2% for LMS and 1.6% for LungCARE®, respectively (both with P < 0.05). LMS measured greater volumes with both filters, 13.6% for soft and 3.8% for hard filters, respectively (P < 0.01 and P > 0.05). Conclusion There is a substantial inter-software (LMS/LungCARE®) as well as intra-software variability (B30/B70) in lung nodule volume measurement; therefore, it is mandatory to use the same equipment with the same reconstruction filter for the follow-up of lung nodule volume.
Incidental findings in computed tomographic angiography for planning percutaneous aortic valve replacement: advanced age, increased cancer prevalence?

Background Increased age is linked with a higher cancer risk according to model calculations. Patients with severe atherosclerotic aortic stenosis are of old age, therefore, a high incidence of malignancies should be found. Purpose To evaluate the prevalence of clinically significant and potentially malignant incidental findings at computed tomographic angiography (CTA) performed in patients with severe aortic stenosis being assessed as to their suitability for transcatheter aortic valve replacement (TAVR). Material and Methods Between August 2008 and April 2010, CTA of the thoraco-abdominal aorta and the pelvic arterial vessels was performed in 131 patients. There were 62 women (47%) and 69 men (53%); the mean age was 81.6 years (range, 64–91 years). Incidental findings were recorded and categorized as potentially malignant, clinically significant, and clinically insignificant. Clinically significant findings were defined as those requiring immediate therapy, intervention or imaging, or follow-up examination. Results Of the 131 study patients, 31 (23.7%) presented significant extravascular incidental findings, 19 (14.5%) in the thorax, and 12 (9.2%) in the abdomen. Five lesions (3.8%) were considered potentially malignant, three of them (2.3%) were new and highly suspicious for malignancies (two renal cell carcinomas and one hepatocellular carcinoma). In two patients (1.5%) mediastinal lymphadenopathy was found (recurrent malignant lymphoma und new metastases from known bladder cancer). Conclusion The prevalence of highly suspicious malignant incidental findings in patients undergoing TAVR is 3.8% with an average age of 81.6 years which is not high compared to prevalence in the literature dealing with patients aged <70 years.
Effects of Acute and Chronic Treatments with Dopamine D2 and D3 Receptor Ligands on Cocaine versus Food Choice in Rats

Dopamine D3 receptor ligands are potential medications for psychostimulant addiction. Medication assessment may benefit from preclinical studies that evaluate chronic medication effects on choice between an abused drug and an alternative, nondrug reinforcer. This study compared acute and chronic effects of dopamine D2- and D3-preferring ligands on choice between intravenous cocaine and palatable food in rats. Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice. Acutely, the D2 agonist R-(−)-norpropylapomorphine (NPA) and antagonist L-741,626 [3-[[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1H-indole] produced leftward and rightward shifts in cocaine dose-effect curves, respectively, whereas the partial agonist terguride had no effect. All three drugs dose-dependently decreased food-maintained responding. Chronically, the effects of R-(−)-norpropylapomorphine and L-741,626 on cocaine self-administration showed marked tolerance, whereas suppression of food-reinforced behavior persisted. Acute effects of the D3 ligands were less systematic and most consistent with nonselective decreases in cocaine- and food-maintained responding. Chronically, the D3 agonist PF-592,379 [5-[(2R,5S)-5-methyl-4-propylmorpholin-2-yl]pyridin-2-amine] increased cocaine choice, whereas an intermediate dose of the D3 antagonist PG01037 [N-[(E)-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]-4-pyridin-2-ylbenzamide] produced a therapeutically desirable decrease in cocaine choice early in treatment; however, tolerance to this effect developed, and lower and higher doses were ineffective. D3 ligands failed to significantly modify total cocaine intake but caused persistent decreases in food intake. Thus, D2-and D3-preferring ligands showed distinct profiles, consistent with different pharmacological actions. In addition, these results highlight the role of acute versus chronic treatment as a determinant of test drug effects. With the possible exception of the D3 antagonist PG01037, no ligand was promising in terms of cocaine addiction treatment.
Absorption, metabolism and excretion of droperidol by human subjects following intramuscular and intravenous administration.

The absorption, metabolism and excretion of droperidol, a neuroleptic agent, was studied in human subjects following intramuscular and intravenous administration of droperido-3PH. Plasma, urinary and fecal levels of droperidol and total radioactivity were measured. Droperidol was rapidly absorbed following intramuscular administration. The plasma-level profiles of droperidol showed characteristic two-compartment open-model kinetics. The initial distribution phase was quite rapid, T1/3=10 minutes. In addition, droperidol was eliminated from the plasma at very similar rates in all subjects (T1/2=134 ± 13 minutes). Approximately 75 per cent of the radioactive dose of droperidol given intramuscularly was excreted in the urine; however, less than 1 per cent of the urinary radioactivity was accounted for by intact droperidol. Approximately 22 per cent of the dose of radioactivity given intramuscularly was recovered in the feces 50 per cent of the fecal radioactivity was intact droperidol), suggesting the possibility of biliary excretion of a portion of the dose.
Histone Deacetylase Inhibitors Relax Mouse Aorta Partly through Their Inhibitory Action on L-Type Ca2+ Channels

Histone deacetylase (HDAC) inhibitors modulate acetylation/deacetylation of histone and nonhistone proteins. They have been widely used for cancer treatment. However, there have been only a few studies investigating the effect of HDAC inhibitors on vascular tone regulation, most of which employed chronic treatment with HDAC inhibitors. In the present study, we found that two hydroxamate-based pan-HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), could partially but acutely relax high extracellular K+-contracted mouse aortas. SAHA and TSA also attenuated the high extracellular K+-induced cytosolic Ca2+ rise and inhibited L-type Ca2+ channel current in whole-cell patch-clamp. These data demonstrate that SAHA could inhibit L-type Ca2+ channels to cause vascular relaxation. In addition, SAHA and TSA dose dependently relaxed the arteries precontracted with phenylephrine. The relaxant effect of SAHA and TSA was greater in phenylephrine-precontracted arteries than in high K+-contracted arteries. Although part of the relaxant effect of SAHA and TSA on phenylephrine-precontracted arteries was related to L-type Ca2+ channels, both agents could also induce relaxation via a mechanism independent of L-type Ca2+ channels. Taken together, HDAC inhibitors SAHA and TSA can acutely relax blood vessels via their inhibitory action on L-type Ca2+ channels and via another L-type Ca2+ channel-independent mechanism.
Clinical and Bronchoscopic Features in Endobronchial Tuberculosis

Background : The incidence of pulmonary tuberculosis has been reducing, but endobronchial tuberculosis continues to be a signigicant heath problem. We performed prospectively bronchoscopy in patients diagnosed with pulmonary tuberculosis in order to evaluate the frequency of endobronchial tuberculosis and its related findings. Follow-up bronchoscopy was also performed after treatment to evaluate the incidence of endobronchial complications such as stenosis and remaining lesions. Methods : From January, 1999 to December, 2003, bronchoscopy was performed on patients newly diagnosed with pulmonary tuberculosis. Results : 458 patients were enrolled in this study, out of 699 patients with pulmonary tuberculosis from 1999 to 2003. 234(51%) had endobronchial tuberculosis. The frequency was 40.3% in males and 66.3% in females, The most common symptom was nonspecific cough and sputum, and the main radiologiy finding was patchy infiltration. The most common subtype of endobronchial tuberculosis was the edema-hyperemic form. The right lung was involved more frequently than the left, and the left upper lobe was the most commonly involved site. 58 patients underwent follow-up bronchoscopy and most of been cured without major sequels. However, 8 patients had a stenosis of trachea and main bronchus, and 6 patients had still had endobronchial lesions. Therefore the treatment was prolonged for 3 months. Conclusion : Endobronchial tuberculosis of pulmonary tuberculosis has been remained of high incidence. bronchoscopic and follow-up bronchoscopy examination needs to evaluate the incidence of endobronchial tuberculosis and its related findings and major complication despite of treatment.
Relationship between cerebrospinal fluid flow, ventricles morphology, and DTI properties in internal capsules: differences between Alzheimer's disease and normal-pressure hydrocephalus

Background Normal-pressure hydrocephalus (NPH) and Alzheimer's disease (AD) have some similar clinical features and both involve white matter and cerebrospinal fluid (CSF) disorders. Purpose To compare putative relationships between ventricular morphology, CSF flow, and white matter diffusion in AD and NPH. Material and Methods Thirty patients (18 with AD and 12 with suspected NPH) were included in the study. All patients underwent a 3-Tesla MRI scan, which included phase-contrast MRI of the aqueduct (to assess the aqueductal CSF stroke volume) and a DTI session (to calculate the fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) in the internal capsules). Results FA was correlated with ventricular volume in the suspected NPH population (P < 0.001; rs = 0.88), whereas the ADC was highly correlated with the aqueductal CSF stroke volume in AD (P < 0.001; rs = 0.79). Conclusion Although AD and NPH both involve CSF disorders, the two diseases do not have the same impact on the internal capsules. The magnitude of the ADC is related to the aqueductal CSF stroke volume in AD, whereas FA is related to ventricular volume in NPH.
Benign Metastasizing Pulmonary Leiomyoma with Hemoptysis.

A benign metastasizing pulmonary leiomyoma(BMPL) is a rare disease that is usually detected years after a hysterectomy or myomectomy. Despite the benign pathological appearance, these tumors can metastasize and become clinically malignant. Recently, we experienced case of BMPL with hemoptysis. A 43-year-old woman, who had undergone a hysterectomy due to uterine leiomyoma 8 years ago, visited our department complaining of intermittent hemoptysis. A chest CT showed bilateral multiple nodular lesions. Video-associated thoracoscopy was performed. The resected small nodular lesion revealed the proliferation of spindle cells without mitosis or nuclear atypism. The lesions tested positive to the smooth muscle marker (actin) by immunohistochemical staining. Therefore, the multiple nodules were considered as benign metastasizing pulmonary leiomyoma from a uterine leiomyoma. GnRH analogue therapy was initiated. A chest CT showed that the size and number of pulmonary lesions did not change after 3 months, and the patient was symptom free.
CARCINOMA OF THE CERVIX OF MICE RECEIVING ESTROGENS

During the past three years hyperplastic epithelial lesions of the cervix have been observed following the injection of estrogens into mice. Recently a carcinoma of the cervix has been obtained which has grown following transplantation without continuing the administration of estrogen to the host. Several investigators have observed abnormal epithelial growths of the uterine cervices of mice following the injection of estrogens. Loeb, Burns, Suntzeff and Moskop 1 reported a precancerous lesion in one mouse. Following the application of estrogen and 1: 2: 5: 6-dibenzanthracene, Perry 2 and Perry and Ginzton 3 observed lesions in the cervices of three mice. Localized infiltrating epithelial overgrowths of the cervix were observed in three partially hysterectomized mice and in two mice with intact uteri following estrogen treatment. 4 Recently precancerous or carcinoma-like lesions of the cervix or vagina have been described. 5 In our laboratory eighteen tumors have been observed in or near
Interactivity — A Key Element of Blended Learning with Flipped Classroom Approach

Blended Learning (BL) with Flipped Classroom (FC) approach could be considered as very useful teaching and learning method for higher education, in particular for master's technical studies. There are different possible paths and e-learning tools available for teachers and students to organize this kind of courses, classes, lectures. This paper presents several case studies focused on the practical implementation and use of various types of interactivities both in the lectures and laboratory classes. The author describes development of ideas and process of activating and interactive collaboration of students in groups as well as implemented ideas for development of interactive educational video materials to be used by students in self-study. Moreover, a project-based and project-oriented learning approach is proposed and discussed to maintain a high level of activity and involvement of students in the teaching process with BL techniques. Finally, some experiences and general reflections are gathered, and the future works are briefly described as well.
Is Clinical Updating a Valuable Mechanism for Enhancing the Student Experience?

This opinion piece aims to clarify the concepts of the theory-practice and practice-theory gaps, and to begin to explore the impact of these gaps on efficacious occupational therapy practice. Any perceived gaps between theoretical knowledge and practice skills may have a detrimental effect on the student experience and, ultimately, upon the production of graduates who are fit for practice and purpose. A number of issues are raised. One significant issue is the value of clinical updating for academic staff and its impact upon the student experience. Another issue is the need for further clarification of the definitions of theory-practice/practice-theory gaps and consideration of the impact of these perceived gaps. A need for further research is identified to explore staff perceptions of these issues.