Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia that leads to acute lung damage, deterioration of lung function, and increased mortality risk. In this study, we investigated ...the effects of the orange coproduct extract (OCE) and the combination of pure hesperidin and oleuropein (HO) on an experimental model of pulmonary fibrosis induced by bleomycin (BLM) in Wistar rats. Rats were divided into six groups: the control group (G1), the BLM group (G2), three groups (G3, G4, G5) receiving a single dose of BLM combined with OCE extract at 100, 200, and 300 mg/kg, and group 6 (G6) receiving a single dose of BLM combined with HO: both pure major phenolic compounds of OCE (hesperidin at 50 mg/kg) and olive leaves (oleuropein at 2.5 mg/kg). Oxidative stress in lung tissues was investigated using catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) assays and the measurement of malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. Treatment with OCE and HO normalized the disturbance in oxidative markers′ levels and showed a significant reduction in fibrosis score with no renal or hepatic toxic effects. In conclusion, OCE and HO exhibit antifibrotic effects on a rat model of pulmonary fibrosis.
Objective:
Many recent studies are pointing out the heterogeneity between pathologists in the classification of malignant pleural mesotheliomas. Besides, they reported the prognostic impact of ...classifying epithelioid mesotheliomas according to the predominant architectural features and the nuclear grade. The authors assessed the interobserver and the intraobserver agreement of subtyping mesotheliomas between 2 pathologists used to thoracic pathology.
Material and Method:
The observers reviewed all the slides of the malignant pleural mesotheliomas diagnosed during the period ranging from 2004 to 2017. The Cohen Kappa was performed in order to evaluate the agreement between both observers into classifying mesotheliomas, subtyping and grading epithelioid mesotheliomas. Two rounds of examination were planned with a delay period of one month. After the first round, the reviewers discussed the different difficulties and challenges they faced. All the statistic tests were performed using the SPSS software version 12.0.
Results:
After the first round, a fair agreement between both observers was reported. After the second round, an improvement of the concordance rate with a good agreement in subtyping epithelioid mesotheliomas was noticed. Concerning the grading of mesotheliomas, the interobserver agreement was poor even after the second round examination. The intraobserver reproducibility of epithelioid mesothelioma subtyping was fair or moderate for both reviewers. The intraobserver agreement was poor concerning the grading of epithelioid mesothelioma.
Conclusion:
Integrating subtyping and grading of epithelioid mesotheliomas into a new classification necessitates an important training of the pathologists. The architectural features’ definitions have to be clarified in order to avoid using own subjective opinions and habits by pathologists.
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic ...acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11.70±1.46 μM, indicating synergic action. TGFβ-transformed HLF, rat lung fibroblasts and L929 cells presented similar sensitivity to CA and CA+RA (20μM+100μM, respectively) treatment. Rat alveolar epithelial cells died only under CA+RA treatment, while A549 cells were not affected. Annexin V staining and DNA quantification suggested that HLF are arrested in G0/G1 cell cycle phase and undergo apoptosis. CA caused sustained activation of phospho-Akt and phospho-p38 expression and inhibition of p21 protein.Addition of RA potentiated these effects, while RA added alone had no action.Only triple combination of inhibitors (MAPK-p38, pan-caspase, PI3K/Akt/autophagy) partially attenuated apoptosis; this suggests that cytotoxicity of CA+RA treatment has a complex mechanism involving several parallel signaling pathways. The in vivo antifibrotic effect of CA and RA was compared with that of Vitamine-E in BLM-induced fibrosis model in rats. We found comparable reduction in fibrosis score by CA, RA and CA+RA, attenuation of collagen deposition and normalization of oxidative stress markers. In conclusion, antifibrotic effect of CA+RA is due to synergistic pro-apoptotic action on lung fibroblasts and myofibroblasts.
IntroductionThe tutor's role has been changing in the active learning methods in comparison to the traditional ones. Tutors are encouraged to become facilitators and to guide the students to ...construct a new knowledge by making bridges with the old one. Tutor's expertise in the active methods has been discussed with different results. The aim of this study was to assess the impact of tutor expertise on the students' scores in active learning methods. MethodsThe authors conducted this meta-analysis under the guidelines of a critical tool for systematic reviews (AMSTAR2). PubMed, Embase, Cochrane library, Scopus and Science Direct were the databases used for searching. The articles included compared students' learning scores according to tutor expertise between 2 groups of students with an active method of learning. The Review Manager software 5.3 was used to conduct this meta-analysis. We considered the mean difference as the effect size. Results3169 students and 222 learning groups of 5 to 10 students were included in this study. The combined mean difference reached 0.84 with 95% CI 0.22, 1.46. A significant difference between the two groups was observed in favour of the non-expert group (p=0.008). The heterogeneity I-square was evaluated to 98%. The Funnel plot reflected no publication bias (p=0.21). A sub-group analysis was performed taking into account the studies dealing with medical curriculum and the assessment methods used. It showed a significant difference between the two groups in favour of non-expert tutors (p<0.05). ConclusionEven if the results of this meta-analysis couldn't be conclusive and can't induce recommendations, they highlighted the tendency of non-expert tutors to be more student-centred. The heterogeneity observed can be decreased by establishing consensual definitions of expertise and assessment tools in further research studies in order to reflect the validity and efficiency of different tutoring styles in active learning methods.
Dear Editor, Mediastinal cysts are benign lesions of mediastinum whose accurate diagnosis is based on the microscopic analysis of the lining epithelium and the cyst wall 1,2. The degeneration of ...mediastinal cysts has been rarely reported in the literature. The authors aimed to describe a well illustrated case of degenerated mediastinal cyst. The authors report the case of a 31-year-old man, without a particular past medical history but with a smoking habit. The patient presented with a cough associated with dyspnea, and a weight loss of 12 kg in a 3-month period. Physical examination revealed a blood pressure of 130/80, a heart rate of 74 bpm, a temperature of 37oC, and a respiratory rate of 16 cycles/min. A search for the Koch bacillus in the sputum was negative. Chest-X-ray revealed a latero-tracheal shadow measuring 10 cm that was situated in the posterior mediastinum (Figure 1A). The CT-scan revealed a posterior and mediastinal mass in contact with D2 and D4 measuring 82x68 mm, without a costal invasion or lymph node metastases (Figure 1B). The diagnoses of a neurogenic tumour or a bronchogenic cyst were suspected. Cystectomy was performed. Perforation of the cyst wall was reported. The gross examination revealed a cystic mass with a necrotic content measuring 80x60x10 mm (Figure 2). The microscopic exam revealed a cystic wall with a largely ulcerated lining and preservation of foci lined by a single cell lining with some calcifications (Figure 3A). Tumour proliferation was observed within the cystic fibrous wall. The epithelium lining was ciliated (Figure 3B). The carcinomatous proliferation was solid and papillary. Tumour cells were ovoid and large, with abundant cytoplasm and nucleated nuclei (Figure 3C-D). Some lesions of dysplasia were noticed (Figure 3E). The possible diagnoses included a seminomatous tumour with a cystic foci, a non seminomatous tumour with cystic foci, thymic carcinoma with a cystic degeneration, a mesothelial cyst degenerated into a mesothelioma, a bronchogenic cyst degenerated into an adenocarcinoma, and an oesophageal cyst degenerated into an adenocarcinoma. Immunohistochemical evaluation was performed using cytokeratin, CD30, PLAP, CD10, cytokeratin 7, cytokeratin 20, CD5, alpha-feto-protein, TTF1, WT1, calretinin, and mesothelin antibodies. The expression of cytokeratin antigen by the tumour cells was detected (Figure 3F). The negativity of PLAP, alpha-feto-protein, and CD30 allowed ruling out the diagnoses of seminomatous or non seminomatous tumour. The negativity of WT1, claretinin, and mesothelin allowed ruling out a mesothelial nature of the cyst and mesothelial nature of the proliferation. The negativity of CD5 helped to rule out a thymic carcinoma. Negativity of CD10, cytokeratin 7, and cytokeratin 20 helped to rule out a possible metastasis. The negativity of TTF1 helped to rule out a pulmonary origin. The diagnosis of a degenerated oesophageal cyst was ruled out because an oesophageal cyst is lined by a multilayer lining. The final diagnosis was degeneration of a bronchogenic cyst. The authors certify that appropriate patient consent was obtained. Mediastinal cysts are benign lesions dominated by bronchogenic cysts in the anterior and middle mediastinum, mesothelial cysts in the middle mediastinum, and oesophageal cysts in the posterior mediastinum 1-3. They are mainly asymptomatic or have a nonspecific presentation 2. In the current case, the presentation was nonspecific and evoked mainly a diagnosis of tuberculosis. Imaging findings may be suggestive of the diagnosis when faced with a cystic lesion. The posterior location of the cyst makes the radiologists consider a neurogenic tumour, mainly a schwannoma or neurofibroma with cystic degeneration 4,5. A positive diagnosis is based on the microscopic exam. The characteristics of the lining are indicative of the diagnosis 6,7. Mesothelial cysts are lined by mesothelial cells that express mesothelial markers such as calretinin and sometimes epithelial markers consisting mainly of cytokeratin antibody. Oesophageal cysts have a gastric lining while bronchogenic cysts have a lining of respiratory epithelium together with bronchogenic glands and muscle fibres in the wall. In our case, the cystic lining was mainly ulcerated with rare remnant foci containing cylindrical or mesothelial-like cells. Besides, some muscle fibres were observed. Immunohistochemistry revealed the expression of epithelial markers by tumour cells, allowing them to show their epithelial nature. In this case, the nature of the cyst was challenging because of the predominance of degenerated foci in the form of adenocarcinoma. The degeneration of mediastinal cysts has been rarely reported in the literature 5,8-12. This case was well illustrated because it represented a dysplastic lesion with a cystic lining showing a continuum with adenocarcinomatous foci.
Context: Pulmonary fibrosis is a devastating disease without effective treatment. Rosemary is appreciated since ancient times for its medicinal properties, while biomolecules originated from the ...plant have an antioxidant and antifibrotic effect.
Objective: The effects of Rosmarinus officinalis L. (Lamiaceae) leaves extract (RO) on bleomycin-induced lung fibrosis were investigated.
Materials and methods: Male Wistar rats were given a single dose of bleomycin (BLM, 4 mg/kg, intratracheal), while RO (75 mg/kg, intraperitoneal) was administered 3 days later and continued for 4 weeks (BLM/RO1-curative group). Alternatively, RO was administered 2 weeks before BLM and continued 15 days thereafter (BLM/RO2-prophylactic group). Antioxidant activities of RO and lung tissues were studied by standard methods. Histological staining revealed lung architecture and collagen deposition. RO was characterized for its polyphenol content and by high-performance liquid chromatography.
Results: RO polyphenol content was 60.52 mg/g of dry weight, carnosic and rosmarinic acids being major components (6.886 and 2.351 mg/g). Antioxidant effect of RO (DPPH and FRAP assay) expressed as IC
50
values were 2.23 μg/mL and 0.074 μg/mL, respectively. In BLM/RO1 and BLM/RO2 lung architecture was less compromised compared to BLM, which was reflected in lower fibrosis score (2.33 ± 0.33 and 1.8 ± 0.32 vs 3.7 ± 0.3). Malondialdehyde levels were attenuated (141% and 108% vs 258% of normal value). Catalase and glutathione-S-transferase activities were normalized (103% and 117% vs 59%, 85% and 69% vs 23%, respectively).
Discussion and conclusion: RO has a protective effect against BLM-induced oxidative stress and lung fibrosis due to its phenolic compounds.
Critical appraisal of medical literature is a challenging step of the evidence-based medicine practice. Many assessment questionnaires have been published in the literature, but they have mainly ...focused on all the evidence-based medicine practice process. The authors aimed to develop and validate a questionnaire assessing the critical appraisal skills of medical students from the same Faculty.
The questionnaire was developed by item generation through a review of the literature and an expert committee. The questionnaire was validated in terms of content validity and construct validity. Fitness of data for analysis was checked through Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity. Construct validity was carried out using a principal axis exploratory factor analysis (EFA) with 'varimax' rotation to study the internal structure of the questionnaire and to extract the test major factors. The questionnaire was administrated to a cohort of under and postgraduate medical students (n=84) to evaluate the test reliability and select the best items. The reliability of the questionnaire was assessed by Cronbach's alpha coefficient to evaluate the internal consistency. The correlations between the self-confidence and satisfaction dimension score, the critical thinking dimension score, the learning style dimension score, the Fresno-adapted test scores and the total score were assessed using the Spearman's correlation test.
The questionnaire consisted of 31 items. A factorial analysis grouped the items into 3 dimensions that consisted of the self-confidence and satisfaction dimension, the critical thinking dimension and the learning style dimension. Cronbach's alpha accounted for 0.95, CI95% 0.9-1 for the entire questionnaire. The factor analysis explained 79.51% of the variance. The external validity assessment based on a Spearman's correlation study highlighted a weak correlation between the total scores and the critical thinking dimension and the self-perception and satisfaction dimension.
In spite of the limitations of this study, mainly the small number of the students recruited, the questionnaire seems to measure with adequate reliability the competences of under and postgraduate medical students.
Pedagogical workshop planning is challenging especially when we aim to promote a reflective practice of the tutees. This practice has been widely discussed in the literature without a real consensus. ...Some authors reported oral exercises or anecdotes, other described writings or even storytelling. The aim of the authors was to describe the different steps performed by the tutors and to assess the tutees’ satisfaction.
This was a pilot study dealing with the use of the prospective strategy principles in order to plan a pedagogical workshop. Included participants were early academic teacher trainees.
The authors illustrated how they planned a pedagogical workshop using the prospective strategy and highlighted the satisfaction of the tutees.
Prospective strategy is mainly used in economic field in order to change the future of the companies by acting on different intervening factors. Associating prospective strategy to pedagogical principles hasn’t been reported in the medical literature and seems to be available in order to induce reflective practice.
La planificación del taller pedagógico es un desafío, especialmente cuando nuestro objetivo es promover una práctica reflexiva de los alumnos. Esta práctica ha sido ampliamente discutida en la literatura sin un consenso real. Algunos autores informaron ejercicios orales o anécdotas, otros escritos descritos o incluso narraciones. El objetivo de los autores fue describir los diferentes pasos realizados por los tutores y evaluar la satisfacción de los alumnos.
Este fue un estudio piloto que trató sobre el uso de los principios de la estrategia prospectiva para planificar un taller pedagógico. Los participantes incluidos fueron los primeros aprendices de docentes académicos.
Los autores ilustraron cómo planearon un taller pedagógico utilizando la estrategia prospectiva y destacaron la satisfacción de los alumnos.
La estrategia prospectiva se utiliza principalmente en el campo económico para cambiar el futuro de las empresas actuando sobre diferentes factores intermedios. Asociar la estrategia prospectiva a los principios pedagógicos no se ha informado en la literatura médica y parece estar disponible para inducir la práctica reflexiva.
Extramedullary hematopoiesis in the posterior mediastinum is rare. Our case interested a 28‐year‐old man with a history of eosinophilia with FIP1L1‐PDGFRA fusion gene who had a mediastinal mass ...surgically excised. Pathological examination concluded to an extramedullary erythropoiesis. This case is original by its location and the presence of only the erythroblastic line rearrangement.
This is the first reported case of extramedullary hematopoiesis interesting only one cell lineage (erythrocytes) presenting as an isolated tumor‐like lesion in the posterior mediastinum in a 28‐year‐old man with a 13‐year history of eosinophilia with FIP1L1‐PDGFRA fusion gene successfully surgically treated.