Mise au point d’un protocole de recellularisation d’une matrice bronchique équine décellularisée

Les interactions entre la matrice extracellulaire et le muscle lisse jouent un rôle important dans l’asthme, principalement dans le remodelage bronchique asthmatique. Leur étude in vitro semble donner des résultats souvent non extrapolables in vivo, les modèles monocouches n’étant pas fidèles aux interactions tridimensionnelles se produisant du vivant des patients. Cette étude est une mise au point d’un protocole de décellularisation et de recellularisation d’une bronche équine par des cellules musculaires lisses bronchiques. Elle a pour but l’investigation d’une manière plus fidèle à un environnement in vivo de l’impact d’une matrice extracellulaire bronchique asthmatique sur la variation du phénotype des cellules musculaires lisses bronchiques et réciproquement. Une bonne décellularisation nous permettrait d’obtenir une bronche équine exempte de cellules, mais qui maintiendrait une architecture et une composition matricielle inchangées. L’élimination du matériel cellulaire est nécessaire afin de ne pas confondre les cellules natives du tissu avec les cellules de culture et de ne pas affecter la qualité de la recellularisation. Suite à la décellularisation d’une bronche équine au moyen du protocole Triton / Sodium déoxycholate, nous avons obtenu une bronche acellulaire (échafaud) présentant une très faible quantité d’ADN double brin (moins de 100 pg/100 mg de poids sec) et l’ADN restant était d’un poids moléculaire inférieur à 100 paires de bases. Cet échafaud a maintenu une très bonne architecture et un contenu protéique presque inchangé en collagènes, en fibronectine et en élastine. La recellularisation de cette matrice avec des cellules musculaires lisses bronchiques primaires a donné des résultats exploitables entre 31 et 41 jours de culture. L’évaluation histologique des recellularisations a montré une colonisation spécifique des cellules musculaires lisses bronchiques de la matrice du muscle lisse bronchique. Cette étude montre qu’il est possible de décellulariser une bronche tout en maintenant un contenu protéique et une architecture favorables à sa recellularisation par des cellules musculaires lisses bronchiques. Ceci représente une base valable pour l’étude subséquente de l’effet de la matrice extracellulaire asthmatique sur le phénotype des cellules musculaires lisses bronchiques.The interactions between the bronchial extracellular matrix and the bronchial smooth muscle contribute to the asthmatic bronchial remodeling. Results from in vitro studies indicate that the in vitro monolayer models do not recapitulate the complex interactions occurring in vivo. Decellularized tissues are natural three-dimensional matrices permitting the investigation of these interactions as closely as possible to the in vivo models. The aim of this study was to develop a protocol for the decellularization and recellularization of an equine bronchus by bronchial smooth muscle cells. Its purpose is to investigate how the asthmatic bronchial extracellular matrix affects the bronchial smooth muscle cells phenotype. A good decellularization is characterized by a respiratory bronchus completely free of cells while the architecture and the matricial composition remain unchanged. The elimination of the cellular material is necessary to not confound the native cells of the tissue with the cells of culture and to not affect the quality of the recellularization. Following the decellularization of an equine respiratory bronchus using Triton / Sodium deoxycholate protocol, we obtained an acellular bronchus (scaffold) presenting very low double-stranded DNA concentrations (less than 100 pg/100 mg dry weight) and the molecular weight of the remnant DNA was less than 100 base pair. This scaffold maintained a very good architecture and the protein content remained almost unchanged. The recellularization of this matrix gave usable results between 31 and 41 days. The histological evaluation of the recellularizations showed a specific colonisation of the muscular extracellular matrix by bronchial smooth muscle cells. This study shows that it is possible to decellularize an equine bronchus while maintaining a protein composition and an architecture favorable to its recellularization by bronchial smooth muscle cells. This represents a valid basis for the subsequent study of the effect of the extracellular asthmatic matrix on the smooth muscle cells phenotype

Possible macrophage activation syndrome following initiation of adalimumab in a patient with adult-onset still’s disease

Macrophage activation syndrome (MAS) has been rarely reported in the course of adult-onset Still’s disease (AOSD) and in the majority of cases, it was triggered by an infection. Here, we report, to our knowledge, the first case of MAS occurring after adalimumab treatment initiation and not triggered by an infection. A  26-yearold woman with classical features of AOSD developed persistent fever, severe bicytopenia associated with extreme hyperferritinemia, hyponatremia and abnormal liver function two months after the initiation of adalimumab treatment. The diagnosis of MAS was made without histological proof. The patient was treated with methylprednisolone pulse therapy and her condition improved. During the disease course, extensive studies could not identify any viral infection or other known underlying etiology for the reactive MAS. The  adalimumab was incriminated in this complication. Currently, the patient is in remission on tocilizumab and low-dose prednisoloneKey words: Adult-onset Still´s disease, macrophage activation syndrome, hemophagocytic syndrome, adalimumab

Haute prévalence du Burnout dans les unités Tunisiennes prenant en charge des patients en fin de vie

Introduction: Chez le personnel soignant, le burnout touche un infirmier sur trois. Ce taux est plus élevé dans les unités prenant en charge des patients en fin de vie. L?objectif de notre travail était d?évaluer la fréquence du burnout chez les infirmiers qui travaillent en soins de fin de vie.Méthodes: Il s'agit d'une étude descriptive transversale réalisée entre le 1er Avril et le 31 Mai 2010. 60 infirmiers de six services de Sousse et de Monastir (Tunisie) ont été recrutés. L'évaluation du burnout a  été réalisée par deux échelles : MBI (Maslach Burnout Inventory) et BMS (Burnout Measure Short  version). Résultats: La prévalence du burnout était de 70% ; il était élevé chez 81.7%. 80% avaient un niveau  élevé d?épuisement émotionnel, 70% avaient un niveau élevé de dépersonnalisation et 17 % avaient un niveau bas de sentiment d'accomplissement personnel. Le burnout était plus élevé chez les hommes (70,8% vs 69,4% ; p=0,013) ; ceux qui voulaient améliorer les conditions du travail (70.2% vs. 66.7% ; p= 0.017) ; du salaire (70.2% vs. 66.7% ; p= 0.017) et chez les infirmiers suivi en psychiatrie (71.4%  vs. 69.8% ; p= 0.008).Conclusion: Dans notre étude le niveau de burnout était élevé chez les infirmiers prenant en charge des patients en fin de vie. Il était associé au sexe masculin et à l'insatisfaction des conditions de travail et du salaire. D'autres études longitudinales sont nécessaires pour suivre l'évolution de ce syndrome et mettre des stratégies de prévention adéquates.Key words: Burnout, infirmiers, soins de fin de vie, Tunisie

Collagenous Colitis and Spondylarthropathy

Collagenous colitis is a recent cause of chronic diarrhea. Cooccurrence with spondylarthropathy is rare. We describe two cases: one man and one woman of 33 and 20 years old were suffering from spondylarthropathy. They then developed collagenous colitis, 4 and 14 years after the onset of spondylarthropathy. The diagnosis was based on histological features. A sicca syndrome and vitiligo were observed with the female case. The presence of colitis leads to therapeutic problems. This association suggests a systemic kind of rheumatic disease of collagenous colitis

Risk Management Practiced Tools in the MENA Region: A Comparative Study between Islamic and Conventional Banks

ABSTRACT The purpose of the study is to investigate the current risk management practices of Islamic and conventional banks in the MENA region. The study is based on a survey of 47 banks, including 24 conventional and 23 Islamic banks. The collected data were analysed using descriptive statistics and t-tests. The findings indicate that banks in MENA region have effective risk strategies and effective risk management frameworks in place. Furthermore, the findings reveal that credit risk is considered the most important for both conventional and Islamic banks followed by liquidity risk. Finally, both conventional and Islamic banks continue to rely on traditional credit risk mitigation tools. These findings have significant contributions to the literature by comprehensively clarifying and critically analysing the current state of risk management among the Islamic banks and conventional banks located in the MENA region. JEL Classifications: G20, G21, G2

Combined FiF+ Tangent-to-tangents VMAT breast SIB technique: Clinical introduction of an optimal class solution

peer reviewe

Systems biology of industrial oxytetracycline production in Streptomyces rimosus: the secrets of a mutagenized hyperproducer

Background Oxytetracycline which is derived from Streptomyces rimosus, inhibits a wide range of bacteria and is industrially important. The underlying biosynthetic processes are complex and hinder rational engineering, so industrial manufacturing currently relies on classical mutants for production. While the biochemistry underlying oxytetracycline synthesis is known to involve polyketide synthase, hyperproducing strains of S. rimosus have not been extensively studied, limiting our knowledge on fundamental mechanisms that drive production. Results In this study, a multiomics analysis of S. rimosus is performed and wild-type and hyperproducing strains are compared. Insights into the metabolic and regulatory networks driving oxytetracycline formation were obtained. The overproducer exhibited increased acetyl-CoA and malonyl CoA supply, upregulated oxytetracycline biosynthe‑ sis, reduced competing byproduct formation, and streamlined morphology. These features were used to synthesize bhimamycin, an antibiotic, and a novel microbial chassis strain was created. A cluster deletion derivative showed enhanced bhimamycin production. Conclusions This study suggests that the precursor supply should be globally increased to further increase the expression of the oxytetracycline cluster while maintaining the natural cluster sequence. The mutagenized hyper‑ producer S. rimosus HP126 exhibited numerous mutations, including large genomic rearrangements, due to natural genetic instability, and single nucleotide changes. More complex mutations were found than those typically observed in mutagenized bacteria, impacting gene expression, and complicating rational engineering. Overall, the approach revealed key traits infuencing oxytetracycline production in S. rimosus, suggesting that similar studies for other antibi‑ otics could uncover general mechanisms to improve production

Incidence, risk factors, and CT characteristics of radiation recall pneumonitis induced by immune checkpoint inhibitor in lung cancer.

BACKGROUND AND PURPOSE: Radiation recall pneumonitis (RRP) is a delayed radiation-induced lung toxicity triggered by systemic agents, typically anticancer drugs. Immune checkpoint inhibitors (ICIs) have recently been identified as potential causal agents of RRP but its real incidence and potential risk factors remain unknown. MATERIALS AND METHODS: Medical records and CTs of patients treated with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors for advanced lung cancer between 2014 and 2019 at our tertiary center, and who had a previous history of lung irradiation were retrospectively analyzed. We identified RRP as lung CT modifications occurring in the irradiation field >6 months after conventionally fractionated radiotherapy completion and >1 year after stereotactic body radiation therapy. Clinical and dosimetric data were analyzed to identify potential risk factors for RRP. RESULTS: Among 348 patients treated with ICIs, data from 80 eligible patients were analyzed (median age, 69 years [interquartile range, 11]; 45 men). Fifteen patients (18.8%) presented with RRP. Median time between end of radiotherapy and RRP was 450 days (range, 231-1859). No risk factor was significantly associated with RRP. ICI-related pneumonitis was associated with RRP in 33.3% of cases (p = 0.0021), developing either concomitantly or after RRP. Incidence of grade ≥ 3 pneumonitis in the RRP population was 13.3 %. CONCLUSION: We demonstrated a high incidence of RRP (18.8%) in our population of previously irradiated patients treated with ICIs for lung cancer. We identified no risk factors for RRP, but an association was noted between RRP and ICI-related pneumonitis.Peer reviewe