RBD and hyposmia in Moroccan patients with a synucleinopathy: prevalence and the timing of occurrence in a large cohort.

INTRODUCTION: Rapid Eye Movement Sleep Behavior Disorder (RBD) and hyposmia are common in synucleinopathies and they tend to occur in connection to the prodromal development of these disorders. In this study, we sought to determine the prevalence of RBD and hyposmia and the timeline of their occurrence in a large cohort of Moroccan patients. METHODS: We recruited 774 consecutive patients with synucleinopathy and tauopathy at Ibn Rochd University Hospital of Casablanca. A group of 100 healthy controls was also recruited. We relied on a questionnaire to collect general characteristics and clinical data filled by the patient and his companion under the supervision of a qualified health professional. RESULTS: The study included 697 patients with PD, 37 with DLB and 40 had a tauopathy disorder (PSP or CBD). The proportion of patients who have RBD was 52% in PD, 100% in DLB, 0% in tauopathies and 12% among healthy controls. Hyposmia symptom was found in 47% of patients with PD, 68% in patients with DLB, 0% in tauopathy patients and in 10% of healthy controls. Moreover, 46% of PD patients and 75% of DLB patients developed RBD during the prodromal phase. Meanwhile, hyposmia occurred in association with the prodromal phase among 67% of PD cases and 85% of DLB patients. CONCLUSION: RBD and hyposmia are both prevalent among Moroccan patients with synucleinopathy and they occur frequently during the prodromal phase. Identifying these premotor signs will improve early and differential diagnosis and enhance our understanding of how a specific synucleinopathy progresses.

An overview of the worldwide distribution of LRRK2 mutations in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder with significant genetic influence. The LRRK2 gene is a major genetic contributor, particularly the Gly2019Ser mutation. This focused review investigates the global distribution of LRRK2 mutations, with emphasis on Gly2019Ser and other pathogenic variants. Prevalence rates of Gly2019Ser are highest in North Africa and the Ashkenazi-Jewish population, indicating a potential common ancestor and founder effect. Other LRRK2 mutations, including Asn1437His, Arg1441Gly/Cys/His, Tyr1699Cys and Ile2020Thr, exhibit varying global prevalences. Understanding these distributions enhances our knowledge of PD genetics and aids personalized medicine. Further research is crucial to unravel clinical implications and develop targeted therapies for LRRK2 mutation carriers.

Design and implementation of the European-Mediterranean Postgraduate Programme on Organ Donation and Transplantation (EMPODaT) for Middle East/North Africa countries.

This prospective study reports the design and results obtained after the EMPODaT project implementation. This project was funded by the Tempus programme of the European Commission with the objective to implement a common postgraduate programme on organ donation and transplantation (ODT) in six selected universities from Middle East/North Africa (MENA) countries (Egypt, Lebanon and Morocco). The consortium, coordinated by the University of Barcelona, included universities from Spain, Germany, Sweden and France. The first phase of the project was to perform an analysis of the current situation in the beneficiary countries, including existing training programmes on ODT, Internet connection, digital facilities and competences, training needs, and ODT activity and accreditation requirements. A total of 90 healthcare postgraduate students participated in the 1-year training programme (30 ECTS academic credits). The methodology was based on e-learning modules and face-to-face courses in English and French. Training activities were evaluated through pre- and post-tests, self-assessment activities and evaluation charts. Quality was assessed through questionnaires and semi-structured interviews. The project results on a reproducible and innovative international postgraduate programme, improvement of knowledge, satisfaction of the participants and confirms the need on professionalizing the activity as the cornerstone to ensure organ transplantation self-sufficiency in MENA countries.

Expression of Histo-blood Group Antigens in Tumor and Adjacent Normal Breast Tissues as Prognostic Markers of Breast Carcinoma.

PURPOSE: Aberrant glycosylation of the histo-blood group antigens (including the angina bullosa haemorrhagica [ABH]) is often observed during malignant transformation in most types of carcinomas. Data concerning their ethnic distributions are diverse which explains why their biological characteristics have to be studied in different populations. Our aim was to analyze the expression of the histo-blood group (specifically the ABH) antigens in breast carcinoma. METHODS: The expression of the histo-blood group (specifically the ABH) antigens was studied in 109 patients with breast carcinoma using immunohistochemistry. Statistical analysis was performed using χ2 and Fisher analyses. RESULTS: The loss of expression of histo-blood group (ABH) antigens in breast carcinoma was observed in 81.13% of patients with blood group O, 37.93% with blood group A, and 96.30% with blood group B. One key finding of this study was that the loss of expression of the ABH antigen was also observed in normal tissues adjacent to the tumor. The loss of expression was associated with higher tumor grade (p < 0.05). Expression of H antigen was observed in 50% of cases with loss of expression of B antigen and was associated with human epidermal growth factor receptor 2 (HER2) overexpression (p < 0.05). The loss of H antigen in patients with blood group O was associated with estrogen receptor expression (p < 0.001). Incompatible A antigen in tumor was expressed in 20.75% of patients with blood group O. CONCLUSION: Loss of the ABH antigens correlated with the Scarff-Bloom-Richardson histologic grading. H antigen was associated with HER2 overexpression in breast cancer. However, further studies are needed to determine the role of incompatible A antigen in mammary carcinogenesis.

Bibliometric profil of medical publication at Faculty of Medicine of Casablanca (2008-2017).

AIM: To measure productivity in scientific publications of teachers of the Faculty of Medicine and Pharmacy of Casablanca (FMPC). METHODS: This is a descriptive bibliometric study of the publications of the FMPC, indexed in the Medline and Scopus databases, between 2008 and 2017. Articles of physicians affiliated to the FMPC or its university hospital center were included in this study. RESULTS: With 1041 articles, the average scientific productivity of the FMPC was 38 articles / 100 teachers-year. These articles were published in 244 journals of which 18% in Pan African Medical Journal and 67% in French. In 58% of the articles, the type was "case reports". Dermatology and Genetics were the most prolific medical disciplines with 122 and 76 articles respectively. In surgery, Oto-Rhino-Laryngology and Gynecology-Obstetrics ranked first, with respectively 75 and 60 articles. The impact factor of the journals that published the articles of the FMPC ranged from 0.05 to 26.56 and was less than two in 84% of the cases. National and international scientific collaboration was 2.6% and 6.4% respectively. CONCLUSION: The publication at the FMPC was largely unproductive in English-language journals with a high impact factor. Training in scientific medical writing would be a priority for faculty development and institutional visibility of the FMPC.

Anti-inflammatory potential of Capparis spinosa L. in vivo in mice through inhibition of cell infiltration and cytokine gene expression.

BACKGROUND: Several chronic inflammatory diseases are characterized by inappropriate CD4+ T cell response. In the present study, we assessed the ability of Capparis spinosa L. (CS) preparation to orientate, in vivo, the immune response mediated by CD4+ T cells towards an anti-inflammatory response. METHODS: The in vivo study was carried out by using the contact hypersensitivity (CHS) model in Swiss mice. Then we performed a histological analysis followed by molecular study by using real time RT-PCR. We also realized a phytochemical screening and a liquid-liquid separation of CS preparation. RESULTS: Our study allowed us to detect a significantly reduced edema in mice treated with CS preparations relative to control. CS effect was dose dependent, statistically similar to that observed with indomethacin, independent of the plant genotype and of the period of treatment. Furthermore, our histology studies revealed that CS induced a significant decrease in immune cell infiltration, in vasodilatation and in dermis thickness in the inflammatory site. Interestingly, we showed that CS operated by inhibiting cytokine gene expression including IFNγ, IL-17 and IL-4. Besides, phytochemical screening of CS extract showed the presence of several chemical families such as saponins, flavonoids and alkaloids. One (hexane fraction) out of the three distinct prepared fractions, exhibited an anti-inflammatory effect similar to that of the raw preparation, and would likely contain the bioactive(s) molecule(s). CONCLUSIONS: Altogether, our data indicate that CS regulates inflammation induced in vivo in mice and thus could be a source of anti-inflammatory molecules, which could be used in some T lymphocyte-dependent inflammatory diseases.

Sirtuin-2 activity is required for glioma stem cell proliferation arrest but not necrosis induced by resveratrol.

Glioblastomas, the most common form of primary brain tumors, are the fourth cause of death by cancer in adults. Increasing evidences suggest that glioblastoma resistance to existing radio- and chemotherapies rely on glioblastoma stem cells (GSCs). GSCs are endowed with a unique combination of stem-like properties alike to normal neural stem cells (NSCs), and of tumor initiating properties. The natural polyphenol resveratrol is known to exert opposite actions on neural cells according to their normal or cancerous status. Here, we used resveratrol to explore the molecular mechanisms differing between GSCs and NSCs. We observed a dual action of resveratrol on GSCs: resveratrol blocked GSC proliferation up to 150 µM and induced their necrosis at higher doses. On the opposite, resveratrol had no effect on NSC behavior. To determine the mechanisms underlying resveratrol effects, we focused our attention on the family of NAD-dependent deacetylases sirtuins (SIRT). A member of this family, SIRT1, has been repetitively shown to constitute a preferential resveratrol target, at least in normal cells. Western blot analysis showed that SIRT1 and SIRT3 were expressed by both GSCs and NSCs whereas SIRT2 expression was restricted to GSCs. Pharmacological blockade of SIRT2 activity or down-regulation of SIRT2 expression with siRNAs counteracted the inhibitory effect of resveratrol on cell proliferation. On the contrary, inhibition of SIRT2 activity or expression did not counteract GSC necrosis observed in presence of high doses of resveratrol. Our results highlight SIRT2 as a novel target for altering GSC properties.

High incidence of MYCN amplification in a Moroccan series of neuroblastic tumors: comparison to current biological data.

MYCN protooncogene status was assessed for the first time in Morocco in peripheral neuroblastic tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Correlations with age at diagnosis, stage, mitosis-karyorrhexis index, differentiation, and Shimada histology were evaluated. Thirty-six formalin-fixed, paraffin-embedded peripheral neuroblastic tumor tissue specimens collected between 2007 and 2010 from the Pathology Department were assessed for MYCN amplification using fluorescence in situ hybridization. MYCN amplification was found in 27.8% of cases. An association of MYCN amplification with unfavorable Shimada grading, higher mitosis-karyorrhexis index, and undifferentiated morphologic phenotype was found. We found no correlation with older age, advanced stage, or the presence of metastasis. Our results suggested that the presence of MYCN amplification is a strong biological indicator of a poor outcome and aggressive disease in neuroblastoma and nodular ganglioneuroblastoma.

Immunohistochemical expression of CD44s in human neuroblastic tumors: Moroccan experience and highlights on current data.

BACKGROUND: Peripheral neuroblastic tumors (pNTs), including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN), are extremely heterogeneous pediatric tumors responsible for 15 % of childhood cancer death. The aim of the study was to evaluate the expression of CD44s ('s': standard form) cell adhesion molecule by comparison with other specific prognostic markers. METHODS: An immunohistochemical profile of 32 formalin-fixed paraffin-embedded pNTs tissues, diagnosed between January 2007 and December 2010, was carried out. RESULTS: Our results have demonstrated the association of CD44s negative pNTs cells to lack of differentiation and tumour progression. A significant association between absence of CD44s expression and metastasis in human pNTs has been reported. We also found that expression of CD44s defines subgroups of patients without MYCN amplification as evidenced by its association with low INSS stages, absence of metastasis and favorable Shimada histology. DISCUSSION: These findings support the thesis of the role of CD44s glycoprotein in the invasive growth potential of neoplastic cells and suggest that its expression could be taken into consideration in the therapeutic approaches targeting metastases. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1034403150888863