Modified Tacrine Derivatives as Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Synthesis, Biological Evaluation, and Molecular Modeling Study.

To develop multitarget-directed ligands (MTDLs) as potential treatments for Alzheimer's disease (AD) and to shed light on the effect of the chromene group in designing these ligands, 35 new tacrine-chromene derivatives were designed, synthesized, and biologically evaluated. Compounds 5c and 5d exhibited the most desirable multiple functions for AD; they were strong hAChE inhibitors with IC50 values of 0.44 and 0.25 µM, respectively. Besides, their potent BuChE inhibitory activity was 10- and 5-fold more active than rivastigmine with IC50 = 0.08 and 0.14 µM, respectively. Moreover, they could bind to the peripheral anionic site (PAS), influencing Aß aggregation and decreasing Aß-related neurodegeneration, especially compound 5d, which was 8 times more effective than curcumin with IC50 = 0.74 µM and 76% inhibition at 10 µM. Compounds 5c and 5d showed strong BACE-1 inhibition at the submicromolar level with IC50 = 0.38 and 0.44 µM, respectively, which almost doubled the activity of curcumin. They also showed single-digit micromolar inhibitory activity against MAO-B with IC50 = 5.15 and 2.42 µM, respectively. They also had antioxidant activities and showed satisfactory metal-chelating properties toward Fe+2, Zn+2, and Cu+2, inhibiting oxidative stress in AD brains. Furthermore, compounds 5c and 5d showed acceptable relative safety upon normal cells SH-SY5Y and HepG2. It was shown that 5c and 5d were blood-brain barrier (BBB) penetrants by online prediction. Taken together, these multifunctional properties highlight that compounds 5c and 5d can serve as promising candidates for the further development of multifunctional drugs against AD.

Immune thrombocytopenia and cerebral thrombophlebitis in a patient on eltrombopag: A rare complication.

Thrombopoietin receptor analogs (TPO-RAs) are indicated for splenectomized immune thrombocytopenia refractory to corticosteroids or immunoglobulins, intravenous, or as second-line therapy when splenectomy is contraindicated. Herein, we report a case of left transverse and superior sagittal sinus thrombophlebitis in a 49-year-old woman with chronic immune thrombocytopenia who received 10 days of eltrombopag treatment. Etiologic assessment ruled out acquired thrombophilia and antiphospholipid syndrome. Pharmacovigilance investigation confirmed causality between eltrombopag and the cerebral events, necessitating the definitive discontinuation of the drug. The patient was treated with anticoagulants and anticonvulsants. This evolution was marked by clinical recovery and significant radiological improvement of the thrombotic event. Cerebral venous thrombophlebitis within TPO-RA treatment remains rare, and without codified recommendations, a strict assessment of patients at risk of thrombotic events remains necessary prior to TPO-RA initiation.

The impact of COVID-19 on the quality of life of southern Moroccan doctors : A gender-based approach.

OBJECTIVES: After the World Health Organisation (WHO) declared COVID-19 a global pandemic, various countries took preventive health measures to limit the spread of the coronavirus. The quality of life (QOL) of many populations was affected by lockdown and social distancing. The pandemic increased healthcare professionals' workload and decreased doctors' QOL. Our study aimed to evaluate the QOL of doctors in southern provinces of Morocco during the COVID-19 pandemic. In addition, the study compared QOL of the two genders at that time. METHODS: This was a cross-sectional and descriptive study. The sample included 257 doctors practicing in the southern provinces of Morocco. To assess QOL, we used the online self-administered WHOQOL-BREF questionnaire, which evaluates QOL in four domains: physical, mental, social and environmental. The cut-off between good and poor QOL was 60. RESULTS: All doctors showed poor QOL in all domains. The mean scores and standard deviations for the physical, mental, social, and environmental domains were 57.88 ± 17.12, 57.09 ± 20.13, 55.57 ± 23.66 and 47.99 ± 17.34, respectively. Comparing the two genders, males had a higher QOL than females with a statistically significant difference (p-value ≤ 0.05) in all domains. Both men and women had poor QOL in the environmental domain (less than 60). Doctors who worked directly in the COVID-19 circuit had poorer QOL in all domains. Even with scores lower than 60, males working in COVID-19 circuit had better QOL compared to females, except in the social domain. CONCLUSION: Southern Moroccan doctors' QOL was reduced in all domains. All doctors working in COVID-19 circuit had poor QOL, and women's scores were even lower than those of men.

[Descriptive cross-sectional study assessing the clinical and paraclinic profiles of monoclonal gammopathies in an agricultural region of Souss-Massa, Morocco]. / Étude transversale descriptive sur les profils cliniques et paracliniques des gammapathies monoclonales au niveau d'une région agricole du Souss-Massa au Maroc.

Introduction: given the lack of information about monoclonal gammopathies, our primary study outcome was to describe the epidemiological, clinical and biochemical profiles of monoclonal gammopathies in the Souss-Massa region, in southern Morocco. Methods: we conducted a retrospective study, by selecting only complete medical records. We used records of patients diagnosed with monoclonal gammopathy at the local oncology center during a period of over 10 years. Results: one hundred and seventeen patients were included in the study, with a high male predominance (65%) and a male/female sex-ratio of 1.85. The average age of our study population was 61.44 (ET 14.54) years. Diagnoses (based on frequency) included: multiple myeloma 82.0% (n=96), solitary plasmacytoma 8.5% (n=10), monoclonal gammopathies of undetermined significance 2.6% (n=3), lymphoma 2.5% (n=3), secondary plasma cell leukaemia 1.7% (n=2), Waldenström´s disease 1.7%(n=2) and chronic lymphoid leukemia (n=1). The isotype distribution was as follows: IgG Kappa 33.7% (n=28), IgG lambda 21.7% (n=18), IgA Kappa 12.0% (n=10), IgA lambda 7.2% (n=6), IgM kappa 3.6% (n=3), and IgD lambda 2.4% (n=2). Biconal peak was reached in two cases, with a percentage of 2.4%. Conclusion: diagnostic delay was observed compared to international studies due to the unavailability of electrophoresis in the care structures.

[Multiple myeloma and autologous haematopoietic stem-cell transplantation without cryopreservation: experiences of the Clinical Hematology Department of Casablanca, Morocco]. / Myélome multiple et autogreffe des cellules souches hématopoïétiques sans cryoconservation: expérience du Service d´Hématologie Clinique de Casablanca au Maroc.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is the gold standard treatment for multiple myeloma in subjects aged ≤ 65 years. In developing countries, AHSCT without cryopreservation reduces the costs of hospitalization and all necessary equipments. We conducted a longitudinal, prospective, open study to evaluate this procedure at the Department of Clinical Hematology, Casablanca, Morocco. Data from the medical records of 64 patients were collected over a period of 24 months. After induction therapy, the overall response (complete remission + very good partial response) was 67.2% (43 patients). The mean CD34-cell count in the autograft was 12.97*106 /kg [2.4- 53*106 Cd34+/kg] and the median length of hospitalization was 20.5 days [14-60 days]. The overall response after autograf was 84% (54 patients). At 24 months follow-up, overall survival (OS) was 83.5%, median OS was not reached and progression-free survival (PFS) was 65.9%, with a median PFS of 24.1 months with 95% confidence interval [21.7-26.5 months]. Autologous hematopoietic stem cell transplantation without cryopreservation is an excellent alternative in our context reducing wait times and freezing costs.

Design, synthesis, and analysis of antiproliferative and apoptosis-inducing activities of nitrile derivatives containing a benzofuran scaffold: EGFR inhibition assay and molecular modelling study.

New cyanobenzofurans derivatives 2-12 were synthesised, and their antiproliferative activity was examined compared to doxorubicin and Afatinib (IC50 = 4.17-8.87 and 5.5-11.2 µM, respectively). Compounds 2 and 8 exhibited broad-spectrum activity against HePG2 (IC50 = 16.08-23.67 µM), HCT-116 (IC50 = 8.81-13.85 µM), and MCF-7 (IC50 = 8.36-17.28 µM) cell lines. Compounds 2, 3, 8, 10, and 11 were tested as EGFR-TK inhibitors to demonstrate their possible anti-tumour mechanism compared to gefitinib (IC50 = 0.90 µM). Compounds 2, 3, 10, and 11 displayed significant EGFR TK inhibitory activity with IC50 of 0.81-1.12 µM. Compounds 3 and 11 induced apoptosis at the Pre-G phase and cell cycle arrest at the G2/M phase. They also increased the level of caspase-3 by 5.7- and 7.3-fold, respectively. The molecular docking analysis of compounds 2, 3, 10, and 11 indicated that they could bind to the active site of EGFR TK.

[Primary colonic extranasal NK/T-cell lymphoma: about a case]. / Lymphome T/NK extra-nasal à localisation colique primitif: à propos d'un cas.

To better understand this cancer, we here report the case of a 43-year old patient diagnosed with localized and isolated primary colonic NK/T-cell lymphoma without associated enteropathy, treated wih 3 cycles of AspaMetDex with a poor response who died during treatment with a clinical picture of acute abdomen. Primary intestinal NK/T-cell lymphoma most commonly affects the young subject with poor prognosis. It is difficult to distinguish between intestinal NK/T-cell lymphoma and inflammatory or infectious intestinal disorders because of its non-specific clinical and endoscopic features. The histopathological and immunohistochemical data as well as the study of DNA allow to adjust the diagnosis and to classify this lymphoma according the European Enteropathy type T-cell lymphoma (ETL).

[Primary hodgkin lymphoma of thyroid: case report]. / Lymphome de hodgkin primitif de la thyroïde: à propos d'un cas.

Primary thyroid lymphoma is a rare clinical entity, which does not exceed 5% of the diagnosed lymphomas, occur more frequently in women than in men, with a peak incidence in the sixth decade of life. The relationship with chronic thyroiditis is well known. The Hodgkin subtype even rarer; little described in the literature; Posing a diagnostic problem. Diagnostic confirmation is usually carried out on the surgical specimen. To better understand this entity, we report the case of a 64-year-old patient, with no notion of chronic thyroiditis, admitted for Hodgkin's lymphoma of the thyroid, diagnosed on an anterior cervical mass. Thyroidectomy with histopathological and immunohistochemical studies confirmed the diagnosis. The patient had received chemotherapy type ABVD (Adriblastin-Bleomycin-Vinblastine-Dacarbazine) and programmed for radiotherapy.