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Ghyzlane EL Haddoumi,1,2 Mariam Mansouri,1,2 Houda Bendani,1,2 El Mehdi Bouricha,1,2 Ilham Kandoussi,1,2 Lahcen Belyamani,2– 4 Azeddine Ibrahimi1– 3 1Biotechnology Lab (MedBiotech), Rabat Medical and Pharmacy School, University Mohammed V, Rabat, Morocco; 2Centre Mohammed VI for Research & Innovation (CM6), Rabat, Morocco; 3Mohammed VI University of Health Sciences (UM6SS), Casablanca, Morocco; 4Emergency Department, Military Hospital Mohammed V, Rabat, MoroccoCorrespondence: Azeddine Ibrahimi, Mohammed VI University of Health Sciences (UM6SS), Casablanca, Morocco, Tel +212660240131, Email aibrahimi@um6ss.maPurpose: The enoyl-acyl carrier protein reductase (InhA) is one of the important key enzymes employed in mycolic acids biosynthesis pathway and an important component of mycobacterial cell walls. This enzyme has also been identified as major target of isoniazid drug, except that isoniazid needs to be activated first by the catalase peroxidase (KatG) protein to form the isonicotinoyl-NAD (INH-NAD) adduct that inhibits the action of InhA enzyme. However, this activation becomes more difficult and unreachable with the problem of mutation-related resistance caused mainly by acquired mutations in KatG and InhA protein. Our main interest in this study is to identify direct InhA inhibitors using computer-aided drug design.Methods: Computer-aided drug design was used to solve this problem by applying three different approaches including mutation impact modelling, virtual screening and 3D-pharmacophore search.Results: A total of 15 mutations were collected from the literature, then a 3D model was generated for each of them and their impact was predicted. Of the 15 mutations, 10 were found to be deleterious and have a direct effect on flexibility, stability and SASA of the protein. In virtual screening, from 1,000 similar INH-NAD analogues obtained by the similarity search method, 823 compounds passed toxicity filter and drug likeness rules, which were then docked to the wild-type of InhA protein. Subsequently, 34 compounds with binding energy score better than that of INH-NAD were selected and docked against the 10 generated mutated models of InhA. Only three leads showed a lower binding affinity better than the reference. The 3D-pharmacophore model approach was used to identify the common features between those three compounds by generating a pharmacophoric map.Conclusion: The result of this study may pave the way to develop more potent mutant-specific inhibitors to overcome this resistance.Keywords: molecular docking, CADD, Mycobacterium tuberculosis, InhA, mutational profile

Introduction: The Stroke Impact Scale 3.0 appears to be a promising measure of health-related quality of life for stroke patients. However, the lack of a cross-cultural adaptation in Arabic dialect may limit its use in the Moroccan context. The objective of this study was to carry out a transcultural adaptation and pilote validation of the Stroke Impact Scale 3.0 in Moroccan Arabic dialect, commonly called « Darija »., Patients and Methods: A cross-sectional design was used for this study. The cross-cultural adaptation of the SIS 3.0 scale into Moroccan Darija was carried out following the guidelines proposed by Beaton et al (2000). Ceiling and floor effects were calculated for all scales. The internal consistency of multi-item scales was assessed using Cronbach's α coefficient. Convergent and divergent validity were evaluated using the Multi-Trait Multi-Method Correlation Matrix method., Results: A total of 102 patients, with a mean age of 49 ± 12.9 years, participated in the study. The results revealed that the dimensions of the translated scale had no floor effect and no ceiling effect. The internal consistency of SIS 3.0 (Cronbach's alpha) was calculated, and all dimensions had good reliability, above the threshold of 0.70 (between 0.705 and 0.945). The results showed that the dimensions and their own items had correlation coefficients greater than 0.4, with good convergent and divergent validity., Conclusion: The darija version appears to be culturally acceptable with good psychometric properties and can be used to measure the quality of life of stroke survivors in Morocco.

Introduction: Adverse drug reactions (ADRs) pose a significant challenge in clinical practice, impacting patient safety and treatment outcomes. Genetic variations in drug-metabolizing enzymes, particularly glutathione S-transferases (GSTs), have been implicated in modulating individual susceptibility to ADRs., Areas Covered: This overview aims to explore the association between GSTs genetic polymorphisms and ADRs across diverse drug categories documented in current literature. Here we cover antiepileptic, immunosuppressive, chemotherapeutic agents, analgesics, antivirals, and antibiotics., Expert Opinion: According to the existing literature, the association between genetic polymorphisms in GST theta (GSTT1), GST mu (GSTM1), and GST pi (GSTP1) and adverse drug reaction occurrence has been frequently reported. However, the strength of these associations varies considerably among studies, with some showing inconsistent or contradictory results, underscoring the need for further investigations.

Anesthesiology is considered a complex medical specialty. Its history has been marked by radical advances and profound transformations, owing to technical and pharmacological developments and innovations in the field, enabling us over the years to improve patient outcomes and perform longer, more complex surgical procedures on more fragile patients. However, anesthesiology has never been safe and free of challenges. Despite the advances made, it still faces risks associated with the practice of anesthesia, for both patients and healthcare professionals, and with some of the specific challenges encountered in low and middle-income countries. In this context, certain actions and initiatives must be carried out collaboratively. In addition, recent technologies and innovations such as simulation, genomics, artificial intelligence, and robotics hold promise for further improving patient safety in anesthesiology and overcoming existing challenges, making it possible to offer safer, more effective, and personalized anesthesia. However, this requires rigorous monitoring of ethical aspects and the reliability of the studies to reap the full benefits of the new technology. This literature review presents the evolution of anesthesiology over time, its current challenges, and its promising future. It underlines the importance of the new technologies and the need to pursue efforts and strengthen research in anesthesiology to overcome the persistent challenges and benefit from the advantages of the latest technology to guarantee safe, high-quality anesthesia with universal access., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Harfaoui et al.)

Background: The number of frail older people is increasing worldwide, and all countries will be confronted with their growing needs for healthcare and social support. The aim of this umbrella review was to summarize the evidence on the factors associated with frailty in older people, using a socioecological approach., Methods: PubMed (MEDLINE), Scopus, Web of Science, ScienceDirect, Hinari (research4life), and the Trip database were systematically searched up to April 2023. Systematic reviews of observational studies that explored factors associated with frailty in older adults aged 60 years and over were considered for inclusion. No language, geographical or setting restrictions were applied. However, we excluded systematic reviews that investigated frailty factors in the context of specific diseases. The Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses and the ROBIS tool were used to assess the quality and risk of bias in the included studies., Results: Forty-four systematic reviews were included, covering 1,150 primary studies with approximately 2,687,911 participants overall. Several risk factors, protective factors and biomarkers were found to be associated with frailty, especially in community-dwelling older people, including 67 significant associations from meta-analyses. The certainty of the evidence was rated as moderate or reached moderate levels for seven factors relevant to older people. These factors include depression (OR 4.66, 95% CI 4.07 to 5.34), loneliness (OR 3.51, 95% CI 2.70 to 4.56), limitations in activities of daily living (OR 2.59, 95% CI 1.71 to 3.48), risk of malnutrition (OR 3.52, 95% CI 2.96 to 4.17), Dietary Inflammatory Index score (OR 1.24, 95% CI 1.16 to 1.33), maximal walking speed (Standardized Mean Difference (SMD) -0.97, 95% CI -1.25 to -0.68), and self-reported masticatory dysfunction (OR 1.83, 95% CI 1.55 to 2.18). Additionally, only greater adherence to a Mediterranean diet showed a high level of evidence (OR 0.44, 95% CI 0.31 to 0.64)., Conclusions: This umbrella review will provide guidance for prevention strategies and clinical practice by promoting healthy lifestyles and addressing all modifiable risk factors associated with frailty. Future systematic reviews should consider heterogeneity and publication bias, as these were the main reasons for downgrading the level of evidence in our review., Registration: PROSPERO 2022, CRD42022328902., (© 2024. The Author(s).)

Introduction: Mental health is considered a major public health issue. Non-psychiatric physicians often engage in the treatment of mental disorders. The aim of this study was to describe psychiatric drug prescription knowledge and practices among non-psychiatric specialists and evaluate their training needs., Methods: A descriptive cross-sectional study was conducted from September 1st to October 15th, 2021, in 3 Moroccan healthcare facilities and among private practitioners in Kenitra. We asked non-psychiatric specialists about their knowledge and current practices regarding psychotropic drugs, and their needs in psychiatric training., Results: The study included a total of 150 participants. The majority of participants demonstrated insufficient knowledge regarding the selection of psychotropic drugs and the duration of pharmacotherapy. Specifically, 61.3% were unaware of the average duration of treatment for depression. 22.7% of participants did not feel comfortable when prescribing psychotropic drugs. Anxiolytics were the most commonly prescribed class of psychotropic drugs, accounting for 30.7% of prescriptions. The most common indications for psychotropic drugs prescription were anxiety (35.3%), followed by insomnia (34.7%) and depression (31.3%). The majority of participants (72%) reported receiving clinical training in psychiatry, with 74.7% expressing varying levels of satisfaction with their undergraduate psychiatry training, while 7.3% expressed dissatisfaction. Regarding CME, only 11.3% of participants engaged in at least one psychiatry-related CME session in the past two years. 54.7% of participants expressed interest in expanding their knowledge of prescribing psychotropic drugs. Around 40% of participants preferred trainings in psychotropic drugs prescription related to their specialty, while 34% were not interested in receiving further training., Conclusions: Our study shows gaps in knowledge of non-psychiatric specialists, which raises concern regarding their ability to care for mental disorders. Educational efforts should be made to improve teaching of psychiatry from the undergraduate level. Continuing Medical Education should be tailored to the specific needs and preferred learning methods of non-psychiatric physicians., (© 2024. The Author(s).)

Argania spinosa (L.) Skeels, an endemic Moroccan plant species from the Sapotaceae family, holds significant ecological, pharmaceutical, and socioeconomic value in the arid mid-western region. However, it is facing rapid degradation. Therefore, understanding its genetic diversity is critical for preserving this national heritage. We sequenced, assembled, and annotated the mitochondrial genome of A. spinosa and compared it to other plants in the Ericales order. Mitochondrial-like sequences from the A. spinosa genome were assembled using GetOrganelle, resulting in a 707,441 base pair mitochondrial genome with 45.75 % GC content. Annotation identified 32 protein-coding genes, 16 transfer RNAs, and 2 ribosomal RNA genes. Phylogenetic analysis of 15 Ericales species affirms that A. spinosa is closely related to the Theaceae family, which is in accordance with results from the chloroplast genome., (© 2024 The Author(s).)

Phosphoinositide-3-kinases (PI3 K) are pivotal regulators of cell signaling implicated in various cancers. Particularly, mutations in the PIK3CA gene encoding the p110α catalytic subunit drive oncogenic signaling, making it an attractive therapeutic target. Our study conducted in silico exploration of 31 PIK3CA mutations across breast, endometrial, colon, and ovarian cancers, assessing their impacts on response to PI3Kα inhibitors and identifying potential non-toxic inhibitors and also elucidating their effects on protein stability and flexibility. Specifically, we observed significant alterations in the stability and flexibility of the PI3 K protein induced by these mutations. Through molecular docking analysis, we evaluated the binding interactions between the selected inhibitors and the PI3 K protein. The filtration of ligands involved calculating chemical descriptors, incorporating Veber and Lipinski rules, as well as IC50 values and toxicity predictions. This process reduced the initial dataset of 1394 ligands to 12 potential non-toxic inhibitors, and four reference inhibitors with significant biological activity in clinical trials were then chosen based on their physico-chemical properties. This analysis revealed Lig5's exceptional performance, exhibiting superior affinity and specificity compared to established reference inhibitors such as pictilisib. Lig5 formed robust binding interactions with the PI3 K protein, suggesting its potential as a highly effective therapeutic agent against PI3 K-driven cancers. Furthermore, molecular dynamics simulations provided valuable insights into Lig5's stability and its interactions with PI3 K over 100 ns. These simulations supported Lig5's potential as a versatile inhibitor capable of effectively targeting various mutational profiles of PI3 K, thereby mitigating issues related to resistance and toxicity commonly associated with current inhibitors., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Accurate prediction of Particulate Matter ( PM 10 ) levels, an indicator of natural pollutants such as those resulting from dust storms, is crucial for public health and environmental planning. This study aims to provide accurate forecasts of PM 10 over Morocco for five days. The Analog Ensemble (AnEn) and the Bias Correction (AnEnBc) techniques were employed to post-process PM 10 forecasts produced by the Copernicus Atmosphere Monitoring Service (CAMS) global atmospheric composition forecasts, using CAMS reanalysis data as a reference. The results show substantial prediction improvements: the Root Mean Square Error (RMSE) decreased from 63.83 μg / m 3 in the original forecasts to 44.73 μg / m 3 with AnEn and AnEnBc, while the Mean Absolute Error (MAE) reduced from 36.70 μg / m 3 to 24.30 μg / m 3 . Additionally, the coefficient of determination ( R 2 ) increased more than twofold from 29.11% to 65.18%, and the Pearson correlation coefficient increased from 0.61 to 0.82. This is the first use of this approach for Morocco and the Middle East and North Africa and has the potential for translation into early and more accurate warnings of PM 10 pollution events. The application of such approaches in environmental policies and public health decision making can minimize air pollution health impacts., Competing Interests: Competing Interests The authors have no relevant financial or non-financial interests to disclose.

Background: Cancer has become a major health concern due to the increasing morbidity and mortality rates, and its negative social, economic consequences and the heavy financial burden incurred by cancer patients. About 40% of cancers are preventable. The aim of this study was to assess the knowledge, attitudes, and practices regarding cancer prevention, and associated characteristics to inform the development of targeted cancer prevention campaigns and policies., Methods: We conducted a cross-sectional survey of adult patients at Mohamed Sekkat and Sidi Othmane Hospitals in Casablanca, Morocco. Data collection was conducted by two trained interviewers who administered the questionnaire in-person in the local language. An unsupervised clustering approach included 17 candidate variables for the cluster analysis. The variables covered a wide range of characteristics, including demographics, health perceptions and attitudes. Survey answers were calculated to compose qualitative ordinal categories, including a cancer attitude score and knowledge score., Results: The cluster-based analysis showed that participants in cluster 1 had the highest mean attitude score (13.9 ± 2.15) and percentage of individuals with a high level of knowledge (50.8%) whereas the lowest mean attitude score (9.48 ± 2.02) and knowledge level (7.5%.) were found in cluster 3. The participants with the lowest cancer attitude scores and knowledge levels were aged 34 to 47 years old (middle age group), predominantly females, living in rural settings, and were least likely to report health professionals as a source of health information., Conclusions: The findings showed that female individuals living in rural settings, belonging to an older age group, who were least likely to use health professionals as an information source had the lowest levels of knowledge and attitudes. These groups are amenable to targeted and tailored interventions aiming to modify their understanding of cancer in order to enhance the outcomes of Morocco's on-going efforts in cancer prevention and control strategies., (© 2024. The Author(s).)

Tuberculosis (TB) remains a global health challenge with the emergence of drug-resistant Mycobacterium tuberculosis variants, necessitating innovative drug molecules. One potential target is the cell wall synthesis enzyme decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), crucial for virulence and survival. This study employed virtual screening of 111 Protein Data Bank (PDB) database molecules known for their inhibitory biological activity against DprE1 with known IC50 values. Six compounds, PubChem ID: 390820, 86287492, 155294899, 155522922, 162651615, and 162665075, exhibited promising attributes as drug candidates and validated against clinical trial inhibitors BTZ043, TBA-7371, PBTZ169, and OPC-167832. Concurrently, this research focused on DprE1 mutation effects using molecular dynamic simulations. Among the 10 mutations tested, C387N significantly influenced protein behavior, leading to structural alterations observed through root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and solvent-accessible surface area (SASA) analysis. Ligand 2 (ID: 390820) emerged as a promising candidate through ligand-based pharmacophore analysis, displaying enhanced binding compared with reference inhibitors. Molecular dynamic simulations highlighted ligand 2's interaction with the C387N mutation, reducing fluctuations, augmenting hydrogen bonding, and influencing solvent accessibility. These collective findings emphasize ligand 2's efficacy, particularly against severe mutations, in enhancing protein-ligand complex stability. Integrated computational and pharmacophore methodologies offer valuable insights into drug candidates and their interactions within intricate protein environments. This research lays a strategic foundation for targeted interventions against drug-resistant TB, highlighting ligand 2's potential for advanced drug development strategies., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Among the numerous variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that have been reported worldwide, the emergence of the Omicron variant has drastically changed the landscape of the coronavirus disease (COVID-19) pandemic. Here, we analyzed the genetic diversity of Moroccan SARS-CoV-2 genomes with a focus on Omicron variant after one year of its detection in Morocco in order to understand its genomic dynamics, features and its potential introduction sources. From 937 Omicron genomes, we identified a total of 999 non-unique mutations distributed across 92 Omicron lineages, of which 13 were specific to the country. Our findings suggest multiple introductory sources of the Omicron variant to Morocco. In addition, we found that four Omicron clades are more infectious in comparison to other Omicron clades. Remarkably, a clade of Omicron is particularly more transmissible and has become the dominant variant worldwide. Moreover, our assessment of Receptor-Binding Domain (RBD) mutations showed that the Spike K444T and N460K mutations enabled a clade higher ability of immune vaccine escape. In conclusion, our analysis highlights the unique genetic diversity of the Omicron variant in Moroccan SARS-CoV-2 genomes, with multiple introductory sources and the emergence of highly transmissible clades. The distinctiveness of the Moroccan strains compared to global ones underscores the importance of ongoing surveillance and understanding of local genomic dynamics for effective response strategies in the evolving COVID-19 pandemic.

The health sector in Morocco has undergone major changes in recent years, thanks to the reform of the national health system. This reform aims to improve accessibility and the equitable distribution of care throughout the country and enhance the quality and safety of health services. Anesthesia plays an important role in improving patients' quality of life and reducing the risks associated with surgical procedures. However, anesthetic practice in Morocco faces several challenges, including territorial disparities, unequal access to anesthetic services, financial constraints, a shortage of qualified staff, insufficient continuing education, and the need for appropriate administrative and legal frameworks regarding current anesthesiology practice. The reform of the Moroccan national health system has the potential to significantly advance the practice of anesthesia in Morocco. Indeed, this reform includes a number of measures that could help to improve access to anesthesia services, enhance the quality of care, ensure patient safety, and promote research in this field. Its success will depend on the effective implementation of planned measures and the ability to overcome potential obstacles., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Harfaoui et al.)

Genetic variations in the human genome represent the differences in DNA sequence within individuals. This highlights the important role of whole human genome sequencing which has become the keystone for precision medicine and disease prediction. Morocco is an important hub for studying human population migration and mixing history. This study presents the analysis of 3 Moroccan genomes; the variant analysis revealed 6 379 606 single nucleotide variants (SNVs) and 1 050 577 small InDels. Of those identified SNVs, 219 152 were novel, with 1233 occurring in coding regions, and 5580 non-synonymous single nucleotide variants (nsSNP) variants were predicted to affect protein functions. The InDels produced 1055 coding variants and 454 non-3n length variants, and their size ranged from -49 and 49 bp. We further analysed the gene pathways of 8 novel coding variants found in the 3 genomes and revealed 5 genes involved in various diseases and biological pathways. We found that the Moroccan genomes share 92.78% of African ancestry, and 92.86% of Non-Finnish European ancestry, according to the gnomAD database. Then, population structure inference, by admixture analysis and network-based approach, revealed that the studied genomes form a mixed population structure, highlighting the increased genetic diversity in Morocco., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Aims: The association of the C677T polymorphism of the Methylenetetrahydrofolate Reductase (MTHFR) gene with susceptibility to type 2 diabetes mellitus (T2DM) has been widely debated. Therefore, our aim is to conclusively resolve this controversy in the Middle East and North Africa region population through a meta-analysis., Materiel and Methods: We identified relevant articles by searching literature databases, such as PubMed, Web of Science, and Science Direct, to retrieve studies that examined the association between the MTHFR C677T polymorphism and the risk of developing T2DM. Using meta-analysis, we calculated the odds ratio (OR) and confidence interval (CI) values of these studies to assess the susceptibility to T2DM related to the C677T polymorphism of MTHFR gene., Results: In this meta-analysis, we included a total of 13 publications comprising 2072 T2DM patients and 2164 control subjects. The results of the meta-analysis suggested that there is a significant association between the C677T polymorphism and T2DM risk in overall comparisons for allele contrasts (T vs C): OR = 1.25, 95% CI = 1.04-1.50, p = 0.015 and homozygous (TT vs CC): OR = 1.44, 95% CI = 1.01-2.05, p = 0.038). Subgroup analysis revealed that the C677T polymorphism is associated with a risk of T2DM in Asian populations, while there is no significant association between this polymorphism and T2DM in Caucasian and African populations. Furthermore, there was no evidence of publication bias., Conclusion: Our study's results suggest that the allele contrast of the C677T polymorphism of the MTHFR gene is associated with an increased risk of T2DM in the overall population, particularly among Asians., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Introduction: Patient safety in anaesthesia has significantly improved over the past decades, largely due to pharmacological and technological advancements, as well as the widespread adoption of guidelines and standards recommended by international organisations. This study aimed to evaluate the practice of anaesthesia and its compliance with the international standards for safe anaesthesia practice recommended by the World Federation of Societies of Anaesthesiologists (WFSA) and the World Health Organization (WHO). This study also describes the operating room within Ibn Sina University Hospital Centre (CHUIS) of Rabat, Morocco, the referral centre, with the aim of identifying its potential and shortcomings., Methods: This was a prospective analytical descriptive study from March 1, 2021, to July 31, 2021. All facilities within an operating room and information regarding patients undergoing general anaesthesia, whether it be emergency or scheduled procedures, administered by an anaesthetist, were included. A survey form based on the WHO-WFSA International Standards for a Safe Practice of Anesthesia was used to collect data about the anaesthesia sites. Sources of information included direct observation of anaesthesia procedures, patient records, registers, and qualified anaesthesia personnel. Manual data analysis and encoding were performed using Microsoft Word and Excel (Microsoft Corporation, Redmond, Washington, United States).  Results: All the facilities within the operating rooms of CHUIS were surveyed. In total, 250 patients were recorded, with 43.6% at Ibn Sina Hospital, 18.4% in the Children's Hospital, 14% at the National Institute of Oncology, 12% at the Specialties, 6% at Maternity Hospital Souissi, and 6% at Orangers Maternity Hospital. The median age of patients was 50 years old with 37% of them aged 36-55 years. Overall, 67.6% of these patients were admitted for scheduled interventions. Anaesthetic risk assessment showed that 67.2% of the patients were in American Society of Anesthesiologists (ASA) class I. Pre-anaesthesia consultations were conducted in 65.6% of cases, and pre-anaesthesia visits were conducted in 89.6% of cases. Anaesthesia checklists were used in 89.6% of cases. General anaesthesia, including tracheal intubation 85.2% and facemask 7.2%, was the most common type of anaesthesia. Regarding anaesthetic agents, propofol was the most used intravenous narcotic, with fentanyl still being used in most cases 92% and rocuronium in 82% of cases. Electrocardiogram, non-invasive blood pressure, and pulse oxygen saturation (SPO2) monitoring were consistently used, while capnography was not available in 6% of cases. Crystalloid fluid resuscitation was used in 91.2% of cases, and colloid resuscitation was used in 1.2% of cases. The post-anesthesia care unit (PACU) was present in 58.8% of cases. Postoperative analgesia was administered in 80% of cases. Adverse events occurred in 58.4% of cases. Preoperative transfusion strategies were employed in 18% of cases. Patient transfers to the intensive care unit were done for 18%., Conclusion: Despite the shortcomings of the healthcare system in Morocco, our study indicates that the anaesthesia practice at CHUIS remains highly acceptable by adhering to the highest international standards., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Harfaoui et al.)

The advent of COVID-19 has brought the use of computer tools to the fore in health research. In recent years, computational methods have proven to be highly effective in a variety of areas, including genomic surveillance, host range prediction, drug target identification, and vaccine development. They were also instrumental in identifying new antiviral compounds and repurposing existing therapeutics to treat COVID-19. Using computational approaches, researchers have made significant advances in understanding the molecular mechanisms of COVID-19 and have developed several promising drug candidates and vaccines. This chapter highlights the critical importance of computational drug design strategies in elucidating various aspects of COVID-19 and their contribution to advancing global drug design efforts during the pandemic. Ultimately, the use of computing tools will continue to play an essential role in health research, enabling researchers to develop innovative solutions to combat new and emerging diseases., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Mutations in the Spleen tyrosine kinase (Syk) protein have significant implications for its function and response to treatments. Understanding these mutations and identifying new inhibitors can lead to more effective therapies for conditions like autosomal dominant hyper-IgE syndrome (AD-HIES) and related immunological disorders. Objective: To investigate the impact of mutations in the Syk protein on its function and response to reference treatments, and to explore new inhibitors tailored to the mutational profile of Syk. Methods: We collected and analyzed mutations affecting the Syk protein to assess their functional impact. We screened 94 deleterious mutations in the kinase domain using molecular docking techniques. A library of 997 compounds with potential inhibitory activity against Syk was filtered based on Lipinski and Veber rules and toxicity assessments. We evaluated the binding affinity of reference inhibitors and 14 eligible compounds against wild-type and mutant Syk proteins. Molecular dynamics simulations were conducted to evaluate the interaction of Syk protein complexes with the reference inhibitor and potential candidate inhibitors. Results: Among the analyzed mutations, 60.5% were identified as deleterious, underscoring their potential impact on cellular processes. Virtual screening identified three potential inhibitors (IDs: 118558008, 118558000, and 118558092) with greater therapeutic potential than reference treatments, meeting all criteria and exhibiting lower IC50 values. Ligand 1 (ID: 118558000) demonstrated the most stable binding, favorable compactness, and extensive interaction with solvents. A 3D pharmacophore model was constructed, identifying structural features common to these inhibitors. Conclusion: This study found that 60.5% of reported mutations affecting the Syk protein are deleterious. Virtual screening revealed three top potential inhibitors, with ligand 1 (ID: 118558000) showing the most stable binding and favorable interactions. These inhibitors hold promise for more effective therapies targeting Syk-mediated signaling pathways. The pharmacophore model provides valuable insights for developing targeted therapies for AD-HIES and related disorders, offering hope for patients suffering from Hyper IgE syndrome with allergic symptoms., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pseudomonas aeruginosa is a major cause of nosocomial infections and is often associated with biofilm-mediated antibiotic resistance. The LasR protein is a key component of the quorum system in P. aeruginosa , allowing it to regulate its biofilm-induced pathogenicity. When the bacterial population reaches a sufficient density, the accumulation of N-(3-oxododecanoyl) acyl homoserine lactone (3O-C12-HSL) leads to the activation of the LasR receptor, which then acts as a transcriptional activator of target genes involved in biofilm formation and virulence, thereby increasing the bacteria's antibiotic resistance and enhancing its virulence. In this study, we performed a structure-based virtual screening of a natural food database of 10 997 compounds against the crystal structure of the ligand-binding domain of the LasR receptor (PDB ID: 3IX4). This allowed us to identify four molecules, namely ZINC000001580795, ZINC000014819517, ZINC000014708292, and ZINC000004098719, that exhibited a favorable binding mode and docking scores greater than -13 kcal/mol. Furthermore, the molecular dynamics simulation showed that these four molecules formed stable complexes with LasR during the 150-ns molecular dynamics (MD) simulation, indicating their potential for use as inhibitors of the LasR receptor in P. aeruginosa . However, further experimental validation is needed to confirm their activity., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The increasing commercialization of new gene panels based on next-generation sequencing for clinical research has significantly improved our understanding of breast cancer genetics and has led to the discovery of new mutation variants. The study included 16 unselected Moroccan breast cancer patients tested with multi-gene panel (HEVA screen panel) using Illumina Miseq, followed by Sanger sequencing to validate the most relevant mutation. Mutational analysis revealed the presence of 13 mutations (11 single-nucleotide polymorphisms [SNPs] and 2 indels), and 6 of 11 identified SNPs were predicted as pathogenic. One of the 6 pathogenic mutations was c.7874G>C, a heterozygous SNP in HD-OB domain of BRCA2 gene, which led to the arginine to threonine change at codon 2625 of the protein. This work describes the first case of a patient with breast cancer harboring this pathogenic variant and analyzes its functional impact using molecular docking and molecular dynamics simulation. Further experimental investigations are needed to validate its pathogenicity and to verify its association with breast cancer., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Dihydrofolate reductase (DHFR) is a crucial enzyme that catalyzes the conversion of folic acid. Its reserved properties and significance in both human (h-DHFR) and mycobacterium (mt-DHFR) make it a challenging target for developing drugs against cancer and bacterial infections. Although methotrexate (MTX) is commonly used for cancer therapy and bacterial infections, it has a toxic profile. In this study, we aimed to identify selective and non-toxic inhibitors against h-DHFR and mt-DHFR using an in silico approach. From a data set of 8 412 inhibitors, 11 compounds passed the toxicity and drug-likeness tests, and their interaction with h-DHFR and mt-DHFR was studied by performing molecular docking. To evaluate the inhibitory activity of the compounds against mt-DHFR, five known reference ligands and the natural ligand (dihydrofolate) were used to generate a pharmacophoric map. Two potential selective inhibitors for mt-DHFR and h-DHFR were selected for further investigation using molecular dynamics for 100 ns. As a result, BDBM18226 was identified as the best compound selective for mt-DHFR, non-toxic, with five features listed in the map, with a binding energy of -9.6 kcal/mol. BDBM50145798 was identified as a non-toxic selective compound with a better affinity than MTX for h-DHFR. Molecular dynamics of the two best ligands suggest that they provide more stable, compact, and hydrogen bond interactions with the protein. Our findings could significantly expand the chemical space for new mt-DHFR inhibitors and provide a non-toxic alternative toward h-DHFR for the respective treatment of tuberculosis and cancer therapy., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The rapid and global spread of the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised serious public health concerns, including in Mauritania. We sequenced and analyzed the entire genome of 13 SARS-CoV-2 virus strains isolated from polymerase chain reaction (PCR)-positive symptomatic patients sampled from March 3 to May 31, 2021 to better understand SARS-CoV-2 introduction, propagation, and evolution in Mauritania. A phylogenetic tree using available data from the EpiCoV GISAID database and a variant network with non-Mauritanian sequences were constructed. Variant analysis of the 13 Mauritanian SARS-CoV-2 genome sequences indicated an average mutational percentage of 0.39, which is similar to that in other countries. Phylogenetic analysis revealed multiple spatiotemporal introductions, mainly from Europe (France, Belgium) and Africa (Senegal, Côte d'Ivoire), which also provided evidence of early community transmission. A total of 2 unique mutations, namely, NSP6_Q208K and NSP15_S273T, were detected in the NSP6 and NSP15 genes, respectively, confirming the aforementioned introduction of SARS-CoV-2 in Mauritania. These findings highlight the relevance of continuous genomic monitoring strategies for understanding virus transmission dynamics and acquiring knowledge to address forthcoming sources of infection in Africa., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Autosomal dominant hyper-IgE syndrome (AD-HIES) is linked to dominant negative mutations of the STAT3 protein whose molecular basis for dysfunction is unclear and presenting with a variety of clinical manifestations with only supportive treatment. To establish the relationship between the impact of STAT3 mutations in different domains and the severity of the clinical manifestations, 105 STAT3 mutations were analyzed for their impact on protein stability, flexibility, function, and binding affinity using in Silico approaches. Our results showed that 73% of the studied mutations have an impact on the physicochemical properties of the protein, altering the stability, flexibility and function to varying degrees. In particular, mutations affecting the DNA binding domain (DBD) and the Src Homology 2 (SH2) have a significant impact on the protein structure and disrupt its interaction either with DNA or other STAT3 to form a heterodomain complex, leading to severe clinical phenotypes. Collectively, this study suggests that there is a close relationship between the domain involving the mutation, the degree of variation in the properties of the protein and the degree of loss of function ranging from partial loss to complete loss, explaining the variability of clinical manifestations between mild and severe., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Breast cancer is one of the main global priorities in terms of public health. It remains the most frequent cancer in women and is the leading cause of their death. The human microbiome plays various roles in maintaining health by ensuring a dynamic balance with the host or in the appearance of various pathologies including breast cancer. In this study, we performed an analysis of bacterial signature differences between tumor and adjacent tissues of breast cancer patients in Morocco. Using 16S rRNA gene sequencing, we observed that adjacent tissue contained a much higher percentage of the Gammaproteobacteria class (35.7%) while tumor tissue was characterized by a higher percentage of Bacilli and Actinobacteria classes, with about 18.8% and 17.2% average abundance, respectively. Analysis of tumor subtype revealed enrichment of genus Sphingomonodas in TNBC while Sphingomonodas was predominant in HER2. The LEfSe and the genus level heatmap analysis revealed a higher abundance of the Rothia genus in tumor tissues. The identified microbial communities can therefore serve as potential biomarkers for prognosis and diagnosis, while also helping to develop new strategies for the treatment of breast cancer patients.

In this paper, we propose a new method for epidemic risk modelling and prediction, based on uncertainty quantification (UQ) approaches. In UQ, we consider the state variables as members of a convenient separable Hilbert space, and we look for their representation in finite dimensional subspaces generated by truncations of a suitable Hilbert basis. The coefficients of the finite expansion can be determined by approaches established in the literature, adapted to the determination of the probability distribution of epidemic risk variables. Here, we consider two approaches: collocation (COL) and moment matching (MM). Both are applied to the case of SARS-CoV-2 in Morocco, as an epidemic risk example. For all the epidemic risk indicators computed in this study (number of detections, number of deaths, number of new cases, predictions and human impact probabilities), the proposed models were able to estimate the values of the state variables with precision, i.e., with very low root mean square errors (RMSE) between predicted values and observed ones. Finally, the proposed approaches are used to generate a decision-making tool for future epidemic risk management, or, more generally, a quantitative disaster management approach in the humanitarian supply chain.

Introduction: The mechanistic target of rapamycin (mTOR) coordinates the growth and metabolism of eukaryotic cells with a central role in the regulation of many fundamental cellular processes. It is strongly connected to phosphatidylinositol 3-kinase (PI3K) and AKT signaling. Activation of the PI3K/AKT/mTOR pathway leads to a profound disruption in the control of cell growth and survival, which ultimately leads to competitive growth advantage, metastatic competence, angiogenesis and therapeutic resistance., Material and Methods: To explore the common competitive adenosine triphosphate (ATP) inhibitors PI3K/AKT and PI3K/mTOR, we built a 2D mTOR-SAR model that predicted the bioactivity of AKT and PI3K inhibitors towards mTOR. The interaction of the best inhibitors was evaluated by docking analysis and compared to that of the standard AZ8055 and XL388 inhibitors., Results: A mechanistic target of rapamycin-quantitative structure-activity relationship (mTOR-QSAR) model with a correlation coefficient (R 2 ) of 0.80813 and a root mean square error of 0.17756 was obtained, validated and evaluated by a cross-validation leave-one-out method. The best predicted AKT and PI3K inhibitor pIC50 activities were 9.36-9.95 and 9.23-9.87 respectively., Conclusions: After docking and several comparisons, the inhibitors with better predictions showed better affinity and interaction with mTOR compared to AZ8055 and XL388, so we have found that 2 AKT inhibitors and 9 mTOR inhibitors met the Lipinski and Veber criteria and could be future drugs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

Microorganisms in hot deserts face heat and other environmental conditions, such as desiccation, UV radiation, or low nutrient availability. Therefore, this hostile environment harbour microorganisms with acquired characteristics related to survival in their habitat, which can be exploited in biotechnology. In this work, the genome of Paenibacillus sp. MDMC362 isolated from the Merzouga desert in Morocco was sequenced to understand its survival strategy's genetic basis; and to evaluate the thermostability of a catalase extracted from genomic annotation files using molecular dynamics. Paenibacillus sp. MDMC362 genome was rich in genetic elements involved in the fight against different stresses, notably temperature stress, UV radiations, osmotic stress, carbon starvation, and oxidative stress. Indeed, we could identify genes of the operons groES-groEL and hrcA-grpE-dnaK and those involved in the different stages of sporulation, which can help the bacteria to survive the high temperatures imposed by a desertic environment. We also observed the genetic components of the UvrABC system and additional mechanisms involved in DNA repair, which help overcome UV radiation damage. Other genes have been identified in the genome, like those coding for ectoine and proline, that aids fight osmotic stress and desiccation. Catalase thermostability investigation using molecular dynamics showed that the protein reached stability and conserved its compactness at temperatures up to 373.15 K. These results suggest a potential thermostability of the enzyme. Since the studied protein is a core protein, thermostability could be conserved among Paenibacillus sp. MDMC362 closely related strains; however, bacteria from harsh environments may have a slight advantage regarding protein stability., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Deserts represent extreme environments for microorganisms, and conditions such as high soil salinity, nutrient deficiency, and increased levels of UV radiation make desert soil communities of high biotechnological potential. In this study, we isolated, sequenced, and assembled the genomes of Bacillus safensis strains BcP62 and Bcs93, to which we performed comparative genome analyses. Using the DDH and ANI of both strains with the available B. safensis genomes, we identified three potential subspecies within this group. Intra-species core genome phylogenetic analysis did not result in clustering genomes by niche type, with some exceptions. This study also revealed that the genomes of the analyzed strains possessed plant growth-promoting characteristics, most of which were conserved in all B. safensis strains. Furthermore, we highlight the genetic features of B. safensis BcP62 and Bcs93 related to survival in the Merzouga desert in Morocco. These strains could be potentially used in agriculture as PGPB in extreme environments, given their high tolerability to unfavorable conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Since the COVID-19 pandemic began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved with many variants of concern emerging across the world., Methodology: In order to monitor the evolution of these variants in Morocco, we analyzed a total of 2130 genomes of the delta variant circulating around the world. We also included 164 Moroccan delta variant sequences in our analysis., Results: Our findings suggest at least four introductions from multiple international sources and a rise of a dominant delta sub-lineage AY.33 in Morocco. Moreover, we report three mutations in the N-terminal domain of the S protein specific to the Moroccan AY.33 isolates, T29A, T250I and T299I. The effect of these mutations on the secondary structure and the dynamic behavior of the S protein N-terminal domain was further determined., Conclusions: We conclude that these mutations might have functional consequences on the S protein of SARS-CoV-2., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Safae El Mazouri, Houda Bendani, Nasma Boumajdi, Tarik Aanniz, Ilham Kandoussi, Saaid Amzazi, Lahcen Belyamani, Azeddine Ibrahimi, Mouna Ouadghiri.)

The leukotoxin (LtxA) of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is a protein exotoxin belonging to the repeat-in-toxin family (RTX). Numerous studies have demonstrated that LtxA may play a critical role in the pathogenicity of A. actinomycetemcomitans since hyper-leukotoxic strains have been associated with severe disease. Accordingly, considerable effort has been made to elucidate the mechanisms by which LtxA interacts with host cells and induce their death. However, these attempts have been hampered by the unavailability of a tertiary structure of the toxin, which limits the understanding of its molecular properties and mechanisms. In this paper, we used homology and template free modeling algorithms to build the complete tertiary model of LtxA at atomic level in its calcium-bound Holo-state. The resulting model was refined by energy minimization, validated by Molprobity and ProSA tools, and subsequently subjected to a cumulative 600ns of all-atom classical molecular dynamics simulation to evaluate its structural aspects. The druggability of the proposed model was assessed using Fpocket and FTMap tools, resulting in the identification of four putative cavities and fifteen binding hotspots that could be targeted by rational drug design tools to find new ligands to inhibit LtxA activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Here, we report the near-complete genome sequence and genetic variations of a clinical sample of SARS-CoV-2 for the newly emerged Omicron variant (BA.1). The sample was collected from a nasopharyngeal swab of a Moroccan patient, and the sequencing was done using Ion S5 technology.

The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than 502,539 deaths worldwide as of June 2020. The explosive spread of the virus and the rapid increase in the number of cases require the immediate development of effective therapies and vaccines as well as accurate diagnosis tools. The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the virus entry into host cells. In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS-CoV-2 to ACE2. First, the RBD-ACE2 interface in the 6M0J structure was studied by the MM-GBSA decomposition module of the HawkDock server, which led to the identification of two critical target regions in the RBD. Next, two virtual screening experiments of 7236 α-helix mimetics from ASINEX were conducted on the above regions using the iDock tool, which resulted in 10 candidates with favorable binding affinities. Finally, the stability of RBD complexes with the top-two ranked compounds was further validated by 100   ns of molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.

Androctonus mauritanicus is a large scorpion indigenous to North Africa. Notable for its extremely potent venom, it is responsible for several human deaths a year. We present the whole genome sequence of this species. Illumina sequencing was performed on a genetic sample from a single wild-caught individual. The reads were assembled using a de novo method followed by a finishing step. The raw and assembled data are publicly available via GenBank: Sequence Read Archive (SRR10738938) and Assembly (GCA_011317285).

Ending COVID-19 pandemic requires a collaborative understanding of SARS-CoV-2 and COVID-19 mechanisms. Yet, the evolving nature of coronaviruses results in a continuous emergence of new variants of the virus. Central to this is the need for a continuous monitoring system able to detect potentially harmful variants of the virus in real-time. In this manuscript, we present the International Database of SARS-CoV-2 Variations (IDbSV), the result of ongoing efforts in curating, analyzing, and sharing comprehensive interpretation of SARS-CoV-2's genetic variations and variants. Through user-friendly interactive data visualizations, we aim to provide a novel surveillance tool to the scientific and public health communities. The database is regularly updated with new records through a 4-step workflow (1-Quality control of curated sequences, 2-Call of variations, 3-Functional annotation, and 4-Metadata association). To the best of our knowledge, IDbSV provides access to the largest repository of SARS-CoV-2 variations and the largest analysis of SARS-CoV-2 genomes with over 60 thousand annotated variations curated from the 1,808,613 genomes alongside their functional annotations, first known appearance, and associated genetic lineages, enabling a robust interpretation tool for SARS-CoV-2 variations to help understanding SARS-CoV-2 dynamics across the world., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Essabbar, Kartti, Alouane, Hakmi, Belyamani and Ibrahimi.)