Cluster analysis of cancer knowledge, attitudes and behaviors in the Moroccan population.

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.

Genomic analysis of Paenibacillus sp. MDMC362 from the Merzouga desert leads to the identification of a potentially thermostable catalase.

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.

Virtual docking screening and quantitative structure-activity relationship studies to explore AKT and PI3K inhibitors acting on mTOR in cancers by theoretical biology and medical modeling.

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 (R2) 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.

Genomic analysis of two Bacillus safensis isolated from Merzouga desert reveals desert adaptive and potential plant growth-promoting traits.

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.

Priapism following erector spinae plane block for the treatment of a complex regional pain syndrome.

Erector spinae plane block (ESPB) is a novel block where local anesthetic is deposited between the erector spinae muscle and the underlying transverse process. Safety of this technique is emphasized in the majority of reports, but with a continued increase of its use, the number of related complications and side effects is likely to expand. We report the case of a patient treated with ESPB for a complex regional pain syndrome, complicated by the development of a priapism.

Akinetic mutism revealing an ischemic stroke.

We describe a 44-year-old man who developed akinetic mutism following a cerebrovascular accident involving his left middle cerebral artery. We discuss this rare condition and its unusual clinical picture.

A Comprehensive Analysis of 3 Moroccan Genomes Revealed Contributions From Both African and European Ancestries.

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.

The New Reform of the National Health System in Morocco: An Opportunity to Meet the Challenges and Improve the Practice of Anesthesiology.

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.

Overcoming Resistance in Cancer Therapy: Computational Exploration of PIK3CA Mutations, Unveiling Novel Non-Toxic Inhibitors, and Molecular Insights Into Targeting PI3Kα.

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.

Targeting decaprenylphosphoryl-ß-D-ribose 2'-epimerase for Innovative Drug Development Against Mycobacterium Tuberculosis Drug-Resistant Strains.

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-ß-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.

Compliance With World Health Organization (WHO)-World Federation of Societies of Anesthesiologists (WFAS) Standards for General Anesthesia at Ibn Sina University Hospital Center, Morocco.

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.

Translation and pilot validation of the Moroccan version of Stroke Impact Scale (SIS) 3.0.

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 ¼. 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.

Meta-analysis of MTHFR C677T polymorphism and type 2 diabetes mellitus in MENA region.

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.

Predicting Particulate Matter (PM 10) Levels in Morocco: A 5-Day Forecast Using the Analog Ensemble Method.

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.

In Silico Identification of Natural Food Compounds as Potential Quorum-Sensing Inhibitors Targeting the LasR Receptor of Pseudomonas aeruginosa.

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.

Genetic diversity and evolutionary dynamics of the Omicron variant of SARS-CoV-2 in Morocco.

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.

Topical Nitric Acid Burns: Initial Assessment and Management.

Nitric acid (NA) is corrosive. On contact with the skin, liquid splashes with nitric acid and may produce severe burns. These burns usually take on a characteristic yellowish hue. We report the case of a 54-year-old man presenting a nitric acid burn with a pathognomonic skin lesion and perfect healing. NA is a chemical that is important in industry, and it is a very strong acid that is used for engraving, metal refining, electroplating, and fertilizer manufacturing. Skin contact with NA leads to severe burns. The pathophysiology depends on the type of concentration, the strength, quality, and duration of contact, and the penetration power of the acids concerned. The early and abundant irrigation with water or sterile isotonic saline solution, the use of panthenol-containing creams and covering with silver sulphadiazine dressing, carefully monitoring wounds, keeping wounds clean and moist, and preventing and managing secondary infection allow the healing.

Facing Antitubercular Resistance: Identification of Potential Direct Inhibitors Targeting InhA Enzyme and Generation of 3D-pharmacophore Model by in silico Approach.

Purpose: 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.