Synthesis and in silico studies of certain benzo[f]quinoline-based heterocycles as antitumor agents.

A series of benzoquinoline-employing heterocycles was synthesized by treating 3-chlorobenzo[f]quinoline-2-carbaldehyde with N-phenyl-3-methylpyrazolone, 4-aminoacetophenone, 1,2-diaminoethane, and 2-cyanoethanohydrazide. Also, pyridine, chromene, α,ß-unsaturated nitrile, thiosemicarbazone, and 1,2-bis-aryl hydrazine derivatives were prepared from the cyanoethanohydrazone obtained. The DFT calculations and experiment outcomes were consistent. In vitro screening of their antiproliferative efficacy was examined against HCT116 and MCF7 cancer cell lines. The pyrazolone 2 and cyanoethanohydrazone 5 derivatives exhibited the most potency, which was demonstrated by their molecular docking towards the CDK-5 enzyme. The binding energies of compounds 2 and 5 were - 6.6320 kcal/mol (with RMSD of 0.9477 Å) and - 6.5696 kcal/mol (with RMSD of 1.4889 Å), respectively, which were near to that of co-crystallized ligand (EFP). This implies a notably strong binding affinity towards the CDK-5 enzyme. Thus, pyrazolone derivative 2 would be considered a promising candidate for further optimization to develop new chemotherapeutic agents. In addition, the ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties.

Assessment of knowledge, attitude, and practice related to brucellosis among livestock farmers and meat handlers in Saudi Arabia.

Background: Brucellosis is a bacterial zoonotic infection that is endemic in Saudi Arabia and associated with clinical and economic impacts. Several studies from countries endemic for brucellosis evaluated the knowledge and attitude of livestock farmers regarding brucellosis. However, no such study was conducted in Saudi Arabia. This study aimed to evaluate the knowledge, attitude, and practice of livestock farmers and meat handlers in Saudi Arabia. Methods: This was a cross-sectional questionnaire-based study, where participants were interviewed in-person in Arabic in livestock markets between September-December 2023. Convenient sampling was utilized. The questionnaire included basic demographics and questions to assess the knowledge, attitude, and practice toward personal protection and protection of the animals from brucellosis. The questionnaire was adapted from a previously validated survey and included 59 questions. Providing at least one correct answer to a certain question indicated a good knowledge about this item or a safe practice. The participants were divided into: farmers (shepherds working for the animal owners), commercial animal owners (those who rent a stockyard in the livestock market and employ farmers to sell their animals), and private animal owners (owners of private farms from which they sell their animals). Results: 545 participants were interviewed (n = 291 farmers, n = 118 commercial animal owners, n = 113 private animal owners, and n = 23 animal slaughterhouse workers). >90% have heard of brucellosis. Lack of education and short experience (<5 years) of working with livestock were negatively associated with good knowledge of brucellosis symptoms and transmission (OR, 0.30; 95%CI, 0.10-0.94; p = 0.038 and OR, 0.23; 95%CI, 0.08-0.62; p = 0.004, respectively). Taking sick animals to the veterinarian was reported by 61.2%, whereas 36.4% follow safe practices when disposing of aborted fetuses. While 34% consume raw milk, only 10% consume rare/medium-rare meat. 51.2% acknowledged the need for more information on brucellosis. Conclusion: This study revealed the need to augment the knowledge of people working with animals, particularly those with no school education and those with short work experience, via providing educational visits or materials or through veterinarians. This should help them identify human and animal brucellosis symptoms and increase the knowledge on how to protect oneself and animals from this disease.

Catalytic reduction of nitroarenes by palladium nanoparticles decorated silica@poly(chitosan-N-isopropylacrylamide-methacrylic acid) hybrid microgels.

Conversion of toxic nitroarenes into less toxic aryl amines, which are the most suitable precursors for different types of compounds, is done with various materials which are costly or take more time for this conversion. In this regards, a silica@poly(chitosan-N-isopropylacrylamide-methacrylic acid) Si@P(CS-NIPAM-MAA) Si@P(CNM) core-shell microgel system was synthesized through free radical precipitation polymerization (FRPP) and then fabricated with palladium nanoparticles (Pd NPs) by in situ-reduction method to form Si@Pd-P(CNM) and characterized with XRD, TEM, FTIR, SEM, and EDX. The catalytic efficiency of Si@Pd-P(CNM) hybrid microgels was studied for reduction of 4-nitroaniline (4NiA) under diverse conditions. Different nitroarenes were successfully transformed into their corresponding aryl amines with high yields using the Si@Pd-P(CNM) system as catalyst and NaBH4 as reductant. The Si@Pd-P(CNM) catalyst exhibited remarkable catalytic efficiency and recyclability as well as maintaining its catalytic effectiveness over multiple cycles.

Biochemical Perspectives on Natural Products in Wound Healing: Exploring Phytochemicals in Tissue Repair and Scar Prevention.

Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages.

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study.

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund's complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.

Unveiling dynamics of nitrogen content and selected nitrogen heterocycles in thrombin inhibitors: a ceteris paribus approach.

BACKGROUND: Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors. RESEARCH DESIGN AND METHODS: A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed. RESULTS: The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%), piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors. CONCLUSIONS: The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine, piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.

Advanced biomechanical analytics: Wearable technologies for precision health monitoring in sports performance.

Objective: This study investigated the impact of wearable technologies, particularly advanced biomechanical analytics and machine learning, on sports performance monitoring and intervention strategies within the realm of physiotherapy. The primary aims were to evaluate key performance metrics, individual athlete variations and the efficacy of machine learning-driven adaptive interventions. Methods: The research employed an observational cross-sectional design, focusing on the collection and analysis of real-world biomechanical data from athletes engaged in sports physiotherapy. A representative sample of athletes from Bahawalpur participated, utilizing Dring Stadium as the primary data collection venue. Wearable devices, including inertial sensors (MPU6050, MPU9250), electromyography (EMG) sensors (MyoWare Muscle Sensor), pressure sensors (FlexiForce sensor) and haptic feedback sensors, were strategically chosen for their ability to capture diverse biomechanical parameters. Results: Key performance metrics, such as heart rate (mean: 76.5 bpm, SD: 3.2, min: 72, max: 80), joint angles (mean: 112.3 degrees, SD: 6.8, min: 105, max: 120), muscle activation (mean: 43.2%, SD: 4.5, min: 38, max: 48) and stress and strain features (mean: [112.3 ], SD: [6.5 ]), were analyzed and presented in summary tables. Individual athlete analyses highlighted variations in performance metrics, emphasizing the need for personalized monitoring and intervention strategies. The impact of wearable technologies on athletic performance was quantified through a comparison of metrics recorded with and without sensors. Results consistently demonstrated improvements in monitored parameters, affirming the significance of wearable technologies. Conclusions: The study suggests that wearable technologies, when combined with advanced biomechanical analytics and machine learning, can enhance athletic performance in sports physiotherapy. Real-time monitoring allows for precise intervention adjustments, demonstrating the potential of machine learning-driven adaptive interventions.

ß-Enaminonitrile in the synthesis of tetrahydrobenzo[b]thiophene candidates with DFT simulation, in vitro antiproliferative assessment, molecular docking, and modeling pharmacokinetics.

Among sulfur-including heterocycles, the benzothiophene skeleton is one of the worthy structure fragments that exhibit structural similarities with active substrates to develop various potent lead molecules in drug design. Thus, some tetrahydrobenzo[b]thiophene candidates were prepared from the ß-enaminonitrile scaffold via reactions with diverse carbon-centered electrophilic reagents and supported with DFT studies. The in vitro antiproliferative effect was screened against MCF7 and HePG2 cancer cell lines, and the results displayed the highest potency of imide 5, Schiff base 11, and phthalimido 12 candidates. A molecular docking study was operated to explore the probable binding modes of interaction, and the results revealed the good binding affinity of compounds 5, 11, and 12 toward the tubulin protein (PDB ID 5NM5) with respect to paclitaxel (a tubulin inhibitor) and co-crystallized ligand (GTP). Besides, modeling pharmacokinetics analyses displayed their desirable drug-likeness and bioavailability properties.

Design, spectroscopic characterizations, and biological investigation of oxospiro[chromine-4,3-indolene]-based compounds as promising antiproliferative EGFR inhibitors and antimicrobial agents.

Utilizing microwave heating and an aqueous saturated solution of K2CO3 as a catalyst, a rapidone-pot synthesis of oxospiro[chromene-4.3-indoline] derivatives was produced in high yields. The experimental results confirmed that the saturated solution of K2CO3 gives outstanding yield to dangerous metals and strong bases during investigations into high-performance catalysts. The used catalyst is green, affordable, incredibly mild, and widely accessible. However, it generates samples, reduces the amount of byproducts, and is expected to be used in industrial-scale heterocyclic derivatives. New oxospiro[chromene-4.3-indoline] derivatives have been created from various isatin by condensing with various phenols. The biological activities results showed that when compared to erlotinib, the derivatives 3b, 4b, 5b, and 6b were the most effective analogues on A549, MCF-7, HepG-2, and HCT-116 cells, with an IC50 range of 3.32 to 11.88 µM. In A549 cells, compounds 3b, 4b, 5b, and 6b induced apoptosis, as shown by the up-regulation of Bax, the up-regulation of Bcl-2, and the stimulation of caspase-3 and -9. With IC50 value of 0.19 ± 0.09, compound3b was demonstrated to be the most effective against EGFRWT. Compounds 4b and 6b have good antibacterial activity toward Staphylococcus aureus, comparable to ciprofloxacin, and about half as much activity as ampicillin, according to the MIC value. Compound 6b's MIC is about 25% lower than clotrimazole drug. The in silico molecular docking outcomes of compounds 3b, 4b, 5b, and 6b in the EGFR active site depicted their ability to adopt essential binding interactions compared to the reference Erlotinib. Moreover, the investigation of the physicochemical properties of the most promising dual acting antiproliferative and antimicrobial compounds 4b and 6b through the egg-boiled method illustrated acceptable lipophilicity, GIT absorption, and blood-brain barrier penetration characteristics.

Comparing Actual and Rounded Serum Creatinine Concentration for Assessing the Accuracy of Vancomycin Dosing in Elderly Patients: A Single-Center Retrospective Study.

Prescribers often face the challenge of predicting creatinine clearance (CrCl) in elderly patients who are 65 years or older and have serum creatinine (SCr) concentrations below 1 mg/dL. Studies have shown that utilizing rounded SCr would underestimate CrCl in this population, which could lead to the under-dosing of some medications like vancomycin. The current study aimed to compare the accuracy of vancomycin dosing using actual SCr versus rounded SCr to 1 mg/dL in elderly patients. A total of 245 patients were included. The therapeutic trough level (10-20 mg/L) was achieved in 138 (56.3%) patients using actual SCr. Sub-therapeutic (<10 mg/L) and supra-therapeutic (>20 mg/L) trough levels were observed in 32 (13.1%) and 75 (30.6%) patients, respectively. The predictive performance of different vancomycin doses based on actual SCr and rounded SCr compared to the targeted maintenance dose (TMD) showed a stronger correlation of dosing based on actual SCr with TMD (r = 0.55 vs. 0.31) compared to rounded SCr dosing; both doses showed similar precision, with ranges of ±552 mg/day for the dosing based on actual SCr and ±691 mg/day for the dosing based on rounded SCr. Furthermore, the dosing based on actual SCr showed a lower error percentage (69%) and a higher accuracy rate (57.6%) within ±10% of the TMD compared to the dosing based on rounded SCr, which had an error percentage of (92.3%) and an accuracy rate of (40%). The prevalence of vancomycin-associated nephrotoxicity (VAN) was seen in 44 (18%) patients. Patients between 75 and 84 years of age, those who were bedridden, and those with vancomycin trough concentrations greater than 20 mg/L had a higher risk of developing VAN. In conclusion, in elderly patients, estimating vancomycin dosing based on actual SCr was more accurate compared to rounded SCr to 1 mg/dL. The efficacy of vancomycin could be negatively affected by rounding up SCr, which could underestimate CrCl and result in the under-dosing of vancomycin.

Unveiling the multifaceted antiproliferative efficacy of Cichorium endivia root extract by dual modulation of apoptotic and inflammatory genes, inducing cell cycle arrest, and targeting COX-2.

Chicory (Cichorium endivia L. divaricatum) is a renowned medicinal plant traditionally used for various ailments, yet the pharmacological potential of its roots, particularly in terms of antitumor activity, remains elusive. In the present study, we explore, for the first time, the metabolomic profile of ethanolic extract from Cichorium endivia roots (CIR) and further unveil its antiproliferative potential. The untargeted phytochemical analysis UPLC/T-TOF-MS/MS identified 131 metabolites in the CIR extract, covering acids, amino acids, flavonoids, alkaloids, nucleotides, and carbohydrates. The antiproliferative activity of the CIR extract was tested in 14 cancer cell lines, revealing significant cytotoxicity (IC50: 2.85-29.15 µg mL-1) and a high selectivity index. Among the cells examined, the CIR extract recorded the most potent antiproliferative activity and selectivity toward HepG2 and Panc-1 cells, with an IC50 of 2.85 µg mL-1 and 3.86 µg mL-1, respectively, and SI > 10. Insights into the mode of action of the antiproliferative activity revealed that CIR extract induces cell arrest in the S phase while diminishing cell distribution in the G0/G1 and G2/M phases in HepG-2 and Panc-1 cells. Flow cytometric and RT-PCR analysis revealed that the CIR extract significantly triggers apoptosis and modulates the expression of pro-apoptotic and anti-apoptotic genes. Furthermore, the CIR extract exhibited a pronounced anti-inflammatory activity, as evidenced by down-regulating key cytokines in LPS-induced RAW 264.7 cells and selectively inhibiting the COX-2 enzyme. Finally, the CIR extract showed a robust total antioxidant capacity, together with potent free radicals and metal scavenging properties, highlighting its role in alleviating oxidative stress. Taken together, this study highlights the multifaceted therapeutic potential of CIR extract as a natural-based antitumor supplement.

From diagnosis to therapy: The critical role of lncRNAs in hepatoblastoma.

According to findings, long non-coding RNAs (lncRNAs) serves an integral part in growth and development of a variety of human malignancies, including Hepatoblastoma (HB). HB is a rare kind of carcinoma of the liver that mostly affects kids and babies under the age of three. Its manifestations include digestive swelling, abdominal discomfort, and losing weight. This thorough investigation digs into the many roles that lncRNAs serve in HB, giving views into their varied activities as well as possible therapeutic consequences. The function of lncRNAs in HB cell proliferation, apoptosis, migratory and penetrating capacities, epithelial-mesenchymal transition, and therapy tolerance is discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell processes such as angiogenesis, apoptosis, immunity, and growth. Circulating lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. In addition to their diagnostic utility, lncRNAs provide curative opportunities as locations and actors, contributing to the expanding landscape of cancer research. Several HB-linked lncRNAs have been demonstrated to exhibit abnormal expression and are involved in tumor-like characteristics via DNA, RNA, or protein binding or encoding short peptides. As a result, a better knowledge of lncRNA instability might bring fresh perspectives into HB etiology as well as innovative strategies for HB early diagnosis and therapy. We describe the abnormalities of lncRNA expression in HB and their tumor-suppressive or carcinogenic activities during HB carcinogenesis in this study. Furthermore, we explore lncRNAs' diagnostic and therapeutic possibilities in HB.

Management of Refractory Functional Gastrointestinal Disorders: What Role Should Psychiatrists Have?

Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists' role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, "psyche," "psychiatry," "psychology," "psychiatrist," "psychotropic," and "refractory functional gastrointestinal disorders" (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.

Analysis of the performance of Faster R-CNN and YOLOv8 in detecting fishing vessels and fishes in real time.

This research conducts a comparative analysis of Faster R-CNN and YOLOv8 for real-time detection of fishing vessels and fish in maritime surveillance. The study underscores the significance of this investigation in advancing fisheries monitoring and object detection using deep learning. With a clear focus on comparing the performance of Faster R-CNN and YOLOv8, the research aims to elucidate their effectiveness in real-time detection, emphasizing the relevance of such capabilities in fisheries management. By conducting a thorough literature review, the study establishes the current state-of-the-art in object detection, particularly within the context of fisheries monitoring, while discussing existing methods, challenges, and limitations. The findings of this study not only shed light on the superiority of YOLOv8 in precise detection but also highlight its potential impact on maritime surveillance and the protection of marine resources.

Synthesis, crystal structure and Hirshfeld surface analysis of 1-[3-(2-oxo-3-phenyl-1,2-di-hydro-quinoxalin-1-yl)prop-yl]-3-phenyl-1,2-di-hydro-quinoxalin-2-one.

In the title compound, C31H24N4O2, the di-hydro-quinoxaline units are both essentially planar with the dihedral angle between their mean planes being 64.82 (4)°. The attached phenyl rings differ significantly in their rotational orientations with respect to the di-hydro-quinoxaline planes. In the crystal, one set of C-H⋯O hydrogen bonds form chains along the b-axis direction, which are connected in pairs by a second set of C-H⋯O hydrogen bonds. Two sets of π-stacking inter-actions and C-H⋯π(ring) inter-actions join the double chains into the final three-dimensional structure.

Synthesis, crystal structure and Hirshfeld surface analysis of 2-[(4-hy-droxy-phen-yl)amino]-5,5-diphenyl-1H-imidazol-4(5H)-one.

In the title mol-ecule, C21H17N3O2, the five-membered ring is slightly ruffled and dihedral angles between the pendant six-membered rings and the central, five-membered ring vary between 50.78 (4) and 86.78 (10)°. The exocyclic nitro-gen lone pair is involved in conjugated π bonding to the five-membered ring. In the crystal, a layered structure is generated by O-H⋯N and N-H⋯O hydrogen bonds plus C-H⋯π(ring) and weak π-stacking inter-actions.

Periodontal Health among Individuals with Intellectual Disabilities Living in a Saudi Institutional Rehabilitation Centre.

The aim of this study was to explore periodontal health among intellectually disabled individuals living in an institutional rehabilitation centre in the Al-Baha Region of Saudi Arabia. A cross-sectional study was conducted from November 2023 to January 2024. Clinical oral examinations were carried out using the World Health Organization criteria for bleeding sites and the presence of periodontal pockets. Simplified oral hygiene and community periodontal indices were employed to evaluate participants' oral health. A total of 89 participants, comprising both males and females with intellectual disabilities, were included in this study. Gender, severity of intellectual disability, type of additional physical disability, tooth brushing habits and oral hygiene status were significantly associated with the presence of periodontal disease. Additionally, poor oral hygiene, not brushing teeth and periodontal pockets of 4-5 mm and 6 mm or more were significantly more prevalent among individuals with severe and moderate intellectual disabilities (p = 0.001, p = 0.001, p = 0.001 and p = 0.001, respectively). The prevalence of periodontal disease among the studied population was 54%. The odds of having periodontal disease were significantly higher in the severe intellectual disability group compared to the mild intellectual disability group (OR = 2.328, 95% CI = 1.430-3.631, p = 0.03). It was also found that intellectually disabled participants with additional physical disabilities suffered more from periodontal disease than those without additional physical disabilities (OR = 0.971, 95% CI = 0.235-4.023, p = 0.025). Overall, individuals with intellectual disabilities had a significant demand for periodontal care. This study highlighted the need for more organised preventive programmes for individuals with intellectual disabilities. Dentists should be vigilant about improving periodontal health, focus on preventive programmes and provide comprehensive dental care with an emphasis on periodic recall and monitoring.

An Observation Study of Caries Experience and Potential Risk Assessments among Disabled Individuals Living in an Institutional Rehabilitation Centre.

The aim of this study was to conduct salivary, microbiological, and caries risk assessments in relation to caries experience among individuals with intellectual disability in an institutional center in the Al-Baha region, Saudi Arabia. A cross-sectional study was conducted among 89 patients residing in special care homes in the Al-Baha region, Saudi Arabia, from October 2023 to February 2024. The demographic details of all participants were recorded. Clinical oral examinations were performed for the decayed, missing, or filled teeth (DMFT) and plaque indices. Salivary and microbiological assessments were also carried out. The mean age of the study sample was 30.11 ± 4.39 years, and the mean duration of years spent residing in the facility was 26.49 ± 4.66. There was no significant difference observed across plaque scores, S. mutans colony count, salivary rate, pH, DFMT, and caries experience when they were compared across the levels of severity of intellectual disability. Statistically significant differences were observed across diet score, circumstance score, and chances to avoid caries and were found to be correlated with the severity of intellectual disability (p = 0.001, p = 0.001, and p = 0.002), respectively. The cariogram revealed that participants in this study had poor oral health status, with participants with severe intellectual disability having higher diet scores, frequency scores, and susceptibility scores; hence lesser chances to avoid dental caries. Regular dental check-ups, including cleanings and other treatments if necessary, seem to be fundamental to prevent dental issues and maintain healthy teeth and gums for this group of people. Developing interventions that focus on improving oral health status among intellectually disabled individuals may be recommended to ensure the optimum level of support and reduce the burden of dental decay among those individuals.

Malaria during COVID-19 Travel Restrictions in Makkah, Saudi Arabia.

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city.

Design and synthesis of novel tetrabromophthalimide derivatives as potential tubulin inhibitors endowed with apoptotic induction for cancer treatment.

Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work was adapted to design and synthesize new anti-tubulin tetrabromophthalimide hybrids (3-17) with colchicine binding site (CBS) inhibitory potential. The conducted in vitro studies showed that compound 16 displayed the lowest IC50 values (11.46 µM) at the FaDu cancer cell lines, whereas compound 17 exhibited the lowest IC50 value (13.62 µM) at the PC3 cancer cell line. However, compound 7b exhibited the lowest IC50 value (11.45 µM) at the MDA-MB-468 cancer cell line. Moreover, compound 17 was observed to be the superior antitumor candidate against all three tested cancer cell lines (MDA-MB-468, PC3, and FaDu) with IC50 values of 17.22, 13.15, and 13.62 µM, respectively. In addition, compound 17 showed a well-established upregulation of apoptotic markers (Caspases 3, 7, 8, and 9, Bax, and P53). Moreover, compound 17 induced downregulation of the antiapoptotic markers (MMP2, MMP9, and BCL-2). Furthermore, the colchicine binding site inhibition assay showed that compounds 15a and 17 exhibited particularly significant inhibitory potentials, with IC50 values of 23.07 and 4.25 µM, respectively, compared to colchicine, which had an IC50 value of 3.89 µM. Additionally, cell cycle analysis was conducted, showing that compound 17 could prompt cell cycle arrest at both the G0-G1 and G2-M phases. On the other hand, a molecular docking approach was applied to investigate the binding interactions of the examined candidates compared to colchicine towards CBS of the ß-tubulin subunit. Thus, the synthesized tetrabromophthalimide hybrids can be regarded as outstanding anticancer candidates with significant apoptotic activity.