Prevalence, Clinical Characteristics and Determinants of Unsuccessful Treatment Outcomes Among Pulmonary Tuberculosis Patients: A 5-Year Registry-Based Retrospective Cohort Study.

Purpose: Despite the existence of effective medications, pulmonary tuberculosis (PTB) remains a significant global public health concern, The evaluation and feedback of national TB control programs are crucial, requiring diligent monitoring of TB treatment outcomes and analysis of the factors influencing these outcomes. This study aims to provide valuable insights into the challenges faced by TB patients, which can inform better strategies for treatment and management in the future. Patients and Methods: We conducted a study in King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia (KSA), from January 1, 2018 to December 31, 2023. The study was a registry-based retrospective cohort study. Patients' data were sourced from the National Tuberculosis Registry database of Saudi Arabia. Treatment outcomes were determined as either success or failure, considering clinical evaluation, changes in chest X-rays, and the results of subsequent sputum examinations during follow-up. To evaluate the data, SPSS version 28.0 was used. Results: A total of 427 PTB patients participated in the study. The results show successful treatment outcomes among 88.5% of patients. Among the patients, males exhibited a higher likelihood of treatment failure as compared to females (aOR 1.3; 95%Cl 1.2-1.5, p < 0.001). Patients with positive sputum smear (aOR 1.3; 95%Cl 1.1-1.3 p < 0.00) and the presence of cough were associated with an increased risk of treatment failure (aOR1.5; 95%Cl 1.1-1.4, p < 0.001). Conclusion: This study shows that the percentage of unsuccessful treatment outcomes is high, ie, 11.5%, due to patients' deaths and loss to follow-up. Enhanced supervision and treatment monitoring for tuberculosis patients at high risk of treatment failure can lead to improved treatment success rates in Saudi Arabia.

Prevalence of Classical Extraintestinal Manifestations among Inflammatory Bowel Disease Patients in Saudi Arabia: A Single Tertiary Center Experience.

Background: Patients with inflammatory bowel disease (IBD) may also experience extraintestinal manifestations (EIMs), which can affect various organ systems, and their occurrence is based on disease activity. Objectives: To determine the prevalence of EIMs and their most common types among IBD patients from Saudi Arabia. Materials and Methods: This retrospective study included all IBD patients aged 14-80 years who visited the Gastroenterology and Hepatology clinics at King Fahad Medical City, Riyadh, between February 2017 and December 2022. The collected data included demographic characteristics, disease characteristics, EIMs, and treatment. Results: The study included 578 IBD patients, of which 65 (11.2%) had at least one EIM, with primary sclerosing cholangitis (46.2%) and sacroiliitis (16.9%) being the most common. Patients with ulcerative colitis were more likely to have EIMs than those with Crohn's disease (15.1% vs. 9%; P = 0.026). Patients with ileocolonic (L3) Crohn's disease reported a higher prevalence of EIMs (7.5%) than those with other disease locations (P = 0.012), while in patients with ulcerative colitis, those with extensive colitis (E3) reported higher prevalence of EIMs (19.2%) (P = 0.001). Patients receiving 6 MP had a significantly high prevalence of EIMs (P = 0.014). Conclusion: The prevalence of extraintestinal manifestations among IBD patients in Saudi Arabia is 11.2%. These findings suggest the need for clinicians to screen for EIMs and manage them early. Further research is needed to understand the mechanisms underlying EIMs for the development of more effective treatments.

Assessment of knowledge towards first aid skills of epilepsy among undergraduate health students in Riyadh province of Saudi Arabia: A cross-sectional study.

BACKGROUND: Applying proper first-aid measures to patients with seizure episodes plays a vital role in preventing the adverse consequences of seizures. Most previous data focused on teachers, healthcare providers and the general public. This study aimed to assess the knowledge of seizure first-aid measures among undergraduate health students. METHODS: This descriptive, cross-sectional study was conducted between May 16 and 31, 2023, with 493 undergraduate health students of Riyadh Province who answered online surveys. The data were collected using the descriptive information form. The chi-square (χ2) test was employed to compare knowledge of seizure first aid between demographic variables. The relationship between knowledge score and independent variables was evaluated using multiple linear regression technique. RESULTS: Only 1.6 % of participants demonstrated good knowledge scores toward seizure first-aid measures. The skill most frequently reported was to remove all harmful objects from their vicinity and loosen the tight clothes around the neck during a seizure; 68.7 % of the participants correctly answered with agreed. Conversely, the skill that received the lowest knowledge score among participants was putting a piece object such as a cloth, wallet, or spoon between the teeth to prevent tongue biting during a seizure; only 37.3 % of the participants correctly answered with disagree. Moreover, participants in the advanced age group, medicine and fifth-year, were found to be significant predictors of knowledge and exhibited better knowledge scores toward seizure first aid measures than their peers (p < 0.001). Furthermore, lectures and books were identified (69.6 %) as the most common source of information about seizure first aid. CONCLUSION: The study concluded that most undergraduate health students demonstrated poor knowledge scores in delivering seizure first aid. This finding suggests that introducing epilepsy education from the first year in all health-related courses is crucial to improving overall awareness and skills in providing seizure first aid.

Factors Underlying Vaccine Hesitancy and Their Mitigations in Saudi Arabia: Protocol for a Systematic Review.

BACKGROUND: Vaccine hesitancy is a growing concern in Saudi Arabia, impacting even well-educated parents. The decision-making process involves various factors such as accessibility, trustworthy information, and the influence of social networks, reflecting a complex interplay of emotional, cultural, social, spiritual, and political dimensions. OBJECTIVE: This review seeks to evaluate the prevalence and trends of vaccine hesitancy, identify contributing factors, and explore potential solutions to enhance immunization rates. This review aligns with global concerns, as the World Health Organization has identified vaccine hesitancy as a top global health threat. METHODS: Our systematic review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and PICOS (Population, Intervention, Comparison, Outcomes, and Study) criteria for comprehensive assessment. We will conduct a thorough search across various databases, encompassing a wide range of vaccines, and pay special attention to vaccination campaigns and refusals. Inclusion criteria involve descriptive, observational, and analytical studies focusing on factors influencing vaccine acceptance or hesitancy. The study will use the Crowe Critical Appraisal Tool for quality assessment and perform a narrative synthesis to summarize findings thematically. RESULTS: This systematic review is expected to unveil the prevalence and trends of vaccine hesitancy in diverse populations in Saudi Arabia, shedding light on cultural, religious, and social factors contributing to hesitancy. It aims to assess the effectiveness of implemented strategies, enable regional and global comparisons, and provide implications for tailored vaccination policies. Additionally, the review may pinpoint research gaps, guiding future investigations to address and mitigate vaccine hesitancy effectively. CONCLUSIONS: The findings are expected to have direct policy implications and guide interventions to strengthen vaccination programs and improve public health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54680.

AI-Driven Models for Diagnosing and Predicting Outcomes in Lung Cancer: A Systematic Review and Meta-Analysis.

(1) Background: Lung cancer's high mortality due to late diagnosis highlights a need for early detection strategies. Artificial intelligence (AI) in healthcare, particularly for lung cancer, offers promise by analyzing medical data for early identification and personalized treatment. This systematic review evaluates AI's performance in early lung cancer detection, analyzing its techniques, strengths, limitations, and comparative edge over traditional methods. (2) Methods: This systematic review and meta-analysis followed the PRISMA guidelines rigorously, outlining a comprehensive protocol and employing tailored search strategies across diverse databases. Two reviewers independently screened studies based on predefined criteria, ensuring the selection of high-quality data relevant to AI's role in lung cancer detection. The extraction of key study details and performance metrics, followed by quality assessment, facilitated a robust analysis using R software (Version 4.3.0). The process, depicted via a PRISMA flow diagram, allowed for the meticulous evaluation and synthesis of the findings in this review. (3) Results: From 1024 records, 39 studies met the inclusion criteria, showcasing diverse AI model applications for lung cancer detection, emphasizing varying strengths among the studies. These findings underscore AI's potential for early lung cancer diagnosis but highlight the need for standardization amidst study variations. The results demonstrate promising pooled sensitivity and specificity of 0.87, signifying AI's accuracy in identifying true positives and negatives, despite the observed heterogeneity attributed to diverse study parameters. (4) Conclusions: AI demonstrates promise in early lung cancer detection, showing high accuracy levels in this systematic review. However, study variations underline the need for standardized protocols to fully leverage AI's potential in revolutionizing early diagnosis, ultimately benefiting patients and healthcare professionals. As the field progresses, validated AI models from large-scale perspective studies will greatly benefit clinical practice and patient care in the future.

Factors Influencing Dentists' Choice of Restorative Materials for Single-Tooth Crowns: A Survey Among Saudi Practitioners.

BACKGROUND Material selection is crucial in restorative dentistry, influenced by aesthetics, material properties, and tooth location. This understanding is key for advancing dental practices and patient outcomes. The present study aimed to assess dentists' preferences for restorative materials in single-tooth crowns (SC) and how abutment tooth location and preparation margins influence these choices. MATERIAL AND METHODS A web-based pre-validated questionnaire survey was conducted among 811 actively practicing dentists in Saudi Arabia. RESULTS In posterior teeth, we found that ceramic was the most preferred material for SC regardless of the abutment tooth location and location of margins, followed by porcelain fused to metal (PFMs). In anterior teeth, ceramics were preferred, followed by CAD/CAM-based resin SC. Among the choice of ceramics in teeth for both supra-gingival margins, monolith zirconia was the most-preferred material for SC fabrication in posterior teeth, followed by zirconia-reinforced lithium silicate ceramic. Similarly, for sub-gingival margins, monolith zirconia crowns were the most popular option in posterior teeth among the respondents, with the highest in the mandibular molar region. In the anterior region, layered zirconia was the least preferred, and lithium disilicate ceramics was the most-favored option. A statistically significant difference existed between supra- and subgingival preparation for teeth 11 (P=0.01), 16 (P=0.03), and 34 (P=0.02). CONCLUSIONS Ceramic was the material of choice among Saudi dentists for replacement of SC, irrespective of the location and preparation margin. Monolith zirconia was usually selected for posterior teeth and lithium disilicate ceramics was the top choice in anterior teeth.

Mild airways obstruction: spirometric diagnostic pitfalls and solutions.

PURPOSE OF REVIEW: Spirometry is a validated tool in the diagnosis of obstructive airways disease. However, it may be insufficiently sensitive in detecting airflow limitation in the small airways. This review highlights common clinical scenarios wherein airflow limitation may be missed or overlooked. RECENT FINDINGS: This article covers recent literature on the interpretation of lung function test, focusing on detection of mild obstructive airways disease. It also sheds light on the contextual difficulties of defining mild airflow limitation on spirometry. SUMMARY: We highlight the consensus definition of mild obstructive airways disease and emphasize that this definition does not necessarily mean mild in certain disease-specific contexts. Several spirometric findings outside of a reduced forced expiratory volume in one second/forced vital capacity ratio should raise suspicion of mild obstruction.

Investigation of natural compounds as methyltransferase inhibitors against dengue virus: an in silico approach.

The global challenge posed by Dengue virus (DENV) infection persists, exacerbated by the absence of specific antiviral therapies. The viral methyltransferase (MTase) enzyme, crucial for viral RNA methylation and immune system evasion, has emerged as a promising drug target for combating Dengue fever. In this study, a comprehensive exploration of natural compounds derived from the COCONUT database was conducted, selecting 224 compounds based on their structural similarity to the native substrate of the MTase enzyme, S-adenosyl-L-methionine (SAM). Employing virtual screening techniques, four natural compounds (CNP0307160, CNP0082902, CNP0449158, and CNP0296775) with acceptable docking scores were selected for further re-docking after geometry optimization by the DFT method. Re-docking analyses unveiled significant interactions, including hydrogen bonds and hydrophobic interactions, between these selected ligands and the MTase protein. To gain deeper insights into the dynamic stability of these complexes, we conducted molecular dynamics simulations which showed lower RMSD values for CNP0307160, CNP0082902, and CNP0296775 when compared to the reference molecule. Furthermore, we assessed the structural and dynamic stability of the protein-ligand complexes through free binding energy calculations and Principal Component Analysis (PCA) of the simulation trajectories. In these analyses, the CNP0296775 compound exhibited promising results compared to the other three compounds. The cumulative findings of these investigations underscore the potential of CNP0296775 as a strong inhibitor of DENV MTase, thus offering a promising starting point for its further experimental validation and optimization.Communicated by Ramaswamy H. Sarma.

Prevalence and Risk Factors of Cytomegalovirus Colitis in Inflammatory Bowel Disease Patients in Riyadh, Saudi Arabia: A Tertiary Center Experience.

Background: Patients with inflammatory bowel disease (IBD) are at a higher risk of cytomegalovirus (CMV) colitis because of their immunocompromised status. There are no studies from Saudi Arabia regarding the prevalence of CMV colitis in patients with IBD. Objective: To determine the prevalence, characteristics, and risk factors of CMV colitis in patients with IBD in Riyadh, Saudi Arabia. Materials and Methods: This retrospective study included patients with a confirmed diagnosis of IBD (aged 14-75 years) who were followed up at King Fahad Medical City, a referral care center in Riyadh, between January 2016 and December 2021; patients with indeterminate colitis or incomplete medical records were excluded. Results: A total of 341 patients with IBD were included, of which 236 (72.2%) had Crohn's disease (CD) and 105 (27.8%) had ulcerative colitis (UC). Qualitative CMV PCR was done for 192 patients (60 UC and 132 CD patients), of which 14 patients were positive for CMV colitis (7.3%), and all positive CMV colitis cases were among UC patients (23.3%). However, the hematoxylin and eosin (H and E) stain and immunohistochemistry were negative for all patients. Most patients with CMV colitis were on steroids (71.4%), had at least one flare-up (64.3%), and were on biologic treatment (71.4%). Significant predictors of CMV colitis were hemoglobin (OR: 0.7; 95% CI: 0.51-0.96), albumin (OR: 0.88; 95% CI: 0.78-0.98), and C-reactive protein (OR: 1.03; 95% CI: 1.01-1.06) levels. Conclusion: This study found that the prevalence of CMV colitis was 7.3% among patients with IBD, and no case was diagnosed in patients with CD. In addition, as all cases diagnosed using qualitative CMV PCR were negative on H and E stain and immunohistochemistry, there is need for large-scale studies to improve the diagnosis of CMV colitis.

Role of Three-Dimensional Printing in Treatment Planning for Orthognathic Surgery: A Systematic Review.

Three-dimensional (3D) printing refers to a wide range of additive manufacturing processes that enable the construction of structures and models. It has been rapidly adopted for a variety of surgical applications, including the printing of patient-specific anatomical models, implants and prostheses, external fixators and splints, as well as surgical instrumentation and cutting guides. In comparison to traditional methods, 3D-printed models and surgical guides offer a deeper understanding of intricate maxillofacial structures and spatial relationships. This review article examines the utilization of 3D printing in orthognathic surgery, particularly in the context of treatment planning. It discusses how 3D printing has revolutionized this sector by providing enhanced visualization, precise surgical planning, reduction in operating time, and improved patient communication. Various databases, including PubMed, Google Scholar, ScienceDirect, and Medline, were searched with relevant keywords. A total of 410 articles were retrieved, of which 71 were included in this study. This article concludes that the utilization of 3D printing in the treatment planning of orthognathic surgery offers a wide range of advantages, such as increased patient satisfaction and improved functional and aesthetic outcomes.

The Psychological Impact of Vitiligo in Saudi Arabia.

Background Vitiligo, the most common pigment disorder, impacts 0.5-2% of the global population, often causing psychological distress due to appearance changes and potential discrimination. Existing data on depressive symptoms and quality of life (QoL) effects in Saudi Arabian vitiligo patients are limited and inconsistent. Hence, this multi-center investigation was conducted in Saudi Arabia to determine the prevalence of depressive symptoms and quality of life (QoL) impairment in patients with vitiligo and to identify factors linked to increased psychological distress in this population. Methods We conducted a multi-center cross-sectional study in Saudi Arabia, employing two validated Arabic questionnaires, the Dermatology Life Quality Index (DLQI) and the Patient Health Questionnaire-9 items (PHQ-9), along with demographic information. Appropriate statistical analyses were performed. Results In total, 204 patients completed the survey. The median DLQI was 4 (range: 25), while the median PHQ-9 was 5 (range: 27). Factors associated with worse QoL included an early age of onset (under 18 years) and a disease duration exceeding five years. Conversely, only disease duration correlated with worse PHQ-9 scores. Vitiligo lesions on the lower extremities, feet, and genitalia were linked to poorer DLQI scores, while only genitalia were associated with worse PHQ-9 scores. We recommend further social awareness campaigns emphasizing the role of supportive families to improve the well-being of vitiligo patients.

Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy.

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

Formulation and evaluation of chitosan-based nanogel for oral delivery of diosmin.

The bioactive flavonoid diosmin (DSN) has a variety of biological activities, excellent therapeutic activity, however, it has a number of biopharmaceutical problems that limit its advantages. The present study aims to develop chitosan-based nanogels (NGs) as drug-delivery platforms for DSN and characterize them using physicochemical methods. DSN-loaded NGs were prepared using the ionic gelation method and particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), loading efficiency (LE) and loading capacity (LC) of 113.07±12.62nm, 0.266±0.08, 22.32± 0.56 mV, 81.56±2.65% and 10.25±1.43% were obtained, respectively. Transmission electron microscopy analysis of DSN-loaded NGs also revealed that the PS ranged from 100 to 200nm, which is comparable to the outcomes of the dynamic light scattering technique. The NGs swelled in pH 6.8 and pH 7.4 buffers and was easily eroded at pH 1.2 and pH 4.5. DSN was released from NGs in acidic buffers by a Fickian process and this release was followed by both swelling and erosion. According to stability experiments, the PS, ZP and PDI at 25oC and 40oC did not significantly change after 90 days. In conclusion, the NGs system proved very effective at delivering DSN orally.

Repurposing Anti-Dengue Compounds against Monkeypox Virus Targeting Core Cysteine Protease.

The monkeypox virus (MPXV) is an enveloped, double-stranded DNA virus belonging to the genus Orthopox viruses. In recent years, the virus has spread to countries where it was previously unknown, turning it into a worldwide emergency for public health. This study employs a structural-based drug design approach to identify potential inhibitors for the core cysteine proteinase of MPXV. During the simulations, the study identified two potential inhibitors, compound CHEMBL32926 and compound CHEMBL4861364, demonstrating strong binding affinities and drug-like properties. Their docking scores with the target protein were -10.7 and -10.9 kcal/mol, respectively. This study used ensemble-based protein-ligand docking to account for the binding site conformation variability. By examining how the identified inhibitors interact with the protein, this research sheds light on the workings of the inhibitors' mechanisms of action. Molecular dynamic simulations of protein-ligand complexes showed fluctuations from the initial docked pose, but they confirmed their binding throughout the simulation. The MMGBSA binding free energy calculations for CHEMBL32926 showed a binding free energy range of (-9.25 to -9.65) kcal/mol, while CHEMBL4861364 exhibited a range of (-41.66 to -31.47) kcal/mol. Later, analogues were searched for these compounds with 70% similarity criteria, and their IC50 was predicted using pre-trained machine learning models. This resulted in identifying two similar compounds for each hit with comparable binding affinity for cysteine proteinase. This study's structure-based drug design approach provides a promising strategy for identifying new drugs for treating MPXV infections.

Clinical Characteristics and Treatment Strategies for Group B Streptococcus (GBS) Infection in Pediatrics: A Systematic Review.

Background and Objectives: Group B streptococcus (GBS) is the leading cause of infections in neonates with high fatality rates. GBS is caused by the streptococcus bacterium known as streptococcus agalactiae, which is highly contagious and can be transmitted from pregnant women to infants. GBS infection can occur as an early onset or late-onset infection and has different treatment strategies. Antibiotics are effective in treating GBS infections at early stages. The aim of this systematic review was to summarize the clinical characteristics and treatment strategies for GBS, with a focus on antibiotics. Material and Methods: The findings of this review were reported in accordance with the PRISMA 2020 guidelines and a flow diagram of the study selection process, a summary of the included studies, a description of the study characteristics, a summary of the results, a discussion of the implications of the findings, and a conclusion are included. Overall, the authors followed a rigorous methodology to ensure that this review is comprehensive and inclusive of relevant studies on GBS infection and its treatment. Results: Overall, 940 studies were reviewed and only the most relevant 22 studies were included in the systematic review. This review describes the characteristics of patients in different studies related to early onset GBS disease and presents various treatment strategies and outcomes for GBS infection in pediatrics. The studies suggest that preventive measures, risk-based intrapartum antibiotic prophylaxis, and maternal vaccination can significantly reduce the burden of GBS disease, but late-onset GBS disease remains a concern, and more strategies are required to decrease its rate. Improvement is needed in the management of the risk factors of GBS. A conjugate vaccine with a serotype (Ia, Ib, II, III, and V) has been proven effective in the prevention of GBS in neonates. Moreover, penicillin is an important core antibiotic for treating early onset GBS (EOD). Conclusions: This systematic review summarizes the treatment comparison for GBS infections in neonates, with a primary focus on antibiotics. IAP (intrapartum antibiotic prophylaxis) according to guidelines, antenatal screening, and the development of a conjugate vaccine may be effective and could lower the incidence of the disease.

Global Advancement in Pharmacy Services for Mental Health: A Review for Evidence-Based Practices.

The symptoms of psychiatric infirmities have variability, and selected drug regimens for mental illness are comparatively complex and individualized; therefore, pharmacy services vary with respect to patients, diseases, healthcare settings, community structures, and countries. Clinical pharmacy services for mental health (MH) are continuously being upgraded. A structured search of the literature was performed in the Cochrane, PubMed (Medline), PsycINFO, Google scholar, Scopus, Science Direct, and Springer Links databases. The title and abstract of each retrieved article were evaluated for relevance. To remove uncertainty and ambiguity, the full-text articles were retrieved and examined for relevance. The articles were further assessed on the basis of inclusion and exclusion criteria. Narrative synthesis was performed, creating new categories and relevant subcategories and further subsections. The articles and the results were assessed for quality and bias. Pharmacists have a range of expertise in psychiatric care. The services can be classified as conventional, extended, and advanced pharmacy services. Conventional services include the quality use of medicines in healthcare settings and medication support services in communities that ensure medication adherence. Pharmacists perform extended roles in collaborative medication therapy management, multidisciplinary community mental health teams, collaborative care, patient education, home medication review, hospital-to-home transit, and screening services. In the USA, the role of pharmacists was advanced by prescribing as collaborative and interim prescribers. Australia launched an accredited program for psychiatric first-aid pharmacists. Pharmacists can provide mental care to rural populations using health technology. The role of pharmacists in MH is appreciated either independently or as a team member. Patients and healthcare providers rank the services of pharmacists in MH highly. Still, there is a margin for improvement in the training of pharmacists. Pharmacists cannot provide sufficient time to their patients. Public awareness about the role of pharmacists in MH needs more attention. Moreover, the training of psychiatric pharmacists should be standardized around the world.

QcrB inhibition as a potential approach for the treatment of tuberculosis: A review of recent developments, patents, and future directions.

The unmet medical need for drug-resistant tuberculosis (DRTB) is a significant concern. Accordingly, identifying new drug targets for tuberculosis (TB) treatment and developing new therapies based on these drug targets is one of the strategies to tackle DRTB. QcrB is an innovative drug target to create treatments for DRTB. This article highlights QcrB inhibitors and their therapeutic compositions for treating TB. The literature for this article was gathered from PubMed and free patent databases utilizing different keywords related to QcrB inhibitor-based inventions. The data was collected from the conceptualization of telacebec (2010) QcrB to December 2022. A little interesting and encouraging research has been performed on QcrB inhibitors. Telacebec and TB47 are established QcrB inhibitors in the clinical trial. The inventive QcrB inhibitor-based drug combinations can potentially handle DRTB and reduce the TB therapy duration. The authors anticipate great opportunities in fostering QcrB inhibitor-based patentable pharmaceutical inventions against TB. Drug repurposing can be a promising strategy to get safe and effective QcrB inhibitors. However, developing drug resistance, drug tolerance, and selectivity of QcrB inhibitors for Mtb will be the main challenges in developing effective QcrB inhibitors. In conclusion, QcrB is a promising drug target for developing effective treatments for active, latent, and drug-resistant TB. Many inventive and patentable combinations and compositions of QcrB inhibitors with other anti-TB drugs are anticipated as future treatments for TB.

No-Cap Flowable Bulk-Fill Composite: Physico-Mechanical Assessment.

(1) Background: A newer class of flowable bulk-fill resin-based composite (BF-RBC) materials requires no capping layer (Palfique Bulk flow, PaBF, Tokuyama Dental, Tokyo, Japan). The objective of this study was to assess the flexural strength, microhardness, surface roughness, and color stability of PaBF compared to two BF-RBCs with different consistencies. (2) Methods: PaBF, SDR Flow composite (SDRf: Charlotte, NC, USA) and One Bulk fill (OneBF: 3M, St. Paul, MN, USA) were evaluated for flexural strength with a universal testing machine, surface microhardness using a pyramidal Vickers indenter, and surface roughness using a high-resolution three-dimensional non-contact optical profiler, a and clinical spectrophotometer to measure the color stability of each BF-RBC material. (3) Results: OneBF presented statistically higher flexural strength and microhardness than PaBF or SDRf. Both PaBF and SDRf presented significantly less surface roughness compared with OneBF. Water storage significantly reduced the flexural strength and increased the surface roughness of all tested materials. Only SDRf showed significant color change after water storage. (4) Conclusions: The physico-mechanical properties of PaBF do not support its use without a capping layer in the stress bearing areas. PaBF showed less flexural strength compared with OneBF. Therefore, its use should be limited to a small restoration with minimal occlusal stresses.

Computer-assisted discovery of safe and effective DprE1/ aaRSs Inhibitors against TB utilizing Drug Repurposing approach.

BACKGROUND: The emergence of various drug-resistant strains of Mycobacterium tuberculosis compelled medicinal chemists to expedite the discovery of novel, safer alternatives to present regimens. Decaprenylphosphoryl-ß-d-ribose 2'-epimerase (DprE1), an essential component of arabinogalactan biosynthesis, has been considered a novel target for developing new inhibitors against Tuberculosis. We aimed to discover DprE1 inhibitors utilizing the drug repurposing approach. METHODS: A structure-based virtual screening of FDA and world-approved drugs database was carried out, and initially, 30 molecules were selected based on their binding affinity. These compounds were further analyzed by molecular docking with extra-precision mode, MMGBSA binding free energy estimation, and prediction of ADMET profile. RESULTS: Based on the docking results and MMGBSA energy values- ZINC000006716957, ZINC000011677911, and ZINC000022448696 were identified to be the top three hit molecules with good binding interactions inside the active site of DprE1. These hit molecules were subjected to molecular dynamics (MD) simulation for a period of 100 ns to study the dynamic nature of the binding complex. MD results were in accordance with molecular docking and MMGBSA analysis showing protein-ligand contacts with key amino acid residues of DprE1. CONCLUSION: Based on their stability throughout the 100 ns simulation, ZINC000011677911 was the best in silico hit with an already known safety profile. This molecule could lead to future optimization and development of new DprE1 inhibitors.