MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options.

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC.

Neglected Posterior Dislocation Hip Post Acetabulum Fixation: Case Report.

Introduction: An acetabular fracture is a relatively uncommon injury. An acetabular fracture can occur in conjunction with a posterior hip dislocation. Oni defined neglected hip dislocation as dislocation lasting more than 1 week after injury. Case Report: We present a 31-year-old male involved in a road traffic accident 6 months ago. He had 5 cm of shortening on examination, and the sciatic nerve was intact. The patient had post-traumatic arthritis and was counseled for total hip arthroplasty (THA) and its complications. Conclusion: Neglected posterior dislocation of the hip after acetabular fracture fixation is rare these days. It is a time-sensitive medical emergency that must be reduced within 6 h to avoid its complications, especially avascular necrosis and post-traumatic arthritis.

Salivary microbial shifting in hypertensive patients with chronic periodontitis after scaling and root surface debridement.

OBJECTIVES: This study aimed to evaluate the impact of scaling and root surface debridement (SRP) on salivary bacterial counts and systolic and diastolic blood pressure in hypertensive patients with chronic periodontitis, with a focus on clinical significance. METHODS: An observational trial included 24 chronic periodontitis patients, eleven of them were hypertensive patients. Non-surgical periodontal treatment was administered to all patients, with clinical parameters including gingival index (GI), plaque index (PI), and probing pocket depth (PPD) recorded. Saliva samples were collected before and after SRP to quantify total bacterial counts and specific bacterial counts. RESULTS: Two months following SRP, PI and PPD in every subject under study demonstrated good responses. In hypertension patients, the salivary bacterial count was significantly higher following SRP (P = 0.0221). The incidence of Porphyromonas gingivalis in hypertension patients significantly decreased after treatment (P = 0.0386). Despite this, there was no discernible decrease in blood pressure following treatment. CONCLUSIONS: SRP alone was ineffective in reducing overall bacterial counts, but P. gingivalis levels responded favorably. Regular periodontal assessment is crucial for hypertensive individuals to mitigate cardiovascular risk. CLINICAL SIGNIFICANCE: Periodontal therapy in hypertensive patients may improve oral health but might not significantly impact blood pressure. Regular periodontal evaluation is essential for managing cardiovascular risk in hypertension.

Penile Carcinoma Secondary to Balanitis Xerotica Obliterans and Its Compounding Resultant Pathologies: A Case Report.

A 57-year-old African-American male presented with urinary retention secondary to a history of balanitis xerotica obliterans (BXO) concurrent with penile carcinoma. BXO, characterized by chronic, sclerosing inflammation of the male external genitalia, presents significant clinical challenges due to its progressive nature and potential for complications. The patient experienced recurrent episodes of urinary retention, leading to multiple hospital visits and disease progression, prompting a comprehensive evaluation and intervention. The patient's medical history revealed a complex array of comorbidities, including penile carcinoma secondary to BXO, urethral strictures, and meatal stenosis. Clinical assessment, including bedside bladder ultrasound and laboratory investigations, confirmed urinary retention secondary to urethral stricture, necessitating urological consultation. Management strategies involved Foley catheter placement, urethral dilation, and pharmacological interventions for pain management. Subsequent follow-up and imaging evaluations identified an increased risk of carcinoma development, highlighting the importance of surveillance and early intervention in patients with BXO. This case report highlights the intricate clinical manifestations and therapeutic considerations encountered in managing BXO and its associated pathologies.

Survival Outcomes in Stage IV Gastric Cancer Patients with Krukenberg Tumors: A Systematic Review and Meta Analysis.

BACKGROUND: Stage IV gastric cancer patients with Krukenberg tumors typically exhibit poor survival outcomes, often less than 2 years. The management of this tumor subgroup remains non-standardized, and the impact of oophorectomy on survival remains uncertain. In this study, we systematically analyzed survival outcomes among gastric cancer patients with ovarian metastases who underwent standard chemotherapy, surgical resection of ovarian metastases, or combined chemotherapy and surgery. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies retrieved from MEDLINE (PubMed), Embase, and the Cochrane Library until January 25, 2024, applying the Boolean logic. Participants included individuals with pathologically and radiologically confirmed ovarian metastasis or clinically symptomatic cases with imaging evidence. Statistical analyses were performed using R (v.4.3.2., Vienna). The study was registered with PROSPERO (ID-CRD42023488373). RESULTS: A total of 1502 patients from 17 retrospective studies were pooled for analysis of overall survival (OS) outcomes. The OS in the standard chemotherapy cohort, as determined by the random effects model, was 6.708 months (95% CI 3.867 to 9.548; P<0.0001), with non-significant heterogeneity (I2 = 5.5%). In the surgical resection cohort, OS was 12.786 months (95% CI 6.9 to 18.671; P<0.0001), with low heterogeneity (I2 = 0%). In the combined chemotherapy and surgical resection cohort, OS was 16.228 months (95% CI 12.254 to 20.202), with insignificant heterogeneity (I2 = 0%). CONCLUSION: This meta-analysis offers key insights into survival outcomes associated with different therapeutic modalities in gastric cancer with Krukenberg metastases. It provides valuable evidence for clinical decision-making and future research directions. While the combined approach of chemotherapy and surgery demonstrates the highest effect size for OS, careful consideration of patient-centric approaches is essential in the oncological care landscape.

Metagenomic 16S rRNA analysis and predictive functional profiling revealed intrinsic organohalides respiration and bioremediation potential in mangrove sediment.

BACKGROUND: Mangrove sediment microbes are increasingly attracting scientific attention due to their demonstrated capacity for diverse bioremediation activities, encompassing a wide range of environmental contaminants. MATERIALS AND METHODS: The microbial communities of five Avicennia marina mangrove sediment samples collected from Al Rayyis White Head, Red Sea (KSA), were characterized using Illumina amplicon sequencing of the 16S rRNA genes. RESULTS: Our study investigated the microbial composition and potential for organohalide bioremediation in five mangrove sediments from the Red Sea. While Proteobacteria dominated four microbiomes, Bacteroidetes dominated the fifth. Given the environmental concerns surrounding organohalides, their bioremediation is crucial. Encouragingly, we identified phylogenetically diverse organohalide-respiring bacteria (OHRB) across all samples, including Dehalogenimonas, Dehalococcoides, Anaeromyxobacter, Desulfuromonas, Geobacter, Desulfomonile, Desulfovibrio, Shewanella and Desulfitobacterium. These bacteria are known for their ability to dechlorinate organohalides through reductive dehalogenation. PICRUSt analysis further supported this potential, predicting the presence of functional biomarkers for organohalide respiration (OHR), including reductive dehalogenases targeting tetrachloroethene (PCE) and 3-chloro-4-hydroxyphenylacetate in most sediments. Enrichment cultures studies confirmed this prediction, demonstrating PCE dechlorination by the resident microbial community. PICRUSt also revealed a dominance of anaerobic metabolic processes, suggesting the microbiome's adaptation to the oxygen-limited environment of the sediments. CONCLUSION: This study provided insights into the bacterial community composition of five mangrove sediments from the Red Sea. Notably, diverse OHRB were detected across all samples, which possess the metabolic potential for organohalide bioremediation through reductive dehalogenation pathways. Furthermore, PICRUSt analysis predicted the presence of functional biomarkers for OHR in most sediments, suggesting potential intrinsic OHR activity by the enclosed microbial community.

Iatrogenic Bladder Injury During Laparoscopic Hysterectomy: A Case Report and Discussion of Anatomic Variations.

Hysterectomy, one of the most common surgical procedures performed in women worldwide, assumes a very important role in the definitive management of diverse gynecologic conditions. This case report presents a compelling instance of an iatrogenic bladder perforation that occurred during laparoscopically assisted vaginal hysterectomy in a 47-year-old woman with a high body mass index, extensive surgical history, and postural orthostatic tachycardia syndrome. Despite considerable preoperative planning and the use of minimally invasive techniques, the occurrence of physician-induced bladder perforation highlights the significance of understanding anatomical relationships and variations. The patient's previous abdominal surgeries including two cesarean sections, appendectomy, and cholecystectomy likely contributed to scar formation and adhesions, making dissection challenging. The case report and following discussion delve into anatomical variations, as well as the diagnosis and management of iatrogenic bladder injuries. The presented case serves as a valuable addition to the literature, contributing insights into the challenges and considerations surrounding urinary tract injuries during hysterectomy. This paper aims to review current research and guide practicing obstetricians and gynecologists in the management of intraoperative bladder injuries.

Capsaicin ameliorate pulmonary fibrosis via antioxidant Nrf-2/ PPAR- γ pathway activation and inflammatory TGF-ß1/ NF-κB/COX II pathway inhibition.

Bleomycin is an effective antibiotic with a significant anticancer properties, but its use is limited due to its potential to induce dose-dependent pulmonary fibrosis. Therefore, this study aimed to assess the therapeutic potential of Capsaicin as an additional treatment to enhance patient tolerance to Bleomycin compared to the antifibrotic drug Pirfenidone. Pulmonary fibrosis was induced in rats through by a single intratracheal Bleomycin administration in day zero, followed by either Capsaicin or Pirfenidone treatment for 7 days. After the animals were sacrificed, their lungs were dissected and examined using various stains for macroscopic and histopathological evaluation. Additionally, the study assessed various antioxidant, anti-inflammatory, and antifibrotic parameters were assessed. Rats exposed to Bleomycin exhibited visible signs of fibrosis, histopathological alterations, increased collagen deposition, and elevated mucin content. Bleomycin also led to heightened increased inflammatory cells infiltration in the bronchoalveolar lavage, elevated fibrosis biomarkers such as hydroxyproline, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-ß1), increased inflammatory markers including tumor necrosis factor-alpha (TNF-α), interlukine-6 (Il-6), interlukine-1ß (Il-1ß) nuclear factor-kappa B (NF-κB), and Cyclooxygenase-2 (COX-2), and transforming growth factor-beta (TGF-ß1),. Furthermore, it reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), increased oxidative stress biomarkers like nitric oxide (NO), malondialdehyde (MDA), myeloperoxidase (MPO) and protein carbonyl. Bleomycin also decreased the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), reduced glutathione (GSH), total antioxidant capacity, and the activities of catalase and superoxide dismutase (SOD). Treating the animals with Capsaicin and Pirfenidone following Bleomycin exposure resulted in improved lung macroscopic and microscopic characteristics, reduced collagen deposition (collagen I and collagen III) and mucin content, decreased inflammatory cell infiltration, lowered levels of hydroxyproline, α-SMA, and TGF-ß1, decreased TNF-α, Il-6, Il-1ß, NF-κB, and COX-2, increased PPAR-γ and Nrf-2 expression, and improvement improved in all oxidative stress biomarkers. In summary, Capsaicin demonstrates significant antifibrotic activity against Bleomycin-induced lung injury that may be attributed, at least in part, to the antioxidant and anti-inflammatory activities of Capsaicin mediated by upregulation of PPAR-γ and Nrf-2 expression and decreasing. TGF-ß1, NF-κB and COX II proteins concentrations.

Retrospective analysis of pediatric sepsis and the burden of antimicrobial resistance in Duhok, Kurdistan Region of Iraq.

Introduction: Sepsis is a life-threatening complication in pediatric patients. This study primarily aimed to investigate sepsis-causing bacteria and their antimicrobial resistance profile and check the change in the antimicrobial resistance trend for some selected bacteria. In addition, we evaluated the incidence of sepsis, the related mortality rate, and the effectiveness and outcome of the treatment regimes in sepsis pediatric patients. Methods: A retrospective analysis was conducted on 4-year data (2018-2021) collected from three intensive care units at the Hevi Pediatric Teaching Hospital. Sepsis screening involved clinical detection and confirmation by blood culture. Results: A total of 520 out of 1,098 (47.35%) blood samples showed positive microbial growth. A decrease in sepsis rate was observed during the COVID-19 pandemic. Coagulase-negative Staphylococci (CoNS) and Klebsiella pneumonia were the most commonly isolated bacteria. A notable variation in the antimicrobial resistance trend was observed among sepsis-causing bacteria. The empirical sepsis treatment recommended by the WHO was ineffective, as certain bacteria exhibited 100% resistance to every antibiotic tested. The mortality rate significantly increased from 1.3% in 2018 to 16.5% in 2021. Discussion: The antimicrobial resistance profile of sepsis causing bacteria is of concerns, indicating a potentially serious situation. Thus, to avoid treatment failure, the monitoring of antimicrobial resistance in pediatric patients is essential.

Synthesis of Some Novel Thiophene Analogues as Potential Anticancer Agents.

The aim of this study involves the synthesis novel thiophene analogues that can be used as anticancer medications through a strategic multicomponent reaction connecting ethyl 4-chloroacetoacetate (1), phenyl isothiocyanate, and a series of active methylene reagents, including ethyl acetoacetate (2), malononitrile, ethyl cyanoacetate, cyanoacetamide 6a-c, N-phenyl cyanoacetamide derivatives 13a-c, and acetoacetanilide derivatives 18. This reaction was facilitated by dry dimethylformamide with a catalytic quantity of K2CO3. The resultant thiophene derivatives were identified as 4, 8a-b, 9, 12a-d, 15a-c, and 20a-b. Further reaction of compound 4 with hydrazine hydrate yielded derivative 5, respectively. When compound 1 was refluxed with ethyl 3-mercapto-3-(phenylamino)-2-(p-substituted phenyldiazenyl)acrylate 10a-e in the presence of sodium ethoxide, it produced thiophene derivatives 12a-d. Comprehensive structural elucidation of these newly synthesized thiophene-analogues was accomplished via elemental and spectral analysis data. Furthermore, the study delves into the cytotoxicity of the newly synthesized thiophenes was evaluated using the HepG2, A2780, and A2780CP cell lines. The amino-thiophene derivative 15b exhibited an increased growth inhibition of A2780, and A2780CP with IC50 values 12±0.17, and 10±0.15 µM, respectively compared to Sorafenib with IC50 values 7.5±0.54 and 9.4±0.14. This research opens new avenues for developing thiophene-based anticancer agents.

Synthesis and Molecular Docking of some new Thiazolidinone and Thiadiazole Derivatives as Anticancer Agents.

New sets of functionalized thiazolidinone and thiadiazole derivatives were synthesized, and their cytotoxicity was evaluated on HepG2, MCF-7, HTC-116, and WI38 cells. The synthetic approach is based on the preparation of 4-(4-acetamidophenyl)thiosemicarbazide (4) and their thiosemicarbazones 5 a-e, which are converted to the corresponding thiazoldin-4-one compounds 6 a-e upon cyclization with ethyl bromoacetate. The thiadiazole compounds 9 and 12 were obtained by reacting 4-(4-acetamidophenyl)thiosemicarbazide with isothiocyanates and/or ethyl 2-cyano-3,3-bis(methylthio)acrylate, respectively. The thiazolidinone compounds 6 c and 6 e exhibited strong cytotoxicity against breast cancer cells, with an IC50 (6.70±0.5 µM) and IC50 (7.51±0.8 µM), respectively, very close to that of doxorubicin (IC50: 4.17±0.2 µM). In addition, the anti-cancer properties of the tested thiazolidinone and thiadiazole scaffolds were further explored by the molecular docking program (MOE)-(PDB Code-1DLS). Compounds 5 d, 5 e, 6 d, 6 e, and 7 have the best binding affinity, ranging from -8.5386 kcal.mol-1 to -8.2830 kcal.mol-1.

Systematic review and pooled analysis of the impact of treatment-induced lymphopenia on survival of glioblastoma patients.

PURPOSE/OBJECTIVE(S): Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival outcomes. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemotherapy and radiation therapy (RT). MATERIALS/METHODS: Following PRISMA guidelines, a systematic literature review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. A pooled analysis was performed using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS. RESULTS: Ten of 104 identified studies met inclusion criteria, representing 1,718 patients. The lymphopenia cutoff value varied (400-1100 cells/uL) and as well as the timing of its onset. Studies were grouped as time-point (i.e., lymphopenia at approximately 2-months post-RT) or time-range (any lymphopenia occurrence from treatment-start to approximately 2-months post-RT. The mean overall pooled incidence of lymphopenia for all studies was 31.8%, and 11.8% vs. 39.9% for time-point vs. time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI 1.46-2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI 1.24-1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies. CONCLUSION: These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between lymphopenia with OS in GBM patients, highlighting lymphopenia as a poor prognostic factor.

Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions.

BACKGROUND: Due to the existence of tumor stem cells with tumorigenicity properties and resistance patterns, treatment of glioblastoma is not easy. Hypoxia is a major concern in glioblastoma therapy. Telomerase activity and telomere length alterations have been known to play a critical role in glioblastoma progression and invasion. OBJECTIVE: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions. METHODS: U251-CSCs were exposed to the HSV-G47Δ virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways. RESULTS: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47Δ in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47Δ in both microenvironments. CONCLUSION: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47Δ in both microenvironments.

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Classification of cancer types based on microRNA expression using a hybrid radial basis function and particle swarm optimization algorithm.

The diagnosis and treatment of cancer is one of the most challenging aspects of the medical profession, despite advances in disease diagnosis. MicroRNAs are small noncoding RNA molecules involved in regulating gene expression and are associated with several cancer types. Therefore, the analysis of microRNA data has become one of the most important areas of cancer research in recent years. This paper presents an improved method for cancer-type classification based on microRNA expression data using a hybrid radial basis function (RBF) and particle swarm optimization (PSO) algorithm. Two datasets containing microRNA information were used, and preprocessing and normalization operations were performed on the raw data. Feature selection was carried out by using the PSO algorithm, which can identify the most relevant and informative features in the data along with helping to prioritize them. Using a PSO algorithm for feature selection is an effective approach to microRNA analysis. This enhances the accuracy and reliability of cancer-type classifications based on microRNA expression data. In the proposed method, we, respectively, achieved an accuracy of 0.95% and 0.91% on both datasets, with an average of 0.93%, using an improved RBF neural network classifier. These results demonstrate that the proposed method outperforms previous works. RESEARCH HIGHLIGHTS: To enhance the accuracy of cancer-type classifications based on microRNA expression data. We present a minimal feature selection method using particle swarm optimization to reduce computational load & radial basis function to improve accuracy.

Evaluation of pharmacokinetic pharmacodynamic target attainment of meropenem in pediatric patients.

BACKGROUND: Meropenem is a widely used carbapenem for treating severe pediatric infections. However, few studies have assessed its pharmacokinetics/pharmacodynamics (PK/PD) in pediatric patients. This study aimed to evaluate the proportion of Saudi pediatric patients achieving the PK/PD target of meropenem. METHODS: A prospective observational study was conducted at King Saud University Medical City from July to September 2022. Pediatric patients receiving meropenem for suspected or proven infections were included in the study. The primary outcome was the percentage of patients achieving the recommended PK/PD target for critically ill or non-critically ill pediatric patients. RESULTS: The study included 30 patients (nine neonates and 21 older pediatric patients). All neonates were critically ill. Among them, 55 % achieved the PK/PD target of 100 % free time above the MIC. In older ICU pediatric patients, only 11 % attained this target, whereas 58 % of older pediatrics in the general wards achieved the PK/PD target of 50 % free time above the MIC. Augmented renal clearance (ARC) was identified in 57 % of our pediatric patient population, none of whom achieved the recommended PK/PD targets. The median trough concentrations in patients with and without ARC were 0.75 and 1.3 µg/mL, respectively (P < 0.05). CONCLUSIONS: The majority of patients in our cohort did not achieve the PK/PD target for meropenem. ARC emerged as a major risk factor for target attainment failure in both critically ill and non-critically ill pediatric patients.

Synthesis biological evaluation and molecular docking of isatin hybrids as anti-cancer and anti-microbial agents.

Isatin, known as 1H-indole-2,3-dione, was originally recognised as a synthetic molecule until its discovery in the fruits of the cannonball tree, Couroupita guianensis. It is naturally occurring in plants of the genus Isatis and serves as a metabolic derivative of adrenaline in humans. Isatin possesses significant pharmacological importance, and its synthetic versatility has prompted extensive interest in its derivative compounds due to their diverse biological and pharmacological properties. These derivatives represent a valuable class of heterocyclic compounds with potential applications as precursors for synthesizing numerous valuable drugs. In the pursuit of advancing our research on isatin hybrids, we investigate the utilisation of readily available hydrazonoindolin-2-one and isatin as starting materials for the synthesis of a wide range of analogues. Characterisation of the synthesized compounds was carried out through various analytical techniques. Furthermore, the obtained compounds were subjected to extensive testing to evaluate their anticancer and antimicrobial activities. Specifically, their efficacy against key proteins, namely Staphylococcus aureus protein (PDB ID: 1JIJ), Escherichia coli protein (PDB ID: 1T9U), Pseudomonas aeruginosa protein (PDB ID: 2UV0), and Acinetobacter baumannii protein (PDB ID: 4HKG), was examined through molecular docking calculations. Several molecules, such as 3, 4, 6, 16, and 19, displayed remarkable activity against the renal cancer cell line UO-31. Additionally, the results of antimicrobial activity testing revealed that compound 16 exhibited significant cytotoxicity against Candida albicans and Cryptococcus neoformans. Subsequently, ADME/T calculations were performed to gain insights into the potential effects and reactions of these molecules within human metabolism. This comprehensive study provides valuable insights into the potential pharmacological applications of isatin derivatives and underscores their significance in drug development.

Investigating the association between asthma and opioid use disorder with interactions of anxiety and depression among a national sample of the US population.

INTRODUCTION: Previous studies have not examined the association between asthma and opioid use disorder (OUD) in a comprehensive national sample of the U.S. population. This study aims to investigate such an association. METHODS: This is a matched retrospective cohort study, with a follow-up period of two years, utilizing longitudinal electronic medical records of a comprehensive national healthcare database in the U.S.-Cerner-Real World DataTM. Patients selected for analysis were ≥12 years old with a hospital encounter between January 2000 and June 2020. Adjusted risk ratios (aRRs) of incident OUD for those with asthma compared to those without asthma were calculated using a modified Poisson regressions with robust standard errors via the Huber-White sandwich estimator, and results were stratified by comorbid mental illnesses. RESULTS: Individuals with asthma had a greater risk of OUD compared to those without asthma (aRR = 2.12; 95% CI 2.03-2.23). When stratified by anxiety and depression status, individuals with asthma and no anxiety or depression had a greater risk of incident OUD compared to individuals with asthma and either anxiety, depression, or both. Additionally, individuals with asthma medication had 1.29 (95% CI: 1.24, 1.35) greater overall risk for incident OUD compared to those without medication. Independent of comorbid mental illnesses, individuals with asthma medication had greater risk for incident OUD compared to those without medication among individuals without severe/obstructive asthma. CONCLUSIONS: Individuals with asthma face a higher OUD risk compared to those without asthma. Comorbid mental illnesses modulate this risk. Caution is advised in opioid prescribing for asthma patients.