Risk of Posterior Capsule Ruptures in Fellow-Eye Cataract Surgeries: A Multicenter Comparative Study.

PURPOSE: To quantify the risk of posterior capsule rupture (PCR) in fellow-eye phacoemulsification surgery and to determine risk factors. METHODS: We pooled data from 8 United Kingdom sites for patients undergoing bilateral non-simultaneous phacoemulsification. Main outcome measures were the incidence and risk factors of the development of PCR during the fellow-eye phacoemulsification. RESULTS: We included 66,288 patients with a mean age of 75.3 ± 10.2 years. PCR during phacoemulsification occurred in the first eye in 932 patients (1.4%) and the fellow eye in 1039 patients (1.5%). The risk of fellow eye developing PCR in patients with PCR in the first eye was significantly higher than in patients without first eye PCR: 30 patients (3.2%) vs. 1009 (1.5%), respectively (odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.1-2.7). Other risk factors for fellow-eye PCR included zonular dialysis (OR = 5.4, CI = 3.3-7.8) and advanced cataract (OR = 2.8, CI = 2.1-3.7). CONCLUSIONS: History of PCR in the first-operated eye is an independent risk factor for PCR in the fellow eye.

Psychological changes among weight loss injection users compared with bariatric surgery patients in Saudi Arabia.

OBJECTIVES: To assess and evaluate the mental health and psychological changes in weight loss injection users and bariatric surgery. METHODS: A descriptive and analytical cross-sectional study was conducted from July 2022 to December 2022. A self-administered questionnaire was given among participants using social media platforms. The questionnaire included socio-demographic characteristics, weight-loss-related characteristics, General Anxiety Disorder (GAD-7) to measure anxiety, and Patient Health Questionnaire (PHQ-9) to measure depression experienced by the patients. RESULTS: Of the 721 patients, 73.9% were females, and 30.1% were aged between 30 to 39 years old. The prevalence of patients who underwent weight loss by surgery and injection was 47.7% and 41.2%, respectively. Overall, symptoms of anxiety and depression were detected in 19.7% and 24%, respectively. Independent risk factor of anxiety and depression was the symptom of the psychiatric disorder prior to surgery, while the independent protective factor for anxiety and depression was older age. Depression was higher in weight loss injection users. CONCLUSION: Nearly one-quarter of the study population experienced anxiety or depression following weight loss treatment. Weight loss treatment by injections increases the risk of depression. However, improved self-confidence, mood, and relationships with family and friends were some of the positive changes exhibited by the patients after undergoing weight loss treatment. Appropriate psychiatric evaluation is necessary before and after weight loss intervention.

Retinal proteome profiling of inherited retinal degeneration across three different mouse models suggests common drug targets in retinitis pigmentosa.

Inherited retinal degenerations (IRDs) are a leading cause of blindness among the population of young people in the developed world. Approximately half of IRDs initially manifest as gradual loss of night vision and visual fields, characteristic of retinitis pigmentosa (RP). Due to challenges in genetic testing, and the large heterogeneity of mutations underlying RP, targeted gene therapies are an impractical largescale solution in the foreseeable future. For this reason, identifying key pathophysiological pathways in IRDs that could be targets for mutation-agnostic and disease-modifying therapies (DMTs) is warranted. In this study, we investigated the retinal proteome of three distinct IRD mouse models, in comparison to sex- and age-matched wild-type mice. Specifically, we used the Pde6ßRd10 (rd10) and RhoP23H/WT (P23H) mouse models of autosomal recessive and autosomal dominant RP, respectively, as well as the Rpe65-/- mouse model of Leber´s congenital amaurosis type 2 (LCA2). The mice were housed at two distinct institutions and analyzed using LC-MS in three separate facilities/instruments following data-dependent and data-independent acquisition modes. This cross-institutional and multi-methodological approach signifies the reliability and reproducibility of the results. The largescale profiling of the retinal proteome, coupled with in vivo electroretinography recordings, provided us with a reliable basis for comparing the disease phenotypes and severity. Despite evident inflammation, cellular stress, and downscaled phototransduction observed consistently across all three models, the underlying pathologies of RP and LCA2 displayed many differences, sharing only four general KEGG pathways. The opposite is true for the two RP models in which we identify remarkable convergence in proteomic phenotype even though the mechanism of primary rod death in rd10 and P23H mice is different. Our data highlights the cAMP and cGMP second-messenger signaling pathways as potential targets for therapeutic intervention. The proteomic data is curated and made publicly available, facilitating the discovery of universal therapeutic targets for RP.

Insight into Predictors of Cytoreduction Score Following Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemotherapy for Gastric Peritoneal Carcinomatosis Improves Patient Selection and Prognostic Outcomes.

BACKGROUND: Peritoneal metastases due to gastric adenocarcinoma (GCPM) carry a dismal prognosis. A promising treatment strategy is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), but clear eligibility criteria for GCPM are lacking. We sought to identify factors associated with overall survival (OS) following CRS-HIPEC for GCPM to help optimize patient selection and clinical outcomes. PATIENTS AND METHODS: In this single-center retrospective cohort study, we examined CRS-HIPEC outcomes for patients with GCPM between 2001 and 2021. After analyzing patient demographic, clinicopathologic, and perioperative variables, we applied multivariable Cox hazard models to assess factors associated with OS. We then assessed associations between baseline predictors and prognostically important variables using multivariable logistic regression. RESULTS: We analyzed 55 patients with GCPM who underwent CRS-HIPEC. Median age was 54 years and 42% were female. Median peritoneal carcinomatosis index (PCI) was 8, and 75% of patients achieved a cytoreduction completeness score (CC score) of 0. Median progression-free survival (PFS) was 6.9 months, and median OS was 14.1 months. On adjusted analysis, a CC score > 0 (HR 2.3, p = 0.02) was significantly associated with worse OS. A peritoneal carcinomatosis index greater than 13 (OR 52.6, p = 0.001) and fewer lymph nodes (especially < 18) resected with the primary tumor (OR 0.86, p = 0.042) in the metachronous setting were significantly associated with incomplete macroscopic cytoreduction (CC score > 0). CONCLUSIONS: We demonstrated that PCI > 13 and primary lymph nodes harvested < 18 in metachronous tumors are associated with CC score > 0, which in turn portends a worse OS. Although these results warrant prospective validation, they provide insight into improved selection of patients with GCPM for CRS-HIPEC.

Interleukin 6 and interleukin 17A serum levels and gene- polymorphisms in the development of early allograft rejection in living donor liver transplant recipients.

The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required.

Design, synthesis, and molecular dynamic simulations of some novel benzo[d]thiazoles with anti-virulence activity against Pseudomonas aeruginosa.

Inhibition of quorum sensing (QS) is an impending approach for targeting bacterial infection. Fourteen benzo[d]thiazole and 2-pyrazolo[1,5-a]pyrimidin-3-yl)benzo[d]thiazoles analogues were designed and synthesized as promising LasR antagonists with QS inhibition activity. Among the investigated compounds, compounds 3c, 3e, and 8d exhibited the highest percentage inhibition in biofilm formation (77 %, 63.9 %, 69.4 %), pyocyanin production (74.6 %, 64.9, 69.4 %), and rhamnolipids production (58.5 %, 51 %, 54.3 %) in P. aeruginosa, respectively. Additionally, compounds 3c, 3e and 8d achieved IC50 values against Las R equal 1.37 ± 0.35, 1.55 ± 0.24, 1.1 ± 0.15 µM respectively. Also, molecular docking of the target compounds into the LasR binding site co-crystalized "odDHL" revealed their binding with the essential residues for protein inhibition. Additionally, molecular dynamics simulation (MDS) experiments over 200 ns of compound 3c showed its ability to interact with the LasR binding site with dissociation of the protein's dimer confirming its action as a LasR antagonist. The obtained findings inspire further investigation for benzo[d]thiazole and 2-pyrazolo[1,5-a]pyrimidin-3-yl)benzo[d]thiazoles aiming to design and synthesize more potential QS inhibitors.

Traumatic retinal detachment: A contemporary update.

Retinal detachment following ocular trauma (TrRD) is one of the leading causes of blindness and visual impairment worldwide. In the absence of a standardized definition, the diagnosis of traumatic retinal detachment relies on identifying a history of trauma that precedes the detachment. There is an increasing pool of data regarding the etiology and epidemiology of TrRD.Various causes of TrRD mentioned in the literature include work-related eye trauma in construction and manufacturing industries, sports injuries, explosive eye injuries, road traffic accidents, and intraocular foreign bodies. Although there is extensive literature on post-trauma retinal detachments, a comprehensive discussion of its pathogenesis, management, outcomes, and complications is lacking. We offer an in-depth review of the epidemiology, risk factors, pathogenesis, diagnosis, management, and outcomes of TrRD based on the current literature.

Testicular seminoma presenting as an acute strangulated hernia: An intraoperative diagnosis.

Testicular seminomas are the most common type of testicular tumor; atypical presentations can make diagnosis more challenging, leading to delayed treatment. Here, we present a 40-year-old previously healthy male who presented to the emergency department with severe right-sided scrotal swelling and pain. He had a diagnosed but untreated inguinal hernia. Physical examination revealed a large irreducible right inguinoscrotal swelling and tenderness. Doppler ultrasound reported herniated content in the right inguinal area, extending to the scrotum. Upon surgical exploration, a large right testicular tumor was discovered, surrounded by hematoma. A radical orchiectomy was performed, and the tumor was identified as a stage pT2 testicular seminoma. This case illustrates the diagnostic challenges posed by atypical presentations of testicular seminomas. A high index of suspicion and thorough clinical and radiological assessments are crucial for accurate diagnosis and management. In conclusion, large testicular seminomas presenting with acute pain mimicking strangulated hernias are rare. Comprehensive clinical and radiological evaluations are essential to avoid misdiagnosis and ensure appropriate surgical planning and patient management.

Race, Ethnicity, and Sex in Pediatric Eye Disease Investigator Group Clinical Studies.

Importance: Racial, ethnic, and sex disparities exist in US clinical study enrollment, and the prevalence of these disparities in Pediatric Eye Disease Investigator Group (PEDIG) clinical studies has not been thoroughly assessed. Objective: To evaluate racial, ethnic, and sex representation in PEDIG clinical studies compared with the 2010 US Census pediatric population. Design, Setting, and Participants: This cross-sectional analysis examined PEDIG clinical studies based in the US from December 1, 1997 to September 12, 2022, 41 of which met inclusion criteria of a completed study, a study population younger than 18 years, and 1 or more accompanying publication. Data analysis was performed between November 2023 and February 2024. Exposure: Study participant race, ethnicity, and sex for each clinical study, as collected from peer-reviewed publications, patient-enrollment datasets, and ClinicalTrials.gov. Main Outcomes and Measures: Median enrollment percentages of female, White, Black, Hispanic, Asian, and other race participants were calculated and compared with the 2010 US Census pediatric population using a 1-sample Wilcoxon rank test. Proportionate enrollment was defined as no difference on a 1-sample Wilcoxon rank test if P ≥ .05. If P < .05, we determined if the median enrollment percentage was greater than or less than 2010 US Census proportion to determine if enrollees were underrepresented or overrepresented. To calculate the magnitude of overrepresentation or underrepresentation, enrollment-census difference (ECD) was defined as the difference between groups' median enrollment percentage and percentage representation in the 2010 US Census. Compound annual growth rate (CAGR) was used to measure temporal trends in enrollment, and logistic regression analysis was used to analyze factors that may have contributed to proportionate representation outcomes. Results: A total of 11 658 study participants in 41 clinical studies were included; mean (SD) participant age was 5.9 (2.8) years and 5918 study participants (50.8%) were female. In clinical studies meeting inclusion criteria, White participants were overrepresented (ECD, 0.19; 95% CI, 0.10-0.28; P < .001). Black participants (ECD, -0.07; 95% CI, -0.10 to -0.03; P < .001), Asian participants (ECD, -0.03; 95% CI, -0.04 to -0.02; P < .001), and Hispanic participants (ECD, -0.09; 95% CI, -0.13 to -0.05; P < .001) were underrepresented. Female participants were represented proportionately (ECD, 0.004; 95% CI, -0.036 to 0.045; P = .21). White and Asian participants demonstrated a decreasing trend in study enrollment from 1997 to 2022 (White: CAGR, -1.5%; 95% CI, -2.3% to -0.6%; Asian: CAGR, -1.7%; 95% CI, -2.0% to -1.4%), while Hispanic participants demonstrated an increasing enrollment trend (CAGR, 7.2%; 95% CI, 3.7%-10.7%). Conclusions and Relevance: In this retrospective cross-sectional study of PEDIG clinical studies from December 1, 1997 to September 12, 2022, Black, Hispanic, and Asian participants were underrepresented, White participants were overrepresented, and female participants were represented proportionally. Trends suggested increasing enrollment of Hispanic participants and decreasing enrollment of White participants over time. This study demonstrates an opportunity to advocate for increased enrollment of underrepresented groups in pediatric ophthalmology clinical studies.

Mitigation of biochemical alterations in streptozotocin-induced gestational diabetes in rats through mesenchymal stem cells and olive leaf extract.

Treatment with mesenchymal stem cells (MSCs) is a new promising therapeutic approach with substantial very auspicious potential. They have been shown to protect various played a role in protecting organs from damage. This current study aims to evaluate the impact of the treatment of olive leaf extract (OLE), bone marrow-derived (BM-MSCs), and their combination on hepatotoxicity in pregnant rats with diabetes. METHODS: Animals were divided into five groups (10 pregnant rats each) as follows: control, GDM group, and OLE group (rats received streptozotocin (STZ) at a dose of 35 mg/kg body weight). GD + OLE set (pregnant rats were administered OLE at a dose of 200 mg extract/kg of body weight). GD + MSCs group (pregnant rats treated with MSCs). GD + OLE + MSCs group (pregnant rats were treated with both MSCs and OLE). RESULTS: STZ induced significant changes in liver parameters, lipid profile, and oxidative stress. Treatment with OLE, BM-MSCs, and their combination significantly ameliorated STZ-induced liver damage and oxidative stress. STZ resulted in a significant change in liver parameters, lipid profile, and oxidative stress. OLE, BM-MSC, and combination have significantly improved STZ-induced deterioration in liver and improved oxidative stress. CONCLUSIONS: The findings demonstrate that OLE and BM-MSCs have beneficial effects in mitigating diabetes-related liver alterations. These outcomes showed that OLE and BM-MSC have beneficial effects in alleviating diabetes-related alterations in the liver.

Effectiveness and Safety of Trabeculectomy Versus Tube Shunt Implantation for Uveitic Glaucoma: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effectiveness and safety of trabeculectomy compared to glaucoma drainage devices (GDDs) in managing uveitic glaucoma (UG). DESIGN: Systematic review. METHODS: We searched seven electronic databases (PubMed, Scopus, Web of Science, ScienceDirect, EMBASE, CENTRAL, and Google Scholar) to compare trabeculectomy with various GDDs in UG. The primary outcome was intraocular pressure (IOP) reduction, and secondary outcomes included postoperative complications. We fitted a random effects model for meta-analysis and assessed the risk of bias using the National Institute of Health quality assessment tool. RESULTS: We included eight studies; 197 eyes underwent trabeculectomy, and 277 eyes had GDDs. The mean age of participants was 48.5 years, with ∼53.5% being male in the trabeculectomy group and 49.3% in the GDDs group. The meta-analysis revealed no significant difference in IOP reduction between trabeculectomy and GDDs (P = .48). Subgroup analyses revealed no significant difference in IOP reduction between trabeculectomy and either the Ahmed glaucoma drainage device group (P = .38) or the Baerveldt glaucoma implant group (P = .90). GDDs were associated with higher rates of complications such as cystoid macular edema (CME) (15% vs. 4%, P < .001), need for revision surgery (11% vs. 6%, P = .04), and uveitic flare (5% vs. 0%, P = .001). However, trabeculectomy had a higher risk of cataract progression (7% vs. 1%, P < .001). CONCLUSION: Trabeculectomy and GDDs demonstrated comparable effectiveness in reducing IOP or glaucoma medication reduction in UG. However, there were significant differences in their safety profiles; CME and revisions were higher in GDD, and cataract progression was higher after trabeculectomy.

Biological effects of Bougainvillea glabra, Delonix regia, Lantana camara, and Platycladus orientalis extracts and their possible metabolomics therapeutics against the West Nile virus vector, Culex pipiens (Diptera: Culicidae).

Plants are a treasure trove of biological materials containing a wide range of potential phytochemicals that are target-specific, rapidly biodegradable, and environmentally friendly, with multiple medicinal effects. Unfortunately, the development of resistance to synthetic pesticides and antibiotics led to the discovery of new antibiotics, antioxidants, and biopesticides. This has also led to the creation of new medications that work very well. The current study aimed to prove that ornamental plants contain specialized active substances that are used in several biological processes. Mosquitoes, one of the deadliest animals on the planet, cause millions of fatalities each year by transmitting several human illnesses. Phytochemicals are possible biological agents for controlling pests that are harmful. The potential of leaf extracts of Bougainvillea glabra, Delonix regia, Lantana camara, and Platycladus orientalis against Culex pipiens and microbial agents was evaluated. Acetone extracts had more toxic effects against Cx. pipiens larvae (99.0-100 %, 72 h post-treatment), and the LC50 values were 142.8, 189.5, 95.4, and 71.1 ppm for B. glabra, D. regia, L. camara, and P. orientalis, respectively. Plant extracts tested in this study showed high insecticidal, antimicrobial, and antioxidant potential. GC-MS and HPLC analyses showed a higher number of terpenes, flavonoids, and phenolic compounds. The ADME analysis of element, caryophyllene oxide, caryophyllene, and copaene showed that they were similar to drugs and that they were better absorbed by the body and able to pass through the blood-brain barrier. Our results confirm the ability of ornamental plants to have promising larvicidal and antimicrobial activity and biotechnology.

Large language models: a new frontier in paediatric cataract patient education.

BACKGROUND/AIMS: This was a cross-sectional comparative study. We evaluated the ability of three large language models (LLMs) (ChatGPT-3.5, ChatGPT-4, and Google Bard) to generate novel patient education materials (PEMs) and improve the readability of existing PEMs on paediatric cataract. METHODS: We compared LLMs' responses to three prompts. Prompt A requested they write a handout on paediatric cataract that was 'easily understandable by an average American.' Prompt B modified prompt A and requested the handout be written at a 'sixth-grade reading level, using the Simple Measure of Gobbledygook (SMOG) readability formula.' Prompt C rewrote existing PEMs on paediatric cataract 'to a sixth-grade reading level using the SMOG readability formula'. Responses were compared on their quality (DISCERN; 1 (low quality) to 5 (high quality)), understandability and actionability (Patient Education Materials Assessment Tool (≥70%: understandable, ≥70%: actionable)), accuracy (Likert misinformation; 1 (no misinformation) to 5 (high misinformation) and readability (SMOG, Flesch-Kincaid Grade Level (FKGL); grade level <7: highly readable). RESULTS: All LLM-generated responses were of high-quality (median DISCERN ≥4), understandability (≥70%), and accuracy (Likert=1). All LLM-generated responses were not actionable (<70%). ChatGPT-3.5 and ChatGPT-4 prompt B responses were more readable than prompt A responses (p<0.001). ChatGPT-4 generated more readable responses (lower SMOG and FKGL scores; 5.59±0.5 and 4.31±0.7, respectively) than the other two LLMs (p<0.001) and consistently rewrote them to or below the specified sixth-grade reading level (SMOG: 5.14±0.3). CONCLUSION: LLMs, particularly ChatGPT-4, proved valuable in generating high-quality, readable, accurate PEMs and in improving the readability of existing materials on paediatric cataract.

Innovating Thiopurine Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis on DNA-Thioguanine Nucleotides (DNA-TG) as an Inclusive Biomarker in Thiopurine Therapy.

BACKGROUND AND OBJECTIVE: Thioguanine (TG), azathioprine (AZA), and mercaptopurine (MP) are thiopurine prodrugs commonly used to treat diseases, such as leukemia and inflammatory bowel disease (IBD). 6-thioguanine nucleotides (6-TGNs) have been commonly used for monitoring treatment. High levels of 6-TGNs in red blood cells (RBCs) have been associated with leukopenia, the cutoff levels that predict this side effect remain uncertain. Thiopurines are metabolized and incorporated into leukocyte DNA. Measuring levels of DNA-incorporated thioguanine (DNA-TG) may be a more suitable method for predicting clinical response and toxicities such as leukopenia. Unfortunately, most methodologies to assay 6-TGNs are unable to identify the impact of NUDT15 variants, effecting mostly ethnic populations (e.g., Chinese, Indian, Malay, Japanese, and Hispanics). DNA-TG tackles this problem by directly measuring thioguanine in the DNA, which can be influenced by both TPMT and NUDT15 variants. While RBC 6-TGN concentrations have traditionally been used to optimize thiopurine therapy due to their ease and affordability of measurement, recent developments in liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have made measuring DNA-TG concentrations in lymphocytes accurate, reproducible, and affordable. The objective of this systematic review was to assess the current evidence of DNA-TG levels as marker for thiopurine therapy, especially with regards to NUDT15 variants. METHODS: A systematic review and meta-analysis were performed on the current evidence for DNA-TG as a marker for monitoring thiopurine therapy, including methods for measurement and the illustrative relationship between DNA-TG and various gene variants (such as TPMT, NUDT15, ITPA, NT5C2, and MRP4). PubMed and Embase were systematically searched up to April 2024 for published studies, using the keyword "DNA-TG" with MeSH terms and synonyms. The electronic search strategy was augmented by a manual examination of references cited in articles, recent reviews, editorials, and meta-analyses. A meta-analysis was performed using R studio 4.1.3. to investigate the difference between the coefficients (Fisher's z-transformed correlation coefficient) of DNA-TG and 6-TGNs levels. A meta-analysis was performed using RevMan version 5.4 to investigate the difference in DNA-TG levels between patients with or without leukopenia using randomized effect size model. The risk of bias was assessed using the Newcastle-Ottowa quality assessment scale. RESULTS: In this systematic review, 21 studies were included that measured DNA-TG levels in white blood cells for either patients with ALL (n = 16) or IBD (n = 5). In our meta-analysis, the overall mean difference between patients with leukopenia (ALL + IBD) versus no leukopenia was 134.15 fmol TG/µg DNA [95% confidence interval (CI) (83.78-184.35), P < 0.00001; heterogeneity chi squared of 5.62, I2 of 47%]. There was a significant difference in DNA-TG levels for patients with IBD with and without leukopenia [161.76 fmol TG/µg DNA; 95% CI (126.23-197.29), P < 0.00001; heterogeneity chi squared of 0.20, I2 of 0%]. No significant difference was found in DNA-TG level between patients with ALL with or without leukopenia (57.71 fmol TG/µg DNA [95% CI (- 22.93 to 138.35), P < 0.80]). DNA-TG monitoring was found to be a promising method for predicting relapse rates in patients with ALL, and DNA-TG levels are likely a better predictor for leukopenia in patients with IBD than RBC 6-TGNs levels. DNA-TG levels have been shown to correlate with various gene variants (TPMT, NUDT15, ITPA, and MRP4) in various studies, points to its potential as a more informative marker for guiding thiopurine therapy across diverse genetic backgrounds. CONCLUSIONS: This systematic review strongly supports the further investigation of DNA-TG as a marker for monitoring thiopurine therapy. Its correlation with treatment outcomes, such as relapse-free survival in ALL and the risk of leukopenia in IBD, underscores its role in enhancing personalized treatment approaches. DNA-TG effectively identifies NUDT15 variants and predicts late leukopenia in patients with IBD, regardless of their NUDT15 variant status. The recommended threshold for late leukopenia prediction in patients with IBD with DNA-TG is suggested to be between 320 and 340 fmol/µg DNA. More clinical research on DNA-TG implementation is mandatory to improve patient care and to improve inclusivity in thiopurine treatment.

Biochemical study of ZNF76 rs10947540 and SCUBE3 rs1888822 single nucleotide polymorphisms in the Egyptian patients with systemic lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a common autoimmune disease marked by the formation of apoptotic debris and the presence of autoantibodies that target nuclear components. At this moment, the actual cause of SLE is uncertain. Genetic variables have been well proven to have a significant role in the propensity of SLE. This study aimed to investigate the effect of (ZNF76) rs (10947540) and (SCUBE) rs (1888822) gene polymorphism in patients with systemic lupus erythematosus. A case control study has been carried out at Medical Biochemistry & Molecular biology and Rheumatology unit of Internal Medicine Departments, Faculty of Medicine, Menoufia University, Egypt, for 1-year duration between 1 June 2022 and 1 June 2023. Sixty patients were females (75%) and twenty patients were males (25%). Their ages ranged from 19 to 53 years. Their disease durations ranged from 7 months to 20 years. The findings indicated that the TC genotype of the ZNF76 rs10947540 gene increases the risk of SLE by 2.274-fold, while the dominant TC + CC increases the risk by 2.472-fold, and the C allele increases the risk by 2.115-fold. Additionally, the results showed that the TT genotype of the SCUBE3 rs1888822 gene increases the risk of SLE by 3.702-fold, the dominant GT + TT increases the risk by 2.304-fold, and the T allele increases the risk by 2.089-fold, while the GT genotype increases the risk by 1.918-fold. The study revealed significant associations between the genotypes of these polymorphisms and certain clinical parameters in SLE patients. These findings highlight the potential genetic contributions to SLE susceptibility and its clinical manifestations, providing valuable insights for future research and potential personalized approaches to the management of this complex autoimmune disease.

Posterior Scleritis in a Pediatric Patient: Importance of Pain Recognition and Early Ultrasound Diagnosis.

Scleritis is a rare and potentially sight-threatening inflammatory disorder affecting the sclera. While anterior scleritis is the more commonly encountered subtype, posterior scleritis represents a larger portion of cases in the pediatric population. Diagnosing posterior scleritis can be challenging due to the overlap with other more common ocular conditions, particularly in the pediatric age group. In this case report, we present a unique case of posterior scleritis in a 12-year-old girl. The patient initially presented with severe right-sided headache and eye pain, which was initially misdiagnosed as atypical optic neuritis. However, subsequent magnetic resonance imaging and ocular ultrasound confirmed the diagnosis of posterior scleritis. This case highlights the significance of recognizing pain as a key symptom and the value of early ultrasound evaluation in diagnosing posterior scleritis in the pediatric population.

Discovery of new 1,3-diphenylurea appended aryl pyridine derivatives as apoptosis inducers through c-MET and VEGFR-2 inhibition: design, synthesis, in vivo and in silico studies.

Interest has been generated in VEGFR-2 and c-MET as potential receptors for the treatment of different malignancies. Using aryl pyridine derivatives with 1,3-diphenylurea attached, a number of promising dual VEGFR-2 and c-MET inhibitors were developed and synthesized. Regarding the molecular target, compounds 2d, 2f, 2j, 2k, and 2n had potent IC50 values of 65, 24, 150, 170, and 18 nM against c-MET, respectively. Additionally, they had potent IC50 values of 310, 35, 290, 320, and 24 nM against VEGFR-2, respectively. Regarding cytotoxicity, compounds 2d, 2f, 2j, 2k and 2n exhibited potent cytotoxicity against MCF-7 with IC50 values in the range 0.76-21.5 µM, and they showed promising cytotoxic activity against PC-3 with IC50 values in the range 1.85-3.42 µM compared to cabozantinib (IC50 = 1.06 µM against MCF-7 and 2.01 µM against PC-3). Regarding cell death, compound 2n caused cell death in MCF-7 cells by 87.34-fold; it induced total apoptosis by 33.19% (8.04% for late apoptosis, 25.15% for early apoptosis), stopping their growth in the G2/M phase, affecting the expression of apoptosis-related genes P53, Bax, caspases 3 and 9 and the anti-apoptotic gene, Bcl-2. In vivo study illustrated the anticancer activity of compound 2n by reduction of tumor mass and volume, and the tumor inhibition ratio reached 56.1% with an improvement of hematological parameters. Accordingly, compound 2n can be further developed as a selective target-oriented chemotherapeutic against breast cancer.

Fractal Changes of the Retinal Microvasculature in Birdshot Chorioretinopathy.

BACKGROUND AND OBJECTIVE: Retinal vascular disorders are associated with lower fractal dimension (FD). We analyzed FD in birdshot chorioretinopathy (BSCR). PATIENTS AND METHODS: This was a retrospective cohort study. We performed optical coherence tomography angiography (OCTA) and analyzed FD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using ImageJ. For each vascular layer, we analyzed the presence of BSCR, subjects' age, sex, and presence of diabetes mellitus to determine which may predict lower FD. RESULTS: We compared 28 eyes (14 patients) with BSCR to 34 control eyes (17 patients). Mean FD of BSCR was lower in SCP (1.584 [± 0.126] vs 1.706 [± 0.118], P < 0.001), DCP (1.637 [± 0.134] vs 1.780 [± 0.096], P < 0.001), and CC (1.884 [± 0.063] vs 1.917 [± 0.047], P = 0.036). FD of SCP was lower per increasing year (0.005 [P = 0.014]). Male patients had lower FD-DCP (0.101 [P = 0.043]). CONCLUSION: In BSCR, fractal analysis showed significant involvement of the SCP, DCP, and to a lesser extent the CC. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Phacofragmentation of Posteriorly Dislocated Lens Fragments: Limbal versus Pars Plana Approach.

PURPOSE: To assess intra-operative complications and feasibility of removing crystalline lens fragments from the vitreous cavity through a limbal incision compared to a pars plana approach. DESIGN: Retrospective cohort study. SUBJECTS: 16 eyes underwent phacofragmentation via a limbal approach (Group A) and 9 eyes through a pars plana approach (Group B) at an academic center over a 10-year period. METHODS: We collected pre-operative, intra-operative, and post-operative data. We compared rates of intraoperative complications, including corneal wound burn, iris or capsular damage, retinal tears, and hemorrhage, and recorded post-operative BCVA and IOP measurements at the one-month post-operative appointment. We also compared rates of post-operative complications, including corneal edema, choroidal detachment, or retinal detachment. MAIN OUTCOME MEASURES: Primary outcomes of the study were the rates of intraoperative complications and the feasibility of crystalline lens removal with the limbal approach. We defined the latter outcome as the ability to complete lens removal without switching to the pars plana route. RESULTS: Mean BCVA for group A was 1.6, and for group B was 2.0 (p = .19). There was no significant difference between the two groups in the incidence of intraoperative complications, including corneal wound burn, iris damage, anterior capsular tear, iatrogenic retinal tear, or suprachoroidal hemorrhage (p > .99). There was no significant difference in the incidence of intra-operative vitreous hemorrhage (p = .36). Additionally, there was no significant difference in post-operative corneal edema (p = .27), choroidal detachment (p = .52), or retinal detachment (p > .99). The mean post-operative BCVA was 1.0 in group A and 1.0 in group B (p = .75). We completed all cases in group A using the limbal approach without switching to the pars plana route. CONCLUSION: Phacofragmentation through a limbal incision provides a feasible option for dropped nuclear fragment removal and is not associated with a higher risk of complications than the pars plana route.

Unraveling the controversy between fasting and nonfasting lipid testing in a normal population: a systematic review and meta-analysis of 244,665 participants.

BACKGROUND: The final decision to fast or not fast for routine lipid profile examination in a standard, healthy population is unclear. Whereas the United States and European protocols state that fasting for regular lipid analysis is unnecessary, the North American and Chinese guidelines still recommend fasting before routine lipid testing. AIM: This study aimed to unravel the contradiction between the different protocols of lipid profile testing worldwide and clarify the effect of diet on lipid profile testing only in a regular, healthy population. METHODS: A literature search was conducted through May 2024. The analyses included studies performed from the date 2000 until now because the contradiction of guidelines for lipid profile testing appeared for the first time in this period. A planned internal validity evaluation was performed using the National Institute of Health (NIH) quality measurement tools for observational cohort, case‒control, controlled interventional, and cross-sectional studies. The data were synthesized according to RevMan 5.3. RESULTS: Eight studies with a total of 244,665 participants were included. The standardized mean difference in cholesterol in six studies showed significant differences in overall effect among fasting and nonfasting states (P < 0.00001), as did high-density lipoprotein cholesterol (P < 0.00001). At the same time, with respect to triglycerides and low-density lipoprotein cholesterol, there were notable variations in the overall effect between the fasted and nonfasted states (P < 0.00001 and P ≤ 0.001, respectively). CONCLUSIONS: This meta-analysis concluded that fasting for lipid profile testing is preferred as a conservative model to reduce variability and increase consistency in patients' metabolic status when sampling for lipid testing.