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.

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.

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.].

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.

Anesthesia Techniques for Vitreoretinal Surgery in the United States: A Report from the Multicenter Perioperative Outcomes Group Research Consortium.

PURPOSE: To explore the patterns of anesthesia use and their determinants during vitreoretinal (VR) surgeries in academic and community hospitals across the US, using data from the Multicenter Perioperative Outcomes Group (MPOG). DESIGN: A retrospective, multicenter, cohort study. METHODS: We queried the MPOG database of 107,066 patients undergoing VR surgeries. Patients (≥18 years) undergoing VR surgery with monitored anesthesia care (MAC) or general anesthesia (GA) from January 1, 2015 to December 31, 2021 were included. Patient-level, case-based, and institutional-level covariates were collected. We performed multivariable mixed-effects models to determine predictors of anesthesia type use. The primary outcome was the type of anesthesia (MAC or GA) used during VR surgeries. As a secondary outcome, MAC cases were further classified based on the additional use of sedation into MAC with or without sedation. RESULTS: We found that 67.45% of VR surgery cases received MAC, and 73.63% of institutions administered MAC to more than half of cases. Random effect modeling revealed that 47.76% of the variation in MAC use was attributed to institutions. A trend toward increased use of MAC with increasing age was observed. Patients diagnosed with chronic pulmonary disease, liver disease, or a history of drug abuse were less likely to receive MAC. Conversely, we found that patients with reported alcohol abuse disorder, diabetes with complications, and those with American Society of Anesthesiologists (ASA) physical status of 4 (vs. 1, 2, or 3) were more likely to use MAC. Compared to non-complex VR surgeries, there was a notably decreased likelihood of MAC use in complex PPV (P = .004), PPV + scleral buckle (SB) for retinal detachment (P < .0001), and primary SB surgery (P < .0001). CONCLUSIONS: Approximately 2/3 of VR anesthesia is under MAC, but GA is still preferred for SBs, complex vitrectomy, and younger patients. We show that large interinstitutional variation for using MAC in practice exists.

Machine learning-based classification of structured light modes under turbulence and eavesdropping effects.

This paper considers the classification of multiplexed structured light modes, aiming to bolster communication reliability and data transfer rates, particularly in challenging scenarios marked by turbulence and potential eavesdropping. An experimental free-space optic (FSO) system is established to transmit 16 modes [8-ary Laguerre Gaussian (LG) and 8-ary superposition LG (Mux-LG) mode patterns] over a 3-m FSO channel, accounting for interception threats and turbulence effects. To the best of authors' knowledge, this paper is the first to consider both factors concurrently. We propose four machine/deep learning algorithms-artificial neural network, support vector machine, 1D convolutional neural network, and 2D convolutional neural network-for classification purposes. By fusing the outputs of these methods, we achieve promising classification results exceeding 92%, 81%, and 69% in cases of weak, moderate, and strong turbulence, respectively. Structured light modes exhibit significant potential for a variety of real-world applications where reliable and high-capacity data transmission is crucial.

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.

Diverse bioactive secondary metabolites from Aspergillus terreus: antimicrobial, anticancer, and anti-SARS-CoV-2 activity studies.

Owing to its high interest as prolific source of diverse bioactive compounds referred in our previous research work, we have scaled-up the fermentation of the marine Aspergillus terreus LGO13 on a liquid culture medium to isolate and identify the very minor/further promising bioactive secondary metabolites and to study their antibacterial, cytotoxic, and antiviral properties. Twenty-three known bioactive metabolites, including the recently discovered microbial natural product N-benzoyl-tryptophan (1), were obtained herein. Their structures were determined using HR-ESI-MS 1D/2D NMR spectroscopy and data from the literature. The biological properties of the microbial extract and the resulting compounds were examined using a set of microorganisms, cervix carcinoma KB-3-1, nonsmall cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulations were used to investigate the potential targets of the separated metabolites as anti-SARS-CoV-2 drugs. According to the current study, a viral protein that may be the target of anticovid drugs is a papain-like protease (PLpro), and chaetominine (2) appears to be a viable choice against this protein. We evaluated the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2 based on MD data. Chaetominine (2) and azaspirofuran A (9) displayed intermediate selectivity indices (SI = 6.6 and 3.2, respectively), while fumitremorgin C (6) displayed a high selectivity index (SI = 19.77). These findings show that fumitremorgin C has promising antiviral action against SARS-CoV-2.

Quality, Reliability, Readability, and Accountability of Online Information on Leukocoria.

PURPOSE: To evaluate the quality, reliability, and readability of online patient educational materials on leukocoria. METHODS: In this cross-sectional study, the Google search engine was searched for the terms "leukocoria" and "white pupil." The first 50 search outcomes were evaluated for each search term based on predefined inclusion criteria, excluding duplicates, peer-reviewed papers, forum posts, paywalled content, and multimedia links. Sources were categorized as "institutional" or "private." Three independent raters assessed each website for quality and reliability using DISCERN, Health on the Net Code of Conduct (HONcode), and JAMA criteria. Readability was evaluated using seven formulas: Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG) Index, Automated Readability Index (ARI), Linsear Write (LW), Gunning Fog Index (GFI), and Coleman-Liau Index (CLI). RESULTS: A total of 51 websites were included. Quality, assessed by the DISCERN tool, showed a median score of 4, denoting moderate to high quality, with no significant differences between institutional and private sites or search terms. HONcode scores indicated variable reliability and trustworthiness (median: 10, range: 3 to 16), with institutional sites excelling in financial disclosure and ad differentiation. Additionally, institutional and private sites performed well in reliability and accountability, as measured by the JAMA Benchmark criteria (median: 3; range: 1 to 4). Readability, averaging an 11.3 ± 3.7 grade level, did not differ significantly between site types or search terms, consistently falling short of the recommended sixth-grade level for patient educational materials. CONCLUSIONS: The patient educational materials on leukocoria demonstrated moderate to high quality, commendable reliability, and accountability. However, the readability scores were above the recommended level for the layperson. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Transporter Protein Expression of Corneal Epithelium in Rabbit and Porcine: Evaluation of Models for Ocular Drug Transport Study.

The transcorneal route is the main entry route for drugs to the intraocular parts, after topical administration. The outer surface, the corneal epithelium (CE), forms the rate-limiting barrier for drug permeability. Information about the role and protein expression of drug and amino acid transporter proteins in the CE is sparse and lacking. The aim of our study was to characterize transporter protein expression in rabbit and porcine CE to better understand potential drug and nutrient absorption after topical administration. Proteins, mainly Abc and Slc transporters, were characterized with quantitative targeted absolute proteomics and global untargeted proteomics methods. In the rabbit CE, 24 of 48 proteins were detected in the targeted approach, and 21 of these were quantified. In the porcine CE, 26 of 58 proteins were detected in the targeted approach, and 20 of these were quantified. Among these, 15 proteins were quantified in both animals: 4f2hc (Slc3a2), Aqp0, Asct1 (Slc1a4), Asct2 (Slc1a5), Glut1 (Slc2a1), Hmit (Slc2a13), Insr, Lat1 (Slc7a5), Mct1 (Slc16a1), Mct2 (Slc16a7), Mct4 (Slc16a3), Mrp 4 (Abcc4), Na+/K+-ATPase, Oatp3a1 (Slco3a1), and Snat2 (Slc38a2). Overall, the global proteomics results supported the targeted proteomics results. Organic anion transporting polypeptide Oatp3a1 was detected and quantified for the first time in both rabbit (1.4 ± 0.4 fmol/cm2) and porcine (11.1 ± 5.3 fmol/cm2) CE. High expression levels were observed for L-type amino acid transporter, Lat1, which was quantified with newly selected extracellular domain peptides in rabbit (48.9 ± 11.8 fmol/cm2) and porcine (37.6 ± 11.5 fmol/cm2) CE. The knowledge of transporter protein expression in ocular barriers is a key factor in the successful design of new ocular drugs, pharmacokinetic modeling, understanding ocular diseases, and the translation to human.

Leptin gene Polymorphism and Leptin protein levels in Pediatric Autoimmune Hepatitis.

BACKGROUND: Leptin plays a role in regulating energy balance, immunity, and inflammation. Studies suggest higher leptin levels might be associated with various autoimmune diseases. Most of them were in adult. To our knowledge, our study is one of the few that describe serum leptin level and leptin gene polymorphism in children with autoimmune hepatitis (AIH). OBJECTIVE: Our study aims to explore the association between serum leptin level and genetic variations in leptin gene with the likelihood of AIH in children. PATIENTS AND METHODS: Thirty-one children with AIH and 29 healthy children serving as a control group were included. Serum leptin levels were measured by ELISA assays. Leptin rs2167270 genotyping was done using the real time-PCR. The relationship of serum leptin level and leptin gene polymorphism with patients' data was studied. Patients follow up to assess treatment response. RESULTS: Children with AIH had significantly higher levels of leptin compared to healthy controls. GG genotype was significantly more prevalent in the AIH group compared to controls. CONCLUSION: High serum leptin levels and leptin gene polymorphism may play a role in AIH development. It is worthy to recognize if leptin can serve as diagnostic and/or therapeutic target in AIH in children.

The Association of Sickle-Cell Disorders With Diabetic Retinopathy: A Large Database Study.

Purpose: To evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM). Design: Population-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 health care organizations worldwide. Participants: Diabetes mellitus patients (type 1 [T1DM] or 2 [T2DM]), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or sickle-cell/hemoglobin-C; (2) DM with SCD; and (3) DM with SCT. Methods: All patients with DM were categorized into 3 cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities. Main Outcome Measures: Risk of DR in DM patients with and without SCD or SCT. Results: There was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable twofold increased risk for T1-proliferative DR (PDR) (relative risk [RR]: 2.03; 95% confidence interval [CI]: 1.33-3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19-1.88), particularly due to higher PDR risks in T2DM patients (RR: 1.83; 95% CI: 1.29-2.60). The risk of mild to moderate T2DM non-PDR was also found to be higher in patients with SCT. Conclusions: The risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for PDR in patients with SCT and T1DM. This indicates there may be a potential role of sickle-cell disorders in diabetic eye disease progression. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of Complications and Visual Outcomes of Combined Phacovitrectomy versus Standalone Phacoemulsification: A Multicenter Database Study.

PURPOSE: To compare the rates of intraoperative complications, cystoid macular edema (CME), and visual outcomes in eyes that underwent combined phacovitrectomy (Phaco-PPV) to those with standalone phacoemulsification. SETTING: A multicenter database study across 8 ophthalmology departments in the United Kingdom. DESIGN: Retrospective, nonrandomized, multicenter comparative study. METHODS: We extracted data for patients who underwent Phaco-PPV and standalone phacoemulsification from January 2000 through May 2015. The primary study outcomes were the rates of intraoperative complications and CME after surgery. RESULTS: The study included 2222 eyes in the combined Phaco-PPV group and 112689 in the standalone phacoemulsification group. The combined Phaco-PPV group had a higher incidence of posterior capsule rupture (2.7% vs. 1.7%), dropped lens fragments (0.5% vs. 0.2%), suprachoroidal hemorrhage (0.4% vs. 0.1%), and cystoid macular edema (3.6 vs. 1.1%) (P<0.001). The mean preoperative visual acuity (VA) was lower in the combined Phaco-PPV group, with a mean VA of 0.98 vs 0.68 logMAR (Snellen ∼20/200 vs. 20/100) in the standalone phacoemulsification group (P<0.001). Visual acuity at 24 weeks was lower in the combined Phaco-PPV group (mean VA 0.67 vs. 0.22 logMAR (Snellen ∼20/100 vs. 20/32), P<0.001). CONCLUSION: Combined Phaco-PPV had higher rates of intraoperative complications and CME, along with a lower postoperative visual acuity when compared to standalone phacoemulsification surgery.

Trifecta in flexible ureteroscopy for treatment of renal and upper ureteral calculi: A multicenter study.

Purpose: To determine predictors for missing trifecta in patients who underwent flexible ureteroscopy (FURS) for treatment of renal and upper ureteric calculi. Patients and Methods: The data of adult patients with renal or upper ureteral stones who underwent FURS from June 2021 through December 2022 were retrospectively reviewed. Stone-free status (no residual stones > 3 mm) was evaluated after 3 months with non-contrast CT. Modified Clavien classification was used to grade complications. A stone-free status after a single intervention of FURS without complications was defined as trifecta. Patients were divided into two groups (trifecta and non-trifecta). Risk factors for missing trifecta were compared between both groups using univariate and multivariate analyses. Results: Three hundred twenty-three patients with mean age 48.9 ± 13 years and mean stone length 16 ± 5.9 mm were included. The trifecta criteria were applicable for 250 patients (71%). On multivariate analysis, risk factors for missing trifecta were stone multiplicity (OR: 3.326, 95%CI: 1.933-5.725) and non-experienced surgeons (OR: 1.819, 95%CI: 1.027-3.220). Conclusions: Multiple stones and performance of FURS by non-experienced surgeons are the independent risk factors for missing trifecta of FURS.

Posterior Segment Manifestations of Syphilis and Correlation With Serologic Markers of Infection.

BACKGROUND AND OBJECTIVE: Retrospective analysis correlating serologic titers of ocular syphilis with posterior segment manifestations. PATIENTS AND METHODS: This study consisted of 40 patients (80 eyes imaged, 68 affected) with positive rapid plasma reagin (RPR) and Treponema Pallidum immunoglobulin G. We collected demographic and presentation data including HIV status, absolute CD4 count, RPR, cerebrospinal fluid-venereal disease research laboratory (CSF-VDRL) test, and retinal zone. We categorized imaging into syphilitic outer retinopathy (SOR), acute syphilitic posterior placoid chorioretinopathy, retinitis/chorioretinitis (RC), and papillitis. Multivariate analysis correlated HIV status, RPR, and VDRL titers with posterior segment findings and zone. RESULTS: Mean age of 42.8 ± 10.7 years, with 70% male patients. Presenting visual acuity (logMAR) 0.66 ± 0.74 did not correlate with RPR, nor was it associated with papillitis, RC, or acute syphilitic posterior placoid chorioretinopathy. Higher RPR (≥ 1:128) positively associated with SOR (P = 0.031) and zone 1 (odds ratio [OR], 1.62; P = 0.02), but negatively associated with zone 2 (OR 0.35; P = 0.005). HIV positivity increased RC odds (OR, 4.45; P = 0.047). CONCLUSION: Higher RPR correlated with SOR and zone 1, whereas HIV positivity correlated with RC. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Physiologically based pharmacokinetics modeling and transporter proteomics to predict systemic and local liver and muscle disposition of statins.

Statins are used to reduce liver cholesterol levels but also carry a dose-related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity. To bridge this gap, we used physiologically based pharmacokinetic (PBPK) modeling to predict intracellular concentrations of statins. Quantitative data on transporter clearance were scaled from in vitro to in vivo conditions by integrating targeted proteomics and transporter kinetics data. The developed PBPK models, informed by proteomics, suggested that organic anion-transporting polypeptide 2B1 (OATP2B1) and multidrug resistance-associated protein 1 (MRP1) play a pivotal role in the distribution of statins in muscle. Using these PBPK models, we were able to predict the impact of alterations in transporter function due to genotype or drug-drug interactions on statin systemic concentrations and exposure in liver and muscle. These results underscore the potential of proteomics-guided PBPK modeling to scale transporter clearance from in vitro data to real-world implications. It is important to evaluate the role of drug transporters when predicting tissue exposure associated with on- and off-target effects.

Robustness in population-structure and demographic-inference results derived from the Aedes aegypti genotyping chip and whole-genome sequencing data.

The mosquito Aedes aegypti is the primary vector of many human arboviruses such as dengue, yellow fever, chikungunya, and Zika, which affect millions of people worldwide. Population genetic studies on this mosquito have been important in understanding its invasion pathways and success as a vector of human disease. The Axiom aegypti1 SNP chip was developed from a sample of geographically diverse A. aegypti populations to facilitate genomic studies on this species. We evaluate the utility of the Axiom aegypti1 SNP chip for population genetics and compare it with a low-depth shotgun sequencing approach using mosquitoes from the native (Africa) and invasive ranges (outside Africa). These analyses indicate that results from the SNP chip are highly reproducible and have a higher sensitivity to capture alternative alleles than a low-coverage whole-genome sequencing approach. Although the SNP chip suffers from ascertainment bias, results from population structure, ancestry, demographic, and phylogenetic analyses using the SNP chip were congruent with those derived from low-coverage whole-genome sequencing, and consistent with previous reports on Africa and outside Africa populations using microsatellites. More importantly, we identified a subset of SNPs that can be reliably used to generate merged databases, opening the door to combined analyses. We conclude that the Axiom aegypti1 SNP chip is a convenient, more accurate, low-cost alternative to low-depth whole-genome sequencing for population genetic studies of A. aegypti that do not rely on full allelic frequency spectra. Whole-genome sequencing and SNP chip data can be easily merged, extending the usefulness of both approaches.

Exposure to Electronic Waterpipes Increases the Risk of Occlusive Cardiovascular Disease in C57BL/6J Mice.

INTRODUCTION: It is well documented that cardiovascular disease (CVD) is the leading cause of death in the US and worldwide, with smoking being the most preventable cause. Additionally, most smokers die from thrombotic-based diseases, in which platelets play a major role. To this end, because of the proven harm of smoking, several novel tobacco products such as electronic(e)-waterpipe have been gaining popularity among different sectors of the population, partly due to their "false" safety claims. While many investigators have focused on the negative health effects of traditional cigarettes and e-cigarettes on the cardiovascular system, virtually little or nothing is known about e-waterpipes, which we investigated herein. METHODS AND MATERIALS: To investigate their occlusive CVD effects, we employed a whole-body mouse exposure model of e-waterpipe vape/smoke and exposed C57BL/6J male mice (starting at 7 weeks of age) for 1 month, with the controls exposed to clean air. Exposures took place seven times a week, according to the well-known Beirut protocol, which has been employed in many studies, as it mimics real-life waterpipe exposure scenarios; specifically, 171 puffs of 530 ml volume of the e-liquid at 2.6 s puff duration and 17 s puff interval. RESULTS: The e-waterpipe exposed mice had shortened bleeding and occlusion times, when compared to the clean air controls, indicating a prothrombotic phenotype. As for the mechanism underlying this phenotype, we found that e-waterpipe exposed platelets exhibited enhanced agonist-triggered aggregation and dense granule secretion. Also, flow cytometry analysis of surface markers of platelet activation showed that both P-selectin and integrin GPIIb-IIIa activation were enhanced in the e-waterpipe exposed platelets, relative to the controls. Finally, platelet spreading and Akt phosphorylation were also more pronounced in the exposed mice. CONCLUSION: We document that e-waterpipe exposure does exert untoward effects in the context of thrombosis-based CVD, in part, via promoting platelet hyperreactivity.