Real-World Experience of Fluocinolone Acetonide 0.19 mg in the Management of Non-Infectious Uveitis.

PURPOSE: This study aims to evaluate the real-world efficacy and safety profile of fluocinolone acetonide (FAc) implants for the treatment of non-infectious uveitis (NIU). METHODS: A retrospective, observational study was conducted at Moorfields Eye Hospital, London, involving patients who received FAc 0.19 mg implants (Iluvien®) for NIU. 2-year follow-up data on baseline characteristics, indications, and outcomes was collected. The primary indicator for treatment failure was defined as the need for rescue treatment with dexamethasone (DEX) implants, while secondary indicators included changes in steroid and systemic immunosuppression requirements, or the need for a second FAc implant before 3 years. The occurrence of complications was collected. RESULTS: Of the 146 eyes treated with FAc implants, 24.0% experienced treatment failure requiring DEX implant within 2 years. About 42.9% required this within the first 6 months. There was an increase in the number of patients requiring steroids and/or systemic immunosuppression. Within the first 2 years post-FAc implant, only 13.7% experienced an IOP rise, with 4.1% requiring IOP-lowering surgery. About 57.9% of the phakic eyes developed cataracts. CONCLUSION: This study provides valuable real-world evidence supporting the efficacy of FAc implant in NIU. It demonstrates a good safety profile at 2 years, with a significant reduction in uveitis recurrence rate and treatment burden. Our results are especially pertinent to the treatment of uveitic cystoid macular oedema (CMO), which was the primary indication in over 75% of our patients. Furthermore, it suggests that while FAc implant controls retinal inflammation effectively, choroidal inflammation would require alternative treatment.

Detection of Parkinson's disease with keystroke data.

Parkinson's disease (PD) is one of the most widespread neurological disorders associated with nerve damage without definitive treatment. Impairments, such as trembling and slowing down in hand movements are among the first symptoms. For this purpose, in this study, machine learning (ML)-based models were developed by using keyboard keystroke dynamics. According to patients' drug use status, disease severity, and gender, we created 14 different sub-datasets and extracted 378 features using raw keystroke data. We developed alternative models with Support Vector Machines (SVM), k-Nearest Neighbors (kNN), and Random Forest (RF) algorithms. We further used Minimum Redundancy Maximum Relevance (mRmR), RELIEF, sequential forward selection (SFS), and RF feature selection methods to investigate prominent features in distinguishing PD. We developed ML models that jointly use the most popular features of selection algorithms (feature ensemble [FE]) and an ensemble classifier by combining multiple ML algorithms utilizing majority vote (model ensemble [ME]). With 14 different sets, FE and ME models provided accuracy (Acc.) in the range of 91.73 - 100% and 81.08 - 100%, respectively.

Outcomes of anti-VEGF treatment for macular edema secondary to central retinal vein occlusion in patients with poor baseline visual acuity.

OBJECTIVE: To report the visual outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for macular edema secondary to central retinal vein occlusion (CRVO) in patients with baseline visual acuity of ≤23 ETDRS letters vision. DESIGN: Retrospective observational cohort study. METHODS: This is a single-institution study. A total of 173 eyes from 173 patients who had completed 3 consecutive monthly anti-VEGF injections for macular edema secondary CRVO and best-corrected visual acuity (BCVA) ≤23 ETDRS letters were included. The main outcome measures were visual acuity at month 3 and month 12. RESULTS: At month 3, BCVA increased to 34.1 ETDRS letters (95% CI, 30.7-37.5), with a gain of 25.0 letters (95% CI, 22.0-28.5; p < 0.001). The mean central subfield thickness decreased by 519 µm (95% CI, 475.5-567.0; p < 0.001). Most patients (67.6%) gained >15 ETDRS letters. A total of 160 patients were followed up for 12 months, and the mean BCVA was 31.2 ETDRS letters (95% CI, 27.5-34.9) at the end of this period. A third of eyes that did not respond (<5-letter gain) after a single injection experienced a 15-letter or more improvement after 3 consecutive injections. CONCLUSIONS: Anti-VEGF treatment in eyes with CRVO and poor baseline visual acuity results in significant visual improvement, and moderate improvement is still noted despite a poor response after a single injection.

Some Thiazole Derivatives Combined with Different Heterocycles: Cytotoxicity Evaluation and Apoptosis Inducing Studies.

BACKGROUND: Thiazole ring is an outstanding structure found in many biologically active compounds and clinically available drugs. Because of synthesis simplicity of its derivatives and having a wide range of biological aspects along with high effectiveness, new thiazole derivatives have been studied by medicinal chemists since many years. OBJECTIVE: Some thiazole compounds combined with different heterocyclic rings were acquired in this study. Novel 5-(4-substituted benzylidene)-2-[(4,5-dimethylthiazol-2-yl)amino]thiazol-4(5H)-one derivatives (4a-g) and 2-(heteroaryl-2/3/5-yl)thio-N-(4,5-dimethylthiazol-2-yl)acetamide (4h-p) derivatives were synthesized starting from 2-amino-4,5-dimethylthiazole. The obtained compounds were evaluated to determine their antiproliferative activity. METHOD: Final compounds (4a-g) were obtained with a ring closure reaction; other final compounds (4h-p) were acquired via the reaction of mercapto heterocycles with Hantzsch thiazole synthesis intermediate. To evaluate antiproliferative activity of them, the compounds were tested on A549 adenocarcinomic human alveolar basal epithelial cells line, C6 rat glioma cell line and NIH/3T3 mouse embryo fibroblast cell line according to the conventional MTT method. Besides, the selected compounds were studied to find out which pathway cell deaths caused via Annexin V/PI staining. RESULTS: Compounds 4f, 4j and 4p exhibited the highest cytotoxicity on A549 with a non-toxic profile. Also, 4f, 4h, 4j and 4p were determined as the most antiproliferative compounds on C6 cell line. Furthermore, compound 4p induced apoptosis of A549 cell with a level of 23.5% and compound 4h induced C6 cell with a level of 37.5%. CONCLUSION: Considering the structure of the compounds, although thiazolidine containing compounds 4a-g exhibited higher activity in general, compounds 4p containing 5-chlorobenzothiazole moiety showed the highest cytotoxicity. It could be expressed with the conspicuous antitumor efficiency of benzothiazole ring.

Biological Activity Evaluation of Novel 1,2,4-Triazine Derivatives Containing Thiazole/Benzothiazole Rings.

BACKGROUND: Triazine ring is a prominent structural motif found in some azanucleosides whose efficiency improved many times in the research area of antitumor agents. OBJECTIVE: In this study, we have designed and synthesized novel 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)thio]-N-(6- substituted benzo/(thiazol)-2-yl)acetamide (2a-d, 3a-f) derivatives using 1,2,4-triazine core along with two important heterocyles, thiazole and benzothiazole rings. METHOD: The acquired ten final compounds were screened to investigate their antitumor activity against lung adenocarcinoma cell line, A549 and mouse fibroblast cell line, NIH/3T3. Five compounds with higher antiproliferative activity have been further studied to evaluate whether the cell death due to necrosis or apoptosis using flow cytometry. RESULTS AND CONCLUSION: Compound 3b bearing 6-methylbenzothiazole moiety has been established as the most active antitumor compound with a selective profile and higher apoptotic cell level. All final componds were also screened against acetylcholine/butyrylcholinesterase enzymes to state their anticholinesterase activity.