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15 ± 0.07 (p = 0.046); near spectacle needs, 26.7% and 14.3% (p &gt; 0.05), respectively. Better visual acuity was achieved in the EDOF Group between the defocus range of -0.50 and -1.75 D (p &lt; 0.05). No significant difference was found regarding photic phenomena and CS evaluated with CSV 1000-E between the two IOL groups at 6 months after surgery (otherwise there are differences at 1 and 3 months in favor of EDOF). However, EDOF Group performed better in mesopic CS evaluated with PRT (p &lt; 0.05).<br />When implanted with mini-monovision better binocular uncorrected visual performance at intermediate and near distances achieved with EDOF than low add MIOL.<br />When implanted with mini-monovision better binocular uncorrected visual performance at intermediate and near distances achieved with EDOF than low add MIOL.Clinical electrophysiological assessment of optic nerve and retinal ganglion cell function can be performed using the Pattern Electroretinogram (PERG), Visual Evoked Potential (VEP) and the Photopic Negative Response (PhNR) amongst other more specialised techniques. In this review, we describe these electrophysiological techniques and their application in diseases affecting the optic nerve and retinal ganglion cells with the exception of glaucoma. The disease groups discussed include hereditary, compressive, toxic/nutritional, traumatic, vascular, inflammatory and intracranial causes for optic nerve or retinal ganglion cell dysfunction. The benefits of objective, electrophysiological measurement of the retinal ganglion cells and optic nerve are discussed, as are their applications in clinical diagnosis of disease, determining prognosis, monitoring progression and response to novel therapies.Glaucoma, its early diagnosis, and monitoring of interventions remain an ongoing challenge. We here review developments in functional assessment and its relation to morphology, evaluating recent insights in electrophysiology in glaucoma and highlighting how glaucoma research and diagnostics benefit from combined approaches of OCT and electrophysiological investigations. After concise overviews of OCT and non-invasive electrophysiology in glaucoma, we evaluate commonalities and complementarities of OCT and electrophysiology for our understanding of glaucoma. As a specific topic, the dynamic range (floor effects) of the various techniques is discussed.<br />Prevention of non-infectious uveitis of the posterior segment (NIU-PS) recurrence using 0.2 μg/day fluocinolone acetonide implant (FAi) was assessed over 3 years (NCT01694186). Outcomes for FAi-treated and fellow eyes with NIU-PS were compared, to evaluate FAi versus conventional treatment strategies.<br />Eligible subjects had &gt;1-year recurrent NIU-PS history and either ≥2 separate recurrences requiring treatment, or corticosteroid therapy (systemic or ocular) in the 12 months preceding study entry. Bilateral disease was present and analysed in 59/87 FAi-treated participants. [https://www.selleckchem.com/products/CGS-21680-hydrochloride.html G Protein agonist] Recurrence rates, best-corrected visual acuity (BCVA) changes, cataract surgery, intraocular pressure (IOP) events and adjunctive medication use were compared for FAi-treated and fellow eyes.<br />Over 36 months, more FAi-treated than fellow eyes remained recurrence-free (28.8% vs. link2 5.1%, P = 0.001; mean 1.9 vs. 4.7 recurrences, respectively, P &lt; 0.0001). FAi-treated eyes gained +9.6 letters BCVA, versus a loss of -4.4 in fellow eyes (tection against ocular inflammation than a reactive approach using standard of care.<br />To analyze the long-term outcomes of eyes with retinal vein occlusion (RVO) 8 years after commencing treatment with anti-vascular endothelial growth factor (VEGF) agents.<br />Retrospective, multicentre study of 221 eyes diagnosed with RVO, which were commenced on anti-VEGF therapy between 2009 and 2011. VA and CRT were recorded at baseline and at subsequent annual time points. The mean number of injections administered each year and the incidence of adverse events were recorded.<br />Of a total of 221 eyes which commenced treatment with anti-VEGF agents for RVO, 95 were diagnosed with BRVO and 126 with CRVO. 8-year data were available for 94 eyes (43%). The mean age of patients was 65.1 ± 12.0 years. Mean VA improved from baseline by 16.9 letters, (57.8-74.7 letters), (P &lt; 0.001). For BRVO eyes, mean VA improved from 60.5 to 74.8 letters (p &lt; 0.001) and for CRVO eyes from 52.0 to 66.4 letters (p &lt; 0.001). In all RVO eyes, there was a reduction in mean CRT from 501.0 to 249.1 µm; in BRVO eyes from 472.4 to 284.7 µm and in CRVO eyes from 533.9 to 267.5 µm. In the 8th year after starting treatment, eyes with RVO were receiving a mean of four injections.<br />Good long-term outcomes of VEGF inhibition for eyes with RVO were found in this study. Patients maintained a gain of 3-lines of vision 8-years after the commencing therapy. This encouraging result contrasts with long-term studies of patients with neovascular age-related macular degeneration, where initial gains are lost over time.<br />Good long-term outcomes of VEGF inhibition for eyes with RVO were found in this study. Patients maintained a gain of 3-lines of vision 8-years after the commencing therapy. This encouraging result contrasts with long-term studies of patients with neovascular age-related macular degeneration, where initial gains are lost over time.<br />To assess the course of neurodegeneration based on retinal layer thickness and integrity analysis in diabetic patients without retinopathy and to evaluate its association with inner retinal reflectivity.<br />This retrospective case-control study included 80 eyes of 80 patients with DM without retinopathy and 40 eyes of 40 healthy subjects with a follow-up of ≥1 year. SD-OCT was used for assessment of retinal reflectivity and macular layer thicknesses. Optical intensity ratios (OIRs) were defined as the mean OCT reflectivity of ganglion cell and inner nuclear layer to the mean reflectivity of RPE.<br />After Bonferroni correction, thinning in pericentral, superior and nasal sectors in total retina, superior ganglion cell, pericentral and nasal inner plexiform, and superior inner retinal layers, as well as thickening in inferior and pericentral outer plexiform layer remained significant in the study group (p &lt; 0.0125). Ganglion cell layer OIR significantly correlated with the changes in superior retina (r = 0.278, p = 0.013), central inner retina (r = 0.247, p = 0.027), and pericentral retinal thickness (r = 0.240, p = 0.032), and no eyes had disruption of retinal layers in the study group initially or finally.<br />Ganglion cell layer reflectivity significantly correlated with the amount of pericentral retinal thinning during the time course in the diabetic group, which was more prominent in the inner retinal layers.<br />Ganglion cell layer reflectivity significantly correlated with the amount of pericentral retinal thinning during the time course in the diabetic group, which was more prominent in the inner retinal layers.Evasion of apoptosis is a hallmark of cancer, which is frequently mediated by upregulation of the antiapoptotic BCL-2 family proteins. In colorectal cancer (CRC), previous work has highlighted differential antiapoptotic protein dependencies determined by the stage of the disease. While intestinal stem cells (ISCs) require BCL-2 for adenoma outgrowth and survival during transformation, ISC-specific MCL1 deletion results in disturbed intestinal homeostasis, eventually contributing to tumorigenesis. Colon cancer stem cells (CSCs), however, no longer require BCL-2 and depend mainly on BCL-XL for their survival. We therefore hypothesized that a shift in antiapoptotic protein reliance occurs in ISCs as the disease progresses from normal to adenoma to carcinoma. By targeting antiapoptotic proteins with specific BH3 mimetics in organoid models of CRC progression, we found that BCL-2 is essential only during ISC transformation while MCL1 inhibition did not affect adenoma outgrowth. BCL-XL, on the other hand, was crucial for stem cell survival throughout the adenoma-to-carcinoma sequence. Furthermore, we identified that the limited window of BCL-2 reliance is a result of its downregulation by miR-17-5p, a microRNA that is upregulated upon APC-mutation driven transformation. Here we show that BCL-XL inhibition effectively impairs adenoma outgrowth in vivo and enhances the efficacy of chemotherapy. In line with this dependency, expression of BCL-XL, but not BCL-2 or MCL1, directly correlated to the outcome of chemotherapy-treated CRC patients. Our results provide insights to enable the rational use of BH3 mimetics in CRC management, particularly underlining the therapeutic potential of BCL-XL targeting mimetics in both early and late-stage disease.<br />Urolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA an appealing strategy.<br />This is the first detailed investigation of the prevalence of UA producers in a healthy population and the ability of direct UA supplementation to overcome both microbiome and dietary variability. Dietary intake of a glass of pomegranate juice (PJ) was used to assess UA producer status (n = 100 participants) and to characterize differences in gut microbiome between UA producers from non-producers.<br />Subjects were randomized (11) to either PJ or a food product containing UA (500 mg). Prevalence of UA producers and non-producers were determined in the PJ group. Diet questionnaires and fecal samples were collected to compare differences between UA producers and non-producers along with plasma samples at different time points to assess levels of UA and its conjugates between the interventions.<br />Only 12% of subjects had detectable levels of UA at baseline. Following PJ intake ~40% of the subjects converted significantly the precursor compounds into UA. UA producers were distinguished by a significantly higher gut microbiome diversity and ratio of Firmicutes to Bacteroides. Direct supplementation with UA significantly increased plasma levels and provided a &gt;6-fold exposure to UA vs. PJ (p &lt; 0.0001).<br />Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation.<br />Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation.Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD). Here, we report that cabozantinib can promote differentiation in erythroid leukemia cells. link3 We found that K562 erythroid leukemia cells treated with 1 μM cabozantinib for 72 h underwent erythroid lineage differentiation. Transcriptomic analysis revealed that various pathways associated with heme biosynthesis, hemoglobin production, and GATA1 targets were upregulated, whereas cell survival pathways were downregulated. Further examination revealed that cabozantinib-induced erythroid differentiation is at least in part regulated by JNK activation and phosphorylation. Levels of phosphorylated BCR-ABL, AKT, STAT5, ERK, and p38 also decreased following cabozantinib treatment.