Haydenriber2387
8%) due to associated ocular comorbidities. The involvement of the cornea was seen in 7338 (38.2%) patients and corneal signs included subepithelial infiltrates (26.3%), epithelial defect (1.4%), corneal oedema (0.9%) and filaments (0.4%). Of the patients who had corneal involvement, 496 (2.6%) patients had a chronic course beyond 1 month of which 105 (0.5%) had a course beyond 1 year.
EKC is a self-limiting condition that is commonly unilateral and predominantly affects males. About one-third of the patients have corneal involvement which rarely has a chronic course.
EKC is a self-limiting condition that is commonly unilateral and predominantly affects males. About one-third of the patients have corneal involvement which rarely has a chronic course.
To investigate the association of genetic polymorphisms of human leucocyte antigens (HLA) class I and II genes with acetaminophen-related Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) who developed severe ocular complications (SOC) in the Thai population.
A prospective case-control study including 20 unrelated Thai acetaminophen-related SJS/TEN patients with SOC and 60 Thai healthy volunteers, recruited at three university hospitals in Bangkok, Thailand, from September 2014 to August 2019. HLA genes were analysed using PCR amplification followed by hybridisation with sequence-specific oligonucleotide (SSO) probes with bead-based typing kits. The carrier and gene frequencies of individual HLA alleles in patients were compared with those in control volunteers based on dominant assumption using Fisher's exact test.
Among HLA class I polymorphisms, HLA-A*3303, HLA-B*4403 and HLA-C*0701 were significantly associated with acetaminophen-related SJS/TEN and SOC with high ORs (95% CI, corrected p value; Pc) in carrier frequency of 5.4 (1.8 to 16.3, Pc=0.0274), 9.0 (95% CI 2.7 to 30.4, Pc=0.0034), and 9.3 (2.8 to 30.2, Pc=0.0022), respectively. There were no significant HLA class II associations with the disease after corrected for a total number of alleles tested.
HLA-B*4403 was strongly associated with acetaminophen-related SJS/TEN patients who developed SOC in Thai population. In addition, we also found moderate to strong associations with HLA-A*3303 and HLA-C*0701 suggesting their potential roles in the pathogenesis of SOC in acetaminophen-related SJS/TEN.
HLA-B*4403 was strongly associated with acetaminophen-related SJS/TEN patients who developed SOC in Thai population. Epigenetic inhibitor solubility dmso In addition, we also found moderate to strong associations with HLA-A*3303 and HLA-C*0701 suggesting their potential roles in the pathogenesis of SOC in acetaminophen-related SJS/TEN.
To evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM).
Central and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 peripheral scars (PS)) using IVCM. Results were compared between patients and 24 age-matched controls. CSND was correlated to corneal sensation for all locations.
Overall patients revealed significant decrease of CSND in the central and peripheral cornea (9.13±0.98 and 6.26±0.53 mm/mm
, p<0.001), compared with controls (22.60±0.77 and 9.88±0.49 mm/mm
). CS group showed a decrease in central (8.09±1.30 mm/mm
) and total peripheral nerves (5.15±0.62 mm/mm
) of the affected eyes, whereas PS group demonstrated a decrease in central (10.34±1.48 mm/mm
) and localised peripheral nerves only in the scar area (4.22±0.77 mm/mm
) (all p<0.001). In contralateral eyes, CSND declocally in the contralateral eyes, corresponding and mirroring the scar location in the affected eyes.
To develop a fully automatic algorithm to segment retinal cavitations on optical coherence tomography (OCT) images of macular telangiectasia type 2 (MacTel2).
The dataset consisted of 99 eyes from 67 participants enrolled in an international, multicentre, phase 2 MacTel2 clinical trial (NCT01949324). Each eye was imaged with spectral-domain OCT at three time points over 2 years. Retinal cavitations were manually segmented by a trained Reader and the retinal cavitation volume was calculated. Two convolutional neural networks (CNNs) were developed that operated in sequential stages. In the first stage, CNN1 classified whether a B-scan contained any retinal cavitations. In the second stage, CNN2 segmented the retinal cavitations in a B-scan. We evaluated the performance of the proposed method against alternative methods using several performance metrics and manual segmentations as the gold standard.
The proposed method was computationally efficient and accurately classified and segmented retinal cavitations on OCT images, with a sensitivity of 0.94, specificity of 0.80 and average Dice similarity coefficient of 0.94±0.07 across all time points. The proposed method produced measurements that were highly correlated with the manual measurements of retinal cavitation volume and change in retinal cavitation volume over time.
The proposed method will be useful to help clinicians quantify retinal cavitations, assess changes over time and further investigate the clinical significance of these early structural changes observed in MacTel2.
The proposed method will be useful to help clinicians quantify retinal cavitations, assess changes over time and further investigate the clinical significance of these early structural changes observed in MacTel2.
To determine long-term outcomes and risk factors for failure after mitomycin C (MMC)-augmented initial trabeculectomy (IT) in Taiwanese patients.
We reviewed medical records of patients with glaucoma undergoing IT during December 2006-December 2016. We defined complete success as an intraocular pressure (IOP) of >5 or ≤21 mm Hg or IOP reduction of ≥20% from baseline without supplemental medications and qualified success as the aforementioned IOP levels with or without supplemental medications. Kaplan-Meier survival and Cox proportional analyses evaluated success rates and risk factors for failure, respectively.
We enrolled 190 patients (237 eyes; mean age 54.0±15.3 years; mean postoperative follow-up period 68.4±35.1 months). Mean IOP and glaucoma medications decreased from 22.2±10.8 to 14.4±5.2 mm Hg (p<0.001) and 3.0±0.7 to 1.8±1.2 (p=0.015), respectively, at the last visit. Cumulative qualified success rates were 93.9%, 93.0%, 86.5% and 67.1% at the 1, 2, 5 and 10 years follow-up, respectively; however, only 7.7% of the eyes reached complete success at the last visit. Eyes with poor preoperative visual acuity were associated with low qualified success rates (HR=1.689, p=0.027); patients aged >70 years had higher complete success rates than did those aged ≤70 years. Five cases (2.11%) exhibited bleb-associated complications.
Despite satisfactory long-term success rates, most eyes needed medication for IOP control, supporting the notion of predisposed scarring vitality in patients of Chinese ethnicity following MMC-augmented trabeculectomy.
Despite satisfactory long-term success rates, most eyes needed medication for IOP control, supporting the notion of predisposed scarring vitality in patients of Chinese ethnicity following MMC-augmented trabeculectomy.Cancer cells need to generate large amounts of glutathione (GSH) to buffer oxidative stress during tumor development. A rate-limiting step for GSH biosynthesis is cystine uptake via a cystine/glutamate antiporter Xc-. Xc- is a sodium-independent antiporter passively driven by concentration gradients from extracellular cystine and intracellular glutamate across the cell membrane. Increased uptake of cystine via Xc- in cancer cells increases the level of extracellular glutamate, which would subsequently restrain cystine uptake via Xc-. Cancer cells must therefore evolve a mechanism to overcome this negative feedback regulation. In this study, we report that glutamate transporters, in particular SLC1A1, are tightly intertwined with cystine uptake and GSH biosynthesis in lung cancer cells. Dysregulated SLC1A1, a sodium-dependent glutamate carrier, actively recycled extracellular glutamate into cells, which enhanced the efficiency of cystine uptake via Xc- and GSH biosynthesis as measured by stable isotope-assisted metabolomics. Conversely, depletion of glutamate transporter SLC1A1 increased extracellular glutamate, which inhibited cystine uptake, blocked GSH synthesis, and induced oxidative stress-mediated cell death or growth inhibition. Moreover, glutamate transporters were frequently upregulated in tissue samples of patients with non-small cell lung cancer. Taken together, active uptake of glutamate via SLC1A1 propels cystine uptake via Xc- for GSH biosynthesis in lung tumorigenesis. SIGNIFICANCE Cellular GSH in cancer cells is not only determined by upregulated Xc- but also by dysregulated glutamate transporters, which provide additional targets for therapeutic intervention.Tumors are complex tissues composed of transformed epithelial cells as well as cancer-activated fibroblasts (CAF) that facilitate epithelial tumor cell invasion. We show here that CAFs and other mesenchymal cells rely much more on glutamine than epithelial tumor cells; consequently, they are more sensitive to inhibition of glutaminase. Glutamine dependence drove CAF migration toward this amino acid when cultured in low glutamine conditions. CAFs also invaded a Matrigel matrix following a glutamine concentration gradient and enhanced the invasion of tumor cells when both cells were cocultured. Accordingly, glutamine directed invasion of xenografted tumors in immunocompromised mice. Stimulation of glutamine-driven epithelial tumor invasion by fibroblasts required previous CAF activation, which involved the TGFβ/Snail1 signaling axis. CAFs moving toward Gln presented a polarized Akt2 distribution that was modulated by the Gln-dependent activity of TRAF6 and p62 in the migrating front, and depletion of these proteins prevented Akt2 polarization and Gln-driven CAF invasion. Our results demonstrate that glutamine deprivation promotes CAF migration and invasion, which in turn facilitates the movement of tumor epithelial cells toward nutrient-rich territories. These results provide a novel molecular mechanism for how metabolic stress enhances invasion and metastasis. SIGNIFICANCE Cancer-associated fibroblasts migrate and invade toward free glutamine and facilitate invasion of tumor epithelial cells, accounting for their movement away from the hostile conditions of the tumor towards nutrient-rich adjacent tissues. GRAPHICAL ABSTRACT http//cancerres.aacrjournals.org/content/canres/81/2/438/F1.large.jpg.Gut barrier dysfunction promotes chronic inflammation, contributing to several gastrointestinal diseases, including colorectal cancer. Preliminary evidence suggests that vitamin D and calcium could prevent colorectal carcinogenesis, in part, by influencing gut barrier function. However, relevant human data are scarce. We tested the effects of supplemental calcium (1,200 mg/day) and/or vitamin D3 (1,000 IU/day) on circulating concentrations of biomarkers of gut permeability (anti-flagellin and anti-lipopolysaccharide IgA and IgG, measured via ELISA) from baseline to 1 and 3 or 5 years postbaseline among 175 patients with colorectal adenoma in a randomized, double-blinded, placebo-controlled clinical trial. We also assessed factors associated with baseline concentrations of these biomarkers. We found no appreciable effects of supplemental vitamin D3 and/or calcium on individual or aggregate biomarkers of gut permeability. At baseline, a combined permeability score (the summed concentrations of all four biomarkers) was 14% lower among women (P = 0.
