Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells

The TWIST1 gene has diverse roles in development and pathologic diseases such as cancer. TWIST1 is a dimeric basic helix-loop-helix (bHLH) transcription factor existing as TWIST1-TWIST1 or TWIST1-E12/47. TWIST1 partner choice and DNA binding can be influenced during development by phosphorylation of Thr125 and Ser127 of the Thr-Gln-Ser (TQS) motif within the bHLH of TWIST1. The significance of these TWIST1 phosphorylation sites for metastasis is unknown. We created stable isogenic prostate cancer cell lines overexpressing TWIST1 wild-type, phospho-mutants, and tethered versions. We assessed these isogenic lines using assays that mimic stages of cancer metastasis. In vitro assays suggested the phospho-mimetic Twist1-DQD mutation could confer cellular properties associated with pro-metastatic behavior. The hypo-phosphorylation mimic Twist1-AQA mutation displayed reduced pro-metastatic activity compared to wild-type TWIST1 in vitro, suggesting that phosphorylation of the TWIST1 TQS motif was necessary for pro-metastatic functions. In vivo analysis demonstrates that the Twist1-AQA mutation exhibits reduced capacity to contribute to metastasis, whereas the expression of the Twist1-DQD mutation exhibits proficient metastatic potential. Tethered TWIST1-E12 heterodimers phenocopied the Twist1-DQD mutation for many in vitro assays, suggesting that TWIST1 phosphorylation may result in heterodimerization in prostate cancer cells. Lastly, the dual phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor BEZ235 strongly attenuated TWIST1-induced migration that was dependent on the TQS motif. TWIST1 TQS phosphorylation state determines the intensity of TWIST1-induced pro-metastatic ability in prostate cancer cells, which may be partly explained mechanistically by TWIST1 dimeric partner choice

Effect of Contrast Sensitivity on Pseudoisochromatic Plate Color Vision Tests (video)

Internuclear opthalmoplegia (INO) is due to a medial longitudinal fasciculus (MLF) lesion causing adduction paresis of ipsilesional eye with abduction nystagmus of contralesional eye. The MLF is the final common pathway not only for all adducting eye movements,except convergence, but also for the vertical-torsional vestibulo-ocular reflex (VOR

Descemet membrane endothelial keratoplasty in a patient with iris-fixated intraocular lens and prior radial keratotomy: a case report

Abstract Background Anterior segment surgeries such as cataract surgery, intraocular lens (IOL) repositioning, and radial keratotomy (RK) may hasten endothelial dysfunction, particularly in the context of pre-existing Fuchs dystrophy, necessitating future corneal transplantation. Case presentation A 68-year-old woman with a history of RK with associated irregular astigmatism in both eyes and iris-fixated intraocular lens (IF-IOL) in the left eye presented with six months of decreased vision in the left eye. She was found to have Fuchs dystrophy and underwent DMEK surgery. She had an uncomplicated postoperative course, with uncorrected visual acuity improving to 20/20 three months after surgery. Conclusion To our knowledge, this is the first reported case of a highly successful DMEK surgery in a patient with prior RK and IF-IOL.http://deepblue.lib.umich.edu/bitstream/2027.42/173597/1/12886_2021_Article_2103.pd

Effect of Contrast Sensitivity on Pseudoisochromatic Plate Color Vision Tests (abstract)

Internuclear opthalmoplegia (INO) is due to a medial longitudinal fasciculus (MLF) lesion causing adduction paresis of ipsilesional eye with abduction nystagmus of contralesional eye. The MLF is the final common pathway not only for all adducting eye movements,except convergence, but also for the vertical-torsional vestibulo-ocular reflex (VOR

Comparison of self-refraction using a simple device, USee, with manifest refraction in adults

<div><p>Background</p><p>The USee device is a new self-refraction tool that allows users to determine their own refractive error. We evaluated the ease of use of USee in adults, and compared the refractive error correction achieved with USee to clinical manifest refraction.</p><p>Methods</p><p>Sixty adults with uncorrected visual acuity <20/30 and spherical equivalent between –6.00 and +6.00 diopters completed manifest refraction and self-refraction.</p><p>Results</p><p>Subjects had a mean (±SD) age of 53.1 (±18.6) years, and 27 (45.0%) were male. Mean (±SD) spherical equivalent measured by manifest refraction and self-refraction were –0.90 D (±2.53) and –1.22 diopters (±2.42), respectively (p = 0.001). The proportion of subjects correctable to ≥20/30 in the better eye was higher for manifest refraction (96.7%) than self-refraction (83.3%, p = 0.005). Failure to achieve visual acuity ≥20/30 with self-refraction in right eyes was associated with increasing age (per year, OR: 1.05; 95% CI: 1.00–1.10) and higher cylindrical power (per diopter, OR: 7.26; 95% CI: 1.88–28.1). Subjectively, 95% of participants thought USee was easy to use, 85% thought self-refraction correction was better than being uncorrected, 57% thought vision with self-refraction correction was similar to their current corrective lenses, and 53% rated their vision as “very good” or “excellent” with self-refraction.</p><p>Conclusion</p><p>Self-refraction provides acceptable refractive error correction in the majority of adults. Programs targeting resource-poor settings could potentially use USee to provide easy on-site refractive error correction.</p></div

Modified Bland Altman (Difference in SE (MR SE minus SR) vs. MR SE) for right eye.

<p>Abbreviations: SE = spherical equivalent, MR = manifest refraction, SR = self-refraction.</p

The effect of social determinants of health on severity of microbial keratitis presentation at a tertiary eye care hospital in Southern India

Purpose: Understanding the association between social determinants of health (SDoHs) and microbial keratitis (MK) can inform underlying risk for patients and identify risk factors associated with worse disease, such as presenting visual acuity (VA) and time to initial presentation. Methods: This was a cross-sectional study was conducted with patients presenting with MK to the cornea clinic at a tertiary care hospital in Madurai, India. Patient demographics, SDoH survey responses, geographic pollution, and clinical features at presentation were collected. Descriptive statistics, univariate analysis, multi-variable linear regression models, and Poisson regression models were utilized. Results: There were 51 patients evaluated. The mean age was 51.2 years (SD = 13.3); 33.3% were female and 55% did not visit a vision center (VC) prior to presenting to the clinic. The median presenting logarithm of the minimum angle of resolution (logMAR) VA was 1.1 [Snellen 20/240, inter-quartile range (IQR) = 20/80 to 20/4000]. The median time to presentation was 7 days (IQR = 4.5 to 10). The average particulate matter 2.5 (PM2.5) concentration, a measure of air pollution, for the districts from which the patients traveled was 24.3 μg/m3 (SD = 1.6). Age- and sex-adjusted linear regression and Poisson regression results showed that higher levels of PM2.5 were associated with 0.28 worse presenting logMAR VA (Snellen 2.8 lines, P = 0.002). Patients who did not visit a VC had a 100% longer time to presentation compared to those who did (incidence rate ratio = 2.0, 95% confidence interval = 1.3–3.0, P = 0.001). Conclusion: Patient SDoH and environmental exposures can impact MK presentation. Understanding SDoH is important for public health and policy implications to mitigate eye health disparities in India

Subjective feedback on USee.

<p>Subjective feedback on USee.</p

Distribution of age, gender, handedness, ethnicity, and race among study participants (N = 60).

<p>Distribution of age, gender, handedness, ethnicity, and race among study participants (N = 60).</p

Distribution of visual acuity before and after refraction.

<p>Distribution of visual acuity before and after refraction.</p