Effects of anthocyanins and their gut metabolites on adenosine diphosphate-induced platelet activation and their aggregation with monocytes and neutrophils.

Accumulating evidence suggests that anthocyanins play an important role in the cardioprotective effects associated with consumption of anthocyanin-rich foods. These benefits may partly be attributed to their effects on platelets, significant contributors to cardiovascular disease development. This study aimed to investigate the impact of physiologically relevant concentrations of anthocyanins and their metabolites on platelet activation and platelet-leukocyte aggregation. Whole blood from seven healthy volunteers was treated with anthocyanins: cyanidin-3-arabinoside, cyanidin-3-glucoside, cyanidin-3-galactoside, delphinidin-3-glucoside and peonidin-3-glucoside at 0.1 µM concentration or gut metabolites: 4-hydroxybenzaldehyde, protocatechuic, vanillic, ferulic and hippuric acids at 0.5 µM, 0.2 µM, 2 µM, 1 µM, 2 µM concentration, respectively. Markers of adenosine diphosphate-induced platelet activation (P-selectin and GPIIb-IIIa expression) and platelet-monocyte and platelet-neutrophil aggregation were analyzed using flow cytometry. Cyanidin-3-arabinoside, delphinidin-3-glucoside, and peonidin-3-glucoside decreased agonist-induced P-selectin expression, while cyanidin-3-galactoside and cyanidin-3-arabinoside reduced platelet-neutrophil aggregation. Hippuric and protocatechuic acids inhibited P-selectin expression, ferulic acid reduced platelet-monocyte aggregation, while 4-hydroxybenzaldehyde affected P-selectin expression, platelet-neutrophil and monocyte aggregation. Only cyanidin-3-glucoside and protocatechuic acid decreased GPIIb-IIIa expression. These results demonstrate the bioactivity of anthocyanins and their gut metabolites at physiologically relevant concentrations on platelet function and interaction with leukocytes, presenting mechanisms by which they contribute to the beneficial effects of habitual consumption of anthocyanin-rich foods on cardiovascular health.

Effect of limbal marking prior to laser ablation on the magnitude of cyclotorsional error.

PURPOSE: To evaluate the residual registration error after limbal-marking-based manual adjustment in cyclotorsional tracker-controlled laser refractive surgery. METHODS: Two hundred eyes undergoing custom surface ablation with the iVIS Suite (iVIS Technologies) were divided into limbal marked (marked) and non-limbal marked (unmarked) groups. Iris registration information was acquired preoperatively from all eyes. Preoperatively, the horizontal axis was recorded in the marked group for use in manual cyclotorsional alignment prior to surgical iris registration. During iris registration, the preoperative iris information was compared to the eye-tracker captured image. The magnitudes of the registration error angle and cyclotorsional movement during the subsequent laser ablation were recorded and analyzed. RESULTS: Mean magnitude of registration error angle (absolute value) was 1.82°±1.31° (range: 0.00° to 5.50°) and 2.90°±2.40° (range: 0.00° to 13.50°) for the marked and unmarked groups, respectively (P<.001). Mean magnitude of cyclotorsional movement during the laser ablation (absolute value) was 1.15°±1.34° (range: 0.00° to 7.00°) and 0.68°±0.97° (range: 0.00° to 6.00°) for the marked and unmarked groups, respectively (P=.005). Forty-six percent and 60% of eyes had registration error >2°, whereas 22% and 20% of eyes had cyclotorsional movement during ablation >2° in the marked and unmarked groups, respectively. CONCLUSIONS: Limbal-marking-based manual alignment prior to laser ablation significantly reduced cyclotorsional registration error. However, residual registration misalignment and cyclotorsional movements remained during ablation.

Transepithelial, Topography-guided Ablation in the Treatment of Visual Disturbances in LASIK Flap or Interface Complications.

PURPOSE: To evaluate the efficacy and safety of a single-step, transepithelial, topography-guided surface ablation in the treatment of visual disturbances including irregular astigmatism and light scattering caused by LASIK flap or interface complications. METHODS: Seventeen eyes of 16 patients with LASIK flap or interface complications and central residual stromal thickness ≥300 µm were treated with a topography-guided custom transepithelial "no touch" (cTEN) technique using the iVIS Suite 1-kHz excimer laser (iVIS Technology). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, corneal irregularity, ocular higher order aberrations (HOAs), and visual symptoms were analyzed. RESULTS: Mean 15.9±11.0 months after surgery, mean UDVA improved from 20/87 to 20/25. Mean CDVA improved from 20/28 to 20/19 (P<.001), with 64.7% of eyes gaining two or more lines of CDVA. Mean corneal irregularity index decreased from 25.82 to 20.36 µm (P=.009). Mean root-mean-square (RMS) of total HOAs decreased from 1.30 to 0.49 (P=.042), whereas RMS of the odd-order (3rd and 5th) and even-order (4th and 6th) HOAs decreased from 0.85 to 0.38 (P=.001) and 0.43 to 0.24 (P=.036), respectively. All patients claimed their visual symptoms were better (8 eyes) or cured (9 eyes). CONCLUSIONS: Corneal regularization and removal of the underlying flap or interface pathology by cTEN ablation appears to be an effective treatment for LASIK flap or interface complications associated with visually disturbing irregular astigmatism and light scattering in cases with sufficient residual stromal thickness.

Coma Influence on Manifest Astigmatism in Coma-Dominant Irregular Corneal Optics.

PURPOSE: To evaluate the influence of coma on manifest refractive cylinder (MRC) in eyes with coma-dominated corneal optics and suggest alternative guidelines for surgical planning of astigmatism correction in topography-guided ablation and toric intraocular lens (IOL) exchange surgery. METHODS: Twelve eyes with coma-dominant corneal optics and low lenticular astigmatism were selected. The astigmatism remaining after subtraction of total corneal astigmatism (TCA) and lenticular astigmatism from MRC, termed discrepant astigmatism, was calculated and correlated to corneal coma at the anterior surface. Refractive and topography data were then used to simulate topography-guided refractive surgery (topography-guided group) in 7 eyes and lenticular exchange surgery with toric intraocular lens (IOL) implantation (toric IOL group) in 5 eyes. The estimated postoperative MRC after correction of TCA or MRC for each group was compared. RESULTS: The axis and amplitude of discrepant astigmatism correlated strongly with the axis and amplitude of coma. In the topography-guided group, where topography-guided ablation eliminated corneal higher order aberrations (HOAs), TCA-based correction led to less estimated postoperative manifest astigmatism than MRC-based correction. In the toric IOL group, where removal of the crystalline lens did not affect corneal HOAs, MRC-based correction via toric IOL implantation led to less estimated postoperative astigmatism than TCA-based correction. CONCLUSIONS: Discrepant astigmatism in eyes with coma-dominant corneal optics correlates with coma. In such eyes, treating TCA, along with corneal HOAs, instead of MRC, seems appropriate in topography-guided treatments, whereas treating MRC may be a better choice in lenticular exchange surgery with toric IOL implantation, where corneal HOAs are not treated. [J Refract Surg. 2021;37(4):274-282.].

NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice.

The development of effective therapies as well as early, molecular diagnosis of Alzheimer's disease is impeded by the lack of understanding of the underlying pathological mechanisms. Metabolomics studies of body fluids as well as brain tissues have shown major changes in metabolic profiles of Alzheimer's patients. However, with analysis performed at the late stages of the disease it is not possible to distinguish causes and consequence. The mouse model APP/PS1 expresses a mutant amyloid precursor protein resulting in early Amyloid ß (Aß) accumulation as well as many resulting physiological changes including changes in metabolic profile and metabolism. Analysis of metabolic profile of cerebrospinal fluid (CSF) and blood of APP/PS1 mouse model can provide information about metabolic changes in these body fluids caused by Aß accumulation. Using our novel method for analysis of correlation and mathematical ranking of significant correlations between metabolites in CSF and blood, we have explored changes in metabolite correlation and connectedness in APP/PS1 and wild type mice. Metabolites concentration and correlation changes in CSF, blood and across the blood brain barrier determined in this work are affected by the production of amyloid plaque. Metabolite changes observed in the APP/PS1 mouse model are the response to the mutation causing plaque formation, not the cause for the plaque suggesting that they are less relevant in the context of early treatment and prevention then the metabolic changes observed only in humans.

One-step transepithelial topography-guided ablation in the treatment of myopic astigmatism.

PURPOSE: To evaluate one-step topography-guided transepithelial ablation in the treatment of low to moderate myopic astigmatism using a 1KHz excimer laser. METHODS: Retrospective study of 117 consecutive eyes available for evaluation 12 months after surgery. Pre- and post-operative visual and refractive data as well as post-operative pain and haze were analyzed. A novel technique integrating custom refractive- and epithelial- ablation in a single uninterrupted procedure was used. RESULTS: The mean pre-operative spherical equivalent (SE) and the mean cylinder were: -3.22 diopters (D) ±1.54 (SD) (range -0.63 to -7.25 D) and -0.77 D ±0.65 (range 0 to -4.50 D), respectively. At 12 months after surgery: no eyes lost ≥2 lines of corrected distant visual acuity (CDVA). Safety and efficacy indexes were 1.27 and 1.09, respectively. Uncorrected distant visual acuity (UDVA) was ≥20/20 in 96.6% of the eyes. Manifest refraction spherical equivalent was within ±0.5 D of the desired refraction in 93.2% of the eyes. Average root mean square (RMS) wavefront error measured at central 6 mm, increased from 0.38 pre-operatively to 0.47 µm post-operatively. Refractive stability was achieved and sustained 1 month after surgery. No visually significant haze was registered during the observation period. Post-operative pain was reported in 4.5% of patients. CONCLUSIONS: One-step transepithelial topography-guided treatment for low to moderate myopia and astigmatism performed with a 1 KHz laser, provided safe, effective, predictable and stable results with low pain and no visually significant haze.

Safety and efficacy of epithelium-on corneal collagen cross-linking using a multifactorial approach to achieve proper stromal riboflavin saturation.

Purpose. To evaluate the efficacy and safety of epithelium-on corneal collagen cross-linking (CXL) using a multifactorial approach to achieve proper stromal riboflavin saturation. Methods. This non-randomized retrospective study comprised 61 eyes with progressive keratoconus treated with epithelium-on CXL. Chemical epithelial penetration enhancement (benzalkonium chloride-containing local medication and hypotonic riboflavin solution), mechanical disruption of the superficial epithelium, and prolongation of the riboflavin-induction time until verification of stromal saturation were used before the UVA irradiation. Uncorrected and corrected distance visual acuity (UDVA, CDVA), refraction, corneal topography, and aberrometry were evaluated at baseline and at 1, 3, 6, and 12 months postoperative. Results. At 12-month, UDVA and CDVA improved significantly. None of the eyes lost lines of CDVA, while 27.4% of the eyes gained 2 or more lines. Mean spherical equivalent decreased by 0.74 D, and mean cylindrical reduction was 1.15 D. Irregularity index and asymmetry from Scheimpflug-based topography and Max-K at the location of cone from Placido-based topography showed a significant decrease. Higher-order-aberration data demonstrated a slight reduction in odd-order aberrations S 3, 5,7 (P = 0.04). Postoperative pain without other complications was recorded. Conclusion. Epithelium-on CXL with our novel protocol appeared to be safe and effective in the treatment of progressive keratoconus.