Subjective and objective accommodation of the Crystalens Advanced Optics (AO) in patients 6 months after bilateral implantation

Background: The aim of this study was to analyze and compare objective and subjective accommodation in patients after bilateral implantation of the FDA-approved accommodating Crystalens Advanced Optics (AO). Material and methods: This study was performed on 8 eyes of 4 patients. The subjective accommodation was measured by monocular and binocular defocus curves under photopic and mesopic conditions. The objective accommodation was analyzed using partial coherence interferometry (PCI) and wavefront aberration. Pupil diameter at different set-ups and refraction were derived from wavefront data. Results: Uncorrected and corrected distance and uncorrected near visual acuity improved significantly following implantation of the Crystalens AO in all eyes. Only one patient needed spectacles to correct distance visual acuity. Mean distance uncorrected visual acuity was 0.05 ± 0.06 logMAR. All patients were able to read newspapers without spectacles. Mean near uncorrected visual acuity was 0.17 ± 0.12 logMAR. Subjective accommodative amplitude under photopic conditions was significantly better binocularly than monocularly (p = 0.03) and was significant worse monocularly under mesopic conditions than photopic conditions (p = 0.016). No significant changes in anterior chamber depth were observed by PCI, with a fixation on optical stimuli at different distances. There were also no significant changes in the wavefront aberrations between the different set-ups. Pupil diameter increased significantly in the near set-up under mesopic conditions. Conclusions: No objective change in lens configuration was observed under different set-ups. Due to a variety of factors involved in pseudoaccommodation (e.g. pupil diameter, astigmatism, and multifocality), the subjective accommodative amplitude tends to be overestimated relative to objective measurements. No real accommodative action was observed

Prevention of Lens Epithelial Cell Growth In Vitro Using Mibefradil-Containing PLGA Micro Particles

The prevention of the posterior capsule opacification is still unsolved. To interfere with proliferating cells the T-type calcium channel antagonist Mibefradil was immobilized in poly-lactic-co-glycolic-acid micro particles which were fixed at a capsular tension ring and tested in a human organ culture model as well as in human lens cells HLE-B3 in vitro. It is feasible to get a release significantly affecting cell viability and growth evaluated by MTT test and cell cycle analysis. In addition, Bionas® sensor chips were used for time-dependent adhesion experiments in living lens cells. Interestingly, the concentration of Mibefradil which inhibited subconfluent cells is not effective in confluent cells. This is an important feature for the protection of the intact tissue in the eye

The HYLAN M Study: Efficacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial

The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this international, multicenter study, patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included. A total of 84 per-protocol patients were randomized in two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the week 8 visit, the average OSDI of the verum group had improved by 13.5 as compared to the control group (p = 0.001). The best corrected visual acuity (BCVA) had improved by 0.04 logMAR (p = 0.033). CFS, tear film break-up time (TBUT), Schirmer I, lid wiper epitheliopathy (LWE), mucocutaneous junction (Yamaguchi score), and tear osmolarity were not significantly different between the verum and control groups (p > 0.050). We conclude that for most patients with severe DED, 0.15% HMWHA eye drops provide excellent improvement of symptoms without impairment of dry eye signs

Importance of calcium and potassium currents in human lens epithelial cells (hLEC) and the effect of the calcium channel blocker mibefradil

Background: To prevent posterior capsule opacification (PCO), we followed the hypothesis that calcium channel blockers (antagonists) interfere with integrin signaling and block cell adhesion in lens epithelial cells (LEC). In primary human LEC we found that the T channel antagonist mibefradil induces apoptosis which was accompanied with cell shape changes and loss of cell adhesion. Although T-type calcium channels are substantially present in membranes of freshly dispersed primary cultured hLEC and calcium currents are inhibited by mibefradil at concentrations of 10-8 M, the antiproliferative site of action of this drug remains unclear, since this feature is observed at concentrations 200-fold higher than that for calcium channel blockade. Methods: Epithelial cells of the human lens were dispersed by enzymatic treatment, recordings of membrane currents were performed using patch clamp technique in the whole cell configuration. Westernblot analysis was used for protein detection. Results: Total current elicited on depolarizing voltage steps from a holding potential of-80 mV was composed of inward (calcium) and outward (potassium) current. Outward current could be inhibited mostly by intracellular application of cesium ions. Currents in inward direction were activated fast (< 2 ms) and inactivated during the following 20 ms. They were characterized as calcium currents since the known calcium channel inhibitor nifedipine blocked these currents in a concentration-dependent manner. Using potassium in the pipette (145 mM) as main charge carrier, additionally a noninactivating potassium current and a voltage- and time-dependent potassium current which slowly inactivated (Kv) were observed (control). Adding mibefradil in concentrations from 10-6 M - 10-5 M to the bath solution, the inwardly directed and the non-inactivating current component were inhibited concentration-dependent. The Kv component was affected in a similar way, however, this component showed an increased inactivation behavior after application of mibefradil in the named concentrations. Conclusion: The total effects of mibefradil are significant for the calcium homeostasis since calcium current itself is inhibited but, moreover, the membrane is permanently depolarized up to 20 mV by the drug. Both effects may contribute to the observed reduced cell adhesion during mibefradil treatment

Adrenomedullin 2.0: Adjusting Key Levers for Metabolic Stability

The 52 amino acid peptide hormone adrenomedullin (ADM) plays a major role in the development and regulation of the cardiovascular and lymphatic system and has therefore gained significant interest for clinical applications. Because adrenomedullin exhibits low metabolic stability, enhancement of the plasma half-life is essential for peptide-based drug design. Fluorescently labeled ADM analogues synthesized by Fmoc/<i>t-</i>Bu solid phase peptide synthesis were used to analyze their enzymatic degradation and specific fragmentation pattern in human blood plasma. The determination of important cleavage sites allowed the development of selectively modified peptides in a rational approach. By combination of palmitoylation, lactam-bridging, and N_α-methylation, ADM analogues protected from enzymatic cleavage in human blood were developed and revealed an explicitly elongated half-life of 5 days in comparison to the wild-type <i>in vitro</i>. This triple-modification did not alter the selectivity of the analogues at the AM₁ receptor, highlighting their potential for therapeutic applications

In Helping a Vulnerable Bot, You Help Yourself: Designing a Social Bot as a Care-Receiver to Promote Mental Health and Reduce Stigma

Helping others can have a positive effect on both the giver and the receiver. However, supporting someone with depression can be complicated and overwhelming. To address this, we proposed a Facebook-based social bot displaying depressive symptoms and disclosing vulnerable experiences that allows users to practice providing reactions online. We investigated how 55 college students interacted with the social bot for three weeks and how these support-giving experiences affected their mental health and stigma. By responding to the bot, the participants reframed their own negative experiences, reported reduced feelings of danger regarding an individual with depression and increased willingness to help the person, and presented favorable attitudes toward seeking treatment for depression. We discuss design opportunities for accessible social bots that could help users to keep practicing peer support interventions without fear of negative consequences.N

Growth rates of mayflies (Ephemeroptera) reared in the field differed under contrasting temperatures

Aquatic insect growth is tightly linked to environmental temperature. Growth rate tends to increase with rising temperatures. Growth rate integrates different factors related to population fitness, being partly responsible for species distribution. We aim to estimate daily growth rates from mayfly nymphs reared under different thermal regimes in the field, during five different periods from 2016 to 2018. Twelve species of mayflies were reared in mesocosms in six streams (from three altitudinal levels with a mean elevation 725, 1069, and 1509 m.a.s.l.). Additionally, we transplanted nymphs between lowest and highest pairs of streams, thus rearing them under a different thermal regime. Temperature and other ambient variables were recorded at regular intervals. Daily growth rate (dgr) of most species resulted lower in the higher pair of streams (colder sites) than in the medium and lower streams (warmer sites). Transplant experiment also clearly showed this tendency: (1) nymphs transplanted to colder thermal regimes grew slower than those reared under their natural (warmer) regime and (2) nymphs transplanted to hotter thermal regimes grew faster than those reared under their original (colder) regime. Nymphs of three species (Americabaetis alphus, Leptohyphes eximius, and Cloeodes penai) did not show differences in growth among treatments. Our findings relating sensitiveness of Ephemeroptera nymphs to small temperature changes suggest that the distribution of some species will modify by increases in temperature derived from climatic change.Fil: Hankel, Guillermo Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biodiversidad Neotropical. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Biodiversidad Neotropical. Instituto de Biodiversidad Neotropical; ArgentinaFil: Molineri, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biodiversidad Neotropical. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Biodiversidad Neotropical. Instituto de Biodiversidad Neotropical; Argentin