Strain variations in cone wavelength peaks in situ during zebrafish development.

There are four cone morphologies in zebrafish, corresponding to UV (U), blue (B), green (G), and red (R)-sensing types; yet genetically, eight cone opsins are expressed. How eight opsins are physiologically siloed in four cone types is not well understood, and in larvae, cone physiological spectral peaks are unstudied. We use a spectral model to infer cone wavelength peaks, semisaturation irradiances, and saturation amplitudes from electroretinogram (ERG) datasets composed of multi-wavelength, multi-irradiance, aspartate-isolated, cone-PIII signals, as compiled from many 5- to 12-day larvae and 8- to 18-month-old adult eyes isolated from wild-type (WT) or roy orbison (roy) strains. Analysis suggests (in nm) a seven-cone, U-360/B1-427/B2-440/G1-460/G3-476/R1-575/R2-556, spectral physiology in WT larvae but a six-cone, U-349/B1-414/G3-483/G4-495/R1-572/R2-556, structure in WT adults. In roy larvae, there is a five-cone structure: U-373/B2-440/G1-460/R1-575/R2-556; in roy adults, there is a four-cone structure, B1-410/G3-482/R1-571/R2-556. Existence of multiple B, G, and R types is inferred from shifts in peaks with red or blue backgrounds. Cones were either high or low semisaturation types. The more sensitive, low semisaturation types included U, B1, and G1 cones [3.0-3.6 log(quanta·µm-2·s-1)]. The less sensitive, high semisaturation types were B2, G3, G4, R1, and R2 types [4.3-4.7 log(quanta·µm-2·s-1)]. In both WT and roy, U- and B- cone saturation amplitudes were greater in larvae than in adults, while G-cone saturation levels were greater in adults. R-cone saturation amplitudes were the largest (50-60% of maximal dataset amplitudes) and constant throughout development. WT and roy larvae differed in cone signal levels, with lesser UV- and greater G-cone amplitudes occurring in roy, indicating strain variation in physiological development of cone signals. These physiological measures of cone types suggest chromatic processing in zebrafish involves at least four to seven spectral signal processing pools.

Method for Quantitative Analysis of Vitreoretinal Adhesion in Ex Vivo Model.

Purpose: Posterior vitreous detachment (PVD) is implicated in numerous retinal pathologies. A necessary step in developing new therapies, an area of significant interest, is a quantifiable assessment of posterior vitreous adhesion (PVA) that is also clinically relevant. Methods: A 23-gauge vitrector was used at varying levels of vacuum to attempt PVD induction in a porcine eye model injected with either balanced salt solution (BSS) (control) or plasmin (2, 3, or 5 U), which can pharmacologically induce PVD. Results: The average minimum vacuum necessary to induce a PVD was 395 ± 28 mm Hg for BSS alone, 385 ± 58 mm Hg for 2 U of plasmin, 265 ± 53 mm Hg for 3 U of plasmin, and 145 ± 28 mm Hg for 5 U of plasmin. We demonstrated a dose-dependent response curve with increasing amounts of plasmin, leading to a statistically significantly lower minimum vacuum necessary to induce a PVD except between BSS and 2 U plasmin. Conclusions: A dose-dependent relationship between plasmin concentration and PVD was demonstrated. We believe that this model offers significant benefits over prior work as it minimizes confounding manipulations and offers a quantitative assessment that is translatable to in vivo surgical models. Translational Relevance: This is the first methodology to quantitatively assess the degree of vitreous adhesion in situ.

Migraine is a risk factor for pseudophakic positive dysphotopsia following monofocal lens implantation.

OBJECTIVE: To identify neuroadaptation-related risk factors for persistent positive dysphotopsia (>6 months) following monofocal lens implantation. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients of an academic institution and a private practice in Saint Louis, Missouri. Inclusion criteria were adults with cataract extraction between January 2010 and April 2021 with monofocal intraocular lens implantation. Exclusion criteria included dementia, <20/40 acuity, visual pathway damage, visual field loss, and significant pathology causing photopsia. METHODS: Participants were surveyed via telephone. RESULTS: There were 385 participants (385 eyes), of whom 66 had persistent dysphotopsia (58 positive), 298 had none, and 21 had nonpersistent dysphotopsia. Among the 58 who had positive persistent dysphotopsia, mean Pseudophakic Dysphotopsia Questionnaire 6 (PDQ-6) score was 14.11 (SD, 8.46). There were no significant differences in sex or race. Migraine prevalence was greater among those with dysphotopsia (21.2%) than among those without (11.4%; p = 0.054). History of migraine was associated with an increase in PDQ-6 score of 2.76 points (p = 0.006). Six people in each group had Visual Aura Rating Scale (VARS) scores greater than zero. Mean VARS score was 0.48 for those with dysphotopsia and 0.14 for those without (p = 0.03). History of migraine or increased VARS score, younger age, and female sex were associated with lower satisfaction. CONCLUSION: History of migraine was associated with increased dysphotopsia severity and decreased patient satisfaction. Although further study with a larger sample size is warranted, these preliminary results highlight the potential of simple questions to individualize lens choice, reduce the risk of dysphotopsia, and improve patient satisfaction.

Growth kinetics of venous tumor thrombus in patients with renal cell carcinoma.

INTRODUCTION: Some patients with renal cell carcinoma (RCC) present with venous tumor thrombus (VTT). The extent of the VTT is related to survival, so prompt surgical care is recommended. However, studies evaluating the natural history of VTT in patients with RCC are rare. We sought to evaluate the growth kinetics of VTT in patients with RCC using preoperative cross-sectional images. MATERIALS AND METHODS: We identified patients who underwent radical nephrectomy and venous tumor thrombectomy at our institution from 01/2009 to 02/2022. We included those with a minimum of 2 adequate preoperative imaging studies (contrast-enhanced Computerized Tomography (CT), noncontrast Magnetic resonance imaging (MRI), or contrast-enhanced MRI), at least 14 days apart. We measured VTT in each study to calculate growth rate, and evaluated predictors of faster growth (demographics, histology, laterality, tumor diameter, and staging). To assess the relation between clinical variables and VTT growth, we used the Wilcoxon Rank-Sum, Kruskal-Wallis, and Spearman correlation tests. RESULTS: A total of 30 patients were included in the analysis. The median time interval between studies was 33 days. Patients were mostly Caucasian and Males (90% and 70%, respectively). Most patients underwent a CT scan as their initial imaging study (66%), followed with an MRI as second study (73%). The mean venous tumor thrombus growth rate was 0.3 mm/d (standard deviation of 0.5mm), and only rhabdoid/sarcomatoid differentiation showed an association with tumor thrombus growth rate (0.3 vs. 0.63 mm/d, P = 0.038). CONCLUSIONS: To the best of our knowledge, this is the first study evaluating the natural growth rate of venous tumor thrombus in patients with renal cell carcinoma. We found that tumor thrombi grew an average of 0.3 mm/d (1.0 cm/month) and that those with sarcomatoid and/or rhabdoid differentiation grew faster (0.63 mm/d). Further studies are needed to validate these results and provide a better understanding of tumor thrombus kinetics.

The Developmental Progression of Eight Opsin Spectral Signals Recorded from the Zebrafish Retinal Cone Layer Is Altered by the Timing and Cell Type Expression of Thyroxin Receptor ß2 (trß2) Gain-Of-Function Transgenes.

Zebrafish retinal cone signals shift in spectral shape through larval, juvenile, and adult development as expression patterns of eight cone-opsin genes change. An algorithm extracting signal amplitudes for the component cone spectral types is developed and tested on two thyroxin receptor ß2 (trß2) gain-of-function lines crx:mYFP-2A-trß2 and gnat2:mYFP-2A-trß2, allowing correlation between opsin signaling and opsin immunoreactivity in lines with different developmental timing and cell-type expression of this red-opsin-promoting transgene. Both adult transgenics became complete, or nearly complete, "red-cone dichromats," with disproportionately large long-wavelength-sensitive (LWS)1 opsin amplitudes as compared with controls, where LWS1 and LWS2 amplitudes were about equal, and significant signals from SWS1, SWS2, and Rh2 opsins were detected. But in transgenic larvae and juveniles of both lines it was LWS2 amplitudes that increased, with LWS1 cone signals rarely encountered. In gnat2:mYFP-2A-trß2 embryos at 5 d postfertilization (dpf), red-opsin immunoreactive cone density doubled, but red-opsin amplitudes (LWS2) increased <10%, and green-opsin, blue-opsin, and UV-opsin signals were unchanged, despite co-expressed red opsins, and the finding that an sws1 UV-opsin reporter gene was shut down by the gnat2:mYFP-2A-trß2 transgene. By contrast both LWS2 red-cone amplitudes and the density of red-cone immunoreactivity more than doubled in 5-dpf crx:mYFP-2A-trß2 embryos, while UV-cone amplitudes were reduced 90%. Embryonic cones with trß2 gain-of-function transgenes were morphologically distinct from control red, blue or UV cones, with wider inner segments and shorter axons than red cones, suggesting cone spectral specification, opsin immunoreactivity and shape are influenced by the abundance and developmental timing of trß2 expression.

Eight Genome Sequences of Cluster BE1 Phages That Infect Streptomyces Species.

Cluster BE1 Streptomyces bacteriophages belong to the Siphoviridae, with genome sizes over 130 kbp, and they contain direct terminal repeats of approximately 11 kbp. Eight newly isolated closely related cluster BE1 phages contain 43 to 48 tRNAs, one transfer-messenger RNA (tmRNA), and 216 to 236 predicted open reading frames (ORFs), but few of their genes are shared with other phages, including those infecting Streptomyces species.