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Aim: The use of intravitreal antiangiogenic therapy has showed good results in angiogenesis-dependent intraocular diseases. In this small case series study, the biologic effects on physiological angiogenesis and pathological angiogenesis in the retina of patients with retinopathy of prematurity (ROP) after treatment of either bevacizumab or ranibizumab, is described. Methods: In this non-comparative, prospective, experimental and interventional case series study, we injected a single dose of either bevacizumab or ranibizumab into the vitreous of 20 eyes of 10 patients with ROP. Patients included in this study were prematures with stage 3, zone I, or posterior zone II with or without plus disease and patients with stage 4 a, any zone. Clinical response and any evidence of ocular toxicities were documented both pre- and post-injection by RetCam retinal images. Results: After one week of intavitreal injection of bevacizumab or ranibizumab, all eyes had significant inhibition of angiogenesis without affecting the development of normal retina vasculature. After six weeks, all eyes showed completed vasculature of the retina without any sign of pathological angiogenesis. We found no differences between bevacizumab and ranibizumab results. Neither local nor systemic adverse effects occurred in 18 eyes, two eyes with ROP stage 4 a, developed a central retinal fibrosis. Conclusions: Intravitreal therapy with bevacizumab or ranibizumab inhibits pathological angiogenesis and allows the developement of normal vasculature of the retina in ROP. This study proves that intravitreal antiangiogenic therapy does not cause inhibition of physiological angiogenesis in the retinal vessels and may suggest that the same could happen in the systemic vasculature process. [ABSTRACT FROM AUTHOR]

Aim: The use of intravitreal antiangiogenic therapy has showed good results in angiogenesis-dependent intraocular diseases. In this small case series study, the biologic effects on physiological angiogenesis and pathological angiogenesis in the retina of patients with retinopathy of prematurity (ROP) after treatment of either bevacizumab or ranibizumab, is described. Methods: In this non-comparative, prospective, experimental and interventional case series study, we injected a single dose of either bevacizumab or ranibizumab into the vitreous of 20 eyes of 10 patients with ROP. Patients included in this study were prematures with stage 3, zone I, or posterior zone II with or without plus disease and patients with stage 4 a, any zone. Clinical response and any evidence of ocular toxicities were documented both pre- and post-injection by RetCam retinal images. Results: After one week of intavitreal injection of bevacizumab or ranibizumab, all eyes had significant inhibition of angiogenesis without affecting the development of normal retina vasculature. After six weeks, all eyes showed completed vasculature of the retina without any sign of pathological angiogenesis. We found no differences between bevacizumab and ranibizumab results. Neither local nor systemic adverse effects occurred in 18 eyes, two eyes with ROP stage 4 a, developed a central retinal fibrosis. Conclusions: Intravitreal therapy with bevacizumab or ranibizumab inhibits pathological angiogenesis and allows the developement of normal vasculature of the retina in ROP. This study proves that intravitreal antiangiogenic therapy does not cause inhibition of physiological angiogenesis in the retinal vessels and may suggest that the same could happen in the systemic vasculature process. [ABSTRACT FROM AUTHOR]

Purpose: To determine the importance of fluorescein angiography in planning laser treatment for the clinically significant diabetic macular edema. Methods: Prospective study of 84 eyes of 54 diabetic patients with clinical significant macular edema, each case was documented with stereoscopic color photographs and a corresponding fluorescein angiogram The therapeutic plan was established after analyzing twice every case, the first time based only on the photographs and the second time based on both, the photographs and the angiograms. We compared the ability of the retina specialist to plan laser treatment with and without the use of fluorescein angiography. Results: In 85.7% of cases the ability of the specialist to decide laser treatment after the photograph analysis without the use of fluorescein angiographies was the same compared with the therapeutic plan based upon using the angiograms 14.3% showed small differences between both analyses. Conclusions: Fluorescein angiography improves the accuracy of laser treatment planning for clinically significant macular edema. [ABSTRACT FROM AUTHOR]

Objective: Genome wide association studies have identified an exon 6 CTRB2 deletion variant that associates with increased risk of pancreatic cancer. To acquire evidence on its causal role, we developed a new mouse strain carrying an equivalent variant in Ctrb1 , the mouse orthologue of CTRB2 ., Design: We used CRISPR/Cas9 to introduce a 707bp deletion in Ctrb1 encompassing exon 6 ( Ctrb1 Δexon6 ). This mutation closely mimics the human deletion variant. Mice carrying the mutant allele were extensively profiled at 3 months to assess their phenotype., Results: Ctrb1 Δexon6 mutant mice express a truncated CTRB1 that accumulates in the ER. The pancreas of homozygous mutant mice displays reduced chymotrypsin activity and total protein synthesis. The histological aspect of the pancreas is inconspicuous but ultrastructural analysis shows evidence of dramatic ER stress and cytoplasmic and nuclear inclusions. Transcriptomic analyses of the pancreas of mutant mice reveals acinar program down-regulation and increased activity of ER stress-related and inflammatory pathways. Heterozygous mice have an intermediate phenotype. Agr2 is one of the most up-regulated genes in mutant pancreata. Ctrb1 Δexon6 mice exhibit impaired recovery from acute caerulein-induced pancreatitis. Administration of TUDCA or sulindac partially alleviates the phenotype. A transcriptomic signature derived from the mutant pancreata is significantly enriched in normal human pancreas of CTRB2 exon 6 deletion variant carriers from the GTEx cohort., Conclusions: This mouse strain provides formal evidence that the Ctrb1 Δexon6 variant causes ER stress and inflammation in vivo , providing an excellent model to understand its contribution to pancreatic ductal adenocarcinoma development and to identify preventive strategies., Summary Box: What is already known about this subject?: - CTRB2 is one of the most abundant proteins produced by human pancreatic acinar cells. - A common exon 6 deletion variant in CTRB2 has been associated with an increased risk of pancreatic ductal adenocarcinoma. - Misfolding of digestive enzymes is associated with pancreatic pathology. What are the new findings?: - We developed a novel genetic model that recapitulates the human CTRB2 deletion variant in the mouse orthologue, Ctrb1 . - Truncated CTRB1 misfolds and accumulates in the ER; yet, mutant mice display a histologically normal pancreas at 3 months age.- CTRB1 and associated chaperones colocalize in the ER, the cytoplasm, and the nucleus of acinar cells.- Transcriptomics analysis reveals reduced activity of the acinar program and increased activity of pathways involved in ER stress, unfolded protein response, and inflammation.- Mutant mice are sensitized to pancreatic damage and do not recover properly from a mild caerulein-induced pancreatitis.- TUDCA administration partially relieves the ER stress in mutant mice. How might it impact on clinical practice in the foreseeable future?: - The new mouse model provides a tool to identify the mechanisms leading to increased pancreatic cancer risk in CTRB2 exon 6 carriers. - The findings suggest that drugs that cause ER stress relief and/or reduce inflammation might provide preventive opportunities.

Motivation: Transposable elements (TE) have played a major role in configuring the structures of mammalian genomes through evolution. In normal conditions, the expression of these elements is repressed by different epigenetic regulation mechanisms such as DNA methylation, histone modification and regulation by small RNAs. TE re-activation is associated with stemness potential acquisition, regulation of innate immunity and disease, such as cancer. However, the vast majority of current knowledge in the field is based on bulk expression studies, and very little is known on cell-type- or state-specific expression of TE-derived transcripts. Therefore, cost-efficient single-cell-resolution TE expression analytical approaches are needed., Results: We have implemented an analytical approach based on pseudoalignment to consensus sequences to incorporate TE expression information to scRNAseq data., Availability and Implementation: All the data and code implemented are available as Supplementary data and in: https://github.com/jmzvillarreal/kallisto_TE_scRNAseq., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)