Impacts of climate change on ocular health: A scoping review

Climate change represents a significant global health crisis, characterized by a complex interplay of environmental shifts and interconnected phenomena. These alterations have given rise to a multitude of health implications, notably impacting ocular health. Our comprehensive review delineates a spectrum of eye conditions associated with climate change-related variables. Extremes in temperature and weather events have been observed to affect the ocular surface, resulting in an increased incidence of conjunctivitis, keratitis, dry eye disease, and pterygium. Furthermore, climate change is linked to a rising occurrence of cataracts, glaucoma, periocular tumors, and infections. Prolonged food insecurity, stemming from droughts, has been associated with nutritional optic neuropathies and consequent vision loss. Elevated temperatures have also been correlated with a heightened risk of retinal detachments necessitating urgent surgical intervention to enhance prognostic outcomes.This review also outlines the influence of climate-warming pollutants on a diverse array of eye conditions, manifesting as ocular surface infections, degenerative changes like pterygium, cataracts, refractive errors (myopia), blepharitis, meibomian gland infections, glaucoma, and vascular retinal occlusions.Mitigating the effects of climate change is an urgent global imperative necessitating collaborative efforts, encompassing research and education, to devise sustainable solutions that safeguard human health and well-being. This review seeks to delineate the current extent of available research, identify gaps in the existing literature, and chart the course for future studies in this intriguing association

A phase 1 study of veliparib, a PARP-1/2 inhibitor, with gemcitabine and radiotherapy in locally advanced pancreatic cancerResearch in context

Background: Locally advanced pancreatic cancer (LAPC) has a dismal prognosis with current treatment modalities and one-third of patients die from local progression of disease. Preclinical studies with orthotopic PC demonstrated dramatic synergy between radiotherapy (RT) and the poly(ADP-ribose) polymerase-1/2 inhibitor (PARPi), veliparib. We conducted a phase I trial of gemcitabine, radiotherapy and dose-escalated veliparib in LAPC. Methods: This was a single institution investigator-initiated open-label, single-arm phase 1 clinical trial (NCT01908478). Weekly gemcitabine with daily IMRT and veliparib dose escalated using a Bayesian adaptive design were administered in treatment naïve LA or borderline resectable PC. The primary end point was identification of the MTD. Secondary endpoints included efficacy, characterization of PAR levels using ELISA, DDR alterations with targeted next generation sequencing and transcriptome analysis, tumor mutation burden (TMB) and microsatellite instability (MSI) status. Findings: Thirty patients were enrolled. The MTD of veliparib was 40 mg BID with gemcitabine 400 mg/m2 and RT (36 Gy/15 fractions). Sixteen DLTs were identified in 12 patients. Grade ≥ 3 adverse events included lymphopenia (96%) and anemia (36%). Median OS for all patients was 15 months. Median OS for DDR pathway gene altered and intact cases was 19 months (95% CI: 6.2–27.2) and 14 months (95% CI: 10.0–21.8), respectively. There were no significant associations between levels of PAR, TMB, or MSI with outcomes. The DDR transcripts PARP3 and RBX1 significantly correlated with OS. Interpretation: This is the first report of a PARPi-chemoradiotherapy combination in PC. The regimen was safe, tolerable at the RP2D, and clinically active as an upfront treatment strategy in patients biologically unselected by upfront chemotherapy. Expression of the DDR transcripts, PARP3 and RBX1, were associated with OS suggesting validation in a follow up phase 2 study. Fund: Phase One Foundation; National Institutes of Health [1R01CA188480-01A1, P01 CA098912]. Veliparib was provided by Abbvie. Keywords: Parp inhibitor, Radiation, Gemcitabine, Pancreas cancer, Velipari

Glycodendrimers: versatile tools for nanotechnology

Combining nanotechnology with glycobiology has triggered an exponential growth of research activities in the design of novel functional bionanomaterials (glyconanotechnology). More specifically, recent synthetic advances towards the tailored and versatile design of glycosylated nanoparticles namely glyconanoparticles, considered as synthetic mimetics of natural glycoconjugates, paved the way toward diverse biomedical applications. The accessibility of a wide variety of these structured nanosystems, in terms of shapes, sizes, and organized around stable nanoparticles have readily contributed to their development and applications in nanomedicine. In this context, glycosylated gold-nanoparticles (GNPs), glycosylated quantum dots (QDs), fullerenes, single-wall natotubes (SWNTs), and self-assembled glycononanoparticles using amphiphilic glycopolymers or glycodendrimers have received considerable attention to afford powerful imaging, therapeutic, and biodiagnostic devices. This review will provide an overview of the most recent syntheses and applications of glycodendrimers in glycoscience that have permitted to deepen our understanding of multivalent carbohydrate-protein interactions. Together with synthetic breast cancer vaccines, inhibitors of bacterial adhesions to host tissues including sensitive detection devices, these novel bionanomaterials are finding extensive relevance