Characterizing Antisense Oligonucleotide-Induced Histopathology Findings in Spinal Cord of Mauritius Cynomolgus Monkeys by Molecular Localization Investigation.

The safety of a 2'--methoxyethyl antisense oligonucleotide (ASO) was investigated in Mauritius cynomolgus monkeys in a 41-week Good Laboratory Practice (GLP) toxicity study after multiple intrathecal (IT) administrations. Histopathological examination revealed ectopic formation of lymphoid follicles in the spinal cord (SC) at the injection site at all doses and the presence of granular material in neurons of the SC in high-dose animals. The granular material was seen in all the segments of the SC, but mainly in the lumbar segment and persisted at the end of the 26-week recovery period, while the lymphoid follicles showed a reversibility trend.

Climate change aggravates bird mortality in pristine tropical forests.

Stable understory microclimates within undisturbed rainforests are often considered refugia against climate change. However, this assumption contrasts with emerging evidence of Neotropical bird population declines in intact rainforests. We assessed the vulnerability of resident rainforest birds to climatic variability, focusing on dry season severity characterized by hotter temperatures and reduced rainfall.

Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.

Aims/hypothesis: Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression.

In-pixel foreground and contrast enhancement circuits with customizable mapping.

This paper presents an in-pixel contrast enhancement circuit that performs image processing directly within the pixel circuit. The circuit leverages HyperFET, a hybrid device combining a MOSFET and a phase transition material (PTM), to enhance performance. It can be tuned for different modes of operation.

The complexities of elexacaftor/tezacaftor/ivacaftor therapeutic drug monitoring in a person with cystic fibrosis and pulmonary disease.

Therapeutic drug monitoring (TDM) of elexacaftor/tezacaftor/ivacaftor (ETI) remains challenging due to a lack of clarity around the parameters that govern ETI plasma concentrations, whilst the use of concomitant CYP3A inducers rifabutin and rifampicin is not recommended. We present the complexities of TDM for ETI performed in a person with cystic fibrosis and refractory pulmonary disease. Utilising National Association of Testing Authorities (NATA) accredited assays and target considerations published by the Therapeutic Goods Administration (TGA), Australia, ETI plasma concentration variability was monitored over the course of an acute admission with added complexity from an antibiotic regimen including rifabutin, a moderate cytochrome P450 3A (CYP3A) inducer, and clofazimine, a mild CYP3A inhibitor.