Endocannabinoids facilitate transitory reward engagement through retrograde gain-control.

Neuromodulatory signaling is poised to serve as a neural mechanism for gain control, acting as a crucial tuning factor to influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) signaling system, the most widely expressed neuromodulatory system in the mammalian brain, is known to filter excitatory and inhibitory inputs through retrograde, pre-synaptic action. However, whether eCBs exert retrograde gain control to ultimately facilitate reward-seeking behaviors in freely moving mammals is not established.

Development, validation and recalibration of a prediction model for prediabetes: an EHR and NHANES-based study.

Background: A prediction model that estimates the risk of elevated glycated hemoglobin (HbA1c) was developed from electronic health record (EHR) data to identify adult patients at risk for prediabetes who may otherwise go undetected. We aimed to assess the internal performance of a new penalized regression model using the same EHR data and compare it to the previously developed stepdown approximation for predicting HbA1c ≥ 5.7%, the cut-off for prediabetes.

'I can't relate to it': Exploring autistic and non-autistic adults' perceptions of the Australian Physical Activity and Sedentary Behaviour Guidelines.

Background: Despite sufficient physical activity (PA) being strongly associated with better health outcomes, half of the Australian population does not meet the Australian PA and Sedentary Behaviour Guidelines. This shortfall is more pronounced among autistic adults, who exhibit poorer health outcomes and lower PA levels than non-autistic adults. Despite these disparities, there is a limited understanding of how autistic and non-autistic individuals perceive and interpret the PA guidelines.

The mammalian Ire1 inhibitor, 4µ8C, exhibits broad anti- activity and in a treatment model of fungal keratitis.

Objective: The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates the mRNA of the transcription factor, HacA. Previously, we demonstrated that is essential for virulence in a murine model of fungal keratitis (FK), suggesting the pathway could serve as a therapeutic target. Here we investigate the antifungal properties of known inhibitors of the mammalian Ire1 protein both and in a treatment model of FK.