Intraoperative changes in large-scale thalamic circuitry following laser ablation of hypothalamic hamartomas.

Background And Objectives: Gelastic seizures due to hypothalamic hamartomas (HH) are challenging to treat, in part due to an incomplete understanding of seizure propagation pathways. Although magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) is a promising intervention to disconnect HH from ictal propagation networks, the optimal site of ablation to achieve seizure freedom is not known. In this study, we investigated intraoperative post-ablation changes in resting-state functional connectivity to identify large-scale networks associated with successful disconnection of HH.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition.

Interictal discharges delay target-directed eye movements and impair attentional set-shifting in children with epilepsy.

Objective: The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye-tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy.

Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists.

Antagonism of the chemokine receptor CXCR2 has been proposed as a strategy for the treatment of inflammatory diseases such as arthritis, chronic obstructive pulmonary disease and asthma. Earlier series of bicyclic CXCR2 antagonists discovered at AstraZeneca were shown to have low solubility and poor oral bioavailability. In this Letter we describe the design, synthesis and characterisation of a new series of monocyclic CXCR2 antagonists with improved solubility and good pharmacokinetic profiles.

Overlapping community detection using Bayesian non-negative matrix factorization.

Identifying overlapping communities in networks is a challenging task. In this work we present a probabilistic approach to community detection that utilizes a Bayesian non-negative matrix factorization model to extract overlapping modules from a network. The scheme has the advantage of soft-partitioning solutions, assignment of node participation scores to modules, and an intuitive foundation.

Evaluation of a series of bicyclic CXCR2 antagonists.

The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists with markedly improved biological and pharmacokinetic properties, which are suitable pharmacological tools to probe the in vivo effects of CXCR2 antagonism combined with the associated CCR2 activity.

A synaptic input portal for a mapped clock oscillator model of neuronal electrical rhythmic activity.

Neuronal electrical oscillations play a central role in a variety of situations, such as epilepsy and learning. The mapped clock oscillator (MCO) model is a general model of transmembrane voltage oscillations in excitable cells. In order to be able to investigate the behaviour of neuronal oscillator populations, we present a neuronal version of the model.