No abstract

Increased concentrations of kynurenic acid (KYNA) in the prefrontal cortex (PFC) are thought to contribute to the development of cognitive deficits observed in schizophrenia. Although this view is consistent with preclinical studies showing a negative impact of prefrontal KYNA elevation on executive function, the mechanism underlying such a disruption remains unclear. Here, we measured changes in local field potential (LFP) responses to ventral hippocampal stimulation in vivo and conducted whole-cell patch-clamp recordings in brain slices to reveal how nanomolar concentrations of KYNA alter synaptic transmission in the PFC of male adult rats. Our data show that prefrontal infusions of KYNA attenuated the inhibitory component of PFC LFP responses, a disruption that resulted from local blockade of ␣7-nicotinic acetylcholine receptors (␣7nAChR). At the cellular level, we found that the inhibitory action exerted by KYNA in the PFC occurred primarily at local GABAergic synapses through an ␣7nAChR-dependent presynaptic mechanism. As a result, the excitatory-inhibitory ratio of synaptic transmission becomes imbalanced in a manner that correlates highly with the level of GABAergic suppression by KYNA. Finally, prefrontal infusion of a GABA A R positive allosteric modulator was sufficient to overcome the disrupting effect of KYNA and normalized the pattern of LFP inhibition in the PFC. Thus, the preferential inhibitory effect of KYNA on prefrontal GABAergic transmission could contribute to the onset of cognitive deficits observed in schizophrenia because proper GABAergic control of PFC output is one key mechanism for supporting such cortical functions.

No abstract

Atrial fibrillation (AF) in the setting of malignancy poses a unique challenge given the confluent pathologies and risks of current treatments. Oral anticoagulation is recommended to reduce the risk of systemic thromboembolism in high-risk individuals with AF. The ‘Watchman’ device for left atrial appendage closure has shown comparable efficacy compared with anticoagulation with warfarin; however, patients with cancer were not included in trials testing Watchman safety and efficacy. We present the current treatment approaches for the management of AF in patients with malignancy. We review contemporary guidelines and propose a novel clinical decision tree by which physicians can consider left atrial appendage closure in cancer patients, and at last, suggest future investigation that might further clarify the clinical benefit of this approach.

No abstract