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Levetiracetam (LEV) suppresses the upregulation of proinflammatory molecules that occurs during epileptogenesis after status epilepticus (SE). Based on previous studies, LEV likely helps prevent the onset of epilepsy after insults to the brain, unlike other conventional anti-epileptic drugs. Recently, we discovered that the increase in Fosl1 expression that occurs after lipopolysaccharide (LPS) stimulation is suppressed by LEV and that Fosl1 inhibition suppresses inflammation in BV-2 microglial cells. These data indicate that Fosl1 is an important target of LEV and a key factor in preventing epilepsy onset. In this study, we examined the effects of LEV on Fosl1 expression and neuroinflammation in vivo. During epileptogenesis, the post-SE upregulation of hippocampal levels of Fosl1 and many inflammatory factors were suppressed by LEV. Fosl1 expression showed a characteristic pattern different from that of the expression of Fos, an immediate-early gene belonging to the same Fos family. At 2 days after SE, Fosl1 was predominantly expressed in astrocytes but was rarely detected in microglia, whereas Fos expression was distributed in various brain cell types. The expression of A2 astrocyte markers was similar to that of Fosl1 and was significantly suppressed by LEV. These results suggest that LEV may regulate astrocyte reactivity through regulation of Fosl1.

Acute brain inflammation after status epilepticus (SE) is involved in blood–brain barrier (BBB) dysfunction and brain edema, which cause the development of post-SE symptomatic epilepsy. Using pilocarpine-induced SE mice, we previously reported that treatment with levetiracetam (LEV) after SE suppresses increased expression levels of proinflammatory mediators during epileptogenesis and prevents the development of spontaneous recurrent seizures. However, it remains unclear how LEV suppresses neuroinflammation after SE. In this study, we demonstrated that LEV suppressed the infiltration of CD11b+CD45high cells into the brain after SE. CD11b+CD45high cells appeared in the hippocampus between 1 and 4 days after SE and contained Ly6G+Ly6C+ and Ly6G−Ly6C+ cells. Ly6G+Ly6C+ cells expressed higher levels of proinflammatory cytokines such as IL-1β and TNFα suggesting that these cells were inflammatory neutrophils. Depletion of peripheral Ly6G+Ly6C+ cells prior to SE by anti-Ly6G antibody (NIMP-R14) treatment completely suppressed the infiltration of Ly6G+Ly6C+ cells into the brain. Proteome analysis revealed the downregulation of a variety of inflammatory cytokines, which exhibited increased expression in the post-SE hippocampus. These results suggest that Ly6G+Ly6C+ neutrophils are involved in the induction of acute brain inflammation after SE. The proteome expression profile of the hippocampus treated with LEV after SE was similar to that after NIMP-R14 treatment. Therefore, LEV may prevent acute brain inflammation after SE by suppressing inflammatory neutrophil infiltration.

The COVID-19 pandemic has brought about various restrictions around the world, and its impact on healthcare has been enormous: RDNs have had to shift from in-person interactions with clients to telenutrition consultations, encountering obstacles. We designed the first survey to investigate the changes in RDN practices related to telenutrition provision after the onset of the pandemic through an online survey in Italy. Four hundred and thirty-six responses were analyzed. Before the pandemic, only 16% of Italian RDNs provided telenutrition; this percentage increased significantly up to 63% (p < 0.001). Among patients, the lack of interest in accessing telenutrition (30.9%) and the Internet (16.7%) were the most frequently reported barriers. Among RDNs, one of the main obstacles was their inability to conduct nutritional evaluation or monitoring activities (24.4%). Our survey indicated that increased adoption of telenutrition can be a valid, safe alternative to face-to-face visits. Telenutrition was mainly used by young RDNs (20–39 years) with fewer years of professional experience (0–20 years) and master’s degrees. Remote nutrition can enable RDNs to maintain normal workloads and provide patients with uninterrupted access to nutritional healthcare. It is important that RDNs using telemedicine resources possess the ability to provide high-quality, efficient, and secure services using evidence-based guidance.

PSD-Zip70 is a postsynaptic protein that regulates glutamatergic synapse formation and maturation by modulation of Rap2 activity. PSD-Zip70 knockout (PSD-Zip70KO) mice exhibit defective glutamatergic synaptic transmission in the prefrontal cortex (PFC) with aberrant Rap2 activation. As prefrontal dysfunction is implicated in the pathophysiology of stress-induced psychiatric diseases, we examined PSD-Zip70KO mice in a social defeat (SD) stress-induced mouse model of depression to investigate stress-induced alterations in synaptic function. Compared with wild-type (WT) mice, PSD-Zip70KO mice exhibited almost normal responses to SD stress in depression-related behaviors such as social activity, anhedonia, and depressive behavior. However, PSD-Zip70KO mice showed enhanced anxiety-like behavior irrespective of stress conditions. The density and size of dendritic spines of pyramidal neurons were reduced in the medial PFC (mPFC) in mice exposed to SD stress. Phosphorylation levels of the AMPA–type glutamate receptor (AMPA-R) GluA2 subunit at Ser880 were prominently elevated in mice exposed to SD stress, indicating internalization of surface-expressed AMPA-Rs and decreased postsynaptic responsiveness. Structural and functional impairments in postsynaptic responsiveness were associated with Rap2 GTPase activation in response to SD stress. Social stress-induced Rap2 activation was regulated by a PSD-Zip70-dependent pathway via interaction with SPAR/PDZ-GEF1. Notably, features such as Rap2 activation, dendritic spine shrinkage, and increased GluA2 phosphorylation were observed in the mPFC of PSD-Zip70KO mice even without SD stress. Together with our previous results, the present findings suggest that SD stress-induced postsynaptic hyporesponsiveness in glutamatergic synapses is mediated by PSD-Zip70-Rap2 signaling pathway and closely relates to anxiety-like behaviors.

Abstract Background Home parenteral nutrition (HPN) can improve survival, quality of life, nutritional and functional status in cancer patients. Bioelectrical impedance analysis (BIA) is a non-invasive, validated method to assess body composition. The objective of this prospective single-arm study was to investigate the impact of HPN in advanced cancer patients receiving chemotherapy assessed by BIA, clinical and laboratory measures. Methods Adult malnourished cancer outpatients with solid tumors receiving anticancer treatments who were candidates for daily HPN were enrolled. Patients were assessed at baseline (T0), 60 (T1) and 90 days (T2) after HPN start. Assessments included anthropometric and clinical-oncological characteristics, performance status, inflammatory response and Patient-Generated Subjective Global Assessment (PG-SGA). Results Sixty-five advanced cancer patients were enrolled. Median overall survival was 317 days. Body weight, BMI, oral calorie and protein intake increased over time (P