Efficacy and safety of evenamide, a glutamate modulator, added to a second-generation antipsychotic in inadequately/poorly responding patients with chronic schizophrenia: Results from a randomized, double-blind, placebo-controlled, phase 3, international clinical trial.

Background: Evenamide, a glutamate modulator, is currently in phase 3 of development as add-on treatment to antipsychotics in patients with inadequate response or treatment-resistant schizophrenia. This study was designed to determine if patients with chronic schizophrenia inadequately responding to a second-generation antipsychotic would benefit from add-on treatment with evenamide at a dose of 30 mg bid.

Methods: Study 008A was a prospective, 4-week, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of oral doses of evenamide of 30 mg bid in patients with chronic schizophrenia treated at stable therapeutic doses of a second-generation antipsychotic.

Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in Patients With Treatment-Resistant Schizophrenia (TRS): Final, 1-Year Results From a Phase 2, Open-Label, Rater-Blinded, Randomized, International Clinical Trial.

The results from a pilot, 1-year, randomized, open-label, add-on treatment study in treatment-resistant schizophrenia (TRS) with evenamide, a glutamate modulator, were not associated with any safety abnormalities at all doses (7.5-30 mg bid), with a high retention rate even at 6-month (~85%), and 1-year (~75%), and the absence of psychotic relapses during the 1-year treatment period. Overall, treatment with evenamide showed a gradual, sustained, and clinically important improvement up to 1 year in all efficacy measures (eg, PANSS mean change ~ -20%; CGI-S mean change ~ -1.

Phase 2 Results Indicate Evenamide, A Selective Modulator of Glutamate Release, Is Associated With Clinically Important Long-Term Efficacy When Added to an Antipsychotic in Patients With Treatment-Resistant Schizophrenia.

Results from a pilot, 6-week, randomized, open-label, rater-blinded study, with 46-week extension, indicate very good tolerability with exceptional, clinically important, increasing efficacy of evenamide (7.5, 15, and 30 mg bid), a glutamate modulator, as add-on treatment to antipsychotics in 161 treatment-resistant, schizophrenia patients. Ninety-five percent of patients completed 6 weeks (1 discontinued for adverse event), and 89% continued in the extension.

Global analysis of Twitter communication in corporate social responsibility area: sustainability, climate change, and waste management.

Many people now consider social media to be an integral part of their daily routines, which has enabled companies to implement successful corporate social responsibility campaigns through these platforms. The direct interaction with stakeholders offered by social media helps companies to build understanding, trust, and their image. The aim of this study was to identify key topics and trends communicated in connection with corporate social responsibility on the Twitter social network from 2017 to 2022.

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring.

Psychosocial Stress and Age Influence Depression and Anxiety-Related Behavior, Drive Tumor Inflammatory Cytokines and Accelerate Prostate Cancer Growth in Mice.

Prostate cancer (PCa) prevalence is higher in older men and poorer coping with psychosocial stressors effect prognosis. Yet, interactions between age, stress and PCa progression are underexplored. Therefore, we characterized the effects of age and isolation combined with restraint (2 h/day) for 14 days post-tumor inoculation on behavior, tumor growth and host defense in the immunocompetent, orthotopic RM-9 murine PCa model.

Healthy Food on Instagram Social Network: Vegan, Homemade and Clean Eating.

Social media platforms have become part of many people's lives. Users are spending more and more time on these platforms, creating an active and passive digital footprint through their interaction. This footprint has high research potential in many research areas because understanding people's communication on social media is essential in understanding their values, attitudes, experiences and behaviors.

Exosomes in Alzheimer's Disease: Potential Role as Pathological Mediators, Biomarkers and Therapeutic Targets.

The concept of exosomes has been progressively changed from the status of cellular trashcans to multitasking organelles involved in many processes, including internalization, transport and transfer of macromolecules such as proteins, lipids and nucleic acids. While underpinning the mechanisms behind neurodegeneration and neuronal loss, exosomes were shown to be involved in carrying pathological misfolded proteins, propagation of β-amyloid protein and hyper-phosphorylated tau proteins across the brain that ultimately leads to the onset of Alzheimer's disease (AD), the most prevailing multifactorial neurodegenerative disorder. A potential novel therapeutic role of exosomes in AD intervention is suggested by their ability to increase Aβ clearance.

A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury.

To date, no stem cell therapy has been directed to specific recipients-and, conversely, withheld from others-based on a clinical or molecular profile congruent with that cell's therapeutic mechanism-of-action (MOA) for that condition. We address this challenge preclinically with a prototypical scenario: human neural stem cells (hNSCs) against perinatal/neonatal cerebral hypoxic-ischemic injury (HII). We demonstrate that a clinically translatable magnetic resonance imaging (MRI) algorithm, hierarchical region splitting, provides a rigorous, expeditious, prospective, noninvasive "biomarker" for identifying subjects with lesions bearing a molecular profile indicative of responsiveness to hNSCs' neuroprotective MOA.

Adverse childhood experiences and depressive symptoms: Protective effects of dietary flavonoids.

Objectives: Adverse childhood experiences (ACEs) are associated with increased inflammation, stress, and depression. Diet patterns rich in flavonoids may buffer the effects of ACEs on depression through neuroprotective mechanisms. No studies have examined the protective effects of dietary flavonoids on depressive symptoms after ACEs.

Dietary Approaches to the Management of Autism Spectrum Disorders.

This chapter reviews the literature surrounding autism spectrum disorders (ASD) and their relation to gastrointestinal (GI), behavioral, neurological, and immunological functioning. Individuals with ASD often have poor GI health, including bowel motility issues, autoimmune and/or other adverse responses to certain foods, and lack of necessary nutrient absorption. These issues may be caused or exacerbated by restrictive behavioral patterns (e.

Repression of the Glucocorticoid Receptor Increases Hypoxic-Ischemic Brain Injury in the Male Neonatal Rat.

Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia is the most common cause of neonatal brain damage and results in significant neurological sequelae, including cerebral palsy. The current therapeutic interventions are extremely limited in improving neonatal outcomes. The present study tests the hypothesis that the suppression of endogenous glucocorticoid receptors (GRs) in the brain increases hypoxic-ischemic (HI) induced neonatal brain injury and worsens neurobehavioral outcomes through the promotion of increased inflammation.

Acute intranasal osteopontin treatment in male rats following TBI increases the number of activated microglia but does not alter lesion characteristics.

Intranasal recombinant osteopontin (OPN) has been shown to be neuroprotective in different models of acquired brain injury but has never been tested after traumatic brain injury (TBI). We used a model of moderate-to-severe controlled cortical impact in male adult Sprague Dawley rats and tested our hypothesis that OPN treatment would improve neurological outcomes, lesion and brain tissue characteristics, neuroinflammation, and vascular characteristics at 1 day post-injury. Intranasal OPN administered 1 hr after the TBI did not improve neurological score, lesion volumes, blood-brain barrier, or vascular characteristics.

Repeated isoflurane in adult male mice leads to acute and persistent motor decrements with long-term modifications in corpus callosum microstructural integrity.

Isoflurane is a commonly used inhalational anesthetic, clinically and in animal experimental studies. Although it has been reported as safe, recent findings suggest that despite widespread use, isoflurane-induced inhalational anesthesia can lead to various pathophysiological and cognitive alterations. Therefore, we aimed to investigate the long-term behavioral and white matter consequences of repeated isoflurane exposure.

Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment.

Fifteen years ago Olney and colleagues began using animal models to evaluate the effects of anesthetic and sedative agents (ASAs) on neurodevelopment. The results from ongoing studies indicate that, under certain conditions, exposure to these drugs during development induces an acute elevated apoptotic neurodegenerative response in the brain and long-term functional impairments. These animal models have played a significant role in bringing attention to the possible adverse effects of exposing the developing brain to ASAs when few concerns had been raised previously in the medical community.

PDGFR-β modulates vascular smooth muscle cell phenotype via IRF-9/SIRT-1/NF-κB pathway in subarachnoid hemorrhage rats.

Platelet-derived growth factor receptor-β (PDGFR-β) has been reported to promote phenotypic transformation of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the role of the PDGFR-β/IRF9/SIRT-1/NF-κB pathway in VSMC phenotypic transformation after subarachnoid hemorrhage (SAH). SAH was induced using the endovascular perforation model in Sprague-Dawley rats.

Pomegranate supplementation improves cognitive and functional recovery following ischemic stroke: A randomized trial.

We tested whether supplementing with pomegranate polyphenols can enhance cognitive/functional recovery after stroke. In this parallel, block-randomized clinical trial, we administered commercially-available pomegranate polyphenol or placebo pills twice per day for one week to adult inpatients in a comprehensive rehabilitation setting starting approximately 2 weeks after stroke. Pills contained 1 g of polyphenols derived from whole pomegranate, equivalent to levels in approximately 8 oz of juice.

Low-dose proton radiation effects in a transgenic mouse model of Alzheimer's disease - Implications for space travel.

Space radiation represents a significant health risk for astronauts. Ground-based animal studies indicate that space radiation affects neuronal functions such as excitability, synaptic transmission, and plasticity, and it may accelerate the onset of Alzheimer's disease (AD). Although protons represent the main constituent in the space radiation spectrum, their effects on AD-related pathology have not been tested.

A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers.

The objectives of this 2-phase study were to elucidate pharmacokinetics (PK), in vivo 24-hour recovery, and red blood cell (RBC) survival properties of RBC-encapsulated dexamethasone sodium phosphate (DSP) prepared using the EryDex System (EDS). The 24-hour RBC recovery and T50 survival phase studied subjects were randomized to receive autologous RBCs loaded with either 15-20 mg DSP (Group 1A) or sham saline (Group 2A). Loaded RBCs were radiolabeled with 51-Cr, and the labeled RBCs were followed over time in vivo.

Effects and mechanisms of actions of phytochemicals on Alzheimer's disease neuropathology.

Alzheimer's disease affects millions of people, yet, there are only a limited number approaches for it pharmacological treatment. Thus, identifying factors that decrease the risk of developing Alzheimer's disease is of paramount importance. A growing body of epidemiological and experimental evidence suggests that dietary fruits and vegetables have neuroprotective effects against the harmful effects of oxidative stress, neuroinflammation, and aging.

Recanalization, reperfusion, and recirculation in stroke.

Recirculation, from arterial inflow routes through venous outflow pathways, was conceptualized in stroke research 50 years ago. As new technologies were developed, blocked arteries could be reopened, capillaries could be reperfused, and the use of recanalization and reperfusion grew to dominate therapeutic strategies. These approaches overwhelmingly focused on restoration of arterial and capillary inflow, but not on veins even though venous disorders may initiate or exacerbate brain injury.

Long-term effects of simulated microgravity and/or chronic exposure to low-dose gamma radiation on behavior and blood-brain barrier integrity.

Astronauts on lengthy voyages will be exposed to an environment of microgravity and ionizing radiation that may have adverse effects on physical abilities, mood, and cognitive functioning. However, little is known about the long-term effects of combined microgravity and low-dose radiation. We exposed mice to gamma radiation using a cobalt-57 plate (0.

Inhibition of stress fiber formation preserves blood-brain barrier after intracerebral hemorrhage in mice.

Intracerebral hemorrhage (ICH) represents the deadliest subtype of all strokes. The development of brain edema, a consequence of blood-brain barrier (BBB) disruption, is the most life-threatening event after ICH. Pathophysiological conditions activate the endothelium, one of the components of BBB, inducing rearrangement of the actin cytoskeleton.

Inhibition of DNA Methylation in the Developing Rat Brain Disrupts Sexually Dimorphic Neurobehavioral Phenotypes in Adulthood.

Accumulating evidence indicates a critical implication of DNA methylation in the brain development. We aim to determine whether the disruption of DNA methylation patterns in the developing brain adversely affects neurobehavioral phenotypes later in life in a sex-dependent manner. 5-Aza-2'-deoxycytidine (5-Aza), a DNA methylation inhibitor, was administered in newborn rats from postnatal day 1 to 3.

Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model.

Objective: Inflammation plays a key role in the pathophysiological processes after intracerebral hemorrhage (ICH). Post-ICH macrophages infiltrate the brain and release pro-inflammatory factors (tumor necrosis factor-α), amplifying microglial activation and neutrophil infiltration. Platelet-derived growth factor receptor-β (PDGFR-β) is expressed on macrophages and it's activation induces the recruitment of macrophages.