Neurobiology of COVID-19-Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling.

COVID-19 exhibits not only respiratory symptoms but also neurological/psychiatric symptoms rarely including delirium/psychosis. Pathological studies on COVID-19 provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role in the progression of viral replication and lung fibrosis. Of note, SARS-CoV-2 virus (specifically, S1 spike domain) mimics EGF and directly transactivates EGFR, preceding the inflammatory process.

Cross-Cancer Type Evaluation of Potential Interstitial Lung Disease Complications of Immune Checkpoint Inhibitors Using JADER.

Interstitial lung disease (ILD) is a serious adverse event caused by the administration of immune checkpoint inhibitors (ICIs). However, only few large-scale studies have explored the association among ICI use, underlying cancer type, and ILD complications. This study aimed to analyze the association between the primary cancer type and ICI-induced ILD in a cross-sectional manner using the Japanese Adverse Drug Event Report (JADER) database.

Periostin Is a Candidate Regulator of the Host Microenvironment in Regeneration of Pulp and Dentin Complex and Periodontal Ligament in Transplantation with Stem Cell-Conditioned Medium.

Purpose: The microenvironment is required for tissues to maintain their properties . This microenvironment encompasses the types and three-dimensional arrangement of cells forming the tissues, and their interactions with neighboring cells and extracellular matrices, as represented by the stem cell niche. Tissue regeneration depends not on the original tissue source of the transplanted cells, but on the microenvironment in which they are transplanted.

External validation of the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 pneumonia managed on high-flow nasal cannula therapy: a multicenter retrospective observational study in Japan.

Background: The HACOR score for predicting treatment failure includes vital signs and acid-base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan.

Methods: This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022.

Epidermal Growth Factor Suppresses the Development of GABAergic Neurons Via the Modulation of Perineuronal Net Formation in the Neocortex of Developing Rodent Brains.

Previously, we reported that epidermal growth factor (EGF) suppresses GABAergic neuronal development in the rodent cortex. Parvalbumin-positive GABAergic neurons (PV neurons) have a unique extracellular structure, perineuronal nets (PNNs). PNNs are formed during the development of PV neurons and are mainly formed from chondroitin sulfate (CS) proteoglycans (CSPGs).

Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons.

Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents).

[A Trial of Practical Training on Online Medication Instructions in Clinical Preparatory Education: Development of Human Resources to Provide New Forms of Medical Care after the COVID-19 Pandemic].

The coronavirus disease 2019 (COVID-19) pandemic has considerably affected several social services. The Ministry of Health, Labour, and Welfare has partially revised the Pharmaceuticals and Medical Devices Law and established legislations on permanent online medication instructions. Based on these social needs, the development of human resources to provide online medication instructions is vital.

Structural characterization of the optical isomers esomeprazole and omeprazole using the JADER and FAERS databases.

Background: It is unclear whether the s (-) form of esomeprazole (EPZ) has an improved safety profile when compared with its racemic form omeprazole (OPZ). We assessed the potential complications of these optical isomers when combined with cilostazol, clopidogrel, and prasugrel, which are frequently used concomitant medications.

Methods: Using two adverse event spontaneous reporting databases, Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS), adverse event names for hemorrhage, venous/arterial embolization, and thrombus were obtained from the Medical Dictionary for Regulatory Activities.

Structural and antigenic characterization of a novel genotype of Mfa1 fimbriae in .

Background: Mfa1 fimbriae of the periodontal pathogen Porphyromonas gingivalis are responsible for biofilm formation and comprise five proteins: Mfa1-5. Two major genotypes, mfa1 and mfa1, encode major fimbrillin. The mfa1 genotype is further divided into the mfa1 and mfa1 subtypes.

Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects.

Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of the alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and, among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev) and pirfenidone (Pirespa) are the first-line drugs.

Cerebrocortical activation following unilateral labyrinthectomy in mice characterized by whole-brain clearing: implications for sensory reweighting.

Posture and gait are maintained by sensory inputs from the vestibular, visual, and somatosensory systems and motor outputs. Upon vestibular damage, the visual and/or somatosensory systems functionally substitute by cortical mechanisms called "sensory reweighting". We investigated the cerebrocortical mechanisms underlying sensory reweighting after unilateral labyrinthectomy (UL) in mice.

Investigation of drugs for the prevention of doxorubicin-induced cardiac events using big data analysis.

Aim: Doxorubicin, an anthracycline anti-tumour agent, is an essential chemotherapeutic drug; however, the adverse events associated with doxorubicin usage, including cardiotoxicity, prevent patients from continuing treatment. Here, we used databases to explore existing approved drugs with potential preventative effects against doxorubicin-induced cardiac events and examined their efficacy and mechanisms.

Methods: The Gene Expression Omnibus (GEO), Library of Integrated Network-based Cellular Signatures (LINCS), and Food and Drug Administration Adverse Events Reporting System (FAERS) databases were used to extract candidate prophylactic drugs.

Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model.

The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by exposing perinatal rats to EGF and reported that the auditory pathophysiological traits of this model such as prepulse inhibition, auditory steady-state response, and mismatch negativity are relevant to those of schizophrenia. We assessed the activation status of the auditory cortex in this model, as well as that in patients with schizophrenia, by monitoring the three neural activity-induced proteins: EGR1 (zif268), c-fos, and Arc.

USP10 Inhibits Aberrant Cytoplasmic Aggregation of TDP-43 by Promoting Stress Granule Clearance.

TAR DNA-binding protein 43 (TDP-43) is a causative factor of amyotrophic lateral sclerosis (ALS). Cytoplasmic TDP-43 aggregates in neurons are a hallmark pathology of ALS. Under various stress conditions, TDP-43 localizes sequentially to two cytoplasmic protein aggregates, namely, stress granules (SGs) first and then aggresomes.

EGF Downregulates Presynaptic Maturation and Suppresses Synapse Formation In Vitro and In Vivo.

Neuronal differentiation, maturation, and synapse formation are regulated by various growth factors. Here we show that epidermal growth factor (EGF) negatively regulates presynaptic maturation and synapse formation. In cortical neurons, EGF maintained axon elongation and reduced the sizes of growth cones in culture.

Rat call-evoked electrocorticographic responses and intercortical phase synchrony impaired in a cytokine-induced animal model for schizophrenia.

Patients with schizophrenia exhibit impaired performance in tone-matching or voice discrimination tests. However, there is no animal model recapitulating these pathophysiological traits. Here, we tested the representation of auditory recognition deficits in an animal model of schizophrenia.

The dopamine D2 agonist quinpirole impairs frontal mismatch responses to sound frequency deviations in freely moving rats.

Aim: A reduced mismatch negativity (MMN) response is a promising electrophysiological endophenotype of schizophrenia that reflects neurocognitive impairment. Dopamine dysfunction is associated with symptoms of schizophrenia. However, whether the dopamine system is involved in MMN impairment remains controversial.

Evaluation of Potential Complications of Interstitial Lung Disease Associated With Antiandrogens Using Data From Databases Reporting Spontaneous Adverse Effects.

From 2002 to 2018, the number of patients with prostate cancer significantly increased from 679,023 to 1276,106 worldwide. Total prostatectomy (including robot-assisted prostatectomy), radiation therapy, and pharmacological treatment are commonly used to treat prostate cancer. The Chief of the Pharmaceutical Safety Division, that is, the Federation of Pharmaceutical Manufacturers' Associations of Japan (FPMAJ), recently called for the revision of package inserts for ethical drugs.