An exploratory study of factors associated with long-term, high-dose opioid prescription in cancer patients in Japan based on a medical claims database.

Purpose: As the cancer survivors increase, patients using long-term and high-dose opioids are also increasing. Therefore, the promotion of appropriate use is important. This study investigated the actual status of opioid prescriptions in Japan and identified factors associated with long-term, high-dose prescription.

The Burden of Undiagnosed Adults With Attention-Deficit/Hyperactivity Disorder Symptoms in Japan: A Cross-Sectional Study.

Background Symptoms experienced by adult patients with attention-deficit/hyperactivity disorder (ADHD) frequently result in functional impairment across academic/occupational functioning, daily life, and social functioning. A substantial proportion of undiagnosed and untreated ADHD has been suggested in Japan. This study aims to better understand the potential undiagnosed ADHD population in Japan by quantifying the burden associated with ADHD symptoms through a comparison of the prevalence of comorbidities, health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and healthcare resource utilization (HRU) between undiagnosed potential ADHD respondents who were screened positive and negative using Adult ADHD Self-Report Scale (ASRS)-v1.

Change in Antidepressant Use After Initiation of ADHD Medication in Japanese Adults with Comorbid Depression: A Real-World Database Analysis.

Purpose: To better understand the treatment of comorbid depression in adults with attention-deficit/hyperactivity disorder (ADHD) by investigating the prescription patterns of antidepressants, anxiolytics, and hypnotics after commencing ADHD medication.

Patients And Methods: In this retrospective observational study in Japan, the data of patients initiating ADHD medication while already receiving antidepressants (ADHD group) and of patients prescribed antidepressants but not diagnosed with ADHD (control group) were extracted from an electronic medical record database. Additionally, one-to-one matching for patients in both groups was performed using sex, age, baseline dosage of antidepressants, and any comorbid psychiatric disorders as covariates.

Efficacy and safety of guanfacine extended-release in Japanese adults with attention-deficit/hyperactivity disorder: Exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study.

Aim: Previously, we reported on the efficacy and safety of guanfacine extended-release (GXR) in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) from a phase 3, double-blind, placebo-controlled, randomized trial. In this exploratory post hoc analysis, we assessed the efficacy and/or safety of GXR in the following subgroups: ADHD-combined (ADHD-C) and ADHD-predominantly inattentive (ADHD-I) subtypes, age (≥31, <31 years), sex (male, female), and body weight (≥50, <50 kg).

Methods: The primary efficacy endpoint was change from baseline in the Japanese version of the investigator-rated ADHD-Rating Scale-IV (ADHD-RS-IV) with adult prompts (total scores) at week 10.

[Pharmacological properties and clinical effects of the ADHD drug, Lisdexamfetamine (Vyvanse capsules 20 mg and 30 mg)].

Lisdexamfetamine dimesylate (hereinafter referred to as "lisdexamfetamine"; brand name, Vyvanse), was developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). This drug, which is classified as a central nervous system (CNS) stimulant for once-daily oral administration, received marketing approval in March 2019 and was launched in December 2019 in Japan. Lisdexamfetamine is a prodrug that is hydrolyzed to its active form d-amphetamine in the blood following oral administration.

An Oncogenic Alteration Creates a Microenvironment that Promotes Tumor Progression by Conferring a Metabolic Advantage to Regulatory T Cells.

Only a small percentage of patients afflicted with gastric cancer (GC) respond to immune checkpoint blockade (ICB). To study the mechanisms underlying this resistance, we examined the immune landscape of GC. A subset of these tumors was characterized by high frequencies of regulatory T (Treg) cells and low numbers of effector T cells.

Selective Cytotoxicity of Dihydroorotate Dehydrogenase Inhibitors to Human Cancer Cells Under Hypoxia and Nutrient-Deprived Conditions.

Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme of pyrimidine biosynthesis pathway. It is located on the mitochondrial inner membrane and contributes to the respiratory chain by shuttling electrons to the ubiquinone pool. We have discovered ascofuranone (), a natural compound produced by , and its derivatives are a potent class of HsDHODH inhibitors.

[Immunosuppressive Environment in Tumors].

Tumor cells establish a unique circumstance called tumor microenvironment(TME)suitable for tumor development and progression. One ofthe most important advantages ofTME for tumor cells is immunosuppressive environment such as higher presence ofregulatory T(Treg)cells, which play a central role for establishment and maintenance of immunological selftolerance and homeostasis. CTLA-4 expressed by Treg cells prevents the maturation ofAPCs resulting in suppression ofT -cell activation.

mutations abrogate iron-sulfur cluster assembly leading to cavitating leukoencephalopathy.

Objective: To determine the molecular factors contributing to progressive cavitating leukoencephalopathy (PCL) to help resolve the underlying genotype-phenotype associations in the mitochondrial iron-sulfur cluster (ISC) assembly system.

Methods: The subjects were 3 patients from 2 families who showed no inconsistencies in either clinical or brain MRI findings as PCL. We used exome sequencing, immunoblotting, and enzyme activity assays to establish a molecular diagnosis and determine the roles of ISC-associated factors in PCL.

ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.

The human ECHS1 gene encodes the short-chain enoyl coenzyme A hydratase, the enzyme that catalyzes the second step of β-oxidation of fatty acids in the mitochondrial matrix. We report on a boy with ECHS1 deficiency who was diagnosed with Leigh syndrome at 21 months of age. The patient presented with hypotonia, metabolic acidosis, and developmental delay.

Homoplasmy of a mitochondrial 3697G>A mutation causes Leigh syndrome.

Herein we report on three siblings with Leigh syndrome (LS) harboring a homoplasmic m.3697G>A mutation (G131S) in the MT-ND1 gene. The siblings' phenotypically normal mother had the same, albeit heteroplasmic, mutation.

Inhibition of cancer cell growth by GRP78 siRNA lipoplex via activation of unfolded protein response.

Proteasome inhibitors are a novel class of molecular-targeted anti-cancer drugs that suppress the degradation of malfolded proteins, trigger endoplasmic reticulum (ER) stress, and activate apoptosis signals. Glucose-regulated protein 78 (GRP78), a major ER chaperone, is one of the most important molecules for transduction of unfolded protein response (UPR) signals. In accordance with past findings that expression of GRP78 is elevated in cancer cells and helps to resist stress-induced apoptosis, GRP78 knockdown could be effective in anticancer therapy.

Type II Fp of human mitochondrial respiratory complex II and its role in adaptation to hypoxia and nutrition-deprived conditions.

The flavoprotein (Fp) subunit of human mitochondrial succinate-ubiquinone reductase (SQR, complex II) has isoforms (type I, type II). Type II Fp is predominantly expressed in some cancer and fetal tissues and those tissues are often exposed to ischemia. The present study shows that complex II with type II Fp has lower optimal pH than complex II with type I Fp, and type II Fp mRNA expression was induced by ischemia.

Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation.

Mitochondrial complex III (CIII) deficiency is a relatively rare disease with high clinical and genetic heterogeneity. CIII comprises 11 subunits encoded by one mitochondrial and 10 nuclear genes. Abnormalities of the nuclear genes such as BCS1L and TTC19 encoding mitochondrial assembly factors are well known, but an explanation of the majority of CIII deficiency remains elusive.

A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55).

Background: Autosomal recessive hereditary spastic paraplegias (AR-HSP) constitute a heterogeneous group of neurodegenerative diseases involving pyramidal tracts dysfunction. The genes responsible for many types of AR-HSPs remain unknown. We attempted to identify the gene responsible for AR-HSP with optic atrophy and neuropathy.

Mitochondrial fumarate reductase as a target of chemotherapy: from parasites to cancer cells.

Recent research on respiratory chain of the parasitic helminth, Ascaris suum has shown that the mitochondrial NADH-fumarate reductase system (fumarate respiration), which is composed of complex I (NADH-rhodoquinone reductase), rhodoquinone and complex II (rhodoquinol-fumarate reductase) plays an important role in the anaerobic energy metabolism of adult parasites inhabiting hosts. The enzymes in these parasite-specific pathways are potential target for chemotherapy. We isolated a novel compound, nafuredin, from Aspergillus niger, which inhibits NADH-fumarate reductase in helminth mitochondria at nM order.