Precision pharmacotherapy of atomoxetine in children with ADHD: how to ensure the right dose for the right person?

Non-stimulant atomoxetine is recognized in various current clinical guidelines as an important alternative to stimulants for the pharmacological treatment of attention deficit/hyperactivity disorder (ADHD) in children. While its efficacy and tolerability for core symptoms are established, there is considerable inter-individual variability in response and exposure, highlighting the need for personalized dosing. In this review, we evaluated existing studies and summarized comprehensive evidence supporting the clinical implementation of therapeutic drug monitoring (TDM) and personalized dosing of atomoxetine, organized around a series of logically structured questions.

GDH1 exacerbates renal fibrosis by inhibiting the transcriptional activity of peroxisome proliferator-activated receptor gamma.

Renal fibrosis is the common outcome of practically all progressive forms of chronic kidney disease (CKD), a significant societal health concern. Glutamate dehydrogenase (GDH) 1 is one of key enzymes in glutamine metabolism to catalyze the reversible conversion of glutamate to α-ketoglutarate and ammonia. However, its function in renal fibrosis has not yet been proven.

PLCL/SF/NGF nerve conduit loaded with RGD-TA-PPY hydrogel promotes regeneration of sciatic nerve defects in rats through PI3K/AKT signalling pathways.

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus.

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD.

Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together.

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children's Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023.

Individual, family and social-related factors of eating behavior among Chinese children with overweight or obesity from the perspective of family system.

Purpose: The purpose of the present study is to examine the factors contributing to the development of eating behavior in overweight and obese children from the perspective of the family system.

Methods: A cross-sectional survey was conducted by using convenience sampling method to select 388 participants in two primary schools in Jiangsu, China. Individual, family and social-related factors were collected.

A retrospective study of consistency between immunohistochemistry and polymerase chain reaction of microsatellite instability in endometrial cancer.

Objectives: Identification of endometrial cancers (EC) with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) is essential for Lynch syndrome screening and treatment stratification. We aimed to assess the utility of immunohistochemistry (IHC) staining for MMR protein expression and polymerase chain reaction (PCR)-based MSI assays in EC and the correlation between MMR/MSI status and various clinicopathological parameters.

Methods: We reviewed the clinical and pathological information of 333 patients with EC.

The link between obesity and insulin resistance among children: Effects of key metabolites.

Background: Childhood obesity became a severe public health challenge, and insulin resistance (IR) was one of the common complications. Both obesity and IR were considered as the basis of metabolic disorders. However, it is unclear which common key metabolites are associated with childhood obesity and IR.

Role of cuproptosis in understanding diseases.

Cell death is involved in a wide range of physiological and pathological processes. Recently, the term "cuproptosis" was coined to describe a novel type of cell death. This type of cell death, characterized by copper accumulation and proteotoxic stress, is a copper-dependent manner of death.

Diagnosis and genetic analysis of a case with mandibuloacral dysplasia type B due to compound heterozygous mutations of the gene.

Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder, mainly caused by pathogenic variants of the and genes. In this study, we reported the first case of a patient with type B cranial and mandibular dysplasia in China. The patient presented with distinctive facial features, feeding difficulties, significant physical retardation, and overall developmental delay with abnormal tooth and bone development.

Reduction of NADPH oxidase 4 in adipocytes contributes to the anti-obesity effect of dihydroartemisinin.

Artemisinin derivatives have been found to have anti-obesity effects recently, but the mechanism is still controversial. Herein, long-term DHA treatment in obese mice significantly reduced the body weight and improved glucose metabolism. However, short-term DHA treatment did not affect glucose metabolism in obese mice, suggesting that the improved glucose metabolism in mice with DHA treatment could be secondary to body weight reduction.

Transvaginal ultrasound parameters to evaluate cervical favorability and predict the outcome of induction of labor.

Objective: To compare the values of transvaginal ultrasound (TVU) and Bishop score (BS) for predicting outcomes of induction of labor (IOL).

Methods: The BS and TVU were assessed before IOL. TVU parameters included cervical length (CL) and E-Cervix comprising the cervical hard ratio (HR) and the mean strain level of internal os (IOS).

Personalizing atomoxetine dosing in children with ADHD: what can we learn from current supporting evidence.

Purpose: There is marked heterogeneity in treatment response of atomoxetine in patients with attention deficit/hyperactivity disorder (ADHD), especially for the pediatric population. This review aims to evaluate current evidence to characterize the dose-exposure relationship, establish clinically relevant metrics for systemic exposure to atomoxetine, define a therapeutic exposure range, and to provide a dose-adaptation strategy before implementing personalized dosing for atomoxetine in children with ADHD.

Methods: A comprehensive search was performed across electronic databases (PubMed and Embase) covering the period of January 1, 1985 to July 10, 2022, to summarize recent advances in the pharmacokinetics, pharmacogenomics/pharmacogenetics (PGx), therapeutic drug monitoring (TDM), physiologically based pharmacokinetics (PBPK), and population pharmacokinetics (PPK) of atomoxetine in children with ADHD.

The lymphatic system: a therapeutic target for central nervous system disorders.

The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis, metabolite clearance, and immune surveillance. The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology. They emerge as major pathways for fluid exchange.

The roles of mutated SPINK1 gene in prostate cancer cells.

SPINK1-positive prostate cancer (PCa) has been identified as an aggressive PCa subtype. However, there is a lack of definite studies to elucidate the underlying mechanism of the loss of SPINK1 expression in most PCa cells except 22Rv1 cells, which are derived from a human prostatic carcinoma xenograft, CWR22R. The aim of this study was to investigate the mechanisms of SPINK1 protein positive/negative expression and its biological roles in PCa cell lines.

The Spectrum of Gene Mutations in a Selected Chinese Cohort of Short Stature: Genotype-Phenotype Correlation.

Mutations in the gene have been reported to cause short stature. However, the prevalence estimates of pathogenic variants in individuals with short stature vary, and the correlation between genotype and clinical phenotype remain to be evaluated. To determine the prevalence of variants among Chinese people with short stature and analyze the relationship between genotype and main clinical manifestations of short stature and advanced bone age among patients with variants.

Publication Trends for Sarcopenia in the World: A 20-Year Bibliometric Analysis.

Background: Sarcopenia, an age-related degenerative disease, seriously affects the health and quality of life of the elder. The research of sarcopenia has changed dramatically around the world. This article aims to analyze global trends in this field over the past 20 years.

The Mechanism, Clinical Efficacy, Safety, and Dosage Regimen of Atomoxetine for ADHD Therapy in Children: A Narrative Review.

Atomoxetine, a selective norepinephrine (NE) reuptake inhibitor, was approved for attention deficit/hyperactivity disorder (ADHD) treatment in children, adolescents and adults. We searched the database PubMed/MEDLINE (2000 to October 1, 2021). Only publications in English were considered.

Antibodies against thyroid-stimulating hormone receptor cause maternal-neonatal transmission of Graves' Disease.

The present study aimed to investigate whether the thyroid-stimulating hormone receptor (TSHR) autoantibodies (Ab) from mothers with Graves' disease (GD) could cause neonatal thyroid disease and the underlying mechanisms of this. An adenovirus expressing the TSHR A-subunit and a control adenovirus expressing β-galactosidase was constructed by Beijing Sino Geno Max Co., Ltd.

[17 beta-hydroxysteroid dehydrogenase 3 deficiency due to novel compound heterozygous variants of HSD17B3 gene in a sib pair].

Objective: To explore the genetic basis for a sib pair featuring 17beta-hydroxysteroid dehydrogenase type 3 deficiency.

Methods: Genomic DNA was extracted from the proband, her sister, and their parents, and was subjected to sequencing analysis with a gene panel for sexual development. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.

Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity.

Background: With the increasing number of children with obesity worldwide, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease among children. It is necessary to recognize the risk factors of NAFLD for prevention in childhood since NAFLD is asymptomatic in the early stage.

Objectives: The objective of this study was to investigate possible risk factors of NAFLD in children with obesity, providing evidence for monitoring and prevention strategies at an early stage for obese children with NAFLD.

Celastrol inhibits intestinal lipid absorption by reprofiling the gut microbiota to attenuate high-fat diet-induced obesity.

Celastrol, a compound extracted from traditional Chinese medicine, has been reported as a potent anti-obesity agent with controversial mechanisms. Here both C57BL/6J and leptin-deficient () mice fed a high-fat diet (HFD) displayed body weight loss after celastrol therapy, opposing the previous viewpoint that celastrol improves obesity by sensitizing leptin signaling. More importantly, celastrol downregulated lipid transporters in the intestine, increased lipid excretion in feces, and reduced body weight gain in HFD mice.