Influence of ABCB1 polymorphisms on aripiprazole and dehydroaripiprazole plasma concentrations.

Aripiprazole (ARI) is an atypical antipsychotic which is a substrate of P-glycoprotein (P-gp), a transmembrane glycoprotein that plays a crucial role in eliminating potentially harmful compounds from the organism. ARI once-monthly (AOM) is a long-acting injectable form which improves treatment compliance. Genetic polymorphisms in ABCB1 may lead to changes in P-gp function, leading to individual differences in drug disposition.

A founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle cramps.

Background And Purpose: Pathogenic variants in the RYR1 gene have been associated with a variety of conditions, ranging from congenital myopathy to adult manifestations. Our aim was to characterize the p.Leu2286Val variant in 17 Basque patients, to accurately determine its correlation with clinical features and to explore the possible founder effect of the variant.

Salivary oxytocin and amygdalar alterations in functional neurological disorders.

Individuals diagnosed with functional neurological disorder experience abnormal movement, gait, sensory processing or functional seizures, for which research into the pathophysiology identified psychosocial contributing factors as well as promising biomarkers. Recent pilot studies suggested that (epi-)genetic variants may act as vulnerability factors, for example, on the oxytocin pathway. This study set out to explore endogenous oxytocin hormone levels in saliva in a cohort of 59 functional neurological disorder patients and 65 healthy controls comparable in sex and age.

The Somogyi hypothesis: a parallelism with Michael Somogyi's life.

Michael Somogyi (Somogyi Mihály, 1883-1971) was a Hungarian biochemist who developed his scientific career in Europe and, primarily, the United States. He gave the name to the eponymous Somogyi effect or Somogyi hypothesis (in short, rebound hyperglycemia after insulin-induced hypoglycemia, particularly nocturnal), which was an axiom in the treatment of diabetes for decades. Although it is currently debated whether the Somogyi hypothesis is a real or relevant phenomenon in patients with diabetes, Somogyi's other significant career achievements are often overlooked.

Integration of multi-omics layers empowers precision diagnosis through unveiling pathogenic mechanisms on maple syrup urine disease.

Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder characterized by deficient activity of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, required to metabolize the amino acids leucine, isoleucine, and valine. Despite its profound metabolic implications, the molecular alterations underlying this metabolic impairment had not yet been completely elucidated. We performed a comprehensive multi-omics integration analysis, including genomic, epigenomic, and transcriptomic data from fibroblasts derived from a cohort of MSUD patients and unaffected controls to genetically characterize an MSUD case and to unravel the MSUD pathophysiology.

Exploring differential miRNA expression profiles in muscular and visceral adipose tissue of patients with severe obesity.

Background: This study aims to investigate the differential miRNA expression profile between the visceral white adipose tissue and the skeletal muscle of people with obesity undergoing bariatric surgery.

Methods: Skeletal muscle and visceral adipose tissue samples of 10 controls and 38 people with obesity (50% also with type 2 diabetes) undergoing bariatric surgery were collected. miRNA expression profiles were analyzed using Next-Generation Sequencing and subsequently validated using RT-PCR.

Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.

Background: Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients.

Methods: Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study.

Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.

The In-between: Time to Talk About Bronchiectasis in Adolescents and Their Transition to Adult Care.

Paediatric and adult bronchiectasis patients have been addressed in the literature as two different populations due to several differences, but there is insufficient evidence to understand how and when disease characteristics really change along patients' lifespan. This lack of knowledge is evident in all aspects of the transition: insufficient data is available about radiology, lung function, microbiology and treatment, and only limited information is currently available about changes in clinical presentation and psychosocial aspects. For instance, symptoms seem to improve during the third and fourth decades of life, a period sometimes referred to as the "honeymoon phase".

Affordable Pricing of CRISPR Treatments is a Pressing Ethical Imperative.

Casgevy, the world's first approved CRISPR-based cell therapy, has been priced at $2.2 million per patient. Although this hefty price tag was widely anticipated, the extremely high cost of this and other cell and gene therapies poses a major ethical issue in terms of equitable access and global health.

Role of CYP2D6 and CYP3A4 polymorphisms on aripiprazole and dehydroaripiprazole concentrations in patients undergoing long-acting treatment.

Aripiprazole once-monthly (AOM) exhibits an important interindividual pharmacokinetic variability with significant implications for its clinical use. CYP2D6 and CYP3A4 highly contributes to this variability, as they metabolize aripiprazole (ARI) into its active metabolite, dehydroaripiprazole (DHA) and the latter into inactive metabolites. This study aims to evaluate the effect of CYP2D6 and CYP3A4 polymorphisms in combination and the presence of concomitant inducers and inhibitors of this cytochromes on ARI and DHA plasma concentrations in a real clinical setting.

The impact of genetic variations in the serotonergic system on symptom severity and clinical outcome in functional neurological disorders.

Objective: We studied gene-environment, as well as gene-gene interaction to elucidate their effects on symptom severity and predict clinical outcomes in functional neurological disorders (FND).

Methods: Eighty-five patients with mixed FND were genotyped for ten single-nucleotide polymorphisms (SNP) from seven different stress-related genes. We tested cross-sectionally the association between genotype and the symptomatology of FND (symptom severity assessed with the examiner-based clinical global impression score [CGI] and age of onset).

Insights into neurosonographic indicators for prenatal diagnosis of fetal neurological anomalies and cortical development: A systematic review of the literature.

Background: Congenital defects of the central nervous system are the second cause of disability in childhood, representing up to 20 % of structural malformations diagnosed prenatally. The accurate prenatal diagnosis of fetal neurological anomalies and the assessment of cortical development are critical for early intervention and improved long-term outcomes. Neurosonography plays a vital role in this process, providing detailed insights into the structural and functional development of the fetal brain.

Hamstrings on focus: Are 72 hours sufficient for recovery after a football (soccer) match? A multidisciplinary approach based on hamstring injury risk factors and histology.

This study aimed to assess acute and residual changes in sprint-related hamstring injury (HSI) risk factors after a football (soccer) match, focusing on recovery within the commonly observed 72-h timeframe between elite football matches. We used a multifactorial approach within a football context, incorporating optical and ultrastructural microscopic analysis of BFlh (biceps femoris long head) muscle fibres, along with an examination of BFlh fibre composition. Changes in sprint performance-related factors and HSI modifiable risk factors were examined until 3 days after the match (MD ) in 20 football players.