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Summary: Multiple myeloma (MM) cells from 1 out of 20 patient expressed high basal levels of membrane B‐cell maturation antigen (BCMA, TNFRSF17, CD269), which was not upregulated by gamma‐secretase inhibitor, suggesting a defective BCMA shedding by gamma‐secretase. Genetic analyses of the patient's bone marrow DNA showed no mutations within the BCMA coding region, but rather partial deletion of PSEN1 and amplification of PSEN2, which encode alternative catalytic units of gamma‐secretase. Altogether the data suggest that pt#12 MM cells express high and dysregulated BCMA with no shedding, due to genetic alterations of one or more gamma‐secretase subunits. [ABSTRACT FROM AUTHOR] more...

Background and Objective: Early‐onset Parkinson's disease (EOPD) commonly recognizes a genetic basis; thus, patients with EOPD are often addressed to diagnostic testing based on next‐generation sequencing (NGS) of PD‐associated multigene panels. However, NGS interpretation can be challenging in a diagnostic setting, and few studies have addressed this issue so far. Methods: We retrospectively collected data from 648 patients with PD with age at onset younger than 55 years who underwent NGS of a minimal shared panel of 15 PD‐related genes, as well as PD‐multiplex ligation‐dependent probe amplification in eight Italian diagnostic laboratories. Data included a minimal clinical dataset, the complete list of variants included in the diagnostic report, and final interpretation (positive/negative/inconclusive). Patients were further stratified based on age at onset ≤40 years (very EOPD, n = 157). All variants were reclassified according to the latest American College of Medical Genetics and Genomics criteria. For classification purposes, PD‐associated GBA1 variants were considered diagnostic. Results: In 186 of 648 (29%) patients, the diagnostic report listed at least one variant, and the outcome was considered diagnostic (positive) in 105 (16%). After reanalysis, diagnosis changed in 18 of 186 (10%) patients, with 5 shifting from inconclusive to positive and 13 former positive being reclassified as inconclusive. A definite diagnosis was eventually reached in 97 (15%) patients, of whom the majority carried GBA1 variants or, less frequently, biallelic PRKN variants. In 89 (14%) cases, the genetic report was inconclusive. Conclusions: This study attempts to harmonize reporting of PD genetic testing across several diagnostic labs and highlights current difficulties in interpreting genetic variants emerging from NGS‐multigene panels, with relevant implications for counseling. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR] more...

The article focuses on the potential use of Aristolochia Olivieri, a plant extract, as a bactericidal agent against Helicobacter pylori (H. pylori) and as an inhibitor of cell viability in gastric cancer cells, suggesting its possible use as a chemo-adjuvant in gastric cancer treatment. more...