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Cerebral beta-amyloid accumulation is the key initiator of Alzheimer's disease (AD) pathology. Most familial early-onset AD mutations in the APP, PSEN1/2 genes increase the ratio of Abeta42:Abeta40, which drives beta-amyloid accumulation in the brain. In 2001, the late Steve Wagner, Maria Kounnas, and I directed an agnostic high-throughput screen for compounds that would reverse the Abeta42:Abeta40, ratio, and discovered the first non-NSAID (second generation) gamma secretase modulators (GSM) at TorreyPines Therapeutics.
View Article and Find Full Text PDFA Patient With NEMO Deficiency, Disseminated M. szulgai, and Post-HSCT Inflammatory Disease.
Pediatr Transplant
February 2025
Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
Background: Disseminated mycobacterium poses a significant risk for patients with NEMO deficiency. Hematopoietic stem cell transplant (HSCT) corrects the NEMO defect in hematopoietic cells thus treating the immunodeficiency.
Methods: We present a patient with NEMO deficiency who successfully underwent HSCT despite a disseminated Mycobacterium szulgai infection.
Comparison of cellular-based therapies following a long-segmental peripheral nerve defect in a rat model.
PLoS One
January 2025
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
Peripheral nerve injury (PNI) is characterized by a loss of cellular and axonal integrity, often leading to limited functional recovery and pain. Many PNIs are not amenable to repair with traditional techniques; however, cell therapies, particularly Schwann cells (SCs), offer the promise of neural tissue replacement and functional improvement. Exosomes, which carry cellular signaling molecules, can be secreted by SCs and have shown promise in PNI.
View Article and Find Full Text PDFSuccessful Treatment of Mycoplasma genitalium Urethritis With High-Dose Tinidazole.
Sex Transm Dis
February 2025
From the Division of Infectious Diseases, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH.
A 30-year-old male patient with symptomatic Mycoplasma genitalium urethritis failed treatment with oral azithromycin, 2-stage doxycycline-moxifloxacin, and minocycline. Molecular testing confirmed the presence of macrolide resistance mutations. Treatment with oral tinidazole 2 g daily for 7 days resulted in clinical and microbiologic cure.
View Article and Find Full Text PDFBreaking the Dogma of Intravenous Treatment for Infective Endocarditis: A Systematic Review and Meta-Analysis.
J Clin Med
December 2024
Division of Infectious Diseases, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland.
The treatment of infective endocarditis (IE) is based on long intravenous administration of antibiotics. This is still a hard-to-die dogma. Throughout the years, different researchers have attempted to demonstrate the safety and efficacy of an oral switch of the antibiotic regimen, with only scarce success.
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