To evaluate the feasibility, safety, and preliminary clinical outcomes of paclitaxel-coated balloon (Optilume®) dilation in women with urethral stricture disease, a condition with limited minimally invasive treatment options. Multicenter, retrospective case series, including nine consecutive female patients treated with Optilume® between May 2023 and November 2025. Clinical characteristics, uroflowmetry, post-void residual (PVR), and patient-reported outcomes were collected. A uroflowmetric response was defined as a ≥ 50
Non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have significantly advanced neuroscience research and clinical practice. However, these approaches can involve costly equipment (particularly TMS) and varying degrees of technical complexity, especially for protocols requiring precise targeting. Transcranial static magnetic field stimulation (tSMS) has recently emerged as a novel, accessible alternative. This technique uses a simple, constant magnetic field—typically generated by a neodymium magnet—to modulate cortical excitability without electrical input, or perceptible sensation. While static magnets have long been associated with pseudoscientific practices, rigorous studies since 2011 have established the physiological effects of tSMS, demonstrating its capacity to transiently reduce cortical excitability in humans. The simplicity, portability, and excellent safety profile of tSMS make it especially well-suited for home-based applications and long-duration protocols. Although its modulatory effects tend to be modest and transient, recent research indicates that longer stimulation durations can extend the effects, and its predominantly inhibitory action may be advantageous for specific clinical targets. While the static nature of the magnetic field limits depth penetration, ongoing innovations may help address this constraint. Overall, tSMS represents a low-cost, well-tolerated, and practical addition to the NIBS toolkit, with growing potential to support individualized neuromodulation strategies in both research and therapeutic settings.
Parkinson's disease (PD) has been historically defined as a disease of striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra pars compacta, related to the presence of Lewy bodies and Lewy neurites. Since the discovery of pathogenic variants in the gene encoding α-synuclein, as well as the finding that α-synuclein is a major constituent of Lewy pathology, PD is considered as a prototypical synucleinopathy. However, neuropathological studies consistently show that most people with PD display copathologies, many of which are linked to specific clinical features and outcomes. In this review, we summarize the spectrum and frequency of these co- and multi-pathologies in idiopathic and genetic PD and their impact on disease initiation and progression. Additionally, we also discuss how this multi-pathological landscape may impact biomarker research and the implementation of emerging disease-modifying therapies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Cerebellar degenerations are a heterogeneous group of disorders that pose significant clinical challenges, and no effective therapies are currently available to halt or slow their progression. Gene therapy offers important therapeutic potential for brain disorders; however, its clinical translation is hindered by critical obstacles, particularly the blood-brain barrier, which limits systemic delivery of therapeutic genes to the brain, an issue especially pronounced in primates. Here, we evaluated the use of low-intensity focused ultrasound combined with intravenously administered microbubbles to transiently open the blood-brain barrier in the cerebellum of macaque monkeys, thus enabling targeted delivery of adeno-associated virus-based gene therapy vectors. Two vector types (scAAV9-CBA-GFP and ssAAV9-CMV-mCherry) were administered systemically, and transgene expression was analyzed to assess delivery efficiency and cell-type distribution. We achieved successful, non-invasive delivery of both vector types to the cerebellum with high spatial precision. Administration of ssAAV9-CMV-mCherry vector resulted in robust transduction of virtually all neurons within the targeted deep cerebellar nuclei. These findings provide a promising and translationally relevant strategy for developing gene-delivery approaches for cerebellar and other neurodegenerative disorders and represent a step forward in advancing the use of focused ultrasound to achieve efficient and less invasive gene delivery to the brain.
Designer receptors exclusively activated by designer drugs (DREADDs) enable reversible control of specific neural circuits, but the pharmacological neutrality of their ligands is increasingly questioned. Here, we introduce an anesthesia emergence paradigm to systematically assess the off-target effects of DREADD ligands in DREADD-naive mice. We show that intraperitoneal administration of clozapine N-oxide (CNO), compound 21 (C21), or deschloroclozapine (DCZ) delays motor recovery from isoflurane anesthesia. CNO produced the largest delay, likely due to its back-conversion to clozapine. DCZ showed the smallest effect magnitude, although its difference from C21 remained inconclusive. We then show that subcutaneous administration, which should reduce clozapine back-conversion, reduces the CNO-induced recovery delay to levels comparable to those of C21. Finally, we provide a freely available, deep-learning-based automated behavioral pipeline that integrates the anesthesia emergence paradigm with a reproducible analysis tool for future studies. Together, these results underscore the importance of accounting for ligand off-target effects through careful dose selection and DREADD-free, ligand-treated controls in chemogenetic experiments.
