This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.
  Although pathological studies usually indicate pure dopaminergic neuronal degeneration in patients with parkin (PRKN) mutations, there is no evidence to date regarding white matter (WM) pathology.  https://www.selleckchem.com/products/OSI-930.html  A previous diffusion MRI study has revealed WM microstructural alterations caused by systemic oxidative stress in idiopathic Parkinson's disease (PD), and we found that PRKN patients have systemic oxidative stress in serum biomarker studies. Thus, we hypothesized that PRKN mutations might lead to WM abnormalities.
 
  To investigate whether there are WM microstructural abnormalities in early-onset PD patients with PRKN mutations using diffusion tensor imaging (DTI).
 
  Nine PRKN patients and 19 age- and sex-matched healthy controls were recruited. DTI measures were acquired on a 3T MR scanner using a b value of 1,000 s/mm2 along 32 isotropic diffusion gradients. The DTI measures were compared between groups using tract-based spatial statistics (TBSS) analysis. Correlation analysis was also performed between the DTI parameters and several serum oxidative stress markers obtained in a previously conducted metabolomic analysis.
 
  Although the WM volumes were not significantly different, the TBSS analysis revealed a corresponding decrease in fractional anisotropy and an increase in mean diffusivity and radial diffusivity in WM areas, such as the anterior and superior corona radiata and uncinate fasciculus, in PRKN patients compared with controls. Furthermore, 9-hydroxystearate, an oxidative stress marker, and disease duration were positively correlated with several parameters in PRKN patients.
 
  This pilot study suggests that WM microstructural impairments occur in PRKN patients and are associated with disease duration and oxidative stress.
 This pilot study suggests that WM microstructural impairments occur in PRKN patients and are associated with disease duration and oxidative stress.Sleep disturbances are among the common nonmotor symptoms in patients with Parkinson's disease (PD). Sleep can be disrupted by nocturnal motor and nonmotor symptoms and other comorbid sleep disorders. Rapid eye movement sleep behavior disorder (RBD) causes sleep-related injury, has important clinical implications as a harbinger of PD and predicts a progressive clinical phenotype. Restless legs syndrome (RLS) and its related symptoms can impair sleep initiation. Excessive daytime sleepiness (EDS) is a refractory problem affecting patients' daytime activities. In particular, during the COVID-19 era, special attention should be paid to monitoring sleep problems, as infection-prevention procedures for COVID-19 can affect patients' motor symptoms, psychiatric symptoms and sleep. Therefore, screening for and managing sleep problems is important in clinical practice, and the maintenance of good sleep conditions may improve the quality of life of PD patients. This narrative review focused on the literature published in the past 10 years, providing a current update of various sleep disturbances in PD patients and their management, including RBD, RLS, EDS, sleep apnea and circadian abnormalities.Communication and swallowing disorders are highly prevalent in people with Parkinson's disease (PD). The negative impact of these disorders on the quality of life of the person with PD and their families cannot be underestimated. Despite a demand for speech-language pathology services to support people with PD, many barriers to services exist. Telerehabilitation provides an alternate and complementary approach to in-person therapy that is patient-centered, enables timely assessment and intervention, and facilitates continuity of care throughout the course of the disease. This review explores the telerehabilitation applications designed for the management of the communication and swallowing disorders in PD, addresses the benefits and challenges of telerehabilitation, identifies future research directions, and highlights the potential of new technologies to enhance the management of communication and swallowing disorders and quality of life for people with PD.
  Verticality perception is frequently altered in Parkinson's disease (PD) with Pisa syndrome (PS). Is it the cause or the consequence of the PS?
 
  We tested the hypothesis that both scenarios coexist.
 
  We performed a double-blind within-person randomized trial (NCT02704910) in 18 individuals (median age 63.5 years) with PD evolving for a median of 17.5 years and PS for 2.5 years and treated with bilateral stimulation of the subthalamus nuclei (STN-DBS) for 6.5 years. We analyzed whether head and trunk orientations were congruent with the visual (VV) and postural (PV) vertical, and whether switching on one or both sides of the STN-DBS could modulate trunk orientation via verticality representation.
 
  The tilted verticality perception could explain the PS in 6/18 (33%) patients, overall in three right-handers (17%) who showed net and congruent leftward trunk and PV tilts. Two of the 18 (11%) had an outstanding clinical picture associating leftward predominant parkinsonian symptoms, whole-body tilt (head -11°, trunk -8°) and transmodal tilt in verticality perception (PV -10°, VV -8.9°). Trunk orientation or VV were not modulated by STN-DBS, whereas PV tilts were attenuated by unilateral or bilateral stimulations if it was applied on the opposite STN.
 
  In most cases of PS, verticality perception is altered by the body deformity. In some cases, PS seems secondary to a biased internal model of verticality, and DBS on the side of the most denervated STN attenuated PV tilts with a quasi-immediate effect. This is an interesting track for further clinical studies.
 In most cases of PS, verticality perception is altered by the body deformity. In some cases, PS seems secondary to a biased internal model of verticality, and DBS on the side of the most denervated STN attenuated PV tilts with a quasi-immediate effect. This is an interesting track for further clinical studies.