Dentists' Perception of Mysmartalign Clear Aligner Treatment.

Aim and Objective: To assess the dentist perception of efficiency, treatment outcome, and stability of the tooth movement treated with mysmartalign clear aligner therapy (MSA CAT). Materials and Method: A cross-sectional web-based questionnaire survey was carried out to evaluate the dentist perception of MYSMARTALIGN (MSA). To determine the sample size, a pilot study has been carried out and the final sample arrived was 4990 subjects. The current study's inclusion criteria took into account those who had finished their BDS and MDS as well as dentists and orthodontists who had been using the MSA CAT system on their patients for the previous 7 years. Results: The result of the study showed that most research participants (3650) used MSA to treat mild to moderate malocclusion, and 3996 participants said that initial digital treatment plans have been authorised with no revisions. In view of efficiency, 3894 doctors were satisfied with the final outcome. Conclusions: Finally concluded that recent survey showed that dentists were very satisfied with the effectiveness and treatment results of the MSA clear aligner procedure.

γ-Butyrolactone derivatives of MSA-2 are STING prodrugs.

STING agonists are potent enhancers of a pro-inflammatory response and, thus, potentially useful therapeutics. Unfortunately, many agonists developed to date require complex drug delivery formulations and often have poor water solubility, limiting their use for systemic administration. Here, we report the discovery and chemical characterization of lactones of MSA-2 as new STING prodrugs with enhanced properties. We show that these prodrugs form efficient inclusion complexes with tumor myeloid cell targeting cyclodextrin nanoparticles and propose a new mechanism of formation and hydrolysis.

Formation of hydrogen bonding network of methane sulfonic acid at low degree of hydration (MSA)m·(H2O)n (m = 1-2 and n = 1-5).

This study employs ab initio calculations based on density functional theory (DFT) to investigate the structural properties, 1H-NMR spectra, and vibrational spectra of methane sulfonic acid (MSA) at low degree of hydration. The findings reveal that energetically stable structures are formed by small clusters consisting of one or two MSA molecules (m = 1 and 2) and one or two water molecules in (MSA)m·(H2O)n (m = 1-2 and n = 1-5).These stable structures arise from the formation of strong cyclic hydrogen bonds between the proton of the hydroxyl (OH) group in MSA and the water molecules. However, clusters containing three or more water molecules (n > 2) exhibit proton transfer from MSA to water, resulting in the formation of ion-pairs composed of CH3SO3- and H3O+species. The measured 1H-NMR spectra demonstrate the presence of hydrogen-bonded interactions between MSA and water, with a single MSA molecule interacting with water molecules. This interaction model accurately represents the hydrogen bonding network, as supported by the agreement between the experimental and calculated NMR chemical shift results.

A novel mouse model for investigating α-synuclein aggregates in oligodendrocytes: implications for the glial cytoplasmic inclusions in multiple system atrophy.

The aggregated alpha-synuclein (αsyn) in oligodendrocytes (OLGs) is one of the pathological hallmarks in multiple system atrophy (MSA). We have previously reported that αsyn accumulates not only in neurons but also in OLGs long after the administration of αsyn preformed fibrils (PFFs) in mice. However, detailed spatial and temporal analysis of oligodendroglial αsyn aggregates was technically difficult due to the background neuronal αsyn aggregates. The aim of this study is to create a novel mouse that easily enables sensitive and specific detection of αsyn aggregates in OLGs and the comparable analysis of the cellular tropism of αsyn aggregates in MSA brains. To this end, we generated transgenic (Tg) mice expressing human αsyn-green fluorescent protein (GFP) fusion proteins in OLGs under the control of the 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter (CNP-SNCAGFP Tg mice). Injection of αsyn PFFs in these mice induced distinct GFP-positive aggregates in the processes of OLGs as early as one month post-inoculation (mpi), and their number and size increased in a centripetal manner. Moreover, MSA-brain homogenates (BH) induced significantly more oligodendroglial αsyn aggregates than neuronal αsyn aggregates compared to DLB-BH in CNP-SNCAGFP Tg mice, suggestive of their potential tropism of αsyn seeds for OLGs. In conclusion, CNP-SNCAGFP Tg mice are useful for studying the development and tropism of αsyn aggregates in OLGs and could contribute to the development of therapeutics targeting αsyn aggregates in OLGs.

Selective and efficient immobilization of cadmium in soil by layered double hydroxides intercalated with the mercaptosuccinic acid.

Cadmium (Cd) contamination in cropland poses a significant threat to the quality of agricultural products, but even though in-situ remediation has been extensively applied, non-selective immobilization remains an issue. In order to develop a material that specifically immobilizes Cd in soil, a layered double hydroxide, intercalated with mercaptosuccinic acid (MSA-CFA), was synthesized through co-precipitation. In this case, the MSA-CFA's maximum adsorption capacity was increased from the 513.8 mg·g-1 for unintercalated hydrotalcite CFA to 692.6 mg·g-1. Besides, MSA-CFA efficiently removed 99.25 % of Cd from soil water-extract solution and immobilized up to 70.03 % of bio-available Cd. However, interestingly, its immobilization effects on beneficial metal elements Fe, Mn and Zn were milder, being equivalent to 2/7, 5/7 and 1/2 that of lime, respectively. Moreover, XRD and XPS techniques revealed isomorphous substitution with calcium and sulfhydryl complexation during the Cd adsorption by MSA-CFA. Compared with CFA, the increased adsorption capacity of MSA-CFA for Cd was due to intercalated MSA acting as a new adsorption site, while the enhanced selectivity was contributed by sulfhydryl's affinity for Cd. Altogether, MSA-CFA showed great promise as a competitive and highly efficient candidate amendment in Cd-contaminated soil remediation.

Pilot therapeutic education program in multiple system atrophy: Safety, quality of life and satisfaction from a national registry based longitudinal study.

BACKGROUND: Therapeutic education programs are effective in several chronic conditions. However, evidence is lacking in multiple system atrophy (MSA). We aimed to assess efficacy and safety of a comprehensive therapeutic education program in people with MSA (PwMSA) and their caregivers. METHODS: In this prospective longitudinal study we included 16 PwMSA and their main caregivers in 4 groups of 4 dyads each. The program consisted of eight 60-min interdisciplinary sessions: introduction, orthostatic hypotension, speech therapy, gait and respiratory physiotherapy, psychological support, urinary dysfunction, occupational therapy/social work. UMSARS, NMSS, PDQ39, EQ5 and Zarit scales were administered at baseline and 6 months later. After each session participants filled-out a modified EduPark satisfaction questionnaire and a Likert scale. Educational material was generated for each session after suggestions by participants. RESULTS: At baseline PwMSA and caregivers were comparable in age and sex, with significant correlation between UMSARS-IV (disability) and PDQ39 (quality of life). Adherence to sessions was of 94,92 %. Total modified EduPark scores and Likert scales did not differ in PwMSA vs. caregivers, mild-moderate vs. severe-advanced cases or between genders. The significant difference in satisfaction across sessions (p = 0.03) was driven by higher scores in speech, respiratory and occupational therapy sessions. Longitudinally there was no significant worsening in any scale, nor a significant increase post-vs. pre-program in the number of consultations. CONCLUSIONS: The healthcare education program in MSA was feasible, satisfactory, and safe for patients and caregivers. The educational material of the program is being forwarded to incident MSA cases attending our clinic.

Genome sequence analyses identify novel risk loci for multiple system atrophy.

Multiple system atrophy (MSA) is an adult-onset, sporadic synucleinopathy characterized by parkinsonism, cerebellar ataxia, and dysautonomia. The genetic architecture of MSA is poorly understood, and treatments are limited to supportive measures. Here, we performed a comprehensive analysis of whole genome sequence data from 888 European-ancestry MSA cases and 7,128 controls to systematically investigate the genetic underpinnings of this understudied neurodegenerative disease. We identified four significantly associated risk loci using a genome-wide association study approach. Transcriptome-wide association analyses prioritized USP38-DT, KCTD7, and lnc-KCTD7-2 as novel susceptibility genes for MSA within these loci, and single-nucleus RNA sequence analysis found that the associated variants acted as cis-expression quantitative trait loci for multiple genes across neuronal and glial cell types. In conclusion, this study highlights the role of genetic determinants in the pathogenesis of MSA, and the publicly available data from this study represent a valuable resource for investigating synucleinopathies.

A next-generation STING agonist MSA-2: From mechanism to application.

The stimulator of interferon genes (STING) connects the innate and adaptive immune system and plays a significant role in antitumor immunity. Over the past decades, endogenous and CDN-derived STING agonists have been a hot topic in the research of cancer immunotherapies. However, these STING agonists are either in infancy with limited biological effects or have failed in clinical trials. In 2020, a non-nucleotide STING agonist MSA-2 was identified, which exhibited satisfactory antitumor effects in animal studies and is amenable to oral administration. Due to its distinctive binding mode and enhanced bioavailability, there have been accumulating interests and an array of studies on MSA-2 and its derivatives, spanning its structure-activity relationship, delivery systems, applications in combination therapies, etc. Here, we provide a comprehensive review of MSA-2 and interventional strategies based on this family of STING agonists to help more researchers extend the investigation on MSA-2 in the future.

In situ administration of STING-activating hyaluronic acid conjugate primes anti-glioblastoma immune response.

Glioblastoma (GBM) is an aggressive brain tumor, with a highly immunosuppressive tumor immune microenvironment (TIME). In this work, we investigated the use of the STimulator of INterferon Genes (STING) pathway as an effective means to remodel the GBM TIME through the recruitment of both innate and adaptive immune cell populations. Using hyaluronic acid (HA), we developed a novel polymer-drug conjugate of a non-nucleotide STING agonist (MSA2), called HA-MSA2 for the in situ treatment of GBM. In JAWSII cells, HA-MSA2 exerted a greater increase of STING signaling and upregulation of STING-related downstream cyto-/chemokines in immune cells than the free drug. HA-MSA2 also elicited cancer cell-intrinsic immunostimulatory gene expression and promoted immunogenic cell death of GBM cells. In the SB28 GBM model, local delivery of HA-MSA2 induced a delay in tumor growth and a significant extension of survival. The analysis of the TIME showed a profound shift in the GBM immune landscape after HA-MSA2 treatment, with higher infiltration by innate and adaptive immune cells including dendritic, natural killer (NK) and CD8 T cell populations. The therapeutic potential of this novel polymer conjugate warrants further investigation, particularly with other chemo-immunotherapeutics or cancer vaccines as a promising combinatorial therapeutic approach.

MRl and MRS hints for the differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia type II.

Background and objectives: The differentiation of spinocerebellar ataxia type II (SCA 2) from idiopathic multiple systemic atrophy of the cerebellar type (MSA-C) is often difficult in patients with cerebellar ataxia when molecular testing is not available. Besides genetic testing, magnetic resonance imagining (MRI) and magnetic resonance spectroscopy (MRS) prove to be beneficial. Nevertheless, the characteristics observed through radiology change as the disease advances. Different radiological criteria may be needed across different stages of the disease. This study aimed to assess the radiological characteristics of MSA-C or SCA 2 patients across various stages of the disease and to identify potential distinguishing factors. Methods: Between January 2000 and January 2020, a total of 390 patients, diagnosed with probable MSA-C according to the second consensus on MSA (317 cases) or with molecularly confirmed SCA 2 (73 cases), who had undergone at least one brain MRI and MRS targeting the cerebellar hemispheres, were enrolled in the study. The clinical parameters and neuroimaging features between these two diseases were compared and analyzed. Results: A greater occurrence of a pontine hot cross bun sign (HCBS), higher scores on the scale for the assessment and rating of ataxia, and reduced levels of cerebellar N-acetyl aspartate (NAA)/creatine (Cr), and cerebellar choline (Cho)/Cr were found in MSA-C patients as compared with SCA 2 patients at similar disease durations. For the patients with an HCBS, a cerebellar Cho/Cr level of <0.53 was indicative of the potential presence of MSA-C, with significant level of specificity (85.96%). Discussion: Discerning SCA2 from MSA-C using MRI and MRS appears to be plausible at various disease stages.

Development of Company-Specific Emission Factors with Confidence Intervals for Natural Gas Customer Meters in Southern California.

Methane is both a significant and short-lived greenhouse gas compared to CO2, and reducing methane emissions from natural gas distribution systems may offer cost-effective reduction opportunities. We report substantial new direct leak rate measurements from customer meter set assemblies (MSAs) in Southern California. In a novel way, emission factors are defined in terms of aboveground Hazardous and Nonhazardous leak categories, which take direct advantage of readily available industry leak data. We also studied leaks that were not detected as part of normal leak survey procedures. As a result, this yields company-specific emission factors that can be used to track progress in reducing methane emissions. This approach also has the advantage of explicitly accounting for the skewed or fat-tail distribution of leak rates by treating high flow rate MSA leaks separately from low flow rate MSA leaks. The Southern California Gas (SoCalGas) methane emission factors, based on 485 leak rate measurements by direct enclosure, were 4.55 (95% confidence interval: 2.32 to 7.14) kg/day for Hazardous leaks, 0.149 (0.119 to 0.183) kg/day for Nonhazardous leaks, and 0.0039 (0.0003 to 0.0198) kg/day for Non-Detected leaks. The percentage of surveyed meters with nondetected leaks was 29.1% (24.3 to 34.6%). Based on a robust Monte Carlo analysis, total leak emissions from MSAs for the SoCalGas system were reduced by 35% based on data from 2015 to 2022. These reductions were attributed to surveying a larger number of MSAs and accelerated leak repair rates. In traditional population-based emission inventories, an individual emission factor for a given asset category is multiplied by the total population of MSAs within the category. This approach simply cannot capture the reduction in leak numbers and methane emissions resulting from leak mitigation and prevention programs.

First-class - biosynthesis of 6-MSA and bostrycoidin type I polyketides in Yarrowia lipolytica.

Fungal polyketides are a large group of secondary metabolites, valuable due to their diverse spectrum of pharmacological activities. Polyketide biosynthesis in filamentous fungi presents some challenges: small yield and low-purity titers. To tackle these issues, we switched to the yeast Yarrowia lipolytica, an easily cultivable heterologous host. As an oleaginous yeast, Y. lipolytica displays a high flux of acetyl- and malonyl-CoA precursors used in lipid synthesis. Likewise, acetyl- and malonyl-CoA are the building blocks of many natural polyketides, and we explored the possibility of redirecting this flux toward polyketide production. Despite its promising prospect, Y. lipolytica has so far only been used for heterologous expression of simple type III polyketide synthases (PKSs) from plants. Therefore, we decided to evaluate the potential of Y. lipolytica by targeting the more complex fungal polyketides synthesized by type I PKSs. We employed a CRISPR-Cas9-mediated genome editing method to achieve markerless gene integration of the genes responsible for bostrycoidin biosynthesis in Fusarium solani (fsr1, fsr2, and fsr3) and 6-methylsalicylic acid (6-MSA) biosynthesis in Aspergillus hancockii (6MSAS). Moreover, we attempted titer optimization through metabolic engineering by overexpressing two enzymes, TGL4 and AOX2, involved in lipid ß-oxidation, but we did not observe an effect on polyketide production. With maximum titers of 403 mg/L 6-MSA and 35 mg/L bostrycoidin, the latter being substantially higher than our previous results in Saccharomyces cerevisiae (2.2 mg/L), this work demonstrates the potential of Y. lipolytica as a platform for heterologous production of complex fungal polyketides.

Development of S Haplotype-Specific Markers to Identify Genotypes of Self-Incompatibility in Radish (Raphanus sativus L.).

Radish (Raphanus sativus L.), a root vegetable belonging to the Brassicaceae family, is considered one of the representative crops displaying sporophytic self-incompatibility (SSI). The utilization of a self-incompatibility system in F1 breeding can improve the efficiency of cross-combinations, leading to a reduction in breeding time and aiding in the development of novel F1 varieties. The successful implementation of this system necessitates the rapid and accurate identification of S haplotypes in parental lines. In this study, we identified a total of nine S haplotypes among 22 elite radish lines through Sanger sequencing. Subsequently, we obtained sequences for showing a 95% similarity to nine S haplotypes, along with sequences identified by other researchers using BLAST. Following this, multiple sequence alignment (MSA) was conducted to identify SRK and SLG sequence similarities, as well as polymorphisms within the class I and II groups. Subsequently, S haplotype-specific marker sets were developed, targeting polymorphic regions of SRK and SLG alleles. These markers successfully amplified each of the nine S haplotypes. These markers will play a crucial role in the rapid and precise identification of parental S haplotypes in the radish F1 breeding process, proving instrumental in the radish F1 purity test.

Short term safety of magnetic sphincter augmentation vs minimally invasive fundoplication: an ACS-NSQIP analysis.

PURPOSE: Magnetic Sphincter Augmentation (MSA) is an FDA-approved anti-reflux procedure with comparable outcomes to fundoplication. However, most data regarding its use are limited to single or small multicenter studies which may limit the generalizability of its efficacy. The purpose of this study is to evaluate the outcomes of patients undergoing MSA vs fundoplication in a national database. MATERIALS AND METHODS: The 2017-2020 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Registry was utilized to evaluate patients undergoing MSA or fundoplication. Patients requiring Collis gastroplasty, paraesophageal hernia repair, and emergency cases, were excluded. Patient outcomes included overall complication rates, readmissions, reoperations, and mortality. RESULTS: A total of 7,882 patients underwent MSA (n = 597) or fundoplication (n = 7285). MSA patients were younger (51 vs 57, p < 0.001), and more often male (49.6 vs 34.3%, p < 0.001). While patients undergoing MSA experienced similar rates of reoperation (1.0 vs 2.0%, p = 0.095), they experienced fewer readmissions (2.2 vs 4.7%, p = 0.005), complications (0.6 vs 4.0%, p < 0.001), shorter mean (SD) hospital length of stay(days) (0.4 ± 4.3 vs 1.8 ± 4.6, p < 0.001) and operative time(min) (80.8 ± 36.1 vs 118.7 ± 63.7, p < 0.001). Mortality was similar between groups (0 vs 0.3%, p = 0.175). On multivariable analysis, MSA was independently associated with reduced postoperative complications (OR 0.23, CI 0.08 to 0.61, p = 0.002), readmissions (OR 0.53, CI 0.30 to 0.94, p = 0.02), operative time (RC - 36.56, CI - 41.62 to - 31.49. p < 0.001) and length of stay (RC - 1.22, CI - 1.61 to - 0.84 p < 0.001). CONCLUSION: In this national database study, compared to fundoplication MSA was associated with reduced postoperative complications, fewer readmissions, and shorter operative time and hospital length of stay. While randomized trials are lacking between MSA and fundoplication, both institutional and national database studies continue to support the use of MSA as a safe anti-reflux operation.

Fetal MRI-Based Mediastinal Shift Angle (MSA) and Percentage Area of Left Ventricle (pALV) as Prognostic Parameters for Congenital Diaphragmatic Hernia.

OBJECTIVE: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due to pulmonary hypertension and left cardiac hypoplasia is decisive for the prognosis. The percentage area of left ventricle (pALV) describes the percentage of the inner area of the left ventricle in relation to the total area, whereas the mediastinal shift angle (MSA) quantifies the extent of cardiac displacement. The prognostic value of pALV and MSA should be evaluated in terms of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD). METHODS: In a total of 122 fetal MRIs, the MSA and pALV were measured retrospectively and complete outcome parameters were determined regarding survival for all 122 subjects, regarding ECMO therapy in 109 cases and about the development of CLD in 78 cases. The prognostic value regarding the endpoints was evaluated using logistic regression and ROC analysis. RESULTS: The MSA was significantly higher in children who received ECMO therapy (p = 0.0054), as well as in children who developed CLD (p = 0.0018). ROC analysis showed an AUC of 0.68 for ECMO requirement and 0.77 with respect to CLD development. The pALV showed a tendency towards higher levels in children who received ECMO therapy (p = 0.0824). The MSA and the pALV had no significant effect on survival (MSA: p = 0.4293, AUC = 0.56; pALV: p = 0.1134, AUC = 0.57). CONCLUSIONS: The MSA determined in fetal MRI is a suitable prognostic parameter for ECMO requirement and CLD development in CDH patients and can possibly be used as a supplement to the established parameters.

Sobetirome rescues α-synuclein-mediated demyelination in an in vitro model of multiple system atrophy.

Multiple system atrophy (MSA) is a rare and rapidly progressive atypical parkinsonian disorder characterized by oligodendroglial cytoplasmic inclusions containing α-synuclein (α-syn), demyelination, inflammation and neuronal loss. To date, no disease-modifying therapy is available. Targeting α-syn-driven oligodendroglial dysfunction and demyelination presents a potential therapeutic approach for restricting axonal dysfunction, neuronal loss and disease progression. The present study investigated the promyelinogenic potential of sobetirome, a blood-brain barrier permeable and central nervous system selective thyromimetic in the context of an in vitro MSA model. Oligodendrocyte precursor cells (OPCs) were obtained from transgenic mice overexpressing human α-syn specifically in oligodendrocytes (MBP29 mouse line), a well-described MSA model, and non-transgenic littermates. mRNA and protein expression analyses revealed a substantial rescue effect of sobetirome on myelin-specific proteins in control and α-syn overexpressing oligodendrocytes. Furthermore, myelination analysis using nanofibres confirmed that sobetirome increases both the length and number of myelinated segments per oligodendrocyte in primary murine α-syn overexpressing oligodendrocytes and their respective control. These results suggest that sobetirome may be a promising thyromimetic compound targeting an important neuropathological hallmark of MSA.

In vivo cerebral metabolic and dopaminergic characteristics in multiple system atrophy with orthostatic hypotension.

PURPOSE: Multiple system atrophy (MSA) is a rare neurodegenerative disease, often presented with orthostatic hypotension (OH), which is a disabling symptom but has not been very explored. Here, we investigated MSA patients with OH by using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) and 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) for in vivo evaluation of the glucose metabolism and dopaminergic function of the brain. METHODS: Totally, 51 patients with MSA and 20 healthy controls (HC) who underwent 18F-FDG PET/CT were retrospectively enrolled, among which 24 patients also underwent 11C-CFT PET/CT. All patients were divided into MSA-OH(+) and MSA-OH(-) groups. Then, statistical parametric mapping (SPM) method was used to reveal the regional metabolic and dopaminergic characteristics of MSA-OH(+) compared with MSA-OH(-). Moreover, the metabolic networks of MSA-OH(+), MSA-OH(-) and HC groups were also constructed and analyzed based on graph theory to find possible network-level changes in MSA patients with OH. RESULTS: The SPM results showed significant hypometabolism in the pons and right cerebellar tonsil, as well as hypermetabolism in the left parahippocampal gyrus and left superior temporal gyrus in MSA-OH(+) compared with MSA-OH(-). A reduced 11C-CFT uptake in the left caudate was also shown in MSA-OH(+) compared with MSA-OH(-). In the network analysis, significantly reduced local efficiency and clustering coefficient were shown in MSA-OH(+) compared with HC, and decreased nodal centrality in the frontal gyrus was found in MSA-OH(+) compared with MSA-OH(-). CONCLUSION: In this study, the changes in glucose metabolism in the pons, right cerebellar tonsil, left parahippocampal gyrus and left superior temporal gyrus were found closely related to OH in MSA patients. And the decreased presynaptic dopaminergic function in the left caudate may contribute to OH in MSA. Taken together, this study provided in vivo pathophysiologic information on MSA with OH from neuroimaging approach, which is essential for a better understanding of MSA with OH.

Rapidly progressive multiple system atrophy in a patient carrying LRRK2 G2019S mutation.

BACKGROUND: Multiple system atrophy (MSA) is considered a primarily sporadic neurodegenerative disease, but the role of genetic is poorly understood. CASE: We present a female patient of Moroccan origin who developed a rapidly progressive non-levodopa responsive parkinsonism, gait and balance problems, and dysautonomia including severe bulbar symptoms. She was diagnosed with MSA Parkinsonian-type (MSA-P) and suddenly died at night at 58 years of age. Reduced striatal DAT-SPECT, putaminal hyperintensity on T2-MRI, and hypometabolism with FDG-PET were present. Genetic testing documented a G2019S mutation in the LRRK2 gene. A skin biopsy was obtained and used to perform alpha-synuclein RT-QuIC, which was negative, and immunohistochemical analysis, which demonstrated abnormal alpha-synuclein deposits in cutaneous nerves. Elevated blood neurofilament light chain levels were also documented. CONCLUSIONS: LRRK2 mutations are the most common cause of monogenic Parkinson's disease (PD) and G2019S is the most frequent variant. Our patient presented with biological, clinical, and radiological features of MSA, but genetic testing revealed a G2019S LRRK2 mutation, which has been previously reported only in one other case of pathologically proven MSA but with mild progression. In our patient, post-mortem confirmation could not be performed, but RT-QuIC and immunohistochemical findings on skin biopsy support the diagnosis of MSA. G2019S LRRK2 may be linked to an increased risk of MSA. Cases of atypical parkinsonism with rapid disease course should be screened for PD-related genes especially in populations with a high prevalence of mutations in known genes.

Tau in Atypical Parkinsonisms: A Meta-Analysis of in Vivo PET Imaging Findings.

Background: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are atypical parkinsonisms (APs) that are classified as tauopathies. Patients with these APs may present with similar early clinical manifestations to Parkinson's disease (PD), but they prove unresponsive to anti-parkinsonian medications. Objective: The main objective of this meta-analysis was to compare first- and second-generation tau PET tracer efficacy in patients with the APs to identify potential diagnostic biomarkers. Methods: PubMed and Web of Science were searched between January 1, 1999 and December 31, 2022. We included case-control studies that were published in English and report tau PET tracer binding as mean ± SD in at least one region of interest (ROI). Differences in tau PET binding values were meta-analyzed using random-effects meta-analytic models and subgroup analyses based on ROIs in the statistical programming language R (version 4.2.1). Results: Overall, 29 studies with 665 patients were included in the final review. [18F]PI-2620 outperformed first-generation tracers when comparing PSP-HC (g = -1.68, 95% CI: -2.05 to -1.30) and CBD-HC (g = -1.37, 95% CI: -2.25 to -0.49). When comparing PSP-PD, the first-generation tracer, [18F]AV-1451, presented with higher binding to PSP patients (g = -0.80, 95% CI: -1.24 to -0.35). Conclusions: Our results demonstrate the efficacy of [18F]PI-2620 PET in imaging AP-tau. These findings contribute towards identifying a diagnostic imaging biomarker for patients with APs. The main limitation of this study was the heterogeneity of the results. Future studies should conduct AP-PD comparisons with second-generation tracers to confirm the preliminary results found here.