The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases.

A positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately the treatment of α-synuclein-related diseases. Here we show that the PET ligand, [F]ACI-12589, displays good in vitro affinity and specificity for pathological α-synuclein in tissues from patients with different α-synuclein-related disorders including Parkinson's disease (PD) and Multiple-System Atrophy (MSA) using autoradiography and radiobinding techniques. In the initial clinical evaluation we include 23 participants with α-synuclein related disorders, 11 with other neurodegenerative disorders and eight controls.

Concordance of hydrogen peroxide-induced 8-oxo-guanine patterns with two cancer mutation signatures of upper GI tract tumors.

Oxidative DNA damage has been linked to inflammation, cancer, and aging. Here, we have mapped two types of oxidative DNA damage, oxidized guanines produced by hydrogen peroxide and oxidized thymines created by potassium permanganate, at a single-base resolution. 8-Oxo-guanine occurs strictly dependent on the G/C sequence context and shows a pronounced peak at transcription start sites (TSSs).

Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial.

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Efficacy of an Internet-Based Program to Promote Physical Activity and Exercise after Inpatient Rehabilitation in Persons with Multiple Sclerosis: A Randomized, Single-Blind, Controlled Study.

Background: Multimodal rehabilitation improves fatigue and mobility in persons with multiple sclerosis (PwMS). Effects are transient and may be conserved by internet-based physical activity promotion programs.

Objective: Evaluate the effects of internet-based physical activity and exercise promotion on fatigue, quality of life, and gait in PwMS after inpatient rehabilitation.

Rapid In-Person Cognitive Screening in the Preoperative Setting: Test Considerations and Recommendations from the Society for Perioperative Assessment and Quality Improvement (SPAQI).

There are few cognitive screening tools appropriate for fast-paced settings with limited staffing, and particularly in preoperative evaluation clinics. The Society for Perioperative Assessment and Quality Improvement (SPAQI) convened experts in neuropsychology, geriatric medicine, and anesthesiology to conduct a review of the literature and compile a comprehensive list of cognitive screening tools used within primary care and preoperative settings. This Recommendations Statement: 1.

Calpain-mediated tau fragmentation is altered in Alzheimer's disease progression.

The aggregation of intracellular tau protein is a major hallmark of Alzheimer's disease (AD). The extent and the stereotypical spread of tau pathology in the AD brain are correlated with cognitive decline during disease progression. Here we present an in-depth analysis of endogenous tau fragmentation in a well-characterized cohort of AD and age-matched control subjects.

The dual role of thiourea in the thiotrifluoromethylation of alkenes.

Alkenes substituted with a thiourea undergo C-CF followed by intramolecular C-S bond formation with the Togni reagent and trifluoroacetic acid (TFA) at room temperature; thiols and thioamides are not suitable S-sources for this reaction. This anti-addition process involves a CF radical, and affords CF-substituted thiazolines and thiazines for medicinal applications. A metal or photoredox catalyst is not required as the thiourea acts as a reductant, as well as serving as an S-source capable of adding to a C-centered radical.

Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin.

Accumulation of amyloid-β (Aβ) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer's disease (AD). The precise pathological species of Aβ remains elusive although evidence suggests soluble oligomers may be primarily responsible for neurotoxicity. Crenezumab is a humanized anti-Aβ monoclonal IgG4 that binds multiple forms of Aβ, with higher affinity for aggregated forms, and that blocks Aβ aggregation, and promotes disaggregation.

Hydrogen-Bonded Homoleptic Fluoride-Diarylurea Complexes: Structure, Reactivity, and Coordinating Power.

Hydrogen bonding with fluoride is a key interaction encountered when analyzing the mode of action of 5'-fluoro-5'-deoxyadenosine synthase, the only known enzyme capable of catalyzing the formation of a C-F bond from F. Further understanding of the effect of hydrogen bonding on the structure and reactivity of complexed fluoride is therefore important for catalysis and numerous other applications, such as anion supramolecular chemistry. Herein we disclose a detailed study examining the structure of 18 novel urea-fluoride complexes in the solid state, by X-ray and neutron diffraction, and in solution phase and explore the reactivity of these complexes as a fluoride source in S2 chemistry.

Clonal spread of highly successful ST15-CTX-M-15 Klebsiella pneumoniae in companion animals and horses.

Objectives: To investigate the clinical relevance and molecular epidemiology of extended-spectrum β-lactamase (ESBL)-producing Klebsiella species in animals.

Methods: Antimicrobial susceptibilities and presence of ESBLs were examined among Klebsiella spp. (n = 1519) from clinical samples (>1200 senders from Germany and other European countries) mainly from companion animals and horses from October 2008 to March 2010.

Aplysinellamides A-C, bromotyrosine-derived metabolites from an Australian Aplysinella sp. marine sponge.

Mass-directed fractionation of an extract from the Australian marine sponge Aplysinella sp., from the Great Barrier Reef, resulted in the isolation of four new bromotyrosine derivatives, aplysinellamides A-C (1-3) and aplysamine-1-N-oxide (4), along with six known compounds (5-10). The structure elucidation of compounds 1-4 was based on their 1D and 2D NMR and MS spectroscopic data.

Investigation of the inter-observer variability effect on the prognostic value of somatosensory evoked potentials of the median nerve (SSEP) in cardiac arrest survivors using an SSEP classification.

Background And Purpose: We investigated the inter-observer variability in interpretation of median nerve SSEPs with regard to neurological prognosis in survivors of cardiac arrest (CA).

Methods: Four experienced neurologists analyzed 163 median nerve SSEPs on the basis of a pre-defined classification of SSEPs into five patterns (A-E), with consideration of cortical potentials up to a latency of 150ms. Of these, 133 recordings were from CA survivors and 30 were from healthy volunteers.

Distribution and expression of porcine endogenous retroviruses in multi-transgenic pigs generated for xenotransplantation.

Background: Multi-transgenic pigs produced for use in xenotransplantation have to be screened for the presence and expression of porcine endogenous retroviruses (PERV) to select animals with low PERV load. The production of transgenic pigs may also be associated with the integration of the transgene adjacent to or into the locus of a PERV provirus, potentially leading to an enhanced virus expression.

Methods: Non-transgenic animals, single-transgenic, and multi-transgenic pigs were screened for the presence of PERV-A, -B, and -C and recombinant PERV-A/C using polymerase chain reaction (PCR).

The RASSF proteins in cancer; from epigenetic silencing to functional characterization.

The Ras-Association Domain Family (RASSF) comprises ten members, termed RASSF1 to RASSF10. RASSF1 to RASSF6 harbor a C-terminal Ras-association (RA) domain and RASSF7 to RASSF10 contain an N-terminal RA domain. Interestingly, it was observed that in various tumor types distinct RASSFs transcripts (e.

Time-resolved Fourier transform infrared study on photoadduct formation and secondary structural changes within the phototropin LOV domain.

Phototropins are plant blue-light photoreceptors containing two light-, oxygen-, or voltage-sensitive (LOV) domains and a C-terminal kinase domain. The two LOV domains bind noncovalently flavin mononucleotide as a chromophore. We investigated the photocycle of fast-recovery mutant LOV2-I403V from Arabidopsis phototropin 2 by step-scan Fourier transform infrared spectroscopy.

3D imaging with an isocentric mobile C-arm comparison of image quality with spiral CT.

The purpose of this study was to evaluate the image quality of the new 3D imaging system (ISO-C-3D) for osteosyntheses of tibial condylar fractures in comparison with spiral CT (CT). Sixteen human cadaveric knees were examined with a C-arm 3D imaging system and spiral computed tomography. Various screws and plates of steel and titanium were used for osteosynthesis in these specimens.

[CT-guided aortic balloon occlusion in traumatic abdominal and pelvic bleeding].

Purpose: To introduce a new interventional method for CT-guided aortic balloon occlusion in patients with life-threatening abdominal or pelvic bleeding.

Materials And Methods: Three male patients (age 18, 30, and 45 years) with multiple trauma underwent CT-guided balloon occlusion of the aorta after CT identified an active abdominal or pelvic bleeding site and the patients became unstable (systolic blood pressure, BP < 80 mm Hg) despite resuscitation continuous volume. Using a right femoral approach, a 9F sheath was immediately introduced and the positions of the guide wire and balloon catheter (20 x 40 mm) were intermittently checked with CT scans and CT fluoroscopy.

CASP, the alternatively spliced product of the gene encoding the CCAAT-displacement protein transcription factor, is a Golgi membrane protein related to giantin.

Large coiled-coil proteins are being found in increasing numbers on the membranes of the Golgi apparatus and have been proposed to function in tethering of transport vesicles and in the organization of the Golgi stack. Members of one class of Golgi coiled-coil protein, comprising giantin and golgin-84, are anchored to the bilayer by a single C-terminal transmembrane domain (TMD). In this article, we report the characterization of another mammalian coiled-coil protein, CASP, that was originally identified as an alternatively spliced product of the CUTL1 gene that encodes CCAAT-displacement protein (CDP), the human homologue of the Drosophila homeodomain protein Cut.

The SOX8 gene is located within 700 kb of the tip of chromosome 16p and is deleted in a patient with ATR-16 syndrome.

SOX proteins are transcription factors that are characterized by a common DNA-binding motif known as the HMG domain. We describe the 5. 4-kb human SOX8 gene that codes for a 446-amino-acid protein and that is expressed strongly in brain and less abundantly in other tissues.