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IntroductionParkinson’s disease (PD) patients in chronic levodopa treatment may experience motor and non-motor fluctuations, which may affect their quality of life. Safinamide is a new monoamine oxidase B inhibitor, also exerting a non-dopaminergic effect, recently approved as add-on therapy in fluctuating PD patients.MethodsWe performed a longitudinal prospective study in a cohort of 20 fluctuating PD patients, to test whether safinamide 50 mg may improve non-motor, cognitive, and behavioral symptoms over a 6-month treatment period. At each timepoint, clinical features were assessed by means of validated PD-specific scales. Neuropsychological assessment was performed by exploring all five cognitive domains.ResultsCompared to baseline, significant improvement was found in PD patients at 6-month follow-up in items investigating interest (p = 0.02), motivation (p = 0.02), and urinary disturbances (p = 0.03). Moreover, neuropsychiatric assessment showed a significant decrease in fatigue and apathy scores (p = 0.02 and p = 0.01, respectively). Motor assessment revealed a significant reduction in the total wake-up time spent in OFF state (p = 0.01). Follow-up neuropsychological evaluation did not reveal any change compared to baseline.ConclusionsOur data reveal that, along with motor fluctuation improvement, treatment with safinamide 50 mg may significantly decrease non-motor symptom burden in PD patients. Interestingly, non-dopaminergic mechanisms, such as glutamatergic overdrive, have been demonstrated to play a role in many pathways underlying these symptoms. Thus, we hypothesize that the neurotransmitter receptor-binding profile of safinamide may explain our findings.

The latest Triassic was characterised by protracted biotic extinctions concluding in the End-Triassic Extinction (~ 200 Ma) and a global carbon cycle perturbation. The onset of declining diversity is closely related to reducing conditions that spread globally from upper Sevatian (uppermost Norian) to across the Norian-Rhaetian boundary, likely triggered by unusually high volcanic activity. We correlate significant organic carbon cycle perturbations to an increase of CO 2 in the ocean–atmosphere system, likely outgassed by the Angayucham igneous province, the onset of which is indicated by the initiation of a rapid decline in 87 Sr/ 86 Sr and 188 Os/ 187 Os seawater values. A possible causal mechanism involves elevated CO 2 levels causing global warming and accelerating chemical weathering, which increased nutrient discharge to the oceans and greatly increased biological productivity. Higher export production and oxidation of organic matter led to a global O 2 decrease in marine water across the Norian/Rhaetian boundary (NRB). Biotic consequences of dysoxia/anoxia include worldwide extinctions in some fossil groups, such as bivalves, ammonoids, conodonts, radiolarians.

By studying deep‐sea drilled records from the North Atlantic Ocean, several magnetic instabilities of short duration, such as the Iceland Basin (188 ka), the Björn (1,255 ka) and the Gardar (1,460 ka) excursions, were discovered. These records have contributed to our understanding of Earth's magnetic field and are the foundation of the Geomagnetic Instability Time Scale (GITS) in the Quaternary. Here, we present the magnetostratigraphy from Sites U1555 (0 to ∼2.7 Ma) and U1563 (0 to ∼5.2 Ma) drilled during the International Ocean Discovery Program Expedition 395C on the eastern side of the modern Mid‐Atlantic Ridge (∼60°N, 20–30°W). Shipboard paleomagnetic and microfossil data provided a preliminary age model, extending the regional record to 3.4 Ma. The Virtual Geomagnetic Pole latitudes from archive halves, corroborated with data from discrete samples, were used to build a high‐resolution magnetostratigraphy, which contained the expected Brunhes and Matuyama Chrons and their respective Subchrons. We also identified most of the magnetic events reported in the GITS, including the less well‐documented ones, such as Osaka, Kamitzukara, Huckleberry Ridge, Reunion, Gardar, Halawa and L4 events. The high‐resolution magnetostratigraphy from Sites U1555 and U1563 is compared with two previous legacy sites and contributes toward an increasingly robust GITS, expanding its use as a correlation and dating tool.

Objective Biallelic mutations in PRDX3 have been linked to autosomal recessive spinocerebellar ataxia type 32. In this study, which aims to contribute to the growing body of knowledge on this rare disease, we identified two unrelated patients with mutations in PRDX3. We explored the impact of PRDX3 mutation in patient skin fibroblasts and the role of the gene in neurodevelopment. Methods We performed trio exome sequencing that identified mutations in PRDX3 in two unrelated patients. We also performed functional studies in patient skin fibroblasts and generated a “crispant” zebrafish (Danio rerio) model to investigate the role of the gene during nervous system development. Results Our study reports two additional patients. Patient 1 is a 19‐year‐old male who showed a novel homozygous c.525_535delGTTAGAAGGTT (p. Leu176TrpfsTer11) mutation as the genetic cause of cerebellar ataxia. Patient 2 is a 20‐year‐old male who was found to present the known c.425C>G/p. Ala142Gly variant in compound heterozygosity with the p. Leu176TrpfsTer11 one. While the fibroblast model failed to recapitulate the pathological features associated with PRDX3 loss of function, our functional characterization of the prdx3 zebrafish model revealed motor defects, increased susceptibility to reactive oxygen species‐triggered apoptosis, and an impaired oxygen consumption rate. Conclusions We identified a new variant, thereby expanding the genetic spectrum of PRDX3‐related disease. We developed a novel zebrafish model to investigate the consequences of prdx3 depletion on neurodevelopment and thus offered a potential new tool for identifying new treatment opportunities.

Patients with Parkinson’s disease (PD), often elderly with various comorbidities, may require a continuous intestinal infusion of carbidopa/levodopa gel by the placement of a percutaneous endoscopic gastrostomy (PEG) with a jejunal tube (PEG-J) to improve their motor outcome and quality of life. However, it is unclear what is the best procedural sedation protocol for PEG-J procedures. Fifty patients with PD and indication for PEG-J procedure (implantation, replacement, removal) underwent, from 2017 to 2022, a sedation protocol characterized by premedication with atropine (0.01 mg/Kg i.v. ), midazolam (0.015–0.03 mg/Kg i.v. ) and induction with bolus propofol (0.5–1 mg/Kg i.v. ) as well as, finally, sedation with continuous infusion propofol (2–5 mg/Kg/h i.v. ) by Target Controlled Infusion (TCI) technique. Ninety-eight per cent of patients experienced no intraprocedural or peri-procedural adverse events. All the procedures were technically successful. A good discharge time was recorded. The vital parameters recorded during the procedure did not vary significantly. A PEG-J procedure conducted within 30 min showed a significant advantage over end-tidal carbon dioxide (EtCO 2 ). Indeed, the latter showed some predictive behavior (OR: 1.318, 95% CI 1.075–1.615, p  = 0.008). In the real world, this sedation protocol showed a good safety and effectiveness profile, even with reduced doses of midazolam and a TCI propofol technique in moderate sedation.

Parkinsonism is a syndrome characterized by bradykinesia in combination with either rest tremor, rigidity, or both. These features are the cardinal manifestations of Parkinson’s disease, the most common cause of parkinsonism, and atypical parkinsonian disorders. However, parkinsonism can be a manifestation of complex neurological and neurodegenerative genetically determined disorders, which have a vast and heterogeneous motor and non-motor phenotypic features. Hereditary dementias, adult-onset ataxias and spastic paraplegias represent only few of this vast group of neurogenetic diseases. This review will provide an overview of parkinsonism’s clinical features within adult-onset neurogenetic diseases which a neurologist could face with. Understanding parkinsonism and its characteristics in the context of the aforementioned neurological conditions may provide insights into pathophysiological mechanisms and have important clinical implications, including diagnostic and therapeutic aspects.

Continental breakup represents the successful process of rifting and thinning of the continental lithosphere, leading to plate rupture and initiation of oceanic crust formation. Magmatism during breakup seems to follow a path of either excessive, transient magmatism (magma-rich margins) or of igneous starvation (magma-poor margins). The latter type is characterized by extreme continental lithospheric extension and mantle exhumation prior to igneous oceanic crust formation. Discovery of magma-poor margins has raised fundamental questions about the onset of ocean-floor type magmatism, and has guided interpretation of seismic data across many rifted margins, including the highly extended northern South China Sea margin. Here we report International Ocean Discovery Program drilling data from the northern South China Sea margin, testing the magma-poor margin model outside the North Atlantic. Contrary to expectations, results show initiation of Mid-Ocean Ridge basalt type magmatism during breakup, with a narrow and rapid transition into igneous oceanic crust. Coring and seismic data suggest that fast lithospheric extension without mantle exhumation generated a margin structure between the two endmembers. Asthenospheric upwelling yielding Mid-Ocean Ridge basalt-type magmatism from normal-temperature mantle during final breakup is interpreted to reflect rapid rifting within thin pre-rift lithosphere.

Arcuate fold-and-thrust belts have been extensively studied in the literature. Less attention, however, has been paid to the characteristics of local-scale arcuate structures, meaning 5–10 km long fold or thrust traces that display map-view curvature. Nevertheless, detailed investigation of small arcuate structures hosted in major arcs can contribute to understanding the pervasiveness of deformation mechanisms. We performed a combined geological and palaeomagnetic study on 21 sites from a c. 60 km2 area in the Northern Apennines in order to analyse minor arcs at a kilometric scale. As evidenced by the geological and structural analysis performed on the 21 sites, the fold axial trend changes from N–S to NW–SE in the study area. The comparison with palaeomagnetic results shows the lack of correlation between vertical axis rotations and fold axial trends. As a consequence, the minor arcuate shapes of thrusts and related folds are interpreted as mostly primary features inherited from the geometry of the palaeomargin, represented by pre-orogenic faults, according to a context of inversion tectonics.

We investigated the geochemical and rock magnetic properties of the magnetostratigraphically calibrated Pignola–Abriola section (Italy) in order to understand the climatic perturbations that characterize the late Norian–early Rhaetian interval (Late Triassic). We performed experiments on anhysteretic and isothermal remanence (ARM and IRM) and on magnetic susceptibility (χ) to obtain the rock magnetic parameters necessary for our paleoclimatic investigation. An episode of increase in the relative quantity of hematite, suggesting the enhanced subaerial oxidation of iron minerals, was identified in the Norian from ∼ 217 Ma in the Alaunian up to ∼ 211 Ma in the early Sevatian, followed by a decline up to 207–206 Ma at the end of the Norian (late Sevatian). The results of geochemical and multivariate statistical analyses support a long-term increase and reduction in rock weathering, confirming and extending previous 87Sr / 86Sr data from the Pizzo Mondello section (Italy). Possible causes of these long-term weathering trends are the multiphase uplifting of the Cimmerian orogen, occurring at mid-northern latitudes along the southern margin of Asia in the Late Triassic, and/or the northward motion of Pangea across the equatorial humid belt. Rapid excursions in oxidized iron minerals have also been observed across the Norian–Rhaetian boundary, the origin of which still has to be determined.