ABSTRACT
Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by the accumulation of 4R-tau protein aggregates in various brain regions. PSP leads to neuronal loss, gliosis, and tau-positive inclusions, such as neurofibrillary tangles, tufted astrocytes, and coiled bodies. These pathological changes mainly affect the brainstem and the basal ganglia, resulting in distinctive MRI features, such as the hummingbird and morning glory signs. PSP shows clinical heterogeneity and presents as different phenotypes, the most classical of which is Richardson's syndrome (PSP-RS). The region of involvement and the mode of atrophy spread can further distinguish subtypes of PSP. PSP patients can experience various signs and symptoms, such as postural instability, supranuclear ophthalmoplegia, low amplitude fast finger tapping, and irregular sleep patterns. The most common symptoms of PSP are postural instability, falls, vertical gaze palsy, bradykinesia, and cognitive impairment. These features often overlap with those of Parkinson's disease (PD) and other Parkinsonian syndromes, making the diagnosis challenging. PSP is an essential clinical topic to research because it is a devastating and incurable disease. However, there are still many gaps in knowledge about its pathophysiology, diagnosis, and treatment. Several clinical trials are underway to test noveltherapies that target tau in various ways, such as modulating its post-translational modifications, stabilizing its interaction with microtubules, or enhancing its clearance by immunotherapy. These approaches may offer new hope for slowing down the progression of PSP. In this review, we aim to provide an overview of the current knowledge on PSP, from its pathogenesis to its management. We also discuss the latest advances and future directions in PSP research.
ABSTRACT
PURPOSE: This in vitro study analyzed the accuracy of a computer-assisted design (CAD)/computer-assisted manufacturing (CAM) guided implant surgery system by comparing linear, angular, and coronal deviations between the planned and final implant placement. METHODS: By using a fully guided surgery workflow, 32 dental implants were placed in 16 partially edentulous models. After virtual design of the restorations, radiological and CAD files were matched and implant positions were planned by using dedicated implant planning software (Galileo Implant version 1.9.2.). Templates were designed (Cerec Omnicam) and milled (Cerec MC XL) by using chairside workflow. Galileo Implant version 1.9.2. was used to evaluate accuracy. RESULTS: Mean horizontal and angular-coronal total deviation values were 0.2 mm (SD = 0.126) and 1.1º (SD = 0.834) respectively. Multivariate analysis of variance showed significant differences in horizontal and angular-coronal total deviation in the 32 implants (P = 0.0001). Multivariate analysis with one-factor interaction showed no statistical difference in implant position or implant type (P = 0.139) between eight maxilla models and eight jaw models. CONCLUSION: Horizontal and angular-coronal deviations of implants placed with chairside digital workflow were within the recommended safety margin for fully guided surgery.
Subject(s)
Dental Implants , Surgery, Computer-Assisted , Computer-Aided Design , Dental Implantation, Endosseous , Patient Care PlanningABSTRACT
BACKGROUND: Wheat growers have limited herbicide options to manage Aegilops cylindrica Host (jointed goatgrass), with many relying on mesosulfuron or imazamox in Clearfield™ winter wheat. Both imazamox and mesosulfuron inhibit acetohydroxyacid synthase/acetolactate synthase (AHAS/ALS). In 2015, a suspected imazamox resistant biotype of Ae. cylindrica was found in eastern Washington. RESULTS: Imazamox and mesosulfuron were applied to the suspected resistant and susceptible Ae. cylindrica biotypes in increasing application rates to evaluate herbicide dose needed to cause 50% growth reduction (GR50 ). The imazamox resistant biotype had a GR50 of 308.5 g ai ha-1 and was more than 5000 times more resistant to imazamox than a known susceptible biotype with a GR50 of 0.06 g ai ha-1 . The Ae. cylindrica resistant biotype was also resistant to mesosulfuron, with an GR50 of 46.82 g ai ha-1 , which was five times more than the susceptible GR50 of 8.6 g ai ha-1 . Sequencing of the AHAS/ALS gene revealed an Ala122 Thr substitution in the herbicide binding region of the AHAS/ALS gene on the D genome of Ae. cylindrica. The resistance trait was inherited as a dominant trait, and the Ala122 Thr co-segregates with the resistance phenotype. CONCLUSIONS: An Ala122 Thr substitution in the AHAS/ALS gene on the D genome of Ae. cylindrica confers resistance to imazamox in Ae. cylindrica. © 2021 Society of Chemical Industry.
Subject(s)
Acetolactate Synthase , Aegilops , Herbicides , Acetolactate Synthase/genetics , Aegilops/genetics , Herbicide Resistance/genetics , Herbicides/pharmacology , ImidazolesABSTRACT
Giving that the pyrazolo[1,5-a][1,3,5]triazine system is a potential source of pharmacological agents for treatment of central nervous system disorders this work was aimed to asses anticonvulsant and acute neurotoxic effects of six molecules obtained by synthesis, using experimental models in mice. A series of six pyrazolo[1,5-a][1,3,5]triazines (EAC-21, EAC-31, EAC-33, MH4a, MH4b1 and MH4c) obtained by one-step reaction from S,S-diethyl aroyl-/hetaroylimidodithiocarbonates and 5-aminopyrazoles were screened in vivo (300 mg/kg, v.o.) for their anticonvulsant activity in the maximal electroshock (MES) test in ICR mice and for acute toxicity in the rota-rod and wiring test. The structures of the obtained compounds were unambiguously established by IR, 1H and 13C-NMR spectroscopic techniques, COSY 1H-1H, HSQC and HMBC experiments, mass spectrometry and elemental analyses. Results shown that only MH4b1 showed protection against MES (p<0.05) and was devoid of gross neurotoxicity signs. Therefore, MH4b1 was chosen for additional anticonvulsant screening against MES, pentilenetetrazole, picrotoxin, strychnine and 6 Hz psychomotor seizure model, in a dose dependent manner (50, 150, 300 mg/kg, v.o.). MH4b1 also protected against 6 Hz seizure test (>150 mg/kg, v.o.). These data suggest that MH4b1 could be a source for anticonvulsant pyrazolo[1,5-a][1,3,5]triazine analogs potentially useful against tonic clonic and refractory seizures.
Dado el interés que el sistema pirazolo[1,5-a][1,3,5]triazina tiene como fuente potencial para la obtención de agentes farmacológicos para el tratamiento de trastornos del sistema nervioso central, en este trabajo se efectuó el cribado anticonvulsivante y el efecto neurotóxico agudo de seis moléculas derivadas de este sistema, en ratones ICR. La serie de compuestos denominados EAC-21, EAC-31, EAC-33, MH4a, MH4b1 y MH4c, obtenidas por la reacción de S,S-dietil aroil-/heteroilimidoditiocarbonatos y 5-aminopirazoles se evaluó in vivo (300 mg/kg, v.o.) en la prueba de convulsiones inducidas por electrochoque y en las pruebas de actividad neurotóxica aguda del eje rodante y del alambre. La estructura de estos compuestos se determinó por técnicas de infrarrojo, espectroscopia de 1H, 13C-NMR, COSY 1H-1H, experimentos de HSQC y HMBC, espectrometría de masas y análisis elemental. Los resultados mostraron que el compuesto MH4b1 confirió protección frente a las convulsiones inducidas por electrochoque (p<0.05) sin producir signos de neurotoxicidad aguda. Por consiguiente, MH4b1 se escogió para las siguientes pruebas de actividad anticonvulsivante, dosis - respuesta (50, 150, 300 mg/kg, v.o.): electrochoque, pentilenetetrazol, picrotoxin, estricnina y el modelo de convulsión psicomotora de 6 Hz. MH4b1 mostró efectos protectores en función de la dosis frente a las pruebas de convulsión por electrochoque (>150 mg/kg) y convulsión de 6 Hz (300 mg/kg, v.o.). Estos resultados sugieren que MH4b1 podría constituirse en fuente anticonvulsivante del sistema pirazolo[1,5-a][1,3,5]triazina eventualmente útil para el tratamiento de las crisis tónicas clónicas generalizadas y las crisis refractarias.
