Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.

Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may promote neurodegeneration. Here we demonstrate that a CNS penetrant small molecule eIF2B activator inhibits the ISR in cellular models of ALS and the brain of an inducible mouse model of TDP-43 pathology, where it transiently slowed progression of locomotor deficits and neurodegeneration.

Telemedicine Evaluations in Neuro-Ophthalmology During the COVID-19 Pandemic: Patient and Physician Surveys.

Background: The novel coronavirus 2019 (COVID-19) pandemic has transformed health care. With the need to limit COVID-19 exposures, telemedicine has become an increasingly important format for clinical care. Compared with other fields, neuro-ophthalmology faces unique challenges, given its dependence on physical examination signs that are difficult to elicit outside the office setting.

Nutrient supplements from selected botanicals mediated immune modulation of the tumor microenvironment and antitumor mechanism.

Specific extracts of selected vegetables (SV) have been shown to benefit the survival of stage IIIb/IV non-small cell lung cancer patients in phase I/II studies and is currently in a phase III trial. However, the underlying mechanism of SV-mediated antitumor immune responses has not been elucidated. Our results indicate that SV modulated the NK and adoptive T cell immune responses in antitumor efficacy.

Tele-Neuro-Ophthalmology During the Age of COVID-19.

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Colored floaters as a manifestation of digoxin toxicity.

Purpose: Since its report in one patient more than 70 years ago, digitalis-induced colored muscae volitantes have not surfaced again in the literature. We report here a case of digoxin induced colored floaters.

Observations: An 89-year-old man on 0.

Corollary Discharge and Oculomotor Proprioception: Cortical Mechanisms for Spatially Accurate Vision.

A classic problem in psychology is understanding how the brain creates a stable and accurate representation of space for perception and action despite a constantly moving eye. Two mechanisms have been proposed to solve this problem: Herman von Helmholtz's idea that the brain uses a corollary discharge of the motor command that moves the eye to adjust the visual representation, and Sir Charles Sherrington's idea that the brain measures eye position to calculate a spatial representation. Here, we discuss the cognitive, neuropsychological, and physiological mechanisms that support each of these ideas.

Facial palsy and idiopathic intracranial hypertension in twins with cystic fibrosis and hypovitaminosis A.

Facial nerve palsies are uncommon in infants. We report on 10-week-old monozygotic twins, diagnosed with cystic fibrosis by newborn screening, who developed facial palsy and increased intracranial pressure. Cranial imaging and cerebrospinal fluid analysis produced normal results.

Hippocampal CA3 NMDA receptors are crucial for memory acquisition of one-time experience.

Lesion and pharmacological intervention studies have suggested that in both human patients and animals the hippocampus plays a crucial role in the rapid acquisition and storage of information from a novel one-time experience. However, how the hippocampus plays this role is poorly known. Here, we show that mice with NMDA receptor (NR) deletion restricted to CA3 pyramidal cells in adulthood are impaired in rapidly acquiring the memory of novel hidden platform locations in a delayed matching-to-place version of the Morris water maze task but are normal when tested with previously experienced platform locations.

Requirement for hippocampal CA3 NMDA receptors in associative memory recall.

Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by generating and analyzing a genetically engineered mouse strain in which the N-methyl-D-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice.