Active compounds and our structure-activity correlated data for the dihydropyridine compound class may provide valuable information for developing a treatment of the trafficking defect in achromatopsia. SIGNIFICANCE STATEMENT This study describes a novel luminescence-based assay to detect the surface expression of mutant trafficking-deficient CNGA3 channels based on the calcium-sensitive photoprotein aequorin. Using this assay for a compound screening, this study identifies novel chemical and pharmacological chaperones that restore the surface localization of mutant trafficking-deficient CNGA3 channels. The results from this work may serve as starting point for the development of potent compounds that rescue trafficking deficiencies in the autosomal recessively inherited retinal disease achromatopsia. To investigate the effects of single sensory impairment (SSI; visual or auditory) or dual sensory impairment (DSI; visual and auditory) on dementia and longitudinal changes of neuropsychological test scores. In this nationwide, prospective, community-based elderly cohort study, KLOSCAD (the Korean Longitudinal Study on Cognitive Aging and Dementia), 6,520 elderly individuals (58-101 years) representing the general population were included. We defined visual and auditory sensory impairment via self-report questionnaire 932 had normal sensory function, 2,957 had an SSI, and 2,631 had a DSI. Demographic and clinical variables including cognitive outcomes were evaluated every 2 years over 6 years. Through logistic regression, Cox regression, and linear mixed model analysis, the relationship between SSI or DSI and dementia prevalence, dementia incidence, and change in neuropsychological scores were evaluated. At baseline, DSI was significantly associated with increased dementia prevalence compared to normal sensory function (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.17-4.02), but SSI was not (OR 1.27, 95% CI 0.66-2.41). During the 6-year follow-up, the incidence of dementia was significantly higher in the DSI group than in the normal sensory function group (hazard ratio 1.9, 95% CI 1.04-3.46) and neuropsychological scores significantly decreased (β -0.87, 95% CI [-1.17 to -0.58]). Our results suggest that coexisting visual and hearing impairments facilitate dementia prevalence, dementia incidence, and cognitive decline, but visual or hearing impairment alone do not. Visual and hearing impairment may lead to dementia or cognitive decline independent of Alzheimer pathology.Our results suggest that coexisting visual and hearing impairments facilitate dementia prevalence, dementia incidence, and cognitive decline, but visual or hearing impairment alone do not. Visual and hearing impairment may lead to dementia or cognitive decline independent of Alzheimer pathology. To determine whether the IV infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients. Twenty patients with migraine without aura participated in a placebo-controlled and double-blind clinical study. In a randomized crossover design, the patients received an IV infusion of human adrenomedullin (19.9 pmol/kg/min) or placebo (saline) administrated via an automated IV pump (20 minutes). The patients participated in 2 study days with a washout period of minimum of 7 days. The primary outcome of the study was predefined as a difference in migraine incidence (0-12 hours), and the secondary outcomes were the area under curve (AUC hours) for the headache intensity score and AUC for mean arterial blood pressure (MAP), flushing, and heart rate (HR). Eleven patients with migraine without aura (55%) fulfilled migraine attacks criteria after adrenomedullin infusion compared to only 3 patients who reported attack (15%) after placebo ( 0.039). We found that patients reported in a period of 0 to 12 hours stronger headache intensity after adrenomedullin compared to placebo infusion ( 0.035). AUC value for HR and flushing ( < 0.05) was significant and for MAP ( = 0.502) remained unchanged. Common reported adverse events were facial flushing, heat sensation, and palpitation ( < 0.001). Our data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount the possibility that adrenomedullin may be acting through the canonical calcitonin gene-related peptide receptor. ClinicalTrials.gov Identifier NCT04111484.ClinicalTrials.gov Identifier NCT04111484. To investigate the effects of rituximab on retinal atrophy in patients with relapsing-remitting multiple sclerosis (RRMS), we performed serial optical coherence tomography (OCT) scans among a cohort of patients with RRMS on rituximab and compared rates of ganglion cell + inner plexiform layer (GCIPL) atrophy to those observed among age- and sex-matched glatiramer acetate (GA)-and natalizumab-treated patients with RRMS and healthy controls (HCs). In this observational study, patients with RRMS treated with a single disease-modifying therapy and HCs were followed with serial OCT for a median duration of 2.8 years. Participants with uncontrolled hypertension, diabetes mellitus, or glaucoma, and eyes with optic neuritis ≤6 months prior to baseline OCT, or during follow-up, were excluded. #link# Statistical analyses were performed using linear mixed-effects regression. During the overall follow-up period, rates of GCIPL atrophy were -0.28 ± 0.11 µm/y among rituximab-treated patients with RRMS (n = 35). This was simmodifying therapies.This study provides Class IV evidence on the difference in rate of change of the GCIPL thickness in patients with RRMS comparing rituximab to other disease-modifying therapies. To investigate whether previously reported increasing Sacituzumab govitecan of pregnancy-associated stroke (PAS) is observed in chart-validated register data in Finland. In an exploratory analysis, we studied risk factors for PAS. We performed a retrospective population-based cohort study and nested case-control study in Finland from 1987 to 2016. The Medical Birth Register (MBR) was linked to the Hospital Discharge Register to identify women with incident stroke (ischemic stroke, cerebral venous thrombosis, intracerebral or subarachnoid hemorrhage) during pregnancy or puerperium. Cases were verified from patient records. Incidence of PAS over the study period in 5-year age groups and pregnancy/postpartum period was calculated per number of deliveries. Three matched controls were selected for each case from MBR to compare risk factors. After chart review, 29.6% (257 of 868) of cases were PAS. The incidence of PAS was 14.5 (95% confidence interval [CI] 12.8-16.3) per 100,000 deliveries. Incidence increased from 11.1 to 25.