-
Kearns Neal posted an update 22 hours, 6 minutes ago
OBJECTIVE Studies that investigate predictive factors for spontaneous recovery (reversion) from mild cognitive impairment (MCI) are only beginning to emerge, and the long-term course of MCI is not properly understood. We aimed to investigate stability of the MCI diagnosis, predictors for reversion, as well as the trajectory of MCI over the course of 12 years. MATERIALS AND METHODS Data were drawn from the Swedish population study Good Aging in Skåne with MCI defined according to the expanded Mayo Clinic criteria. A total of 331 participants, aged 60-95 years with MCI, were used to investigate 6-year MCI stability and reversion, and 410 participants were used to inspect 12-year MCI trajectory. Predictors for reversion included demographical factors, psychological status, and factors tied to the cognitive testing session and the operationalization of the MCI criteria. RESULTS Over half (58%, 95% CI 52.7-63.3) of the participants reverted back to normal cognitive functioning at 6-year follow-up. Of those with stable MCI, 56.5% (95% CI 48.2-64.8) changed subtype. A total of 23.9% (95% CI 13.7-34.1) of the 6-year follow-up reverters re-transitioned back to MCI at 12-year follow-up. ORs for reversion were significantly higher in participants with lower age (60-year-olds OR 2.19, 95% CI 1.08-4.43, 70-year-olds OR 3.11, 95% CI 1.27-7.62), better global cognitive functioning (OR 1.15, 95% CI 1.03-1.29), good concentration (OR 2.53, 95% CI 1.06-6.05), and single-domain subtype (OR 2.68, 95% CI 1.51-4.75). CONCLUSION Our findings provide further support that MCI reversion to normal cognitive functioning as well as re-transitioning to MCI is fairly common, suggesting that the MCI trajectory does not necessarily lead straight to dementia. Additionally, assessment of factors associated with reversion can aid clinicians to make accurate MCI progression prognosis. © 2020 The Author(s) Published by S. Karger AG, Basel.INTRODUCTION Distal clot migration (DCM) is a known complication of mechanical thrombectomy (MT), but neither risk factors for DCM nor ways of how it might affect clinical outcomes have been extensively studied to date. METHODS To identify risk factors for and outcomes in the setting of DCM, the records of all patients with acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) treated with MT at a single center between May 2016 and June 2018 were retrospectively reviewed. Uni- and multivariable analyses were performed to evaluate predictors of DCM and good functional outcome (90-day modified Rankin Scale; mRS 0-2). RESULTS A total of 65 patients were included, DCM was identified in 22 patients (33.8%). Patients with DCM had significantly higher pre-procedural intravenous tissue plasminogen activator (IV-tPA) administration (81.8 vs. 53.5%, p = 0.03), stentrievers thrombectomy (95.5 vs. 62.8%, p = 0.006), and longer median puncture to recanalization time (44 [34-97] vs. 30 [20-56] min,0 days. Selleckchem JTC-801 IV-tPA administration and MT with short stentrievers are independent predictors of DCM development. © 2020 S. Karger AG, Basel.The cyanobacterial circadian oscillator can be reconstituted by mixing the purified clock proteins KaiA, KaiB, and KaiC with ATP in vitro, leading to a 24-h oscillation of KaiC phosphorylation. The cyanobacterial mutant pr1 carrying valine instead of alanine at position 422 of KaiC (KaiC-A422V) lost the ability to shift the phase of the circadian rhythm. In this study, we analyzed KaiC-A422V to investigate the effect of this single-residue substitution on the in vitro reconstitution of KaiC oscillation. KaiC-A422V exhibited low amplitude oscillations of phosphorylation with a smaller amount of Kai complex than wild-type KaiC (KaiC-WT). Although KaiA can stimulate KaiC phosphorylation, the phosphorylation level of KaiC-A422V is much lower than that of KaiC-WT even at higher KaiA concentrations. It has been suggested that monomer shuffling of KaiC is involved in entraining the in vitro rhythm. To examine whether KaiC-A422V has the capacity for monomer shuffling, we used the difference in the amplitude of the phosphorylation rhythms between KaiC-WT and KaiC-A422V as the indicator of monomer shuffling. When KaiC-A422V and KaiC-WT were mixed, the amplitude of the phosphorylation rhythm changed according to the mixing ratio. This suggests that KaiC-A422V has a reduced ability to shuffle monomers in hexameric KaiC. In addition, the A422V mutation resulted in a change of the stability of the KaiC protein.Second messenger molecules are crucial components of environmental signaling systems to integrate multiple inputs and elicit physiological responses. Among various kinds of second messengers, cyclic nucleotides cAMP and cyclic di-GMP (c-di-GMP) play pivotal roles in bacterial environmental responses. However, how these signaling systems are interconnected for a concerted regulation of cellular physiology remains elusive. In a thermophilic cyanobacterium Thermosynechococcus vulcanus strain RKN, incident light color is sensed by cyanobacteriochrome photoreceptors to transduce the light information to the levels of c-di-GMP, which induces cellular aggregation probably via cellulose synthase activation. Herein, we identified that Tlr0485, which is composed of a cGMP-specific phosphodiesterases, adenylate cyclases, and FhlA (GAF) domain and an HD-GYP domain, is a cAMP-activated c-di-GMP phosphodiesterase. We also show biochemical evidence that the two class-III nucleotide cyclases, Cya1 and Cya2, are both adenylate cyclases to produce cAMP in T. vulcanus. The prevalence of cAMP-activated c-di-GMP phosphodiesterase genes in cyanobacterial genomes suggests that the direct crosstalk between cAMP and c-di-GMP signaling systems may be crucial for cyanobacterial environmental responses.Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.