Background
Early-onset Alzheimer’s disease (EOAD) has been overshadowed by the more common late-onset AD (LOAD). Yet, the literature indicates EOAD may have less hippocampal-memory presentations and more focal neocortical localization early in the disease.
Objective
To evaluate these proposed differences between these two forms of AD and to explore what they inform about differences in AD-pathophysiology.
Methods
21 EOAD and 24 LOAD patients matched for disease progression and severity were compared on neurocognitive measures and resting state fluorodeoxy-glucose positron emission tomography (FDG-PET).
Results
EOAD patients had worse executive functions with greater hypometabolism in the parietal regions; whereas LOAD patients had worse confrontation naming and verbal recognition memory with greater hypometabolism in inferior frontotemporal regions.
Conclusions
In addition to highlighting significant differences between EOAD and LOAD, these results reveal dissociation between executive deficits in AD and frontal hypometabolism, suggesting early disturbances of the parietal-frontal network in EOAD.
Abstract-Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity.
Coexisting long QT gene mutations/polymorphisms in Tetralogy of Fallot (TOF) patients may aggravate the repolarization abnormality from cardiac repair. We investigated the impact of these genes on the risk of life-threatening events. Genetic variants of the three common long QT genes were identified from patients with repaired TOF. Life-threatening events were defined as sudden cardiac death and hemodynamic unstable ventricular arrhythmia. Biophysical characterization of the alleles of the genetic variants was performed using a whole-cell voltage clamp with expression in Xenopus oocytes. A total of 84 patients (56.0 % male with 1,215 patients-year follow-up) were enrolled. Six rare variants and six non-synonymous single nucleotide polymorphisms (SNPs) were found in 40 (47.6 %) patients. Life-threatening events occurred in five patients; four received implantable cardioverter defibrillator and one died of sudden cardiac death. Life-threatening events occurred more often in those with genetic variants than those without (5/40 vs. 0/44, P = 0.021); particularly, the hERG or SCN5A gene mutations/polymorphisms (2/5 vs. 3/79, P = 0.027 and 5/27 vs. 0/57, P = 0.003, respectively). Among the five patients with life-threatening events, three had compound variants (hERG p.M645R/SCN5A p.R1193Q, hERG p.K897T/SCN5A p.H558R, and KVLQT1 p.G645S/SCN5A p.P1090L), that also increased the risk of events. Their QTc and JTc were all prolonged. Functional study of the novel variant (hERG gene p.M645R) from patients with life-threatening events revealed a dominant negative effect. In conclusion, in repaired TOF patients, coexisting long QT mutations/polymorphisms might have additive effects on the repolarization abnormality from surgery and thereby increase the risks of life-threatening events.
For patients with dry eye that has been controlled with tCSA twice daily for at least 1 year, decreasing to tCSA once daily may still allow suppression of the dry eye disease.
SiC devices are promising for outperforming Si counterparts in high-frequency applications due to its superior material properties. Conventional wirebonded packaging scheme has been one of the most preferred package structures for power modules. However, the technique limits the performance of a SiC power module due to parasitic inductance and heat dissipation issues that are inherent with aluminum wires. In this article, low parasitic inductance and high-efficient cooling interconnection techniques for Si power modules, which are the foundation of packaging methods of SiC ones, are reviewed first. Then, attempts on developing packaging techniques for SiC power modules are thoroughly overviewed. Finally, scientific challenges in the packaging of SiC power module are summarized.
Background Enhanced neural plasticity early after stroke suggests the potential to improve outcomes with intensive rehabilitation therapy. Most patients do not get such therapy, however, due to limited access, changing rehabilitation therapy settings, low therapy doses, and poor compliance. Objective To examine the feasibility, safety, and potential efficacy of an established telerehabilitation (TR) program after stroke initiated during admission to an inpatient rehabilitation facility (IRF) and completed in the patient’s home. Methods Participants with hemiparetic stroke admitted to an IRF received daily TR targeting arm motor function in addition to usual care. Treatment consisted of 36, 70-minute sessions (half supervised by a licensed therapist via videoconference), over a 6-week period, that included functional games, exercise videos, education, and daily assessments. Results Sixteen participants of 19 allocated completed the intervention (age 61.3 ± 9.4 years; 6 female; baseline Upper Extremity Fugl–Meyer [UEFM] score 35.9 ± 6.4 points, mean ± SD; NIHSS score 4 (3.75, 5.25), median, IQR; intervention commenced 28.3 ± 13.0 days post-stroke). Compliance was 100%, retention 84%, and patient satisfaction 93%; 2 patients developed COVID-19 and continued TR. Post-intervention UEFM improvement was 18.1 ± 10.9 points ( P < .0001); Box and Blocks, 22.4 ± 9.8 blocks ( P = .0001). Digital motor assessments, acquired daily in the home, were concordant with these gains. The dose of rehabilitation therapy received as usual care during this 6-week interval was 33.9 ± 20.3 hours; adding TR more than doubled this to 73.6 ± 21.8 hours ( P < .0001). Patients enrolled in Philadelphia could be treated remotely by therapists in Los Angeles. Conclusions These results support feasibility, safety, and potential efficacy of providing intense TR therapy early after stroke. Clinical Trial Registration: clinicaltrials.gov; NCT04657770
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