RESUMO
This study aimed to evaluate whether genetic polymorphism is associated with an increased risk of infection, specifically post-stroke aspiration pneumonia. Blood samples were obtained from a total of 206 post-stroke participants (males, n = 136; mean age, 63.8 years). Genotyping was performed for catechol-O-methyltransferase (rs4680, rs165599), dopamine receptors (DRD1; rs4532, DRD2; rs1800497, DRD3; rs6280), brain-derived neurotrophic factor (rs6265), apolipoprotein E (rs429358, rs7412), and the interleukin-1 receptor antagonist gene (rs4251961). The subjects were stratified into two groups, aged < 65 (young) and ≥ 65 (elderly). Functional parameters and swallowing outcomes were measured at enrollment and at 3 months post-onset. The primary outcome was the incidence of aspiration pneumonia. Analysis of the association between genetic polymorphisms and aspiration pneumonia history showed that a minor C rs429358 allele was associated with the occurrence of aspiration pneumonia in the young group, both in the additive and the dominant models (odds ratio: 4.53; 95% CI: 1.60−12.84, p = 0.004). In the multivariable analysis, the minor C rs429358 allele increased the risk of post-stroke aspiration pneumonia in young stroke patients by 5.35 (95% CI: 1.64−20.88). In contrast, no such association was observed in the elderly group. Apolipoprotein E polymorphism may affect the risk of post-stroke aspiration pneumonia.
RESUMO
The Voice Handicap Index (VHI) is a patient-centered evaluation tool specifically designed for assessing voice-related quality of life. Although the VHI has been extensively used in patients with voice disorders, its applicability in stroke patients has not been fully established. This prospective cross-sectional study aimed to investigate the feasibility of using the VHI questionnaire in identifying stroke patients with voice problems. The study included a cohort of acute to subacute first-ever stroke patients (n = 48), with or without voice problems, as well as other non-stroke patients (n = 31) who agreed to complete the VHI questionnaire. Stroke patients with self-reported voice problems demonstrated significantly higher VHI scores and poorer life quality scores compared to the control groups. These patients also had lower Mini-Mental State Examination (MMSE), Modified Barthel Index (MBI), and Euro-QoL-5D-5L (EQ-5D-5L) scores. Spearman correlation analysis revealed an inverse association between VHI scores and EQ-5D-5L (rho = -0.77, p < 0.001), Korean Mann Assessment of Swallowing Ability (rho = -0.51, p < 0.001), and other functional parameters, including the National Institutes of Health Stroke Scale, MMSE, and MBI scores. Multiple regression analysis indicated that the VHI score was the biggest contributing factor to EQ scores. This is the first study to demonstrate that stroke patients with voice problems may experience reduced quality of life, even after controlling for other confounding factors such as dysphagia or neurological deficits. Future studies are needed whether addressing these issues by implementing the VHI may facilitate the improvement of patients' quality of life.
RESUMO
Transcranial direct current stimulation (tDCS) is one of the latest post-stroke dysphagia treatment modalities, and the effect of tDCS is known to be affected by various factors including genetic polymorphisms. However, the role of catechol-O-methyltransferase (COMT) polymorphisms on tDCS in swallowing is unclear. In this prospective pilot study, we aim to explore the effect of tDCS on the swallowing cortex and subsequent swallowing motor function according to COMT polymorphism. Twenty-four healthy participants received either anodal tDCS or sham mode tDCS on the mylohyoid motor cortex at random order, after inhibitory repetitive transcranial magnetic stimulation (rTMS) for preconditioning. The primary outcome was the changes of mylohyoid-motor-evoked potentials (MH-MEP) amplitude in each COMT polymorphism group, from the post-inhibitory rTMS baseline state to immediate, 30, and 60 min after tDCS. The secondary outcomes were the changes in swallowing function. The results showed that COMT Val/Val polymorphism showed improvement across time in the MH-MEP amplitudes and triggering time of swallowing after tDCS, whereas COMT Met carrier group did not show significant changes of MH-MEP or swallowing function across time. This therapeutic response variability of tDCS in the mylohyoid motor system according to COMT polymorphism support the importance of genetic analysis in individualized dysphagia treatment.
RESUMO
Background Arginase II activity contributes to reciprocal regulation of endothelial nitric oxide synthase ( eNOS ). We tested the hypotheses that arginase II activity participates in the regulation of Ca2+/Ca2+/calmodulin-dependent kinase II / eNOS activation, and this process is dependent on mitochondrial p32. Methods and Results Downregulation of arginase II increased the concentration of cytosolic Ca2+ ([Ca2+]c) and decreased mitochondrial Ca2+ ([Ca2+]m) in microscopic and fluorescence-activated cell sorting analyses, resulting in augmented eNOS Ser1177 phosphorylation and decreased eNOS Thr495 phosphorylation through Ca2+/Ca2+/calmodulin-dependent kinase II . These changes were observed in human umbilical vein endothelial cells treated with small interfering RNA against p32 (sip32). Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, fluorescence immunoassay, and ion chromatography, inhibition of arginase II reduced the amount of spermine, a binding molecule, and the release of Ca2+ from p32. In addition, arginase II gene knockdown using small interfering RNA and knockout arginase II -null mice resulted in reduced p32 protein level. In the aortas of wild-type mice, small interfering RNA against p32 induced eNOS Ser1177 phosphorylation and enhanced NO -dependent vasorelaxation. Arginase activity, p32 protein expression, spermine amount, and [Ca2+]m were increased in the aortas from apolipoprotein E (ApoE-/-) mice fed a high-cholesterol diet, and intravenous administration of small interfering RNA against p32 restored Ca2+/Ca2+/calmodulin-dependent kinase II -dependent eNOS Ser1177 phosphorylation and improved endothelial dysfunction. The effects of arginase II downregulation were not associated with elevated NO production when tested in aortic endothelia from eNOS knockout mice. Conclusions These data demonstrate a novel function of arginase II in regulation of Ca2+-dependent eNOS phosphorylation. This novel mechanism drives arginase activation, mitochondrial dysfunction, endothelial dysfunction, and atherogenesis.