Role Of Hcy Research Articles

The Imbalance of Homocysteine, Vitamin B12 and Folic Acid in Parkinson Plus Syndromes: A Review beyond Parkinson Disease.

While there is a link between homocysteine (Hcy), B12 and folic acid and neurodegeneration, especially in disorders like Parkinson's and Alzheimer's diseases, its role in Parkinson plus syndromes (PPS) has only been partially investigated. It appears that elevated Hcy, along with an imbalance of its essential vitamin cofactors, are both implicated in the development and progression of parkinsonian syndromes, which represent different disease pathologies, namely alpha-synucleinopathies and tauopathies. Attributing a potential pathogenetic role in hyperhomocysteinemia would be crucial in terms of improving the diagnostic and prognostic accuracy of these syndromes and also for providing a new target for possible therapeutic intervention. The scope of this review is to focus on vitamin imbalance in PPS, with a special emphasis on the role of Hcy, B12 and folic acid in the neurodegenerative process and their implication in the therapeutic approach of these disorders.

Breaking Down Barriers: the Role of HCI in Bridging the Digital Divide

Breaking Down Barriers: the Role of HCI in Bridging the Digital Divide

Effects of New Antiepileptic Drugs on Homocysteine in Epileptic Patients: A Systematic Review and Meta-Analysis

Background. Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and new antiepileptic drugs (AEDs). In this meta-analysis, we aimed to assess the effects of new AEDs on Hcy. Methods. PubMed, Embase, Cochrane, and Web of Science databases were searched from inception to June 2022 for articles that focused on the effects of new AEDs on Hcy. A meta-analysis was performed using Stata 16.0 software. The results were presented as the mean difference (MD) and corresponding to 95% confidence intervals (CIs) comparing epileptic patients with new AEDs to the control subjects. Results. A total of 11 studies were included in the meta-analysis. Hcy was markedly increased in the new AEDs group compared with the control group (MD = 2.220, 95% CI: 0.596–3.844, P = 0.007 ), with a high degree of heterogeneity (I2 = 99.5%). In the drugs subgroup, the oxcarbazepine (OXC) (MD = 2.30, 95% CI: −1.11–5.72, P = 0.187 ) and lamotrigine (LTG) (MD = 1.14, 95% CI: −0.209–2.482, P < 0.001 ) groups had no significant differences when compared with the control group. The levetiracetam (LEV) (MD = 1.81, 95% CI: 1.03–2.18, P < 0.001 ) and topiramate (TPM) (MD = 6.922, 95% CI: 0.788–13.055, P = 0.027 ) groups were significantly higher than the control group. Conclusions. The new AEDs, especially TPM and LEV, may increase the plasma of Hcy. The role of Hcy in patients with epilepsy who are given TPM and LEV should not be ignored in clinical situations. Patients with epilepsy who also have a high-risk vascular profile are recommended to use OXC and LTG.

Clinical implication of homocysteine in premature acute coronary syndrome female patients: Its distribution and association with clinical characteristics and major adverse cardiovascular events risk.

Homocysteine (Hcy) is a risk factor for the presence of atherosclerotic vascular disease and hypercoagulability states, which is associated with increased risk of cardiovascular events in cardiovascular disease patients. Whereas the role of Hcy in premature acute coronary syndrome (ACS) female patients is still obscure. Hence, we aimed to explore the relationship of Hcy with clinical features, and more importantly, to probe its predictive value for major adverse cardiovascular events (MACE) risk in premature ACS female patients.By retrospectively reviewing the medical charts of 1441 premature ACS female patients, we collected patients’ Hcy level (at diagnosis) and other clinical data. According to the follow-up records, the accumulating MACE occurrence was calculated.Hcy presented with a skewed distribution with median value 11.3 μmol/L (range: 4.4–64.0 μmol/L, inter quartile: 9.2–14.1 μmol/L). Hcy was associated with older age, heavy body mass index, dysregulated liver/renal/cardiac indexes, hypertension history, and old myocardial infarction history. The 1-year, 3-year, 5-year MACE incidence was 2.9%, 10.7%, and 12.6%, respectively. Interestingly, Hcy was increased in 1-year MACE patients compared with 1-year non-MACE patients, in 3-year MACE patients compared with 3-year non-MACE patients, in 5-year MACE patients compared with 5-year non-MACE patients, and it had a good value for predicting 1-year/3-year/5-year MACE risk. Furthermore, Hcy was also correlated with increased accumulating MACE occurrence.Hcy associates with increased age and body mass index, dysregulated liver, renal, and cardiac indexes; more interestingly, it predicts increased MACE risk in premature ACS female patients.

Chatbot personality preferences in Global South urban English speakers

Recent years have seen a major shift in focus when it comes to chatbot literature, moving from only considering their technical capacities to emphasizing their social and conversational abilities, as well as personality. This shift towards the more social end of the AI research spectrum possibly occurred as a response to social interface theory, which suggests that humans respond to technologically mediated communication in the same way as they respond to interactions with natural partners (i.e. other human beings), since both interactions are social in nature. Given this, many prominent personalities in the sphere of chatbots and artificial intelligence have wondered if personality may play as important of a role in HCI as it does in social relations. To that effect, two studies were carried out in the Global South, on a largely South Asian demographic to see if personality does influence user experiences with reference to enterprise chatbots across three domains: likelihood of re-engagement, comfort levels and estimation of productivity and efficiency. Three key personality types were developed using the Five Factor Model and IBM’s Primary and Secondary Characteristics Table, labelled Transactional, Prosocial and Friendly. The first study involved having participants interact with the three chatbot personalities and then rate themacross the aforementioned domains, while the second study had participants view interactions with the different chatbot personality and provide reviews. The results strongly suggest that inserting an evident, fun personality into the chatbot can influence user experience across these domains. • Friendly chatbot personalities have the highest median ratings for likelihood of re-interaction. • Positive perception of friendly chatbot personality attributed to how anthropomorphic the interaction appears. • Preference for friendly personality constant across use-cases and demographics. • Significant difference between user ratings for transactional, prosocial and friendly personalities across domains.

Homocysteine and diabetes: Role in macrovascular and microvascular complications.

Diabetes mellitus (DM) can lead to the development of macro- and microvascular complications. Homocysteine (Hcy) may play a role in the development of cardiovascular (CV) diseases (CVDs). The role of Hcy in the development of the vascular complications associated with DM is not clearly defined. Despite a strong initial assumption regarding the importance of Hcy in DM and its complications, over time "enthusiasm has waned" because several studies showed unconvincing and occasionally contradictory results. A universal conclusion is not easy to draw given the diversity of studies (e.g. number of patients, design, folic acid and vitamin B status, ethnic differences, genetic background). For some complications, most results encourages further investigation. Impaired renal function is a major independent determinant of high total Hcy (tHcy) levels. However, the role of hyperhomocysteinaemia (HHcy) in the development of diabetic kidney disease (DKD) has yet to be determined. Hcy-lowering therapies can significantly decrease Hcy levels but their effects on CVD risk reduction are conflicting. Further studies are needed to determine the influence of Hcy-lowering therapy on CVD risk reduction, especially in patients with DM.

Serum Homocysteine Is Associated With HDL Only in Stroke Patients With Small Vessel Occlusion.

Background: Although controversial, homocysteine (Hcy) and lipid parameters have been associated with particular stroke subtypes. However, there are limited studies concerning the relationship between Hcy and lipid levels in acute ischemic stroke (AIS). We evaluated the impact of Hcy levels on lipid profiles in terms of specific stroke subtypes.Methods: A total of 2,324 patients with first-ever AIS were recruited from two hospitals in South Korea. The exclusion criteria were as follows: (a) pre-stroke modified Rankin scale (mRS) ≥ 1, (b) undetermined or other stroke etiology, and (c) absence of Hcy data. Among the 1,580 eligible patients, the Hcy level was divided into tertile groups. Logistic regression was used to assess association of Hcy levels with lipid levels by stroke subtypes.Results: Significant downward trends in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were only observed in patients with small vessel occlusion (SVO) as Hcy increased. In logistic regression analysis, while in patients with SVO subtype, the highest level of Hcy tertiles (OR = 1.648, 95% CI = 1.047–2.594) was associated with the lower HDL level (≤40 mg/dL), the significance disappeared in patients with LAA and CE subtypes.Conclusion: Although our study does not demonstrate causal relationship, we suggest that Hcy might play a mediating role between HDL and SVO stroke development. To clarify the role of Hcy on AIS, this study will provide academic support for designing future research.

Inbodied interaction design example

The sense of smell has long played a minor role in HCI [1]. However, its somewhat limited use could be transformed through an inbodied interaction approach that leverages the physiology of smell—specifically, the possibilities to combine the cogitate, sleep, and eat areas of the in5 model (see article on tuning in this section) to yield benefits, from health to performance.

Homocysteine and psoriasis.

Psoriasis is caused by a complex interplay among the immune system, genetic background, autoantigens, and environmental factors. Recent studies have demonstrated that patients with psoriasis have a significantly higher serum homocysteine (Hcy) level and a higher prevalence of hyperhomocysteinaemia (HHcy). Insufficiency of folic acid and vitamin B12 can be a cause of HHcy in psoriasis. Hcy may promote the immuno-inflammatory process in the pathogenesis of psoriasis by activating Th1 and Th17 cells and neutrophils, while suppressing regulatory T cells. Moreover, Hcy can drive the immuno-inflammatory process by enhancing the production of the pro-inflammatory cytokines in related to psoriasis. Hcy can induce nuclear factor kappa B activation, which is critical in the immunopathogenesis of psoriasis. There may be a link between the oxidative stress state in psoriasis and the effect of HHcy. Hydrogen sulfide (H2S) may play a protective role in the pathogenesis of psoriasis and the deficiency of H2S in psoriasis may be caused by HHcy. As the role of Hcy in the pathogenesis of psoriasis is most likely established, Hcy can be a potential therapeutic target for the treatment of psoriasis. Systemic folinate calcium, a folic acid derivative, and topical vitamin B12 have found to be effective in treating psoriasis.

The Role of HCI in the Age of AI

ABSTRACTThis article examines some of the mystique surrounding AI, including the interrelated notions of explainability and complexity, and argues that these notions suggest that designing human-centered AI is difficult. It explains how, once these are put aside, an HCI perspective can help define interaction between AI and users that can enhance rather than substitute one important aspect of human life: creativity. Key to developing such creative interactions are abstractions and grammars of action and other notions; the article explores the history of these in HCI and how they are to be used in the contemporary interaction and design space, in relation to AI. The article is programmatic rather than empirical though its argument uses real-world examples.

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407.

Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases peroxisome proliferator-activated receptor γ (PPARγ) levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals, which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu2+ and Zn2+, but this role of Hcy has not been established in relationship with obesity. It has been known for a while that PPARγ dysregulation results in various metabolic disorders including glucose and lipid metabolism. Recently, zinc finger protein 407 (Zfp407) is reported to regulate PPARγ target gene expression without affecting PPARγ transcript and protein levels by synergistically working with PPARγ. However, the mechanism(s) of this synergy, as well as other factors contributing to or inhibiting this synergism, have not been proven. This review suggests that Hcy contributes to pyroptosis, changes gut microbiome, and alters PPARγ-dependent mechanism(s) via Zfp407-mediated upregulated adipogenesis and misbalanced fatty acid metabolism, which can predispose to obesity and, consequently, obesity-related metabolic disorders.

Homocysteine Aggravates Intestinal Epithelial Barrier Dysfunction in Rats with Experimental Uremia

Background/Aims: Previous studies have shown that homocysteine (Hcy) is an important intestinal-derived uremic toxin. However, whether Hcy is involved in the epithelial barrier dysfunction observed in uremia remains unclear. This study aimed to investigate the effect of Hcy on intestinal permeability and intestinal barrier structure and function in adenine-induced uremic rats. Methods: Sprague-Dawley rats were divided into five groups: normal control (group NC), Hcy (group H), uremia (group U), uremia + Hcy (group UH), and uremia + Hcy + VSL#3 (group UHV). Experimental uremia was induced by intragastric adenine administration, and Hcy was injected subcutaneously. The animal models were assessed for renal function and pathological tissue staining. The pathological changes of intestinal tissue were observed by hematoxylin and eosin staining and electron microscopy. The serum and intestinal tissue levels of Hcy, interleukin (IL)-6, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), and malondialdehyde (MDA) as well as serum endotoxin and intestinal permeability were assessed. The levels of the tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) were assessed by western blotting. Results: Blood analyses and renal pathology indicated that experimental uremia was induced successfully. Pathological damage to intestinal structure was most obvious in group UH. Serum and tissue Hcy, serum endotoxin, and intestinal permeability were significantly elevated in group UH. The protein levels of claudin-1, occludin, and ZO-1 were decreased to various degrees in group UH compared with groups NC, H, and U. The serum and tissue levels of IL-6, TNF-α, and MDA were significantly increased, while SOD activity was markedly decreased. Supplementation with the probiotic VSL#3 improved these parameters to various degrees and up-regulated the abundance of tight junction proteins, which indicated a role for Hcy in the increase of intestinal permeability and destruction of the epithelial barrier in uremia. Conclusion: Hcy aggravates the increase of intestinal permeability and destruction of the epithelial barrier by stimulating inflammatory and oxidative damage. Probiotic administration can ameliorate this damage by reducing the levels of Hcy-induced inflammation and oxidation.

Toward a More Secure HRIS: The Role of HCI and Unconscious Behavior

By design, human resource information systems (HRIS) hold confidential and sensitive information. Therefore, one needs to ensure the security of these systems from unintentional mistakes that may compromise such information. Current systems design and training procedures of HRIS unintentionally help reinforce unsecure behaviors that result in non-malicious security breaches. Measures to improve security through design and training may only occur by breaking the use/impact cycle that individuals have habitually formed. Using strong contexts and cues allow trainers to interrupt individuals’ habits. Then, they have the opportunity to enforce the repetition of the desired behavior. This paper introduces a model of habit formation from consumer behavior that one may apply to HRIS.

Introduction

With the rise of ubiquitous computing, the role of HCI and interaction design in making everyday futures is becoming ever more encompassing and profound. The articles in this Special Topic offer perspectives on how these implications might be researched, understood, and challenged.

Affective Modelling of Users in HCI Using EEG

Emotions have potential to play a role in HCI which is primarily dominated by cognitive measures. Human physiological communication channels are dominated by emotions. Emotion affects several human activities like communication, learning, decision making, cognition, perception etc. Further, as emotions are difficult to interpret and hard to measure, technologists and designers have been struggling to incorporate them in design and technology. On the other hand, advancement of technology has both necessitated and enabled us to understand emotions and put them to use in contexts like human computer interaction. This study reports an attempt to model emotions by means of electroencephalography (EEG). Video stimuli of four representative basic emotions based on Navarasa theory of Ancient Indian treatise called Natya Shastra were shown to participants and EEG data was collected. Power spectrum analysis of EEG signals associated with emotions was done. Further, the EEG analysis findings were compared with the subject's self-reports about their emotional states during the experiment. EEG results have shown significantly consistent frequency patterns across the brain lobes for a given emotion. This study suggests that human emotions can be modeled for use in HCI either as an affect assessment tool or for affect based intelligent interactions.

Association of homocysteine and inflammatory-related molecules in sickle cell anemia

Objective: Investigate the role of homocysteine (Hcy), Th17-related cytokines, and adhesion molecules in the inflammatory state seen in the sickle cell anemia (SCA).Methods: We studied the Hcy, interleukin (IL)-17, and transforming growth factor β (TGF-β) cytokine levels of 62 SCA patients, as well as the expression levels of inflammatory and endothelial activation markers.Results: We found significant associations between Hcy levels and increased expression of IL-17 and TGF-β among SCA patients, and a positive significant correlation between Hcy and soluble vascular cellular adhesion molecules (sVCAM). SCA individuals had raised IL-17 levels when compared with controls.Discussion: These results suggest a possible role of Hyc in the induction of TGF-β and IL-17. Other authors proposed that Hcy may contribute to the initiation and progression of vascular disease by monocyte activation, resulting in the secretion of cytokines that amplify the inflammatory response. The role of Hcy in cytokine production and oxidative stress in the endothelium may explain the increase of sVCAM expression and, the vascular activation currently described among the SCA individuals with the highest Hcy serum levels. The chronic inflammation was observed in hyperhomocysteinemic mice, with an increased expression of VCAM-1 and plasma levels of tumor necrosis factor-alpha, showing an association of this inflammatory molecule and vascular changes.Conclusion: Our findings suggest that the increased levels of IL-17,Hcy and sVCAM contributes contributes to the vascular inflammation and activation presented by SCA patients, which probably have an important role in vaso-occlusion. On the basis of the presented data, IL-17 and Hcy might be considered as important components in the pathogenesis of SCA.

PP02.3 – 2478: Hyperhomocysteinemia and MTHFR polymorphisms as antenatal risk factors of white matter abnormalities in two cohorts of late preterm and full term newborns

Objective High plasma homocysteine (Hcy) levels and, C677T and A1298C MTHFR polymorphysms, have been reported in preterm or full term newborns with neonatal encephalopathy following an hypoxic-ischemic insult. Beyond the well-defined pattern of white matter injury such as periventricular leukomalacia, several qualitative neonatal white matter abnormalities (WMA) may account for different degrees of neurobehavioral impairment at long-term observation, either in very preterm or full term infants. Environmental factors may contribute to WMA. We assessed the causal role of Hcy and MTHFR polymorphisms together with acquired risk factors on the occurrence of WMA detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. Methods Newborn infants were recruited at the Intensive Care Unit of University Hospital of Messina. Antenatal, perinatal and neonatal details were obtained. Hcy levels were assessed in whole blood within the first week of life. The assessment of C677T and A1298C MTHFR genotypes was carried out. Cerebral ultrasound was performed to all newborns from 1 to 3 days of life and 44 postmenstrual age. Results 171 newborns (81 M, 47.4%), 45 (26.3%) born Conclusion Hcy and MTHFR polymorphisms significantly predisposed to WMA, either full-term or late preterm newborns, in our study. However, WMA was also significantly associated to acquired factors as GA and perinatal status, measured by Apgar scores. The role of A1298C polymorphism might be taken into account for prenatal assessment and treatment counseling.

Effect of B vitamin (folate, B6, and B12) supplementation on osteoporotic fracture and bone turnover markers: a meta-analysis.

BackgroundB vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies.Material/MethodsRelevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation.ResultsBased on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover.ConclusionsB vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future.

Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson’s disease

Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial. The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A). A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging, and the Schwab-England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1). The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41-0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 μmol/l) as compared with the controls (14.0±9.6 μmol/l, P=10(-8)) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients. The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

Homocysteine as a Risk Factor for Atherosclerosis: Is Its Conversion toS-Adenosyl-L-Homocysteine the Key to Deregulated Lipid Metabolism?

Homocysteine (Hcy) has been recognized for the past five decades as a risk factor for atherosclerosis. However, the role of Hcy in the pathological changes associated with atherosclerosis as well as the pathological mechanisms triggered by Hcy accumulation is poorly understood. Due to the reversal of the physiological direction of the reaction catalyzed by S-adenosyl-L-homocysteine hydrolase Hcy accumulation leads to the synthesis of S-adenosyl-L-homocysteine (AdoHcy). AdoHcy is a strong product inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases, and to date more than 50 AdoMet-dependent methyltransferases that methylate a broad spectrum of cellular compounds including nucleic acids, proteins and lipids have been identified. Phospholipid methylation is the major consumer of AdoMet, both in mammals and in yeast. AdoHcy accumulation induced either by Hcy supplementation or due to S-adenosyl-L-homocysteine hydrolase deficiency results in inhibition of phospholipid methylation in yeast. Moreover, yeast cells accumulating AdoHcy also massively accumulate triacylglycerols (TAG). Similarly, Hcy supplementation was shown to lead to increased TAG and sterol synthesis as well as to the induction of the unfolded protein response (UPR) in mammalian cells. In this review a model of deregulation of lipid metabolism in response to accumulation of AdoHcy in Hcy-associated pathology is proposed.