314 research outputs found
Wild-type HTT modulates the enzymatic activity of the neuronal palmitoyl transferase HIP14
No full textHuntington disease (HD) is caused by polyglutamine expansion in the huntingtin (HTT) protein. Huntingtin-interacting protein 14 (HIP14), one of 23 DHHC domain-containing palmitoyl acyl transferases (PATs), binds to HTT and robustly palmitoylates HTT at cysteine 214. Mutant HTT exhibits reduced palmitoylation and interaction with HIP14, contributing to the neuronal dysfunction associated with HD. In this study, we confirmed that, among 23 DHHC PATs, HIP14 and its homolog DHHC-13 (HIP14L) are the two major PATs that palmitoylate HTT. Wild-type HTT, in addition to serving as a palmitoylation substrate, also modulates the palmitoylation of HIP14 itself. In vivo , HIP14 palmitoylation is decreased in the brains of mice lacking one HTT allele ( hdh +/−) and is further reduced in mouse cortical neurons treated with HTT antisense oligos (HTT-ASO) that knockdown HTT expression by ∼95%. Previously, it has been shown that palmitoylation of DHHC proteins may affect their enzymatic activity. Indeed, palmitoylation of SNAP25 by HIP14 is potentiated in vitro in the presence of wild-type HTT. This influence of HTT on HIP14 activity is lost in the presence of CAG expansion. Furthermore, in both brains of hdh +/− mice and neurons treated with HTT-ASO, we observe a significant reduction in palmitoylation of endogenous SNAP25 and GluR1, synaptic proteins that are substrates of HIP14, suggesting wild-type HTT also influences HIP14 enzymatic activity in vivo . This study describes an important biochemical function for wild-type HTT modulation of HIP14 palmitoylation and its enzymatic activity.Peer reviewedfinal article publishe
Data Compensation with Gaussian Processes Regression: Application in Smart Building’s Sensor Network
No full textData play an essential role in the optimal control of smart buildings’ operation, especially in building energy-management for the target of nearly zero buildings. The building monitoring system is in charge of collecting and managing building data. However, device imperfections and failures of the monitoring system are likely to produce low-quality data, such as data loss and inconsistent data, which then seriously affect the control quality of the buildings. This paper proposes a new approach based on Gaussian process regression for data-quality monitoring and sensor network data compensation in smart buildings. The proposed method is proven to effectively detect and compensate for low-quality data thanks to the application of data analysis to the energy management monitoring system of a building model in Viet Nam. The research results provide a good opportunity to improve the efficiency of building energy-management systems and support the development of low-cost smart buildings
Depressive symptoms among elderly diabetic patients in Vietnam
No full textHuyen Thi Thanh Vu,1,2 Thanh Xuan Nguyen,2,3 Huong Thi Thu Nguyen,1,2 Tu Anh Le,4 Tam Ngoc Nguyen,1,2 Anh Trung Nguyen,2 Thu Thi Hoai Nguyen,1,2 Hoang Long Nguyen,5 Cuong Tat Nguyen,6 Bach Xuan Tran,7,8 Carl A Latkin,8 Thang Pham,2 Melvyn WB Zhang,9 Roger CM Ho10 1Department of Gerontology, Hanoi Medical University, Hanoi, Vietnam; 2National Geriatric Hospital, Hanoi, Vietnam; 3Dinh Tien Hoang Institute of Medicine, Hanoi, Vietnam; 4Department of Endocrinology, Nghe An Endocrinology Hospital, Nghe An, Vietnam; 5Center of Excellence in Behavioral Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 6Institute for Global Health Innovations, Duy Tan University, Da Nang, Vietnam; 7Department of Health Economics, Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam; 8Department of Health, Behavior and Society, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 9Biomedical Global Institute of Healthcare Research & Technology (BIGHEART), National University of Singapore, Singapore; 10Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Background and aims: Depression and diabetes are becoming increasingly prevalent within the Vietnamese elderly population. However, the linkage between these health conditions in the Vietnamese elderly has not yet been fully investigated. This study aimed to assess the level of depressive symptoms and associated factors among elderly diabetic patients.Methods: A cross-sectional study was conducted at National Geriatric Hospital in the elder patients aged ≥60 years with type 2 diabetes mellitus (T2DM). Depressive symptoms were assessed using the Geriatric Depression Scale, with three categories: normal (0–4 points), mild (5–9 points), and moderate/severe depressive symptoms (≥10 points). We obtained information on the patient’s sociodemographic, medical history, glycemic control (fasting plasma glucose and HbA1c), daily activities (activities of daily living [ADLs] and instruments activities of daily living [IADLs] scale), and fall risks (Time Up and Go test). Logistic regression was used to analyze the factors associated with the presence of depressive symptoms.Results: Among 412 patients, 236 (57.3%) had HbA1c level at 7.0% or higher. There were 327 (79.4%) patients having depressive symptoms. The level of HbA1c was significantly different between the depressive symptom group and the non-depressive symptom group (7.74% and 6.61%, P<0.05). The increased likelihood of having depressive symptoms was associated with having risk of falls (OR: 5.50; 95% CI: 1.88–16.11), suffering from 5–10 years of diabetes (OR: 2.74, 95% CI: 1.28–5.85), uncontrolled fasting plasma glucose (OR: 4.06, 95% CI: 1.81–9.12), and an impairment of IADLs (OR: 5.74, 95% CI: 2.24–14.7).Conclusion: This study highlights a high prevalence of depressive symptoms among elderly T2DM patients in Vietnam, suggesting an urgent need for screening depressive symptoms and providing mental health care services to this population promptly, particularly to those suffering from diabetes for a long period of time or co-functional impairments. Keywords: elder, depressive symptoms, diabetes, Vietna
Individual and Occupational Differences in Perceived Organisational Culture of a Central Hospital in Vietnam
No full textMany hospitals in developing countries, including Vietnam, are facing the challenges of increasingly noncommunicable diseases and the financial autonomy policy from the government. To adapt to this new context requires understanding and changing the current organisational culture of the hospitals. However, little has been known about this in resource-constrained healthcare settings. The objectives of this study were to examine the four characteristics of the organisational culture and test selected individual and occupational differences in the organisational culture of a Vietnam central hospital. In a cross-sectional study using the Organisation Culture Assessment Instrument (OCAI) with the Competing Value Framework (CVF), including 4 factors, Clan, Adhocracy, Hierarchy, and Market, health workers currently working at Quang Nam General Hospital were interviewed. The results indicated the current cultural model was more internally focused with two dominant cultures, Clan and Hierarchy, while, for the desired model, the Clan culture was the most expected one. Comparing between the current and desired pattern, the down trend was found for all types of culture, except the Clan culture, and there were significant differences by domains of organisational culture. Furthermore, the current and desired models were differently distributed by key individual characteristics. These differences have raised a number of interesting directions for future research. They also suggest that, to build a hospital organisational culture to suit both current and future contexts as per employees' assessment and expectation, it is important to take individual and institutional variations into account.Full Tex
Mutations in the gyrA, parC, and mexR genes provide functional insights into the fluoroquinolone-resistant Pseudomonas aeruginosa isolated in Vietnam
No full textKinh Van Nguyen,1,2,* Trung Vu Nguyen,1,3,* Hang Thi Thuy Nguyen,4 Duyet Van Le1 1Clinical Laboratories, National Hospital for Tropical Diseases, 2Infectious Department, Hanoi Medical University, 3Microbiology Department, Hanoi Medical University, 4Department of Microbiology, National Geriatric Hospital, Hanoi, Vietnam *These authors contributed equally to this work Introduction: Pseudomonas aeruginosa has many mechanisms of resistance to fluoroquinolones. The main mechanism is to change the effect of two enzymes that open the DNA helix – the enzyme DNA gyrase (gyrA) and the topoisomerase IV (parC). In addition, mutations that render the MexAB-oprM pump (mexR) dysfunctional, leading to its overexpression, also enhance resistance to fluoroquinolones. In this study, we aim to detect point mutations of gyrA, parC, and mexR genes that are predicted to be associated with fluoroquinolone resistance in 141 fluoroquinolone-resistant clinical isolates of P. aeruginosa isolated in Vietnam during 2013–2016.Methods: We tested minimum inhibitory concentrations (MICs) of fluoroquinolone antibiotics in 141 clinical isolates of P. aeruginosa using the VITEK 2 Compact System, followed by PCR assay, to detect and clone the fluoroquinolone resistance-determining region (FRDR) of gyrA, parC, and mexR. Point mutations were analyzed through Sanger sequencing, and the correlation between genetic mutations and phenotypic resistance of 141 clinical isolates was undertaken.Results: Fluoroquinolone-resistant substitution mutations such as Ile for Thr83 and Met for Thr133 in gyrA, Leu for Ser87 in parC, and Val for Glu126 in the repressor of mexR were mainly detected. Comparative analytical data indicated that amino acid alterations within the gyrA and parC genes are highly associated with resistance to ciprofloxacin (CIP) and levofloxacin (LEV) in the isolates, whereas alterations in the efflux regulatory mexR gene are not highly consistent with resistance in these isolates. Moreover, fluoroquinolone-resistant clinical isolates of P. aeruginosa were mainly isolated from pus and sputum specimens.Conclusion: In clinical isolates of P. aeruginosa, a high correlation was observed between MICs of CIP and LEV and alterations in gyrA and parC genes. However, mutations occurring in mexR did not highly correlate with the antibiotic resistance of the bacterium. Keywords: fluoroquinolone-resistant Pseudomonas aeruginosa, fluoroquinolone resistance-determining region, FRDR, mutation, gyrA, parC, mex
Mechanisms of aberrant HTT splicing and its implications on RNA homeostasis in Huntington’s disease
No full textHuntington disease (HD) is an autosomal dominant monogenic neurological disorder. The elongation of the CAG repeat in exon 1 of huntingtin (HTT) leads to the production of a short novel HTT isoform called HTT1a. HTT1a is a functional polyadenylated mRNA that contains the sequences of HTT exon 1 and a part of intron 1. Both the HTT1a mRNA as well as the encoded HTT exon 1 protein are known to be toxic. The generation of HTT1a is CAG repeat length dependent but the exact mechanism leading to HTT1a production remains unknown. In addition, it is unclear whether there is a tissue specific expression profile of HTT1a outside of the brain. Thus, a first approach in this study was to detect HTT1a in several different tissues and cell types. In addition to the involvement of the splicing machinery also regulators of transcription like R-loops and epigenetic modifications could contribute to the generation of HTT1a. Therefore, the involvement of DNA methylation, histone H3K27 trimethylations and R-loops at the HTT1a genomic region was analysed. The role of R-loops and epigenetics is not only interesting with regards to the production of HTT1a but also general transcriptional dysregulation in HD. Hence, the genome wide distribution of differentially methylated regions (DMRs), H3K27me3 marks and R-loops was investigated. For the detection of the HTT1a transcript in human peripheral tissues and brain a highly sensitive digital PCR (dPCR) assay was established. The analysis of transcriptional changes, epigenetics and R-loops was performed in primary human fibroblasts derived from healthy controls, adult onset and juvenile onset HD patients. Amplification-free, long read Nanopore sequencing was used for the analysis of the transcriptome and methylome. R-loops and H3K27me3 were detected by the novel method Cleavage under targets and tagmentation (CUT&Tag). Using dPCR, the HTT1a transcript could be detected not only in human post-mortem tissue in several brain regions but also in human muscle tissue, peripheral blood mononuclear cells (PBMCs) and fibroblasts. A significant, positive linear correlation between the expression levels of HTT1a and the CAG repeat length was found in the motor cortex and in PBMCs. Consequently, the measurement of HTT1a levels in easily accessible PBMCs could be a feasible biomarker in studies aiming at HTT lowering. The analysis of DNA methylation, H3K27me3 and R-loops in HTT exon 1 and intron 1 resulted in no significant differences neither between control and adult onset nor control and juvenile onset HD human fibroblasts. Based on the data obtained, the effect of the studied epigenetic factors on the generation of HTT1a in fibroblasts could not be clarified. However, fibroblasts are much less affected by transcriptional and possibly also epigenetic changes in HD than neurons and therefore these factors may well play a role in the generation of HTT1a in neuronal cells. On the genome wide level, the biggest differences in the transcriptome, epigenome and R-loops were found between control and juvenile onset HD fibroblasts. In contrast, HD mutation state was associated with fewer significant differences in the transcriptome, epigenome and R-loops. This was most likely due to the distinct findings in adult and juvenile onset HD fibroblasts. Overall, the number of significant differentially expressed genes or enriched epigenetic/R-loop regions was low. Only a few genes were identified that had a significant differentially enriched region of more than one type. Moreover, the overlap of genes with significant differentially enriched epigenetic or R-loop regions and differentially expressed genes was low. Nevertheless, TBX5 which was found to be significantly upregulated on the transcript level in juvenile onset HD fibroblasts also
showed reduced H3K27me3 and DNA methylation, an epigenetic state associated with active transcription, at its transcription start site. TBX5, encoding T-box binding transcription
factor 5, is interacting with transcription factors involved in HD pathogenesis. Consequently, TBX5 might be an interesting candidate to study in the context of transcriptional dysregulation in HD. The gene ontology and pathway enrichment analysis of the differentially expressed genes and genes containing at least one DMR or differential H3K27me3 region or R-loop resulted in multiple inconclusive pathways and processes. However, SUZ12 and EZH2 were identified as potential regulators in all juvenile HD onset gene sets. This is especially interesting as they are both part of the polycomb repressive complex 2, which is discussed to play a role in transcriptional dysregulation in HD. To sum up, in this work the CAG length dependent expression of HTT1a in PBMCs was shown which implies the assessment of HTT1a as potential future biomarker in clinical HD studies. Additionally, this study could further broaden the knowledge about transcriptional dysregulation in HD by analysing genome wide changes in epigenetic marks and R-loops
Patients versus healthy controls; 5-HTT genotype distribution.
No full text<p><sup>a</sup> Pearson Chi-square test</p><p>Patients versus healthy controls; 5-HTT genotype distribution.</p
The impact of frailty on prolonged hospitalization and mortality in elderly inpatients in Vietnam: a comparison between the frailty phenotype and the Reported Edmonton Frail Scale
No full textAnh Trung Nguyen,1,2 Thanh Xuan Nguyen,1,2 Tu N Nguyen,1,3 Thu Hoai Thi Nguyen,1,2,4 Thang Pham,1,2 Robert Cumming,5 Sarah N Hilmer,6 Huyen Thi Thanh Vu1,2 1The National Geriatric Hospital, Hanoi, Vietnam; 2Department of Geriatrics and Gerontology, Hanoi Medical University, Hanoi, Vietnam; 3Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; 4Dinh Tien Hoang Institute of Medicine, Hanoi, Vietnam; 5Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia; 6Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia Aims: To investigate the impact of frailty on outcomes in older hospitalized patients, including prolonged length of stay and all-cause mortality 6 months after admission, using both the frailty phenotype and the Reported Edmonton Frail Scale (REFS).Patients and methods: This study is the follow-up phase of a study designed to investigate the prevalence of frailty and its impact on adverse outcomes in older hospitalized patients at the National Geriatric Hospital in Hanoi, Vietnam.Results: A total of 461 participants were included, with a mean age 76.2±8.9 years, and 56.8% were female. The prevalence of frailty was 31.9% according to the REFS and 35.4% according to Fried’s criteria. The kappa coefficient was 0.57 (95% CI =0.49–0.66) between the two frailty criteria in identifying frail and non-frail participants. There was a trend toward increasing the likelihood of prolonged hospitalization in participants with frailty defined by Fried’s criteria (adjusted OR =1.49, 95% CI =0.94–2.35) or by REFS (adjusted OR =1.43, 95% CI =0.89–2.29). During 6 months of follow-up, 210 were lost and 18/251 (7.2%) participants died. Mortality was higher in those with frailty defined by either Fried’s criteria or REFS. On multivariable survival analysis, adjusted HRs for mortality were 2.65 (95% CI =1.02–6.89) for Fried’s criteria and 4.19 (95% CI =1.59–10.99) for REFS.Conclusion: Fried’s frailty phenotype or REFS can be used as a screening tool to detect frailty in older inpatients in Vietnam and predict mortality. Frailty screening can help prioritize targeted frailty-tailored treatments, such as nutrition, early mobility and medication review, for these vulnerable patients to improve clinical outcomes. Keywords: frailty, elderly, inpatients, Vietna
Role of polymorphisms in the 5-HTT promotor region.
No full text<p><b>A)</b> The 5-HTT short (S) allele consists of 14 repeats at 22 bp while the long (L) allele consists of 16 repeats and a possible A to G SNP. AP2 is a transcription inhibitor found to bind the sequence if a G substitution is present [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140883#pone.0140883.ref005" target="_blank">5</a>]. <b>B)</b> Five possible allele combinations ranged by their predicted rate of transcription. Frequency of the allele combinations in the Caucasian population: SS: 20%, SL<sub>G</sub>: 4%, L<sub>A</sub>L<sub>G</sub>: 5%, SL<sub>A</sub>: 41% and L<sub>A</sub>L<sub>A</sub>: 26% [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140883#pone.0140883.ref006" target="_blank">6</a>]. A: adenosine, G: guanosine, AP2: activating enhancer-binding protein. <b>C)</b> 5-HTT mRNA in blood in the CFS patients.</p
Health-related quality of life in elderly diabetic outpatients in Vietnam
No full textHuong Thi Thu Nguyen,1,2 Mackenzie PI Moir,3 Thanh Xuan Nguyen,2,4 Anh Phuong Vu,5 Long Hoang Luong,2,4 Tam Ngoc Nguyen,1,2 Long Hoang Nguyen,6 Bach Xuan Tran,7,8 Tung Thanh Tran,9 Carl A Latkin,8 Melvyn WB Zhang,10 Roger CM Ho,11 Huyen Thanh Thi Vu1,2 1Department of Gerontology, Hanoi Medical University, Hanoi, Vietnam; 2National Geriatric Hospital, Hanoi, Vietnam; 3School of Public Health, University of Alberta, Edmonton, AB, Canada; 4Dinh Tien Hoang Institute of Medicine, Hanoi, Vietnam; 5Hanoi Medical University, Hanoi, Vietnam; 6School of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam; 7Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam; 8Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 9Institute for Global Health Innovations, Duy Tan University, Da Nang, Vietnam; 10Biomedical Global Institute of Healthcare Research & Technology (BIGHEART), National University of Singapore, Singapore; 11Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Background: Health-related quality of life (HRQoL) is an important indicator for designing care and treatment services for patients with diabetes. This is especially true given its rapid increase among the elderly population in Vietnam. HRQoL data in elderly diabetic Vietnamese are currently limited. This study aimed to 1) measure the HRQoL of elderly patients with type 2 diabetes (T2DM) in Vietnam and 2) identify related factors and their relationship with HRQoL. Patients and methods: A cross-sectional study was conducted. We recruited 171 patients aged ≥60 years with T2DM at the Outpatient Department, National Geriatric Hospital from June to November 2015. Patients were asked to evaluate their health status using the EuroQol Five Dimensions Three Levels (EQ-5D-3L) and the Visual Analog Scale (VAS). Sociodemographic, diabetic treatment, and management characteristics were collected. Multivariate Tobit regression was used to determine which factors were associated with HRQoL, and the strength of this relationship. Results: Patients reported some problems in all areas of the EQ-5D: pain/discomfort (50.9%), mobility (33.3%), anxiety/depression (24.0%), usual activities (21.1%), and self-care (10.5%). The mean EQ-5D index score was 0.80 (SD=0.20), and the mean EQ-VAS was 57.5 (SD=14.4). Patients who were male, lived in an urban area, could afford treatment, were taking fewer medications, and monitored blood pressure often (1–4 times a week) had a higher EQ-5D index when compared to other groups. Meanwhile, a longer duration of diabetes and older age were negatively associated with the EQ-5D index. Patients with any comorbidity had lower VAS scores than their counterparts. Conclusion: The presence of diabetes and comorbidity were responsible for a significant decrease in HRQoL. Screening and identifying health problems, providing prompt treatment, and facilitating self-management among patients have the potential to increase diabetic patients’ HRQoL. Keywords: elder, quality of life, diabetes, Vietna
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