Displaying publications 1181 - 1200 of 5421 in total

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  1. Hussein EA, Hair-Bejo M, Liew PS, Adamu L, Omar AR, Arshad SS, et al.
    Microb Pathog, 2019 Apr;129:195-205.
    PMID: 30738178 DOI: 10.1016/j.micpath.2019.01.049
    Infectious bursal disease is one of an OIE list of notifiable diseases. Chicken is the only host that manifests clinical signs and its pathogenicity is correlated with the distribution of antigens in organs. This study was conducted to determine disease pathogenesis and virus tissue tropism by in situ PCR, immunoperoxidase staining (IPS), and HE staining. Twenty four chickens were infected with very virulent Infectious Bursal Disease Virus (vvIBDV). Fifteen chickens were kept as a control group. Infected chickens were sacrificed at hrs 2, 4, 6, 12, days 1, 2, 4, and 6 post-inoculation (pi). While, control chickens were euthanized on days 0, 1, 2, 4, and 6 pi. Different tissues were collected, fixed in 10% buffered formalin, and processed. At hr 2 pi, virus was detected in intestinal, junction of the proventriculus and gizzard, cecal tonsil, liver, kidney, and bursa of Fabricius. At hr 4 pi, virus reached spleen, and at hr 6 pi, it entered thymus. At hr 12 pi, virus concentration increased in positive tissues. The latest invaded tissue was muscle on day 1 pi. Secondary viraemia occurred during 12-24 h pi. In situ PCR was the most sensitive technique to highlight obscure points of infection in this study.
    Matched MeSH terms: Infectious bursal disease virus/pathogenicity*; Infectious bursal disease virus/physiology*
  2. Kelly AM, Keijzers G, Klim S, Craig S, Kuan WS, Holdgate A, et al.
    Age Ageing, 2021 01 08;50(1):252-257.
    PMID: 32997140 DOI: 10.1093/ageing/afaa121
    OBJECTIVES: To describe the epidemiology and outcomes of non-traumatic dyspnoea in patients aged 75 years or older presenting to emergency departments (EDs) in the Asia-Pacific region.

    METHODS: A substudy of a prospective interrupted time series cohort study conducted at three time points in EDs in Australia, New Zealand, Singapore, Hong Kong and Malaysia of patients presenting to the ED with dyspnoea as a main symptom. Data were collected over three 72-h periods and included demographics, co-morbidities, mode of arrival, usual medications, ED investigations and treatment, ED diagnosis and disposition, and outcome. The primary outcomes of interest are the epidemiology and outcome of patients aged 75 years or older presenting to the ED with dyspnoea.

    RESULTS: 1097 patients were included. Older patients with dyspnoea made up 1.8% [95% confidence interval (CI) 1.7-1.9%] of ED presentations. The most common diagnoses were heart failure (25.3%), lower respiratory tract infection (25.2%) and chronic obstructive pulmonary disease (17.6%). Hospital ward admission was required for 82.6% (95% CI 80.2-84.7%), with 2.5% (95% CI 1.7-3.6%) requiring intensive care unit (ICU) admission. In-hospital mortality was 7.9% (95% CI 6.3-9.7%). Median length of stay was 5 days (interquartile range 2-8 days).

    CONCLUSION: Older patients with dyspnoea make up a significant proportion of ED case load, and have a high admission rate and significant mortality. Exacerbations or worsening of pre-existing chronic disease account for a large proportion of cases which may be amenable to improved chronic disease management.

    Matched MeSH terms: Chronic Disease; Disease Management; Pulmonary Disease, Chronic Obstructive
  3. Prathap K, Montgomery GL
    Pathology, 1974 Jul;6(3):255-61.
    PMID: 4412062
    Matched MeSH terms: Coronary Disease/epidemiology*; Coronary Disease/pathology
  4. Rahimi R, Singh MKC, Noor NM, Omar E, Noor SM, Mahmood MS, et al.
    J Atheroscler Thromb, 2018 May 01;25(5):405-409.
    PMID: 29118310 DOI: 10.5551/jat.39107
    AIMS: The present study aimed to determine the epidemiological aspects of medico-legal autopsies and manifestation of coronary atherosclerosis.

    METHODS: This was a cross sectional study involving 222 cases recruited from National Institute of Forensic Medicine (NIFM) Hospital Kuala Lumpur (HKL) and Department of Forensic Medicine Hospital Sungai Buloh (HSgB) for a period of 15 months, from December 2012 to April 2014. Sociodemographic and autopsy findings, including the cause and manner of death were documented.

    RESULTS: Male and female subjects aged 18-70 years were recruited. Males contributed to 86% of the total subjects and comprised 61% of young adults. Road traffic accidents were the primary cause of death, contributing almost 50% of the subjects. One third of the cases comprised of death due to natural causes, wherein almost 75% of the subjects within this category succumbed to sudden cardiac death. Coronary artery disease (CAD) contributed to 60% of the sudden cardiac death (SCD). Single and double-vessel diseases were the most common pattern of atherosclerosis. In almost 80% of CAD cases, atherosclerosis affected the left anterior descending artery (LAD).

    CONCLUSION: Cardiovascular diseases were the most significant natural cause of sudden death with a staggering figure of 75%. CAD was the single most commonly encountered pathology within the SCD. Most cases presented with single and double-vessel diseases, observed in all subjects, as well as the young adult population.

    Matched MeSH terms: Coronary Artery Disease/complications*; Coronary Artery Disease/mortality*
  5. Anwar F, Saleem U, Ahmad B, Ashraf M, Rehman AU, Froeyen M, et al.
    Comput Biol Chem, 2020 Dec;89:107378.
    PMID: 33002716 DOI: 10.1016/j.compbiolchem.2020.107378
    Neurodegenerative diseases have complex etiology and pose a challenge to scientists to develop simple and cost-effective synthetic compounds as potential drug candidates for such diseases. Here, we report an extension of our previously published in silico screening, where we selected four new compounds as AChE inhibitors. Further, based on favorable binding possess, MD simulation and MMGBSA, two most promising compounds (3a and 3b) were selected, keeping in view the ease of synthesis and cost-effectiveness. Due to the critical role of BChE, LOX and α-glucosidase in neurodegeneration, the selected compounds were also screened against these enzymes. The IC50 values of 3a against AChE and BChE found to be 12.53 and 352.42 μM, respectively. Moderate to slight inhibitions of 45.26 % and 28.68 % were presented by 3a against LOX and α-glucosidase, respectively, at 0.5 mM. Insignificant inhibitions were observed with 3b against the four selected enzymes. Further, in vivo trial demonstrated that 3a could significantly diminish AChE levels in the mice brain as compared to the control. These findings were in agreement with the histopathological analysis of the brain tissues. The results corroborate that selected compounds could serve as a potential lead for further development and optimization as AChE inhibitors to achieve cost-effective anti-Alzheimer's drugs.
    Matched MeSH terms: Alzheimer Disease/drug therapy; Alzheimer Disease/enzymology
  6. Lau ET, Khew CY, Hwang SS
    J Biotechnol, 2020 May 20;314-315:53-62.
    PMID: 32302654 DOI: 10.1016/j.jbiotec.2020.03.014
    Black pepper is an important commodity crop in Malaysia that generates millions of annual revenue for the country. However, black pepper yield is affected by slow decline disease caused by a soil-borne fungus Fusarium solani. RNA sequencing transcriptomics approach has been employed in this study to explore the differential gene expression in susceptible Piper nigrum L. and resistant Piper colubrinum Link. Gene expression comparative analysis of the two pepper species has yielded 2,361 differentially expressed genes (DEGs). Among them, higher expression of 1,426 DEGs was detected in resistant plant. These DEGs practically demonstrated the major branches of plant-pathogen interaction pathway (Path: ko04626). We selected five groups of defence-related DEGs for downstream qRT-PCR analysis. Cf-9, the gene responsible for recognizing fungal avirulence protein activity was found inexpressible in susceptible plant. However, this gene exhibited promising expression in resistant plant. Inactivation of Cf-9 could be the factor that causes susceptible plant fail in recognition of F. solani and subsequently delay activation of adaptive response to fungal invasion. This vital study advance the understanding of pepper plant defence in response to F. solani and aid in identifying potential solution to manage slow decline disease in black pepper cultivation.
    Matched MeSH terms: Disease Resistance/genetics; Disease Resistance/immunology
  7. Tan HL, Zain SM, Mohamed R, Rampal S, Chin KF, Basu RC, et al.
    J Gastroenterol, 2014 Jun;49(6):1056-64.
    PMID: 23800943 DOI: 10.1007/s00535-013-0850-x
    BACKGROUND: Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity.

    METHODS: The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform.

    RESULTS: The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09-2.05, p = 0.012; and OR 1.51, 95 % CI 1.09-2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10-2.17, p = 0.013; and OR 1.56, 95 % CI 1.10-2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01-2.21, p = 0.044; and OR 1.52, 95 % CI 1.03-2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28-5.43, p = 0.009; and OR 4.35, 95 % CI 1.93-9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41-12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08-2.85, p = 0.04).

    CONCLUSION: This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.

    Matched MeSH terms: Genetic Predisposition to Disease; Non-alcoholic Fatty Liver Disease/genetics*
  8. Yasmin AR, Omar AR, Farhanah MI, Hiscox AJ, Yeap SK
    Avian Dis, 2019 06 01;63(2):275-288.
    PMID: 31251527 DOI: 10.1637/11936-072418-Reg.1
    Chicken dendritic cells (DCs) have been demonstrated to be susceptible to infectious bursal disease virus (IBDV), a causative agent of acute and immunosuppressed disease in young chicks known as infectious bursal disease. Further functional characterization of IBDV-infected DCs of chickens is required to provide a better understanding on the influence of the virus on chicken bone marrow-derived dendritic cells (BM-DCs) following very virulent (vv) IBDV infection. Membrane proteins of BM-DCs were extracted and the proteins were further denatured and reduced before performing labeling with isobaric tags for relative and absolute quantitation. The differential expression protein profiles were identified and quantified using liquid chromatography coupled with tandem mass spectrometry, and later validated using flow cytometry and real-time reverse transcriptase PCR. The analysis has identified 134 differentially regulated proteins from a total of 283 proteins (cutoff values of ≤0.67, ≥1.5, and ProtScore >1.3 at 95% confidence interval), which produced high-yield membrane fractions. The entry of vvIBDV into the plasma membrane of BM-DCs was observed at 3 hr postinfection by the disruption of several important protein molecule functions, namely apoptosis, RNA/DNA/protein synthesis, and transport and cellular organization, without the activation of proteins associated with signaling. At the later stage of infection, vvIBDV induced expression of several proteins, namely CD200 receptor 1-A, integrin alpha-5, HSP-90, cathepsin, lysosomal-associated membrane protein, and Ras-related proteins, which play crucial roles in signaling, apoptosis, stress response, and antigen processing as well as in secretion of danger-associated proteins. These findings collectively indicated that the chicken DCs are expressing various receptors regarded as potential targets for pathogen interaction during viral infection. Therefore, fundamental study of the interaction of DCs and IBDV will provide valuable information in understanding the role of professional antigen-presenting cells in chickens and their molecular interactions during IBDV infection and vaccination.
    Matched MeSH terms: Infectious bursal disease virus/pathogenicity; Infectious bursal disease virus/physiology*
  9. Tan AH, Lim SY, Chong KK, A Manap MAA, Hor JW, Lim JL, et al.
    Neurology, 2021 02 02;96(5):e772-e782.
    PMID: 33046607 DOI: 10.1212/WNL.0000000000010998
    OBJECTIVE: To determine whether probiotics are effective for constipation, a common and often difficult-to-treat problem, in Parkinson disease (PD).

    METHODS: In this double-blind, randomized, placebo-controlled, single-center trial, 280 patients with PD were screened, and 72 eligible patients were block-randomized (1:1) to receive either multistrain probiotics capsules (n = 34) or identical-appearing placebo (n = 38), for 4 weeks. The primary endpoint was the change in the average number of spontaneous bowel movements (SBM) per week during the last 2 weeks of intervention compared with the 2-week preintervention phase, recorded by daily stool diary. Secondary outcome measures included changes in stool consistency, constipation severity score, and quality of life related to constipation. Satisfaction with intervention received was assessed. Change in levels of fecal calprotectin, a marker of intestinal inflammation, was an exploratory outcome.

    RESULTS: SBM increased by 1.0 ± 1.2 per week after treatment with probiotics and decreased by 0.3 ± 1.0 per week in the placebo group (mean difference 1.3, 95% confidence interval 0.8-1.8, p < 0.001). Significant improvements were also seen for secondary outcomes after correction for multiple comparisons, including stool consistency (p = 0.009) and quality of life related to constipation (p = 0.001). In the treatment group, 65.6% reported satisfaction with the intervention vs only 21.6% in the placebo group (p < 0.001). One patient (2.9%) in the treatment group withdrew due to a nonserious adverse event. Fecal calprotectin did not change significantly during the study.

    CONCLUSIONS: Multistrain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action.

    CLINICALTRIALSGOV IDENTIFIER: NCT03377322.

    CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for people with PD, multistrain probiotics significantly increased the average number of SBM per week.

    Matched MeSH terms: Parkinson Disease/complications; Parkinson Disease/physiopathology*
  10. Yanagisawa D, Ibrahim NF, Taguchi H, Morikawa S, Kato T, Hirao K, et al.
    J Neurosci Res, 2018 05;96(5):841-851.
    PMID: 29063641 DOI: 10.1002/jnr.24188
    Aggregation of tau into neurofibrillary tangles (NFTs) is characteristic of tauopathies, including Alzheimer's disease. Recent advances in tau imaging have attracted much attention because of its potential contributions to early diagnosis and monitoring of disease progress. Fluorine-19 magnetic resonance imaging (19 F-MRI) may be extremely useful for tau imaging once a high-quality probe has been formulated. In this investigation, a novel fluorine-19-labeling compound has been developed as a probe for tau imaging using 19 F-MRI. This compound is a buta-1,3-diene derivative with a polyethylene glycol side chain bearing a CF3 group and is known as Shiga-X35. Female rTg4510 mice (a mouse model of tauopathy) and wild-type mice were intravenously injected with Shiga-X35, and magnetic resonance imaging of each mouse's head was conducted in a 7.0-T horizontal-bore magnetic resonance scanner. The 19 F-MRI in rTg4510 mice showed an intense signal in the forebrain region. Analysis of the signal intensity in the forebrain region revealed a significant accumulation of fluorine-19 magnetic resonance signal in the rTg4510 mice compared with the wild-type mice. Histological analysis showed fluorescent signals of Shiga-X35 binding to the NFTs in the brain sections of rTg4510 mice. Data collected as part of this investigation indicate that 19 F-MRI using Shiga-X35 could be a promising tool to evaluate tau pathology in the brain.
    Matched MeSH terms: Alzheimer Disease/metabolism; Disease Models, Animal
  11. Wahab WA, Šuligoj T, Ellis J, Côrtez-Real B, Ciclitira PJ
    Int J Exp Pathol, 2016 Aug;97(4):303-309.
    PMID: 27659035 DOI: 10.1111/iep.12199
    Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of (3) H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. ω-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared.
    Matched MeSH terms: Celiac Disease/immunology*; Celiac Disease/pathology
  12. Kabbani T, Abdullah N, Rsheadat Y, Hassan MI
    J Orofac Orthop, 2017 Jan;78(1):62-69.
    PMID: 27896416 DOI: 10.1007/s00056-016-0064-y
    PURPOSE: This research is designed to obtain a better understanding and provide more insight of this phenomenon through evaluating the prevalence of congenital absence of maxillary lateral incisors in a Syrian population.

    METHODS: The method involved clinical examination of 8000 school children with an equal number of males and females (age range 12-15 years) to identify students only affected by bilateral or unilateral congenital absence of maxillary lateral incisors. Agenesis was determined based on radiological evidence.

    RESULTS: The results of this study showed that the prevalence of isolated maxillary lateral incisors agenesis was 1.15%. In the sample studied, 66.3% of the patients were female and 33.7% were male (p 

    Matched MeSH terms: Genetic Predisposition to Disease/genetics; Genetic Predisposition to Disease/epidemiology
  13. Mohamad Isa II, Abu Bakar S, Md Tohid SF, Mat Jais AM
    J Ethnopharmacol, 2016 Dec 24;194:469-474.
    PMID: 27732902 DOI: 10.1016/j.jep.2016.10.033
    ETHNOPHARMACOLOGICAL RELEVANCE: Haruan, Channa striatus, is a freshwater fish which has been well-known locally to accelerate wound healing during post-operative and post-partum periods. The fish extract also has potent anti-inflammatory and analgesic properties.

    AIM OF THE STUDY: To assess topical anti-inflammatory effect of Haruan cream on 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced chronic-like dermatitis in mice.

    MATERIALS AND METHODS: Male ICR mice were randomized into six groups of five mice each: acetone (vehicle), TPA alone (negative control), three Haruan treatment groups (Haruan 1%, Haruan 5% and Haruan 10%) and hydrocortisone 1% (positive control). Briefly, both surfaces of mouse ears were applied with TPA (2.5μg/20μl acetone) for five times on alternate days and with Haruan or hydrocortisone 1% cream for the last three days. Mouse ear thickness was measured 24h after final treatment with the cream and the ears were harvested for further histological analysis and gene expression studies of TNF-α by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR).

    RESULTS: Topical application of Haruan cream had reduced the mouse ear thickness 18.1-28%) with comparable effect to the positive control. In addition, histopathological comparison had shown evident reduction in various parameters of cutaneous inflammation including dermal oedema, inflammatory cells infiltration and proliferation of epidermal keratinocytes. Furthermore, TPA application had resulted in the up-regulation of TNF-α gene expression by 353-fold, which was subsequently down-regulated by the Haruan cream (34- to 112-fold).

    CONCLUSION: Haruan is an effective topical anti-inflammatory agent in this mouse model of chronic-like dermatitis, thus suggesting its potential as a non-steroidal treatment option for chronic inflammatory dermatoses.

    Matched MeSH terms: Chronic Disease; Disease Models, Animal*
  14. Chee KY, Ong KY, Mak CY, Yacob S, Yeo SC, Thrichelam N, et al.
    Asia Pac Psychiatry, 2017 Dec;9(4).
    PMID: 28326670 DOI: 10.1111/appy.12278
    INTRODUCTION: The objective of this study was to establish the psychometric properties of the AD8 Dementia Screening Interview in patients with Parkinson disease (PD) with or without cognitive impairment using the Montreal Cognitive Assessment Tool (MoCA) for comparison.

    METHODS: The AD8 was translated into Malay for Malay-speaking participants. A correlation analysis and a receiver operator characteristic curve were generated to establish the psychometric properties of the AD8 in relation to the MoCA.

    RESULTS: One hundred fifty patients and their caretakers completed the AD8 and MoCA. Using a cutoff score of 1/8, the AD8 had 81% sensitivity and 59% specificity for the detection of cognitive impairment in PD. With a cutoff score of 2/8, the AD8 had 83% specificity and 64% sensitivity. The area under the receiver operator characteristic curve was 80%, indicating good-to-excellent discriminative ability.

    DISCUSSION: These findings suggest that the AD8 can reliably differentiate between cognitively impaired and cognitively normal patients with PD and is a useful caregiver screening tool for PD.

    Matched MeSH terms: Parkinson Disease/complications; Parkinson Disease/diagnosis*
  15. Yeong KY, Liew WL, Murugaiyah V, Ang CW, Osman H, Tan SC
    Bioorg Chem, 2017 02;70:27-33.
    PMID: 27863748 DOI: 10.1016/j.bioorg.2016.11.005
    A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease.
    Matched MeSH terms: Alzheimer Disease/drug therapy; Alzheimer Disease/enzymology
  16. Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.
    COPD, 2017 Oct;14(5):476-483.
    PMID: 28753067 DOI: 10.1080/15412555.2017.1335697
    Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/drug therapy*; Pulmonary Disease, Chronic Obstructive/physiopathology
  17. Kim WJ, Gupta V, Nishimura M, Makita H, Idolor L, Roa C, et al.
    Int J Tuberc Lung Dis, 2018 07 01;22(7):820-826.
    PMID: 29914609 DOI: 10.5588/ijtld.17.0524
    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment.

    OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup.

    METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis.

    RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score.

    CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/epidemiology*; Pulmonary Disease, Chronic Obstructive/physiopathology
  18. Mandary MB, Poh CL
    Viruses, 2018 06 12;10(6).
    PMID: 29895721 DOI: 10.3390/v10060320
    Enterovirus 71 (EV-A71) is a major etiological agent of hand, foot and mouth disease (HFMD) that mainly affects young children less than five years old. The onset of severe HFMD is due to neurological complications bringing about acute flaccid paralysis and pulmonary oedema. In this review, we address how genetic events such as recombination and spontaneous mutations could change the genomic organization of EV-A71, leading to an impact on viral virulence. An understanding of the recombination mechanism of the poliovirus and non-polio enteroviruses will provide further evidence of the emergence of novel strains responsible for fatal HFMD outbreaks. We aim to see if the virulence of EV-A71 is contributed solely by the presence of fatal strains or is due to the co-operation of quasispecies within a viral population. The phenomenon of quasispecies within the poliovirus is discussed to reflect viral fitness, virulence and its implications for EV-A71. Ultimately, this review gives an insight into the evolution patterns of EV-A71 by looking into its recombination history and how spontaneous mutations would affect its virulence.
    Matched MeSH terms: Hand, Foot and Mouth Disease/pathology; Hand, Foot and Mouth Disease/virology
  19. Krishna Moorthy PS, Sivalingam S, Dillon J, Kong PK, Yakub MA
    Interact Cardiovasc Thorac Surg, 2019 02 01;28(2):191-198.
    PMID: 30085022 DOI: 10.1093/icvts/ivy234
    OBJECTIVES: Contemporary experience in mitral valve (MV) repair for children with rheumatic heart disease (RHD) is limited, despite the potential advantages of repair over replacement. We reviewed our long-term outcomes of rheumatic MV repair and compared them with the outcomes of MV replacement in children with RHD.

    METHODS: This study is a review of 419 children (≤18 years) with RHD who underwent primary isolated MV surgery between 1992 and 2015, which comprised MV repair (336 patients; 80.2%) and MV replacement (83 patients; 19.8%). The replacement group included mechanical MV replacements (MMVRs) (n = 69 patients; 16.5%) and bioprosthetic MV replacements (n = 14 patients; 3.3%). The mean age with standard deviation at the time of operation was 12.5 ± 3.5 (2-18) years. Mitral regurgitation (MR) was predominant in 390 (93.1%) patients, and 341 (81.4%) patients showed ≥3+ MR. The modified Carpentier reconstructive techniques were used for MV repair.

    RESULTS: Overall early mortality was 1.7% (7 patients). The mean follow-up was 5.6 years (range 0-22.3 years; 94.7% complete). Survival of patients who underwent repair was 93.9% both at 10 and 20 years, which was superior than that of replacement (P 

    Matched MeSH terms: Rheumatic Heart Disease/diagnosis; Rheumatic Heart Disease/surgery*
  20. Okamura T, Tsujimura Y, Soma S, Takahashi I, Matsuo K, Yasutomi Y
    J Gen Virol, 2016 Dec;97(12):3413-3426.
    PMID: 27902330 DOI: 10.1099/jgv.0.000641
    Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian countries. In the present study, we analysed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated into cynomolgus macaques in Indonesian, Malaysian or Philippine origin. The plasma viral loads in macaques infected with either SIVmac239 or SHIV89.6P were maintained at high levels. CD4+ T cell levels in macaques infected with SIVmac239 gradually decreased. All of the macaques infected with SHIV89.6P showed greatly reduced CD4+ T-cell numbers within 6 weeks of infection. Eight of the 11 macaques infected with SIVmac239 were killed due to AIDS symptoms after 2-4.5 years, while four of the five macaques infected with SHIV89.6P were killed due to AIDS symptoms after 1-3.5 years. We also analysed cynomolgus macaques infected intrarectally with repeated low, medium or high doses of SIVmac239, SIVmac251 or SHIV89.6P. Infection was confirmed by quantitative RT-PCR at more than 5000, 300 and 500 TCID50 for SIVmac239, SIVmac251 and SHIV89.6P, respectively. The present study indicates that cynomolgus macaques of Asian origin are highly susceptible to SIVmac and SHIV infection by both intravenous and mucosal routes. These models will be useful for studies on virus pathogenesis, vaccination and therapeutics against human immunodeficiency virus/AIDS.
    Matched MeSH terms: Disease Models, Animal*; Disease Progression
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