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  1. Yew KL
    Int J Cardiol, 2016 Jan 15;203:1007-8.
    PMID: 26630622 DOI: 10.1016/j.ijcard.2015.11.124
    Matched MeSH terms: Coronary Artery Disease/drug therapy; Coronary Artery Disease/pathology; Coronary Artery Disease/surgery; Coronary Artery Disease/therapy*
  2. Chan WK, Tan AT, Vethakkan SR, Tah PC, Vijayananthan A, Goh KL
    Clin Res Hepatol Gastroenterol, 2014 Jun;38(3):284-91.
    PMID: 24736032 DOI: 10.1016/j.clinre.2014.02.009
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both common among patients with diabetes mellitus.
    OBJECTIVE: The aim of this study is to determine if ultrasonography-diagnosed NAFLD is associated with prevalent ischemic heart disease (IHD) among patients with diabetes mellitus.
    METHODS: This is a cross-sectional study on consecutive patients seen at the Diabetic Clinic, University of Malaya Medical Centre. The medical record for each patient was reviewed for documented IHD. Patients without documented IHD but had symptoms and/or electrocardiographic changes suggestive of IHD were referred for cardiac evaluation.
    RESULTS: Data for 399 patients were analyzed. Mean age was 62.8±10.5 years with 43.1% male. NAFLD and IHD were present in 49.6 and 26.6%, respectively. The prevalence of IHD among patients with and without NAFLD was 24.7 and 28.4%, respectively (P=0.414). The prevalence of IHD was highest among the Indians (34.1%) followed by the Malays (29.2%) and the Chinese (20.1%). No association was found between NAFLD and IHD when analyzed according to ethnicity. On multivariate analysis, independent factors associated with IHD were older age, lower levels of physical activity, greater waist circumference and higher serum glycated hemoglobin level.
    CONCLUSIONS: Ultrasonography-diagnosed NAFLD was not associated with prevalent IHD among patients with diabetes mellitus in a multiracial Asian hospital clinic population.

    Study site: Diabetic clinc, University Malaya Medical Centre (UMMC)
    Matched MeSH terms: Coronary Artery Disease/epidemiology*; Non-alcoholic Fatty Liver Disease/epidemiology; Non-alcoholic Fatty Liver Disease/ultrasonography*
  3. Tayib S, van Wijk L, Denny L
    Int. J. Gynecol. Cancer, 2011 Dec;21(9):1684-91.
    PMID: 21997172 DOI: 10.1097/IGC.0b013e31822d8ffd
    OBJECTIVES: The objective of the study was to describe the management of gestational trophoblastic neoplasia (GTN), with particular reference to concurrent human immunodeficiency virus (HIV) infection.

    METHODS: This retrospective descriptive study comprised all cases of GTN managed at Groote Schuur Hospital over a 10-year period (1999-2008).

    RESULTS: Seventy-six patients, with a median age of 30 years at presentation, were included in the study. Only 36 patients (47.4%) had known HIV status. Fourteen (18.4%) were HIV positive, and of these, 4 (28.6%) were on antiretroviral treatment (ARV). The mean CD4 count was 142 cells/μL for those on ARV and 543 cells/μL for those not on ARV (P = 0.001). Histologically, 44 patients (58%) had hydatidiform mole, and 21 (28%) had choriocarcinoma. In the remaining 10 cases, a clinical diagnosis was made. Based on the revised International Federation of Gynecology and Obstetrics (FIGO)/modified World Health Organization scoring, 43 patients (56.6%) were low risk, and 33 (43.4%) were high risk. Thirty-eight patients (50%) were staged as FIGO stage I. Of 73 patients who received chemotherapy, 56 (76.7%) achieved complete remission, 9 (12.3%) did not achieve any remission, 7 (9.6%) had a relapse, and 1 (1.4%) was lost to follow-up. Patients who never went into remission had frequent treatment delays due to poor compliance or inadequate blood counts. The overall survival at 60 months was 81.9%. Of the 13 patients (17.1%) who have died, 5 (38.5%) were HIV positive. The overall 5-year survival rates for FIGO stages I, II, III, and IV were 97.4%, 66.7%, 77.8%, and 46.2%, respectively. The overall 5-year survival for HIV-positive patients was 64.3% versus more than 85% for both the HIV-negative and HIV-unknown groups.

    CONCLUSIONS: Apart from more advanced stage, HIV seropositivity and poor compliance with treatment also portend poorer outcome in GTN patients. In HIV-positive patients with poor CD4, little clarity is available whether ARV should be commenced speedily, and the administration of chemotherapy delayed until immune reconstitution occurs.

    Matched MeSH terms: Gestational Trophoblastic Disease/diagnosis; Gestational Trophoblastic Disease/drug therapy*; Gestational Trophoblastic Disease/epidemiology; Gestational Trophoblastic Disease/virology*
  4. Le VP, Nguyen T, Lee KN, Ko YJ, Lee HS, Nguyen VC, et al.
    Vet Microbiol, 2010 Jul 29;144(1-2):58-66.
    PMID: 20097490 DOI: 10.1016/j.vetmic.2009.12.033
    Foot-and-mouth disease (FMD) is a major cause of endemic outbreaks in Vietnam in recent years. In this work, six serotype A foot-and-mouth disease viruses (FMDV), collected from endemic outbreaks during January and February of 2009 in four different provinces in Vietnam, were genetically characterized for their complete genome sequences. Genetic analysis based on the complete viral genome sequence indicated that they were closely related to each other and shared 99.0-99.8% amino acid (aa) identity. Genetic and deduced aa analysis of the capsid coding gene VP1 showed that the six Vietnamese strains were all classified into the genotype IX from a total of 10 major genotypes worldwide, sharing 98.1-100% aa identity each other. They were most closely related to the type A strains recently isolated in Laos (A/LAO/36/2003, A/LAO/1/2006, A/LAO/6/2006, A/LAO/7/2006, and A/LAO/8/2006), Thailand (A/TAI/2/1997 and A/TAI/118/1987), and Malaysia (A/MAY/2/2002), sharing 88.3-95.5% nucleotide (nt) identities. In contrast, Vietnamese type A strains showed low nt identities with the two old type A FMDVs, isolated in 1960 in Thailand (a15thailand iso43) and in 1975 in the Philippines (aphilippines iso50), ranging from 77.3 to 80.9% nt identity. A multiple alignment based on the deduced amino acid sequences of the capsid VP1 coding gene of type A FMDV revealed three amino acid substitutions between Vietnamese strains and the strains of other Southeast Asian countries (Laos, Thailand, Malaysia, and the Philippines). Alanine was replaced by valine at residue 24, asparagine by arginine at residue 85, and serine by threonine at residue 196. Furthermore, type A FMDV strains recently isolated in Vietnam, Laos, Thailand, and Malaysia all have one amino acid deletion at residue 140 of the capsid VP1 protein compared with the two old type A FMDV strains from Thailand and the Philippines as well as most other type A representatives worldwide. This article is the first to report on the comprehensive genetic characterization of type A FMDV circulating in Vietnam.
    Matched MeSH terms: Foot-and-Mouth Disease/genetics*; Foot-and-Mouth Disease/epidemiology; Foot-and-Mouth Disease Virus/genetics*
  5. Landman WJ, Schrier CC
    Tijdschr Diergeneeskd, 2004 Dec 1;129(23):782-96.
    PMID: 15624878
    Avian influenza viruses are highly infectious micro-organisms that primarily affect birds. Nevertheless, they have also been isolated from a number of mammals, including humans. Avian influenza virus can cause large economic losses to the poultry industry because of its high mortality. Although there are pathogenic variants with a low virulence and which generally cause only mild, if any, clinical symptoms, the subtypes H5 and H7 can mutate from a low to a highly virulent (pathogenic) virus and should be taken into consideration in eradication strategies. The primary source of infection for commercial poultry is direct and indirect contact with wild birds, with waterfowl forming a natural reservoir of the virus. Live-poultry markets, exotic birds, and ostriches also play a significant role in the epidemiology of avian influenza. The secondary transmission (i.e., between poultry farms) of avian influenza virus is attributed primarily to fomites and people. Airborne transmission is also important, and the virus can be spread by aerosol in humans. Diagnostic tests detect viral proteins and genes. Virus-specific antibodies can be traced by serological tests, with virus isolation and identification being complementary procedures. The number of outbreaks of avian influenza seems to be increasing - over the last 5 years outbreaks have been reported in Italy, Hong Kong, Chile, the Netherlands, South Korea, Vietnam, Japan, Thailand, Cambodia, Indonesia, Laos, China, Pakistan, United States of America, Canada, South Africa, and Malaysia. Moreover, a growing number of human cases of avian influenza, in some cases fatal, have paralleled the outbreaks in commercial poultry. There is great concern about the possibility that a new virus subtype with pandemic potential could emerge from these outbreaks. From the perspective of human health, it is essential to eradicate the virus from poultry; however, the large number of small-holdings with poultry, the lack of control experience and resources, and the international scale of transmission and infection make rapid control and long-term prevention of recurrence extremely difficult. In the Western world, the renewed interest in free-range housing carries a threat for future outbreaks. The growing ethical objections to the largescale culling of birds require a different approach to the eradication of avian influenza.
    Matched MeSH terms: Disease Outbreaks/prevention & control; Disease Outbreaks/veterinary; Disease Reservoirs/veterinary
  6. Bukhari SN, Jantan I
    Mini Rev Med Chem, 2015;15(13):1110-21.
    PMID: 26420724
    There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.
    Matched MeSH terms: Alzheimer Disease/diagnosis; Alzheimer Disease/drug therapy*; Alzheimer Disease/metabolism; Alzheimer Disease/pathology
  7. Suwarnalata G, Tan AH, Isa H, Gudimella R, Anwar A, Loke MF, et al.
    PLoS One, 2016;11(4):e0153725.
    PMID: 27100827 DOI: 10.1371/journal.pone.0153725
    Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity.
    Matched MeSH terms: Parkinson Disease/blood; Parkinson Disease/complications*; Parkinson Disease/immunology*; Parkinson Disease/microbiology
  8. Al Aqqad SMH, Tangiisuran B, Hyder Ali IA, Md Kassim RMN, Wong JL, Tengku Saifudin TI
    Clin Respir J, 2017 Nov;11(6):960-967.
    PMID: 26763195 DOI: 10.1111/crj.12448
    INTRODUCTION: The elderly, with chronic obstructive pulmonary disease (COPD), are at a higher risk of hospitalisation due to acute exacerbation of COPD (AECOPD). They also often encounter multiple co-morbidities.

    OBJECTIVES: This study was aimed to explore the occurrence of anxiety, depression and to identify the factors associated with hospital readmission among older patients after AECOPD discharge.

    METHODS: A multicentre prospective study was conducted in Malaysia (from 1st September 2012 till 31st September 2013) among older patients (≥60 years) hospitalised for AECOPD. Anxiety and depression were assessed on discharge using previously validated questionnaires, Generalized Anxiety Disorder-7 (GAD-7 and Geriatric Depression Scale (GDS-15), respectively. Patients were followed up for a period of 3 months after discharge.

    RESULTS: A total of 81 patients with a median age of 72 years (IQR 66.40-78.00) were recruited. Anxiety was observed in 34.57% while 38.27% had depression. Both anxiety and depression were detected in 25.93% of the patients. A history of frequent AECOPD admissions was found to be associated with developing depressive symptoms, while anxiety scores were associated with severe dyspnoea. Severe depression was more commonly identified among patients aged 60-75 and in those with a history of tuberculosis. A high readmission rate (40.74%) during the 3-month period was noticed. History of frequent AECOPD admissions (OR = 2.87; 95% CI 1.05-7.85, P = 0.040) and ischemic heart disease (IHD) (OR = 4.04; 95% CI 1.1-14.6, P = 0.032) were identified as the factors associated with the risk of hospital readmission.

    CONCLUSIONS: Anxiety and depression were found to be relatively common among older patients with AECOPD. IHD and history of frequent COPD hospitalisation were associated with short-term readmission among the elderly.

    Matched MeSH terms: Disease Progression; Pulmonary Disease, Chronic Obstructive/epidemiology; Pulmonary Disease, Chronic Obstructive/physiopathology; Pulmonary Disease, Chronic Obstructive/psychology*
  9. Nagendrakumar SB, Hong NT, Geoffrey FT, Jacqueline MM, Andrew D, Michelle G, et al.
    Vaccine, 2015 Aug 26;33(36):4513-9.
    PMID: 26192355 DOI: 10.1016/j.vaccine.2015.07.014
    Pigs play a significant role during outbreaks of foot-and-mouth disease (FMD) due to their ability to amplify the virus. It is therefore essential to determine what role vaccination could play to prevent clinical disease and lower virus excretion into the environment. In this study we investigated the efficacy of the double oil emulsion A Malaysia 97 vaccine (>6PD50/dose) against heterologous challenge with an isolate belonging to the A SEA-97 lineage at 4 and 7 days post vaccination (dpv). In addition, we determined whether physical separation of pigs in the same room could prevent virus transmission. Statistically there was no difference in the level of protection offered by 4 and 7 dpv. However, no clinical disease or viral RNA was detected in the blood of pigs challenged 4 dpv, although three of the pigs had antibodies to the non-structural proteins (NSPs), indicating viral replication. Viral RNA was also detected in nasal and saliva swabs, but on very few occasions. Two of the pigs vaccinated seven days prior to challenge had vesicles distal from the injection site, but on the inoculated foot, and two pigs had viral RNA detected in the blood. One pig sero-converted to the NSPs. In contrast, all unvaccinated and inoculated pigs had evidence of infection. No infection occurred in any of the susceptible pigs in the same room, but separated from the infected pigs, indicating that strict biosecurity measures were sufficient under these experimental conditions to prevent virus transmission. However, viral RNA was detected in the nasal swabs of one group of pigs, but apparently not at sufficient levels to cause clinical disease. Vaccination led to a significant decrease in viral RNA in vaccinated pigs compared to unvaccinated and infected pigs, even with this heterologous challenge, and could therefore be considered as a control option during outbreaks.
    Matched MeSH terms: Foot-and-Mouth Disease/prevention & control*; Foot-and-Mouth Disease Virus/immunology*; Foot-and-Mouth Disease Virus/isolation & purification
  10. Geoghegan JL, Tan le V, Kühnert D, Halpin RA, Lin X, Simenauer A, et al.
    J Virol, 2015 Sep;89(17):8871-9.
    PMID: 26085170 DOI: 10.1128/JVI.00706-15
    Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia.

    IMPORTANCE: EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study, we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus.

    Matched MeSH terms: Disease Outbreaks; Hand, Foot and Mouth Disease/genetics*; Hand, Foot and Mouth Disease/epidemiology*; Hand, Foot and Mouth Disease/virology
  11. Brown BA, Oberste MS, Alexander JP, Kennett ML, Pallansch MA
    J Virol, 1999 Dec;73(12):9969-75.
    PMID: 10559310
    Enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae), a common cause of hand, foot, and mouth disease (HFMD), may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity and rate of evolution of EV71, we have determined and analyzed complete VP1 sequences (891 nucleotides) for 113 EV71 strains isolated in the United States and five other countries from 1970 to 1998. Nucleotide sequence comparisons demonstrated three distinct EV71 genotypes, designated A, B, and C. The genetic variation within genotypes (12% or fewer nucleotide differences) was less than the variation between genotypes (16.5 to 19.7%). Strains of all three genotypes were at least 94% identical to one another in deduced amino acid sequence. The EV71 prototype strain, BrCr-CA-70, isolated in California in 1970, is the sole member of genotype A. Strains isolated in the United States and Australia during the period from 1972 to 1988, a 1994 Colombian isolate, and isolates from a large HFMD outbreak in Malaysia in 1997 are all members of genotype B. Although strains of genotype B continue to circulate in other parts of the world, none have been isolated in the United States since 1988. Genotype C contains strains isolated in 1985 or later in the United States, Canada, Australia, and the Republic of China. The annual rate of evolution within both the B and C genotypes was estimated to be approximately 1.35 x 10(-2) substitutions per nucleotide and is similar to the rate observed for poliovirus. The results indicate that EV71 is a genetically diverse, rapidly evolving virus. Its worldwide circulation and potential to cause severe disease underscore the need for additional surveillance and improved methods to identify EV71 in human disease.
    Matched MeSH terms: Disease Outbreaks*; Hand, Foot and Mouth Disease/epidemiology*; Hand, Foot and Mouth Disease/virology*
  12. Hoque MM, Omar AR, Hair-Bejo M, Aini I
    J. Biochem. Mol. Biol. Biophys., 2002 Apr;6(2):93-9.
    PMID: 12186763
    Previously we have shown that very virulent infectious bursal disease viruses (vvIBDV) that are SspI, TaqI and StyI positive (92/04, 97/61 and 94/B551) but not SspI and TaqI positive and StyI negative (94/273) cause high mortality, up to 80% in specific-pathogen-free chickens with significant damage of the bursal as well as nonbursal tissues. In this study, we sequenced the VP2 gene (1351 bp) of the 92/04, 94/273 and 94/B551 and compared them with other IBDV strains. All the isolates have the unique amino acid residues at positions 222A, 256I, 294I and 299S found in other vvIBDV strains. The deduced VP2 amino acids encoded by 92/04 is identical to the vvIBDV strains from Israel (IBDVKS), Japan (OKYM) and Europe (UK661), whereas the 94/273 and 94/B551 isolates have one to three amino acid substitutions. The 94/273 has two amino acid substitutions at positions 254 G to S and at 270 A to E that have not been reported before from vvIBDV strains. The 94/B551 also has one amino acid substitution at position 300 E to S, which is uncommon among other vvIBDV strains. However, phylogenetic analysis suggested that the isolates are very close to each other and all of them may have derived from the same origin as vvIBDV strains isolated from China, Japan and Europe. Even though antigenic index analysis of the 94/273 and 94/B551 indicated that the isolates are unique compared to other IBDV strains, their antigenic variation remain to be determined by monoclonal antibody study.
    Matched MeSH terms: Infectious bursal disease virus/genetics*; Infectious bursal disease virus/immunology; Infectious bursal disease virus/isolation & purification; Infectious bursal disease virus/pathogenicity
  13. Saleem Z, Hassali MA
    Travel Med Infect Dis, 2018 10 16;27:127.
    PMID: 30339826 DOI: 10.1016/j.tmaid.2018.10.013
    Matched MeSH terms: Centers for Disease Control and Prevention (U.S.)*; Disease Outbreaks/prevention & control; Disease Outbreaks/statistics & numerical data*
  14. Wang YH, Bychkov A, Chakrabarti I, Jain D, Liu Z, He S, et al.
    Cancer Cytopathol, 2020 Dec;128(12):895-904.
    PMID: 32931161 DOI: 10.1002/cncy.22354
    BACKGROUND: The purpose of the current study was to examine the impact of coronavirus disease 2019 (COVID-19) on various aspects of cytology practice in the Asia-Pacific region.

    METHODS: An online questionnaire was distributed to cytopathology laboratories in 24 Asia-Pacific countries to explore the impact of restrictive measures on access to health care, use of general and personal protective equipment (PPE), and changes in cytology workflow and workload from February to April 2020.

    RESULTS: A total of 167 cytopathology laboratories from 24 countries responded to the survey; the majority reported that restrictive measures that limited the accessibility of health care services had been implemented in their cities and/or countries (80.8%) and their hospitals (83.8%). The respondents noted that COVID-19 had an impact on the cytologic workflow as well as the workload. Approximately one-half of the participants reported the implementation of new biosafety protocols (54.5%) as well as improvements in laboratory facilities (47.3%). Rearrangement or redeployment of the workforce was reported in 53.3% and 34.1% of laboratories, respectively. The majority of the respondents reported a significant reduction (>10%) in caseload associated with both gynecological (82.0%) and nongynecological specimens (78.4%). Most laboratories reported no significant change in the malignancy rates of both gynecological (67.7%) and nongynecological specimens (58.7%) compared with the same period in 2019.

    CONCLUSIONS: The results of the survey demonstrated that the COVID-19 pandemic resulted in a significant reduction in the number of cytology specimens examined along with the need to implement new biosafety protocols. These findings underscore the need for the worldwide standardization of biosafety protocols and cytology practice.

    Matched MeSH terms: Communicable Disease Control/instrumentation; Communicable Disease Control/standards*; Infectious Disease Transmission, Patient-to-Professional/prevention & control*
  15. Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, et al.
    Nat Genet, 2017 Jul;49(7):1113-1119.
    PMID: 28530674 DOI: 10.1038/ng.3874
    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10-8, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
    Matched MeSH terms: Coronary Artery Disease/genetics*; Coronary Artery Disease/pathology; Coronary Artery Disease/physiopathology; Genetic Predisposition to Disease
  16. Mihardja M, Roy J, Wong KY, Aquili L, Heng BC, Chan YS, et al.
    Ann N Y Acad Sci, 2020 10;1478(1):43-62.
    PMID: 32700392 DOI: 10.1111/nyas.14436
    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the hallmark pathologies of amyloid-beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin-the pineal hormone primarily responsible for the regulation of the circadian rhythm-targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.
    Matched MeSH terms: Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Alzheimer Disease/therapy*; Disease Models, Animal
  17. Yasmin AR, Yeap SK, Hair-Bejo M, Omar AR
    Avian Dis, 2016 12;60(4):739-751.
    PMID: 27902915
    Studies have shown that infectious bursal disease virus (IBDV) infects lymphoid cells, mainly B cells and macrophages. This study was aimed to examine the involvement of chicken splenic-derived dendritic cells (ch-sDCs) in specific-pathogen-free chickens following inoculation with IBDV vaccine strain (D78) and a very virulent (vv) strain (UPM0081). Following IBDV infection, enriched activated ch-sDCs were collected by using the negative selection method and were examined based on morphology and immunophenotyping to confirm the isolation method for dendritic cells (DCs). The presence of IBDV on enriched activated ch-sDCs was analyzed based on the immunofluorescence antibody test (IFAT), flow cytometry, and quantitative real-time PCR (RT-qPCR) while the mRNAs of several cytokines were detected using RT-qPCR. The isolated ch-sDCs resembled typical DC morphologies found in mammals by having a veiled shape and they grew in clusters. Meanwhile, the expression of DC maturation markers, namely CD86 and MHCII, were increased at day 2 and day 3 following vvIBDV and vaccine strain inoculation, respectively, ranging from 10% to 40% compared to the control at 2.55% (P < 0.05). At day 3 postinfection, IBDV VP3 proteins colocalized with CD86 were readily detected via IFAT and flow cytometry in both vaccine and vvIBDV strains. In addition, enriched activated ch-sDCs were also detected as positive based on the VP4 gene by RT-qPCR; however, a higher viral load was detected on vvIBDV compared to the vaccine group. Infection with vaccine and vvIBDV strains induced the enriched activated ch-sDCs to produce proinflammatory cytokines and Th1-like cytokines from day 3 onward; however, the expressions were higher in the vvIBDV group (P < 0.05). These data collectively suggest that enriched activated ch-sDCs were permissive to IBDV infection and produced a strong inflammatory and Th1-like cytokine response following vvIBDV infection as compared to the vaccine strain.
    Matched MeSH terms: Infectious bursal disease virus/genetics; Infectious bursal disease virus/immunology*; Infectious bursal disease virus/pathogenicity; Infectious bursal disease virus/physiology
  18. Chu SY, Barlow SM, Lee J, Wang J
    Int J Speech Lang Pathol, 2017 12;19(6):616-627.
    PMID: 28425760 DOI: 10.1080/17549507.2016.1265587
    PURPOSE: This research characterised perioral muscle reciprocity and amplitude ratio in lower lip during bilabial syllable production [pa] at three rates to understand the neuromotor dynamics and scaling of motor speech patterns in individuals with Parkinson's disease (PD).

    METHOD: Electromyographic (EMG) signals of the orbicularis oris superior [OOS], orbicularis oris inferior [OOI] and depressor labii inferioris [DLI] were recorded during syllable production and expressed as polar-phase notations.

    RESULT: PD participants exhibited the general features of reciprocity between OOS, OOI and DLI muscles as reflected in the EMG during syllable production. The control group showed significantly higher integrated EMG amplitude ratio in the DLI:OOS muscle pairs than PD participants. No speech rate effects were found in EMG muscle reciprocity and amplitude magnitude across all muscle pairs.

    CONCLUSION: Similar patterns of muscle reciprocity in PD and controls suggest that corticomotoneuronal output to the facial nucleus and respective perioral muscles is relatively well-preserved in our cohort of mild idiopathic PD participants. Reduction of EMG amplitude ratio among PD participants is consistent with the putative reduction in the thalamocortical activation characteristic of this disease which limits motor cortex drive from generating appropriate commands which contributes to bradykinesia and hypokinesia of the orofacial mechanism.

    Matched MeSH terms: Parkinson Disease/complications; Parkinson Disease/diagnosis; Parkinson Disease/drug therapy; Parkinson Disease/physiopathology*
  19. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    J Gastroenterol Hepatol, 2019 Aug;34(8):1296-1315.
    PMID: 30848854 DOI: 10.1111/jgh.14648
    The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
    Matched MeSH terms: Crohn Disease/diagnosis; Crohn Disease/drug therapy*; Crohn Disease/immunology; Crohn Disease/epidemiology
  20. Ye Q, Zou B, Yeo YH, Li J, Huang DQ, Wu Y, et al.
    Lancet Gastroenterol Hepatol, 2020 08;5(8):739-752.
    PMID: 32413340 DOI: 10.1016/S2468-1253(20)30077-7
    BACKGROUND: Although non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, it is increasingly being identified in non-obese individuals. We aimed to characterise the prevalence, incidence, and long-term outcomes of non-obese or lean NAFLD at a global level.

    METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library from inception to May 1, 2019, for relevant original research articles without any language restrictions. The literature search and data extraction were done independently by two investigators. Primary outcomes were the prevalence of non-obese or lean people within the NAFLD group and the prevalence of non-obese or lean NAFLD in the general, non-obese, and lean populations; the incidence of NAFLD among non-obese and lean populations; and long-term outcomes of non-obese people with NAFLD. We also aimed to characterise the demographic, clinical, and histological characteristics of individuals with non-obese NAFLD.

    FINDINGS: We identified 93 studies (n=10 576 383) from 24 countries or areas: 84 studies (n=10 530 308) were used for the prevalence analysis, five (n=9121) were used for the incidence analysis, and eight (n=36 954) were used for the outcomes analysis. Within the NAFLD population, 19·2% (95% CI 15·9-23·0) of people were lean and 40·8% (36·6-45·1) were non-obese. The prevalence of non-obese NAFLD in the general population varied from 25% or lower in some countries (eg, Malaysia and Pakistan) to higher than 50% in others (eg, Austria, Mexico, and Sweden). In the general population (comprising individuals with and without NAFLD), 12·1% (95% CI 9·3-15·6) of people had non-obese NAFLD and 5·1% (3·7-7·0) had lean NAFLD. The incidence of NAFLD in the non-obese population (without NAFLD at baseline) was 24·6 (95% CI 13·4-39·2) per 1000 person-years. Among people with non-obese or lean NALFD, 39·0% (95% CI 24·1-56·3) had non-alcoholic steatohepatitis, 29·2% (21·9-37·9) had significant fibrosis (stage ≥2), and 3·2% (1·5-5·7) had cirrhosis. Among the non-obese or lean NAFLD population, the incidence of all-cause mortality was 12·1 (95% CI 0·5-38·8) per 1000 person-years, that for liver-related mortality was 4·1 (1·9-7·1) per 1000 person-years, cardiovascular-related mortality was 4·0 (0·1-14·9) per 1000 person-years, new-onset diabetes was 12·6 (8·0-18·3) per 1000 person-years, new-onset cardiovascular disease was 18·7 (9·2-31·2) per 1000 person-years, and new-onset hypertension was 56·1 (38·5-77·0) per 1000 person-years. Most analyses were characterised by high heterogeneity.

    INTERPRETATION: Overall, around 40% of the global NAFLD population was classified as non-obese and almost a fifth was lean. Both non-obese and lean groups had substantial long-term liver and non-liver comorbidities. These findings suggest that obesity should not be the sole criterion for NAFLD screening. Moreover, clinical trials of treatments for NAFLD should include participants across all body-mass index ranges.

    FUNDING: None.

    Matched MeSH terms: Non-alcoholic Fatty Liver Disease/complications; Non-alcoholic Fatty Liver Disease/mortality*; Non-alcoholic Fatty Liver Disease/epidemiology*; Non-alcoholic Fatty Liver Disease/pathology
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