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  1. Wongnak P, Thanapongtharm W, Kusakunniran W, Karnjanapreechakorn S, Sutassananon K, Kalpravidh W, et al.
    BMC Vet Res, 2020 Aug 24;16(1):300.
    PMID: 32838786 DOI: 10.1186/s12917-020-02502-4
    BACKGROUND: Nipah virus (NiV) is a fatal zoonotic agent that was first identified amongst pig farmers in Malaysia in 1998, in an outbreak that resulted in 105 fatal human cases. That epidemic arose from a chain of infection, initiating from bats to pigs, and which then spilled over from pigs to humans. In Thailand, bat-pig-human communities can be observed across the country, particularly in the central plain. The present study therefore aimed to identify high-risk areas for potential NiV outbreaks and to model how the virus is likely to spread. Multi-criteria decision analysis (MCDA) and weighted linear combination (WLC) were employed to produce the NiV risk map. The map was then overlaid with the nationwide pig movement network to identify the index subdistricts in which NiV may emerge. Subsequently, susceptible-exposed-infectious-removed (SEIR) modeling was used to simulate NiV spread within each subdistrict, and network modeling was used to illustrate how the virus disperses across subdistricts.

    RESULTS: Based on the MCDA and pig movement data, 14 index subdistricts with a high-risk of NiV emergence were identified. We found in our infectious network modeling that the infected subdistricts clustered in, or close to the central plain, within a range of 171 km from the source subdistricts. However, the virus may travel as far as 528.5 km (R0 = 5).

    CONCLUSIONS: In conclusion, the risk of NiV dissemination through pig movement networks in Thailand is low but not negligible. The risk areas identified in our study can help the veterinary authority to allocate financial and human resources to where preventive strategies, such as pig farm regionalization, are required and to contain outbreaks in a timely fashion once they occur.

    Matched MeSH terms: Disease Outbreaks/prevention & control
  2. Mustafa S, Abd-Aziz N, Saw WT, Liew SY, Yusoff K, Shafee N
    Vaccines (Basel), 2020 Dec 07;8(4).
    PMID: 33297428 DOI: 10.3390/vaccines8040742
    Enterovirus 71 (EV71) is the major causative agent in hand, foot, and mouth disease (HFMD), and it mainly infects children worldwide. Despite the risk, there is no effective vaccine available for this disease. Hence, a recombinant protein construct of truncated nucleocapsid protein viral protein 1 (NPt-VP1198-297), which is capable of inducing neutralizing antibody against EV71, was evaluated in a mouse model. Truncated nucleocapsid protein Newcastle disease virus that was used as immunological carrier fused to VP1 of EV71 as antigen. The recombinant plasmid carrying corresponding genes was constructed by recombinant DNA technology and the corresponding protein was produced in Escherichia coli expression system. The recombinant NPt-VP1198-297 protein had elicited neutralizing antibodies against EV71 with the titer of 1:16, and this result is higher than the titer that is elicited by VP1 protein alone (1:8). It was shown that NPt containing immunogenic epitope(s) of VP1 was capable of inducing a greater functional immune response when compared to full-length VP1 protein alone. It was capable to carry larger polypeptide compared to full-length NP protein. The current study also proved that NPt-VP1198-297 protein can be abundantly produced in recombinant protein form by E. coli expression system. The findings from this study support the importance of neutralizing antibodies in EV71 infection and highlight the potential of the recombinant NPt-VP1198-297 protein as EV71 vaccine.
    Matched MeSH terms: Hand, Foot and Mouth Disease; Newcastle disease virus
  3. Anasir MI, Poh CL
    Int J Mol Sci, 2019 Mar 13;20(6).
    PMID: 30871133 DOI: 10.3390/ijms20061256
    Hand, foot, and mouth disease (HFMD) commonly produces herpangina, but fatal neurological complications have been observed in children. Enterovirus 71 (EV-A71) and Coxsackievirus 16 (CV-A16) are the predominant viruses causing HFMD worldwide. With rising concern about HFMD outbreaks, there is a need for an effective vaccine against EV-A71 and CV-A16. Although an inactivated vaccine has been developed against EV-A71 in China, the inability of the inactivated vaccine to confer protection against CV-A16 infection and other HFMD etiological agents, such as CV-A6 and CV-A10, necessitates the exploration of other vaccine platforms. Thus, the antigenic peptide-based vaccines are promising platforms to develop safe and efficacious multivalent vaccines, while the monoclonal antibodies are viable therapeutic and prophylactic agents against HFMD etiological agents. This article reviews the available information related to the antigenic peptides of the etiological agents of HFMD and their neutralizing antibodies that can provide a basis for the design of future therapies against HFMD etiological agents.
    Matched MeSH terms: Hand, Foot and Mouth Disease/immunology*
  4. Teo CH, Soga T, Parhar IS
    Neurosignals, 2018 02 22;26(1):31-42.
    PMID: 29490303 DOI: 10.1159/000487764
    Beta-catenin is a protein with dual functions in the cell, playing a role in both adhesion between cells as well as gene transcription via the canonical Wnt signalling pathway. In the canonical Wnt signalling pathway, beta-catenin again plays multiple roles. In the embryonic stage, the regulation of beta-catenin levels activates genes that govern cell proliferation and differentiation. In an adult organism, beta-catenin continues to regulate the cell cycle - as a result over-expression of beta-catenin may lead to cancer. In the brain, dysfunctions in Wnt signalling related to beta-catenin levels may also cause various pathological conditions like Alzheimer's disease, Parkinson's disease, and depression. Beta-catenin can be influenced by stressful conditions and increases in glucocorticoid levels. In addition, beta-catenin can be regulated by neurotransmitters such as serotonin and dopamine. Fluctuations in beta-catenin in brain regions under duress have been associated with depressive-like behaviours. It is theorized that the change in behaviour can be attributed to the regulation of Dicer by beta-catenin. Dicer, a protein that produces micro-RNAs in the cell, is a target gene for beta-catenin. Amongst the micro-RNA that it produces are those involved in stress resilience. In this way, beta-catenin has taken its place in the well-studied biochemistry of stress and depression, and future research into this interesting protein may yet yield fruitful results in that field.
    Matched MeSH terms: Alzheimer Disease; Parkinson Disease
  5. Dinh TC, Bac ND, Minh LB, Ngoc VTN, Pham VH, Vo HL, et al.
    Eur J Clin Microbiol Infect Dis, 2019 Sep;38(9):1585-1590.
    PMID: 31044332 DOI: 10.1007/s10096-019-03563-6
    Vietnam, Laos, and Cambodia have reported first cases of Zika virus (ZIKV) infection since 2010 (Cambodia) and 2016 (Vietnam and Laos). One case of ZIKV-related microcephaly was recognized among a hundred infected cases in these areas, raising a great concern about the health risk related to this virus infection. At least 5 cases of ZIKV infection among travelers to Vietnam, Laos, and Cambodia were recorded. It is noticeable that ZIKV in these areas can cause birth defects. This work aims to discuss the current epidemics of ZIKV in Vietnam, Laos, and Cambodia and update the infection risk of ZIKV for travelers to these areas.
    Matched MeSH terms: Disease Outbreaks/statistics & numerical data
  6. Mohd Razali Salleh
    MyJurnal
    The global burden of disease (GBD) has shifted from communicable to non-communicable diseases, and from premature death to years live with disabilities (YLDs) over the past 30 years. Mental and substance use disorders constitute a major component in the scenario of the global health with a significant impact on the global burden of disease, especially in the developing countries. The 1990 GBD study listed depression as the fourth common cause of global burden of disease; while lower respiratory infections, diarrheal diseases and conditions arising during perinatal period are top in the list. In GBD 2000 study depressive disorders climbed to the third place, however still behind lower respiratory infections and diarrheal diseases. The subsequent 2010 GBD study ranked depression in the second place of the global disability burden, and are also considered as a major contributor to the burden of suicide and ischaemic heart disease. The WHO predicted that depressive disorders will be the leading cause of global burden in 2030.
    Matched MeSH terms: Coronary Artery Disease; Global Burden of Disease
  7. Nicqeshen N, Dilashini S, Kirthana S
    Med J Malaysia, 2020 05;75(3):316-321.
    PMID: 32467556
    INTRODUCTION: Ultrasound is widely available, easy-to-use and less expensive than most other imaging methods. It is widely used as a non-invasive method to diagnose acute appendicitis; however, its efficiency still remains questionable, especially when compared to costlier and invasive methods such as computed tomography.

    METHODS: An exploratory review of past literatures on the usage of ultrasound technique in the diagnosis of acute appendicitis in adult patients, and the role of other imaging techniques were undertaken for the study.

    RESULTS: The gold standard for the diagnosis of acute appendicitis still remains a histopathological confirmation after appendectomy. The study further shows imaging has high diagnostic accuracy in the diagnosis of acute appendicitis with low rate of negative appendectomy (<10%). Multiple reasons are identified, including the introduction of computed tomography imaging especially in those patients where ultrasound was unequivocal, more education on imaging which leads to better operator skill or improved performances of machines.

    CONCLUSION: Imaging undoubtedly plays an important role in the diagnosis of acute appendicitis with ultrasound remaining the first-line method in patients referred with clinically suspected acute appendicitis. Nevertheless, those with borderline ultrasound findings or unable to visualize appendix on ultrasound with highly suspicious sign and symptoms were offered other imaging modalities such as CT scan.

    RECOMMENDATION: It is recommended that the managing team balance the risk of radiation exposure, risk of delay in urgent operation and risk of perforation prior to a decision.

    Matched MeSH terms: Acute Disease*
  8. Ahmed K, Dony JJF, Mori D, Haw LY, Giloi N, Jeffree MS, et al.
    Sci Rep, 2020 04 28;10(1):7137.
    PMID: 32346119 DOI: 10.1038/s41598-020-64148-4
    Outbreaks of diarrhea in kindergartens are underreported and frequently go unnoticed in developing countries. To better understand the etiology this study was performed during an outbreak of diarrhea in a kindergarten in Sabah, Malaysia. Outbreak investigation was performed according to the standard procedures. In this outbreak a total of 34 (36.5%) children and 4 (30.8%) teachers suffered from gastroenteritis. Stool samples from seven children and 13 teachers were tested for rotavirus and norovirus. During the investigation stool samples were collected and sent in cold chain to the laboratory. The samples were subjected to rotavirus enzyme linked immunosorbent assay, and reverse transcription PCR for norovirus. All samples were negative for rotavirus but positive for norovirus. To determine the genogroup and genotype of norovirus, nucleotide sequencing of the amplicons was performed. All norovirus from the outbreak was of genotype GII.2[16]. To determine the relatedness of the strains phylogenetic analysis was done using neighbor-joining method. Phylogenetically these strains were highly related to GII.2[P16] noroviruses from China and Japan. This study provided evidence that a diarrheal outbreak in a kindergarten was caused by GII.2[P16] norovirus which is an emerging strain in East Asia and Europe.
    Matched MeSH terms: Disease Outbreaks*
  9. Jex AR, Lim YA, Bethony JM, Hotez PJ, Young ND, Gasser RB
    Adv Parasitol, 2011;74:231-65.
    PMID: 21295679 DOI: 10.1016/B978-0-12-385897-9.00004-5
    Soil-transmitted helminths (STHs) pose significant public health challenges in many countries of Southeast Asia (SEA). Overall, approximately one-third of the world's cases of ascariasis, trichuriasis, and hookworm disease occur in the 11 major SEA countries. Various countries are at different stages in their response to controlling these diseases. For instance, in Malaysia and Thailand, the major burden of disease is confined to rural/remote, indigenous and/or refugee populations. In countries, such as Cambodia, Lao People's Democratic Republic and Vietnam, the burden remains high, although extensive deworming programmes are underway and are yielding encouraging results. The present chapter reviews the current status of STH infections in SEA, identifies knowledge gaps and offers a perspective on the development of improved, integrated surveillance and control in this geographical region. It indicates that advances in our understanding of the epidemiology of these parasites, through the strategic use of molecular and predictive (e.g. geographical information systems (GIS) and remote sensing (RS)) technologies, could readily underpin future research and control programmes. It is hoped that the gradual move towards integrated treatment/control programmes will assist substantially in decreasing the chronic disease burden linked to STHs, thus increasing human health and welfare, and supporting socio-economic growth and development in SEA countries.
    Matched MeSH terms: Communicable Disease Control*
  10. Wan KS, Tok PSK, Yoga Ratnam KK, Aziz N, Isahak M, Ahmad Zaki R, et al.
    PLoS One, 2021;16(4):e0249394.
    PMID: 33852588 DOI: 10.1371/journal.pone.0249394
    INTRODUCTION: The reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described.

    MATERIAL AND METHODS: A COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020.

    RESULTS: A total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (p<0.001). Fever (p<0.001), cough (p = 0.003), shortness of breath (p = 0.015) and sore throat (p = 0.002) were associated with case positivity.

    CONCLUSION: COVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

    Matched MeSH terms: Disease Outbreaks/prevention & control*
  11. Ang KC, Kathirgamanathan S, Ch'ng ES, Lee YY, Roslani AL, Naidu B, et al.
    J Assist Reprod Genet, 2017 Apr;34(4):517-524.
    PMID: 28108842 DOI: 10.1007/s10815-017-0871-0
    PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out.

    METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups.

    RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers.

    CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.

    Matched MeSH terms: Genetic Predisposition to Disease*
  12. Gnanasegaran N, Thimiri Govinda Raj DB, Arumugam S
    Methods Mol Biol, 2020;2125:193-196.
    PMID: 31489601 DOI: 10.1007/7651_2019_261
    Several research groups have utilized dental pulp stem cells for numerous studies as treatment modality for Parkinson's disease (PD). However, the roles of dental pulp stem cells in governing the Parkinson's disease inflammatory microenvironment remain to be evaluated. In this article, we elaborate the method where we can investigate the effects of dental pulp stem cells on neurons and microglia in an in vitro inflammatory microenvironment.
    Matched MeSH terms: Parkinson Disease/pathology*
  13. Deshpande PS, Kotresha D, Noordin R, Yunus MH, Saadatnia G, Golkar M, et al.
    Rev Inst Med Trop Sao Paulo, 2013 4 9;55(2):79-83.
    PMID: 23563759
    Toxoplasmosis is an important cause of congenital infection. The present study was performed to evaluate the usefulness of recombinant (r) GRA-7 cloned from nucleotides (n) 39-711 in discriminating between acute and chronic toxoplasmosis. First, commercial IgM, IgG and IgG avidity ELISAs were used to determine the serological profile of the sera. Serum samples were from 20 symptomatic patients with acute infection (low IgG avidity, IgM positive), 10 with chronic infection (high IgG avidity, IgM negative) and 10 with indeterminate IgG avidity (IgM positive) which were tested for IgG avidity status with an in-house developed IgG avidity Western blot using the rGRA-7 recombinant antigen. All 20 sera from cases of probable acute infection showed bands which either faded out completely or reduced significantly in intensity after treatment with 8 M urea, whereas the band intensities of the 10 serum samples from chronic cases remained the same. Of the 10 sera with indeterminate IgG avidity status, after treatment with 8 M urea the band intensities with six sera remained the same, two sera had completely faded bands and another two sera had significantly reduced band intensities. Discrimination between acute and chronic toxoplasmosis was successfully performed by the in-house IgG avidity Western blot.
    Matched MeSH terms: Acute Disease; Chronic Disease
  14. Bhidayasiri R, Panyakaew P, Trenkwalder C, Jeon B, Hattori N, Jagota P, et al.
    Parkinsonism Relat Disord, 2020 03;72:82-87.
    PMID: 32146380 DOI: 10.1016/j.parkreldis.2020.02.013
    An international panel of movement disorders specialists explored the views and perceptions of people with Parkinson's disease (PD) about their condition and its treatment, including the potential mismatch between the clinician's view of the patient's condition and their own view of what aspects of the disease most affect their daily lives. The initiative was focused on Asian countries, so participants comprised experts in the management of PD from key centers in Asia, with additional insight provided by European and the North American movement disorders experts. Analysis of peer-reviewed publications on patient perceptions of PD and the factors that they consider important to their wellbeing identified several contributing factors to the mismatch of views, including gaps in knowledge of PD and its treatment, an understanding of the clinical heterogeneity of PD, and the importance of a multidisciplinary approach to patient care. The faculty proposed options to bridge these gaps to ensure that PD patients receive the personalized treatment they need to achieve the best possible outcomes. It was considered essential to improve patient knowledge about PD and its treatment, as well as increasing the awareness of clinicians of PD heterogeneity in presentation and treatment response. A multidisciplinary and shared-care approach to PD was needed alongside the use of patient-centered outcome measures in clinical trials and clinical practice to better capture the patient experience and improve the delivery of individualized therapy.
    Matched MeSH terms: Parkinson Disease/therapy*
  15. Huan NC, Ng KL, Tang JT, Kua HN, Daut UN, Muhammad NA, et al.
    Ann Acad Med Singap, 2020 12;49(12):1013-1017.
    PMID: 33463660 DOI: 10.47102/annals-acadmedsg.2020364
    The ongoing pandemic of COVID-19 has presented multiple challenges to global healthcare services, dictating changes in almost every aspect of daily medical practice. Performing aerosol generating procedures (AGPs) in the field of interventional pulmonology can lead to profound formation of aerosols, leading to a high risk of infection among healthcare workers (HCWs). We share our experiences on performing AGPs in the midst of a COVID-19 pandemic by focusing on changes in AGP practices. In a pandemic, HCWs ought to adapt to the ever-changing situation and use available resources to provide the best possible healthcare to patients, ensure safety of staff, and continue medical education of future pulmonologists.
    Matched MeSH terms: Infectious Disease Transmission, Patient-to-Professional/prevention & control*
  16. Thean Hock T, Bogdanova N, Kai Cheen A, Kathirgamanathan S, Bin Abdullah R, Mohd Yusoff N, et al.
    Reprod Biomed Online, 2015 Apr;30(4):434-9.
    PMID: 25682309 DOI: 10.1016/j.rbmo.2014.12.014
    Recurrent spontaneous abortion (RSA) is a prevalent condition among the Malay population of Malaysia, where carriage risk of conventional hereditary thrombophilia factors has been generally ruled out. The contribution of M2/ANXA5, a common haplotype in the annexin A5 gene promoter, was evalauted for RSA in Malay. Seventy-seven women who had experienced two or more unexplained RSA and 41 available male partners were selected for study, with 360 population controls recruited from healthy Malay individuals. Incidence of M2 carriage and odds ratios were calculated between control and patient groups, and clinically defined subgroups and RSA risk was evaluated. M2/ANXA5, found in 42.2% of the general Malay population, was associated with greater risks for women with primary and secondary RSA with early (gestational week 5-15) losses. The risk was somewhat higher in Malay couples when both partners were carriers and a trend of higher prevalence was seen for the male partners patients who had experienced RSA. M2 carriage seems to be a risk factor with unusually high incidence in Malay women and couples with primary and secondary RSA with 'early' spontaneous abortions. The associated male partner risk confirms the proposed role of M2/ANXA5 as a genetic trait impeding embryonic anticoagulation.
    Matched MeSH terms: Genetic Predisposition to Disease*
  17. Hor SL, Teoh SL, Lim WL
    Curr Drug Targets, 2020;21(5):458-476.
    PMID: 31625473 DOI: 10.2174/1389450120666191017120505
    Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  18. Saleem M, Ghazali MB, Wahab MAMA, Yusoff NM, Mahsin H, Seng CE, et al.
    Adv Exp Med Biol, 2020;1292:1-12.
    PMID: 29687286 DOI: 10.1007/5584_2018_147
    Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.
    Matched MeSH terms: Genetic Predisposition to Disease*
  19. Ali MA, Ismail R, Choon TS, Yoon YK, Wei AC, Pandian S, et al.
    Bioorg Med Chem Lett, 2010 Dec 1;20(23):7064-6.
    PMID: 20951037 DOI: 10.1016/j.bmcl.2010.09.108
    Series of pyrolidine analogues were synthesized and examined as acetylcholinesterase (AChE) inhibitors. Among the compounds, compounds 4k and 6k were the most potent inhibitors of the series. Compound 4k, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.10 μmol/L. Pyrolidine analogues might be potential acetyl cholinesterase agents for AD.
    Matched MeSH terms: Alzheimer Disease/drug therapy
  20. Lim LL, Lau ESH, Kong APS, Davies MJ, Levitt NS, Eliasson B, et al.
    Diabetes Care, 2018 06;41(6):1312-1320.
    PMID: 29784698 DOI: 10.2337/dc17-2010
    OBJECTIVE: The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes.

    RESEARCH DESIGN AND METHODS: We searched PubMed and Ovid MEDLINE (January 2000-August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality.

    RESULTS: In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooled mean differences in HbA1c of -0.28% (95% CI -0.35 to -0.21) (-3.1 mmol/mol [-3.9 to -2.3]), in systolic blood pressure (SBP) of -2.3 mmHg (-3.1 to -1.4), in diastolic blood pressure (DBP) of -1.1 mmHg (-1.5 to -0.6), and in LDL cholesterol (LDL-C) of -0.14 mmol/L (-0.21 to -0.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (-0.31 vs. -0.10 mmol/L for <3.4 mmol/L; Pdifference = 0.013), studies from Asia (HbA1c -0.51% vs. -0.23% for North America [-5.5 vs. -2.5 mmol/mol]; Pdifference = 0.046), and studies lasting >12 months (SBP -3.4 vs. -1.4 mmHg, Pdifference = 0.034; DBP -1.7 vs. -0.7 mmHg, Pdifference = 0.047; LDL-C -0.21 vs. -0.07 mmol/L for 12-month studies, Pdifference = 0.049). Patients with median age <60 years had greater HbA1c reduction (-0.35% vs. -0.18% for ≥60 years [-3.8 vs. -2.0 mmol/mol]; Pdifference = 0.029). Team change, patient education/self-management, and improved patient-provider communication had the largest effect sizes (0.28-0.36% [3.0-3.9 mmol/mol]).

    CONCLUSIONS: Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings.
    Matched MeSH terms: Chronic Disease/therapy
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