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  1. Yew SM, Tan KL, Yeo SK, Ng KP, Kuan CS
    J Thorac Dis, 2019 Nov;11(11):4626-4633.
    PMID: 31903251 DOI: 10.21037/jtd.2019.10.69
    BACKGROUND: In many developing countries, acute respiratory tract infections (ARTIs) are the main cause of morbidity and mortality among young children. This study aims to evaluate the molecular epidemiology of respiratory viruses among Malaysian children with confirmed respiratory infections between July 2014 and July 2015.

    METHODS: A total of 394 nasopharyngeal swabs were collected prospectively from children age 0-5 years old with ARTIs from hospitals in Kuala Lumpur. Respiratory viral panel (RVP) assay was used to identify the viral aetiology of respiratory infections.

    RESULTS: From a total of 394 samples, the positive detection rate was 79.9% (n=315). A total of 15 types of RNA viruses and a single type of DNA virus were detected. Enterovirus/rhinovirus (n=112, 28.4%), respiratory syncytial virus (RSV) (n=85, 21.6%), adenovirus (n=64, 16.2%), human bocavirus (n=34, 8.6%), and human metapneumovirus (n=29, 7.4%) were the five predominant viruses. Enterovirus/rhinovirus and RSV constituted most of the viral respiratory infections among young children, especially among children less than 1 year old. No coronavirus was detected among children between 3 and 5 years old. Co-infection caused by 2 or 3 respiratory viruses were detected in 52 patients (13.2%). Enterovirus/rhinovirus, adenovirus, and human bocavirus demonstrated pronounced seasonality. The infection rate peaked during mid-year, while the lowest activity occurred during early of the year.

    CONCLUSIONS: The use of molecular assay as a routine diagnostic in the hospitals can improve the diagnosis and management of respiratory tract infections among children.

  2. Tan JSJ, Ong KC, Ong DBL, Wu YS, Razack A, Kuppusamy S, et al.
    Malays J Pathol, 2019 Dec;41(3):243-251.
    PMID: 31901908
    INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene.

    MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies.

    RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent.

    CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

  3. Tan JS, Lee SY, Chew KW, Lam MK, Lim JW, Ho SH, et al.
    Bioengineered, 2020 12;11(1):116-129.
    PMID: 31909681 DOI: 10.1080/21655979.2020.1711626
    The richness of high-value bio-compounds derived from microalgae has made microalgae a promising and sustainable source of useful product. The present work starts with a review on the usage of open pond and photobioreactor in culturing various microalgae strains, followed by an in-depth evaluation on the common harvesting techniques used to collect microalgae from culture medium. The harvesting methods discussed include filtration, centrifugation, flocculation, and flotation. Additionally, the advanced extraction technologies using ionic liquids as extractive solvents applied to extract high-value bio-compounds such as lipids, carbohydrates, proteins, and other bioactive compounds from microalgae biomass are summarized and discussed. However, more work needs to be done to fully utilize the potential of microalgae biomass for the application in large-scale production of biofuels, food additives, and nutritive supplements.
  4. Low CX, Ng WY, Putra ZA, Aviso KB, Promentilla MAB, Tan RR
    Heliyon, 2020 Jan;6(1):e03083.
    PMID: 31909259 DOI: 10.1016/j.heliyon.2019.e03083
    Identification of appropriate clean technologies for industrial implementation requires systematic evaluation based on a set of criteria that normally reflect economic, technical, environmental and other aspects. Such multiple attribute decision-making (MADM) problems involve rating a finite set of alternatives with respect to multiple potentially conflicting criteria. Conventional MADM approaches often involve explicit trade-offs in between criteria based on the expert's or decision maker's priorities. In practice, many experts arrive at decisions based on their tacit knowledge. This paper presents a new induction approach, wherein the implicit preference rules that estimate the expert's thinking pathways can be induced. P-graph framework is applied to the induction approach as it adds the advantage of being able to determine both optimal and near-optimal solutions that best approximate the decision structure of an expert. The method elicits the knowledge of experts from their ranking of a small set of sample alternatives. Then, the information is processed to induce implicit rules which are subsequently used to rank new alternatives. Hence, the expert's preferences are approximated by the new rankings. The proposed induction approach is demonstrated in the case study on the ranking of Negative Emission Technologies (NETs) viability for industry implementation.
  5. Salam DSDA, Thit EE, Teoh SH, Tan SY, Peh SC, Cheah SC
    J Cancer, 2020;11(1):190-198.
    PMID: 31892985 DOI: 10.7150/jca.36954
    C-MYC, BCL2 and BCL6 genes are the most commonly oncogenes involved in B-Cell lymphomas. Translocations of these oncogenes are associated with an aggressive clinical course. This study aims to elucidate the patterns of BCL6, BCL2 and C-MYC gene aberrations among Malaysian B-cell Non-Hodgkin Lymphoma (NHL) using fluorescence in situ hybridization (FISH). Eighty-one B-cell NHL tissue blocks were retrieved between the year 2011 to 2015 and investigated using immunohistochemistry and interphase FISH dual colour break-apart probes of BCL2, BCL6, C-MYC and IgH. A significant difference was detected between the nodal and extranodal sites in all the BCL2 (p=0.01), C-MYC (p=0.03) and IgH (p=0.006) cases except for BCL6 (p=0.2). Our study showed that BCL6 had the highest gene translocation while BCL2/BCL6 had the most mixed aberrations of gain copies and translocation, however no mixed aberrations of gain copies and translocation was found in C-MYC. None of the mixed gain copies and translocation was found in any of the germinal centre B-cell (GCB) subtype of Diffuse Large B-cell Lymphoma, however, five were found in BCL6 and IgH gene in the non-GCB subtype; while mixed gain copies and translocation cases of BCL2 gene was found in the Follicular Lymphoma cases only. The study found interesting findings of BCL2, C-MYC and IgH gene aberrations between nodal and extranodal sites. This information might benefit future study in predicting prognosis and determine effective therapeutic strategies in the multi-ethnic populations of Malaysia as well as the Asian population.
  6. Tan HL, Kai D, Pasbakhsh P, Teow SY, Lim YY, Pushpamalar J
    Colloids Surf B Biointerfaces, 2020 Apr;188:110713.
    PMID: 31884080 DOI: 10.1016/j.colsurfb.2019.110713
    Electrospinning is a common method to prepare nanofiber scaffolds for tissue engineering. One of the common cellulose esters, cellulose acetate butyrate (CAB), has been electrospun into nanofibers and studied. However, the intrinsic hydrophobicity of CAB limits its application in tissue engineering as it retards cell adhesion. In this study, the properties of CAB nanofibers were improved by fabricating the composite nanofibers made of CAB and hydrophilic polyethylene glycol (PEG). Different ratios of CAB to PEG were tested and only the ratio of 2:1 resulted in smooth and bead-free nanofibers. The tensile test results show that CAB/PEG composite nanofibers have 2-fold higher tensile strength than pure CAB nanofibers. The hydrophobicity of the composite nanofibers was also reduced based on the water contact angle analysis. As the hydrophilicity increases, the swelling ability of the composite nanofiber increases by 2-fold with more rapid biodegradation. The biocompatibility of the nanofibers was tested with normal human dermal fibroblasts (NHDF). The cell viability assay results revealed that the nanofibers are non-toxic. In addition to that, CAB/PEG nanofibers have better cell attachment compared to pure CAB nanofibers. Based on this study, CAB/PEG composite nanofibers could potentially be used as a nanofiber scaffold for applications in tissue engineering.
  7. Lau TTV, Tan JMA, Puthucheary SD, Puah SM, Chua KH
    Braz J Microbiol, 2020 Sep;51(3):909-918.
    PMID: 32067209 DOI: 10.1007/s42770-020-00239-8
    Aeromonas dhakensis is an emergent human pathogen with medical importance. This study was aimed to determine the sequence types (STs), genetic diversity, and phylogenetic relationships of different clinical sources of 47 A. dhakensis from Malaysia using multilocus sequence typing (MLST), goeBURST, and phylogenetic analyses. The analysis of a concatenated six-gene tree with a nucleotide length of 2994 bp based on six housekeeping genes (gyrB, groL, gltA, metG, ppsA, and recA) and independent analyses of single gene fragments was performed. MLST was able to group 47 A. dhakensis from our collection into 36 STs in which 34 STs are novel STs. The most abundant ST521 consisted of five strains from peritoneal fluid and two strains from stools. Comparison of 62 global A. dhakensis was carried out via goeBURST; 94.4% (34/36) of the identified STs are novel and unique in Malaysia. Two STs (111 and 541) were grouped into clonal complexes among our strains and 32 STs occurred as singletons. Single-gene phylogenetic trees showed varying topologies; groL and rpoD grouped all A. dhakensis into a tight-cluster with bootstrap values of 100% and 99%, respectively. A poor phylogenetic resolution encountered in single-gene analyses was buffered by the multilocus phylogenetic tree that offered high discriminatory power (bootstrap value = 100%) in resolving all A. dhakensis from A. hydrophila and delineating the relationship among other taxa. Genetic diversity analysis showed groL as the most conserved gene and ppsA as the most variable gene. This study revealed novel STs and high genetic diversity among clinical A. dhakensis from Malaysia.
  8. Suhaimi AF, Ibrahim N, Tan KA, Silim UA, Moore G, Ryan B, et al.
    BMJ Open, 2020 02 16;10(2):e033920.
    PMID: 32066607 DOI: 10.1136/bmjopen-2019-033920
    INTRODUCTION: People with diabetes are often associated with multifaceted factors and comorbidities. Diabetes management frameworks need to integrate a biopsychosocial, patient-centred approach. Despite increasing efforts in promotion and diabetes education, interventions integrating both physical and mental health components are still lacking in Malaysia. The Optimal Health Programme (OHP) offers an innovative biopsychosocial framework to promote overall well-being and self-efficacy, going beyond education alone and has been identified as relevant within the primary care system. Following a comprehensive cultural adaptation process, Malaysia's first OHP was developed under the name 'Pohon Sihat' (OHP). The study aims to evaluate the effectiveness of the mental health-based self-management and wellness programme in improving self-efficacy and well-being in primary care patients with diabetes mellitus.

    METHODS AND ANALYSIS: This biopsychosocial intervention randomised controlled trial will engage patients (n=156) diagnosed with type 2 diabetes mellitus (T2DM) from four primary healthcare clinics in Putrajaya. Participants will be randomised to either OHP plus treatment as usual. The 2-hour weekly sessions over five consecutive weeks, and 2-hour booster session post 3 months will be facilitated by trained mental health practitioners and diabetes educators. Primary outcomes will include self-efficacy measures, while secondary outcomes will include well-being, anxiety, depression, self-care behaviours and haemoglobin A1c glucose test. Outcome measures will be assessed at baseline, immediately postintervention, as well as at 3 months and 6 months postintervention. Where appropriate, intention-to-treat analyses will be performed.

    ETHICS AND DISSEMINATION: This study has ethics approval from the Medical Research and Ethics Committee, Ministry of Health Malaysia (NMRR-17-3426-38212). Study findings will be shared with the Ministry of Health Malaysia and participating healthcare clinics. Outcomes will also be shared through publication, conference presentations and publication in a peer-reviewed journal.

    TRIAL REGISTRATION NUMBER: NCT03601884.

  9. Tan FHP, Liu G, Lau SA, Jaafar MH, Park YH, Azzam G, et al.
    Benef Microbes, 2020 Feb 19;11(1):79-89.
    PMID: 32066253 DOI: 10.3920/BM2019.0086
    Alzheimer's disease (AD) is a progressive disease and one of the most common forms of neurodegenerative disorders. Emerging evidence is supporting the use of various strategies that modulate gut microbiota to exert neurological and psychological changes. This includes the utilisation of probiotics as a natural and dietary intervention for brain health. Here, we showed the potential AD-reversal effects of Lactobacillus probiotics through feeding to our Drosophila melanogaster AD model. The administration of Lactobacillus strains was able to rescue the rough eye phenotype (REP) seen in AD-induced Drosophila, with a more prominent effect observed upon the administration of Lactobacillus plantarum DR7 (DR7). Furthermore, we analysed the gut microbiota of the AD-induced Drosophila and found elevated levels of Wolbachia. The administration of DR7 restored the gut microbiota diversity of AD-induced Drosophila with a significant reduction in Wolbachia's relative abundance, accompanied by an increase of Stenotrophomonas and Acetobacter. Through functional predictive analyses, Wolbachia was predicted to be positively correlated with neurodegenerative disorders, such as Parkinson's, Huntington's and Alzheimer's diseases, while Stenotrophomonas was negatively correlated with these neurodegenerative disorders. Altogether, our data exhibited DR7's ability to ameliorate the AD effects in our AD-induced Drosophila. Thus, we propose that Wolbachia be used as a potential biomarker for AD.
  10. Seng RX, Tan LL, Lee WPC, Ong WJ, Chai SP
    J Environ Manage, 2020 Feb 01;255:109936.
    PMID: 32063312 DOI: 10.1016/j.jenvman.2019.109936
    Growing concerns of water pollution by dye pollutants from the textile industry has led to vast research interest to find green solutions to address this issue. In recent years, heterogeneous photocatalysis has harvested tremendous attention from researchers due to its powerful potential applications in tackling many important energy and environmental challenges at a global level. To fully utilise the broad spectrum of solar energy has been a common aim in the photocatalyst industry. This study focuses on the development of an efficient, highly thermal and chemical stable, environmentally friendly and metal-free graphitic carbon nitride (g-C3N4) to overcome the problem of fast charge recombination which hinders photocatalytic performances. Nitrogen-doped carbon quantum dots (NCQDs) known for its high electronic and optical functionality properties is believed to achieve photocatalytic enhancement by efficient charge separation through forming heterogeneous interfaces. Hence, the current work focuses on the hybridisation of NCQDs and g-C3N4 to produce a composite photocatalyst for methylene blue (MB) degradation under LED light irradiation. The optimal hybridisation method and the mass loading required for maximum attainable MB degradation were systematically investigated. The optimum photocatalyst, 1 wt% NCQD/g-C3N4 composite was shown to exhibit a 2.6-fold increase in photocatalytic activity over bare g-C3N4. Moreover, the optimum sample displayed excellent stability and durability after three consecutive degradation cycles, retaining 91.2% of its original efficiency. Scavenging tests were also performed where reactive species, photon-hole (h+) was identified as the primary active species initiating the pollutant degradation mechanism. The findings of this study successfully shed light on the hybridisation methods of NCQDs which improve existing g-C3N4 photocatalyst systems for environmental remediation by utilising solar energy.
  11. Ng ZQ, Wijesuriya R, Misur P, Tan JH, Moe KS, Theophilus M
    Surg Endosc, 2021 02;35(2):636-643.
    PMID: 32072285 DOI: 10.1007/s00464-020-07427-5
    BACKGROUND: Diverticular disease has been linked to obesity. Recent studies have assessed the role of visceral adiposity with diverticulitis and its complications. The aim of this study was to evaluate the association of quantitative radiological measures of visceral adiposity in patients with diverticulitis with vital signs, biochemistry results, uncomplicated versus complicated diverticulitis and its interventions.

    METHODS: A retrospective analysis of all patients with diverticulitis admitted from November 2015 to April 2018 at a single institution was performed. Data collected included demographics, vital signs, biochemistry results, CT scan findings and management outcomes. The patients were divided into uncomplicated (U) and complicated diverticulitis (C) groups. Visceral fat area (VFA), subcutaneous fat area (SFA) and VFA/SFA ratio (V/S) were measured at L4/L5 level by the radiologist. Statistical analysis was performed to evaluate the association of VFA, SFA, V/S with the parameters in both U and C groups.

    RESULTS: 352 patients were included in this study (U:C = 265:87). There was no significant difference in vital signs and biochemistry results in both groups. There was no significant difference in VFA, SFA, V/S ratios in both groups. In patients with V/S ratio > 0.4, they were 5.06 times more likely to undergo emergency intervention (95% CI 1.10-23.45) (p = 0.03). On multivariate analysis, a heart rate > 100 (OR 2.9, 95% CI 1.2-6.7), CRP > 50 (OR 3.4, 95% CI 1.9-6.0), WCC  12 (OR 2.1, 95% CI 1.2-3.6) and V/S ratio > 0.4 (OR 2.8, 95% CI 1.5-5.4) were predictive of complicated diverticulitis.

    CONCLUSION: The quantitative radiological measurement of visceral adiposity is useful in prognostication in patients presenting with diverticulitis.

  12. Tan YA, Ng KC, Cheo SW, Low QJ, Chia YK
    QJM, 2020 07 01;113(7):485-487.
    PMID: 32053172 DOI: 10.1093/qjmed/hcaa025
  13. Tan SN, Sani D, Lim CW, Ideris A, Stanslas J, Lim CTS
    PMID: 32051689 DOI: 10.1155/2020/8068797
    Edible bird's nest (EBN) which is solidified swiftlet's saliva contains high nutritional value. It is widely consumed in countries like Malaysia, Indonesia, and Thailand. However, previous proximate analysis of Malaysia EBN was not representative of all the regions in Malaysia. In recent years, safety issues such as high nitrate and nitrite contents, presence of heavy metal, adulteration, fungal infection, and cancer cell stimulation were associated with EBN. Hence, this study aimed to determine the proximate analysis, safety profile during normal weather and hazy periods, and its effect on cancer cells stimulation in Malaysia-farmed EBN. Seven raw cleaned EBN samples were sourced from 6 different regions in Malaysia. Proximate analysis and safety profile were performed using official AOCA methods and Malaysian Standard. High protein (53.03-56.37%) and carbohydrate content (27.97-31.68%) with an acceptable level of moisture (10.8-14.04%) and ash (2.22-3.38%) were reported. A good safety profile was obtained with low nitrite and nitrate levels, with undetectable heavy metals and no significant growth of pathogenic microorganism except mould. Epidermal growth factor was detected but below the quantification level with the chicken EGF ELISA kit. The microculture tetrazolium (MTT) assay was performed for growth stimulation assessment comparing human EGF and EBN. There was no significant cell growth observed in cancer cells after EBN treatment. In conclusion, EBN Malaysia has a good nutritional profile, free of heavy metals, and an acceptable level of nitrate, nitrite, and microorganism profile except for mould contents. Furthermore, the in vitro study indicated that EBN was not associated with cancer cell growth.
  14. Elfikrie N, Ho YB, Zaidon SZ, Juahir H, Tan ESS
    Sci Total Environ, 2020 Apr 10;712:136540.
    PMID: 32050383 DOI: 10.1016/j.scitotenv.2020.136540
    Agricultural activities have been arising along with the use of pesticides. The use of pesticides can impact not only on vector or other pest but also able to harm human health. Pesticide may leach from the irrigation of plant into the groundwater and in surface water. These waters could be sources of drinking water in a pesticides polluted area. This study aims to determine the occurrence pesticides in surface water and pesticides removal efficiency in a conventional drinking water treatment plant (DWTP) and the potential health risk to consumers. The study was conducted in Tanjung Karang, Selangor, Malaysia. Thirty river water samples and eighteen water samples from DWTP were collected. The water samples were extracted using solid phase extraction (SPE) before injected to the ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Five hundreds and ten respondents were interviewed using questionnaires to obtain information for health risk assessments. The results showed that propiconazole had the highest mean concentration (4493.1 ng/L) while pymetrozine had the lowest mean concentration (1.3 ng/L) in river water samples. The pesticides removal efficiencies in the conventional DWTP were 77% (imidacloprid), 86% (propiconazole and buprofezin), 88% (tebuconazole) and 100% (pymetrozine, tricyclazole, chlorantraniliprole, azoxystrobin and trifloxystrobin), respectively. The hazard quotients (HQs) and hazard index (HI) for all target pesticides were <1, indicating there was no significant chronic non-carcinogenic health risk due to consumption of the drinking water. Conventional DWTP was not able to completely remove four pesticide; thus, advanced treatment systems need to be considered to safeguard the health of the community in future.
  15. Tan BK, Chua SS, Chen LC, Chang KM, Balashanker S, Bee PC
    Support Care Cancer, 2020 Jul;28(7):3237-3247.
    PMID: 31734798 DOI: 10.1007/s00520-019-05133-0
    PURPOSE: Suboptimal adherence to tyrosine kinase inhibitors (TKIs) contributes to poor clinical outcomes in chronic myeloid leukemia (CML). This randomised controlled trial (RCT) aimed to evaluate the impact of a medication management service (MMS) on adherence to TKIs and clinical outcomes.

    METHODS: A parallel RCT was conducted in two hospitals in Malaysia, where 129 CML patients were randomised to MMS or control (usual care) groups using a stratified 1:1 block randomisation method. The 6-month MMS included three face-to-face medication use reviews, CML and TKI-related education, two follow-up telephone conversations, a printed information booklet and two adherence aids. Medication adherence (primary outcome), molecular responses and health-related quality of life (HRQoL) scores were assessed at baseline, 6th and 12th month. Medication adherence and HRQoL were assessed using medication possession ratio and the European Organisation for Research and Treatment in Cancer questionnaire (EORTC_QLQ30_CML24) respectively.

    RESULTS: The MMS group (n = 65) showed significantly higher adherence to TKIs than the control group (n = 64) at 6th month (81.5% vs 56.3%; p = 0.002), but not at 12th month (72.6% vs 60.3%; p = 0.147). In addition, a significantly higher proportion of participants in the MMS group achieved major molecular response at 6th month (58.5% vs 35.9%; p = 0.010), but not at 12th month (66.2% vs 51.6%; p = 0.092). Significant deep molecular response was also obtained at 12th month (24.6% vs 10.9%; p = 0.042). Six out of 20 subscales of EORTC-QLQ30-CML24 were significantly better in the MMS group.

    CONCLUSIONS: The MMS improved CML patients' adherence to TKI as well as achieved better clinical outcomes.

    TRIAL REGISTRATION: Clinicaltrial.gov (ID: NCT03090477).

  16. Tan YH, Lim PE, Beardall J, Poong SW, Phang SM
    Aquat Toxicol, 2019 Dec;217:105349.
    PMID: 31734626 DOI: 10.1016/j.aquatox.2019.105349
    Ocean acidification, due to increased levels of anthropogenic carbon dioxide, is known to affect the physiology and growth of marine phytoplankton, especially in polar regions. However, the effect of acidification or carbonation on cellular metabolism in polar marine phytoplankton still remains an open question. There is some evidence that small chlorophytes may benefit more than other taxa of phytoplankton. To understand further how green polar picoplankton could acclimate to high oceanic CO2, studies were conducted on an Antarctic Chlorella sp. Chlorella sp. maintained its growth rate (∼0.180 d-1), photosynthetic quantum yield (Fv/Fm = ∼0.69) and chlorophyll a (0.145 fg cell-1) and carotenoid (0.06 fg cell-1) contents under high CO2, while maximum rates of electron transport decreased and non-photochemical quenching increased under elevated CO2. GCMS-based metabolomic analysis reveal that this polar Chlorella strain modulated the levels of metabolites associated with energy, amino acid, fatty acid and carbohydrate production, which could favour its survival in an increasingly acidified ocean.
  17. Lai NM, Chang SMW, Ng SS, Tan SL, Chaiyakunapruk N, Stanaway F
    Cochrane Database Syst Rev, 2019 11 25;2019(11).
    PMID: 31763689 DOI: 10.1002/14651858.CD013243.pub2
    BACKGROUND: Dementia is a chronic condition which progressively affects memory and other cognitive functions, social behaviour, and ability to carry out daily activities. To date, no treatment is clearly effective in preventing progression of the disease, and most treatments are symptomatic, often aiming to improve people's psychological symptoms or behaviours which are challenging for carers. A range of new therapeutic strategies has been evaluated in research, and the use of trained animals in therapy sessions, termed animal-assisted therapy (AAT), is receiving increasing attention.

    OBJECTIVES: To evaluate the efficacy and safety of animal-assisted therapy for people with dementia.

    SEARCH METHODS: We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialised Register on 5 September 2019. ALOIS contains records of clinical trials identified from monthly searches of major healthcare databases, trial registries, and grey literature sources. We also searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), ISI Web of Science, ClinicalTrials.gov, and the WHO's trial registry portal.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-randomised trials, and randomised cross-over trials that compared AAT versus no AAT, AAT using live animals versus alternatives such as robots or toys, or AAT versus any other active intervention.

    DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of Cochrane Dementia. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with their 95% confidence intervals (CIs) where appropriate.

    MAIN RESULTS: We included nine RCTs from 10 reports. All nine studies were conducted in Europe and the US. Six studies were parallel-group, individually randomised RCTs; one was a randomised cross-over trial; and two were cluster-RCTs that were possibly related where randomisation took place at the level of the day care and nursing home. We identified two ongoing trials from trial registries. There were three comparisons: AAT versus no AAT (standard care or various non-animal-related activities), AAT using live animals versus robotic animals, and AAT using live animals versus the use of a soft animal toy. The studies evaluated 305 participants with dementia. One study used horses and the remainder used dogs as the therapy animal. The duration of the intervention ranged from six weeks to six months, and the therapy sessions lasted between 10 and 90 minutes each, with a frequency ranging from one session every two weeks to two sessions per week. There was a wide variety of instruments used to measure the outcomes. All studies were at high risk of performance bias and unclear risk of selection bias. Our certainty about the results for all major outcomes was very low to moderate. Comparing AAT versus no AAT, participants who received AAT may be slightly less depressed after the intervention (MD -2.87, 95% CI -5.24 to -0.50; 2 studies, 83 participants; low-certainty evidence), but they did not appear to have improved quality of life (MD 0.45, 95% CI -1.28 to 2.18; 3 studies, 164 participants; moderate-certainty evidence). There were no clear differences in all other major outcomes, including social functioning (MD -0.40, 95% CI -3.41 to 2.61; 1 study, 58 participants; low-certainty evidence), problematic behaviour (SMD -0.34, 95% CI -0.98 to 0.30; 3 studies, 142 participants; very-low-certainty evidence), agitation (SMD -0.39, 95% CI -0.89 to 0.10; 3 studies, 143 participants; very-low-certainty evidence), activities of daily living (MD 4.65, 95% CI -16.05 to 25.35; 1 study, 37 participants; low-certainty evidence), and self-care ability (MD 2.20, 95% CI -1.23 to 5.63; 1 study, 58 participants; low-certainty evidence). There were no data on adverse events. Comparing AAT using live animals versus robotic animals, one study (68 participants) found mixed effects on social function, with longer duration of physical contact but shorter duration of talking in participants who received AAT using live animals versus robotic animals (median: 93 seconds with live versus 28 seconds with robotic for physical contact; 164 seconds with live versus 206 seconds with robotic for talk directed at a person; 263 seconds with live versus 307 seconds with robotic for talk in total). Another study showed no clear differences between groups in behaviour measured using the Neuropsychiatric Inventory (MD -6.96, 95% CI -14.58 to 0.66; 78 participants; low-certainty evidence) or quality of life (MD -2.42, 95% CI -5.71 to 0.87; 78 participants; low-certainty evidence). There were no data on the other outcomes. Comparing AAT using live animals versus a soft toy cat, one study (64 participants) evaluated only social functioning, in the form of duration of contact and talking. The data were expressed as median and interquartile ranges. Duration of contact was slightly longer in participants in the AAT group and duration of talking slightly longer in those exposed to the toy cat. This was low-certainty evidence.

    AUTHORS' CONCLUSIONS: We found low-certainty evidence that AAT may slightly reduce depressive symptoms in people with dementia. We found no clear evidence that AAT affects other outcomes in this population, with our certainty in the evidence ranging from very-low to moderate depending on the outcome. We found no evidence on safety or effects on the animals. Therefore, clear conclusions cannot yet be drawn about the overall benefits and risks of AAT in people with dementia. Further well-conducted RCTs are needed to improve the certainty of the evidence. In view of the difficulty in achieving blinding of participants and personnel in such trials, future RCTs should work on blinding outcome assessors, document allocation methods clearly, and include major patient-important outcomes such as affect, emotional and social functioning, quality of life, adverse events, and outcomes for animals.

  18. Kho JPY, Tang IP, Tan KS, Koa AJ, Prepageran N, Rajagopalan R
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 3):1994-1999.
    PMID: 31763282 DOI: 10.1007/s12070-018-1415-3
    We studied the ethmoidal arteries using preexisting computer tomography of the paranasal sinuses (CT PNS) and statistically scrutinized data obtained between genders. A descriptive study from 77 CT PNS dated January 2016-December 2016 were collected and reviewed by two radiologists. A total of 54 (108 sides) CT PNS were studied of patients aged 18-77 years. 37 are male, 17 are female; with Bumiputera Sarawak predominance of 25 patients, 12 Malays, 16 Chinese and one Indian. Rate of identification are as follows: anterior ethmoidal artery (AEA)-100%, middle ethmoidal artery (MEA)-30%, posterior ethmoidal artery (PEA)-86%. The average distance from AEA-MEA is 8.1 ± 1.52 mm, MEA-PEA is 5.5 ± 1.29 mm and AEA-PEA is 12.9 ± 1.27 mm. The mean distance from PEA-the anterior wall of sphenoid is 7.7 ± 3.96 mm, and PEA-optic canal is 8.5 ± 3.1 mm with no statistical difference when compared between gender. AEA frequently presented with a long mesentery 57.4%, while 87.1% of PEA was hidden in a bony canal. The vertical distance of the AEA-skull base ranges from 0 to 12.5 mm whilst PEA-skull base is 0-4.7 mm. There is no statistical difference in distances of AEA, MEA nor PEA to skull base when analyzed between genders; t(82) = 1.663, p > 0.05, t(32) = 0.403, p > 0.05 and t(75) = 1.333, p > 0.05 respectively. We newly discovered, that 50% of MEA is hidden in a bony canal, and its distance to skull base ranged 0-5.3 mm. MEA and PEA less commonly have a short or long mesentery. Knowledge on the ethmoidal arteries especially in our unstudied population of diverse ethnicity, gains to assist surgeons worldwide, when embarking in endoscopic transnasal surgeries.
  19. El-Kenawy A, Benarba B, Neves AF, de Araujo TG, Tan BL, Gouri A
    EXCLI J, 2019;18:908-930.
    PMID: 31762718 DOI: 10.17179/excli2019-1833
    Gene therapy became in last decade a new emerging therapeutic era showing promising results against different diseases such as cancer, cardiovascular diseases, diabetes, and neurological disorders. Recently, the genome editing technique for eukaryotic cells called CRISPR-Cas (Clustered Regulatory Interspaced Short Palindromic Repeats) has enriched the field of gene surgery with enhanced applications. In the present review, we summarized the different applications of gene surgery for treating human diseases such as cancer, diabetes, nervous, and cardiovascular diseases, besides the molecular mechanisms involved in these important effects. Several studies support the important therapeutic applications of gene surgery in a large number of health disorders and diseases including β-thalassemia, cancer, immunodeficiencies, diabetes, and neurological disorders. In diabetes, gene surgery was shown to be effective in type 1 diabetes by triggering different signaling pathways. Furthermore, gene surgery, especially that using CRISPR-Cas possessed important application on diagnosis, screening and treatment of several cancers such as lung, liver, pancreatic and colorectal cancer. Nevertheless, gene surgery still presents some limitations such as the design difficulties and costs regarding ZFNs (Zinc Finger Nucleases) and TALENs (Transcription Activator-Like Effector Nucleases) use, off-target effects, low transfection efficiency, in vivo delivery-safety and ethical issues.
  20. Chan CK, Low JS, Lim KS, Low SK, Tan CT, Ng CC
    Neurol Sci, 2020 Mar;41(3):591-598.
    PMID: 31720899 DOI: 10.1007/s10072-019-04122-9
    INTRODUCTION: Genetic (idiopathic) generalized epilepsy (GGE) is a common form of epilepsy characterized by unknown aetiology and a presence of genetic component in its predisposition.

    METHODS: To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.

    RESULTS: Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.

    CONCLUSION: The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.

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