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  1. Tan ESS, Chin SAFX, Sathapan MSP, Dewi AD, Amini F, Bustami NA, et al.
    PMID: 36901057 DOI: 10.3390/ijerph20054046
    The interplay of physical, social, and economic factors during the pandemic adversely affected the mental health of healthy people and exacerbated pre-existing mental disorders. This study aimed to determine the impact of the COVID-19 pandemic on the mental health of the general population in Malaysia. A cross-sectional study involving 1246 participants was conducted. A validated questionnaire consisting of the level of knowledge and practice of precautionary behaviors, the Depression, Anxiety, and Stress Scales (DASS), and the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) was used as an instrument to assess the impacts of the COVID-19 pandemic. Results revealed that most participants possessed a high level of knowledge about COVID-19 and practiced wearing face masks daily as a precautionary measure. The average DASS scores were beyond the mild to moderate cut-off point for all three domains. The present study found that prolonged lockdowns had significantly impacted (p < 0.05), the mental health of the general population in Malaysia, reducing quality of life during the pandemic. Employment status, financial instability, and low annual incomes appeared to be risk factors (p < 0.05) contributing to mental distress, while older age played a protective role (p < 0.05). This is the first large-scale study in Malaysia to assess the impacts of the COVID-19 pandemic on the general population.
  2. Siew ZY, Tan YF, Iswara RP, Wong SF, Wong ST, Tan BK, et al.
    Microbes Infect, 2024;26(1-2):105243.
    PMID: 38380604 DOI: 10.1016/j.micinf.2023.105243
    Pteropine orthoreovirus (PRV) causes respiratory tract infections in humans. Despite its emergence as a zoonotic and respiratory virus, little is known about its cell tropism, which hampers progress in fully understanding its pathogenesis in humans. Hek293 cells are most susceptible to PRV infection, while HeLa cells are the least. Human cytokeratin 1 (CK1) was identified as the protein that interacts with PRV. The immunofluorescence assay and qPCR results revealed prior treatment with anti-CK1 may provide Hek293 cells protection against PRV. The KRT1-knockout Hek293 cells were less susceptible to PRV infection. Further study into the pathogenesis of PRV in humans is needed.
  3. Lee SY, Tan YH, Lau SY, Mubarak NM, Tan YY, Tan IS, et al.
    Environ Res, 2024 Jun 27;259:119448.
    PMID: 38942255 DOI: 10.1016/j.envres.2024.119448
    Dye wastewater consists of high solids concentrations, heavy metals, minor contaminants, dissolved chemical oxygen demand, and microorganisms. Nanoflowers are nanoparticles that resemble flowers when viewed at a microscopic level. Inorganic metal oxide nanoflowers have been discovered to be a potential source for overcoming this situation. Their flower-like features give them a higher surface area to volume ratio and porosity structure, which can absorb a significant amount of dye. The metal oxide nanoflower synthesized from different synthesis methods is used to compare which one is cost-effective and capable of generating a large scale of nanoflower. This review has demonstrated outstanding dye removal efficiency by applying inorganic nanoflowers to dye removal. Since both adsorption and photocatalytic reactions enhance the dye degradation process, complete dye degradation could be achieved. Meanwhile, the inorganic metal oxide nanoflowers' exemplary reusability characteristics with negligible performance drop further prove that this approach is highly sustainable and may help to save costs. This review has proven the momentum of obtaining high dye removal efficiency in wastewater treatment to conclude that the metal oxide nanoflower study is worth researching.
  4. Mat S, Ng CT, Tan PJ, Ramli N, Fadzli F, Rozalli FI, et al.
    PM R, 2018 03;10(3):254-262.
    PMID: 28827207 DOI: 10.1016/j.pmrj.2017.08.405
    BACKGROUND: Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited.
    OBJECTIVE: To evaluate the effect of a personalized home-based exercise program to improve postural balance, fear of falling, and falls risk in older fallers with knee OA and gait and balance problems.
    DESIGN: Randomized controlled trial.
    SETTING: University of Malaya Medical Centre.
    PARTICIPANTS: Fallers who had both radiological OA and a Timed Up and Go (TUG) score of over 13.5 seconds.
    MAIN OUTCOME MEASURE: Postural sway (composite sway) was quantified with the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB) under 4 different sensory conditions: eyes open on firm surface, eyes closed on firm surface, eyes open on unstable foam surface, and eyes closed on unstable foam surface. Participants were asked to stand upright and to attempt to hold their position for 10 seconds for each test condition. The average reading for all conditions were calculated.
    METHODS: Participants randomized to the intervention arm received a home-based modified Otago Exercise Program (OEP) as part of a multifactorial intervention, whereas control participants received general health advice and conventional treatment. This was a secondary subgroup analysis from an original randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT) (trial registration number: ISRCTN11674947). Posturography using a long force plate balance platform (Balancemaster, NeuroCom, USA), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the short-form Falls Efficacy Scale-International (short FES-I) were assessed at baseline and 6 months.
    RESULTS: Results of 41 fallers with radiological evidence of OA and impaired TUG (intervention, 17; control, 24) were available for the final analysis. Between-group analysis revealed significant improvements in the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB), Limits of Stability (LOS), and short FES-I scores by the intervention group compared to the control group at 6 months. No significant difference in time to first fall or in fall-free survival between the intervention and control groups was found.

    CONCLUSION: Home-based balance and strength exercises benefited older fallers with OA and gait and balance disorders by improving postural control, with no observable trend in reduction of fall recurrence. Our findings will now inform a future, adequately powered, randomized controlled study using fall events as definitive outcomes.

    LEVEL OF EVIDENCE: I.
  5. Tan BK, Tan SB, Chen LC, Chang KM, Chua SS, Balashanker S, et al.
    Patient Prefer Adherence, 2017;11:1027-1034.
    PMID: 28652712 DOI: 10.2147/PPA.S132894
    PURPOSE: Poor adherence to tyrosine kinase inhibitors (TKIs) could compromise the control of chronic myeloid leukemia (CML) and contributes to poorer survival. Little is known about how medication-related issues affect CML patients' adherence to TKI therapy in Malaysia. This qualitative study aimed to explore these issues.

    PATIENTS AND METHODS: Individual face-to-face, semistructured interviews were conducted at the hematology outpatient clinics of two medical centers in Malaysia from August 2015 to January 2016. CML patients aged ≥18 years who were prescribed a TKI were invited to participate in the study. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed.

    RESULTS: Four themes were identified from 18 interviews: 1) concerns about adverse reactions to TKIs, 2) personal beliefs regarding the use of TKIs, 3) mismanagement of TKIs in daily lives, and 4) financial burden in accessing treatment. Participants skipped their TKIs due to ineffective emesis control measures and perceived wastage of medication from vomiting. Participants also modified their TKI therapy due to fear of potential harm from long-term use, and stopped taking their TKIs based on belief in curative claims of traditional medicines and misconception about therapeutic effects of TKIs. Difficulty in integrating the dosing requirements of TKIs into daily lives led to unintentional skipping of doses, as well as the risk of toxicities from inappropriate dosing intervals or food interactions. Furthermore, financial constraints also resulted in delayed initiation of TKIs, missed clinic appointments, and treatment interruptions.

    CONCLUSION: Malaysian CML patients encountered a range of medication-related issues leading to a complex pattern of nonadherence to TKI therapy. Further studies should investigate whether regular contact with patients to improve understanding of treatment rationale, to elicit and address patients' concerns about adverse reactions, and to empower patients with skills to self-manage their medications might promote better adherence to TKIs and improve CML patients' outcome.

    Study site: hematology outpatient clinics of Ampang Hospital (AH) and University Malaya Medical Centre (UMMC) in Malaysia
  6. Maherally Z, Fillmore HL, Tan SL, Tan SF, Jassam SA, Quack FI, et al.
    FASEB J, 2018 01;32(1):168-182.
    PMID: 28883042 DOI: 10.1096/fj.201700162R
    The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most in vitro models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, in vitro 3-dimensional (3D) models incorporating relevant human, in vivo cell types and BL proteins. The 3D BBB models were constructed with human brain endothelial cells, human astrocytes, and human brain pericytes in mono-, co-, and tricultures. TEER was measured in 3D models using a volt/ohmmeter and cellZscope. Influence of BL proteins-laminin, fibronectin, collagen type IV, agrin, and perlecan-on adhesion and TEER was assessed using an electric cell-substrate impedance-sensing system. TJ protein expression was assessed by Western blotting (WB) and immunocytochemistry (ICC). Perlecan (10 µg/ml) evoked unreportedly high, in vitro TEER values (1200 Ω) and the strongest adhesion. Coculturing endothelial cells with astrocytes yielded the greatest resistance over time. ICC and WB results correlated with resistance levels, with evidence of prominent occludin expression in cocultures. BL proteins exerted differential effects on TEER, whereas astrocytes in contact yielded higher TEER values and TJ expression.-Maherally, Z., Fillmore, H. L., Tan, S. L., Tan, S. F., Jassam, S. A., Quack, F. I., Hatherell, K. E., Pilkington, G. J. Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.
  7. Fong JYM, Tan VJH, Lee JR, Tong ZGM, Foong YK, Tan JME, et al.
    Eur J Dent Educ, 2018 Aug;22(3):160-166.
    PMID: 29266663 DOI: 10.1111/eje.12297
    AIM: To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates.

    METHODS: Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test.

    RESULTS: Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001).

    CONCLUSION: Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT.

  8. Chin PS, Ang GY, Yu CY, Tan EL, Tee KK, Yin WF, et al.
    J Food Prot, 2018 Feb;81(2):284-289.
    PMID: 29360399 DOI: 10.4315/0362-028X.JFP-17-186
    Listeria spp. are ubiquitous in nature and can be found in various environmental niches such as soil, sewage, river water, plants, and foods, but the most frequently isolated species are Listeria monocytogenes and Listeria innocua. In this study, the presence of Listeria spp. in raw chicken meat and chicken-related products sold in local markets in Klang Valley, Malaysia was investigated. A total of 44 Listeria strains (42 L. innocua and 2 L. welshimeri) were isolated from 106 samples. Antibiotic susceptibility tests of the L. innocua strains revealed a high prevalence of resistance to clindamycin (92.9%), ceftriaxone (76.2%), ampicillin (73.8%), tetracycline (69%), and penicillin G (66.7%). Overall, 31 L. innocua and 1 L. welshimeri strain were multidrug resistant, i.e., nonsusceptible to at least one antimicrobial agent in three or more antibiotic classes. The majority of the L. innocua strains were placed into five AscI pulsogroups, and overall 26 distinct AscI pulsotypes were identified. The detection of multidrug-resistant Listeria strains from different food sources and locations warrants attention because these strains could serve as reservoirs for antimicrobial resistance genes and may facilitate the spread and emergence of other drug-resistant strains.
  9. Tan JH, Hagiwara Y, Pang W, Lim I, Oh SL, Adam M, et al.
    Comput Biol Med, 2018 03 01;94:19-26.
    PMID: 29358103 DOI: 10.1016/j.compbiomed.2017.12.023
    Coronary artery disease (CAD) is the most common cause of heart disease globally. This is because there is no symptom exhibited in its initial phase until the disease progresses to an advanced stage. The electrocardiogram (ECG) is a widely accessible diagnostic tool to diagnose CAD that captures abnormal activity of the heart. However, it lacks diagnostic sensitivity. One reason is that, it is very challenging to visually interpret the ECG signal due to its very low amplitude. Hence, identification of abnormal ECG morphology by clinicians may be prone to error. Thus, it is essential to develop a software which can provide an automated and objective interpretation of the ECG signal. This paper proposes the implementation of long short-term memory (LSTM) network with convolutional neural network (CNN) to automatically diagnose CAD ECG signals accurately. Our proposed deep learning model is able to detect CAD ECG signals with a diagnostic accuracy of 99.85% with blindfold strategy. The developed prototype model is ready to be tested with an appropriate huge database before the clinical usage.
  10. Adam M, Oh SL, Sudarshan VK, Koh JE, Hagiwara Y, Tan JH, et al.
    Comput Methods Programs Biomed, 2018 Jul;161:133-143.
    PMID: 29852956 DOI: 10.1016/j.cmpb.2018.04.018
    Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide. The rising mortality rate can be reduced by early detection and treatment interventions. Clinically, electrocardiogram (ECG) signal provides useful information about the cardiac abnormalities and hence employed as a diagnostic modality for the detection of various CVDs. However, subtle changes in these time series indicate a particular disease. Therefore, it may be monotonous, time-consuming and stressful to inspect these ECG beats manually. In order to overcome this limitation of manual ECG signal analysis, this paper uses a novel discrete wavelet transform (DWT) method combined with nonlinear features for automated characterization of CVDs. ECG signals of normal, and dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and myocardial infarction (MI) are subjected to five levels of DWT. Relative wavelet of four nonlinear features such as fuzzy entropy, sample entropy, fractal dimension and signal energy are extracted from the DWT coefficients. These features are fed to sequential forward selection (SFS) technique and then ranked using ReliefF method. Our proposed methodology achieved maximum classification accuracy (acc) of 99.27%, sensitivity (sen) of 99.74%, and specificity (spec) of 98.08% with K-nearest neighbor (kNN) classifier using 15 features ranked by the ReliefF method. Our proposed methodology can be used by clinical staff to make faster and accurate diagnosis of CVDs. Thus, the chances of survival can be significantly increased by early detection and treatment of CVDs.
  11. Kwan Z, Bong YB, Tan LL, Lim SX, Yong ASW, Ch'ng CC, et al.
    Arch. Dermatol. Res., 2018 Jul;310(5):443-451.
    PMID: 29687328 DOI: 10.1007/s00403-018-1832-x
    We investigated whether disease severity and clinical manifestations were associated with depression, anxiety, stress and quality of life in adults with psoriasis. Participants were recruited from a dermatology outpatient clinic at a teaching hospital. Information on sociodemographic characteristics, disease severity, presence of arthropathy and head involvement was specifically recorded. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). Quality of life and psychological symptoms were measured using the Dermatology Life Quality Index (DLQI) and the Depression Anxiety Stress Scale (DASS), respectively. One hundred individuals were recruited. Unadjusted analysis revealed that head involvement was associated with depression [odds ratio (OR) 8.509; 95% confidence interval (CI) 1.077-67.231] and anxiety (OR 6.46; 95% CI 1.401-29.858). Severe disease was associated with a poorer quality of life compared to mild disease (OR 3.750; 95% CI 1.330-10.577). Younger age was associated with an increased risk of depression [mean difference (MD) - 8.640; 95% CI - 16.390 to - 0.890], anxiety (MD - 11.553; 95% CI - 18.478 to- 4.628), stress (MD - 11.440; 95% CI - 19.252 to - 3.628) and severely impaired quality of life (MD - 12.338; 95% CI - 19.548 to - 5.127). Following adjustments for age and disease severity, anxiety, stress and depression remained associated with severely impaired quality of life.
    Study site: Dermatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  12. Jaafar MH, Mahadeva S, Tan KM, Chin AV, Kamaruzzaman SB, Khor HM, et al.
    Nutr Clin Pract, 2019 Apr;34(2):280-289.
    PMID: 30251336 DOI: 10.1002/ncp.10195
    BACKGROUND: A barrier to gastrostomy feeding exists among Asian clinicians and caregivers due to negative perceptions regarding complications. We compared clinical and nutrition outcomes in older dysphagic Asian patients with nasogastric (NG) or gastrostomy tube feeding using a pragmatic study design.

    METHODS: The choice of enteral tube access was determined by managing clinicians and patients/caregivers. Comparisons of tube feeding methods were made during a 4-month period, adjusting statistically for inherent confounders.

    RESULTS: A total of 102 participants (NG: n = 52, gastrostomy: n = 50) were recruited over 2 years from 2013 to 2015. Subjects on long-term NG tube feeding were older (82.67 ± 7.15 years vs 76.88 ± 7.37 years; P < .001) but both groups had similar clinical indications (stroke: 63.5% NG vs 54% gastrostomy; P = .33). After adjustment for confounders, gastrostomy feeding was associated with fewer tube-related complications (adjusted odds ratio [aOR] = 0.19; 95% confidence interval [CI] = 0.06-0.60) and better complication-free survival rate (aOR = 0.32; 95% CI = 0.12-0.89) at 4-month follow-up. Anthropometric and biochemical nutrition parameters improved significantly in both groups at 4 months, but no significant differences were observed at the end of the study.

    CONCLUSION: Gastrostomy feeding is associated with a greater 4-month complication-free survival and lower tube-related complications compared with long-term NG feeding in older Asians with dysphagia. However, no differences in nutrition outcomes were observed between NG and gastrostomy feeding at 4 months.

  13. Tan TK, Low VL, Ng WH, Ibrahim J, Wang D, Tan CH, et al.
    Parasitol Int, 2019 Apr;69:110-113.
    PMID: 30590124 DOI: 10.1016/j.parint.2018.12.007
    This report describes the detection of zoonotic Cryptosporidium muris, C. parvum subgenotype IIa and Giardia duodenalis genotype B in urban rodents in Malaysia. A rare occurrence of C. meleagridis was also reported suggesting a role of rodents in mechanical transmission of this pathogen. Utilization of DNA sequencing and subtyping analysis confirmed the presence of zoonotic C. parvum subtypes IIaA17G2R1 and IIaA16G3R1 for the first time in rodents.
  14. Tan WN, Tan ZH, Zulkifli NI, Nik Mohamed Kamal NNS, Rozman NAS, Tong WY, et al.
    Nat Prod Res, 2020 Dec;34(23):3404-3408.
    PMID: 30773054 DOI: 10.1080/14786419.2019.1569012
    Garcinia celebica L., locally known as "manggis hutan" in Malaysia is widely used in folkloric medicine to treat various diseases. The present study was aimed to examine the chemical composition of the essential oil from the leaves of G. celebica L. (EO-GC) and its cytotoxic and antimicrobial potential. EO-GC obtained by hydrodistillation was analysed using capillary GC and GC-MS. Twenty-two compounds were identified, dominated by α-copaene (61.25%), germacrene D (6.72%) and β-caryophyllene (5.85%). In the in vitro MTT assay, EO-GC exhibited significant anti-proliferative effects towards MCF-7 human breast cancer cells with IC50 value of 45.2 μg/mL. Regarding the antimicrobial activity, it showed better inhibitory effects on Gram-positive bacteria than Gram-negative bacteria and none on the fungi and yeasts tested.
  15. Tan GW, Sivanesan VM, Abdul Rahman FI, Hassan F, Hasbullah HH, Ng CC, et al.
    Int J Cancer, 2019 Oct 15;145(8):2260-2266.
    PMID: 30698824 DOI: 10.1002/ijc.32173
    Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein-Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low- and middle-income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non-invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA-1 and hsa-miR-21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed-up. In summary, the non-invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non-invasive detection tool for NPC.
  16. Tan KK, Tan YC, Chang LY, Lee KW, Nor'e SS, Yee WY, et al.
    J Infect Dev Ctries, 2017 Jun 01;11(5):420-425.
    PMID: 30943180 DOI: 10.3855/jidc.7598
    INTRODUCTION: Currently available tests have limitations for the identification of Brucella species and strains, and their genetic lineage. The genome sequence of the rpoB gene encoding the β-subunit of DNA-dependent RNA polymerase was investigated for its use in genotyping Brucella melitensis.

    METHODOLOGY: Complete rpoB gene sequences of globally distributed Brucella melitensis strains were analyzed. Single nucleotides polymorphisms (SNPs) of the rpoB gene sequences were identified and used to type Brucella melitensis strains.

    RESULTS: Six DNA polymorphisms were identified, of which two (nucleotides 3201 and 558) were novel. Analysis of the geographical distribution of the strains revealed a spatial clustering pattern with rpoB type 1 representing European and American strains, rpoB type 2 representing European, African, and Asian strains, rpoB type 3 representing Mediterranean strains, and rpoB type 4 representing African (C3201T) and European (C3201T/T558A) strains.

    CONCLUSIONS: We report the discovery of two novel SNPs of rpoB gene that can serve as useful markers for epidemiology and geographical tracking of B. melitensis.

  17. Ng JC, Tan CY, Ong BH, Matsuda A, Basirun WJ, Tan WK, et al.
    J Nanosci Nanotechnol, 2019 Nov 01;19(11):7236-7243.
    PMID: 31039881 DOI: 10.1166/jnn.2019.16717
    Small sized electrocatalysts, which can be obtained by rapid nucleation and high supersaturation are imperative for outstanding methanol oxidation reaction (MOR). Conventional microwave synthesis processes of electrocatalysts include ultrasonication, stirring, pH adjustment, and microwave irradiation of the precursor mixture. Ethylene glycol (EG), which serves as a reductant and solvent was added during the ultrasonication or stirring stage. However, this step and pH adjustment resulted in unintended multi-stage gradual nucleation. In this study, the microwave reduction approach was used to induce rapid nucleation and high supersaturation in order to fabricate small-sized reduced graphene oxide-supported palladium (Pd/rGO) electrocatalysts via the delayed addition of EG, elimination of the pH adjustment step, addition of sodium carbonate (Na₂CO₃), prior microwave irradiation of the EG mixed with Na₂CO₃, and addition of room temperature precursor mixture. Besides its role as a second reducing agent, the addition of Na₂CO₃ was primarily intended to generate an alkaline condition, which is essential for the high-performance of electrocatalysts. Moreover, the microwave irradiation of the EG and Na₂CO₃ mixture generated highly reactive free radicals that facilitate rapid nucleation. Meanwhile, the room temperature precursor mixture increased supersaturation. Results showed improved electrochemically active surface area (78.97 m² g-1, 23.79% larger), MOR (434.49 mA mg-1, 37.96% higher) and stability.
  18. Kan FK, Tan CC, Von Bahr Greenwood T, Khalid KE, Supramaniam P, Hed Myrberg I, et al.
    Clin Infect Dis, 2020 05 23;70(11):2247-2255.
    PMID: 31188423 DOI: 10.1093/cid/ciz499
    BACKGROUND: Globally, ~500 000 people with severe dengue (SD) require hospitalization yearly; ~12 500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors in SD.

    METHODS: A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia.

    RESULTS: Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability ≥70% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling ≥4 and 7 of 9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P < .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death.

    CONCLUSIONS: Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH.

  19. Tan YJ, Lee YT, Petersen SH, Kaur G, Kono K, Tan SC, et al.
    Ther Adv Med Oncol, 2019;11:1758835919878977.
    PMID: 31632470 DOI: 10.1177/1758835919878977
    Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC).

    Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry.

    Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC.

    Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.

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