Displaying publications 1 - 20 of 64 in total

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  1. Arumugam A, Tan SE, Tan SL, Tan JE, Hussin FH, Zenian MS, et al.
    Malays J Med Sci, 2023 Jun;30(3):93-102.
    PMID: 37425386 DOI: 10.21315/mjms2023.30.3.8
    BACKGROUND: Intracerebral haemorrhage (ICH) can be devastating, particularly if haematoma expansion occurs. The efficacy of tranexamic acid (TXA), an anti-fibrinolytic agent, in reducing haematoma expansion is now being studied worldwide. However, the optimal dosage of TXA has yet to be determined. This study was designed to further establish the potential of different doses of TXA.

    METHODS: A double-blinded, randomised, placebo-controlled study was carried out among adults with non-traumatic ICH. Eligible study subjects were randomly assigned to receive placebo, 2-g TXA treatment or 3-g TXA treatment. Haematoma volumes before and after intervention were measured using the planimetric method.

    RESULTS: A total of 60 subjects with 20 subjects in each treatment group were recruited for this study. Among the 60 subjects, the majority were male (n = 36, 60%), had known cases of hypertension (n = 43, 71.7%) and presented with full Glasgow coma scale (GCS) (n = 41, 68.3%). The results showed that there was no statistically significant difference (P = 0.315) in the mean changes of haematoma volume when compared with three study groups using ANCOVA, although the 3-g TXA group was the only group that showed haematoma volume reduction (mean reduction of 0.2 cm3) instead of expansion as in placebo (mean expansion 1.8 cm3) and 2-g TXA (mean expansion 0.3 cm3) groups. Good recovery was observed in all study groups, with only three subjects being moderately disabled. No adverse effects were reported in any of the study groups.

    CONCLUSION: To the best of our knowledge, this is the first clinical study using 3 g of TXA in the management of non-traumatic ICH. From our study, 3 g of TXA may potentially be helpful in reducing haematoma volume. Nonetheless, a larger-scale randomised controlled trial should be carried out to further establish the role of 3 g of TXA in non-traumatic ICH.

  2. Baharin SNAN, Tan SL, Sam IC, Chan YF
    Trop Biomed, 2023 Dec 01;40(4):478-485.
    PMID: 38308836 DOI: 10.47665/tb.40.4.014
    Hand, foot, and mouth disease (HFMD) is a contagious childhood disease caused by enteroviruses including enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6) and CV-A16 transmitted via direct and indirect contact. Different types of toy surfaces can affect the stability of viruses. Understanding the stability of enteroviruses on toys provides insightful data for effective disinfection in kindergartens or homes. Porous (ethylene-vinyl acetate mat foam, paper, pinewood, polyester fabric, and squishy polyurethane foam) and non-porous (acrylonitrile butadiene styrene plastic and stainless-steel coin) surfaces were inoculated with EV-A71 at 4, 24, and 35°C, and coxsackieviruses at 24°C. Infectious enteroviruses were recovered and titred in median tissue culture infectious dose assay (TCID50). Atomic force microscopy (AFM) images were taken from surfaces to examine association of surface roughness with virus stability. Overall, infectious enteroviruses were persistent on all non-porous and porous surfaces. Virus persistence was longest at 4°C followed by 24°C and 35°C. EV-A71 half-lives ranged between 6.4-12.8 hours at 4°C, 2.4-6.7 hours at 24°C, and 0.13-2.7 hours at 35°C. At lower virus titres exposed to 24°C, half-lives of enteroviruses ranged from 0.1-1.4 hours. Surface roughness values from AFM suggested smooth surfaces of non-porous surfaces were associated with better virus stability. Temperature, enterovirus concentration, and type of surface affected persistence and stability of enteroviruses. Our findings suggest both porous and non-porous surfaces in kindergartens allow enterovirus persistence and should be frequently disinfected to curb HFMD outbreaks in kindergartens.
  3. Chan YQ, Lee ZM, Tan SL
    Med J Malaysia, 2020 07;75(4):433-435.
    PMID: 32724010
    Intracranial haemorrhage (ICH) in a patient with relapse of idiopathic thrombocytopaenic purpura (ITP) can be lethal. The site of haemorrhage, compounded by low platelets in this disease, makes its management extremely challenging, especially when a neurosurgical procedure is warranted. We report a case report of an unconventional way of increasing platelet counts in ITP rapidly in an emergency setting.
  4. David NCE, Juliana H, Chok M, Gan YZ, Tan YC, Nur Adlina MN, et al.
    Med J Malaysia, 2023 Jan;78(1):80-86.
    PMID: 36715196
    INTRODUCTION: The COVID-19 pandemic has reached a phase where many have been infected at least once. Healthcare workers were not spared from being infected. This study aimed to determine the period prevalence of COVID-19 among the paediatric healthcare workers in Negeri Sembilan as the country transitioned into an endemic phase of the pandemic. Additionally, we investigate potential sociodemographic and occupational characteristics associated with SARS-CoV-2 infection among healthcare workers.

    MATERIALS AND METHODS: A cross-sectional study was conducted among the healthcare workers in the paediatric department at three public specialist hospitals in Negeri Sembilan between 15 and 21 April 2022. Data were collected through a self-administered questionnaire.

    RESULTS: Out of the 504 eligible healthcare workers, 493 participated in this study (response rate 97.8%). The overall prevalence of COVID-19 (11 March 2020-15 April 2022) among healthcare workers was 50.9%. The majority (80.1%) were infected during the Omicron wave two months before the survey. Household contacts accounted for 35.9% of infection sources. The proportion of non-doctors in the COVID-19-infected group was significantly higher compared to the non-infected group (74.1% vs 64.0%, p=0.016). The COVID-19-infected group had a higher proportion of schoolgoing children (44.6% vs 30.6%, p=0.001) and children who attended pre-school/sent to the babysitter (49.0% vs 24.4%, p<0.001). There were no significant differences between infection rates among the healthcare workers working in the tertiary hospital and the district hospitals. There were also no significant differences in the proportion of COVID-19- infected doctors and nurses when analysed by seniority.

    CONCLUSION: Our study provided an estimate on the prevalence of COVID-19 among paediatric healthcare workers in Negeri Sembilan and the factors associated with infection, which captures the extent and magnitude of this pandemic on the state's paediatric department. Most infections resulted from household contact, with a higher proportion of infected healthcare workers having young children.

  5. Goh TX, Tan SL, Roebuck MM, Teo SH, Kamarul T
    Tissue Eng Part C Methods, 2022 10;28(10):511-528.
    PMID: 35959742 DOI: 10.1089/ten.TEC.2022.0092
    The state of host cells is reflected in the cargo carried by their extracellular vesicles (EVs). This makes EV a potential source of biomarkers for human diseases. Piwi-interacting RNA (piRNA) regulates gene expression through epigenetic regulation and post-transcriptional gene silencing. Thus, piRNA profiling in EVs derived from human clinical samples could identify markers that characterize disease stages and unveil their roles in disease pathology. This review aimed to report the expression profiles of EV-derived piRNA (EV-piRNA) in various human samples, as well as their role in each pathology. A systematic review was conducted to collate the findings of human EV-piRNA from original research articles published in indexed scientific journals up to February 16, 2022. Article searches were performed in PubMed, Web of Science, and Scopus databases, using a combination of keywords, including "EV" and "piRNA." A total of 775 nonredundant original articles were identified. After subjecting articles to inclusion and exclusion criteria, 34 articles were accepted for this review. The piRNA expression levels among the small RNA profiles of human-derived EVs range from 0.09% to 43.84%, with the lowest expression level reported in urine-derived EVs and the highest percentage in plasma-derived EVs. Differentially expressed EV-piRNAs have been identified in patients with specific disease conditions compared to their counterparts (healthy control), suggesting an association between piRNA and progression in various diseases. Seven articles identified piRNA putative target genes and/or the pathway enrichment of piRNA target genes, and one study demonstrated a direct role of piRNA candidates in disease pathology. In conclusion, EV-piRNA has been isolated successfully from various human body fluids. EV-piRNA is a new research niche in human disease pathology. The expression profiles of EV-piRNA in various tissue types and disease conditions remain largely unexplored. Furthermore, there is currently a lack of guidelines on piRNA bioinformatics analysis, which could lead to inconsistent results and thus hinder the progression of piRNA discoveries. Finally, the lack of published scientific evidence on the role of EV-piRNA supports the need for future research to focus on the functional analysis of EV-piRNA as part of the route in piRNA discoveries.
  6. Harith S, Tan SL
    Ann Geriatr Med Res, 2020 Jun;24(2):115-124.
    PMID: 32743332 DOI: 10.4235/agmr.20.0005
    Background: This study aimed to translate and validate the comprehensive geriatric assessment (CGA) questionnaire among older adult patients in Malaysia in the Malay language.

    Methods: The questionnaire contained items on the socio-demographic characteristics, medical condition, quality of life (QOL), nutritional status, functional capacity, and depression status. The forward and backward translation processes of the original English language version of the questionnaire were undertaken by three independent linguistic translators, while its content was validated by an expert team consisting of seven geriatricians, physicians, dietitian, and lecturers. The Malay version of the questionnaire was tested for face validity in 10 older adult patients over 65 years of age. The internal consistency reliability and construct validity were evaluated among 166 older adult patients (mean age, 71.0 years; 73.5% male). The questionnaire was administered through face-to-face interviews with the patients. Minor amendments were made after the content and face validity tests.

    Results: The internal consistency reliability was good, as the Cronbach's alpha for most of the scales surpassed 0.70, ranging from 0.70 to 0.98, with only one exception (Mini Nutritional Assessment Short-Form, Cronbach's alpha=0.62). The factor loadings for all scales were satisfactory (>0.40), ranging from 0.45 to 0.90.

    Conclusion: The Malay-version CGA showed evidence of satisfactory internal consistency reliability and construct validity in Malaysian geriatric patients.

  7. Jamal J, Roebuck MM, Lee SY, Frostick SP, Abbas AA, Merican AM, et al.
    Int J Biochem Cell Biol, 2020 09;126:105800.
    PMID: 32673644 DOI: 10.1016/j.biocel.2020.105800
    OBJECTIVES: To compare mechanobiological response of synovial fibroblasts (SFb) from OA patient cohorts under mechanical load and inflammatory stressors for better understanding of SFb homeostatic functions.

    METHODS: Primary SFb isolated from knee synovium of OA obese (OA-ob:SFb), OA-pre-obese (OA-Pob:SFb), non-OA arthroscopic (scope:SFb), and non-OA arthroscopic with cartilage damage (scope-CD:SFb) were exposed to OA-conditioned media (OACM), derived from OA obese (OA-ob:CM), OA-pre-obese (OA-Pob:CM), and mechanical stretch at either 0 %, 6 % or 10 % for 24 h. Differences in the mRNA levels of genes involved in extracellular matrix production, inflammation and secretory activity were measured.

    RESULTS: Despite the significant BMI differences between the OA-ob and OA-Pob groups, OA-Pob has more patients with underlying dyslipidaemia, and low-grade synovitis with higher levels of secreted proteins, CXCL8, COL4A1, CCL4, SPARC and FGF2 in OA-Pob:CM. All primary SFb exhibited anti-proliferative activity with both OA-CM. Mechanical stretch stimulated lubricin production in scope:SFb, higher TGFβ1 and COL1A1 expressions in scope-CD:SFb. OA-Pob:CM stimulated greater detrimental effects than the OA-ob:CM, with higher pro-inflammatory cytokines, IL1β, IL6, COX2 and proteases such as aggrecanases, ADAMTS4 and ADAMTS5, and lower ECM matrix, COL1A1 expressions in all SFb. OA-ob:SFb were unresponsive but expressed higher pro-inflammatory cytokines under OA-Pob:CM treatment.

    CONCLUSION: Both mechanical and inflammatory stressors regulate SFb molecular functions with heterogeneity in responses that are dependent on their pathological tissue of origins. While mechanical stretch promotes a favorable effect with enhanced lubricin production in scope:SFb and TGFβ1 and COL1A1 in scope-CD:SFb, the presence of excessively high OA-associated inflammatory mediators in OA-Pob:CM, predominantly SPARC, CXCL8 and FGF2 drive all SFb regardless of pathology, towards greater pro-inflammatory activities.

  8. Khairuanuar NL, Crouse KA, Kwong HC, Tan SL, Tiekink ERT
    Acta Crystallogr E Crystallogr Commun, 2020 Jul 01;76(Pt 7):990-997.
    PMID: 32695439 DOI: 10.1107/S2056989020007070
    The title hydrazine carbodi-thio-ate chloro-form hemisolvate, 2C15H14N2O2S2·CHCl3, comprises two independent hydrazine carbodi-thio-ate mol-ecules, A and B, and a chloro-form mol-ecule; the latter is statistically disordered about its mol-ecular threefold axis. The common features of the organic mol-ecules include an almost planar, central CN2S2 chromophore [r.m.s. deviation = 0.0203 Å (A) and 0.0080 Å (B)], an E configuration about the imine bond and an intra-molecular hydroxyl-O-H⋯N(imine) hydrogen bond. The major conformational difference between the mol-ecules is seen in the relative dispositions of the phenyl rings as indicated by the values of the dihedral angles between the central plane and phenyl ring of 71.21 (6)° (A) and 54.73 (7)° (B). Finally, a difference is seen in the disposition of the outer hydroxyl-H atoms, having opposite relative orientations. In the calculated gas-phase structure, the entire mol-ecule is planar with the exception of the perpendicular phenyl ring. In the mol-ecular packing, the A and B mol-ecules assemble into a two-mol-ecule aggregate via N-H⋯S hydrogen bonds and eight-membered {⋯HNCS}2 synthons. The dimeric assemblies are connected into supra-molecular chains via hydroxyl-O-H⋯O(hydrox-yl) hydrogen bonds and these are linked into a double-chain through hy-droxy-O-H⋯π(phen-yl) inter-actions. The double-chains are connected into a three-dimensional architecture through phenyl-C-H⋯O(hydrox-yl) and phenyl-C-H⋯π(phen-yl) inter-actions. The overall assembly defines columns along the a-axis direction in which reside the chloro-form mol-ecules, which are stabilized by chloro-form-methine-C-H⋯S(thione) and phenyl-C-H⋯Cl contacts. The analysis of the calculated Hirshfeld surfaces, non-covalent inter-action plots and inter-action energies confirm the importance of the above-mentioned inter-actions, but also of cooperative, non-standard inter-actions such as π(benzene)⋯π(hydrogen-bond-mediated-ring) contacts.
  9. Ko SM, Tan SL, Leong B
    Singapore Med J, 1996 Apr;37(2):168-71.
    PMID: 8942256
    In a prospective study of fifty consecutive outpatients (30 men and 20 women) attending the Behaviour Therapy Clinic at a general hospital, the commonest conditions were obsessive compulsive disorders (n = 16), phobic disorders (n = 11) and generalised anxiety disorders (n = 9). Three-quarters of the referrals were from psychiatrists and family physicians. The patients received between 2 to 10 sessions of behaviour treatment; most had 4 to 6 sessions with a mean of 4.7, SD 1.82. The commonest behavioural techniques administered were exposure therapy with response prevention and relaxation therapy. Initially, treatment was therapist-aided, but subsequently self-help was encouraged with regular reviews of the patient's homework. After one month, 42 patients (84%) were assessed to have improved somewhat, with 20 (40%) showing moderate improvement. After three months, 41 (82%) continued to improve, with 33 (66%) showing moderate to great improvement. Nine patients were considered to have failed in therapy-six defaulted and three were non-responders. The reasons for defaulting treatment were unwillingness to bear with the discomfort involved in exposure therapy, lack of motivation or returning to own hometown in Malaysia. Sixteen patients (n = 32%) were treated solely with behavioural techniques while the rest had a combination of behaviour therapy and drugs, especially anxiolytics and antidepressants. However, at the end of treatment, the dosages of most medications were reduced or else discontinued completely.

    Study site: Behavior therapy clinic at a general hospital
  10. Kwan MSK, Tan SL, Keowmani T, Goh SL, Voo JYH, Tan HS, et al.
    Asia Pac Allergy, 2023 Sep;13(3):121-126.
    PMID: 37744958 DOI: 10.5415/apallergy.0000000000000115
    BACKGROUND: Given the deficits in allergists and testing capacity, the diagnosis of drug allergy is largely dependent on the clinician's and pharmacist's judgment. The ability to recognize drug allergies and respond appropriately is crucial to patient safety. Currently, there is a void in the evidence that limits the ability to recommend comprehensive and swift improvements on this front.

    OBJECTIVE: This study thus aimed to evaluate the knowledge, attitude, and practice toward drug allergy among doctors and pharmacists working in public healthcare facilities in Sabah, Malaysia.

    METHODS: This cross-sectional study was conducted in 24 hospitals and 11 clinics in Sabah. A validated Drug Allergy Knowledge, Attitude, and Practice Questionnaire was adapted from a published study and developed on an online survey platform. The questionnaire was distributed to all listed eligible respondents via email and personal messenger service.

    RESULTS: A total of 549 doctors and pharmacists responded, with an overall response rate of 18.2%. The total mean knowledge, attitude, and practice scores were 8.3 (SD, 1.98), 18.9 (SD, 2.55), and 17.3 (SD, 4.4), respectively. It was found that pharmacists performed significantly poorer than both medical officers (mean score difference = -0.5; P = 0.006) and specialists (mean score difference = -0.9; P = 0.020) in the knowledge domain. As the time in service doubles, the knowledge score increases significantly by 0.3 (P = 0.015).

    CONCLUSION: Knowledge, attitude, and practice on drug allergy among doctors and pharmacists in Sabah were poor. It is thus timely for advanced educational programs on drug allergy to be formalized and implemented.

  11. 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.

  12. Lee SM, Lo KM, Tan SL, Tiekink ER
    Acta Crystallogr E Crystallogr Commun, 2016 Oct 1;72(Pt 10):1390-1395.
    PMID: 27746926
    The Yb(III) atom in the title complex, [Yb(C27H24Cl3N4O3)] [systematic name: (2,2',2''-{(nitrilo)-tris-[ethane-2,1-di-yl(nitrilo)-methylyl-idene]}tris-(4-chloro-phenolato)ytterbium(III)], is coordinated by a trinegative, hepta-dentate ligand and exists within an N4O3 donor set, which defines a capped octa-hedral geometry whereby the amine N atom caps the triangular face defined by the three imine N atoms. The packing features supra-molecular layers that stack along the a axis, sustained by a combination of aryl-C-H⋯O, imine-C-H⋯O, methyl-ene-C-H⋯π(ar-yl) and end-on C-Cl⋯π(ar-yl) inter-actions. A Hirshfeld surface analysis points to the major contributions of C⋯H/ H⋯C and Cl⋯H/H⋯Cl inter-actions (along with H⋯H) to the overall surface but the Cl⋯H contacts are at distances greater than the sum of their van der Waals radii.
  13. Lee SM, Lo KM, Tan SL, Tiekink ER
    Acta Crystallogr E Crystallogr Commun, 2016 Aug 1;72(Pt 8):1223-7.
    PMID: 27536419 DOI: 10.1107/S2056989016012159
    In the solid state, the title compound, C12H16BrNO5 [systematic name: 4-bromo-2-((1E)-{[1,3-dihy-droxy-2-(hy-droxy-meth-yl)propan-2-yl]iminium-yl}meth-yl)-6-meth-oxy-benzen-1-olate], C12H16BrNO5, is found in the keto-amine tautomeric form, with an intra-molecular iminium-N-H⋯O(phenolate) hydrogen bond and an E conformation about the C=N bond. Both gauche (two) and anti relationships are found for the methyl-hydroxy groups. In the crystal, a supra-molecular layer in the bc plane is formed via hy-droxy-O-H⋯O(hy-droxy) and charge-assisted hy-droxy-O-H⋯O(phenolate) hydrogen-bonding inter-actions; various C-H⋯O inter-actions provide additional cohesion to the layers, which stack along the a axis with no directional inter-actions between them. A Hirshfeld surface analysis confirms the lack of specific inter-actions in the inter-layer region.
  14. Low YS, Tan SL, Wan AS
    J Pediatr Pharmacol Ther, 2015 Mar-Apr;20(2):119-27.
    PMID: 25964729 DOI: 10.5863/1551-6776-20.2.119
    OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing practiced in neonatal intensive care unit (NICU) and special care nursery (SCN) of a Malaysian hospital.
    METHODS: Cross-sectional observational study with pharmacokinetic analysis of all patients aged ≤28 days who received gentamicin treatment in NICU/SCN. Subjects received dosing according to a regimen modified from an Australian-based pediatric guideline. During a study period of 3 months, subjects were evaluated for gestational age, body weight, serum creatinine concentration, gentamicin dose/interval, serum peak and trough concentrations, and pharmacokinetic parameters. Descriptive percentages were used to determine the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to compare the accuracy rates among different gestational ages. Pharmacokinetic profile among different gestational age and body weight groups were compared by using ANOVA.
    RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved therapeutic concentrations at the first drug-monitoring assessment. There was no significant difference found between the percentage of term neonates who achieved therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085. A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration of <2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence interval [Cl], 8.13-8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI, 0.48-0.60 mg/L). Mean volume of distribution, half-life, and elimination rate were 0.65 L/kg (95% CI, 0.62-0.68 L/kg), 6.96 hours (95% CI, 6.52-7.40 hours), and 0.11 hour(-1) (95% CI, 0.10-0.11 hour(-1)), respectively.
    CONCLUSION: The larger percentage of subjects attaining therapeutic range with extended-interval gentamicin dosing suggests that this regimen is appropriate and can be safely used among Malaysian neonates.
    KEYWORDS: aminoglycosides; extended-interval; gentamicin; neonate; pharmacokinetics
  15. 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.
  16. Maryam M, Tan SL, Crouse KA, Mohamed Tahir MI, Chee HY
    Turk J Chem, 2020;44(5):1395-1409.
    PMID: 33488239 DOI: 10.3906/kim-2006-22
    A series of Schiff bases have been successfully synthesized through the acid-catalyzed condensation of S-substituted dithiocarbazates and three enantiomerically pure monoterpenes, (1 R )-(+)-camphor, (1 S )-(-)-camphor, (1 R )-(-)-camphorquinone, (1 S )-(+)-camphorquinone, ( R )-(-)-carvone and ( S )-(+)-carvone. Spectroscopic results revealed that the Schiff bases containing camphor or carvone likely adopted an E -configuration along the characteristic imine bond while those containing camphorquinone assumed a Z -configuration. The antidengue potential of these compounds was evaluated based on DENV 2 caused cytopathic effect (CPE) reduction-based in vitro evaluation. The compounds were validated through secondary foci forming unit reduction assay (FFURA). Compounds were also tested for their cytotoxicity against Vero cells. The compounds showed variable degrees of antiviral activity with the camphor compounds displaying the highest antidengue potential. The enantiomers of the compounds behaved almost similarly during the antiviral evaluation.
  17. Ng SF, Tan SL
    Int J Pharm, 2015 Nov 30;495(2):798-806.
    PMID: 26434999 DOI: 10.1016/j.ijpharm.2015.09.057
    Topical chemotherapy is the application of cancer drugs directly onto the skin, which has become a standard treatment for basal cell carcinoma. Due to the promising results in the treatment of skin cancer, topical chemotherapy has recently been applied to breast cancer patients because some breast cancer tissues are only superficial. Hydroxytyrosol, a phenolic compound from olives that is present in high amounts in Hidrox(®) olive extract, has been shown to have a protective effect on normal cells and selective antitumor activities on cancerous cells. The aims of the present study were to develop an alginate bilayer film containing Hidrox(®) and to investigate its potential use as a topical chemotherapeutic agent. Alginate films were characterized for swelling and for physical, thermal, rheological, and mechanical properties. Drug content uniformity and in vitro drug release tests were also investigated. The alginate bilayer films containing Hidrox(®), HB2, showed controlled release of hydroxytyrosol at a flux of 0.094±0.009 mg/cm(2)/h. The results of the cytotoxic assay showed that the HB2 films were dose-dependent and could significantly reduce the growth of breast cancer cells (MCF-7) at 150 μg/mL for a cell viability of 29.34±4.64%. In conclusion, an alginate bilayer film containing Hidrox(®) can be a potential alternative for topical chemotherapeutic agent for skin and breast cancer treatment.
  18. Ngim CF, Lai NM, Hong JY, Tan SL, Ramadas A, Muthukumarasamy P, et al.
    Cochrane Database Syst Rev, 2020 05 28;5:CD012284.
    PMID: 32463488 DOI: 10.1002/14651858.CD012284.pub3
    BACKGROUND: Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. This review on the role of growth hormone was originally published in September 2017 and updated in April 2020.

    OBJECTIVES: To assess the benefits and safety of growth hormone therapy in people with thalassaemia.

    SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 14 November 2019. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Date of latest search: 06 January 2020.

    SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity.

    DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The certainty of the evidence was assessed using GRADE criteria.

    MAIN RESULTS: We included one parallel trial conducted in Turkey. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The certainty of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate-certainty evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate-certainty evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period.

    AUTHORS' CONCLUSIONS: A small single trial contributed evidence of moderate certainty that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.

  19. Ngim CF, Lai NM, Hong JY, Tan SL, Ramadas A, Muthukumarasamy P, et al.
    Cochrane Database Syst Rev, 2017 09 18;9:CD012284.
    PMID: 28921500 DOI: 10.1002/14651858.CD012284.pub2
    BACKGROUND: Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency.

    OBJECTIVES: To assess the benefits and safety of growth hormone therapy in people with thalassaemia.

    SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Our database and trial registry searches are current to 10 August 2017 and 08 August 2017, respectively.

    SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity.

    DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The quality of the evidence was assessed using GRADE criteria.

    MAIN RESULTS: One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate quality evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate quality evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period.

    AUTHORS' CONCLUSIONS: A small single trial contributed evidence of moderate quality that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.

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