Displaying publications 501 - 520 of 1087 in total

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  1. Bapat RA, Dharmadhikari S, Chaubal TV, Amin MCIM, Bapat P, Gorain B, et al.
    Heliyon, 2019 Oct;5(10):e02544.
    PMID: 31687479 DOI: 10.1016/j.heliyon.2019.e02544
    Dendrimers are hyperbranched nanoparticle structures along with its surface modifications can to be used in dental biomaterials for biomimetic remineralisation of enamel and dentin. The review highlights the therapeutic applications of dendrimers in the field of dentistry. It addresses the possible mechanisms of enhancement of mechanical properties of adhesives and resins structure. Dendrimers due to its unique construction of possessing inner hydrophobic and outer hydrophilic structure can act as drug carrier for delivery of antimicrobial drugs for treatment of periodontal diseases and at peripheral dental implant areas. Dendrimers due to its hyperbranched structures can provides a unique drug delivery vehicle for delivery of a drug at specific site for sustained release for therapeutic effects. Thus, dendrimers can be one of the most important constituents which can be incorporated in dental biomaterials for better outcomes in dentistry.
  2. Bahmanrokh G, Cazorla C, Mofarah SS, Shahmiri R, Yao Y, Ismail I, et al.
    Nanoscale, 2020 Feb 27;12(8):4916-4934.
    PMID: 31967150 DOI: 10.1039/c9nr08604h
    The present work reports a detailed mechanistic interpretation of the role of the solubility of dopants and resultant midgap defect energies in band gap engineering. While there is a general perception that a single dopant is associated with single solubility and defect mechanisms, in reality, the potential for multiple solubility and defect mechanisms requires a more nuanced interpretation. Similarly, Kröger-Vink defect equilibria assume that stoichiometries during substitutional and interstitial solid solubility as well as Schottky and Frenkel pair formation are compensated by the diffusion of matrix ions to the grain boundaries or surface. However, this approach does not allow the possibility that stoichiometry is uncompensated, where diffusion of the matrix ion to lattice interstices occurs, followed by charge compensation by redox of this ion. Consequently, a modified defect equilibria formalism has been developed in order to allow description of this situation. Experimental data for the structural, chemical, semiconducting, and photocatalytic properties as a function of doping level are correlated with conceptual structural models, a comprehensive energy band diagram, and the corresponding defect equilibria. These correlations reveal the complex mechanisms of the interrelated solubility and defect formation mechanisms, which change significantly and irregularly as a function of small changes in doping level. The analyses confirm that the assumption of single mechanisms of solid solubility and defect formation may be simplifications of more complex processes. The generation of (1) a matrix of complementary characterisation and analytical data, (2) the calculation of a complete energy band diagram, (3) consideration of charge compensation mechanisms and redox beyond the limitations of Kröger-Vink approaches, and (4) the development of models of corresponding structural analogies combine to create a new approach to interpret and explain experimental data. These strategies allow deconstruction of these complex issues and thus targeting of optimal and possibly unique doping levels to achieve lattice configurations that may be energetically and structurally unfavorable. These approaches then can be applied to other doped semiconducting systems.
  3. Gómez Román R, Wang LF, Lee B, Halpin K, de Wit E, Broder CC, et al.
    mSphere, 2020 07 08;5(4).
    PMID: 32641430 DOI: 10.1128/mSphere.00602-20
    Nipah disease is listed as one of the WHO priority diseases that pose the greatest public health risk due to their epidemic potential. More than 200 experts from around the world convened in Singapore last year to mark the 20th anniversary of the first Nipah virus outbreaks in Malaysia and Singapore. Most of these experts are now involved in responding to the coronavirus disease 2019 (COVID-19) pandemic. Here, members of the Organizing Committee of the 2019 Nipah Virus International Conference review highlights from the Nipah@20 Conference and reflect on key lessons learned from Nipah that could be applied to the understanding of the COVID-19 pandemic and to preparedness against future emerging infectious diseases (EIDs) of pandemic potential.
  4. Elnaem MH, Mohd Taufek NH, Ab Rahman NS, Mohd Nazar NI, Zin CS, Nuffer W, et al.
    Vaccines (Basel), 2021 Oct 09;9(10).
    PMID: 34696264 DOI: 10.3390/vaccines9101156
    This study aimed to investigate the attitudes, perceptions, and experiences of side effects with the COVID-19 vaccines in Malaysia among participants in the National Vaccination Program. A cross-sectional survey was conducted among a sample of vaccine-eligible and vaccinated individuals in Malaysia between May and July 2021. A total of 428 respondents completed the survey. A vast majority (98.6%) of the respondents had registered to be vaccinated. Twenty participants (4.7%) expressed concerns about either registering or receiving the COVID-19 vaccination, mainly due to their uncertainty of vaccine safety. Approximately 77.5% received their vaccinations. Of them, 76.8% had experienced vaccine-related side effects. About 40% of the side effects occurred more with the second dose, particularly those who received the Pfizer-BioNTech vaccine (p < 0.001). Pain at the injection site (61.1%) and tiredness (48.8%) were the most reported side effects. Compared to those aged ≥60 years, all age groups were more likely to exhibit vaccine-related side effects; meanwhile, males (OR: 0.51, 95% CI: 0.27-0.93) were less likely to experience side effects than females. Those who received the Sinovac vaccine were at lower risk of experiencing side effects (OR: 0.08, 95% CI: 0.03-0.22) and were more likely to report fewer side effects than Pfizer-BioNTech (p = 0.012) and Oxford-AstraZeneca groups (p= 0.001). The overall attitudes toward the COVID-19 vaccination program were positive. Several differences in the experiences of vaccine-related side effects, in terms of prevalence and numbers, were attributed to age, gender, and received vaccine type.
  5. Myint K, Jacobs K, Myint AM, Lam SK, Lim YA, Boey CC, et al.
    Front Immunol, 2021;12:702301.
    PMID: 34539633 DOI: 10.3389/fimmu.2021.702301
    Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography. Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p<0.05, but lower concentrations of IL-10, p<0.001, IL-6, p<0.001 and brain-derived neurotrophic factors (BDNF) p<0.01. In addition, a significant increase in the metabolite of the kynurenine pathway, 3-hydroxyanthranilic acid (3-HAA) p<0.01, a significant decrease in the concentrations of anthranilic acid (AA) p<0.001, together with an increased ratio of serum 3-HAA to AA (3-HAA/AA) p<0.001, was found in this cohort. These findings indicate the significant activation of the immune system and presence of inflammation in children with RAP than those with subclinical parasitic infections. Moreover, children with RAP tested with the Strengths and Difficulties Questionnaire (SDQ), displayed high psychological problems though these SDQ scores were not statistically associated with measured cytokines and kynurenine metabolites. We however could hypothesize that the pro-inflammatory state together with concomitant low concentrations of BDNF in those children with RAP could play a role in psychological stress and experiencing medically unexplained symptoms.
  6. Barber BE, Bird E, Wilkes CS, William T, Grigg MJ, Paramaswaran U, et al.
    J Infect Dis, 2015 Apr 1;211(7):1104-10.
    PMID: 25301955 DOI: 10.1093/infdis/jiu562
    BACKGROUND: Plasmodium knowlesi is the commonest cause of malaria in Malaysia, but little is known regarding infection during pregnancy.
    METHODS: To investigate comparative risk and consequences of knowlesi malaria during pregnancy, we reviewed (1) Sabah Health Department malaria-notification records created during 2012-2013, (2) prospectively collected data from all females with polymerase chain reaction (PCR)-confirmed malaria who were admitted to a Sabah tertiary care referral hospital during 2011-2014, and (3) malaria microscopy and clinical data recorded at a Sabah tertiary care women and children's hospital during 2010-2014.
    RESULTS: During 2012-2013, 774 females with microscopy-diagnosed malaria were notified, including 252 (33%), 172 (20%), 333 (43%), and 17 (2%) with Plasmodium falciparum infection, Plasmodium vivax infection, Plasmodium malariae/Plasmodium knowlesi infection, and mixed infection, respectively. Among females aged 15-45 years, pregnancy was reported in 18 of 124 (14.5%), 9 of 93 (9.7%), and 4 of 151 (2.6%) P. falciparum, P. vivax, and P. malariae/P. knowlesi notifications respectively (P = .002). Three females with knowlesi malaria were confirmed as pregnant: 2 had moderate anemia, and 1 delivered a preterm low-birth-weight infant. There were 17, 7, and 0 pregnant women with falciparum, vivax, and knowlesi malaria, respectively, identified from the 2 referral hospitals.
    CONCLUSIONS: Although P. knowlesi is the commonest malaria species among females in Sabah, P. knowlesi infection is relatively rare during pregnancy. It may however be associated with adverse maternal and pregnancy outcomes.
    KEYWORDS: Plasmodium knowlesi; malaria; maternal anemia; pregnancy; preterm delivery
  7. Ayoub AA, Mahmoud AH, Ribeiro JS, Daghrery A, Xu J, Fenno JC, et al.
    Int J Mol Sci, 2022 Nov 09;23(22).
    PMID: 36430238 DOI: 10.3390/ijms232213761
    This study was aimed at engineering photocrosslinkable azithromycin (AZ)-laden gelatin methacryloyl fibers via electrospinning to serve as a localized and biodegradable drug delivery system for endodontic infection control. AZ at three distinct amounts was mixed with solubilized gelatin methacryloyl and the photoinitiator to obtain the following fibers: GelMA+5%AZ, GelMA+10%AZ, and GelMA+15%AZ. Fiber morphology, diameter, AZ incorporation, mechanical properties, degradation profile, and antimicrobial action against Aggregatibacter actinomycetemcomitans and Actinomyces naeslundii were also studied. In vitro compatibility with human-derived dental pulp stem cells and inflammatory response in vivo using a subcutaneous rat model were also determined. A bead-free fibrous microstructure with interconnected pores was observed for all groups. GelMA and GelMA+10%AZ had the highest fiber diameter means. The tensile strength of the GelMA-based fibers was reduced upon AZ addition. A similar pattern was observed for the degradation profile in vitro. GelMA+15%AZ fibers led to the highest bacterial inhibition. The presence of AZ, regardless of the concentration, did not pose significant toxicity. In vivo findings indicated higher blood vessel formation, mild inflammation, and mature and thick well-oriented collagen fibers interweaving with the engineered fibers. Altogether, AZ-laden photocrosslinkable GelMA fibers had adequate mechanical and degradation properties, with 15%AZ displaying significant antimicrobial activity without compromising biocompatibility.
  8. Biswas R, Lugo A, Genitsaridi E, Trpchevska N, Akeroyd MA, Cederroth CR, et al.
    Prog Brain Res, 2021;263:1-24.
    PMID: 34243884 DOI: 10.1016/bs.pbr.2021.04.005
    INTRODUCTION: Tinnitus is a symptom and not a disease in its own right. A number of medical conditions are known to increase the risk of developing tinnitus. Most known risk factors are otological or neurological, but general health and lifestyle can also precipitate the condition. Understanding these modifiable risk factors can help to identify vulnerable groups and can inform preventive actions to reduce likelihood of developing tinnitus. Smoking, alcohol consumption, body mass index (BMI) and caffeine intake are all lifestyle risk factors hypothesized to be related to tinnitus. Nonetheless, research findings in support of those relationships are somewhat mixed.

    METHODS: A systematic review was conducted to identify all relevant studies on the specific risk factors. Findings were summarized using a narrative synthesis and meta-analysis, where possible.

    RESULTS: Overall 384 studies were included, mostly using cross-sectional designs. Findings indicated significantly increased risk of tinnitus among current (based on 26 studies) and ever smokers (based on 16 studies) and among obese people (based on seven studies), but no effect of alcohol consumption (based on 11 studies). With respect to caffeine intake or coffee drinking, only three studies examined this risk factor and so we were unable to draw conclusions.

    CONCLUSION: Our results contribute to quantifying the relationship between tinnitus and specific lifestyle-related risk factors, and we highlight some of the gaps and inconsistencies across published studies.

  9. Lee YK, Ng CJ, Sim JH, Firdaus A, Foong CC, Hong WH, et al.
    Malays Fam Physician, 2021 Nov 30;16(3):77-86.
    PMID: 34938395 DOI: 10.51866/oa1222
    Introduction: A compulsory research component is becoming increasingly common for clinical residents. However, integrating research into a busy clinical training schedule can be challenging. This study aimed to explore barriers to research supervision in specialist training programmes from the perspectives of clinical supervisors and trainees at a Malaysian university hospital.

    Methods: Qualitative interviews and focus group discussions were conducted (December 2016 to July 2017) with clinical supervisors (n=11) and clinical trainees (n=26) utilising a topic guide exploring institutional guidelines, research culture and supervisor-student roles. Interviews were transcribed verbatim and analysed thematically to identify barriers to research supervision.

    Results: Supervisors and trainees from 11 out of 18 departments participated. Both clinical supervisors and trainees struggled to successfully integrate a compulsory research component into residency training. Among the reasons identified included a lack of supervisory access due to the nature of clinical rotations and placements, clashing training priorities (clinical vs research) that discouraged trainees and supervisors from engaging in research, poor research expertise and experience among clinical supervisors hampering high-quality supervision, and a frustrating lack of clear standards between the various parties involved in research guidance and examination.

    Conclusion: Both clinical supervisors and trainees struggled to successfully integrate a compulsory research component into residency training. This was not only an issue of resource limitation since questions regarding clinical priorities and unclear research standards emerged. Thus, institutional coordinators need to set clear standards and provide adequate training to make research meaningful and achievable for busy clinical supervisors and trainees.

  10. Bainomugisa A, Meumann EM, Rajahram GS, Ong RT, Coin L, Paul DC, et al.
    Microb Genom, 2021 05;7(5).
    PMID: 33945455 DOI: 10.1099/mgen.0.000573
    Tuberculosis is a leading public health priority in eastern Malaysia. Knowledge of the genomic epidemiology of tuberculosis can help tailor public health interventions. Our aims were to determine tuberculosis genomic epidemiology and characterize resistance mutations in the ethnically diverse city of Kota Kinabalu, Sabah, located at the nexus of Malaysia, Indonesia, Philippines and Brunei. We used an archive of prospectively collected Mycobacterium tuberculosis samples paired with epidemiological data. We collected sputum and demographic data from consecutive consenting outpatients with pulmonary tuberculosis at the largest tuberculosis clinic from 2012 to 2014, and selected samples from tuberculosis inpatients from the tertiary referral centre during 2012-2014 and 2016-2017. Two hundred and eight M. tuberculosis sequences were available for analysis, representing 8 % of cases notified during the study periods. Whole-genome phylogenetic analysis demonstrated that most strains were lineage 1 (195/208, 93.8 %), with the remainder being lineages 2 (8/208, 3.8 %) or 4 (5/208, 2.4 %). Lineages or sub-lineages were not associated with patient ethnicity. The lineage 1 strains were diverse, with sub-lineage 1.2.1 being dominant (192, 98 %). Lineage 1.2.1.3 isolates were geographically most widely distributed. The greatest diversity occurred in a border town sub-district. The time to the most recent common ancestor for the three major lineage 1.2.1 clades was estimated to be the year 1966 (95 % HPD 1948-1976). An association was found between failure of culture conversion by week 8 of treatment and infection with lineage 2 (4/6, 67 %) compared with lineage 1 strains (4/83, 5 %) (P<0.001), supporting evidence of greater virulence of lineage 2 strains. Eleven potential transmission clusters (SNP difference ≤12) were identified; at least five included people living in different sub-districts. Some linked cases spanned the whole 4-year study period. One cluster involved a multidrug-resistant tuberculosis strain matching a drug-susceptible strain from 3 years earlier. Drug resistance mutations were uncommon, but revealed one phenotype-genotype mismatch in a genotypically multidrug-resistant isolate, and rare nonsense mutations within the katG gene in two isolates. Consistent with the regionally mobile population, M. tuberculosis strains in Kota Kinabalu were diverse, although several lineage 1 strains dominated and were locally well established. Transmission clusters - uncommonly identified, likely attributable to incomplete sampling - showed clustering occurring across the community, not confined to households or sub-districts. The findings indicate that public health priorities should include active case finding and early institution of tuberculosis management in mobile populations, while there is a need to upscale effective contact investigation beyond households to include other contacts within social networks.
  11. Krzemińska U, Morales HE, Greening C, Nyári ÁS, Wilson R, Song BK, et al.
    Heredity (Edinb), 2018 04;120(4):296-309.
    PMID: 29180719 DOI: 10.1038/s41437-017-0020-7
    The House Crow (Corvus splendens) is a useful study system for investigating the genetic basis of adaptations underpinning successful range expansion. The species originates from the Indian subcontinent, but has successfully spread through a variety of thermal environments across Asia, Africa and Europe. Here, population mitogenomics was used to investigate the colonisation history and to test for signals of molecular selection on the mitochondrial genome. We sequenced the mitogenomes of 89 House Crows spanning four native and five invasive populations. A Bayesian dated phylogeny, based on the 13 mitochondrial protein-coding genes, supports a mid-Pleistocene (~630,000 years ago) divergence between the most distant genetic lineages. Phylogeographic patterns suggest that northern South Asia is the likely centre of origin for the species. Codon-based analyses of selection and assessments of changes in amino acid properties provide evidence of positive selection on the ND2 and ND5 genes against a background of purifying selection across the mitogenome. Protein homology modelling suggests that four amino acid substitutions inferred to be under positive selection may modulate coupling efficiency and proton translocation mediated by OXPHOS complex I. The identified substitutions are found within native House Crow lineages and ecological niche modelling predicts suitable climatic areas for the establishment of crow populations within the invasive range. Mitogenomic patterns in the invasive range of the species are more strongly associated with introduction history than climate. We speculate that invasions of the House Crow have been facilitated by standing genetic variation that accumulated due to diversifying selection within the native range.
  12. Tsai JW, Liew HJ, Jhang JJ, Hung SH, Meng PJ, Leu MY, et al.
    Fish Physiol Biochem, 2018 Apr;44(2):489-502.
    PMID: 29192359 DOI: 10.1007/s10695-017-0448-y
    The mosquitofish (Gambusia affinis) naturally inhabits freshwater (FW; 1-3‰) and seawater (SW; 28-33‰) ponds in constructed wetland. To explore the physiological status and molecular mechanisms for salinity adaptation of the mosquitofish, cytoprotective responses and osmoregulation were examined. In the field study, activation of protein quality control (PQC) mechanism through upregulation of the abundance of heat shock protein (HSP) 90 and 70 and ubiquitin-conjugated proteins was found in the mosquitofish gills from SW pond compared to the individuals of FW pond. The levels of aggregated proteins in mosquitofish gills had no significant difference between FW and SW ponds. Furthermore, the osmoregulatory responses revealed that the body fluid osmolality and muscle water contents of the mosquitofish from two ponds were maintained within a physiological range while branchial Na+/K+-ATPase (NKA) expression was higher in the individuals from SW than FW ponds. Subsequently, to further clarify whether the cellular stress responses and osmoregulation were mainly induced by hypertonicity, a laboratory salinity acclimation experiment was conducted. The results from the laboratory experiment were similar to the field study. Branchial PQC as well as NKA responses were induced by SW acclimation compared to FW-acclimated individuals. Taken together, induction of gill PQC and NKA responses implied that SW represents an osmotic stress for mosquitofish. Activation of PQC was suggested to provide an osmoprotection to prevent the accumulation of aggregated proteins. Moreover, an increase in branchial NKA responses for osmoregulatory adjustment was required for the physiological homeostasis of body fluid osmolality and muscle water content.
  13. Chadda KR, Ahmad S, Valli H, den Uijl I, Al-Hadithi AB, Salvage SC, et al.
    Sci Rep, 2017 09 11;7(1):11070.
    PMID: 28894151 DOI: 10.1038/s41598-017-11210-3
    Long QT Syndrome 3 (LQTS3) arises from gain-of-function Nav1.5 mutations, prolonging action potential repolarisation and electrocardiographic (ECG) QT interval, associated with increased age-dependent risk for major arrhythmic events, and paradoxical responses to β-adrenergic agents. We investigated for independent and interacting effects of age and Scn5a+/ΔKPQ genotype in anaesthetised mice modelling LQTS3 on ECG phenotypes before and following β-agonist challenge, and upon fibrotic change. Prolonged ventricular recovery was independently associated with Scn5a+/ΔKPQ and age. Ventricular activation was prolonged in old Scn5a+/ΔKPQ mice (p = 0.03). We associated Scn5a+/ΔKPQ with increased atrial and ventricular fibrosis (both: p 
  14. Sagisaka M, Ono S, James C, Yoshizawa A, Mohamed A, Guittard F, et al.
    Colloids Surf B Biointerfaces, 2018 Aug 01;168:201-210.
    PMID: 29276082 DOI: 10.1016/j.colsurfb.2017.12.012
    Previous work (M. Sagisaka, et al. Langmuir 31 (2015) 7479-7487), showed the most effective fluorocarbon (FC) and hydrocarbon (HC) chain lengths in the hybrid surfactants FCm-HCn (sodium 1-oxo-1-[4-(perfluoroalkyl)phenyl]alkane-2-sulfonates, where m = FC length and n = HC length) were m and n = 6 and 4 for water solubilization, whereas m 6 and n 6, or m 6 and n 5, were optimal chain lengths for reversed micelle elongation in supercritical CO2. To clarify why this difference of only a few methylene chain units is so effective at tuning the solubilizing power and reversed micelle morphology, nanostructures of water-in-CO2 (W/CO2) microemulsions were investigated by high-pressure small-angle neutron scattering (SANS) measurements at different water-to-surfactant molar ratios (W0) and surfactant concentrations. By modelling SANS profiles with cylindrical and ellipsoidal form factors, the FC6-HCn/W/CO2 microemulsions were found to increase in size with increasing W0 and surfactant concentration. Ellipsoidal cross-sectional radii of the FC6-HC4/W/CO2 microemulsion droplets increased linearly with W0, and finally reached ∼39 Å and ∼78 Å at W0 = 85 (close to the upper limit of solubilizing power). These systems appear to be the largest W/CO2 microemulsion droplets ever reported. The aqueous domains of FC6-HC6 rod-like reversed micelles increased in size by 3.5 times on increasing surfactant concentration from 35 mM to 50 mM: at 35 mM, FC6-HC5 formed rod-like reversed micelles 5.3 times larger than FC6-HC6. Interestingly, these results suggest that hybrid HC-chains partition into the microemulsion aqueous cores with the sulfonate headgroups, or at the W/CO2 interfaces, and so play important roles for tuning the W/CO2 interfacial curvature. The super-efficient W/CO2-type solubilizer FC6-HC4, and the rod-like reversed micelle forming surfactant FC6-HC5, represent the most successful cases of low fluorine content additives. These surfactants facilitate VOC-free, effective and energy-saving CO2 solvent systems for applications such as extraction, dyeing, dry cleaning, metal-plating, enhanced oil recovery and organic/inorganic or nanomaterial synthesis.
  15. Altokhis AI, Hibbert AM, Allen CM, Mougin O, Alotaibi A, Lim SY, et al.
    Mult Scler, 2022 Dec;28(14):2202-2211.
    PMID: 36000485 DOI: 10.1177/13524585221114750
    BACKGROUND: Iron rims (IRs) surrounding white matter lesions (WMLs) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without iron rim lesions (IRLs) have been reported so far.

    OBJECTIVE: To assess whether the presence and number of IRLs in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) are associated with long-term disability or progressive disease.

    METHODS: Ninety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7 T magnetic resonance imaging (MRI). Expanded Disability Status Scale (EDSS) was used to calculate Age-related Multiple Sclerosis Severity Score (ARMSS) at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using Susceptibility weighted imaging (SWI)-filtered phase images.

    RESULTS: In all, 132 IRLs were detected in 42 patients (46%); 9% of WMLs had IRs; 54% of the cohort had no rims, 30% had 1-3 rims and 16% had ⩾4. Patients with IRL had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability, especially in patients with ⩾4 IRLs. IRLs have a greater impact on disability compared to the WML number and volume.

    CONCLUSION: The presence and number of perilesional IR on MRI hold prognostic value for long-term clinical disability in MS.

  16. Ahmad B, Friar EP, Taylor E, Vohra MS, Serpell CJ, Garrett MD, et al.
    Eur J Pharmacol, 2023 Jan 05;938:175445.
    PMID: 36473593 DOI: 10.1016/j.ejphar.2022.175445
    In this study, the anti-obesity effects of 5,7,3',4',5-pentamethoxyflavone (PMF) and 6,2',4'-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase (PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2 (aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects.
  17. Choon SE, Wright AK, Griffiths CEM, Tey KE, Wong KW, Lee YW, et al.
    Br J Dermatol, 2022 Nov;187(5):713-721.
    PMID: 35830199 DOI: 10.1111/bjd.21768
    BACKGROUND: There are no population-based epidemiological data on psoriasis in Southeast Asia, including Malaysia.

    OBJECTIVES: To determine the incidence and prevalence of psoriasis over 11 years in multiethnic Johor Bahru, Malaysia.

    METHODS: A population-based cohort study was made using the Teleprimary Care database between January 2010 and December 2020. Cases of psoriasis, identified by ICD-10 diagnostic codes, were validated by dermatologists. Annual prevalence and incidence were estimated and stratified by age, sex and ethnicity.

    RESULTS: We identified 3932 people with dermatologist-confirmed psoriasis, including 1830 incident cases, among 1 164 724 Malaysians, yielding an 11-year prevalence of 0·34% [95% confidence interval (CI) 0·33-0·35] and incidence of 34·2 per 100 000 person-years (95% CI 32·6-35·8). Rates were higher in Indian patients; the prevalences were 0·54% (0·50-0·58) in Indian, 0·38% (0·36-0·40) in Chinese and 0·29% (0·28-0·30) in Malay patients, and the respective incidences per 100 000 person-years were 52·5 (47·3-57·7), 38·0 (34·1-41·8) and 30·0 (28·2-31·8). Rates were higher in males; the prevalence was 0·39% (0·37-0·41) in males and 0·29% (0·27-0·30) in females, and the respective incidences per 100 000 person-years were 40·7 (38·2-43·2) and 28·3 (26·4-30·3). Between 2010 and 2020, annual psoriasis prevalence and incidence increased steadily from 0·27% to 0·51% and from 27·8 to 60·9 per 100 000 person-years, respectively. Annual rates were consistently higher in male and Indian patients. Overall, psoriasis was significantly more common in males than females [odds ratio (OR) 1·37, 95% CI 1·29-1·46] and in Indian and Chinese patients vs. Malay (OR 1·85, 1·71-2·01 and OR 1·30, 1·20-1·41, respectively). Prevalence increased with age, with the highest rates in the groups aged 50-59 and 60-69 years at 0·67% and 0·66%, respectively. A modest bimodal trend in age of psoriasis onset was observed, with first and second peaks at 20-29 and 50-59 years. Disease onset was significantly earlier in females than males [mean (SD) 36·8 (17·3) vs. 42·0 (17·2) years, P 

  18. Gnanasegaran N, Govindasamy V, Simon C, Gan QF, Vincent-Chong VK, Mani V, et al.
    Eur J Clin Invest, 2017 Mar 30.
    PMID: 28369799 DOI: 10.1111/eci.12753
    BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic (DA-ergic) neurons in the substantia nigra (SN) and represented as a huge threat to the geriatric population. Cell replacement therapies (CRTs) have been proposed as a promising strategy to slow down or replace neuronal loss. Among the widely available cell sources, dental pulp stem cells (DPSCs) portray as an attractive source primarily due to their neural crest origin, ease of tissue procurement and less ethical hurdles.

    MATERIALS AND METHODS: We first demonstrated the in vitro differentiation ability of DPSCs towards DA-ergic-like cells before evaluating their neuro-protection/neuro-restoration capacities in MPTP-induced mice. Transplantation via intrathecal was performed with behavioural assessments being evaluated every fortnight. Subsequent analysis investigating their immuno-modulatory behaviour was conducted using neuronal and microglial cell lines.

    RESULTS: It was apparent that the behavioural parameters began to improve corresponding to tyrosine hydroxylase (TH), dopamine transporter (DAT) and dopamine decarboxylase (AADC) immunostaining in SN and striatum as early as 8-week post-transplantation (P < 0·05). About 60% restoration of DA-ergic neurons was observed at SN in MPTP-treated mice after 12-week post-transplantation. Similarly, their ability to reduce toxic effects of MPTP (DNA damages, reactive oxygen species and nitric oxide release) and regulate cytokine levels was distinctly noted (P < 0·05) upon exposure in in vitro model.

    CONCLUSIONS: Our results suggest that DPSCs may provide a therapeutic benefit in the old-aged PD mice model and may be explored in stem cell-based CRTs especially in geriatric population as an attempt towards 'personalized medicine'.

  19. Chiang YH, Chear NJ, Berthold EC, Kuntz MA, Kanumuri SRR, Senetra AS, et al.
    Drug Test Anal, 2024 May 15.
    PMID: 38747129 DOI: 10.1002/dta.3703
    Villocarine A is a bioactive indole alkaloid isolated from the Uncaria genus. It has demonstrated vasorelaxation activity and potential to protect the central nervous system. To identify the pharmacokinetic properties of villocarine A, a series of in vitro and in vivo studies have been performed. Villocarine A was found to be highly permeable (15.6 ± 1.6*10-6 cm/s) across human colorectal adenocarcinoma cell monolayer with high protein binding (>91%) in both rat and human plasma. Hepatic extraction ratio of villocarine A was 0.1 in pooled rat liver and 0.2 in human liver microsomes and was found stable in rat plasma at 37°C. Due to the high permeability and low rate of metabolism properties, villocarine A was initially considered suitable for preclinical development and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification (linearity: 1-150 ng/ml) in rat plasma was developed and validated for in vivo studies. Essential pharmacokinetic parameters included the volume of distribution and clearance of villocarine A, which were found to be 100.3 ± 15.6 L/kg and 8.2 ± 1.1 L/h/kg, respectively, after intravenous administration in rats. Following oral dosing, villocarine A exhibited rapid absorption as the maximum plasma concentration (53.2 ± 10.4 ng/ml) occurred at 0.3 ± 0.1 h, post-dose. The absolute oral bioavailability of villocarine A was 16.8 ± 0.1%. To our knowledge, this was the first pharmacokinetic study of villocarine A, which demonstrated the essential pharmacokinetic properties of villocarine A: large volume distribution, high clearance, and low oral bioavailability in rats.
  20. Khor V, Sidhu S, Muhammad Afiq MFO, Pushpanathan M, Fahmy O, Khairul Asri MG, et al.
    Singapore Med J, 2024 Mar 01;65(Suppl 1):S35-S40.
    PMID: 35139632 DOI: 10.11622/smedj.2022008
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