Browse publications by year: 2018

  1. Yong KW, Choi JR, Dolbashid AS, Wan Safwani WKZ
    Regen Med, 2018 03;13(2):219-232.
    PMID: 29509072 DOI: 10.2217/rme-2017-0078
    An outstanding amount of resources has been used in research on manipulation of human stem cells, especially mesenchymal stem cells (MSCs), for various clinical applications. However, human MSCs have not been fully utilized in clinical applications due to restrictions with regard to their certain biosafety and bioefficacy concerns, for example, genetic abnormality, tumor formation, induction of host immune response and failure of homing and engraftment. This review summarizes the biosafety and bioefficacy assessment of human MSCs in terms of genetic stability, tumorigenicity, immunogenicity, homing and engraftment. The strategies used to reduce the biosafety concerns and improve the bioefficacy of human MSCs are highlighted. In addition, the approaches that can be implemented to improve their biosafety and bioefficacy assessment are briefly discussed.
    MeSH terms: Containment of Biohazards*; Humans; Stem Cell Transplantation/adverse effects; Stem Cell Transplantation/trends*; Genomic Instability; Mesenchymal Stromal Cells*
  2. Woon LS, Tee CK, Gan LLY, Deang KT, Chan LF
    J Psychiatr Pract, 2018 Mar;24(2):121-124.
    PMID: 29509183 DOI: 10.1097/PRA.0000000000000292
    Leukopenia is a known hematological side effect of atypical antipsychotics. We report a case of an antipsychotic-naive patient with schizophrenia who developed leukopenia after a single dose of olanzapine, which worsened during subsequent treatment with risperidone. Normalization of the white blood cell counts occurred within 24 hours of risperidone discontinuation. Possible synergistic mechanisms underlying olanzapine-induced and risperidone-induced leukopenia are discussed. This case highlights the challenges in identifying and managing nonclozapine antipsychotic-induced leukopenia in a susceptible patient.
    MeSH terms: Drug Synergism; Female; Humans; Leukopenia/chemically induced*; Middle Aged; Schizophrenia/drug therapy*; Antipsychotic Agents/administration & dosage; Antipsychotic Agents/adverse effects*; Risperidone/administration & dosage; Risperidone/adverse effects*
  3. Ubuka T, Parhar IS, Tsutsui K
    Gen Comp Endocrinol, 2018 09 01;265:202-206.
    PMID: 29510150 DOI: 10.1016/j.ygcen.2018.03.004
    Gonadotropin-inhibitory hormone (GnIH) is an inhibitor of the hypothalamic-pituitary-gonadal (HPG) axis. GnIH is also called RFamide-related peptide (RFRP) as GnIH peptides have a characteristic C-terminal LPXRFiamide (X = L or Q) sequence. GnIH is thought to be the mediator of stress by negatively regulating the HPG axis as various stressors increase GnIH mRNA, GnIH peptide or GnIH neuronal activity. On the other hand, GnIH may also mediate behavioral stress responses as GnIH neuronal fibers and GnIH receptors are widely located in the limbic system of telencephalon, diencephalon and midbrain area. Previous studies have shown that intracerebroventricular (i.c.v.) administration of GnIH (RFRP) blocks morphine-induced analgesia in hot plate and formalin injection tests in rats suggesting that GnIH increases sensitivity to pain. GnIH (RFRP) also increases anxiety-like behavior in rats. RNA interference of GnIH gene (GnIH RNAi) increases locomotor activity of white-crowned sparrow and Japanese quail and i.c.v. administration of GnIH decreases GnIH RNAi induced locomotor activity. It was further shown that i.c.v. administration of GnIH (RFRP) decreases aggressive behavior in male quail and sexual behavior in male rats, female white-crowned sparrow and female hamsters. These results suggest that GnIH decreases threat to homeostasis of the organism by increasing pain sensitivity, anxiety and decreasing locomotor activity, aggressive behavior and sexual behavior. GnIH may also mediate the effect of stress on behavior.
    MeSH terms: Aggression/drug effects; Animals; Hypothalamic Hormones/metabolism; Neurons/drug effects; Neurons/metabolism; Neuropeptides/pharmacology*; Receptors, Cell Surface/metabolism
  4. Evaristus NA, Wan Abdullah WN, Gan CY
    Peptides, 2018 04;102:61-67.
    PMID: 29510154 DOI: 10.1016/j.peptides.2018.03.001
    The potential of N. lappacheum and N. mutabile seed as a source of α-amylase inhibitor peptides was explored based on the local traditional practice of using the seed. Different gastro-digestive enzymes (i.e. pepsin or chymotrypsin) or a sequential digestion were used to extract the peptides. The effects of digestion time and enzyme to substrate (E:S) ratio on the α-amylase inhibitory activity were investigated. Results showed that chymotrypsin was effective in producing the inhibitor peptides from rambutan seed protein at E:S ratio 1:20 for 1 h, whereas pepsin was more effective for pulasan seed protein under the same condition. A total of 20 and 31 novel inhibitor peptides were identified, respectively. These peptides could bind with the subsites of α-amylase (i.e. Trp58, Trp59, Tyr62, Asp96, Arg195, Asp197, Glu233, His299, Asp300, and His305) and formed a sliding barrier that preventing the formation of enzyme/substrate intermediate leading to lower α-amylase activity.
    MeSH terms: alpha-Amylases/antagonists & inhibitors; alpha-Amylases/chemistry*; Binding Sites; Digestion; Enzyme Inhibitors/isolation & purification; Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/chemistry*; Pepsin A/chemistry; Peptides/isolation & purification; Peptides/pharmacology; Peptides/chemistry*; Plant Extracts/isolation & purification; Plant Extracts/pharmacology; Plant Extracts/chemistry*; Seeds/chemistry; Computational Biology; Sapindaceae/chemistry
  5. Ab-Murat N, Mason L, Kadir RA, Yusoff N
    Int J Occup Saf Ergon, 2018 Jun;24(2):233-239.
    PMID: 28010176 DOI: 10.1080/10803548.2016.1268869
    PURPOSE: To assess Malaysian dentists' perceptions of their mental well-being.

    METHODS: A self-administered questionnaire was developed based on a conceptual framework of mental health and well-being model. Two aspects were assessed, namely the physiological (two domains) and the psychological (six domains). Participants were asked to rate their experiences of the aforementioned aspects using a 5-point Likert scale ranging from all the time to never.

    RESULTS: The response rate was 81%. Most of the dentists (61.7%) perceived having positive mental well-being. Under the physiological aspect, most respondents reported that they were 'generally happy' (93.3%), but about 30% stated they were 'stressed physically and emotionally'. Of the six domains under the psychological aspect, positive well-being was observed in the 'sense of coherence' and 'behavioural stress' domains. Participants who were above 40 years old, married and had children reported having a more positive mental well-being when compared with their counterparts.

    CONCLUSION: Overall, most Malaysian dentists perceived having a positive mental well-being. It is crucial, however, to closely monitor and initiate early interventions for those with negative symptoms to ensure the safe practice of dentistry.

    MeSH terms: Adult; Cross-Sectional Studies; Dentists/psychology*; Female; Humans; Malaysia/epidemiology; Male; Mental Health/statistics & numerical data*; Surveys and Questionnaires; Self Concept*; Stress, Physiological; Stress, Psychological/epidemiology; Occupational Health
  6. Naning H, Al-Darraji HAA, McDonald S, Ismail NA, Kamarulzaman A
    Asia Pac J Public Health, 2018 04;30(3):235-243.
    PMID: 29502429 DOI: 10.1177/1010539518757229
    The aim of this study was to simulate the effects of tuberculosis (TB) treatment strategies interventions in an overcrowded and poorly ventilated prison with both high (5 months) and low (3 years) turnover of inmates against improved environmental conditions. We used a deterministic transmission model to simulate the effects of treatment of latent TB infection and active TB, or the combination of both treatment strategies. Without any intervention, the TB prevalence is estimated to increase to 8.8% for a prison with low turnover of inmates but modestly stabilize at 5.8% for high-turnover prisons in a 10-year period. Reducing overcrowding from 6 to 4 inmates per housing cell and increasing the ventilation rate from 2 to 12 air changes per hour combined with any treatment strategy would further reduce the TB prevalence to as low as 0.98% for a prison with low inmate turnover.
    MeSH terms: Crowding*; Humans; Malaysia/epidemiology; Models, Biological; Prisoners/statistics & numerical data*; Prisons*; Tuberculosis/epidemiology; Tuberculosis/prevention & control*; Program Evaluation; Prevalence
  7. Ude CC, Miskon A, Idrus RBH, Abu Bakar MB
    Mil Med Res, 2018 02 26;5(1):7.
    PMID: 29502528 DOI: 10.1186/s40779-018-0154-9
    The dynamic nature of modern warfare, including threats and injuries faced by soldiers, necessitates the development of countermeasures that address a wide variety of injuries. Tissue engineering has emerged as a field with the potential to provide contemporary solutions. In this review, discussions focus on the applications of stem cells in tissue engineering to address health risks frequently faced by combatants at war. Human development depends intimately on stem cells, the mysterious precursor to every kind of cell in the body that, with proper instruction, can grow and differentiate into any new tissue or organ. Recent reports have suggested the greater therapeutic effects of the anti-inflammatory, trophic, paracrine and immune-modulatory functions associated with these cells, which induce them to restore normal healing and tissue regeneration by modulating immune reactions, regulating inflammation, and suppressing fibrosis. Therefore, the use of stem cells holds significant promise for the treatment of many battlefield injuries and their complications. These applications include the treatment of injuries to the skin, sensory organs, nervous system tissues, the musculoskeletal system, circulatory/pulmonary tissues and genitals/testicles and of acute radiation syndrome and the development of novel biosensors. The new research developments in these areas suggest that solutions are being developed to reduce critical consequences of wounds and exposures suffered in warfare. Current military applications of stem cell-based therapies are already saving the lives of soldiers who would have died in previous conflicts. Injuries that would have resulted in deaths previously now result in wounds today; similarly, today's permanent wounds may be reduced to tomorrow's bad memories with further advances in stem cell-based therapies.
    MeSH terms: Humans; Military Medicine/trends*; Warfare; Wounds and Injuries/therapy; Tissue Engineering/methods; Tissue Engineering/trends*; Stem Cell Transplantation/methods; Stem Cell Transplantation/trends*
  8. Samuel S, Ahmad RE, Ramasamy TS, Manan F, Kamarul T
    Injury, 2018 Apr;49(4):775-783.
    PMID: 29503013 DOI: 10.1016/j.injury.2018.02.020
    BACKGROUND: It has been previously suggested that the use of regenerative promoters, which include bone marrow-derived mesenchymal stem cells (MSCs) or natural growth factors supplement such as platelet-rich concentrate (PRC) could promote cartilage regeneration. However, the notion that the concurrent use of both promoters may provide a synergistic effect that improves the repair outcome of focal cartilage injury has not been previously demonstrated. This study was thus conducted to determine whether the concomitant use of PRC could further enhance the reparative potential of MSCs encapsulated in alginate transplanted into focal cartilage injury in rabbits.

    METHODS: Artifically created full thickness cartilage defects were made on the weight-bearing region of medial femoral condyles in bilateral knees of New Zealand White rabbits (N = 30). After one month, the right knee was treated with either i) PRC (n = 10), ii) MSCs (n = 10), or, iii) a combination of PRC and MSCs (PRC + MSC) (n = 10), all encapsulated in alginate. The left knee remained untreated (control). Rabbits were sacrificed at 3 and 6 months after treatment. Cartilage tissue regeneration was accessed using ICRS morphologic scoring, histologic grading by O'Driscoll scoring, immunohistochemical staining and quantitative analysis of glycosaminoglycans (GAG) per total protein content.

    RESULTS: At 3 months, transplantation using PRC alone was equally effective as MSCs in inducing the repair of cartilage defects. However, PRC + MSC resulted in significantly higher ICRS and O'Driscoll scores (p 

    MeSH terms: Alginates; Animals; Blood Platelets; Bone Marrow; Cartilage Diseases; Cartilage, Articular; Glycosaminoglycans; Hexuronic Acids; Phenazines; Rabbits; Regeneration; Staining and Labeling; Weight-Bearing; Glucuronic Acid; Collagen Type II; Mesenchymal Stromal Cells
  9. Ishak AR, Hamid FS, Mohamad S, Tay KS
    Waste Manag, 2018 Jun;76:575-581.
    PMID: 29503052 DOI: 10.1016/j.wasman.2018.02.047
    In this work, the feasibility of coagulation-flocculation coupled with UV-based sulfate radical oxidation process (UV/SRAOP) in the removal of chemical oxygen demand (COD) of stabilized landfill leachate (SLL) was evaluated. For coagulation-flocculation, ferric chloride (FeCl3) was used as the coagulant. The effect of initial pH of SLL and COD:FeCl3 ratio on the COD removal was evaluated. The result revealed that COD:FeCl3 ratio of 1:1.3 effectively removed 76.9% of COD at pH 6. The pre-treated SLL was then subjected to UV/SRAOP treatment. For UV/SRAOP, the sulfate radical (SR) was generated using UV-activated persulfate (UV/PS) and peroxymonosulfate (UV/PMS). The dosage of oxidant and reaction time were found to be the main parameters that influence the efficiency of COD removal. On the other hand, the effect of initial pH (3-7) and the type of oxidant (PS and PMS) was found to have no significant influence on COD removal efficiency. At optimum conditions, approximately 90.9 and 91.5% of COD was successfully removed by coagulation-flocculation coupled with UV/PS and UV/PMS system, respectively. Ecotoxicity study using zebrafish showed a reduction in toxicity of SLL from 10.1 to 1.74 toxicity unit (TU) after coagulation-flocculation. The TU remained unchanged after UV/PS treatment but slightly increased to 1.80 after UV/PMS treatment due to the presence of residual sulfate ion in the treated effluent. In general, it can be concluded that coagulation-flocculation coupled with UV/SRAOP could be a potential water treatment method for SLL treatment.
    MeSH terms: Flocculation; Oxidation-Reduction; Sulfates/chemistry*; Waste Disposal, Fluid*; Water Pollutants, Chemical*; Biological Oxygen Demand Analysis
  10. Abd Rani NZ, Husain K, Kumolosasi E
    Front Pharmacol, 2018;9:108.
    PMID: 29503616 DOI: 10.3389/fphar.2018.00108
    Moringa
    is a genus of medicinal plants that has been used traditionally to cure wounds and various diseases such as colds and diabetes. In addition, the genus is also consumed as a source of nutrients and widely used for purifying water. The genus consists of 13 species that have been widely cultivated throughout Asia and Africa for their multiple uses. The purpose of this review is to provide updated and categorized information on the traditional uses, phytochemistry, biological activities, and toxicological research ofMoringaspecies in order to explore their therapeutic potential and evaluate future research opportunities. The literature reviewed for this paper was obtained from PubMed, ScienceDirect, and Google Scholar journal papers published from 1983 to March 2017.Moringaspecies are well-known for their antioxidant, anti-inflammatory, anticancer, and antihyperglycemic activities. Most of their biological activity is caused by their high content of flavonoids, glucosides, and glucosinolates. By documenting the traditional uses and biological activities ofMoringaspecies, we hope to support new research on these plants, especially on those species whose biological properties have not been studied to date.
    MeSH terms: Africa; Anti-Inflammatory Agents; Antioxidants; Asia; Diabetes Mellitus; Flavonoids; Glucosides; Glucosinolates; Hypoglycemic Agents; Plants, Medicinal; Moringa; PubMed
  11. Ariffin EY, Lee YH, Futra D, Tan LL, Karim NHA, Ibrahim NNN, et al.
    Anal Bioanal Chem, 2018 Mar;410(9):2363-2375.
    PMID: 29504083 DOI: 10.1007/s00216-018-0893-1
    A novel electrochemical DNA biosensor for ultrasensitive and selective quantitation of Escherichia coli DNA based on aminated hollow silica spheres (HSiSs) has been successfully developed. The HSiSs were synthesized with facile sonication and heating techniques. The HSiSs have an inner and an outer surface for DNA immobilization sites after they have been functionalized with 3-aminopropyltriethoxysilane. From field emission scanning electron microscopy images, the presence of pores was confirmed in the functionalized HSiSs. Furthermore, Brunauer-Emmett-Teller (BET) analysis indicated that the HSiSs have four times more surface area than silica spheres that have no pores. These aminated HSiSs were deposited onto a screen-printed carbon paste electrode containing a layer of gold nanoparticles (AuNPs) to form a AuNP/HSiS hybrid sensor membrane matrix. Aminated DNA probes were grafted onto the AuNP/HSiS-modified screen-printed electrode via imine covalent bonds with use of glutaraldehyde cross-linker. The DNA hybridization reaction was studied by differential pulse voltammetry using an anthraquinone redox intercalator as the electroactive DNA hybridization label. The DNA biosensor demonstrated a linear response over a wide target sequence concentration range of 1.0×10-12-1.0×10-2 μM, with a low detection limit of 8.17×10-14 μM (R2 = 0.99). The improved performance of the DNA biosensor appeared to be due to the hollow structure and rough surface morphology of the hollow silica particles, which greatly increased the total binding surface area for high DNA loading capacity. The HSiSs also facilitated molecule diffusion through the silica hollow structure, and substantially improved the overall DNA hybridization assay. Graphical abstract Step-by-step DNA biosensor fabrication based on aminated hollow silica spheres.
    MeSH terms: Amination; Conductometry/methods; DNA, Bacterial/analysis*; DNA, Bacterial/genetics; Escherichia coli/genetics; Escherichia coli/isolation & purification*; Escherichia coli Infections/microbiology*; Gold/chemistry; Humans; Nucleic Acid Hybridization/methods; Silicon Dioxide/chemistry*; Water Microbiology*; Biosensing Techniques/methods*; Metal Nanoparticles/chemistry; Limit of Detection; Immobilized Nucleic Acids/genetics; Immobilized Nucleic Acids/chemistry
  12. Chew BH, Vos RC, Stellato RK, Ismail M, Rutten GEHM
    Diabet Med, 2018 06;35(6):750-759.
    PMID: 29505098 DOI: 10.1111/dme.13615
    AIMS: To evaluate the effectiveness of a brief, value-based emotion-focused educational programme (VEMOFIT) in Malay adults with Type 2 diabetes mellitus compared with a programme of active listening to participants' emotional experiences, social support and their opinion on the health clinic diabetes care services (attention control).

    METHODS: Malay adults with severe diabetes distress [Diabetes Distress Scale (DDS-17) mean score ≥ 3] were included. VEMOFIT consisted of four biweekly group sessions, a booster session after 3 months and a follow-up 6 months post intervention. The attention control programme consisted of three sessions over the same period. Outcomes included diabetes distress, depressive symptoms, self-efficacy and disease control. Required total sample size was 165.

    RESULTS: Participants (n = 124) were randomized to either VEMOFIT (n = 53) or the attention control programme (n = 71). Participants had a mean (sd) age of 55.7 (9.7) years, median diabetes duration of 7.0 (8.0) years and mean HbA1c level of 82 mmol/mol (9.7%). The mean DDS-17 level decreased significantly in both the VEMOFIT and the attention control programmes (3.4 to 2.9 vs. 3.1 to 2.7, respectively). The adjusted between-group DDS-17 difference was not significant [-0.01, 95% confidence interval (CI) -0.38, 0.35]. The proportion of individuals with severe diabetes distress decreased in both groups, from 89% to 47% vs. 69% to 39% (odds ratio 0.88; 95% CI 0.26, 2.90). Other outcomes did not differ between groups.

    CONCLUSIONS: Both interventions decreased diabetes distress significantly. The theory-based VEMOFIT programme was not superior to the attention control programme. The latter approach is a simpler way to decrease severe diabetes distress (Trial registration: NCT02730078; NMRR-15-1144-24803).

    Study site: Klinik Kesihatan, Negeri Sembilan, Malaysia
    MeSH terms: Adult; Ambulatory Care Facilities; Analysis of Variance; Depression/etiology; Diabetes Mellitus, Type 2/psychology*; Emotions*; Female; Humans; Malaysia; Male; Middle Aged; Patient Education as Topic/methods*; Pilot Projects; Psychotherapy, Brief/methods*; Quality of Life; Self Care/methods; Self Care/psychology; Stress, Psychological/prevention & control*; Cluster Analysis; Treatment Outcome; Self Efficacy
  13. Mohamad NA, Mustafa S, Khairil Mokhtar NF, El Sheikha AF
    J Sci Food Agric, 2018 Sep;98(12):4570-4577.
    PMID: 29505123 DOI: 10.1002/jsfa.8985
    BACKGROUND: The pharmaceutical industry has boosted gelatin consumption worldwide. This is supported by the availability of cost-effective gelatin production from porcine by-products. However, cross-contamination of gelatin materials, where porcine gelatin was unintentionally included in the other animal sources of gelatin, has caused significant concerns about halal authenticity. The real-time polymerase chain reaction (PCR) has enabled a highly specific and sensitive animal species detection method in various food products. Hence, such a technique was employed in the present study to detect and quantify porcine DNA in gelatin using a molecular beacon probe, with differences in performance between mitochondrial (cytochrome b gene) and chromosomal DNA-(MPRE42 repetitive element) based porcine-specific PCR assays being compared.

    RESULTS: A higher sensitivity was observed in chromosomal DNA (MPRE-PCR assay), where this assay allows the detection of gelatin DNA at amounts as as low as 1 pg, whereas mitochondrial DNA (CBH-PCR assay) can only detect at levels down to 10 pg of gelatin DNA. When an analysis with commercial gelatin and gelatin capsule samples was conducted, the same result was observed, with a significantly more sensitive detection being provided by the repetitive element of chromosomal DNA.

    CONCLUSION: The present study has established highly sensitive DNA-based porcine detection systems derived from chromosomal DNA that are feasible for highly processed products such as gelatin and gelatin capsules containing a minute amount of DNA. This sensitive detection method can also be implemented to assist the halal authentication process of various food products available on the market. © 2018 Society of Chemical Industry.

    MeSH terms: Animals; Capsules/chemistry*; Food Contamination/analysis; Gelatin/genetics*; Meat/analysis; Swine; DNA Primers/genetics; Cytochromes b/genetics; Real-Time Polymerase Chain Reaction/instrumentation; Real-Time Polymerase Chain Reaction/methods*
  14. Lam SS, Liew RK, Cheng CK, Rasit N, Ooi CK, Ma NL, et al.
    J Environ Manage, 2018 May 01;213:400-408.
    PMID: 29505995 DOI: 10.1016/j.jenvman.2018.02.092
    Fruit peel, an abundant waste, represents a potential bio-resource to be converted into useful materials instead of being dumped in landfill sites. Palm oil mill effluent (POME) is a harmful waste that should also be treated before it can safely be released to the environment. In this study, pyrolysis of banana and orange peels was performed under different temperatures to produce biochar that was then examined as adsorbent in POME treatment. The pyrolysis generated 30.7-47.7 wt% yield of a dark biochar over a temperature ranging between 400 and 500 °C. The biochar contained no sulphur and possessed a hard texture, low volatile content (≤34 wt%), and high amounts of fixed carbon (≥72 wt%), showing durability in terms of high resistance to chemical reactions such as oxidation. The biochar showed a surface area of 105 m2/g and a porous structure containing mesopores, indicating its potential to provide many adsorption sites for use as an adsorbent. The use of the biochar as adsorbent to treat the POME showed a removal efficiency of up to 57% in reducing the concentration of biochemical oxygen demand (BOD), chemical oxygen demand COD, total suspended solid (TSS) and oil and grease (O&G) of POME to an acceptable level below the discharge standard. Our results indicate that pyrolysis shows promise as a technique to transform banana and orange peel into value-added biochar for use as adsorbent to treat POME. The recovery of biochar from fruit waste also shows advantage over traditional landfill approaches in disposing this waste.
    MeSH terms: Charcoal*; Fruit*; Industrial Waste*; Plant Oils
  15. Melling GE, Flannery SE, Abidin SA, Clemmens H, Prajapati P, Hinsley EE, et al.
    Carcinogenesis, 2018 05 28;39(6):798-807.
    PMID: 29506142 DOI: 10.1093/carcin/bgy032
    The dissemination of cancer cells to local and distant sites depends on a complex and poorly understood interplay between malignant cells and the cellular and non-cellular components surrounding them, collectively termed the tumour microenvironment. One of the most abundant cell types of the tumour microenvironment is the fibroblast, which becomes corrupted by locally derived cues such as TGF-β1 and acquires an altered, heterogeneous phenotype (cancer-associated fibroblasts, CAF) supportive of tumour cell invasion and metastasis. Efforts to develop new treatments targeting the tumour mesenchyme are hampered by a poor understanding of the mechanisms underlying the development of CAF. Here, we examine the contribution of microRNA to the development of experimentally-derived CAF and correlate this with changes observed in CAF derived from tumours. Exposure of primary normal human fibroblasts to TGF-β1 resulted in the acquisition of a myofibroblastic CAF-like phenotype. This was associated with increased expression of miR-145, a miRNA predicted in silico to target multiple components of the TGF-β signalling pathway. miR-145 was also overexpressed in CAF derived from oral cancers. Overexpression of miR-145 blocked TGF-β1-induced myofibroblastic differentiation and reverted CAF towards a normal fibroblast phenotype. We conclude that miR-145 is a key regulator of the CAF phenotype, acting in a negative feedback loop to dampen acquisition of myofibroblastic traits, a key feature of CAF associated with poor disease outcome.
    MeSH terms: Cell Differentiation/physiology; Humans; Mouth Neoplasms/metabolism*; Phenotype; Signal Transduction/physiology; MicroRNAs/metabolism*; Cell Line, Tumor; Transforming Growth Factor beta1/metabolism*; Myofibroblasts/metabolism; Tumor Microenvironment/physiology; Cancer-Associated Fibroblasts/metabolism*
  16. Umat C, Mukari SZS, Nordin N, A/L Annamalay T, Othman BF
    Int J Pediatr Otorhinolaryngol, 2018 Apr;107:69-74.
    PMID: 29501315 DOI: 10.1016/j.ijporl.2018.01.031
    OBJECTIVES: The aims of the study were to compare the mainstream school readiness skills of young cochlear implant (CI) users to that of a group of normal hearing (NH) children and assessed the inter-rater agreement between parents and teachers on school readiness skills of the CI children.

    METHODS: A total of 11 parents and 8 teachers of the 6-year old CI children participated and rated the children using the School Readiness Scale to Year One. Data from 207 6-year old NH children from five states in Malaysia were also collected using the same scale which has nine domains. Results from the NH children were categorized into the 25th and 75th percentile scores to be the reference cut-offs for below average (below the 25th percentile), average (25th to 75th percentile) and above average (above 75th percentile).

    RESULTS: The school readiness skills of the CI children were lower than the NH group as rated by teachers especially in the civic and language and communication domains. Comparisons between parents' and teachers' ratings for 8 CI children indicated that teachers tended to rate the CI children's school readiness poorer than that of parents especially in the academic domain. Intra-class correlation analysis revealed poor inter-rater agreement.

    CONCLUSIONS: The results suggest that our CI children, generally, need an intervention 'bridging' program to improve their school readiness skills. Parents and teachers had different views on the readiness of the CI children at school entry level.

    MeSH terms: Child; Child Development*; Child, Preschool; Cochlear Implants/statistics & numerical data*; Female; Humans; Language; Mainstreaming (Education)/statistics & numerical data*; Malaysia; Male; Parents; Schools; Cochlear Implantation/statistics & numerical data*; School Teachers
  17. Sahimin N, Douadi B, Yvonne Lim AL, Behnke JM, Mohd Zain SN
    Acta Trop, 2018 Jun;182:178-184.
    PMID: 29501402 DOI: 10.1016/j.actatropica.2018.02.033
    The influx of low skilled workers from socioeconomically deprived neighbouring countries to Malaysia has raised concerns about the transmission of communicable gastrointestinal diseases such as giardiasis and cryptosporidiosis to the local population. Therefore, a cross sectional study was conducted to investigate the prevalence of both diseases and the genetic diversity of these pathogens in the migrant population. Microscopic examination of faecal samples from 388 migrant workers involved in five working sectors were screened and 10.8% (n = 42) were found to be positive with Giardia spp. and 3.1% (n = 12) with Cryptosporidium spp. infections. PCR amplicons at the triosephosphate isomerase (tpi) gene were successfully obtained for Giardia duodenalis from 30 (30/388; 7.73%) samples with assemblages AII and B in 13 (13/30; 43.3%) and 17 (17/30; 56.7%) positive samples, respectively. Nine samples (9/388; 2.3%) were identified as Cryptosporidium parvum using PCR-RFLP analysis. Country of origin, duration of residence in Malaysia and working sectors significantly influenced G. duodenalis assemblage AII infections amongst the targeted population. Meanwhile, C. parvum infection was significantly associated with those working in the food service sector. Despite the low presence of pathogenic G. duodenalis and C. parvum in the study population, the results highlight the risk of anthroponotic foodborne and waterborne transmission and therefore call for implementation of control strategies through improvements in personal hygiene and sanitation standards.
    MeSH terms: Adult; Aged; Animals; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Middle Aged; Transients and Migrants*; Genetic Variation; Prevalence; Polymerase Chain Reaction; Cryptosporidium parvum/genetics; Cryptosporidium parvum/isolation & purification*; Giardia lamblia/genetics; Giardia lamblia/isolation & purification*
  18. Mahmood S, Mandal UK, Chatterjee B
    Int J Pharm, 2018 May 05;542(1-2):36-46.
    PMID: 29501737 DOI: 10.1016/j.ijpharm.2018.02.044
    Raloxifene HCl belongs to a class of selective estrogen receptor modulators (SERMs) which is used for the management of breast cancer. The major problem reported with raloxifene is its poor bioavailability which is only up to 2%. The main objective of the present work was to formulate raloxifene loaded ethosomal preparation for transdermal application and compare it with an oral formulation of the drug. Five ethosomal formulations with different concentrations of ethanol and a conventional liposomes formulation were prepared by rotary evaporation method. The prepared systems were characterised by high resolution transmission electron microscopy (HRTEM), force emission electron microscopy (FESEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and 31P NMR study. All these advanced characterization study established that the ethosome formulation was well defined by its size, shape and its bilayer formation. Transdermal flux of the optimized ethosome formulation was 22.14 ± 0.83 µg/ml/cm2 which was 21 times higher when compared to the conventional liposomes. Confocal microscopy study revealed an enhanced permeation of coumarin-6 dye loaded ethosomes to much deeper layers of skin when compared with conventional liposomes. The gel was found to be pseudoplastic with elastic behaviour. In-vivo studies on rats showed a higher bioavailability of RXL (157% times) for ethosomal formulation when compared with the oral formulation. In conclusion, RXL loaded ethosomal formulation via transdermal route showed superior drug delivery properties as compared to oral formulation.
    MeSH terms: Administration, Cutaneous; Ethanol/administration & dosage*; Ethanol/pharmacokinetics; Ethanol/chemistry; Animals; Biological Availability; Liposomes; Skin/metabolism; Skin Absorption; Rats, Sprague-Dawley; Selective Estrogen Receptor Modulators/administration & dosage*; Selective Estrogen Receptor Modulators/blood; Selective Estrogen Receptor Modulators/pharmacokinetics; Selective Estrogen Receptor Modulators/chemistry; Raloxifene Hydrochloride/administration & dosage*; Raloxifene Hydrochloride/blood; Raloxifene Hydrochloride/pharmacokinetics; Raloxifene Hydrochloride/chemistry
  19. Nasir AM, Goh PS, Ismail AF
    Chemosphere, 2018 Jun;200:504-512.
    PMID: 29501887 DOI: 10.1016/j.chemosphere.2018.02.126
    A novel hydrous iron-nickel-manganese (HINM) trimetal oxide was successfully fabricated using oxidation and coprecipitation method for metalloid arsenite removal. The atomic ratio of Fe:Ni:Mn for this adsorbent is 3:2:1. HINM adsorbent was identified as an amorphous nanosized adsorbent with particle size ranged from 30 nm to 60 nm meanwhile the total active surface area and pore diameter of HINM area of 195.78 m2/g and 2.43 nm, respectively. Experimental data of arsenite adsorption is best fitted into pseudo-second order and Freundlich isotherm model. The maximum adsorption capacity of arsenite onto HINM was 81.9 mg/g. Thermodynamic study showed that the adsorption of arsenite was a spontaneous and endothermic reaction with enthalpy change of 14.04 kJ/mol and Gibbs energy of -12 to -14 kJ/mol. Zeta potential, thermal gravimetric (TGA) and Fourier transform infrared (FTIR) analysis were applied to elucidate the mechanism of arsenite adsorption by HINM. Mechanism of arsenite adsorption by HINM involved both chemisorption and physisorption based on the electrostatic attraction between arsenite ions and surface charge of HINM. It also involved the hydroxyl substitution by arsenite ions through the formation of inner-sphere complex. Reusability of HINM trimetal oxide was up to 89% after three cycles of testing implied that HINM trimetal oxide is a promising and practical adsorbent for arsenite.
    MeSH terms: Adsorption; Ferric Compounds/chemistry*; Hydrogen-Ion Concentration; Kinetics; Nickel/chemistry*; Oxidation-Reduction; Oxides/chemistry*; Particle Size; Thermodynamics; Manganese Compounds/chemistry*; Arsenites/isolation & purification*
  20. Eldem B, Lai TYY, Ngah NF, Vote B, Yu HG, Fabre A, et al.
    Graefes Arch Clin Exp Ophthalmol, 2018 May;256(5):963-973.
    PMID: 29502232 DOI: 10.1007/s00417-017-3890-8
    PURPOSE: To describe intravitreal ranibizumab treatment frequency, clinical monitoring, and visual outcomes (including mean central retinal thickness [CRT] and visual acuity [VA] changes from baseline) in neovascular age-related macular degeneration (nAMD) in real-world settings across three ranibizumab reimbursement scenarios in the Middle East, North Africa, and the Asia-Pacific region.

    METHODS: Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed.

    RESULTS: More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 μm. The greatest mean CRT change was observed in the self-paid group, with -92.6 μm.

    CONCLUSIONS: UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.

    MeSH terms: Ranibizumab/administration & dosage*; Africa, Northern; Aged; Aged, 80 and over; Asia, Southeastern; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Middle East; Primary Health Care; Vision Disorders/diagnosis; Vision Disorders/drug therapy*; Vision Disorders/physiopathology; Visual Acuity/physiology*; Cohort Studies; Fee-for-Service Plans; Retreatment; Angiogenesis Inhibitors/administration & dosage*; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A/antagonists & inhibitors; Wet Macular Degeneration/diagnosis; Wet Macular Degeneration/drug therapy*; Wet Macular Degeneration/physiopathology; Intravitreal Injections
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