Browse publications by year: 2018

  1. Ng NT, Kamaruddin AF, Wan Ibrahim WA, Sanagi MM, Abdul Keyon AS
    J Sep Sci, 2018 Jan;41(1):195-208.
    PMID: 28834218 DOI: 10.1002/jssc.201700689
    The efficiency of the extraction and removal of pollutants from food and the environment has been an important issue in analytical science. By incorporating inorganic species into an organic matrix, a new material known as an organic-inorganic hybrid material is formed. As it possesses high selectivity, permeability, and mechanical and chemical stabilities, organic-inorganic hybrid materials constitute an emerging research field and have become popular to serve as sorbents in various separaton science methods. Here, we review recent significant advances in analytical solid-phase extraction employing organic-inorganic composite/nanocomposite sorbents for the extraction of organic and inorganic pollutants from various types of food and environmental matrices. The physicochemical characteristics, extraction properties, and analytical performances of sorbents are discussed; including morphology and surface characteristics, types of functional groups, interaction mechanism, selectivity and sensitivity, accuracy, and regeneration abilities. Organic-inorganic hybrid sorbents combined with extraction techniques are highly promising for sample preparation of various food and environmental matrixes with analytes at trace levels.
    MeSH terms: Adsorption; Environment; Environmental Pollutants/analysis*; Food Contamination/analysis*; Materials Testing; Organic Chemicals; Permeability; Polymers/chemistry; Silicon Dioxide; Solid Phase Extraction*; Nanocomposites/chemistry*; Metal Nanoparticles
  2. Gan CS, Lim SK, Chee CF, Yusof R, Heh CH
    Chem Biol Drug Des, 2018 02;91(2):448-455.
    PMID: 28834304 DOI: 10.1111/cbdd.13091
    Dengvaxia® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue.
    MeSH terms: Sofosbuvir/therapeutic use; Dengue/therapy*
  3. Kar Wei L, Zamakshshari NH, Ee GCL, Mah SH, Mohd Nor SM
    Nat Prod Res, 2018 Sep;32(18):2147-2151.
    PMID: 28826239 DOI: 10.1080/14786419.2017.1367781
    Two naturally occurring xanthones, ananixanthone (1) and β-mangostin (2), were isolated using column chromatographic method from the n-hexane and methanol extracts of Calophyllum teysmannii, respectively. The major constituent, ananixanthone (1), was subjected to structural modifications via acetylation, methylation and benzylation yielding four new xanthone derivatives, ananixanthone monoacetate (3), ananixanthone diacetate (4), 5-methoxyananixanthone (5) and 5-O-benzylananixanthone (6). Compound 1 together with its four new derivatives were subjected to MTT assay against three cancer cell lines; SNU-1, K562 and LS174T. The results indicated that the parent compound has greater cytotoxicity capabilities against SNU-1 and K562 cell lines with IC50 values of 8.97 ± 0.11 and 2.96 ± 0.06 μg/mL, respectively. Compound 5 on the other hand exhibited better cytotoxicity against LS174T cell line with an IC50 value of 5.76 ± 1.07 μg/mL.
    MeSH terms: Humans; Plant Extracts; Cell Death/drug effects; Calophyllum/chemistry*; Xanthones/isolation & purification; Xanthones/toxicity; Xanthones/chemistry*; Cell Line, Tumor
  4. Lo TS, Chua S, Kao CC, Uy-Patrimonio MC, Ibrahim R, Tan YL
    J Minim Invasive Gynecol, 2018 Jan;25(1):116-123.
    PMID: 28826955 DOI: 10.1016/j.jmig.2017.08.647
    STUDY OBJECTIVE: To evaluate the effectiveness and safety of the MiniArc single-incision sling in the treatment of urodynamic stress incontinence (USI) through 5 years.

    DESIGN: Retrospective observational study (Canadian Task Force classification II-2).

    SETTING: Tertiary referral center.

    PATIENTS: Eighty-five patients with USI without needing concurrent procedures who underwent anti-incontinence surgery using the MiniArc SIMS from February 2010 to December 2011.

    INTERVENTIONS: Anti-incontinence surgery.

    MEASUREMENTS AND MAIN RESULTS: Objective cure was defined as no demonstrable leakage of urine on the cough stress test and 1-hour pad test weight <2 g. Subjective cure was based on negative response to Urinary Distress Inventory question 3, no leakage on coughing, sneezing, or laughing. Most patients were postmenopausal, overweight, and multiparous. Postoperative USI significantly improved (p 

  5. Mat S, Ng CT, Tan PJ, Ramli N, Fadzli F, Rozalli FI, et al.
    PM R, 2018 03;10(3):254-262.
    PMID: 28827207 DOI: 10.1016/j.pmrj.2017.08.405
    BACKGROUND: Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited.
    OBJECTIVE: To evaluate the effect of a personalized home-based exercise program to improve postural balance, fear of falling, and falls risk in older fallers with knee OA and gait and balance problems.
    DESIGN: Randomized controlled trial.
    SETTING: University of Malaya Medical Centre.
    PARTICIPANTS: Fallers who had both radiological OA and a Timed Up and Go (TUG) score of over 13.5 seconds.
    MAIN OUTCOME MEASURE: Postural sway (composite sway) was quantified with the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB) under 4 different sensory conditions: eyes open on firm surface, eyes closed on firm surface, eyes open on unstable foam surface, and eyes closed on unstable foam surface. Participants were asked to stand upright and to attempt to hold their position for 10 seconds for each test condition. The average reading for all conditions were calculated.
    METHODS: Participants randomized to the intervention arm received a home-based modified Otago Exercise Program (OEP) as part of a multifactorial intervention, whereas control participants received general health advice and conventional treatment. This was a secondary subgroup analysis from an original randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT) (trial registration number: ISRCTN11674947). Posturography using a long force plate balance platform (Balancemaster, NeuroCom, USA), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the short-form Falls Efficacy Scale-International (short FES-I) were assessed at baseline and 6 months.
    RESULTS: Results of 41 fallers with radiological evidence of OA and impaired TUG (intervention, 17; control, 24) were available for the final analysis. Between-group analysis revealed significant improvements in the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB), Limits of Stability (LOS), and short FES-I scores by the intervention group compared to the control group at 6 months. No significant difference in time to first fall or in fall-free survival between the intervention and control groups was found.

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

    LEVEL OF EVIDENCE: I.
    MeSH terms: Accidental Falls*; Postural Balance; Exercise Therapy; Fear; Gait; Hospitals, University; Humans; Knee Injuries; Knee Joint; Malaysia; Reading; Risk Factors; Outcome Assessment (Health Care); Osteoarthritis, Knee; Control Groups
  6. Bhawani SA, Husaini A, Ahmad FB, Asaruddin MR
    Curr Protein Pept Sci, 2018;19(10):972-982.
    PMID: 28828988 DOI: 10.2174/1389203718666170821162823
    Proteins have played a very important role in the drug industry for developing treatments of various diseases such as auto-immune diseases, cancer, diabetes, mental disorder, metabolic disease, and others. Therapeutic proteins have high activity and specificity but they have some limitations such as short half-life, poor stability, low solubility and immunogenicity, so they cannot prolong their therapeutic activity. These shortcomings have been rectified by using polymers for the conjugation with proteins. The conjugates of protein-polymer improves the half-lives, stability and makes them non-immunogenic. Poly(ethylene glycol) (PEG), is widely used in the delivery of proteins because it is the current gold standard for stealth polymers in the emerging field of polymer-based delivery as compared to various biodegradable polymers. PEGylation enhances the retention of therapeutic proteins, effectively alters the pharmacokinetics and enhances the pharmaceutical value. Smart polymer have been used to cope with the pathophysiological environment of target site and have imposed less toxic effects.The contents of this article are challenges in formulation of therapeutic proteins, synthetic routes of conjugates, smart polymer-protein conjugates and also some advantages/disadvantages of polymers as a carrier system of proteins.
    MeSH terms: Mental Disorders; Diabetes Mellitus; Drug Industry; Pharmaceutical Preparations; Half-Life; Immune System Diseases; Metabolic Diseases; Neoplasms; Polyethylene Glycols; Polymers; Proteins; Solubility
  7. Abas ZA, Ramli MR, Desa MI, Saleh N, Hanafiah AN, Aziz N, et al.
    Health Care Manag Sci, 2018 Dec;21(4):573-586.
    PMID: 28822005 DOI: 10.1007/s10729-017-9413-7
    The paper aims to provide an insight into the significance of having a simulation model to forecast the supply of registered nurses for health workforce planning policy using System Dynamics. A model is highly in demand to predict the workforce demand for nurses in the future, which it supports for complete development of a needs-based nurse workforce projection using Malaysia as a case study. The supply model consists of three sub-models to forecast the number of registered nurses for the next 15 years: training model, population model and Full Time Equivalent (FTE) model. In fact, the training model is for predicting the number of newly registered nurses after training is completed. Furthermore, the population model is for indicating the number of registered nurses in the nation and the FTE model is useful for counting the number of registered nurses with direct patient care. Each model is described in detail with the logical connection and mathematical governing equation for accurate forecasting. The supply model is validated using error analysis approach in terms of the root mean square percent error and the Theil inequality statistics, which is mportant for evaluating the simulation results. Moreover, the output of simulation results provides a useful insight for policy makers as a what-if analysis is conducted. Some recommendations are proposed in order to deal with the nursing deficit. It must be noted that the results from the simulation model will be used for the next stage of the Needs-Based Nurse Workforce projection project. The impact of this study is that it provides the ability for greater planning and policy making with better predictions.
    MeSH terms: Computer Simulation*; Education, Nursing; Health Manpower/statistics & numerical data*; Health Planning/organization & administration; Health Policy; Health Services Needs and Demand/organization & administration; Humans; Malaysia; Models, Theoretical*; Nurses/statistics & numerical data*
  8. Nugroho AE, Hashimoto A, Wong CP, Yokoe H, Tsubuki M, Kaneda T, et al.
    J Nat Med, 2018 Jan;72(1):64-72.
    PMID: 28822030 DOI: 10.1007/s11418-017-1109-2
    Ceramicines are a series of limonoids which were isolated from the bark of Malaysian Chisocheton ceramicus (Meliaceae) and show various biological activities. Ceramicine B, in particular, has been reported to show a strong lipid droplet accumulation (LDA) inhibitory activity on a mouse pre-adipocyte cell line (MC3T3-G2/PA6). With the purpose of discovering compounds with stronger activity than ceramicine B, we further investigated the constituents of C. ceramicus. As a result, from the bark of C. ceramicus four new ceramicines (ceramicines M-P, 1-4) were isolated, and their structures were determined on the basis of NMR and mass spectroscopic analyses in combination with NMR chemical shift calculations. LDA inhibitory activity of 1-4 was evaluated. Compounds 1-3 showed LDA inhibitory activity, and 3 showed better selectivity than ceramicine B while showing activity at the same order of magnitude as ceramicine B. Since 3, which possess a carbonyl group at C-7, showed better selectivity than 5, which possess a 7α-OH group, while showing activity at the same order of magnitude as 5, we also investigated the effect of the substituent at C-7 by synthesizing several derivatives and evaluating their LDA inhibitory activity. Accordingly, we confirmed the importance of the presence of a 7α-OH group to the LDA inhibitory activity.
    MeSH terms: Structure-Activity Relationship; Molecular Structure; Limonins/chemistry*
  9. Mousavi SA, Mehralian M, Khashij M, Ibrahim S
    Environ Technol, 2018 Nov;39(22):2891-2899.
    PMID: 28820045 DOI: 10.1080/09593330.2017.1369578
    The CANON process is a promising method for nitrogen removal in wastewaters with low organic carbon content like reject water. This study investigated the effect of important factors for optimization of the CANON process through inhibition of nitrite-oxidizing bacteria (NOB). In the acclimation period, complete ammonium removal and 43.3% total N removal were obtained at hydraulic retention time of 12 h, temperature of 30°C ± 0.5°C and DO equal to 7-9 mg/L. The effects of air flow rate (AFR) (representative of DO), SRT and C/N were evaluated. Air flow rate was the most important factor for controlling the process, but the effect of SRT was negligible. When AFR was increased from 100 to 500 mL/min, both ammonium removal efficiency (33-43% to 81-83%) and nitrite accumulation (nitritation, 40 mgN/L to 100-120 mgN/L) were increased, but with increasing AFR to 1000 mL/min only ammonium removal efficiency was increased and because of better condition (high DO) for NOBs, nitritation was decreased. C/N had an effect like AFR of 1000 and only increased ammonium removal efficiency and total N removal. With increasing AFR and C/N, both OUR and AUR were increased, but SVI was decreased.
    MeSH terms: Nitrites; Nitrogen*; Water; Bioreactors*; Denitrification
  10. Ball V, Chiu CS, Lian YP, Lingeswaran L
    Physiother Theory Pract, 2018 Jan;34(1):54-57.
    PMID: 28816591 DOI: 10.1080/09593985.2017.1360423
    BACKGROUND: Newly qualified physiotherapists may be required to interpret an unreported chest X-ray (CXR) as part of their physiotherapy assessment in "on call" situations. Their interpretation may influence the patient management strategies they adopt. There is no research published which have tested the reliability of final year physiotherapy students in CXR interpretation.

    METHODS: Twenty-five final year physiotherapy students were asked to view and interpret the findings of six CXRs, together with a brief vignette, typical of a single commonly encountered diagnosis. Students were also asked if they had received additional CXR training on placement or had a desire to specialize in respiratory care.

    RESULTS: The CXR interpretations were scored as incorrect 0, partially correct 1 (abnormality detected but not able to diagnose or missed some detail) and 2 correct. Scores for each of the six CXRs were added to give a total score (out of 12). The median score was 3 out of 12, (range 0-9). Median scores were slightly higher at 4 out of 12 in those students with additional training or a desire to specialize (range 1-7), but this was not statistically significant (p = 0.43).

    CONCLUSIONS: Final year physiotherapy students were not able to reliably interpret CXRs. These findings were consistent with previous published research involving medical students. Therefore on graduation before starting "on call" duties it is recommended newly qualified physiotherapists receive additional training in CXR interpretation.

    MeSH terms: Clinical Competence*; Humans; Predictive Value of Tests; Prospective Studies; Students, Health Occupations*; Radiography, Thoracic*; Reproducibility of Results; Observer Variation; Physical Therapy Modalities/education*; Physical Therapy Specialty/education*; Physical Therapists/education*
  11. Usman MG, Rafii MY, Martini MY, Yusuff OA, Ismail MR, Miah G
    Cell Stress Chaperones, 2018 Mar;23(2):223-234.
    PMID: 28812232 DOI: 10.1007/s12192-017-0836-3
    Backcrossing together with simple sequence repeat marker strategy was adopted to improve popular Malaysian chilli Kulai (Capsicum annuum L.) for heat tolerance. The use of molecular markers in backcross breeding and selection contributes significantly to overcoming the main drawbacks such as increase linkage drag and time consumption, in the ancient manual breeding approach (conventional), and speeds up the genome recovery of the recurrent parent. The strategy was adopted to introgress heat shock protein gene(s) from AVPP0702 (C. annuum L.), which are heat-tolerant, into the genetic profile of Kulai, a popular high-yielding chilli but which is heat sensitive. The parents were grown on seed trays, and parental screening was carried out with 252 simple sequence repeat markers. The selected parents were crossed and backcrossed to generate F1 hybrids and backcross generations. Sixty-eight markers appeared to be polymorphic and were used to assess the backcross generation; BC1F1, BC2F1 and BC3F1. The average recipient allele of the selected four BC1F1 plants was 80.75% which were used to produce the BC2F1 generation. BC1-P7 was the best BC1F1 plant because it had the highest recovery at 83.40% and was positive to Hsp-linked markers (Hsp70-u2 and AGi42). After three successive generations of backcrossing, the average genome recovery of the recurrent parent in the selected plants in BC3F1 was 95.37%. Hsp gene expression analysis was carried out on BC1F1, BC2F1 and BC3F1 selected lines. The Hsp genes were found to be up-regulated when exposed to heat treatment. The pattern of Hsp expression in the backcross generations was similar to that of the donor parent. This confirms the successful introgression of a stress-responsive gene (Hsp) into a Kulai chilli pepper variety. Furthermore, the yield performance viz. plant height, number of fruits, fruit length and weight and total yield of the improved plant were similar with the recurrent parent except that the plant height was significantly lower than the Kulai (recurrent) parent.
    MeSH terms: Capsicum/genetics*; Genetic Markers; Heterozygote; Inbreeding*; Polymorphism, Genetic; Genes, Plant*; Gene Expression Regulation, Plant; HSP70 Heat-Shock Proteins/genetics*; HSP70 Heat-Shock Proteins/metabolism; Microsatellite Repeats/genetics; Genotyping Techniques
  12. Mohamed NN, Loy SL, Lim PY, Al Mamun A, Jan Mohamed HJ
    Sci Total Environ, 2018 Jan 01;610-611:147-153.
    PMID: 28803192 DOI: 10.1016/j.scitotenv.2017.08.030
    Exposure to secondhand smoke (SHS) can affect fetal brain development as well as subsequent neurodevelopment. This study aimed to determine the association between prenatal and postnatal SHS exposure with children's neurodevelopment at 2years of age. Among 107 mother-child pairs from a Malaysia prospective cohort, prenatal and postnatal SHS exposure was determined based on maternal and child hair nicotine concentrations. Multiple linear regressions were used to determine the association between prenatal and postnatal levels of nicotine in maternal and children's' hair with children's neurodevelopment. After adjustment for confounders, prenatal nicotine concentration levels were negatively associated with communication (β=-2.059; p=0.015) and fine motor skills (β=-2.120; p=0.002) while postnatal nicotine concentration levels were inversely associated with fine motors (β=-0.124; p=0.004) and problem solving skills (β=-0.117; p=0.013). In conclusion, this study suggests that early life exposure to SHS may affect children's neurodevelopment.
    MeSH terms: Child Development/drug effects*; Child, Preschool; Communication; Female; Hair/chemistry*; Humans; Malaysia; Motor Skills; Nicotine; Pregnancy; Prospective Studies; Tobacco Smoke Pollution/adverse effects*; Biomarkers/chemistry; Maternal Exposure/adverse effects*
  13. Bazazi AR, Vijay A, Crawford FW, Heimer R, Kamarulzaman A, Altice FL
    AIDS Care, 2018 Jan;30(1):59-64.
    PMID: 28803503 DOI: 10.1080/09540121.2017.1363852
    HIV testing services are the gateway into HIV treatment and are critical for monitoring the epidemic. HIV testing is recommended at least annually in high-risk populations, including people who inject drugs (PWID). In Malaysia, the HIV epidemic is concentrated among PWID, but their adherence to testing recommendations and the proportion of HIV-positive PWID who are aware of their status remain unknown. We recruited 460 PWID in Greater Kuala Lumpur using respondent-driven sampling and conducted HIV testing. We examined past testing behaviors, estimating testing frequency, correlates of testing in the past 12 months, and the proportion of those living with HIV who were aware of their status. Results showed that most PWID living with HIV (90.4%, 95% CI: 83.6%-95.9%) were aware of their status. Among those never previously diagnosed with HIV, few had accessed HIV testing in the past 12 months (14.3%, 95% CI: 11.1%-18.0%). Prison (57.0%) and compulsory drug detention centers (36.1%) were the primary locations where PWID reported ever being HIV tested, and the main correlate of recent testing in regression was recent criminal justice involvement. Although awareness of HIV status may be high among PWID living with HIV in Kuala Lumpur, testing occurs primarily in prisons and compulsory drug detention centers, where it is involuntary and linkage to care is limited. A shift in HIV testing policy is needed to align health and human rights objectives, replacing mandatory testing with voluntary testing in settings where individuals can be rapidly linked to HIV care.
    MeSH terms: Adult; Awareness; Female; Humans; Health Knowledge, Attitudes, Practice*; Malaysia/epidemiology; Male; Mass Screening; Middle Aged; Risk Factors; Serologic Tests; HIV Infections/diagnosis; HIV Infections/epidemiology*; HIV Infections/psychology; Substance Abuse, Intravenous/diagnosis; Substance Abuse, Intravenous/epidemiology*; Substance Abuse, Intravenous/psychology; Drug Users/psychology*
  14. Li G, Tang H, Chen Y, Yin Y, Ogawa S, Liu M, et al.
    Mol Cell Endocrinol, 2018 02 05;461:1-11.
    PMID: 28801227 DOI: 10.1016/j.mce.2017.08.003
    The LHb expression is up-regulated during puberty in female zebrafish. However, the molecular mechanism underlying how LHb expression is regulated during puberty remains largely unknown. In this study, we found that the mRNA expression levels of lhb, fshb and cyp19a1b were up-regulated along with the puberty onset in zebrafish. Among the three nuclear estrogen receptors (nERs), the esr2b is the only type whose expression is significantly up-regulated during puberty onset in the pituitary. However, in situ hybridization results revealed that lhb mRNA was colocalized with esr1 and esr2a but not esr2b. Exposure to estradiol (E2) significantly stimulates LHb expression in both wild-type and kiss1-/-;kiss2-/-;gnrh3-/- triple knockout pubertal zebrafish. Moreover, exposure of cultured pituitary cells to E2 increased the LHb expression, indicating that the estrogenic effect on LHb expression could be acted at the pituitary level. Finally, we cloned and analyzed the promoter of lhb by luciferase assay. Our results indicated that the E2 responsive regions of lhb promoter for ERα and ERβ2 are identical, suggesting that ERα and ERβ2 could bind to the same half ERE region of the promoter of lhb, exhibiting a classical ERE-dependent pathway. In summary, we demonstrate that E2 could directly act on the pituitary level to stimulate LHb transcription during puberty in zebrafish.
    MeSH terms: Animals; Base Sequence; Cell Nucleus/drug effects; Cell Nucleus/metabolism; Cells, Cultured; DNA Mutational Analysis; Estrogens/pharmacology*; Female; Gonads/cytology; Humans; Pituitary Gland/drug effects; Pituitary Gland/metabolism*; Promoter Regions, Genetic/genetics; Receptors, Estrogen/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Sapogenins; Sexual Maturation/drug effects*; Zebrafish/metabolism*; Sequence Deletion; Response Elements/genetics; Zebrafish Proteins/metabolism; Ginsenosides; Luteinizing Hormone, beta Subunit/genetics; Luteinizing Hormone, beta Subunit/metabolism*; HEK293 Cells
  15. Saoin S, Wisitponchai T, Intachai K, Chupradit K, Moonmuang S, Nangola S, et al.
    Asian Pac J Allergy Immunol, 2018 06;36(2):126-135.
    PMID: 28802032 DOI: 10.12932/AP-280217-0037
    BACKGROUND: AnkGAG1D4 is an artificial ankyrin repeat protein which recognizes the capsid protein (CA) of the human immunodeficiency virus type 1 (HIV-1) and exhibits the intracellular antiviral activity on the viral assembly process. Improving the binding affinity of AnkGAG1D4 would potentially enhance the AnkGAG1D4-mediated antiviral activity.

    OBJECTIVE: To augment the affinity of AnkGAG1D4 scaffold towards its CA target, through computational predictions and experimental designs.

    METHOD: Three dimensional structure of the binary complex formed by AnkGAG1D4 docked to the CA was used as a model for van der Waals (vdW) binding energy calculation. The results generated a simple guideline to select the amino acids for modifications. Following the predictions, modified AnkGAG1D4 proteins were produced and further evaluated for their CA-binding activity, using ELISA-modified method and bio-layer interferometry (BLI).

    RESULTS: Tyrosine at position 56 (Y56) in AnkGAG1D4 was experimentally identified as the most critical residue for CA binding. Rational substitutions of this residue diminished the binding affinity. However, vdW calculation preconized to substitute serine for tyrosine at position 45. Remarkably, the affinity for the viral CA was significantly enhanced in AnkGAG1D4-S45Y mutant, with no alteration of the target specificity.

    CONCLUSIONS: The S-to-Y mutation at position 45, based on the prediction of interacting amino acids and on vdW binding energy calculation, resulted in a significant enhancement of the affinity of AnkGAG1D4 ankyrin for its CA target. AnkGAG1D4-S45Y mutant represented the starting point for further construction of variants with even higher affinity towards the viral CA, and higher therapeutic potential in the future.

    MeSH terms: Amino Acid Sequence; Amino Acids; Antiviral Agents/metabolism; Antiviral Agents/pharmacology*; Antiviral Agents/chemistry*; Humans; Protein Binding; Recombinant Fusion Proteins/metabolism; Recombinant Fusion Proteins/pharmacology*; Recombinant Fusion Proteins/chemistry*; Structure-Activity Relationship; HIV-1/drug effects*; Ankyrins/metabolism; Ankyrins/pharmacology; Ankyrins/chemistry; Capsid Proteins/metabolism
  16. Lim SY, Tan AH
    Parkinsonism Relat Disord, 2018 Jan;46 Suppl 1:S47-S52.
    PMID: 28793970 DOI: 10.1016/j.parkreldis.2017.07.029
    BACKGROUND: Conventional outcome measures (COMs) in Parkinson's disease (PD) refer to rating scales, questionnaires, patient diaries and clinically-based tests that do not require specialized equipment.

    METHODS: It is timely at this juncture - as clinicians and researchers begin to grapple with the "invasion" of digital technologies - to review the strengths and weaknesses of these outcome measures.

    RESULTS: This paper discusses advances (including an enhanced understanding of PD itself, and the development of clinimetrics as a field) that have led to improvements in the COMs used in PD; their strengths and limitations; and factors to consider when selecting and using a measuring instrument.

    CONCLUSIONS: It is envisaged that in the future, a combination of COMs and technology-based objective measures will be utilized, with different methods having their own strengths and weaknesses. Judgement is required on the part of the clinician and researcher in terms of which instrument(s) are appropriate to use, depending on the particular clinical or research setting or question.

    MeSH terms: Humans; Parkinson Disease/diagnosis*; Psychometrics; Reproducibility of Results; Outcome Assessment (Health Care)*
  17. Chua PY, Day AC, Lai KL, Hall N, Tan LL, Khan K, et al.
    Br J Ophthalmol, 2018 Apr;102(4):539-543.
    PMID: 28794074 DOI: 10.1136/bjophthalmol-2017-310725
    PURPOSE: To estimate the incidence, and describe the clinical features and short-term clinical outcomes of acute angle closure (AAC).

    METHODS: Patients with newly diagnosed AAC were identified prospectively over a 12-month period (November 2011 to October 2012) by active surveillance through the Scottish Ophthalmic Surveillance Unit reporting system. Data were collected at case identification and at 6 months follow-up.

    RESULTS: There were 114 cases (108 patients) reported, giving an annual incidence of 2.2 cases (95% CI 1.8 to 2.6) or 2 patients (95% CI 1.7 to 2.4) per 1 00 000 in the whole population in Scotland. Precipitating factors were identified in 40% of cases. Almost one in five cases was associated with topical dilating drops. Best-corrected visual acuity (BCVA) at presentation ranged from 6/6 to perception of light. The mean presenting intraocular pressure (IOP) was 52 mm Hg (SD 11). Almost 30% cases had a delayed presentation of 3 or more days. At 6 months follow-up, 75% had BCVA of 6/12 or better and 30% were found to have glaucoma at follow-up. Delayed presentation (≥3 days) was associated with higher rate of glaucoma at follow-up (22.6% vs 60.8%, p<0.001), worse VA (0.34 vs 0.74 LogMAR, p<0.0001) and need for more topical medication (0.52 vs 1.2, p=0.003) to control IOP.

    CONCLUSION: The incidence of AAC in Scotland is relatively low compared with the Far East countries, but in line with previous European data. Almost one in five cases were associated with pupil dilation for retinal examination.

    MeSH terms: Far East; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Pupil; Scotland; Tonometry, Ocular; Visual Acuity; Precipitating Factors; Incidence; Tetrahymenina; Watchful Waiting
  18. Ahmed I, Shaukat MZ, Usman A, Nawaz MM, Nazir MS
    Int J Occup Saf Ergon, 2018 Jun;24(2):240-250.
    PMID: 28795938 DOI: 10.1080/10803548.2017.1366145
    This research covers the current status of occupational health and safety (OHS)-related practices in the informal construction segment of Pakistan. Data were collected, through interviews, from 316 construction sites employing 3577 workers. The results of the study reveal that both employers and workers lack knowledge of OHS laws/standards and no practices of this nature are enacted at these construction sites. Alarmingly, work-related accidents, whenever they happen, are not given due attention and there is no formal injury-report system. The informal construction industry employs a huge portion of the informal workforce, and lack of OHS happens at tremendous human cost. These research findings may thus play their role in strengthening the case for reforms in the sector. This study, if properly utilized, may also enable employers of the sector by increasing their knowledge about OHS practices and, as a result, trying to offer safer environments for their workers.
    MeSH terms: Accidents, Occupational/legislation & jurisprudence; Accidents, Occupational/prevention & control; Accidents, Occupational/statistics & numerical data*; Adult; Employment; Female; Humans; Male; Middle Aged; Pakistan; Surveys and Questionnaires; Occupational Health/legislation & jurisprudence; Occupational Health/standards; Occupational Health/statistics & numerical data*; Workplace; Construction Industry*; Informal Sector*
  19. Voon HY, Amin R, Kok JL, Tan KS
    Fetal Diagn Ther, 2018;43(1):77-80.
    PMID: 28796996 DOI: 10.1159/000479105
    We illustrate a case of giant placental chorioangioma presenting at 20 weeks of gestation. Subsequent monitoring revealed enlargement of the lesion, associated with fetal anemia and cardiac failure, prompting in utero intervention. Amnioreduction followed by percutaneous embolization of the tumour with enbucrilate:Lipiodol Ultra-Fluid™ at a dilution of 1:5 was successfully performed. No repeat intervention or additional supportive measures were required throughout pregnancy and the baby was delivered at 36 weeks of gestation, following spontaneous labour. Due to prolonged neonatal jaundice, further investigations were undertaken, demonstrating subacute right portal vein thrombosis. Other previously reported causes of neonatal portal vein thrombosis such as umbilical vein thrombosis, neonatal umbilical vein catheterization, thrombophilia and sepsis were excluded. There was resolution of the thrombus by 6 months of life. A brief discussion of measures to minimize the risk of such an event and the long-term outcomes of neonatal portal vein thrombosis was included. Whilst the simplicity and efficacy of the procedure has been demonstrated in a handful of patients, judgment on its safety is best deferred. Counselling should be comprehensive, as even rare complications can result in significant postnatal morbidity.
    MeSH terms: Choriocarcinoma/therapy*; Embolization, Therapeutic/adverse effects*; Enbucrilate/adverse effects*; Female; Fetus/blood supply*; Humans; Infant, Newborn; Pregnancy; Remission, Spontaneous; Time Factors; Uterine Neoplasms/therapy*; Ultrasonography, Prenatal/methods; Ultrasonography, Doppler, Color; Venous Thrombosis/etiology*; Young Adult
  20. Alslaibi TM, Abunada Z, Abu Amr SS, Abustan I
    Environ Technol, 2018 Nov;39(21):2691-2702.
    PMID: 28789588 DOI: 10.1080/09593330.2017.1365936
    Landfills are one of the main point sources of groundwater pollution. This research mainly aims to assess the risk of nitrate [Formula: see text] transport from the unlined landfill to subsurface layers and groundwater using experimental results and the SESOIL model. Samples from 12 groundwater wells downstream of the landfill were collected and analyzed in 2008, 21 years after the landfill construction. The average [Formula: see text] concentration in the wells was 54 mg/L, slightly higher than the World Health Organization ([Formula: see text] 50 mg/L) standards. SESOIL model was used to predict the [Formula: see text] concentration at the bottom of the unsaturated zone. Results indicated that the current mean [Formula: see text] concentration at the bottom of the unsaturated zone is 75 mg/L. the model predicted that the level of NO3 will increased up to 325 mg/L within 30 years. Accordingly, the [Formula: see text] concentration in groundwater wells near the landfill area is expected to gradually increase with time. Although the current risk associated with the [Formula: see text] level might not be harm to adults, however, it might pose severe risks to both adults and infants in the near future due to [Formula: see text] leaching. Urgent mitigation measures such as final cell cover (cap), lining system and vertical expansion should be considered at the landfill to protect the public health in the area.
    MeSH terms: Nitrates; Water Pollutants, Chemical*; Risk Assessment; Groundwater*; Waste Disposal Facilities
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