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  1. Fulltext Criteria and Indicators for Centers of Clinical Excellence in Stroke Recovery and Rehabilitation: A Global Consensus Facilitated by ISRRA
    Stockley RC, Walker MF, Alt Murphy M, Azah Abd Aziz N, Amooba P, Churliov L, et al.
    Neurorehabil Neural Repair, 2024 Feb;38(2):87-98.
    PMID: 38212946 DOI: 10.1177/15459683231222026
    BACKGROUND: The aim of the International Stroke Recovery and Rehabilitation Alliance is to create a world where worldwide collaboration brings major breakthroughs for the millions of people living with stroke. A key pillar of this work is to define globally relevant criteria for centers that aspire to deliver excellent clinical rehabilitation and generate exceptional outcomes for patients.

    OBJECTIVES: This paper presents consensus work conducted with an international group of expert stroke recovery and rehabilitation researchers, clinicians, and people living with stroke to identify and define criteria and measurable indicators for Centers of Clinical Excellence (CoCE) in stroke recovery and rehabilitation. These were intentionally developed to be ambitious and internationally relevant, regardless of a country's development or income status, to drive global improvement in stroke services.

    METHODS: Criteria and specific measurable indicators for CoCE were collaboratively developed by an international panel of stroke recovery and rehabilitation experts from 10 countries and consumer groups from 5 countries.

    RESULTS: The criteria and associated indicators, ranked in order of importance, focused upon (i) optimal outcome, (ii) research culture, (iii) working collaboratively with people living with stroke, (iv) knowledge exchange, (v) leadership, (vi) education, and (vii) advocacy. Work is currently underway to user-test the criteria and indicators in 14 rehabilitation centers in 10 different countries.

    CONCLUSIONS: We anticipate that use of the criteria and indicators could support individual organizations to further develop their services and, more widely, provide a mechanism by which clinical excellence can be articulated and shared to generate global improvements in stroke care.

  2. Antiviral activity of SP81 peptide against Enterovirus A71 (EV-A71)
    Abd-Aziz N, Lee MF, Ong SK, Poh CL
    Virology, 2024 Jan;589:109941.
    PMID: 37984152 DOI: 10.1016/j.virol.2023.109941
    The hand, food, and mouth disease (HFMD) is primarily caused by Enterovirus A71 (EV-A71). EV-A71 outbreaks in the Asia Pacific have been associated with severe neurological disease and high fatalities. Currently, there are no FDA-approved antivirals for the treatment of EV-A71 infections. In this study, the SP81 peptide, derived from the VP1 capsid protein of EV-A71 was shown to be a promising antiviral candidate for the treatment of EV-A71 infections. SP81 peptide was non-toxic to RD cells up to 45 μM, with a half-maximal cytotoxic concentration (CC50) of 90.32 μM. SP81 peptide exerted antiviral effects during the pre- and post-infection stages with 50% inhibitory concentrations (IC50) of 4.529 μM and 1.192 μM, respectively. Direct virus inactivation of EV-A71 by the SP81 peptide was also observed with an IC50 of 8.076 μM. Additionally, the SP81 peptide exhibited direct virus inactivation of EV-A71 at 95% upon the addition of the SP81 peptide within 5 min. This study showed that the SP81 peptide exhibited significant inhibition of EV-A71 and could serve as a promising antiviral agent for further clinical development against EV-A71 infections.
  3. Fulltext Passively Q-switching an all polarization-maintaining erbium-doped fiber laser with a rhenium disulfide (ReS2) saturable absorber
    Fadhel MM, Hamzah AE, Abd Aziz N, Dzulkefly Zan MS, Arsad N
    Heliyon, 2023 Oct;9(10):e20678.
    PMID: 37860525 DOI: 10.1016/j.heliyon.2023.e20678
    This study demonstrates a linearly polarized Er-doped fiber laser system featuring an all-polarization-maintaining (all-PM) architecture. Short pulses were generated by Q-switching operation based on drop-casting rhenium disulfide (ReS2) saturable absorber (SA) onto a fiber connector placed inside the laser cavity. The Q-switching operation of the laser was able to self-start at a low (23 mW) threshold power of the pump and without the need to use a polarization controller. The proposed laser was able to produce stable pulses with a center wavelength and 3-dB bandwidth of 1558.4 nm and 0.13 nm, respectively. The shortest pulse duration measured (2.8 μs) was achieved at a repetition rate of 37.6 kHz while the highest average output power and pulse energy were 2.2 mW and 76.5 nJ, respectively. Furthermore, as the cavity of the laser was designed to be all-PM the laser that it produced was linearly polarized and had a degree of polarization (DOP) at the level of 94.5 % and 40 dB polarization extinction ratio (PER). Therefore, the proposed laser is a suitable light source for optical applications in environments that are complex.
  4. Fulltext The Reduction Factor of Pultrude Glass Fibre-Reinforced Polyester Composite Cross-Arm: A Comparative Study on Mathematical Modelling for Life-Span Prediction
    Abu Bakar MS, Syamsir A, Alhayek A, Asyraf MRM, Itam Z, Shaik SMM, et al.
    Materials (Basel), 2023 Jul 29;16(15).
    PMID: 37570032 DOI: 10.3390/ma16155328
    This paper presents an experimental and numerical investigation of pultruded composite glass fibre-reinforced polymer (pGFRP) cross-arms subjected to flexural creep behaviour to assess their performance and sustainability in composite cross-arm structure applications. The primary objective of this study was to investigate the failure creep behaviour of pGFRP cross-arms with different stacking sequences. Specifically, the study aimed to understand the variations in strain rate exhibited during different stages of the creep process. Therefore, this study emphasizes a simplified approach within the experiment, numerical analysis, and mathematical modelling of three different pGFRP composites to estimate the stiffness reduction factors that determine the prediction of failure. The findings show that Findley's power law and the Burger model projected very different strains and diverged noticeably outside the testing period. Findley's model estimated a minimal increase in total strain over 50 years, while the Burger model anticipated PS-1 and PS-2 composites would fail within about 11 and 33 years, respectively. The Burger model's forecasts might be more reasonable due to the harsh environment the cross-arms are expected to withstand. The endurance and long-term performance of composite materials used in overhead power transmission lines may be predicted mathematically, and this insight into material property factors can help with design and maintenance.
  5. Comparing the performance of body mass index, waist circumference and waist-to-height ratio in predicting Malaysians with excess adiposity
    Low NY, Chan CY, Subramaniam S, Chin KY, Ima Nirwana S, Muhammad N, et al.
    Ann Hum Biol, 2022 Dec;49(7-8):299-304.
    PMID: 36373795 DOI: 10.1080/03014460.2022.2147585
    BACKGROUND: Body mass index (BMI) is a widely used surrogate tool to screen for obesity/adiposity, but it cannot differentiate between lean and fat mass. Thus, alternative tools to detect excess adiposity should be identified.

    AIM: This study aimed to compare the performance of BMI, waist circumference (WC) and waist-to-height ratio (WtHR) in predicting Malaysians with excess body fat defined by dual-energy X-ray absorptiometry (DXA).

    SUBJECTS AND METHODS: A total of 399 men and women aged ≥40 years were recruited from Klang Valley, Malaysia. The body composition of the subjects, including body fat percentage, was measured by DXA. The weight, height, WC and WHtR of the subjects were also determined.

    RESULTS: BMI [sensitivity = 55.7%, specificity = 86.1%, area under curve (AUC) = 0.709] and WC (sensitivity = 62.7%, specificity = 90.3%, AUC = 0.765) performed moderately in predicting excess adiposity. Their performance and sensitivity improved with lower cut-off values. The performance of WHtR (sensitivity = 96.6%, specificity = 36.1, AUC = 0.664) was optimal at the standard cut-off value and no modification was required.

    CONCLUSION: The performance of WC in identifying excess adiposity was greater than BMI and WHtR based on AUC values. Modification of cut-off values for BMI and WC could improve their performance and should be considered by healthcare providers in screening individuals with excess adiposity.

  6. Development of oncolytic viruses for cancer therapy
    Abd-Aziz N, Poh CL
    Transl Res, 2021 11;237:98-123.
    PMID: 33905949 DOI: 10.1016/j.trsl.2021.04.008
    Oncolytic virotherapy is a therapeutic approach that uses replication-competent viruses to kill cancers. The ability of oncolytic viruses to selectively replicate in cancer cells leads to direct cell lysis and induction of anticancer immune response. Like other anticancer therapies, oncolytic virotherapy has several limitations such as viral delivery to the target, penetration into the tumor mass, and antiviral immune responses. This review provides an insight into the different characteristics of oncolytic viruses (natural and genetically modified) that contribute to effective applications of oncolytic virotherapy in preclinical and clinical trials, and strategies to overcome the limitations. The potential of oncolytic virotherapy combining with other conventional treatments or cancer immunotherapies involving immune checkpoint inhibitors and CAR-T therapy could form part of future multimodality treatment strategies.
  7. Implementation of video modeling in the occupational therapy intervention process for children and adolescents with special needs: A scoping review
    Abd Aziz N, Kadar M, Harun D, Mohd Rasdi HF
    Occup Ther Health Care, 2021 Apr;35(2):227-244.
    PMID: 33511894 DOI: 10.1080/07380577.2021.1876967
    This scoping review explores the implementation of video modeling (VM) by occupational therapists during the intervention process for children and adolescents with special needs. Four primary electronic databases were used to conduct the scoping review: PubMed, Scopus, CINAHL, and Proquest (Nursing and Allied Health). Research methodologies by Arksey and O'Malley were used as a framework to perform the review process. From the review, two themes emerged: (1) implementing VM by occupational therapists during the intervention process can successfully improve a client's desired skills; (2) VM can be applied through several types of technologies. The findings support occupational therapists' use of VM during interventions to positively enhance and promote desired skills among children and adolescents with special needs. Also, it can be incorporated into technological devices to suit a client's specific needs.
  8. A single centre experience of metabolic syndrome and endometrial carcinoma: 5 years review
    Shafiee MN, Razak N, Ahmad MF, Abd Aziz N, Adeeb N
    J Obstet Gynaecol, 2021 Feb;41(2):285-289.
    PMID: 33258710 DOI: 10.1080/01443615.2020.1819210
    Endometrial cancer (EC) has been found to have a strong association with overweight and obesity. The aim of this study was to evaluate the link between metabolic syndrome and EC among patients. A total of 119 patients with histologically confirmed EC were recruited. About 102 cases of endometrioid carcinoma (Type I) and serous (n = 7), clear cell (n = 3) and carcinosarcoma (n = 7) were the Type II. Metabolic syndrome was significantly associated with increased risk of Type I EC (OR = 3.43, 95% CI = 1.12-10.46, p  .05). Metabolic syndrome was positively associated with an increased risk of Type I EC with obesity being the most influential risk factor.Impact statementWhat already known on this subject? Endometrial cancer (EC) is one of the most prevalent cancers worldwide and have a strong association with overweight and obesity of at least 40%, but there is conflicting evidence of an association of EC with metabolic syndrome (MS).What result of this study add? This study evaluated the link between EC and MS, such as high blood pressure, BMI, fasting blood sugar, triglyceride, Hyper Density Lipoprotein (HDL).What implications are of these findings for clinical practice & further research? Type I EC had and association with MS with obesity is the most potent risk factor. As the prevalence of metabolic syndrome is alarmingly high among adult Malaysians, the incidence of EC is projected to increase in the coming years. Proactive preventative measures and intervention essential for reducing the incidence of endometrial cancers. Future research to clarify the association between metabolic syndrome and endometrial cancer survival and to investigate other lifestyle factors that may affect the prognosis is needed.
  9. Recombinant Enterovirus 71 Viral Protein 1 Fused to a Truncated Newcastle Disease Virus NP (NPt) Carrier Protein
    Mustafa S, Abd-Aziz N, Saw WT, Liew SY, Yusoff K, Shafee N
    Vaccines (Basel), 2020 Dec 07;8(4).
    PMID: 33297428 DOI: 10.3390/vaccines8040742
    Enterovirus 71 (EV71) is the major causative agent in hand, foot, and mouth disease (HFMD), and it mainly infects children worldwide. Despite the risk, there is no effective vaccine available for this disease. Hence, a recombinant protein construct of truncated nucleocapsid protein viral protein 1 (NPt-VP1198-297), which is capable of inducing neutralizing antibody against EV71, was evaluated in a mouse model. Truncated nucleocapsid protein Newcastle disease virus that was used as immunological carrier fused to VP1 of EV71 as antigen. The recombinant plasmid carrying corresponding genes was constructed by recombinant DNA technology and the corresponding protein was produced in Escherichia coli expression system. The recombinant NPt-VP1198-297 protein had elicited neutralizing antibodies against EV71 with the titer of 1:16, and this result is higher than the titer that is elicited by VP1 protein alone (1:8). It was shown that NPt containing immunogenic epitope(s) of VP1 was capable of inducing a greater functional immune response when compared to full-length VP1 protein alone. It was capable to carry larger polypeptide compared to full-length NP protein. The current study also proved that NPt-VP1198-297 protein can be abundantly produced in recombinant protein form by E. coli expression system. The findings from this study support the importance of neutralizing antibodies in EV71 infection and highlight the potential of the recombinant NPt-VP1198-297 protein as EV71 vaccine.
  10. Stress and Deformation of Optimally Shaped Silicon Microneedles for Transdermal Drug Delivery
    Zainal Abidin HE, Ooi PC, Tiong TY, Marsi N, Ismardi A, Mohd Noor M, et al.
    J Pharm Sci, 2020 Aug;109(8):2485-2492.
    PMID: 32380181 DOI: 10.1016/j.xphs.2020.04.019
    In this study, we demonstrated the fabrication of the concave conic shape microneedle with the aid of COMSOL Multiphysics simulation. The stress and buckling of the microneedle structure were simulated by applying various loads ranging from 50 to 800 g perpendiculars to the tip in order to predict the occurrence of microneedles structure deformation. The simulation study indicated that the surface buckling deformation does not occur to the microneedle structure with the increment of the load. The microneedles with dimensions of height and diameter tip ranging from 60 to 100 μm and 1 to 4 μm, respectively had been fabricated via an etching process in a mixture of hydrofluoric acid, nitric acid, and acetic acid. Three optimized microneedles but different in the structures were fabricated via the acidic etching process. The reproducibility of 3 different microneedle structures was 15, 20, and 60%, respectively. Stress and buckling analyses of the fabricated microneedles were further carried out on the rat skin. The obtained experimental results show promising applications for the deep dermis, stratum corneum to epidermis layer penetration.
  11. Fulltext Development of Osteoporosis Screening Algorithm for Population Aged 50 Years and above in Klang Valley, Malaysia
    Subramaniam S, Chan CY, Soelaiman IN, Mohamed N, Muhammad N, Ahmad F, et al.
    Int J Environ Res Public Health, 2020 04 07;17(7).
    PMID: 32272697 DOI: 10.3390/ijerph17072526
    Background: The current osteoporosis screening instruments are not optimized to be used among the Malaysian population. This study aimed to develop an osteoporosis screening algorithm based on risk factors for Malaysians. Methods: Malaysians aged ≥50 years (n = 607) from Klang Valley, Malaysia were interviewed and their bone health status was assessed using a dual-energy X-ray absorptiometry device. The algorithm was constructed based on osteoporosis risk factors using multivariate logistic regression and its performance was assessed using receiver operating characteristics analysis. Results: Increased age, reduced body weight and being less physically active significantly predicted osteoporosis in men, while in women, increased age, lower body weight and low-income status significantly predicted osteoporosis. These factors were included in the final algorithm and the optimal cut-offs to identify subjects with osteoporosis was 0.00120 for men [sensitivity 73.3% (95% confidence interval (CI) = 54.1%-87.7%), specificity 67.8% (95% CI = 62.7%-85.5%), area under curve (AUC) 0.705 (95% CI = 0.608-0.803), p < 0.001] and 0.161 for women [sensitivity 75.4% (95% CI = 61.9%-73.3%), specificity 74.5% (95% CI = 68.5%-79.8%), AUC 0.749 (95% CI = 0.679-0.820), p < 0.001]. Conclusion: The new algorithm performed satisfactorily in identifying the risk of osteoporosis among the Malaysian population ≥50 years. Further validation studies are required before applying this algorithm for screening of osteoporosis in public.
  12. Appropriateness of empirical antibiotics: risk factors of adult patients with sepsis in the ICU
    Al-Sunaidar KA, Prof Abd Aziz N, Prof Hassan Y
    Int J Clin Pharm, 2020 Apr;42(2):527-538.
    PMID: 32144611 DOI: 10.1007/s11096-020-01005-4
    Background The appropriateness of antibiotics is the basis for improving the survival of patients with sepsis. Objective This study aimed to determine the appropriateness of empirical antibiotics, reasons for non-appropriate empirical antibiotics, risk factors of mortality, length of stay in intensive care unit (ICU-LOS) and Acute Physiology And Chronic Health Evaluation II (APACHE II) score predictors in adult patients with sepsis. Setting An adult ICU of a tertiary hospital in  Malaysia. Methods A retrospective cohort study was conducted amongst patients with sepsis. Data were retrieved from the patients' files and computer system. Each case was reviewed for the appropriateness of empirical antibiotics based on ICU local guidelines, bacterial sensitivity, dose, frequency, creatinine clearance and time of administration of empirical antibiotics. Multivariable logistic and Cox regression modelling were performed to compute the adjusted association of receiving appropriate or inappropriate empirical antibiotics with ICU mortality. Multivariable linear regression modelling was performed using ICU-LOS and APACHE II scores. Main outcome measures were ICU mortality, severity score (APACHE II scores) and ICU-LOS. Results The total mortality rate amongst the 228 adult ICU patients was 84.6%. Males showed a higher mortality rate (119 [52.2%]) than females (74 [32.5%]). Inappropriate empirical antibiotics were significantly associated with mortality and ICU-LOS (P 
  13. A New Plant Expression System for Producing Pharmaceutical Proteins
    Abd-Aziz N, Tan BC, Rejab NA, Othman RY, Khalid N
    Mol Biotechnol, 2020 Apr;62(4):240-251.
    PMID: 32108286 DOI: 10.1007/s12033-020-00242-2
    In the past decade, interest in the production of recombinant pharmaceutical proteins in plants has tremendously progressed because plants do not harbor mammalian viruses, are economically competitive, easily scalable, and capable of carrying out complex post-translational modifications required for recombinant pharmaceutical proteins. Mucuna bracteata is an essential perennial cover crop species widely planted as an underground cover in oil palm and rubber plantations. As a legume, they have high biomass, thrive in its habitat, and can fix nitrogen. Thus, M. bracteata is a cost-efficient crop that shows ideal characteristics as a platform for mass production of recombinant protein. In this study, we established a new platform for the transient production of a recombinant protein in M. bracteata via vacuum-assisted agro-infiltration. Five-week-old M. bracteata plants were vacuum infiltrated with Agrobacterium tumefaciens harboring a plasmid that encodes for an anti-toxoplasma immunoglobulin (IgG) under different parameters, including trifoliate leaf positional effects, days to harvest post-infiltration, and the Agrobacterium strain used. Our results showed that vacuum infiltration of M. bracteata plant with A. tumefaciens strain GV3101 produced the highest concentration of heterologous protein in its bottom trifoliate leaf at 2 days post-infiltration. The purified anti-toxoplasma IgG was then analyzed using Western blot and ELISA. It was demonstrated that, while structural heterogeneity existed in the purified anti-toxoplasma IgG from M. bracteata, its transient expression level was two-fold higher than the model platform, Nicotiana benthamiana. This study has laid the foundation towards establishing M. bracteata as a potential platform for the production of recombinant pharmaceutical protein.
  14. Fulltext Role of microRNAs in antiviral responses to dengue infection
    Wong RR, Abd-Aziz N, Affendi S, Poh CL
    J Biomed Sci, 2020 Jan 03;27(1):4.
    PMID: 31898495 DOI: 10.1186/s12929-019-0614-x
    Dengue virus (DENV) is the etiological agent of dengue fever. Severe dengue could be fatal and there is currently no effective antiviral agent or vaccine. The only licensed vaccine, Dengvaxia, has low efficacy against serotypes 1 and 2. Cellular miRNAs are post-transcriptional regulators that could play a role in direct regulation of viral genes. Host miRNA expressions could either promote or repress viral replications. Induction of some cellular miRNAs could help the virus to evade the host immune response by suppressing the IFN-α/β signaling pathway while others could upregulate IFN-α/β production and inhibit the viral infection. Understanding miRNA expressions and functions during dengue infections would provide insights into the development of miRNA-based therapeutics which could be strategized to act either as miRNA antagonists or miRNA mimics. The known mechanisms of how miRNAs impact DENV replication are diverse. They could suppress DENV multiplication by directly binding to the viral genome, resulting in translational repression. Other miRNA actions include modulation of host factors. In addition, miRNAs that could modulate immunopathogenesis are discussed. Major hurdles lie in the development of chemical modifications and delivery systems for in vivo delivery. Nevertheless, advancement in miRNA formulations and delivery systems hold great promise for the therapeutic potential of miRNA-based therapy, as supported by Miravirsen for treatment of Hepatitis C infection which has successfully completed phase II clinical trial.
  15. Development of MicroRNAs as Potential Therapeutics against Cancer
    Abd-Aziz N, Kamaruzman NI, Poh CL
    J Oncol, 2020;2020:8029721.
    PMID: 32733559 DOI: 10.1155/2020/8029721
    MicroRNAs (miRNAs) are small noncoding RNAs that function at the posttranscriptional level in the cellular regulation process. miRNA expression exerts vital effects on cell growth such as cell proliferation and survival. In cancers, miRNAs have been shown to initiate carcinogenesis, where overexpression of oncogenic miRNAs (oncomiRs) or reduced expression of tumor suppressor miRNAs has been reported. In this review, we discuss the involvement of miRNAs in tumorigenesis, the role of synthetic miRNAs as either mimics or antagomirs to overcome cancer growth, miRNA delivery, and approaches to enhance their therapeutic potentials.
  16. Fulltext Levels of Knowledge, Beliefs, and Practices Regarding Osteoporosis and the Associations with Bone Mineral Density among Populations More Than 40 Years Old in Malaysia
    Chan CY, Subramaniam S, Chin KY, Ima-Nirwana S, Muhammad N, Fairus A, et al.
    Int J Environ Res Public Health, 2019 Oct 25;16(21).
    PMID: 31731507 DOI: 10.3390/ijerph16214115
    Osteoporosis is a skeletal disorder commonly found among the elderly, in which the bones become weak, brittle, and more susceptible to fracture. Adequate knowledge and positive attitude towards the disease and osteoprotective activities may prevent osteoporosis, but comprehensive studies to verify this hypothesis are limited in Malaysia. This study aims to bridge the research gap by determining the levels of knowledge, beliefs, and practices regarding osteoporosis and their associations with bone mineral density (BMD) among men and women ≥ 40 years in Klang Valley, Malaysia. In this cross-sectional study, 786 Malaysians (382 men, 404 women) completed a questionnaire on knowledge, beliefs, and osteoprotective practices, and underwent BMD scan using a dual-energy X-ray absorptiometry device. The current study found moderate levels of knowledge and beliefs regarding osteoporosis but poor osteoprotective practices. Osteoporosis knowledge, beliefs, and practices were significantly different based on subjects' demographic characteristics (p < 0.05). Osteoporosis knowledge and beliefs were correlated significantly with osteoprotective practices (p < 0.05). Bone health status of the subjects was associated positively with calcium supplement intake, and negatively with exercise barriers and smoking status of the subjects (p < 0.05). However, no significant correlation was noted between osteoporosis knowledge and bone health (p > 0.05). Conclusively, despite some correlations between individual components, the detachment between bone health knowledge and beliefs, and osteoprotective practices among Malaysians is apparent. Integrating all three components into a comprehensive osteoporosis prevention program is warranted.
  17. A rapid MCM-41 dispersive micro-solid phase extraction coupled with LC/MS/MS for quantification of ketoconazole and voriconazole in biological fluids
    Yahaya N, Sanagi MM, Abd Aziz N, Wan Ibrahim WA, Nur H, Loh SH, et al.
    Biomed Chromatogr, 2017 Feb;31(2).
    PMID: 27474795 DOI: 10.1002/bmc.3803
    A rapid dispersive micro-solid phase extraction (D-μ-SPE) combined with LC/MS/MS method was developed and validated for the determination of ketoconazole and voriconazole in human urine and plasma samples. Synthesized mesoporous silica MCM-41 was used as sorbent in d-μ-SPE of the azole compounds from biological fluids. Important D-μ-SPE parameters, namely type desorption solvent, extraction time, sample pH, salt addition, desorption time, amount of sorbent and sample volume were optimized. Liquid chromatographic separations were carried out on a Zorbax SB-C18 column (2.1 × 100 mm, 3.5 μm), using a mobile phase of acetonitrile-0.05% formic acid in 5 mm ammonium acetate buffer (70:30, v/v). A triple quadrupole mass spectrometer with positive ionization mode was used for the determination of target analytes. Under the optimized conditions, the calibration curves showed good linearity in the range of 0.1-10,000 μg/L with satisfactory limit of detection (≤0.06 μg/L) and limit of quantitation (≤0.3 μg/L). The proposed method also showed acceptable intra- and inter-day precisions for ketoconazole and voriconazole from urine and human plasma with RSD ≤16.5% and good relative recoveries in the range 84.3-114.8%. The MCM-41-D-μ-SPE method proved to be rapid and simple and requires a small volume of organic solvent (200 μL); thus it is advantageous for routine drug analysis.
  18. Fulltext Drug Utilization on Neonatal Wards: A Systematic Review of Observational Studies
    Rosli R, Dali AF, Abd Aziz N, Abdullah AH, Ming LC, Manan MM
    Front Pharmacol, 2017;8:27.
    PMID: 28228724 DOI: 10.3389/fphar.2017.00027
    Despite limited evidence on safety and efficacy of drug use in neonates, drugs are extensively used in this age group. However, the availability of information on drug consumption in neonates, especially inpatient neonates, is limited. This paper systematically reviews published studies on drug utilization in hospitalized neonates. A systematic literature review was carried out to identify observational studies published from inception of databases used till August 2016. Four search engines, namely Medline, CINAHL, Embase, and PubMed, were used. Publications written in English that described drug utilization in neonatal wards were selected. Assessment of the data was based on the category of the study design, the objective of study and the method used in reporting drug consumption. A total of 20 drug utilization studies were identified, 12 of which focused on all drug classes, while the other eight evaluated antimicrobials. Studies were reported in Europe (n = 7), the United States (n = 6), India (n = 5), Brazil (n = 1), and Iran (n = 1). Substantial variance with regard to study types (study design and methods), data source, and sample size were found among the selected studies. Of the studies included, 45% were cross-sectional or retrospective, 40% were prospective studies, and the remaining 15% were point prevalence surveys. More than 70% of the studies were descriptive studies, describing drug consumption patterns. Fifteen per cent of the descriptive studies evaluated changes in drug utilization patterns in neonates. Volume of units was the most prevalent method used for reporting all drug categories. The ATC/DDD system for reporting drug use was only seen in studies evaluating antimicrobials. The most commonly reported drugs across all studies are anti-infectives for systemic use, followed by drugs for the cardiovascular system, the nervous system and the respiratory system. Ampicillin and gentamicin were the most prescribed antimicrobials in hospitalized neonates. The present review reveals that neonates are exposed to a high number of drugs and various methods are used to report drug consumption in this age group. The best measure of drug consumption to quantify prevalence of drug use in neonates remains to be identified and additional research in this area is warranted.
  19. Fulltext Newcastle disease virus degrades HIF-1α through proteasomal pathways independent of VHL and p53
    Abd-Aziz N, Stanbridge EJ, Shafee N
    J Gen Virol, 2016 Dec;97(12):3174-3182.
    PMID: 27902314 DOI: 10.1099/jgv.0.000623
    Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated α (HIF-1α) and a constitutive β subunit (HIF-1β). To investigate the effects of NDV infection on HIF-1α in cancer cells, the osteosarcoma (Saos-2), breast carcinoma (MCF-7), colon carcinoma (HCT116) and fibrosarcoma (HT1080) cell lines were used in the present study. Data obtained showed that a velogenic NDV infection diminished hypoxia-induced HIF-1α accumulation, leading to a decreased activation of its downstream target gene, carbonic anhydrase 9. This NDV-induced downregulation of HIF-1α occurred post-translationally and was partially abrogated by proteasomal inhibition. The process appeared to be independent of the tumour suppressor protein p53. These data revealed a correlation between NDV infection and HIF-1α downregulation, which highlights NDV as a promising agent to eliminate hypoxic cancer cells.
  20. Impacts of Thermal Treatments on Major and Minor Allergens of Sea Snail, Cerithidea obtusa (Obtuse Horn Shell)
    Misnan R, Salahudin Abd Aziz N, Mohamad Yadzir ZH, Bakhtiar F, Abdullah N, Murad S
    Iran J Allergy Asthma Immunol, 2016 Aug;15(4):309-316.
    PMID: 27921412
    Snail is one of the worst causes of food allergy. Thus, the aim of this study was to identify the major and minor allergens of the local marine snail (Cerithidea obtusa) and subsequently to investigate the impacts of heat treatment on the IgE-binding activity of snail allergens. Proteins from raw and heat-treated snails (boiled, roasted and fried) were extracted and then resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunoblotting of all extracts were then performed using sera from patients with snail allergy. The results showed that the raw extract contains numerous protein bands between 12 to>250 kDa. Some thermostable proteins, predominantly the 33 and 42 kDa bands, remained detected in all cooked extracts with decreasing intensities from boiled to roasted to fried extracts, while the majority of thermolabile bands denatured after heating. Boiled snail had more protein bands compared to roasted and fried snails. Immunoblotting of raw extract demostrated 19 IgE-binding bands ranging from 15 to 240 kDa. The thermostable bands of 33 and 42 kDa and a thermolabile of 30 kDa band were identified as the major allergens of this snail. The cooked extracts yielded less allergenic bands. The boiled extract yielded approximately 14 IgE-binding bands with some smeared bands at high molecular weight regions. The roasted extract had lesser IgE-binding bands and the majority appeared as smears, while the IgE-reactivity in the fried extract was less visible and appeared as weak smears. This study indicated that both raw and cooked snails played a crucial role in snail allergenicity, as this species of snail contains both thermostable and thermolabile major allergens. The degree of snail allergenicity was revealed in the order: raw> boiled > roasted> fried. Thus, the results would facilitate in the development of effective diagnosis and management strategies of snail allergy in this country.
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