Browse publications by year: 2019

  1. James JG, Izam AS, Nabil S, Rahman NA, Ramli R
    J Craniofac Surg, 2019 8 27;31(1):e22-e26.
    PMID: 31449209 DOI: 10.1097/SCS.0000000000005812
    AIM: The objective of this review was to determine the different types of surgical intervention in the management of nasal bone fractures, the outcomes, and complications associated with each intervention.

    METHODS: A search was conducted using the PubMed and Cochrane Database of Systematic Review databases from January 1, 1997 until September 9, 2017. The search strategy was constructed using the Population Intervention Comparison Outcome framework with keywords related to nasal fracture and its treatment. Two sets of independent researchers performed the analysis. Qualitative analysis was performed using the Methodological Index for Non-Randomized Studies and National Institute for Clinical Excellence methodology for randomized controlled trial checklists.

    RESULTS: The 4276 titles were obtained from PubMed database alone. Exclusion was made based on the title, abstract and full-text analysis. Finally, 23 papers were included and analyzed. Of the 23 papers, 13 (56.5%) were retrospective record review, 2 (8.7%) were randomized clinical trial or a randomized study and 8 case series (34.8%). 16 (69.6%) studies addressed closed reduction, 3 studies (13%) on open reduction and 4 studies (17.4%) addressed both open and closed reduction. The main focus in the outcome in all studies was accuracy of the anatomical reduction of the nasal bones. Three studies (13.0%) reported restoration of function such as breathing comfort or release in respiratory obstruction and another 3 (13.0%) addressed both cosmetic and breathing outcomes. Residual deformity was the most described complications in the studies (30.4%). In general, most of the studies were not of high quality as they lacked in some key elements in the Methodological Index for Non-Randomized Studies checklist.

    CONCLUSION: Both closed and open reduction provided good outcomes in cosmetic and breathing. Septoplasty is recommended to be performed simultaneously with fracture reduction.

    MeSH terms: Fracture Fixation*; Humans; Nasal Bone/surgery*; Respiration; Rhinoplasty; Skull Fractures/surgery*; Open Fracture Reduction
  2. Lee TJ, Roslan A, Teh KC, Ghazi A
    Eur Heart J Case Rep, 2019 Jun 01;3(2).
    PMID: 31449618 DOI: 10.1093/ehjcr/ytz056
    BACKGROUND: Intramyocardial dissecting haematoma is a rare complication of myocardial infarction (MI) associated with high mortality rates. Studies and research of this occurrence are limited largely to isolated case reports or case series.

    CASE SUMMARY: We report a case of late presenting MI, where on initial echocardiogram had what was thought to be an intraventricular clot. However, upon further evaluation, the patient actually had an intramyocardial haematoma, with the supporting echocardiographic features to distinguish it from typical left ventricular (LV) clot. While this prevented the patient from receiving otherwise unnecessary anticoagulation, this diagnosis also put him at a much higher risk of mortality. Despite exhaustive medical and supportive management, death as consequence of pump failure occurred after 2 weeks.

    DISCUSSION: This report highlights the features seen on echocardiography which support the diagnosis of an intramyocardial haematoma rather than an LV clot, notably the various acoustic densities, a well visualized myocardial dissecting tear leading into a neocavity filled with blood, and an independent endocardial layer seen above the haematoma. Based on this report, we wish to highlight the importance of differentiating intramyocardial haematomas from intraventricular clots in patients with recent MI.

    MeSH terms: Echocardiography; Endocardium; Hematoma; Humans; Male; Myocardial Infarction; Myocardium
  3. Daud KM, Mohamad MS, Zakaria Z, Hassan R, Shah ZA, Deris S, et al.
    Comput Biol Med, 2019 10;113:103390.
    PMID: 31450056 DOI: 10.1016/j.compbiomed.2019.103390
    Metabolic engineering is defined as improving the cellular activities of an organism by manipulating the metabolic, signal or regulatory network. In silico reaction knockout simulation is one of the techniques applied to analyse the effects of genetic perturbations on metabolite production. Many methods consider growth coupling as the objective function, whereby it searches for mutants that maximise the growth and production rate. However, the final goal is to increase the production rate. Furthermore, they produce one single solution, though in reality, cells do not focus on one objective and they need to consider various different competing objectives. In this work, a method, termed ndsDSAFBA (non-dominated sorting Differential Search Algorithm and Flux Balance Analysis), has been developed to find the reaction knockouts involved in maximising the production rate and growth rate of the mutant, by incorporating Pareto dominance concepts. The proposed ndsDSAFBA method was validated using three genome-scale metabolic models. We obtained a set of non-dominated solutions, with each solution representing a different mutant strain. The results obtained were compared with the single objective optimisation (SOO) and multi-objective optimisation (MOO) methods. The results demonstrate that ndsDSAFBA is better than the other methods in terms of production rate and growth rate.
    MeSH terms: Algorithms*; Computer Simulation*; Models, Biological*; Metabolic Engineering*
  4. Chin DWK, Lim S, Pang YL, Lim CH, Lee KM
    Bioresour Technol, 2019 Nov;292:121967.
    PMID: 31450064 DOI: 10.1016/j.biortech.2019.121967
    Ethylene glycol in the presence of sodium hydroxide was utilised as pretreatment for effective delignification and reduced the recalcitrance of lignocellulosic biomass which ramified the exposure of cellulose. Two-staged acid hydrolysis was also investigated which demonstrated its synergistic efficiency by minimising the deficiency of single stage acid hydrolysis. The operating parameters including acid concentration, temperature, residence time and cellulose loading for two-staged acid hydrolysis were studied by using ethylene glycol delignified degraded oil palm empty fruit bunch (DEFB) to recover the sugar based substrates for potential biofuels and other bio-chemicals production. In this study, stage I 45 wt% acid at 65 °C for 30 min coupled with high cellulose loading 21.25 w/v% and 12 wt% acid at 100 °C for 120 min was able to release a total of 89.8% optimum sugar yield with minimal formation of degradation products including 0.058 g/L furfural, 0.0251 g/L hydroxymethylfurfural and 0.200 g/L phenolic compounds.
    MeSH terms: Carbohydrates; Cellulose; Fruit; Furaldehyde; Hydrolysis; Lignin; Sodium Hydroxide; Temperature; Biomass; Ethylene Glycol; Biofuels
  5. Pang WY, Ahmad AL, Zaulkiflee ND
    J Environ Manage, 2019 Nov 01;249:109358.
    PMID: 31450197 DOI: 10.1016/j.jenvman.2019.109358
    The aim of this study is to evaluate the performance and antifouling properties of polyethersulfone (PES) membrane incorporated with dual nanofiller, zinc oxide (ZnO) and multi-walled carbon nanotube (MWCNT). The synergistic effect of the these nanofillers in PES membrane is studied by blending different ratio of ZnO/MWCNT nanofiller into the PES membrane. The fabricated membranes were characterized in terms of cross-section and surface morphology, surface hydrophilicity, pore size and porosity. The filtration performance of the membranes was tested using 50 mg/L humic acid (HA) solution as model solution. SEM image and gravimetric evaluation reported that the incorporation of both MWCNT and ZnO into the PES membrane improved porosity significantly up to 46.02%. Lower water contact angle of PES membrane incorporated with equal ratio of MWCNT and ZnO (PES 3) revealed that it has neat PES membrane properties and more hydrophilic membrane surface than single filler. PES 3 outperform other membranes with excellent HA permeate flux of 40.00 L/m2.h and rejection of 88.51%. Due to hydrophilic membrane surface, PES 3 membrane demonstrate efficient antifouling properties with lower relative flux reduction (RFR) and higher flux recovery ratio (FRR). PES 3 also showed notable antibacterial properties with less bacterial attached to the membrane compared to neat PES membrane (PES 0).
    MeSH terms: Anti-Bacterial Agents; Membranes, Artificial; Polymers; Sulfones; Zinc Oxide*
  6. Nealon J, Lim WY, Moureau A, Linus Lojikip S, Junus S, Kumar S, et al.
    Vaccine, 2019 09 16;37(39):5891-5898.
    PMID: 31445770 DOI: 10.1016/j.vaccine.2019.07.083
    BACKGROUND: The world's first dengue vaccine [Dengvaxia; Sanofi Pasteur] was licensed in 2015 and others are in development. Real-world evaluations of dengue vaccines will therefore soon be needed. We assessed feasibility of case control (CC) and test-negative (TN) design studies for dengue vaccine effectiveness by measuring associations between socio-demographic risk factors, and hospitalized dengue outcomes, in Malaysia.

    METHODS: Following ethical approval, we conducted hospital-based dengue surveillance for one year in three referral hospitals. Suspected cases aged 9-25 years underwent dengue virological confirmation by RT-PCR and/or NS1 Ag ELISA at a central laboratory. Two age- and geography-matched hospitalized non-dengue case-controls were recruited for a traditional CC study. Suspected cases testing negative were test-negative controls. Socio-demographic, risk factor and routine laboratory data were collected. Logistic regression models were used to estimate associations between confirmed dengue and risk factors.

    RESULTS: We recruited 327 subjects; 155 were suspected of dengue. The planned sample size was not met. 124 (80%) of suspected cases were dengue-confirmed; seven were assessed as severe. Three had missing RT-PCR results; the study recruited 28 test-negative controls. Only 172 matched controls could be recruited; 90 cases were matched with ≥1 controls. Characteristics of cases and controls were mostly similar. By CC design, two variables were significant risk factors for hospitalized dengue: recent household dengue contact (OR: 54, 95% CI: 7.3-397) and recent neighbourhood insecticidal fogging (OR: 2.1; 95% CI: 1.3-3.6). In the TN design, no risk factors were identified. In comparison with gold-standard diagnostics, routine tests performed poorly.

    CONCLUSIONS: The CC design may be more appropriate than the TN design for hospitalized dengue vaccine effectiveness studies. Selection bias in case control selection could be minimized by protocol changes more easily than increasing TN design control numbers, because early-stage dengue diagnosis in endemic countries is highly specific. MREC study approval: (39)KKM/NIHSEC/P16-1334.

    MeSH terms: Adolescent; Adult; Dengue/immunology*; Dengue/prevention & control*; Dengue Virus/immunology*; Feasibility Studies; Female; Humans; Malaysia; Male; Case-Control Studies; Dengue Vaccines/immunology*; Young Adult
  7. Tang ELH, Tan NH, Fung SY, Tan CH
    Toxicon, 2019 Aug 22;169:91-102.
    PMID: 31445943 DOI: 10.1016/j.toxicon.2019.08.004
    The intraspecific geographical venom variations of Calloselasma rhodostoma from Malaysia (CR-M), Indonesia (CR-I), Thailand (CR-T) and Vietnam (CR-V) were investigated through 1D SDS-PAGE and nano-ESI-LCMS/MS. The venom antigenicity, procoagulant activities and neutralization using Thai C. rhodostoma Monovalent Antivenom (CRMAV) were also investigated. SDS-PAGE patterns of the venoms were relatively similar with minor variations. Proteomic analysis revealed that snake venom metalloproteinases (SVMPs, particularly P-I class), serine proteases (SVSPs) and snaclecs dominated the venom protein composition (68.96-81.80%), followed by L-amino acid oxidase (LAAO) and phospholipase A2 (PLA2) (7.37-11.08% and 5.18-13.81%, respectively), corroborating C. rhodostoma envenoming effects (hemorrhage, consumptive coagulopathy, thrombocytopenia and local tissue necrosis). Other proteins of lower abundances (2.82-9.13%) identified include cysteine-rich secretory proteins (CRISP), phospholipase B, phosphodiesterase, nerve growth factor, 5'-nucleotidase, aminopeptidase and hyaluronidase. All four venoms exhibited strong procoagulant effects which were neutralized by CRMAV to different extents. CRMAV immunoreactivity was high toward venoms of CR-M, CR-I and CR-T but relatively low for CR-V venom. Among the venom samples from different locales, CR-V venom proteome has the smallest SVMP composition while SVSP, PLA2 and phosphodiesterase were more abundant in the venom. These variations in C. rhodostoma venom protein composition could partly explain the differences seen in immunoreactivity. (198 words).
    MeSH terms: Aminopeptidases; Antivenins; Cysteine; Electrophoresis, Polyacrylamide Gel; Hyaluronoglucosaminidase; Indonesia; Lysophospholipase; Malaysia; Phosphoric Diester Hydrolases; Snake Venoms; Thailand; Thrombocytopenia; Vietnam; 5'-Nucleotidase; Proteome; Nerve Growth Factor; Proteomics; Metalloproteases; L-Amino Acid Oxidase; Phospholipases A2; Serine Proteases; GPI-Linked Proteins
  8. Rajadurai P, Cheah PL, How SH, Liam CK, Annuar MAA, Omar N, et al.
    Lung Cancer, 2019 10;136:65-73.
    PMID: 31446227 DOI: 10.1016/j.lungcan.2019.08.005
    In the recent years, increased understanding of the molecular profiles of non-small cell lung cancer (NSCLC) has allowed for targeted treatment of actionable genetic mutations. The management of NSCLC now requires multiple molecular tests to guide the treatment strategy. In the light of this, there is a need to establish a molecular testing consensus statement for advanced NSCLC patients in Malaysia. This Malaysian consensus statement was developed by a panel of experts, chaired by a pathologist and composed of three other pathologists, four respiratory physicians and three oncologists. It reflects currently available scientific data and adaptations of recommendations from international guidelines to the local landscape. Expert recommendations on different aspects of molecular testing agreed upon by the panel are provided as structured discussions. These recommendations address the appropriate patients and samples to be tested, as well as when and how these tests should be performed. The algorithms for molecular testing in metastatic NSCLC, in the first line setting and upon disease progression beyond first line therapy, were developed.
    MeSH terms: Biopsy; Carcinoma, Non-Small-Cell Lung/diagnosis*; Carcinoma, Non-Small-Cell Lung/etiology*; Female; Humans; Lung Neoplasms/diagnosis*; Lung Neoplasms/etiology*; Malaysia; Male; Neoplasm Staging; Biomarkers, Tumor; Genetic Predisposition to Disease; Molecular Diagnostic Techniques*; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing
  9. Hassan M, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Shahzadi S, Raza H, et al.
    Bioorg Chem, 2019 10;91:103138.
    PMID: 31446329 DOI: 10.1016/j.bioorg.2019.103138
    In the designed research work, a series of 2-furoyl piperazine based sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer's disease. The structures of the newly synthesized compounds were characterized through spectral analysis and their inhibitory potential was evaluated against butyrylcholinesterase (BChE). The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. Furthermore, compounds were inspected by Lipinki Rule and their binding profiles against BChE were discerned by molecular docking. The protein fluctuations in docking complexes were recognized by dynamic simulation. From our in vitro and in silico results 5c, 5j and 5k were identified as promising lead compounds for the treatment of targeted disease.
    MeSH terms: Alzheimer Disease/drug therapy; Animals; Binding Sites; Butyrylcholinesterase/metabolism; Butyrylcholinesterase/chemistry; Cattle; Cholinesterase Inhibitors/chemical synthesis; Cholinesterase Inhibitors/metabolism; Cholinesterase Inhibitors/pharmacokinetics; Cholinesterase Inhibitors/chemistry*; Hemolysis/drug effects; Humans; Piperazines/chemical synthesis; Piperazines/metabolism; Piperazines/pharmacokinetics; Piperazines/chemistry*; Protein Binding; Structure-Activity Relationship; Sulfonamides/chemical synthesis; Sulfonamides/metabolism; Sulfonamides/pharmacokinetics; Sulfonamides/chemistry*; Drug Design; Molecular Structure; Nootropic Agents/chemical synthesis; Nootropic Agents/metabolism; Nootropic Agents/pharmacokinetics; Nootropic Agents/chemistry*; Molecular Dynamics Simulation; Enzyme Assays; Molecular Docking Simulation
  10. Song Y, Bai W, Wang M, Liu X, Zhang L, Yu W, et al.
    J Affect Disord, 2019 12 01;259:195-200.
    PMID: 31446380 DOI: 10.1016/j.jad.2019.08.042
    BACKGROUND: Suicide is a major global mental health problem among college students. The aim of the current study was to explore the association between the psychological strains of the strain theory of suicide and suicidal behaviors among college students.

    METHODS: Participants comprised 1912 college students (16-28 years old, 47.2% female) from three universities in Jilin Province, China, who completed the self-report assessments of psychological strains (40 items Psychological Strains Scale) and suicidal behaviors (Suicidal Behaviors Questionnaire-Revised). The demographic characteristics included four variables: health status, psychological status, academic status and economic status.

    RESULTS: Approximately 15.0% (286/1912) of participants were classified as having suicide risk, based on the cut-off scores of the SBQ-R. The prevalence of suicidal behaviors among males and females was 11.9% (120/1009) and 18.4% (166/903), respectively. Value strain (OR = 1.075, 95%CI: 1.057-1.094), aspiration strain (OR = 1.082, 95%CI: 1.064-1.101), deprivation strain (OR = 1.073, 95%CI: 1.052-1.093), and coping strain (OR = 1.095, 95%CI: 1.075-1.116) were risk factors for suicidality in college students. Coping strain (OR = 1.050, 95%CI: 1.023-1.077) was still positively associated with suicide risk in multivariate logistic regression. Logistic regression analysis indicated that coping strain had the highest correlation with suicidal behaviors.

    LIMITATIONS: The directionality of the relationships cannot be deduced because this study is cross-sectional.

    CONCLUSION: This study confirms a strong association between psychological strains and suicidal behaviors in college students. Some measures can be taken to reduce psychological strains to mitigate suicide risk among college students. More studies investigating coping strain among college students are warranted.

    MeSH terms: Adaptation, Psychological*; Adolescent; Adult; China/epidemiology; Cross-Sectional Studies; Female; Health Surveys; Humans; Male; Surveys and Questionnaires; Risk Factors; Self-Assessment; Students/psychology*; Students/statistics & numerical data; Suicide/psychology*; Suicide/statistics & numerical data; Universities/statistics & numerical data; Prevalence; Logistic Models; Young Adult; Self Report; Suicidal Ideation*
  11. Stephens TJ, Bamber JR, Beckingham IJ, Duncan E, Quiney NF, Abercrombie JF, et al.
    Implement Sci, 2019 08 23;14(1):84.
    PMID: 31443689 DOI: 10.1186/s13012-019-0932-0
    BACKGROUND: Acute gallstone disease is the highest volume Emergency General Surgical presentation in the UK. Recent data indicate wide variations in the quality of care provided across the country, with national guidance for care delivery not implemented in most UK hospitals. Against this backdrop, the Royal College of Surgeons of England set up a 13-hospital quality improvement collaborative (Chole-QuIC) to support clinical teams to reduce time to surgery for patients with acute gallstone disease requiring emergency cholecystectomy.

    METHODS: Prospective, mixed-methods process evaluation to answer the following: (1) how was the collaborative delivered by the faculty and received, understood and enacted by the participants; (2) what influenced teams' ability to improve care for patients requiring emergency cholecystectomy? We collected and analysed a range of data including field notes, ethnographic observations of meetings, and project documentation. Analysis was based on the framework approach, informed by Normalisation Process Theory, and involved the creation of comparative case studies based on hospital performance during the project.

    RESULTS: Chole-QuIC was delivered as planned and was well received and understood by participants. Four hospitals were identified as highly successful, based upon a substantial increase in the number of patients having surgery in line with national guidance. Conversely, four hospitals were identified as challenged, achieving no significant improvement. The comparative analysis indicate that six inter-related influences appeared most associated with improvement: (1) achieving clarity of purpose amongst site leads and key stakeholders; (2) capacity to lead and effective project support; (3) ideas to action; (4) learning from own and others' experience; (5) creating additional capacity to do emergency cholecystectomies; and (6) coordinating/managing the patient pathway.

    CONCLUSION: Collaborative-based quality improvement is a viable strategy for emergency surgery but success requires the deployment of effective clinical strategies in conjunction with improvement strategies. In particular, achieving clarity of purpose about proposed changes amongst key stakeholders was a vital precursor to improvement, enabling the creation of additional surgical capacity and new pathways to be implemented effectively. Protected time, testing ideas, and the ability to learn quickly from data and experience were associated with greater impact within this cohort.

    MeSH terms: Acute Disease; Attitude of Health Personnel; Cholecystectomy/methods*; Cholecystectomy/standards; Cooperative Behavior; Emergency Service, Hospital/organization & administration*; Emergency Service, Hospital/standards; Great Britain; Humans; Leadership; Patient Care Team/organization & administration; Prospective Studies; Case-Control Studies; Gallstones/surgery*; Quality Improvement/organization & administration*; Time-to-Treatment
  12. Abdar M, Książek W, Acharya UR, Tan RS, Makarenkov V, Pławiak P
    Comput Methods Programs Biomed, 2019 Oct;179:104992.
    PMID: 31443858 DOI: 10.1016/j.cmpb.2019.104992
    BACKGROUND AND OBJECTIVE: Coronary artery disease (CAD) is one of the commonest diseases around the world. An early and accurate diagnosis of CAD allows a timely administration of appropriate treatment and helps to reduce the mortality. Herein, we describe an innovative machine learning methodology that enables an accurate detection of CAD and apply it to data collected from Iranian patients.

    METHODS: We first tested ten traditional machine learning algorithms, and then the three-best performing algorithms (three types of SVM) were used in the rest of the study. To improve the performance of these algorithms, a data preprocessing with normalization was carried out. Moreover, a genetic algorithm and particle swarm optimization, coupled with stratified 10-fold cross-validation, were used twice: for optimization of classifier parameters and for parallel selection of features.

    RESULTS: The presented approach enhanced the performance of all traditional machine learning algorithms used in this study. We also introduced a new optimization technique called N2Genetic optimizer (a new genetic training). Our experiments demonstrated that N2Genetic-nuSVM provided the accuracy of 93.08% and F1-score of 91.51% when predicting CAD outcomes among the patients included in a well-known Z-Alizadeh Sani dataset. These results are competitive and comparable to the best results in the field.

    CONCLUSIONS: We showed that machine-learning techniques optimized by the proposed approach, can lead to highly accurate models intended for both clinical and research use.

    MeSH terms: Algorithms; Coronary Artery Disease/diagnosis*; Diagnosis, Computer-Assisted/statistics & numerical data; Female; Humans; Male; Models, Cardiovascular; Databases, Factual/statistics & numerical data; Data Mining/statistics & numerical data; Support Vector Machine/statistics & numerical data
  13. Kosalishkwaran G, Parasuraman S, Singh DKJ, Natarajan E, Elamvazuthi I, George J
    Med Biol Eng Comput, 2019 Oct;57(10):2305-2318.
    PMID: 31444622 DOI: 10.1007/s11517-019-02026-6
    Degenerative disc disease (DDD) is a common condition in elderly population that can be painful and can significantly affect individual's quality of life. Diagnosis of DDD allows prompt corrective actions but it is challenging due to the absence of any symptoms at early stages. In studying disc degeneration, measurement of the range of motion (RoM) and loads acting on the spine are crucial factors. However, direct measurement of RoM involves increased instrumentation and risk. In this paper, an innovative method is proposed for calculating RoM, emphasizing repeatability and reliability by considering the posterior thickness of the spine. This is achieved by offsetting the position of markers in relation to the actual vertebral loci. Three geometrically identical finite element models of L3-L4 are developed from a CT scan with different types of elements, and thereafter, mesh element-related metrics are provided for the assessment of the quality of models. The model with the best mesh quality is used for further analysis, where RoM are within ranges as reported in literature and in vivo experiment results. Various kinds of stresses acting on individual components including facet joints are analysed for normal and abnormal loading conditions. The results showed that the stresses in abnormal load conditions for all components including cortical (76.67 MPa), cancellous (69.18 MPa), annulus (6.30 MPa) and nucleus (0.343 MPa) are significantly greater as compared to normal loads (49.96 MPa, 44.2 MPa, 4.28 MPa and 0.23 MPa respectively). However, stress levels for both conditions are within safe limits (167-215 MPa for cortical, 46 MPa for the annulus and 3 MPa for facets). The results obtained could be used as a baseline motion and stresses of healthy subjects based on their respective lifestyles, which could benefit clinicians to suggest corrective actions for those affected by DDD.
    MeSH terms: Aged; Dichlorodiphenyldichloroethane; Humans; Life Style; Motion; Quality of Life; Spine; Tomography, X-Ray Computed; Reproducibility of Results; Range of Motion, Articular; Finite Element Analysis; Zygapophyseal Joint; Intervertebral Disc Degeneration; Healthy Volunteers
  14. Kua KP, Saw PS, Lee SWH
    Int J Clin Pharm, 2019 Oct;41(5):1131-1132.
    PMID: 31444688 DOI: 10.1007/s11096-019-00891-7
    Understanding older adult and caregiver attitudes towards deprescribing will contribute to medication optimization in clinical practice. The objectives of this study were to explore quantitatively the attitudes and beliefs of older adults and caregivers towards deprescribing and identify participant characteristics that were associated with willingness to have a medication deprescribed. This study was conducted in a government-led primary care health clinic and three private community pharmacies in Malaysia with older adults and caregivers of older adults. The revised patients' attitudes towards deprescribing (rPATD) questionnaire was administered. The rPATD questionnaire had four factors in both older adults' and caregivers' versions of the questionnaire (with four to five questions retained in each factor) alongside two global questions that were not included in any of the scoring factors. Our revised statement of main findings now states that most of older adult (n = 340, 67.7%) and caregiver (n = 34, 65.4%) participants agreed or strongly agreed that they would be willing to stop one or more of their or their care recipient's medications if their or their care recipient's doctor said it was possible to do so.
    MeSH terms: Deprescriptions*; Aged; Aged, 80 and over; Attitude*; Cross-Sectional Studies; Ethnic Groups; Female; Humans; Malaysia; Male; Physicians; Surveys and Questionnaires; Caregivers*; Polypharmacy; Independent Living*
  15. Isyraqiah F, Kutty MK, Durairajanayagam D, Singh HJ
    Mol Biol Rep, 2019 Dec;46(6):5967-5975.
    PMID: 31444698 DOI: 10.1007/s11033-019-05030-z
    Individuals who are obese are at a greater risk of developing gastric cancer. They are however also hyperleptinaemic. Chronic leptin treatment has been shown to upregulate numerous cancer-causing genes in the stomach of male Sprague-Dawley rats. It is however unclear if leptin enhances the effect of gastric carcinogens in vivo. This study was therefore done to investigate the effect of leptin on gastric carcinogenesis in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Twenty-four, 6-week old male Sprague-Dawley rats were divided equally into three groups: G1 served as age-matched controls; G2 was treated with MNNG in drinking water ad libitum (200 mg L-1); G3 was given leptin and MNNG. Rats were euthanized after 40 weeks of treatment and their stomachs were removed for histopathology, microarray, and RT-qPCR analysis. Fisher's exact test and one-way ANOVA were used to analyse the data. Fifty percent of the MNNG-treated rats developed gastric hyperplasia (p 
    MeSH terms: Adenocarcinoma/pathology; Animals; Gastric Mucosa/drug effects*; Gastric Mucosa/metabolism; Hyperplasia/pathology; Male; Methylnitronitrosoguanidine/pharmacology; Stomach/pathology; Stomach Neoplasms/etiology*; Stomach Neoplasms/metabolism; Stomach Neoplasms/pathology; Rats, Sprague-Dawley; Leptin/metabolism*; Leptin/pharmacology; Leptin/physiology; Cell Proliferation; Rats; Carcinogenesis/pathology
  16. Osman AY, Kadir AA, Jesse FF, Saharee AA
    Microb Pathog, 2019 Nov;136:103669.
    PMID: 31445124 DOI: 10.1016/j.micpath.2019.103669
    Brucella melitensis is one of the leading zoonotic pathogens with significant economic implications in animal industry worldwide. Lipopolysaccharide, however, remains by far the major virulence with substantial role in diseases pathogenesis. Nonetheless, the effect of B. melitensis and its lipopolysaccharide on immunopathophysiological aspects largely remains an enigma. This study examines the effect of B.melitensis and its lipopolysaccharide on immunopathophysiological parameters following experimental infection using mouse model. Eighty four (n = 84) mice, BALB/c, both sexes with equal gender distribution and 6-8 weeks-old were randomly assigned into three groups. Group 1-2 (n = 72) were orally inoculated with 0.4 mL containing 109 CFU/mL of B. melitensis and its LPS, respectively. Group 3 (n = 12) was challenged orally with phosphate buffered saline and served as a control group. Animals were observed for clinical signs, haematological and histopathological analysis for a period of 24 days post-infection. We hereby report that B.melitensis infected group demonstrated significant clinical signs and histopathological changes than LPS infected group. However, both infected groups showed elevated levels of interleukins (IL-1β and IL-6) and antibody levels (IgM and IgG) with varying degrees of predominance in LPS infected group than B. melitensis infected group. For hormone analysis, low levels of progesterone, estradiol and testosterone were observed in both B. melitensis and LPS groups throughout the study period. Moreover, in B. melitensis infected group, the organism was re-isolated from the organs and tissues of gastrointestinal, respiratory and reproductive systems thereby confirming the infection and transmission dynamics. This report is the first detailed investigation comparing the infection progression and host responses in relation to the immunopathophysiological aspects in a mouse model after oral inoculation with B. melitensis and its lipopolysaccharide.
    MeSH terms: Administration, Oral; Animals; Animal Structures/microbiology; Brucellosis/immunology*; Brucellosis/pathology*; Disease Models, Animal; Female; Histocytochemistry; Immunoglobulin G/blood; Immunoglobulin M/blood; Interleukins/blood; Lipopolysaccharides/immunology*; Lipopolysaccharides/toxicity*; Male; Mice, Inbred BALB C; Brucella melitensis/growth & development*; Brucella melitensis/pathogenicity*; Mice
  17. Md Zin SR, Kassim NM, Mohamed Z, Fateh AH, Alshawsh MA
    J Ethnopharmacol, 2019 Dec 05;245:112180.
    PMID: 31445135 DOI: 10.1016/j.jep.2019.112180
    ETHNOPHARMACOLOGICAL RELEVANCE: Anastatica hierochuntica (A. hierochuntica) is a plant consumed in folk medicine for the treatment of reproductive system related problems and metabolic disorders. It is of concern that the herb is commonly consumed by pregnant women towards the end of pregnancy to ease the process of labour, despite the lack of studies evaluating its safety.

    AIM OF THIS STUDY: This study aimed to investigate the potential toxicity effects of A. hierochuntica in pregnant Sprague-Dawley rats and their developing foetuses.

    MATERIALS AND METHODS: Experiments were conducted in accordance to the Organisation for Economic Co-operation and Development guideline 414. Animals were randomly divided into four groups (n = 10 females per group): negative control (received the vehicle only), experimental animals received 250, 500, and 1000 mg/kg A. hierochuntica aqueous extracts (AHAE), respectively. Treatment was administered daily by oral gavage from gestational day (GD) 6-20, and caesarian section performed on GD21.

    RESULTS: There were significant reduction in the corrected maternal weight gain of dams and body weight of foetuses in the lowest and highest dose of AHAE-treated animals compared to the control. These findings were associated with the increase in anogenital distance index and multiple congenital anomalies observed in some of the offspring. On the other hand, rats treated with 500 mg/kg showed higher embryonic survival rate with absence of significant treatment-related effect.

    CONCLUSION: Findings showed that highest and lowest doses of AHAE have prenatal toxicity effects in SD rats. Therefore, AHAE is potentially harmful to the developing foetuses especially when consumed during the period of implantation and organogenesis. As for the rats treated with 500 mg/kg AHAE, there was no significant treatment-related effect. Hence, we postulate that this finding suggests that the disruption on the hormonal regulation could have been compensated by negative feedback response. The compensated effects of AHAE at 500 mg/kg and the presence of lowest observed adverse effect level (LOAEL) at 250 mg/kg has resulted in a non-monotonous dose response curve (NMDRC), which complicates the determination of the value of no-observed-adverse effect level (NOAEL).

    MeSH terms: Abnormalities, Drug-Induced/etiology*; Abnormalities, Multiple/chemically induced*; Animals; Female; Male; Embryo Implantation; Plant Extracts/toxicity*; Pregnancy; Rats, Sprague-Dawley; Brassicaceae*; Fetal Development/drug effects*
  18. Mehdi WA, Mehde AA, Yusof F, Raus RA, Resen AK, Ghazali H
    Int J Biol Macromol, 2019 Nov 01;140:719-726.
    PMID: 31445152 DOI: 10.1016/j.ijbiomac.2019.08.184
    BACKGROUND: The genetic features indicate a crucial role in nephrolithiasis. The present study was aimed to investigate the role of Glutathione-S-transferase Mu (GSTM1), Glutathione-S- transferase Theta (GSTT1) and endothelial nitric oxide synthase (eNOs) gene polymorphism in nephrolithiasis.

    METHODS: We involved a case-control study in which 480 individuals were divided into 240 healthy control and 240 patients with nephrolithiasis. For each patient and control, we measured biochemical criteria, levels of glutathione S-transferase, eNOs, GSTM1, GSTT1genes and eNOS genes polymorphism by PCR-RFLP.

    RESULTS: GSTM1 and GSTT1 null genotypes are not a risk features for nephrolithiasis. The eNOS frequency GG, GT, and TT genotypes by using Ban II enzyme as restriction enzyme were found to be (48.33, 36.67, and 15.00) %. The eNOS frequency TT, GT, and GG genotypes by using the Ban II enzyme as restriction enzyme were found to be 15.84, 25.83, and 58.33%, respectively. The result showed an increase in serum eNOs levels were in the patient's group comparing to control.

    CONCLUSIONS: This work is the first in the literature to study the relation between eNOs genes polymorphisms and nephrolithiasis. The results conclude that TT genotypes in the eNOs genes are associated with an increase the oxidative stress in patients.

    MeSH terms: Female; Genotype; Glutathione Transferase/genetics*; Humans; Male; Middle Aged; Polymorphism, Genetic/genetics*; Polymorphism, Restriction Fragment Length/genetics; Risk Factors; Case-Control Studies; Genetic Predisposition to Disease/genetics; Nitric Oxide Synthase Type III/genetics*; Nephrolithiasis/genetics*
  19. Dige NC, Mahajan PG, Raza H, Hassan M, Vanjare BD, Hong H, et al.
    Bioorg Chem, 2019 11;92:103201.
    PMID: 31445195 DOI: 10.1016/j.bioorg.2019.103201
    We have carried out the synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamide derivatives by the reaction between isatoic anhydride, 2-furoic hydrazide and substituted salicylaldehydes in ethanol: water (5:5 v/v) solvent system using p-TSA as a catalyst under ultrasound irradiation at room temperature. The structures of newly synthesized compounds were confirmed through spectral techniques such as IR, 1H NMR, 13C NMR, and LCMS. The important features of this protocol include simple and easy workup procedure, reaction carried out at ambient temperature, use of ultrasound and high yield of oxoquinazolin-3(4H)-yl)furan-2-carboxamides in short reaction time. The synthesized compounds 4a-4j were screened against tyrosinase enzyme and all these compounds found to be potent inhibitors with much lower IC50 value of 0.028 ± 0.016 to 1.775 ± 0.947 µM than the standard kojic acid (16.832 ± 1.162 µM). The kinetics mechanism for compound 4e was analyzed by Lineweaver-Burk plots which revealed that compound inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. Along with this all the synthesized compounds (4a-4j) were scanned for their DPPH free radical scavenging ability. The outputs received through in vitro and in silico analysis are coherent to the each other with good binding energy values (kcal/mol) posed by synthesized ligands.
    MeSH terms: Ultrasonic Waves; Amino Acid Sequence; Binding Sites; Computer Simulation; Enzyme Inhibitors/chemical synthesis*; Enzyme Inhibitors/metabolism; Furans/chemistry; Kinetics; Protein Binding; Pyrones/metabolism; Structure-Activity Relationship; Monophenol Monooxygenase/antagonists & inhibitors*; Drug Design; Quinolones/chemical synthesis*; Molecular Structure; Molecular Docking Simulation
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