Browse publications by year: 2018

  1. Lin C, Travis RC, Appleby PN, Tipper S, Weiderpass E, Chang-Claude J, et al.
    Int J Cancer, 2018 Nov 15;143(10):2351-2358.
    PMID: 29971779 DOI: 10.1002/ijc.31650
    Previous in vitro and case-control studies have found an association between the insulin-like growth factor (IGF)-axis and bladder cancer risk. Circulating concentrations of IGF-I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre-diagnostic circulating IGF-I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre-diagnostic plasma concentrations of IGF-I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow-up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre-diagnostic circulating IGF-I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66-1.24, ptrend = 0.40) or UCC (n of cases = 776; 0.91, 0.65-1.26, ptrend = 0.40). There was no significant evidence of heterogeneity in the association of IGF-I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (pheterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF-I concentrations and bladder cancer risk.
    MeSH terms: Adult; Aged; Urinary Bladder Neoplasms/blood*; Urinary Bladder Neoplasms/epidemiology; Europe/epidemiology; Female; Humans; Insulin-Like Growth Factor I/metabolism*; Male; Middle Aged; Prospective Studies; Risk; Case-Control Studies
  2. Abdullah KA, Reed W
    J Med Radiat Sci, 2018 Sep;65(3):237-239.
    PMID: 29971971 DOI: 10.1002/jmrs.292
    Three-dimensional (3D) printing technology has demonstrated a huge potential for the future of medicine. Since its introduction, it has been used in various areas, for example building anatomical models, personalising medical devices and implants, aiding in precision medical interventions and the latest development, 3D bioprinting. This commentary is provided to outline the current use of 3D printing in medical imaging and its future directions for advancing the healthcare services.
    MeSH terms: Diagnostic Imaging/methods*; Printing, Three-Dimensional/economics; Printing, Three-Dimensional/instrumentation*; Printing, Three-Dimensional/trends; Printing, Three-Dimensional/statistics & numerical data
  3. Chew KT, Salim N, Abu MA, Abdul Karim AK
    BMJ Sex Reprod Health, 2018 Jun 01.
    PMID: 29972367 DOI: 10.1136/bmjsrh-2017-101869
    BACKGROUND AND OBJECTIVE: Intrauterine contraceptive devices (IUDs) are an important method to reduce unmet need for family planning and for prevention of unintended pregnancy. However, IUD use in Malaysia is still low. Doctors play a major role in influencing IUD uptake among women. This study was designed to evaluate doctors' knowledge, attitudes and perceptions towards IUDs and factors associated with their current practice.

    METHODS: A questionnaire was mailed to public and private contraceptive providers who practise in Kuala Lumpur, Malaysia.

    RESULTS: A total of 400 doctors were invited and 240 (60%) of them responded to the survey. Of the respondents, 161 (65.9%) were from the public or government sector and 89 (34.1%) were from the private sector. The knowledge score of doctors was classed as 'average', and correlated well with their previous training level, working position, number of patients seen in a week and number of contraceptive methods available in their facilities. The age, gender, working duration, availability of IUDs in the premises and number of IUD insertions in a month were not statistically associated with the providers' knowledge. The use of IUDs was low, especially among private doctors, and was significantly related to their knowledge of the method. Knowledge scores, perception and practice were significantly lower in the private sector.

  4. Cowley JA, Rao M, Coman GJ
    Dis Aquat Organ, 2018 Jul 04;129(2):145-158.
    PMID: 29972375 DOI: 10.3354/dao03243
    Infectious hypodermal and hematopoietic necrosis virus (IHHNV) can cause mass mortalities in western blue shrimp Penaeus stylirostris, runt deformity syndrome in Pacific white shrimp P. vannamei and scalloped abdominal shell deformities in black tiger shrimp P. monodon. In P. monodon, however, PCR-based diagnosis of IHHNV can be complicated by the presence of a chromosome-integrated, non-replicating endogenous viral element (EVE). To facilitate high-throughput screening of P. monodon for IHHNV infection and/or EVE sequences, here we report real-time PCR tests designed to specifically detect IHHNV Lineage I, II and III but not EVE Type A sequences and vice versa. Using 108 dsDNA copies of plasmid (p)DNA controls containing either IHHNV or EVE-Type A sequences, both tests displayed absolute specificity. The IHHNV-q309 PCR reliably detected down to ≤10 copies of pDNA, at which levels a 309F/R PCR amplicon was just detectable, and the presence of an IHHNV-EVE sequence did not significantly impact its sensitivity. The IHHNV-qEVE PCR was similarly sensitive. Testing of batches of P. monodon clinical samples from Vietnam/Malaysia and Australia identified good diagnostic concordance between the IHHNV-q309 and 309F/R PCR tests. As expected for a sequence integrated into host chromosomal DNA, IHHNV-qEVE PCR Ct values were highly uniform among samples from shrimp in which an EVE was present. The highly specific and sensitive IHHNV-q309 and IHHNV-qEVE real-time PCR tests described here should prove useful for selecting broodstock free of IHHNV infection and in maintaining breeding populations of P. monodon specific pathogen free for IHHNV, and if desired, also free of IHHNV-EVE sequences.
    MeSH terms: Animals; DNA, Viral/genetics*; Genome, Viral; Densovirinae/genetics; Densovirinae/physiology*; Penaeidae/virology*; Host-Pathogen Interactions; Real-Time Polymerase Chain Reaction/methods*
  5. Arrivé E, Ayaya S, Davies MA, Chimbetete C, Edmonds A, Lelo P, et al.
    J Int AIDS Soc, 2018 Jul;21(7):e25157.
    PMID: 29972632 DOI: 10.1002/jia2.25157
    INTRODUCTION: Disclosure of HIV status to HIV-infected children and adolescents is a major care challenge. We describe current site characteristics related to disclosure of HIV status in resource-limited paediatric HIV care settings within the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

    METHODS: An online site assessment survey was conducted across the paediatric HIV care sites within six global regions of IeDEA. A standardized questionnaire was administered to the sites through the REDCap platform.

    RESULTS: From June 2014 to March 2015, all 180 sites of the IeDEA consortium in 31 countries completed the online survey: 57% were urban, 43% were health centres and 86% were integrated clinics (serving both adults and children). Almost all the sites (98%) reported offering disclosure counselling services. Disclosure counselling was most often provided by counsellors (87% of sites), but also by nurses (77%), physicians (74%), social workers (68%), or other clinicians (65%). It was offered to both caregivers and children in 92% of 177 sites with disclosure counselling. Disclosure resources and procedures varied across geographical regions. Most sites in each region reported performing staff members' training on disclosure (72% to 96% of sites per region), routinely collecting HIV disclosure status (50% to 91%) and involving caregivers in the disclosure process (71% to 100%). A disclosure protocol was available in 14% to 71% of sites. Among the 143 sites (79%) routinely collecting disclosure status process, the main collection method was by asking the caregiver or child (85%) about the child's knowledge of his/her HIV status. Frequency of disclosure status assessment was every three months in 63% of the sites, and 71% stored disclosure status data electronically.

    CONCLUSION: The majority of the sites reported offering disclosure counselling services, but educational and social support resources and capacities for data collection varied across regions. Paediatric HIV care sites worldwide still need specific staff members' training on disclosure, development and implementation of guidelines for HIV disclosure, and standardized data collection on this key issue to ensure the long-term health and wellbeing of HIV-infected youth.

    MeSH terms: Adolescent; Adult; Child; Counseling; Female; Health Resources; Humans; Male; Models, Theoretical; Surveys and Questionnaires; Social Support; Cohort Studies; HIV Infections/diagnosis*; HIV Infections/drug therapy; Caregivers*; Disclosure*
  6. Arinima P, Ishak A
    Korean J Fam Med, 2018 Jul;39(4):266-269.
    PMID: 29972896 DOI: 10.4082/kjfm.17.0117
    A 16-year-old Malay boy presented to Kota Bharu Health Care Centre, Kelantan, with left shoulder pain after sustaining a fall. On further history taking, it was noted that the pain preceded the fall by 1 month. The early changes of osteosarcoma were visible on an X-ray during the initial presentation; however, this was missed by the primary care doctors. Three months later, the patient presented with persistent pain in the left shoulder and was diagnosed with osteosarcoma.
    MeSH terms: Accidental Falls; Humans; Malaysia; Male; Medical History Taking; Primary Health Care; Radiography; Osteosarcoma; Shoulder; X-Rays; Shoulder Pain
  7. Maleki A, Ghafourian S, Pakzad I, Badakhsh B, Sadeghifard N
    Curr Pharm Des, 2018;24(11):1204-1210.
    PMID: 29237374 DOI: 10.2174/1381612824666171213094730
    BACKGROUND: Neisseria meningitidis is considered as a dangerous pathogen threatening human health. Nowadays, the new drug target is focused. Toxin antitoxin (TA) system is recently identified as an antimicrobial drug target. Also, in N. meningitidis, iron-uptake system could be an interesting target for drug discovery.

    METHODS: In this study, fbpA and mazE genes were chosen as new antimicrobial targets and treated with antisense peptide nucleic acid (PNA). Firstly, they were evaluated by bioinformatics and then analyzed by experimental procedures. Secondly, the functionality was evaluated by stress conditions.

    RESULTS: Our results interestingly demonstrated that when fbpA and mazE loci of N. meningitidis were targeted by antisense PNA, 8 µM concentration of fbpA-PNA as well as 30 µM concentration of mazE-PNA inhibited the growth of N. meningitides and were found to be bacteriostatic, whereas 10 μM concentration of fbpA-PNA showed bacteriocidal activity.

    CONCLUSION: Our findings demonstrated the bactriocidal activity of fbpA-PNA and bacteriostatic activity of mazEPNA. Therefore, mazE and fbpA genes should be potent antimicrobial targets but further analysis including in vivo analysis should be performed.

    MeSH terms: Anti-Bacterial Agents/pharmacology*; Bacterial Proteins/drug effects*; Bacterial Proteins/genetics; Dose-Response Relationship, Drug; Microbial Sensitivity Tests; Neisseria meningitidis/drug effects*; Neisseria meningitidis/genetics
  8. Abdalla AN, Ali K, Paw JKS, Rifai D, Faraj MA
    Sensors (Basel), 2018 Jun 30;18(7).
    PMID: 29966367 DOI: 10.3390/s18072108
    Eddy current testing (ECT) is an accurate, widely used and well-understood inspection technique, particularly in the aircraft and nuclear industries. The coating thickness or lift-off will influence the measurement of defect depth on pipes or plates. It will be an uncertain decision condition whether the defects on a workpiece are cracks or scratches. This problem can lead to the occurrence of pipe leakages, besides causing the degradation of a company’s productivity and most importantly risking the safety of workers. In this paper, a novel eddy current testing error compensation technique based on Mamdani-type fuzzy coupled differential and absolute probes was proposed. The general descriptions of the proposed ECT technique include details of the system design, intelligent fuzzy logic design and Simulink block development design. The detailed description of the proposed probe selection, design and instrumentation of the error compensation of eddy current testing (ECECT) along with the absolute probe and differential probe relevant to the present research work are presented. The ECECT simulation and hardware design are proposed, using the fuzzy logic technique for the development of the new methodology. The depths of the defect coefficients of the probe’s lift-off caused by the coating thickness were measured by using a designed setup. In this result, the ECECT gives an optimum correction for the lift-off, in which the reduction of error is only within 0.1% of its all-out value. Finally, the ECECT is used to measure lift-off in a range of approximately 1 mm to 5 mm, and the performance of the proposed method in non-linear cracks is assessed.
    MeSH terms: Aircraft; Equipment Design; Industry; Risk; Fuzzy Logic; Uncertainty
  9. Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, et al.
    J Thorac Oncol, 2018 10;13(10):1539-1548.
    PMID: 29966800 DOI: 10.1016/j.jtho.2018.06.012
    INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population.

    METHODS: In this open-label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration-time curve of 5-6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point.

    RESULTS: Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286-0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6-93.2%) with crizotinib versus 45.6% (95% CI: 35.8-55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient-reported outcomes were seen in crizotinib-treated versus chemotherapy-treated patients.

    CONCLUSIONS: First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.

    MeSH terms: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols/pharmacology; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*; Carcinoma, Non-Small-Cell Lung/drug therapy*; Carcinoma, Non-Small-Cell Lung/pathology; Female; Humans; Lung Neoplasms/drug therapy*; Lung Neoplasms/pathology; Male; Middle Aged; Asian Continental Ancestry Group; Young Adult
  10. Lunze K, Lermet O, Andreeva V, Hariga F
    Int J Drug Policy, 2018 09;59:10-15.
    PMID: 29966803 DOI: 10.1016/j.drugpo.2018.06.009
    BACKGROUND: Several Southeast Asian countries have implemented compulsory drug detention centres in which people who use or are suspected of using drugs, mainly amphetamine-type stimulants, are confined without their consent and in most cases without due process and clinical evaluation of their substance use disorder. Given these facilities' lack of access to evidence-based drug dependence treatment, and the human rights implications of peoples' arbitrary detention under the pretext of "treatment", international organizations have called for their closure. The aim of this study was to estimate recent numbers of compulsory drug treatment centres and of people in these centres in the region.

    METHODS: We conducted an analysis of cross-sectional governmental data collected from seven countries in the region with compulsory drug detention centres, namely Cambodia, China, Lao PDR, Malaysia, the Philippines, Thailand and Viet Nam. We computed descriptive data provided by government representatives for the period between 2012 and 2014.

    RESULTS: The total number of people in compulsory detention centres overall decreased by only 4% between 2012 and 2014. In 2014, over 450,000 people were detained in 948 facilities in the seven countries. While only two countries decreased the number of compulsory detention centres, most countries increased the number of people detained.

    CONCLUSIONS: In spite of international calls for the closure of compulsory detention centres, the number of facilities and detained people remained high in the seven countries included in the analysis. These officially reported figures are concerning regarding access to effective drug dependence treatment and given the potential for additional human rights abuses within compulsory detention centers. Further concerted policy and advocacy efforts should support transition of treatment for people with drug dependence towards human rights-based and evidence-based drug dependence treatment. Expansion of existing drug and HIV services in the community rather than compulsory treatment modalities will effectively address the region's drug and HIV burden.

    MeSH terms: Asia, Southeastern; Cross-Sectional Studies; Humans; HIV Infections/etiology; HIV Infections/therapy; Substance Abuse Treatment Centers/legislation & jurisprudence*; Substance-Related Disorders/therapy*; Substance-Related Disorders/virology; Mandatory Programs/legislation & jurisprudence*; Human Rights Abuses/legislation & jurisprudence; Drug Users/legislation & jurisprudence*
  11. Anwar A, Siddiqui R, Shah MR, Khan NA
    PMID: 29967024 DOI: 10.1128/AAC.00630-18
    trans-Cinnamic acid (CA) is a natural organic compound. Using amoebicidal assays, for the first time we showed that CA affected the viability of the protist pathogen Acanthamoeba castellanii Conjugation with gold nanoparticles (AuNPs) enhanced the antiamoebic effects of CA. CA-coated AuNPs (CA-AuNPs) also exhibited significant excystation and encystation activity, compared to CA and AuNPs alone. Pretreatment of amoebae with CA-AuNPs inhibited A. castellanii-mediated host cell cytotoxicity. Moreover, CA-AuNPs exhibited potent effects against methicillin-resistant Staphylococcus aureus and neuropathogenic Escherichia coli K1 and protected host cells against bacteria-mediated host cell death.
    MeSH terms: Amebiasis/drug therapy; Amebiasis/parasitology; Amebicides/pharmacology*; Anti-Bacterial Agents/pharmacology*; Cinnamates/pharmacology*; Gold/administration & dosage*; HeLa Cells; Humans; Cell Line, Tumor; Acanthamoeba castellanii/drug effects*; Metal Nanoparticles/administration & dosage*; Methicillin-Resistant Staphylococcus aureus/drug effects
  12. Sun J, Zhang H, Tan Q, Zhou H, Guan D, Zhang X, et al.
    Sci Rep, 2018 07 02;8(1):9976.
    PMID: 29967414 DOI: 10.1038/s41598-018-28349-2
    In 2015, an unexpected multiple outbreak of dengue occurred in Guangdong, China. In total, 1,699 cases were reported, of which 1,627 cases were verified to have DENV infections by nucleic acid or NS1 protein, including 44 DENV-1, 1126 DENV-2, 18 DENV-3 and 6 DENV-4, and the other cases were confirmed by NS1 ELISA. Phylogenetic analyses of DENV-1 isolates identified two genotypes (I and V). The predominant DENV-2 outbreak isolates were the Cosmopolitan genotypes, which likely originated from Malaysia. The DENV-3 isolates were assigned into genotype I and genotype III. All 6 DENV-4 isolates from imported cases were likely originally from Cambodia, Thailand and the Philippines. The entomological surveillance showed a moderate risk for the BI index in Chaozhou and Foshan and a low risk in Guangzhou. The imported cases were mostly detected in Guangzhou and Foshan. Surprisingly, the most serious outbreak occurred in Chaozhou, but not in Guangzhou or Foshan. A combined analyses demonstrated the multiple geographical origins of this outbreak, and highlight the detection of suspected cases after the alerting of imported cases, early implementation of control policies and reinforce the vector surveillance strategies were the key points in the chain of prevention and control of dengue epidemics.
    MeSH terms: Adolescent; Adult; Aged; Animals; Child; Child, Preschool; China/epidemiology; Dengue/epidemiology*; Dengue Virus/genetics*; Dengue Virus/pathogenicity; Disease Outbreaks; Female; Humans; Male; Middle Aged; Phylogeny*; Mosquito Vectors/virology
  13. Strand TA, Ulak M, Kvestad I, Henjum S, Ulvik A, Shrestha M, et al.
    Pediatr Res, 2018 11;84(5):611-618.
    PMID: 29967525 DOI: 10.1038/s41390-018-0072-2
    BACKGROUND: Many children worldwide have poor vitamin B12 status. The objective of this study was to estimate association between maternal and infant vitamin B12 status and long-term growth.

    METHODS: We randomly selected 500 Nepali mother-infant pairs and measured maternal intake and infant and maternal vitamin B12 status using plasma cobalamin, total plasma homocysteine, and methylmalonic acid concentrations. We revisited available children when they were 5 years old and measured growth. The associations between intake and maternal and infant markers of vitamin B12 and growth were estimated in multiple linear regression models adjusting for relevant confounders (n = 331).

    RESULTS: Maternal vitamin B12 intake and status and vitamin B12 status in infancy predicted linear growth at 5 years of age, but not during infancy. Each microgram increase in the vitamin B12 intake of the mother during infancy was associated with an increase in height of 0.4 (0.2, 0.6) height-for-age z-scores and 1.7 (0.7, 2.7) cm around the child's fifth birthday.

    CONCLUSION: Vitamin B12 status and intake in early life is an important determinant for linear growth at school age. Our findings should be verified in randomized, placebo controlled trials before translated into public health recommendations.

    MeSH terms: Adolescent; Adult; Breast Feeding; Child, Preschool; Diet; Female; Folic Acid/blood; Growth*; Homocysteine/blood; Humans; Infant; Lactation; Male; Methylmalonic Acid/blood; Middle Aged; Nepal; Random Allocation; Vitamin B 12/blood*; Young Adult; Limit of Detection
  14. Muraya N, Kadowaki D, Miyamura S, Kitamura K, Uchimura K, Narita Y, et al.
    Oxid Med Cell Longev, 2018;2018:7635274.
    PMID: 29967665 DOI: 10.1155/2018/7635274
    Oxidative stress induced by hyperuricemia is closely associated with the renin-angiotensin system, as well as the onset and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). It is therefore important to reduce oxidative stress to treat hyperuricemia. We previously found that benzbromarone, a uricosuric agent, has a direct free radical scavenging effect in vitro. The antioxidant effects of benzbromarone were evaluated in vivo via oral administration of benzbromarone for 4 weeks to model rats with angiotensin II- and salt-induced hypertension. Benzbromarone did not alter plasma uric acid levels or blood pressure but significantly reduced the levels of advanced oxidation protein products, which are oxidative stress markers. Furthermore, dihydroethidium staining of the kidney revealed a reduction in oxidative stress after benzbromarone administration. These results suggest that benzbromarone has a direct antioxidant effect in vivo and great potential to prevent CVD and CKD.
    MeSH terms: Angiotensin II/toxicity; Animals; Antioxidants/pharmacology*; Benzbromarone/pharmacology*; Disease Models, Animal; Male; Sodium Chloride/toxicity; Rats, Sprague-Dawley; Sodium Chloride, Dietary/adverse effects; Oxidative Stress/drug effects*; Rats
  15. Abbasi MA, Hassan M, Aziz-Ur-Rehman, Siddiqui SZ, Shah SAA, Raza H, et al.
    PeerJ, 2018;6:e4962.
    PMID: 29967717 DOI: 10.7717/peerj.4962
    The present study comprises the synthesis of a new series of sulfonamides derived from 4-methoxyphenethylamine (1). The synthesis was initiated by the reaction of 1 with 4-methylbenzenesulfonyl chloride (2) in aqueous sodium carbonate solution at pH 9 to yield N-(4-methoxyphenethyl)-4-methylbenzensulfonamide (3).This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides, (4a-j), using N,N-dimethylformamide (DMF) as solvent and LiH as activator to produce a series of new N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides (5a-j). The structural characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. The elemental analysis data was also coherent with spectral data of these molecules. The inhibitory effects on acetylcholinesterase and DPPH were evaluated and it was observed that N-(4-Methoxyphenethyl)-4-methyl-N-(2-propyl)benzensulfonamide (5c) showed acetylcholinesterase inhibitory activity 0.075 ± 0.001 (IC50 0.075 ± 0.001 µM) comparable to Neostigmine methylsulfate (IC50 2.038 ± 0.039 µM).The docking studies of synthesized ligands 5a-j were also carried out against acetylcholinesterase (PDBID 4PQE) to compare the binding affinities with IC50 values. The kinetic mechanism analyzed by Lineweaver-Burk plots demonstrated that compound (5c) inhibits the acetylcholinesterase competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (5c) is 2.5 µM. It was also found from kinetic analysis that derivative 5c irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound 5c may serve as lead structure for the design of more potent acetylcholinesterase inhibitors.
    MeSH terms: Acetylcholinesterase; Carbon Isotopes; Carbonates; Cholinesterase Inhibitors; Dimethylformamide; Kinetics; Ligands; Neostigmine; Sulfonamides; Inhibitory Concentration 50; Proton Magnetic Resonance Spectroscopy
  16. Manley S
    J Gen Intern Med, 2018 10;33(10):1822-1823.
    PMID: 29968052 DOI: 10.1007/s11606-018-4549-9
    MeSH terms: Attitude to Health*; Empathy; Humans; Nevus, Pigmented/psychology; Nevus, Pigmented/surgery*; Physician-Patient Relations; Touch; Dermatologic Surgical Procedures/psychology
  17. Arshad L, Jantan I, Bukhari SNA, Fauzi MB
    Curr Pharm Biotechnol, 2018;19(6):468-482.
    PMID: 29968535 DOI: 10.2174/1389201019666180703092723
    BACKGROUND: 3,5-Bis[4-(diethoxymethyl)benzylidene]-1-methyl-piperidin-4-one (BBP), a novel synthetic curcumin analogue has previously been shown to manifest potent immunosuppressive effects on the in vitro phagocytosis process of human neutrophils.

    OBJECTIVE: In the present study, BBP was investigated for it's in vivo innate and adaptive immune responses mediated by different humoral and cellular immune factors.

    METHODS: Male Balb/c mice were orally fed with BBP (5, 10 and 20 mg/kg) for a period of 14 days and immunized with sheep red blood cells (sRBC) on day 0 for the determination of adaptive responses. The effects of BBP on phagocytosis process of neutrophils isolated from blood of treated/untreated animals were determined. The ceruloplasmin and lysozyme serum levels and myeloperoxidase (MPO) plasma level were also monitored. The mechanism was further explored by assessing its effects on the proliferation of T and B lymphocytes, T-lymphocytes subsets CD4+ and CD8+ and on the secretion of Th1/Th2 cytokines as well as serum immunoglobulins (IgG, IgM) and delayed type hypersensitivity (DTH) reaction.

    RESULTS: BBP showed a significant dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity and reactive oxygen species (ROS) production. In comparison to the sensitized control group, a dose-dependent inhibition was observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines. Moreover, a statistically significant decrease was perceived in serum levels of ceruloplasmin, lysozyme and immunoglobulins and MPO plasma level of BBP-treated mice. BBP also dose-dependently inhibited sheep red blood cells (sRBC)-induced swelling rate of mice paw in DTH.

    CONCLUSION: These findings suggest the potential of BBP as a potent immunosuppressive agent.

    MeSH terms: Animals; Ceruloplasmin/analysis; Curcumin/analogs & derivatives*; Curcumin/pharmacology; Curcumin/chemistry; Humans; Immunity, Cellular/drug effects*; Lymphocyte Activation/drug effects; Male; Mice, Inbred BALB C; Neutrophils/drug effects; Neutrophils/immunology; Phagocytosis/drug effects; Piperidines/pharmacology; Piperidines/chemistry*; Sheep; Mice; Immunity, Humoral/drug effects*
  18. Auburn S, Benavente ED, Miotto O, Pearson RD, Amato R, Grigg MJ, et al.
    Nat Commun, 2018 Jul 03;9(1):2585.
    PMID: 29968722 DOI: 10.1038/s41467-018-04965-4
    The incidence of Plasmodium vivax infection has declined markedly in Malaysia over the past decade despite evidence of high-grade chloroquine resistance. Here we investigate the genetic changes in a P. vivax population approaching elimination in 51 isolates from Sabah, Malaysia and compare these with data from 104 isolates from Thailand and 104 isolates from Indonesia. Sabah displays extensive population structure, mirroring that previously seen with the emergence of artemisinin-resistant P. falciparum founder populations in Cambodia. Fifty-four percent of the Sabah isolates have identical genomes, consistent with a rapid clonal expansion. Across Sabah, there is a high prevalence of loci known to be associated with antimalarial drug resistance. Measures of differentiation between the three countries reveal several gene regions under putative selection in Sabah. Our findings highlight important factors pertinent to parasite resurgence and molecular cues that can be used to monitor low-endemic populations at the end stages of P. vivax elimination.
  19. Larsson HM, Vythilingam G, Pinnagoda K, Vardar E, Engelhardt EM, Sothilingam S, et al.
    Sci Rep, 2018 07 03;8(1):10057.
    PMID: 29968749 DOI: 10.1038/s41598-018-27621-9
    There is a need for efficient and "off-the-shelf" grafts in urethral reconstructive surgery. Currently available surgical techniques require harvesting of grafts from autologous sites, with increased risk of surgical complications and added patient discomfort. Therefore, a cost-effective and cell-free graft with adequate regenerative potential has a great chance to be translated into clinical practice. Tubular cell-free collagen grafts were prepared by varying the collagen density and fiber distribution, thereby creating a polarized low fiber density collagen graft (LD-graft). A uniform, high fiber density collagen graft (HD-graft) was engineered as a control. These two grafts were implanted to bridge a 2 cm long iatrogenic urethral defect in a rabbit model. Histology revealed that rabbits implanted with the LD-graft had a better smooth muscle regeneration compared to the HD-graft. The overall functional outcome assessed by contrast voiding cystourethrography showed patency of the urethra in 90% for the LD-graft and in 66.6% for the HD-graft. Functional regeneration of the rabbit implanted with the LD-graft could further be demonstrated by successful mating, resulting in healthy offspring. In conclusion, cell-free low-density polarized collagen grafts show better urethral regeneration than high-density collagen grafts.
    MeSH terms: Animals; Collagen/metabolism*; Dietary Fiber; Extracellular Matrix; Male; Muscle, Smooth; Rabbits; Regeneration; Urethra/pathology*; Urethra/transplantation; Reconstructive Surgical Procedures; Transplants/metabolism; Transplants/surgery; Models, Animal; Tissue Engineering/methods*
  20. Y., Ganesan, P., Talwar, Norsiah Fauzan, Yin,Bee Oon
    MyJurnal
    Feelings of stress are a part of university students’ life. Stress is simply the body's response to changes that create taxing demands. There is a difference between eustress, which is a term for positive stress, and distress, which refers to negative stress. Coping mechanism plays a significant part to overcome or reduce the stress experienced by individuals. People use different types of coping strategies to overcome their stress. The purpose of the study was to study the relationship between stress and coping strategies among university students. Eighty- six university students participated in the study. A quantitative study utilizing a cross sectional non-probability sampling research design was used to gather data. The data was collected using a questionnaire with the addition of Perceived Stress Scale (PSS) and the Adolescent Coping Scale (ACS) were administered. The result of this study indicated that majority of the university students have moderate level of stress. There was a significant inverse relationship between stress level and coping strategies among undergraduates. In conclusion, some levels of stress can be good, as the right kind of stress encourages them towards change and growth. However, when students are unable to cope with stress, they can become a burden. It is recommended that students should be
    encouraged to take part in extra-curricular activities such as sports to reduce stress.
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