Browse publications by year: 2018

  1. Fornace KM, Herman LS, Abidin TR, Chua TH, Daim S, Lorenzo PJ, et al.
    PLoS Negl Trop Dis, 2018 Jun;12(6):e0006432.
    PMID: 29902171 DOI: 10.1371/journal.pntd.0006432
    BACKGROUND: Primarily impacting poor, rural populations, the zoonotic malaria Plasmodium knowlesi is now the main cause of human malaria within Malaysian Borneo. While data is increasingly available on symptomatic cases, little is known about community-level patterns of exposure and infection. Understanding the true burden of disease and associated risk factors within endemic communities is critical for informing evidence-based control measures.

    METHODOLOGY/PRINCIPAL FINDINGS: We conducted comprehensive surveys in three areas where P. knowlesi transmission is reported: Limbuak, Pulau Banggi and Matunggung, Kudat, Sabah, Malaysia and Bacungan, Palawan, the Philippines. Infection prevalence was low with parasites detected by PCR in only 0.2% (4/2503) of the population. P. knowlesi PkSERA3 ag1 antibody responses were detected in 7.1% (95% CI: 6.2-8.2%) of the population, compared with 16.1% (14.6-17.7%) and 12.6% (11.2-14.1%) for P. falciparum and P. vivax. Sero-prevalence was low in individuals <10 years old for P. falciparum and P. vivax consistent with decreased transmission of non-zoonotic malaria species. Results indicated marked heterogeneity in transmission intensity between sites and P. knowlesi exposure was associated with agricultural work (OR 1.63; 95% CI 1.07-2.48) and higher levels of forest cover (OR 2.40; 95% CI 1.29-4.46) and clearing (OR 2.14; 95% CI 1.35-3.40) around houses. Spatial patterns of P. knowlesi exposure differed from exposure to non-zoonotic malaria and P. knowlesi exposed individuals were younger on average than individuals exposed to non-zoonotic malaria.

    CONCLUSIONS/SIGNIFICANCE: This is the first study to describe serological exposure to P. knowlesi and associated risk factors within endemic communities. Results indicate community-level patterns of infection and exposure differ markedly from demographics of reported cases, with higher levels of exposure among women and children. Further work is needed to understand these variations in risk across a wider population and spatial scale.

    MeSH terms: Farmers; Adolescent; Adult; Animals; Antibodies, Protozoan/blood; Child; Female; Humans; Malaria/immunology; Malaria/epidemiology*; Malaria/parasitology; Malaria/transmission; Malaysia/epidemiology; Male; Middle Aged; Philippines/epidemiology; Public Health; Risk Factors; Zoonoses; Seroepidemiologic Studies*; Polymerase Chain Reaction; Plasmodium knowlesi/genetics; Plasmodium knowlesi/immunology; Plasmodium knowlesi/isolation & purification*; Young Adult; Asymptomatic Infections/epidemiology; Forests
  2. Herman LS, Fornace K, Phelan J, Grigg MJ, Anstey NM, William T, et al.
    PLoS Negl Trop Dis, 2018 Jun;12(6):e0006457.
    PMID: 29902183 DOI: 10.1371/journal.pntd.0006457
    BACKGROUND: Plasmodium knowlesi is the most common cause of malaria in Malaysian Borneo, with reporting limited to clinical cases presenting to health facilities and scarce data on the true extent of transmission. Serological estimations of transmission have been used with other malaria species to garner information about epidemiological patterns. However, there are a distinct lack of suitable serosurveillance tools for this neglected disease.

    METHODOLOGY/PRINCIPAL FINDINGS: Using in silico tools, we designed and expressed four novel P. knowlesi protein products to address the distinct lack of suitable serosurveillance tools: PkSERA3 antigens 1 and 2, PkSSP2/TRAP and PkTSERA2 antigen 1. Antibody prevalence to these antigens was determined by ELISA for three time-points post-treatment from a hospital-based clinical treatment trial in Sabah, East Malaysia (n = 97 individuals; 241 total samples for all time points). Higher responses were observed for the PkSERA3 antigen 2 (67%, 65/97) across all time-points (day 0: 36.9% 34/92; day 7: 63.8% 46/72; day 28: 58.4% 45/77) with significant differences between the clinical cases and controls (n = 55, mean plus 3 SD) (day 0 p<0.0001; day 7 p<0.0001; day 28 p<0.0001). Using boosted regression trees, we developed models to classify P. knowlesi exposure (cross-validated AUC 88.9%; IQR 86.1-91.3%) and identified the most predictive antibody responses.

    CONCLUSIONS/SIGNIFICANCE: The PkSERA3 antigen 2 had the highest relative variable importance in all models. Further validation of these antigens is underway to determine the specificity of these tools in the context of multi-species infections at the population level.

    MeSH terms: Antibodies, Protozoan/blood*; Antigens, Protozoan/blood; Antigens, Protozoan/genetics; Antigens, Protozoan/immunology*; Computer Simulation; Enzyme-Linked Immunosorbent Assay/methods; Humans; Malaria/diagnosis*; Malaria/immunology; Malaria/epidemiology; Malaria/transmission; Malaysia/epidemiology; Recombinant Proteins/immunology; Biomarkers/blood; Prevalence; Plasmodium knowlesi/immunology; Plasmodium knowlesi/isolation & purification*
  3. Zhao C, Wong L, Zhu Q, Yang H
    PLoS One, 2018;13(6):e0199006.
    PMID: 29902222 DOI: 10.1371/journal.pone.0199006
    BACKGROUND: The escalating problem of multiple chronic conditions among older adults in China draws public health attention due to increasing proportion of the elderly population. This study sought to assess the prevalence of and factors associated with four chronic diseases in older adults in Haikou, the capital city of Hainan Province, China.

    METHOD: In this cross-sectional study, 9432 community-dwelling elderly people aged 60 years and older living in rural or urban areas in Haikou were investigated. The interviews collected self-reported information on the presence of four major chronic diseases, as well as socio-demographic characteristics, lifestyle factors and self-reported height and weight.

    FINDINGS: Overall, 31.7% (2961/9344) reported at least one of the four chronic diseases. The prevalence of hypertension, diabetes mellitus, COPD, and stroke was 26.0% (2449/9407), 8.0% (749/9371), 1.0% (95/9360), and 1.9% (175/9382), respectively. Common correlates of the four major chronic diseases were older age, being engaged in intellectual work, currently being a smoker and obesity. Gender, locality of residence, and alcohol consumptions were also found to be associated to some of the chronic conditions.

    CONCLUSION: This finding indicates that multiple chronic conditions among elderly people in Haikou are prevalent and warrant special attention to reduce diseases burden and align health care services to cater the holistic elderly patients' need.

    MeSH terms: Aged; Aged, 80 and over; China/epidemiology; Chronic Disease/epidemiology*; Female; Humans; Male; Middle Aged; Surveys and Questionnaires*; Risk Factors; Rural Population/statistics & numerical data; Prevalence; Self Report
  4. Praveena SM, Shaifuddin SNM, Sukiman S, Nasir FAM, Hanafi Z, Kamarudin N, et al.
    Sci Total Environ, 2018 Nov 15;642:230-240.
    PMID: 29902621 DOI: 10.1016/j.scitotenv.2018.06.058
    This study investigated the occurrence of nine pharmaceuticals (amoxicillin, caffeine, chloramphenicol, ciprofloxacin, dexamethasone, diclofenac, nitrofurazone, sulfamethoxazole, and triclosan) and to evaluate potential risks (human health and ecotoxicological) in Lui, Gombak and Selangor (Malaysia) rivers using commercial competitive Enzyme-Linked Immunosorbent Assay (ELISA) kit assays. Physicochemical properties of these rivers showed the surface samples belong to Class II of Malaysian National Water Quality Standards which requires conventional treatment before consumption. All the pharmaceuticals were detected in all three rivers except for triclosan, dexamethasone and diclofenac which were not detected in few of sampling locations in these three rivers. Highest pharmaceutical concentrations were detected in Gombak river in line of being as one of the most polluted rivers in Malaysia. Ciprofloxacin concentrations were detected in all the sampling locations with the highest at 299.88 ng/L. While triclosan, dexamethasone and diclofenac concentrations were not detected in a few of sampling locations in these three rivers. All these nine pharmaceuticals were within the levels reported previously in literature. Pharmaceutical production, wastewater treatment technologies and treated sewage effluent were found as the potential sources which can be related with pharmaceuticals occurrence in surface water samples. Potential human risk assessment showed low health risk except for ciprofloxacin and dexamethasone. Instead, ecotoxicological risk assessment indicated moderate risks were present for these rivers. Nevertheless, results confirmation using instrumental techniques is needed for higher degree of specificity. It is crucial to continuously monitor the surface water bodies for pharmaceuticals using a cost-effective prioritisation approach to assess sensitive sub-populations risk.
    MeSH terms: Pharmaceutical Preparations/analysis*; Environmental Monitoring*; Humans; Malaysia; Water Pollutants, Chemical/analysis*; Risk Assessment; Rivers/chemistry
  5. Koyama M, Nagao N, Syukri F, Rahim AA, Kamarudin MS, Toda T, et al.
    Bioresour Technol, 2018 Oct;265:207-213.
    PMID: 29902653 DOI: 10.1016/j.biortech.2018.05.109
    Development of thermophilic composting for maximizing NH3 gas recovery would enable the production of a nitrogen source which is free from pathogen/heavy metal, for the cultivation of high-value microalgae. The present study examined the effect of NH3 recovery, nitrogen mass balance, and microbial community dynamics on thermophilic composting of shrimp aquaculture sludge. The emission of NH3 gas at 60 and 70 °C was 14.7% and 15.6%, respectively, which was higher than that at 50 °C (9.0%). The nitrogen mass balance analysis revealed that higher temperatures enhanced the solubilization of non-dissolved nitrogen and liberation of NH3 gas from the produced NH4+-N. High-throughput microbial community analysis revealed the shift of the dominant bacterial group from Bacillus to Geobacillus with the rise of composting temperature. In conclusion, thermophilic composting of shrimp aquaculture sludge at 60-70 °C was the most favorable condition for enhancing NH3 gas recovery.
    MeSH terms: Ammonia; Nitrogen/chemistry*; Sewage*; Soil; Temperature; Aquaculture*
  6. Patmanathan SN, Gnanasegaran N, Lim MN, Husaini R, Fakiruddin KS, Zakaria Z
    Curr Stem Cell Res Ther, 2018;13(8):632-644.
    PMID: 29895256 DOI: 10.2174/1574888X13666180613081443
    The clustered regularly interspaced short palindromic repeats-associated protein 9 or CRISPR/Cas9 system is one of the hottest topics discussed lately due to its robustness and effectiveness in genome editing. The technology has been widely used in life science research including microbial, plant, animal, and human cell studies. Combined with the pluripotency of stem cells, the technology represents a powerful tool to generate various cell types for disease modeling, drug screening, toxicology, and targeted therapies. Generally, the CRISPR/Cas9 system has been applied in genetic modification of pluripotent or multipotent stem cells, after which the cells are differentiated into specific cell types and used for functional analysis or even clinical transplantation. Recent advancement in CRISPR/Cas9 technology has widened the scope of stem cell research and its therapeutic application. This review provides an overview of the current application and the prospect of CRISPR/Cas9 technology, particularly in stem cell research and therapy.
    MeSH terms: Animals; Humans; Stem Cells/metabolism; Genetic Therapy; Regenerative Medicine; Stem Cell Research*; Clustered Regularly Interspaced Short Palindromic Repeats/genetics*
  7. Ovesen C, Jakobsen JC, Gluud C, Steiner T, Law Z, Flaherty K, et al.
    BMC Res Notes, 2018 Jun 13;11(1):379.
    PMID: 29895329 DOI: 10.1186/s13104-018-3481-8
    OBJECTIVE: We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants' spot sign status.

    RESULTS: Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients. Trial registration ISRCTN93732214 ( http://www.isrctn.com ).

    MeSH terms: Antifibrinolytic Agents/administration & dosage; Antifibrinolytic Agents/pharmacology*; Cerebral Hemorrhage/drug therapy*; Data Interpretation, Statistical*; Hematoma/drug therapy*; Humans; Tranexamic Acid/administration & dosage; Tranexamic Acid/pharmacology*; Outcome Assessment (Health Care)/statistics & numerical data*; Disease Progression
  8. Mandary MB, Poh CL
    Viruses, 2018 06 12;10(6).
    PMID: 29895721 DOI: 10.3390/v10060320
    Enterovirus 71 (EV-A71) is a major etiological agent of hand, foot and mouth disease (HFMD) that mainly affects young children less than five years old. The onset of severe HFMD is due to neurological complications bringing about acute flaccid paralysis and pulmonary oedema. In this review, we address how genetic events such as recombination and spontaneous mutations could change the genomic organization of EV-A71, leading to an impact on viral virulence. An understanding of the recombination mechanism of the poliovirus and non-polio enteroviruses will provide further evidence of the emergence of novel strains responsible for fatal HFMD outbreaks. We aim to see if the virulence of EV-A71 is contributed solely by the presence of fatal strains or is due to the co-operation of quasispecies within a viral population. The phenomenon of quasispecies within the poliovirus is discussed to reflect viral fitness, virulence and its implications for EV-A71. Ultimately, this review gives an insight into the evolution patterns of EV-A71 by looking into its recombination history and how spontaneous mutations would affect its virulence.
    MeSH terms: Hand, Foot and Mouth Disease/pathology; Hand, Foot and Mouth Disease/virology; Humans; Mutation*; Recombination, Genetic*; Genetic Variation*; Virulence; Genome, Viral*; Enterovirus A, Human/classification; Enterovirus A, Human/genetics*; Enterovirus A, Human/pathogenicity*
  9. Mohamad M, Loy SL, Lim PY, Wang Y, Soo KL, Mohamed HJJ
    PMID: 29895806 DOI: 10.3390/ijerph15061250
    The prevalence of childhood obesity is increasing at an alarming rate in Malaysia. Metabolic changes during pregnancy are critical to the development of infant adiposity, due to imbalanced adipokines production. Hence, we aimed to investigate the association of maternal serum and breast milk adipokines with infant adiposity development. The study was conducted from April 2010 until December 2012. A total of 155 healthy pregnant mothers aged 19 to 40 years were recruited during the first and second trimester in Kelantan, Malaysia. Data consisted of maternal sociodemographic details, anthropometry and clinical biochemistry analysis; and the infant’s anthropometry and feeding patterns. Maternal fasting serum and breast milk samples were analysed for adiponectin and leptin levels. Data collection was performed in the second and third trimester of pregnancy, and continued with follow-up visits at birth, two, six, and 12 months postpartum. Multiple linear regression (MLR) analyses were performed to examine the associations between maternal serum and breast milk adiponectin and leptin and infant adiposity development. MLR models showed that, in the first year, as maternal serum and breast milk adiponectin increased, infant weight, BMI-for-age Z scores and abdominal circumference significantly decreased (p < 0.05). Maternal serum and/or breast milk adiponectin was associated with first-year infant adiposity development.
    MeSH terms: Adult; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Malaysia; Male; Milk, Human/metabolism*; Pregnancy; Pregnancy Trimester, Second/metabolism*; Pregnancy Trimester, Third/metabolism*; Prenatal Exposure Delayed Effects/diagnosis; Prenatal Exposure Delayed Effects/etiology; Prenatal Exposure Delayed Effects/pathology; Prospective Studies; Regression Analysis; Risk Factors; Biomarkers/metabolism; Leptin/metabolism; Maternal Nutritional Physiological Phenomena; Adiposity*; Adiponectin/metabolism*; Pediatric Obesity/diagnosis; Pediatric Obesity/etiology*; Pediatric Obesity/pathology
  10. Beck MW, Losada IJ, Menéndez P, Reguero BG, Díaz-Simal P, Fernández F
    Nat Commun, 2018 06 12;9(1):2186.
    PMID: 29895942 DOI: 10.1038/s41467-018-04568-z
    Coral reefs can provide significant coastal protection benefits to people and property. Here we show that the annual expected damages from flooding would double, and costs from frequent storms would triple without reefs. For 100-year storm events, flood damages would increase by 91% to $US 272 billion without reefs. The countries with the most to gain from reef management are Indonesia, Philippines, Malaysia, Mexico, and Cuba; annual expected flood savings exceed $400 M for each of these nations. Sea-level rise will increase flood risk, but substantial impacts could happen from reef loss alone without better near-term management. We provide a global, process-based valuation of an ecosystem service across an entire marine biome at (sub)national levels. These spatially explicit benefits inform critical risk and environmental management decisions, and the expected benefits can be directly considered by governments (e.g., national accounts, recovery plans) and businesses (e.g., insurance).
    MeSH terms: Algorithms; Animals; Conservation of Natural Resources/economics; Conservation of Natural Resources/methods; Conservation of Natural Resources/statistics & numerical data; Cuba; Geography; Indonesia; Malaysia; Mexico; Models, Theoretical; Philippines; Water Movements*; Anthozoa/physiology*; Floods*; Hydrodynamics; Coral Reefs*
  11. Ganeshan M, Bujang MA, Soelar SA, Karalasingam SD, Suharjono H, Jeganathan R
    J Obstet Gynaecol India, 2018 Jun;68(3):173-178.
    PMID: 29895995 DOI: 10.1007/s13224-017-1000-9
    Aims: The aim of this study is to compare obstetric outcomes between overweight and class 1 obesity among pregnant women in their first pregnancy based on WHO's BMI cut-offs and the potential public health action points identified by WHO expert consultations specific for high-risk population such as Asians.

    Methods: This is a retrospective cohort review of data obtained from the Malaysian National Obstetrics and Gynaecology Registry between the year 2010 and year 2012. All women in their first pregnancy with a booking BMI in their first trimester were included in this study. The association between BMI classifications as defined by the WHO cut-offs and the potential public health action points identified by WHO expert consultations towards adverse obstetric outcomes was compared.

    Results: A total of 88,837 pregnant women were included in this study. We noted that the risk of adverse obstetric outcomes was significantly higher using the public health action points identified by WHO expert consultations even among the overweight group as the risk of stillbirths was (OR 1.2; 95% CI 1.0,1.4), shoulder dystocia (OR 1.9; 95% CI 1.2,2.9), foetal macrosomia (OR 1.8; 95% CI 1.6,2.0), caesarean section (OR 1.9; 95% CI 1.8,2.0) and assisted conception (OR 1.9; 95% CI 1.6,2.1).

    Conclusion: A specifically lower BMI references based on the potential public health action points for BMI classifications were a more sensitive predictor of adverse obstetric outcomes, and we recommend the use of these references in pregnancy especially among Asian population.

    MeSH terms: Cesarean Section; Dystocia; Female; Fetal Macrosomia; Gynecology; Humans; Obesity; Obstetrics; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Public Health; Referral and Consultation; Registries; Retrospective Studies; Shoulder; World Health Organization; Body Mass Index; Overweight; Stillbirth
  12. Goulding TC, Khalil M, Tan SH, Dayrat B
    Zookeys, 2018.
    PMID: 29896045 DOI: 10.3897/zookeys.763.21252
    A new genus of onchidiid slugs, Wallaconchis Goulding & Dayrat, gen. n., is described, including ten species. Five species were previously described but known only from the type material: Wallaconchis ater (Lesson, 1830), W. graniferum (Semper, 1880), W. nangkauriense (Plate, 1893), W. buetschlii (Stantschinsky, 1907), and W. gracile (Stantschinsky, 1907), all of which were originally classified in Onchidium Buchannan, 1800. Many new records are provided for these five species, which greatly expand their known geographic distributions. Five species are new: Wallaconchis achleitneri Goulding, sp. n., W. comendadori Goulding & Dayrat, sp. n., W. melanesiensis Goulding & Dayrat, sp. n., W. sinanui Goulding & Dayrat, sp. n., and W. uncinus Goulding & Dayrat, sp. n. Nine of the ten Wallaconchis species are found in the Coral Triangle (eastern Indonesia and the Philippines). Sympatry is high, with up to six species found on the island of Bohol (Philippines) and eight species overlapping in northern Sulawesi (Indonesia). Wallaconchis is distinguished from other onchidiids by its bright dorsal colors (red, yellow, orange) but those are extremely variable and not useful for specific identification. Internally, the reproductive system can be used to identify all Wallaconchis species. The copulatory organs of Wallaconchis species are especially diverse compared to other onchidiid genera, and the possible role of reproductive incompatibility in species diversification is discussed. All specimens examined were freshly collected for the purpose of a worldwide revision of the Onchidiidae Rafinesque, 1815. The species are well delineated using DNA sequences and comparative anatomy. Mitochondrial DNA analysis yields thirteen molecular units separated by a large barcode gap, while nuclear DNA yields nine units. By integrating nuclear DNA and mitochondrial DNA with morphology, ten species are recognized. The natural history of each species (e.g., the microhabitat where they are found) is also documented. Nomenclature is addressed thoroughly (the types of all onchidiid species were examined, lectotypes were designated when needed, nomina dubia are discussed). Morphological characters, transitions to new microhabitats, and diversification processes are discussed in the context of a robust molecular phylogeny.
    MeSH terms: Anatomy, Comparative; Animals; Base Sequence; Cell Nucleus; Color; DNA, Mitochondrial; Genitalia; Indonesia; Mitochondria; Philippines; Phylogeny; Citrus sinensis; Anthozoa; Gastropoda; Sympatry; Islands
  13. Bojanić L, Marković-Peković V, Škrbić R, Stojaković N, Ðermanović M, Bojanić J, et al.
    Front Pharmacol, 2018;9:442.
    PMID: 29896100 DOI: 10.3389/fphar.2018.00442
    Introduction: There are increasing concerns world-wide with growing rates of antibiotic resistance necessitating urgent action. There have been a number of initiatives in the Republic of Srpska in recent years to address this and improve rational antibiotic prescribing and dispensing despite limited resources to fund multiple initiatives. Objective: Analyse antibiotic utilization patterns in the Republic of Srpska following these multiple initiatives as a basis for developing future programmes in the Republic if needed. Methods: Observational retrospective study of total outpatient antibiotic utilization from 2010 to 2015, based on data obtained from the Public Health Institute, alongside documentation of ongoing initiatives to influence utilization. The quality of antibiotic utilization principally assessed according to ESAC, ECDC, and WHO quality indicators and DU 90% (the drug utilization 90%) profile as well as vs. neighboring countries. Results: Following multiple initiatives, antibiotic utilization remained relatively stable in the Republic at 15.6 to 18.4 DIDs, with a decreasing trend in recent years, with rates comparable or lower than neighboring countries. Amoxicillin and the penicillins accounted for 29-40 and 50% of total utilization, respectively. Overall, limited utilization of co-amoxiclav (7-11%), cephalosporins, macrolides, and quinolones, as well as low use of third and fourth generation cephalosporins vs. first and second cephalosporins. However, increasing utilization of co-amoxiclav and azithromycin, as well as higher rates of quinolone utilization compared to some countries, was seen. Conclusions: Multiple interventions in the Republic of Srpska in recent years have resulted in one of the lowest utilization of antibiotics when compared with similar countries, acting as an exemplar to others. However, there are some concerns with current utilization of co-amoxiclav and azithromycin which are being addressed. This will be the subject of future research activities.
  14. Alias H, Lau SCD, Schuitema I, de Sonneville LMJ
    Front Psychol, 2018;9:703.
    PMID: 29896137 DOI: 10.3389/fpsyg.2018.00703
    Objective: This study aimed to evaluate neuropsychological consequences in survivors of childhood brain tumor. Method: A case-control study was conducted over a period of 4 months in a tertiary referral center in Kuala Lumpur, Malaysia. Fourteen survivors of childhood brain tumor aged 7-18 years, who were off-treatment for at least 1 year and were in remission, and 31 unrelated healthy controls were recruited. The median age at diagnosis was 8.20 years (range: 0.92-12.96 years). The diagnoses of brain tumors were medulloblastoma, germ cell tumor, pineocytoma, pilocystic astrocytoma, suprasellar germinoma, and ependymoma. Eleven survivors received central nervous system irradiation. Seven tasks were selected from the Amsterdam Neuropsychological Tasks program to evaluate alertness (processing speed), and major aspects of executive functioning, such as working memory capacity, inhibition, cognitive flexibility, and sustained attention. Speed, stability and accuracy of responses were the main outcome measures. Results: Survivors of childhood brain tumor showed statistically significant poorer performance on all tasks compared to healthy controls. Both processing speed and accuracy were impaired in the survivors, in particular under more complex task conditions. The survivors demonstrated deficits in alertness, sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Longer duration off treatment appeared to be correlated with poorer alertness, memory capacity, and inhibition. Conclusion: Survivors of childhood brain tumor in our center showed impaired neuropsychological functioning. Development of less toxic treatment protocols is important to prevent late effects of cognitive deficits in survivors of childhood brain tumor.
    MeSH terms: Adolescent; Astrocytoma; Attention; Brain Neoplasms; Cerebellar Neoplasms; Child; Child, Preschool; Clinical Protocols; Cognition; Ependymoma; Humans; Infant; Malaysia; Medulloblastoma; Memory, Short-Term; Pinealoma; Case-Control Studies; Outcome Assessment (Health Care); Survivors; Germinoma; Tertiary Care Centers
  15. Wong YC, Abd El Ghany M, Ghazzali RNM, Yap SJ, Hoh CC, Pain A, et al.
    Front Microbiol, 2018;9:1118.
    PMID: 29896180 DOI: 10.3389/fmicb.2018.01118
    A Burkholderia cenocepacia infection usually leads to reduced survival and fatal cepacia syndrome in cystic fibrosis patients. The identification of B. cenocepacia essential genes for in vivo survival is key to designing new anti-infectives therapies. We used the Transposon-Directed Insertion Sequencing (TraDIS) approach to identify genes required for B. cenocepacia survival in the model infection host, Caenorhabditis elegans. A B. cenocepacia J2315 transposon pool of ∼500,000 mutants was used to infect C. elegans. We identified 178 genes as crucial for B. cenocepacia survival in the infected nematode. The majority of these genes code for proteins of unknown function, many of which are encoded by the genomic island BcenGI13, while other gene products are involved in nutrient acquisition, general stress responses and LPS O-antigen biosynthesis. Deletion of the glycosyltransferase gene wbxB and a histone-like nucleoid structuring (H-NS) protein-encoding gene (BCAL0154) reduced bacterial accumulation and attenuated virulence in C. elegans. Further analysis using quantitative RT-PCR indicated that BCAL0154 modulates B. cenocepacia pathogenesis via transcriptional regulation of motility-associated genes including fliC, fliG, flhD, and cheB1. This screen has successfully identified genes required for B. cenocepacia survival within the host-associated environment, many of which are potential targets for developing new antimicrobials.
    MeSH terms: Animals; Anti-Infective Agents; Cystic Fibrosis; Gene Expression Regulation; Histones; Humans; Lipopolysaccharides; Virulence; Glycosyltransferases; Caenorhabditis elegans; O Antigens; Burkholderia Infections; Genes, Essential; Reverse Transcriptase Polymerase Chain Reaction; Genomic Islands; Burkholderia cenocepacia
  16. Farah AH, Lee SY, Gao Z, Yao TL, Madon M, Mohamed R
    Front Plant Sci, 2018;9:712.
    PMID: 29896211 DOI: 10.3389/fpls.2018.00712
    The tribe Aquilarieae of the family Thymelaeaceae consists of two genera, Aquilaria and Gyrinops, with a total of 30 species, distributed from northeast India, through southeast Asia and the south of China, to Papua New Guinea. They are an important botanical resource for fragrant agarwood, a prized product derived from injured or infected stems of these species. The aim of this study was to estimate the genome size of selected Aquilaria species and comprehend the evolutionary history of Aquilarieae speciation through molecular phylogeny. Five non-coding chloroplast DNA regions and a nuclear region were sequenced from 12 Aquilaria and three Gyrinops species. Phylogenetic trees constructed using combined chloroplast DNA sequences revealed relationships of the studied 15 members in Aquilarieae, while nuclear ribosomal DNA internal transcribed spacer (ITS) sequences showed a paraphyletic relationship between Aquilaria species from Indochina and Malesian. We exposed, for the first time, the estimated divergence time for Aquilarieae speciation, which was speculated to happen during the Miocene Epoch. The ancestral split and biogeographic pattern of studied species were discussed. Results showed no large variation in the 2C-values for the five Aquilaria species (1.35-2.23 pg). Further investigation into the genome size may provide additional information regarding ancestral traits and its evolution history.
  17. Vassiliev P, Iezhitsa I, Agarwal R, Marcus AJ, Spasov A, Zhukovskaya O, et al.
    Data Brief, 2018 Jun;18:340-347.
    PMID: 29896521 DOI: 10.1016/j.dib.2018.02.067
    This article contains data that relate to the study carried out in the work of Marcus et al. (2018) [1]. Data represent an information about pharmacophore analysis of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole derivatives and results of construction of the relationship between intraocular pressure (IOP) lowering activity and hypotensive activity of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole derivatives using a multilayer perceptron artificial neural network. In particular, they include the ones listed in this article: 1) table of all pharmacophores of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole derivatives that showed IOP lowering activity; 2) table of all pharmacophores of the compounds that showed absence of IOP lowering activity; 3) table of initial data for artificial neural network analysis of relationship between IOP activity and hypotensive activity of this chemical series; 4) graphical representation of the best neural network model of this dependence; 5) original txt-file of results of pharmacophore analysis; 6) xls-file of initial data for neural network modeling; 7) original stw-file of results of neural network modeling; 8) original xml-file of the best neural network model of dependence between IOP lowering activity and hypotensive activity of these azole derivatives. The data may be useful for researchers interested in designing new drug substances and will contribute to understanding of the mechanisms of IOP lowering activity.
    MeSH terms: Azoles; Benzimidazoles; Intraocular Pressure; Tonometry, Ocular; Drug Design; Neural Networks (Computer)
  18. Marcus AJ, Iezhitsa I, Agarwal R, Vassiliev P, Spasov A, Zhukovskaya O, et al.
    Data Brief, 2018 Jun;18:523-554.
    PMID: 29896529 DOI: 10.1016/j.dib.2018.03.019
    This data is to document the intraocular pressure (IOP) lowering activity of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds in ocular normotensive rats. Effects of single drop application of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds on IOP in ocular normotensive rats are presented at 3 different concentrations (0.1%, 0.2% and 0.4%). Time course of changes in IOP is presented over 6 h period post-instillation. The IOP lowering activities of test compounds were determined by assessing maximum decrease in IOP from baseline and corresponding control, duration of IOP lowering and area under curve (AUC) of time versus response curve. Data shown here may serve as benchmarks for other researchers studying IOP-lowering effect of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds and would be useful in determining therapeutic potential of these test compounds as IOP lowering agents.
    MeSH terms: Animals; Benzimidazoles; Eye; Intraocular Pressure; Tonometry, Ocular; Area Under Curve; Benchmarking; Rats
  19. Yusufzai SK, Osman H, Khan MS, Abd Razik BM, Ezzat MO, Mohamad S, et al.
    Chem Cent J, 2018 Jun 12;12(1):69.
    PMID: 29896651 DOI: 10.1186/s13065-018-0435-0
    A series of novel 4-thiazolidinone inhibitors SKYa-SKYg, containing coumarin as a core structure were synthesized via facile and efficient method. The structures of the synthesized compounds were established by extensive spectroscopic studies (FT IR, 1D NMR, 2D NMR, LC-MS) and elemental analysis. All the synthesized hybrids were further evaluated for their potential as anti-tubercular agents against Mycobacterium tuberculosis H37Rv ATCC 25618, and anti-bacterial agents against Escherichia coli, Enterobacter aerogenes, Salmonella typhi, Streptococcus pneumoniae and Staphylococcus aureus. Interestingly, the hybrids displayed potent bioactivity. However, compounds SKYc, SKYd, and SKYe appeared to be more effective against the tested bacterial strains, among which compound SKYb showed the highest inhibition against all the bacterial strains ranging from 41 to 165 μg/mL, as compared to the standards, streptomycin, kanamycin and vancomycin. Moreover, derivative SKYa was found to be the strongest against M. tuberculosis (83 μg/mL). Additionally, the anti-dengue potential of the coumarin hybrids as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors was calculated using computational molecular docking approach, with reference to the standards 4-hydroxypanduratin, panduratin and ethyl 3-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy)propanoate with DS of - 3.379, - 3.189 and - 3.381, respectively. The docking results revealed that the synthesized hybrids exhibited potent anti-dengue activity among which compounds SKYf, SKYd, SKYc and SKYe were found to be the best ones with docking scores of - 4.014, - 3.964, - 3.905 and - 3.889. In summary, we discovered 4-thiazolidinone coumarin derivatives as a new scaffold that may eventually yield useful compounds in the treatment of bacterial and viral infections.
  20. Zainal Abidin SA, Rajadurai P, Hoque Chowdhury ME, Othman I, Naidu R
    Molecules, 2018 06 08;23(6).
    PMID: 29890640 DOI: 10.3390/molecules23061388
    The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC50 value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer.
    MeSH terms: Antineoplastic Agents/pharmacology*; Colonic Neoplasms/enzymology; Colonic Neoplasms/pathology*; Crotalid Venoms/enzymology*; Humans; Apoptosis/drug effects*; Cell Line, Tumor; Cell Proliferation/drug effects*; L-Amino Acid Oxidase/pharmacology*; Caspase 3/metabolism
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