Browse publications by year: 2019

  1. Mohamad N, Abdul Khanan MF, Ahmad A, Md Din AH, Shahabi H
    Sensors (Basel), 2019 Aug 31;19(17).
    PMID: 31480412 DOI: 10.3390/s19173778
    Evaluating water level changes at intertidal zones is complicated because of dynamic tidal inundation. However, water level changes during different tidal phases could be evaluated using a digital surface model (DSM) captured by unmanned aerial vehicle (UAV) with higher vertical accuracy provided by a Global Navigation Satellite System (GNSS). Image acquisition using a multirotor UAV and vertical data collection from GNSS survey were conducted at Kilim River, Langkawi Island, Kedah, Malaysia during two different tidal phases, at high and low tides. Using the Structure from Motion (SFM) algorithm, a DSM and orthomosaics were produced as the main sources of data analysis. GNSS provided horizontal and vertical geo-referencing for both the DSM and orthomosaics during post-processing after field observation at the study area. The DSM vertical accuracy against the tidal data from a tide gauge was about 12.6 cm (0.126 m) for high tide and 34.5 cm (0.345 m) for low tide. Hence, the vertical accuracy of the DSM height is still within a tolerance of ±0.5 m (with GNSS positioning data). These results open new opportunities to explore more validation methods for water level changes using various aerial platforms besides Light Detection and Ranging (LiDAR) and tidal data in the future.
    MeSH terms: Algorithms; Malaysia; Motion; Surveys and Questionnaires; Water; Geographic Information Systems; Rivers; Islands
  2. Ibrahim R, Hussein MZ, Yusof NA, Abu Bakar F
    Nanomaterials (Basel), 2019 Aug 31;9(9).
    PMID: 31480466 DOI: 10.3390/nano9091239
    Carbon nanotube-quicklime nanocomposites (CQNs) have been synthesized via the chemical vapor deposition (CVD) of n-hexane using a nickel metal catalyst supported on calcined carbonate stones at temperatures of 600-900 °C. The use of a Ni/CaO(10 wt%) catalyst required temperatures of at least 700 °C to obtain XRD peaks attributable to carbon nanotubes (CNTs). The CQNs prepared using a Ni/CaO catalyst of various Ni contents showed varying diameters and the remaining catalyst metal particles could still be observed in the samples. Thermogravimetric analysis of the CQNs showed that there were two major weight losses due to the amorphous carbon decomposition (300-400 °C) and oxidation of CNTs (400-600 °C). Raman spectroscopy results showed that the CQNs with the highest graphitization were synthesized using Ni/CaO (10 wt%) at 800 °C with an IG/ID ratio of 1.30. The cyclic voltammetry (CV) of screen-printed carbon electrodes (SPCEs) modified with the CQNs showed that the performance of nanocomposite-modified SPCEs were better than bare SPCEs. When compared to carboxylated multi-walled carbon nanotubes or MWNT-COOH-modified SPCEs, the CQNs synthesized using Ni/CaO (10 wt%) at 800 °C gave higher CV peak currents and comparable electron transfer, making it a good alternative for screen-printed electrode modification.
    MeSH terms: Carbonates; Electrodes; Electron Transport; Electrons; Nickel; Oxides; Spectrum Analysis, Raman; Temperature; Weight Loss; Calcium Compounds; Nanotubes, Carbon; Nanocomposites
  3. Okolo C, Rafique R, Iqbal SS, Subhani T, Saharudin MS, Bhat BR, et al.
    Molecules, 2019 Sep 01;24(17).
    PMID: 31480573 DOI: 10.3390/molecules24173176
    A novel tweakable nanocomposite was prepared by spark plasma sintering followed by systematic oxidation of carbon nanotube (CNT) molecules to produce alumina/carbon nanotube nanocomposites with surface porosities. The mechanical properties (flexural strength and fracture toughness), surface area, and electrical conductivities were characterized and compared. The nanocomposites were extensively analyzed by field emission scanning electron microscopy (FE-SEM) for 2D qualitative surface morphological analysis. Adding CNTs in ceramic matrices and then systematically oxidizing them, without substantial reduction in densification, induces significant capability to achieve desirable/application oriented balance between mechanical, electrical, and catalytic properties of these ceramic nanocomposites. This novel strategy, upon further development, opens new level of opportunities for real-world/industrial applications of these relatively novel engineering materials.
    MeSH terms: Aluminum Oxide/chemistry; Ceramics/chemistry*; Electric Conductivity; Nanotubes, Carbon/ultrastructure; Nanotubes, Carbon/chemistry*; Nanocomposites/ultrastructure; Nanocomposites/chemistry*
  4. Koloor SSR, Rahimian-Koloor SM, Karimzadeh A, Hamdi M, Petrů M, Tamin MN
    Polymers (Basel), 2019 Sep 02;11(9).
    PMID: 31480660 DOI: 10.3390/polym11091435
    The mechanical behavior of graphene/polymer interfaces in the graphene-reinforced epoxy nanocomposite is one of the factors that dictates the deformation and damage response of the nanocomposites. In this study, hybrid molecular dynamic (MD) and finite element (FE) simulations of a graphene/polymer nanocomposite are developed to characterize the elastic-damage behavior of graphene/polymer interfaces under a tensile separation condition. The MD results show that the graphene/epoxy interface behaves in the form of elastic-softening exponential regressive law. The FE results verify the adequacy of the cohesive zone model in accurate prediction of the interface damage behavior. The graphene/epoxy cohesive interface is characterized by normal stiffness, tensile strength, and fracture energy of 5 × 10-8 (aPa·nm-1), 9.75 × 10-10 (nm), 2.1 × 10-10 (N·nm-1) respectively, that is followed by an exponential regressive law with the exponent, α = 7.74. It is shown that the commonly assumed bilinear softening law of the cohesive interface could lead up to 55% error in the predicted separation of the interface.
    MeSH terms: Epoxy Resins; Graphite; Musculoskeletal Physiological Phenomena; Polymers; Tensile Strength; Finite Element Analysis; Fractures, Bone; Nanocomposites; Physical Phenomena; Molecular Dynamics Simulation
  5. Cioffi MB, Ráb P, Ezaz T, Bertollo LAC, Lavoué S, Oliveira EA, et al.
    Int J Mol Sci, 2019 Sep 02;20(17).
    PMID: 31480792 DOI: 10.3390/ijms20174296
    Arowanas (Osteoglossinae) are charismatic freshwater fishes with six species and two genera (Osteoglossum and Scleropages) distributed in South America, Asia, and Australia. In an attempt to provide a better assessment of the processes shaping their evolution, we employed a set of cytogenetic and genomic approaches, including i) molecular cytogenetic analyses using C- and CMA3/DAPI staining, repetitive DNA mapping, comparative genomic hybridization (CGH), and Zoo-FISH, along with ii) the genotypic analyses of single nucleotide polymorphisms (SNPs) generated by diversity array technology sequencing (DArTseq). We observed diploid chromosome numbers of 2n = 56 and 54 in O. bicirrhosum and O. ferreirai, respectively, and 2n = 50 in S. formosus, while S. jardinii and S. leichardti presented 2n = 48 and 44, respectively. A time-calibrated phylogenetic tree revealed that Osteoglossum and Scleropages divergence occurred approximately 50 million years ago (MYA), at the time of the final separation of Australia and South America (with Antarctica). Asian S. formosus and Australian Scleropages diverged about 35.5 MYA, substantially after the latest terrestrial connection between Australia and Southeast Asia through the Indian plate movement. Our combined data provided a comprehensive perspective of the cytogenomic diversity and evolution of arowana species on a timescale.
    MeSH terms: Animals; Chromosome Banding; Chromosome Mapping; Biological Evolution*; Fishes/genetics*; Geography; Genetic Variation; Genomics*; Principal Component Analysis; Karyotype; Genotyping Techniques
  6. Finnegan SR, White NJ, Koh D, Camus MF, Fowler K, Pomiankowski A
    Proc Biol Sci, 2019 Sep 11;286(1910):20191414.
    PMID: 31480972 DOI: 10.1098/rspb.2019.1414
    A number of species are affected by Sex-Ratio (SR) meiotic drive, a selfish genetic element located on the X-chromosome that causes dysfunction of Y-bearing sperm. SR is transmitted to up to 100% of offspring, causing extreme sex ratio bias. SR in several species is found in a stable polymorphism at a moderate frequency, suggesting there must be strong frequency-dependent selection resisting its spread. We investigate the effect of SR on female and male egg-to-adult viability in the Malaysian stalk-eyed fly, Teleopsis dalmanni. SR meiotic drive in this species is old, and appears to be broadly stable at a moderate (approx. 20%) frequency. We use large-scale controlled crosses to estimate the strength of selection acting against SR in female and male carriers. We find that SR reduces the egg-to-adult viability of both sexes. In females, homozygous females experience greater reduction in viability (sf = 0.242) and the deleterious effects of SR are additive (h = 0.511). The male deficit in viability (sm = 0.214) is not different from that in homozygous females. The evidence does not support the expectation that deleterious side effects of SR are recessive or sex-limited. We discuss how these reductions in egg-to-adult survival, as well as other forms of selection acting on SR, may maintain the SR polymorphism in this species.
    MeSH terms: Animals; Diptera/physiology*; Eye*; Female; Male; Meiosis*; Polymorphism, Genetic; Sex Ratio*; Spermatozoa; X Chromosome
  7. Dong M, Zeng LN, Zhang Q, Yang SY, Chen LY, Sim K, et al.
    J Geriatr Psychiatry Neurol, 2019 11;32(6):304-311.
    PMID: 31480982 DOI: 10.1177/0891988719862636
    BACKGROUND AND OBJECTIVE: Antipsychotic polypharmacy (APP) is a controversial topic in the treatment of older adults with schizophrenia. The objective of this study was to examine the use of APP in older adult Asian patients with schizophrenia and its associated demographic and clinical factors.

    METHODS: This study was based on the fourth survey of the consortium known as the Research on Asian Psychotropic Prescription Pattern for Antipsychotics. Fifteen Asian countries/territories participated in this survey, including Bangladesh, Mainland China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam. Basic demographic and clinical characteristics were collected using a standardized data collection form.

    RESULTS: Among the 879 older adults with schizophrenia included in the survey, the rate of APP was 40.5%. Multiple logistic regression analysis revealed that higher antipsychotic doses (P < .001, odds ratio [OR] = 1.003, 95% confidence interval [CI]: 1.002-1.003), longer duration of illness (P = .02, OR = 1.845, 95% CI: 1.087-3.132), and the prescription of anticholinergics (P < .001, OR = 1.871, 95% CI: 1.329-2.635), second-generation antipsychotics (P = .001, OR = 2.264, 95% CI: 1.453-3.529), and first-generation antipsychotics (P < .001, OR = 3.344, 95% CI: 2.307-4.847) were significantly associated with APP.

    CONCLUSION: Antipsychotic polypharmacy was common in older adult Asian patients with schizophrenia. Compared to the results of previous surveys, the use of APP showed a declining trend over time. Considering the general poor health status of older patients with schizophrenia and their increased risk of drug-induced adverse events, the use of APP in this population needs careful consideration.

    MeSH terms: Aged; Aged, 80 and over; Aging; Female; Humans; Male; Middle Aged; Schizophrenia/drug therapy*; Antipsychotic Agents/pharmacology; Antipsychotic Agents/therapeutic use*; Polypharmacy*; Asian Continental Ancestry Group
  8. Masood M, Aggarwal A, Reidpath DD
    BMC Public Health, 2019 Sep 03;19(1):1212.
    PMID: 31481044 DOI: 10.1186/s12889-019-7536-0
    BACKGROUND: To investigate the association between national culture and national BMI in 53 low-middle- and high-income countries.

    METHODS: Data from World Health Survey conducted in 2002-2004 in low-middle- and high-income countries were used. Participants aged 18 years and over were selected using multistage, stratified cluster sampling. BMI was used as an outcome variable. Culture of the countries was measured using Hofstede's cultural dimensions: Uncertainty avoidance, individualism, Power Distance and masculinity. The potential determinants of individual-level BMI were participants' sex, age, marital status, education, occupation as well as household-wealth and location (rural/urban) at the individual-level. The country-level factors used were average national income (GNI-PPP), income inequality (Gini-index) and Hofstede's cultural dimensions. A two-level random-intercepts and fixed-slopes model structure with individuals nested within countries were fitted, treating BMI as a continuous outcome variable.

    RESULTS: A sample of 156,192 people from 53 countries was included in this analysis. The design-based (weighted) mean BMI (SE) in these 53 countries was 23.95(0.08). Uncertainty avoidance (UAI) and individualism (IDV) were significantly associated with BMI, showing that people in more individualistic or high uncertainty avoidance countries had higher BMI than collectivist or low uncertainty avoidance ones. This model explained that one unit increase in UAI or IDV was associated with 0.03 unit increase in BMI. Power distance and masculinity were not associated with BMI of the people. National level Income was also significantly associated with individual-level BMI.

    CONCLUSION: National culture has a substantial association with BMI of the individuals in the country. This association is important for understanding the pattern of obesity or overweight across different cultures and countries. It is also important to recognise the importance of the association of culture and BMI in developing public health interventions to reduce obesity or overweight.

    MeSH terms: Adult; Cross-Cultural Comparison*; Female; Humans; Male; Middle Aged; Obesity/epidemiology*; Global Health/statistics & numerical data*; Body Mass Index*; Multilevel Analysis
  9. Md Roduan MR, Abd Hamid R, Mohtarrudin N
    BMC Complement Altern Med, 2019 Sep 03;19(1):238.
    PMID: 31481122 DOI: 10.1186/s12906-019-2650-1
    BACKGROUND: Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting activity has not been reported yet. Therefore, this study was aimed to investigate antitumor-promoting activity of annonacin via in vivo two-stage mouse skin tumorigenesis model and its molecular pathways involved.

    METHODS: Mice were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 μL) followed by, in subsequent week, repeated promotion (twice weekly; 22 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μL). Annonacin (85 nM) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application for 22 weeks. Upon termination, histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted to elucidate the potential mechanism of annonacin.

    RESULTS: With comparison to the carcinogen control, Annonacin significantly increased the tumor latency period and reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, mTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis.

    CONCLUSIONS: Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.

    MeSH terms: Animals; Carcinogens/toxicity; Female; Furans/pharmacology*; Kidney/drug effects; Lactones/pharmacology*; Liver/drug effects; Mice, Inbred ICR; Skin/drug effects; Skin/pathology; Tetradecanoylphorbol Acetate/toxicity; 9,10-Dimethyl-1,2-benzanthracene/toxicity; Signal Transduction/drug effects*; Anticarcinogenic Agents/pharmacology*; Mice; Carcinogenesis/drug effects*
  10. Butt J, Jenab M, Pawlita M, Overvad K, Tjonneland A, Olsen A, et al.
    Cancer Epidemiol Biomarkers Prev, 2019 Sep;28(9):1552-1555.
    PMID: 31481495 DOI: 10.1158/1055-9965.EPI-19-0313
    BACKGROUND: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort.

    METHODS: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).

    RESULTS: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62-1.06).

    CONCLUSIONS: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.

    IMPACT: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.

    MeSH terms: Female; Humans; Prospective Studies; Colorectal Neoplasms/blood; Colorectal Neoplasms/pathology; Colorectal Neoplasms/virology*; Fusobacterium nucleatum/pathogenicity*
  11. Kohno A, Dahlui M, Nik Farid ND, Ali SH, Nakayama T
    BMJ Open, 2019 09 03;9(9):e027377.
    PMID: 31481551 DOI: 10.1136/bmjopen-2018-027377
    OBJECTIVE: To examine individual, familial, community and societal issues surrounding the reasons for child marriage in Kelantan, Malaysia.

    DESIGN: Qualitative study by means of semistructured interviews with women and key informants, using social-ecological model as a conceptual framework.

    SETTING: Interviews were conducted in Kota Bharu district, Kelantan, a northeast state in Peninsular Malaysia.

    PARTICIPANTS: Eighteen women of reproductive age (18 to 44 years old) that experienced their first marriage below the age of 18, as well as five key informants, consisting of a government officer, a community leader, an officer from religious department and two mothers. The women were recruited from a reproductive health clinic. The key informants who had specialised knowledge related to child marriage were selectively chosen.

    RESULTS: Three themes emerged that aligned with the social-ecological model: immaturity in decision-making, family poverty and religious and cultural norms.

    CONCLUSIONS: The findings imply that sex education and awareness-building activities regarding the consequences of child marriage must be implemented to eradicate child marriage in Malaysia. Such implementation must be coordinated as a team-based approach involving experts in such fields as law, religion, psychology, social-welfare and public health. In order to increase the awareness of child marriage consequences, the target for awareness must extend not only to the adolescent girls and their families, but also to the community and society at large by clearly communicating the negative consequences of and addressing the drivers for child marriage.

    MeSH terms: Adolescent; Female; Humans; Health Knowledge, Attitudes, Practice; Malaysia; Male; Poverty*; Religion*; Social Environment; Women's Rights; Needs Assessment; Qualitative Research; Reproductive Health/standards; Social Validity, Research
  12. Taheripour F, Hertel TW, Ramankutty N
    Proc Natl Acad Sci U S A, 2019 09 17;116(38):19193-19199.
    PMID: 31481625 DOI: 10.1073/pnas.1903476116
    The global demand for palm oil has grown rapidly over the past several decades. Much of the output expansion has occurred in carbon- and biodiversity-rich forest lands of Malaysia and Indonesia (M&I), contributing to record levels of terrestrial carbon emissions and biodiversity loss. This has led to a variety of voluntary and mandatory regulatory actions, as well as calls for limits on palm oil imports from M&I. This paper offers a comprehensive, global assessment of the economic and environmental consequences of alternative policies aimed at limiting deforestation from oil palm expansion in M&I. It highlights the challenges of limiting forest and biodiversity loss in the presence of market-mediated spillovers into related oilseed and agricultural commodity and factor markets, both in M&I and overseas. Indeed, limiting palm oil production or consumption is unlikely to halt deforestation in M&I in the absence of active forest conservation incentives. Policies aimed at restricting palm oil production in M&I also have broader consequences for the economy, including significant impacts on consumer prices, real wages, and welfare, that vary among different global regions. A crucial distinction is whether the initiative is undertaken domestically, in which case the M&I region could benefit, or by major palm oil importers, in which case M&I loses income. Nonetheless, all policies considered here pass the social welfare test of global carbon dioxide mitigation benefits exceeding their costs.
    MeSH terms: Agriculture; Carbon Dioxide; Conservation of Natural Resources; Indonesia; Malaysia; Motivation; Salaries and Fringe Benefits; Social Welfare; Biodiversity; Forests
  13. Mohamed Nor NMI, Salleh B, Leslie JF
    Plant Pathol J, 2019 Aug;35(4):301-312.
    PMID: 31481853 DOI: 10.5423/PPJ.OA.03.2019.0049
    Sorghum is the fifth most important cereal worldwide, spreading from Africa throughout the world. It is particularly important in the semi-arid tropics due to its drought tolerance, and when cultivated in Southeast Asia commonly occurs as a second crop during the dry season. We recovered Fusarium from sorghum in Thailand and found F. proliferatum, F. thapsinum and F. verticillioides most frequently, and intermittent isolates of F. sacchari and F. beomiforme. The relatively high frequencies of F. proliferatum and F. verticillioides, suggest mycotoxin contamination, particularly fumonisins and moniliformin, should be evaluated. Genetic variation within the three commonly recovered species was characterized with vegetative compatibility, mating type, Amplified Fragment Length Polymorphisms (AFLPs), and female fertility. Effective population number (N e ) was highest for F. verticillioides and lowest for F. thapsinum with values based on mating type allele frequencies higher than those based on female fertility. Based on AFLP genetic variation, the F. thapsinum populations were the most closely related, the F. verticillioides populations were the most distantly related, and the F. proliferatum populations were in an intermediate position. The genetic variation observed could result if F. thapsinum is introduced primarily with seed, while F. proliferatum and F. verticillioides could arrive with seed or be carried over from previous crops, e.g., rice or maize, which sorghum is following. Confirmation of species transmission patterns is needed to understand the agricultural systems in which sorghum is grown in Southeast Asia, which are quite different from the systems found in Africa, Australia, India and the Americas.
  14. Liang Y, Ahmad Mohiddin MN, Bahauddin R, Hidayatul FO, Nazni WA, Lee HL, et al.
    Comput Math Methods Med, 2019;2019:1923479.
    PMID: 31481976 DOI: 10.1155/2019/1923479
    In this paper, we will start off by introducing the classical Ross-Macdonald model for vector-borne diseases which we use to describe the transmission of dengue between humans and Aedes mosquitoes in Shah Alam, which is a city and the state capital of Selangor, Malaysia. We will focus on analysing the effect of using the Mosquito Home System (MHS), which is an example of an autodissemination trap, in reducing the number of dengue cases by changing the Ross-Macdonald model. By using the national dengue data from Malaysia, we are able to estimate λ, which represents the initial growth rate of the dengue epidemic, and this allows us to estimate the number of mosquitoes in Malaysia. A mathematical expression is also constructed which allows us to estimate the potential number of breeding sites of Aedes mosquitoes. By using the data available from the MHS trial carried out in Section 15 of Shah Alam, we included the potential effect of the MHS into the dengue model and thus modelled the impact MHS has on the spread of dengue within the trial area. We then extended our results to analyse the effect of the MHSs on reducing the number of dengue cases in the whole of Malaysia. A new model was constructed with a basic reproduction number, R0,MalaMHS, which allows us to identify the required MHSs coverage needed to achieve extinction in Malaysia. Numerical simulations and tables of results were also produced to illustrate our results.
    MeSH terms: Aedes/virology; Animals; Cities/epidemiology; Computer Simulation; Dengue/epidemiology; Dengue/prevention & control*; Dengue/transmission*; Humans; Malaysia/epidemiology; Models, Biological; Mosquito Control/instrumentation*; Mosquito Control/statistics & numerical data; Basic Reproduction Number/statistics & numerical data; Mathematical Concepts; Epidemics; Mosquito Vectors/virology
  15. Al-Khdhairawi AAQ, Cordell GA, Thomas NF, Shivanagere Nagojappa NB, Weber JF
    Org Biomol Chem, 2019 10 28;17(40):8943-8957.
    PMID: 31482157 DOI: 10.1039/c9ob01501a
    Diterpene pyrones (DTPs) are a group of well-known, mainly fungal, natural products, first isolated in 1966. As the name indicates, they are composed of two main structural features: a diterpenyl moiety and a pyrone ring. Various names have been given to this class of metabolites; however, biogenetic evidence indicates that they originate through the same metabolic pathway. Based on their biosynthesis, which leads to differences in their structural architecture, the DTPs can be classified into three main types. In addition to their intriguing chemistry, these compounds demonstrate a wide range of biological activities rendering them a desirable target for total synthesis. To date, sixty-seven DTPs have been isolated from various fungal species, with one example originating from the plant kingdom. This review aims at unifying the classification of these compounds, in addition to presenting a detailed description of their isolation, bioactivities, biosynthesis, and total synthesis.
    MeSH terms: Biological Products/chemical synthesis; Biological Products/metabolism*; Biological Products/chemistry*; Diterpenes/chemical synthesis; Diterpenes/metabolism*; Diterpenes/chemistry*; Pyrones/chemical synthesis; Pyrones/metabolism*; Pyrones/chemistry*; Molecular Structure
  16. Hoo WPY, Siak PY, In LLA
    Curr Top Med Chem, 2019;19(23):2158-2175.
    PMID: 31483231 DOI: 10.2174/1568026619666190904163524
    The occurrence of somatic substitution mutations of the KRAS proto-oncogene is highly prevalent in certain cancer types, which often leads to constant activation of proliferative pathways and subsequent neoplastic transformation. It is often seen as a gateway mutation in carcinogenesis and has been commonly deemed as a predictive biomarker for poor prognosis and relapse when conventional chemotherapeutics are employed. Additionally, its mutational status also renders EGFR targeted therapies ineffective owing to its downstream location. Efforts to discover new approaches targeting this menacing culprit have been ongoing for years without much success, and with incidences of KRAS positive cancer patients being on the rise, researchers are now turning towards immunotherapies as the way forward. In this scoping review, recent immunotherapeutic developments and advances in both preclinical and clinical studies targeting K-ras directly or indirectly via its downstream signal transduction machinery will be discussed. Additionally, some of the challenges and limitations of various K-ras targeting immunotherapeutic approaches such as vaccines, adoptive T cell therapies, and checkpoint inhibitors against KRAS positive cancers will be deliberated.
    MeSH terms: Animals; Humans; Immunotherapy*; Mutation*; Neoplasms/genetics; Neoplasms/immunology; Neoplasms/therapy*; T-Lymphocytes/immunology*; Vaccines/immunology*; Oncogene Protein p21(ras)/antagonists & inhibitors*; Oncogene Protein p21(ras)/genetics; Oncogene Protein p21(ras)/immunology
  17. Chan SJ, Niu W, Hayakawa K, Hamanaka G, Wang X, Cheah PS, et al.
    Stem Cells Transl Med, 2019 Dec;8(12):1242-1248.
    PMID: 31483567 DOI: 10.1002/sctm.19-0159
    Biomaterials provide novel platforms to deliver stem cell and growth factor therapies for central nervous system (CNS) repair. The majority of these approaches have focused on the promotion of neural progenitor cells and neurogenesis. However, it is now increasingly recognized that glial responses are critical for recovery in the entire neurovascular unit. In this study, we investigated the cellular effects of epidermal growth factor (EGF) containing hydrogels on primary astrocyte cultures. Both EGF alone and EGF-hydrogel equally promoted astrocyte proliferation, but EGF-hydrogels further enhanced astrocyte activation, as evidenced by a significantly elevated Glial fibrillary acidic protein (GFAP) gene expression. Thereafter, conditioned media from astrocytes activated by EGF-hydrogel protected neurons against injury and promoted synaptic plasticity after oxygen-glucose deprivation. Taken together, these findings suggest that EGF-hydrogels can shift astrocytes into neuro-supportive phenotypes. Consistent with this idea, quantitative-polymerase chain reaction (qPCR) demonstrated that EGF-hydrogels shifted astrocytes in part by downregulating potentially negative A1-like genes (Fbln5 and Rt1-S3) and upregulating potentially beneficial A2-like genes (Clcf1, Tgm1, and Ptgs2). Further studies are warranted to explore the idea of using biomaterials to modify astrocyte behavior and thus indirectly augment neuroprotection and neuroplasticity in the context of stem cell and growth factor therapies for the CNS. Stem Cells Translational Medicine 2019;8:1242&1248.
    MeSH terms: Animals; Astrocytes/cytology*; Astrocytes/drug effects; Cell Differentiation; Cells, Cultured; Epidermal Growth Factor/pharmacology*; Neuroprotective Agents/pharmacology*; Hydrogels/chemistry*; Rats; Neural Stem Cells/cytology*; Neural Stem Cells/drug effects
  18. Izadi E, Afshan G, Patel RP, Rao VM, Liew KB, Meor Mohd Affandi MMR, et al.
    Front Pharmacol, 2019;10:881.
    PMID: 31474853 DOI: 10.3389/fphar.2019.00881
    Counterfeit and substandard medicines are recognized as one of serious threats to public health. The product quality of antibacterial medicine will compromise patients' recovery and increase the chance of antibacterial resistance. The review aims to provide a summary of low quality levofloxacin issues and the risk factors as well as suggesting the aspects of product quality that need to be regulated strictly. Quality of the active ingredient, levofloxacin, has an important role to contribute to successful therapy. The poor quality of raw material, directly and indirectly, causes treatment failure as the presence of insufficient dose, mislabeled content, and poor dissolution characteristics can lead to lower bioavailability. Identifying and reporting these factors can potentially help in improving the quality of drug marketed in various developing countries and may also reduce the incidences of treatment failure. Dissolution test is used for testing the dissolution profiles and the rate of drug release from solid formulation such as oral formulations, thus providing information regarding the in vivo performance of a formulation and its bioequivalence. On the other hand, quality-testing procedures are used for comparing the quality of products.
    MeSH terms: Anti-Bacterial Agents; Biological Availability; Developing Countries; Emollients; Humans; Public Health; Risk Factors; Solubility; Therapeutic Equivalency; Incidence; Treatment Failure; Drug Resistance, Bacterial; Levofloxacin; Drug Liberation
  19. Ee CL, Mohd Abdullah AA, Samsudin A, Khaliddin N
    Ulus Travma Acil Cerrahi Derg, 2019 09;25(5):527-530.
    PMID: 31475330 DOI: 10.5505/tjtes.2018.57059
    Non-accidental injury (NAI) is not an uncommon problem worldwide, which leads to significant morbidity and mortality in infants. The presence of retinal or subdural haemorrhages, or encephalopathy with injuries inconsistent with the clinical history is highly suggestive of NAI. In this study, we report on a case of a a 3-month-old infant who presented to the casualty department with a very sudden onset of recurrent generalised tonic-clonic seizures. There was no history of trauma or visible external signs. She was found to have bilateral subdural haemorrhages and atypical unilateral ischaemic retinopathy. Retinal photocoagulation was performed with subsequent resolution of vitreous and retinal haemorrhages. However, visual recovery in that eye remained poor. The findings showed that a high index of suspicion of NAI is required in infants with intracranial haemorrhage and unilateral retinal haemorrhages.
    MeSH terms: Child Abuse*; Female; Hematoma, Subdural*; Humans; Infant; Light Coagulation; Retinal Hemorrhage*; Seizures
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