Browse publications by year: 2018

Fulltext Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia

Subramaniam P, Jabar KA, Kee BP, Chong CW, Nathan AM, de Bruyne J, et al.

Indian J Med Res, 2018 Aug;148(2):225-231.
PMID: 30381546 DOI: 10.4103/ijmr.IJMR_1987_16

Background & objectives: Streptococcus pneumoniae: (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia.
Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated.
Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F.
Interpretation & conclusions: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.

MeSH terms: Child; Child, Preschool; Female; Hospitals, Teaching*; Humans; Infant; Male; Microbial Sensitivity Tests; Nasopharynx/microbiology; Penicillins/adverse effects; Penicillins/therapeutic use; Pneumococcal Infections/drug therapy*; Pneumococcal Infections/genetics; Pneumococcal Infections/microbiology; Pneumococcal Infections/epidemiology; Pneumonia/drug therapy*; Pneumonia/genetics; Pneumonia/microbiology; Pneumonia/epidemiology; Serotyping; Streptococcus pneumoniae/pathogenicity; Drug Resistance, Bacterial/genetics; Tertiary Care Centers*
Insights into the Electrocatalytic Hydrogen Evolution Reaction Mechanism on Two-Dimensional Transition-Metal Carbonitrides (MXene)

Huang B, Zhou N, Chen X, Ong WJ, Li N

Chemistry, 2018 Dec 10;24(69):18479-18486.
PMID: 30381861 DOI: 10.1002/chem.201804686

Developing highly active, non-noble-metal H2 -evolution catalysts is appealing yet still remains a great challenge in the field of electrocatalytic and photocatalytic H2 production. In this work, high quality transition-metal carbonitrides M3 CN (MXene) are investigated using well-defined density functional theory (DFT) calculations. The structural configurations, H-adsorption free energy (ΔGH ) and charge transfer for bare, surface-terminated and transition-metal (TM)-modified M3 CNO2 are systematically studied. The calculated results indicate that all bare transition metal carbonitrides exhibit strong binding between H atom and catalysts. In addition, only Ti3 CNO2 and Nb3 CNO2 have the potential to be HER active catalysts based on the ΔGH results. In an attempt to overcome poor HER activity limitations, we apply O as well as OH mixed groups and TMs modification on the Ti3 CNO2 surface for tuning HER activity, and a significant improvement of HER activity is observed. Overall, this work presents in-depth investigations for transition-metal carbonitrides (MXene) and opens up new designs for robust metal carbonitrides as noble-metal-free cocatalysts for highly efficient and low-cost MXene-based nanocomposites for water splitting applications.
Influence of Maternal Characteristics during Pregnancy on the Infant Early Life Immune Responses in a High HIV Burdened Setting in Harare, Zimbabwe

Nhidza AF, Naicker T, Stray-Pedersen B, Gumbo F, Chisango T, Sibanda E, et al.

Afr J Reprod Health, 2018 Sep;22(3):43-50.
PMID: 30381931 DOI: 10.29063/ajrh2018/v22i3.5

This study aimed at investigating the maternal characteristics that in turn influence the immunological status of infants in asymptomatic enteric pathogen carriers in mother baby pairs (MBPs) in a high HIV burdened population in Harare, Zimbabwe. BIOPLEX immunoassay was used to analyse serum samples from 39 MBPs for 27 cytokines and 6 immunoglobulins. The MBP were purposively selected based on HIV infection and Entamoeba histolytica carriage. Logistic regression was used to identify any link between maternal demographic and clinical data with infant cytokine and immunoglobulin levels. Maternal E. histolytica carriers were more likely to have infants with low levels of IL-12p70, FGF-basic, GM-CSF and TNF-α cytokines (OR: 0.14; 95% CI: 0.03-0.79) and high levels of IgA immunoglobulin (OR: 8.1; 95% CI: 1.45-45.06). HIV infected mothers were more likely to have infants with low levels of IgG2 (OR: 0.24; 95% CI: 0.06-1.00) and IgA (OR: 0.22; 95% CI: 0.05-0.90) immunoglobulins. Notably, it was highly likely to deliver infants with low IgG4 levels (OR: 0.24; 95% CI: 0.06-1.02) for maternal mean age above 30.38 years (Standard deviation 6.09) though not significant (p=0.05). Maternal E. histolytica asymptomatic carriage, and HIV-infection status result in low levels of pro-inflammatory cytokines IL-12p70, FGF-basic, GM-CSF and TNF-α and immunoglobulins IgG2, IgG4 and IgA on their infants.

MeSH terms: Adult; Female; Fetal Blood/immunology*; Humans; Immunoglobulins/blood*; Infant; Infant, Newborn/blood; Infant, Newborn/immunology*; Mothers; Pregnancy; Pregnancy Complications/immunology*; Pregnancy Complications/virology; Pregnancy Complications, Infectious/epidemiology; Zimbabwe/epidemiology; HIV Infections/immunology*; HIV Infections/epidemiology; HIV Infections/transmission; HIV Infections/virology; Cytokines/blood; Cytokines/immunology*; Infectious Disease Transmission, Vertical/statistics & numerical data*
Fulltext Molecular Diagnosis of Microsporidia among Immunocompromised Patients in Kuala Lumpur, Malaysia

Hassan NA, Lim YAL, Mahmud R, Mohd-Shaharuddin N, Wan Sulaiman WY, Ngui R

Am J Trop Med Hyg, 2018 Dec;99(6):1562-1566.
PMID: 30382015 DOI: 10.4269/ajtmh.17-0901

Microsporidia are obligate intracellular parasitic fungi causing chronic diarrhea, particularly among immunocompromised patients. The current method used for diagnosis is based on conventional microscopy, which does not differentiate parasites at the species level. The present study was carried out to identify microsporidian species in immunocompromised patients. From March 2016 to March 2017, a total of 289 archived stool samples were examined microscopically for microsporidian spores using Gram-chromotrope Kinyoun (GCK) stain. Positive stool samples by microscopy were subjected to polymerase chain reaction and sequencing for species identification. Based on microscopy examination, the overall prevalence of microsporidian infections was 32.2% (93/289; 95% CI = 27.1-37.8). Of these stool samples, 45 samples were successfully amplified and confirmed as Enterocytozoon bieneusi. No Encephalitozoon intestinalis was detected. Accurate identification of species might help clinicians to decide appropriate management strategies as dissemination risks and treatment response vary for different species, hence improving the management of microsporidian infections.

MeSH terms: Adolescent; Adult; Animals; Child; Diarrhea/diagnosis; Diarrhea/immunology*; Diarrhea/microbiology; Diarrhea/epidemiology; DNA, Fungal/genetics*; Feces/microbiology; Female; Humans; Malaysia/epidemiology; Middle Aged; Neoplasms/diagnosis; Neoplasms/immunology*; Neoplasms/microbiology; Neoplasms/epidemiology; Spores, Fungal/genetics; Spores, Fungal/isolation & purification; HIV Infections/diagnosis; HIV Infections/immunology*; HIV Infections/microbiology; HIV Infections/epidemiology; Prevalence; Immunocompromised Host*; Microsporidiosis/diagnosis; Microsporidiosis/immunology*; Microsporidiosis/microbiology; Microsporidiosis/epidemiology; Enterocytozoon/classification; Enterocytozoon/genetics*; Enterocytozoon/isolation & purification
Recent Development in Omics Studies

Aizat WM, Ismail I, Noor NM

Adv Exp Med Biol, 2018 11 2;1102:1-9.
PMID: 30382565 DOI: 10.1007/978-3-319-98758-3_1

The central dogma of molecular biology (DNA, RNA, protein and metabolite) has engraved our understanding of genetics in all living organisms. While the concept has been embraced for many decades, the development of high-throughput technologies particularly omics (genomics, transcriptomics, proteomics and metabolomics) has revolutionised the field to incorporate big data analysis including bioinformatics and systems biology as well as synthetic biology area. These omics approaches as well as systems and synthetic biology areas are now increasingly popular as seen by the growing numbers of publication throughout the years. Several journals which have published most of these related fields are also listed in this chapter to overview their impact and target journals.

MeSH terms: Computational Biology; Gene Expression Profiling/trends*; Genomics/trends*; Proteomics/trends*; Systems Biology; Metabolomics/trends*
Functional Genomics

Goh HH, Ng CL, Loke KK

Adv Exp Med Biol, 2018 11 2;1102:11-30.
PMID: 30382566 DOI: 10.1007/978-3-319-98758-3_2

Functional genomics encompasses diverse disciplines in molecular biology and bioinformatics to comprehend the blueprint, regulation, and expression of genetic elements that define the physiology of an organism. The deluge of sequencing data in the postgenomics era has demanded the involvement of computer scientists and mathematicians to create algorithms, analytical software, and databases for the storage, curation, and analysis of biological big data. In this chapter, we discuss on the concept of functional genomics in the context of systems biology and provide examples of its application in human genetic disease studies, molecular crop improvement, and metagenomics for antibiotic discovery. An overview of transcriptomics workflow and experimental considerations is also introduced. Lastly, we present an in-house case study of transcriptomics analysis of an aromatic herbal plant to understand the effect of elicitation on the biosynthesis of volatile organic compounds.

MeSH terms: Plant Breeding; Humans; Software; Computational Biology*; Genomics/trends*; Systems Biology; Metagenomics
Proteomics in Systems Biology

Aizat WM, Hassan M

Adv Exp Med Biol, 2018 11 2;1102:31-49.
PMID: 30382567 DOI: 10.1007/978-3-319-98758-3_3

Proteomics is the study of proteins, the workhorses of cells. Proteins can be subjected to various post-translational modifications, making them dynamic to external perturbation. Proteomics can be divided into four areas: sequence, structural, functional and interaction and expression proteomics. These different areas used different instrumentations and have different focuses. For example, sequence and structural proteomics mainly focus on elucidating a particular protein sequence and structure, respectively. Meanwhile, functional and interaction proteomics concentrate on protein function and interaction partners, whereas expression proteomics allows the cataloguing of total proteins in any given samples, hence providing a holistic overview of various proteins in a cell. The application of expression proteomics in cancer and crop research is detailed in this chapter. The general workflow of expression proteomics consisting the use of mass spectrometry instrumentation has also been described, and some examples of proteomics studies are also presented.

MeSH terms: Protein Processing, Post-Translational; Proteins/chemistry*; Mass Spectrometry; Proteomics*; Systems Biology*
Metabolomics in Systems Biology

Baharum SN, Azizan KA

Adv Exp Med Biol, 2018 11 2;1102:51-68.
PMID: 30382568 DOI: 10.1007/978-3-319-98758-3_4

Over the last decade, metabolomics has continued to grow rapidly and is considered a dynamic technology in envisaging and elucidating complex phenotypes in systems biology area. The advantage of metabolomics compared to other omics technologies such as transcriptomics and proteomics is that these later omics only consider the intermediate steps in the central dogma pathway (mRNA and protein expression). Meanwhile, metabolomics reveals the downstream products of gene and expression of proteins. The most frequently used tools are nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Some of the common MS-based analyses are gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These high-throughput instruments play an extremely crucial role in discovery metabolomics to generate data needed for further analysis. In this chapter, the concept of metabolomics in the context of systems biology is discussed and provides examples of its application in human disease studies, plant responses towards stress and abiotic resistance and also microbial metabolomics for biotechnology applications. Lastly, a few case studies of metabolomics analysis are also presented, for example, investigation of an aromatic herbal plant, Persicaria minor metabolome and microbial metabolomics for metabolic engineering applications.

MeSH terms: Chromatography, Liquid; Humans; Gas Chromatography-Mass Spectrometry; Magnetic Resonance Spectroscopy; Mass Spectrometry; Systems Biology*; Metabolomics*; Metabolome; Metabolic Engineering
Integrative Multi-Omics Through Bioinformatics

Goh HH

Adv Exp Med Biol, 2018 11 2;1102:69-80.
PMID: 30382569 DOI: 10.1007/978-3-319-98758-3_5

This chapter introduces different aspects of bioinformatics with a brief discussion in the systems biology context. Example applications in network pharmacology of traditional Chinese medicine, systems metabolic engineering, and plant genome-scale modelling are described. Lastly, this chapter concludes on how bioinformatics helps to integrate omics data derived from various studies described in previous chapters for a holistic understanding of secondary metabolite production in P. minus.

MeSH terms: Genome, Plant; Computational Biology*; Systems Biology*; Metabolic Engineering*
Metabolic Engineering and Synthetic Biology

Ramzi AB

Adv Exp Med Biol, 2018 11 2;1102:81-95.
PMID: 30382570 DOI: 10.1007/978-3-319-98758-3_6

In the modern era of next-generation genomics and Fourth Industrial Revolution, there is a growing demand for translational research that brings about not only impactful research but also potential commercialisation of R- and D-based products. Advancement of metabolic engineering and synthetic biology has put forward a viable and innovative biotechnological platform for bioproduct development especially using microbial chassis. In this chapter, readers will be introduced on the concepts of metabolic engineering, synthetic biology and microbial chassis and the applications of these biological engineering (BioE) components in the advancement of industrial and agricultural biotechnology. Main strategies in employing BioE platform are discussed especially for waste bioconversion and value-added product development. More importantly, this chapter will also discuss current endeavours in integrating systems and synthetic biology for microbial production of natural products by introducing flavonoid biosynthesis genes of Polygonum minus, a medicinally important tropical plant in engineered yeast.

MeSH terms: Biotechnology; Genomics; Translational Medical Research; Synthetic Biology*; Metabolic Engineering*
Fulltext Prevalence of schistosomiasis and associated risk factors among school children in Um-Asher Area, Khartoum, Sudan

Hajissa K, Muhajir AEMA, Eshag HA, Alfadel A, Nahied E, Dahab R, et al.

BMC Res Notes, 2018 Oct 31;11(1):779.
PMID: 30382901 DOI: 10.1186/s13104-018-3871-y

OBJECTIVE: Schistosomiasis remains one of the most common parasitic diseases worldwide. This is a cross-sectional study aimed to determine the prevalence of schistosomiasis and its associated risk factors among primary school children in Um-Asher area. The study was conducted among 170 primary school students in Um-Asher area from November 2017 to February 2018. Urine and stool samples were collected and examined for schistosomiasis infections. Moreover, data on sociodemographic characteristics and associated risk factors were obtained using a questionnaire.
RESULTS: The overall prevalence of Schistosoma haematobium was 12.9%, whereas that of Schistosoma mansoni was 2.95%. Additionally, the males had higher prevalence (60%) of S. mansoni than females (40%). However, both gender were equally infected with S. haematobium (50%). With regard to risk factors, distance of residence from water source and source of drinking water are relatively associated with the infection.

MeSH terms: Animals; Child; Cross-Sectional Studies; Female; Humans; Male; Surveys and Questionnaires; Risk Factors; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis haematobia; Schools; Students; Prevalence; Drinking Water
A soft computing approach for diabetes disease classification

Nilashi M, Bin Ibrahim O, Mardani A, Ahani A, Jusoh A

Health Informatics J, 2018 12;24(4):379-393.
PMID: 30376769 DOI: 10.1177/1460458216675500

As a chronic disease, diabetes mellitus has emerged as a worldwide epidemic. The aim of this study is to classify diabetes disease by developing an intelligence system using machine learning techniques. Our method is developed through clustering, noise removal and classification approaches. Accordingly, we use expectation maximization, principal component analysis and support vector machine for clustering, noise removal and classification tasks, respectively. We also develop the proposed method for incremental situation by applying the incremental principal component analysis and incremental support vector machine for incremental learning of data. Experimental results on Pima Indian Diabetes dataset show that proposed method remarkably improves the accuracy of prediction and reduces computation time in relation to the non-incremental approaches. The hybrid intelligent system can assist medical practitioners in the healthcare practice as a decision support system.

MeSH terms: Machine Learning*; Algorithms*; Diabetes Mellitus/classification*; Diabetes Mellitus/diagnosis; Humans; Models, Statistical
Fulltext Using a dynamic adherence Markov model to assess the efficiency of Respiratory Medication Therapy Adherence Clinic (RMTAC) on asthma patients in Malaysia

Yong YV, Shafie AA

Cost Eff Resour Alloc, 2018;16:36.
PMID: 30377414 DOI: 10.1186/s12962-018-0156-1

Background: Respiratory Medication Therapy Adherence Clinic (RMTAC) is an initiative by the Ministry of Health (MOH) Malaysia to improve patients' medication adherence, as an adjunct to the usual physician care (UC). This study aimed to evaluate the cost-effectiveness of combined strategy of RMTAC and UC (RMTAC + UC) vs. UC alone in asthma patients, from the MOH Malaysia perspective.
Methods: A lifetime horizon dynamic adherence Markov model with monthly cycle was developed, for quality-adjusted life year (QALY) gained and hospitalization averted outcomes. Transition probabilities of composite asthma control and medication adherence, utilities, costs, and mortality rates due to all causes were measured from local data sources. Effectiveness, exacerbation rates, and asthma mortality rates were taken from non-local data sources. One-way sensitivity analysis (SA) was conducted for assessing parameter uncertainties, whereas probabilistic SA (PSA) was conducted on a different set of utilities and effectiveness data. Costs were adjusted to 2014 US dollars ($). Both costs and benefits were discounted at a 3% rate annually.
Results: RMTAC + UC was found to be a dominant alternative compared to UC alone; $- 13,639.40 ($- 109,556.90 to $104,445.54) per QALY gained and $- 428.93 ($- 521.27 to ($- 328.69)) per hospitalization averted. These results were found to be robust against changes in all parameters except utilities in the one-way SA, and for both scenarios in PSA.
Conclusions: RMTAC + UC is more effective and yet cheaper than UC alone, from the MOH perspective. For the benefit of both MOH and patients, RMTAC is thus recommended to be remained, and expanded to more healthcare settings where possible.

MeSH terms: Asthma; Costs and Cost Analysis; Humans; Malaysia; Outpatient Clinics, Hospital; Medication Adherence
Physiological and perceptual responses to exercising in restrictive heat loss attire with use of an upper-body sauna suit in temperate and hot conditions

Willmott AGB, Gibson OR, James CA, Hayes M, Maxwell NS

Temperature (Austin), 2018;5(2):162-174.
PMID: 30377634 DOI: 10.1080/23328940.2018.1426949

The aim of this experiment was to quantify physiological and perceptual responses to exercise with and without restrictive heat loss attire in hot and temperate conditions. Ten moderately-trained individuals (mass; 69.44±7.50 kg, body fat; 19.7±7.6%) cycled for 30-mins (15-mins at 2 W.kg-1 then 15-mins at 1 W.kg-1) under four experimental conditions; temperate (TEMP, 22°C/45%), hot (HOT, 45°C/20%) and, temperate (TEMPSUIT, 22°C/45%) and hot (HOTSUIT, 45°C/20%) whilst wearing an upper-body "sauna suit". Core temperature changes were higher (P<0.05) in TEMPSUIT (+1.7±0.4°C.hr-1), HOT (+1.9±0.5°C.hr-1) and HOTSUIT (+2.3±0.5°C.hr-1) than TEMP (+1.3±0.3°C.hr-1). Skin temperature was higher (P<0.05) in HOT (36.53±0.93°C) and HOTSUIT (37.68±0.68°C) than TEMP (33.50±1.77°C) and TEMPSUIT (33.41±0.70°C). Sweat rate was greater (P<0.05) in TEMPSUIT (0.89±0.24 L.hr-1), HOT (1.14±0.48 L.hr-1) and HOTSUIT (1.51±0.52 L.hr-1) than TEMP (0.56±0.27 L.hr-1). Peak heart rate was higher (P<0.05) in TEMPSUIT (155±23 b.min-1), HOT (163±18 b.min-1) and HOTSUIT (171±18 b.min-1) than TEMP (151±20 b.min-1). Thermal sensation and perceived exertion were greater (P<0.05) in TEMPSUIT (5.8±0.5 and 14±1), HOT (6.4±0.5 and 15±1) and HOTSUIT (7.1±0.5 and 16±1) than TEMP (5.3±0.5 and 14±1). Exercising in an upper-body sauna suit within temperate conditions induces a greater physiological strain and evokes larger sweat losses compared to exercising in the same conditions, without restricting heat loss. In hot conditions, wearing a sauna suit increases physiological and perceptual strain further, which may accelerate the stimuli for heat adaptation and improve HA efficiency.
Fulltext Effect of transforming growth factor-β2 on biological regulation of multilayer primary chondrocyte culture

Khaghani SAB, Akbarova G, Soon CF, Dilbazi G

Cell Tissue Bank, 2018 Dec;19(4):763-775.
PMID: 30377863 DOI: 10.1007/s10561-018-9732-z

Cytokines are extremely potent biomolecules that regulate cellular functions and play multiple roles in initiation and inhibition of disease. These highly specialised macromolecules are actively involved in control of cellular proliferation, apoptosis, cell migration and adhesion. This work, investigates the effect of transforming growth factor-beta2 (TGF-β2) on the biological regulation of chondrocyte and the repair of a created model wound on a multilayer culture system. Also the effect of this cytokine on cell length, proliferation, and cell adhesion has been investigated. Chondrocytes isolated from knee joint of rats and cultured at 4 layers. Each layer consisted of 2 × 105 cells/ml with and without TGF-β2. The expression of mRNA and protein levels of TGF-β receptors and Smad1, 3, 4, and 7 have been analysed by RT-PCR and western blot analysis. The effect of different supplementations in chondrocyte cell proliferation, cell length, adhesion, and wound repair was statistically analysed by One-way ANOVA test. Our results showed that the TGFβ2 regulates mRNA levels of its own receptors, and of Smad3 and Smad7. Also the TGF-β2 caused an increase in chondrocyte cell length, but decreased its proliferation rate and the wound healing process. TGF-β2 also decreased cell adhesion ability to the surface of the culture flask. Since, TGF-β2 increased the cell size, but showed negative effect on cell proliferation and adhesion of CHC, the effect of manipulated TGF-β2 with other growth factors and/or proteins needs to be investigated to finalize the utilization of this growth factor and design of scaffolding in treatment of different types of arthritis.

MeSH terms: Animals; Animals, Newborn; Cells, Cultured; Phosphorylation/drug effects; Wound Healing/drug effects; Rats, Sprague-Dawley; Receptors, Transforming Growth Factor beta/metabolism; Chondrocytes/cytology*; Chondrocytes/drug effects; Chondrocytes/metabolism; Cell Proliferation/drug effects; Smad Proteins/metabolism; Transforming Growth Factor beta2/pharmacology*
Natural and synthetic estrogens in leafy vegetable and their risk associated to human health

Adeel M, Zain M, Fahad S, Rizwan M, Ameen A, Yi H, et al.

Environ Sci Pollut Res Int, 2018 Dec;25(36):36712-36723.
PMID: 30377972 DOI: 10.1007/s11356-018-3588-4

Since the inception of global industrialization, the growth of steroid estrogens becomes a matter of emerging serious concern for the rapid population. Steroidal estrogens are potent endocrine-upsetting chemicals that are excreted naturally by vertebrates (e.g., humans and fish) and can enter natural waters through the discharge of treated and raw sewage. Steroidal estrogens in plants may enter the food web and become a serious threat to human health. We evaluated the uptake and accumulation of ethinylestradiol (EE2) and 17β-estradiol (17β-E2) in lettuce plants (Lactuca sativa) grown under controlled environmental condition over 21 days growth period. An effective analytical method based on ultrasonic liquid extraction (ULE) for solid samples and solid phase extraction (SPE) for liquid samples with gas chromatography-mass spectrometry (GC/MS) has been developed to determine the steroid estrogens in lettuce plants. The extent of uptake and accumulation was observed in a dose-dependent manner and roots were major organs for estrogen deposition. Unlike the 17β-E2, EE2 was less accumulated and translocated from root to leaves. For 17β-E2, the distribution in lettuce was primarily to roots after the second week (13%), whereas in leaves it was (10%) over the entire study period. The distribution of EE2 at 2000 μg L-1 in roots and leaves was very low (3.07% and 0.54%) during the first week and then was highest (12% in roots and 8% in leaves) in last week. Bioaccumulation factor values of 17β-E2 and EE2 in roots were 0.33 and 0.29 at 50 μg L-1 concentration as maximum values were found at 50 μg L-1 rather than 500 and 2000 in all observed plant tissues. Similar trend was noticed in roots than leaves for bioconcentration factor as the highest bioconcentration values were observed at 50 μg L-1 concentration instead of 500 and 2000 μg L-1 spiked concentration. These findings mainly indicate the potential for uptake and bioaccumulation of estrogens in lettuce plants. Overall, the estrogen contents in lettuce were compared to the FAO/WHO recommended toxic level and were found to be higher than the toxic level which is of serious concern to the public health. This analytical procedure may aid in future studies on risks associated with uptake of endocrine-disrupting chemicals in lettuce plants.

MeSH terms: Estradiol/analysis; Estradiol/toxicity; Ethinyl Estradiol/analysis; Ethinyl Estradiol/toxicity; Humans; Sewage/chemistry; Vegetables/chemistry*; Water Pollutants, Chemical/analysis*; Water Pollutants, Chemical/toxicity; Plant Leaves/chemistry; Lettuce/chemistry*; Risk Assessment; Estradiol Congeners/analysis*; Estradiol Congeners/toxicity; Endocrine Disruptors/analysis*; Endocrine Disruptors/toxicity
Fulltext Attitudes of the public towards halal food and associated animal welfare issues in two countries with predominantly Muslim and non-Muslim populations

Jalil NSA, Tawde AV, Zito S, Sinclair M, Fryer C, Idrus Z, et al.

PLoS One, 2018;13(10):e0204094.
PMID: 30379818 DOI: 10.1371/journal.pone.0204094

Halal food is that which is permissible or lawful for Muslims to consume. Meat products must abide by a number of requirements in relation to their preparation, condition and content to be considered halal. We conducted a survey in order to assess the knowledge of, and attitudes towards, halal meat products in two contrasting countries, one with a majority non-Muslim population (Australia, respondent n = 565), where the most commonly followed religion is Christianity, and one with a majority Muslim population (Malaysia, n = 740). The most common reasons for avoiding halal food were animal welfare, religion and meat quality. Malaysians generally believed that halal processes led to improved meat quality, whereas Australians did not. The general consensus was in favour of legally controlling animal welfare during slaughter, supported by both Muslims and Christians. Malaysians were more aware of the main tenets of halal slaughter than Australians. However, some non-compulsory, incorrect practices were thought to be required practices by respondents in both countries, but especially in Australia. Muslims were more concerned about humane treatment of animals during halal slaughter. They generally believed that stunning is never allowed and that this view was acceptable, whereas people from other belief systems generally held the view that this was unacceptable. Religion and education were the most common factors associated with attitudes, beliefs and consumer habits concerning halal. Information from this study can help to improve understanding of attitudes to halal and provide insights to policy makers seeking to address animal welfare concerns.

MeSH terms: Abattoirs/legislation & jurisprudence*; Abattoirs/standards; Adult; Animal Welfare/legislation & jurisprudence*; Animal Welfare/standards; Attitude*; Australia; Female; Humans; Islam; Malaysia; Male; Middle Aged; Pilot Projects; Public Opinion; Surveys and Questionnaires; Age Distribution; Qualitative Research; Young Adult; Food Quality
Fulltext Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations

Low YM, Chong CW, Yap IKS, Chai LC, Clarke SC, Ponnampalavanar S, et al.

Pathog Glob Health, 2018 10;112(7):378-386.
PMID: 30380366 DOI: 10.1080/20477724.2018.1538281

The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.

MeSH terms: Anti-Bacterial Agents/pharmacology*; Bacterial Proteins/genetics; Bacterial Proteins/physiology; Humans; Klebsiella Infections/drug therapy*; Klebsiella Infections/microbiology*; Klebsiella pneumoniae/drug effects*; Klebsiella pneumoniae/genetics; Microbial Sensitivity Tests; Phenotype; Bacterial Typing Techniques; Imipenem/pharmacology*; Drug Resistance, Bacterial/drug effects*; Drug Resistance, Bacterial/genetics; Drug Resistance, Bacterial/physiology*
Fulltext Gene therapy and type 1 diabetes mellitus

Chellappan DK, Sivam NS, Teoh KX, Leong WP, Fui TZ, Chooi K, et al.

Biomed Pharmacother, 2018 Dec;108:1188-1200.
PMID: 30372820 DOI: 10.1016/j.biopha.2018.09.138

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet β cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors.
METHODS: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review.
FINDINGS: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.

MeSH terms: Animals; Clinical Trials as Topic; Diabetes Mellitus, Type 1/genetics*; Diabetes Mellitus, Type 1/prevention & control; Diabetes Mellitus, Type 1/therapy*; Genetic Engineering; Humans; Immunotherapy; Vaccination; Genetic Therapy*
Fulltext Protective effect of α-asarone against nicotine-induced seizures in mice, but not by its interaction with nicotinic acetylcholine receptors

Chellian R, Pandy V

Biomed Pharmacother, 2018 Dec;108:1591-1595.
PMID: 30372861 DOI: 10.1016/j.biopha.2018.09.137

Alpha-asarone is one of the bioactive phytochemicals present in the rhizomes of Acorus species and demonstrated its anticonvulsant activity in rodents. Alpha-asarone protected mice from the gamma-aminobutyric acid (GABA) type A receptor antagonist or N-methyl-d-aspartate (NMDA) receptor agonist-induced seizures. In our recent study, α-asarone attenuated the nicotine withdrawal-induced depression-like behavior in mice. The seizures induced by nicotine is mediated through the activation of nicotinic acetylcholine receptors (nAChRs) and stimulation of NMDA receptors. Therefore, we hypothesized that α-asarone might be effective against nicotine-induced seizures. Also, the interaction of α-asarone with nAChRs is unknown. In this study, we investigated the effect of α-asarone on the locomotor activity and body temperature in mice. In addition, we studied the effect of α-asarone on nicotine-induced seizures in mice. Finally, we assessed in vivo pharmacodynamic interaction of α-asarone with nAChRs using nicotine-induced hypomotility and hypothermia tests in mice. The results of this study showed that the α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) treatment significantly decreased the locomotor activity and body temperature in mice. Furthermore, α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) pretreatment significantly prolonged the onset time of nicotine-induced seizures in mice. However, α-asarone (30 and 50 mg/kg, i.p.) pretreatment did not inhibit the nicotine-induced hypomotility or hypothermia in mice. Conversely, mecamylamine (1 mg/kg, s.c.) pretreatment completely blocked the nicotine-induced seizures and significantly prevents the nicotine-induced hypomotility and hypothermia in mice. Overall, these results suggest that the protective effect of α-asarone against nicotine-induced seizures did not mediate through the antagonism of nAChRs. We also postulated that the GABAergic and glutamatergic activities of α-asarone could be involved in its protective effect against nicotine-induced seizures and based on this aspect further studies are required.

MeSH terms: Animals; Anisoles/pharmacology; Anisoles/therapeutic use*; Anticonvulsants/pharmacology; Anticonvulsants/therapeutic use; Dose-Response Relationship, Drug; Locomotion/drug effects; Locomotion/physiology; Male; Mice, Inbred ICR; Nicotine/toxicity*; Receptors, Nicotinic/physiology*; Seizures/chemically induced*; Seizures/metabolism; Seizures/prevention & control*; Neuroprotective Agents/pharmacology; Neuroprotective Agents/therapeutic use*; Nicotinic Antagonists/pharmacology; Nicotinic Antagonists/therapeutic use; Mice

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