Browse publications by year: 2019

  1. Barber BE, Grigg MJ, Piera K, Amante FH, William T, Boyle MJ, et al.
    J Infect Dis, 2019 09 26;220(9):1435-1443.
    PMID: 31250022 DOI: 10.1093/infdis/jiz334
    BACKGROUND: Anemia is a major complication of vivax malaria. Antiphosphatidylserine (PS) antibodies generated during falciparum malaria mediate phagocytosis of uninfected red blood cells that expose PS and have been linked to late malarial anemia. However, their role in anemia from non-falciparum Plasmodium species is not known, nor their role in early anemia from falciparum malaria.

    METHODS: We measured PS immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in Malaysian patients with vivax, falciparum, knowlesi, and malariae malaria, and in healthy controls, and correlated antibody titres with hemoglobin. PS antibodies were also measured in volunteers experimentally infected with Plasmodium vivax and Plasmodium falciparum.

    RESULTS: PS IgM and IgG antibodies were elevated in patients with vivax, falciparum, knowlesi, and malariae malaria (P < .0001 for all comparisons with controls) and were highest in vivax malaria. In vivax and falciparum malaria, PS IgM and IgG on admission correlated inversely with admission and nadir hemoglobin, controlling for parasitemia and fever duration. PS IgM and IgG were also increased in volunteers infected with blood-stage P. vivax and P. falciparum, and were higher in P. vivax infection.

    CONCLUSIONS: PS antibodies are higher in vivax than falciparum malaria, correlate inversely with hemoglobin, and may contribute to the early loss of uninfected red blood cells found in malarial anemia from both species.

    MeSH terms: Adolescent; Adult; Anemia/physiopathology*; Female; Hemoglobins/analysis; Humans; Immunoglobulin G/blood*; Immunoglobulin M/blood*; Malaysia; Male; Malaria, Falciparum/complications*; Malaria, Vivax/complications*; Antibodies, Antiphospholipid/blood*; Young Adult
  2. Gregory PJ, Mayes S, Hui CH, Jahanshiri E, Julkifle A, Kuppusamy G, et al.
    Planta, 2019 Sep;250(3):979-988.
    PMID: 31250097 DOI: 10.1007/s00425-019-03179-2
    MAIN CONCLUSION: Crops For the Future (CFF), as an entity, has established a broad range of research activities to promote the improvement and adoption of currently underutilised crops. This paper summarises selected research activities at Crops For the Future (CFF) in pursuit of its mission 'to develop solutions for diversifying future agriculture using underutilised crops'. CFF is a research company focussed on the improvement of underutilised crops, so that they might be grown and consumed more widely with benefits to human food and nutritional security; its founding guarantors were the Government of Malaysia and the University of Nottingham. From its base in Malaysia, it engages in research around the world with a focus on species and system diversification. CFF has adopted a food system approach that adds value by delivering prototype food, feed and knowledge products. Bambara groundnut (Vigna subterranea) was adopted as an exemplar crop around which to develop CFF's food system approach with emphasis on the short-day photoperiod requirement for pod-filling and the hard-to-cook trait. Selective breeding has allowed the development of lines that are less susceptible to photoperiod but also provided a range of tools and approaches that are now being exploited in other crops such as winged bean (Psophocarpus tetragonolobus), amaranth (Amaranthus spp.), moringa (Moringa oleifera) and proso (Panicum miliaceum) and foxtail (Setaria italica) millets. CFF has developed and tested new food products and demonstrated that several crops can be used as feed for black soldier fly which can, in turn, be used to feed fish thereby reducing the need for fishmeal. Information about underutilised crops is widely dispersed; so, a major effort has been made to develop a knowledge base that can be interrogated and used to answer practical questions about potential exploitation of plant and nutritional characteristics. Future research will build on the success with Bambara groundnut and include topics such as urban agriculture, rural development and diversification, and the development of novel foods.
    MeSH terms: Plant Breeding; Food Supply; Forecasting; Research
  3. Krishnankutty N, Idris M, Hamzah FM, Manan Y
    Environ Sci Pollut Res Int, 2019 Aug;26(24):25046-25056.
    PMID: 31250391 DOI: 10.1007/s11356-019-05680-3
    Bauxite and iron ore mining is the major contributor to metal pollution in Tasik Chini, Malaysia. Deforestation of the protected zone of reserve forest exacerbates the problem. The current study is to understand the speciation of metals spatially in sediment to analyse the risk associated in terms of its mobility and bioavailability. The samples of sediment are collected from Sungai Jemberau, Laut Jemberau, and Laut Gumum of Tasik Chini. Four samplings were conducted for a year, by collecting the surface sediment. Sequential extraction method was followed for speciation of sediment and classified it into exchangeable, reducible, Fe-Mn oxides, organic and residual fractions. The results were also analyzed using principal component analysis (PCA) and cluster analysis (CA). The result reveals that Fe, Al, Mn, Zn, and Pb are the primary constituents of sediment contributing to about 98% of residual fraction. Co, Cd, Cr, As, and Ni are found in trace metal concentration and are identified to be mainly released from anthropogenic sources nearby. Although the individual proportion is less than major metals in exchangeable and carbonate fraction, they possess geochemically significant concentration above the permissible limit. More than 70-80% of all its total concentration proportion is hence found in mobile and bioavailable state. These possess toxic and have chronic effects to aquatic life and public health even in trace elemental concentration. Hence, these metals are the most toxic and bioavailable metals pausing risk for aquatic and public health. PCA analysis highlights that the enrichment of heavy metals in bioavailable fraction is mostly contributed from anthropogenic sources. The same results are emphasized by cluster analysis.
    MeSH terms: Malaysia; Mining; Trace Elements/analysis*; Geologic Sediments/analysis*; Metals, Heavy/analysis*
  4. Nakamukai S, Ise Y, Ohtsuka S, Okada S, Matsunaga S
    Biosci Biotechnol Biochem, 2019 Nov;83(11):1985-1988.
    PMID: 31250707 DOI: 10.1080/09168451.2019.1630258
    N6-Isopentenyladenosine (i6A) was isolated from a marine sponge Oceanapia sp. as the major cytotoxic constituent along with N6-isopentenyladenosine 5'-monophosphate (i6AP) which was inactive. The structures of i6A and i6AP were assigned by a combination of the analysis of NMR spectroscopy and mass spectrometry. This is the first isolation of i6A and i6AP from a marine sponge.
    MeSH terms: Animals; Isopentenyladenosine/isolation & purification*; Isopentenyladenosine/chemistry*; Models, Molecular; Molecular Conformation; Porifera/chemistry*
  5. Jaafar MHM, Hamid KA
    Curr Drug Deliv, 2019;16(7):672-686.
    PMID: 31250754 DOI: 10.2174/1567201816666190620110748
    BACKGROUND: In this study, four nanoparticle formulations (F1 to F4) comprising varying ratios of alginate, Pluronic F-68 and calcium chloride with a constant amount of insulin and chitosan as a coating material were prepared using polyelectrolyte complexation and ionotropic gelation methods to protect insulin against enzymatic degradation.

    METHODS: This study describes the formulation design, optimisation, characterisation and evaluation of insulin concentration via oral delivery in rats. A reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated to quantify insulin concentration in rat plasma. The proposed method produced a linear response over the concentration range of 0.39 to 50 µg/ml.

    RESULTS: In vitro release study showed that dissolution of insulin in simulated gastric juice of pH 1.2 was prevented by alginate core and chitosan coating but rapidly released in simulated intestinal fluid (pH 6.8). Additionally, Formulation 3 (F3) has a particle size of 340.40 ± 2.39 nm with narrow uniformity exhibiting encapsulation efficiency (EE) of 72.78 ± 1.25 % produced highest absorption profile of insulin with a bioavailability of 40.23 ±1.29% and reduced blood glucose after its oral administration in rats.

    CONCLUSION: In conclusion, insulin oral delivery system containing alginate and chitosan as a coating material has the ability to protect the insulin from enzymatic degradation thus enhance its absorption in the intestine. However, more work should be done for instance to involve human study to materialise this delivery system for human use.

    MeSH terms: Administration, Oral; Alginates; Animals; Biological Availability; Blood Glucose; Calcium Chloride; Chromatography, High Pressure Liquid; Gastric Juice; Hexuronic Acids; Humans; Insulin; Intestines; Particle Size; Solubility; Poloxamer; Glucuronic Acid; Chitosan; Rats; Nanoparticles; Polyelectrolytes
  6. Pogorelov K, Suman S, Azmadi Hussin F, Saeed Malik A, Ostroukhova O, Riegler M, et al.
    J Appl Clin Med Phys, 2019 Aug;20(8):141-154.
    PMID: 31251460 DOI: 10.1002/acm2.12662
    Wireless capsule endoscopy (WCE) is an effective technology that can be used to make a gastrointestinal (GI) tract diagnosis of various lesions and abnormalities. Due to a long time required to pass through the GI tract, the resulting WCE data stream contains a large number of frames which leads to a tedious job for clinical experts to perform a visual check of each and every frame of a complete patient's video footage. In this paper, an automated technique for bleeding detection based on color and texture features is proposed. The approach combines the color information which is an essential feature for initial detection of frame with bleeding. Additionally, it uses the texture which plays an important role to extract more information from the lesion captured in the frames and allows the system to distinguish finely between borderline cases. The detection algorithm utilizes machine-learning-based classification methods, and it can efficiently distinguish between bleeding and nonbleeding frames and perform pixel-level segmentation of bleeding areas in WCE frames. The performed experimental studies demonstrate the performance of the proposed bleeding detection method in terms of detection accuracy, where we are at least as good as the state-of-the-art approaches. In this research, we have conducted a broad comparison of a number of different state-of-the-art features and classification methods that allows building an efficient and flexible WCE video processing system.
    MeSH terms: Machine Learning; Algorithms*; Color*; Gastrointestinal Hemorrhage/diagnosis*; Humans; Pattern Recognition, Automated/methods*; Video Recording/methods*; Gastrointestinal Tract/pathology*; Capsule Endoscopy/methods*; Wireless Technology
  7. Yasmin AR, Omar AR, Farhanah MI, Hiscox AJ, Yeap SK
    Avian Dis, 2019 06 01;63(2):275-288.
    PMID: 31251527 DOI: 10.1637/11936-072418-Reg.1
    Chicken dendritic cells (DCs) have been demonstrated to be susceptible to infectious bursal disease virus (IBDV), a causative agent of acute and immunosuppressed disease in young chicks known as infectious bursal disease. Further functional characterization of IBDV-infected DCs of chickens is required to provide a better understanding on the influence of the virus on chicken bone marrow-derived dendritic cells (BM-DCs) following very virulent (vv) IBDV infection. Membrane proteins of BM-DCs were extracted and the proteins were further denatured and reduced before performing labeling with isobaric tags for relative and absolute quantitation. The differential expression protein profiles were identified and quantified using liquid chromatography coupled with tandem mass spectrometry, and later validated using flow cytometry and real-time reverse transcriptase PCR. The analysis has identified 134 differentially regulated proteins from a total of 283 proteins (cutoff values of ≤0.67, ≥1.5, and ProtScore >1.3 at 95% confidence interval), which produced high-yield membrane fractions. The entry of vvIBDV into the plasma membrane of BM-DCs was observed at 3 hr postinfection by the disruption of several important protein molecule functions, namely apoptosis, RNA/DNA/protein synthesis, and transport and cellular organization, without the activation of proteins associated with signaling. At the later stage of infection, vvIBDV induced expression of several proteins, namely CD200 receptor 1-A, integrin alpha-5, HSP-90, cathepsin, lysosomal-associated membrane protein, and Ras-related proteins, which play crucial roles in signaling, apoptosis, stress response, and antigen processing as well as in secretion of danger-associated proteins. These findings collectively indicated that the chicken DCs are expressing various receptors regarded as potential targets for pathogen interaction during viral infection. Therefore, fundamental study of the interaction of DCs and IBDV will provide valuable information in understanding the role of professional antigen-presenting cells in chickens and their molecular interactions during IBDV infection and vaccination.
    MeSH terms: Animals; Bone Marrow; Chickens*; Dendritic Cells/immunology*; Infectious bursal disease virus/pathogenicity; Infectious bursal disease virus/physiology*; Poultry Diseases/genetics; Poultry Diseases/immunology*; Poultry Diseases/virology; Virulence; Birnaviridae Infections/genetics; Birnaviridae Infections/immunology; Birnaviridae Infections/veterinary*; Birnaviridae Infections/virology; Proteome; Avian Proteins/genetics*; Avian Proteins/metabolism
  8. Perehudoff SK, Alexandrov NV, Hogerzeil HV
    PLoS One, 2019;14(6):e0215577.
    PMID: 31251737 DOI: 10.1371/journal.pone.0215577
    Persistent barriers to universal access to medicines are limited social protection in the event of illness, inadequate financing for essential medicines, frequent stock-outs in the public sector, and high prices in the private sector. We argue that greater coherence between human rights law, national medicines policies, and universal health coverage schemes can address these barriers. We present a cross-national content analysis of national medicines policies from 71 countries published between 1990-2016. The World Health Organization's (WHO) 2001 guidelines for developing and implementing a national medicines policy and all 71 national medicines policies were assessed on 12 principles, linking a health systems approach to essential medicines with international human rights law for medicines affordability and financing for vulnerable groups. National medicines policies most frequently contain measures for medicines selection and efficient spending/cost-effectiveness. Four principles (legal right to health; government financing; efficient spending; and financial protection of vulnerable populations) are significantly stronger in national medicines policies published after 2004 than before. Six principles have remained weak or absent: pooling user contributions, international cooperation, and four principles for good governance. Overall, South Africa (1996), Indonesia and South Sudan (2006), Philippines (2011-2016), Malaysia (2012), Somalia (2013), Afghanistan (2014), and Uganda (2015) include the most relevant texts and can be used as models for other settings. We conclude that WHO's 2001 guidelines have guided the content and language of many subsequent national medicines policies. WHO and national policy makers can use these principles and the practical examples identified in our study to further align national medicines policies with human rights law and with Target 3.8 for universal access to essential medicines in the Sustainable Development Goals.
    MeSH terms: South Sudan; Government Programs/legislation & jurisprudence*; Health Policy/legislation & jurisprudence; Humans; Indonesia; Legislation, Drug; Malaysia; Philippines; Somalia; South Africa; Uganda; World Health Organization; Guidelines as Topic; Drugs, Essential/economics*; Universal Coverage/legislation & jurisprudence*; Vulnerable Populations
  9. Raihan R, Akbar SMF, Al Mahtab M, Takahashi K, Masumoto J, Tabassum S, et al.
    PLoS One, 2019;14(6):e0218744.
    PMID: 31251754 DOI: 10.1371/journal.pone.0218744
    The direct cytopathic effects of the hepatitis B virus (HBV) on subsequent liver damage are not fully understood in HBV-infected patients. However, associations between the prevalence of various HBV genotypes and the extent of liver damage have been reported from different parts of the world. The purpose of this study was to determine the distribution of HBV genotypes in patients with chronic HBV infection in Bangladesh, a country of 160 million people, of which approximately 3-6 million are chronically infected HBV patients. In addition, whole and partial genome sequencing of HBV was performed to evaluate the relationship between HBV mutations and genotypes. We found that 42% of the patients with low HBV DNA and normal levels of alanine aminotransferase (ALT) had HBV genotype D. In contrast, the HBV genotype C was dominant among patients with high HBV DNA levels (>2000 IU/ml) and elevated ALT and in patients with liver cirrhosis (LC) and hepatocellular carcinomas (HCC). Whole and partial genome sequences of HBV revealed that most patients with LC and HCC had HBV genotype C with mutations at the T1762/A1764 positions. It seems that Bangladesh represents a borderline country, situated within East Asia, which mainly consists of individuals with HBV genotypes B and C, whereas in the western parts of Asia, HBV genotypes A and D are prevalent. Bangladesh is, therefore, an excellent model for the comparison of the pathophysiology of three major HBV genotypes in a single population. The findings of this study suggest a possible association between HBV viral factors and the extent of liver damage in chronic HBV-infected patients.
    MeSH terms: Alanine Transaminase; Asia; Bangladesh; DNA, Viral; Far East; Genotype; Hepatitis B virus; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Mutation; Prevalence; Hepatitis B, Chronic; D-Alanine Transaminase
  10. Syafri E, Jamaluddin, Wahono S, Irwan A, Asrofi M, Sari NH, et al.
    Int J Biol Macromol, 2019 Sep 15;137:119-125.
    PMID: 31252021 DOI: 10.1016/j.ijbiomac.2019.06.174
    The cellulose microfibers (CMF) from water hyacinth (WH) fiber as a filler in sago starch (SS) biocomposites was investigated. The CMF was isolated by pulping, bleaching and acid hydrolysis methods. The addition of CMF in sago matrix was varied i.e. 0, 5, 10, 15 and 20 wt%. Biocomposites were made by using solution casting and glycerol as a plasticizer. The biocomposites were also determined by tensile test, FTIR, X-Ray, thermogravimetric, SEM, and soil burial tests. The results show that the SS15CMF sample has the highest tensile strength of 10.23 MPa than those other samples. Scanning Electron Microscope (SEM) images show that the strong interaction was formed between CMF WH and matrix. Fourier Transform Infra-red (FTIR) indicated that the functional group of biocomposites was a hydrophilic cluster. The addition of CMF WH in sago starch biocomposites lead to the moisture barrier, crystallinity, and thermal stability increased; it is due to the pure sago starch film was more rapidly degraded than its biocomposites.
    MeSH terms: Cellulose/chemistry*; Hydrolysis; Materials Testing; Plasticizers; Soil/chemistry; Starch/chemistry*; Temperature; Tensile Strength; Arecaceae/chemistry*; Eichhornia/chemistry*
  11. Fong SL, Lim KS, Tan L, Aris T, Khalid RA, Ali RA, et al.
    Epilepsy Behav, 2019 08;97:206-211.
    PMID: 31252280 DOI: 10.1016/j.yebeh.2019.05.033
    INTRODUCTION: Prevalence studies of epilepsy in Asia revealed a prevalence ranging from 1.5 to 14.0 per 1000 among Asian populations. However, the prevalence of epilepsy in Malaysia is not available for comparison with other countries. This study aimed to translate and validate a Malay brief screening instruments for ascertainment of epilepsy.

    METHOD: We translated into Malay a brief screening instrument for ascertainment of epilepsy designed and validated by Ottman et al., using the three-stage cross-cultural adaptation process developed by the International Quality of Life Assessment (IQOLA) project. We then administered the translated questionnaire via online survey to 162 cases (patients with epilepsy under follow-up care at the neurology clinic in University of Malaya Medical Centre, Kuala Lumpur) and 146 controls with no known history of epilepsy for validation.

    RESULTS: Applying the most liberal definition for a positive screen, we obtained a sensitivity of 96.3% (95% confidence interval [CI]: 91.8-98.5%), with a specificity of 66.4% (95% CI: 58.1-73.0%) and positive predictive value (PPV) of 2.0%. The most stringent definition for a positive screen (only epilepsy) resulted in a sensitivity of 97.4% (95% CI: 62.0-72.6%), specificity of 98.6% (95% CI: 94.6-99.7%), and PPV of 26.6%. Narrowing the definition of a positive screen decreased sensitivity but improved PPVs. When compared to the original English questionnaire, the sensitivities were similar for all four definitions of a positive screen.

    CONCLUSION: This is the first validated epilepsy screening questionnaire in the Malay language and represents a useful tool for the ascertainment of epilepsy in population-based studies.

    MeSH terms: Cross-Cultural Comparison; Epilepsy/diagnosis*; Epilepsy/psychology; Humans; Malaysia; Mass Screening; Predictive Value of Tests; Quality of Life; Surveys and Questionnaires; Sensitivity and Specificity; Translations; Reproducibility of Results; Asian Continental Ancestry Group
  12. Fong MJB, Loy ACM, Chin BLF, Lam MK, Yusup S, Jawad ZA
    Bioresour Technol, 2019 Oct;289:121689.
    PMID: 31252316 DOI: 10.1016/j.biortech.2019.121689
    In the present study, catalytic pyrolysis of Chlorella vulgaris biomass was conducted to analyse the kinetic and thermodynamic performances through thermogravimetric approach. HZSM-5 zeolite, limestone (LS), bifunctional HZSM-5/LS were used as catalysts and the experiments were heated from 50 to 900 °C at heating rates of 10-100 °C/min. Iso-conversional model-free methods such as Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS), Starink's, and Vyazovkin (V) were employed to evaluate the kinetic parameters meanwhile the thermodynamic parameters were determined by using FWO and KAS methods. The calculated EA values of non-catalytic and catalytic pyrolysis of HZSM-5 zeolite, LS, and bifunctional HZSM-5/LS were determined to be in the range of 156.16-158.10 kJ/mol, 145.26-147.84 kJ/mol, 138.81-142.06 kJ/mol, and 133.26 kJ/mol respectively. The results have shown that catalytic pyrolysis with the presence of bifunctional HZSM-5/LS resulted to a lower average EA and ΔH compared to HZSM-5, and LS which indicated less energy requirement in the process.
    MeSH terms: Hot Temperature; Kinetics; Thermodynamics; Thermogravimetry; Biomass; Chlorella vulgaris/metabolism*; Biocatalysis
  13. Lin Y, Hu J, Li S, Hamzah SS, Jiang H, Zhou A, et al.
    Molecules, 2019 Jun 27;24(13).
    PMID: 31252525 DOI: 10.3390/molecules24132374
    Fresh-cut fruits and vegetables are the main sources of foodborne illness outbreaks with implicated pathogens such as Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes. This study aimed at investigating the influence of two key parameters (concentration of curcumin and illumination time) on the effects of curcumin-based photodynamic sterilization on the preservation of fresh-cut Hami melons. The results indicated that illumination with 50 μmol/L curcumin for 60 min using a blue LED lamp reduced the total aerobic microorganism count by ~1.8 log CFU/g in fresh-cut Hami melons. Besides this, the effects of photodynamic sterilization on the soluble solids content, color, water content, firmness, and sensory indices of the fresh-cut Hami melons were also evaluated. Compared to the control group, photodynamic sterilization can effectively delay the browning rate and maintain the luminosity, firmness, water content, and soluble solids content of fresh-cut Hami melon. The sensory quality was indeed preserved well after 9 days of storage in a fridge. These results showed that photodynamic sterilization is an effective and promising technology to prolong the shelf life of fresh-cut Hami melons.
    MeSH terms: Curcumin/pharmacology*; Food Handling; Food Microbiology; Food Preservation; Light; Colony Count, Microbial; Cucurbitaceae/drug effects; Cucurbitaceae/microbiology*; Cucurbitaceae/radiation effects; Pasteurization/methods*; Food Quality
  14. Al-Hindi B, Yusoff NA, Ahmad M, Atangwho IJ, Asmawi MZ, Al-Mansoub MA, et al.
    BMC Complement Altern Med, 2019 Jun 28;19(1):152.
    PMID: 31253153 DOI: 10.1186/s12906-019-2573-x
    BACKGROUND: The leaves of Gongronema latifolium Benth. have long been recognized traditionally as a remedy for a variety of ailments in Africa. This study was conducted to evaluate the safety profile of the ethanolic extract of G. latifolium (GLES) leaves through a repeated dose 90-day oral toxicity study in male and female of Sprague Dawley rats.

    METHODS: GLES was orally administered at doses of 250, 500 and 1000 mg/kg/day consecutively for 90 days.

    RESULTS: No behavioral or physiological changes and mortality were observed. GLES did not have a marked impact on general hematological parameters and did not precipitate nephrotoxicity. However, compared to the control, serum triglycerides, total cholesterol and low-density lipoprotein levels were lower and white adipose tissue paired retroperitoneal fat depots were depleted in male rats treated with GLES3 by the end of the experiment. The liver was significantly enlarged in GLES-treated rats of both sexes. Negative gender-specific alterations were observed with the highest dose. Adverse risk was evident in the female rats mainly due to marked body weight gain and cerebrum weight reduction.

    CONCLUSION: Further research is needed to reach more specific conclusions about to the safety of ingesting high doses of GLES for long periods of time.

  15. Tegginamani AS, Kallarakkal TG, Vanishree HS, Muttalib KBA
    J Coll Physicians Surg Pak, 2019 Jul;29(7):688.
    PMID: 31253228 DOI: 10.29271/jcpsp.2019.07.688
    MeSH terms: Humans; Leukoplakia, Oral/metabolism*; Malaysia; Biomarkers/metabolism; AC133 Antigen/metabolism*
  16. Ting HY, Sthaneshwar P, Bee PC, Shanmugam H, Lim M
    Pathology, 2019 Aug;51(5):507-511.
    PMID: 31253381 DOI: 10.1016/j.pathol.2019.04.002
    Serum protein (SPE) and immunofixation electrophoresis (IFE) have been extensively validated for the routine use of identifying, characterising and quantifying monoclonal proteins. However, accurate quantitation of IgA monoclonal proteins can be difficult when they migrate in to the β fraction, due to co-migration with transferrin and complement components. The heavy/light chain (HLC) immunoassay is an additional tool for measuring intact immunoglobulin monoclonal proteins. Therefore, we aimed to examine the clinical utility of the HLC assay for the disease monitoring of IgG and IgA multiple myeloma (MM) patients. A total of 177 samples from 30 MM patients (21 IgG and 9 IgA) were analysed retrospectively with median number of six follow up samples per patient (range 3-13). Serum free light chains (sFLC) and HLC were quantified using Freelite and Hevylite immunoassays. Details of M-protein concentration, β-globulin levels, total immunoglobulin levels and disease treatment response were obtained from the laboratory and patient information system. Passing-Bablok regression analysis was performed to compare (i) M-protein quantification with involved HLC (iHLC) and (ii) total immunoglobulin with summated HLC pairs for each immunoglobulin type (e.g., IgGκ+IgGλ). For 127 IgG MM samples, IgG iHLC levels showed a good correlation with SPE quantification (iHLC y=0.96x+4.9; r=0.917) and summated HLC showed a good correlation with total IgG concentration (summated HLC y=0.94x+5.74; r=0.91). In total, 95/127 (75%) IgG MM follow-up samples had an abnormal HLC ratio and 122/127 (96%) had a positive SPE, probably due to the lower sensitivity of HLC assay in detecting clonality in patients with IgG MM. Consistent with this, one patient assigned a very good partial response by International Myeloma Working Group criteria would be assigned a complete response based on HLC measurements. For 50 IgA MM samples, 42/50 (84%) had an abnormal HLC ratio. Conversely, 50/50 (100%) of M-proteins showed β fraction migration and were difficult to accurately quantify by SPE. Therefore, M-protein concentration and iHLC did not correlate as well in IgA MM (y=1.9x-8.4; r=0.8) compared to IgG MM. However, there was good correlation between total IgA and summated IgA HLC (IgAκ+IgAλ y=1.35x-0.33; r=0.95). Of the 8/50 (16%) IgA samples with a normal HLC ratio, 6/8 (75%) were consistent with the disease status being in complete remission. Interestingly, in one IgA MM patient, SPE and IFE were negative, but the serum FLC ratio and involved FLC were highly abnormal, consistent with the presence of light chain escape. Our data suggest HLC measurements could add value to the current disease monitoring of MM patients. In IgG MM patients, the M-protein level correlated well with HLC values. The HLC assay complements the serum FLC assay and is especially useful for monitoring of IgA MM patients who display M-proteins migrating in the β region on SPE.
    MeSH terms: Aged; Aged, 80 and over; Female; Humans; Immunoassay/methods*; Immunoglobulin Heavy Chains/blood*; Immunoglobulin Light Chains/blood*; Male; Middle Aged; Multiple Myeloma/blood*; Multiple Myeloma/diagnosis*; Multiple Myeloma/immunology
  17. Contreras E, Masuyer G, Qureshi N, Chawla S, Dhillon HS, Lee HL, et al.
    Nat Commun, 2019 06 28;10(1):2869.
    PMID: 31253776 DOI: 10.1038/s41467-019-10732-w
    Clostridial neurotoxins, including tetanus and botulinum neurotoxins, generally target vertebrates. We show here that this family of toxins has a much broader host spectrum, by identifying PMP1, a clostridial-like neurotoxin that selectively targets anopheline mosquitoes. Isolation of PMP1 from Paraclostridium bifermentans strains collected in anopheline endemic areas on two continents indicates it is widely distributed. The toxin likely evolved from an ancestral form that targets the nervous system of similar organisms, using a common mechanism that disrupts SNARE-mediated exocytosis. It cleaves the mosquito syntaxin and employs a unique receptor recognition strategy. Our research has an important impact on the study of the evolution of clostridial neurotoxins and provides the basis for the use of P. bifermentans strains and PMP1 as innovative, environmentally friendly approaches to reduce malaria through anopheline control.
    MeSH terms: Amino Acid Sequence; Animals; Anopheles/drug effects*; Bacteria/metabolism; Bacterial Toxins/pharmacology*; Larva/drug effects; Models, Molecular; Neurotoxins/pharmacology*; Protein Conformation; Protein Domains
  18. Mollerup S, Asplund M, Friis-Nielsen J, Kjartansdóttir KR, Fridholm H, Hansen TA, et al.
    J Infect Dis, 2019 09 13;220(8):1312-1324.
    PMID: 31253993 DOI: 10.1093/infdis/jiz318
    BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data.

    METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.

    RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.

    CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

    MeSH terms: Biopsy; Female; Herpesviridae/genetics; Herpesviridae/isolation & purification; Humans; Male; Neoplasms/pathology; Neoplasms/virology*; Parvovirus/genetics; Parvovirus/isolation & purification; Papillomaviridae/genetics; Papillomaviridae/isolation & purification; Anelloviridae/genetics; Anelloviridae/isolation & purification; Metagenome/genetics*; High-Throughput Nucleotide Sequencing/methods*; Datasets as Topic
  19. Ali SM, Khan NA, Sagathevan K, Anwar A, Siddiqui R
    AMB Express, 2019 Jun 28;9(1):95.
    PMID: 31254123 DOI: 10.1186/s13568-019-0816-3
    The discovery of novel antimicrobials from animal species under pollution is an area untapped. Chinese red-headed centipede is one of the hardiest arthropod species commonly known for its therapeutic value in traditional Chinese medicine. Here we determined the antibacterial activity of haemolymph and tissue extracts of red-headed centipede, Scolopendra subspinipes against a panel of Gram-positive and Gram-negative bacteria. Lysates exhibited potent antibacterial activities against a broad range of bacteria tested. Chemical characterization of biologically active molecules was determined via liquid chromatography mass spectrometric analysis. From crude haemolymph extract, 12 compounds were identified including: (1) L-Homotyrosine, (2) 8-Acetoxy-4-acoren-3-one, (3) N-Undecylbenzenesulfonic acid, (4) 2-Dodecylbenzenesulfonic acid, (5) 3H-1,2-Dithiole-3-thione, (6) Acetylenedicarboxylate, (7) Albuterol, (8) Tetradecylamine, (9) Curcumenol, (10) 3-Butylidene-7-hydroxyphthalide, (11) Oleoyl Ethanolamide and (12) Docosanedioic acid. Antimicrobial activities of the identified compounds were reported against Gram-positive and Gram-negative bacteria, fungi, viruses and parasites, that possibly explain centipede's survival in harsh and polluted environments. Further research in characterization, molecular mechanism of action and in vivo testing of active molecules is needed for the development of novel antibacterials.
  20. Lingam TMC, Tan KY, Tan CH
    Toxicon, 2019 Oct;168:95-97.
    PMID: 31254600 DOI: 10.1016/j.toxicon.2019.06.227
    Daboia siamensis monovalent antivenom (DSMAV, Thailand) exhibited comparable immunoreactivity toward the venoms of eastern Russell's vipers from Thailand and Indonesia. It also effectively neutralized the procoagulant and lethal effects of both venoms, showing high potency. The Indonesian heterologous trivalent antivenom SABU (Serum Anti Bisa Ular), however, has very weak immunoreactivity and it failed to neutralize the Russell's viper venoms. DSMAV appears to be the appropriate choice of antivenom to treat Russell's viper envenoming.
    MeSH terms: Animals; Antivenins/immunology*; Antivenins/pharmacology*; Enzyme-Linked Immunosorbent Assay; Humans; Indonesia; Lethal Dose 50; Neutralization Tests; Thailand; Viper Venoms/toxicity*; Viperidae*; Mice
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