Browse publications by year: 2018

  1. Qin X, Rui J, Xia Y, Mu H, Song SH, Raja Aziddin RE, et al.
    Ann Lab Med, 2018 Mar;38(2):85-94.
    PMID: 29214751 DOI: 10.3343/alm.2018.38.2.85
    BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs).

    METHODS: This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow).

    RESULTS: Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types.

    CONCLUSIONS: The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types.

    MeSH terms: China; Humans; Immunoassay*; Immunosuppressive Agents/blood*; Luminescent Measurements*; Malaysia; Reagent Kits, Diagnostic; Reproducibility of Results; Organ Transplantation; Tacrolimus/blood*; Cyclosporine/blood*; Republic of Korea
  2. Vimalraj S, Rajalakshmi S, Raj Preeth D, Vinoth Kumar S, Deepak T, Gopinath V, et al.
    Mater Sci Eng C Mater Biol Appl, 2018 Feb 01;83:187-194.
    PMID: 29208278 DOI: 10.1016/j.msec.2017.09.005
    Copper(II) complex of quercetin Cu+Q, mixed ligand complexes, quercetin-Cu(II)-phenanthroline [Cu+Q(PHt)] and quercetin-Cu(II)-neocuproine [Cu+Q(Neo)] have been synthesized and characterized. From the FT-IR spectroscopic studies, it was evident that C-ring of quercetin is involved in the metal chelation in all the three copper complexes. C-ring chelation was further proven by UV-Visible spectra and the presence of Cu(II) from EPR spectroscopic investigations. These complexes were found to have osteogenic and angiogenic properties, observed through in vitro osteoblast differentiation and chick embryo angiogenesis assay. In osteoblast differentiation, quercetin-Cu(II) complexes treatment increased calcium deposition and alkaline phosphatase activity (ALP) activity at the cellular level and stimulated Runx2 mRNA and protein, ALP mRNA and type 1 collagen mRNA expression at the molecular level. Among the complexes, Q+Cu(PHt) showed more effects on osteoblast differentiation when compared to that of other two copper complexes. Additionally, Q+Cu(Neo) showed more effect compared to Q+Cu. Furthermore, the effect of these complexes on osteoblast differentiation was confirmed by the expression of osteoblast specific microRNA, pre-mir-15b. The chick embryo angiogenesis assay showed that angiogenic parameters such as blood vessel length, size and junctions were stimulated by these complexes. Thus, the present study demonstrated that quercetin copper(II) complexes exhibit as a pharmacological agent for the orthopedic application.
    MeSH terms: Cell Differentiation/drug effects; Copper/pharmacology*; Copper/chemistry*; Osteoblasts/cytology; Osteoblasts/drug effects; Osteogenesis/drug effects*; Quercetin/pharmacology*; Quercetin/chemistry*; MicroRNAs/genetics
  3. Su TT, Azzani M, Tan FL, Loh SY
    Support Care Cancer, 2018 May;26(5):1617-1624.
    PMID: 29209834 DOI: 10.1007/s00520-017-3987-y
    PURPOSE: This study aimed, firstly, to assess the determinants of return to work (RTW), secondly, to explore the amount of annual wage loss, and finally, to discover the determinants of wage loss among breast cancer (BC) survivors.

    METHODS: A cross-sectional study design was used in this research. The data was collected via interview using a validated questionnaire. Logistic regression models were developed to discover the significant determinants of RTW and of wage loss among BC survivors.

    RESULTS: A total of 256 BC survivors were included in this study. The analysis showed that there was a 21% loss of or reduction in mean income within 1 year after diagnosis. The significant predictors of RTW are being a government employee, having reduced wages or wage loss, and if the case had been diagnosed 1 year or more ago. Being a private sector employee and having a late stage of cancer was a barrier to RTW. The main risk factors for reduced wages or wage loss were belonging to the age group of 40-59 years, being of Chinese or Indian ethnicity, having low educational status, and not returning to work. However, belonging to the higher monthly income group (earning > RM 2000) is a protective factor against the risk of reduced wages or wage loss.

    CONCLUSIONS: Non-RTW and wage loss after diagnosis of BC may result in the survivors experiencing a significant financial burden. Assessment of these patients is becoming more crucial because more women participate in the workforce in Malaysia nowadays and because BC is managed using multiple treatment modalities with their consequences could lead to long absences from work.

    MeSH terms: Adult; Aged; Cross-Sectional Studies; Female; Humans; Malaysia; Middle Aged; Surveys and Questionnaires; Salaries and Fringe Benefits/economics*; Young Adult; Return to Work/economics*; Return to Work/psychology*; Return to Work/statistics & numerical data
  4. Shi W, Massaia A, Louzada S, Banerjee R, Hallast P, Chen Y, et al.
    Hum Genet, 2018 Jan;137(1):73-83.
    PMID: 29209947 DOI: 10.1007/s00439-017-1857-9
    We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0-3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0-2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur.
    MeSH terms: Gene Conversion*; Humans; Phylogeny; Sequence Analysis, DNA; Chromosomes, Human, Y/genetics*; DNA Copy Number Variations*; RNA, Long Noncoding/genetics
  5. Ramlee MH, Beng GK, Bajuri N, Abdul Kadir MR
    Med Biol Eng Comput, 2018 Jul;56(7):1161-1171.
    PMID: 29209961 DOI: 10.1007/s11517-017-1762-3
    The provision of the most suitable rehabilitation treatment for stroke patient remains an ongoing challenge for clinicians. Fully understanding the pathomechanics of the upper limb will allow doctors to assist patients with physiotherapy treatment that will aid in full arm recovery. A biomechanical study was therefore conducted using the finite element (FE) method. A three-dimensional (3D) model of the human wrist was reconstructed using computed tomography (CT)-scanned images. A stroke model was constructed based on pathological problems, i.e. bone density reductions, cartilage wane, and spasticity. The cartilages were reconstructed as per the articulation shapes in the joint, while the ligaments were modelled using linear links. The hand grip condition was mimicked, and the resulting biomechanical characteristics of the stroke and healthy models were compared. Due to the lower thickness of the cartilages, the stroke model reported a higher contact pressure (305 MPa), specifically at the MC1-trapezium. Contrarily, a healthy model reported a contact pressure of 228 MPa. In the context of wrist extension and displacement, the stroke model (0.68° and 5.54 mm, respectively) reported a lower magnitude than the healthy model (0.98° and 9.43 mm, respectively), which agrees with previously reported works. It was therefore concluded that clinicians should take extra care in rehabilitation treatment of wrist movement in order to prevent the occurrence of other complications. Graphical abstract ᅟ.
    MeSH terms: Humans; Ligaments/physiopathology; Middle Aged; Models, Biological; Pressure; Stress, Mechanical; Wrist/physiopathology*; Reproducibility of Results; Hand Strength/physiology*; Finite Element Analysis*; Stroke/physiopathology*
  6. Ramakreshnan L, Aghamohammadi N, Fong CS, Bulgiba A, Zaki RA, Wong LP, et al.
    Environ Sci Pollut Res Int, 2018 Jan;25(3):2096-2111.
    PMID: 29209970 DOI: 10.1007/s11356-017-0860-y
    Seasonal haze episodes and the associated inimical health impacts have become a regular crisis among the ASEAN countries. Even though many emerging experimental and epidemiological studies have documented the plausible health effects of the predominating toxic pollutants of haze, the consistency among the reported findings by these studies is poorly understood. By addressing such gap, this review aimed to critically highlight the evidence of physical and psychological health impacts of haze from the available literature in ASEAN countries. Systematic literature survey from six electronic databases across the environmental and medical disciplines was performed, and 20 peer-reviewed studies out of 384 retrieved articles were selected. The evidence pertaining to the health impacts of haze based on field survey, laboratory tests, modelling and time-series analysis were extracted for expert judgement. In specific, no generalization can be made on the reported physical symptoms as no specific symptoms recorded in all the reviewed studies except for throat discomfort. Consistent evidence was found for the increase in respiratory morbidity, especially for asthma, whilst the children and the elderly are deemed to be the vulnerable groups of the haze-induced respiratory ailments. A consensual conclusion on the association between the cardiovascular morbidity and haze is unfeasible as the available studies are scanty and geographically limited albeit of some reported increased cases. A number of modelling and simulation studies demonstrated elevating respiratory mortality rates due to seasonal haze exposures over the years. Besides, evidence on cancer risk is inconsistent where industrial and vehicular emissions are also expected to play more notable roles than mere haze exposure. There are insufficient regional studies to examine the association between the mental health and haze. Limited toxicological studies in ASEAN countries often impede a comprehensive understanding of the biological mechanism of haze-induced toxic pollutants on human physiology. Therefore, the lack of consistent evidence among the reported haze-induced health effects as highlighted in this review calls for more intensive longitudinal and toxicological studies with greater statistical power to disseminate more reliable and congruent findings to empower the institutional health planning among the ASEAN countries.
    MeSH terms: Air Pollutants/analysis*; Air Pollutants/toxicity; Asia, Southeastern; Humans; Risk Assessment; Particulate Matter
  7. Malakahmad A, Manan TSBA, Sivapalan S, Khan T
    Environ Sci Pollut Res Int, 2018 Feb;25(6):5421-5436.
    PMID: 29209979 DOI: 10.1007/s11356-017-0721-8
    Allium cepa assay was carried out in this study to evaluate genotoxic effects of raw and treated water samples from Perak River in Perak state, Malaysia. Samples were collected from three surface water treatment plants along the river, namely WTPP, WTPS, and WTPK. Initially, triplicates of equal size Allium cepa (onions) bulbs, 25-30 mm in diameter and average weight of 20 g, were set up in distilled water for 24 h at 20 ± 2 °C and protected from direct sunlight, to let the roots to grow. After germination of roots (0.5-1.0 cm in length), bulbs were transferred to collected water samples each for a 96-h period of exposure. The root physical deformations were observed. Genotoxicity quantification was based on mitotic index and genotoxicity level. Statistical analysis using cross-correlation function for replicates from treated water showed that root length has inverse correlation with mitotic indices (r = - 0.969) and frequencies of cell aberrations (r = - 0.976) at lag 1. Mitotic indices and cell aberrations of replicates from raw water have shown positive correlation at lag 1 (r = 0.946). Genotoxicity levels obtained were 23.4 ± 1.98 (WTPP), 26.68 ± 0.34 (WTPS), and 30.4 ± 1.13 (WTPK) for treated water and 17.8 ± 0.18 (WTPP), 37.15 ± 0.17 (WTPS), and 47.2 ± 0.48 (WTPK) for raw water. The observed cell aberrations were adherence, chromosome delay, C-metaphase, chromosome loss, chromosome bridge, chromosome breaks, binucleated cell, mini cell, and lobulated nuclei. The morphogenetic deformations obtained were likely due to genotoxic substances presence in collected water samples. Thus, water treatment in Malaysia does not remove genotoxic compounds.
    MeSH terms: Environmental Monitoring*; Malaysia; Mitotic Index; Mutagenicity Tests; Mutagens/toxicity*; Water Pollutants, Chemical/toxicity*; Water Purification/statistics & numerical data*; Plant Roots/cytology; Plant Roots/drug effects; Plant Roots/genetics; Plant Roots/growth & development; Onions/cytology; Onions/drug effects*; Onions/genetics; Onions/growth & development; Rivers/chemistry*
  8. Ho SH, Uedo N, Aso A, Shimizu S, Saito Y, Yao K, et al.
    J Clin Gastroenterol, 2018 04;52(4):295-306.
    PMID: 29210900 DOI: 10.1097/MCG.0000000000000960
    Endoscopy imaging of the gastrointestinal (GI) tract has evolved tremendously over the last few decades. Key milestones in the development of endoscopy imaging include the use of various dyes for chromoendoscopy, the application of optical magnification in endoscopy, the introduction of high-definition image capturing and display technology and the application of altered illuminating light to achieve vascular and surface enhancement. Aims of this review paper are to summarize the development and evolution of modern endoscopy imaging and in particular, imaged-enhanced endoscopy (IEE), to promote appropriate usage, and to guide future development of good endoscopy practice. A search of PubMed database was performed to identify articles related to IEE of the GI tract. Where appropriate, landmark trials and high-quality meta-analyses and systematic reviews were used in the discussion. In this review, the developments and evolutions in endoscopy imaging and in particular, IEE, were summarized into discernible eras and the literature evidence with regard to the strengths and weaknesses in term of their detection and characterization capability in each of these eras were discussed. It is in the authors' opinion that IEE is capable of fairly good detection and accurate characterization of various GI lesions but such benefits may not be readily reaped by those who are new in the field of luminal endoscopy. Exposure and training in making confident diagnoses using these endoscopy imaging technologies are required in tandem with these new developments in order to fully embrace and adopt the benefits.
    MeSH terms: Humans; Image Enhancement; Endoscopy, Gastrointestinal/history*; Endoscopy, Gastrointestinal/instrumentation; History, 20th Century; History, 21st Century; Narrow Band Imaging
  9. Jeong W, Snell GI, Levvey BJ, Westall GP, Morrissey CO, Wolfe R, et al.
    J Antimicrob Chemother, 2018 Mar 01;73(3):748-756.
    PMID: 29211913 DOI: 10.1093/jac/dkx440
    Objectives: This study describes therapeutic drug monitoring (TDM) of posaconazole suspension and modified release (MR) tablets in lung transplant (LTx) recipients and evaluates factors that may affect posaconazole trough plasma concentration (Cmin).

    Methods: A single-centre, retrospective study evaluating posaconazole Cmin in LTx recipients receiving posaconazole suspension or MR tablets between January 2014 and December 2016.

    Results: Forty-seven LTx patients received posaconazole suspension, and 78 received the MR tablet formulation; a total of 421 and 617 Cmin measurements were made, respectively. Posaconazole was concurrently administered with proton pump inhibitor in ≥ 90% of patients. The median (IQR) of initial posaconazole Cmin following 300 mg daily of posaconazole tablet was significantly higher than that of 800 mg daily of posaconazole suspension [1.65 (0.97-2.13) mg/L versus 0.81 (0.48-1.15) mg/L, P 

    MeSH terms: Fatigue; Humans; Nausea; Retrospective Studies; Suspensions; Sweating; Tablets; Tremor; Triazoles; Vomiting; Weight Loss; Lung Transplantation; Drug Monitoring; Lethargy; Proton Pump Inhibitors
  10. Viecelli AK, O'Lone E, Sautenet B, Craig JC, Tong A, Chemla E, et al.
    Am J Kidney Dis, 2018 03;71(3):382-391.
    PMID: 29203125 DOI: 10.1053/j.ajkd.2017.09.018
    BACKGROUND: Many randomized controlled trials have been performed with the goal of improving outcomes related to hemodialysis vascular access. If the reported outcomes are relevant and measured consistently to allow comparison of interventions across trials, such trials can inform decision making. This study aimed to assess the scope and consistency of vascular access outcomes reported in contemporary hemodialysis trials.

    STUDY DESIGN: Systematic review.

    SETTING & POPULATION: Adults requiring maintenance hemodialysis.

    SELECTION CRITERIA: All randomized controlled trials and trial protocols reporting vascular access outcomes identified from ClinicalTrials.gov, Embase, MEDLINE, and the Cochrane Kidney and Transplant Specialized Register from January 2011 to June 2016.

    INTERVENTIONS: Any hemodialysis-related intervention.

    OUTCOMES: The frequency and characteristics of vascular access outcome measures were analyzed and classified.

    RESULTS: From 168 relevant trials, 1,426 access-related outcome measures were extracted and classified into 23 different outcomes. The 3 most common outcomes were function (136 [81%] trials), infection (63 [38%]), and maturation (31 [18%]). Function was measured in 489 different ways, but most frequently reported as "mean access blood flow (mL/min)" (37 [27%] trials) and "number of thromboses" (30 [22%]). Infection was assessed in 136 different ways, with "number of access-related infections" being the most common measure. Maturation was assessed in 44 different ways at 15 different time points and most commonly characterized by vein diameter and blood flow. Patient-reported outcomes, including pain (19 [11%]) and quality of life (5 [3%]), were reported infrequently. Only a minority of trials used previously standardized outcome definitions.

    LIMITATIONS: Restricted sampling frame for feasibility and focus on contemporary trials.

    CONCLUSIONS: The reporting of access outcomes in hemodialysis trials is very heterogeneous, with limited patient-reported outcomes and infrequent use of standardized outcome measures. Efforts to standardize outcome reporting for vascular access are critical to optimizing the comparability, reliability, and value of trial evidence to improve outcomes for patients requiring hemodialysis.

    MeSH terms: Adult; Age Factors; Equipment Failure/statistics & numerical data*; Female; Renal Dialysis/adverse effects; Renal Dialysis/methods*; Humans; Kidney Failure, Chronic/diagnosis; Kidney Failure, Chronic/mortality; Kidney Failure, Chronic/therapy*; Maintenance; Male; Middle Aged; Sex Factors; Time Factors; Incidence; Survival Rate; Randomized Controlled Trials as Topic; Outcome Assessment (Health Care)*; Risk Assessment; Internationality; Vascular Access Devices/adverse effects*
  11. Moey LH, Abdul Azize NA, Yakob Y, Leong HY, Keng WT, Chen BC, et al.
    Pediatr Neonatol, 2018 08;59(4):397-403.
    PMID: 29203193 DOI: 10.1016/j.pedneo.2017.11.006
    BACKGROUND: Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare autosomal recessive inborn error of gluconeogenesis. We reported the clinical findings and molecular genetic data in seven Malaysian patients with FBPase deficiency.

    METHODS: All patients diagnosed with FBPase deficiency from 2010 to 2015 were included in this study. Their clinical and laboratory data were collected retrospectively.

    RESULTS: All the patients presented with recurrent episodes of hypoglycemia, metabolic acidosis, hyperlactacidemia and hepatomegaly. All of them had the first metabolic decompensation prior to 2 years old. The common triggering factors were vomiting and infection. Biallelic mutations in FBP1 gene (MIM*611570) were identified in all seven patients confirming the diagnosis of FBPase deficiency. In four patients, genetic study was prompted by detection of glycerol or glycerol-3-phosphate in urine organic acids analysis. One patient also had pseudo-hypertriglyceridemia. Seven different mutations were identified in FBP1, among them four mutations were new: three point deletions (c.392delT, c.603delG and c.704delC) and one splice site mutation (c.568-2A > C). All four new mutations were predicted to be damaging by in silico analysis. One patient presented in the neonatal period and succumbed due to sepsis and multi-organ failure. Among six survivors (current age ranged from 4 to 27 years), four have normal growth and cognitive development. One patient had short stature and another had neurological deficit following status epilepticus due to profound hypoglycemia.

    CONCLUSION: FBPase deficiency needs to be considered in any children with recurrent hypoglycemia and metabolic acidosis. Our study expands the spectrum of FBP1 gene mutations.

    MeSH terms: Acidosis/etiology*; Adult; Child; Child, Preschool; DNA Helicases/genetics*; DNA-Binding Proteins/genetics*; Female; Humans; Hypoglycemia/etiology*; Male; Mutation*; Recurrence; Retrospective Studies; Fructose-1,6-Diphosphatase Deficiency/complications*
  12. Uchenna UE, Shori AB, Baba AS
    J Ayurveda Integr Med, 2018;9(4):258-265.
    PMID: 29203351 DOI: 10.1016/j.jaim.2017.06.004
    BACKGROUND: The tamarind seeds have a lot of nutrients that may be used to control cholesterol or glucose levels.

    OBJECTIVE(S): The effects of tamarind seeds (T) on lipid and carbohydrate metabolism in rats were studied. Rats were offered basal diet (BD) with T (2%, 4% or 8%) or without T.

    MATERIALS AND METHODS: Feeding and growth performance in rats were measured and samples of liver and blood were analyzed for glycogen content and levels of cholesterol and glucose respectively.

    RESULTS: The inclusion of T in the diet influences the feeding and growth performance in rats. The serum cholesterol level was reduced (p 

  13. Basher MHA, Ithoi I, Mahmud R, Abdulsalam AM, Foead AI, Dawaki S, et al.
    Acta Trop, 2018 Feb;178:219-228.
    PMID: 29203378 DOI: 10.1016/j.actatropica.2017.11.015
    Acanthamoeba species are ubiquitous free-living protozoa that can be found worldwide. Occasionally, it can become parasitic and the causative agent of acanthamoebic keratitis (AK) and Granulomatous Amoebic Encephalitis (GAE) in man. A total of 160 environmental samples and 225 naturally-infected animal corneal swabs were collected for Acanthamoeba cultivation. Acanthamoeba was found to be high in samples collected from environments (85%, 136/160) compared to infected animal corneas (24.89%, 56/225) by microscopic examination. Analysis of nucleotide sequence of 18S rRNA gene of all the 192 cultivable Acanthamoeba isolates revealed 4 genotypes (T3, T4. T5 and T15) with T4 as the most prevalent (69.27%, 133/192) followed by T5 (20.31%), T15 (9.90%) and T3 (0.52%). Genotype T4 was from the strain of A. castellanii U07401 (44.27%), A. castellanii U07409 (20.83%) and A. polyphagaAY026243 (4.17%), but interestingly, only A. castellanii U07401 was detected in naturally infected corneal samples. In environmental samples, T4 was commonly detected in all samples including dry soil, dust, wet debris, wet soil and water. Among the T4, A. castellanii (U07409) strains were detected high occurrence in dry (45%) followed by aquatic (32.50%) and moist (22.50%) samples but however A. castellanii (U07401) strains were dominant in dry samples of soil and dust (93.10%). Subsequently, genotype T5 of A. lenticulata (U94741) strains were dominant in samples collected from aquatic environments (58.97%). In summary, A. castellanii (U07401) strains were found dominant in both environmental and corneal swab samples. Therefore, these strains are possibly the most virulent and dry soil or dusts are the most possible source of Acanthamoeba infection in cats and dogs corneas.
    MeSH terms: Acanthamoeba; Amebiasis; Animals; Base Sequence; Cats; Cornea; Dogs; Dust; Encephalitis; Genotype; Humans; Male; Soil; Water; Acanthamoeba Keratitis; Genes, rRNA
  14. Trottet A, Wilson B, Sew Wei Xin G, George C, Casten L, Schmoker C, et al.
    Environ Manage, 2018 02;61(2):275-290.
    PMID: 29204675 DOI: 10.1007/s00267-017-0966-5
    Resting strategies of planktonic organisms are important for the ecological processes of coastal waters and their impacts should be taken into consideration in management of water bodies used by multiple industries. We combined different approaches to evaluate the importance of resting stages in Singapore coastal waters. We used molecular approaches to improve the knowledge on Singapore biodiversity, we sampled and extracted cysts from sediments to evaluate the density of resting stages in Johor Strait, and we compared systematically information on Singapore planktonic biodiversity to existing published information on resting stages from these reported organisms. This is the first study evaluating the importance of resting stages in Singapore waters. Above 120 species reported in Singapore are known to produce resting stages though no previous work has ever been done to evaluate the importance of these strategies in these waters. The results from the resting stage survey confirmed 0.66 to 5.34 cyst g-1 dry weight sediment were present in the Johor Strait suggesting that cysts may be flushed by tidal currents into and out of the strait regularly. This also suggest that the blooms occurring in Singapore are likely due to secondary growth of Harmful Algae Bloom species in the water rather than from direct germination of cysts from sediment. Finally, we discuss the importance of these resting eggs for three main national industries in Singapore (shipping, marine aquaculture and provision of drinking water through seawater desalination). We argue that this study will serve as a baseline for some of the future management of Singapore waters.
    MeSH terms: Bacteria/isolation & purification*; Conservation of Natural Resources*; DNA, Bacterial/analysis; Plankton/isolation & purification*; Seawater/microbiology*; Singapore; Water Microbiology; Geologic Sediments/microbiology; Biodiversity; Harmful Algal Bloom*
  15. Mohamad Rosdi MN, Mohd Arif S, Abu Bakar MH, Razali SA, Mohamed Zulkifli R, Ya'akob H
    Apoptosis, 2018 01;23(1):27-40.
    PMID: 29204721 DOI: 10.1007/s10495-017-1434-7
    Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant's bioactive constituents have not yet been unveiled for most of these mechanisms. In the current study, we aim to elucidate the binding interaction of ten bioactive phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis software, Autodock 4.2. The stability of the complex with highest affinity was evaluated using MD simulation. We compared the docking analysis of these substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study identified the potential chemopreventive agent among the bioactive compounds. We also characterized the important interacting residues of protein targets which involve in the binding interaction. Results displayed that anonaine, a benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic family of proteins.
    MeSH terms: Antineoplastic Agents, Phytogenic/isolation & purification; Antineoplastic Agents, Phytogenic/pharmacology; Antineoplastic Agents, Phytogenic/chemistry*; Aporphines/isolation & purification; Aporphines/pharmacology; Aporphines/chemistry*; Binding Sites; Dioxoles/isolation & purification; Dioxoles/pharmacology; Dioxoles/chemistry*; Humans; Plant Extracts/chemistry; Protein Binding; Pyrroles/isolation & purification; Pyrroles/pharmacology; Pyrroles/chemistry*; Gene Expression; Apoptosis/drug effects; Plant Leaves/chemistry; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors*; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Proto-Oncogene Proteins c-bcl-2/chemistry; Annona/chemistry*; Structural Homology, Protein; Apoptosis Regulatory Proteins/antagonists & inhibitors*; Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/metabolism; Apoptosis Regulatory Proteins/chemistry; Protein Interaction Domains and Motifs; Hydrophobic and Hydrophilic Interactions; Molecular Docking Simulation; Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors*; Myeloid Cell Leukemia Sequence 1 Protein/genetics; Myeloid Cell Leukemia Sequence 1 Protein/metabolism; Myeloid Cell Leukemia Sequence 1 Protein/chemistry; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand
  16. Kherad B, Waliszewski M, Leschke M, Kader MA, Bang LH, Ruiz-Poveda FL, et al.
    J Interv Cardiol, 2018 Jun;31(3):338-344.
    PMID: 29205492 DOI: 10.1111/joic.12472
    OBJECTIVES: To evaluate the 9-month safety and efficacy of polymer-free sirolimus eluting drug eluting stents in septuagenarians and octogenarians.

    METHODS: An all-comer, worldwide single armed trial (ClinicalTrials.gov Identifier NCT02629575) was conducted to demonstrate the safety and efficacy of an ultra-thin strut, polymer-free sirolimus eluting stent (PF-SES). The primary endpoint was the 9-month target revascularization rate (TLR). Secondary endpoints included the rates of major adverse cardiac events (MACE), stent thrombosis (ST) and bleeding (BARC) in septuagenarians (≥70 years, <80 years), and in octogenarians (≥80 years) to be compared to the younger patient group (<70 years).

    RESULTS: A total of 1607 patients were treated with PF-SES in the sub-70-year-old age group, 694 in septuagenarians, and 371 in the octogenarian patient group. At 9 months, the MACE rates were 7.2% in octogenarians, 5.3% in septuagenarians, and 3.0% in the younger patient group (P = 0.001). These were mostly driven by all-cause mortality (4.4% vs 1.9% vs 0.6%, P 

    MeSH terms: Age Factors; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents/therapeutic use*; Male; Middle Aged; Polymers*; Time Factors; Treatment Outcome; Sirolimus/therapeutic use*; Coronary Occlusion/etiology; Coronary Occlusion/surgery*; Drug-Eluting Stents*
  17. Lee LY, Muhardi L, Cheah FC, Supapannachart S, Teller IC, Bindels J, et al.
    J Paediatr Child Health, 2018 Apr;54(4):370-376.
    PMID: 29205630 DOI: 10.1111/jpc.13775
    AIM: To understand feeding practices, nutrition management and postnatal growth monitoring of term small-for-gestational age (tSGA) infants in Southeast Asia.

    METHODS: Anonymous questionnaires to assess practices on feeding, nutrition management and post-natal growth monitoring of tSGA infants were distributed among health-care professionals (HCPs) participating in regional/local perinatology symposia in Malaysia, Thailand and Singapore.

    RESULTS: Three hundred seventy-seven respondents from Malaysia (37%), Thailand (27%), Singapore (18%) and other Asian countries (19%) participated in the survey. Respondents were neonatologists (35%), paediatricians (25%) and other HCPs (40%) including nurses and midwives. Exclusive human milk feeding was reported the most preferred feeding option for tSGA infants, followed by fortified human milk feeding (60% and 20%, respectively). This was consistent among the different countries. The perceived nutrient requirements of tSGA infants varied between countries. Most respondents from Malaysia and Singapore reported requirements to be similar to preterm infants, while the majority from Thailand reported that it was less than those of preterm infants. The World Health Organization Growth Chart of 2006 and Fenton Growth Charts of 2013 were the most frequently used charts for growth monitoring in the hospital and after discharge.

    CONCLUSIONS: Nutrition management and perceived nutrient requirements for tSGA infants among practising HCPs in Southeast Asia showed considerable variation. The impetus to form standardised and evidence based feeding regimens is important as adequate nutritional management and growth monitoring particularly in this population of infants will have long term impact on population health.

    MeSH terms: Humans; Infant Food*; Infant Nutritional Physiological Phenomena*; Infant, Newborn/growth & development; Infant, Small for Gestational Age/growth & development*; Malaysia; Milk, Human; Nutritional Requirements*; Practice Patterns, Physicians'/statistics & numerical data*; Singapore; Thailand; Health Care Surveys; Growth Charts
  18. Deuchars SA, Lall VK, Clancy J, Mahadi M, Murray A, Peers L, et al.
    Exp Physiol, 2018 Mar 01;103(3):326-331.
    PMID: 29205954 DOI: 10.1113/EP086433
    What is the topic of this review? This review briefly considers what modulates sympathetic nerve activity and how it may change as we age or in pathological conditions. It then focuses on transcutaneous vagus nerve stimulation, a method of neuromodulation in autonomic cardiovascular control. What advances does it highlight? The review considers the pathways involved in eliciting the changes in autonomic balance seen with transcutaneous vagus nerve stimulation in relationship to other neuromodulatory techniques. The autonomic nervous system, consisting of the sympathetic and parasympathetic branches, is a major contributor to the maintenance of cardiovascular variables within homeostatic limits. As we age or in certain pathological conditions, the balance between the two branches changes such that sympathetic activity is more dominant, and this change in dominance is negatively correlated with prognosis in conditions such as heart failure. We have shown that non-invasive stimulation of the tragus of the ear increases parasympathetic activity and reduces sympathetic activity and that the extent of this effect is correlated with the baseline cardiovascular parameters of different subjects. The effects could be attributable to activation of the afferent branch of the vagus and, potentially, other sensory nerves in that region. This indicates that tragus stimulation may be a viable treatment in disorders where autonomic activity to the heart is compromised.
    MeSH terms: Autonomic Nervous System Diseases/physiopathology*; Cardiovascular Diseases/physiopathology*; Transcutaneous Electric Nerve Stimulation*; Heart Rate/physiology; Humans; Sympathetic Nervous System/physiology*; Sympathetic Nervous System/physiopathology; Vagus Nerve Stimulation*
  19. Valli H, Ahmad S, Jiang AY, Smyth R, Jeevaratnam K, Matthews HR, et al.
    Mech Ageing Dev, 2018 01;169:1-9.
    PMID: 29197478 DOI: 10.1016/j.mad.2017.11.016
    INTRODUCTION: Recent studies reported that energetically deficient murine Pgc-1β-/- hearts replicate age-dependent atrial arrhythmic phenotypes associated with their corresponding clinical conditions, implicating action potential (AP) conduction slowing consequent upon reduced AP upstroke rates.

    MATERIALS AND METHODS: We tested a hypothesis implicating Na+ current alterations as a mechanism underlying these electrophysiological phenotypes. We applied loose patch-clamp techniques to intact young and aged, WT and Pgc-1β-/-, atrial cardiomyocyte preparations preserving their in vivo extracellular and intracellular conditions.

    RESULTS AND DISCUSSION: Depolarising steps activated typical voltage-dependent activating and inactivating inward (Na+) currents whose amplitude increased or decreased with the amplitudes of the activating, or preceding inactivating, steps. Maximum values of peak Na+ current were independently influenced by genotype but not age or interacting effects of genotype and age on two-way ANOVA. Neither genotype, nor age, whether independently or interactively, influenced voltages at half-maximal current, or steepness factors, for current activation and inactivation, or time constants for recovery from inactivation following repolarisation. In contrast, delayed outward (K+) currents showed similar activation and rectification properties through all experimental groups. These findings directly demonstrate and implicate reduced Na+ in contrast to unchanged K+ current, as a mechanism for slowed conduction causing atrial arrhythmogenicity in Pgc-1β-/- hearts.

    MeSH terms: Action Potentials*; Aging/genetics; Aging/metabolism*; Aging/pathology; Animals; Arrhythmias, Cardiac/genetics; Arrhythmias, Cardiac/metabolism; Arrhythmias, Cardiac/pathology; Heart Atria/metabolism; Heart Atria/pathology; Potassium/metabolism*; Sodium/metabolism*; Ion Transport/genetics; Mice, Knockout; Myocytes, Cardiac/metabolism*; Myocytes, Cardiac/pathology; Mice; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/deficiency*
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