Browse publications by year: 2017

  1. Hassan T, de Santi C, Mooney C, McElvaney NG, Greene CM
    Sci Rep, 2017 10 23;7(1):13803.
    PMID: 29062067 DOI: 10.1038/s41598-017-14310-2
    Alpha-1 antitrypsin (AAT) augmentation therapy involves infusion of plasma-purified AAT to AAT deficient individuals. Whether treatment affects microRNA expression has not been investigated. This study's objectives were to evaluate the effect of AAT augmentation therapy on altered miRNA expression in monocytes and investigate the mechanism. Monocytes were isolated from non-AAT deficient (MM) and AAT deficient (ZZ) individuals, and ZZs receiving AAT. mRNA (qRT-PCR, microarray), miRNA (miRNA profiling, qRT-PCR), and protein (western blotting) analyses were performed. Twenty one miRNAs were differentially expressed 3-fold between ZZs and MMs. miRNA validation studies demonstrated that in ZZ monocytes receiving AAT levels of miR-199a-5p, miR-598 and miR-320a, which are predicted to be regulated by NFκB, were restored to levels similar to MMs. Validated targets co-regulated by these miRNAs were reciprocally increased in ZZs receiving AAT in vivo and in vitro. Expression of these miRNAs could be increased in ZZ monocytes treated ex vivo with an NFκB agonist and decreased by NFκB inhibition. p50 and p65 mRNA and protein were significantly lower in ZZs receiving AAT than untreated ZZs. AAT augmentation therapy inhibits NFκB and decreases miR-199a-5p, miR-598 and miR-320a in ZZ monocytes. These NFκB-inhibitory properties may contribute to the anti-inflammatory effects of AAT augmentation therapy.
    MeSH terms: Adult; Cells, Cultured; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Monocytes/drug effects; Monocytes/metabolism*; Monocytes/pathology; Trypsin Inhibitors/therapeutic use*; Serine Proteinase Inhibitors; Case-Control Studies; NF-kappa B/antagonists & inhibitors*; NF-kappa B/genetics; NF-kappa B/metabolism; alpha 1-Antitrypsin Deficiency/drug therapy; alpha 1-Antitrypsin Deficiency/genetics*; alpha 1-Antitrypsin Deficiency/metabolism; Gene Expression Profiling; MicroRNAs/genetics*
  2. Sengupta P, Nwagha U, Dutta S, Krajewska-Kulak E, Izuka E
    Afr Health Sci, 2017 Jun;17(2):418-427.
    PMID: 29062337 DOI: 10.4314/ahs.v17i2.16
    PURPOSE: This meta-analysis, following our previous reports those documented an overall 57% diminution in mean sperm concentration around the globe over past 35 years and 32.5% decline in past 50 years in European population, attempts to report the declining trend of sperm concentrations in African population between 1965 and 2015.

    METHODS: In the course of retrieval of data following MOOSE guidelines and PRISMA checklist, we found a total of fourteen studies that have been conducted during that period on altering sperm concentration in the African male.

    RESULTS: Following analysis of the data, a time-dependent decline of sperm concentration (r = -0.597, p = 0.02) and an overall 72.6% decrease in mean sperm concentration was noted in the past 50 years. The major matter of concern is the present mean concentration (20.38×106/ml) is very near to WHO cut-off value of 2010 of 15×106/ml. Several epidemic diseases, genital tract infection, pesticides and heavy metal toxicity, regular consumption of tobacco and alcohol are reported as predominant causative factors.

    CONCLUSION: This comprehensive, evidence-based meta-analysis and systematic review concisely presents the evidence of decreased sperm concentration in the African male over past 50 years with possible causative factors to serve the scientific research zone related to male reproductive health.

    MeSH terms: Adult; Africa/epidemiology; Humans; Male; Middle Aged; Risk Factors; Sperm Count/statistics & numerical data*; Young Adult
  3. Sharif Nia H, Pahlevan Sharif S, Lehto RH, Allen KA, Goudarzian AH, Yaghoobzadeh A, et al.
    Iran J Psychiatry, 2017 Jul;12(3):172-181.
    PMID: 29062368
    Objective: Limited research has examined the psychometric properties of death depression scales in Persian populations with cardiac disease despite the need for valid assessment tools for evaluating depressive symptoms in patients with life-limiting chronic conditions. The present study aimed at evaluating the reliability and validity of the Persian Version of Death Depression Scale - Revised (DDS-R) in Iranian patients who had recent acute myocardial infarction (AMI). Method: This psychometric study was conducted with a convenience sample of 407 patients with AMI diagnosis who completed the Persian version of the DDS-R. The face, content, and construct validity of the scale were ascertained. Internal consistency, test-retest, and construct reliability (CR) were used to assess reliability of the Persian Version of DDS-R. Results: Based on maximum likelihood exploratory factor analysis and consideration of conceptual meaning, a 4-factor solution was identified, explaining 75.89% of the total variance. Goodness-of-fit indices (GFI), Comparative Fit Index (CFI), Normed Fit Index (NFI), Incremental Fit Index (IFI), and Root Mean Square Error of Approximation (RMSEA) in the final DDS-R structure demonstrated the adequacy of the 4-domain structure. The internal consistency, construct reliability, and Intra-class Correlation Coefficients (ICC) were greater than .70. Conclusion: The DDS-R was found to be a valid and reliable assessment tool for evaluating death depression symptoms in Iranian patients with AMI.
  4. Shahidatul-Adha M, Zunaina E, Liza-Sharmini AT, Wan-Hazabbah WH, Shatriah I, Mohtar I, et al.
    Ann Med Surg (Lond), 2017 Dec;24:25-30.
    PMID: 29062482 DOI: 10.1016/j.amsu.2017.10.003
    INTRODUCTION: Ocular tuberculosis (TB) encompasses a broad spectrum of clinical manifestations affecting different structures of the eye. It is caused by Mycobacterium tuberculosis, a great ancient organism that induces various types of diseases and unfavorable outcomes if unrecognized and not well treated.

    PURPOSE: To report the clinical profile of 34 ocular TB cases observed during 6 years period in Hospital Universiti Sains Malaysia (HUSM).

    METHOD: A retrospective review of medical records from 34 patients diagnosed with ocular TB in HUSM from January 2011 until December 2016.

    RESULTS: The mean age was 43 ± 14.6 years old. Both male and female affected in about 1:1 ratio. The majority of subjects were local Malays (91.2%). Risk factors included previous contact with pulmonary TB patients (38.2%), and patients with underlying diabetes mellitus (26.5%). Most patients showed normal chest radiography (79.4%). However they had positive Mantoux test (94.1%) and raised erythrocyte sedimentation rate (ESR) value (58.8%). Uveitis was the most common ocular manifestation of ocular TB (70.6%) while the rare ocular manifestations included optic perineuritis and optic neuritis, orbital apex syndrome, orbital cellulitis, sclerokeratitis, corneal ulcer and conjunctival abscess. All patients responded well to anti-TB treatment, but visual outcome was variable.

    CONCLUSIONS: This review shows the diverse entity of ocular TB spectrum in an endemic area. Good clinical response to anti-tuberculous therapy supported the presumed diagnosis of ocular TB in majority of the cases.

    MeSH terms: Abscess; Adult; Blood Sedimentation; Corneal Ulcer; Eye; Female; Humans; Malaysia; Male; Middle Aged; Mycobacterium tuberculosis; Optic Neuritis; Retrospective Studies; Risk Factors; Tuberculin Test; Tuberculosis; Tuberculosis, Ocular; Tuberculosis, Pulmonary; Uveitis; Orbital Cellulitis
  5. Jawi ZM, Deros BM, Rashid AAA, Isa MHM, Awang A
    Sultan Qaboos Univ Med J, 2017 Aug;17(3):e277-e285.
    PMID: 29062549 DOI: 10.18295/squmj.2017.17.03.004
    This review article aimed to analyse existing literature regarding the roles and performance of professional driving instructors (PDIs) in novice driver education (DE). A systematic classification scheme was adopted to analyse identified articles to determine the study context of PDIs in novice DE, the competency level of PDIs in relation to experienced and learner drivers and the contributions of PDIs to the novice driver learning process. A total of 14 original research articles were identified, with no systematic reviews or meta-analyses available. Overall, all of the articles were found to be inadequate in providing an in-depth understanding of the roles and performance of PDIs in novice DE. There is an urgent need to improve current understanding of the roles of PDIs in novice DE and to work towards an internationally recognised PDI management approach.
    MeSH terms: Automobile Driving/education*; Humans; Professional Competence/standards*; Professional Role; Educational Personnel/standards*
  6. Cheng HS, Ton SH, Phang SCW, Tan JBL, Abdul Kadir K
    J Adv Res, 2017 Nov;8(6):743-752.
    PMID: 29062573 DOI: 10.1016/j.jare.2017.10.002
    The present study aimed to examine the effects of the types of high-calorie diets (high-fat and high-fat-high-sucrose diets) and two different developmental stages (post-weaning and young adult) on the induction of metabolic syndrome. Male, post-weaning and adult (3- and 8-week old, respectively) Sprague Dawley rats were given control, high-fat (60% kcal), and high-fat-high-sucrose (60% kcal fat + 30% sucrose water) diets for eight weeks (n = 6 to 7 per group). Physical, biochemical, and transcriptional changes as well as liver histology were noted. Post-weaning rats had higher weight gain, abdominal fat mass, fasting glucose, high density lipoprotein cholesterol, faster hypertension onset, but lower circulating advanced glycation end products compared to adult rats. This is accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR) α and γ in the liver and receptor for advanced glycation end products (RAGE) in the visceral adipose tissue. Post-weaning rats on high-fat diet manifested all phenotypes of metabolic syndrome and increased hepatic steatosis, which are linked to increased hepatic and adipocyte PPARγ expression. Adult rats on high-fat-high-sucrose diet merely became obese and hypertensive within the same treatment duration. Thus, it is more effective and less time-consuming to induce metabolic syndrome in male post-weaning rats with high-fat diet compared to young adult rats. As male rats were selectively included into the study, the results may not be generalisable to all post-weaning rats and further investigation on female rats is required.
    MeSH terms: Animals; Fasting; Female; Glucose; Humans; Hypertension; Cholesterol, HDL; Male; Obesity; Phenotype; Sucrose; Water; Weaning; Weight Gain; Up-Regulation; Rats, Sprague-Dawley; Adipocytes; PPAR alpha; PPAR gamma; Intra-Abdominal Fat; Rats; Diet, High-Fat
  7. Nittami T, Mukai M, Uematsu K, Yoon LW, Schroeder S, Chua ASM, et al.
    Appl Microbiol Biotechnol, 2017 Dec;101(23-24):8607-8619.
    PMID: 29063174 DOI: 10.1007/s00253-017-8571-3
    Previous studies have shown that enhanced biological phosphorus removal (EBPR) performance under continuous aerobic conditions always eventually deteriorates; however, the speed at which this happens depends on the carbon source supplied. The published data suggest that propionate is a better carbon source than acetate is for maintaining operational stability, although it is not clear why. A lab-scale sequencing batch reactor was run initially under conventional anaerobic/aerobic conditions with either acetate or propionate as the carbon source. Chemical and microbiological analyses revealed that both sources performed as expected for such systems. When continuous aerobic conditions were imposed on both these established communities, marked shifts of the "Candidatus Accumulibacter" clades were recorded for both carbon sources. Here, we discuss whether this shift could explain the prolonged EBPR stability observed with propionate.
    MeSH terms: Acetates/metabolism; Aerobiosis; Carbon/metabolism*; Phosphorus/metabolism*; Propionates/metabolism; Bioreactors/microbiology; Betaproteobacteria/classification*; Betaproteobacteria/metabolism*; Biota*
  8. Chaubal TV, Bapat RA, Bapat PR
    Contact Derm., 2017 Nov;77(5):325-326.
    PMID: 29063688 DOI: 10.1111/cod.12819
    MeSH terms: Adult; Female; Humans; Patch Tests; Plants, Medicinal/adverse effects; Stomatitis/diagnosis*; Stomatitis/etiology; Toothpastes/adverse effects*; Dermatitis, Allergic Contact/diagnosis*; Dermatitis, Allergic Contact/etiology; Salvadoraceae/adverse effects*
  9. Shah K, Chan LW, Wong TW
    Drug Deliv, 2017 Nov;24(1):1631-1647.
    PMID: 29063794 DOI: 10.1080/10717544.2017.1384298
    The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.
    MeSH terms: Administration, Inhalation; Antitubercular Agents/administration & dosage*; Antitubercular Agents/pharmacokinetics*; Cell Line; Chemistry, Pharmaceutical/methods; Emulsions/chemistry; Macrophages/drug effects; Particle Size; Rifampin/administration & dosage*; Rifampin/pharmacokinetics*; Tuberculosis/drug therapy*; Viscosity; Oleic Acid/chemistry; Chitosan; Nanoparticles/chemistry; Drug Liberation
  10. Li HB, You QS, Xu LX, Sun LX, Abdul Majid AS, Xia XB, et al.
    Cell Physiol Biochem, 2017;43(5):2117-2132.
    PMID: 29065394 DOI: 10.1159/000484231
    BACKGROUND/AIMS: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma.

    METHODS: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis.

    RESULTS: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups.

    CONCLUSION: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

    MeSH terms: Animals; Glaucoma/genetics; Glaucoma/metabolism*; Immunohistochemistry; Intraocular Pressure/genetics; Intraocular Pressure/physiology; Male; Retinal Ganglion Cells/metabolism*; Rats, Sprague-Dawley; Apoptosis/genetics; Apoptosis/physiology; Antigens, Thy-1/genetics; Antigens, Thy-1/metabolism; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism; In Situ Nick-End Labeling; Microscopy, Electron, Transmission; Transcription Factor Brn-3A/genetics; Transcription Factor Brn-3A/metabolism; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; Rats; RNA, Long Noncoding/genetics; RNA, Long Noncoding/metabolism*
  11. Subramaniam M, Abdin E, Vaingankar JA, Picco L, Seow E, Chua BY, et al.
    Ann Acad Med Singap, 2017 Mar;46(3):91-101.
    PMID: 28417133
    INTRODUCTION: The objectives of this current study were to: 1) examine the prevalence and correlates of diabetes mellitus (DM) among older adults (aged 60 years and above) in a multi-ethnic population; 2) examine the prevalence and correlates of comorbid DM and depression among them; and 3) assess the effect of comorbid depression on disability, cognition and healthcare utilisation.

    MATERIALS AND METHODS: Data for the current study came from the Well-being of the Singapore Elderly (WiSE) study; a single phase, cross-sectional survey conducted among Singapore residents aged 60 years and above. A total of 2565 respondents completed the survey; depression was assessed using the Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) while a diagnosis of DM was considered if respondents stated that a doctor had diagnosed them with DM.

    RESULTS: DM was reported by 25.5% of the population. The prevalence of depression was significantly higher in those diagnosed with DM than those without DM (6% vs 3%). After adjusting for sociodemographic correlates, smoking and other chronic conditions, DM remained significantly associated with depression and subsyndromal depression. However, after including measures of functioning and cognitive impairment as covariates, DM was not significantly related to depression and subsyndromal depression. Those with comorbid DM and depression were more likely to be of Indian and Malay ethnicity, aged 75 to 84 years (versus 60 to 74 years) and widowed.

    CONCLUSION: Given the significant association of certain sociodemographic groups with comorbid depression among those with DM, targeted interventions for prevention and early diagnosis in these groups should be considered.

    MeSH terms: Aged; Aged, 80 and over; Cross-Sectional Studies; Depression/epidemiology*; Depressive Disorder/epidemiology*; Diabetes Mellitus/epidemiology*; Ethnic Groups/statistics & numerical data; Female; Health Services/statistics & numerical data*; Humans; India/ethnology; Malaysia/ethnology; Male; Middle Aged; Surveys and Questionnaires; Severity of Illness Index; Singapore/epidemiology; Comorbidity; Prevalence; Asian Continental Ancestry Group/statistics & numerical data
  12. Mohamad NE, Yeap SK, Ky H, Ho WY, Boo SY, Chua J, et al.
    Food Nutr Res, 2017;61(1):1368322.
    PMID: 29056887 DOI: 10.1080/16546628.2017.1368322
    Obesity has become a serious health problem worldwide. Various types of healthy food, including vinegar, have been proposed to manage obesity. However, different types of vinegar may have different bioactivities. This study was performed to evaluate the anti-obesity and anti-inflammatory effects of coconut water vinegar on high-fat-diet (HFD)-induced obese mice. Changes in the gut microbiota of the mice were also evaluated. To induce obesity, C57/BL mice were continuously fed an HFD for 33 weeks. Coconut water vinegar (0.08 and 2 ml/kg body weight) was fed to the obese mice from early in week 24 to the end of week 33. Changes in the body weight, fat-pad weight, serum lipid profile, expression of adipogenesis-related genes and adipokines in the fat pad, expression of inflammatory-related genes, and nitric oxide levels in the livers of the untreated and coconut water vinegar-treated mice were evaluated. Faecal samples from the untreated and coconut water vinegar-treated mice (2 ml/kg body weight) were subjected to 16S metagenomic analysis to compare their gut microbiota. The oral intake of coconut water vinegar significantly (p 
  13. Annuar S, Mahmoodian R, Hamdi M, Tu KN
    Sci Technol Adv Mater, 2017;18(1):693-703.
    PMID: 29057024 DOI: 10.1080/14686996.2017.1364975
    The high performance and downsizing technology of three-dimensional integrated circuits (3D-ICs) for mobile consumer electronic products have gained much attention in the microelectronics industry. This has been driven by the utilization of chip stacking by through-Si-via and solder microbumps. Pb-free solder microbumps are intended to replace conventional Pb-containing solder joints due to the rising awareness of environmental preservation. The use of low-volume solder microbumps has led to crucial constraints that cause several reliability issues, including excessive intermetallic compounds (IMCs) formation and solder microbump embrittlement due to IMCs growth. This article reviews technologies related to 3D-ICs, IMCs formation mechanisms and reliability issues concerning IMCs with Pb-free solder microbumps. Finally, future outlook on the potential growth of research in this area is discussed.
  14. Chai KS, Norsarwany M, Shatriah I
    Cureus, 2017 Aug 16;9(8):e1573.
    PMID: 29057185 DOI: 10.7759/cureus.1573
    Ptosis is a rare side effect of vincristine chemotherapy in patients treated for cancer. We report a case of a child with common B-cell acute lymphoblastic leukemia who developed bilateral moderate ptosis following the chemotherapy protocol of the United Kingdom Acute Lymphoblastic Leukemia (ALL) regimen A. The patient showed dramatic clinical improvement after a combination of oral pyridoxine and thiamine treatment. We provide a literature review of this uncommon presentation.
    MeSH terms: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Blepharoptosis; Burkitt Lymphoma; Child; Humans; Pyridoxine; Thiamine; Vincristine; Precursor Cell Lymphoblastic Leukemia-Lymphoma
  15. Sharifzadeh G, Hosseinkhani H
    Adv Healthc Mater, 2017 Dec;6(24).
    PMID: 29057617 DOI: 10.1002/adhm.201700801
    Recent advances and applications of biomolecule-responsive hydrogels, namely, glucose-responsive hydrogels, protein-responsive hydrogels, and nucleic-acid-responsive hydrogels are highlighted. However, achieving the ultimate purpose of using biomolecule-responsive hydrogels in preclinical and clinical areas is still at the very early stage and calls for more novel designing concepts and advance ideas. On the way toward the real/clinical application of biomolecule-responsive hydrogels, plenty of factors should be extensively studied and examined under both in vitro and in vivo conditions. For example, biocompatibility, biointegration, and toxicity of biomolecule-responsive hydrogels should be carefully evaluated. From the living body's point of view, biocompatibility is seriously depended on the interactions at the tissue/polymer interface. These interactions are influenced by physical nature, chemical structure, surface properties, and degradation of the materials. In addition, the developments of advanced hydrogels with tunable biological and mechanical properties which cause no/low side effects are of great importance.
    MeSH terms: Biocompatible Materials/chemistry*; Boronic Acids/chemistry; Glucose/chemistry; Humans; Polyethylene Glycols/chemistry; Polyethyleneimine/chemistry; Polymers/chemistry; Proteins/chemistry; Drug Delivery Systems; Hydrogels/chemistry*
  16. Sim PF, Furusawa G, Teh AH
    Sci Rep, 2017 10 20;7(1):13656.
    PMID: 29057942 DOI: 10.1038/s41598-017-13288-1
    AlyQ from Persicobacter sp. CCB-QB2 is an alginate lyase with three domains - a carbohydrate-binding domain modestly resembling family 16 carbohydrate-binding module (CBM16), a family 32 CBM (CBM32) domain, and an alginate lyase domain belonging to polysaccharide lyase family 7 (PL7). Although AlyQ can also act on polyguluronate (poly-G) and polymannuronate (poly-M), it is most active on alginate. Studies with truncated AlyQ showed that the CBM32 domain did not contribute to enhancing AlyQ's activity under the assayed conditions. Nevertheless, it could bind to cleaved but not intact alginate, indicating that the CBM32 domain recognises alginate termini. The crystal structure containing both CBM32 and catalytic domains show that they do not interact with one another. The CBM32 domain contains a conserved Arg that may bind to the carboxyl group of alginate. The catalytic domain, meanwhile, shares a conserved substrate-binding groove, and the presence of two negatively charged Asp residues may dictate substrate specificity especially at subsite +1. As Persicobacter sp. CCB-QB2 was unable to utilise alginate, AlyQ may function to help the bacterium degrade cell walls more efficiently.
    MeSH terms: Alginates/chemistry; Amino Acid Sequence; Bacterial Proteins/metabolism*; Bacterial Proteins/chemistry; Escherichia coli; Kinetics; Polysaccharide-Lyases/metabolism*; Polysaccharide-Lyases/chemistry; Protein Conformation; Catalytic Domain; Bacteroidetes
  17. Guarino V, Cruz Maya I, Altobelli R, Abdul Khodir WK, Ambrosio L, Alvarez Pèrez MA, et al.
    Nanotechnology, 2017 Oct 23.
    PMID: 29058684 DOI: 10.1088/1361-6528/aa9542
    Main limitation of conventional antibiotic therapies concerns the low efficacy to bacteria attacks for long treatment times. In this context, the integrated use of electrofluidodynamics (EFDs) - basically electrospinning and electrospraying - may represent an interesting route to design nanostructured platforms with controlled release to prevent the formation of bacterial biofilms in oral implant sites. They allow for the deposition of nanofibres and nanoparticles by different modes - i.e., sequential, simultaneous - for the fabrication of more efficacious systems in terms of degradation protection, pharmacokinetic control and drug distribution to the surrounding tissues. Herein, we will investigate EFDs processing modes and conditions to decorate polycaprolactone (PCL) nanofibres surfaces by chitosan (CS) nano-reservoirs for the administration of Amoxicillin Trihydrate (AMX-DHT) as innovative antibacterial treatment of the periodontal pocket.
  18. Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, et al.
    Nat Genet, 2017 Dec;49(12):1767-1778.
    PMID: 29058716 DOI: 10.1038/ng.3785
    Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
    MeSH terms: Breast Neoplasms/ethnology; Breast Neoplasms/genetics*; Breast Neoplasms/metabolism; Female; Heterozygote; Humans; Mutation*; Receptors, Estrogen/metabolism; Risk Factors; BRCA1 Protein/genetics*; Genetic Predisposition to Disease/ethnology; Genetic Predisposition to Disease/genetics*; Polymorphism, Single Nucleotide*; European Continental Ancestry Group/genetics; Genome-Wide Association Study/methods
  19. Ponomarenko O, La Porte PF, Singh SP, Langan G, Fleming DEB, Spallholz JE, et al.
    Metallomics, 2017 Nov 15;9(11):1585-1595.
    PMID: 29058732 DOI: 10.1039/c7mt00201g
    Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking water, currently affects millions of people in South-East Asia and elsewhere. Previous animal studies revealed that the toxicity of arsenite essentially can be abolished if selenium is co-administered as selenite. Although subsequent studies have provided some insight into the biomolecular basis of this striking antagonism, many details of the biochemical pathways that ultimately result in the detoxification and excretion of arsenic using selenium supplements have yet to be thoroughly studied. To this end and in conjunction with the recent Phase III clinical trial "Selenium in the Treatment of Arsenic Toxicity and Cancers", we have applied synchrotron X-ray techniques to elucidate the mechanisms of this arsenic-selenium antagonism at the tissue and organ levels using an animal model. X-ray fluorescence imaging (XFI) of cryo-dried whole-body sections of laboratory hamsters that had been injected with arsenite, selenite, or both chemical species, provided insight into the distribution of both metalloids 30 minutes after treatment. Co-treated animals showed strong co-localization of arsenic and selenium in the liver, gall bladder and small intestine. X-ray absorption spectroscopy (XAS) of freshly frozen organs of co-treated animals revealed the presence in liver tissues of the seleno bis-(S-glutathionyl) arsinium ion, which was rapidly excreted via bile into the intestinal tract. These results firmly support the previously postulated hepatobiliary excretion of the seleno bis-(S-glutathionyl) arsinium ion by providing the first data pertaining to organs of whole animals.
  20. Kar SK, Dwibedi B, Das BK, Agrawala BK, Ramachandran CP, Horton J
    PLoS Negl Trop Dis, 2017 Oct;11(10):e0005631.
    PMID: 29059186 DOI: 10.1371/journal.pntd.0005631
    BACKGROUND: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally.

    METHODS: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years.

    FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs.

    INTERPRETATION: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration.

    TRIAL REGISTRATION: ClinicalTrials.gov No CTRI/2013/10/004121.

    MeSH terms: Administration, Oral; Adolescent; Animals; Child; Child, Preschool; Diethylcarbamazine/administration & dosage; Diethylcarbamazine/therapeutic use*; Elephantiasis, Filarial/drug therapy*; Elephantiasis, Filarial/parasitology; Elephantiasis, Filarial/pathology*; Female; Filaricides/therapeutic use*; Humans; India; Lymphatic System/pathology*; Lymphedema/drug therapy; Lymphedema/parasitology; Male; Wuchereria bancrofti/isolation & purification; Albendazole/administration & dosage; Albendazole/therapeutic use*; Treatment Outcome; Asymptomatic Infections; Lymphoscintigraphy
External Links