Browse publications by year: 2018

  1. Zulkepli SNIS, Hamid NH, Shukla V
    Biosensors (Basel), 2018 May 08;8(2).
    PMID: 29738428 DOI: 10.3390/bios8020045
    In recent years, the number of interdisciplinary research works related to the development of miniaturized systems with integrated chemical and biological analyses is increasing. Digital microfluidic biochips (DMFBs) are one kind of miniaturized systems designed for conducting inexpensive, fast, convenient and reliable biochemical assay procedures focusing on basic scientific research and medical diagnostics. The role of a dielectric layer in the digital microfluidic biochips is prominent as it helps in actuating microliter droplets based on the electrowetting-on-dielectric (EWOD) technique. The advantages of using three different material layers of dielectric such as parafilm, polytetrafluoroethylene (PTFE) and ethylene tetrafluoroethylene (ETFE) were reported in the current work. A simple fabrication process of a digital microfluidic device was performed and good results were obtained. The threshold of the actuation voltage was determined for all dielectric materials of varying thicknesses. Additionally, the OpenDrop device was tested by utilizing a single-plate system to transport microliter droplets for a bioassay operation. With the newly proposed fabrication methods, these dielectric materials showed changes in contact angle and droplet velocity when the actuation voltage was applied. The threshold actuation voltage for the dielectric layers of 10⁻13 μm was 190 V for the open plate DMFBs.
    MeSH terms: Equipment Design; Microfluidics/methods*; Microfluidic Analytical Techniques/methods*; Electrowetting/methods*
  2. Gubartallah EA, Makahleh A, Quirino JP, Saad B
    Molecules, 2018 05 08;23(5).
    PMID: 29738463 DOI: 10.3390/molecules23051112
    A rapid and green analytical method based on capillary electrophoresis with capacitively coupled contactless conductivity detection (C⁴D) for the determination of eight environmental pollutants, the biogenic amines (putrescine, cadaverine, spermidine, spermine, tyramine, 2-phenylamine, histamine and tryptamine), is described. The separation was achieved under normal polarity mode at 24 °C and 25 kV with a hydrodynamic injection (50 mbar for 5 s) and using a bare fused-silica capillary (95 cm length × 50 µm i.d.) (detection length of 10.5 cm from the outlet end of the capillary). The optimized background electrolyte consisted of 400 mM malic acid. C⁴D parameters were set at a fixed amplitude (50 V) and frequency (600 kHz). Under the optimum conditions, the method exhibited good linearity over the range of 1.0⁻100 µg mL−1 (R² ≥ 0.981). The limits of detection based on signal to noise (S/N) ratios of 3 and 10 were ≤0.029 µg mL−1. The method was used for the determination of seawater samples that were spiked with biogenic amines. Good recoveries (77⁻93%) were found.
    MeSH terms: Biogenic Amines/isolation & purification*; Biogenic Amines/chemistry; Electric Conductivity; Seawater/chemistry*; Spermidine/isolation & purification*; Spermidine/chemistry; Spermine/isolation & purification*; Spermine/chemistry; Electrophoresis, Capillary
  3. Jaafaru MS, Abd Karim NA, Enas ME, Rollin P, Mazzon E, Abdull Razis AF
    Nutrients, 2018 May 08;10(5).
    PMID: 29738500 DOI: 10.3390/nu10050580
    Crucifer vegetables, Brassicaceae and other species of the order Brassicales, e.g., Moringaceae that are commonly consumed as spice and food, have been reported to have potential benefits for the treatment and prevention of several health disorders. Though epidemiologically inconclusive, investigations have shown that consumption of those vegetables may result in reducing and preventing the risks associated with neurodegenerative disease development and may also exert other biological protections in humans. The neuroprotective effects of these vegetables have been ascribed to their secondary metabolites, glucosinolates (GLs), and their related hydrolytic products, isothiocyanates (ITCs) that are largely investigated for their various medicinal effects. Extensive pre-clinical studies have revealed more than a few molecular mechanisms of action elucidating multiple biological effects of GLs hydrolytic products. This review summarizes the most significant and up-to-date in vitro and in vivo neuroprotective actions of sulforaphane (SFN), moringin (MG), phenethyl isothiocyanate (PEITC), 6-(methylsulfinyl) hexyl isothiocyanate (6-MSITC) and erucin (ER) in neurodegenerative diseases.
    MeSH terms: Brassica/chemistry; Glucosinolates/pharmacology*; Humans; Sulfides/pharmacology; Thiocyanates/pharmacology; Vegetables/chemistry; Isothiocyanates/pharmacology; Neuroprotective Agents/pharmacology*; Neurodegenerative Diseases/drug therapy*
  4. Mujtaba G, Shuib L, Raj RG, Rajandram R, Shaikh K, Al-Garadi MA
    J Biomed Inform, 2018 06;82:88-105.
    PMID: 29738820 DOI: 10.1016/j.jbi.2018.04.013
    Text categorization has been used extensively in recent years to classify plain-text clinical reports. This study employs text categorization techniques for the classification of open narrative forensic autopsy reports. One of the key steps in text classification is document representation. In document representation, a clinical report is transformed into a format that is suitable for classification. The traditional document representation technique for text categorization is the bag-of-words (BoW) technique. In this study, the traditional BoW technique is ineffective in classifying forensic autopsy reports because it merely extracts frequent but discriminative features from clinical reports. Moreover, this technique fails to capture word inversion, as well as word-level synonymy and polysemy, when classifying autopsy reports. Hence, the BoW technique suffers from low accuracy and low robustness unless it is improved with contextual and application-specific information. To overcome the aforementioned limitations of the BoW technique, this research aims to develop an effective conceptual graph-based document representation (CGDR) technique to classify 1500 forensic autopsy reports from four (4) manners of death (MoD) and sixteen (16) causes of death (CoD). Term-based and Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) based conceptual features were extracted and represented through graphs. These features were then used to train a two-level text classifier. The first level classifier was responsible for predicting MoD. In addition, the second level classifier was responsible for predicting CoD using the proposed conceptual graph-based document representation technique. To demonstrate the significance of the proposed technique, its results were compared with those of six (6) state-of-the-art document representation techniques. Lastly, this study compared the effects of one-level classification and two-level classification on the experimental results. The experimental results indicated that the CGDR technique achieved 12% to 15% improvement in accuracy compared with fully automated document representation baseline techniques. Moreover, two-level classification obtained better results compared with one-level classification. The promising results of the proposed conceptual graph-based document representation technique suggest that pathologists can adopt the proposed system as their basis for second opinion, thereby supporting them in effectively determining CoD.
    MeSH terms: Machine Learning; Algorithms; Automation; Autopsy/methods*; Cause of Death*; Computer Graphics; Forensic Medicine/methods*; Humans; Medical Informatics/methods*; Software; Information Storage and Retrieval; Systematized Nomenclature of Medicine*
  5. Liew SQ, Teoh WH, Tan CK, Yusoff R, Ngoh GC
    Int J Biol Macromol, 2018 Sep;116:128-135.
    PMID: 29738869 DOI: 10.1016/j.ijbiomac.2018.05.013
    Low methoxyl (LM) pectin was extracted from pomelo peels using subcritical water in a dynamic mode. The effects of pressure and temperature were analyzed through a face-centred central composite design. Extraction yield and the rate of extraction were found to be predominantly influenced by temperature. Optimization of the subcritical water extraction (SWE) yielded an optimized operating condition of 120°C and 30bar with a predicted pectin yield of 18.8%. The corresponding experimental yield was 19.6%, which is in close agreement with the predicted data. The pectin obtained from the optimized condition was further analyzed for its physicochemical properties. The kinetics of the SWE was also evaluated whereby the one-site kinetic desorption model was found to be in good agreement with experimental data (R2>0.94).
    MeSH terms: Citrus/chemistry*; Fruit/chemistry; Kinetics; Pectins/chemistry*; Temperature; Water/chemistry*
  6. Hudu SA, Niazlin MT, Nordin SA, Saeed MI, Tan SS, Omar H, et al.
    Clin. Lab., 2018 Apr 01;64(4):443-449.
    PMID: 29739076 DOI: 10.7754/Clin.Lab.2017.170916
    BACKGROUND: Hepatitis B surface antigen is usually secreted by infected hepatocytes in the form of subviral particles rather than infectious virions, while the hepatitis B e antigen originates from the core gene and is modified and secreted by hepatocytes into the circulation and functions as a marker of active viral replication. This study aimed to study the relationship between HBV DNA and quantitative hepatitis B surface and e antigen in Malaysian patients.

    METHODS: A total of 82 chronic hepatitis B patients were recruited for this study from the Hepatology Department of Selayang Hospital. Quantitative hepatitis surface and e antigen was performed retrospectively on frozen plasma using enzyme linked immunosorbent assay according to the manufacturer's instructions. Hepatitis B viral DNA was extracted from all plasma samples and quantified using real-time PCR.

    RESULTS: Quantitative hepatitis B surface and e antigens were found be high in 54.9% and 52.4% of the patients, respectively, while hepatitis B virus DNA level was high in 70.7%. The median of the viral load of HBV was 8,934.89 IU/mL and both hepatitis B surface and e antigens were also found to be high on average for qHBsAg (M = 5.19 IU/mL, SD ± 4. 33) and qHBeAg (M = 4.74IU/mL, SD ± 4.20), with qHBeAg being more strongly correlated to HBV DNA than qHBsAg (r = 0.893; p < 0.01).

    CONCLUSIONS: This study revealed HBeAg to be the most appropriate marker that correlates well with HBV DNA, thus not completely novel but confirmative, and related to the Malaysian situation.

  7. Samsudin I, Page MM, Hoad K, Chubb P, Gillett M, Glendenning P, et al.
    Ann. Clin. Biochem., 2018 Nov;55(6):679-684.
    PMID: 29660998 DOI: 10.1177/0004563218774590
    Background Plasma-free metanephrines (PFM) or urinary fractionated metanephrines (UFM) are the preferred biochemical tests for the diagnosis of phaeochromocytoma and paraganglioma (PPGL). Borderline increased results should be followed up to either exclude or confirm diagnosis. Methods We extracted all PFM and UFM results reported by our laboratory over a six-month period from the laboratory information system. We categorized patients with borderline increased results according to whether follow-up testing had been performed as suggested in the initial laboratory report. Questionnaires were then sent to all requesting doctors and medical notes reviewed where available. Results Two hundred and four patients with borderline increased PFM or UFM were identified. Sixty-five (38.5%) of 169 patients with borderline increased PFM had a repeat test out of which 36 were normal and 29 did not normalize. Of 35 patients with borderline increased UFM, 17 (48.6%) had subsequent PFM measurement, out of which 15 were normal. Questionnaires were returned to 106 (52%) patients. Of these, the most frequent indication for testing was hypertension ( n = 50); 15 patients had an incidental adrenal mass and two of these patients were diagnosed with a phaeochromocytoma. Conclusion Only 38% of patients with borderline increased PFM had a repeat PFM measurement. This was not significantly higher when compared with the 28% in a previous audit that we reported in 2010 ( P = 0.10). Forty-nine per cent of patients with a borderline increased UFM had a repeat UFM or PFM measurement. There remains a substantial possibility of missed detection of PPGL.
    MeSH terms: Adrenal Gland Neoplasms/diagnosis*; Diagnosis, Differential; Follow-Up Studies; Metanephrine/urine*; Paraganglioma/diagnosis*; Pheochromocytoma/diagnosis*; Reference Standards; Retrospective Studies
  8. Adebayo IA, Arsad H, Samian MR
    Pharmacogn Mag, 2018 04 10;14(54):191-194.
    PMID: 29720830 DOI: 10.4103/pm.pm_212_17
    Background: Academic reports have confirmed Moringa oleifera leaves to possess significant antioxidant capacities; however, such studies are unavailable for its ripe seeds even though they are more desirous for consumption due to their sweet taste.

    Objective: In this study, we investigated antioxidant capacities of four polar extracts (crude water, ethanol, butanol, and aqueous residue) from the plant's ripe seeds.

    Materials and Methods: Phytochemicals were extracted from the ripe seeds of M. oleifera using ethanol and water solvents at initial stage. Butanol and aqueous residue were then subsequently fractioned out from the ethanol extract. Phenolic and flavonoid contents of the polar extracts were determined. Then, their antioxidant capacities were quantified by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Finally, gas chromatography-mass spectrometry (GC-MS) analyses of the extracts were performed.

    Results: DPPH and ABTS tests showed that the polar extracts possess significant antioxidant capacities that ranged from 29 to 35.408 μM Trolox equivalence antioxidant capacity (TEAC)/mg sample and 7 to 29 μM TEAC/mg sample, respectively. The antioxidant capacities of the extracts corresponded to their phenolic and flavonoid contents that varied from 13.61 to 20.42 mg gallic acid equivalence/g sample and 0.58 to 9.81 mg quercetin equivalence/g sample, respectively. Finally, GC-MS analyses revealed antimicrobial phenolic compounds, 4-hydroxybenzaldehyde in crude water extract and 4-hydroxybenzene acetonitrile in the ethanol and butanol extracts, and aqueous residue.

    Conclusion: Our results established that M. oleifera ripe seeds have significant antioxidant activity which may be due to its phenolic and nonphenolic compounds content.

    SUMMARY: In this study, polar phytochemicals from ripe seeds of Moringa oleifera were extracted by water and ethanol solvents, and butanol extract and aqueous residue were subsequently fractioned out of the ethanol extract. The four polar extracts were shown to have significant antioxidant capacities which correspond to their phenolic contents. Further, antimicrobial compounds 4-hydroxybenzaldehyde and 4-hydroxybenzene acetonitrile were identified in the extracts by gas chromatography-mass spectrometry analyses. Abbreviations used: ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); DPPH: 2,2-diphenyl-1-picrylhydrazyl; TEAC: Trolox equivalence antioxidant capacity; QE: Quercetin equivalence; GAE: Gallic acid equivalence; GC-MS: Gas chromatography-mass spectrometry.

  9. Tan ST, Ong HC, Chai TT, Wong FC
    Pharmacogn Mag, 2018 04 10;14(54):227-230.
    PMID: 29720836 DOI: 10.4103/pm.pm_282_17
    Background: Medicinal fern species represent a potentially important source for both food and medicinal applications. Previously, two underutilized tropical fern species (Blechnum orientale and Phymatopteris triloba) were reported with cytotoxic activities against selected cancer cell lines. However, the exact mechanism remains elusive.

    Objective: In this paper, we reported the identification of six differentially expressed proteins isolated from cancer cells, following exposure to the cytotoxic fern extracts.

    Materials and Methods: The identities of these cancer proteins were determined by matrix-assisted laser desorption ionization time-of-flight protein sequencing.

    Results: The cancer proteins were identified as follows: elongation factor 1-γ, glyceraldehydes-3-phosphate dehydrogenase, heat shock protein 90-β, heterogeneous nuclear ribonucleoprotein-A2/B1, truncated nucleolar phosphoprotein B23, and tubulin-β chain. To the best of our knowledge, this paper represents the first time these cancer proteins are being reported, following exposure to the aforementioned cytotoxic fern extracts.

    Conclusion: It is hoped that further efforts in this direction could lead to the identification and development of target-specific chemotherapeutic agents.

    SUMMARY: Cytotoxic fern extracts were tested in anti-cancer proteomic works.Six differentially-expressed cancer proteins were identified.Potential anti-cancer protein targets were reported. Abbreviations used: EF: Elongation factor; HRP: Horseradish peroxidase; HSP: Heat shock protein; MALDI: Matrix-assisted laser desorption/ionization.

  10. Ahmad N, Khan AH, Khan I, Khan A, Atif M
    Int J Hypertens, 2018;2018:8524063.
    PMID: 29721335 DOI: 10.1155/2018/8524063
    Aim: To evaluate doctors' knowledge, attitude, and practices and predictors of adherence to Malaysian hypertension guidelines (CPG 2008).
    Methods: Twenty-six doctors involved in hypertension management at Penang General Hospital were enrolled in a cross-sectional study. Doctors' knowledge and attitudes towards guidelines were evaluated through a self-administered questionnaire. Their practices were evaluated by noting their prescriptions written to 520 established hypertensive outpatients (20 prescriptions/doctor). SPSS 17 was used for data analysis.
    Results: Nineteen doctors (73.07%) had adequate knowledge of guidelines. Specialists and consultants had significantly better knowledge about guidelines' recommendations. Doctors were positive towards guidelines with mean attitude score of 23.15 ± 1.34 points on a 30-point scale. The median number of guidelines compliant prescriptions was 13 (range 5-20). Statistically significant correlation (rs = 0.635, P < 0.001) was observed between doctors' knowledge and practice scores. A total of 349 (67.1%) prescriptions written were guidelines compliant. In multivariate analysis hypertension clinic (OR = 0.398, P = 0.008), left ventricular hypertrophy (OR = 0.091, P = 0.001) and heart failure (OR = 1.923, P = 0.039) were significantly associated with guidelines adherence.
    Conclusion: Doctors' knowledge of guidelines is reflected in their practice. The gap between guidelines recommendations and practice was seen in the pharmacotherapy of uncomplicated hypertension and hypertension with left ventricular hypertrophy, renal disease, and diabetes mellitus.
    Study site: Cardiology, nephrology, diabetic, and hypertension clinics of Hospital Pulau Pinang, Malaysia
    MeSH terms: Adult; Cross-Sectional Studies; Health Personnel; Hospitals, General; Humans; Hypertension; Health Knowledge, Attitudes, Practice; Malaysia; Outpatient Clinics, Hospital; Guideline Adherence
  11. Sahebi M, Hanafi MM, Mohidin H, Rafii MY, Azizi P, Idris AS, et al.
    Biomed Res Int, 2018;2018:1494157.
    PMID: 29721500 DOI: 10.1155/2018/1494157
    Oil palm (Elaeis guineensis Jacq) is one of the major sources of edible oil. Reducing the effect of Ganoderma, main cause of basal stem rot (BSR) on oil palm, is the main propose of this study. Understanding the oil palm defense mechanism against Ganoderma infection through monitoring changes in the secondary metabolite compounds levels before/after infection by Ganoderma under different fertilizing treatment is required. Oil palm requires macro- and microelements for growth and yield. Manipulating the nutrient for oil palm is a method to control the disease. The 3-4-month-old oil palm seedlings were given different macronutrient treatments to evaluate induction of defense related enzymes and production of secondary metabolite compounds in response to G. boninense inoculation. The observed trend of changes in the infected and uninfected seedlings was a slightly higher activity for β-1,3-glucanases, chitinase, peroxidase, and phenylalanine ammonia-lyase during the process of pathogenesis. It was found that PR proteins gave positive response to the interaction between oil palm seedlings and Ganoderma infection. Although the responses were activated systematically, they were short-lasting as the changes in enzymes activities appeared before the occurrence of visible symptoms. Effect of different nutrients doses was obviously observed among the results of the secondary metabolite compounds. Many identified/unidentified metabolite compounds were presented, of which some were involved in plant cell defense mechanism against pathogens, mostly belonging to alkaloids with bitter-tasting nitrogenous-compounds, and some had the potential to be used as new markers to detect basal stem rot at the initial step of disease.
    MeSH terms: Antioxidants/metabolism*; Fertilizers*; Oxidoreductases/metabolism*; Plant Diseases/microbiology*; Plant Proteins/metabolism*; Ganoderma*
  12. Handool KO, Ibrahim SM, Kaka U, Omar MA, Abu J, Yusoff MSM, et al.
    J Exp Orthop, 2018 May 02;5(1):13.
    PMID: 29721763 DOI: 10.1186/s40634-018-0128-6
    BACKGROUND: The use of a closed fracture model has become the preferred model to study the fracture healing process, given that the periosteum and the soft tissue surrounding the fracture site play an important role in the fracture healing process. Some techniques like osteotomy, drilling the long bones and the use of the guillotine-like apparatus to induce fracture are characterized by some undesirable effects and complications. The aim of this study is to optimize and evaluate an in vivo fracture model using three-point bending pliers that can be used to study secondary bone fracture healing in rats.

    METHODS: Modified three-point bending pliers were used as a device to create the closed rat tibial bone fracture that was prefixed with an intramedullary pin (23 G × 11/2″) in rats. The exact location of the induced closed fracture was along the long bone. The presence of bone comminution, and the fracture bone alignment were immediately examined after the induction of the fracture until the 6th week.

    RESULTS: All fractures induced were transverse, located in the middle to proximal one third of the tibia, and they all healed without complications. Bone union as shown radiographically occurred within 2-3 weeks postoperative. The average angle of the fracture line with the axis of the tibia was 89.41 ± 2.11°. The lateral and anterio-posterior pin angulation views were 167.33 ± 3.67° and 161.60 ± 4.87° respectively. The average length of proximal end of the fractured bone in comparison with the whole length of intact bone was 41.02 ± 3.27%. There was a significant difference in percentage of the gross callus area and gross callus index, while there was no significant difference in X-ray callus index. There was no significant difference of the gross callus area between slight comminution (n = 4) and non comminution (n = 21).

    CONCLUSION: The optimized rat tibial fracture model resulted in mainly transverse tibial mid-shaft fractures with minimal bone comminution and absence of surrounding soft tissue damage. The size area of consequent soft callus formation and the extent to which the closed fracture model was reproducible are very good outcomes making it feasible for in vivo laboratory research use.

  13. Muhamad N, Abdullah N, Rahman MA, Abas KH, Aziz AA, Othman MHD, et al.
    Environ Sci Pollut Res Int, 2018 Jul;25(19):19054-19064.
    PMID: 29721796 DOI: 10.1007/s11356-018-2074-3
    This work describes the development of supported zeolite-Y membranes, prepared using the hydrothermal method, for the removal of nickel from an aqueous solution. Alumina hollow fibers prepared using the phase inversion and sintering technique were used as an inert support. The supported zeolite-Y membranes were characterized using the field emission scanning electron microscope (FESEM), X-ray diffraction (XRD), and the water permeation and rejection test. The performance of the supported zeolite-Y membranes for heavy metal removal using batch adsorption and filtration test was studied using the atomic absorption spectroscopy (AAS). The adsorption study shows that the removal of nickel was pH-dependent but affected by the presence of α-alumina. The seeded zeolite-Y membrane gave the highest adsorption capacity which was 126.2 mg g-1. This enabled the membrane to remove 63% of nickel ions from the aqueous solution within 180 min of contact time. The adsorption mechanism of nickel onto the zeolite-Y membrane was best fitted to the Freundlich isotherm. The kinetic study concluded that the adsorption was best fitted to pseudo-second-order model with higher correlation coefficient (R2 = 0.9996). The filtration study proved that the zeolite-Y membrane enabled to reduce the concentration of heavy metal at parts per billion level.
    MeSH terms: Adsorption; Aluminum Oxide; Filtration; Ions; Microscopy, Electron, Scanning; Nickel; Spectrophotometry, Atomic; Water; X-Ray Diffraction; Zeolites; Metals, Heavy
  14. Damanik N, Ong HC, Tong CW, Mahlia TMI, Silitonga AS
    Environ Sci Pollut Res Int, 2018 Jun;25(16):15307-15325.
    PMID: 29721797 DOI: 10.1007/s11356-018-2098-8
    Biodiesels have gained much popularity because they are cleaner alternative fuels and they can be used directly in diesel engines without modifications. In this paper, a brief review of the key studies pertaining to the engine performance and exhaust emission characteristics of diesel engines fueled with biodiesel blends, exhaust aftertreatment systems, and low-temperature combustion technology is presented. In general, most biodiesel blends result in a significant decrease in carbon monoxide and total unburned hydrocarbon emissions. There is also a decrease in carbon monoxide, nitrogen oxide, and total unburned hydrocarbon emissions while the engine performance increases for diesel engines fueled with biodiesels blended with nano-additives. The development of automotive technologies, such as exhaust gas recirculation systems and low-temperature combustion technology, also improves the thermal efficiency of diesel engines and reduces nitrogen oxide and particulate matter emissions.
    MeSH terms: Vehicle Emissions/analysis*; Carbon Monoxide/analysis*; Carbon Monoxide/chemistry; Gasoline/analysis*; Nitrogen Oxides/analysis*; Nitrogen Oxides/chemistry; Biofuels/analysis*
  15. Williams M, Valayannopoulos V, Altassan R, Chung WK, Heijboer AC, Keng WT, et al.
    J Inherit Metab Dis, 2018 May 02.
    PMID: 29721915 DOI: 10.1007/s10545-018-0184-1
    BACKGROUND: Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation.

    METHODS: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients.

    RESULTS AND CONCLUSIONS: Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.

    MeSH terms: Anemia; Carbohydrate Metabolism, Inborn Errors; Counseling; Fetal Growth Retardation; Follicle Stimulating Hormone; Genotype; Heart Diseases; Hepatomegaly; Humans; Luteinizing Hormone; Pentose Phosphate Pathway; Phenotype; Prognosis; Surveys and Questionnaires; Retrospective Studies; Testosterone; Thrombocytopenia; Transaldolase; Genetic Association Studies
  16. Ambaras Khan R, Aziz Z
    J Clin Pharm Ther, 2018 Aug;43(4):450-459.
    PMID: 29722052 DOI: 10.1111/jcpt.12696
    WHAT IS KNOWN AND OBJECTIVES: Clinical practice guidelines serve as a framework for physicians to make decisions and to support best practice for optimizing patient care. However, if the guidelines do not address all the important components of optimal care sufficiently, the quality and validity of the guidelines can be reduced. The objectives of this study were to systematically review current guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), evaluate their methodological quality and highlight the similarities and differences in their recommendations for empirical antibiotic and antibiotic de-escalation strategies.

    METHODS: This review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic databases including MEDLINE, CINAHL, PubMed and EMBASE were searched up to September 2017 for relevant guidelines. Other databases such as NICE, Scottish Intercollegiate Guidelines Network (SIGN) and the websites of professional societies were also searched for relevant guidelines. The quality and reporting of included guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) instrument.

    RESULTS AND DISCUSSION: Six guidelines were eligible for inclusion in our review. Among 6 domains of AGREE-II, "clarity of presentation" scored the highest (80.6%), whereas "applicability" scored the lowest (11.8%). All the guidelines supported the antibiotic de-escalation strategy, whereas the majority of the guidelines (5 of 6) recommended that empirical antibiotic therapy should be implemented in accordance with local microbiological data. All the guidelines suggested that for early-onset HAP/VAP, therapy should start with a narrow spectrum empirical antibiotic such as penicillin or cephalosporins, whereas for late-onset HAP/VAP, the guidelines recommended the use of a broader spectrum empirical antibiotic such as the penicillin extended spectrum carbapenems and glycopeptides.

    WHAT IS NEW AND CONCLUSIONS: Expert guidelines promote the judicious use of antibiotics and prevent antibiotic overuse. The quality and validity of available HAP/VAP guidelines would be enhanced by improving their adherence to accepted best practice for the management of HAP and VAP.

    MeSH terms: Anti-Bacterial Agents/standards*; Anti-Bacterial Agents/therapeutic use*; Cross Infection/drug therapy*; Humans; Drug Prescriptions/standards*; Practice Guidelines as Topic; Pneumonia, Ventilator-Associated/drug therapy*
  17. Cheah PL, Koh CC, Khang TF, Goh KL, Lau PC, Chin KF, et al.
    J Dig Dis, 2018 May;19(5):272-278.
    PMID: 29722130 DOI: 10.1111/1751-2980.12605
    OBJECTIVE: With an age-standardized incidence rate of 2 per 100 000, esophageal cancer is not common among Malaysians, but they are nevertheless important due to its poor prognosis. The study is to clarify whether the human papillomavirus (HPV) is associated with esophageal cancer in Malaysians as there has been no report to date on this in Malaysians and other South East Asians.

    METHODS: Altogether 67 esophageal squamous cell carcinomas histologically diagnosed between 1 January 2004 and 31 December 2014 at the Department of Pathology, University of Malaya Medical Center, Malaysia were considered for HPV analysis using two commercially available methods, polymerase chain reaction with flow-through hybridization (21 HPV GenoArray Diagnostic Kit) and multiplex real-time polymerase chain reaction (Anyplex II HPV28 Detection). The DNA amplifiability of the formalin-fixed, paraffin-embedded tumor was checked by amplification of a 268 bp segment of the human β-globin gene (GH20/PC04) prior to HPV detection.

    RESULTS: HPV detection was finally carried out in 51 patients. HPV16 was detected in the moderately differentiated, stage IV lower esophageal tumor of a 32-year-old Malaysian-born Chinese woman by both methods. Except for a predilection for Indians, the clinical characteristics of esophageal squamous cell carcinomas in this Malaysian cohort were generally similar to those of other populations.

    CONCLUSION: It appears that HPV is rare and an unlikely oncovirus in esophageal squamous cell carcinomas of Malaysians.

    MeSH terms: Aged; Aged, 80 and over; Carcinoma, Squamous Cell/microbiology*; Carcinoma, Squamous Cell/mortality; Esophageal Neoplasms/microbiology*; Esophageal Neoplasms/mortality; Female; Humans; Malaysia; Male; Middle Aged; Cohort Studies; Papillomaviridae/isolation & purification*
  18. Kuche K, Maheshwari R, Tambe V, Mak KK, Jogi H, Raval N, et al.
    Nanoscale, 2018 May 17;10(19):8911-8937.
    PMID: 29722421 DOI: 10.1039/c8nr01383g
    The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.
    MeSH terms: Administration, Cutaneous; Iontophoresis; Liposomes; Skin; Hydrogels; RNA Interference; Nanotubes, Carbon; Dendrimers; Transdermal Patch; Drug Liberation
  19. Mohd-Assaad N, McDonald BA, Croll D
    Genome Biol Evol, 2018 Apr 01;10(5):1315-1332.
    PMID: 29722810 DOI: 10.1093/gbe/evy087
    Coevolution between hosts and pathogens generates strong selection pressures to maintain resistance and infectivity, respectively. Genomes of plant pathogens often encode major effect loci for the ability to successfully infect specific host genotypes. Hence, spatial heterogeneity in host genotypes coupled with abiotic factors could lead to locally adapted pathogen populations. However, the genetic basis of local adaptation is poorly understood. Rhynchosporium commune, the pathogen causing barley scald disease, interacts at least partially in a gene-for-gene manner with its host. We analyzed global field populations of 125 R. commune isolates to identify candidate genes for local adaptation. Whole genome sequencing data showed that the pathogen is subdivided into three genetic clusters associated with distinct geographic and climatic regions. Using haplotype-based selection scans applied independently to each genetic cluster, we found strong evidence for selective sweeps throughout the genome. Comparisons of loci under selection among clusters revealed little overlap, suggesting that ecological differences associated with each cluster led to variable selection regimes. The strongest signals of selection were found predominantly in the two clusters composed of isolates from Central Europe and Ethiopia. The strongest selective sweep regions encoded protein functions related to biotic and abiotic stress responses. Selective sweep regions were enriched in genes encoding functions in cellular localization, protein transport activity, and DNA damage responses. In contrast to the prevailing view that a small number of gene-for-gene interactions govern plant pathogen evolution, our analyses suggest that the evolutionary trajectory is largely determined by spatially heterogeneous biotic and abiotic selection pressures.
    MeSH terms: Adaptation, Physiological/genetics; Agriculture; Ascomycota/genetics*; Ascomycota/isolation & purification; Hordeum/microbiology*; Environment; Genes, Fungal/genetics*; Genes, Fungal/physiology; Genotype; Plant Diseases/microbiology; Selection, Genetic/genetics*; Genome, Fungal; Polymorphism, Single Nucleotide; Metagenomics*; Phylogeography
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