Browse publications by year: 2017

  1. Writing Committee for the VISION Study Investigators, Devereaux PJ, Biccard BM, Sigamani A, Xavier D, Chan MTV, et al.
    JAMA, 2017 Apr 25;317(16):1642-1651.
    PMID: 28444280 DOI: 10.1001/jama.2017.4360
    Importance: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS).

    Objective: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality).

    Design, Setting, and Participants: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013.

    Exposures: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement.

    Main Outcomes and Measures: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality.

    Results: Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom.

    Conclusions and Relevance: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

    MeSH terms: Aged; Female; Humans; Male; Middle Aged; Myocardial Infarction/mortality*; Postoperative Complications; Postoperative Period; Prospective Studies; Myocardial Ischemia/mortality*; Risk Assessment; Troponin T/blood*
  2. Oon CE, Bridges E, Sheldon H, Sainson RCA, Jubb A, Turley H, et al.
    Oncotarget, 2017 Jun 20;8(25):40115-40131.
    PMID: 28445154 DOI: 10.18632/oncotarget.16969
    Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in tumour angiogenesis. They were shown to have opposite effects on mouse retinal and adult regenerative angiogenesis. In tumours, both ligands are upregulated but their relative effects and interactions in tumour biology, particularly in tumour response to therapeutic intervention are unclear. Here we demonstrate that DLL4 and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1 endothelial cells but had opposing effects on sprouting angiogenesis in vitro. Mouse DLL4 or JAG1 expressed in glioblastoma cells decreased tumour cell proliferation in vitro but promoted tumour growth in vivo. mDLL4-expressing tumours showed fewer but larger vessels whereas mJAG1-tumours produced more vessels. In both tumour types pericyte coverage was decreased but the vessels were more perfused. Both ligands increased tumour resistance towards anti-VEGF therapy but the resistance was higher in mDLL4-tumours versus mJAG1-tumours. However, their sensitivity to the therapy was restored by blocking Notch signalling with dibenzazepine. Importantly, anti-DLL4 antibody blocked the effect of JAG1 on tumour growth and increased vessel branching in vivo. The mechanism behind the differential responsiveness was due to a positive feedback loop for DLL4-Notch signalling, rendering DLL4 more dominant in activating Notch signalling in the tumour microenvironment. We concluded that DLL4 and JAG1 promote tumour growth by modulating tumour angiogenesis via different mechanisms. JAG1 is not antagonistic but utilises DLL4 in tumour angiogenesis. The results suggest that anti-JAG1 therapy should be explored in conjunction with anti-DLL4 treatment in developing anti-Notch therapies in clinics.
    MeSH terms: Bevacizumab/pharmacology; Animals; Cell Line; Cells, Cultured; Dibenzazepines/pharmacology; Humans; Membrane Proteins/genetics; Membrane Proteins/metabolism*; Neoplasms/blood supply; Neoplasms/drug therapy; Neoplasms/metabolism*; Neovascularization, Pathologic/genetics; Neovascularization, Pathologic/metabolism*; Neovascularization, Pathologic/prevention & control; Xenograft Model Antitumor Assays; RNA Interference; Cell Line, Tumor; Tumor Burden/drug effects; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism*; Cell Proliferation/drug effects; Cell Proliferation/genetics; Mice; Kaplan-Meier Estimate; Jagged-1 Protein/genetics; Jagged-1 Protein/metabolism*
  3. Phisalprapa P, Supakankunti S, Charatcharoenwitthaya P, Apisarnthanarak P, Charoensak A, Washirasaksiri C, et al.
    Medicine (Baltimore), 2017 Apr;96(17):e6585.
    PMID: 28445256 DOI: 10.1097/MD.0000000000006585
    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients is not clear. This study aims to estimate economic and clinical outcomes of ultrasonography in Thailand.

    METHODS: Cost-effectiveness analysis used decision tree and Markov models to estimate lifetime costs and health benefits from societal perspective, based on a cohort of 509 metabolic syndrome patients in Thailand. Data were obtained from published literatures and Thai database. Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of 3%. Sensitivity analyses were performed to assess the influence of parameter uncertainty on the results.

    RESULTS: The ICER of ultrasonography screening of 50-year-old metabolic syndrome patients with intensive weight reduction program was 958 USD/QALY gained when compared with no screening. The probability of being cost-effective was 67% using willingness-to-pay threshold in Thailand (4848 USD/QALY gained). Screening before 45 years was cost saving while screening at 45 to 64 years was cost-effective.

    CONCLUSIONS: For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Study can be used as part of evidence-informed decision making.

    TRANSLATIONAL IMPACTS: Findings could contribute to changes of NAFLD diagnosis practice in settings where economic evidence is used as part of decision-making process. Furthermore, study design, model structure, and input parameters could also be used for future research addressing similar questions.

    MeSH terms: Cost-Benefit Analysis*; Decision Trees; Humans; Markov Chains; Middle Aged; Oxadiazoles; Sensitivity and Specificity; Thailand; Ultrasonography/economics*; Cohort Studies; Multivariate Analysis; Treatment Outcome; Models, Economic; Quality-Adjusted Life Years; Metabolic Syndrome X/complications; Metabolic Syndrome X/economics*; Metabolic Syndrome X/therapy; Weight Reduction Programs/economics; Non-alcoholic Fatty Liver Disease/complications*; Non-alcoholic Fatty Liver Disease/economics*; Non-alcoholic Fatty Liver Disease/therapy
  4. Ali A, Abd Razak S, Othman SH, Mohammed A, Saeed F
    PLoS One, 2017;12(4):e0176223.
    PMID: 28445486 DOI: 10.1371/journal.pone.0176223
    With the rapid development of technology, mobile phones have become an essential tool in terms of crime fighting and criminal investigation. However, many mobile forensics investigators face difficulties with the investigation process in their domain. These difficulties are due to the heavy reliance of the forensics field on knowledge which, although a valuable resource, is scattered and widely dispersed. The wide dispersion of mobile forensics knowledge not only makes investigation difficult for new investigators, resulting in substantial waste of time, but also leads to ambiguity in the concepts and terminologies of the mobile forensics domain. This paper developed an approach for mobile forensics domain based on metamodeling. The developed approach contributes to identify common concepts of mobile forensics through a development of the Mobile Forensics Metamodel (MFM). In addion, it contributes to simplifying the investigation process and enables investigation teams to capture and reuse specialized forensic knowledge, thereby supporting the training and knowledge management activities. Furthermore, it reduces the difficulty and ambiguity in the mobile forensics domain. A validation process was performed to ensure the completeness and correctness of the MFM. The validation was conducted using two techniques for improvements and adjustments to the metamodel. The last version of the adjusted metamodel was named MFM 1.2.
    MeSH terms: Algorithms; Crime; Models, Theoretical*; Cell Phones*; Forensic Sciences/methods*
  5. Kueh CL, Yong CY, Masoomi Dezfooli S, Bhassu S, Tan SG, Tan WS
    Biotechnol Prog, 2017 Mar;33(2):549-557.
    PMID: 27860432 DOI: 10.1002/btpr.2409
    Macrobrachium rosenbergii nodavirus (MrNV) is a virus native to giant freshwater prawn. Recombinant MrNV capsid protein has been produced in Escherichia coli, which self-assembled into virus-like particles (VLPs). However, this recombinant protein is unstable, degrading and forming heterogenous VLPs. In this study, MrNV capsid protein was produced in insect Spodoptera frugiperda (Sf9) cells through a baculovirus system. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed that the recombinant protein produced by the insect cells self-assembled into highly stable, homogenous VLPs each of approximately 40 nm in diameter. Enzyme-linked immunosorbent assay (ELISA) showed that the VLPs produced in Sf9 cells were highly antigenic and comparable to those produced in E. coli. In addition, the Sf9 produced VLPs were highly stable across a wide pH range (2-12). Interestingly, the Sf9 produced VLPs contained DNA of approximately 48 kilo base pairs and RNA molecules. This study is the first report on the production and characterization of MrNV VLPs produced in a eukaryotic system. The MrNV VLPs produced in Sf9 cells were about 10 nm bigger and had a uniform morphology compared with the VLPs produced in E. coli. The insect cell production system provides a good source of MrNV VLPs for structural and immunological studies as well as for host-pathogen interaction studies. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:549-557, 2017.
    MeSH terms: Animals; Cells, Cultured; Cloning, Molecular/methods; Escherichia coli/genetics; Escherichia coli/metabolism*; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Recombinant Proteins/chemistry; Species Specificity; Spodoptera; Nodaviridae/genetics; Nodaviridae/metabolism*; Palaemonidae/virology*; Vaccines, Virus-Like Particle/biosynthesis*; Vaccines, Virus-Like Particle/genetics; Vaccines, Virus-Like Particle/chemistry*; Sf9 Cells/metabolism*
  6. Osland E, Yunus RM, Khan S, Memon B, Memon MA
    Obes Surg, 2017 May;27(5):1208-1221.
    PMID: 27896647 DOI: 10.1007/s11695-016-2469-5
    PURPOSE: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic vertical sleeve gastrectomy (LVSG) have been proposed as cost-effective strategies to manage obesity-related chronic disease. The aim of this systematic review was to study the peer review literature regarding postoperative nondiabetic comorbid disease resolution or improvement reported from randomized controlled trials (RCTs) comparing LVSG and LRYGB procedures.

    MATERIAL AND METHODS: RCTs comparing postoperative comorbid disease resolution such as hypertension, dyslipidemia, obstructive sleep apnea, joint and musculoskeletal conditions, gastroesophageal reflux disease, and menstrual irregularities following LVSG and LRYGB were included for analysis. The studies were selected from PubMed, Medline, EMBASE, Science Citation Index, Current Contents, and the Cochrane database and reported on at least one comorbidity resolution or improvement. The present work was undertaken according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA). The Jadad method for assessment of methodological quality was applied to the included studies.

    RESULTS: Six RCTs performed between 2005 and 2015 involving a total of 695 patients (LVSG n = 347, LRYGB n = 348) reported on the resolution or improvement of comorbid disease following LVSG and LRYGB procedures. Both bariatric procedures provide effective and almost comparable results in improving or resolving these comorbidities.

    CONCLUSIONS: This systematic review of RCTs suggests that both LVSG and LRYGB are effective in resolving or improving preoperative nondiabetic comorbid diseases in obese patients. While results are not conclusive at this time, LRYGB may provide superior results compared to LVSG in mediating the remission and/or improvement in some conditions such as dyslipidemia and arthritis.

    MeSH terms: Arthritis/complications; Chronic Disease; Gastroesophageal Reflux/complications; Gastroesophageal Reflux/surgery; Humans; Hypertension/complications; Hypertension/surgery; Obesity/complications*; Obesity/surgery*; Obesity, Morbid/surgery; Laparoscopy/methods; Postoperative Period; Comorbidity; Randomized Controlled Trials as Topic; Disease Management; Sleep Apnea, Obstructive/complications; Sleep Apnea, Obstructive/surgery; Dyslipidemias/complications; Dyslipidemias/surgery
  7. Rahman T, Hamzan NS, Mokhsin A, Rahmat R, Ibrahim ZO, Razali R, et al.
    Lipids Health Dis, 2017 Apr 24;16(1):81.
    PMID: 28438163 DOI: 10.1186/s12944-017-0470-1
    BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers.

    METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis.

    RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p  0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p 

    MeSH terms: Adult; C-Reactive Protein/metabolism; Coronary Artery Disease/etiology; Endothelium, Vascular/metabolism*; Endothelium, Vascular/physiopathology; Family; Fasting; Female; Humans; Hyperlipoproteinemia Type II/blood*; Hyperlipoproteinemia Type II/complications; Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/physiopathology; Cholesterol, HDL/blood; Lipoproteins, LDL/blood; Cholesterol, LDL/blood; Male; Malondialdehyde/blood; Middle Aged; Risk Factors; Triglycerides/blood; Biomarkers/blood; Logistic Models; Case-Control Studies; Oxidative Stress; Intercellular Adhesion Molecule-1/blood; E-Selectin/blood; F2-Isoprostanes/blood
  8. Beshay N, Keay L, Dunn H, Kamalden TA, Hoskin AK, Watson SL
    Injury, 2017 Jul;48(7):1348-1354.
    PMID: 28438416 DOI: 10.1016/j.injury.2017.04.035
    BACKGROUND: Open globe injuries (OGIs) account for 44% of the cost of ocular trauma within Australia. It is estimated that 90% of ocular trauma is preventable. However, there have been few epidemiological studies within Australia that have identified groups at risk of OGIs specifically. The aim of our study was to review the epidemiology of OGIs presenting to a tertiary referral eye hospital in Australia.

    METHODS: The Birmingham Eye Trauma Terminology (BETT) system was used to classify injuries as globe ruptures, penetrating eye injuries (PEIs), intraocular foreign bodies (IOFBs) or perforating injuries. Demographic data, past ocular history, mechanism of trauma, ocular injuries, and best-corrected visual acuity (BCVA) before and after treatment were recorded.

    RESULTS: The 205 OGIs included 80 globe ruptures, 71 PEIs, 48 IOFBs and six perforating injuries. Falls predominated in older age groups compared to the other mechanisms of injury (p<0.0001). A fall was responsible for 33 globe ruptures and 82% of these had a history of previous intraocular surgery. Globe rupture and perforating injuries had poorer visual outcomes (p<0.05), consistent with previous studies. Alcohol was implicated in 20 cases of OGI, with 11 of these due to assault. PEIs and IOFBs commonly occurred while working with metal. BCVA was significantly worse following removal of an intraocular foreign body. We found presenting BCVA to be a good predictor of BCVA at the time of discharge.

    CONCLUSIONS: The causes of OGI varied in association with age, with older people mostly incurring their OGI through falls and younger adults through assault and working with metal. Globe ruptures occurring after a fall often had a history of intraocular surgery. The initial BCVA is useful for non-ophthalmologists who are unfamiliar with the ocular trauma score to help predict the BCVA following treatment.

    MeSH terms: Australia/epidemiology; Eye Foreign Bodies/epidemiology*; Eye Foreign Bodies/physiopathology; Humans; Terminology as Topic; Orbital Diseases/epidemiology*; Orbital Diseases/physiopathology; Retrospective Studies; Rupture/epidemiology*; Visual Acuity; Trauma Severity Indices; Eye Injuries, Penetrating/epidemiology*; Eye Injuries, Penetrating/physiopathology; Age Distribution; Sex Distribution; Tomography, Optical Coherence*; Tertiary Care Centers*
  9. Osman NH, Sathar J, Leong CF, Zulkifli NF, Raja Sabudin RZA, Othman A, et al.
    Transfus Apher Sci, 2017 Jun;56(3):410-416.
    PMID: 28438419 DOI: 10.1016/j.transci.2017.03.009
    Blood group antigen systems are not limited to the ABO blood groups. There is increasing interest in the detection of extended blood group systems on the red cell surface. The conventional method used to determine extended blood group antigens or red cell phenotype is by serological testing, which is based on the detection of visible haemagglutination or the presence of haemolysis. However, this technique has many limitations due to recent exposure to donor red cell, certain drugs or medications or other diseases that may alter the red cell membrane. We aimed to determine the red cell blood group genotype by SNP real time PCR and to compare the results with the conventional serological methods in multiply transfused patients. Sixty-three patients participated in this study whose peripheral blood was collected and blood group phenotype was determined by serological tube method while the genotype was performed using TaqMan®Single Nucleotide Polymorphism (SNP) RT-PCR assays for RHEe, RHCc, Kidd and Duffy blood group systems. Discrepancies were found between the phenotype and genotype results for all blood groups tested. Accurate red blood cell antigen profiling is important for patients requiring multiple transfusions. The SNP RT-PCR platform is a reliable alternative to the conventional method.
    MeSH terms: Adolescent; Adult; Aged; Blood Group Antigens/genetics*; Blood Transfusion/methods*; Female; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Young Adult
  10. Yapp JH, Kamil R, Rozi M, Mohtarrudin N, Loqman MY, Ezamin AR, et al.
    J Tissue Viability, 2017 Aug;26(3):196-201.
    PMID: 28438463 DOI: 10.1016/j.jtv.2017.03.002
    Tissue recovery is important in preventing tissue deterioration, which is induced by pressure and may lead to pressure ulcers (PU). Reactive hyperaemia (RH) is an indicator used to identify people at risk of PU. In this study, the effect of different recovery times on RH trend is investigated during repetitive loading. Twenty-one male Sprague-Dawley rats (seven per group), with body weight of 385-485 g, were categorised into three groups and subjected to different recovery times with three repetitive loading cycles. The first, second, and third groups were subjected to short (3 min), moderate (10 min), and prolonged (40 min) recovery, respectively, while fixed loading time and pressure (10 min and 50 mmHg, respectively). Peak hyperaemia was measured in the three cycles to determine trends associated with different recovery times. Three RH trends (increasing, decreasing, and inconsistent) were observed. As the recovery time is increased (3 min vs. 10 min vs. 40 min), the number of samples with increasing RH trend decreases (57% vs. 29% vs. 14%) and the number of samples with inconsistent RH trend increases (29% vs. 57% vs. 72%). All groups consists of one sample with decreasing RH trend (14%). Results confirm that different recovery times affect the RH trend during repetitive loading. The RH trend may be used to determine the sufficient recovery time of an individual to avoid PU development.
    MeSH terms: Animals; Pressure Ulcer/prevention & control; Humans; Hyperemia/physiopathology*; Perfusion/standards*; Pressure/adverse effects; Regional Blood Flow/physiology*; Skin/blood supply*; Skin/injuries; Rats, Sprague-Dawley/blood; Rats, Sprague-Dawley/injuries; Rats
  11. De Blasio MJ, Ramalingam A, Cao AH, Prakoso D, Ye JM, Pickering R, et al.
    Eur J Pharmacol, 2017 Jul 15;807:12-20.
    PMID: 28438648 DOI: 10.1016/j.ejphar.2017.04.026
    Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes. An additional age-matched group of rats was administered with citrate vehicle as controls. After 4 weeks of untreated diabetes, rats received tempol (1.5mM/kg/day subcutaneously, n=8), ramipril (1mg/kg/day in drinking water, n=8) or remained untreated for an additional 4 weeks (n=7). After 8 weeks of diabetes in total, kidneys were collected for histological analysis, gene expression and protein abundance. Tempol and ramipril blunted diabetes-induced upregulation of NADPH oxidase isoforms (Nox4, Nox2, p47phox), accompanied by an amelioration of diabetes-induced glomerular injury (podocin, nephrin, Kim-1), tubulo-interstitial fibrosis (TGFβ1, TGFβ-R2, pSMAD3, α-SMA) and pro-inflammatory cytokines (TNFα, MCP-1, ANX-A1, FPR2) expression. In addition, the diabetes-induced renal ER stress, evidenced by increased expression of GRP-78 chaperone and stress-associated markers ATF4, TRB3, as well as XBP1s, phospho-p38 mitogen-activated protein kinase (MAPK) and 3-nitrotyrosination, were all attenuated by tempol and ramipril. These observations suggest that antioxidant approaches that blunt NADPH upregulation may attenuate diabetic nephropathy, at least in part by negatively regulating ER stress and inflammation, and hence ameliorating kidney damage.
    MeSH terms: Animals; Cyclic N-Oxides/pharmacology*; Cyclic N-Oxides/therapeutic use; Diabetic Nephropathies/drug therapy*; Diabetic Nephropathies/metabolism; Diabetic Nephropathies/pathology; Disease Models, Animal; Fibrosis; Kidney Glomerulus/drug effects; Kidney Glomerulus/pathology; Kidney Tubules/drug effects; Kidney Tubules/pathology; Male; Nitric Oxide/metabolism; Spin Labels; Superoxide Dismutase/metabolism*; Up-Regulation/drug effects*; Rats, Sprague-Dawley; Ramipril/pharmacology; Oxidative Stress/drug effects; NADPH Oxidase/metabolism*; Biomimetic Materials/pharmacology*; Biomimetic Materials/therapeutic use; Rats; Endoplasmic Reticulum Stress/drug effects*
  12. Mansor MS, Ramli R
    Behav Processes, 2017 Jul;140:121-126.
    PMID: 28438691 DOI: 10.1016/j.beproc.2017.04.010
    Niche theory suggests that sympatric species reduce interspecific competition through segregation of shared resources by adopting different attack manoeuvres. However, the fact that flycatcher-like bird species exclusively use the sally manoeuvre may thus challenge this view. We studied the foraging ecology of three flycatcher-like species (i.e. Paradise-flycatcher Terpsiphone sp., Black-naped Monarch Hypothymis azurea, and Rufous-winged Philentoma Philentoma pyrhoptera) in the Krau Wildlife Reserve in central Peninsular Malaysia. We investigated foraging preferences of each bird species and the potential niche partitioning via spatial or behavioural segregation. Foraging substrate was important parameter that effectively divided paradise-flycatcher from Black-naped Monarch and Rufous-winged Philentoma, where monarch and philentoma foraged mainly on live green leaves, while paradise-flycatcher foraged on the air. They also exhibited different foraging height preferences. Paradise-flycatcher, for instance, preferred the highest studied strata, while Black-naped Monarch foraged mostly in lower strata, and Rufous-winged Philentoma made use of the lowest strata. This study indicates that niche segregation occurs among sympatric species through foraging substrate and attack manoeuvres selection.
    MeSH terms: Animals; Feeding Behavior; Female; Malaysia; Male; Population Density; Social Support; Species Specificity; Ecosystem*; Songbirds/physiology*; Rainforest*
  13. Khairuddin NH, Sullivan M, Pollock PJ
    Ir Vet J, 2017 04 20;70:12.
    PMID: 28439406 DOI: 10.1186/s13620-017-0090-0
    BACKGROUND: In horses, the extracranial and intracranial pathway of the internal carotid artery has been described. The extracranial pathway of the internal carotid artery begins at the carotid termination and runs on the dorsal surface of the medial compartment of the guttural pouch. Thereafter the internal carotid artery passes through the foramen lacerum to continue intracranially, forming part of the rostrolateral quadrants of the cerebral arterial circle (Circle of Willis). The objectives of this study were to define and record the anatomy of the carotid arterial tree and the internal carotid artery in donkeys using angiographic techniques. This is a prospective descriptive study on 26 cadaveric donkeys.

    METHODS: Twenty six donkey cadavers of mixed, age, sex and use presented for reasons unrelated to disease of the guttural pouch were subjected to carotid and cerebral angiography using rotational angiography. Rotational angiographic and 3 dimensional multiplanar reconstructive (3D-MPR) findings were verified with an arterial latex casting technique followed by dissection and photography.

    RESULTS: The following variations of the carotid arterial tree were identified: [1] the internal carotid and occipital arteries shared a common trunk, [2] the linguofacial trunk originated from the common carotid artery causing the common carotid artery to terminate as four branches, [3] the external carotid artery was reduced in length before giving rise to the linguofacial trunk, mimicking the appearance of the common carotid artery terminating in four branches, [4] the internal carotid artery originated at a more caudal position from the common carotid artery termination.

    CONCLUSION: Veterinarians should be aware that considerable variation exists in the carotid arterial tree of donkeys and that this variation may differ markedly from that described in the horse.

    MeSH terms: Animals; Cadaver; Carotid Artery, External; Carotid Artery, Internal; Cerebral Angiography; Circle of Willis; Horses; Latex; Photography; Prospective Studies; Equidae; Veterinarians; Intracellular Signaling Peptides and Proteins
  14. Lee YS, Howell SM, Won YY, Lee OS, Lee SH, Vahedi H, et al.
    Knee Surg Sports Traumatol Arthrosc, 2017 Nov;25(11):3467-3479.
    PMID: 28439636 DOI: 10.1007/s00167-017-4558-y
    PURPOSE: A systematic review was conducted to answer the following questions: (1) Does kinematically aligned (KA) total knee arthroplasty (TKA) achieve clinical outcomes comparable to those of mechanically aligned (MA) TKA? (2) How do the limb, knee, and component alignments differ between KA and MA TKA? (3) How is joint line orientation angle (JLOA) changed from the native knee in KA TKA compared to that in MA TKA?

    METHODS: Nine full-text articles in English that reported the clinical and radiological outcomes of KA TKA were included. Five studies had a control group of patients who underwent MA TKA. Data on patient demographics, clinical scores, and radiological results were extracted. There were two level I, one level II, three level III, and three level IV studies. Six of the nine studies used patient-specific instrumentation, one study used computer navigation, and two studies used manual instrumentation.

    RESULTS: The clinical outcomes of KA TKA were comparable or superior to those of MA TKA with a minimum 2-year follow-up. Limb and knee alignment in KA TKA was similar to those in MA TKA, and component alignment showed slightly more varus in the tibial component and slightly more valgus in the femoral component. The JLOA in KA TKA was relatively parallel to the floor compared to that in the native knee and not oblique (medial side up and lateral side down) compared to that in MA TKA. The implant survivorship and complication rate of the KA TKA were similar to those of the MA TKA.

    CONCLUSION: Similar or better clinical outcomes were produced by using a KA TKA at early-term follow-up and the component alignment differed from that of MA TKA. KA TKA seemed to restore function without catastrophic failure regardless of the alignment category up to midterm follow-up. The JLOA in KA TKA was relatively parallel to the floor similar to the native knee compared to that in MA TKA. The present review of nine published studies suggests that relatively new kinematic alignment is an acceptable and alternative alignment to mechanical alignment, which is better understood. Further validation of these findings requires more randomized clinical trials with longer follow-up.

    LEVEL OF EVIDENCE: Level II.

    MeSH terms: Biomechanical Phenomena; Humans; Knee Joint/physiopathology; Knee Joint/surgery; Tibia/physiopathology; Tibia/surgery; Bone Malalignment/etiology; Bone Malalignment/physiopathology; Arthroplasty, Replacement, Knee/methods*; Osteoarthritis, Knee/physiopathology; Osteoarthritis, Knee/surgery*
  15. Tan GW, Tan LP
    Methods Mol Biol, 2017;1580:7-19.
    PMID: 28439823 DOI: 10.1007/978-1-4939-6866-4_2
    Reverse transcription followed by real-time or quantitative polymerase chain reaction (RT-qPCR) is the gold standard for validation of results from transcriptomic profiling studies such as microarray and RNA sequencing. The current need for most studies, especially biomarker studies, is to evaluate the expression levels or fold changes of many transcripts in a large number of samples. With conventional low to medium throughput qPCR platforms, many qPCR plates would have to be run and a significant amount of RNA input per sample will be required to complete the experiments. This is particularly challenging when the size of study material (small biopsy, laser capture microdissected cells, biofluid, etc.), time, and resources are limited. A sensitive and high-throughput qPCR platform is therefore optimal for the evaluation of many transcripts in a large number of samples because the time needed to complete the entire experiment is shortened and the usage of lab consumables as well as RNA input per sample are low. Here, the methods of high-throughput RT-qPCR for the analysis of circulating microRNAs are described. Two distinctive qPCR chemistries (probe-based and intercalating dye-based) can be applied using the methods described here.
    MeSH terms: Humans; Sequence Analysis, RNA/methods; Sample Size; Gene Expression Profiling/methods; High-Throughput Screening Assays/methods; Real-Time Polymerase Chain Reaction/methods*
  16. Agustian J, Kamaruddin AH, Aboul-Enein HY
    Chirality, 2017 Jul;29(7):376-385.
    PMID: 28439969 DOI: 10.1002/chir.22702
    As the (R)-enantiomer of racemic atenolol has no β-blocking activity and no lack of side effects, switching from the racemate to the (S)-atenolol is more favorable. Transesterification of racemic atenolol using free enzymes investigated as a resource to resolve the racemate via this method is limited. Screenings of enzyme, medium, and acetyl donor were conducted first to give Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate. A statistical design of the experiment was then developed using Central Composite Design on some operational factors, which resulted in the conversions of 11.70-61.91% and substrate enantiomeric excess (ee) of 7.31-100%. The quadratic models are acceptable with R2 of 95.13% (conversion) and 89.63% (ee). The predicted values match the observed values reasonably well. Temperature, agitation speed, and substrate molar ratio factor have low effects on conversion and ee, but enzyme loading affects the responses highly. The interaction of temperature-agitation speed and temperature-substrate molar ratio show significant effects on conversion, while temperature-agitation speed, temperature-substrate molar ratio, and agitation speed-substrate molar ratio affect ee highly. Optimum conditions for the use of Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate were found at 45°C, 175 rpm, 2000 U, and 1:3.6 substrate molar ratio.
    MeSH terms: Acetylation; Atenolol/isolation & purification; Atenolol/chemistry*; Esterification; Kinetics; Lipase/metabolism*; Models, Chemical; Pseudomonas fluorescens/enzymology*; Solvents/chemistry*; Stereoisomerism
  17. Fareen N, Alam MK, Khamis MF, Mokhtar N
    Orthod Craniofac Res, 2017 Aug;20(3):134-139.
    PMID: 28440029 DOI: 10.1111/ocr.12179
    OBJECTIVE: Reverse Twin-Block (RTB) and Reverse Pull Face Mask (RPFM) appliances are used to correct Class III malocclusion in growing patients. Aim of this retrospective study was to compare and analyse craniofacial changes produced by RTB and RPFM in the early and late mixed dentition in Malay children with Class III malocclusion.

    METHODS: Data consisted of pre- and post-treatment lateral cephalograms of 95 children, 49 patients with RTB and 46 patients with RPFM, divided into an early (8-9 year) and late (10-11 year) group. Treatment changes were assessed by the Ricketts analysis using CASSOS software, where 71 anatomic landmarks were identified in each cephalogram. Paired and independent t tests were performed for statistical comparison.

    RESULTS: Paired t test revealed significant changes in facial axis, facial angle, MD plane to FH, lower facial height, mandibular arc, maxillary convexity, U1 to APog, L1 to APog, L1 to APog angle and upper lip to E-plane measurements in RPFM, whereas significant changes were found in facial taper, U1 to APog and lower lip to E-plane values with RTB in the early treatment group. Independent t test revealed significant changes in U1 to APog, L1 to APog and U6 to PtV values in the RTB group. Post-treatment comparison of RTB and RPFM showed significant differences in L1 to APog and L1 to APog angle values.

    CONCLUSIONS: RPFM revealed more favourable craniofacial changes than RTB, particularly in the late mixed dentition stage.

    MeSH terms: Cephalometry; Child; Cross-Sectional Studies; Dentition, Mixed*; Extraoral Traction Appliances; Female; Humans; Malaysia; Male; Malocclusion, Angle Class III/therapy*; Maxillofacial Development; Orthodontic Appliances*; Orthodontics, Interceptive/instrumentation*; Retrospective Studies; Treatment Outcome; Anatomic Landmarks
  18. Abbasi S, Rasouli M
    Mol Med Rep, 2017 Jun;15(6):3983-3988.
    PMID: 28440412 DOI: 10.3892/mmr.2017.6489
    Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure and Fanconi anemia complementation group A (FANCA) is also a potential breast and ovarian cancer susceptibility gene. A novel allele with tandem duplication of 13 base pair sequence in promoter region was identified. To investigate whether the 13 base pair sequence of tandem duplication in promoter region of the FANCA gene is of high penetrance in patients with breast cancer and to determine if the presence of the duplicated allele was associated with an altered risk of breast cancer, the present study screened DNA in blood samples from 304 breast cancer patients and 295 normal individuals as controls. The duplication allele had a frequency of 35.4 and 21.2% in patients with breast cancer and normal controls, respectively. There was a significant increase in the frequency of the duplication allele in patients with familial breast cancer compared with controls (45.1%, P=0.001). Furthermore, the estimated risk of breast cancer in individuals with a homozygote [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957‑8.561] or heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996‑5.506) was higher compared with the corresponding normal homozygote genotype. In conclusion, the present study indicated that the higher the frequency of the duplicated allele, the higher the risk of breast cancer. To the best of our knowledge, the present study is the first to report FANCA gene duplication in patients with breast cancer.
    MeSH terms: Adult; Aged; Alleles*; Breast Neoplasms/genetics*; Breast Neoplasms/epidemiology*; Female; Genotype; Humans; Iran/epidemiology; Middle Aged; Population Surveillance; Promoter Regions, Genetic; Risk Factors; Genetic Variation*; Odds Ratio; Case-Control Studies; Genetic Predisposition to Disease*; Gene Duplication; Fanconi Anemia Complementation Group A Protein/genetics*
  19. Chan CYW, Loo SF, Ong JY, Lisitha KA, Hasan MS, Lee CK, et al.
    Spine (Phila Pa 1976), 2017 Dec 15;42(24):E1415-E1422.
    PMID: 28441311 DOI: 10.1097/BRS.0000000000002206
    STUDY DESIGN: A prospective cohort study.

    OBJECTIVE: The aim of this study was to determine the feasibility of an accelerated recovery protocol for Asian adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF).

    SUMMARY OF BACKGROUND DATA: There has been successful implementation of an accelerated recovery protocol for AIS patients undergoing PSF in the western population. No similar studies have been reported in the Asian population.

    METHODS: Seventy-four AIS (65 F, 9 M) patients scheduled for PSF surgery were recruited. The accelerated protocol encompasses preoperative regime, preoperative day of surgery counseling, intraoperative strategies, an accelerated postoperative rehabilitation and pain management regime. All patients were operated using a dual attending surgeon strategy. Outcome measures included pain scores at five time intervals, length of stay, and detailed recovery milestones. Any complications or readmissions during the first 4 months postoperative period were recorded.

    RESULTS: Mean duration of operation was 2.2 ± 0.3 hours with a mean blood loss of 824.3 ± 418.2 mL. No patients received allogenic blood transfusion. The mean length of stay was 3.6 ± 0.6 days. Surgical wound pain score was 6.4 ± 2.1 at 12 hours, which reduced to 5.0 ± 2.0 at 60 hours. Abdominal pain peaked at 36 hours with pain scores 2.4 ± 2.9. First liquid intake was at 5.2 ± 7.5 hours, urinary catheter removal at 18.7 ± 4.8 hours, sitting up at 20.6 ± 9.1 hours, ambulation at 27.2 ± 0.5 hours, consumption of solid food at 32.2 ± 0.5 hours, first flatus at 39.0 ± 0.7 hours, and first bowel movement at 122.1 ± 2.0 hours. The complication rate was 1.4% due to superficial wound infection with one patient failed to comply with the accelerated protocol.

    CONCLUSION: An accelerated recovery protocol following PSF for AIS is feasible without increasing the complication or readmission rates. The total length of stay was 3.6 days and this is comparable with the outcome in western population.

    LEVEL OF EVIDENCE: 4.

    MeSH terms: Adolescent; Feasibility Studies; Female; Humans; Length of Stay; Male; Postoperative Period; Prospective Studies; Scoliosis/surgery*; Spinal Fusion/methods*; Time Factors; Treatment Outcome; Pain Management
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