Browse publications by year: 2017

  1. Xiong L, Gong X, Siah KT, Pratap N, Ghoshal UC, Abdullah M, et al.
    J Gastroenterol Hepatol, 2017 Aug;32(8):1450-1456.
    PMID: 28084664 DOI: 10.1111/jgh.13730
    BACKGROUND AND AIM: Information on real world treatment experiences of patients with functional bowel disorders is lacking from Asia. This study aimed to describe the medication exposure and treatment satisfaction of patients presenting to gastroenterology clinics across a sampling of Asian cities.

    METHODS: From March 2011 to October 2013, adult patients presenting to hospital-based gastroenterology outpatient clinics in 11 cities across Asia, who fulfilled screening criteria for any functional gastrointestinal disorder, were asked to complete a validated culturally adapted translation of the Rome III diagnostic questionnaire, a checklist of medications received in the preceding 3 months and questions on treatment satisfaction.

    RESULTS: A total of 1376 patients (female 755, male 621, 41.36 ± 13.25 years) comprising irritable bowel (621, 45.1%), unspecified functional bowel disorder (372, 27.8%), functional constipation (202, 14.7%), functional bloating (144, 10.5%), and functional diarrhea (56, 4.1%) completed the study. Of 1105 patients with a previous consultation, 509 (46.1%) were dissatisfied with their treatment, with ineffective treatment being the commonest reason. Satisfaction with previous consultation was lowest by diagnosis for functional constipation (29.2%), and the most bothersome symptom was straining (37.5%). Of 1046 patients who had taken medications for their gastrointestinal symptoms in the last 3 months, 793 (75.8%) had received two or more drugs. For irritable bowel syndrome patients, treatment with proton pump inhibitors and antispasmodics was recorded in 57% and 31%, with overlapping epigastric pain and heartburn predicting proton pump inhibitors use.

    CONCLUSIONS: More attention should be given to treatment gaps with regards to possible under-treatment with antispasmodics in irritable bowel syndrome and to critically evaluating the efficacy of constipation management.
    MeSH terms: Adult; Ambulatory Care Facilities; Asia/epidemiology; Constipation/diagnosis; Constipation/drug therapy; Constipation/epidemiology; Constipation/psychology; Cross-Sectional Studies; Diarrhea/diagnosis; Diarrhea/drug therapy; Diarrhea/epidemiology; Diarrhea/psychology; Drug Therapy, Combination; Female; Humans; Malaysia; Male; Middle Aged; Parasympatholytics/therapeutic use*; Surveys and Questionnaires; Patient Satisfaction; Irritable Bowel Syndrome/diagnosis; Irritable Bowel Syndrome/drug therapy*; Irritable Bowel Syndrome/epidemiology; Irritable Bowel Syndrome/psychology; Asian Continental Ancestry Group; Proton Pump Inhibitors/therapeutic use*; Private Facilities
  2. Wee SY, Aris AZ
    Environ Int, 2017 09;106:207-233.
    PMID: 28552550 DOI: 10.1016/j.envint.2017.05.004
    To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water.
    MeSH terms: Environmental Exposure*; Environmental Monitoring; Humans; Water Pollutants, Chemical/toxicity*; Risk Assessment; Endocrine Disruptors/toxicity*; Drinking Water/analysis*
  3. Tan WM, Lau SF, Ajat M, Mansor R, Abd Rani PAM, Rahmad NB
    Top Companion Anim Med, 2017 Mar;32(1):24-27.
    PMID: 28750786 DOI: 10.1053/j.tcam.2017.05.002
    This case study is to report the proteins detected by proteomic analysis of synovial fluid from a dog diagnosed with idiopathic immune-mediated polyarthritis, and to compare it with healthy dogs. Synovial fluid was collected via arthrocentesis from a dog diagnosed with immune-mediated polyarthritis. Protein precipitation was performed on the synovial fluid, followed by isoelectric focusing and 2-dimensional gel electrophoresis. The spots on the 2-dimensional gels were analyzed using MALDI-TOF/MS. The results were then analyzed against the MASCOT database. The results from the proteomic analysis revealed an abundance of several types of immunoglobulins together with the presence of complement C4b-binding protein alpha chain. Actin and keratin were also among the proteins detected. Proteomic studies, facilitate a better understanding of the different levels of proteins expressed during disease activity. Potential disease biomarkers can aid in the diagnosis of disease, as well as help in monitoring treatment efficacy and providing prognosis for the patient.
    MeSH terms: Animals; Arthritis/blood; Arthritis/immunology; Arthritis/veterinary*; Dog Diseases/immunology; Dog Diseases/metabolism*; Dogs; Synovial Fluid/immunology*; Synovial Fluid/chemistry; Electrophoresis, Gel, Two-Dimensional/veterinary; Case-Control Studies; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/veterinary; Proteomics/methods*
  4. Mohan V, Perri M, Paungmali A, Sitilertpisan P, Joseph LH, Jathin R, et al.
    J Bodyw Mov Ther, 2017 Jul;21(3):694-698.
    PMID: 28750986 DOI: 10.1016/j.jbmt.2016.10.007
    Faulty breathing is an aspect of alteration in the normal fundamental pattern of breathing. The available existence of scales in assessing faulty breathing has not frequently been used. Measurement errors in assessing and quantifying breathing patterns may originate from unclear directions and variation between observers. This study determined the measure reliability of the Total Faulty Breathing Scale (TFBS) for quantifying breathing patterns. Twenty seven participants were recruited comprising healthy and unhealthy subjects. Two examiners assessed their breathing patterns using the TFBS on two different occasions with visual observation and a videogrammetry method. Evaluation of the observational breathing pattern method for intra-rater and inter-rater showed agreement of 96.30% and a kappa score of greater than 0.78, which indicated substantial agreements. The videogrammetry method showed a percent agreement of (100%) with a kappa score of (1.00). This study indicates that the TFBS is a considerably reliable tool for evaluating breathing patterns with both visual observation and a videogrammetry method.
    MeSH terms: Adolescent; Disability Evaluation*; Humans; Male; Respiration*; Reproducibility of Results; Observer Variation*; Physical Therapy Modalities*; Young Adult
  5. Higuchi A, Kumar SS, Benelli G, Alarfaj AA, Munusamy MA, Umezawa A, et al.
    Trends Biotechnol, 2017 11;35(11):1102-1117.
    PMID: 28751147 DOI: 10.1016/j.tibtech.2017.06.016
    Current clinical trials that evaluate human pluripotent stem cell (hPSC)-based therapies predominantly target treating macular degeneration of the eyes because the eye is an isolated tissue that is naturally weakly immunogenic. Here, we discuss current bioengineering approaches and biomaterial usage in combination with stem cell therapy for macular degeneration disease treatment. Retinal pigment epithelium (RPE) differentiated from hPSCs is typically used in most clinical trials for treating patients, whereas bone marrow mononuclear cells (BMNCs) or mesenchymal stem cells (MSCs) are intravitreally transplanted, undifferentiated, into patient eyes. We also discuss reported negative effects of stem cell therapy, such as patients becoming blind following transplantation of adipose-derived stem cells, which are increasingly used by 'stem-cell clinics'.
    MeSH terms: Animals; Cell Differentiation*; Humans; Mesenchymal Stem Cell Transplantation*
  6. Beh BK, Mohamad NE, Yeap SK, Ky H, Boo SY, Chua JYH, et al.
    Sci Rep, 2017 07 27;7(1):6664.
    PMID: 28751642 DOI: 10.1038/s41598-017-06235-7
    Recently, food-based bioactive ingredients, such as vinegar, have been proposed as a potential solution to overcome the global obesity epidemic. Although acetic acid has been identified as the main component in vinegar that contributes to its anti-obesity effect, reports have shown that vinegar produced from different starting materials possess different degrees of bioactivity. This study was performed to compare the anti-obesity and anti-inflammatory effects of synthetic acetic acid vinegar and Nipa vinegar in mice fed a high-fat diet. In this work, mice were fed a high-fat diet for 33 weeks. At the start of week 24, obese mice were orally fed synthetic acetic acid vinegar or Nipa vinegar (0.08 and 2 ml/kg BW) until the end of week 33. Mice fed a standard pellet diet served as a control. Although both synthetic acetic acid vinegar and Nipa vinegar effectively reduced food intake and body weight, a high dose of Nipa vinegar more effectively reduced lipid deposition, improved the serum lipid profile, increased adipokine expression and suppressed inflammation in the obese mice. Thus, a high dose of Nipa vinegar may potentially alleviate obesity by altering the lipid metabolism, inflammation and gut microbe composition in high-fat-diet-induced obese mice.
    MeSH terms: Animals; Anti-Inflammatory Agents/pharmacology; Cholesterol/blood*; Gene Expression Regulation; Lipoproteins, HDL/blood*; Lipoproteins, LDL/blood*; Mice, Inbred C57BL; Mice, Obese; Obesity/blood; Obesity/drug therapy*; Obesity/metabolism; Obesity/prevention & control; Triglycerides/blood; Acetic Acid/pharmacology*; Anti-Obesity Agents/pharmacology; Lipid Metabolism/drug effects; Adipokines/genetics; Diet, High-Fat/adverse effects
  7. Ooi CHR, Ho WL, Bandrauk AD
    Sci Rep, 2017 07 27;7(1):6739.
    PMID: 28751648 DOI: 10.1038/s41598-017-05915-8
    We study the photoelectron spectra by intense laser pulses with arbitrary time dependence and phase within the Keldysh framework. An efficient semianalytical approach using analytical transition matrix elements for hydrogenic atoms in any initial state enables efficient and accurate computation of the photoionization probability at any observation point without saddle point approximation, providing comprehensive three dimensional photoelectron angular distribution for linear and elliptical polarizations, that reveal the intricate features and provide insights on the photoionization characteristics such as angular dispersions, shift and splitting of photoelectron peaks from the tunneling or above threshold ionization(ATI) regime to non-adiabatic(intermediate) and multiphoton ionization(MPI) regimes. This facilitates the study of the effects of various laser pulse parameters on the photoelectron spectra and their angular distributions. The photoelectron peaks occur at multiples of 2ħω for linear polarization while  odd-ordered peaks are suppressed in the direction perpendicular to the electric field. Short pulses create splitting and angular dispersion where the peaks are strongly correlated to the angles. For MPI and elliptical polarization with shorter pulses the peaks split into doublets and the first peak vanishes. The carrier envelope phase(CEP) significantly affects the ATI spectra while the Stark effect shifts the spectra of intermediate regime to higher energies due to interference.
    MeSH terms: Cardiovascular Physiological Phenomena; Probability; Problem Solving; Physical Phenomena
  8. Lithanatudom SK, Chaowasku T, Nantarat N, Jaroenkit T, Smith DR, Lithanatudom P
    Sci Rep, 2017 07 27;7(1):6716.
    PMID: 28751754 DOI: 10.1038/s41598-017-07045-7
    Dimocarpus longan, commonly known as the longan, belongs to the family Sapindaceae, and is one of the most economically important fruits commonly cultivated in several regions in Asia. There are various cultivars of longan throughout the Thai-Malay peninsula region, but until now no phylogenetic analysis has been undertaken to determine the genetic relatedness of these cultivars. To address this issue, 6 loci, namely ITS2, matK, rbcL, trnH-psbA, trnL-I and trnL-trnF were amplified and sequenced from 40 individuals consisting of 26 longan cultivars 2 types of lychee and 8 herbarium samples. The sequencing results were used to construct a phylogenetic tree using the neighbor-joining (NJ), maximum likelihood (ML) and Bayesian inference (BI) criteria. The tree showed cryptic groups of D. longan from the Thailand-Malaysia region (Dimocarpus longan spp.). This is the first report of the genetic relationship of Dimocarpus based on multi-locus molecular markers and morphological characteristics. Multiple sequence alignments, phylogenetic trees and species delimitation support that Dimocarpus longan spp. longan var. obtusus and Dimocarpus longan spp. malesianus var. malesianus should be placed into a higher order and are two additional species in the genus Dimocarpus. Therefore these two species require nomenclatural changes as Dimocarpus malesianus and Dimocarpus obtusus, respectively.
    MeSH terms: Base Sequence; Bayes Theorem; Fruit/genetics*; Malaysia; Phylogeny*; Sequence Homology, Nucleic Acid; Thailand; Sequence Alignment; Sapindaceae/classification; Sapindaceae/genetics*; Litchi/classification; Litchi/genetics*; Genetic Loci*; Multilocus Sequence Typing; Phylogeography
  9. Tan MK, Siddiqi A, Yeo LY
    Sci Rep, 2017 07 27;7(1):6652.
    PMID: 28751783 DOI: 10.1038/s41598-017-07025-x
    The Miniaturised Lab-on-a-Disc (miniLOAD) platform, which utilises surface acoustic waves (SAWs) to drive the rotation of thin millimeter-scale discs on which microchannels can be fabricated and hence microfluidic operations can be performed, offers the possibility of miniaturising its larger counterpart, the Lab-on-a-CD, for true portability in point-of-care applications. A significant limitation of the original miniLOAD concept, however, is that it does not allow for flexible control over the disc rotation direction and speed without manual adjustment of the disc's position, or the use of multiple devices to alter the SAW frequency. In this work, we demonstrate the possibility of achieving such control with the use of tapered interdigitated transducers to confine a SAW beam such that the localised acoustic streaming it generates imparts a force, through hydrodynamic shear, at a specific location on the disc. Varying the torque that arises as a consequence by altering the input frequency to the transducers then allows the rotational velocity and direction of the disc to be controlled with ease. We derive a simple predictive model to illustrate the principle by which this occurs, which we find agrees well with the experimental measurements.
    MeSH terms: Acoustics; Miniaturization; Rotation; Sound; Sound Localization; Transducers; Point-of-Care Systems; Torque; Microfluidics; Hydrodynamics
  10. Salim MS, Mazlan M, Hasnan N
    Spinal Cord Ser Cases, 2017;3:17043.
    PMID: 28751978 DOI: 10.1038/scsandc.2017.43
    INTRODUCTION: We describe a case of intracerebral haemorrhage (ICH) following uncontrolled episodes of autonomic dysreflexia (AD) within 24 h of a minor urological procedure.

    CASE PRESENTATION: A 33-year-old active paraplegic patient T1 Association Impairment Scale A underwent an elective suprapubic catheter (SPC) placement for bladder management. The surgery was done under general anaesthesia and was uneventful. Four hours after surgery, he developed haematuria and multiple blood clots in the urine, which eventually caused blockage of the SPC and resulted in symptomatic AD. The clots and blockage persisted, which continued to trigger repeated episodes of increased blood pressure (BP) and AD. Despite medical treatment with sublingual nitrate to lower the increased BP, the patient subsequently developed massive left ICH presenting with right upper limb weakness, facial asymmetry and inability to speak. He continued to have fluctuating BP measurements for 11 days post event with severe hypertensive and hypotensive episodes. This presented a challenge in the BP management as well as post-ICH management. He underwent an intensive neurorehabilitation programme as soon as the BP had stabilized.

    DISCUSSION: Severe neurological complications of AD are rare. In this case report, we highlight the importance of close monitoring of BP and AD symptoms after an SPC procedure, the challenges in BP management and the subsequent importance of an early rehabilitation programme after ICH secondary to uncontrolled AD.

  11. Osman H, Idris NH, Kamarulzaman EE, Wahab HA, Hassan MZ
    Acta Pharm Sin B, 2017 Jul;7(4):479-484.
    PMID: 28752033 DOI: 10.1016/j.apsb.2017.04.009
    Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a-4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28 µmol/L.
  12. Gew LT, Misran M
    J Biol Phys, 2017 Sep;43(3):397-414.
    PMID: 28752254 DOI: 10.1007/s10867-017-9459-2
    In this study, we address the effect of the cis-double bond in 1,2-dioleoyl-sn-glycero-3-phosphoethanolamide-N-[methoxy(polyethylene glycol)-2000, DOPE PEG2000 (DP), on the Langmuir monolayer of C18 fatty acids-namely, stearic acid (SA), oleic acid (L1), linoleic acid (L2), and linolenic acid (L3)-with the same head group but different degrees of saturation on their hydrocarbon chains. Negative values of Gibbs free energy of mixing (ΔG mix) were obtained throughout the investigated ranges of the unsaturated C18 fatty-acid (L1, L2 and L3) mixed systems, indicating that very strong attractions occurred between molecules in the monolayers. The bend and kink effects from the cis-double bond(s) in the hydrocarbon chain affected the membrane fluidity and molecular packing in the monolayers, which resulted in a greater interaction between unsaturated C18 fatty acids and DP. The most thermodynamically stable mole composition of unsaturated C18 fatty acids to DP was observed at 50:1; this ratio is suggested to be the best mole ratio and will be subsequently used to prepare DP-C18 fatty-acid nanoliposomes. The presence of cis-double bonds in both hydrocarbon chains of DOPE in DP also created an imperfection in the membrane structure of lipid-drug delivery systems, which is expected to enhance lipid-based systems for antibody conjugation and drug encapsulation.
    MeSH terms: Fatty Acids/chemistry*; Phosphatidylethanolamines/chemistry*; Polyethylene Glycols/chemistry*; Thermodynamics
  13. Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.
    COPD, 2017 Oct;14(5):476-483.
    PMID: 28753067 DOI: 10.1080/15412555.2017.1335697
    Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.
    MeSH terms: Adult; Aged; Antibodies, Monoclonal/adverse effects; Antibodies, Monoclonal/pharmacokinetics; Antibodies, Monoclonal/therapeutic use*; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Interleukin-17/antagonists & inhibitors*; Pulmonary Disease, Chronic Obstructive/drug therapy*; Pulmonary Disease, Chronic Obstructive/physiopathology
  14. Iftikhar F, Ali Y, Ahmad Kiani F, Fahad Hassan S, Fatima T, Khan A, et al.
    Bioorg Chem, 2017 10;74:53-65.
    PMID: 28753459 DOI: 10.1016/j.bioorg.2017.07.003
    In our previous report, we have identified 3,4-dihydropyrimidine scaffold as promising class of urease inhibitor in a structure based virtual screen (SBVS) experiment. In present study, we attempted to optimize the scaffold by varying C-5 substituent. The elongation of the C-5 chain was achieved by the reaction of C-5 ester with hydrazine leading to C-5 carbohydrazides which were further used as building blocks for the synthesis of fifteen new compounds having diverse moieties. A significantly higher in vitro urease inhibitory activity with IC50 values in submicromolar range was observed for semithiocarbazide derivatives (4a-c, 0.58-0.79µM) and isatin Schiff base derivative 5a (0.23µM). Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its key amino acid residues. The overall results of urease inhibition have shown that these compounds can be further optimized and developed as lead urease inhibitors.
    MeSH terms: Dose-Response Relationship, Drug; Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry; Pyrimidines/chemical synthesis; Pyrimidines/pharmacology*; Pyrimidines/chemistry; Quantum Theory; Structure-Activity Relationship; Urease/antagonists & inhibitors*; Urease/metabolism; Drug Design*; Molecular Structure; Canavalia/enzymology*; Molecular Docking Simulation*
  15. Wo SW, Ong LC, Low WY, Lai PSM
    Epilepsy Res, 2017 10;136:35-45.
    PMID: 28753498 DOI: 10.1016/j.eplepsyres.2017.07.009
    PURPOSE: To systematically examine published literature which assessed the prevalence of academic difficulties in children with epilepsy (CWE) of normal intelligence, and its associating factors.

    METHODS: A search was conducted on five databases for articles published in English from 1980 till March 2015. Included were studies who recruited children (aged 5-18 years), with a diagnosis or newly/recurrent epilepsy, an intelligent quotient (IQ) of ≥70 or attending regular school, with or without a control group, which measured academic achievement using a standardised objective measure, and published in English. Excluded were children with learning difficulties, intellectual disabilities (IQ<70) and other comorbidities such as attention deficits hyperactive disorder or autism. Two pairs of reviewers extracted the data, and met to resolve any differences from the data extraction process.

    RESULTS: Twenty studies were included. The majority of the studies assessed "low achievement" whist only two studies used the IQ-achievement discrepancy definition of "underachievement". Fourteen studies (70%) reported that CWE had significantly lower academic achievement scores compared to healthy controls, children with asthma or reported norms. The remaining six studies (30%) did not report any differences. CWE had stable academic achievement scores over time (2-4 years), even among those whose seizure frequency improved. Higher parental education and children with higher IQ, and had better attention or had a positive attitude towards epilepsy, were associated with higher academic achievement score. Older children were found to have lower academic achievement score.

    CONCLUSIONS: In CWE of normal intelligence, the majority of published literature found that academic achievement was lower than controls or reported norms. The high percentages of low achievement in CWE, especially in the older age group, and the stability of scores even as seizure frequency improved, highlights the need for early screening of learning problems, and continued surveillance.

    MeSH terms: Child; Epilepsy/psychology*; Humans; Underachievement
  16. Boyd MA, Amin J, Mallon PW, Kumarasamy N, Lombaard J, Wood R, et al.
    Lancet HIV, 2017 01;4(1):e13-e20.
    PMID: 27815068 DOI: 10.1016/S2352-3018(16)30189-8
    BACKGROUND: Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir.

    METHODS: Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122.

    FINDINGS: Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N(t)RTI group and 28·0% (37·6) in the raltegravir group (mean difference 10·2%, 95% CI 0·1-20·4; p=0·048). Mean absolute change was 1·04 kg (SD 2·29) in the N(t)RTI group and 1·81 kg (2·50) in the raltegravir group (mean difference 0·6, 95% CI -0·1 to 1·3; p=0·10).

    INTERPRETATION: Our findings suggest that for people with virological failure of a first-line regimen containing efavirenz plus tenofovir and lamivudine or emtricitabine, the WHO-recommended switch to a ritonavir-boosted protease inhibitor plus zidovudine (a thymidine analogue nucleoside reverse transcriptase inhibitor) and lamivudine might come at the cost of peripheral lipoatrophy. Further study could help to define specific groups of people who might benefit from a switch to an N(t)RTI-sparing second-line ART regimen.

    FUNDING: The Kirby Institute and the Australian National Health and Medical Research Council.

    MeSH terms: Emtricitabine/administration & dosage; Emtricitabine/adverse effects; Tenofovir/administration & dosage; Tenofovir/adverse effects; Raltegravir Potassium/administration & dosage; Raltegravir Potassium/adverse effects; Raltegravir Potassium/therapeutic use*; Adult; Body Composition*; Drug Therapy, Combination; Female; Humans; International Cooperation; Male; HIV-1/drug effects; Absorptiometry, Photon; HIV Infections/drug therapy*; HIV Infections/metabolism; HIV Infections/virology; HIV Protease Inhibitors/administration & dosage; HIV Protease Inhibitors/adverse effects; CD4 Lymphocyte Count; Reverse Transcriptase Inhibitors/administration & dosage; Reverse Transcriptase Inhibitors/adverse effects; Reverse Transcriptase Inhibitors/therapeutic use*; Lamivudine/administration & dosage; Lamivudine/adverse effects; Anti-HIV Agents/administration & dosage; Anti-HIV Agents/adverse effects; Anti-HIV Agents/therapeutic use*; Ritonavir/administration & dosage; Ritonavir/adverse effects; Ritonavir/therapeutic use*; Viral Load; Antiretroviral Therapy, Highly Active; HIV-Associated Lipodystrophy Syndrome/epidemiology*; Lopinavir/administration & dosage; Lopinavir/adverse effects; Lopinavir/therapeutic use*
  17. Chin CT, Ong TK, Krittayaphong R, Lee SW, Sawhney JPS, Kim HS, et al.
    Int J Cardiol, 2017 Sep 15;243:15-20.
    PMID: 28747021 DOI: 10.1016/j.ijcard.2017.04.059
    BACKGROUND: Many patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are medically managed without coronary revascularization. The reasons vary and may impact prognosis.

    METHODS: EPICOR Asia (NCT01361386) is a prospective study of hospital survivors post-ACS enrolled in 218 hospitals from 8 countries/regions in Asia (06/2011-05/2012). All medically managed NSTE-ACS patients were classified into 3 groups: 1) no coronary angiography (CAG-); 2) non-significant coronary artery disease (CAD) on angiogram (CAG+ CAD-); and 3) significant CAD (CAG+ CAD+). We compared baseline differences between patients medically managed and patients undergoing revascularization, and also between the medically managed groups. Adverse events were reported and compared up to 2years.

    RESULTS: Of 6163 NSTE-ACS patients, 2272 (37%) were medically managed, with 1339 (59%), 254 (11%), and 679 (30%) in the CAG-, CAG+ CAD-, and CAG+ CAD+ groups, respectively. There were marked differences in the proportion of medically managed patients among the 8 countries/regions (13-81%). Medically managed patients had higher mortality at 2years compared with revascularization (8.7% vs. 3.0%, p<0.001). Among medically managed patients, CAG- patients were older, more likely to have pre-existing cardiovascular disease, and had the highest 2-year mortality (10.5% vs. 4.3% [CAG+ CAD-] and 6.6% [CAG+ CAD+], p<0.001). Mortality differences persisted after adjusting for other patient risk factors.

    CONCLUSIONS: Medically managed NSTE-ACS patients are a heterogeneous group with different risk stratification and variable prognosis. Identification of reasons underlying different management strategies, and key factors adversely influencing long-term prognosis, may improve outcomes.

    MeSH terms: Aged; Asia/epidemiology; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Treatment Outcome; Disease Management*; Internationality; Acute Coronary Syndrome/diagnosis; Acute Coronary Syndrome/epidemiology*; Acute Coronary Syndrome/therapy*; Non-ST Elevated Myocardial Infarction/diagnosis; Non-ST Elevated Myocardial Infarction/epidemiology*; Non-ST Elevated Myocardial Infarction/therapy*
  18. Mohammad N, Besari AM, Nair PK, Wan Ghazali WS
    BMJ Case Rep, 2017 Jul 26;2017.
    PMID: 28747414 DOI: 10.1136/bcr-2017-220490
    A previously healthy 20-year-old man presented with prolonged intermittent low grade fever and cough for 6months. He had bilateral calf pain and lower limb weakness 2days prior to admission. Physical examination revealed multiple enlarged lymph nodes with hepatomegaly. There was bilateral calf tenderness with evidence of proximal myopathy. Full blood picture showed lymphocytosis with reactive lymphocytes and eosinophilia. Creatine kinase and lactate dehydrogenase were markedly elevated. Over 2 weeks of admission, patient was treated symptomatically until the muscle biopsy of right calf revealed eosinophilic myositis with muscular sarcocystosis. He was treated with albendazole and high-dose corticosteroids. Symptoms subsided on reviewed at 2weeks and the dose of corticosteroid was tapered down slowly over a month. Due to poor compliance, he was readmitted 1month later because of relapsed. High-dose corticosteroid was restarted and duration for albendazole was prolonged for 1month. His symptom finally resolved over 2weeks.
    MeSH terms: Adrenal Cortex Hormones/therapeutic use; Biopsy; Hepatomegaly/etiology*; Humans; Malaysia; Male; Sarcocystosis/diagnosis*; Sarcocystosis/drug therapy; Sarcocystosis/pathology; Albendazole/therapeutic use; Treatment Outcome; Young Adult; Lymphadenopathy/etiology*
  19. Wang P, Yang J, Li X, Liu M, Zhang X, Sun D, et al.
    Sci Rep, 2017 07 26;7(1):6615.
    PMID: 28747656 DOI: 10.1038/s41598-017-06007-3
    Uncovering energy absorption and surface effects of various penetrating velocities on laminar structures is essential for designing protective structures. In this study, both quasi-static and dynamic penetration tests were systematical conducted on the front surfaces of metal sheets coated with a graphene oxide (GO) solution and other media. The addition of a GO fluid film to the front impact surface aided in increasing the penetration strength, improving the failure extension and dissipating additional energy under a wide-range of indentation velocity, from 3.33 × 10-5 m/s to 4.42 m/s. The coated -surfaces improved the specific energy dissipation by approximately 15~40% relative to the dry-contact configuration for both single-layer and double-layer configurations, and specific energy dissipations of double-layer configurations were 20~30% higher than those of the single-layer configurations. This treatment provides a facile strategy in changing the contact state for improving the failure load and dissipate additional energy.
    MeSH terms: Graphite; Metals; Drug Delivery Systems; Physical Phenomena
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