Browse publications by year: 2016

Neuroelectrophysiological approaches in heroin addiction research: A review of literatures

Motlagh F, Ibrahim F, Menke JM, Rashid R, Seghatoleslam T, Habil H

J Neurosci Res, 2016 Apr;94(4):297-309.
PMID: 26748947 DOI: 10.1002/jnr.23703

Neuroelectrophysiological properties have been used in human heroin addiction studies. These studies vary in their approach, experimental conditions, paradigms, and outcomes. However, it is essential to integrate previous findings and experimental methods for a better demonstration of current issues and challenges in designing such studies. This Review examines methodologies and experimental conditions of neuroelectrophysiological research among heroin addicts during withdrawal, abstinence, and methadone maintenance treatment and presents the findings. The results show decrements in attentional processing and dysfunctions in brain response inhibition as well as brain activity abnormalities induced by chronic heroin abuse. Chronic heroin addiction causes increased β and α2 power activity, latency of P300 and P600, and diminished P300 and P600 amplitude. Findings confirm that electroencephalography (EEG) band power and coherence are associated with craving indices and heroin abuse history. First symptoms of withdrawal can be seen in high-frequency EEG bands, and the severity of these symptoms is associated with brain functional connectivity. EEG spectral changes and event-related potential (ERP) properties have been shown to be associated with abstinence length and tend to normalize within 3-6 months of abstinence. From the conflicting criteria and confounding effects in neuroelectrophysiological studies, the authors suggest a comprehensive longitudinal study with a multimethod approach for monitoring EEG and ERP attributes of heroin addicts from early stages of withdrawal until long-term abstinence to control the confounding effects, such as nicotine abuse and other comorbid and premorbid conditions.

MeSH terms: Brain/physiopathology*; Electroencephalography/methods; Electrophysiology/methods*; Evoked Potentials/physiology; Heroin Dependence/physiopathology*; Humans; Substance Withdrawal Syndrome/physiopathology*
The Significance of Tinospora crispa in Treatment of Diabetes Mellitus

Thomas A, Rajesh EK, Kumar DS

Phytother Res, 2016 Mar;30(3):357-66.
PMID: 26749336 DOI: 10.1002/ptr.5559

Tinospora crispa is a medicinal plant belonging to the botanical family Menispermiaceae. The plant is widely distributed in Southeast Asia and the northeastern region of India. A related species Tinospora cordifolia is used in Ayurveda for treating a large spectrum of diseases. Traditional healers of Thailand, Malaysia, Guyana, Bangladesh and the southern Indian province of Kerala use this plant in the treatment of diabetes. Many diterpenes, triterpenes, phytosteroids, alkaloids and their glycosides have been isolated from T. crispa. Cell culture and animal studies suggest that the herb stimulates secretion of insulin from β-cells. It also causes dose-dependent and time-dependent enhancement of glucose uptake in muscles. However, in view of the reported hepatotoxicity, this herb may be used with caution. This article reviews the animal studies and human clinical trials carried out using this herb. Areas of future research are also identified.

MeSH terms: Alkaloids/pharmacology; Alkaloids/therapeutic use; Animals; Diabetes Mellitus/drug therapy*; Diabetes Mellitus/metabolism; Glucose/metabolism*; Humans; Hypoglycemic Agents/pharmacology; Hypoglycemic Agents/therapeutic use*; Insulin/metabolism*; Phytotherapy*; Muscles/drug effects; Muscles/metabolism; Phytosterols/pharmacology; Phytosterols/therapeutic use; Plant Extracts/adverse effects; Plant Extracts/pharmacology; Plant Extracts/therapeutic use*; Terpenes/pharmacology; Terpenes/therapeutic use; Tinospora/adverse effects; Tinospora/chemistry*
The enablers and barriers to continue breast milk feeding in women returning to work

Sulaiman Z, Liamputtong P, Amir LH

J Adv Nurs, 2016 Apr;72(4):825-35.
PMID: 26749396 DOI: 10.1111/jan.12884

AIM: To describe the enablers and barriers working women experience in continuing breast milk feeding after they return to work postpartum in urban Malaysia.
BACKGROUND: In Malaysia, urban working women have low rates of breastfeeding and struggle to achieve the recommended 6 months exclusive breastfeeding.
DESIGN: A qualitative enquiry based on a phenomenological framework and multiple methods were used to explore women's experiences in depth.
METHODS: Multiple qualitative methods using face-to-face interview and participant diary were used. Data collection took place in urban suburbs around Penang and Klang Valley, Malaysia from March-September 2011. Participants were 40 employed women with infants less than 24 months.
FINDINGS: Only 11 of the participants worked from home. Based on the women's experiences, we categorized them into three groups: 'Passionate' women with a strong determination and exclusively breastfed for 6 months, 'Ambivalent' women who initiated breastfeeding, but were unable to sustain exclusive breastfeeding after returning to work and 'Equivalent' women who introduced infant formula prior to returning to work.
CONCLUSION: Passion and to a lesser extent intention, influenced women's choice. Women's characteristics played a greater role in their infant feeding outcomes than their work environment.
KEYWORDS: Malaysia; barriers; breastfeeding; enablers; interviews; nursing; qualitative; working women
Zinc Carnosine Inhibits Lipopolysaccharide-Induced Inflammatory Mediators by Suppressing NF-κb Activation in Raw 264.7 Macrophages, Independent of the MAPKs Signaling Pathway

Ooi TC, Chan KM, Sharif R

Biol Trace Elem Res, 2016 Aug;172(2):458-464.
PMID: 26749414 DOI: 10.1007/s12011-015-0615-x

This study aimed to investigate the role of the mitogen-activated protein kinases (MAPKs) signaling pathway in the anti-inflammatory effects of zinc carnosine (ZnC) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cells were pretreated with ZnC (0-100 μM) for 2 h prior to the addition of LPS (1 μg/ml). Following 24 h of treatment, ZnC was found not to be cytotoxic to RAW 264.7 cells up to the concentration of 100 μM. Our current findings showed that ZnC did not protect RAW 264.7 cells from LPS-induced "respiratory burst". Significant increment in intracellular glutathione (GSH) level and reduction in thiobarbituric acid reactive substances (TBARS) concentration can only be observed in cell pretreated with high doses of ZnC only (50 and 100 μM for GSH and 100 μM only for TBARS). On the other hand, pretreatment of cells with ZnC was able to inhibit LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression significantly. Furthermore, results from immunoblotting showed that ZnC was able to suppress nuclear factor-kappaB (NF-κB) activation, and highest suppression can be observed at 100 μM of ZnC pretreatment. However, pretreatment of ZnC did not inhibit the early activation of MAPKs. In conclusion, pretreatment with ZnC was able to inhibit the expression of inflammatory mediators in LPS-induced RAW 264.7 cells, mainly via suppression of NF-κB activation, and is independent of the MAPKs signaling pathway.

MeSH terms: Animals; Anti-Inflammatory Agents, Non-Steroidal/pharmacology*; Carnosine/analogs & derivatives*; Carnosine/pharmacology; Cells, Cultured; Lipopolysaccharides/antagonists & inhibitors*; Lipopolysaccharides/pharmacology; Macrophages/drug effects*; Macrophages/metabolism; Organometallic Compounds/pharmacology*; NF-kappa B/metabolism*; Zinc Compounds/pharmacology; Inflammation Mediators/metabolism*; Mice
Effects of 1α-Calcidol (Alfacalcidol) on Microvascular Endothelial Function, Arterial Stiffness, and Blood Pressure in Type II Diabetic Nephropathy Patients

Munisamy S, Daud KM, Mokhtar SS, Rasool AH

Microcirculation, 2016 Jan;23(1):53-61.
PMID: 26749451 DOI: 10.1111/micc.12256

To determine the effects of six months alfacalcidol on microvascular endothelial function, arterial stiffness, and BP in DN patients.

MeSH terms: Adult; Aged; Blood Pressure/drug effects*; Endothelium, Vascular/physiopathology*; Female; Humans; Hydroxycholecalciferols/administration & dosage*; Male; Middle Aged; Vitamin D Deficiency/drug therapy; Vitamin D Deficiency/physiopathology; Vascular Stiffness/drug effects*
Fulltext Human Heat shock protein 40 (Hsp40/DnaJB1) promotes influenza A virus replication by assisting nuclear import of viral ribonucleoproteins

Batra J, Tripathi S, Kumar A, Katz JM, Cox NJ, Lal RB, et al.

Sci Rep, 2016;6:19063.
PMID: 26750153 DOI: 10.1038/srep19063

A unique feature of influenza A virus (IAV) life cycle is replication of the viral genome in the host cell nucleus. The nuclear import of IAV genome is an indispensable step in establishing virus infection. IAV nucleoprotein (NP) is known to mediate the nuclear import of viral genome via its nuclear localization signals. Here, we demonstrate that cellular heat shock protein 40 (Hsp40/DnaJB1) facilitates the nuclear import of incoming IAV viral ribonucleoproteins (vRNPs) and is important for efficient IAV replication. Hsp40 was found to interact with NP component of IAV RNPs during early stages of infection. This interaction is mediated by the J domain of Hsp40 and N-terminal region of NP. Drug or RNAi mediated inhibition of Hsp40 resulted in reduced nuclear import of IAV RNPs, diminished viral polymerase function and attenuates overall viral replication. Hsp40 was also found to be required for efficient association between NP and importin alpha, which is crucial for IAV RNP nuclear translocation. These studies demonstrate an important role for cellular chaperone Hsp40/DnaJB1 in influenza A virus life cycle by assisting nuclear trafficking of viral ribonucleoproteins.

MeSH terms: Cell Nucleus; Influenza A virus; Ribonucleoproteins; Viral Core Proteins; Virus Replication; RNA-Binding Proteins; Genome, Viral; Nuclear Localization Signals; Active Transport, Cell Nucleus; alpha Karyopherins; RNA Interference; HSP40 Heat-Shock Proteins
Atherosclerotic cardiovascular disease: a review of initiators and protective factors

Ellulu MS, Patimah I, Khaza'ai H, Rahmat A, Abed Y, Ali F

Inflammopharmacology, 2016 Feb;24(1):1-10.
PMID: 26750181 DOI: 10.1007/s10787-015-0255-y

Atherosclerotic cardiovascular disease (CVD) is a collective term comprising of a group of disorders of the heart and blood vessels. These diseases are the largest cause of morbidity and premature death worldwide. Coronary heart disease and cerebrovascular disease (stroke) are the most frequently occurring diseases. The two major initiators involved in the development of atherosclerotic CVD are vascular production of reactive oxygen species (ROS) and lipid oxidation. In atherosclerosis development, ROS is associated with rapid loss of anti-inflammatory and anti-atherogenic activities of the endothelium-derived nitric oxide (NO(·)) resulting in endothelial dysfunction. In part involving activation of the transcription factor NF-κB, ROS have been involved in signaling cascades leading to vascular pro-inflammatory and pro-thrombotic gene expression. ROS is also a potent activator of matrix metalloproteinases (MMPs), which indicate plaque destabilization and rupture. The second initiator involved in atherosclerotic CVD is the oxidation of low-density lipoproteins (LDL). Oxidation of LDL in vessel wall leads to an inflammatory cascade that activates atherogenic pathway leading to foam cell formation. The accumulation of foam cells leads to fatty streak formation, which is the earliest visible atherosclerotic lesion. In contrast, the cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and hepatic apolipoprotein E (apoE) expression can improve cardiovascular function. SERCA2a regulates the cardiac contractile function by lowering cytoplasmic calcium levels during relaxation, and affecting NO(·) action in vascular cells, while apoE is a critical ligand in the plasma clearance of triglyceride- and cholesterol-rich lipoproteins.

MeSH terms: Animals; Cardiovascular Diseases/etiology; Cardiovascular Diseases/physiopathology*; Humans; Nitric Oxide/metabolism; Risk Factors; Lipid Peroxidation/physiology; Reactive Oxygen Species/metabolism*; Oxidative Stress/physiology; Atherosclerosis/etiology; Atherosclerosis/physiopathology*; Protective Factors
Fulltext Intergroup Contact Effects via Ingroup Distancing among Majority and Minority Groups: Moderation by Social Dominance Orientation

Kauff M, Schmid K, Lolliot S, Al Ramiah A, Hewstone M

PLoS One, 2016;11(1):e0146895.
PMID: 26751203 DOI: 10.1371/journal.pone.0146895

Five studies tested whether intergroup contact reduces negative outgroup attitudes through a process of ingroup distancing. Based on the deprovincialization hypothesis and Social Dominance Theory, we hypothesized that the indirect effect of cross-group friendship on outgroup attitudes via reduced ingroup identification is moderated by individuals' Social Dominance Orientation (SDO), and occurs only for members of high status majority groups. We tested these predictions in three different intergroup contexts, involving conflictual relations between social groups in Germany (Study 1; N = 150; longitudinal Study 2: N = 753), Northern Ireland (Study 3: N = 160; Study 4: N = 1,948), and England (Study 5; N = 594). Cross-group friendship was associated with reduced ingroup identification and the link between reduced ingroup identification and improved outgroup attitudes was moderated by SDO (the indirect effect of cross-group friendship on outgroup attitudes via reduced ingroup only occurred for individuals scoring high, but not low, in SDO). Although there was a consistent moderating effect of SDO in high-status majority groups (Studies 1-5), but not low-status minority groups (Studies 3, 4, and 5), the interaction by SDO was not reliably stronger in high- than low-status groups. Findings are discussed in terms of better understanding deprovincialization effects of contact.

MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Attitude; England; Female; Germany; Group Processes; Humans; Interpersonal Relations; Longitudinal Studies; Male; Middle Aged; Minority Groups*; Northern Ireland; Prejudice; Social Behavior; Social Dominance*; Social Identification*; Students; Universities; Friends*; Young Adult
Seven root canals in a deciduous maxillary molar detected by the dental operating microscope and micro-computed tomography

Ahmed HM, Khamis MF, Gutmann JL

Scanning, 2016 Nov;38(6):554-557.
PMID: 26751249 DOI: 10.1002/sca.21299

The root and root canal morphology of deciduous molars shows considerable variations. Consequently, a comprehensive understanding of the normal and unusual root and root canal configuration types in deciduous teeth is of prime importance. The purpose of this report is to describe a rare anatomical variation in a double-rooted maxillary deciduous molar examined by the dental operating microscope and micro-computed tomography. SCANNING 38:554-557, 2016. © 2016 Wiley Periodicals, Inc.

MeSH terms: Dental Pulp Cavity/anatomy & histology*; Humans; Maxilla; Microscopy; Molar/anatomy & histology*; Tooth, Deciduous/anatomy & histology*; X-Ray Microtomography/methods*
Synthesis and characterization of a new vertebroplasty cement based on gold-containing PMMA microspheres

Jacobs E, Saralidze K, Roth AK, de Jong JJ, van den Bergh JP, Lataster A, et al.

Biomaterials, 2016 Mar;82:60-70.
PMID: 26751820 DOI: 10.1016/j.biomaterials.2015.12.024

There are a number of drawbacks to incorporating large concentrations of barium sulfate (BaSO4) as the radiopacifier in PMMA-based bone cements for percutaneous vertebroplasty. These include adverse effects on injectability, viscosity profile, setting time, mechanical properties of the cement and bone resorption. We have synthesized a novel cement that is designed to address some of these drawbacks. Its powder includes PMMA microspheres in which gold particles are embedded and its monomer is the same as that used in commercial cements for vertebroplasty. In comparison to one such commercial cement brand, VertaPlex™, the new cement has longer doughing time, longer injection time, higher compressive strength, higher compressive modulus, and is superior in terms of cytotoxicity. For augmentation of fractured fresh-frozen cadaveric vertebral bodies (T6-L5) using simulated vertebroplasty, results for compressive strength and compressive stiffness of the construct and the percentage of the volume of the vertebral body filled by the cement were comparable for the two cements although the radiopacity of the new cement was significantly lower than that for VertaPlex™. The present results indicate that the new cement warrants further study.

MeSH terms: Adhesiveness; Barium Sulfate/chemistry*; Bone Cements/chemical synthesis*; Contrast Media; Gold/chemistry*; Hardness; Materials Testing; Microspheres*; Viscosity; Compressive Strength; Polymethyl Methacrylate/chemistry*; Vertebroplasty/methods*
Goniothalamin induces cell cycle arrest and apoptosis in H400 human oral squamous cell carcinoma: A caspase-dependent mitochondrial-mediated pathway with downregulation of NF-κβ

Li LK, Rola AS, Kaid FA, Ali AM, Alabsi AM

Arch Oral Biol, 2016 Apr;64:28-38.
PMID: 26752226 DOI: 10.1016/j.archoralbio.2015.12.002

Goniothalamin is a natural occurring styryl-lactone compound isolated from Goniothalamus macrophyllus. It had been demonstrated to process promising anticancer activity on various cancer cell lines. However, little study has been carried out on oral cancer. The aim of this study was to determine the cytotoxic effects of goniothalamin against H400 oral cancer cells and its underlying molecular pathways. Results from MTT assay demonstrated that goniothalamin exhibited selective cytotoxicity as well as inhibited cells growth of H400 in dose and time-dependent manner. This was achieved primarily via apoptosis where apoptotic bodies and membrane blebbing were observed using AO/PI and DAPI/Annexin V-FITC fluorescence double staining. In order to understand the apoptosis mechanisms induced by goniothalamin, apoptosis assessment based on mitochondrial membrane potential assay and cytochrome c enzyme-linked immunosorbent assay were carried out. Results demonstrated that the depolarization of mitochondrial transmembrane potential facilitated the release of mitochondrial cytochrome c into cytosol. Caspases assays revealed the activation of initiator caspase-9 and executioner caspase-3/7 in dose-dependent manners. This form of apoptosis was closely associated with the regulation on Bcl-2 family proteins, cell cycle arrest at S phase and inhibition of NF-κβ translocation from cytoplasm to nucleus. Conclusion, goniothalamin has the potential to act as an anticancer agent against human oral squamous cell carcinoma (H400 cells).

MeSH terms: Carcinoma, Squamous Cell; Cytosol; Fluorescence; Humans; Mouth Neoplasms; S Phase; Proto-Oncogene Proteins c-bcl-2; Caspases; Cytochromes c; Membrane Potential, Mitochondrial; Caspase 3; Goniothalamus
Public Knowledge and Attitudes Regarding the Use of Antibiotics and Resistance: Findings from a Cross-Sectional Study Among Palestinian Adults

Abu Taha A, Abu-Zaydeh AH, Ardah RA, Al-Jabi SW, Sweileh WM, Awang R, et al.

Zoonoses Public Health, 2016 09;63(6):449-57.
PMID: 26752329 DOI: 10.1111/zph.12249

Antibiotics are considered to be among the most commonly sold drug classes in Palestine. Resistance to antibiotics has increased for reasons relating to the use and misuse of antibiotics. The aim of this study was to evaluate the knowledge, and attitudes regarding antibiotic use and awareness about resistance among adults visiting the emergency departments at hospitals in North Palestine. A self-administered cross-sectional questionnaire survey involving participants aged 18 or over was conducted from June 2012 to February 2013. Adults who visited the emergency departments at hospitals in North Palestine were included. Demographic characteristics, knowledge and attitudes towards antibiotic use were included in the questionnaire. Poor and good knowledge were defined as a total knowledge score of 0-7 and 8-15 of 15 questions, respectively. Attitude scores of 0-3 and 4-7 of 7 questions were considered poor and good, respectively. A total of 375 questionnaires were included in the study. A response rate of 83.3% was attained. About 55.0% of the participants had a good knowledge and 56.5% had a good attitude towards rational antibiotic use. A significant positive correlation was shown between participants' knowledge scores and participants' attitude scores towards antibiotic use (R = 0.344, P = 0.001. Participants with a high family income were more likely to be aware of appropriate antibiotic use than participants with a low family income (P-value <0.001). Participants with a higher educational level (university) had a good attitude towards rational antibiotic use than those with a lower education level (P-value <0.001). This study has documented important knowledge and attitude gaps in antibiotic use. These findings will help health policymakers in Palestine to implement intervention programmes to rationalize antibiotic use. Continuing medical education, professional development and training workshops for healthcare professionals regarding rational use of antibiotics and health risks associated with the spread of antibiotic resistance are needed. In addition, minimizing non-prescription use of antibiotics and increasing the public awareness about the health and economic hazards of antibiotic resistance are also required.

MeSH terms: Adolescent; Adult; Anti-Bacterial Agents/pharmacology*; Bacterial Infections/drug therapy; Bacterial Infections/microbiology; Cross-Sectional Studies; Data Collection; Drug Utilization; Ear/abnormalities; Ear Diseases; Humans; Health Knowledge, Attitudes, Practice*; Middle Aged; Arabs*; Drug Resistance, Bacterial*; Young Adult
Invadopodia proteins, cortactin, N-WASP and WIP differentially promote local invasiveness in ameloblastoma

Siar CH, Rahman ZA, Tsujigiwa H, Mohamed Om Alblazi K, Nagatsuka H, Ng KH

J Oral Pathol Med, 2016 Sep;45(8):591-8.
PMID: 26752341 DOI: 10.1111/jop.12417

BACKGROUND: Cell migration and invasion through interstitial tissues are dependent upon several specialized characteristics of the migratory cell notably generation of proteolytic membranous protrusions or invadopodia. Ameloblastoma is a benign odontogenic epithelial neoplasm with a locally infiltrative behaviour. Cortactin and MMT1-MMP are two invadopodia proteins implicated in its local invasiveness. Other invadopodia regulators, namely N-WASP, WIP and Src kinase remain unclarified. This study addresses their roles in ameloblastoma.
MATERIALS AND METHOD: Eighty-seven paraffin-embedded ameloblastoma cases (20 unicystic, 47 solid/multicystic, 3 desmoplastic and 17 recurrent) were subjected to immunohistochemistry for expression of cortactin, N-WASP, WIP, Src kinase and F-actin, and findings correlated with clinicopathological parameters.
RESULTS: Invadopodia proteins (except Src kinase) and F-actin were widely detected in ameloblastoma (cortactin: n = 73/87, 83.9%; N-WASP: n = 59/87; 67.8%; WIP: n = 77/87; 88.5%; and F-actin: n = 87/87, 100%). Protein localization was mainly cytoplasmic and/or membranous, and occasionally nuclear for F-actin. Cortactin, which functions as an actin-scaffolding protein, demonstrated significantly higher expression levels within ameloblastoma tumoral epithelium than in stroma (P < 0.05). N-WASP, which coordinates actin polymerization and invadopodia-mediated extracellular matrix degradation, was overexpressed in the solid/multicystic subtype (P < 0.05). WIP, an upstream regulator of N-WASP, and F-actin were significantly upregulated along the tumour invasive front compared to tumour centres (P < 0.05). Except for males with cortactin overexpression, other clinical parameters (age, ethnicity and anatomical site) showed no significant correlations.
CONCLUSIONS: Present results suggest that local invasiveness of ameloblastoma is dependent upon the migratory potential of its tumour cells as defined by their distribution of cortactin, N-WASP and WIP in correlation with F-actin cytoskeletal dynamics.

MeSH terms: Podosomes/physiology*; Actins/analysis; Actins/biosynthesis; Actins/physiology; Adolescent; Adult; Aged; Ameloblastoma/metabolism*; Ameloblastoma/pathology; Cell Movement/physiology; Child; Cytoskeletal Proteins/biosynthesis; Cytoskeletal Proteins/physiology*; Female; Humans; Immunohistochemistry; Jaw Neoplasms/metabolism*; Jaw Neoplasms/pathology; Male; Middle Aged; Neoplasm Invasiveness; Neoplasms, Glandular and Epithelial/metabolism; Stromal Cells/metabolism; Stromal Cells/pathology; src-Family Kinases/analysis; src-Family Kinases/physiology; Intracellular Signaling Peptides and Proteins/biosynthesis; Intracellular Signaling Peptides and Proteins/physiology*; Wiskott-Aldrich Syndrome Protein, Neuronal/biosynthesis; Wiskott-Aldrich Syndrome Protein, Neuronal/physiology*; Cortactin/biosynthesis; Cortactin/physiology*; Young Adult
Fulltext Vascular leakage in dengue - clinical spectrum and influence of parenteral fluid therapy

Rosenberger KD, Lum L, Alexander N, Junghanss T, Wills B, Jaenisch T, et al.

Trop Med Int Health, 2016 Mar;21(3):445-53.
PMID: 26752720 DOI: 10.1111/tmi.12666

OBJECTIVE: Clinical management of dengue relies on careful monitoring of fluid balance combined with judicious intravenous (IV) fluid therapy. However, in patients with significant vascular leakage, IV fluids may aggravate serosal fluid accumulation and result in respiratory distress.
METHODS: Trained physicians followed suspected dengue cases prospectively at seven hospitals across Asia and Latin America, using a comprehensive case report form that included daily clinical assessment and detailed documentation of parenteral fluid therapy. Applying Cox regression, we evaluated risk factors for the development of shock or respiratory distress with fluid accumulation.
RESULTS: Most confirmed dengue patients (1524/1734, 88%) never experienced dengue shock syndrome (DSS). Among those with DSS, 176/210 (84%) had fluid accumulation, and in the majority (83%), this was detectable clinically. Among all cases with clinically detectable fluid accumulation, 179/447 (40%) were diagnosed with shock or respiratory distress. The risk for respiratory distress with fluid accumulation increased significantly as the infused volume over the preceding 24 h increased (hazard ratio 1.18 per 10 ml/kg increase; P < 0.001). Longer duration of IV therapy, use of a fluid bolus in the preceding 24 h, female gender and poor nutrition also constituted independent risk factors.
CONCLUSIONS: Shock and respiratory distress are relatively rare manifestations of dengue, but some evidence of fluid accumulation is seen in around 50% of cases. IV fluids play a crucial role in management, but they must be administered with caution. Clinically and/or radiologically detectable fluid accumulations have potential as intermediate severity endpoints for therapeutic intervention trials and/or pathogenesis studies.
KEYWORDS: IV fluid therapy; clinical spectrum; dengue; espectro clínico; fluidothérapie IV; fuga vascular; fuite vasculaire; prospectif; prospective; prospectivo; spectre clinique; terapia IV de fluidos; vascular leakage

MeSH terms: Dengue*; Fluid Therapy*; Humans; Malaysia; Prospective Studies
Fulltext Roles of cofactors and chromatin accessibility in Hox protein target specificity

Beh CY, El-Sharnouby S, Chatzipli A, Russell S, Choo SW, White R

Epigenetics Chromatin, 2016;9:1.
PMID: 26753000 DOI: 10.1186/s13072-015-0049-x

The regulation of specific target genes by transcription factors is central to our understanding of gene network control in developmental and physiological processes yet how target specificity is achieved is still poorly understood. This is well illustrated by the Hox family of transcription factors as their limited in vitro DNA-binding specificity contrasts with their clear in vivo functional specificity.
Fulltext A cross-sectional study on quality of life among the elderly in non-governmental organizations' elderly homes in Kuala Lumpur

Onunkwor OF, Al-Dubai SA, George PP, Arokiasamy J, Yadav H, Barua A, et al.

Health Qual Life Outcomes, 2016;14:6.
PMID: 26753811 DOI: 10.1186/s12955-016-0408-8

There is a rapid increase in the population of the elderly globally, and Malaysia is anticipated to become an ageing nation in 2030. Maintaining health, social participation, reducing institutionalization, and improving quality of life of the elderly are public health challenges of the 21(st) century. Quality of life among elderly in Elderly Homes in Malaysia is under researched. This study aims to determine the quality of life and its associated factors among the Elderly in Elderly Homes in Kuala Lumpur.

MeSH terms: Aged; Aging; Homes for the Aged; Humans; Institutionalization; Malaysia; Public Health; Quality of Life; Social Participation
Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis

Abdul-Aziz MH, Sulaiman H, Mat-Nor MB, Rai V, Wong KK, Hasan MS, et al.

Intensive Care Med, 2016 Oct;42(10):1535-1545.
PMID: 26754759 DOI: 10.1007/s00134-015-4188-0

PURPOSE: This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/pharmacodynamic (PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis.
METHODS: This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation.
RESULTS: A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p MIC than the IB arm on day 1 (97 versus 70 %, p

MeSH terms: Adult; Anti-Bacterial Agents/administration & dosage*; Critical Care/methods*; Female; Humans; Infusions, Intravenous/methods*; Male; Middle Aged; Prospective Studies; Chi-Square Distribution; Critical Illness/therapy; Statistics, Nonparametric; Sepsis/drug therapy*; Sepsis/physiopathology; beta-Lactams/administration & dosage*; Kaplan-Meier Estimate
Fulltext MK886 inhibits the pioglitazone-induced anti-invasion of MDA-MB-231 cells is associated with PPARα/γ, FGF4 and 5LOX

Nadarajan K, Balaram P, Khoo BY

Cytotechnology, 2016 Oct;68(5):1771-87.
PMID: 26754842 DOI: 10.1007/s10616-015-9930-5

The goal of this study was to determine the effects of PGZ and MK886 on the mRNA expression of PPARα and other associated genes in MDA-MB-231 cells, and the biological mechanisms induced by both drugs were also assessed. The levels of PPARα mRNA expression in PGZ-treated and MK886-treated MDA-MB-231 cells were determined using real-time PCR; the growth inhibitory effects of PGZ and MK886 were determined using the trypan blue exclusion assay; the induction of apoptosis by PGZ and MK886 was determined using DNA fragmentation assay and real-time PCR; and the invasion of PGZ-treated and MK886-treated MDA-MB-231 cells was determined using the wound healing and transwell migration assays. In addition, we correlated the expression of PPARα mRNA with other genes, including PPARγ, FGF4 and 5LOX, in drug-treated MDA-MB-231 cells. Our results demonstrated that the treatment of MDA-MB-231 cells with PGZ increased the expression of PPARα/γ mRNA and that this expression could be inhibited by treatment with MK886. Both drugs reduced the viability of MDA-MB-231 cells independently of PPARα/γ mRNA expression but did not induce apoptosis. The wound caused by invasion was not healed by PGZ-treated MDA-MB-231 cells, but it was healed by MK886-treated cancer cells, indicating that the reduction of invasion in PGZ-treated MDA-MB-231 cells was eliminated by treatment with MK886, and this finding was validated by the transwell migration assay. This phenomenon might also be associated with the expression of PPARα/γ, FGF4 and 5LOX mRNA in the treated cancer cells. This study provides useful information regarding the mRNA expression levels of PPARα and other related genes in MDA-MB-231 cells. These genes could be attractive targets for reducing the invasion of breast cancer.
Synthesis, in vitro antimycobacterial evaluation and docking studies of some new 5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one schiff bases

Narender M, Jaswanth S B, Umasankar K, Malathi J, Raghuram Reddy A, Umadevi KR, et al.

Bioorg Med Chem Lett, 2016 Feb 01;26(3):836-840.
PMID: 26755393 DOI: 10.1016/j.bmcl.2015.12.083

Development of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) has been considered as major health burden, globally. In order to develop novel, potential molecules against drug resistant TB, twenty two (22) new 3-substituted-7-benzyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one (6a-k) and 3-substituted-7-benzyl-2-methyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one (7a-k) derivatives were designed and synthesized by using appropriate synthetic protocols. Pantothenate synthetase (PS) was considered as the target for the molecular docking studies and evaluated the binding pattern at active site, as PS plays a significant role in the biosynthesis of pantothenate in Mycobacterium tuberculosis (MTB). The preliminary in vitro antibacterial screening of test compounds was carried out against two strains of Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria. The antimycobacterial screening was performed against MTB H37Rv and an isoniazid-resistant clinical isolate of MTB. The compounds 6b, 6c, 6d, 6k, 7b, 7c, 7d and 7k exhibited promising antibacterial activity MIC in the range of 15-73 μM against all bacterial strains used and compounds 6d and 7b showed antimycobacterial activity (IC50 <340 μM in LRP assay) and (MIC <9 μM in broth microdilution method).

MeSH terms: Anti-Bacterial Agents/chemical synthesis*; Anti-Bacterial Agents/pharmacology; Bacterial Proteins/antagonists & inhibitors; Bacterial Proteins/metabolism; Binding Sites; Gram-Negative Bacteria/drug effects; Gram-Negative Bacteria/metabolism; Gram-Positive Bacteria/drug effects; Gram-Positive Bacteria/metabolism; Isoniazid/pharmacology; Microbial Sensitivity Tests; Mycobacterium tuberculosis/drug effects; Mycobacterium tuberculosis/metabolism; Pyrimidines/chemical synthesis; Pyrimidines/pharmacology; Pyrimidines/chemistry*; Schiff Bases/chemical synthesis; Schiff Bases/pharmacology; Schiff Bases/chemistry*; Structure-Activity Relationship; Protein Structure, Tertiary; Drug Resistance, Bacterial/drug effects; Molecular Docking Simulation
Simultaneous analysis of silicon and boron dissolved in water by combination of electrodialytic salt removal and ion-exclusion chromatography with corona charged aerosol detection

Mori M, Sagara K, Arai K, Nakatani N, Ohira S, Toda K, et al.

J Chromatogr A, 2016 Jan 29;1431:131-7.
PMID: 26755416 DOI: 10.1016/j.chroma.2015.12.064

Selective separation and sensitive detection of dissolved silicon and boron (DSi and DB) in aqueous solution was achieved by combining an electrodialytic ion isolation device (EID) as a salt remover, an ion-exclusion chromatography (IEC) column, and a corona charged aerosol detector (CCAD) in sequence. DSi and DB were separated by IEC on the H(+)-form of a cation exchange resin column using pure water eluent. DSi and DB were detected after IEC separation by the CCAD with much greater sensitivity than by conductimetric detection. The five-channel EID, which consisted of anion and cation acceptors, cathode and anode isolators, and a sample channel, removed salt from the sample prior to the IEC-CCAD. DSi and DB were scarcely attracted to the anion accepter in the EID and passed almost quantitatively through the sample channel. Thus, the coupled EID-IEC-CCAD device can isolate DSi and DB from artificial seawater and hot spring water by efficiently removing high concentrations of Cl(-) and SO4(2-) (e.g., 98% and 80% at 0.10molL(-1) each, respectively). The detection limits at a signal-to-noise ratio of 3 were 0.52μmolL(-1) for DSi and 7.1μmolL(-1) for DB. The relative standard deviations (RSD, n=5) of peak areas were 0.12% for DSi and 4.3% for DB.

MeSH terms: Aerosols; Anions; Boron; Cation Exchange Resins; Cations; Chromatography, Gel; Electrodes; Seawater; Silicon; Sodium Chloride; Water; Hot Springs; Limit of Detection; Signal-To-Noise Ratio

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