Browse publications by year: 2018

Clinical and radiographic periodontal parameters and release of collagen degradation biomarkers in naswar dippers

Daood U, Abduljabbar T, Al-Hamoudi N, Akram Z

J Periodontal Res, 2018 Feb;53(1):123-130.
PMID: 28940417 DOI: 10.1111/jre.12496

BACKGROUND AND OBJECTIVE: The aim of the present study was to compare clinical periodontal parameters and to assess the release of C-telopeptides pyridinoline cross-links (ICTP) and C-terminal crosslinked telopeptide (CTX) from gingival collagen of naswar (NW) and non-naswar (control) dippers.
MATERIAL AND METHODS: Eighty-seven individuals (42 individuals consuming NW and 45 controls) were included. Clinical (plaque index, bleeding on probing, probing depth and clinical attachment loss) and radiographic (marginal bone loss) periodontal parameters were compared among NW and control groups. Gingival specimens were taken from subjects in NW and control groups, assessed for ICTP and CTX levels (using ELISA) and analyzed using micro-Raman spectroscopy. The significance of differences in periodontal parameters between the groups was determined using Kruskal-Wallis and Mann-Whitney U tests. The percent loss of dry mass over exposure time and the rate of release of ICTP and CTX from all groups were compared using the paired t-test to examine the effects of exposure time.
RESULTS: Clinical and radiographic periodontal parameters were significantly higher in the NW group than the control group (P

MeSH terms: Adult; Collagen/metabolism*; Dental Plaque Index; Gingiva/metabolism; Humans; Male; Peptides/metabolism*; Periodontal Index; Periodontal Pocket/pathology; Spectrum Analysis, Raman; Tobacco, Smokeless/adverse effects*; Biomarkers/metabolism; Case-Control Studies; Alveolar Bone Loss/pathology; Periodontal Attachment Loss/pathology; Collagen Type I/metabolism*
Detection of copy number variations in epilepsy using exome data

Tsuchida N, Nakashima M, Kato M, Heyman E, Inui T, Haginoya K, et al.

Clin Genet, 2018 03;93(3):577-587.
PMID: 28940419 DOI: 10.1111/cge.13144

Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole-exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants in known epilepsy-associated genes to further validate CNVs using 2 different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and 2 deletions and 2 duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10 kb in size, which might be difficult to detect by conventional microarray. We revealed 2 cases with pathogenic CNVs that one of the 2 CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with <10 kb in size, CNV detection by WES may be able to surrogate, or at least complement, conventional microarray analysis.

MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Child; Child, Preschool; Epilepsy/diagnosis; Epilepsy/genetics*; Female; Humans; Male; Middle Aged; Mutation; Computational Biology/methods; Genetic Predisposition to Disease*; Comparative Genomic Hybridization; Young Adult; DNA Copy Number Variations*; High-Throughput Nucleotide Sequencing; Exome
Fulltext Continuous infusion vs. intermittent bolus injection of furosemide in acute decompensated heart failure: systematic review and meta-analysis of randomised controlled trials

Ng KT, Yap JLL

Anaesthesia, 2018 Feb;73(2):238-247.
PMID: 28940440 DOI: 10.1111/anae.14038

Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent randomised controlled trials have examined the clinical benefit of continuous vs. bolus furosemide in acute decompensated heart failure, but have reported conflicting findings. The aim of this review was to compare the effects of continuous and bolus furosemide with regard to mortality, length of hospital stay and its efficacy profile in acute decompensated heart failure. All parallel-arm randomised controlled trials from MEDLINE, EMBASE, PubMed and the Cochrane Database of Systematic Reviews from inception until May 2017 were included. Cross-over randomised controlled trials, observational studies, case reports, case series and non-systematic reviews that involved children were excluded. Eight trials (n = 669) were eligible for inclusion. There was no difference between furosemide continuous infusion and bolus administration for all-cause mortality (four studies; n = 491; I2 = 0%; OR 1.65; 95%CI 0.93-2.91; p = 0.08) or duration of hospitalisation (six studies; n = 576; I2 = 71%; mean difference 0.27; 95%CI -1.35 to 1.89 days; p = 0.74). Continuous infusion of intravenous furosemide was associated with increased weight reduction (five studies; n = 516; I2 = 0%; mean difference 0.70; 95%CI 0.12-1.28 kg; p = 0.02); increased total urine output in 24 h (four studies; n = 390; I2 = 33%; mean difference 461.5; 95%CI 133.7-789.4 ml; p < 0.01); and reduced brain natriuretic peptide (two studies; n = 390; I2 = 0%; mean difference 399.5; 95%CI 152.7-646.3 ng.l-1 ; p < 0.01), compared with the bolus group. There was no difference in the incidence of raised creatinine and hypokalaemia between the two groups. In summary, there was no difference between continuous infusion and bolus of furosemide for all-cause mortality, length of hospital stay and electrolyte disturbance, but continuous infusion was superior to bolus administration with regard to diuretic effect and reduction in brain natriuretic peptide.

MeSH terms: Acute Disease; Diuretics/administration & dosage*; Diuretics/therapeutic use*; Furosemide/administration & dosage*; Furosemide/therapeutic use*; Heart Failure/drug therapy*; Heart Failure/mortality; Heart Failure/prevention & control; Humans; Infusions, Intravenous; Injections, Intravenous; Length of Stay
Fulltext Nitrogen dynamics in flooded soil systems: an overview on concepts and performance of models

Nurulhuda K, Gaydon DS, Jing Q, Zakaria MP, Struik PC, Keesman KJ

J Sci Food Agric, 2018 Feb;98(3):865-871.
PMID: 28940491 DOI: 10.1002/jsfa.8683

Extensive modelling studies on nitrogen (N) dynamics in flooded soil systems have been published. Consequently, many N dynamics models are available for users to select from. With the current research trend, inclined towards multidisciplinary research, and with substantial progress in understanding of N dynamics in flooded soil systems, the objective of this paper is to provide an overview of the modelling concepts and performance of 14 models developed to simulate N dynamics in flooded soil systems. This overview provides breadth of knowledge on the models, and, therefore, is valuable as a first step in the selection of an appropriate model for a specific application. © 2017 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

MeSH terms: Models, Biological; Nitrogen/chemistry*; Soil/chemistry*; Water Pollutants, Chemical/chemistry; Floods
Morphological and transcript changes in the biosynthesis of lignin in oil palm (Elaeis guineensis) during Ganoderma boninense infections in vitro

Goh KM, Dickinson M, Supramaniam CV

Physiol Plant, 2018 Mar;162(3):274-289.
PMID: 28940509 DOI: 10.1111/ppl.12645

Lignification of the plant cell wall could serve as the first line of defense against pathogen attack, but the molecular mechanisms of virulence and disease between oil palm and Ganoderma boninense are poorly understood. This study presents the biochemical, histochemical, enzymology and gene expression evidences of enhanced lignin biosynthesis in young oil palm as a response to G. boninense (GBLS strain). Comparative studies with control (T1), wounded (T2) and infected (T3) oil palm plantlets showed significant accumulation of total lignin content and monolignol derivatives (syringaldehyde and vanillin). These derivatives were deposited on the epidermal cell wall of infected plants. Moreover, substantial differences were detected in the activities of enzyme and relative expressions of genes encoding phenylalanine ammonia lyase (EC 4.3.1.24), cinnamate 4-hydroxylase (EC 1.14.13.11), caffeic acid O-methyltransferase (EC 2.1.1.68) and cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195). These enzymes are key intermediates dedicated to the biosynthesis of lignin monomers, the guaicyl (G), syringyl (S) and ρ-hydroxyphenyl (H) subunits. Results confirmed an early, biphasic and transient positive induction of all gene intermediates, except for CAD enzyme activities. These differences were visualized by anatomical and metabolic changes in the profile of lignin in the oil palm plantlets such as low G lignin, indicating a potential mechanism for enhanced susceptibility toward G. boninense infection.

MeSH terms: Alcohol Oxidoreductases/genetics; Alcohol Oxidoreductases/metabolism; Benzaldehydes/metabolism; Cell Wall/genetics; Cell Wall/metabolism; Cell Wall/microbiology; Lignin/biosynthesis*; Methyltransferases/genetics; Methyltransferases/metabolism; Phenylalanine Ammonia-Lyase/genetics; Phenylalanine Ammonia-Lyase/metabolism; Plant Diseases/genetics*; Plant Diseases/microbiology; Plant Proteins/genetics; Plant Proteins/metabolism; Gene Expression Regulation, Plant*; Plant Epidermis/genetics; Plant Epidermis/metabolism; Plant Epidermis/microbiology; Arecaceae/genetics*; Arecaceae/metabolism; Arecaceae/microbiology; Ganoderma/physiology; Trans-Cinnamate 4-Monooxygenase/genetics; Trans-Cinnamate 4-Monooxygenase/metabolism; Host-Pathogen Interactions
Development of a battery of tests to measure attitudes and intended behaviours of dental students towards people with disability or those in marginalised groups

Faulks D, Dougall A, Ting G, Ari T, Nunn J, Friedman C, et al.

Eur J Dent Educ, 2018 May;22(2):e278-e290.
PMID: 28940883 DOI: 10.1111/eje.12292

INTRODUCTION: Recommended curricula in Special Care Dentistry (SCD) outline learning objectives that include the domain of attitudes and behaviours, but these are notoriously difficult to measure. The aims of this study were (i) to develop a test battery comprising adapted and new scales to evaluate values, attitudes and intentions of dental students towards people with disability and people in marginalised groups and (ii) to determine reliability (interitem consistency) and validity of the scales within the test battery.
MATERIALS AND METHODS: A literature search identified pre-existing measures and models for the assessment of attitudes in healthcare students. Adaptation of three pre-existing scales was undertaken, and a new scale was developed based upon the Theory of Planned Behaviour (TPB) using an elicitation survey. These scales underwent a process of content validation. The three adapted scales and the TPB scale were piloted by 130 students at 5 different professional stages, from 4 different countries.
RESULTS: The scales were adjusted to ensure good internal reliability, variance, distribution, and face and content validity. In addition, the different scales showed good divergent validity.
DISCUSSION: These results are positive, and the scales now need to be validated in the field.
CONCLUSIONS: It is hoped that these tools will be useful to educators in SCD to evaluate the impact of teaching and clinical exposure on their students.

MeSH terms: Attitude of Health Personnel*; Education, Dental*; Female; Great Britain; Disabled Persons*; Humans; Male; Pilot Projects; Students, Dental/psychology*; Reproducibility of Results; Vulnerable Populations*
Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis

Miura F, Okamoto K, Takada T, Strasberg SM, Asbun HJ, Pitt HA, et al.

J Hepatobiliary Pancreat Sci, 2018 Jan;25(1):31-40.
PMID: 28941329 DOI: 10.1002/jhbp.509

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

MeSH terms: Clinical Decision-Making; Acute Disease; Anti-Bacterial Agents/therapeutic use; Cholangitis/pathology; Cholangitis/therapy*; Drainage/methods; Female; Follow-Up Studies; Humans; Male; Monitoring, Physiologic/methods; Severity of Illness Index; Software Design; Tokyo; Sphincterotomy, Endoscopic/methods*; Treatment Outcome; Practice Guidelines as Topic*; Risk Assessment; Cholecystitis, Acute/pathology; Cholecystitis, Acute/therapy*
New crosslinked-chitosan graft poly(N-vinyl-2-pyrrolidone) for the removal of Cu(II) ions from aqueous solutions

Sutirman ZA, Sanagi MM, Abd Karim J, Abu Naim A, Wan Ibrahim WA

Int J Biol Macromol, 2018 Feb;107(Pt A):891-897.
PMID: 28935540 DOI: 10.1016/j.ijbiomac.2017.09.061

Crosslinked chitosan beads were grafted with N-vinyl-2-pyrrolidone (NVP) using ammonium persulfate (APS) as free radical initiator. Important variables on graft copolymerization such as temperature, reaction time, concentration of initiator and concentration of monomer were optimized. The results revealed optimum conditions for maximum grafting of NVP on 1g crosslinked chitosan as follows: reaction temperature, 60°C; reaction time, 2h and concentrations of APS and NVP of 2.63×10-1M and 26.99×10-1M, respectively. The modified chitosan beads were characterized by FTIR spectroscopy, 13C NMR, SEM and BET to provide evidence of successful crosslinking and grafting reactions. The resulting material (cts(x)-g-PNVP) was evaluated as adsorbent for the removal of Cu(II) ions from aqueous solutions in a batch experiment. The Langmuir and Freundlich adsorption models were also applied to describe the equilibrium isotherms. The results showed that the adsorption of the copper ions onto the beads agreed well with Langmuir model with the maximum capacity (qmax) of 122mgg-1.

MeSH terms: Copper/toxicity; Copper/chemistry*; Cross-Linking Reagents/chemistry; Ions/toxicity; Ions/chemistry; Kinetics; Pyrrolidinones/chemistry; Water/chemistry; Water Pollutants, Chemical/toxicity; Water Pollutants, Chemical/chemistry*; Water Purification*; Chitosan/chemistry*
Reactive oxygen species and glutathione antioxidants in the testis of the soil biosentinel Podarcis sicula (Rafinesque 1810)

Guerriero G, D'Errico G, Di Giaimo R, Rabbito D, Olanrewaju OS, Ciarcia G

Environ Sci Pollut Res Int, 2018 Jul;25(19):18286-18296.
PMID: 28936697 DOI: 10.1007/s11356-017-0098-8

Important toxicological achievements have been made during the last decades using reptiles. We focus our investigation on gonadal reproductive health of the soil biosentinel Podarcis sicula which is very sensitive to endocrine-disrupting chemicals. The aim of this study is to quantitatively detect, by sensitive microassays, reactive oxygen species and the glutathione antioxidants in the testis and investigate if they are differentially expressed before and after remediation of a site of the "Land of Fires" (Campania, Italy) subject to illicit dumping of unknown material. The oxidative stress level was evaluated by electron spin resonance spectroscopy applying a spin-trapping procedure able to detect products of lipid peroxidation, DNA damage and repair by relative mobility shift, and poly(ADP-ribose) polymerase enzymatic activity, respectively, the expression of glutathione peroxidase 4 transcript by real-time quantitative PCR analysis, the antioxidant glutathione S-transferase, a well-assessed pollution index, by enzymatic assay and the total soluble antioxidant capacity. Experimental evidences from the different techniques qualitatively agree, thus confirming the robustness of the combined experimental approach. Collected data, compared to those from a reference unpolluted site constitute evidence that the reproductive health of this lizard is impacted by pollution exposure. Remediation caused significant reduction of reactive oxygen species and downregulation of glutathione peroxidase 4 mRNAs in correspondence of reduced levels of glutathione S-transferase, increase of antioxidant capacity, and repair of DNA integrity. Taken together, our results indicate directions to define new screening approaches in remediation assessment.

MeSH terms: Animals; Antioxidants/metabolism*; Environmental Monitoring/methods*; Glutathione/metabolism*; Italy; Lizards/metabolism*; Male; Soil/chemistry; Soil Pollutants/toxicity; Testis/drug effects; Testis/metabolism*; Reactive Oxygen Species/metabolism*; Oxidative Stress/drug effects; Endocrine Disruptors/toxicity; Environmental Restoration and Remediation
Post-hepatectomy Lactate: Should We Add More?

Ariffin AC

World J Surg, 2018 05;42(5):1563-1564.
PMID: 28932972 DOI: 10.1007/s00268-017-4252-8
MeSH terms: Hepatectomy*; Humans; Liver; Lactic Acid*
Fulltext Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats

Suliman NA, Taib CNM, Moklas MAM, Basir R

Neurotox Res, 2018 02;33(2):402-411.
PMID: 28933048 DOI: 10.1007/s12640-017-9806-x

Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis. Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured. Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective. Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.

MeSH terms: Animals; Brain/drug effects; Brain/metabolism; Cognition/drug effects*; Glial Fibrillary Acidic Protein/metabolism; Hippocampus/drug effects*; Male; Memory/drug effects*; Dronabinol/pharmacology*; Rats, Sprague-Dawley; Maze Learning/drug effects; Brain-Derived Neurotrophic Factor/metabolism; Neurogenesis/drug effects*; Nestin/metabolism
Fulltext Factors involved in human papillomavirus (HPV) vaccine hesitancy among women in the South-East Asian Region (SEAR) and Western Pacific Region (WPR): A scoping review

Santhanes D, Wong CP, Yap YY, San SP, Chaiyakunapruk N, Khan TM

Hum Vaccin Immunother, 2018 Jan 02;14(1):124-133.
PMID: 28933635 DOI: 10.1080/21645515.2017.1381811

A scoping review was performed to identify factors that may lead to human papillomavirus (HPV) vaccine hesitancy among women in low- and middle-income countries in South East Asian Region (SEAR) and Western Pacific Region (WPR). A systematic search of English and non-English articles using Pubmed, EMBASE, PsycINFO, Cochrane, MEDLINE, and CINAHL plus was conducted. Only 63 studies conducted in SEAR and WPR were included from inception until December 2016. Results of these studies have shown that poor awareness and knowledge of practices on cervical cancer prevention was evident in both SEAR and WPR. Concerns on safety and efficacy of the vaccine, and costs in getting vaccinated were significant barriers. Most women stated that they needed more information, and strongly welcomed a physician's recommendation in both geographical regions. Women also felt they have a low risk of acquiring HPV infection and cervical cancer. Most women in SEAR and WPR were unable to decide on whether to accept HPV vaccination.

MeSH terms: Asia, Southeastern/epidemiology; Uterine Cervical Neoplasms/epidemiology; Uterine Cervical Neoplasms/prevention & control*; Uterine Cervical Neoplasms/virology; Decision Making; Female; Humans; Health Knowledge, Attitudes, Practice; Socioeconomic Factors; Vaccination/adverse effects; Vaccination/economics; Vaccination/psychology*; Vaccination/statistics & numerical data; Treatment Outcome; Papillomaviridae/immunology*; Papillomaviridae/isolation & purification; Papillomavirus Infections/epidemiology; Papillomavirus Infections/prevention & control*; Papillomavirus Infections/virology; Papillomavirus Vaccines/adverse effects; Papillomavirus Vaccines/economics; Papillomavirus Vaccines/therapeutic use*
Fulltext Comparative aspects of microRNA expression in canine and human cancers

Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC

J Vet Sci, 2018 Mar 31;19(2):162-171.
PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162

MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.

MeSH terms: Animals; Breast Neoplasms/metabolism; Dog Diseases/metabolism*; Dogs; Female; Humans; Lymphoma/metabolism; Lymphoma/veterinary; Mastocytosis/metabolism; Mastocytosis/veterinary; Neoplasms/metabolism*; Neoplasms/veterinary; Mammary Neoplasms, Animal/metabolism; Gene Expression Regulation, Neoplastic; MicroRNAs/metabolism*
Real-time human respiration carbon dioxide measurement device for cardiorespiratory assessment

Singh OP, Howe TA, Malarvili MB

J Breath Res, 2018 01 04;12(2):026003.
PMID: 28928295 DOI: 10.1088/1752-7163/aa8dbd

The development of a human respiration carbon dioxide (CO2) measurement device to evaluate cardiorespiratory status inside and outside a hospital setting has proven to be a challenging area of research over the few last decades. Hence, we report a real-time, user operable CO2 measurement device using an infrared CO2 sensor (Arduino Mega2560) and a thin film transistor (TFT, 3.5″), incorporated with low pass (cut-off frequency, 10 Hz) and moving average (span, 8) filters. The proposed device measures features such as partial end-tidal carbon dioxide (EtCO2), respiratory rate (RR), inspired carbon dioxide (ICO2), and a newly proposed feature-Hjorth activity-that annotates data with the date and time from a real-time clock, and is stored onto a secure digital (SD) card. Further, it was tested on 22 healthy subjects and the performance (reliability, validity and relationship) of each feature was established using (1) an intraclass correlation coefficient (ICC), (2) standard error measurement (SEM), (3) smallest detectable difference (SDD), (4) Bland-Altman plot, and (5) Pearson's correlation (r). The SEM, SDD, and ICC values for inter- and intra-rater reliability were less than 5% and more than 0.8, respectively. Further, the Bland-Altman plot demonstrates that mean differences ± standard deviations for a set limit were 0.30 ± 0.77 mmHg, -0.34 ± 1.41 mmHg and 0.21 ± 0.64 breath per minute (bpm) for CO2, EtCO2 and RR. The findings revealed that the developed device is highly reliable, providing valid measurements for CO2, EtCO2, ICO2 and RR, and can be used in clinical settings for cardiorespiratory assessment. This research also demonstrates that EtCO2 and RR (r, -0.696) are negatively correlated while EtCO2 and activity (r, 0.846) are positively correlated. Thus, simultaneous measurement of these features may possibly assist physicians in understanding the subject's cardiopulmonary status. In future, the proposed device will be tested with asthmatic patients for use as an early screening tool outside a hospital setting.

MeSH terms: Adult; Breath Tests/instrumentation*; Breath Tests/methods*; Carbon Dioxide/analysis*; Computer Systems*; Female; Heart/physiology*; Humans; Male; Posture; Respiration*; Signal Processing, Computer-Assisted; Reproducibility of Results; Young Adult
Status, source identification, and health risks of potentially toxic element concentrations in road dust in a medium-sized city in a developing country

Praveena SM, Aris AZ

Environ Geochem Health, 2018 Apr;40(2):749-762.
PMID: 28929262 DOI: 10.1007/s10653-017-0021-8

This study aims to determine the status of potentially toxic element concentrations of road dust in a medium-sized city (Rawang, Malaysia). This study adopts source identification via enrichment factor, Pearson correlation analysis, and Fourier spectral analysis to identify sources of potentially toxic element concentrations in road dust in Rawang City, Malaysia. Health risk assessment was conducted to determine potential health risks (carcinogenic and non-carcinogenic risks) among adults and children via multiple pathways (i.e., ingestion, dermal contact, and inhalation). Mean of potentially toxic element concentrations were found in the order of Pb > Zn > Cr(IV) > Cu > Ni > Cd > As > Co. Source identification revealed that Cu, Cd, Pb, Zn, Ni, and Cr(IV) are associated with anthropogenic sources in industrial and highly populated areas in northern and southern Rawang, cement factories in southern Rawang, as well as the rapid development and population growth in northwestern Rawang, which have resulted in high traffic congestion. Cobalt, Fe, and As are related to geological background and lithologies in Rawang. Pathway orders for both carcinogenic and non-carcinogenic risks are ingestion, dermal contact, and inhalation, involving adults and children. Non-carcinogenic health risks in adults were attributed to Cr(IV), Pb, and Cd, whereas Cu, Cd, Cr(IV), Pb, and Zn were found to have non-carcinogenic health risks for children. Cd, Cr(IV), Pb, and As may induce carcinogenic risks in adults and children, and the total lifetime cancer risk values exceeded incremental lifetime.

MeSH terms: Adult; Vehicle Emissions; Carcinogens/toxicity; Child; Cities; Developing Countries*; Dust/analysis*; Environmental Exposure; Environmental Monitoring/methods*; Fourier Analysis; Humans; Industry; Malaysia; Risk Assessment; Metals, Heavy/analysis*; Metals, Heavy/toxicity
Modulation of oncogenic transcription factors by bioactive natural products in breast cancer

Hasanpourghadi M, Pandurangan AK, Mustafa MR

Pharmacol Res, 2018 02;128:376-388.
PMID: 28923544 DOI: 10.1016/j.phrs.2017.09.009

Carcinogenesis, a multi-step phenomenon, characterized by alterations at genetic level and affecting the main intracellular pathways controlling cell growth and development. There are growing number of evidences linking oncogenes to the induction of malignancies, especially breast cancer. Modulations of oncogenes lead to gain-of-function signals in the cells and contribute to the tumorigenic phenotype. These signals yield a large number of proteins that cause cell growth and inhibit apoptosis. Transcription factors such as STAT, p53, NF-κB, c-JUN and FOXM1, are proteins that are conserved among species, accumulate in the nucleus, bind to DNA and regulate the specific genes targets. Oncogenic transcription factors resulting from the mutation or overexpression following aberrant gene expression relay the signals in the nucleus and disrupt the transcription pattern. Activation of oncogenic transcription factors is associated with control of cell cycle, apoptosis, migration and cell differentiation. Among different cancer types, breast cancer is one of top ten cancers worldwide. There are different subtypes of breast cancer cell-lines such as non-aggressive MCF-7 and aggressive and metastatic MDA-MB-231 cells, which are identified with distinct molecular profile and different levels of oncogenic transcription factor. For instance, MDA-MB-231 carries mutated and overexpressed p53 with its abnormal, uncontrolled downstream signalling pathway that account for resistance to several anticancer drugs compared to MCF-7 cells with wild-type p53. Appropriate enough, inhibition of oncogenic transcription factors has become a potential target in discovery and development of anti-tumour drugs against breast cancer. Plants produce diverse amount of organic metabolites. Universally, these metabolites with biological activities are known as "natural products". The chemical structure and function of natural products have been studied since 1850s. Investigating these properties leaded to recognition of their molecular effects as anticancer drugs. Numerous natural products extracted from plants, fruits, mushrooms and mycelia, show potential inhibitory effects against several oncogenic transcription factors in breast cancer. Natural compounds that target oncogenic transcription factors have increased the number of candidate therapeutic agents. This review summarizes the current findings of natural products in targeting specific oncogenic transcription factors in breast cancer.

MeSH terms: Animals; Biological Products/pharmacology*; Breast Neoplasms/drug therapy; Breast Neoplasms/genetics; Breast Neoplasms/metabolism*; Humans; Transcription Factors/metabolism*; MicroRNAs
Orthosiphon stamineus (Misai Kucing) ameliorated postmenopausal osteoporosis in rat model

Bokhari RA, Lau SF, Mohamed S

Menopause, 2018 02;25(2):202-210.
PMID: 28926512 DOI: 10.1097/GME.0000000000000980

OBJECTIVE: Orthosiphon stamineus (OS) or Misai Kucing (Java tea) is a popular herbal supplement from Southeast Asia for various metabolic, age-related diseases. This study investigated the potential use of OS leaf extracts to ameliorate osteoporosis in ovariectomized rats.
METHODS: Fifty-six female Sprague-Dawley rats were randomly allocated into eight groups (n = 7): SHAM (healthy sham control); OVX (ovarietomized) nontreated rats (negative control); OVX + Remifemin (100 mg/kg body weight), and 2% green tea extract (positive controls); OVX + OS 50% ethanolic and aqueous extracts, both at either 150 or 300 mg/kg. After 16 weeks, the rats' bones and blood were evaluated for osteoporosis indicators (protein and mRNA expressions), micro-computed tomography for bone histomorphometry, and three-point bending test for tibia mechanical strength.
RESULTS: The extracts dose-dependently and significantly (P

MeSH terms: Teas, Herbal*; Animals; Bone and Bones/physiopathology; Bone Resorption/genetics; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Humans; Inflammation/blood; Ovariectomy; Peptide Fragments/blood; Plant Extracts/pharmacology*; Plant Extracts/therapeutic use*; Procollagen/blood; Random Allocation; Bone Density/drug effects; Osteoporosis, Postmenopausal/metabolism; Osteoporosis, Postmenopausal/pathology; Osteoporosis, Postmenopausal/prevention & control*; Interleukin-6/blood; Gene Expression/drug effects; NF-kappa B/genetics; Rats, Sprague-Dawley; Plant Leaves; Pliability/drug effects; Collagen Type I/genetics; Orthosiphon*; Rats; Osteoprotegerin/blood; RANK Ligand/metabolism; X-Ray Microtomography; Bone Morphogenetic Protein 2/genetics
Novel biallelic SZT2 mutations in 3 cases of early-onset epileptic encephalopathy

Tsuchida N, Nakashima M, Miyauchi A, Yoshitomi S, Kimizu T, Ganesan V, et al.

Clin Genet, 2018 02;93(2):266-274.
PMID: 28556953 DOI: 10.1111/cge.13061

The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that is associated with epileptogenesis. In mice, Szt2 is abundantly expressed in the central nervous system. Recently, biallelic SZT2 mutations were found in 7 patients (from 5 families) presenting with epileptic encephalopathy with dysmorphic features and/or non-syndromic intellectual disabilities. In this study, we identified by whole-exome sequencing compound heterozygous SZT2 mutations in 3 patients with early-onset epileptic encephalopathies. Six novel SZT2 mutations were found, including 3 truncating, 1 splice site and 2 missense mutations. The splice-site mutation resulted in skipping of exon 20 and was associated with a premature stop codon. All individuals presented with seizures, severe developmental delay and intellectual disabilities with high variability. Brain MRIs revealed a characteristic thick and short corpus callosum or a persistent cavum septum pellucidum in each of the 2 cases. Interestingly, in the third case, born to consanguineous parents, had unexpected compound heterozygous missense mutations. She showed microcephaly despite the other case and previous ones presenting with macrocephaly, suggesting that SZT2 mutations might affect head size.

MeSH terms: Child, Preschool; Epilepsy, Generalized/genetics*; Epilepsy, Generalized/pathology; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Intellectual Disability/genetics*; Intellectual Disability/pathology; Nerve Tissue Proteins/genetics*; Pedigree; Spasms, Infantile/genetics*; Spasms, Infantile/pathology; Mutation, Missense/genetics; RNA Splice Sites/genetics
Effects of acute salt stress on modulation of gene expression in a Malaysian salt-tolerant indigenous rice variety, Bajong

Yeo BPH, Bhave M, Hwang SS

J Plant Res, 2018 Jan;131(1):191-202.
PMID: 28921169 DOI: 10.1007/s10265-017-0977-6

The small genome size of rice relative to wheat and barley, together with its salt sensitivity, make it an ideal candidate for studies of salt stress response. Transcriptomics has emerged as a powerful technique to study salinity responses in many crop species. By identifying a large number of differentially expressed genes (DEGs) simultaneously after the stress induction, it can provide crucial insight into the immediate responses towards the stressor. In this study, a Malaysian salt-tolerant indigenous rice variety named Bajong and one commercial rice variety named MR219 were investigated for their performance in plant growth and ion accumulation properties after salt stress treatment. Bajong was further investigated for the changes in leaf's transcriptome after 6 h of stress treatment using 100 mM NaCl. Based on the results obtained, Bajong is found to be significantly more salt tolerant than MR219, showing better growth and a lower sodium ion accumulation after the stress treatment. Additionally, Bajong was analysed by transcriptomic sequencing, generating a total of 130 millions reads. The reads were assembled into de novo transcriptome and each transcript was annotated using several pre-existing databases. The transcriptomes of control and salt-stressed samples were then compared, leading to the discovery of 4096 DEGs. Based on the functional annotation results obtained, the enrichment factor of each functional group in DEGs was calculated in relation to the total reads obtained. It was found that the group with the highest gene modulation was involved in the secondary metabolite biosynthesis of plants, with approximately 2.5% increase in relation to the total reads obtained. This suggests an extensive transcriptional reprogramming of the secondary metabolic pathways after stress induction, which could be directly responsible for the salt tolerance capability of Bajong.

MeSH terms: Malaysia; Osmotic Pressure; Oryza/genetics; Oryza/physiology*; Stress, Physiological; Gene Expression Regulation, Plant*; Plant Leaves/physiology; Salinity; Salt-Tolerance*; Transcriptome*
Alternative models of DSM-5 PTSD: Examining diagnostic implications

Murphy S, Hansen M, Elklit A, Yong Chen Y, Raudzah Ghazali S, Shevlin M

Psychiatry Res, 2018 04;262:378-383.
PMID: 28917443 DOI: 10.1016/j.psychres.2017.09.011

The factor structure of DSM-5 posttraumatic stress disorder (PTSD) has been extensively debated with evidence supporting the recently proposed seven-factor Hybrid model. However, despite myriad studies examining PTSD symptom structure few have assessed the diagnostic implications of these proposed models. This study aimed to generate PTSD prevalence estimates derived from the 7 alternative factor models and assess whether pre-established risk factors associated with PTSD (e.g., transportation accidents and sexual victimisation) produce consistent risk estimates. Seven alternative models were estimated within a confirmatory factor analytic framework using the PTSD Checklist for DSM-5 (PCL-5). Data were analysed from a Malaysian adolescent community sample (n = 481) of which 61.7% were female, with a mean age of 17.03 years. The results indicated that all models provided satisfactory model fit with statistical superiority for the Externalising Behaviours and seven-factor Hybrid models. The PTSD prevalence estimates varied substantially ranging from 21.8% for the DSM-5 model to 10.0% for the Hybrid model. Estimates of risk associated with PTSD were inconsistent across the alternative models, with substantial variation emerging for sexual victimisation. These findings have important implications for research and practice and highlight that more research attention is needed to examine the diagnostic implications emerging from the alternative models of PTSD.

MeSH terms: Accidents, Traffic/psychology*; Adolescent; Female; Humans; Male; Models, Psychological; Risk Factors; Stress Disorders, Post-Traumatic/diagnosis*; Stress Disorders, Post-Traumatic/epidemiology; Prevalence; Crime Victims/psychology*; Diagnostic and Statistical Manual of Mental Disorders; Checklist

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