Browse publications by year: 2016

Echocardiographic agreement in the diagnostic evaluation for infective endocarditis

Lauridsen TK, Selton-Suty C, Tong S, Afonso L, Cecchi E, Park L, et al.

Int J Cardiovasc Imaging, 2016 Jul;32(7):1041-51.
PMID: 27100526 DOI: 10.1007/s10554-016-0873-5

Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data. IE reproducibility was assessed on a subset of echocardiograms from subjects enrolled in the International Collaboration on Endocarditis registry. Specific echocardiographic case report forms were used. Intra-observer agreement was assessed from six site readers on ten randomly selected echocardiograms. Inter-observer agreement between sites and an echocardiography core laboratory was assessed on a separate random sample of 110 echocardiograms. Agreement was determined using intraclass correlation (ICC), coverage probability (CP), and limits of agreement for continuous variables and kappa statistics (κweighted) and CP for categorical variables. Intra-observer agreement for LVEF was excellent [ICC = 0.93 ± 0.1 and all pairwise differences for LVEF (CP) were within 10 %]. For IE categorical echocardiographic variables, intra-observer agreement was best for aortic abscess (κweighted = 1.0, CP = 1.0 for all readers). Highest inter-observer agreement for IE categorical echocardiographic variables was obtained for vegetation location (κweighted = 0.95; 95 % CI 0.92-0.99) and lowest agreement was found for vegetation mobility (κweighted = 0.69; 95 % CI 0.62-0.86). Moderate to excellent intra- and inter-observer agreement is observed for echocardiographic variables in the diagnostic assessment of IE. A pragmatic approach for determining echocardiographic data reproducibility in a large, multicentre, site interpreted observational cohort is feasible.

MeSH terms: Adult; Aged; Endocarditis/physiopathology; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Registries; Retrospective Studies; Stroke Volume; Reproducibility of Results; Observer Variation; Ventricular Function, Left; Echocardiography, Transesophageal*
Fulltext Healthy Lifestyle and Risk of Cancer in the European Prospective Investigation Into Cancer and Nutrition Cohort Study

McKenzie F, Biessy C, Ferrari P, Freisling H, Rinaldi S, Chajès V, et al.

Medicine (Baltimore), 2016 Apr;95(16):e2850.
PMID: 27100409 DOI: 10.1097/MD.0000000000002850

It has been estimated that at least a third of the most common cancers are related to lifestyle and as such are preventable. Key modifiable lifestyle factors have been individually associated with cancer risk; however, less is known about the combined effects of these factors.This study generated a healthy lifestyle index score (HLIS) to investigate the joint effect of modifiable factors on the risk of overall cancers, alcohol-related cancers, tobacco-related cancers, obesity-related cancers, and reproductive-related cancers. The study included 391,608 men and women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The HLIS was constructed from 5 factors assessed at baseline (diet, physical activity, smoking, alcohol consumption, and anthropometry) by assigning scores of 0 to 4 to categories of each factor, for which higher values indicate healthier behaviors. Hazard ratios (HR) were estimated by Cox proportional regression and population attributable fractions (PAFs) estimated from the adjusted models.There was a 5% lower risk (adjusted HR 0.952, 95% confidence interval (CI): 0.946, 0.958) of all cancers per point score of the index for men and 4% (adjusted HR 0.961, 95% CI: 0.956, 0.966) for women. The fourth versus the second category of the HLIS was associated with a 28% and 24% lower risk for men and women respectively across all cancers, 41% and 33% for alcohol-related, 49% and 46% for tobacco-related, 41% and 26% for obesity-related, and 21% for female reproductive cancers.Findings suggest simple behavior modifications could have a sizeable impact on cancer prevention, especially for men.

MeSH terms: Alcohol Drinking; Anthropometry; Behavior Therapy; Diet; Factor V; Female; Humans; Life Style; Male; Neoplasms; Obesity; Prospective Studies; Smoking; Tobacco; Cohort Studies; Health Behavior; Exercise; Healthy Lifestyle
Fulltext Intracellular Delivery of Proteins via Fusion Peptides in Intact Plants

Ng KK, Motoda Y, Watanabe S, Sofiman Othman A, Kigawa T, Kodama Y, et al.

PLoS One, 2016;11(4):e0154081.
PMID: 27100681 DOI: 10.1371/journal.pone.0154081

In current plant biotechnology, the introduction of exogenous DNA encoding desired traits is the most common approach used to modify plants. However, general plant transformation methods can cause random integration of exogenous DNA into the plant genome. To avoid these events, alternative methods, such as a direct protein delivery system, are needed to modify the plant. Although there have been reports of the delivery of proteins into cultured plant cells, there are currently no methods for the direct delivery of proteins into intact plants, owing to their hierarchical structures. Here, we demonstrate the efficient fusion-peptide-based delivery of proteins into intact Arabidopsis thaliana. Bovine serum albumin (BSA, 66 kDa) was selected as a model protein to optimize conditions for delivery into the cytosol. The general applicability of our method to large protein cargo was also demonstrated by the delivery of alcohol dehydrogenase (ADH, 150 kDa) into the cytosol. The compatibility of the fusion peptide system with the delivery of proteins to specific cellular organelles was also demonstrated using the fluorescent protein Citrine (27 kDa) conjugated to either a nuclear localization signal (NLS) or a peroxisomal targeting signal (PTS). In conclusion, our designed fusion peptide system can deliver proteins with a wide range of molecular weights (27 to 150 kDa) into the cells of intact A. thaliana without interfering with the organelle-targeting peptide conjugated to the protein. We expect that this efficient protein delivery system will be a powerful tool in plant biotechnology.

MeSH terms: Amino Acid Sequence; Molecular Weight; Peptides/metabolism*; Peptides/chemistry; Recombinant Fusion Proteins/metabolism*; Recombinant Fusion Proteins/chemistry; Serum Albumin, Bovine/administration & dosage*; Organelles/metabolism; Arabidopsis/metabolism*
Fulltext Augmentation of Autoantibodies by Helicobacter pylori in Parkinson's Disease Patients May Be Linked to Greater Severity

Suwarnalata G, Tan AH, Isa H, Gudimella R, Anwar A, Loke MF, et al.

PLoS One, 2016;11(4):e0153725.
PMID: 27100827 DOI: 10.1371/journal.pone.0153725

Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity.

MeSH terms: Aged; Autoantibodies/blood; Autoantibodies/immunology*; Female; Humans; Male; Middle Aged; Parkinson Disease/blood; Parkinson Disease/complications*; Parkinson Disease/immunology*; Parkinson Disease/microbiology; Helicobacter pylori/immunology*; Helicobacter Infections/blood; Helicobacter Infections/complications*; Helicobacter Infections/immunology*; Helicobacter Infections/microbiology; Proto-Oncogene Proteins c-sis/immunology; Eukaryotic Initiation Factor-4A/immunology; NFI Transcription Factors/immunology
Fulltext Ultra-Sensitive Humidity Sensor Based on Optical Properties of Graphene Oxide and Nano-Anatase TiO2

Ghadiry M, Gholami M, Lai CK, Ahmad H, Chong WY

PLoS One, 2016;11(4):e0153949.
PMID: 27101247 DOI: 10.1371/journal.pone.0153949

Generally, in a waveguide-based humidity sensors, increasing the relative humidity (RH) causes the cladding refractive index (RI) to increase due to cladding water absorption. However, if graphene oxide (GO) is used, a reverse phenomenon is seen due to a gap increase in graphene layers. In this paper, this interesting property is applied in order to fabricate differential humidity sensor using the difference between RI of reduced GO (rGO) and nano-anatase TiO2 in a chip. First, a new approach is proposed to prepare high quality nano-anatase TiO2 in solution form making the fabrication process simple and straightforward. Then, the resulted solutions (TiO2 and GO) are effortlessly drop casted and reduced on SU8 two channels waveguide and extensively examined against several humid conditions. Investigating the sensitivity and performance (response time) of the device, reveals a great linearity in a wide range of RH (35% to 98%) and a variation of more than 30 dB in transmitted optical power with a response time of only ~0.7 sec. The effect of coating concentration and UV treatment are studied on the performance and repeatability of the sensor and the attributed mechanisms explained. In addition, we report that using the current approach, devices with high sensitivity and very low response time of only 0.3 sec can be fabricated. Also, the proposed device was comprehensively compared with other state of the art proposed sensors in the literature and the results were promising. Since high sensitivity ~0.47dB/%RH and high dynamic performances were demonstrated, this sensor is a proper choice for biomedical applications.

MeSH terms: Graphite/chemistry*; Humidity*; Microscopy, Electron, Scanning; Oxides/chemistry*; Spectrum Analysis, Raman; Titanium/chemistry*; Powder Diffraction; Metal Nanoparticles/chemistry*
Fulltext Quorum Sensing Inhibitory Activity of Giganteone A from Myristica cinnamomea King against Escherichia coli Biosensors

Sivasothy Y, Krishnan T, Chan KG, Abdul Wahab SM, Othman MA, Litaudon M, et al.

Molecules, 2016 Mar 21;21(3):391.
PMID: 27102164 DOI: 10.3390/molecules21030391

Malabaricones A-C (1-3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, namely Escherichia coli [pSB401] and Escherichia coli [pSB1075], whereby the potential of giganteone A (4) as a suitable anti-quorum sensing agent was demonstrated.

MeSH terms: Anti-Bacterial Agents/isolation & purification; Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/chemistry; Biphenyl Compounds/pharmacology*; Biphenyl Compounds/chemistry; Escherichia coli/drug effects; Escherichia coli/pathogenicity; Humans; Pseudomonas aeruginosa/drug effects; Pseudomonas aeruginosa/pathogenicity; Resorcinols/isolation & purification; Resorcinols/pharmacology*; Resorcinols/chemistry; Biosensing Techniques*; Myristicaceae/chemistry; Quorum Sensing/drug effects*
Fulltext Searching for Common Mammalian Retroviruses in Pediatric Idiopathic Diseases

Jeziorski E, Foulongne V, Ludwig C, Louhaem D, Rodiere M, Sitbon M, et al.

Viruses, 2016 Mar;8(3):86.
PMID: 27102168 DOI: 10.3390/v8030086

Mammalian retroviruses cause a variety of diseases in their hosts, including hematological and immunodeficiency disorders. Both human T-cell leukemia (HTLV) and human immunodeficiency (HIV) viruses originated from several independent zoonotic transmissions, indicating that cross-species transmissions from animal to humans may still occur. Thus, as the risk for retroviral transmissions from animals to humans increase, we investigated whether mammalian retroviruses are involved in selected pediatric idiopathic diseases whose symptoms evoke retroviral infections. Blood samples, sera, and synovial fluids, or bone marrow cells were collected from pediatric patients under 18 years of age with different autoimmune idiopathic diseases. Overall, we screened clinical samples from 110 children using sensitive nested and semi-nested PCR strategies targeting env genes, and a C-type retrovirus reverse transcriptase (RT) activity kit. All clinical samples were free of retroviral signatures, indicating the unlikelihood of an etiological role of the retroviruses we assessed in the pediatric diseases we tested.
Treatment of dental complications in sickle cell disease

Mulimani P, Ballas SK, Abas AB, Karanth L

Cochrane Database Syst Rev, 2016;4:CD011633.
PMID: 27103509 DOI: 10.1002/14651858.CD011633.pub2

Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health.Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease.
Fulltext A meta-synthesis on parenting a child with autism

Ooi KL, Ong YS, Jacob SA, Khan TM

Neuropsychiatr Dis Treat, 2016;12:745-62.
PMID: 27103804 DOI: 10.2147/NDT.S100634

BACKGROUND: The lifelong nature of autism in a child has deep implications on parents as they are faced with a range of challenges and emotional consequences in raising the child. The aim of this meta-synthesis was to explore the perspectives of parents in raising a child with autism in the childhood period to gain an insight of the adaptations and beliefs of parents toward autism, their family and social experiences, as well as their perceptions toward health and educational services.
METHODS: A systematic search of six databases (PubMed, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects [DARE]) was conducted from inception up to September 30, 2014. Full-text English articles of qualitative studies describing parents' perceptions relating to the care of children younger than 12 years of age and diagnosed with a sole disorder of autism were included.
RESULTS: A total of 50 eligible articles were appraised and analyzed, identifying four core themes encompassing all thoughts, emotions, and experiences commonly expressed by parents: 1) The Parent, 2) Impact on the Family, 3) Social Impact, and 4) Health and Educational Services. Findings revealed that parents who have a child with autism experienced multiple challenges in different aspects of care, impacting on parents' stress and adaptation.
CONCLUSION: Health care provision should be family centered, addressing and supporting the needs of the whole family and not just the affected child, to ensure the family's well-being and quality of life in the face of a diagnosis of autism.
Fulltext Evaluation of Glucose-6-Phosphate Dehydrogenase stability in stored blood samples

Jalil N, Azma RZ, Mohamed E, Ithnin A, Alauddin H, Baya SN, et al.

EXCLI J, 2016;15:155-62.
PMID: 27103895 DOI: 10.17179/excli2015-604

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is the commonest cause of neonatal jaundice in Malaysia. Recently, OSMMR2000-D G6PD Assay Kit has been introduced to quantitate the level of G6PD activity in newborns delivered in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). As duration of sample storage prior to analysis is one of the matters of concern, this study was conducted to identify the stability of G6PD enzyme during storage. A total of 188 cord blood samples from normal term newborns delivered at UKMMC were selected for this study. The cord bloods samples were collected in ethylene-diamine-tetra-acetic acid (EDTA) tubes and refrigerated at 2-8 °C. In addition, 32 out of 188 cord blood samples were spotted on chromatography paper, air-dried and stored at room temperature. G6PD enzyme activities were measured daily for 7 days using the OSMMR2000-D G6PD Assay Kit on both the EDTA blood and dried blood samples. The mean value for G6PD activity was compared between days of analysis using Student Paired T-Test. In this study, 172 out of 188 cord blood samples showed normal enzyme levels while 16 had levels corresponding to severe enzyme deficiency. The daily mean G6PD activity for EDTA blood samples of newborns with normal G6PD activity showed a significant drop on the fourth day of storage (p < 0.005) while for samples with severely deficient G6PD activity, significant drop was seen on third day of storage (p = 0.002). Analysis of dried cord blood showed a significant reduction in enzyme activity as early as the second day of storage (p = 0.001). It was also noted that mean G6PD activity for spotted blood samples were lower compared to those in EDTA tubes for all days (p = 0.001). Thus, EDTA blood samples stored at 2-8 °C appeared to have better stability in terms of their G6PD enzyme level as compared to dried blood samples on filter paper, giving a storage time of up to 3 days.

MeSH terms: Chromatography; Edetic Acid; Clinical Enzyme Tests; Ethylenediamines; Ethylenes; Fetal Blood; Glucosephosphate Dehydrogenase; Humans; Infant, Newborn; Jaundice, Neonatal; Malaysia; Students; Temperature; Acetic Acid
Fulltext Use and toxicity of complementary and alternative medicines among patients visiting emergency department: Systematic review

Jatau AI, Aung MM, Kamauzaman TH, Chedi BA, Sha'aban A, Rahman AF

J Intercult Ethnopharmacol, 2016 Mar 2;5(2):191-7.
PMID: 27104042 DOI: 10.5455/jice.20160223105521

Many studies have been conducted in health-care settings with regards to complementary and alternative medicine (CAM) use among patients. However, information regarding CAM use among patients in the emergency department (ED) is scarce. The aim of this article was to conduct a systematic review of published studies with regards to CAM use among the ED patients. A literature search of published studies from inception to September 2015 was conducted using PubMed, Scopus, and manual search of the reference list. 18 studies that met the inclusion criteria were reviewed. The prevalence rate of CAM use among ED patients across the studies ranged of 1.4-68.1%. Herbal therapy was the sub-modality of CAM most commonly used and frequently implicated in CAM-related ED visits. Higher education, age, female gender, religious affiliation, and chronic diseases were the most frequent factors associated with CAM use among the ED patients. Over 80% of the ED physicians did not ask the patients about the CAM therapy. Similarly, 80% of the ED patients were ready to disclose CAM therapy to the ED physician. The prevalence rate of CAM use among patients at ED is high and is growing with the current increasing popularity, and it has been a reason for some of the ED visits. There is a need for the health-care professionals to receive training and always ask patients about CAM therapy to enable them provide appropriate medical care and prevent CAM-related adverse events.

MeSH terms: Complementary Therapies; Chronic Disease; Emergency Service, Hospital; Female; Health Personnel; Humans; Phytotherapy; Physicians; Prevalence; Disclosure; PubMed
Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study

Leong DP, Teo KK, Rangarajan S, Kutty VR, Lanas F, Hui C, et al.

J Cachexia Sarcopenia Muscle, 2016 12;7(5):535-546.
PMID: 27104109

BACKGROUND: The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions.
METHODS: HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study.
RESULTS: HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th-75th percentile) 50 kg (43-56 kg) in men <40 years from Europe/North America to 18 kg (14-20 kg) in women >60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported.
CONCLUSIONS: Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges.

MeSH terms: Adult; Aged; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Population Surveillance; Surveys and Questionnaires; Reference Values; Hand Strength*; Healthy Volunteers
Fulltext A review on high-resolution CMOS delay lines: towards sub-picosecond jitter performance

Abdulrazzaq BI, Abdul Halin I, Kawahito S, Sidek RM, Shafie S, Yunus NA

Springerplus, 2016;5:434.
PMID: 27104122 DOI: 10.1186/s40064-016-2090-z

A review on CMOS delay lines with a focus on the most frequently used techniques for high-resolution delay step is presented. The primary types, specifications, delay circuits, and operating principles are presented. The delay circuits reported in this paper are used for delaying digital inputs and clock signals. The most common analog and digitally-controlled delay elements topologies are presented, focusing on the main delay-tuning strategies. IC variables, namely, process, supply voltage, temperature, and noise sources that affect delay resolution through timing jitter are discussed. The design specifications of these delay elements are also discussed and compared for the common delay line circuits. As a result, the main findings of this paper are highlighting and discussing the followings: the most efficient high-resolution delay line techniques, the trade-off challenge found between CMOS delay lines designed using either analog or digitally-controlled delay elements, the trade-off challenge between delay resolution and delay range and the proposed solutions for this challenge, and how CMOS technology scaling can affect the performance of CMOS delay lines. Moreover, the current trends and efforts used in order to generate output delayed signal with low jitter in the sub-picosecond range are presented.
Fulltext Turbulence Model Selection for Low Reynolds Number Flows

Aftab SM, Mohd Rafie AS, Razak NA, Ahmad KA

PLoS One, 2016;11(4):e0153755.
PMID: 27104354 DOI: 10.1371/journal.pone.0153755

One of the major flow phenomena associated with low Reynolds number flow is the formation of separation bubbles on an airfoil's surface. NACA4415 airfoil is commonly used in wind turbines and UAV applications. The stall characteristics are gradual compared to thin airfoils. The primary criterion set for this work is the capture of laminar separation bubble. Flow is simulated for a Reynolds number of 120,000. The numerical analysis carried out shows the advantages and disadvantages of a few turbulence models. The turbulence models tested were: one equation Spallart Allmars (S-A), two equation SST K-ω, three equation Intermittency (γ) SST, k-kl-ω and finally, the four equation transition γ-Reθ SST. However, the variation in flow physics differs between these turbulence models. Procedure to establish the accuracy of the simulation, in accord with previous experimental results, has been discussed in detail.

MeSH terms: Models, Theoretical*; Viscosity
Fulltext Neutralization of Bacterial YoeBSpn Toxicity and Enhanced Plant Growth in Arabidopsis thaliana via Co-Expression of the Toxin-Antitoxin Genes

Abu Bakar F, Yeo CC, Harikrishna JA

Int J Mol Sci, 2016 Apr 20;17(4).
PMID: 27104531 DOI: 10.3390/ijms17040321

Bacterial toxin-antitoxin (TA) systems have various cellular functions, including as part of the general stress response. The genome of the Gram-positive human pathogen Streptococcus pneumoniae harbors several putative TA systems, including yefM-yoeBSpn, which is one of four systems that had been demonstrated to be biologically functional. Overexpression of the yoeBSpn toxin gene resulted in cell stasis and eventually cell death in its native host, as well as in Escherichia coli. Our previous work showed that induced expression of a yoeBSpn toxin-Green Fluorescent Protein (GFP) fusion gene apparently triggered apoptosis and was lethal in the model plant, Arabidopsis thaliana. In this study, we investigated the effects of co-expression of the yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic A. thaliana. When co-expressed in Arabidopsis, the YefMSpn antitoxin was found to neutralize the toxicity of YoeBSpn-GFP. Interestingly, the inducible expression of both yefMSpn antitoxin and yoeBSpn toxin-GFP fusion in transgenic hybrid Arabidopsis resulted in larger rosette leaves and taller plants with a higher number of inflorescence stems and increased silique production. To our knowledge, this is the first demonstration of a prokaryotic antitoxin neutralizing its cognate toxin in plant cells.

MeSH terms: Bacterial Proteins/genetics*; Bacterial Proteins/metabolism; Bacterial Toxins/genetics*; Bacterial Toxins/metabolism; Recombinant Fusion Proteins/analysis; Recombinant Fusion Proteins/genetics; Apoptosis/genetics; Arabidopsis/genetics*; Arabidopsis/growth & development; Arabidopsis/metabolism; Plants, Genetically Modified/growth & development; Green Fluorescent Proteins/analysis
Fulltext Reply to C. Stewart's Letter to the Editor Re: Teoh SL et al., Nutrients 2016, 8, 57

Teoh SL, Sudfangsai S, Lumbiganon P, Laopaiboon M, Lai NM, Chaiyakunapruk N

Nutrients, 2016;8(4).
PMID: 27104559 DOI: 10.3390/nu8040228

In a recent systematic review and meta-analysis report (Nutrients 2016, 8, 57), we critically appraised and summarized current evidence to determine the effects of chicken essence in improving cognitive functions as well as its safety. [...].

MeSH terms: Animals; Chickens; Cognition; Oils, Volatile
Age-Stage, Two-Sex Life Table Characteristics of Aedes albopictus and Aedes Aegypti in Penang Island, Malaysia

Maimusa HA, Ahmad AH, Kassim NF, Rahim J

J Am Mosq Control Assoc, 2016 Mar;32(1):1-11.
PMID: 27105211 DOI: 10.2987/moco-32-01-1-11.1

The life table developmental attributes of laboratory colonies of wild strains of Aedes albopictus and Aedes aegypti were analyzed and compared based on the age-stage, two-sex life table. Findings inclusive in this study are: adult preoviposition periods, total preoviposition period, mean intrinsic rate of increase (r), mean finite rate of increase (λ), net reproductive rates (R0), and mean generation time (T). The total preadult development time was 9.47 days for Ae. albopictus and 8.76 days for Ae. aegypti. The life expectancy was 19.01 days for Ae. albopictus and 19.94 days for Ae. aegypti. Mortality occurred mostly during the adult stage. The mean development time for each stage insignificantly correlated with temperature for Ae. albopictus (r = -0.208, P > 0.05) and (r = -0.312, P > 0.05) for Ae. aegypti. The population parameters suggest that Ae. albopictus and Ae. aegypti populations are r-strategists characterized by a high r, a large R0, and short T. This present study provides the first report to compare the life parameters of Ae. albopictus and Ae. aegypti strains from Penang island, Malaysia.

MeSH terms: Aedes; Animals; Family Characteristics; Laboratories; Life Expectancy; Malaysia; Reproduction; Temperature; Life Tables; Islands
Enantiomeric pair of copper(II) polypyridyl-alanine complexes: Effect of chirality on their interaction with biomolecules

Ng CH, Chan CW, Lai JW, Ooi IH, Chong KV, Maah MJ, et al.

J Inorg Biochem, 2016 07;160:1-11.
PMID: 27105312 DOI: 10.1016/j.jinorgbio.2016.04.003

Like chiral organic drugs, the chemical and biological properties of metal complexes can be dependent on chirality. Two pairs of [Cu(phen)(ala)(H2O)]X·xH2O (phen=1.10-phenanthroline: X=NO3(-); ala: l-alanine (l-ala), 1 and d-alanine (d-ala) 2; and (X=Cl(-); ala: l-ala, 3 and d-ala, 4) complex salts (x=number of lattice water molecules) have been synthesized and characterized. The crystal structure of 3 has been determined. The same pair of enantiomeric species, viz. [Cu(phen)(l-ala)(H2O)](+) and [Cu(phen)(d-ala)(H2O)](+), have been identified to be present in the aqueous solutions of both 1 and 3, and in those of both 2 and 4 respectively. Both 3 and 4 bind more strongly to ds(AT)6 than ds(CG)6. There is no or insignificant effect of the chirality of 3 and 4 on the production of hydroxyl radicals, binding to deoxyribonucleic acid from calf thymus (CT-DNA), ds(CG)6, G-quadruplex and 17-base pair duplex, and inhibition of both topoisomerase I and proteasome. Among the three proteasome proteolytic sites, the trypsin-like site is inhibited most strongly by these complexes. However, the chirality of 3 and 4 does affect the number of restriction enzymes inhibited, and their binding constants towards ds(AT)6 and serum albumin.

MeSH terms: Alanine/chemistry*; Animals; Cations, Divalent; Cattle; Copper/chemistry*; DNA/chemistry*; DNA Topoisomerases, Type I/chemistry; Humans; Phenanthrolines/chemistry; Pyridines/chemistry*; Serum Albumin/chemistry; Stereoisomerism; Hydroxyl Radical/chemistry; Proteasome Endopeptidase Complex/chemistry*; Coordination Complexes/chemical synthesis; Coordination Complexes/chemistry*; Topoisomerase I Inhibitors/chemistry; Proteolysis
Fulltext The clinical significance of interleukin-1 receptor antagonist +2018 polymorphism in rheumatoid arthritis

Ismail E, Nofal OK, Sakthiswary R, Shaharir SS, Sridharan R

PLoS One, 2016;11(4):e0153752.
PMID: 27105431 DOI: 10.1371/journal.pone.0153752

OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA.
METHODS: Polymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS).
RESULTS: The frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05.
CONCLUSIONS: C/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA.
Study site: Outpatient clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

MeSH terms: Adult; Aged; Arthritis, Rheumatoid/genetics*; Cross-Sectional Studies; Female; Hospitals, University; Humans; Malaysia; Male; Middle Aged; Outpatient Clinics, Hospital; Polymorphism, Genetic*; Case-Control Studies; Interleukin 1 Receptor Antagonist Protein/genetics*
Modulation of LOX and COX pathways via inhibition of amyloidogenesis contributes to mitoprotection against β-amyloid oligomer-induced toxicity in an animal model of Alzheimer's disease in rats

Kalra J, Kumar P, Majeed AB, Prakash A

Pharmacol. Biochem. Behav., 2016 Jul-Aug;146-147:1-12.
PMID: 27106205 DOI: 10.1016/j.pbb.2016.04.002

Several lines of evidence indicate that beta amyloid (β-A) production, neurofibrillary tangles and neuroinflammation are interrelated in the pathogenesis of Alzheimer's disease (AD). AD is associated with enhanced β-A production and accumulation resulting in neuroinflammation probably via activation of lipoxygenase (LOX) and cyclooxygenase (COX) pathways. Therefore, the present study was designed to investigate the role of LOX and COX inhibitors (zafirlukast and valdecoxib) in amyloidogenesis in β-A1-42 oligomer induced experimental AD in rats. The behavioral activities were assessed using actophotometer, novel object recognition test (ORT), Morris water maze (MWM) followed by biochemical assessments, determination of proinflammatory cytokines and mediators (TNF-α, IL-1β and PGE2), β-A1-42 levels and histopathological analysis. ICV administration of β-A1-42 oligomer produced significant impairment in memory consolidation. In addition to this significant increase in mito-oxidative stress, neuroinflammatory markers, acetylcholinesterase (AChE) toxicity, β-A1-42 level, neuronal cell death and neuroinflammation are more profound in β-A1-42 oligomer treated AD rats. Administration of zafirlukast (15 and 30mg/kg), and valdecoxib (5 and 10mg/kg) significantly improved the behavioral performances and showed significant reversal of mito-oxidative damage declining the neuroinflammation in β-A1-42 oligomer treated rats. Furthermore, more profound effects were observed at the sub-therapeutic dose combination of zafirlukast (15mg/kg) and valdecoxib (5mg/kg). The results of the present study indicate that protective effects of zafirlukast and valdecoxib are achieved through the blockade of release of LOX and COX metabolites therefore, representing a new therapeutic target for treating AD and other neurodegenerative disorders.

MeSH terms: Alzheimer Disease/chemically induced; Alzheimer Disease/metabolism*; Amyloid/biosynthesis*; Animals; Brain/drug effects; Brain/metabolism; Disease Models, Animal; Injections, Intraventricular; Isoxazoles/pharmacology; Lipoxygenase/metabolism*; Locomotion/drug effects; Male; Memory/drug effects; Mitochondria/drug effects*; Mitochondria/metabolism; Peptide Fragments/administration & dosage; Peptide Fragments/metabolism; Peptide Fragments/toxicity*; Prostaglandin-Endoperoxide Synthases/metabolism*; Sulfonamides/pharmacology; Tosyl Compounds/pharmacology; Signal Transduction/drug effects; Amyloid beta-Peptides/administration & dosage; Amyloid beta-Peptides/metabolism; Amyloid beta-Peptides/toxicity*; Cell Death/drug effects; Oxidative Stress/drug effects*; Neuroprotective Agents/pharmacology*; Recognition (Psychology)/drug effects; Rats

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