Browse publications by year: 2016

Fulltext Adapting Document Similarity Measures for Ligand-Based Virtual Screening

Himmat M, Salim N, Al-Dabbagh MM, Saeed F, Ahmed A

Molecules, 2016 Apr 13;21(4):476.
PMID: 27089312 DOI: 10.3390/molecules21040476

Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these similarity methods give good results in document retrieval and can achieve good results in virtual screening. In this work, we propose a similarity measure for ligand-based virtual screening, which has been derived from a text processing similarity measure. It has been adopted to be suitable for virtual screening; we called this proposed measure the Adapted Similarity Measure of Text Processing (ASMTP). For evaluating and testing the proposed ASMTP we conducted several experiments on two different benchmark datasets: the Maximum Unbiased Validation (MUV) and the MDL Drug Data Report (MDDR). The experiments have been conducted by choosing 10 reference structures from each class randomly as queries and evaluate them in the recall of cut-offs at 1% and 5%. The overall obtained results are compared with some similarity methods including the Tanimoto coefficient, which are considered to be the conventional and standard similarity coefficients for fingerprint-based similarity calculations. The achieved results show that the performance of ligand-based virtual screening is better and outperforms the Tanimoto coefficients and other methods.

MeSH terms: Algorithms; Computer Simulation; Drug Evaluation, Preclinical*; Humans; Ligands; User-Computer Interface; Molecular Structure; Data Mining*
A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model

Lim JC, Goh FY, Sagineedu SR, Yong AC, Sidik SM, Lajis NH, et al.

Toxicol Appl Pharmacol, 2016 07 01;302:10-22.
PMID: 27089844 DOI: 10.1016/j.taap.2016.04.004

Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6-8weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1h before and 11h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30μM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model.

MeSH terms: Animals; Anti-Inflammatory Agents/pharmacology; Anti-Inflammatory Agents/therapeutic use*; Asthma/blood; Asthma/drug therapy*; Asthma/immunology; Asthma/physiopathology; Bronchoalveolar Lavage Fluid/cytology; Bronchoalveolar Lavage Fluid/chemistry; Cell Count; Disease Models, Animal; Diterpenes/pharmacology; Diterpenes/therapeutic use*; Female; Humans; Immunoglobulin E/blood; Immunoglobulin G/blood; Lactones/pharmacology; Lactones/therapeutic use*; Mice, Inbred BALB C; Ovalbumin; Signal Transduction; Cytokines/immunology; NF-kappa B/antagonists & inhibitors*; NF-kappa B/genetics; NF-kappa B/immunology; Anti-Asthmatic Agents/pharmacology; Anti-Asthmatic Agents/therapeutic use*; A549 Cells
Improved Diagnosis of the Polysensitized Allergic Rhinitis Patients Using Component Resolved Diagnosis Method

Mohamad Yadzir ZH, Bakhtiar F, Misnan R, Abdullah N, Leecyous B, Murad S

Iran J Allergy Asthma Immunol, 2016 Apr;15(2):156-60.
PMID: 27090369

Allergy diagnosis needs to be improved in polysensitized patients due to the existence of possible confounding factors in this type of patients. Component resolved diagnosis (CRD) is a new concept in the investigation of polysensitized patients. The aim of this study was to evaluate if the utilization of ImmunoCAP ISAC improve the diagnosis of the polysensitized allergic rhinitis patients. Skin prick test (SPT) to 58 crude allergen extracts and CRD (ImmunoCAP ISAC) were carried out for 5 polysensitized allergic rhinitis patients. Two patients had a shellfish allergy and avoidance of shellfish was the only way to prevent an allergic reaction. In contrast, although the remaining three patients had low risk for shellfish allergy, but they were the best candidates for immunotherapy using mite extracts. CRD and particularly ImmunoCAP ISAC have proven to be a valuable diagnostic tool in polysensitized patients. ImmunoCAP ISAC helps refine the individual patient's sensitization profile and predict the potential risk of allergic reactions and improve the selection of patients for immunotherapy.

MeSH terms: Shellfish Hypersensitivity/diagnosis*; Shellfish Hypersensitivity/immunology; Adult; Allergens/administration & dosage; Allergens/immunology; Female; Humans; Male; Shellfish; Skin Tests/methods; Complex Mixtures/administration & dosage; Complex Mixtures/immunology; Rhinitis, Allergic/diagnosis*; Rhinitis, Allergic/immunology
Biorefineries of carbon dioxide: From carbon capture and storage (CCS) to bioenergies production

Cheah WY, Ling TC, Juan JC, Lee DJ, Chang JS, Show PL

Bioresour Technol, 2016 Sep;215:346-56.
PMID: 27090405 DOI: 10.1016/j.biortech.2016.04.019

Greenhouse gas emissions have several adverse environmental effects, like pollution and climate change. Currently applied carbon capture and storage (CCS) methods are not cost effective and have not been proven safe for long term sequestration. Another attractive approach is CO2 valorization, whereby CO2 can be captured in the form of biomass via photosynthesis and is subsequently converted into various form of bioenergy. This article summarizes the current carbon sequestration and utilization technologies, while emphasizing the value of bioconversion of CO2. In particular, CO2 sequestration by terrestrial plants, microalgae and other microorganisms are discussed. Prospects and challenges for CO2 conversion are addressed. The aim of this review is to provide comprehensive knowledge and updated information on the current advances in biological CO2 sequestration and valorization, which are essential if this approach is to achieve environmental sustainability and economic feasibility.

MeSH terms: Animals; Biodegradation, Environmental*; Carbon/metabolism*; Carbon Dioxide/isolation & purification*; Conservation of Energy Resources/methods*; Humans; Photosynthesis; Biomass; Biofuels; Bioengineering/trends; Climate Change*; Carbon Sequestration*; Microalgae
Generation of a naïve human single chain variable fragment (scFv) library for the identification of monoclonal scFv against Salmonella Typhi Hemolysin E antigen

Lim BN, Chin CF, Choong YS, Ismail A, Lim TS

Toxicon, 2016 Jul;117:94-101.
PMID: 27090555 DOI: 10.1016/j.toxicon.2016.04.032

Antibody phage display is a useful tool for the isolation and identification of monoclonal antibodies. Naive antibody libraries are able to overcome the limitations associated with the traditional hybridoma method for monoclonal antibody generation. Antibody phage display is also a preferred method for antibody generation against toxins as it does not suffer from toxicity mediated complications. Here, we describe a naïve multi ethnic scFv antibody library generated via two-step cloning with an estimated diversity of 2 × 10(9). The antibody library was used to screen for monoclonal antibodies against Hemolysin E antigen, a pore forming toxin produced by Salmonella enterica serovar Typhi. A soluble monoclonal scFv antibody against the HlyE toxin (IgM scFv D7 anti-hlyE) was isolated from the library. This shows the value of the naïve library to generate antibodies against toxin targets in addition to the potential use of the library to isolate antibodies against other immunogenic targets.

MeSH terms: Antibodies, Monoclonal/isolation & purification*; Enzyme-Linked Immunosorbent Assay; Hemolysin Proteins/immunology*; Humans; Salmonella typhi/genetics; Salmonella typhi/immunology*; Peptide Library*; Escherichia coli Proteins/immunology*; Single-Chain Antibodies/immunology*; Single-Chain Antibodies/isolation & purification
Fulltext Salinity-induced changes in the morphology and major mineral nutrient composition of purslane (Portulaca oleracea L.) accessions

Alam MA, Juraimi AS, Rafii MY, Hamid AA, Aslani F, Hakim MA

Biol Res, 2016 Apr 18;49:24.
PMID: 27090643 DOI: 10.1186/s40659-016-0084-5

This study was undertaken to determine the effects of varied salinity regimes on the morphological traits (plant height, number of leaves, number of flowers, fresh and dry weight) and major mineral composition of 13 selected purslane accessions. Most of the morphological traits measured were reduced at varied salinity levels (0.0, 8, 16, 24 and 32 dS m(-1)), but plant height was found to increase in Ac1 at 16 dS m(-1) salinity, and Ac13 was the most affected accession. The highest reductions in the number of leaves and number of flowers were recorded in Ac13 at 32 dS m(-1) salinity compared to the control. The highest fresh and dry weight reductions were noted in Ac8 and Ac6, respectively, at 32 dS m(-1) salinity, whereas the highest increase in both fresh and dry weight was recorded in Ac9 at 24 dS m(-1) salinity compared to the control. In contrast, at lower salinity levels, all of the measured mineral levels were found to increase and later decrease with increasing salinity, but the performance of different accessions was different depending on the salinity level. A dendrogram was also constructed by UPGMA based on the morphological traits and mineral compositions, in which the 13 accessions were grouped into 5 clusters, indicating greater diversity among them. A three-dimensional principal component analysis also confirmed the output of grouping from cluster analysis.

MeSH terms: Calcium/analysis; Iron/analysis; Magnesium/analysis; Minerals/analysis*; Phosphorus/analysis; Potassium/analysis; Reference Values; Sodium/analysis; Zinc/analysis; Plant Leaves/anatomy & histology; Portulaca/anatomy & histology*; Portulaca/chemistry*; Flowers/anatomy & histology; Salinity*; Salt-Tolerance
Fulltext Unsteady stagnation-point flow and heat transfer of a special third grade fluid past a permeable stretching/shrinking sheet

Naganthran K, Nazar R, Pop I

Sci Rep, 2016;6:24632.
PMID: 27091085 DOI: 10.1038/srep24632

In this paper, the unsteady stagnation-point boundary layer flow and heat transfer of a special third grade fluid past a permeable stretching/shrinking sheet has been studied. Similarity transformation is used to transform the system of boundary layer equations which is in the form of partial differential equations into a system of ordinary differential equations. The system of similarity equations is then reduced to a system of first order differential equations and has been solved numerically by using the bvp4c function in Matlab. The numerical solutions for the skin friction coefficient and heat transfer coefficient as well as the velocity and temperature profiles are presented in the forms of tables and graphs. Dual solutions exist for both cases of stretching and shrinking sheet. Stability analysis is performed to determine which solution is stable and valid physically. Results from the stability analysis depict that the first solution (upper branch) is stable and physically realizable, while the second solution (lower branch) is unstable.

MeSH terms: Endoscopy; Hot Temperature; Physical Examination; Research; Temperature; Friction; Physical Phenomena
Tobacco Consumption Among HIV-Positive Respondents: Findings From the Third Round of the National Family Health Survey

Lall P, Saifi R, Kamarulzaman A

Nicotine Tob Res, 2016 12;18(12):2185-2193.
PMID: 27091832 DOI: 10.1093/ntr/ntw111

INTRODUCTION: HIV-positive people are often more susceptible to illnesses associated with smoking, for example, cardiovascular disease, than those in the general population. The purpose of this article is to examine the association between tobacco use and HIV-status in India.

METHODS: This article analyzed data from the National Family Health Survey III, which provides a representative sample of the Indian population. Patterns in tobacco consumption among HIV-positive and negative respondents were assessed through logistic and ordinal regression models. Associations between smoking, asthma, and tuberculosis were examined through bivariate logistic regressions.

RESULTS: A greater percentage of male HIV-positive participants (68%) reported current tobacco use in comparison to male HIV-negative respondents (58%) and female HIV-positive (12%) and negative (11%) participants. Multivariable logistic regression analyses revealed that there was a positive correlation between male respondents' HIV-status and their propensity to use tobacco (odds ratio [OR] = 1.48, confidence interval [CI] = 1.05-2.1, P < .05) when controlled for extraneous variables. Results from ordinal regression analyses illustrated that male HIV-positive respondents had a twofold increased OR of smoking 20 or more cigarettes (OR = 2.1, CI = 1.4-3.2, P < .005). Finally, there was a positive association between being HIV-infected (adjusted odds ratio [AOR] = 4.6, CI = 2.02-10.6, P < .005), smoking 15-19 cigarettes (AOR = 2.11, CI = 1.1-4.1, P < .05) and male participants' TB-status.

CONCLUSIONS: Results in this article suggest HIV-positive men in India were not only significantly more likely to consume tobacco, but they also smoked a higher number of cigarettes compared to their HIV-negative counterparts. This is a cause for concern as our analyses revealed a possible association between the number of cigarettes smoked and TB-status.

IMPLICATIONS: This article contributes to knowledge on the intertwining epidemics of HIV and smoking through using cross-sectional data from the National Family Survey III to demonstrate that HIV-positive men in India display patterns of tobacco consumption which differs to that of HIV-negative men. These findings could have strong implications for long-term treatment of HIV-positive patients as smoking has been proven to increase the likelihood of contracting HIV-related illnesses.

MeSH terms: Adolescent; Adult; Cross-Sectional Studies; Family Health; Female; Humans; India/epidemiology; Male; Middle Aged; Regression Analysis; Smoking/epidemiology*; Socioeconomic Factors; Tobacco Use Disorder/epidemiology*; HIV Infections*; Odds Ratio; Smoking Cessation/statistics & numerical data*; Health Care Surveys; Young Adult
Fulltext National Economic Burden Associated with Management of Periodontitis in Malaysia

Mohd Dom TN, Ayob R, Abd Muttalib K, Aljunid SM

Int J Dent, 2016;2016:1891074.
PMID: 27092180 DOI: 10.1155/2016/1891074

Objectives. The aim of this study is to estimate the economic burden associated with the management of periodontitis in Malaysia from the societal perspective. Methods. We estimated the economic burden of periodontitis by combining the disease prevalence with its treatment costs. We estimated treatment costs (with 2012 value of Malaysian Ringgit) using the cost-of-illness approach and included both direct and indirect costs. We used the National Oral Health Survey for Adults (2010) data to estimate the prevalence of periodontitis and 2010 national census data to estimate the adult population at risk for periodontitis. Results. The economic burden of managing all cases of periodontitis at the national level from the societal perspective was approximately MYR 32.5 billion, accounting for 3.83% of the 2012 Gross Domestic Product of the country. It would cost the nation MYR 18.3 billion to treat patients with moderate periodontitis and MYR 13.7 billion to treat patients with severe periodontitis. Conclusion. The economic burden of periodontitis in Malaysia is substantial and comparable with that of other chronic diseases in the country. This is attributable to its high prevalence and high cost of treatment. Judicious application of promotive, preventive, and curative approaches to periodontitis management is decidedly warranted.
Fulltext Translation and validation of the Malay version of the Stroke Knowledge Test

Sowtali SN, Yusoff DM, Harith S, Mohamed M

J Arrhythm, 2016 Apr;32(2):112-8.
PMID: 27092192 DOI: 10.1016/j.joa.2015.10.003

To date, there is a lack of published studies on assessment tools to evaluate the effectiveness of stroke education programs.
Fulltext Glibenclamide-induced profound hypoglycaemic crisis: a case report

Hussain A, Ali I, Khan AU, Khan TM

Ther Adv Endocrinol Metab, 2016 Apr;7(2):84-7.
PMID: 27092233 DOI: 10.1177/2042018816632440

The value of sulphonylureas in the long-term treatment of type II diabetes has been questioned. The potential benefits of an antidiabetic drug must be carefully weighed against the risk of developing hazardous adverse effects like hypoglycaemia. We present drug-induced hypoglycaemia in a 77-year-old Pakistani male who had hypertension, type II diabetes and renal parenchymal disease (grade I), presented to the emergency department complaining of a 1-day history of fever, loose motions and drowsiness. His fever was low grade, intermittent, and not associated with rigors and chills. He had four episodes of watery stools for 1 day, with no associated vomiting but with drowsiness. He was aphasic, unable to walk and did not recognize his family members. The patient was taken to his local doctor who found him to be hypoglycaemic, with a blood sugar of 45 mg/dl. He was managed with intravenous (IV) dextrose and referred to the hospital. Hypoglycaemia is perhaps the most widespread and underreported complication of oral hypoglycaemic agents and may lead to overwhelming morbidity and mortality. Patient evaluation and proper counselling may help in identifying patients at greatest risk and avoid complications associated with these commonly prescribed drugs.
Fulltext Overview of Antagonists Used for Determining the Mechanisms of Action Employed by Potential Vasodilators with Their Suggested Signaling Pathways

Loh YC, Tan CS, Ch'ng YS, Ahmad M, Asmawi MZ, Yam MF

Molecules, 2016 Apr 15;21(4):495.
PMID: 27092479 DOI: 10.3390/molecules21040495

This paper is a review on the types of antagonists and the signaling mechanism pathways that have been used to determine the mechanisms of action employed for vasodilation by test compounds. Thus, we exhaustively reviewed and analyzed reports related to this topic published in PubMed between the years of 2010 till 2015. The aim of this paperis to suggest the most appropriate type of antagonists that correspond to receptors that would be involved during the mechanistic studies, as well as the latest signaling pathways trends that are being studied in order to determine the route(s) that atest compound employs for inducing vasodilation. The methods to perform the mechanism studies were included. Fundamentally, the affinity, specificity and selectivity of the antagonists to their receptors or enzymes were clearly elaborated as well as the solubility and reversibility. All the signaling pathways on the mechanisms of action involved in the vascular tone regulation have been well described in previous review articles. However, the most appropriate antagonists that should be utilized have never been suggested and elaborated before, hence the reason for this review.

MeSH terms: Blood Vessels/drug effects; Blood Vessels/metabolism; Blood Vessels/pathology; Humans; Muscle, Smooth, Vascular/drug effects*; Muscle, Smooth, Vascular/metabolism; Muscle, Smooth, Vascular/pathology; Vasodilation/drug effects*; Vasodilator Agents/therapeutic use*; Vasodilator Agents/chemistry; Signal Transduction/drug effects
Fulltext Isolation and Characterization of Aquatic-Borne Klebsiella pneumoniae from Tropical Estuaries in Malaysia

Barati A, Ghaderpour A, Chew LL, Bong CW, Thong KL, Chong VC, et al.

Int J Environ Res Public Health, 2016 Apr 15;13(4):426.
PMID: 27092516 DOI: 10.3390/ijerph13040426

Klebsiella pneumoniae is an opportunistic pathogen that is responsible for causing nosocomial and community-acquired infections. Despite its common presence in soil and aquatic environments, the virulence potential of K. pneumoniae isolates of environmental origin is largely unknown. Hence, in this study, K. pneumoniae isolated from the estuarine waters and sediments of the Matang mangrove estuary were screened for potential virulence characteristics: antibiotic susceptibility, morphotype on Congo red agar, biofilm formation, presence of exopolysaccharide and capsule, possession of virulence genes (fimH, magA, ugE, wabG and rmpA) and their genomic fingerprints. A total of 55 strains of K. pneumoniae were isolated from both human-distributed sites (located along Sangga Besar River) and control sites (located along Selinsing River) where less human activity was observed, indicated that K. pneumoniae is ubiquitous in the environment. However, the detection of potentially virulent strains at the downstream of Kuala Sepetang village has suggested an anthropogenic contamination source. In conclusion, the findings from this study indicate that the Matang mangrove estuary could harbor potentially pathogenic K. pneumoniae with risk to public health. More studies are required to compare the environmental K. pneumoniae strains with the community-acquired K. pneumoniae strains.

MeSH terms: Hospitals; Humans; Klebsiella Infections/microbiology; Klebsiella Infections/epidemiology*; Klebsiella pneumoniae/isolation & purification*; Klebsiella pneumoniae/pathogenicity; Malaysia/epidemiology; Tropical Climate; Water Microbiology*; Community-Acquired Infections; Geologic Sediments/microbiology*; Drug Resistance, Bacterial/drug effects*; Virulence Factors/genetics; Estuaries*
Skin Picking Heralding Parkinson's Disease

Chee KY, Evans AH, Velakoulis D

J Neuropsychiatry Clin Neurosci, 2016;28(2):e23-4.
PMID: 27093384 DOI: 10.1176/appi.neuropsych.15100250
Amyotrophic lateral sclerosis and motor neuron syndromes in Asia

Shahrizaila N, Sobue G, Kuwabara S, Kim SH, Birks C, Fan DS, et al.

J Neurol Neurosurg Psychiatry, 2016 08;87(8):821-30.
PMID: 27093948 DOI: 10.1136/jnnp-2015-312751

While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.

MeSH terms: Amyotrophic Lateral Sclerosis/complications*; Amyotrophic Lateral Sclerosis/genetics; Amyotrophic Lateral Sclerosis/mortality; Amyotrophic Lateral Sclerosis/epidemiology*; Asia/epidemiology; Humans; Phenotype; Syndrome; Motor Neuron Disease/complications*; Motor Neuron Disease/genetics; Motor Neuron Disease/mortality; Motor Neuron Disease/epidemiology*; Disease Progression
Fulltext Distribution pattern of black fly (Diptera: Simuliidae) assemblages along an altitudinal gradient in Peninsular Malaysia

Ya'cob Z, Takaoka H, Pramual P, Low VL, Sofian-Azirun M

Parasit Vectors, 2016 Apr 19;9:219.
PMID: 27094088 DOI: 10.1186/s13071-016-1492-7

BACKGROUND: Preimaginal black flies (Diptera: Simuliidae) are important components of the stream ecosystem. However, there has been limited research undertaken on the vertical distribution of preimaginal black flies and their associated ecological factors. Stream conditions are generally variable along the altitudinal gradient. Therefore, we conducted an in-depth entomological survey to investigate the simuliid distribution pattern along an altitudinal gradient in Peninsular Malaysia.
METHODS: A total of 432 collections were performed in this study (24 samplings at each of 18 fixed-streams at monthly intervals) from February 2012 to January 2014. Larvae and pupae attached on aquatic substrates such as grasses, leaves and stems, twigs, plant roots and rocks were collected by hand using fine forceps. Stream depth (m), width (m), velocity (m/s), water temperature (°C), acidity (pH), conductivity (mS/cm) and dissolved oxygen (mg/L) were measured at the time of each collection.
RESULTS: A total of 35 black fly species were recorded in the present study. The most frequently collected species were Simulium tani (31.7%) and S. whartoni (21.5%), while the relatively common species were Simulium sp. (nr. feuerborni) (16.2%), S. decuplum (15.5%), S. angulistylum (14.8%), S. bishopi (13.2%) and S. izuae (11.8%). Total estimated species richness ranged between 39.8 and 41.3, which yielded more than 80% of sampling efficiency. Six simuliid species were distributed below 500 m, whereas eight species were distributed above 1400 m. Simulium sp. (nr. feuerborni) and S. asakoae were found from middle to high altitudes (711-1813 m). Simulium whartoni, S. brevipar and S. bishopi were distributed widely from low to high altitudes (159-1813 m). Regression analysis between species richness and PCs revealed that the species richness was significantly associated with wider, deeper and faster streams at low altitude, normal water temperature (23-25 °C), low conductivity, higher discharge, more canopy cover and riparian vegetation and with larger streambed particles (F = 20.8, df = 1, 422, P

MeSH terms: Altitude; Animals; Female; Larva/classification; Larva/growth & development; Larva/physiology; Malaysia; Male; Pupa/classification; Pupa/growth & development; Pupa/physiology; Simuliidae/classification; Simuliidae/growth & development; Simuliidae/physiology*; Temperature; Ecosystem; Animal Distribution*
Repetitive cryotherapy attenuates the in vitro and in vivo mononuclear cell activation response

Lindsay A, Othman MI, Prebble H, Davies S, Gieseg SP

Exp Physiol, 2016 07 01;101(7):851-65.
PMID: 27094349 DOI: 10.1113/EP085795

What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise. Single and repeated cold exposure (5°C) of a mixed cell culture (T cells and monocytes) was investigated using in vitro tissue culture experimentation for total neopterin production (neopterin plus 7,8-dihydroneopterin). Fourteen elite mixed martial art fighters were also randomly assigned to either a cold water immersion (15 min at 10°C) or passive recovery protocol, which they completed three times per week during a 6 week training camp. Urine was collected and analysed for neopterin and total neopterin three times per week, and perceived soreness, fatigue, physical performance (broad jump, push-ups and pull-ups) and training performance were also assessed. Single and repetitive cold exposure significantly (P

MeSH terms: Adult; Cells, Cultured; Cold Temperature; Fatigue/metabolism; Fatigue/physiopathology; Humans; Leukocytes, Mononuclear/metabolism; Leukocytes, Mononuclear/physiology*; T-Lymphocytes/metabolism; T-Lymphocytes/physiology; Exercise/physiology*; Cryotherapy/methods; Neopterin/analogs & derivatives; Neopterin/metabolism; Athletes
Fulltext The Cytochrome P450 gene CYP6P12 confers pyrethroid resistance in kdr-free Malaysian populations of the dengue vector Aedes albopictus

Ishak IH, Riveron JM, Ibrahim SS, Stott R, Longbottom J, Irving H, et al.

Sci Rep, 2016 Apr 20;6:24707.
PMID: 27094778 DOI: 10.1038/srep24707

Control of Aedes albopictus, major dengue and chikungunya vector, is threatened by growing cases of insecticide resistance. The mechanisms driving this resistance remain poorly characterised. This study investigated the molecular basis of insecticide resistance in Malaysian populations of Ae. albopictus. Microarray-based transcription profiling revealed that metabolic resistance (cytochrome P450 up-regulation) and possibly a reduced penetration mechanism (consistent over-expression of cuticular protein genes) were associated with pyrethroid resistance. CYP6P12 over-expression was strongly associated with pyrethroid resistance whereas CYP6N3 was rather consistently over-expressed across carbamate and DDT resistant populations. Other detoxification genes also up-regulated in permethrin resistant mosquitoes included a glucuronosyltransferase (AAEL014279-RA) and the glutathione-S transferases GSTS1 and GSTT3. Functional analyses further supported that CYP6P12 contributes to pyrethroid resistance in Ae. albopictus as transgenic expression of CYP6P12 in Drosophila was sufficient to confer pyrethroid resistance in these flies. Furthermore, molecular docking simulations predicted CYP6P12 possessing enzymatic activity towards pyrethroids. Patterns of polymorphism suggested early sign of selection acting on CYP6P12 but not on CYP6N3. The major role played by P450 in the absence of kdr mutations suggests that addition of the synergist PBO to pyrethroids could improve the efficacy of this insecticide class and overcome resistance in field populations of Ae. albopictus.

MeSH terms: Aedes/drug effects*; Aedes/genetics*; Aedes/virology; Animals; Dengue/transmission; Gene Expression Regulation; Genetics, Population; Insecticide Resistance/genetics*; Insecticides/pharmacology*; Insecticides/chemistry; Malaysia; Models, Molecular; Molecular Conformation; Polymorphism, Genetic; Protein Binding; Pyrethrins/pharmacology*; Pyrethrins/chemistry; Reproducibility of Results; Gene Expression Profiling; Animals, Genetically Modified; Gene Knockdown Techniques; Cytochrome P450 Family 6/genetics*; Cytochrome P450 Family 6/chemistry
Fulltext Burden of chronic kidney disease and its risk factors in Malaysia

Begum R, Khan TM, Ming LC

J Epidemiol Glob Health, 2016 12;6(4):325-326.
PMID: 27095074 DOI: 10.1016/j.jegh.2016.03.004
MeSH terms: Humans; Malaysia/epidemiology; Public Health/methods*; Risk Factors; Cost of Illness; Renal Insufficiency, Chronic/epidemiology*
Fulltext Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance

Mohamad M, Mitchell SJ, Wu LE, White MY, Cordwell SJ, Mach J, et al.

Aging Cell, 2016 08;15(4):706-15.
PMID: 27095270 DOI: 10.1111/acel.12481

While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis. To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling. Loss of fenestrations in the liver sinusoidal endothelium is a hallmark of aging that has previously been shown to cause deficits in hepatic drug and lipoprotein metabolism and now insulin. Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.

MeSH terms: Aging/metabolism*; Animals; Disease Models, Animal; Glucose/metabolism; Glycogen/metabolism; Insulin/metabolism*; Insulin Resistance*; Liver/blood supply*; Liver/cytology; Liver/metabolism; Liver/ultrastructure*; Male; Mice, Inbred C57BL; Microcirculation*; Rats, Inbred F344; Staining and Labeling; Porosity; Poloxamer; Endothelial Cells/metabolism

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