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26.  Perceptions of students in different phases of medical education of the educational environment: Universiti Sultan Zainal Abidin 
The Dundee Ready Education Environment Measure (DREEM) was planned and designed to quantify the educational environment precisely for medical schools and health-related professional schools. DREEM is now considered a valid and reliable tool, which is globally accepted for measuring the medical educational environment. The educational environment encountered by students has an impact on satisfaction with the course of study, perceived sense of well-being, aspirations, and academic achievement. In addition to being measurable, the educational environment can also be changed, thus enhancing the quality of medical education and the environment, and the medical education process. The objective of this study was to assess the educational environment of the Universiti Sultan Zainal Abidin (UniSZA) undergraduate medical program from the students’ perspective. The study expected to explore UniSZA medical students’ overall perceptions, perceptions of learning, teachers, atmosphere, academic self-perception, and social self-perception using the DREEM questionnaire.
A cross-sectional survey was conducted to study the perceptions of the students toward the educational environment of UniSZA as a new medical school, using the DREEM questionnaire. All medical students of UniSZA from Years I–V enrolled in the Bachelor of Medicine and Bachelor of Surgery programs were the target population (n=270). Therefore, the universal sampling technique was used. The data were analyzed using the SPSS 20 software. This study obtained ethical clearance from the Faculty of Medicine and Health Sciences, UniSZA.
A total of 195 out of 270 students responded. Respondents included 31% males and 69% females. The overall DREEM scores were significantly higher (P<0.001) for females than males.
The medical students at UniSZA showed a positive perception of their educational environment. The new medical faculty, established for only a few years, has achieved an above-average, conducive educational environment for students. Most of the students showed a positive perception for the entire five domains tested in the DREEM survey. Females were consistently satisfied with UniSZA’s educational environment, and self-perception was high, as compared to male undergraduates.
Video abstract
PMCID: PMC4378299  PMID: 25848333
perceptions; medical students; educational environment; DREEM; UniSZA
27.  Assessment of Routine Immunization Coverage in Nyala Locality, Reasons behind Incomplete Immunization in South Darfur State, Sudan 
Little is known about the coverage of routine immunization service in South Darfur state, Sudan. Therefore, this study was conducted to determine the vaccination rate and barriers for vaccination. A cross-sectional community-based study was undertaken in Nyala locality, south Darfur, Sudan, including urban, rural and Internal Displaced Peoples (IDPs) population in proportional representation. Survey data were collected by a questionnaire which was applied face to face to parents of 213 children 12-23 months. The collected data was then analyzed with SPSS software package. Results showed that vaccination coverage as revealed by showed vaccination card alone was 63.4% while it was increased to 82.2% when both history and cards were used. Some (5.6%) of children were completely non-vaccinated. The factors contributing to the low vaccination coverage were found to be knowledge problems of mothers (51%), access problems (15%) and attitude problems (34%). Children whose mother attended antenatal care and those from urban areas were more likely to complete their immunization schedule. In conclusion, the vaccination coverage in the studied area was low compared to the national coverage. Efforts to increase vaccination converge and completion of the scheduled plan should focus on addressing concerns of caregivers particularly side effects and strengthening the Expanded Programmer on Immunization services in rural areas.
PMCID: PMC4340504  PMID: 25729558
Expanded programme on immunization; routine immunization; vaccination coverage
28.  Low Serum High Density Lipoprotein Cholesterol Concentration is an Independent Predictor for Enhanced Inflammation and Endothelial Activation 
PLoS ONE  2015;10(1):e0116867.
Inflammation, endothelial activation and oxidative stress have been established as key events in the initiation and progression of atherosclerosis. High-density lipoprotein cholesterol (HDL-c) is protective against atherosclerosis and coronary heart disease, but its association with inflammation, endothelial activation and oxidative stress is not well established.
(1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers.
422 subjects (mean age±SD = 43.2±11.9years) of whom 207 had low HDL-c concentrations (HDL-c <1.0mmol/L and <1.3mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)].
Subjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors.
Low serum HDL-c concentration is strongly correlated with enhanced status of inflammation, endothelial activation and oxidative stress. It is also an independent predictor for enhanced inflammation and endothelial activation, which are pivotal in the pathogenesis of atherosclerosis and atherosclerosis-related complications.
PMCID: PMC4304817  PMID: 25614985
29.  CT and MR Imaging in a Large Series of Patients with Craniofacial Fibrous Dysplasia 
Polish Journal of Radiology  2015;80:232-240.
In this retrospective review of patients with craniofacial fibrous dysplasia (FD), the clinical and radiological findings of CT and MR scan were analyzed.
The study material included 32 patients, at 9 to 68 years of age that were directed for differential diagnostics of several disorders in the head. We recorded CT and MRI data related to the lesion number, location, sidedness, appearance, and sex of the cases with craniofacial FD.
Of 32 patients involved in this study, 17 had monostotic and 15 had polyostotic involvement pattern. Bones most commonly involved by monostotic involvement in females were, in descending order, mandibular, maxillary, and sphenoid bones, while the sphenoid bone was involved the most in males. Leontiasis ossea was observed in 2 patients. Sclerotic and mixed lesion types were more common in both females and males. In T1- and T2-weighted MRI sequences, hypointensity was more common compared to hyperintensity or heterogeneous intensity. The type of enhancement of lesions was found similar after contrast medium administration.
In the presence of craniofacial FD during CT or MRI imaging of the head, a detailed description of FD lesions may provide an important clinical benefit by increasing radiological experience during the diagnostics of this rare disorder.
PMCID: PMC4424911  PMID: 26000068
Craniofacial Abnormalities; Fibrous Dysplasia of Bone; Magnetic Resonance Imaging; Tomography Scanners, X-Ray Computed
30.  Mechanistic basis for protection of differentiated SH-SY5Y cells by oryzanol-rich fraction against hydrogen peroxide-induced neurotoxicity 
Apoptosis is often the end result of oxidative damage to neurons. Due to shared pathways between oxidative stress, apoptosis and antioxidant defence systems, an oxidative insult could end up causing cellular apoptosis or survival depending on the severity of the insult and cellular responses. Plant bioresources have received close attention in recent years for their potential role in regulating the pathways involved in apoptosis and oxidative stress in favour of cell survival. Rice bran is a bioactive-rich by-product of rice milling process. It possesses antioxidant properties, making it a promising source of antioxidants that could potentially prevent oxidative stress-induced neurodegenerative diseases.
Thus, the present study investigated the neuroprotective properties of oryzanol-rich fraction (ORF) against hydrogen peroxide (H2O2)-induced neurotoxicity in differentiated human neuroblastoma SH-SY5Y cells. ORF was extracted from rice bran using a green technology platform, supercritical fluid extraction system. Furthermore, its effects on cell viability, morphological changes, cell cycle, and apoptosis were evaluated. The underlying transcriptomic changes involved in regulation of oxidative stress, apoptosis and antioxidant defence systems were equally studied.
ORF protected differentiated SH-SY5Y cells against H2O2-induced neurotoxicity through preserving the mitochondrial metabolic enzyme activities, thus reducing apoptosis. The mechanistic basis for the neuroprotective effects of ORF included upregulation of antioxidant genes (catalase, SOD 1 and SOD 2), downregulation of pro-apoptotic genes (JNK, TNF, ING3, BAK1, BAX, p21 and caspase-9), and upregulation of anti-apoptotic genes (ERK1/2, AKT1 and NF-Kβ).
These findings suggest ORF may be an effective antioxidant that could prevent oxidative stress-induced neurodegenerative disorders.
PMCID: PMC4528700  PMID: 25475556
Neuroprotective; Rice bran; Oryzanol-rich fraction; Hydrogen peroxide; Supercritical fluid extraction system; Multiplex GeXP; SH-SY5Y cells
31.  Detection of airflow limitation using a handheld spirometer in a primary care setting 
Respirology (Carlton, Vic.)  2014;19(5):689-693.
Background and objective
Early diagnosis of chronic obstructive pulmonary disease (COPD) in primary care settings is difficult to achieve chiefly due to lack of availability of spirometry. This study estimated the prevalence of airflow limitation among chronic smokers using a handheld spirometer in this setting.
This is a cross-sectional study performed on consecutive patients who were ≥40 years old with ≥10 pack-years smoking history. Face-to-face interviews were carried out to obtain demographic data and relevant information. Handheld spirometry was performed according to a standard protocol using the COPd-6 device (Model 4000, Vitalograph, Ennis, Ireland) in addition to standard spirometry. Airflow limitation was defined as ratio of forced expiratory volume in 1 s (FEV1)/forced expiratory volume in 6 s <0.75 (COPd-6) or FEV1/forced vital capacity <0.7. Multiple logistic regression analyses were used to determine predictors of airflow limitation.
A total of 416 patients were recruited with mean age of 53 years old. The prevalence of airflow limitation was 10.6% (n = 44) with COPd-6 versus 6% as gauged using standard spirometry. Risk factors for airflow limitation were age >65 years (odds ratio (OR) 3.732 95% confidence interval (CI): 1.100–1.280), a history of ‘bad health’ (OR 2.524, 95% CI: 1.037–6.142) and low to normal body mass index (OR 2.914, 95% CI: 1.191–7.190).
In a primary care setting, handheld spirometry (COPd-6) found a prevalence of airflow limitation of ∼10% in smokers. Patients were older, not overweight and had an ill-defined history of health problems.
Prevalence of COPD is unknown in Malaysia. The prevalence of COPD using a handheld spirometer (COPd-6TM) was 10.6% versus 6% as gauged using standard spirometry. Predictors of COPD were older age, lower BMI and a history of ‘bad health’. Case-finding for COPD should be targeted in this special population.
PMCID: PMC4230390  PMID: 24708063
chronic obstructive pulmonary disease; Malaysia; prevalence; primary care; smoke
32.  A new isometric quadriceps-strengthening exercise using EMG-biofeedback 
A new isometric contraction quadriceps-strengthening exercise was developed to restore the quadriceps strength lost after knee surgery more rapidly. This study evaluated the results of this new method. Patients were taught to perform the isometric quadriceps-strengthening exercise in the unaffected knee in the supine position, and then they performed it in the affected knee. First, patients were taught the classical isometric quadriceps-strengthening exercise, and then they were taught our new alternative method: “pull the patella superiorly tightly and hold the leg in the same position for 10 seconds”. Afterward, the quadriceps contraction was evaluated using a non-invasive Myomed 932 EMG-biofeedback device (Enraf-Nonius, The Netherlands) with gel-containing 48 mm electrodes (Türklab, The Turkey) placed on both knees. The isometric quadriceps-strengthening exercise performed using our new method had stronger contraction than the classical method (P < 0.01). The new method involving pulling the patella superiorly appears to be a better choice, which can be applied easily, leading to better patient compliance and greater quadriceps force after arthroscopic and other knee surgeries.
PMCID: PMC4211772  PMID: 25356122
EMG biofeedback; quadriceps; strengthening; exercise
33.  Multiplex amplification refractory mutation system (MARMS) for the detection of β-globin gene mutations among the transfusion-dependent β-thalassemia Malay patients in Kelantan, Northeast of Peninsular Malaysia 
The aim of this study was to adapt MARMS with some modifications to detect beta mutation in our cohort of thalassemia patients. We focused only on transfusion-dependent thalassemia Malay patients, the predominant ethnic group (95%) in the Kelantanese population. Eight mutations were identified in 46 out of 48 (95.83%) beta thalassemia alleles. Most of the patients (54.2%) were compound heterozygous with co-inheritance Cd 26 (G>A). The frequencies of spectrum beta chain mutation among these patients are presented in Table 2. Among the transfusion dependent beta thalassemia Malay patients studied, 26 patients were found to be compound heterozygous and the main alleles were Cd 26 (G>A). Compound heterozygous mutation of Cd 26 (G>A) and IVS 1-5 (G>C) were 12 (46.2%), Cd 26 (G>A) and Cd 41/42 (TTCT) were 9 (34.6%), Cd 26 (G>A) and IVS 1-1 (G>C) were 2 (7.7%) respectively. Meanwhile the minority were made of a single compound heterozygous of Cd 26 (G>A) and Cd 71/72, Cd 26 (>A) and Cd 17 (A>T), Cd 26 (G>A) and -28 (G>A) respectively. Twenty out of forty six patients were shown to have homozygous of IVS 1-5 (G>C) were 2 (10.0%), Cd 26 (G>A) were 15 (75.0%), Cd 19 (A>G) were 1 (5.0%), and IVS 1-1 (G>T) were 2 (10.0%). The beta chain mutations among the Kelantanese Malays followed closely the distribution of beta chain mutations among the Thais and the Malays of the Southern Thailand. The G-C transition at position 5 of the IVS 1-5 mutation was predominant among the Malay patients. In conclusion, this method has successfully identified the mutation spectrum in our cohort of transfusion-dependent beta thalassemia patients, and this method is equally effective in screening for mutation among thalassemia patients.
PMCID: PMC4165115  PMID: 25232503
MARMS-PCR; β-globin gene; thalassemia; Malay; mutation
34.  A simple method to improve adenoma detection rate during colonoscopy: Altering patient position 
Colonoscopy is currently considered to be the gold standard method for detecting and removing adenomatous polyps. However, tandem colonoscopy studies reveal a pooled polyp miss rate of 22%.
A prospective randomized trial was conducted to assess whether alteration of patient position during colonoscopy withdrawal increases the adenoma detection rate (ADR).
The study group included 120 patients who presented for elective colonoscopic examination. After reaching the cecum, patients were randomly assigned in a 1:1 ratio to examination in either the left lateral position or other positions (left lateral position for the cecum, ascending colon and hepatic flexure; supine for transverse colon; and supine and right lateral position for splenic flexure, descending and sigmoid colon) first. Examination of the colon was performed segment by segment. The size, morphology and location of all polyps were recorded. Polyps were removed immediately after examination of a colon segment when all positions were completed. ADR and polyp detection rates (PDR) were calculated.
A total of 102 patients completed the study. Examination in the left lateral position revealed 66 polyps in 31 patients (PDR 30.3%) and 42 adenomas in 24 patients (ADR 23.5%). PDR increased to 43.1% (81 polyps in 44 patients) and the ADR to 33.3% (53 adenomas in 34 patients) after the colon was examined in the additional positions (P<0.001 and P=0.002, respectively). The increase in the number of adenomas detected was statistically significant in the transverse and sigmoid colon. The addition of position changes led to a 9.8% increase in the ADR in the transverse colon, splenic flexure, and descending and sigmoid colon. The frequency of surveillance interval was shortened in nine (8.8%) patients after examination of the colon in dynamic positions.
Alteration of patient position during colonoscopy withdrawal is a simple and effective method to improve ADR.
PMCID: PMC3956008  PMID: 24078934
Adenoma detection rate; Adenomatous polyp; Colon; Colonoscopy
35.  Inhibition of Corneal Neovascularization by Topical and Subconjunctival Tigecycline 
Journal of Ophthalmology  2014;2014:452685.
Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization. Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1) or subconjunctival instillation of 1 mg/mL tigecycline (group 3) for 7 days. Control rats received topical (group 2) or subconjunctival (group 4) 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically. Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI), 44.2–55.8%) and 33.5% (95% CI, 26.6–39.2%), respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (P = 0.03 and P < 0.001, resp.). Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups. Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.
PMCID: PMC4150514  PMID: 25197558
36.  Polycomb repressive complex 2 contributes to DNA double-strand break repair 
Cell Cycle  2013;12(16):2675-2683.
Polycomb protein histone methyltransferase, enhancer of Zeste homolog 2 (EZH2), is frequently overexpressed in human malignancy and is implicated in cancer cell proliferation and invasion. However, it is largely unknown whether EZH2 has a role in modulating the DNA damage response. Here, we show that polycomb repressive complex 2 (PRC2) is recruited to sites of DNA damage. This recruitment is independent of histone 2A variant X (H2AX) and the PI-3-related kinases ATM and DNA-PKcs. We establish that PARP activity is required for retaining PRC2 at sites of DNA damage. Furthermore, depletion of EZH2 in cells decreases the efficiency of DSB repair and increases sensitivity of cells to gamma-irradiation. These data unravel a crucial role of PRC2 in determining cancer cellular sensitivity following DNA damage and suggest that therapeutic targeting of EZH2 activity might serve as a strategy for improving conventional chemotherapy in a given malignancy.
PMCID: PMC3865057  PMID: 23907130
PARP; DNA damage; polycomb group proteins; chromatin; epigenetics
37.  Parasitism Performance and Fitness of Cotesia vestalis (Hymenoptera: Braconidae) Infected with Nosema sp. (Microsporidia: Nosematidae): Implications in Integrated Pest Management Strategy 
PLoS ONE  2014;9(6):e100671.
The diamondback moth (DBM) Plutella xylostella (L.) has traditionally been managed using synthetic insecticides. However, the increasing resistance of DBM to insecticides offers an impetus to practice integrated pest management (IPM) strategies by exploiting its natural enemies such as pathogens, parasitoids, and predators. Nevertheless, the interactions between pathogens and parasitoids and/or predators might affect the effectiveness of the parasitoids in regulating the host population. Thus, the parasitism rate of Nosema-infected DBM by Cotesia vestalis (Haliday) (Hym., Braconidae) can be negatively influenced by such interactions. In this study, we investigated the effects of Nosema infection in DBM on the parasitism performance of C. vestalis. The results of no-choice test showed that C. vestalis had a higher parasitism rate on non-infected host larvae than on Nosema-treated host larvae. The C. vestalis individuals that emerged from Nosema-infected DBM (F1) and their progeny (F2) had smaller pupae, a decreased rate of emergence, lowered fecundity, and a prolonged development period compared to those of the control group. DBM infection by Nosema sp. also negatively affected the morphometrics of C. vestalis. The eggs of female C. vestalis that developed in Nosema-infected DBM were larger than those of females that developed in non-infected DBM. These detrimental effects on the F1 and F2 generations of C. vestalis might severely impact the effectiveness of combining pathogens and parasitoids as parts of an IPM strategy for DBM control.
PMCID: PMC4072679  PMID: 24968125
38.  Induction of cell cycle arrest and apoptosis in caspase-3 deficient MCF-7 cells by Dillenia suffruticosa root extract via multiple signalling pathways 
Dillenia suffruticosa root dichloromethane extract (DCM-DS) has been reported to exhibit strong cytotoxicity towards breast cancer cells. The present study was designed to investigate the cell cycle profile, mode of cell death and signalling pathways of DCM-DS-treated human caspase-3 deficient MCF-7 breast cancer cells.
Dillenia suffruticosa root was extracted by sequential solvent extraction. The anti-proliferative activity of DCM-DS was determined by using MTT assay. The mode of cell death was evaluated by using inverted light microscope and Annexin-V/PI-flow cytometry analysis. Cell cycle analysis and measurement of intracellular reactive oxygen species (ROS) were performed by using flow cytometry. MCF-7 cells were co-treated with antioxidants α-tocopherol and ascorbic acid to evaluate whether the cell death was mainly due to oxidative stress. GeXP-based multiplex system was employed to investigate the expression of apoptotic, growth and survival genes in MCF-7 cells. Western blot analysis was performed to confirm the expression of the genes.
DCM-DS was cytotoxic to the MCF-7 cells in a time-and dose-dependent manner. The IC50 values of DCM-DS at 24, 48 and 72 hours were 20.3 ± 2.8, 17.8 ± 1.5 and 15.5 ± 0.5 μg/mL, respectively. Cell cycle analysis revealed that DCM-DS induced G0/G1 and G2/M phase cell cycle arrest in MCF-7 cells at low concentration (12.5 and 25 μg/mL) and high concentration (50 μg/mL), respectively. Although Annexin-V/PI-flow cytometry analysis has confirmed that DCM-DS induced apoptosis in MCF-7 cells, the distinct characteristics of apoptosis such as membrane blebbing, chromatin condensation, nuclear fragmentation and formation of apoptotic bodies were not observed under microscope. DCM-DS induced formation of ROS in MCF-7 cells. Nevertheless, co-treatment with antioxidants did not attenuate the cell death at low concentration of DCM-DS. The pro-apoptotic gene JNK was up-regulated whereby anti-apoptotic genes AKT1 and ERK1/2 were down-regulated in a dose-dependent manner. Western blot analysis has confirmed that DCM-DS significantly up-regulated the expression of pro-apoptotic JNK1, pJNK and down-regulated anti-apoptotic AKT1, ERK1 in MCF-7 cells.
DCM-DS induced cell cycle arrest and apoptosis in MCF-7 cells via multiple signalling pathways. It shows the potential of DCM-DS to be developed to target the cancer cells with mutant caspase-3.
PMCID: PMC4096536  PMID: 24947113
Dillenia suffruticosa; Dichloromethane extract; Cell cycle; Apoptosis; Oxidative stress
39.  A Giant Juvenile Nasopharyngeal Angiofibroma 
The Journal of craniofacial surgery  2013;24(3):e207-e209.
Juvenile nasopharyngeal angiofibroma (JNA) are locally growing highly vascular tumours. They are treated primarily by surgical excision ranging from open approach to endoscopic approach. We presented a 20-year-old male with a giant nasopharyngeal juvenile angiofibroma obliterating the pterygopalatine fossa bilaterally, invasing the sphenoid bone and extending to the left nasal passage. His complaints were epistaxis and nasal obstruction. After embolization, the patient was treated surgically with endoscopic approach and discharged as cured without any complication.
PMCID: PMC3668308  PMID: 23714961
Juvenile nasopharyngeal angiofibroma; Endoscopic surgery; Bipolar cautery
40.  Indications of Brain Computed Tomography Scan in Children Younger Than 3 Years of Age with Minor Head Trauma 
Objective. To investigate the indications to receive brain computed tomography (CT) scan and to define the pathological findings in children younger than three years of age with minor head trauma in emergency departments. Methods. In this study, hospital case notes of 1350 children attending the emergency department of Bitlis State Hospital between January 2011 and June 2013 were retrospectively reviewed. 508 children under 3 years of age with minor head trauma were included in this study. We also asked 37 physicians about the indications for requiring CT in these children. Results. This study included 508 children, 233 (45,9%) of whom were female and 275 were male. In 476 (93,7%) children, the brain CT was completely normal. 89,2% of physicians asked in the emergency department during that time interval reported that they requested CT scan to protect themselves against malpractice litigation. Conclusion. In infants and children with minor head trauma, most CT scans were unnecessary and the fear of malpractice litigation of physicians was the most common reason for requesting a CT.
PMCID: PMC3958781  PMID: 24724031
41.  The Effects of Babesiosis on Oxidative Stress and DNA Damage in Anatolian Black Goats Naturally Infected with Babesia ovis 
A reactive oxygen and nitrogen intermediate produced during an inflammatory response is the important part of host-defense strategies of organisms to kill the parasite. However, it is not well known whether these intermediates cause DNA damage and oxidative stress in goats infected with Babesia ovis. The purpose of this study was to clarify the effects of babesiosis on basal levels of DNA damage and oxidative status of goats naturally infected with B.ovis.
DNA damage and antioxidant parameters were determined in B. ovis infected goats. Ten infected Anatolian Black Goats with B. ovis diagnosed via clinical signs and microscopic findings and ten healthy were used in the study.
The Babesia infection increased the levels of DNA damage, malondialdehyde (MDA), protein carbonyl content (PCO) and plasma concentration of nitric oxide metabolites (NOx), and decreased total antioxidant activities (AOA) and reduced glutathione (GSH). A significant positive correlation between DNA damage, MDA, PCO, and NOx concentrations was found in the infected goats. DNA damage showed a negative association with AOA and GSH concentrations in the infected goats.
The Babesia infection increases oxidative stress markers and DNA damage and decreases AOA in goats. These results suggest that the increases in the production of free radicals due to Babesia infection not only contribute to host-defense strategies of organisms to kill the parasite but also induce oxidative damage in other cells.
PMCID: PMC4289885  PMID: 25642264
Babesia ovis; oxidative stress; DNA damage; Antioxidant activity
42.  Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa 
Breast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.
EADs was obtained from the root of D. suffruticosa by using sequential solvent extraction. Cytotoxicity was determined by using MTT assay, mode of cell death by cell cycle analysis and apoptosis induction by Annexin-FITC/PI assay. Morphology changes in cells were observed under inverted light microscope. Involvement of selected genes in the oxidative stress-mediated signaling pathway was explored using multiplex gene expression analysis.
The treatment of EADs caused cytotoxicity to MCF-7 cells in a dose- and time-dependent manner at 24, 48 and 72 hours with IC50 of 76 ± 2.3, 58 ± 0.7 and 39 ± 3.6 μg/mL, respectively. The IC50 of tamoxifen-treated MCF-7 cells was 8 ± 0.5 μg/mL. Induction of apoptosis by EADs was dose- and time- dependent. EADs induced non-phase specific cell cycle arrest at different concentration and time point. The multiplex mRNA expression study indicated that EADs-induced apoptosis was accompanied by upregulation of the expression of SOD1, SOD2, NF-κB, p53, p38 MAPK, and catalase, but downregulation of Akt1.
It is suggested that EADs induced apoptosis in MCF-7 cells by modulating numerous genes which are involved in oxidative stress pathway. Therefore, EADs has the potential to act as an effective intervention against breast cancer cells.
PMCID: PMC3927215  PMID: 24524627
Dillenia suffruticosa; Breast cancer; Cytotoxic; Apoptosis; Oxidative stress pathway
43.  Effect of pheniramine maleate on reperfusion injury in brain tissue 
The aim of this study was to investigate the protective effects of methylprednisolone (Pn), which is a potent anti-inflammatory agent, and pheniramine maleate (Ph), which is an antihistaminic with some anti-inflammatory effects, on reperfusion injury in brain developing after ischemia of the left lower extremity of rats.
Twenty-eight randomly selected male Sprague-Dawley rats were divided into 4 groups: Group 1 was the control group, Group 2 was the sham group (I/R), Rats in Group 3 were subjected to I/R and given Ph, and rats in Group 4 were subjected to I/R and given Pn. A tourniquet was applied at the level of left groin region of subjects in the I/R group after induction of anesthesia. One h of ischemia was performed with no drug administration. In the Ph group, half of a total dose of 10 mg/kg Ph was administered intraperitoneally before ischemia and the remaining half before reperfusion. In the Pn group, subjects received a single dose of 50 mg/kg Pn intraperitoneally at the 30th min of ischemia. Brains of all subjects were removed after 24 h for examination.
Malondialdehyde (MDA) levels of the prefrontal cortex were significantly lower in the Ph group than in the I/R group (p<0.05). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were found to be significantly higher in the Ph group than in the I/R group (p<0.05). Histological examination demonstrated that Ph had protective effects against I/R injury developing in the brain tissue.
Ph has a protective effect against ischemia/reperfusion injury created experimentally in rat brains.
PMCID: PMC3867399  PMID: 24309384
ischemia/reperfusion injury; pheniramine maleate; brain
44.  Noise-Induced Hearing Loss Among Quarry Workers in a North-Eastern State of Malaysia: A Study on Knowledge, Attitude and Practice 
Oman Medical Journal  2013;28(5):331-336.
Noise is known to be one of the environmental and occupational hazards listed in the Factory and Machinery Act 1967. Quarries with loud deafening sounds from trucks and machineries pose the risk of noise-induced hearing loss to workers. This study was designed to assess the knowledge, attitude and practice towards noise-induced hearing loss and to determine the prevalence of noise-induced hearing loss and its associated factors among quarry workers in a north-eastern state of Malaysia.
A cross-sectional study was conducted at six quarries in a north-eastern state of Malaysia, with 97 consented respondents who answered a validated version of a questionnaire and underwent pure tone audiogram. The respondents were male, aged between 18 to 50 years, working in the quarry area for at least 6-months duration with no family history of ear diseases.
The mean percentage scores of knowledge, attitude and practice were 44 (11), 70 (10) and 28 (16) percent, respectively. The prevalence of noise-induced hearing loss was found to be 57 (95% CI: 47, 67) with 46 (84%) having mild and moderate noise-induced hearing loss, and 34 (62%) involved both ears. Multiple logistic regressions showed that age and practice score were the associated factors with odd ratios of 1.1 (95% CI: 1.1, 1.2; p<0.001) and 0.9 (95% CI: 0.8, 1.0; p=0.008), respectively.
The knowledge, attitude and practice scores of the respondents were poor and the high prevalence of noise-induced hearing loss was contributed by factors such as poor practice and old age.
PMCID: PMC3769125  PMID: 24044059
Noise-induced hearing loss; Knowledge, attitude and practice; Prevalence; Quarry workers
45.  Ethyl acetate extract of germinated brown rice attenuates hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuroblastoma cells: role of anti-apoptotic, pro-survival and antioxidant genes 
There are reports of improved metabolic outcomes due to consumption of germinated brown rice (GBR). Many of the functional effects of GBR can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of neurodegenerative diseases like Alzheimer’s disease (AD). This effect of dietary components is mostly based on their ability to prevent apoptosis, which is believed to link oxidative damage to pathological changes in AD. In view of the rich antioxidant content of GBR, we studied its potential to modulate processes leading up to AD.
The total phenolic content and antioxidant capacity of the ethyl acetate extract of GBR were compared to that of brown rice (BR), and the cytotoxicity of both extracts were determined on human SH-SY5Y neuronal cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay. Based on its higher antioxidant potentials, the effect of the GBR extract on morphological changes due to hydrogen peroxide (H2O2)-induced oxidative damage in human SH-SY5Y neuronal cells was examined using inverted light microscope and fluorescence microscope by means of acridine orange-propidium iodide (AO/PI) staining. Also, evaluation of the transcriptional regulation of antioxidant and apoptotic genes was carried out using Multiplex Gene Expression System.
The ethyl acetate extract of GBR had higher total phenolic content and antioxidant capacity compared to BR. The cytotoxicity results showed that GBR extract did not cause any damage to the human SH-SY5Y neuronal cells at concentrations of up to 20 ppm, and the morphological analyses showed that the GBR extract (up to 10 ppm) prevented H2O2-induced apoptotic changes in the cells. Furthermore, multiplex gene expression analyses showed that the protection of the cells by the GBR extract was linked to its ability to induce transcriptional changes in antioxidant (SOD 1, SOD 2 and catalase) and apoptotic (AKT, NF-Kβ, ERK1/2, JNK, p53 and p38 MAPK) genes that tended towards survival.
Taken together, the results of our study showed that the ethyl acetate extract of GBR, with high antioxidant potentials, could prevent H2O2-induced oxidative damage in SH-SY5Y cells. The potential of GBR and its neuroprotective mechanism in ameliorating oxidative stress-related cytotoxicity is therefore worth exploring further.
PMCID: PMC3726323  PMID: 23866310
Germinated brown rice; Antioxidant; Oxidative stress; Neuroprotective; SH-SY5Y
46.  Periodontal Disease: A Covert Source of Inflammation in Chronic Kidney Disease Patients 
The prevalence of atherosclerotic complications (myocardial infarction, stroke, and sudden death) is increased in end-stage renal disease (ESRD) patients, especially in haemodialysis patients. Increasing evidence suggests that both in general population and in dialysis patients, systemic inflammation plays a dominant role in the pathogenesis of atherosclerotic complications. In general population, also, evidence shows that moderate to severe periodontitis can contribute to inflammatory burden by increasing serum CRP levels and may increase the prevalence of atherosclerotic events. Moreover, the results of some new interventional studies reveal that effective phase I periodontal therapy may decrease serum CRP levels, the most important acute phase protein, monitored as a systemic marker of inflammation and endothelial dysfunction as well, used as an initial predictor of atherosclerotic events. Considering that moderate to severe periodontal diseases have a higher prevalence in CKD and in dialysis population and that periodontal examination is not part of the standard medical assessment, destructive periodontitis might be an ignored source of systemic inflammation in end-stage renal disease patients and may add to the chronic inflammatory status in CKD.
PMCID: PMC3690231  PMID: 23840952
47.  Cytotoxic Activity of Kenaf Seed Oils from Supercritical Carbon Dioxide Fluid Extraction towards Human Colorectal Cancer (HT29) Cell Lines 
Kenaf (Hibiscus cannabinus) from the family Malvaceae, is a valuable fiber plant native to India and Africa and is currently planted as the fourth commercial crop in Malaysia. Kenaf seed oil contains alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E, and other antioxidants with chemopreventive properties. Kenaf seeds oil (KSO) was from supercritical carbon dioxide extraction fluid (SFE) at 9 different permutations of parameters based on range of pressures from 200 to 600 bars and temperature from 40 to 80°C. They were 200/40, 200/60, 200/80, 400/40, 400/60, 400/80, 600/40, 600/60, and 600/80. Extraction from 9 parameters of KSO-SFE was screened for cytotoxicity towards human colorectal cancer cell lines (HT29) and mouse embryonic fibroblast (NIH/3T3) cell lines using MTS assay. KSO-SFE at 600/40 showed the strongest cytotoxicity towards HT29 with IC50 of 200 µg/mL. The IC50 for NIH/3T3 was not detected even at highest concentration employed. Cell cycle analysis showed a significant increase in the accumulation of KSO-SFE-treated cells at sub-G1 phase, indicating the induction of apoptosis by KSO-SFE. Further apoptosis induction was confirmed by Annexin V/PI and AO/PI staining.
PMCID: PMC3626181  PMID: 23606884
48.  Gender, airborne chemical monitoring, and physical work environment are related to indoor air symptoms among nonindustrial workers in the Klang Valley, Malaysia 
The purpose of this study was to analyze the relationship of airborne chemicals and the physical work environment risk element on the indoor air symptoms of nonindustrial workers.
A cross-sectional study consisting of 200 office workers. A random selection of 200 buildings was analyzed for exposure and indoor air symptoms based on a pilot study in the Klang Valley, Malaysia.
A set of modified published questionnaires by the Department of Occupational Safety and Health (DOSH), Malaysia and a previous study (MM040NA questionnaire) pertaining to indoor air symptoms was used in the evaluation process of the indoor air symptoms. Statistical analyses involving logistic regression and linear regression were used to determine the relationship between exposure and indoor air symptoms for use in the development of an indoor risk matrix.
The results indicate that some indoor air pollutants (carbon monoxide, formaldehyde, total volatile organic compound, and dust) are related to indoor air symptoms of men and women. Temperature and relative humidity showed a positive association with complaints related to the perceived indoor environmental condition (drafts and inconsistency of temperature). Men predominantly reported general symptoms when stratification of gender involved exposure to formaldehyde. Women reported high levels of complaints related to mucosal and general symptoms from exposure to the dust level indoors.
Exposure to pollutants (total volatile organic compounds, carbon monoxide, and formaldehyde) and physical stressors (air temperature and relative humidity) influence reported symptoms of office workers. These parameters should be focused upon and graded as one of the important elements in the grading procedure when qualitatively evaluating the indoor environment.
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PMCID: PMC3596155  PMID: 23526736
sick building syndrome (SBS); regression analysis; environmental climate factor; occupational exposure; asthma; allergy
50.  Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study 
Intensive Care Medicine  2013;39(5):910-918.
To ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality.
We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤−3.
The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7 %) and 110/237 (46.4 %). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93 %) versus 72 (28 %) patients (P < 0.0001) for 966 (39.6 %) versus 183 (7.5 %) study days respectively. Deep sedation occurred in (182/257) 71 % patients at first assessment and in 159 (61 %) patients and 1,658 (59 %) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.89–0.97, P = 0.003], hospital death (HR 1.11, 95 % CI 1.05–1.18, P < 0.001) and 180-day mortality (HR 1.09, 95 % CI 1.04–1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44 %) of patients.
Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.
PMCID: PMC3625407  PMID: 23344834
Sedation depth; Mechanical ventilation; Delirium; Critically ill; Mortality

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