A Glimpse into the Genome-wide DNA Methylation Changes in 6-hydroxydopamine-induced In Vitro Model of Parkinson’s Disease

A cell-based model of Parkinson’s disease (PD) is a well-established in vitro experimental prototype to investigate the disease mechanism and therapeutic approach for a potential anti-PD drug. The SH-SY5Y human neuroblastoma cells and 6-OHDA combo is one of the many neurotoxininduced neuronal cell models employed in numerous neuroscience-related research for discovering neuroprotective drug compounds. Emerging studies have reported a significant correlation between PD and epigenetic alterations, particularly DNA methylation. However, the DNA methylation changes of PD-related CpG sites on the 6-OHDA-induced toxicity on human neuronal cells have not yet been reported. We performed a genome-wide association study (GWAS) using Infinium Epic beadchip array surveying 850000 CpG sites in differentiated human neuroblastoma cells exposed to 6-OHDA. We identified 236 differentially methylated probes (DMPs) or 163 differentially methylated regions (DMRs) in 6-OHDA treated differentiated neuroblastoma cells than the untreated reference group with p<0.01, Δbeta cut-off of 0.1. Among 236 DMPs, hypermethylated DMPs are 110 (47%), whereas 126 (53%) are hypomethylated. Our bioinformatic analysis revealed 3 DMRs that are significantly hypermethylated and associated with neurological disorders, namely AKT1, ITPR1 and GNG7. This preliminary study demonstrates the methylation status of PD-related CpGs in the 6-OHDA-induced toxicity in the differentiated neuroblastoma cells model.

Patterns of Impaired Neurocognitive Performance on the Global Neuropsychological Assessment, and Their Brain Structural Correlates in Recent-onset and Chronic Schizophrenia

Objective@#Schizophrenia is associated with impairment in multiple cognitive domains. There is a paucity of research on the effect of prolonged illness duration (≥ 15 years) on cognitive performance along multiple domains. In this pilot study, we used the Global Neuropsychological Assessment (GNA), a brief cognitive battery, to explore the patterns of cognitive impairment in recent-onset (≤ 2 years) compared to chronic schizophrenia (≥ 15 years), and correlate cognitive performance with brain morphometry in patients and healthy adults. @*Methods@#We assessed cognitive performance in patients with recent-onset (n = 17, illness duration ≤ 2 years) and chronic schizophrenia (n = 14, duration ≥ 15 years), and healthy adults (n = 16) using the GNA and examined correlations between cognitive scores and gray matter volumes computed from T1-weighted magnetic resonance imaging images. @*Results@#We observed cognitive deficits affecting multiple domains in the schizophrenia samples. Selectively greater impairment of perceptual comparison speed was found in adults with chronic schizophrenia (p = 0.009, η2partial = 0.25).In the full sample (n = 47), perceptual comparison speed correlated significantly with gray matter volumes in the anterior and medial temporal lobes (TFCE, FWE p ＜ 0.01). @*Conclusion@#Along with generalized deficit across multiple cognitive domains, selectively greater impairment of perceptual comparison speed appears to characterize chronic schizophrenia. This pattern might indicate an accelerated or premature cognitive aging. Anterior-medial temporal gray matter volumes especially of the left hemisphere might underlie the impairment noted in this domain in schizophrenia.

Floating Ball Sign: A Rare But Specific Sign Of Mature Cystic Teratoma

Mature cystic teratoma are the most common neoplasm of the ovary which includes at least two well – differentiated germ cell layers. The varying arrangements of tumor contents and combination of the mature tissue derivatives are responsible for spectrum of the imaging appearance of these lesions. However due to the presence of fat and calcification which forms the predominant content of the lesion, these tumors are readily identified by CT. However they are rarely missed on USG and MRI due to its classical tumor components and signs which were reported in various studies in the past. In this case report we presented a classical but rare presentation of cystic teratoma which was diagnosed by CT with further characterization by MRI

Assessment of the level of knowledge regarding the intramuscular administration of medication among staff nurses

Background and Objectives: Intramuscular injection is an everyday procedure which is not without its hazards. Although insuring bodies have pointed out that the lateral thigh is the least unsafe site for an IM injection. The commonly used sites in the adult are gluteal and deltoid muscle. The present study was undertaken to assess the level of knowledge related to intramuscular administration of medication among staff nurses.Material and Methods: 30 samples were selected and descriptive research approach was used in the study. The level of study was assessed using self-administered questionnaire.Results: 46.67 % had inadequate knowledge, 40% had moderate knowledge regarding g the administration of IM injection. Efforts were also made to find the association between the level of knowledge and selected demographic variables. There is significant association between knowledge and educational status and years of clinical experience.Conclusion: The present study assessed the knowledge of staff nurses regarding the administration of intramuscular (IM) medication and tries to find association between the level of knowledge and selected demographic variables. At the nd of the study, the investigators found that there is association between the level of knowledge, age, educational status and year of experience.

The usefulness of osteocalcin measurements in Malaysian patients with rheumatoid arthritis

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory condition that can be associated with abnormal bone turnover and hence osteoporosis. Osteocalcin (OC) levels are increased in conditions with high bone turnover, including high RA disease activity. Thus, OC levels could possibly be used as a marker to assess bone health and disease activity in RA patients. As there have been no previous studies looking at serum OC levels in Malaysian RA patients, this study was performed to examine possible correlations between OC, bone mineral density (BMD) and disease activity in this population.Methods: A cross-sectional study of 75 female RA patients and 29 healthy controls was performed. Serum OC was measured using a Quantikine® ELISA kit. Dual-energy x-ray absorptiometry (DXA) was used to assess BMD.Results: Serum OC levels were not significantly different between RA patients (median 14.44 ng/mL, interquartile range [IQR 12.99]) compared to healthy controls (median 11.04 ng/mL IQR 12.29) (p=0.198). Serum OC increased with age (Spearman’s rho r=0.230, p=0.047). There was no significant correlation between serum OC and body mass index (BMI), menopause status, BMD, DAS28, swollen or tender joint counts. Overall, there were 11 (14.7%) patients with osteoporosis and 27 (36.0%) with osteopenia. Menopause status was significantly associated with BMD at all sites (lumbar spine p=0.002, femoral neck p=0.004, total hip p=0.002). Conclusions: Serum OC were similar in RA patients compared to healthy controls. In RA patients, serum OC did not correlate with RA disease activity or BMD. Menopause status remains an important influence on BMD. Thus, measuring serum OC levels in Malaysian RA patients was not useful in identifying those at risk of low BMD.

Keeping up the morale of the foot soldiers of Indian public health: an appraisal of the economic aspects of ASHAs in Uttarakhand, India.

Background: Accredited social health activist (ASHA) is a voluntary community health worker and an important human resource for public health system of India. Their motivation to become a community health worker and continued efforts is a mix of monetary and non-monetary factors. Their motivation to work comes partly from desire to work for the community and prestige, but is furthered by the monetary compensation. Objectives: To study the economic status of ASHAs in Uttarakhand, and their contribution to household income and the role the monetary incentives play in their work. Methods: This cross sectional study was conducted in Haridwar and Dehradun districts of Uttarakhand. Eighty one ASHAs were interviewed using pre-piloted semi-structured questionnaire. Their economic status was assessed using Modified BG Prasad Classification. Results: Majority of the ASHAs belonged to class 4 according to modified B G Prasad Classification. Mean monthly earning as ASHA was 1335 rupees (SD: 748) and the mean contribution to the total household income was 28%. Financial incentive was an important motivating factor with associated concerns about delay in payments. About 75% felt that the amount was inadequate considering the time and effort involved. Conclusions: There is need to review the financial and non-financial incentives with due consideration to inflation and consumer price index.

Therapeutic Effect of Curcumin Supplementation in the Modulation of NF-κB Responsive Genes in a Collagen-induced Arthritis Rat Model.

Aims: To assess the therapeutic effect of curcumin supplementation in modulating the expression of NF-κB in the joints of collagen-induced arthritis (CIA) rats. Place and Duration of Study: Department of Postgraduate Studies and Research, International Medical University, between July 2011 and May 2012. Methodology: Arthritis was induced in each group of Dark Agouti (DA) rats, by intradermal injection with collagen emulsified in complete Freund’s adjuvant. Treatment groups which were induced with CIA were treated with: 500 mg/kg curcumin; 1000 mg/kg curcumin; 2000 mg/kg curcumin; 25 mg/kg aspirin. Combination treatment groups which were induced with CIA were treated with: 500 mg/kg curcumin and 25 mg/kg aspirin; 1000 mg/kg curcumin and 25 mg/kg aspirin; 2000 mg/kg curcumin and 25 mg/kg aspirin from day 25 to 38. Efficacy was assessed based on ability to reduce paw oedema, histopathological changes, NF-κB expression, serum tumour necrosis factor alpha (TNF- α), interleukin 1-beta (IL-1β) and gluthathione peroxidase (GPx) levels. Results: Based on histopathological study, immunohistochemical scoring of NF-κB and ELISA analysis of TNF-α, IL-1β and GPx levels, our study found that curcumin given after arthritis in high doses, shows effects of healing and this results were comparable to positive control group, which is the arthritic group treated with 25 mg/kg aspirin. Curcumin given in combination with aspirin, showed better reduction in pathology in arthritic group compared to positive control group, especially with higher doses of curcumin. Conclusion: Curcumin was effective in reducing inflammatory changes seen in CIA joints which were proved through histopathological, immunohistochemical and biochemical analysis, however only at high doses.

Current concepts in cancer research

Cancer research is an extremely broad topic covering many scientific disciplines including biology (e.g. biochemistry and signal transduction), chemistry (e.g. drug discover and development), physics (e.g. diagnostic devices) and even computer science (e.g. bioinformatics). Some would argue that cancer research will continue in much the same way as it is by adding further layers of complexity to the scientific knowledge that is already complex and almost beyond measure. But we anticipate that cancer research will undergo a dramatic paradigm shift due to the recent explosion of new discoveries in cancer biology. This review article focuses on the latest horizons in cancer research concerning cancer epigenetics, cancer stem cells, cancer immunology and cancer metabolism.

The influence of admission qualifications on the performance of first and second year medical students at the International Medical University

Background: Medical schools have long been concerned with establishing a suitable process of admission. The criteria used to select students have traditionally focussed on high academic achievement. Method: The International Medical University (IMU) accepts students from a wide range of pre-university entry qualifications for admission into the medical programme. The criteria for the various pre-university entry qualifications used by the IMU were agreed and accepted by the IMU Academic Council (AC), which consist of deans of the IMU’s partner medical schools (PMS). In this study, the various entry qualifications were first grouped into five categories based on the educational pedagogy. Then, this was aligned with the entry qualification data of all students who had been admitted into the IMU medical programme for the period of December 1993 to March 2000. During this period 1,281 students were enrolled into the IMU medical programme. The relationship between the five groups of pre-university entry qualifications and the students’ academic achievement in three end-ofsemester (EOS) examinations namely EOS 1, EOS 3, and EOS 5 were analysed. Results: Students with better grades in their preuniversity examinations showed better performance in their EOS examinations, regardless of the subjects that they took at the pre-university level. Cluster analysis revealed that students who came in with certain preuniversity qualifications generally performed poorly than the more conventional qualifications. However, after their first year in medical school, there were no significant differences in the clustering of the students. Conclusion: Students with better grades in their preuniversity examinations showed better performance in their EOS examinations, regardless of the science subjects that they took at the pre-university level.

Advances in immunotherapy using dendritic cells

The immune system is the host natural defence against cancer. Cancers are caused by progressive growth of the progeny of a single transformed host cell. The immune system is generally not able to mount immune responses to “self-antigens”, due to various mechanisms of immunological tolerance that are in place. This means that despite possessing a natural defence against tumours, many of the cancer patients may not be able to mount an effective immune response to fight the tumours. Dendritic cells (DC) are highly specialised in antigen presenting that can initiate and stimulate immune responses. These cells have the ability to stimulate naïve T cell proliferation and perform specific stimulatory and tolerogenic functions respectively. When the DC are activated by antigens, these cells undergoes further maturation and migrate to secondary lymphoid tissues, present antigen to T cells and finally induce an immune response. The ability of the DC to activate naïve and primed T-lymphocytes makes these cells a good candidate to be explored as a potential immunotherapeutic agent that can modulate antitumour immune responses in the affected host.

Production and characterization of poly-3-hydroxybutyrate from crude glycerol by Bacillus sphaericus NII 0838 and improving its thermal properties by blending with other polymers

The aim of this work was to study the production of poly-3-hydroxybutyrate (PHB) under nitrogen limited conditions by Bacillus sphaericus NII 0838 using crude glycerol from biodiesel industry as sole carbon source. Effect of various process parameters on PHB production such as glycerol concentration, inoculum size and pH of the medium were optimized. Characterization of extracted PHB was carried out by FT-IR, ¹H and 13C NMR. Results showed that the bacterial culture accumulated about 31 percent PHB in crude glycerol medium. The extracted PHB was blended with other polymers to improve its physical characteristics. The thermal properties of the polymer like melting temperature (Tm) and heat of fusion (ΔHf) were determined using DSC.

Transfected human mesenchymal stem cells do not lose their surface markers and differentiation properties

In this study, we evaluated the biological properties of human mesenchymal stem cells transfected (hMSC) with a plasmid vector expressing human cytokine interleukin-12 (IL-12). Surface markers were analysed by immunophenotyping using flow cytometry. Differentiation capability was evaluated towards adipogenesis and osteogenesis. We demonstrated that successfully transfected hMSC retained their surface immunophenotypes and differentiation potential into adipocytes and osteocytes. These results indicate that hMSC may be a suitable vehicle for gene transduction.

Research On Bioactive Molecules: Achievements And The Way Forward

Research on bioactive molecules is one of the thrust areas of research at the International Medical University (IMU). The bioactive molecules that have attracted the interest of IMU researchers include tocotrienol, astaxanthin, zingerone, apigenin, carrageenan and phycocyanin. There are also projects which focus on the screening of extracts from local plants such as Elephantopus mollis, Morinda citrifolia, Pereskia bleo, Euphorbia hirta, Zinger officinale, Mangifera indica and Nephelium lappaceum and algae such as Spirulina and Gracilaria. Characterisation of the toxin from Bacillus thuringiensis is another area of active research at IMU. The compounds and extracts from the various organisms are screened for anticancer, antioxidative, antiviral and immuno-modulating activity. There are also studies on the production of recombinant molecules, especially monoclonal antibodies for the detection of house dust mites, Salmonella typhi and Candida. The pool of faculty with diverse expertise and the active collaboration with public universities and institutions have enhanced the progress of bioactive research at IMU. With the current postgraduate and Bachelor of Medical Science (B. MSc.) programme and the introduction of new programmes in health sciences, there are good opportunities for training of students in the research on bioactive molecules. The future research direction should focus on the mechanisms of action of the bioactive molecules using new approaches such as ‘omic’ technologies and in silico modelling.

Luminescent bacteria as biosensor for mercury toxicity.

Agricultural activities and human industrialization are mainly responsible for the release of heavy metals into the environment, especially the air and the water. The first step towards the effective management of water resources is the assessment of pollution levels. Biosensors for the detection of pollutants in the environment can complement analytical methods by distinguishing bioavailable from inert, unavailable forms of contaminants. A bioassay system for detecting heavy metals in water using bioluminescent bacteria, Vibrio harveyi and Vibrio fischeri has been developed, which offers the advantages of simplicity and rapidity for screening heavy metals in water sources. Bioluminescence was found to be species specific and strain specific. Mercury, zinc and copper showed definite microbial toxicity and inhibition of bioluminescence. The inhibition range for each strain of a species was standardized and its reproducibility verified. The utility of the biosensors to detect heavy metals in tap water was demonstrated with samples supplemented with Hg (II).