Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.
This study proposed a new information and commutation technology assisted blind telephone interview (ICT-ABTI) system to help visually impaired people to do telephone interview jobs as normal sighted people and create more diverse employment opportunities for them. The study also used an ABAB design to assess the system with seven visually impaired people. As the results, they can accomplish 3070 effective telephone interviews per month independently. The results also show that working performance of the visually impaired can be improved effectively with appropriate design of operation working flow and accessible software. The visually impaired become productive, lucrative, and self-sufficient by using ICT-ABTI system to do telephone interview jobs. The results were also shared through the APEC Digital Opportunity Center platform to help visually impaired in Philippines, Malaysia and China.
MeSH terms: Adult; Communication Aids for Disabled; Female; Humans; Interviews as Topic*; Job Application*; Male; Sensory Aids*; Telecommunications*; Visually Impaired Persons*; Young Adult
Paramyxoviruses and other negative-strand RNA viruses encode matrix proteins that coordinate the virus assembly process. The matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. Using a co-affinity purification strategy, we have identified the beta subunit of the AP-3 adapter protein complex, AP3B1, as a binding partner for the M proteins of the zoonotic paramyxoviruses Nipah virus and Hendra virus. Binding function was localized to the serine-rich and acidic Hinge domain of AP3B1, and a 29-amino-acid Hinge-derived polypeptide was sufficient for M protein binding in coimmunoprecipitation assays. Virus-like particle (VLP) production assays were used to assess the relationship between AP3B1 binding and M protein function. We found that for both Nipah virus and Hendra virus, M protein expression in the absence of any other viral proteins led to the efficient production of VLPs in transfected cells, and this VLP production was potently inhibited upon overexpression of short M-binding polypeptides derived from the Hinge region of AP3B1. Both human and bat (Pteropus alecto) AP3B1-derived polypeptides were highly effective at inhibiting the production of VLPs. VLP production was also impaired through small interfering RNA (siRNA)-mediated depletion of AP3B1 from cells. These findings suggest that AP-3-directed trafficking processes are important for henipavirus particle production and identify a new host protein-virus protein binding interface that could become a useful target in future efforts to develop small molecule inhibitors to combat paramyxoviral infections.
MeSH terms: Humans; Mass Spectrometry; Viral Matrix Proteins/metabolism*; Protein Interaction Mapping*; Adaptor Protein Complex 3/metabolism*; Adaptor Protein Complex beta Subunits/metabolism*; Hendra Virus/physiology*; Nipah Virus/physiology*; Immunoprecipitation; Host-Pathogen Interactions*; Virus Release*
THE DIVERSITIES OF MANGROVE TREES AND OF THEIR ASSOCIATED GASTROPODS WERE ASSESSED FOR TWO MANGROVE REGIONS ON THE WEST COAST OF PENINSULAR MALAYSIA: Langkawi Island and Sungai Merbok. The mangrove area sampled on Langkawi Island was recently logged and replanted, whereas the area sampled in Sungai Merbok was part of a protected nature reserve. Mangrove and gastropod diversity were assessed in four 50 m(2) (10 × 5 m) sites per region. The species richness (S), Shannon Index (H') and Evenness Index (J') were calculated for each site, and the mean S, H' and J' values were calculated for each region. We report low tree and gastropod S, H' and J' values in all sites from both regions. For Langkawi Island, the mean S, H' and J' values for mangrove trees were S = 2.00±0, H' = 0.44±0.17 and J' = 0.44±0.17; the mean S, H' and J' values for gastropods were S = 4.00±1.63, H' = 0.96±0.41 and J' = 0.49±0.06. In Sungai Merbok, the mean S, H' and J' values for mangrove trees were S = 1.33±0.58, H' = 0.22±0.39 and J' = 0.22 ±0.39; the mean S, H' and J' values for gastropods were S = 4.75±2.22, H' = 1.23±0.63 and J' = 0.55±0.12. This study emphasises the need for baseline biodiversity measures to be established in mangrove ecosystems to track the impacts of anthropogenic disturbances and to inform management and restoration efforts.
A field study was performed to describe the functional feeding groups (FFGs) of Ephemeroptera, Plecoptera and Trichoptera (EPT) in the Tupah, Batu Hampar and Teroi Rivers in the Gunung Jerai Forest Reserve (GJFR), Kedah, Malaysia. Twenty-nine genera belonging to 19 families were identified. The EPTs were classified into five FFGs: collector-gatherers (CG), collector-filterers (CF), shredders (SH), scrapers (SC) and predators (P). In this study, CG and CF were the dominant groups inhabiting all three rivers. Ephemeroptera dominated these rivers due to their high abundance, and they were also the CG (90.6%). SC were the lowest in abundance among all groups. Based on the FFGs, the Teroi River was suitable for CG, whereas the Tupah and Batu Hampar Rivers were suitable for CG and CF. The distribution of FFGs differed among the rivers (CG, χ(2) = 23.6, p = 0.00; SH, χ(2) = 10.02, p = 0.007; P, χ(2) = 25.54, p = 0.00; CF, χ(2) = 21.95, p = 0.00; SC, χ(2) = 9.31, p = 0.01). These findings indicated that the FFGs found in rivers of the GJFR represent high river quality.
The acute and sub-chronic antihyperglycaemic activity, safety margin evaluations and chemical composition of ethanol extract (EE) and fractions of Gynura procumbens (GP) were studied. Streptozotocin (STZ)-induced diabetic rats (SDRs) and the Organisation for Economic Cooperation and Development (OECD) guidelines 425 and 407 were used in the antidiabetic and toxicity studies, respectively. Biochemical and haematological data obtained from both acute and sub-chronic procedures suggest that the extract is safe at the limit test dose (2000 mg/kg); thus, the oral lethal dose (LD50) exceeds 2000 mg/kg. The acceptable daily intake (ADI) was determined to be 700 mg/kg/day. In the acute antihyperglycaemic study, the n-butanol fraction (n-BF) was found to consistently lower glucose levels the most effectively, which was also demonstrated in the 14-day study. Not only did the n-BF show the highest dose-dependent glucose-lowering action (51.2% and 62.0% at 500 mg/kg and 1000 mg/kg, respectively), its effect was the closest to that of metformin (63.6%, p<0.05). The estimated amount of flavonoids in n-BF were 62.90% and 79.68% higher than the ethyl acetate fraction (EAF) and aqueous fraction (AF), respectively (p<0.05), with a corresponding value of 61.22% and 49.33% for phenolics (p<0.05). GP leaves have a no-observed-adverse-effect-level (NOAEL) and antihyperglycaemic activity corresponding to the high content of phenols and flavonoids. Therefore, GP leaves are a promising source of new antidiabetic natural products.
We conducted a series of experiments to test the numerical competency of two species of birds, Corvus splendens (House Crow) and Acridotheres tristis (Common Myna). Both species were allowed to choose from seven different groups of mealworms with varying proportions. We considered the birds to have made a correct choice when it selected the food group with the highest number of mealworms. Our overall results indicated that the Common Myna is able to count numbers (161 successful choices out of 247 trials) better than House Crows (133 successful choices out of 241 trials). We suspect that House Crows do not rely on a numerical sense when selecting food. Although House Crows mostly chose the cup with more mealworms (from seven food item proportions), only one proportion was chosen at rate above random chance. The Common Myna, however, were slow performers at the beginning but became increasingly more capable of numerical sense during the remainder of the experiment (four out of seven food proportion groups were chosen at a rate above random chance).
The Fukushima Daiichi Nuclear Power Plant (F1NPP) accident released large amounts of radioactive substances into the environment and contaminated the terrestrial and marine ecosystems in East Japan. The unpredicted nuclear accident is of global concern for human health and ecosystems. Investigations of radionuclides in the local environments were performed shortly after the accident began; however the temporal and spatial effects and variations in the released radionuclides on the natural environment remain unclear. In the present study, three-year (May 2011 to March 2014) fluctuations and accumulations of total Cs, (134)Cs and (137)Cs in freshwater fishes in Fukushima prefecture after the F1NPP accident were examined. The total Cs, (134)Cs and (137)Cs concentrations decreased gradually during the three-year period that followed the F1NPP accident. However higher levels, i.e., exceeding 100 Bq kg(-1), which is the interim limit of radiocesium level in Japan, were detected in several fish species. Radiocesium accumulation patterns in fishes in Fukushima prefecture varied between regions and corresponded to the environmental radiocesium levels in the Fukushima region. These radionuclides are widely distributed and remain in the natural environment. Moreover, a fresh input of radiocesium substances from the F1NPP site into the terrestrial environment remains.
Obese subjects are at risk of multiple comorbidities including stroke and coronary heart disease (CHD), which is partly due to disturbances in the hemostatic system.
The incorporation of lipophilic nutrients, such as astaxanthin (a fat soluble carotenoid) in nanodispersion systems can either increase the water solubility, stability and bioavailability or widen their applications in aqueous food and pharmaceutical formulations. In this research, gelatin and its combinations with sucrose oleate as a small molecular emulsifier, sodium caseinate (SC) as a protein and gum Arabic as a polysaccharide were used as stabilizer systems in the formation of astaxanthin nanodispersions via an emulsification-evaporation process. The results indicated that the addition of SC to gelatin in the stabilizer system could increase the chemical stability of astaxanthin nanodispersions significantly, while using a mixture of gelatin and sucrose oleate as a stabilizer led to production of nanodispersions with the smallest particle size (121.4±8.6 nm). It was also shown that a combination of gelatin and gum Arabic could produce optimal astaxanthin nanodispersions in terms of physical stability (minimum polydispersity index (PDI) and maximum zeta-potential). This study demonstrated that the mixture of surface active compounds showed higher emulsifying and stabilizing functionality compared to using them individually in the preparation of astaxanthin nanodispersions.
MeSH terms: Drug Stability; Emulsions; Excipients/chemistry*; Gelatin/chemistry*; Particle Size; Xanthophylls/chemistry
A total of 20 new indole alkaloids comprising mainly oxidized derivatives of macroline- (including alstofonidine, a macroline indole incorporating a butyrolactone ring-F), pleiocarpamine-, and sarpagine-type alkaloids were isolated from the bark and leaf extracts of Alstonia angustifolia. The structures and relative configurations of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 3, 7, 35, and 41 showed moderate to weak activity, while 21 showed strong activity in reversing multidrug resistance in vincristine-resistant KB cells.
Neurokinin B (NKB) was recently identified as a key regulator of reproduction in mammals and fish. Fish were found to possess a specific novel neurokinin termed NKF. To study the role of NKB/NKF in the regulation of fish reproduction and to investigate the role of NKB/NKF and their receptors in the piscine pituitary, we have identified the NKB/tachikinin 3 receptor (tac3r) system in tilapia. Bioinformatics and phylogenetic analyses have demonstrated that the tilapia holds 1 putative tac3 gene and 2 NKB receptor genes (tac3ra and tac3rb) that clustered with other piscine Tac3 and NKB receptor lineages. Furthermore, we found that in African cichlids, NKB peptides differ from other vertebrate NKBs in their C-terminal sequence, possessing isoleucine instead of valine as the X in the NKB FXGLM-NH2-terminal consensus sequence. Signal transduction analysis demonstrated that tilapia NKB (tiNKB), tiNKF, and human NKB activated both CRE-luc and SRE-luc transcriptional activity of both tilapia and human NKB receptors. Two hours after ip injection of tiNKB, the plasma levels of both FSH and LH were increased, whereas tiNKF was more effective in increasing LH levels. However, tiNKB was more effective than tiNKF in increasing both FSH and LH from tilapia pituitary dispersed cells. Using in situ hybridization and fluorescent immunohistochemistry, we have shown that LH cells possess tac3, tac3ra, and tac3rb mRNAs, whereas FSH cells possess mainly tac3rb and tac3ra and tac3 to a much lesser extent. These results suggest that the members of the NKB/tac3r system may serve as paracrine/autocrine regulators of gonadotropin release in fish pituitary.
Computational epigenetics is a new area of research focused on exploring how DNA methylation patterns affect transcription factor binding that affect gene expression patterns. The aim of this study was to produce a new protocol for the detection of DNA methylation patterns using computational analysis which can be further confirmed by bisulfite PCR with serial pyrosequencing. The upstream regulatory element and pre-initiation complex relative to CpG islets within the methylenetetrahydrofolate reductase gene were determined via computational analysis and online databases. The 1,104 bp long CpG island located near to or at the alternative promoter site of methylenetetrahydrofolate reductase gene was identified. The CpG plot indicated that CpG islets A and B, within the island, contained 62 and 75 % GC content CpG ratios of 0.70 and 0.80-0.95, respectively. Further exploration of the CpG islets A and B indicates that the transcription start sites were GGC which were absent from the TATA boxes. In addition, although six PROSITE motifs were identified in CpG B, no motifs were detected in CpG A. A number of cis-regulatory elements were found in different regions within the CpGs A and B. Transcription factors were predicted to bind to CpGs A and B with varying affinities depending on the DNA methylation status. In addition, transcription factor binding may influence the expression patterns of the methylenetetrahydrofolate reductase gene by recruiting chromatin condensation inducing factors. These results have significant implications for the understanding of the architecture of transcription factor binding at CpG islets as well as DNA methylation patterns that affect chromatin structure.
Many individuals with type 2 diabetes in emerging countries are transitioning from vial-and-syringe insulin delivery to that of insulin pens (disposable or reusable). As with all insulin delivery methods, patient preferences and comfort are of utmost importance to optimize adherence to treatment. Patient-preferred characteristics for reusable insulin pens and barriers to appropriate injection, particularly in these regions, have not been widely reported in the clinical literature, highlighting a key information gap for clinicians considering these methods as part of a comprehensive diabetes management approach.
Antibodies have been used efficiently for the treatment and diagnosis of many diseases. Recombinant antibody technology allows the generation of fully human antibodies. Phage display is the gold standard for the production of human antibodies in vitro. To generate monoclonal antibodies by phage display, the generation of antibody libraries is crucial. Antibody libraries are classified according to the source where the antibody gene sequences were obtained. The most useful library for infectious diseases is the immunized library. Immunized libraries would allow better and selective enrichment of antibodies against disease antigens. The antibodies generated from these libraries can be translated for both diagnostic and therapeutic applications. This review focuses on the generation of immunized antibody libraries and the potential applications of the antibodies derived from these libraries.
Background: Diabetes mellitus is a lifelong chronic condition that requires self-management. Lifestyle modification and adherence to antidiabetes medications are the major determinants of therapeutic success in the management of diabetes.
Purpose: To assess the effects of a pharmaceutical care (PC) model on medication adherence and glycemic levels of people with type 2 diabetes mellitus.
Patients and methods: A total of 241 people with type 2 diabetes were recruited from a major teaching hospital in Malaysia and allocated at random to the control (n=121) or intervention (n=120) groups. Participants in the intervention group received PC from an experienced pharmacist, whereas those in the control group were provided the standard pharmacy service. Medication adherence was assessed using the Malaysian Medication Adherence Scale, and glycemic levels (glycated hemoglobin values and fasting blood glucose [FBG]) of participants were obtained at baseline and after 4, 8, and 12 months.
Results: At baseline, there were no significant differences in demographic data, medication adherence, and glycemic levels between participants in the control and intervention groups. However, statistically significant differences in FBG and glycated hemoglobin values were observed between the control and intervention groups at months 4, 8, and 12 after the provision of PC (median FBG, 9.0 versus 7.2 mmol/L [P<0.001]; median glycated hemoglobin level, 9.1% versus 8.0% [P0.001] at 12 months). Medication adherence was also significantly associated with the provision of PC, with a higher proportion in the intervention group than in the control group achieving it (75.0% versus 58.7%; P=0.007).
Conclusion: The provision of PC has positive effects on medication adherence as well as the glycemic control of people with type 2 diabetes. Therefore, the PC model used in this study should be duplicated in other health care settings for the benefit of more patients with type 2 diabetes.
Keywords: pharmaceutical care, medication adherence, glycemic control, type 2 diabetes mellitus
Study site: major teaching hospital in Malaysia
Epidemiologic evidence has demonstrated significant associations between atherosclerosis and Porphyromonas gingivalis (Pg). We had investigated the effect of andrographolide (AND) on atherosclerosis induced by Pg in rabbits. For experimental purpose, we separated thirty male white New Zealand rabbits into 5 groups. Group 1 received standard food pellets; Groups 2-5 were orally challenged with Pg; Group 3 received atorvastatin (AV, 5 mg/kg), and Groups 4-5 received 10 and 20 mg/kg of AND, respectively, over 12 weeks. Groups treated with AND showed significant decrease in TC, TG, and LDL levels (P<0.05) and significant increase in HDL level in the serum of rabbits. Furthermore, the treated groups (G3-G5) exhibited reductions in interleukins (IL-1β and IL-6) and C-reactive protein (CRP) as compared to atherogenicgroup (G2). The histological results showed that the thickening of atherosclerotic plaques were less significant in treated groups (G3-G5) compared with atherogenicgroup (G2). Also, alpha-smooth muscle actin (α-SMA) staining decreased within the plaques of atherogenicgroup (G2), while it was increased in treated groups (G3-G5). Lastly, groups treated with AV and AND (G3-G5) showed significant reduction of CD36 expression (P<0.05) compared to atherogenicgroup (G2). These results substantially proved that AND contain antiatherogenic activity.