Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure-activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by ¹H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques.
A number of health databases is now available in Malaysia, but few are accessible to the general public. However, recently a service was launched nationwide via a videotex system to also target the Malaysia public. This service is provided by the School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM) in collaboration with several Malaysian Government ministries and agencies. Access to health information via videotex, be it medical, pharmaceutical or environmental is viewed as an effective means of on-line information dissemination. It provides not only rapid retrieval but is also economical and interactive, particularly suitable for a developing country.
Assessment of asthma management competency using conventional methods remains challenging. This study aimed to explore the baseline knowledge, diagnosis accuracy and clinical management accuracy of acute asthma among emergency doctors using simulation-based assessment. We conducted a cross-sectional study involving 65 emergency department medical officers at a tertiary center. Participants were evaluated using 2 components: knowledge assessment of acute asthma and clinical performance assessment. Knowledge was evaluated using a standardized knowledge questionnaire. Clinical performance in managing acute asthma was assessed using a simulated acute asthma scenario and a standardized asthma management checklist using real-time assessments. The mean knowledge score was 14.69 ± 2.16. No significant differences were found in diagnosis and management accuracy in relation to knowledge (H = 0.644, P = .725, df = 6; H = 1.337, P = .512, df = 2). Acute-asthma attacks of all severities were poorly assessed, with accuracies of 27.3, 41.9, and 20.1% in mild, moderate, severe, and life-threatening cases, respectively. However, all participants provided high-quality treatment (accuracy = 82.3%) regardless of severity. Knowledge score does not influence the ability to differentiate asthma severity and management accuracy according to established asthma guidelines. The overall treatment accuracy was high, regardless of the severity of asthma. However, assessment of acute asthma requires further refinement.
In the last 2 years, there has been a significant upswing in oil prices, leading to a decline in economic activity and demand. This trend holds substantial implications for the global economy, particularly within the emerging business landscape. Among the influential risk factors impacting the returns of shipping stocks, none looms larger than the volatility in oil prices. Yet, only a limited number of studies have explored the complex relationship between oil price shocks and the dynamics of the liner shipping industry, with specific focus on uncertainty linkages and potential diversification strategies. This study aims to investigate the co-movements and asymmetric associations between oil prices (specifically, West Texas Intermediate and Brent) and the stock returns of three prominent shipping companies from Germany, South Korea, and Taiwan. The results unequivocally highlight the indispensable role of oil prices in shaping both short-term and long-term shipping stock returns. In addition, the research underscores the statistical significance of exchange rates and interest rates in influencing these returns, with their effects varying across different time horizons. Notably, shipping stock prices exhibit heightened sensitivity to positive movements in oil prices, while exchange rates and interest rates exert contrasting impacts, one being positive and the other negative. These findings collectively illuminate the profound influence of market sentiment regarding crucial economic indicators within the global shipping sector.
Acute ischemic stroke (AIS) and acute ST-elevation myocardial infarction (STEMI) are leading causes of mortality worldwide. Concurrent AIS presentation with STEMI is rare and potentially fatal. Most importantly to date many centres in Malaysia are still not aware on how to treat this condition. We report a case of AIS, which was treated with intravenous tenecteplase (TNK) according to ischemic stroke dosage and lead to improvement of neurological deficit.
Microbiologically influenced corrosion (MIC) is among the common corrosion types for buried and deep-water pipelines that result in costly repair and pipeline failure. Sulfate-reducing bacteria (SRB) are commonly known as the culprit of MIC. The aim of this work is to investigate the performance of combination of ultrasound (US) irradiation and ultraviolet (UV) radiation (known as Hybrid soliwave technique, HyST) at pilot scale to inactivate SRB. The influence of different reaction times with respect to US irradiation and UV radiation and synergistic effect toward SRB consortium was tested and discussed. In this research, the effect of HyST treatment toward SRB extermination and corrosion studies of carbon steel coupon upon SRB activity before and after the treatment were performed using weight loss method. The carbon steel coupons immersed in SRB sample were exposed to HyST treatment at different time of exposure. Additionally, Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy were used to investigate the corrosion morphology in verifying the end product of SRB activity and corrosion formation after treatment. Results have shown that the US irradiation treatment gives a synergistic effect when combined with UV radiation in mitigating the SRB consortium.
There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.
A cross—sectional study conducted in the fasting month of Ramadan targeting muslim males assessed their religious beliefs in relation to smoking and their intentions t0 quit smoking in Ramadan. It was found that there law; is a strong association between their perceptions on the religious ruling of smoking as haram (prohibited) in relation to their smoking status. Among the non smokers and ex smokers, 87.8% and 73.6% respectively accept the ruling on smoking as prohibitea'(haram), while only 31.6% of smokers accept smoking as prohibited. Among the smokers, 97.7% smoke a lesser number of cigarettes during Ramadan, while 96.7% of them felt that it is easier to quit during the fasting month. The findings suggest that the religious department needs to provide more information and education to the Muslim population as to the reasons of the ruling on smoking as haram(prohibited) on religious grounds . It was also found that the majority felt it is easier to quit during quit smoking programmes can be emphasized and carried out on a bigger scale during fasting months in the future.
The aim of this study was to estimate the levels of leptin in the amnion, chorion laeve, and placenta and to examine for any differences in leptin levels in these tissues from preeclamptic and normotensive pregnant women.
Jaafar S, Mohd Noh K, Abdul Muttalib K, Othman NH, Healy J, Maskon K, et al.
ISBN: 978-92-9061-584-2
Citation: Jaafar S, Mohd Noh K, Abdul Muttalib K, Othman NH, Healy J, Maskon K, et al. Malaysia Health System Review. Geneva: World Health Organization; 2013
Malaysia is a federation of 13 states and 2 territories in a parliamentary democracy, with the Prime Minister the head of government and a constitutional monarch elected by the Sultans. Malaysia is a multicultural society and a secular state with Sunni Islam as the official religion. Classified by the World Bank as an upper middle-income country, its society and economy were transformed by rapid economic growth in the latter half of the 20th century. Malaysia’s population (now numbering over 28 million with 70% living in urban areas) has benefited from a well developed health care system, good access to clean water and sanitation, and strong social and economic programmes. Life expectancy at birth is 73 years. Noncommunicable diseases now account for most mortality and morbidity but communicable diseases remain a concern. Section 2 describes the organization and governance of the health system. Health care services consist of tax-funded and governmentrun primary health care centres and hospitals, and fast-growing private services mainly located in physician clinics and hospitals in urban areas. Public sector health services are administered by the Ministry of Health through its central, state and district offices. The Ministry of Health regulates the private sector, pharmaceutical industry and food safety and plans and regulates its own health care services. Legislation governing health care professionals requires them to register with statutory professional bodies. Section 3 reports on health care financing. Malaysia’s public health system is financed mainly through general revenue and taxation collected by the federal government, while the private sector is funded principally through out-of-pocket payments from patients and some private health insurance. Spending on health reached 4.6% of GDP in 2009 with the majority from public spending, reaching 56% of total health expenditure (THE) in 2009. The main sources of THE in 2008 were the Ministry of Health (42%), followed by household out-of-pocket expenditure at nearly 34%. The Ministry of Health funds public facilities through line item budgets and patients pay private physicians and private hospitals on a fee-for-service basis. Physical and human resources are described in Section 4. The number of public primary care facilities (currently 802 centres and over 2000 small community clinics) and dental clinics were expanded steadily in earlier decades, particularly to reach people in under-served rural areas. Secondary care is offered in smaller public hospitals and more complex tertiary care, in regional and national hospitals (including university teaching hospitals run by the Ministry of Higher Education). Growth has slowed in recent years, however, and public services in urban areas have not kept pace with rapid urbanization, while the population ratio of hospital beds has declined slightly. Private clinics and hospitals in urban areas have grown rapidly over the last decade. The supply of health professionals remains seriously below the required number, although the government has increased the number of training places. Section 5 looks at provision of services. National health policies stress public health and health promotion, that is, ‘a wellness’ as well as a ‘disease’ perspective. The Ministry of Health has developed an extensive network of public primary care centres and also dental services especially for children, but these services are under strain and have staff shortages, so patients often encounter long waits. Primary care exerts only a limited gatekeeper function since people can bypass a referral from a general practitioner and for a small additional fee (if in the public sector) can go directly to specialists and hospitals. Government services increasingly serve the poor and private services the better-off people who live in urban areas. Hospital policy currently has three main thrusts: strengthening specialty care in large public hospitals; increasing the number of day surgery centres; and expanding top-end private hospital care to cater to the medical tourism market (with 35 participating hospitals in 2010). Malaysia has a large pharmaceutical manufacturing sector that exports to other countries and also supplies 30% of domestic demand. The principal health care reforms are discussed in Section 6. The government has stepped up its surveillance and early response to infectious disease outbreaks as a result of recent pandemics such as SARS and avian flu, which had a major impact on the country’s economy. The Ministry of Health has maintained its extensive vaccination programmes, has consolidated its primary health care clinics and upgraded its hospitals, and is slowly introducing information communication technology into its public facilities. The government has increased training places to counter shortages of health professionals, has strengthened food and drug safety regulation, is considering price xv regulation of pharmaceuticals, and is positioning the country as a medical tourism destination. Section 7 provides an assessment of the health system. Malaysia has a strong population health tradition and well-established and extensive health care services. Although total health expenditure at 4.6% of GDP in 2008 is in the range for middle-income countries, the government is concerned about future sustainable financing. Successive administrators have prioritized the provision of cost-effective, preventative and mainly free primary health care in public clinics. The rapid growth of private health care means that private spending has risen faster than public spending, including out-of-pocket payments by the public, with the government share (from general revenue) just above half (56%) of health expenditure in 2009. In conclusion, Malaysia has achieved impressive health gains for its population with a low-cost health care system funded through general revenue that provides universal and comprehensive services. Like many other countries in the region, Malaysia has struggled to produce an adequate supply of health professionals, and to integrate and regulate its rapidly growing private health sector. Public services have not kept pace with population growth in urban areas and those with higher purchasing power use private rather than public doctors and hospitals, which leaves the public sector with more poorer and sicker patients. The Malaysian Government recently revived the debate over options for a national social health insurance scheme. The financing challenge is to agree on a scheme for fair and sustainable funding and its respective contributions from general revenue and private payments. The regulatory challenge for the Malaysian Government is to strengthen its governance of both public and private health services in order to ensure high quality and safe services and fair charges. The structural challenge is to determine the balance between public and private sector delivery and to engage in a more productive partnership between public and private sectors. The administrative challenge is to consider whether the community would be better served by more decentralized and responsive services. As Malaysia seeks to attain high income country status, and as demographic and epidemiological transitions continue and new technology expands the possibilities for intervention, the demand for xvi health care by the population will continue to rise. The government will need to address growing concerns about equity, efficiency and budgetary constraints and balance conflicting policy principles. Pressures are building up for health system reform in Malaysia looking towards the year 2020 and beyond.
Cerebral arteriovenous malformation (AVM) is a rare entity with an estimated prevalence of 0.01-0.05% in the general population. We reviewed hospital obstetric records during 2010-2017 and reported a case series of six patients with cerebral AVM in pregnancy, of which five patients had successful pregnancy, and one maternal mortality.
Melaleuca cajuputi essential oil in aerosol spray was evaluated against the dengue vectors Aedes aegypti and Ae. albopictus at low cost housing flats in Section 10, Setapak, Kuala Lumpur, Malaysia.
Zinc is the authoritative metal which is present in our body, and reactive zinc metal is crucial for neuronal signaling and is largely distributed within presynaptic vesicles. Zinc also plays an important role in synaptic function. At cellular level, zinc is a modulator of synaptic activity and neuronal plasticity in both development and adulthood. Different importers and transporters are involved in zinc homeostasis. ZnT-3 is a main transporter involved in zinc homeostasis in the brain. It has been found that alterations in brain zinc status have been implicated in a wide range of neurological disorders including impaired brain development and many neurodegenerative disorders such as Alzheimer's disease, and mood disorders including depression, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion disease. Furthermore, zinc has also been implicated in neuronal damage associated with traumatic brain injury, stroke, and seizure. Understanding the mechanisms that control brain zinc homeostasis is thus critical to the development of preventive and treatment strategies for these and other neurological disorders.
The murine cytochrome P450 2a5 (Cyp2a5) gene is regulated by complex interactions of various stress-activated transcription factors (TFs). Elevated Cyp2a5 transcription under chemical-induced stress conditions is achieved by interplay between the various TFs - including as aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 wild-type (Nrf2) - at the 'stress-responding' cluster of response elements on the Cyp2a5 promoter, as well as through mRNA stabilization mediated by interaction of the stress-activated heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) with the 3'-UTR of the CYP2A5 mRNA. We designed a unique toxicity pathway-based reporter assay to include regulatory regions from both the 5' and the 3' untranslated regions of Cyp2a5 in a luciferase reporter plasmid to reflect in vivo responses to chemical insult. Human breast cancer MCF-7 cells were stably transfected with pGL4.38-Cyp2a5_Wt3k (wild-type) or mutant - pGL4.38-Cyp2a5_StREMut and pGL4.38-Cyp2a5_XREMut - reporter gene to monitor chemical-induced cellular response mediated by AhR and Nrf2 signalling. The recombinant cells were treated with representative of AhR agonist, polycyclic aromatic hydrocarbons, brominated flame retardant, fluorosurfactant, aromatic organic compound and metal, to determine the sensitivity of the Cyp2a5 promoter-based gene reporter assays to chemical insults by measuring the LC50 and EC50 of the respective chemicals. The three assays are sensitive to sublethal cellular responses of chemicals, which is an ideal feature for toxicity pathway-based bioassay for toxicity prediction. The wild-type reporter responded well to chemicals that activate crosstalk between the AhR and Nrf2, whilst the mutant reporters effectively gauge cellular response driven by either Nrf2/StRE or AhR/XRE signalling. Thus, the three gene reporter assays could be used tandemly to determine the predominant toxicity pathway of a given compound.
The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.
Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.
OBJECTIVE: To assess Malaysian dental therapists' perceptions of their job satisfaction and future roles.
METHODS: A nationwide postal survey involving all Malaysian dental therapists who met the inclusion criteria (n = 1726).
RESULTS: The response rate was 76.8%. All respondents were females; mean age 35.4 years (SD = 8.4). Majority were married (85.5%) and more than one-half had a working experience of <10 years (56.1%). Majority worked in community dental service (94.3%) and in urban areas (61.7%). Overall, they were highly satisfied with most aspects of their career. However, they were least satisfied with administrative workload (58.1%), career advancement opportunities (51.9%) and remuneration package; specifically income (45.2%), allowances (45.2%) and non-commensurate between pay and performance (44.0%). Majority perceived their role as very important in routine clinical tasks such as examination and diagnosis, preventive treatment, extraction of deciduous teeth and oral health promotion. However, fewer than one-half consider complex treatment such as placement of preformed crowns on deciduous teeth (37.1%) and extraction of permanent teeth (37.2%) as very important tasks.
CONCLUSION: Majority expressed high career satisfaction with most aspects of their employment but expressed low satisfaction in remuneration, lack of career advancement opportunities and administrative tasks. We conclude that most Malaysian dental therapists have positive perceptions of their current roles but do not favour wider expansion of their roles. These findings imply that there was a need to develop a more attractive career pathway for therapists to ensure sustainability of effective primary oral healthcare delivery system for Malaysia's children.
Poly (p-phenylene vinylene) (PPV) was synthesized from p-xylylene bis(tetrahydrothiophenium chloride) using the Wessling route and characterized by Fourier Transform Infra-Red (FTIR) and UV-visible (UV-VIS) spectroscopic techniques. The significance of thermal treatment along with evolution of precursor polymer to polymer PPV was also studied through these spectroscopic techniques. Thermally Stimulated Current (TSC) measurements indicated the presence of crystallization, sulphonium group which occurred through the evolution from precursor polymer to polymer PPV during thermal treatment.
The spreading of sewage sludge from wastewater treatment plants and various industries arouses the growing interest due to the contamination by trace elements. Sludges were collected from one sewage treatment plant and two industries in Dhaka City, Bangladesh to assess physicochemical parameters and total and fraction content of trace elements like Cr, Ni, Cu, As, Cd, Pb, Fe, Mn and Zn in sludges. We evaluated the bioavailability of theses metals by determining their speciation by sequential extraction, each metal being distributed among five fractions: exchangeable fraction, bound to carbonate fraction, Fe-Mn oxide bound fraction, organic matter bound fraction and residual fractions. We found that all the analyzed sludges had satisfactory properties from an agronomic quality point of view. The average concentration (mg/kg) of trace metals in sludge samples were in the following decreasing order Fe (12807) > Cr (200) > Mn (158) > Zn (132) > Cu (68.2) > Ni (42.5) > Pb (36.4) > As (35.1) > Cd (3.7). The results of the sequential extraction showed that Cr, Ni, Cu, Fe and Mn were largely associated with the residual fraction where As, Cd and Pb was dominantly associated with the exchangeable and carbonate bound fractions and Zn showed a considerable proportion in carbonate bound fraction. These results showed that regulations must take into account the bioavailability with regard to the characteristics of the agricultural soils on which sludge will be spread.