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Nguyen Dang Thang,1 Björn Wilgot Karlson,1,2 Thomas Karlsson,3 Johan Herlitz1,4 1Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg, 2AstraZeneca R&D, Mölndal, 3Health Metrics, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 4School of Health Sciences, Research Centre PreHospen, University of Borås, The Pre-hospital Research Centre of Western Sweden, Borås, Sweden Objectives: This study analyzed age-adjusted sex differences among acute myocardial infarction (AMI) patients aged 75 years and above with regard to 7-year mortality (primary end point) and the frequency of angiograms and admission to the coronary care unit (CCU) as well as 1-year mortality (secondary end points).Methods: A retrospective cohort study comprised 1,414 AMI patients (748 females and 666 males) aged at least 75 years, who were admitted to Sahlgrenska University Hospital in Gothenburg, Sweden, during two periods (2001/2002 and 2007). All comparisons between female and male patients were age adjusted.Results: Females were older and their previous history included fewer AMIs, coronary artery bypass grafting procedures, and renal diseases, but more frequent incidence of hypertension. On the contrary, males had higher age-adjusted 7-year mortality in relation to females (hazard ratio [HR] 1.16 with corresponding 95% confidence interval [95% CI 1.03, 1.31], P=0.02). Admission to the CCU was more frequent among males than females (odds ratio [OR] 1.38 [95% CI 1.11, 1.72], P=0.004). There was a nonsignificant trend toward more coronary angiographies performed among males (OR 1.34 [95% CI 1.00, 1.79], P=0.05), as well as a nonsignificant trend toward higher 1-year mortality (HR 1.18 [95% CI 0.99, 1.39], P=0.06).Conclusion: In an AMI population aged 75 years and above, males had higher age-adjusted 7-year mortality and higher rate of admission to the CCU than females. One-year mortality did not differ significantly between the sexes, nor did the frequency of performed coronary angiograms. Keywords: acute myocardial infarction, elderly patients, characteristics, cardiovascular outcomes, death

AIM: The aims of this study were to describe the characteristics of and outcome of patients with chest pain in relation to transport by the emergency medical services (EMS) and to describe possible changes in this relationship in a 20-year perspective. METHODS: In the 2 periods, 1986 to 1987 and 2008, all patients with chest pain admitted to hospitals in Gothenburg, Sweden, were retrospectively evaluated in terms of previous history, final diagnosis, and mortality. P values were age adjusted. RESULTS: In 1986 to 1987 and 2008, 34% of 4270 patients with chest pain and 39% of 2286 patients, respectively, were transported to the hospital by the EMS (P = .0001). In both periods, patients who used EMS were older and had a higher prevalence of previous cardiovascular diseases and more often had a final diagnosis of acute myocardial infarction (AMI) than those who did not use EMS. The EMS users were more frequently hospitalized in 1986 to 1987 than in 2008 (P < .0001). Emergency medical service use was related to a significantly higher age-adjusted 1-year mortality in both periods for all patients with chest pain as well as for those hospitalized. Among hospitalized patients with myocardial ischemia and among patients with a final diagnosis of AMI, EMS use was associated with a higher 30-day mortality in 1986 to 1987. Regardless of the use of EMS, there was a decrease in the proportion of patients developing AMI as well as the rate of death at 30 days and 1 year in 2008 as compared with 1986 to 1987. CONCLUSIONS: For 20 years, the proportion of patients with chest pain using the EMS increased. EMS users were more frequently hospitalized in 1986 to 1987 than in 2008. In overall terms, mortality was higher among EMS users than among nonusers in both periods. Among hospitalized patients with myocardial ischemia and among patients with a final diagnosis of AMI, EMS use was associated with a higher 30-day mortality only in 1986 to 1987. [ABSTRACT FROM AUTHOR]

Designing policy in public health is a complex process requiring decision making that incorporates available evidence and is suitable to a country's epidemiological and health system context. The main objective of this study was to develop an options assessment toolkit (OAT) to provide a pragmatic and evidence-based approach to the development of policies for the radical cure (prevention of relapse) of vivax malaria for national malaria control programs in the Asia-Pacific region. The OAT was developed using participatory research methods and a Delphi process using a sequential multi-phase design, adapted with a pre-development phase, a development phase, and a final development phase. In the pre-development phase, a literature review was conducted to inform the toolkit development. Data collection in the development phase consisted of core research team discussions, multiple rounds of consultation with participants from National Malaria Control Programs (NMP) (online and in person), and two separate modified e-Delphi processes with experts. The final development phase was the piloting of the toolkit during the annual meeting of the Asia Pacific Malaria Elimination Network (APMEN) Vivax Working Group. We developed a tool kit containing the following elements: i) Baseline Assessment Tool (BAT) to assess the readiness of NMPs for new or improved coverage of radical cure, ii) eight scenarios representative of Asia Pacific region, iii) matching test and treat options based on available options for G6PD testing and radical cure for the given scenarios, iv) an approaches tool to allow NMPs to visualize considerations for policy change process and different implementation strategies/approaches for each test and treat option. The OAT can support vivax radical cure policy formulation among NMPs and stakeholders tailoring for their unique country context. Future studies are needed to assess the utility and practicality of using the OAT for specific country context., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Acharya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Recent advances in G6PD deficiency screening and treatment are rapidly changing the landscape of radical cure of vivax malaria available for National Malaria Programs (NMPs). While NMPs await the WHO's global policy guidance on these advances, they will also need to consider different contextual factors related to the vivax burden, health system capacity, and resources available to support changes to their policies and practices. Therefore, we aim to develop an Options Assessment Toolkit (OAT) that enables NMPs to systematically determine optimal radical cure options for their given environments and potentially reduce decision-making delays. This protocol outlines the OAT development process., Methods: Utilizing participatory research methods, the OAT will be developed in four phases where the NMPs and experts will have active roles in designing the research process and the toolkit. In the first phase, an essential list of epidemiological, health system, and political & economic factors will be identified. In the second phase, 2-3 NMPs will be consulted to determine the relative priority and measurability of these factors. These factors and their threshold criteria will be validated with experts using a modified e-Delphi approach. In addition, 4-5 scenarios representing country contexts in the Asia Pacific region will be developed to obtain the expert-recommended radical cure options for each scenario. In the third phase, additional components of OAT, such as policy evaluation criteria, latest information on new radical cure options, and others, will be finalized. The OAT will be pilot-tested with other Asia Pacific NMPs in the final phase., Ethics and Dissemination: Human Research Ethics Committee approval has been received from the Northern Territory, Department of Health, and Menzies School of Health Research (HREC Reference Number: 2022-4245). The OAT will be made available for the NMPs, introduced at the APMEN Vivax Working Group annual meeting, and reported in international journals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shrestha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Malaria rapid diagnostic tests (RDTs) remain the main point-of-care tests for diagnosis of symptomatic Plasmodium falciparum malaria in endemic areas. However, parasites with gene deletions in the most common RDT target, histidine rich protein 2 (pfhrp2/HRP2), can produce false-negative RDT results leading to inadequate case management. The objective of this study was to determine the prevalence of hrp2/3 deletions causing false-negative RDT results in Vietnam (Gia Lai and Dak Lak provinces)., Methods: Individuals presenting with malaria symptoms at health facilities were screened for P. falciparum infection using light microscopy and HRP2-RDT (SD Bioline Malaria Antigen Pf/Pv RDT, Abbott). Microscopically confirmed P. falciparum infections were analysed for parasite species by 18S rRNA qPCR, and pfhrp2 and pfhrp3 exon2 deletions were investigated by nested PCR. pfhrp2 amplicons were sequenced by the Sanger method and HRP2 plasma levels were determined by enzyme-linked immunosorbent assay (ELISA)., Results: The prevalence of false-negative RDT results among symptomatic cases was 5.6% (15/270). No pfhrp2 and pfhrp3 deletions were identified. False-negative RDT results were associated with lower parasite density (p = 0.005) and lower HRP2 plasma concentrations (p < 0.001), as compared to positive RDT., Conclusions: The absence of hrp2/3 deletions detected in this survey suggests that HRP2-based malaria RDTs remain effective for the diagnosis of symptomatic P. falciparum malaria in Central Vietnam., (© 2022. The Author(s).)

Cyanobacteria are phototrophic organisms widely found in most types of natural habitats in the tropical regions of the world. In this study, we isolated and identified cyanobacterial strains from paddy soil in Hanoi (Vietnam) and investigated their cytotoxic activities. Five isolated cyanobacterial strains showed distinctive profiles of gene sequences (rRNA 16S and rbcL ), phylogenetic placements, and morphological characteristics. Based on the polyphasic evaluation, they were classified as Scytonema bilaspurense NK13, Hapalosiphon welwitschii MD2411, Aulosira sp. XN1103, Desikacharya sp. NS2000, and Desmonostoc sp. NK1813. The cytotoxic screening revealed that the extract of strain Scytonema bilaspurense NK13 exhibited potent cytotoxic activities against four human cell lines of HeLa cells, OVCAR-8 cells, HaCaT cells, and HEK-293T cells, with IC 50 values of 3.8, 34.2, 21.6, and 0.6 μg/mL, respectively. This is the first time a well-classified Scytonema strain from tropical habitat in Southeast Asia has been recognized as a potential producer of cytotoxic compounds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ngo, Nguyen, Duong, Nguyen, Nguyen, Kieu, Do, Nguyen, Thang and Pham.)

Human leucocyte antigen (HLA) alleles are very diverse and characterized by ethnicity. To date, information about the frequencies and distributions of HLA alleles among the Vietnamese population is still limited. In this study, HLA-DQB1 alleles of 2076 cord blood units from individuals belonging to Vietnam's Kinh ethnic people were genotyped using Luminex-based polymerase chain reaction sequence-specific oligonucleotide. The results of the study demonstrated that there were 23 alleles on the locus HLA-DQB1. Among those, there were six alleles with high frequencies of over 5%, including DQB1 * 03:01 (35.9%), DQB1 * 05:01 (12.8%), DQB1 * 03:03 (12.2%); DQB1 * 06:01 (7.20%), DQB1 * 05:02 (6.62%) and DQB1 * 02:01 (5.30%) and five rare alleles with low frequencies of below 0.1%. More importantly, this study for the first time reported the presence of two new rare alleles including DQB1 * 01:01 and DQB1 * 01:02. Conclusively, this study provided significant information about HLA-DQB1 alleles for further investigations and clinical applications., (© 2022 John Wiley & Sons Ltd.)

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A-B, HLA-A-C, HLA-A-DRB1, HLA-B-C, HLA-B-DRB1, and HLA-C-DRB1 haplotypes were A*11:01-B*15:02 (7.63%), A*11:01-C*08:01 (7.98%), A*11:01-DRB1*12:02 (10.56%), B*15:02-C*08:01 (14.0%), B*15:02-DRB1*12:02 (10.47%), and C*08:01-DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A-B-C, HLA-A-B-DRB1, HLA-A-C-DRB1, HLA-B-C-DRB1, and HLA-A-B-C-DRB1 were A*11:01-B*15:02-C*08:01 (7.57%), A*11:01-B*15:02-DRB1*12:02 (5.39%), A*11:01-C*08:01-DRB1*12:02 (5.54%), B*15:02-C*08:01-DRB1*12:02 (10.21%), and A*11:01-B*15:02-C*08:01-DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Que, Khanh, Khanh, Van Son, Van Anh, Anh, Tung and Thang.)

Allopurinol (ALP) is commonly used as a drug for gout treatment. However, ALP is known to cause cutaneous adverse reactions (CARs) in patients. The HLA-B * 58:01 allele is considered a biomarker of severe CAR (SCAR) in patients with gout, with symptoms of Stevens Johnson syndrome, and with toxic epidermal necrolysis. However, in patients with gout and mild cutaneous adverse drug reactions (MCARs), the role of HLA-allele polymorphisms has not been thoroughly investigated. In this study, 50 samples from ALP-tolerant patients and ALP-induced MCARs patients were genotyped in order to examine the polymorphisms of their HLA-A and HLA-B alleles. Our results showed that the frequencies of HLA-A * 02:01/HLA-A * 24:02 and HLA-A * 02:01/HLA-A * 29:01, the dual haplotypes in HLA-A, in patients with ALP-induced MCARs were relatively high, at 33.3% (7/21), which was HLA-B * 58:01-independent, while the frequency of these dual haplotypes in the HLA-A locus in ALP-tolerant patients was only 3.45% (1/29). The HLA-B * 58:01 allele was detected in 38% (8/21) of patients with ALP-induced MCARs, and in 3.45% (1/29) of ALP-tolerant patients. Notably, although HLA-B * 58:01 may be a cause for the occurrence of MCARs in patients with gout, this correlation was not as strong as that previously reported in patients with SCAR. In conclusion, in addition to the HLA-B * 58:01 allele, the presence of the dual haplotypes of HLA-A * 02:01/HLA-A * 24:02 and/or HLA-A * 02:01/HLA-A * 29:01 in the HLA-A locus may also play an important role in the appearance of ALP-induced MCARs in the Vietnamese population. The obtained primary data may contribute to the development of suitable treatments for patients with gout not only in Vietnam but also in other Asian countries.

The concentrations and temporal variations of polychlorodibenzo-p-dioxins and polychlorodibenzofurans (PCDDs/PCDFs) in ambient air between March 2013 and February 2017 were investigated by passive air samplers containing polyurethane foam (PUF) disks in the dioxin remediation area using in-pile thermal desorption (IPTD) technology at Da Nang airport, Vietnam. The PCDD/PCDF concentrations in ambient air at each site depended on the location of the emission sources and the wind direction, the dioxin contamination level of excavated materials, the periods of excavation and transport, and the operation of the IPTD treatment system. The PCDD/PCDF concentrations were the highest in the former Agent Orange mixing and loading area (AOMLA), which was the closest to the IPTD system, with total toxic equivalent (TEQ) values ranging from 0.437 to 15.3 pg/PUF/day. The total TEQ concentrations in the Sen Lake area ranged from 0.138 to 2.41 pg/PUF/day. The lowest concentration of PCDDs/PCDFs occurred in the northern perimeter area, with total TEQ values ranging from 0.164 to 0.972 pg/PUF/day. The decreasing trend of the PCDD/PCDF concentrations in ambient air was confirmed over time at all three monitoring sites, among which there was a strong decrease in the former AOMLA after February 2015. Residents living near the Da Nang airport were at a low risk of being exposed to PCDDs/PCDFs through inhalation during remediation project implementation, while residents living close to the former AOMLA faced elevated risks with an average daily dose of PCDDs/PCDFs through inhalation ranging from 0.017 to 0.82 pg TEQ/kg body weight/day.

In this study, we showed that crude extract of Anisomeles indica (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. More interestingly, flow cytometry revealed that AI-EtE significantly promoted the number of cells entering apoptotic. Accordingly, the transcript levels of BAX , CASPASE-8 , and CASPASE-3 in the cells treated with AI-EtE at IC50 dose were 1.55-, 1.62-, and 2.45-fold higher than those in the control cells, respectively. Moreover, treatment with AI-EtE caused cell cycle arrest at the G1 phase in a p53-independent manner. Particularly, percentages of AI-EtE-treated cells in G1, S, G2/M were, respectively 85%, 6.7% and 6.4%; while percentages of control cells in G1, S, G2/M were 64%, 15% and 19%, respectively. Consistent with cell cycle arrest, the expressions of CDKN1A and CDNK2A in AI-EtE-treated cells were up-regulated 1.9- and 1.64-fold, respectively. Significantly, treatment with AI-EtE also decreased anchorage-independent growth of HeLa cells. In conclusion, we suggest that Anisomeles indica can be considered as a medicinal plant with a possible use against cervical cancer cells; however, the used dose should be carefully monitored, especially when applying to pregnant women.

Background: Despite great success in significantly reducing the malaria burden in Viet Nam over recent years, the ongoing presence of malaria vectors and Plasmodium infection in remote forest areas and among marginalised groups presents a challenge to reaching elimination and a threat to re-emergence of transmission. Often transmission persists in a population despite high reported coverage of long-lasting insecticidal nets (LLINs), the mainstay control method for malaria. To investigate what factors may contribute to this, a mixed-methods study was conducted in Son Thai commune, a community in south-central Viet Nam that has ongoing malaria cases despite universal LLIN coverage. A cross-sectional behavioural and net-coverage survey was conducted along with observations of net use and entomological collections in the village, farm huts and forest sites used by members of the community., Results: Most community members owned a farm hut plot and 71.9% of adults aged 18+ years sometimes slept overnight in the farm hut, while one-third slept overnight in the forest. Ownership and use of nets in the village households was high but in the farm huts and forest was much lower; only 44.4% reported regularly using a bednet in the farm and 12.1% in the forest. No primary anopheline species were captured in the village, but Anopheles dirus (s.l.) (n = 271) and An. maculatus (s.l.) (n = 14) were captured as far as 4.5 km away in farm huts and forest. A high proportion of biting was conducted in the early evening before people were under nets. Entomological inoculation rates (EIR) of An. dirus (s.l.) were 17.8 and 25.3 infectious bites per person per year in the outdoor farm hut sites and forest, respectively, for Plasmodium falciparum and 25.3 in the forest sites for P. vivax., Conclusions: Despite high net coverage in the village, gaps in coverage and access appear in the farm huts and forest where risk of anopheline biting and parasite transmission is much greater. Since subsistence farming and forest activities are integral to these communities, new personal protection methods need to be explored for use in these areas that can ideally engage with the community, be durable, portable and require minimal behavioural change.

Background: Ricin has been reported as a potential chemical for cancer treatment. However, so far, the application of ricin in cancer treatment is very limited because of its non-specificity. Methods: In this study, ricin were conjugated/ encapsulated with DOTAP/DOPE liposome to form ricin-liposome complexes (ricin-lipososme1, ricin-liposome2, ricin-liposome3 and ricin-liposome4). Characteristics of ricin-liposome complexes were analyzed and their effects on survival, apoptosis, migration, invasion and tumor formation of SKMEL-28 melanoma cells were examined by carrying out the MTT assay, apoptosis assay, scratch wound healing assay, invasion assay and soft-agar colony formation assay, respectively. Results: Ricin-liposome complexes had even size-distribution with average size of around 340 nm. These ricin-liposome complexes were able to penetrate into the cells via endocytosis with the highest ability of the ricinliposome3. It also showed that ricin-liposome3 expressed very high toxicity with the IC50 of 62.4 ng/mL and followed by ricin-liposome4 (286.4 mg/mL), ricin-liposome2 (417.5 ng/mL), and ricin-liposome1 (604.3 ng/mL) to SKMEL-28 cells at 36 hours post treatment. At the concentrations of IC10 (10.1 ng/mL), ricin-liposome3 strongly induced necrosis and apoptosis of SKMEL-28 cells up to 25.6% and 11.4%, respectively. Moreover, ricin-liposome3 expressed great anticancer properties by decreasing the migration, invasion and tumor formation abilities of SKMEL-28 cells of 7.5 folds, 4.3 folds and 5.9 folds, respectively, compared with those of control SKMEL-28 cells. Conclusion: The obtained results from our study suggest that although ricin is listed as one of the most poisonous substances in nature, it can be used in the complex forms with liposome to increase its specificity to apply in treatment of melanoma and other cancers.

Purpose: Following interventions against trachoma in Viet Nam, impact surveys conducted in 2003-2011 suggested that trachoma was no longer a public health problem. In 2014, we undertook surveillance surveys to estimate prevalence of trachomatous inflammation-follicular (TF) and trichiasis., Methods: A population-based prevalence survey was undertaken in 11 evaluation units (EUs) encompassing 24 districts, using Global Trachoma Mapping Project methods. A two-stage cluster sampling design was used in each EU, whereby 20 clusters and 60 children per cluster were sampled. Consenting eligible participants (children aged 1-9 years and adults aged ≥50 years) were examined for trachoma., Results: A total of 9391 households were surveyed, and 20,185 participants (98.8% of those enumerated) were examined for trachoma. EU-level TF prevalence in 1-9-year-olds ranged from 0% to 1.6%. In one cluster (in Hà Giang Province), the percentage of children with TF was 10.3%. The overall pattern of cluster-level percentages of children with TF, however, was consistent with an exponential distribution, which would be consistent with trachoma disappearing. Among people aged ≥50 years, prevalence of trichiasis by EU ranged from 0% to 0.75%; these estimates are equivalent to 0-0.13% in all ages. The prevalence of trichiasis unknown to the health system among people aged ≥50 years, by EU, ranged from 0% to 0.17%, which is equivalent to 0-0.03% in all ages., Conclusion: Findings suggest that trachoma is no longer a public health problem in any of the 11 EUs surveyed. However, given the high proportion of children with TF in one cluster in Hà Giang Province, further investigations will be undertaken.

Background: Despite the well-documented clinical efficacy of artemisinin-based combination therapy (ACT) against malaria, the population-level effects of ACT have not been studied thoroughly until recently. An ideal case study for these population-level effects can be found in Vietnam's gradual adoption of artemisinin in the 1990s., Methods and Results: Analysis of Vietnam's national annual malaria reports (1991-2014) revealed that a 10% increase in artemisinin procurement corresponded to a 32.8% (95% CI 27.7-37.5%) decline in estimated malaria cases. There was no consistent national or regional effect of vector control on malaria. The association between urbanization and malaria was generally negative and sometimes statistically significant., Conclusions: The decline of malaria in Vietnam can largely be attributed to the adoption of artemisinin-based case management. Recent analyses from Africa showed that insecticide-treated nets had the greatest effect on lowering malaria prevalence, suggesting that the success of interventions is region-specific. Continuing malaria elimination efforts should focus on both vector control and increased access to ACT.

Background: Currently, it is recognized that water polluted with toxic heavy metal ions may cause serious effects on human health. Therefore, the development of new materials for effective removal of heavy metal ions from water is still a widely important area. Melanin is being considered as a potential material for removal of heavy metal from water., Methods: In this study, we synthesized two melanin-embedded beads from two different melanin powder sources and named IMB (Isolated Melanin Bead originated from squid ink sac) and CMB (Commercial Melanin Bead originated from sesame seeds). These beads were of globular shape and 2-3 mm in diameter. We investigated and compared the sorption abilities of these two bead materials toward hexavalent-chromium (Cr VI ) in water. The isotherm sorption curves were established using Langmuir and Freundlich models in the optimized conditions of pH, sorption time, solid/liquid ratio, and initial concentration of Cr VI . The FITR analysis was also carried out to show the differences in surface properties of these two beads., Results: The optimized conditions for isotherm sorption of Cr VI on IMB/CMB were set at pH values of 2/2, sorption times of 90/300 min, and solid-liquid ratios of 10/20 mg/mL. The maximum sorption capacities calculated based on the Langmuir model were 19.60 and 6.24 for IMB and CMB, respectively. However, the adsorption kinetic of Cr VI on the beads fitted the Freundlich model with R 2 values of 0.992 for IMB and 0.989 for CMB. The deduced Freundlich constant, 1/n, in the range of 0.2-0.8 indicated that these beads are good adsorption materials. In addition, structure analysis data revealed great differences in physical and chemical properties between IMB and CMB. Interestingly, FTIR analysis results showed strong signals of -OH (3295.35 cm - 1 ) and -C=O (1608.63 cm - 1 ) groups harboring on the IMB but not CMB. Moreover, loading of Cr VI on the IMB caused a shift of broad peaks from 3295.35 cm - 1 and 1608.63 cm - 1 to 3354.21 cm - 1 and 1597.06 cm - 1 , respectively, due to -OH and -C=O stretching., Conclusions: Taken together, our study suggests that IMB has great potential as a bead material for the elimination of Cr VI from aqueous solutions and may be highly useful for water treatment applications.

Background: Vietnam has successfully reduced malaria incidence by more than 90% over the past 10 years, and is now preparing for malaria elimination. However, the remaining malaria burden resides in individuals that are hardest to reach, in highly remote areas, where many malaria cases are treated through the informal private sector and are not reported to public health systems. This qualitative study aimed to contextualize and characterize the role of private providers, care-seeking behaviour of individuals at high risk of malaria, as well as risk factors that should be addressed through malaria elimination programmes in Vietnam., Methods: Semi-structured qualitative interviews were conducted with 11 key informants in Hanoi, 30 providers, 9 potential patients, and 11 individuals at risk of malaria in Binh Phuoc and Kon Tum provinces. Audio recorded interviews were transcribed and uploaded to Atlas TI™, themes were identified, from which programmatic implications and recommendations were synthesized., Results: Qualitative interviews revealed that efforts for malaria elimination in Vietnam should concentrate on reaching highest-risk populations in remote areas as well their care providers, in particular private pharmacies, private clinics, and grocery stores. Among these private providers, diagnosis is currently based on symptoms, leaving unconfirmed cases that are not reported to public health surveillance systems. Among at-risk individuals, knowledge of malaria was limited, and individuals reported not taking full courses of treatment, a practice that threatens selection for drug resistance. Access to insecticide-treated hammock nets, a potentially important preventive measure for settings with outdoor biting Anopheles vectors, was also limited., Conclusions: Malaria elimination efforts in Vietnam can be accelerated by targeting improved treatment, diagnosis, and reporting practices to private pharmacies, private clinics, and grocery stores. Programmes should also seek to increase awareness and understanding of malaria among at-risk populations, in particular the importance of using preventive measures and adhering to complete courses of anti-malarial medicines.

Despite Polygonum multiflorum (PM) has been experiencely used as a drug to treat early graying hair phenomenon in Asian countries for a long time, there is limited study examined the real biological effects of PM on hair graying in vitro and in vivo . In this study, we investigated the effects of PM root extract (PM-RE) on melanin synthesis in human melanoma SKMEL-28 cells and embryos/larvae of wild-type strain AB zebrafish. We also preliminary revealed the molecular mechanism of early hair graying phenomenon in both in vitro and in vivo models. Our results showed that PM-RE significantly induced melanin synthesis in melanin-producing SKMEL-28 melanoma cells and also in zebrafish embryos/larvae at 4-day postfertilization through activation of MC1R/MITF/tyrosinase-signaling pathway. We also investigated the differences in genotype between graying hair follicle and black hair follicle of young peoples and found that early hair graying phenomenon may be related to downregulation of MC1R/MITF/tyrosinase pathway. Taken together, we suggested that PM-RE at safe doses could be used as a potential agent for the treatment of early hair graying and other loss pigmentation-related diseases., Competing Interests: There are no conflicts of interest.

To the best of our knowledge, the present study is the first to demonstrate that treatment of vemurafenib-resistant SKMEL28 (SKMEL28-R) cells with paclitaxel leads to a shift in localization of the E3-ligase BBAP from the cytoplasm to the nucleus, consequently decreasing the metastatic ability of this cell line. The present study revealed that the movement of BBAP from the cytoplasm to nucleus initiated a change in cell morphology. In addition, the translocation of BBAP led to a decrease of metastatic characteristics in SKMEL28‑R cells, including migration and invasion via downregulation of the phosphorylated form of focal adhesion kinase and N‑cadherin, as well as an upregulation of p21 and E-cadherin. The results of the present study suggested that BBAP may not only be a novel biomarker for melanoma, but also a novel therapeutic target for treatment of metastatic melanoma.

Since well water utilized for domestic purposes in the Red River Delta of North Vietnam has been reported to be polluted by arsenic, barium, iron, and manganese, household sand filters consisting of various components are used. Information regarding the effectiveness of various sand filters for removal of the four toxic elements in well water is limited. In this study, arsenic levels in 13/20 of well water samples and 1/7 of tap water samples exceeded World Health Organization (WHO) health-based guideline value for drinking water. Moreover, 2/20, 6/20, and 4/20 of well water samples had levels exceeding the present and previous guideline levels for barium, iron, and manganese, respectively. Levels of iron and manganese, but not arsenic, in well water treated by sand filters were lower than those in untreated water, although previous studies showed that sand filters removed all of those elements from water. A low ratio of iron/arsenic in well water may not be sufficient for efficient removal of arsenic from household sand filters. The levels of barium in well water treated by sand filters, especially a filter composed of sand and charcoal, were significantly lower than those in untreated water. Thus, we demonstrated characteristics of sand filters in North Vietnam.

Background: Wound healing has being extensively investigated over the world. Healing impairment is caused by many reasons including increasing of free-radicals-mediated damage, delaying in granulation tissue formation, reducing in angiogenesis and decreasing in collagen reorganization. These facts consequently lead to chronic wound healing. Piper betle Linn (Betle) leaves have been folklore used as an ingredient of drugs for cutaneous wound treatment. However, the effect of betle leaf on wound healing is not yet well elucidated. In this study, we aimed to investigate the healing efficacy of methanol leaf extract of Piper betle Linn on proliferation of fibroblast NIH3T3 cells as well as full-thickness burn and excision wounds in swiss mice., Methods: Scratch wound healing assays were conducted to examine the effects of betle leaf extract on healing activity of fibroblast cells. Burn and excision wounds on swiss mouse skins were created for investigating the wound healing progress caused by the betle leaf extract. Malondialdehyde (MDA) was also evaluated to examine the products of lipid hydroperoxide (LPO) under conditions of with or without betle leaf extract treatment., Results: The results of this study showed that Piper betle Linn leaf extract in methanol increased proliferation of NIH3T3 cells and promoted wound healing in vitro and in vivo with both burn wound and excision wound models. In addition, this extract significant decreased level of malondialdehyde (MDA) in liver of treated-mice compared with that in non-treated mice., Conclusions: Our results suggest that Piper betle Linn can be used as an ingredient in developing natural origin drugs for treatment of cutaneous wounds.

We showed that 2.1% of 233 pieces of lumber debris after the Great East Japan Earthquake was chromated copper arsenate (CCA)-treated wood. Since hexavalent chromium (Cr), copper (Cu) and pentavalent arsenic (As) in the debris may be diffused in the air via incineration, we exposed human lung normal (BEAS-2B) and carcinoma (A549) cells to Cr, Cu and As at the molar ratio in a representative CCA-treated wood. Co-exposure to 0.10 μM Cr and 0.06 μM As, which solely had no effect on colony formation, synergistically promoted colony formation in BEAS-2B cells, but not A549 cells, with activation of the PI3K/AKT pathway. Sole exposure and co-exposure to Cu showed limited effects. Since previous reports showed Cr and As concentrations to which human lungs might be exposed, our results suggest the importance to avoid diffusion of Cr and As in the air via incineration of debris including CCA-treated wood after the disaster., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Deltex-3-like (DTX3L), an E3 ligase, is a member of the Deltex (DTX) family and is also called B-lymphoma and BAL-associated protein (BBAP). Previously, we established RFP/RET-transgenic mice, in which systemic hyperpigmented skin, benign melanocytic tumor(s) and melanoma(s) develop stepwise. Here we showed that levels of Dtx3l/DTX3L in spontaneous melanoma in RFP/RET-transgenic mice and human melanoma cell lines were significantly higher than those in benign melanocytic cells and primarily cultured normal human epithelial melanocytes, respectively. Immunohistochemical analysis of human tissues showed that more than 80% of the melanomas highly expressed DTX3L. Activity of FAK/PI3K/AKT signaling, but not that of MEK/ERK signaling, was decreased in Dtx3l/DTX3L-depleted murine and human melanoma cells. In summary, we demonstrated not only increased DTX3L level in melanoma cells but also DTX3L-mediated regulation of invasion and metastasis in melanoma through FAK/PI3K/AKT but not MEK/ERK signaling. Our analysis in human BRAFV600E inhibitor-resistant melanoma cells showed about 80% decreased invasion in the DTX3L-depleted cells compared to that in the DTX3L-intact cells. Thus, DTX3L is clinically a potential therapeutic target as well as a potential biomarker for melanoma.

Objectives: To identify pre-hospital predictors of a) death or the development of cardiovascular complications during hospitalisation (primary objective) and b) all-cause death during one year of follow-up (secondary objective), in chest pain patients with suspected acute coronary syndrome (ACS)., Methods: A prospective study that comprised patients in western Sweden, who were transported to hospital by the emergency medical service (EMS) due to chest pain and suspected ACS. Multiple logistic regression was used to identify independent predictors of adverse outcomes., Results: Among all 1600 eligible patients, 21% died or had a cardiovascular complication during hospitalisation and 10% died during one year of follow-up. Nine factors were identified pre-hospitalisation as independent predictors of death or cardiovascular complications during hospitalisation. They were increasing age, a history of congestive heart failure, nausea and/or vomiting, rapid breathing rate, low oxygen saturation, high heart rate, together with ST-segment elevation, ST-segment depression and right bundle branch block on the pre-hospital electrocardiogram (ECG). For the secondary objective of death during one year of follow-up, the following five factors were identified as independent predictors: increasing age, a history of congestive heart failure, dyspnea, low oxygen saturation and left bundle branch block on the pre-hospital ECG., Conclusions: In the pre-hospital setting of chest pain and suspected ACS, we identified nine predictors of the primary adverse outcome. They were factors representing previous history, symptoms and ECG findings. This information may contribute to the development of a decision support system for the EMS, which then needs to be clinically tested., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion., (© 2013 Wiley Periodicals, Inc.)

Vemurafenib has recently been used as drug for treatment of melanomas with BRAFV600E mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant BRAFV600E melanoma cell lines, A375PR, A375MR and SKMEL-28R, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-28R cells. Treatment of SKMEL-28R cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-28R were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of BRAFV600E-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.

Aims: The aims of this study were (a) to determine the prehospital prevalence of electrocardiographic (ECG) signs of acute myocardial ischemia in patients with suspected acute coronary syndrome and (b) to describe the relationships between the various ECG patterns and the diagnosis of acute myocardial infarction (AMI) and outcomes., Methods: Prospective cohort study using data from an interventional trial in acute chest pain patients transported by the emergency medical services. These patients were classified into 3 groups: patients with ECG showing signs of acute myocardial ischemia, patients with ECG showing other abnormal changes (bundle-branch block, pacemaker rhythm, Q-wave or T-wave inversion) and patients without significant pathologic findings. All P values are age-adjusted., Results: Among 1546 patients, 312 (20%) had ECG signs of acute myocardial ischemia. Of them, 57% had a final diagnosis of AMI versus 26% of those with other abnormal ECGs and 12% of those with ECG without significant pathologic findings (P<.0001). In all, 53% of all AMI cases involved patients without ECG signs of acute myocardial ischemia. Although ECG signs of acute myocardial ischemia predicted heart failure and ventricular tachyarrhythmias both prior to and after hospital admission, there was no significant difference in 30-day mortality between the 3 patient groups (4.3%, 3.7%, and 1.2%, respectively, P=.11)., Conclusion: Among patients with a clinical suspicion of AMI in the prehospital setting, the prevalence of ECG signs suggesting AMI was low, as was the ability to identify AMI patients using ECG findings only. We therefore need better instruments in the prehospital triage of patients with acute chest pain., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Bidirectional cancer-promoting and anti-cancer effects of arsenic for cancer cells have been revealed in previous studies. However, each of these effects (cancer-promoting or anti-cancer) was found in different cells at different treated-concentration of arsenic. In this study, we for the first time indicated that arsenic at concentration of 3 µM, equal to average concentration in drinking water in cancer-prone areas in Bangladesh, simultaneously expressed its bidirectional effects on human squamous cell carcinoma HSC5 cells with distinct pathways. Treatment with 3 µM of arsenic promoted cell invasion via upregulation of expression of MT1-MMP and downregulation of expression of p14ARF and simultaneously induced cell apoptosis through inhibition of expression of N-cadherin and increase of expression of p21(WAF1/CIP1) at both transcript and protein levels in HSC5 cells. We also showed that inhibition of MT1-MMP expression by NSC405020 resulted in decrease of arsenic-mediated invasion of HSC5 cells involving decrease in phosphorylated extracellular signal-regulated kinases (pERK). Taken together, our biological and biochemical findings suggested that arsenic expressed bidirectional effects as a carcinogen and an anti-cancer agent in human squamous cell carcinoma HSC5 cells with distinct pathways. Our results might play an important scientific evident for further studies to find out a better way in treatment of arsenic-induced cancers, especially in squamous cell carcinoma.

We have modified an existing semi-nested multiplex polymerase chain reaction (PCR) by adding one Plasmodium knowlesi-specific nested PCR, and validated the latter against laboratory and clinical samples. This new method has the advantage of being relatively affordable in low resource settings while identifying the five human Plasmodium species with a three-step PCR.

Objectives: To describe the differences in characteristics and outcome between two consecutive series of patients admitted to hospital with chest pain in a 20-year perspective. Particular emphasis is placed on changes in outcome in relation to the initial electrocardiogram (ECG)., Subjects: In the two periods, 1986-1987 and 2008, all patients with chest pain admitted to the study hospitals in Gothenburg, Sweden, were included., Results: Five thousand and sixteen patients were registered in a period of 21 months in 1986-1987 and 2287 patients were registered during 3 months in 2008. In a comparison of the two time periods, the age of chest pain patients was not significantly different (mean age 60.1 ± 17.8 years in 1986-1987 and 59.8 ± 19.1 years in 2008, p=0.50). There was a lower prevalence of previous angina pectoris, congestive heart failure and current smoking in the second period, whereas a history of acute myocardial infarction, hypertension and diabetes mellitus had become more prevalent. The use of cardio-protective drugs increased and ECG changes indicating acute myocardial ischemia on admission to hospital decreased. Length of hospitalisation was reduced from a median of 5 days to 3 days (p<0.0001). A significant decrease in 30-day and 1-year mortality was found (3.8% in 1986-1987 vs 2.0% in 2008 and 9.9% vs 6.3% respectively, p<0.0001 for both comparisons)., Conclusions: During a period of 20 years, the characteristics and outcome of patients admitted to hospital with chest pain changed. The most important changes were a lower prevalence of ECG signs indicating acute myocardial ischemia on admission, shorter hospitalisation time and a lower 30-day and 1-year mortality., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Despite much success in reducing the burden of malaria in Vietnam, pockets of malaria persist and eliminating them remains an important development goal. In central Vietnam, insecticide-treated hammocks have recently been introduced to help counter the disease in the highly forested, mountainous areas, where other measures have so far been unsuccessful. This study assesses the cost-effectiveness of using long-lasting insecticide-treated hammocks in this area., Methods and Findings: This cost-effectiveness study was run alongside a randomized control trial testing the efficacy of the long-lasting insecticide-treated hammocks. Data were collected through an exit survey, a household survey, expenditure records and key informant interviews. The study estimates that under normal (non-trial) conditions the total net societal cost per malaria episode averted in using long-lasting insecticide-treated hammocks in this area was 126 USD. Cost per hammock, including insecticidal netting, sewing, transport, and distribution was found to be approximately 11.76 USD per hammock. Average savings per episode averted were estimated to be $14.60 USD for the health system and 14.37 USD for households (including both direct and indirect cost savings). The study estimates that the annual financial outlay required of government to implement this type of programme to be 3.40 USD per person covered per year., Conclusion: The study finds that the use of a hammock intervention could represent good value for money to help prevent malaria in more remote areas, where traditional control measures such as insecticide-treated bednets and indoor residual spraying are insufficient or inappropriate to control malaria. However, the life span of the hammock-the number of years over which it effectively deters mosquitoes-has a significant impact on the cost-effectiveness of the intervention and study results should be interpreted in light of the evidence on effectiveness gathered in the years to come.

In Vietnam, Plasmodium falciparum and P. vivax are responsible for most malaria infections, and P. malariae and P. ovale infections are rarely reported. Nevertheless, species-specific polymerase chain reaction analysis on 2,303 blood samples collected during a cross-sectional survey conducted in a forest area of central Vietnam identified 223 (9.7%) P. falciparum, 170 (7.4%) P. vivax, 95 (4.1%) P. malariae, and 19 (0.8%) P. ovale mono-infections and 164 (7.1%) mixed infections. Of the 671 Plasmodium-positive samples by polymerase chain reaction, only 331 were detected by microscopy. Microscopy poorly diagnosed P. malariae, P. ovale, and mixed infections. Clinical and sub-clinical infections occurred in all age groups. The risk for infection and disease decreased with age, probably because of acquired partial immunity. The common occurrence of sub-patent infections seems to indicate that the malaria burden is underestimated and that diagnostic and therapeutic policies should be adapted accordingly.

Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

Background: An appropriate animal model for malignant melanoma could be a strong tool to develop biomarkers through analysis of melanomagenesis., Objective: Development of a novel animal model that spontaneously develops malignant melanoma with a high percentage., Methods: We crossed oncogenic RET (RFP-RET)-carrying transgenic mice of line 304/B6 (RET-mice) with hairless mice (hr/hr) and newly established hairless RFP-RET-transgenic mice of line 304-hr/hr (HL-RET-mice)., Results: The HL-RET-mice developed hyperpigmented skin and benign melanocytic tumors without exception. More importantly, 63.8% (46/72) of the benign tumors were transformed to malignant melanoma in the HL-RET-mice. Mean time until the development of benign melanocytic tumors (2.4 months; n = 102) in the HL-RET-mice was about half of that in the original RET-mice (4.6 months; n = 20). Mean life span in the HL-RET-mice (9.7 months; n = 38) was also significantly (p < 0.01) shorter than that in the original RET-mice (10.8 months; n = 20). Since early development of tumors could contribute to shortening of the research period, HL-RET-mice could be a useful model for analysis of melanomagenesis. We then found that the expression level of Mps one binder kinase activator-like-2B (Mobkl2b) in benign tumors was higher than that in malignant melanoma in HL-RET-mice. Expression level of MOBKL2B in malignant melanoma cell lines was also lower than that in non-malignant melanocytic cells in mice and humans, suggesting that MOBKL2B could be a novel marker for malignant melanoma., Conclusion: We established a novel hairless RET-transgenic mouse line spontaneously developing cutaneous malignant melanomas from benign melanocytic tumors. This mouse model may be useful to find new candidates of melanoma-related molecule., (Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Cutaneous malignant melanoma is one of the most serious skin cancers and is highly invasive and markedly resistant to conventional therapy. Melanomagenesis is initially triggered by environmental agents including ultraviolet (UV), which induces genetic/epigenetic alterations in the chromosomes of melanocytes. In human melanomas, the RAS/RAF/MEK/ERK (MAPK) and the PI3K/PTEN/AKT (AKT) signaling pathways are two major signaling pathways and are constitutively activated through genetic alterations. Mutations of RAF, RAS, and PTEN contribute to antiapoptosis, abnormal proliferation, angiogenesis, and invasion for melanoma development and progression. To find better approaches to therapies for patients, understanding these MAPK and AKT signaling mechanisms of melanoma development and progression is important. Here, we review MAPK and AKT signaling networks associated with melanoma development and progression.

Aims: To present a new approach for estimating the "true prevalence" of malaria and apply it to datasets from Peru, Vietnam, and Cambodia., Methods: Bayesian models were developed for estimating both the malaria prevalence using different diagnostic tests (microscopy, PCR & ELISA), without the need of a gold standard, and the tests' characteristics. Several sources of information, i.e. data, expert opinions and other sources of knowledge can be integrated into the model. This approach resulting in an optimal and harmonized estimate of malaria infection prevalence, with no conflict between the different sources of information, was tested on data from Peru, Vietnam and Cambodia., Results: Malaria sero-prevalence was relatively low in all sites, with ELISA showing the highest estimates. The sensitivity of microscopy and ELISA were statistically lower in Vietnam than in the other sites. Similarly, the specificities of microscopy, ELISA and PCR were significantly lower in Vietnam than in the other sites. In Vietnam and Peru, microscopy was closer to the "true" estimate than the other 2 tests while as expected ELISA, with its lower specificity, usually overestimated the prevalence., Conclusions: Bayesian methods are useful for analyzing prevalence results when no gold standard diagnostic test is available. Though some results are expected, e.g. PCR more sensitive than microscopy, a standardized and context-independent quantification of the diagnostic tests' characteristics (sensitivity and specificity) and the underlying malaria prevalence may be useful for comparing different sites. Indeed, the use of a single diagnostic technique could strongly bias the prevalence estimation. This limitation can be circumvented by using a Bayesian framework taking into account the imperfect characteristics of the currently available diagnostic tests. As discussed in the paper, this approach may further support global malaria burden estimation initiatives.

Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl(2)) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5-50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5-5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro.

Various environmental and genetic factors affect the development and progression of skin cancers including melanoma. Melanoma development is initially triggered by environmental factors including ultraviolet (UV) light, and then genetic/epigenetic alterations occur in skin melanocytes. These first triggers alter the conditions of numerous genes and proteins, and they induce and/or reduce gene expression and activate and/or repress protein stability and activity, resulting in melanoma progression. Microphthalmia-associated transcription factor (MITF) is a master regulator gene of melanocyte development and differentiation and is also associated with melanoma development and progression. To find better approaches to molecular-based therapies for patients, understanding MITF function in skin melanoma development and progression is important. Here, we review the molecular networks associated with MITF in skin melanoma development and progression.

We examined the biochemical effects of arsenic on the activities of RET proto-oncogene (c-RET protein tyrosine kinases) and RET oncogene (RET-MEN2A and RET-PTC1 protein tyrosine kinases) products. Arsenic activated c-RET kinase with promotion of disulfide bond-mediated dimerization of c-RET protein. Arsenic further activated RET-MEN2A kinase, which was already 3- to 10-fold augmented by genetic mutation compared with c-RET kinase activity, with promotion of disulfide bond-mediated dimerization of RET-MEN2A protein (superactivation). Arsenic also increased extracellular domain-deleted RET-PTC1 kinase activity with promotion of disulfide bond-mediated dimerization of RET-PTC1 protein. Arsenic increased RET-PTC1 kinase activity with cysteine 365 (C365) replaced by alanine with promotion of dimer formation but not with cysteine 376 (C376) replaced by alanine. Our results suggest that arsenic-mediated regulation of RET kinase activity is dependent on conformational change of RET protein through modulation of a special cysteine sited at the intracellular domain in RET protein (relevant cysteine of C376 in RET-PTC1 protein). Moreover, arsenic enhanced the activity of immunoprecipitated RET protein with increase in thiol-dependent dimer formation. As arsenic (14.2 microM) was detected in the cells cultured with arsenic (100 microM), direct association between arsenic and RET in the cells might modulate dimer formation. Thus, we demonstrated a novel redox-linked mechanism of activation of arsenic-mediated RET proto-oncogene and oncogene products., ((c) 2010 Wiley-Liss, Inc.)

Fourteen published and three newly identified polymorphic microsatellites were used to genotype 69 Plasmodium vivax samples obtained from 39 patients detected over a period of two years who lived in a rural community of central Vietnam. All samples were polyclonal with an average expected heterozygosity of 0.86. Among the 39 patients, 16 experienced 1-5 recurrent episodes of P. vivax malaria, most of them (83%) with a different genotype profile compared with previous infections. The minimal set of microsatellites required for differentiating the genotype profiles of the recurrent infections compared with the full set of 17 microsatellites was explored. A combination of five markers was sufficient to identify all recurrent infections with an unrelated or different genotype profile compared with all previous episodes.

Background: In Vietnam, malaria remains a problem in some remote areas located along its international borders and in the central highlands, partly due to the bionomics of the local vector, mainly found in forested areas and less vulnerable to standard control measures. Long Lasting Insecticidal Hammocks (LLIH), a tailored and user-friendly tool for forest workers, may further contribute in reducing the malaria burden. Their effectiveness was tested in a large community-based intervention trial carried out in Ninh Thuan province in Central Vietnam., Methods and Findings: Thirty villages (population 18,646) were assembled in 20 clusters (1,000 individuals per cluster) that were randomly allocated to either the intervention or control group (no LLIH) after stratification according to the pre-intervention P. falciparum antibody prevalence (<30%; > or =30%). LLIH were distributed to the intervention group in December 2004. For the following 2 years, the incidence of clinical malaria and the prevalence of infection were determined by passive case detection at community level and by bi-annual malariometric surveys. A 2-fold larger effect on malaria incidence in the intervention as compared to the control group was observed. Similarly, malaria prevalence decreased more substantially in the intervention (1.6-fold greater reduction) than in the control group. Both for incidence and prevalence, a stronger and earlier effect of the intervention was observed in the high endemicity stratum. The number of malaria cases and infections averted by the intervention overall was estimated at 10.5 per 1,000 persons and 5.6/100 individuals, respectively, for the last half of 2006. In the high endemicity stratum, the impact was much higher, i.e. 29/1000 malaria cases and 15.7 infections/100 individuals averted., Conclusions: LLIH reduced malaria incidence and prevalence in this remote and forested area of Central Vietnam. As the targets of the newly-launched Global Malaria Action Plan include the 75% reduction of the global malaria cases by 2015 and eventually the elimination/eradication of malaria in the long term, LLIH may represent an additional tool for reaching such objectives, particularly in high endemicity areas where standard control tools have a modest impact, such as in remote and forested areas of Southeast Asia and possibly South America., Trial Registration: ClinicalTrials.gov NCT00853281.