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RATIONALE & OBJECTIVE: Acute kidney injury (AKI) carries high rates of morbidity and mortality. This study quantified various short- and long-term outcomes after hospitalization with AKI. STUDY DESIGN: Retrospective propensity score (PS)-matched cohort study. SETTING & PARTICIPANTS: Optum Clinformatics, a national claims database, was used to identify patients hospitalized with and without an AKI discharge diagnosis between January 2007 and September 2020. EXPOSURE: Among patients with prior continuous enrollment for at least 2years without AKI hospitalization, 471,176 patients hospitalized with AKI were identified and PS-matched to 471,176 patients hospitalized without AKI. OUTCOME(S): All-cause and selected-cause rehospitalizations and mortality 90 and 365 days after index hospitalization. ANALYTICAL APPROACH: After PS matching, rehospitalization and death incidences were estimated using the cumulative incidence function method and compared using Gray's test. The association of AKI hospitalization with each outcome was tested using Cox models for all-cause mortality and, with mortality as competing risk, cause-specific hazard modeling for all-cause and selected-cause rehospitalization. Overall and stratified analyses were performed to evaluate for interaction between an AKI hospitalization and preexisting chronic kidney disease (CKD). RESULTS: After PS matching, AKI was associated with higher rates of rehospitalization for any cause (hazard ratio [HR], 1.62; 95% CI, 1.60-1.65), end-stage renal disease (HR, 6.21; 95% CI, 1.04-36.92), heart failure (HR, 2.81; 95% CI, 2.66, 2.97), sepsis (HR, 2.62; 95% CI, 2.49-2.75), pneumonia (HR, 1.47; 95% CI, 1.37-1.57), myocardial infarction (HR, 1.48; 95% CI, 1.33-1.65), and volume depletion (HR, 1.64; 95% CI, 1.37-1.96) at 90 days after discharge compared with the group without AKI, with similar findings at 365 days. Mortality rate was higher in the group with AKI than in the group without AKI at 90 (HR, 2.66; 95% CI, 2.61-2.72) and 365 days (HR, 2.11; 95% CI, 2.08-2.14). The higher risk of outcomes persisted when participants were stratified by CKD status (P<0.01). LIMITATIONS: Causal associations between AKI and the reported outcomes cannot be inferred. CONCLUSIONS: AKI during hospitalization in patients with and without CKD is associated with increased risk of 90- and 365-day all-cause/selected-cause rehospitalization and death.
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Injúria Renal Aguda , Insuficiência Renal Crônica , Humanos , Readmissão do Paciente , Estudos de Coortes , Estudos Retrospectivos , Hospitalização , Insuficiência Renal Crônica/epidemiologia , Injúria Renal Aguda/diagnóstico , Fatores de RiscoRESUMO
GroES/GroEL is the only bacterial chaperone essential under all conditions, making it a potential antibiotic target. Rationally targeting ESKAPE GroES/GroEL as an antibiotic strategy necessitates studying their structure and function. Herein, we outline the structural similarities between Escherichia coli and ESKAPE GroES/GroEL and identify significant differences in intra- and inter-ring cooperativity, required in the refolding cycle of client polypeptides. Previously, we observed that one-half of ESKAPE GroES/GroEL family members could not support cell viability when each was individually expressed in GroES/GroEL-deficient E. coli cells. Cell viability was found to be dependent on the allosteric compatibility between ESKAPE and E. coli subunits within mixed (E. coli and ESKAPE) tetradecameric GroEL complexes. Interestingly, differences in allostery did not necessarily result in differences in refolding rate for a given homotetradecameric chaperonin. Characterization of ESKAPE GroEL allostery, ATPase, and refolding rates in this study will serve to inform future studies focused on inhibitor design and mechanism of action studies.
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Sítio Alostérico , Proteínas de Escherichia coli/química , Proteínas de Choque Térmico/química , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Regulação Alostérica , Chaperonina 10/química , Chaperonina 10/genética , Chaperonina 10/metabolismo , Escherichia coli , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismoRESUMO
BACKGROUND: To enhance malaria elimination, Vietnam adopted a Reactive Surveillance and Response (RASR) Strategy in which malaria case notification and investigation must be completed within 2 days followed by a focus investigation within 7 days. The nationwide performance of Vietnam's RASR strategy has yet to be evaluated. This study aims to evaluate the performance and feasibility of RASR in Vietnam, thereby providing recommendations for improved RASR. METHODS: To assess malaria RASR in Vietnam, a mixed-methods study of (1) secondary data analysis of nationwide malaria case-based dataset from 2017 to 2021; (2) a quantitative survey, and (3) qualitative in-depth interviews and focus group discussions administered to central, provincial and district level stakeholders/staff and to the commune and community level front line health services providers was conducted. RESULTS: In Vietnam, there are guidelines and procedures for implementation of each step of RASR. The completeness of case notification on the reported monthly aggregated data was very high in both the paper-based (12,463/12,498, 99.7% in 2017-2020) and electronic reporting systems (467/467, 100% in 2021 when electronic reporting was introduced); however, there were delays in notification while using the paper-based system (timely notification-7,978/12,498, 63.8%). In 2021, the completeness (453/467, 97.0%) and timeliness (371/467, 79.4%) of case investigation were found to be high. Reactive case detection was the major focus investigation response, with fever screening achievement of 88.6% (11,481 / 12,965) and 88.5% (11,471 / 12,965) among index case and neighbouring household members, respectively. CONCLUSIONS: Overall, there was policy commitment for implementation of RASR in Vietnam. The completeness and timeliness of case notification and case investigation were high and improved after the introduction of the electronic reporting system. More evidence is required for reactive case detection in defining the screening area or population.
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Malária , Humanos , Vietnã/epidemiologia , Estudos de Viabilidade , Malária/epidemiologia , Malária/prevenção & controle , Malária/diagnóstico , Serviços de Saúde Comunitária , Projetos de PesquisaRESUMO
Image-based ship detection is a critical function in maritime security. However, lacking high-quality training datasets makes it challenging to train a robust supervision deep learning model. Conventional methods use data augmentation to increase training samples. This approach is not robust because the data augmentation may not present a complex background or occlusion well. This paper proposes to use an information bottleneck and a reparameterization trick to address the challenge. The information bottleneck learns features that focus only on the object and eliminate all backgrounds. It helps to avoid background variance. In addition, the reparameterization introduces uncertainty during the training phase. It helps to learn more robust detectors. Comprehensive experiments show that the proposed method outperforms conventional methods on Seaship datasets, especially when the number of training samples is small. In addition, this paper discusses how to integrate the information bottleneck and the reparameterization into well-known object detection frameworks efficiently.
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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.
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Malária Falciparum , Plasmodium falciparum , Humanos , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Deleção de Genes , Vietnã/epidemiologia , Testes Diagnósticos de Rotina/métodos , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Malária Falciparum/genética , Antígenos de Protozoários/genética , Antígenos de Protozoários/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
This study examines the projected precipitation extremes for the end of 21st century (2081-2100) over Southeast Asia (SEA) using the output of the Southeast Asia Regional Climate Downscaling/Coordinated Regional Climate Downscaling Experiment - Southeast Asia (SEACLID/CORDEX-SEA). Eight ensemble members, representing a subset of archived CORDEX-SEA simulations at 25 km spatial resolution, were examined for emission scenarios of RCP4.5 and RCP8.5. The study utilised four different indicators of rainfall extreme, i.e. the annual/seasonal rainfall total (PRCPTOT), consecutive dry days (CDD), frequency of extremely heavy rainfall (R50mm) and annual/seasonal maximum of daily rainfall (RX1day). In general, changes in extreme indices are more pronounced and covering wider area under RCP8.5 than RCP4.5. The decrease in annual PRCPTOT is projected over most of SEA region, except for Myanmar and Northern Thailand, with magnitude as much as 20% (30%) under RCP4.5 (RCP8.5) scenario. The most significant and robust changes were noted in CDD, which is projected to increase by as much as 30% under RCP4.5 and 60% under RCP8.5, particularly over Maritime Continent (MC). The projected decrease in PRCPTOT over MC is significant and robust during June to August (JJA) and September to November (SON). During March to May (MAM) under RCP8.5, significant and robust PRCPTOT decreases are also projected over Indochina. The CDD changes during JJA and SON over MC are even higher, more robust and significant compared to the annual changes. At the same time, a wetting tendency is also projected over Indochina. The R50mm and RX1day are projected to increase, during all seasons with significant and robust signal of RX1day during JJA and SON.
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Mudança Climática , Sudeste Asiático , Mianmar , Estações do Ano , TailândiaRESUMO
We demonstrate an advanced approach using state of the art inâ situ transmission electron microscopy (TEM) to understand the interplay between nanostructures and thermoelectric (TE) properties of high-performance Mg-doped Zn4 Sb3 TE systems. By using the technique, microstructure and crystal evolutions of TE material have been dynamically captured as a function of temperature from 300â K to 573â K. On heating, we have clearly observed precipitation and growth of a Zn-rich secondary phase as nanoinclusions in the matrix of primary Zn4 Sb3 phase. Elemental mapping by STEM-EDX spectroscopy reveals enrichment of Zn in the secondary Zn6 Sb5 nanoinclusions during the thermal processing without decomposition. Such nanostructures strongly enhances phonon scattering, resulting in a decrease in the thermal conductivity leading to a zT value of 1.4 at 718â K.
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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.
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Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária/epidemiologia , Malária/prevenção & controle , Controle de Mosquitos , Plasmodium/efeitos dos fármacos , Administração de Caso , Incidência , Vietnã/epidemiologiaRESUMO
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.
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Malária/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Setor Privado/estatística & dados numéricos , Adulto , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa , Fatores de Risco , Vietnã , Adulto JovemRESUMO
In recent years, outbreaks of infectious diseases caused by pathogenic micro-organisms pose a serious threat to public health. In this work, Fe3O4-Ag hybrid nanoparticles were synthesized by simple chemistry method and these prepared nanoparticles were used to investigate their antibacterial properties and mechanism against methicilline-resistant Staphylococcus aureus (MRSA) pathogen. The formation of dimer-like nanostructure of Fe3O4-Ag hybrid NPs was confirmed by X-ray diffraction and High-resolution Transmission Electron Microscopy. Our biological analysis revealed that the Fe3O4-Ag hybrid NPs showed more noticeable bactericidal activity than that of plain Fe3O4 NPs and Ag-NPs. We suggest that the enhancement in bactericidal activity of Fe3O4-Ag hybrid NPs might be likely from main factors such as: (i) enhanced surface area property of hybrid nanoparticles; (ii) the high catalytic activity of Ag-NPs with good dispersion and aggregation stability due to the iron oxide magnetic carrier, and (iii) large direct physical contacts between the bacterial cell membrane and the hybrid nanoparticles. The superparamagnetic hybrid nanoparticles of iron oxide magnetic nanoparticles decorated with silver nanoparticles can be a potential candidate to effectively treat infectious MRSA pathogen with recyclable capability, targeted bactericidal delivery and minimum release into environment.
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Antibacterianos/química , Antibacterianos/farmacologia , Nanopartículas de Magnetita/química , Nanopartículas Metálicas/química , Viabilidade Microbiana/efeitos dos fármacos , Nanotecnologia , Prata/química , Processos Fotoquímicos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
These days, photodetectors are a crucial part of optoelectronic devices, ranging from environmental monitoring to international communication systems. Therefore, fabricating these devices at a low cost but obtaining high sensitivity in a wide range of wavelengths is of great interest. This report introduces a simple solution-processed hybrid 2D structure of CuO and rGO for broadband photodetector applications. Particularly, 2D CuO acts as the active material, absorbing light to generate electron-hole pairs, while 2D rGO plays the role of a transport layer, driving charge carriers between two electrodes. Our device exhibits remarkable sensitivity to a wide wavelength range from 395 nm to 945 nm (vis-NIR region). Interestingly, our devices' responsivity and photoconductive gain were calculated (under 395 nm wavelength excitation) to be up to 8 mA W-1 and 28 fold, respectively, which are comparable values with previous publications. Our hybrid 2D structure between rGO and CuO enables a potential approach for developing low-cost but high-performance optoelectronic devices, especially photodetectors, in the future.
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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.
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Aim: To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN). Methods: We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye. Results: The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients. Conclusion: Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients.
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This work presented the design and fabrication of a blood vessel and breast tumor detection device (BKA-06) based on optical energy spectroscopy. The BKA-06 device uses red-to-near-infrared light-emitting diodes that allow physicians or physicians to visualize blood vessels and surface structures such as breast tumors with the naked eye. The device consists of a built-in current control circuit to have the appropriate brightness (maximum illuminance of 98,592 lux) for the examination of superficial tumors deep under the skin, with a scan time of 3-5 min. The device BKA-06 can facilely observe each layer of blood vessels at the depth of the skin. For breast tumors, the location, size, and invasive areas around the tumor can also be visualized with the naked eye using the BKA-06 sensor. The results show that the BKA-06 sensor can provide clear breast tumor and vascular images, with a penetration of up to 15 cm in the skin and tissue layers of the breast. The breast tumor scanning tests with the BKA-06 sensor gave patients quick results and compared them through cell biopsy and MRI, respectively. The device has the advantages of being simple and easy to use, providing potential practical applications in the medical field and reducing costs for patients when taking MRI or CT scans. Therefore, the BKA-06 device is expected to help doctors and medical staff overcome difficulties in infusion, as well as identify breast tumors to support early breast cancer diagnosis and treatment.
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High-resolution climate projections are mandatory for many applications and impact assessments in environmental and management studies. In response to the needs in Vietnam, this study constructs a new precipitation and temperature daily dataset for Vietnam, at a high spatial resolution of 0.1° × 0.1°, based on the outputs of 35 global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6). The Bias Correction and Spatial Disaggregation (BCSD) method is adopted to bias-correct monthly GCM simulations using observation data, then subsequently temporally disaggregate them into daily data. The new dataset is called CMIP6-VN, covering the present-time period 1980-2014 and future projections for 2015-2099 from both CMIP6 tier-1 (Shared Socioeconomic Pathways (SSPs) 1-1.26, 2-4.5, 3-7.0, and 5-8.5) and tier-2 (SSPs 1-1.9, 4-3.4, 4-6.0) experiments. Results indicated the good performance of CMIP6-VN for the historical period, suggesting that the dataset could be used for studies on climate change assessment and impacts in Vietnam.
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Optoelectronic devices have various applications in medical equipment, sensors, and communication systems. Photodetectors, which convert light into electrical signals, have gained much attention from many research teams. This study describes a low-cost photodetector based on CuO nanoparticles and ZnO nanorods operating in a wide range of light wavelengths (395, 464, 532, and 640 nm). Particularly, under 395 nm excitation, the heterostructure device exhibits high responsivity, photoconductive gain, detectivity, and sensitivity with maximum values of 1.38 A·W-1, 4.33, 2.58 × 1011 Jones, and 1934.5% at a bias of 2 V, respectively. The sensing mechanism of the p-n heterojunction of CuO/ZnO is also explored. Overall, this study indicates that the heterostructure of CuO nanoparticles and ZnO nanorods obtained via a simple and cost-effective synthesis process has great potential for optoelectronic applications.
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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.
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Antimaláricos , Malária Vivax , Malária , Humanos , Antimaláricos/uso terapêutico , Avena , Malária/diagnóstico , Malária/epidemiologia , Malária/prevenção & controle , Malária Vivax/diagnóstico , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , ÁsiaRESUMO
A pulldown using a biotinylated natural product of interest in the 17ß-hydroxywithanolide (17-BHW) class, physachenolide C (PCC), identified the bromodomain and extra-terminal domain (BET) family of proteins (BRD2, BRD3, and BRD4), readers of acetyl-lysine modifications and regulators of gene transcription, as potential cellular targets. BROMOscan bromodomain profiling and biochemical assays support PCC as a BET inhibitor with increased selectivity for bromodomain (BD)-1 of BRD3 and BRD4, and X-ray crystallography and NMR studies uncovered specific contacts that underlie the potency and selectivity of PCC toward BRD3-BD1 over BRD3-BD2. PCC also displays characteristics of a molecular glue, facilitating proteasome-mediated degradation of BRD3 and BRD4. Finally, PCC is more potent than other withanolide analogues and gold-standard pan-BET inhibitor (+)-JQ1 in cytotoxicity assays across five prostate cancer (PC) cell lines regardless of androgen receptor (AR)-signaling status.
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Fatores de Transcrição , Vitanolídeos , Masculino , Humanos , Proteínas Nucleares , Domínios Proteicos , Proteínas de Ciclo CelularRESUMO
Photodetectors are essential elements for various applications like fiber optic communication systems, biomedical imaging, and so on. Thus, improving the performance and reducing the material costs of photodetectors would act as a motivation toward the future advancement of those applications. This study introduces the development of a nanohybrid of zinc oxide nanorods (ZnONRs) and multi-shaped silver nanoparticles MAgNPs through a simple solution process; in which ZnONRs are hybridized with MAgNPs to enable visible absorption through the surface plasmon resonance (SPR) effect. The photodetector based on ZnONRs/MAgNPs is responsive to visible light with representative wavelengths of 395, 464, 532 and 640 nm, and it exhibits high responsivity (R), photoconductive gain (G) and detectivity (D). The maximum R is calculated from the fitting curve of the responsivity-power relation with the value of 5.35 × 103 (mA W-1) at 395 nm excitation. The highest G and D reach 8.984 and 3.71 × 1010 Jones at that wavelength. This reveals the promise of our innovative broadband photodetector for practical usage.
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OBJECTIVE: To report methods and results from a national sample mortality surveillance programme implemented in Viet Nam in 2009. METHODS: A national sample of 192 communes located in 16 provinces and covering a population of approximately 2.6 million was selected using multi-stage cluster sampling. Deaths for 2009 were identified from several local data sources. Record reconciliation and capture-recapture methods were used to compile data and assess completeness of the records. Life tables were computed using reported and adjusted age-specific death rates. Each death was followed up by verbal autopsy to ascertain the probable cause(s) of death. Underlying causes were certified and coded according to international guidelines. FINDINGS: A total of 9921 deaths were identified in the sample population. Completeness of death records was estimated to be 81%. Adjusted life expectancies at birth were 70.4 and 78.7 years for males and females, respectively. Stroke was the leading cause of death in both sexes. Other prominent causes were road traffic accidents, cancers and HIV infection in males, and cardiovascular conditions, pneumonia and diabetes in females. CONCLUSION: Viet Nam is undergoing the epidemiological transition. Although data are relatively complete, they could be further improved through strengthened local collaboration. Medical certification for deaths in hospitals, and shorter recall periods for verbal autopsy interviews would improve cause of death ascertainment.