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OBJECTIVE: Develop a novel technique to identify an optimal number of regression units corresponding to a single risk point, while creating risk scoring systems from logistic regression-based disease predictive models. The optimal value of this hyperparameter balances simplicity and accuracy, yielding risk scores of small scale and high accuracy for patient risk stratification. MATERIALS AND METHODS: The proposed technique applies an adapted line search across all potential hyperparameter values. Additionally, DeLong test is integrated to ensure the selected value produces an accuracy insignificantly different from the best achievable risk score accuracy. We assessed the approach through two case studies predicting diabetic retinopathy (DR) within six months and hip fracture readmissions (HFR) within 30 days, involving cohorts of 90 400 diabetic patients and 18 065 hip fracture patients. RESULTS: Our scores achieve accuracies insignificantly different from those obtained by existing approaches, reaching AUROCs of 0.803 and 0.645 for DR and HFR predictions, respectively. Regarding the scale, our scores ranged 0-53 for DR and 0-15 for HFR, while scores produced by existing methods frequently spanned hundreds or thousands. DISCUSSION: According to the assessment, our risk scores offer simple and accurate predictions for diseases. Furthermore, our new DR score provides a competitive alternative to state-of-the-art risk scores for DR, while our HFR case study presents the first risk score for this condition. CONCLUSION: Our technique offers a generalizable framework for crafting precise risk scores of compact scales, addressing the demand for user-friendly and effective risk stratification tool in healthcare.
Subject(s)
Diabetic Retinopathy , Hip Fractures , Patient Readmission , Humans , Diabetic Retinopathy/diagnosis , Risk Assessment/methods , Logistic Models , Female , Male , AgedABSTRACT
Microplastics (MPs, plastic items from 1 µm to 5 mm in size) are present in all environmental compartments. The evaluation of their concentration, fate, and spatial distribution is still a challenge for the scientific community. This concern is just debuting in developing countries, (i.e., Asia, South America, and Africa). This study deals with the MP contamination in the abiotic marine compartments of Northern Vietnam: seawater and intertidal sediments. Four sites located in the intertidal zone or near the coastline in Tonkin Bay, Vietnam were studied. A total of 16 samples (eight for each compartment) were collected in July 2020 (rainy season) and January 2021 (dry season). Anthropogenic particles (total observed fibers and fragments) were found at levels ranging from 3 to 303 particles/m3 in seawater and from 63 to 955 particles/kg dry weight in sediments. Most of these were fibers less than 300-µm long. Higher levels of seawater at the Nam Dinh site were found in the rainy season compared to the dry one. As the river flow was estimated six times higher during the rainy season than during the dry season, these results suggest the river discharge is a potential source of contamination for the coastal zone. The temporal variability was lower for the sediments than for the seawater, suggesting the long-term integration of the anthropogenic particles in this compartment. A small portion of sorted particles were analyzed by µFTIR (8.35%), and this sub-sample was only composed of fragments. Still, fragments were mostly composed of polypropylene (PP, 82%), polyethylene (PE, 9%), and polystyrene (PS, 9%). The fragment size was similar in the two studied compartments, but it was dependent on polymer types since PS fragments (140 ± 17 µm) were smaller than those made of PE (622 ± 123 µm) and PP (869 ± 905 µm). Future works should investigate the smallest fraction of MP (even nanoplastics) as well as find solutions in order to mitigate MP contamination in the marine environment.
Subject(s)
Bays , Environmental Monitoring , Geologic Sediments , Microplastics , Seawater , Water Pollutants, Chemical , Vietnam , Seawater/chemistry , Geologic Sediments/chemistry , Water Pollutants, Chemical/analysis , Microplastics/analysisABSTRACT
BACKGROUND: Accurate diagnosis and subsequent delineated treatment planning require the experience of clinicians in the handling of their case numbers. However, applying deep learning in image processing is useful in creating tools that promise faster high-quality diagnoses, but the accuracy and precision of 3-D image processing from 2-D data may be limited by factors such as superposition of organs, distortion and magnification, and detection of new pathologies. The purpose of this research is to use radiomics and deep learning to develop a tool for lung cancer diagnosis. METHODS: This study applies radiomics and deep learning in the diagnosis of lung cancer to help clinicians accurately analyze the images and thereby provide the appropriate treatment planning. 86 patients were recruited from Bach Mai Hospital, and 1012 patients were collected from an open-source database. First, deep learning has been applied in the process of segmentation by U-NET and cancer classification via the use of the DenseNet model. Second, the radiomics were applied for measuring and calculating diameter, surface area, and volume. Finally, the hardware also was designed by connecting between Arduino Nano and MFRC522 module for reading data from the tag. In addition, the displayed interface was created on a web platform using Python through Streamlit. RESULTS: The applied segmentation model yielded a validation loss of 0.498, a train loss of 0.27, a cancer classification validation loss of 0.78, and a training accuracy of 0.98. The outcomes of the diagnostic capabilities of lung cancer (recognition and classification of lung cancer from chest CT scans) were quite successful. CONCLUSIONS: The model provided means for storing and updating patients' data directly on the interface which allowed the results to be readily available for the health care providers. The developed system will improve clinical communication and information exchange. Moreover, it can manage efforts by generating correlated and coherent summaries of cancer diagnoses.
Subject(s)
Deep Learning , Lung Neoplasms , Tomography, X-Ray Computed , Humans , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Male , Female , Middle Aged , Aged , Lung/diagnostic imaging , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methodsABSTRACT
Background: In Vietnam, lung cancer ranks second among common types of cancer. Although there have been many advances in the diagnosis and treatment of lung cancer, it is still one of the deadliest types of cancer. Objective: We investigated the prognostic value of pretreatment white blood cell (WBC) and platelet counts of patients with lung cancer. Methods: This was a prospective, descriptive study with longitudinal follow-up. Data from 203 patients with stage IIIA-IV lung cancer presenting at Can Tho City Oncology Hospital between June 2020 and June 2022 were analyzed. Complete blood cell counts were obtained using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. The optimal overall survival cutoff point for pretreatment WBC and platelet counts was determined using maximally selected rank statistics. Results: The median follow-up was 6 (interquartile range 4-8) months and the median age was 61.3 years. The number of male patients was higher than the number of female patients. Most (71.4%) patients had adenocarcinoma; 62.1% of the patients had a WBC count of > 10 × 109/L and 38.4% had a platelet count of > 400 × 109/L. The median overall survival (OS) of all patients was 8 months. The 3-month, 6-month, and 1-year OS was 88.7%, 62.4%, and 28.3%, respectively. Patients with a WBC count of <9.18 × 109/L had a higher OS than those with a count of ≥ 9.18 × 109/L (17 months versus 8 months; p < 0.001) Patients with a platelet count of < 453 × 109/L had a higher OS than those with a count of ≥ 453 × 109/L (8 months versus 7 months; p < 0.001). Conclusion: White blood cell and platelet count tests are routine investigations that are valuable, in combination with other factors, for predicting OS of lung cancer patients. They can help clinicians to monitor treatment response and survival.
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Three-dimensional (3D) cell culture systems are becoming increasingly popular due to their ability to mimic the complex process of angiogenesis in cancer, providing more accurate and physiologically relevant data than traditional two-dimensional (2D) cell culture systems. Microwell systems are particularly useful in this context as they provide a microenvironment that more closely resembles the in vivo environment than traditional microwells. Poly(ethylene glycol) (PEG) microwells are particularly advantageous due to their bio-inertness and the ability to tailor their material characteristics depending on the PEG molecular weight. Although there are several methods available for microwell fabrication, most of them are time-consuming and expensive. The current study utilizes a low-cost laser etching technique on poly(methyl methacrylate) materials followed by molding with PDMS to produce microwells. The optimal conditions for making concave microwells are an engraving parameter speed of 600 mm/s, power of 20%, and a design diameter of the microwell of 0.4 mm. The artificial tumor achieved its full size after 7 days of cell growth in a microwell system, and the cells developed drugs through a live/dead assay test. The results of the drug testing revealed that the IC50 value of zerumbone-loaded liposomes in HepG2 was 4.53 pM, which is greater than the IC50 value of zerumbone. The HepG2 cancer sphere's 3D platform for medication testing revealed that zerumbone-loaded liposomes were very effective at high doses. These findings generally imply that zerumbone-loaded liposomes have the capacity to target the liver and maintain medication delivery.
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Despite the global threat of antimicrobial resistance (AMR), evidence on the use and quality of medicines at community level is limited, particularly in impoverished, rural areas where prevalence of (bacterial) infections is high. To better understand the processes that drive vulnerability to AMR' effects, this study aimed to assess social factors underpinning access to-and use of-medical products and healthcare, among people from the Raglai ethnic minority in Ninh Thuan Province, Vietnam. We conducted ethnographic research in eight villages in 2018-2019, using interviewing and participant observation methods for data collection. Different types of informants (including community members and healthcare providers) were selected using purposive sampling strategies and analysis was retroductive. Our findings show that, despite the existence of a government-funded health insurance scheme, Raglai people's flexible therapeutic itineraries did not systematically start with formal healthcare. Different types of care (private/informal, public, shamanic) were combined in parallel or in alternation, determined by distance to the provider, cost, workload, perceived diagnostic capacity, perceived severity and aetiology of the illness, and trust in the provider. Available medicines were often tablets dispensed in plastic bags containing labelled tablets, unlabelled tablets (in bulk) or tablets ground to powder. Treatment was often considered effective when it relieved symptoms, which led to abandonment of the treatment course. When symptoms did not speedily abate, the illness aetiology would be reinterpreted, and "stronger" medicines would be sought. The precarious socio-economic status of some Raglai drove them in cycles of severe poverty when additional unforeseen factors such as illness, animal disease or loss of crops arose, hampering access to (in)formal healthcare providers and/or appropriate diagnosis and treatment. We conclude that Raglai communities are structurally unable to buffer themselves against the threat and consequences of AMR. Despite this vulnerability, they are among the least targeted by efforts to optimize antibiotic use, which are concentrated in secondary and tertiary healthcare facilities targeted at urban populations.
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Verticillium dahliae, a fungal pathogen that affects more than 200 plant species, including tomatoes, requires specific proteins for its early steps in plant infection. One such crucial protein, VdPBP1, exhibits high expression in the presence of tomato roots. Its 313-amino acid C-terminal section restores adhesion in nonadhesive Saccharomyces cerevisiae strains. To uncover its role, we employed a combination of bioinformatics, genetics, and morphological analyses. Our findings underscore the importance of VdPBP1 in fungal growth and pathogenesis. Bioinformatic analysis revealed that the VdPBP1 gene consists of four exons and three introns, encoding a 952-codon reading frame. The protein features a 9aaTAD domain, LsmAD, and PAB1 DNA-binding sites, as well as potential nuclear localization and transmembrane helix signals. Notably, the deletion of a 1.1 kb fragment at the gene's third end impedes microsclerotia formation and reduces pathogenicity. Mutants exhibit reduced growth and slower aerial mycelial development compared to the wild type. The VdPBP1 deletion strain does not induce disease symptoms in tomato plants. Furthermore, VdPBP1 deletion correlates with downregulated microsclerotia formation-related genes, and promoter analysis reveals regulatory elements, including sites for Rfx1, Mig1, and Ste12 proteins. Understanding the regulation and target genes of VdPBP1 holds promise for managing Verticillium wilt disease and related fungal pathogens.
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Two new vernonioside K (1) and vernonioside L (2) and four known Δ7,9(11) stigmastane-type steroidal saponins-vernonioside B2 (3), vernoniacum B (4), vernonioside B1 (5), and vernoamyoside A (6)-were isolated from the leaves of Vernonia amygdalina. Their structures were determined by comprehensive spectroscopic analysis with one-dimensional nuclear magnetic resonance, two-dimensional nuclear magnetic resonance, and high-resolution mass spectrometry. All isolated compounds (1-6) were evaluated to determine their inhibitory effects on α-glucosidase and xanthine oxidase. Among them, two new compounds 1 and 2 showed significant inhibition of α-glucosidase with IC50 values of 78.56 ± 7.28 and 14.74 ± 1.57 (µM), respectively, comparable with acarbose as a positive control (127.53 ± 1.73 µM); none of these compounds inhibited xanthine oxidase activity. Compounds 1 and 2 are promising candidates for the development of antidiabetic agents from natural sources.
Subject(s)
Saponins , Vernonia , alpha-Glucosidases , Vernonia/chemistry , Xanthine Oxidase , Saponins/pharmacology , Saponins/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Steroids/chemistryABSTRACT
Rho GTPases play a key role in the spatio-temporal coordination of cytoskeletal dynamics during cell migration. Here, we directly investigate crosstalk between the major Rho GTPases Rho, Rac and Cdc42 by combining rapid activity perturbation with activity measurements in mammalian cells. These studies reveal that Rac stimulates Rho activity. Direct measurement of spatio-temporal activity patterns show that Rac activity is tightly and precisely coupled to local cell protrusions, followed by Rho activation during retraction. Furthermore, we find that the Rho-activating Lbc-type GEFs Arhgef11 and Arhgef12 are enriched at transient cell protrusions and retractions and recruited to the plasma membrane by active Rac. In addition, their depletion reduces activity crosstalk, cell protrusion-retraction dynamics and migration distance and increases migration directionality. Thus, our study shows that Arhgef11 and Arhgef12 facilitate exploratory cell migration by coordinating cell protrusion and retraction by coupling the activity of the associated regulators Rac and Rho.
Subject(s)
Cell Size , rho GTP-Binding Proteins , Animals , cdc42 GTP-Binding Protein/genetics , cdc42 GTP-Binding Protein/metabolism , Cell Membrane/metabolism , Cell Movement , Cytoskeleton/metabolism , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Mammals/metabolism , rho GTP-Binding Proteins/genetics , rho GTP-Binding Proteins/metabolismABSTRACT
Numerous genetic resources of major crops have been introduced from around the world and deposited in Japanese National Agriculture and Food Research Organization (NARO) Genebank. Understanding their genetic variation and selecting a representative subset ("core collection") are essential for optimal management and efficient use of genetic resources. In this study, we conducted genotyping-by-sequencing (GBS) to characterize the genetic relationships and population structure in 755 accessions of melon genetic resources. The GBS identified 39,324 single-nucleotide polymorphisms (SNPs) that are distributed throughout the melon genome with high density (one SNP/10.6 kb). The phylogenetic relationships and population structure inferred using this SNP dataset are highly associated with the cytoplasm type and geographical origin. Our results strongly support the recent hypothesis that cultivated melon was established in Africa and India through multiple independent domestication events. Finally, we constructed a World Melon Core Collection that covers at least 82% of the genetic diversity and has a wide range of geographical origins and fruit morphology. The genome-wide SNP dataset, phylogenetic relationships, population structure, and the core collection provided in this study should largely contribute to genetic research, breeding, and genetic resource preservation in melon.
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Purpose: The objective of this research is to compare the efficacy of conventional and hypofractionated radiotherapy treatment plans for breast cancer patients, with a specific focus on the unique features of the Halcyon system. Methods and materials: The study collected and analyzed dose volume histogram (DVH) data for two groups of treatment plans implemented using the Halcyon system. The first group consisted of 19 patients who received conventional fractionated (CF) treatment with a total dose of 50 Gy in 25 fractions, while the second group comprised 9 patients who received hypofractionated (HF) treatment with a total dose of 42.56 Gy in 16 fractions. The DVH data was used to calculate various parameters, including tumor control probability (TCP), normal tissue complication probability (NTCP), and equivalent uniform dose (EUD), using radiobiological models. Results: The results indicated that the CF plan resulted in higher TCP but lower NTCP for the lungs compared to the HF plan. The EUD for the HF plan was approximately 49 Gy (114% of its total dose) while that for the CF plan was around 53 Gy (107% of its total dose). Conclusions: The analysis suggests that while the CF plan is better at controlling tumors, it is not as effective as the HF plan in minimizing side effects. Additionally, it is suggested that there may be an optimal configuration for the HF plan that can provide the same or higher EUD than the CF plan.
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Gender inequality and women's empowerment are two closely related issues. While the gender inequality index has been assessed by different studies, that of women's empowerment remained limited. In the present work, we attempted to evaluate the women's empowerment index by comparing it with the male partner's empowerment index in the same household. We used the Women's Empowerment in Agriculture Index (WEAI) as a framework for reference. A questionnaire was designed to interview 300 people including both men and women in the same ethnic minority household in central Vietnam. The difference in the empowerment level between men and women was assessed through five-component empowerment indicators: agricultural participation, resource ownership, financial control, social organizations participation, and time usage. The results showed that up to 70% of women were disempowered compared to only 15% of men. The binary logistic model revealed the age at first marriage, the level of children's education, education level, distance to the nearest urban area, and the number of children were associated with women's empowerment; whereas age, income, and the level of gender awareness did not show any correlation.
Subject(s)
Ethnic and Racial Minorities , Ethnicity , Child , Humans , Female , Male , Vietnam , Minority Groups , AgricultureABSTRACT
Eu3+-doped phosphors have been much attractive owing to their narrow-band red emission peak at 610-630 nm with high color purity; however, the weak and narrow absorption band in the NUV region limits their applications. Doping a higher amount of Eu3+ ions into a non-concentration quenching host could be key to enhancing the efficiency of the absorption value and emission intensity. Hence, the design of Eu3+-heavily doped phosphors with a suitable host lattice is key for applications. In this study, red-emitting Eu3+-doped Gd(BO2)3-Y3BO6-GdBO3 (GdYGd:Eu3+) phosphor with a high quantum efficiency of 58.4% and excellent color purity of 99.5% is reported for the first time. The phosphor is efficiently excited by NUV light at 394 nm and emits a strong red emission band in the 590-710 nm range, peaking at 612 nm. The optimal annealing temperature and Eu3+ doping content to obtain the strongest PL intensity are 1100 °C and 20 mol%, respectively. The optimized GdYGd:Eu3+ phosphor possesses a high activation energy of 0.319 eV and a lifetime of 1.14 ms. An illustration of phosphor-coated NUV LED with chromaticity coordinates (x = 0.5636,y = 0.2961) was successfully synthesized, demonstrating the great potential of GdYGd:Eu3+ phosphor for NUV-pumped WLED applications.
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To uncover population structure, phylogenetic relationship, and diversity in melons along the famous Silk Road, a seed size measurement and a phylogenetic analysis using five chloroplast genome markers, 17 RAPD markers and 11 SSR markers were conducted for 87 Kazakh melon accessions with reference accessions. Kazakh melon accessions had large seed with exception of two accessions of weedy melon, Group Agrestis, and consisted of three cytoplasm types, of which Ib-1/-2 and Ib-3 were dominant in Kazakhstan and nearby areas such as northwestern China, Central Asia and Russia. Molecular phylogeny showed that two unique genetic groups, STIa-2 with Ib-1/-2 cytoplasm and STIa-1 with Ib-3 cytoplasm, and one admixed group, STIAD combined with STIa and STIb, were prevalent across all Kazakh melon groups. STIAD melons that phylogenetically overlapped with STIa-1 and STIa-2 melons were frequent in the eastern Silk Road region, including Kazakhstan. Evidently, a small population contributed to melon development and variation in the eastern Silk Road. Conscious preservation of fruit traits specific to Kazakh melon groups is thought to play a role in the conservation of Kazakh melon genetic variation during melon production, where hybrid progenies were generated through open pollination.
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BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding. METHODS: The SNEEP (SNP exploration and analysis using epigenomics data) pipeline was used to identify regulatory SNPs, which alter the binding behavior of TFs and link GWAS SNPs to their potential target genes for six CVDs. The human-induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. Gene expression, cardiomyocyte size and cardiac contractility were assessed. RESULTS: By using our integrative computational pipeline, we identified 1905 regulatory SNPs in CVD GWAS data. These were associated with hundreds of genes, half of them non-coding RNAs (ncRNAs), suggesting novel CVD genes. We experimentally tested 40 CVD-associated non-coding RNAs, among them RP11-98F14.11, RPL23AP92, IGBP1P1, and CTD-2383I20.1, which were upregulated in hiPSC-CMs, MCOs and SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued expression of hypertrophic marker genes, reduced hypoxia-induced cardiomyocyte size and improved hypoxia-reduced cardiac contractility in hiPSC-CMs and MCOs. CONCLUSIONS: IGBP1P1 is a novel ncRNA with key regulatory functions in modulating cardiomyocyte size and cardiac function in our disease models. Our data suggest ncRNA IGBP1P1 as a potential therapeutic target to improve cardiac function in CVDs.
Subject(s)
Cardiovascular Diseases , Polymorphism, Single Nucleotide , Humans , Polymorphism, Single Nucleotide/genetics , Genome-Wide Association Study , Cardiovascular Diseases/genetics , Genomics , GenomeABSTRACT
Food choices that shape human diets and health are influenced by various socio-economic factors. Vietnam struggles to meet many nutrition targets where links between food choice and diet have not been widely explored. This study assesses the food choice motives, based on a 28-item food choice questionnaire (FCQ), and the diet quality of 603 adults in three sites (urban, peri-urban, and rural) in northern Vietnam. We assess diet quality using the Diet Quality Index-Vietnam (DQI-V) which consists of variety, adequacy, moderation, and balance components. Using factor analysis, we grouped FCQ items into five factors: health focus, sensory appeal, mood ethics, convenience, and familiarity. The structural equation modeling indicates that food choice motives significantly impact the DQI-V and its components but in different directions. The results show that sensory appeal has a positive association with the overall DQI-V score, while having a negative impact on the variety component. Findings present a potential trade-off issue for interventions and policies related to food products. Nutrition knowledge is positively associated with all elements of diet quality across all three study sites. Vietnamese agrobiodiversity could be better utilized to increase dietary diversity. Differentiated policies are necessary to address the poor dietary diversity and adequacy in northern Vietnam.
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This paper investigates the use of machine learning algorithms to aid medical professionals in the detection and risk assessment of diabetes. The research employed a dataset gathered from individuals with type 2 diabetes in Ninh Binh, Vietnam. A variety of classification algorithms, including Decision Tree Classifier, Logistic Regression, SVC, Ada Boost Classifier, Gradient Boosting Classifier, Random Forest Classifier, and K Neighbors Classifier, were utilized to identify the most suitable algorithm for the dataset. The results of the present study indicate that the Random Forest Classifier algorithm yielded the most promising results, exhibiting a cross-validation score of 0.998 and an accuracy rate of 100%. To further evaluate the effectiveness of the selected model, it was subjected to a testing phase involving a new dataset comprising 67 patients that had not been previously seen. The performance of the algorithm on this dataset resulted in an accuracy rate of 94%, especially the study's notable finding is the algorithm's accurate prediction of the probability of patients developing diabetes, as indicated by the class 1 (diabetes) probabilities. This innovative approach offers a meticulous and quantifiable method for diabetes detection and risk evaluation, showcasing the potential of machine learning algorithms in assisting clinicians with diagnosis and management. By communicating the diabetes score and probability estimates to patients, the comprehension of their disease status can be enhanced. This information empowers patients to make informed decisions and motivates them to adopt healthier lifestyle habits, ultimately playing a crucial role in impeding disease progression. The study underscores the significance of leveraging machine learning in healthcare to optimize patient care and improve long-term health outcomes.
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Contamination of aquaculture products by pathogenic organisms is a major concern in areas where this activity is of high economic importance. The abundances of total coliforms (TC), Escherichia coli (EC) and faecal streptococci (FS) (in CFU.100 mL-1) in seawater in the Red River coastal aquaculture zone were determined. The results showed TC numbers (200 to 9100; average 1822), EC (<100 to 3400; average 469) and FS (<100 to 2100; average 384), of which TC exceeded the allowable threshold of the Vietnam regulation for coastal aquaculture water. TC and EC numbers in 4 wastewater types (domestic, livestock farming sewage, agricultural runoff, and mixed sewage canals) were investigated and revealed the importance of point sources of faecal contamination in seawater. These results underline the need to reduce the release of untreated wastewater and to put into place seawater microbial quality monitoring in areas where the development of sustainable aquaculture is an objective.
Subject(s)
Sewage , Wastewater , Vietnam , Escherichia coli , Aquaculture , Feces , Gram-Negative Bacteria , Environmental Monitoring/methods , Water MicrobiologyABSTRACT
Drug development is a complex and expensive process from new drug discovery to product approval. Most drug screening and testing rely on in vitro 2D cell culture models; however, they generally lack in vivo tissue microarchitecture and physiological functionality. Therefore, many researchers have used engineering methods, such as microfluidic devices, to culture 3D cells in dynamic conditions. In this study, a simple and low-cost microfluidic device was fabricated using Poly Methyl Methacrylate (PMMA), a widely available material, and the total cost of the completed device was USD 17.75. Dynamic and static cell culture examinations were applied to monitor the growth of 3D cells. α-MG-loaded GA liposomes were used as the drug to test cell viability in 3D cancer spheroids. Two cell culture conditions (i.e., static and dynamic) were also used in drug testing to simulate the effect of flow on drug cytotoxicity. Results from all assays showed that with the velocity of 0.005 mL/min, cell viability was significantly impaired to nearly 30% after 72 h in a dynamic culture. This device is expected to improve in vitro testing models, reduce and eliminate unsuitable compounds, and select more accurate combinations for in vivo testing.
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BACKGROUND: In previous trials, point-of-care testing of C-reactive protein (CRP) concentrations safely reduced antibiotic use in non-severe acute respiratory infections in primary care. However, these trials were done in a research-oriented context with close support from research staff, which could have influenced prescribing practices. To better inform the potential for scaling up point-of-care testing of CRP in respiratory infections, we aimed to do a pragmatic trial of the intervention in a routine care setting. METHODS: We did a pragmatic, cluster-randomised controlled trial at 48 commune health centres in Viet Nam between June 1, 2020, and May 12, 2021. Eligible centres served populations of more than 3000 people, handled 10-40 respiratory infections per week, had licensed prescribers on site, and maintained electronic patient databases. Centres were randomly allocated (1:1) to provide point-of-care CRP testing plus routine care or routine care only. Randomisation was stratified by district and by baseline prescription level (ie, the proportion of patients with suspected acute respiratory infections to whom antibiotics were prescribed in 2019). Eligible patients were aged 1-65 years and visiting the commune health centre for a suspected acute respiratory infection with at least one focal sign or symptom and symptoms lasting less than 7 days. The primary endpoint was the proportion of patients prescribed an antibiotic at first attendance in the intention-to-treat population. The per-protocol analysis included only people who underwent CRP testing. Secondary safety outcomes included time to resolution of symptoms and frequency of hospitalisation. This trial is registered with ClinicalTrials.gov, NCT03855215. FINDINGS: 48 commune health centres were enrolled and randomly assigned, 24 to the intervention group (n=18 621 patients) and 24 to the control group (n=21 235). 17 345 (93·1%) patients in the intervention group were prescribed antibiotics, compared with 20 860 (98·2%) in the control group (adjusted relative risk 0·83 [95% CI 0·66-0·93]). Only 2606 (14%) of 18 621 patients in the intervention group underwent CRP testing and were included in the per-protocol analysis. When analyses were restricted to this population, larger reductions in prescribing were noted in the intervention group compared with the control group (adjusted relative risk 0·64 [95% CI 0·60-0·70]). Time to resolution of symptoms (hazard ratio 0·70 [95% CI 0·39-1·27]) and frequency of hospitalisation (nine in the intervention group vs 17 in the control group; adjusted relative risk 0·52 [95% CI 0·23-1·17]) did not differ between groups. INTERPRETATION: Use of point-of-care CRP testing efficaciously reduced prescription of antibiotics in patients with non-severe acute respiratory infections in primary health care in Viet Nam without compromising patient recovery. The low uptake of CRP testing suggests that barriers to implementation and compliance need to be addressed before scale-up of the intervention. FUNDING: Australian Government, UK Government, and the Foundation for Innovative New Diagnostics.