Scalable RT-LAMP-based SARS-CoV-2 testing for infection surveillance with applications in pandemic preparedness.

Throughout the SARS-CoV-2 pandemic, limited diagnostic capacities prevented sentinel testing, demonstrating the need for novel testing infrastructures. Here, we describe the setup of a cost-effective platform that can be employed in a high-throughput manner, which allows surveillance testing as an acute pandemic control and preparedness tool, exemplified by SARS-CoV-2 diagnostics in an academic environment. The strategy involves self-sampling based on gargling saline, pseudonymized sample handling, automated RNA extraction, and viral RNA detection using a semiquantitative multiplexed colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay with an analytical sensitivity comparable with RT-qPCR. We provide standard operating procedures and an integrated software solution for all workflows, including sample logistics, analysis by colorimetry or sequencing, and communication of results. We evaluated factors affecting the viral load and the stability of gargling samples as well as the diagnostic sensitivity of the RT-LAMP assay. In parallel, we estimated the economic costs of setting up and running the test station. We performed > 35,000 tests, with an average turnover time of < 6 h from sample arrival to result announcement. Altogether, our work provides a blueprint for fast, sensitive, scalable, cost- and labor-efficient RT-LAMP diagnostics, which is independent of potentially limiting clinical diagnostics supply chains.

Optimal allocation of resources among general and species-specific tools for plant pest biosecurity surveillance.

This paper proposes a surveillance model for plant pests that can optimally allocate resources among survey tools with varying properties. While some survey tools are highly specific for the detection of a single pest species, others are more generalized. There is considerable variation in the cost and sensitivity of these tools, but there are no guidelines or frameworks for identifying which tools are most cost-effective when used in surveillance programs that target the detection of newly invaded populations. To address this gap, we applied our model to design a trapping surveillance program in New Zealand for bark- and wood-boring insects, some of the most serious forest pests worldwide. Our findings show that exclusively utilizing generalized traps (GTs) proves to be highly cost-effective across a wide range of scenarios, particularly when they are capable of capturing all pest species. Implementing surveillance programs that only employ specialized traps (ST) is cost-effective only when these traps can detect highly damaging pests. However, even in such cases, they significantly lag in cost-effectiveness compared to GT-only programs due to their restricted coverage. When both GTs and STs are used in an integrated surveillance program, the total expected cost (TEC) generally diminishes when compared to programs relying on a single type of trap. However, this relative reduction in TEC is only marginally larger than that achieved with GT-only programs, as long as highly damaging species can be detected by GTs. The proportion of STs among the optimal required traps fluctuates based on several factors, including the relative pricing of GTs and STs, pest arrival rates, potential damage, and, more prominently, the coverage capacity of GTs. Our analysis suggests that deploying GTs extensively across landscapes appears to be more cost-effective in areas with either very high or very low levels of relative risk density, potential damage, and arrival rate. Finally, STs are less likely to be required when the pests that are detected by those tools have a higher likelihood of successful eradication because delaying detection becomes less costly for these species.

Structure and elasticity of healthy and Alzheimer's disease cell membranes revealed by molecular dynamics simulations.

Interactions of amyloid-ß (Aß) peptides with neuronal membrane are associated with the development of Alzheimer's disease (AD). Ganglioside monosialotetrahexosylganglioside (GM1) lipids have been shown to form clusters that induce the structural conversion of Aß and promote the incorporation of Aß into the membrane via the membrane surface electrical potential. Prior to the onset of AD symptoms, GM1 clusters may not have formed but the concentration of GM1 may have already changed, and our question is whether this early concentration modification affects the structure and mechanical properties of the membrane. Using one model for healthy cell membranes and three models for AD cell membranes, we carry out 2 µs all-atom molecular dynamics simulations for each model to compare the structure and elasticity of the two membrane types. The simulations show that at the physiological concentration, 1%-3%, GM1 does not form clusters. The reduction of the GM1 lipid does not significantly alter the area per lipid, the membrane thickness, and the lipid order parameters of the AD membranes. However, the dipole potential, the bending, and twist moduli are decreased for the AD membranes. We suggest that these changes in the AD membranes are factors that could trigger the interaction and incorporation of Aß to the membranes. Finally, we show that changes in the sphingomyelin lipid concentrations do not affect the membrane structure and elasticity.

Effects of a low-iodine diet in post-thyroidectomy thyroid cancer patients undergoing I131 therapy at the Vietnam National Cancer Hospital.

Background: I131 therapy is regarded as an "internal surgery" (i.e., a non-invasive approach involving no incision or bleeding) that supports "external surgery" (i.e., using a scalpel) in completely eradicating the root cause of thyroid cancer. Limiting iodine intake is of paramount importance in I131 therapy. I131 therapy protocols recommend that patients follow a low-iodine diet, ideally with a maximum iodine intake of 50 µg/day for two weeks before the I131 therapy. Methods: A pre-post compassion uncontrolled clinic intervention study was conducted on a group of over 70 post-thyroidectomy thyroid cancer patients with indications for I131 therapy at the Vietnam National Cancer Hospital from December 2020 to December 2022. Aim: It aimed to assess the effects of a low-iodine diet on post-thyroidectomy thyroid cancer patients with indications for I131 therapy. Results: The study found that following the intervention, the percentage of participants at risk of mild to moderate malnutrition, as assessed by the PG-SGA tool, decreased to 4.3% from 40.0% before the intervention, with a statistically significant difference of p < 0.001. There was a considerable improvement in the low calcemia level among the study participants, with 35.7% of patients experiencing hypocalcemia prior to the intervention, which reduced to 17.1% after the intervention. This difference was statistically significant (p = 0.01). The study also revealed a urinary iodine level improvement among the study participants. Before the intervention, patients' average urinary iodine level was 14.9 ± 11.3 µg/dl. Following the intervention, it reduced to 12.7 ± 3.9 µg/dl, although this difference was not statistically significant (p = 0.29). Patients' quality of life after adhering to the low-iodine diet tended to decline; however, the change in scores before and after the intervention did not show a significant difference. Conclusion: Despite its negative impact on patients' quality of life, active nutrition counseling and intervention during the low-iodine diet contributed to the substantial improvement in the hypocalcemia level and the reduced urinary iodine level among patients, which in turn could enhance the efficacy of the subsequent I131 therapy.

Global Neuroblastoma Network: An international multidisciplinary neuroblastoma tumor board for resource-limited countries.

BACKGROUND: Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. METHODS: De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. RESULTS: Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. CONCLUSION: This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.

Impact of pharmacist-initiated educational interventions on improving medication reconciliation practice in geriatric inpatients during hospital admission in Vietnam.

WHAT IS KNOWN AND OBJECTIVE: Unintentional medication discrepancies (UMDs) are common in geriatric patients during care transitions, resulting in frequent undesirable consequences. Medication reconciliation could be a useful practice to prevent or ameliorate UMD. However, this practice in Vietnamese hospitals has not been well established or standardized. This study aims to determine the effect of pharmacist-initiated educational interventions on improving medication reconciliation practice. METHODS: This prospective 6-month pre-and post-study was conducted in two internal medicine wards in a Vietnamese 800-bed public hospital. Pharmacists provided training and short-term support to physicians on medication reconciliation. Primary outcome measures were the proportions of patients with at least one UMD at admission. Secondary outcome measures were the proportions of patients with preventable adverse drug events (pADEs) score ≥0.1 due to these UMDs. Odds ratio and 95% confidence intervals were assessed based on a multivariate logistic regression model. RESULTS AND DISCUSSION: One hundred fifty-two patients were recruited in the pre-intervention phase, and 146 in the post-intervention phase. Following the intervention, the proportion of geriatric patients with ≥1 UMD at admission significantly decreased from 55.3 to 25.3 % (ORadj 0.255, 95% CI: 0.151-0.431). Similarly, the proportion of patients with a pADE ≥0.1 at admission reduced from 44.1 to 11.6% [ORadj 0.188, 95% CI: 0.105-0.340] post-intervention. WHAT IS NEW AND CONCLUSION: Our pharmacist-initiated educational interventions have demonstrated the ability to produce substantial improvement in medication reconciliation practice, reducing UMDs and potential harm. Our approach may provide an alternate option to implement medication reconciliation for jurisdictions with limited healthcare resources.

Streamflow Prediction in Highly Regulated, Transboundary Watersheds Using Multi-Basin Modeling and Remote Sensing Imagery.

Despite the potential of remote sensing for monitoring reservoir operation, few studies have investigated the extent to which reservoir releases can be inferred across different spatial and temporal scales. Through evaluating 21 reservoirs in the highly regulated Greater Mekong region, remote sensing imagery was found to be useful in estimating daily storage volumes for within-year and over-year reservoirs (correlation coefficients [CC] ≥ 0.9, normalized root mean squared error [NRMSE] ≤ 31%), but not for run-of-river reservoirs (CC < 0.4, 40% ≤ NRMSE ≤ 270%). Given a large gap in the number of reservoirs between global and local databases, the proposed framework can improve representation of existing reservoirs in the global reservoir database and thus human impacts in hydrological models. Adopting an Integrated Reservoir Operation Scheme within a multi-basin model was found to overcome the limitations of remote sensing and improve streamflow prediction at ungauged cascade reservoir systems where previous modeling approaches were unsuccessful. As a result, daily regulated streamflow was predicted competently across all types of reservoirs (median values of CC = 0.65, NRMSE = 8%, and Kling-Gupta efficiency [KGE] = 0.55) and downstream hydrological stations (median values of CC = 0.94, NRMSE = 8%, and KGE = 0.81). The findings are valuable for helping to understand the impacts of reservoirs and dams on streamflow and for developing more useful adaptation measures to extreme events in data sparse river basins.

Testicular involvement of acute lymphoblastic leukemia in children and adolescents: Diagnosis, biology, and management.

Acute lymphoblastic leukemia (ALL) in children and adolescents can involve the testes at diagnosis or upon relapse. The testes were long considered pharmacologic sanctuary sites, presumably because of the blood-testis barrier, which prevents the entry of large-molecular-weight compounds into the seminiferous tubule. Patients with testicular involvement were historically treated with testicular irradiation or orchiectomy. With the advent of contemporary intensive chemotherapy, including high-dose methotrexate, vincristine/glucocorticoid pulses, and cyclophosphamide, testicular leukemia present at diagnosis can be eradicated, with the risk of testicular relapse being 2% or lower. However, the management of testicular leukemia is not well described in the recent literature and remains relevant in low- and middle-income countries where testicular relapse is still experienced. Chemotherapy can effectively treat late, isolated testicular B-cell ALL relapses without the need for irradiation or orchiectomy in patients with an early response and thereby preserve testicular function. For refractory or early-relapse testicular leukemia, newer treatment approaches such as chimeric antigen receptor-modified T (CAR-T) cell therapy are under investigation. The control of testicular relapse with CAR-T cells and their penetration of the blood-testis barrier have been reported. The outcome of pediatric ALL has been improved remarkably by controlling the disease in the bone marrow, central nervous system, and testes, and such success should be extended globally. LAY SUMMARY: Acute lymphoblastic leukemia (ALL) in children and adolescents can involve the testes at diagnosis or upon relapse. Modern intensive chemotherapy has largely eradicated testicular relapse in high-income countries. Consequently, most current clinicians are not familiar with how to manage it if it does occur, and testicular relapse continues to be a significant problem in low- and middle-income countries that have not had access to modern intensive chemotherapy. The authors review the historical progress made in eradicating testicular ALL and use the lessons learned to make recommendations for treatment.

Novel mutations of the PAX6, FOXC1, and PITX2 genes cause abnormal development of the iris in Vietnamese individuals.

Purpose: Congenital iris abnormality is a feature of several genetic conditions, such as aniridia syndrome and anterior segment degeneration (ASD) disorders. Aniridia syndrome is caused by mutations in the PAX6 gene or its regulatory elements in the locus 11p13 or deletions of contiguous genes, while ASDs are the result of mutations in various genes, such as PAX6, FOXC1, PITX2, and CYP1B1. This study aims to identify pathogenic mutations in Vietnamese individuals with congenital anomalies of the iris. Methods: Genomic DNA was extracted from peripheral blood of 24 patients belonging to 15 unrelated families and their available family members. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the deletions or duplications in the 11p13-14 region, including the PAX6 gene and its neighboring genes. Direct PCR sequencing was used to screen mutations in 13 exons and flanking sequences of the PAX6 gene. The patients without mutation in the PAX6 locus were further analyzed with whole exome sequencing (WES). Identified mutations were tested with segregation analysis in proband family members. Results: We identified a total of 8 novel and 4 recurrent mutations in 20 of 24 affected individuals from 12 families. Among these mutations, one large deletion of the whole PAX6 gene and another deletion of the PAX6 downstream region containing the DCDC1 and ELP4 genes were identified. Eight mutations were detected in PAX6, including four nonsense, three frameshift, and one splice site. In addition, two point mutations were identified in the FOXC1 and PITX2 genes in patients without mutation in PAX6. Some of the mutations segregated in an autosomal dominant pattern where family members were available. Conclusions: This study provides new data on causative mutations in individuals with abnormal development of iris tissue in Vietnam. These results contribute to clinical management and genetic counseling for affected people and their families.

Improved photodegradation of anionic dyes using a complex graphitic carbon nitride and iron-based metal-organic framework material.

Introducing heterostructures to graphitic carbon nitrides (g-C3N4) can improve the activity of visible-light-driven catalysts for the efficient treatment of multiple toxic pollutants in water. Here, we report for the first time that a complex material can be constructed from oxygen-doped g-C3N4 and a MIL-53(Fe) metal-organic framework using facile hydrothermal synthesis and recycled polyethylene terephthalate from plastic waste. The novel multi-walled nanotube structure of the O-g-C3N4/MIL-53(Fe) composite, which enables the unique interfacial charge transfer at the heterojunction, showed an obvious enhancement in the separation efficiency of the photochemical electron-hole pairs. This resulted in a narrow bandgap energy (2.30 eV, compared to 2.55 eV in O-g-C3N4), high photocurrent intensity (0.17 mA cm-2, compared to 0.12 mA cm-2 and 0.09 mA cm-2 in MIL-53(Fe) and O-g-C3N4, respectively) and excellent catalytic performance in the photodegradation of anionic azo dyes (95% for RR 195 and 99% for RY 145 degraded after 4 h, and only a minor change in the efficiency observed after four consecutive tests). These results demonstrate the development of new catalysts made from waste feedstocks that show high stability, ease of fabrication and can operate in natural light for environmental remediation.

Optimal surveillance against bioinvasions: a sample average approximation method applied to an agent-based spread model.

Trade-offs exist between the point of early detection and the future cost of controlling any invasive species. Finding optimal levels of early detection, with post-border active surveillance, where time, space and randomness are explicitly considered, is computationally challenging. We use a stochastic programming model to find the optimal level of surveillance and predict damages, easing the computational challenge by combining a sample average approximation (SAA) approach and parallel processing techniques. The model is applied to the case of Asian Papaya Fruit Fly (PFF), a highly destructive pest, in Queensland, Australia. To capture the non-linearity in PFF spread, we use an agent-based model (ABM), which is calibrated to a highly detailed land-use raster map (50 m × 50 m) and weather-related data, validated against a historical outbreak. The combination of SAA and ABM sets our work apart from the existing literature. Indeed, despite its increasing popularity as a powerful analytical tool, given its granularity and capability to model the system of interest adequately, the complexity of ABM limits its application in optimizing frameworks due to considerable uncertainty about solution quality. In this light, the use of SAA ensures quality in the optimal solution (with a measured optimality gap) while still being able to handle large-scale decision-making problems. With this combination, our application suggests that the optimal (economic) trap grid size for PFF in Queensland is ˜0.7 km, much smaller than the currently implemented level of 5 km. Although the current policy implies a much lower surveillance cost per year, compared with the $2.08 million under our optimal policy, the expected total cost of an outbreak is $23.92 million, much higher than the optimal policy of roughly $7.74 million.

A Systematic Review and Narrative Synthesis of Health Economic Evaluations of Hepatocellular Carcinoma Screening Strategies.

OBJECTIVES: Many economic evaluations of hepatocellular carcinoma (HCC) screenings have been conducted; however, these vary substantially with regards to screening strategies, patient group, and setting. This review aims to report the current knowledge of the cost-effectiveness of screening and describe the published data. METHODS: We conducted a search of biomedical and health economic databases up to July 2020. We included full and partial health economic studies if they evaluated the costs or outcomes of HCC screening strategies. RESULTS: The review included 43 studies. Due to significant heterogeneity in key aspects across the studies, a narrative synthesis was conducted. Most studies reported using ultrasound or alpha fetoprotein as screening strategies. Screening intervals were mostly annual or biannual. Incidence, diagnostic performance, and health state utility values were the most critical parameters affecting the cost-effectiveness of screening. The majority of studies reported HCC screening to be cost-effective, with the biannual ultrasound + alpha fetoprotein standing out as the most cost-effective strategy. However, few studies considered the utilization rate, and none considered the diagnostic performance of ultrasound in the context of central adiposity. Computed tomography and magnetic resonance imaging were also evaluated, but its cost-effectiveness was still controversial. CONCLUSIONS: Although many studies suggested HCC screening was cost-effective, substantial limitations of the quality of these studies means the results should be interpreted with caution. Future modeling studies should consider the impact of central adiposity on the precision of ultrasound, real-world utilization rates and projections of increased HCC incidence.

Economic Evaluation of User-Fee Exemption Policies for Maternal Healthcare in Burkina Faso: Evidence From a Cost-Effectiveness Analysis.

OBJECTIVES: The reduction and removal of user fees for essential care services have recently become a key instrument to advance universal health coverage in sub-Saharan Africa, but no evidence exists on its cost-effectiveness. We aimed to address this gap by estimating the cost-effectiveness of 2 user-fee exemption interventions in Burkina Faso between 2007 and 2015: the national 80% user-fee reduction policy for delivery care services and the user-fee removal pilot (ie, the complete [100%] user-fee removal for delivery care) in the Sahel region. METHODS: We built a single decision tree to evaluate the cost-effectiveness of the 2 study interventions and the baseline. The decision tree was populated with an own impact evaluation and the best available epidemiological evidence. RESULTS: Relative to the baseline, both the national 80% user-fee reduction policy and the user-fee removal pilot are highly cost-effective, with incremental cost-effectiveness ratios of $210.22 and $252.51 per disability-adjusted life-year averted, respectively. Relative to the national 80% user-fee reduction policy, the user-fee removal pilot entails an incremental cost-effectiveness ratio of $309.74 per disability-adjusted life-year averted. CONCLUSIONS: Our study suggests that it is worthwhile for Burkina Faso to move from an 80% reduction to the complete removal of user fees for delivery care. Local analyses should be done to identify whether it is worthwhile to implement user-fee exemptions in other sub-Saharan African countries.

CYP2C19 genetic polymorphism in the Vietnamese population.

Background: Genetic polymorphism of CYP2C19 has been shown to affect enzyme activity and thereby contribute to inter-individual variability in drug metabolism and response. The complete genetic variation of CYP2C19 in Vietnam still remains obscure even though data of common alleles in Vietnamese Kinh have been reported.Aim: To establish the extent of CYP2C19 polymorphism in Vietnamese.Subjects and methods: The promoter and all nine exons of CYP2C19 in 100 healthy unrelated Vietnamese Kinh subjects were sequenced. Additionally, the CYP2C19 variants, *2, *3 and *17 were analysed by RFLP-PCR in 275 subjects of four minor ethnic groups in Vietnam (Tay, Muong, H'Mong and Nung).Results: In 100 Kinh subjects, the percentages of CYP2C19*1, CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles were 76%, 20.5%, 2.5% and 1%, respectively. Three novel variants in introns 2, 5 and 8 had no impact on mRNA splicing according to the Human Splicing Finder. The prevalence of CYP2C19*17 in Vietnamese Kinh was significantly lower compared with figures found in Western Asia and Europe, while CYP2C19*2 frequency was statistically higher than that in Western Asia and several countries in Europe. The frequency of CYP2C19*2 in Kinh was significantly lower than in the other four ethnic minorities.Conclusion: These results provide information on CYP2C19 polymorphism in the Vietnamese population, which could be useful for optimising drug therapies and precision medicine studies.

Mutational screening of germline RB1 gene in Vietnamese patients with retinoblastoma reveals three novel mutations.

Purpose: Retinoblastoma (Rb) is a rare and unique eye cancer that usually develops in the retinas of children less than 5 years old due to mutations in the RB1 gene. About 40% of affected individuals have the heritable form making genetics testing of the RB1 gene important for disease management. This study aims to identify germline mutations in RB1 in a cohort of patients with Rb from northern Vietnam. Methods: Genomic DNA was extracted from peripheral blood of 34 patients with Rb (nine unilateral and 25 bilateral cases) and their available parents. Twenty-seven exons, flanking sequences, and the promoter region of RB1 gene were screened for mutations with direct PCR sequencing. Multiplex ligation-dependent probe amplification (MLPA) was applied for patients with negative sequencing results. In the mutation-positive patients, their available parental DNA was analyzed to determine the parental origin of the mutation. Results: Germline mutations in RB1 were identified in 25 (73.53%) of 34 patients (four unilateral and 21 bilateral cases). Of these mutations, 19 were detected, including seven nonsense, six frameshift, four splice-site (one was identified in two siblings), and one missense, with Sanger sequencing. Three novel frameshift mutations were discovered in one unilateral and two bilateral patients. MLPA detected mutations in the RB1 gene in six bilateral cases, of whom five had a whole gene deletion (three familial cases) and one had a partial gene deletion (from exon 4 to exon 27) in one allele of the RB1 gene. Parental testing showed five mutations originated from the fathers and one was inherited from a mother who was mosaic for the mutation. Conclusions: This study provides a data set of germline mutations in the RB1 gene in Vietnamese patients with retinoblastoma. Screening of mutations in the RB1 gene can help to identify heritable Rb and contribute to clinical management and genetic counseling for affected families.

Bacterial bloodstream infections in a tertiary infectious diseases hospital in Northern Vietnam: aetiology, drug resistance, and treatment outcome.

BACKGROUND: Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam. METHODS: A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn ≤48 h after hospitalization or hospital acquired if >48 h. RESULTS: A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36-60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities. CONCLUSIONS: Enterobacteriaceae (predominantly K. pneumoniae and E. coli) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam.

Characterization and mechanisms of anti-influenza virus metabolites isolated from the Vietnamese medicinal plant Polygonum chinense.

BACKGROUND: Polygonum chinense Linn. is a common medicinal plant in Southeast Asia and has been used in traditional medicine in Vietnam. The plant contains phytochemicals with various biological properties; however, its antiviral effect has not yet been demonstrated. This study was aimed to evaluate the anti-influenza virus activity of crude extracts of P. chinense, to characterize antiviral metabolites therefrom and to investigate their mechanisms of antiviral action. METHODS: The methanol (MeOH) extract and organic solvent layers of P. chinense were prepared by extraction and partition with relevant solvents. The ethyl acetate (EtOAc) layer showing antiviral activity was chromatographed repeatedly on SiO2 and Sephadex LH-20 columns to give eight pure metabolites. Their chemical structures were determined by NMR and MS spectral data. Anti-influenza virus activity of the eight metabolites against virus strains A/Puerto Rico/8/34 (H1N1, PR8), A/Hong Kong/8/68 (H3N2, HK) and B/Lee/40 (Lee) was evaluated on the basis of cytopathic effect (CPE) and plaque inhibition assays. Time-of-addition, confocal microscopy and neuraminidase inhibition assay were performed for mode-of-action studies of active ingredients. RESULTS: The MeOH extract of P. chinense showed anti-influenza virus activity with EC50 values ranging from 38.4 to 55.5 µg/mL in a CPE inhibition assay. Among the eight pure metabolites isolated from P. chinense, ellagic acid (PC5), methyl gallate (PC7) and caffeic acid (PC8) significantly inhibited viral replication in a dose-dependent manner in both plaque inhibition and CPE inhibition assays with EC50 values ranging from 14.7 to 81.1 µg/mL and CC50 values higher than 300 µg/mL. Mode-of-action studies suggested that PC5 and PC7 suppress virus entry into or replication in cells, while PC8 targets influenza viral neuraminidase, even oseltamivir-resistant one. CONCLUSION: These results demonstrated that P. chinense and its metabolites possess effective anti-influenza virus activities. The botanical materials of P. chinense could be a promising multitargeted inhibitor of influenza A and B viruses and applied to development of a novel herbal medicine.

In vitro antibacterial activity of selected medicinal plants traditionally used in Vietnam against human pathogenic bacteria.

BACKGROUND: Medicinal plants are widely used for the treatment of different infectious diseases. Infectious diseases caused by bacteria have a large impact on public health. This study aimed to determine the in vitro antibacterial activity of the medicinal plants traditionally used in Vietnam against the bacterial strains associated with infectious diseases. METHODS: Methanol extracts of twelve Vietnamese medicinal plants were tested for their antibacterial activity against five bacterial species including Gram-positive bacteria (Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using the broth microdilution method. RESULTS: All the plant extracts showed antibacterial activity, especially against Gram-positive bacteria (Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus). Baeckea frutescens extract revealed a potent activity against the Gram-positive bacteria with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 62.5 µg/ml. High activity against all the three Gram-positive bacteria was also observed for the extracts of Cratoxylum formosum ssp. pruniflorum, Pogostemon cablin, and Pedilanthus tithymaloides with MICs of 125, 125 and 250 µg/ml and MBCs of 125-250, 125-250 and 250-500 µg/ml, respectively. The extracts of C. formosum ssp. pruniflorum and P. tithymaloides showed a broad-spectrum antibacterial activity against all the bacteria tested with the MICs of 125-2,000 µg/ml. CONCLUSION: This study indicates clear evidence supporting the traditional use of the plants in treating infectious diseases related to bacteria. In particular, these plant species showed moderate to high antibacterial activity against the Gram-positive bacteria tested.

A mutation that eliminates bundle sheath extensions reduces leaf hydraulic conductance, stomatal conductance and assimilation rates in tomato (Solanum lycopersicum).

Bundle sheath extensions (BSEs) are key features of leaf structure whose distribution differs among species and ecosystems. The genetic control of BSE development is unknown, so BSE physiological function has not yet been studied through mutant analysis. We screened a population of ethyl methanesulfonate (EMS)-induced mutants in the genetic background of the tomato (Solanum lycopersicum) model Micro-Tom and found a mutant lacking BSEs. The leaf phenotype of the mutant strongly resembled the tomato mutant obscuravenosa (obv). We confirmed that obv lacks BSEs and that it is not allelic to our induced mutant, which we named obv-2. Leaves lacking BSEs had lower leaf hydraulic conductance and operated with lower stomatal conductance and correspondingly lower assimilation rates than wild-type leaves. This lower level of function occurred despite similarities in vein density, midvein vessel diameter and number, stomatal density, and leaf area between wild-type and mutant leaves, the implication being that the lack of BSEs hindered water dispersal within mutant leaves. Our results comparing near-isogenic lines within a single species confirm the hypothesised role of BSEs in leaf hydraulic function. They further pave the way for a genetic model-based analysis of a common leaf structure with deep ecological consequences.