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Abstract Continued efforts to discover new antibacterial molecules are critical to achieve a robust pre-clinical pipeline for new antibiotics. Screening of compound or natural product extract libraries remains a widespread approach and can benefit from the development of whole cell assays that are robust, simple and versatile, and allow for high throughput testing of antibacterial activity. In this study, we created and validated two bioluminescent reporter strains for high-throughput screening, one in Pseudomonas aeruginosa, and another in a hyperporinated and efflux-deficient Escherichia coli. We show that the bioluminescent strains have a large dynamic range that closely correlates with cell viability and is superior to conventional optical density (OD600) measurements, can detect dose-dependent antibacterial activity and be used for different drug discovery applications. We evaluated the assays’ performance characteristics (signal to background ratio, signal window, Z’ robust) and demonstrated their potential utility for antibiotic drug discovery in two examples. The P. aeruginosa bioluminescent reporter was used in a pilot screen of 960 repurposed compound libraries to identify adjuvants that potentiate the fluoroquinolone antibiotic ofloxacin. The E. coli bioluminescent reporter was used to test the antibacterial activity of bioactive bacterial supernatants and assist with bioassay-guided fractionation of the crude extracts.

Abstract Slow progress towards implementation of conventional clinical bacteriology in low resource settings and strong interest in greater speed for antimicrobial susceptibility testing (AST) more generally has focused attention on next-generation rapid AST technologies. In this Review, we systematically synthesize publications and submissions to regulatory agencies describing technologies that provide phenotypic AST faster than conventional methods. We characterize over ninety technologies in terms of underlying technical innovations, technology readiness level, extent of clinical validation, and time-to-results. This work provides a guide for technology developers and clinical microbiologists to understand the rapid phenotypic AST technology landscape, current development pipeline, and AST-specific validation milestones.

Abstract Background Breast screening recommendation based on individual risk assessment is emerging as an alternative approach to improve compliance and efficiency to detect breast cancer (BC) early. In Vietnam, prior knowledge to stratify risk based on genetic factors is currently lacking. Methods This study recruited 892 BC patients and 735 healthy Vietnamese women from 2016 to 2021. DNA from blood samples of BC patients was first analyzed for pathogenic variants associated with hereditary breast and ovarian cancer syndrome (HBOC). For patients with no HBOC and healthy participants, DNA was genotyped for 398 BC susceptibility single-nucleotide polymorphism (SNPs) by next-generation sequencing to identify significantly associated SNPs and construct a polygenic risk score (PRS). Results The prevalence of HBOC predisposition gene mutations in Vietnamese women with BC was 5.4%. HBOC cases were significantly younger and enriched in the age group of 20–39 years old. In patients with no HBOC, we found 36 SNPs significantly associated with BC that were mostly similar to other Asian ethnicities; 34 of them were used to build a PRS model achieving an area under the receiver operating characteristics curve of 0.61 (95% CI: 0.56–0.68). Women in the top 1% PRS percentile had an odds ratio of 5.09 (95% CI: 3.10–7.86) while those in the bottom 1% had an odds ratio of 0.21 (95% CI: 0.09–0.39) to develop BC. Conclusions This study provides the first large datasets for HBOC gene analysis, BC susceptibility SNP association testing, and PRS modeling for Vietnamese women. Together, these data could aid the development of personalized BC screening recommendations for women in Vietnam.

BackgroundIn Vietnam, PrEP was introduced in 2017 and scaled up from 2019. Private sector engagement (PSE) in PrEP service delivery was deployed as a strategy from the start to increase PrEP access. We assessed the effectiveness of this approach to inform ongoing efforts to accelerate epidemic control by 2030.MethodsWe implemented a process evaluation with longitudinal design using retrospective programmatic data collected and uploaded onto a secure online system (HMED) from 23 public and 17 private PrEP clinics in Hanoi, Ho Chi Minh City (HCMC), and Dong Nai. We measured the effectiveness of PrEP service delivery by PrEP initiation/reinitiation, uptake, persistence, discontinuation, and HIV seroconversion. We used the Kaplan-Meier time-to-event approach to estimate PrEP persistence and mixed-effects logistic regression analysis to assess factors associated with the PrEP persistence.ResultsFrom October 2017 to September 2023, 29,944 individuals initiated PrEP, and among these, 79.3% started PrEP at a private sector clinic while 20.7% initiated in a public sector clinic. The median duration of PrEP use persistence at private clinics was significantly longer than that at public clinics (268 days vs. 148 days, respectively). Mixed-effects logistic regression analysis results indicated a significant statistical association between PrEP persistence for at least three months and initiating PrEP at a private clinic [adjusted odds ratio [aOR] = 4.28; 95% confidence interval [CI]: 2.96–6.19], opting for TelePrEP (aOR = 3.42; 95% CI: 2.12–5.53), or being 20 years of age or older (aOR = 1.86; 95% CI: 1.62–2.13). HIV seroconversion was significantly lower among PrEP users at private clinics compared to public clinics (0.03 vs. 0.13 per 100 person-years, respectively; p

AbstractThe research goal is to identify the essential components of visitor satisfaction that influence future return intentions. The quantitative method and the deductive approach were implemented with a sample size of 300 tourists in Can Tho city, Vietnam after sending the survey questionnaire to 15 experts and receiving positive feedback within two weeks. The researchers used the main method to evaluate the data, which was structural equation modeling. The findings illustrated those three factors including cultural contact, perceived value, and green practices noticeably impact visitor satisfaction leading to their intention to visit again, with cultural contact being the most significant influence. At the same time, this helps researchers better understand the intention of tourists to return. Service quality and novelty seeking have negligible influence on tourists’ willingness to revisit the location. The valuable data of this study can inform tourism and hotel managers about their customer groups by encouraging visitors to engage in value-creating activities, cultural exposure and promotion of ideas related to green tourism. On the other side, this study contributes hospitality-related material resources for the following research and provides recommendations to create strategies for tourism regulators and hospitality businesses to promote visitor satisfaction and return.

Antibiotic tolerance in Mycobacterium tuberculosis reduces bacterial killing, worsens treatment outcomes, and contributes to resistance. We studied rifampicin tolerance in isolates with or without isoniazid resistance (IR). Using a minimum duration of killing assay, we measured rifampicin survival in isoniazid-susceptible (IS, n=119) and resistant (IR, n=84) isolates, correlating tolerance with bacterial growth, rifampicin minimum inhibitory concentrations (MICs), and isoniazid-resistant mutations. Longitudinal IR isolates were analyzed for changes in rifampicin tolerance and genetic variant emergence. The median time for rifampicin to reduce the bacterial population by 90% (MDK90) increased from 1.23 days (IS) and 1.31 days (IR) to 2.55 days (IS) and 1.98 days (IR) over 15–60 days of incubation, indicating fast and slow-growing tolerant sub-populations. A 6 log10-fold survival fraction classified tolerance as low, medium, or high, showing that IR is linked to increased tolerance and faster growth (OR = 2.68 for low vs. medium, OR = 4.42 for low vs. high, p-trend = 0.0003). High tolerance in IR isolates was associated with rifampicin treatment in patients and genetic microvariants. These findings suggest that IR tuberculosis should be assessed for high rifampicin tolerance to optimize treatment and prevent the development of multi-drug-resistant tuberculosis.

Cases of vulvovaginitis caused by Cryptococcus genus are exceedingly uncommon, with only a handful of instances having been described for this causative species. This report describes a rare case of vulvovaginitis suspected to be caused by Cryptococcus victoriae in a 58-year-old woman residing in an urban area of Hanoi city, Vietnam. The patient with a 10-year history of depression and type 2 diabetes mellitus was admitted to the hospital due to vulvar itching and vaginal discharge. Vaginal swabs confirmed the presence of a yeast infection by direct microscopic examination with 10% KOH and culture on CHROMagar Candida. The yeast was identified as C victoriae using genetic sequencing tools. The patient’s treatment plan involved topical clotrimazole and a daily oral dose of 200 mg of itraconazole for 7 days. This comprehensive treatment approach resulted in the patient’s full recovery. This is the first reported case of vulvovaginitis attributed to C victoriae in humans worldwide.

Our main purpose is to establish Gagliardo-Nirenberg-type inequalities using fractional homogeneous Sobolev spaces and homogeneous Besov spaces. In particular, we extend some of the results obtained by the authors in previous studies.

ObjectiveTo investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory failure requiring mechanical ventilation support and to assess the predictive capability of OSI in determining clinically relevant OI cutoffs.MethodsA prospective study was conducted on neonates who received invasive mechanical ventilation at the neonatal intensive care unit of tertiary hospital in Vietnam. Bland-Altman analysis was utilized to evaluate the agreement between OSI and OI.ResultsA total of 123 neonates, including both term and preterm infants, were included in the study. A high agreement rate of 94.3% within the 95% limits of agreement (between OI and OSI), with a narrow similarity value of 3.3 (95% CI: -5.1 to 11.8) and high correlation coefficient (r = 0.791, p15 was determined to be 7.45, with a sensitivity of 100% and a specificity of 87.4% (AUC 0.955; 95% CI: 0.922-0.989, p < 0.05). Similarly, an OSI cutoff value of 9.9 corresponded to an OI of 25, displaying a sensitivity of 100% and specificity of 87.4% (AUC 0.92). The receiver operating characteristic (ROC) curves for OSI exhibited statistically significant results (p < 0.05).ConclusionThe findings demonstrate a strong correlation between OSI and OI in neonates with respiratory failure. Furthermore, OSI, as a non-invasive method, can serve as a substitute for OI to evaluate the severity of hypoxic respiratory failure and lung injury in neonates.

Abstract Background Retinoblastoma (RB), an intraocular malignancy commonly diagnosed in children, is mostly caused by inactivating mutations of both alleles of the RB1 gene. Early genetic screening for RB1 gene mutations would greatly improve treatment outcomes and patient management. Methods In this study, both somatic and germline mutations were detected in blood and tumour samples of 42 RB patients using direct sequencing and multiplex ligation‐dependent probe amplification. Results In total, 34 different mutations were found in 36 patients, including 1 SNP, 4 large deletions, 5 splicing sites, 1 missense, 7 frameshifts and 17 nonsense mutations. There were five novel mutations and one unreported which have not been found in large databases such as Leiden Open Variation Database (LOVD) and ClinVar. Conclusion A higher rate of RB patients carrying heterozygous germline mutation and highly prevalent with pathogenic truncated mutation, hence, early detection of RB is essential for vision salvation and genetic counselling.

Research on ridesharing platforms under the gig economy has focused much on the incentives and barriers of users, leaving many gaps in understanding drivers’ intention to provide ridesharing services. This paper aims to explore, from the perspective of driver-partners, motives that encourage them to continue being gig workers. Data for the study are based on a cross-sectional survey of ridesharing drivers in three metropolitan areas in three regions (North, Central, and South) of Vietnam, conducted from June to July 2022. The paper regresses behavioral intention to continue being a gig driver on their demographic characteristics and self-estimation of economic benefit, time preference, and enjoyment of being a gig driver via ordered probit models. For all three regions, the result suggests that economic benefit, time preference, and enjoyment are good predictors of drivers’ intention to provide the services. Specifically, the probability of remaining in gig work among drivers decreases with their educational and economic status. Higher economic benefit does not predict a higher intention of drivers to stay longer in gig work. Similarly, those with higher levels of enjoyment of traveling and vehicles have a lower intention to remain in this sphere. In the North, the interaction terms between time preference and enjoyment level are significant, suggesting that the effect of enjoyment levels becomes less damaging with an increase in time preference. In other words, time preference is vital in keeping gig drivers in this type of work.

Abstract We previously demonstrated that P. aeruginosa isolates that persisted in children with cystic fibrosis (CF) despite inhaled tobramycin treatment had increased anti-Psl antibody binding in vitro compared to those successfully eradicated. We aimed to validate these findings by directly visualizing P. aeruginosa in CF sputum. This was a prospective observational study of children with CF with new-onset P. aeruginosa infection who underwent inhaled tobramycin eradication treatment. Using microbial identification passive clarity technique (MiPACT), P. aeruginosa was visualized in sputum samples obtained before treatment and classified as persistent or eradicated based on outcomes. Pre-treatment isolates were also grown as biofilms in vitro. Of 11 patients enrolled, 4 developed persistent infection and 7 eradicated infection. P. aeruginosa biovolume and the number as well as size of P. aeruginosa aggregates were greater in the sputum of those with persistent compared with eradicated infections (p

Background Computed tomography (CT) is increasingly used for assessing skeletal muscle characteristics. In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), reduced limb muscle mass predicts poor clinical outcomes. However, the degree to which quantity or quality of respiratory and nonrespiratory muscles is affected by these diseases remains controversial. Methods Thoracic CT images of 29 CF, 21 COPD and 20 normal spirometry control subjects were analysed to measure indices of muscle quantity (volume or cross-sectional area) and quality (radiodensity) in respiratory (diaphragm, abdominal) and nonrespiratory (pectoralis, lumbar paraspinal) muscles. Multivariable linear regression assessed relationships of CT measurements with body mass index (BMI), forced expiratory volume in 1 s (FEV1) % pred, inflammation and infection biomarkers, nutritional status and CF genotype. Results Diaphragm volume in CF was significantly higher than in COPD (by 154%) or controls (by 140%). Abdominal muscle area in CF was also greater than in COPD (by 130%). Nonrespiratory muscles in COPD had more low radiodensity muscle (marker of lipid content) compared to CF and controls. In CF but not COPD, higher BMI and FEV1 % pred were independently associated with higher diaphragm and/or abdominal muscle quantity indices. Serum creatinine also predicted respiratory and nonrespiratory muscle quantity in CF, whereas other biomarkers including genotype correlated poorly with muscle CT parameters. Conclusions Our data suggest that the CF diaphragm undergoes hypertrophic remodelling, whereas in COPD the nonrespiratory muscles show altered muscle quality consistent with greater lipid content. Thoracic CT can thus identify distinctive respiratory and nonrespiratory muscle remodelling signatures associated with different chronic lung diseases.

Age-related macular degeneration (AMD) is a chronic disease leading to blindness in older adults and poses a significant economic burden to the healthcare system. The macula is regularly exposed to light, oxidative and inflammatory stress which play a central role in AMD pathogenesis. Lutein, zeaxanthin and their isomer meso-zeaxanthin are carotenoids from plants accumulating in the human macula that scavenge light, and reduce oxidation and inflammation. This review of relevant cellular, animal and human clinical trials investigated the benefits of the plant carotenoids, as a preventative and therapeutic treatment for AMD. Factors influencing the protective effects of the carotenoids were dependent on dose and treatment duration that could be important for translational applications leading to visual improvement in AMD patients. The application of carotenoid supplementation was discussed to provide non-invasive alternatives for the prevention and treatment of AMD.

Simulation-based inferences have attracted much attention in recent years, as the direct computation of the likelihood function in many real-world problems is difficult or even impossible. Iterated filtering (Ionides, Bretó, and King 2006; Ionides, Bhadra, Atchadé, and King 2011) enables maximization of likelihood function via model perturbations and approximation of the gradient of loglikelihood through sequential Monte Carlo filtering. By an application of Stein’s identity, Doucet, Jacob, and Rubenthaler (2013) developed a second-order approximation of the gradient of log-likelihood using sequential Monte Carlo smoothing. Based on these gradient approximations, we develop a new algorithm for maximizing the likelihood using the Nesterov accelerated gradient. We adopt the accelerated inexact gradient algorithm (Ghadimi and Lan 2016) to iterated filtering framework, relaxing the unbiased gradient approximation condition. We devise a perturbation policy for iterated filtering, allowing the new algorithm to converge at an optimal rate for both concave and non-concave log-likelihood functions. It is comparable to the recently developed Bayes map iterated filtering approach and outperforms the original iterated filtering approach.

Background: Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism. Methods: We studied 1069 Indonesian and Vietnamese adults with TBM (26.6% HIV-positive), 54 non-infectious controls, 50 with bacterial meningitis, and 60 with cryptococcal meningitis. Tryptophan and downstream metabolites were measured in cerebrospinal fluid (CSF) and plasma using targeted liquid chromatography–mass spectrometry. Individual metabolite levels were associated with survival, clinical parameters, CSF bacterial load and 92 CSF inflammatory proteins. Results: CSF tryptophan was associated with 60-day mortality from TBM (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 1.10–1.24, for each doubling in CSF tryptophan) both in HIV-negative and -positive patients. CSF tryptophan concentrations did not correlate with CSF bacterial load nor CSF inflammation but were negatively correlated with CSF interferon-gamma concentrations. Unlike tryptophan, CSF concentrations of an intercorrelating cluster of downstream kynurenine metabolites did not predict mortality. These CSF kynurenine metabolites did however correlate with CSF inflammation and markers of blood–CSF leakage, and plasma kynurenine predicted death (HR 1.54, 95% CI = 1.22–1.93). These findings were mostly specific for TBM, although high CSF tryptophan was also associated with mortality from cryptococcal meningitis. Conclusions: TBM patients with a high baseline CSF tryptophan or high systemic (plasma) kynurenine are at increased risk of death. These findings may reveal new targets for host-directed therapy. Funding: This study was supported by National Institutes of Health (R01AI145781) and the Wellcome Trust (110179/Z/15/Z and 206724/Z/17/Z).

In this study, we conducted experiments to assess the forecasting capabilities for tropical cyclone (TC) genesis over the east sea of Vietnam using the ensemble-based data assimilation system (EPS-DA) by WRF-LETKF. These experiments covered forecast lead times of up to 5 days and spanned a period from 2012 to 2019, involving a total of 45 TC formation events. The evaluation involved forecast probability assessments and positional and timing error analysis. Results indicated that successful forecasting depends on the lead time and initial condition quality. For TC formation from an embryo vortex to tropical depression intensity, the EPS-DA system demonstrated improved accuracy as the forecast cycle approached the actual formation time. TC centers converged towards observed locations, highlighting the potential of assimilation up to 5 days before formation. We examined statistical variations in dynamic and thermodynamic variables relevant to TC processes, offering an objective system assessment. Our study emphasized that early warnings of TC development appear linked to formation-time environmental conditions, particularly strong vorticity and enhanced moisture processes.

Climate change (CC) is likely to have a long-term influence on regional water resources, including surface water and groundwater. Therefore, quantifying the CC influence is indispensable for proper management of water resources. This study scrutinized the influence of CC on river discharge and groundwater recharge (GWR) in Ho Chi Minh City (HCMC), Vietnam, utilizing the Soil and Water Assessment Tool (SWAT). The calibrated SWAT was utilized to simulate the discharge and GWR under projected climate scenarios in reliance on an ensemble of seven General Circulation Models (GCMs) derived from Coupled Model Intercomparison Project Phase 6 (CMIP6) under three Shared Socioeconomic Pathways (SSPs), including SSP1-2.6, SSP2-4.5, and SSP5-8.5. Results pointed out that the climate of HCMC is warmer and wetter in the 21st century. Under the CC influence, the future discharge is envisaged to rise from 0.1 to 4.5% during the near-future period of 2030s (2021–2045), 8.1 to 11.6% during the mid-future period of 2055s (2046–2070), and 7.7 to 19.6% during the far-future period of 2080s (2071–2095) under the three SSP scenarios. In addition, the GWR is prognosticated to have rising trends of 0.9–4.9%, 5.3–7.9%, and 5.7– 13.5% during the near-future, mid-future, and far-future periods, respectively. Furthermore, uncertainties in the discharge and GWR projections connected with SSP scenarios and CMIP6 GCMs are considerable. HIGHLIGHTS This study investigated the projected influence of climate change on discharge and groundwater recharge (GWR).; Discharge and GWR will rise in the 21st century under three SSPs.; Uncertainties related to SSPs and CMIP6 GCMs are considerable.;

In this paper, the responses of hydro-meteorological drought to changing climate in the Be River Basin located in Southern Vietnam are investigated. Climate change scenarios for the study area were statistically downscaled using the Long Ashton Research Station Weather Generator tool, which incorporates climate projections from Coupled Model Intercomparison Project 5 (CMIP5) based on an ensemble of five general circulation models (Can-ESM2, CNRM-CM5, HadGEM2-AO, IPSL-CM5A-LR, and MPI-ESM-MR) under two Representative Concentration Pathway (RCP) scenarios (RCP4.5 and RCP8.5). The Soil and Water Assessment Tool model was employed to simulate streamflow for the baseline time period and three consecutive future 20-year periods of 2030s (2021–2040), 2050s (2041–2060), and 2070s (2061–2080). Based on the simulation results, the Standardized Precipitation Index and Standardized Discharge Index were estimated to evaluate the features of hydro-meteorological droughts. The hydrological drought has a 1-month lag time from the meteorological drought and the hydro-meteorological droughts have negative correlations with the El Niño Southern Oscillation and Pacific Decadal Oscillation. Under the climate change impacts, the trends of drought severity will decrease in the future; while the trends of drought frequency will increase in the near future period (2030s), but decrease in the following future periods (2050 and 2070s). The findings of this study can provide useful information for the policy- and decisionmakers for a better future planning and management of water resources in the study region. HIGHLIGHTS There is a lack of knowledge about how climate change will affect the hydro-meteorological drought in the tropical region.; The hydro-meteorological droughts have negative correlations with the global climate oscillation.; The drought frequency will have a rising trend in the near future period (2030s) and downward trends in the following future periods (2050 and 2070s).;

Multi-strain pathogens, such as influenza, present challenges for interpretation of seroprevalence data as estimates may vary by strain. Here, the authors develop a method for estimating age-specific seroprevalence based on principal components analysis and apply it to influenza data from Vietnam.

nimble is an R package for constructing algorithms and conducting inference on hierarchical models. The nimble package provides a unique combination of flexible model specification and the ability to program model-generic algorithms. Specifically, the package allows users to code models in the BUGS language, and it allows users to write algorithms that can be applied to any appropriate model. In this paper, we introduce the nimbleSMC R package. nimbleSMC contains algorithms for state-space model analysis using sequential Monte Carlo (SMC) techniques that are built using nimble. We first provide an overview of state-space models and commonly-used SMC algorithms. We then describe how to build a state-space model in nimble and conduct inference using existing SMC algorithms within nimbleSMC. SMC algorithms within nimbleSMC currently include the bootstrap filter, auxiliary particle filter, ensemble Kalman filter, IF2 method of iterated filtering, and a particle Markov chain Monte Carlo (MCMC) sampler. These algorithms can be run in R or compiled into C++ for more efficient execution. Examples of applying SMC algorithms to linear autoregressive models and a stochastic volatility model are provided. Finally, we give an overview of how model-generic algorithms are coded within nimble by providing code for a simple SMC algorithm. This illustrates how users can easily extend nimble's SMC methods in high-level code.

Abstract The exopolysaccharide Psl contributes to biofilm structure and antibiotic tolerance and may play a role in the failure to eradicate Pseudomonas aeruginosa from cystic fibrosis (CF) airways. The study objective was to determine whether there were any differences in Psl in P. aeruginosa isolates that were successfully eradicated compared to those that persisted, despite inhaled tobramycin treatment, in children with CF. Initial P. aeruginosa isolates were collected from children with CF undergoing eradication treatment, grown as biofilms and labeled with 3 anti-Psl monoclonal antibodies (Cam003/Psl0096, WapR001, WapR016) before confocal microscopy visualization. When grown as biofilms, P. aeruginosa isolates from children who failed antibiotic eradication therapy, had significantly increased Psl0096 binding compared to isolates from those who cleared P. aeruginosa. This was confirmed in P. aeruginosa isolates from the SickKids Eradication Cohort as well as the Early Pseudomonas Infection Control (EPIC) trial. Increased anti-Psl antibody binding was associated with bacterial aggregation and tobramycin tolerance. The biofilm matrix represents a potential therapeutic target to improve P. aeruginosa eradication treatment.

Abstract Background Vaginal candidiasis is frequent in women of reproductive age. Accurate identification Candida provides helpful information for successful therapy and epidemiology study; however, there are very limited data from the Vietnam have been reported. This study was performed to determine the prevalence, species distribution of yeast causing vaginal discharge and antifungal susceptibility patterns of Candida albicans among symptomatic non-pregnant women of reproductive age. Methods Vaginal discharge samples were collected from 462 women of reproductive age in Hanoi, Vietnam between Sep 2019 and Oct 2020. Vaginal swabs from these patients were examined by direct microscopic examination (10% KOH). CHROMagar™ Candida medium and Sabouraud dextrose agar supplemented with chloramphenicol (0.5 g/l) were used to isolate yeast, and species identification was performed using morphological tests and molecular tools (PCR and sequencing). Antifungal susceptibility testing was determined according to the Clinical and Laboratory Standards Institute guidelines (M27-A3 and M27-S4). Results The prevalence of vaginal yeast colonization in non-pregnant women was 51.3% of 462 participants. Nine different yeast species were identified. Among these isolates, C. albicans (51.37%) was the most frequent, followed by C. parapsilosis (25.88%), C. glabrata (11.37%), C. tropicalis (4.31%), C. krusei (3.92%), C. africana (1.57%), Saccharomyces cerevisiae (0.78%), C. nivariensis (1 isolates, 0.39%), and C. lusitaniae (1 isolates, 0.39%), respectively. Among C. albicans, all 46 isolates were 100% susceptible to micafungin, caspofungin, and miconazole. The susceptibility rates to amphotericine B, 5-flucytosine, fluconazole, itraconazole and voriconazole were 95.65, 91.30, 91.30, 82.61 and 86.95%, respectively. Conclusions The prevalence of VVC among symptomatic non-pregnant women of reproductive age in Vietnam was higher than many parts of the world. The high frequency of non-albicans Candida species, which were often more resistant to antifungal agents, was a notable feature. Resistance rates of vaginal C. albicans isolates to antifungal agents was low. Our findings suggest that continued surveillance of changes in species distribution and susceptibility to antifungals should be routinely screened and treated.

We consider the high-dimensional equation ∂t⁡u-Δ⁢um+u-β⁢χ{u>0}=0{\partial_{t}u-\Delta u^{m}+u^{-\beta}{\chi_{\{u>0\}}}=0}, extending the mathematical treatment made in 1992 by B. Kawohl and R. Kersner for the one-dimensional case. Besides the existence of a very weak solution u∈𝒞⁢([0,T];Lδ1⁢(Ω)){u\in\mathcal{C}([0,T];L_{\delta}^{1}(\Omega))}, with u-β⁢χ{u>0}∈L1⁢((0,T)×Ω){u^{-\beta}\chi_{\{u>0\}}\in L^{1}((0,T)\times\Omega)}, δ⁢(x)=d⁢(x,∂⁡Ω){\delta(x)=d(x,\partial\Omega)}, we prove some pointwise gradient estimates for a certain range of the dimension N, m≥1{m\geq 1} and β∈(0,m){\beta\in(0,m)}, mainly when the absorption dominates over the diffusion (1≤m

Abstract Background Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam. Methods This retrospective study included 2266 patients who initiated MDR-TB treatment between 2011 and 2015 in HCMC. Treatment outcomes were available for 2240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program. Results Among 2266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011 to 2015. The treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty or 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1 kg/m2 of BMI for patients with BMI

The aim of the present study is to assess the effect of hydropower dams on the streamflow in the Be river basin using the Soil and Water Assessment Tool (SWAT). Model calibration and validation of SWAT were conducted using the historical data collected from two stream gauges, namely Phuoc Long and Phuoc Hoa, and the obtained results indicated that SWAT shows a good reliability in reproducing streamflow with R2>0.90 and NSE>0.70 for both periods of calibration (1980-1990) and validation (1991-1993). Considering the results of SWAT’s calibration, the hydrological impact on the streamflow needs to be taken into consideration. The study results show that the separate impact of each hydrological dam (Thac Mo reservoir, Can Don reservoir, and Srok Phu Mieng reservoir) significantly increases streamflow in the dry season (89-101%) and decreases it in the wet season (6-33%). Moreover, there is a considerable rise in the dry season (89%) and a significant decline in the wet season (33%) of streamflow under the combined impact of the three dams.

In recent years, magnesium hydroxide has been widely studied due to its bioactivity and biocompatibility. The bactericidal effects of magnesium hydroxide nanoparticles on oral bacteria have also been reported. Therefore, in this study, we investigated the biological effects of magnesium hydroxide nanoparticles on inflammatory responses induced by periodontopathic bacteria. Macrophage-like cells, namely J774.1 cells, were treated with LPS derived from Aggregatibacter actinomycetemcomitans and two different sizes of magnesium hydroxide nanoparticles (NM80/NM300) to evaluate their effects on the inflammatory response. Statistical analysis was performed using an unresponsive Student’s t-test or one-way ANOVA followed by Tukey’s post hoc test. NM80 and NM300 inhibited the expression and secretion of IL-1β induced by LPS. Furthermore, IL-1β inhibition by NM80 was dependent on the downregulation of PI3K/Akt-mediated NF-κB activation and the phosphorylation of MAPK molecules such as JNK, ERK1/2, and p38 MAPK. By contrast, only the deactivation of the ERK1/2-mediated signaling cascade is involved in IL-1β suppression by NM300. Although the molecular mechanism involved varied with size, these results suggest that magnesium hydroxide nanoparticles have an anti-inflammatory effect against the etiologic factors of periodontopathic bacteria. These properties of magnesium hydroxide nanoparticles can be applied to dental materials.

Although various caries-preventive agents have been developed, dental caries is still a leading global disease, mostly caused by biological factors such as mutans streptococci. Magnesium hydroxide nanoparticles have been reported to exhibit antibacterial effects; however, they are rarely used in oral care practical applications. In this study, we examined the inhibitory effect of magnesium hydroxide nanoparticles on biofilm formation by Streptococcus mutans and Streptococcus sobrinus—two typical caries-causing bacteria. Three different sizes of magnesium hydroxide nanoparticles (NM80, NM300, and NM700) were studied, all of which inhibited biofilm formation. The results showed that the nanoparticles were important for the inhibitory effect, which was not influenced by pH or the presence of magnesium ions. We also determined that the inhibition process was mainly contact inhibition and that medium (NM300) and large (NM700) sizes were particularly effective in this regard. The findings of our study demonstrate the potential applications of magnesium hydroxide nanoparticles as caries-preventive agents.

Pseudomonas aeruginosa is a gram-negative opportunistic pathogen capable of causing both acute and chronic infections, particularly in individuals with compromised host defenses. The quorum sensing transcriptional activator LasR is widely recognized for its role in regulating the expression of acute virulence factors, notably several secreted proteases which cause direct host damage and subvert host immunity in acute infections. Paradoxically, lung infections caused by LasR-deficient variants, which are found in at least a third of cystic fibrosis (CF) patients with chronic P. aeruginosa infections, are associated with accelerated lung disease and increased markers of inflammation compared to infections caused by strains with a functional LasR system. While the loss of LasR function often (although not always) results in impaired production of LasR-controlled acute virulence factors, the implication of this pathoadaptation on host-pathogen interactions and chronic disease pathology is less well recognized. We recently observed that loss of LasR function in lasR variants, which results in impaired secreted protease production, led to increased expression of the membrane-bound surface adhesion molecule mICAM-1 in the airway epithelium, and increased neutrophilic inflammation. Specifically, human airway epithelial cells stimulated with lasR variants had higher mICAM-1 expression and greater neutrophil binding in vitro compared to stimulation with wild-type P. aeruginosa. In a subacute non-lethal P. aeruginosa lung infection model, lasR variant infection also induced higher mICAM-1 expression in the murine airway epithelium and was associated with increased neutrophilic pulmonary inflammation in vivo. Here, we discuss how (loss of) LasR function and LasR-regulated proteases affect host immunity, inflammation and tissue pathology in acute vs. chronic P. aeruginosa lung infection.

Momordica cochinchinensis is a herbal medicine used throughout Asia and this study investigated the antimelanoma potentials and molecular mechanisms of M. cochinchinensis seed with emphasis on extraction to optimise bioactivity. Overall, the aqueous extract was superior, with a wider diversity and higher concentration of proteins and peptides that was more cytotoxic to the melanoma cells than other extraction solvents. The IC50 of the aqueous extract on melanoma cells were similar to treatment with current anticancer drugs, vemurafenib and cisplatin. This cytotoxicity was cancer-specific with lower cytotoxic effects on HaCaT epidermal keratinocytes. Cytotoxicity correlated with MAPK signalling pathways leading to apoptosis and necrosis induced by triggering tumour necrosis factor receptor-1 (TNFR1), reducing the expression of nuclear factor kappa B (NF-kB), and suppression of BRAF/MEK. This efficacy of M. cochinchinensis seed extracts on melanoma cells provides a platform for future clinical trials as potent adjunctive therapy for metastatic melanoma.

Abstract In recent years, droughts have strongly affected the Central Highlands of Vietnam and have resulted in crop damage, yield decline, and serious water shortage. This study investigated the livelihood vulnerability of five communities of farmers who are exposed to droughts in one of the more vulnerable regions of Vietnam—Dak Nong Province. A survey of 250 households was conducted in the five communities to collect data on the region’s sociodemographic profile, livelihood systems, social networks, health status, food and water security, drought conditions, and climate variability. Data were aggregated using a livelihood vulnerability index and the IPCC vulnerability index. The survey results indicate that Quang Phu community is the most vulnerable of the study’s communities, followed by Nam N’dir, Dak Nang, Duc Xuyen, and Dak D’ro in descending order of vulnerability. Water availability and livelihood strategies are the most important variables in determining the vulnerability of the five surveyed communities. In order to reduce vulnerability to droughts, water management practices and livelihood diversification in farming and nonfarming activities are recommended for the study area.

Rainfall data with an appropriate spatial resolution is a key input to hydrological models. However, networks of rain gauges are often sparsely and unevenly distributed in large catchments, especially in developing countries. High-resolution rainfall datasets, such as the Asian Precipitation Highly Resolved Observational Data Integration Towards Evaluation of Water Resources (APHRODITE), the Climate Forecast System Reanalysis (CFSR), the Climatic Research Unit Time Series (CRU-TS), the Global Precipitation Climatology Centre (GPCC) and the Tropical Rainfall Measuring Mission (TRMM), have become available to overcome such limitations. The objective of this study was to evaluate the impacts of four land-based rainfall products (APHRODITE, CFSR, CRU-TS, and GPCC) and a satellite-based rainfall product (TRMM) on streamflow of the upper catchment of Tri An reservoir in Vietnam using the Hydrological Modeling System (HEC-HMS). In addition, the available rain gauges data were used for comparison purpose. Result indicates that the TRMM and GPCC data show their best match to rain gauges data in simulating the streamflow in the period 1999–2007. Generally, the results indicate that the TRMM and GPCC data could be alternative solutions.

The regulation of protein synthesis is essential for maintaining cellular homeostasis, especially during stress responses, and its dysregulation could underlie the development of human diseases. The critical step during translation regulation is the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α). Here we report the identification of a direct kinase of eIF2α, microtubule affinity-regulating kinase 2 (MARK2), which phosphorylates eIF2α in response to proteotoxic stress. The activity of MARK2 was confirmed in the cells lacking the 4 previously known eIF2α kinases. MARK2 itself was found to be a substrate of protein kinase C delta (PKCδ), which serves as a sensor for protein misfolding stress through a dynamic interaction with heat shock protein 90 (HSP90). Both MARK2 and PKCδ are activated via phosphorylation in proteotoxicity-associated neurodegenerative mouse models and in human patients with amyotrophic lateral sclerosis (ALS). These results reveal a PKCδ-MARK2-eIF2α cascade that may play a critical role in cellular proteotoxic stress responses and human diseases.

Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during chronic CF infections, are associated with accelerated lung function decline in CF patients and induce exaggerated neutrophilic inflammation in model systems. In this study, we investigated how lasR mutants modulate airway epithelial membrane bound ICAM-1 (mICAM-1), a surface adhesion molecule, and determined its impact on neutrophilic inflammation in vitro and in vivo. We demonstrated that LasR-deficient strains induce increased mICAM-1 levels in airway epithelial cells compared to wild-type strains, an effect attributable to the loss of mICAM-1 degradation by LasR-regulated proteases and associated with enhanced neutrophil adhesion. In a subacute airway infection model, we also observed that lasR mutant-infected mice displayed greater airway epithelial ICAM-1 expression and increased neutrophilic pulmonary inflammation. Our findings provide new insights into the intricate interplay between lasR mutants, LasR-regulated proteases and airway epithelial ICAM-1 expression, and reveal a new mechanism involved in the exaggerated inflammatory response induced by lasR mutants.

Given the present climate change context, accurate and timely coffee yield prediction is critical to all farmers who work in the coffee industry worldwide. The aim of this study is to develop and assess a coffee yield forecasting method at the regional scale in Dak Lak province in the central highlands of Vietnam using the Crop Growth Monitoring System Statistical Tool (CGMSstatTool—CST) software and vegetation biophysical variables (NDVI, LAI, and FAPAR) derived from satellite remote sensing (SPOT-VEGETATION and PROBA-V). There has been no research to date applying this approach to this specific crop, which is the main contribution of this study. The findings of this research reveal that the elaboration of multiple linear regression models based on a combination of information from satellite-derived vegetation biophysical variables (LAI, NDVI, and FAPAR) corresponding to the first six months of the years 2000–2019 resulted in coffee yield forecast models presenting satisfactory accuracy (Adj.R2 = 64 to 69%, RMSEp = 0.155 to 0.158 ton/ha and MAPE = 3.9 to 4.7%). These results demonstrate that the CST may efficiently predict coffee yields on a regional scale by using only satellite-derived vegetation biophysical variables. This study findings are likely to aid local governments and decision makers in precisely forecasting coffee production early and promptly, as well as in recommending relevant local agricultural policies.

Stressors and environmental cues shape the physiological state of bacteria, and thus how they subsequently respond to antibiotic toxicity. To understand how superoxide stress can modulate survival to bactericidal antibiotics, we examined the effect of intracellular superoxide generators, paraquat and menadione, on stationary-phase antibiotic tolerance of the opportunistic pathogen, Pseudomonas aeruginosa. We tested how pre-challenge with sublethal paraquat and menadione alters the tolerance to ofloxacin and meropenem in wild-type P. aeruginosa and mutants lacking superoxide dismutase (SOD) activity (sodAB), the paraquat responsive regulator soxR, (p)ppGpp signaling (relA spoT mutant), or the alternative sigma factor rpoS. We confirmed that loss of SOD activity impairs ofloxacin and meropenem tolerance in stationary phase cells, and found that sublethal superoxide generators induce drug tolerance by stimulating SOD activity. This response is rapid, requires de novo protein synthesis, and is RpoS-dependent but does not require (p)ppGpp signaling nor SoxR. We further showed that pre-challenge with sublethal paraquat induces a SOD-dependent reduction in cell-envelope permeability and ofloxacin penetration. Our results highlight a novel mechanism of hormetic protection by superoxide generators, which may have important implications for stress-induced antibiotic tolerance in P. aeruginosa cells.

Cystic fibrosis (CF) patients frequently acquire Pseudomonas aeruginosa infections that have been associated with a bad prognosis and an increased rate of pulmonary exacerbations. Respiratory viruses can cause exacerbations in chronic pulmonary diseases including COPD or asthma and have been suggested to contribute to exacerbations also in CF. In this study we investigated a possible link between P. aeruginosa infection and susceptibility to respiratory viruses. We show that P. aeruginosa is able to block the antiviral response of airway epithelial cells thereby promoting virus infection and spread. Mechanistically, P. aeruginosa secretes the protease AprA in a LasR dependent manner, which is able of directly degrading epithelial-derived IFNλ resulting in inhibition of IFN signaling. In addition, we correlate the virus infection status of CF patients with the ability of patients' P. aeruginosa isolates to degrade IFNλ. In line with this, the infection status of CF patients correlated significantly with the amount of respiratory viruses in sputum. Our data suggest that the interplay between P. aeruginosa and respiratory virus infections might partially explain the association of increased rates of pulmonary exacerbations and P. aeruginosa infections in CF patients.

The mold Aspergillus fumigatus and bacterium Pseudomonas aeruginosa form biofilms in the airways of individuals with cystic fibrosis. Biofilm formation by A. fumigatus depends on the self-produced cationic exopolysaccharide galactosaminogalactan (GAG), while P. aeruginosa biofilms can contain the cationic exopolysaccharide Pel. GAG and Pel are rendered cationic by deacetylation mediated by either the secreted deacetylase Agd3 (A. fumigatus) or the periplasmic deacetylase PelA (P. aeruginosa). Given the similarities between these polymers, the potential for biofilm interactions between these organisms were investigated. P. aeruginosa were observed to adhere to A. fumigatus hyphae in a GAG-dependent manner and to GAG-coated coverslips of A. fumigatus biofilms. In biofilm adherence assays, incubation of P. aeruginosa with A. fumigatus culture supernatants containing de-N-acetylated GAG augmented the formation of adherent P. aeruginosa biofilms, increasing protection against killing by the antibiotic colistin. Fluorescence microscopy demonstrated incorporation of GAG within P. aeruginosa biofilms, suggesting that GAG can serve as an alternate biofilm exopolysaccharide for this bacterium. In contrast, Pel-containing bacterial culture supernatants only augmented the formation of adherent A. fumigatus biofilms when antifungal inhibitory molecules were removed. This study demonstrates biofilm interaction via exopolysaccharides as a potential mechanism of co-operation between these organisms in chronic lung disease.

Abstract Background The depletion of CD4 cell is the underlying reason for TB hyper-susceptibility among people with HIV. Consequently, the trend of TB dynamics is usually hidden by the HIV outbreak. Methods Here, we aim to evaluate the trend of TB dynamics quantitatively by a simple mathematical model using the known prevalence of hyper-susceptible individuals in the population. In order to estimate the parameters governing transmission we fit this model in a maximum likelihood framework to both reported TB cases and data from samples tested with Interferon Gamma Assay from Ho Chi Minh City - a city with high TB transmission and strong synchronization between HIV/AIDS and TB dynamics. Results Our results show that TB transmission in HCMC has been declining among people without HIV; we estimate a 18% (95% CI: 9–25%) decline in the transmission parameter between 1996 and 2015. Furthermore, we show that co-infected patients have limited contribution to the transmission process. For hyper-susceptible individuals, our model suggests that the risk of a new active TB infection occurring is significantly higher than the risk of relapsed active TB, while this is not the case for people without hyper-susceptibility. Conclusions The increase of TB notifications in Ho Chi Minh City from 1996 to 2008 is evitable when, as occurred, the number of hyper-susceptible individuals increased faster than the decrease of TB transmission rate. The sharp decrease in TB notifications observed in this city from 2008 to 2015 is the combined result of the decrease of TB transmission rate and the decrease of hyper-susceptible individuals in the population. For hyper-susceptible individuals, we propose that the reason for the reduced relapsed active TB risk is HIV treatment delay. According to HIV treatment guidelines issued by Vietnam’s Ministry of Health, hyper-susceptible individuals usually have to wait until their CD4 cell count falls under 350 cells/μl to start ART. Once patients begin ART, they will remain on ART for the rest of their life and thus have greater protection against relapses of TB. We therefore hypothesize that the delay in using ART imposes considerable TB burden on HCMC despite the declining transmission process.

In this contribution we present an experimental study of 3D opal photonic crystals. The samples are opals constituted by colloidal silica spheres, realized with self-assembly technique. The sphere diameter is selected in order to obtain coupling of the photonic band gap with the emission from CdSe/ZnS colloidal quantum dots. The quantum dots infiltrated in the opals is expected to be enhanced or suppressed depending on the detection angle from the photonic crystal. The structural and optical characterization of the SiO2 opal photonic crystals are performed by field-emission scanning electron microscopy and reflectivity spectroscopy. Measurements performed on samples permits to put into evidence the influence of the different preparation methods on the optical properties. Study of self-activated luminescence of the pure opals is also presented. It is shown that the luminescence of the sample with QDs have original QD emission and not due to the photonic crystal structure. The optical properties of colloidal core-shell semiconductor quantum dots of CdSe/ZnS which are prepared in our lab will be mention.

Abstract Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Their results are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A population’s natural distribution of antibody titers to an endemic infectious disease may include information on multiple serological states – naiveté, recent infection, non-recent infection, childhood infection – depending on the disease in question and the acquisition and waning patterns of immunity. In this study, we investigate 20,152 general-population serum samples from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent and historical infection, which is consistent with 2009 pandemic attack rates. Similar interpretations are available for H3N2, but right-censoring of titers makes these interpretations difficult to validate.

The goal of this study was to isolate, screen, and characterize Arctic microbial isolates from Expedition Fjord, Axel Heiberg Island, Nunavut, Canada capable of inhibiting the growth of foodborne and clinically relevant pathogens. Arctic bacteria were isolated from twelve different high Arctic habitats pertaining to active layer permafrost soil, saline spring sediments, lake sediments, and endoliths. This was achieved using (1) the cryo-iPlate, an innovative in situ cultivation device within active layer permafrost soil and (2) bulk plating of Arctic samples by undergraduate students that applied standard culturing methods. To mitigate the possibility of identifying isolates with already-known antibacterial activities, a cell-based dereplication platform was used. Ten out of the twelve Arctic habitats tested were found to yield cold-adapted isolates with antibacterial activity. Eight cold-adapted Arctic isolates were identified with the ability to inhibit the entire dereplication platform, suggesting the possibility of new mechanisms of action. Two promising isolates, initially cultured from perennial saline spring sediments and from active layer permafrost soil (Paenibacillus sp. GHS.8.NWYW.5 and Pseudomonas sp. AALPS.10.MNAAK.13, respectively), displayed antibacterial activity against foodborne and clinically relevant pathogens. Paenibacillus sp. GHS.8.NWYW.5 was capable of inhibiting methicillin resistant and susceptible Staphylococcus aureus (MRSA and MSSA), Listeria monocytogenes, Salmonella enterica and Escherichia coli O157:H7. Pseudomonas sp. AALPS.10.MNAAK.13 was observed to have antagonistic activity against MRSA, MSSA, Acinetobacter baumanii, Enterococcus faecium, and Enterococcus faecalis. After whole genome sequencing and mining, the genome of Paenibacillus sp. GHS.8.NWYW.5 was found to contain seven putative secondary metabolite biosynthetic gene clusters that displayed low homology ( 0) to clusters identified within the genome of the type strain pertaining to the same species. These findings suggest that cold-adapted Arctic microbes may be a promising source of novel secondary metabolites for potential use in both industrial and medical settings.

Pseudomonas aeruginosa is the most prevalent opportunistic pathogen in the airways of cystic fibrosis (CF) patients. The pulmonary disorder is characterized by recurrent microbial infections and an exaggerated host inflammatory immune response led primarily by influx of neutrophils. Under these conditions, chronic colonization with P. aeruginosa is associated with diminished pulmonary function and increased morbidity and mortality. P. aeruginosa has a wide array of genetic mechanisms that facilitate its persistent colonization of the airway despite extensive innate host immune responses. Loss of function mutations in the quorum sensing regulatory gene lasR have been shown to confer survival advantage and a more pathogenic character to P. aeruginosa in CF patients. However, the strategies used by LasR-deficient P. aeruginosa to modulate neutrophil-mediated bactericidal functions are unknown. We sought to understand the role of LasR in P. aeruginosa-mediated neutrophil extracellular trap (NET) formation, an important anti-microbial mechanism deployed by neutrophils, the first-line responder in the infected airway. We observe mechanistic and phenotypic differences between NETs triggered by LasR-sufficient and LasR-deficient P. aeruginosa strains. We uncover that LasR-deficient P. aeruginosa strains fail to induce robust NET formation in both human and murine neutrophils, independently of bacterial motility or LPS expression. LasR does not mediate NET release via downstream quorum sensing signaling pathways but rather via transcriptional regulation of virulence factors, including, but not restricted to, LasB elastase and LasA protease. Finally, our studies uncover the differential requirements for NADPH oxidase in NET formation triggered by different P. aeruginosa strains.

Magnesium hydroxide nanoparticles are widely used in medicinal and hygiene products because of their low toxicity, environment-friendliness, and low cost. Here, we studied the effects of three different sizes of magnesium hydroxide nanoparticles on antibacterial activity: NM80, NM300, and NM700. NM80 (D50 = 75.2 nm) showed a higher bactericidal effect against Escherichia coli than larger nanoparticles (D50 = 328 nm (NM300) or 726 nm (NM700)). Moreover, NM80 showed a high bactericidal effect against not only exponential cells but also persister cells, which are difficult to eliminate owing to their high tolerance to antibiotics. NM80 eliminated strains in which magnesium-transport genes were knocked out and exhibited a bactericidal effect similar to that observed in the wild-type strain. The bactericidal action involved physical cell damage, as confirmed using scanning electron microscopy, which showed that E. coli cells treated with NM80 were directly injured.