Study protocol: Early neurological deterioration in patients with minor stroke, frequency, predictors, and outcomes in Vietnam single-centre study.

Early neurological deterioration (END) is progressive neurological deterioration with an increase in NIHSS score of 2 points or more in the first 72 hours from the onset of acute ischemic stroke. END increases the risk of poor clinical outcomes at day 90 of ischemic stroke. We will study the frequency, predictors, and outcomes of patients with END in a case-control study at a comprehensive stroke centre in Vietnam. of the design is a descriptive observational study, longitudinal follow-up of patients with minor stroke hospitalized at the Stroke Center of Bach Mai Hospital from December 1, 2023, to December 1, 2024. Minor stroke patients characterized by NIHSS score ≤ 5 hospitalized within 24 hours of symptom onset will be recruited. The estimated END rate is about 30%, relative accuracy ε = 0.11, 95% reliability, expected 5% of patients lost data or follow-up, and an estimated sample size of 779 patients. This study will help determine the END rate in patients with minor stroke and related factors, thereby building a prognostic model for END. Our study determined the END rate in patients with minor stroke in Vietnam and also proposed risk factors for minor stroke management and treatment.

Norepinephrine and Dobutamine-Induced Dynamic Left Ventricular Outflow Tract Obstruction Caused by Systolic Anterior Motion.

This study presents a case of norepinephrine and dobutamine-induced dynamic left ventricular outflow tract obstruction (LVOTO) caused by systolic anterior motion (SAM) in a patient experiencing acute anterior myocardial infarction (MI). In a 76-year-old patient presenting with acute MI, intensive use of norepinephrine and dobutamine may lead to the development of dynamic LVOTO and SAM. The presence of hypotension and a new cardiac murmur may suggest a mechanical complication such as acute mitral regurgitation (MR) or ventricular septal rupture (VSR). The assessment of the left ventricular outflow tract (LVOT) using echocardiography plays a critical role in the diagnosis of SAM and its associated MR and dynamic LVOTO. The patient's condition was stabilized through the cessation of inotropes and the implementation of aggressive fluid resuscitation, resulting in improved hemodynamics. In conclusion, prompt identification of the underlying pathophysiological mechanisms is imperative for effectively managing this condition and preventing hemodynamic exacerbation.

Synthesis of new DOPO derivatives and investigation of their synergistic effect with APP-PEI on the flame retardancy of epoxy composite.

Epoxy resin has been extensively used in many industrial and daily applications due to its unique properties. However, the high flammability of epoxy has limited its further development. DOPO derivatives, which are organophosphorus compounds, are highly effective components of flame retardant epoxy composites due to their good compatibility with the resin and their lower toxicity compared to halogenated compounds. This study synthesized sixteen new DOPO derivatives, characterizing their chemical structures with NMR spectroscopy. The combination of synthesized DOPO derivatives and APP-PEI (ammonium polyphosphate-polyethyleneimine) has shown a synergistic effect on enhancing the flame retardancy of epoxy resin with the UL-94 V-0 rating and the LOI value of 28.6%. Moreover, the epoxy composites displayed relatively high mechanical performance with the impact strength of 26-28 kJ m-2.

LiOtBu-promoted synthesis of bis(3-indolyl)methanes by the alkylation of indoles with alcohols under air.

Bis(3-indolyl)methanes (BIMs) are known for their important bioactivities, which include anti-cancer, anti-inflammatory, antibacterial, and antioxidant properties. In this study, we are disclosing a metal catalyst-free synthesis of BIMs in high yields via the alkylation reaction of indoles and alcohols in the presence of lithium tert-butoxide base. Notably, oxygen in air played an important role as an oxidant for the facilitation of this transformation. Interestingly, unactivated aliphatic alcohols could be successfully used as alkylating reagents in the alkylation reactions of indole. Especially, several chemical intermediates detected by GC-MS gave important information about the mechanism insights. This method demonstrated cost and environmental advantages for the development of green processes.

Spatial epidemiology of human anthrax in Son La province, Vietnam, 2003-2022.

AIMS: Anthrax is reported with frequency but poorly understood in Southeast Asian countries including Vietnam. In Vietnam, anthrax surveillance is national. However, case detection, prevention, and control are implemented locally at the provincial level. Here, we describe the epidemiological characteristics, identify spatial clusters of human anthrax, and compare the variation in livestock anthrax vaccine coverage to disease incidence in humans and livestock using historical data in Son La province, Vietnam (2003-2020). METHODS AND RESULTS: Most human cases occurred between April and September. Most of the patients were male, aged 15-54 years old. The human cases were mainly reported by public district hospitals. There was a delay between disease onset and hospitalization of ~5 days. We identified spatial clusters of high-high incidence communes in the northern communes of the province using the local Moran's I statistic. The vaccine coverage sharply decreased across the study period. The province reported sporadic human anthrax outbreaks, while animal cases were only reported in 2005 and 2022. CONCLUSIONS: These results suggest underreporting for human and livestock anthrax in the province. Intersectoral information sharing is needed to aid livestock vaccination planning, which currently relies on reported livestock cases. The spatial clusters identify areas for targeted surveillance and livestock vaccination, while the seasonal case data suggest prioritizing vaccination campaigns for February or early March ahead of the April peak. A regional approach for studying the role of livestock trading between Son La and neighbouring provinces in anthrax occurrence is recommended.

Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure.

BACKGROUND: Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. METHODS: This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. RESULTS: In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40-55 kg, 55-70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. CONCLUSIONS: Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients.

Synthesis, in vitro Α-Glucosidase, and acetylcholinesterase inhibitory activities of novel Indol-Fused Pyrano[2,3-D]Pyrimidine compounds.

In this study, new indol-fused pyrano[2,3-d]pyrimidines were designed and synthesized. These products were obtained in moderate to good yields and their structures were assigned by NMR, MS, and IR analysis. Afterwards, the biological important of the products was highlighted by evaluating in vitro for α-glucosidase inhibitory activity as well as acetylcholinesterase (AChE) inhibitory activity. Eleven products revealed substantial inhibitory activity against α-glucosidase enzyme, among which, two most potent products 11d,e were approximately 93-fold more potent than acarbose as a standard antidiabetic drug. Besides that, product 11k exhibited good AChE inhibition. The substituents on the 5-phenyl ring, attached to the pyran ring, played a critical role in inhibitory activities. The biological potencies have provided an opportunity to further investigations of indol-fused pyrano[2,3-d]pyrimidines as potential anti-diabetic agents.

Facile access to 5H-thiazolo[2',3':2,3]imidazo[4,5-b]indole derivatives by two-fold Cu-catalysed C-N coupling reactions.

In four simple steps, a series of 5H-thiazolo[2',3':2,3]imidazo[4,5-b]indole and 11H-benzo[4',5']thiazolo[2',3':2,3]imidazo[4,5-b]indole derivatives were prepared with high yields. The key step in this procedure was demonstrated to be two-fold Cu-catalysed C-N coupling reactions of 5-bromo-6-(2-bromophenyl)imidazo[2,1-b]thiazole and 3-bromo-2-(2-bromophenyl)benzo[d]imidazo[2,1-b]thiazole with various amines.

Spatial and phylogenetic patterns reveal hidden infection sources of Bacillus anthracis in an anthrax outbreak in Son La province, Vietnam.

Bacillus anthracis, the bacterial cause of anthrax, is a zoonosis affecting livestock and wildlife often spilling over into humans. In Vietnam, anthrax has been nationally reportable since 2015 with cases occurring annually, mostly in the northern provinces. In April 2022, an outbreak was reported in Son La province following the butchering of a water buffalo, Bubalus bubalis. A total of 137 humans from three villages were likely exposed to contaminated meat from the animal. Early epidemiological investigations suggested a single animal was involved in all exposures. Five B. anthracis isolates were recovered from human clinical cases along with one from the buffalo hide, another from associated maggots, and one from soil at the carcass site. The isolates were whole genome sequenced, allowing global, regional, and local molecular epidemiological analyses of the outbreak strains. All recovered B. anthracis belong to the A.Br.001/002 lineage based on canonical single nucleotide polymorphism analysis (canSNP). Although not previously identified in Vietnam, this lineage has been identified in the nearby countries of China, India, Indonesia, Thailand, as well as Australia. A twenty-five marker multi-locus variable number tandem repeat analysis (MLVA-25) was used to investigate the relationship between human, soil, and buffalo strains. Locally, four MLVA-25 genotypes were identified from the eight isolates. This level of genetic diversity is unusual for the limited geography and timing of cases and differs from past literature using MLVA-25. The coupled spatial and phylogenetic data suggest this outbreak originated from multiple, likely undetected, animal sources. These findings were further supported by local news reports that identified at least two additional buffalo deaths beyond the initial animal sampled in response to the human cases. Future outbreak response should include intensive surveillance for additional animal cases and additional molecular epidemiological traceback to identify pathogen sources.

Insights into Structural Behaviors of Thiolated and Aminated Reduced Graphene Oxide Supports to Understand Their Effect on MOR Efficiency.

It is essential to develop novel catalysts with high catalytic activity, strong durability, and good stability for further application in methanol fuel cells. In this work, we present for the first time the effect of the chemical functional groups (thiol and amine) with different electron affinity in reduced graphene oxide supports on the morphology and catalytic activity of platinum nanoparticles for the methanol oxidation reaction. Hydroxyl groups on graphene oxide were initially brominated and then transformed to the desired functional groups. The good dispersion of metal nanoparticles over functionalized carbon substrates (particle size less than 5 nm) with good durability, even at a limited functionalization degree (less than 7%) has been demonstrated by morphological and structural studies. The durability of the catalysts was much improved via strong coordination between the metal and nitrogen or sulfur atoms. Impressively, the catalytic activity of platinum nanoparticles on aminated reduced graphene oxide was found to be much better than that on thiolated graphene oxide despite the weaker affinity between amine and noble metals. These findings support further developing new graphene derivatives with the desired functionalization for electronics and energy applications..

Clinical Features and Treatment Outcomes of COVID-19 Admissions in the Can Tho City Hospital of Tuberculosis and Respiratory Diseases, Vietnam: A Hospital-Based Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is among the top global health crises. As confirmed by the Vietnam Ministry of Health on 25th January 2023, Vietnam had a cumulative total of more than 11.52 million COVID-19 patients, including 10.61 million recoveries and 43,186 deaths. OBJECTIVES: This study aimed to describe the clinical and subclinical characteristics, treatment progress, and outcomes of 310 cases of SARS-CoV-2 infection. METHODS: A total of 310 patients with medical records of SARS-CoV-2 were admitted to Can Tho City Hospital of Tuberculosis and Lung Diseases, Can Tho city, Vietnam, between July 2021 and December 2021. Demographic and clinical data, including laboratory examinations, of all the patients were collected and analyzed. RESULTS: The median duration of hospital stay was 16.4 ± 5.3 days. There were 243 (78.4%) patients with clinical symptoms of COVID-19 and 67 (21.6%) patients without clinical symptoms. The common symptoms included cough (71.6% of 310 patients), fever (35.4%), shortness of breath (22.6%), sore throat (21.4%), loss of smell/taste (15.6%), and diarrhea (14.4%). Regarding treatment outcomes, 92.3% of the patients were discharged from the hospital, 1.9% of the patients suffered a more severe illness and were transferred to a higher-level hospital, and 5.8% of the patients died. The RT-PCR results were negative in 55.2% of the patients, and 37.1% of the patients had positive RT-PCR results with Ct values of >30 on the discharge/transfer day. Multivariate logistic regression analyses showed that comorbidity and decreased blood pH were statistically significantly related to the treatment outcomes of the patients with COVID-19 (p < 0.05). CONCLUSIONS: This study provides useful information (i.e., the clinical characteristics and treatment outcomes) on the COVID-19 pandemic in Vietnam during its biggest outbreak; the information may be used for reference and for making improvements in the handling of future health crises.

Prevalence and Associated Factors of optrA-Positive-Enterococcus faecalis in Different Reservoirs around Farms in Vietnam.

Linezolid is an antibiotic of last resort for the treatment of infections caused by Gram-positive bacteria, including vancomycin-resistant enterococci. Enterococcus faecalis, a member of enterococci, is a significant pathogen in nosocomial infections. E. faecalis resistance to linezolid is frequently related to the presence of optrA, which is often co-carried with fex, phenicol exporter genes, and erm genes encoding macrolide resistance. Therefore, the common use of antibiotics in veterinary might promote the occurrence of optrA in livestock settings. This is a cross-sectional study aiming to investigate the prevalence of optrA positive E. faecalis (OPEfs) in 6 reservoirs in farms in Ha Nam province, Vietnam, and its associated factors and to explore genetic relationships of OPEfs isolates. Among 639 collected samples, the prevalence of OPEfs was highest in flies, 46.8% (51/109), followed by chickens 37.3% (72/193), dogs 33.3% (17/51), humans 18.7% (26/139), wastewater 16.4% (11/67) and pigs 11.3%, (14/80). The total feeding area and total livestock unit of the farm were associated with the presence of OPEfs in chickens, flies, and wastewater. Among 186 OPEfs strains, 86% were resistant to linezolid. The presence of optrA was also related to the resistant phenotype against linezolid and levofloxacin of E. faecalis isolates. Close genotypic relationships identified by Pulsed Field Gel Electrophoresis between OPEfs isolates recovered from flies and other reservoirs including chickens, pigs, dogs, and wastewater suggested the role of flies in the transmission of antibiotic-resistant pathogens. These results provided warnings of linezolid resistance although it is not used in livestock.

A new chromanone acid derivative from the nut oil resin of Calophyllum inophyllum.

One novel chromanone acid derivative, namely inocalophylline C (1), together with one known compound calophyllolide (2), were isolated from the methanolic extract of nut oil resin of Calophyllum inophyllum L., a medicinal plant widely distributed in Vietnam. The isolated compound structures were elucidated by spectroscopic methods and the absolute configuration of 1 was established by the single-crystal X-ray crystallography as ethyl (R) 3-((2 R,3R,6R)-4-hydroxy-2,3-dimethyl-6-((R)-5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-yl)-6-(3-methylbut-2-en-1-yl)-5,7-dioxo-3,5,6,7-tetrahydro-2H-chromen-8-yl)-3-phenylpropanoate.

Recommendation of pharmacokinetics/pharmacodynamics target of ethambutol to suppress tuberculosis resistance: A population pharmacokinetics study on a large prospective cohort.

BACKGROUND: The ability of ethambutol (EMB) to suppress bacterial resistance has been demonstrated in a time-dependent manner. Through the development of a population pharmacokinetics (PK) model, this study aimed to suggest the PK/pharmacodynamics (PD) target and identify the significant covariates that influence interindividual variability (IIV) in the PK of EMB. METHODS: In total, 837 patients from 20 medical centres across Korea were enrolled in this study. The non-linear mixed-effect method was used to establish and validate the population PK model. RESULTS: A two-compartment model with transit compartment absorption was sufficient to describe the PK of EMB. Body weight and renal function were identified as significant covariates that affect IIV of the apparent clearance (CL/F) of EMB. Patients with moderate renal function showed 35% and 55% lower CL/F (CL/F 89.9 L/h) compared with those with mild and normal renal function, respectively. All the renal function groups with simulated doses ranging from 800 to 1200 mg achieved area under the curve over minimum inhibitory concentration (MIC) >119, and maintained T>MIC for >23 h for MIC of 0.5 µg/mL. Based on our simulation result, it is suggested that doses of 800, 1000, and 1200 mg should obtain the T>MIC target of 4, 6, and 8 h, respectively. This model was validated internally and externally. CONCLUSION: This study provides insight into the PK/PD indexes of EMB for three different renal function groups and T>MIC targets for different doses. The results could be used to provide optimal-dose suggestions for EMB.

Practical Synthesis of 1,4-Dihydropyridines on Heterogeneous Sulfonicmodified Silica (SBA-15-SO3H) Catalyst Under Mild Condition.

AIMS: Synthesis of 1,4-Dihydropyridines (1,4-DHP) using heterogeneous catalyst under mild condition. OBJECTIVE: Our objective is to explore new applications of non-metal heterogeneous catalysts in the synthesis of 1,4-DHP derivatives in a greener and more efficient approach. METHODS: A greener and more efficient method for the synthesis of 1,4-DHPs and an asymmetric 1,4-DHP (Felodipine drug) was successfully developed in high yields using a heterogeneous SBA- 15-SO3H catalyst. RESULTS: A series of symmetric 1,4-DHP and an asymmetric 1,4-DHP (Felodipine drug) were successfully prepared in high yields using a heterogeneous SBA-15-SO3H catalyst. CONCLUSION: The catalyst, SBA-15-SO3H, exhibited an efficient catalyst activity for the synthesis of 1,4-DHP derivatives in high yields from the aldehyde, ß-ketoester, and NH4OAc as a nitrogen source under mild conditions and short reaction time. Bronsted acid sites of this solid catalyst were figured out to play a key role in this transformation. Interestingly, our catalyst is air-stable and can be recycled at least 5 times without losing catalytic activity.

Mapping access to drug outlets in Vietnam: distribution of drug outlets and the sociodemographic characteristics of the communities they serve.

Background: Drug outlets are a vital first point of healthcare contact in low- and middle-income countries (LMICs), but they are often poorly regulated and counter staff may be unqualified to provide advice. This introduces the risk of easy access to potentially harmful products, including unnecessary antimicrobials. Over-the-counter antimicrobial sales are a major driver of antimicrobial resistance (AMR) in LMICs. We aimed to investigate the distribution of different types of drug outlets and their association with socio-economic factors. Methods: We mapped the location of drug outlets in 40 randomly selected geographic clusters, covering a population of 1.96 million people. Data including type of drug outlet, context, operating hours, chief pharmacist name and qualification, and business registration identification were collected from mandatory public signage. We describe the density of drug outlets and levels of staff qualifications in relation to population density, urban vs rural areas, and poverty indices. Findings: We characterised 1972 drug outlets. In the study area, there was an average of 102 outlets/per 100,000 population, compared to the global average of 25. Predictably, population density was correlated with the density of drug outlets. We found that drug outlets were less accessible in rural vs urban areas, and for the poor. Furthermore, for these populations, degree-qualified pharmacists were less accessible and public signage frequently lacked mandatory registration information. Interpretation: Drug outlets appear over-supplied in Vietnam compared to other countries. Unregistered outlets and outlets without degree-qualified pharmacists are prevalent, especially in poor and rural areas, posing a risk for inappropriate supply of antimicrobials, which may contribute to AMR, and raises questions of equitable healthcare access. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

Advancing personalized medicine for tuberculosis through the application of immune profiling.

While early and precise diagnosis is the key to eliminating tuberculosis (TB), conventional methods using culture conversion or sputum smear microscopy have failed to meet demand. This is especially true in high-epidemic developing countries and during pandemic-associated social restrictions. Suboptimal biomarkers have restricted the improvement of TB management and eradication strategies. Therefore, the research and development of new affordable and accessible methods are required. Following the emergence of many high-throughput quantification TB studies, immunomics has the advantages of directly targeting responsive immune molecules and significantly simplifying workloads. In particular, immune profiling has been demonstrated to be a versatile tool that potentially unlocks many options for application in TB management. Herein, we review the current approaches for TB control with regard to the potentials and limitations of immunomics. Multiple directions are also proposed to hopefully unleash immunomics' potential in TB research, not least in revealing representative immune biomarkers to correctly diagnose TB. The immune profiles of patients can be valuable covariates for model-informed precision dosing-based treatment monitoring, prediction of outcome, and the optimal dose prediction of anti-TB drugs.

Prehistoric human migration between Sundaland and South Asia was driven by sea-level rise.

Rapid sea-level rise between the Last Glacial Maximum (LGM) and the mid-Holocene transformed the Southeast Asian coastal landscape, but the impact on human demography remains unclear. Here, we create a paleogeographic map, focusing on sea-level changes during the period spanning the LGM to the present-day and infer the human population history in Southeast and South Asia using 763 high-coverage whole-genome sequencing datasets from 59 ethnic groups. We show that sea-level rise, in particular meltwater pulses 1 A (MWP1A, ~14,500-14,000 years ago) and 1B (MWP1B, ~11,500-11,000 years ago), reduced land area by over 50% since the LGM, resulting in segregation of local human populations. Following periods of rapid sea-level rises, population pressure drove the migration of Malaysian Negritos into South Asia. Integrated paleogeographic and population genomic analysis demonstrates the earliest documented instance of forced human migration driven by sea-level rise.

Traditional Vietnamese medicine Kovir capsule for non-severe COVID-19 patients: A phase III double-blind randomized controlled trial.

The number of COVID-19 infections is still increasing with the omicron variant. Although vaccination has shown its effectiveness, efficacious treatments are still required. Kovir, a Vietnamese herbal medicine, has shown potential effects for non-severe COVID-19 patients in terms of symptom resolution and prevention of disease progression in previous studies. This phase-3 trial evaluated the safety and efficacy of Kovir for non-severe COVID-19 adults. Participants were randomized to the Kovir (381 patients) or placebo (192 patients) groups. Outcomes were progression to severe/critical COVID-19, a daily symptom score based on 11 pre-defined symptoms, time to symptom resolution, a negative reverse transcription polymerase chain reaction, an EQ-5D-5L quality of life (QOL) score, and serious adverse events. Only one patient (in the placebo group) progressed to severe COVID-19, thus we could not conclude the effect of Kovir on the prevention of disease progression. Kovir significantly reduced time to symptom resolution (median: 7 vs. 11 days, hazard ratio [95% confidence interval]: 2.03 [1.66-2.48]) compared to placebo. Kovir also increased the QOL score on days 7 and 14. No safety concerns were observed. To conclude, Kovir is safe and facilitates symptom relief for non-severe COVID-19 patients. We advocate using Kovir in the early phase of COVID-19 for non-severe adult patients.

Facile iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethanes and exploration of applications.

A practical strategy for the iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethane and its derivatives has been developed. These compounds exhibit high cytotoxicity toward various cancer cell lines and moreover they are promising ligands for the Cu-catalysed synthesis of quinolines.