Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Beneficial effects of pulmonary embolism response team establishment in patients with pulmonary embolism in a developing country: a single-center experience.

Objective: The impact of establishing a pulmonary embolism response team (PERT) in patients with pulmonary embolism (PE) has been proven in many developed countries. However, the efficacy of a PERT largely depends on expertise and infrastructure. This study explored the benefit of establishing a PERT in developing countries with limited healthcare resources by comparing the outcomes of patients with acute PE before and after PERT establishment at University Medical Center Ho Chi Minh City in Vietnam. Methods: We conducted a single-center observational study from January 1, 2019, to August 1, 2021. All patients with PE confirmed on computed tomography were included. Patients admitted before PERT establishment were treated by cardiologists alone, while those hospitalized after PERT establishment were managed by the PERT. Results: A total of 130 patients were included (pre-PERT estab-lishment: 51 patients; post-PERT establishment: 79 patients). The demographic characteristics, severity of PE, and clinical and laboratory findings were similar between the two groups. The post-PERT establishment group had a lower incidence rate of major and clinically relevant nonmajor bleeding (11.3% vs. 31.4%, p = 0.005) and required more interventional therapies (16.5% vs. 3.9%, p = 0.046) than did the pre-PERT establishment group. The in-hospital mortality rate decreased in the post-PERT establishment group compared with that in the pre-PERT establishment group (8.9% vs. 21.6%, p = 0.041). Conclusions: Involvement of the PERT in PE management was associated with improved outcomes of patients with PE, including reduced bleeding and mortality rates in a resource-constrained hospital.

Neuromorphic sensing of biomolecules covalently immobilised on polydimethyl glutarimide.

Polydimethyl glutarimide (PMGI) layers with sub-micron thicknesses have been modified in a 2.5 kV Ar plasma immersion ion implantation (PIII) process to introduce free radical covalent binding sites. The surface roughness of the PMGI increased after the PIII treatment but no through-layer defects were observed. When applied to the treated PMGI, horseradish peroxidase (HRP) enzyme remained bound to the surface after extended immersion in sodium dodecyl sulfate solution (SDS). Hence, covalent binding between the activated surface and enzyme was confirmed. This covalent binding was achieved up to 24-h after the PIII process. The treated PMGI was then incorporated as a gate dielectric layer within a lateral three-terminal electrolyte-gated device. The device output characteristics resembled those of post-synaptic outputs; as successive (pre-synaptic) voltage pulses were applied to the gate, paired pulse depression and spike rate dependent plasticity were observed in the source-drain (post-synaptic) current. These characteristics were altered by the presence of HRP immobilised on the plasma-modified PMGI gate dielectric layer thus providing readout detection. These results and preliminary device characteristics show the potential for the plasma functionalized PMGI as a sensitive and reproducible biosensing technology.

Multidimensional Analysis of the Mother-to-child Transmission Risk Factors in Chronic Hepatitis B Virus Infection in Pregnant Women in Vietnam.

Background: Hepatitis B virus (HBV) infection remains a major public health problem. The interaction between HBV and the host inflammatory response is an important factor contributing to liver damage and disease development. We investigate of the correlation between peripheral blood cell levels, HBV DNA, and the risk of transmission to the baby in pregnant women infected with hepatitis B. Methods: A multidimensional analysis was performed on data collected from 60 Vietnamese pregnant women and their babies (cord blood). Results: Taking the risk ratio test results of cord blood HBsAg as a positive probability, the boundary of maternal PBMC concentration is 8.03x106 cells/ml (with negative correlation) and for CBMCs is 6.64x106 cells/ml (with positive correlation). That means that HBsAg positivity in the blood may be related to the increasing of CBMCs and the diminution of maternal PBMCs. When the maternal viral load is higher than 5x107 copies/ml, the risk of being HBsAg-positive in cord blood is 123% (RR=2.23 [1.48,3.36]); when the viral load is lower than this baseline, the risk is decreased by 55% (RR=0.45 [0.30,0.67]) (p<0.001). Conclusions: With several steps of the analysis, this study found maternal peripheral blood cell levels and cord blood positively cor-related in pregnant women with a load lower than 5x107 copies of HBV DNA/ml. The study's results suggest that the role of PBMCs and HBV DNA in vertical infection is essential.

Household Dietary Diversity among the Ethnic Minority Groups in the Mekong Delta: Evidence for the Development of Public Health and Nutrition Policy in Vietnam.

Poor household dietary diversity has been linked to malnutrition in individuals, households, and cumulatively in populations. High rates of malnutrition among Khmer ethnic children aged five years and younger have been reported in Tri Ton district, Vietnam. This paper aims to further investigate household dietary diversity and associated factors among Khmer ethnic minority populations in Vietnam. A cross sectional study was conducted from October 2018 to April 2019 in Tri Ton District, An Giang Province. By employing a multistage sampling technique, a total of 402 (99.8% response rate) participants were interviewed to measure household dietary diversity using a structured and validated questionnaire developed by FAO. Both bivariate and multivariate logistic regression analyses were carried out to identify factors associated with household dietary diversity. The results showed that the prevalence of low, medium and high dietary diversity scores were 21.4%, 70.4% and 8.2%, respectively. Male-headed households, literacy level, household income, exposure to mass media on nutrition and health information, and frequency of eating were positively associated with household dietary diversity (p < 0.05). However, owning a vegetable and rice farm was not statistically related to households' dietary diversification. The paper concludes that the magnitude of household diversified dietary intakes was essentially low to medium in participants' households. These findings have provided evidence to inform the development of the National Nutrition Strategy­2021−2030 in Vietnam, to be revised in 2045. This national strategy proposes appropriate interventions, programs and policies to improve socioeconomic status in ethnic groups and in mountainous areas to enhance populations' health and well-being including controlling childhood malnutrition. In order to improve population health and wellbeing in Tri Ton District, further actions to address effective dietary practices including strengthening nutrition and health communication about the need to improve household dietary diversity to high levels are recommended.

Rare-Earth-Metal-Catalyzed Kinetic Resolution of Chiral Aminoalkenes via Hydroamination: The Effect of the Silyl Substituent of the Binaphtholate Ligand on Resolution Efficiency.

The kinetic resolution of α-substituted aminopentenes via intramolecular hydroamination was investigated using various 3,3'-silyl-substituted binaphtholate yttrium catalysts. High efficiencies in the kinetic resolution were observed for methyl-, benzyl-, and phenyl-substituted substrates utilizing the cyclohexyldiphenylsilyl-substituted catalyst 2c with resolution factors reaching as high as 90(5) for hex-5-en-2-amine (3a). Kinetic analysis of the enantioenriched substrates with the matching and mismatching catalyst revealed that the efficiency of catalyst 2c benefits significantly from a favorable Curtin-Hammett pre-equilibrium and by a large kfast/kslow ratio. Other binaphtholate catalysts were less efficient due to a less favorable Curtin-Hammett pre-equilibrium, which often favored the mismatching substrate-catalyst combination. Cyclization of the matched substrate proceeds generally with large trans-selectivity, whereas the trans/cis-ratio for mismatched substrates is significantly diminished, favoring the cis-cyclization product isomer in some instances.

Tin oxide artificial synapses for low power temporal information processing.

Lateral memristors configured with inert Pt contacts and mixed phase tin oxide layers have exhibited immediate, forming-free, low-power bidirectional resistance switching. Activity dependent conductance and relaxation in the low resistance state resembled short term potentiation in biological synapses. After scanning probe microscopy, x-ray photoelectron spectroscopy and electrical measurements, the device characteristics were attributed to Joule heating induced decomposition of the minority SnO phase and formation of a SnO2 conducting filament with higher effective n-type doping. Finally, the devices recognized input voltage pulse sequences and spectral data by returning unique conductance states, suggesting suitability for bio-inspired pattern recognition systems.

Genetic diversity of the endemic flat-needle pine Pinus krempfii (Pinaceae) from Vietnam revealed by SSR markers.

Pinus krempfii Lecomte (Pinaceae) is an endemic tree to Vietnam with restricted habitats at higher altitudes in the highlands. In this study, genetic variation of four populations of P. krempfii was assessed using 17 microsatellite markers (single sequence repeats). Of these 17 markers, eight were polymorphic, and among the 42 putative alleles amplified, 32 were polymorphic (accounting for 76.19%). The Cong Troi population was found to be the most genetically diverse (Shannon's information index, I = 0.415, and percentage of polymorphic bands, PPB = 52.95%), whereas the Hon Giao population was found to have the lowest diversity (I = 0.330 and PPB = 47.06%). The genetic diversity at species level was also estimated (I = 0.414, PPB = 76.19%). Molecular variance was found to be low among populations (11.94%) and high among individuals within the populations (88.06%). Private alleles were not detected in the Hon Giao population. The Yang Ly population had a positive FIS (inbreeding coefficient) value of 0.071, while the three remaining populations had negative values (-0.116 for Cong Troi, -0.316 for Chu Yang Sin, and -0.350 for Hon Giao). The results obtained show an excess of homozygosity in the Yang Ly population, and also suggest a deficiency of heterozygosity for this population. Several approaches and measures of conservation for P. krempfii are discussed and proposed.

Ethnobotanical approach versus random approach in the search for new bioactive compounds: support of a hypothesis.

CONTEXT: Whether natural product drug discovery programs should rely on wild plants collected "randomly" from the natural environment, or whether they should also include plants collected on the basis of use in traditional medicine remains an open question. OBJECTIVE: This study analyzes whether plants with ethnomedical uses from Vietnam and Laos have a higher hit rate in bioassay testing than plants collected from a national park in Vietnam with the goal of maximizing taxonomic diversity ("random" collection). MATERIALS AND METHODS: All plants were extracted and subjected to bioassay in the same laboratories. Results of assays of plant collections and plant parts (samples) were scored as active or inactive based on whether any extracts had a positive result in a bioassay. Contingency tables were analyzed using χ(2) statistics. RESULTS: Random collections had a higher hit rate than ethnomedical collections, but for samples, ethnomedical plants were more likely to be active. Ethnomedical collections and samples had higher hit rates for tuberculosis, while samples, but not collections, had a higher hit rate for malaria. Little evidence was found to support an advantage for ethnomedical plants in HIV, chemoprevention and cancer bioassays. Plants whose ethnomedical uses directly correlated to a bioassay did not have a significantly higher hit rate than random plants. DISCUSSION: Plants with ethnomedical uses generally had a higher rate of activity in some drug discovery bioassays, but the assays did not directly confirm specific uses. CONCLUSIONS: Ethnomedical uses may contribute to a higher rate of activity in drug discovery screening.

Ethnobotany/ethnopharmacology and mass bioprospecting: issues on intellectual property and benefit-sharing.

Ethnobotany/ethnopharmacology has contributed to the discovery of many important plant-derived drugs. Field explorations to seek and document indigenous/traditional medical knowledge (IMK/TMK), and/or the biodiversity with which the IMK/TMK is attached, and its conversion into a commercialized product is known as bioprospecting or biodiversity prospecting. When performed in a large-scale operation, the effort is referred to as mass bioprospecting. Experiences from the mass bioprospecting efforts undertaken by the United States National Cancer Institute, the National Cooperative Drug Discovery Groups (NCDDG) and the International Cooperative Biodiversity Groups (ICBG) programs demonstrate that mass bioprospecting is a complex process, involving expertise from diverse areas of human endeavors, but central to it is the Memorandum of Agreement (MOA) that recognizes issues on genetic access, prior informed consent, intellectual property and the sharing of benefits that may arise as a result of the effort. Future mass bioprospecting endeavors must take heed of the lessons learned from past and present experiences in the planning for a successful mass bioprospecting venture.

Hypermutable and fluoroquinolone-resistant clinical isolates of Staphylococcus aureus.

Over 124 methicillin-susceptible Staphylococcus aureus 0/74 fluoroquinolone-susceptible versus 5/50 fluoroquinolone-resistant isolates were hypermutable. Hypermutable isolates combined mutations in gyrA, parC, and/or parE genes. One strain had a large deletion of the mutator mutS and mutL genes. No relevant mutation in mutS and mutL genes was found in the other isolates.

Mutation of L4 ribosomal protein conferring unusual macrolide resistance in two independent clinical isolates of Staphylococcus aureus.

The aim of this study was to characterize the resistance mechanisms of two strains of Staphylococcus aureus UCN42 and UCN43 isolated from cystic fibrosis patients that displayed an unusual phenotype of resistance to macrolides. The strains were resistant to erythromycin and the 16-membered macrolide spiramycin but susceptible to clindamycin. None of the strains contained erm or msr(A) genes by PCR. Sequencing of genes encoding ribosomal targets of macrolides revealed mutations in conserved regions of the L4 ribosomal protein, a R168S mutation for S. aureus UCN43 and mutations at positions G69A and T70P for both strains. This observation extends previous reports of similar mutations in streptococci and mycoplasma to S. aureus.

The UIC ICBG (University of Illinois at Chicago International Cooperative Biodiversity Group) Memorandum of Agreement: a model of benefit-sharing arrangement in natural products drug discovery and development.

The Convention on Biodiversity mandates a new approach to the discovery of natural product drugs, one that incorporates concepts of national ownership of genetic resources, intellectual property rights in traditional knowledge, and sharing of economic benefits with countries that are the source of new natural products. The International Cooperative Biodiversity Group (ICBG) program was established to support experimentation in implementation of the Convention through development and execution of international agreements for bioprospecting. The agreement of one such ICBG program, between the University of Illinois at Chicago and institutions in Vietnam and Laos, is presented here. The core elements contained in the single, five-way Memorandum of Agreement are the arrangements for intellectual property rights, treatment of informed consent, and plans for benefit-sharing (including the sharing of short- and long-term royalty benefits, capacity building, and community reciprocity). Program participants were able to develop a practical and flexible agreement that satisfies the wishes of all institutions that are parties to it.