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1.
Angew Chem Int Ed Engl ; : e202409973, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837490

ABSTRACT

Prenylation of peptides is widely observed in the secondary metabolites of diverse organisms, granting peptides unique chemical properties distinct from proteinogenic amino acids. Discovery of prenylated peptide agents has largely relied on isolation or genome mining of naturally occurring molecules. To devise a platform technology for de novo discovery of artificial prenylated peptides targeting a protein of choice, here we have integrated the thioether-macrocyclic peptide (teMP) library construction/selection technology, so-called RaPID (Random nonstandard Peptides Integrated Discovery) system, with a Trp-C3-prenyltransferase KgpF involved in the biosynthesis of a prenylated natural product. This unique enzyme exhibited remarkably broad substrate tolerance, capable of modifying various Trp-containing teMPs to install a prenylated residue with tricyclic constrained structure. We constructed a vast library of prenylated teMPs and subjected it to in vitro selection against a phosphoglycerate mutase. This selection platform has led to the identification of a pseudo-natural prenylated teMP inhibiting the target enzyme with an IC50 of 30 nM. Importantly, the prenylation was essential for the inhibitory activity, enhanced serum stability, and cellular uptake of the peptide, highlighting the benefits of peptide prenylation. This work showcases the de novo discovery platform for pseudo-natural prenylated peptides, which is readily applicable to other drug targets.

2.
MethodsX ; 12: 102624, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38435640

ABSTRACT

The mean sea surface in different regions is non-equipotential, rendering Vietnam's traditional approach, which relies on the Hon-Dau tide gauge station as a reference, not yet scientifically invalid. To overcome this, our study utilized the Vietnam national mean dynamic topography model (MDTVN22) for depth observations, particularly in the Gulf of Tonkin. Covering 3430 monitoring sites in Hai Phong and 813 sites in Quang Ninh, our experiments highlighted a 5 to 6 mm difference between the mean sea surface and MDTVN22 references. •Our research establishes a resilient methodology, integrating shore tide gauge station data and the MDTVN22 model, aimed at enhancing precision in depth observations.•Validation experiments in Hai Phong demonstrate a minimal discrepancy of ±0.006 m between measurements obtained from the traditional mean sea surface and the MDTVN22 model.•These findings underscore the significance of adopting the MDTVN22 model for improved accuracy in assessing Vietnam's seabed topography.

3.
Arch Pharm (Weinheim) ; 357(5): e2300557, 2024 May.
Article in English | MEDLINE | ID: mdl-38321839

ABSTRACT

A series of sulfonyl thioureas 6a-q containing a benzo[d]thiazole ring with an ester functional group was synthesized from corresponding substituted 2-aminobenzo[d]thiazoles 3a-q and p-toluenesulfonyl isothiocyanate. They had remarkable inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO)-A, and MAO-B. Among thioureas, several compounds had notable activity in the order of 6k > 6 h > 6c (AChE), 6j > 6g > 6k (BChE), 6k > 6g > 6f (MAO-A), and 6i > 6k > 6h (MAO-B). Compound 6k was an inhibitor of interest due to its potent or good activity against all studied enzymes, with IC50 values of 0.027 ± 0.008 µM (AChE), 0.043 ± 0.004 µM (BChE), 0.353 ± 0.01 µM (MAO-A), and 0.716 ± 0.02 µM (MAO-B). This inhibitory capacity was comparable to that of the reference drugs for each enzyme. Kinetic studies of two compounds with potential activity, 6k (against AChE) and 6j (against BChE), had shown that both 6k and 6j followed competitive-type enzyme inhibition, with Ki constants of 24.49 and 12.16 nM, respectively. Induced fit docking studies for enzymes 4EY7, 7BO4, 2BXR, and 2BYB showed active interactions between sulfonyl thioureas of benzo[d]thiazoles and the residues in the active pocket with ligands 6k, 6i, and 6j, respectively. The stability of the ligand-protein complexes while each ligand entered the active site of each enzyme (4EY7, 7BO4, 2BXR, or 2BYB) was confirmed by molecular dynamics simulations.


Subject(s)
Acetylcholinesterase , Butyrylcholinesterase , Cholinesterase Inhibitors , Molecular Docking Simulation , Monoamine Oxidase Inhibitors , Monoamine Oxidase , Humans , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase/metabolism , Acetylcholinesterase/metabolism , Butyrylcholinesterase/metabolism , Structure-Activity Relationship , Molecular Structure , Thiourea/pharmacology , Thiourea/chemistry , Thiourea/chemical synthesis , Dose-Response Relationship, Drug , Benzothiazoles/pharmacology , Benzothiazoles/chemistry , Benzothiazoles/chemical synthesis , Thiazoles/pharmacology , Thiazoles/chemistry , Thiazoles/chemical synthesis
4.
PLoS One ; 19(1): e0297187, 2024.
Article in English | MEDLINE | ID: mdl-38241315

ABSTRACT

BACKGROUND: The Coronavirus disease of 2019 (COVID-19) pandemic and the corresponding mitigation measures have had a discernible impact on drug utilization among outpatients. However, limited research exists on the prescription trends in the elderly population during the pandemic period in Viet Nam. OBJECTIVES: This study aims to analyze the effects of COVID-19 on outpatient drug utilization patterns at a national geriatric hospital in Ho Chi Minh City before and after the early onset of the pandemic. METHODS: Data was collected from the prescriptions and administration claims, encompassing the period from January 2016 to December 2022. The dataset was divided into two periods: Period 1: January 2016 to December 2020 and Period 2: January 2021 to December 2022. The drug utilization was measured using DDD/1000P (defined daily doses-DDD per 1000 prescriptions) on a monthly basis. The analysis employed interrupted time series using Autoregressive Integrated Moving Average (ARIMA) to detect changes in drug use levels and rates. RESULTS: A total of 1,060,507 and 644,944 outpatient prescriptions from Thong Nhat Hospital were included in Period 1 and Period 2, respectively. The median age of the patients were 58 in Period 1 and 67 years old in Period 2. The most common comorbidities were dyslipidemia, hypertension, and diabetes mellitus. In terms of medication utilization, cardiovascular drugs were the most frequently prescribed, followed by drugs active on the digestive and hormonal systems. The study observed significant surges in the number of prescriptions and the average number of drugs per prescription. However, there were no significant changes in the overall consumption of all drugs. Among the drug groups related to the cardiovascular system, three subgroups experienced a sudden and significant increase: cardiac therapy, beta-blocking agents, and antihypertensives, with increasing consumption levels of 1,177.73 [CI 95%: 79.29; 2,276.16], 73.32 [CI 95%: 28.18; 118.46], and 36.70 [CI 95%: 6.74; 66.66] DDD/1000P, respectively. On the other hand, there was a significant monthly decrease of -31.36 [CI 95%: -57.02; -5.70] DDD/1000P in the consumption of anti-inflammatory and antirheumatic products. Interestingly, there was a significant increase of 74.62 [CI 95%: -0.36; 149.60] DDD/1000P in the use of antigout preparations. CONCLUSION: COVID-19 resulted in a sudden, non-significant increase in overall drug consumption levels among outpatients. Notably, our findings highlight significant increases in the utilization of three drug groups related to the cardiovascular system, specifically cardiac therapy, beta-blocking agents, and antihypertensives. Intriguingly, there was a statistically significant increase in the consumption of antigout preparations, despite a decline in the monthly consumption rate of non-steroidal anti-flammatory drugs (NSAIDs). Further studies in the following years are necessary to provide a more comprehensive understanding of the impact of COVID-19 on outpatient drug utilization patterns.


Subject(s)
COVID-19 , Cardiovascular Agents , Humans , Aged , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Antihypertensive Agents/therapeutic use , COVID-19/epidemiology , Drug Utilization , Cardiovascular Agents/therapeutic use , Diuretics/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Drug Prescriptions
5.
RSC Med Chem ; 14(12): 2751-2767, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38107183

ABSTRACT

Some substituted thioureas (6a-i) containing a 1,3,4-thiadiazole ring were synthesized by the reaction of the corresponding substituted 2-amino-1,3,4-thiadiazoles 3a-i with p-toluenesulfonyl isocyanate in a one-pot procedure. The antibacterial and antifungal activities of these sulfonyl thioureas were estimated using a minimum inhibitory concentration protocol. Almost all the thioureas exhibited remarkable antimicrobial activity. Amongst the studied compounds, thioureas 6a, 6c, 6h, and 6i were better inhibitors against the bacterium S. aureus, with MIC values of 0.78-3.125 µg mL-1. These compounds were also tested for their inhibition against S. aureus enzymes, including enzymes of DNA gyrase, DNA topoisomerase IV (Topo IV), and dihydrofolate reductase. Amongst the compounds, 6h was a strong inhibitor, with IC50 values of 1.22, 53.78, and 0.23, respectively. Induced fit docking calculations were performed to observe the binding efficiency and steric interactions of these compounds. The obtained results showed that compound 6h was compatible with the active sites of S. aureus DNA gyrase 2XCS. This ligand interacted with residues ASP1083 (chain D), MET1121 (chain B), ARG1122 (chain D), and also with HOH2035, HOH2089, HOH2110, HOH2162. Molecular dynamics simulation in a water solvent system showed that the active interactions with residues ASP083 and MET1121 (chain B), along with ASP1083, MET1121, and ARG1122 (chain D), played an important role in stabilizing complex 6h/2XCS in the active pocket.

6.
Opt Express ; 31(16): 26383-26397, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37710501

ABSTRACT

Here we demonstrate the results of investigating the damage threshold of a LiF crystal after irradiating it with a sequence of coherent femtosecond pulses using the European X-ray Free Electron Laser (EuXFEL). The laser fluxes on the crystal surface varied in the range ∼ 0.015-13 kJ/cm2 per pulse when irradiated with a sequence of 1-100 pulses (tpulse ∼ 20 fs, Eph = 9 keV). Analysis of the surface of the irradiated crystal using different reading systems allowed the damage areas and the topology of the craters formed to be accurately determined. It was found that the ablation threshold decreases with increasing number of X-ray pulses, while the depth of the formed craters increases non-linearly and reaches several hundred nanometers. The obtained results have been compared with data already available in the literature for nano- and picosecond pulses from lasers in the soft X-ray/VUV and optical ranges. A failure model of lithium fluoride is developed and verified with simulation of material damage under single-pulse irradiation. The obtained damage threshold is in reasonably good agreement with the experimentally measured one.

8.
Opt Lett ; 48(19): 5041-5044, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37773380

ABSTRACT

Damage thresholds and structures on a metal aluminum and an aluminum oxide crystal induced by the soft x-ray free electron laser irradiations were evaluated. Distinctive differences in damage thresholds and structures were observed for these materials. On the aluminum oxide crystal surface, in particular, a novel, to the best of our knowledge, surface processing, which we suggest defining as "peeling," was recognized. Surface structures formed by peeling had extremely shallow patterning of sub-nanometer depth. For the newly observed peeling process, we proposed a scission of chemical bond, i.e., binding energy model, in the crystal.

9.
Drug Alcohol Rev ; 42(7): 1667-1679, 2023 11.
Article in English | MEDLINE | ID: mdl-37614129

ABSTRACT

INTRODUCTION: Methamphetamine use threatens positive treatment outcomes in substance use and HIV, for people with opioid use disorders (POUD) in many countries. This paper describes the adaptation of four evidence-based interventions (EBI) (motivational interviewing, contingency management, Matrix group model and SMS text messaging) for treating methamphetamine use among POUD receiving methadone maintenance therapy in Vietnam. METHODS: Following the ADAPT-ITT (Assessment-Decision-Administration-Production-Topical experts-Training-Testing) framework, we conducted 16 focus group discussions with POUD (n = 25) and providers (n = 22) at four methadone clinics in two largest cities (Hanoi in the North, Ho Chi Minh City in the South) to assess patterns of methamphetamine use and to get feedback on proposed EBIs. The proposed EBIs were properly adapted and used to train providers in two of the four methadone clinics. The revised EBIs were tested over 12 weeks among 42 POUD on methadone who use methamphetamine. Post-intervention feedback served to fine-tune the revised EBIs. RESULTS: Insights about patterns of methamphetamine use suggested that EBIs should focus on different triggers to methamphetamine use among POUD receiving methadone treatment in the two cities. All EBIs should emphasise family-related topics to build a strong motivation for treatment. Participants suggested when, where and how each EBI should be delivered. Most participants were satisfied with the adapted EBIs. Limited human resources at methadone clinics might hinder implementation of the adapted EBIs. DISCUSSION AND CONCLUSIONS: We successfully completed the adaptation of EBIs for POUD who use methamphetamine on methadone in Vietnam. The pilot testing of the adapted EBIs demonstrated feasibility and acceptability. TRIAL REGISTRATION: NCT04706624. Registered 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624.


Subject(s)
Methamphetamine , Opioid-Related Disorders , Humans , Methadone/therapeutic use , Methamphetamine/adverse effects , Vietnam , Opiate Substitution Treatment , Opioid-Related Disorders/drug therapy , Evidence-Based Medicine
10.
Methods Mol Biol ; 2686: 131-162, 2023.
Article in English | MEDLINE | ID: mdl-37540357

ABSTRACT

The flower is a hallmark feature that has contributed to the evolutionary success of land plants. Diverse mutagenic agents have been employed as a tool to genetically perturb flower development and identify genes involved in floral patterning and morphogenesis. Since the initial studies to identify genes governing processes such as floral organ specification, mutagenesis in sensitized backgrounds has been used to isolate enhancers and suppressors to further probe the molecular basis of floral development. Here, we first describe two commonly employed methods for mutagenesis (using ethyl methanesulfonate (EMS) or T-DNAs as mutagens), and then describe three methods for identifying a mutation that leads to phenotypic alterations: traditional map-based cloning, modified high-efficiency thermal asymmetric interlaced PCR (mhiTAIL-PCR), and deep sequencing in the plant model Arabidopsis thaliana.


Subject(s)
Arabidopsis , Arabidopsis/genetics , Genetic Testing , Mutation , Mutagenesis , Mutagens
11.
Anal Chem ; 95(30): 11181-11186, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37468162

ABSTRACT

A nanoelectrode with a controllable area was developed using commercial atomic force microscopy and a hydrogel. Although tremendous advantages of small electrodes from micrometer scale down to nanometer scale have been previously reported for a wide range of applications, precise and high-throughput fabrication remains an obstacle. In this work, the set-point feedback current in a modified scanning ionic conductance microscopy system controlled the formation of electrodes with a nanometer-sized area by contact between the boron-doped diamond (BDD) tip and the agarose hydrogel. The modulation of the electroactive area of the BDD-coated nanoelectrode in the hydrogel was successively investigated by the finite element method and cyclic voltammetry with the use of a redox-contained hydrogel. Moreover, this nanoelectrode enables the simultaneous imaging of both the topography and electrochemical activity of a polymeric microparticle embedded in a hydrogel.

12.
J Plant Physiol ; 286: 154000, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37207503

ABSTRACT

Numerous environmental stresses have a significant impact on plant growth and development. By 2050, it is anticipated that high salinity will destroy more than fifty percent of the world's agricultural land. Understanding how plants react to the excessive use of nitrogen fertilizers and salt stress is crucial for enhancing crop yield. However, the effect of excessive nitrate treatment on plant development is disputed and poorly understood; so, we evaluated the effect of excessive nitrate supply and high salinity on abi5 plant growth performance. We demonstrated that abi5 plants are tolerant to the harmful environmental conditions of excessive nitrate and salt. abi5 plants have lower amounts of endogenous nitric oxide than Arabidopsis thaliana Columbia-0 plants due to their decreased nitrate reductase activity, caused by a decrease in the transcript level of NIA2, a gene encoding nitrate reductase. Nitric oxide appeared to have a critical role in reducing the salt stress tolerance of plants, which was diminished by an excess of nitrate. Discovering regulators such as ABI5 that can modulate nitrate reductase activity and comprehending the molecular activities of these regulators are crucial for the application of gene-editing techniques. This would result in the appropriate buildup of nitric oxide to increase the production of crops subjected to a variety of environmental stresses.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Nitrates/metabolism , Nitric Oxide/metabolism , Nitrate Reductase/genetics , Nitrate Reductase/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant
13.
Dev Cell ; 58(12): 1037-1051.e4, 2023 06 19.
Article in English | MEDLINE | ID: mdl-37119815

ABSTRACT

The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.


Subject(s)
Stem Cell Niche , Transcription Factors , Animals , Transcription Factors/genetics , Transcription Factors/metabolism , Endothelial Cells/metabolism , Zebrafish/genetics , Zebrafish/metabolism , Gene Expression Regulation
14.
Pharmaceutics ; 15(2)2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36839877

ABSTRACT

In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells was investigated in C57BL/6J mice with PTX-induced neuropathic pain (PIPN). The particle size of EVs and CBD-EVs, surface roughness, nanomechanical properties, stability, and release studies were all investigated. To develop neuropathy in mice, PTX (8 mg/kg, i.p.) was administered every other day (four doses). In terms of decreasing mechanical and thermal hypersensitivity, CBD-EVs treatment was superior to EVs treatment or CBD treatment alone (p < 0.001). CBD and CBD-EVs significantly reduced mitochondrial dysfunction in dorsal root ganglions and spinal homogenates of PTX-treated animals by modulating the AMPK pathway (p < 0.001). Studies inhibiting the AMPK and 5HT1A receptors found that CBD did not influence the neurobehavioral or mitochondrial function of PIPN. Based on these results, we hypothesize that CBD and CBD-EVs mitigated PIPN by modulating AMPK and mitochondrial function.

15.
Wound Repair Regen ; 31(2): 199-204, 2023 03.
Article in English | MEDLINE | ID: mdl-36633904

ABSTRACT

Our main objective was to validate that hyperspectral imaging via a new portable camera carries the potential to provide a reliable clinical biomarker that can predict DFU healing. We recruited patients with diabetic foot ulceration (DFU) without peripheral arterial disease, infection or other serious illness. Using an hyperspectral imaging (HSI) apparatus, post-debridement hyperspectral images were taken evaluating the ulcer size, periwound oxyhemoglobin (OxyHb), deoxyhemoglobin level (DeoxyHb) and oxygen saturation (O2 Sat) for four consecutive visits. Twenty-seven patients were followed, out of whom seven healed their DFU while the remaining 20 failed to heal their DFU. The average time between each visit was 3 weeks. Binary logistic regression of healers versus non-healers on Visit 1 oxyHb and on Visit 2 showed a significant inverse association, OR = 0.85 (95% CI: 0.73-0.98, p < 0.001). An inverse correlation was observed between the Visit 1 oxyHb and the percentage of ulcer size reduction between Visit 1 and Visit 4 (r = -0.46, p = 0.02) and between the Visit 2 oxyHb and the percentage of ulcer size reduction between Visits 2 and 4 (r = -0.65, p = 0.001). Using oxyHb 50 as the cut-off point to predict DFU complete healing, Visit 1 oxyHb measurement provided 85% sensitivity, 70% specificity, 50% positive predictive value and 93% negative predictive value. For Visit 2, oxyHb had 85% sensitivity, 85% specificity, 66% positive predictive value and 94% negative predictive value. We conclude that this preliminary study, which involved a relatively small number of patients, indicates that hyperspectral imaging is a simple exam that can easily be added to daily clinical practice and has the potential to provide useful information regarding the healing potential of DFU over a short period of time.


Subject(s)
Diabetes Mellitus , Diabetic Foot , Foot Ulcer , Humans , Wound Healing , Ulcer , Hyperspectral Imaging
16.
Anal Chem ; 95(5): 2901-2908, 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36691706

ABSTRACT

The structure of an electrical double layer (EDL) at the interface of electrode/electrolyte or air/electrode/electrolyte is a fundamental aspect, however not fully understood. The potential of zero charge (PZC) is one of the clues to dictate the EDL, where the excess charge on the electrode surface is zero. Here, a nanoscale configuration of immersion method was proposed by integrating an electrochemical system into conductive atomic force spectroscopy under the amplitude modulation (AM) mode and agarose gel as the solid-liquid electrolyte. The PZC of boron-doped diamond was determined to be at 0.2 V (vs Ag/AgCl). By AM spectroscopy, the capacitive force shows remote electrification without direct electrode/electrolyte contact, which is dependent on the population of ions at the air/electrolyte interface. The surface potential by alignment of water is also evaluated. Prospectively, our study could benefit applications such as PZC measurement and non-electrode electrochemical processes at the air/electrolyte interface.

17.
Nat Commun ; 13(1): 7448, 2022 12 02.
Article in English | MEDLINE | ID: mdl-36460642

ABSTRACT

Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.


Subject(s)
Endothelial Cells , Veins , Morphogenesis/genetics , Arteries , Cell Movement
18.
Langmuir ; 38(50): 15604-15613, 2022 Dec 20.
Article in English | MEDLINE | ID: mdl-36507853

ABSTRACT

Manganese dioxide nanomaterials have wide applications in many areas from catalysis and Li-ion batteries to gas sensing. Understanding the crystallization pathways, morphologies, and formation of defects in their structure is particularly important but still a challenging issue. Herein, we employed an arsenal of X-ray diffraction (XRD), scanning electron microscopy (SEM), neutron diffraction, positron annihilation spectroscopies, and ab initio calculations to investigate the evolution of the morphology and structure of α-MnO2 nanomaterials prepared via reduction of KMnO4 solution with C2H5OH prior to being annealed in air at 200-600 °C. We explored a novel evolution that α-MnO2 nucleation can be formed even at room temperature and gradually developed to α-MnO2 nanorods at above 500 °C. We also found the existence of H+ or K+ ions in the [1 × 1] tunnels of α-MnO2 and observed the simultaneous presence of Mn and O vacancies in α-MnO2 crystals at low temperatures. Increasing the temperature removed these O vacancies, leaving only the Mn vacancies in the samples.

19.
Infect Drug Resist ; 15: 4575-4583, 2022.
Article in English | MEDLINE | ID: mdl-36003989

ABSTRACT

Purpose: The purpose of this study was to characterize the population-based pharmacokinetic (POP-PK) profile of imipenem in Vietnamese adult patients and to assess the probability of target attainment (PTA) of the pharmacokinetic/pharmacodynamic (PK/PD) parameter to determine the optimal dose. Patients and Methods: A POP-PK model of imipenem was developed in patients with severe infection from a 1500-bed general hospital in Vietnam, using MONOLIX 2019. After the initial dose infusion, 6 blood samples per patient were collected to measure plasma imipenem levels. Eight covariates (eg, age, weight) were investigated to ascertain their influence on imipenem's PK. Monte Carlo simulations were performed to determine the PTA for the time in which the total steady-state imipenem concentrations remained above the MIC (T>MIC) for 40% and 100% of the dosing interval. Results: The best fit to the PK data was a two-compartment model with inter-individual variability (IIV) in clearance (CL), central volume of distribution (Vc), intercompartmental clearance (Q), and peripheral volume of distribution (Vp). Only creatinine clearance was retained as a covariate on CL in the final model. The typical value of CL and Vc were estimated to be 4.79 L/h and 11.1 L, respectively. The between-subject variability in this population was noted to be high (>38%, especially for IIV on Q at 110%). Prolonged or continuous infusion demonstrated efficacy (40% T>MIC) against bacteria with a MIC of 4mg/L. To achieve 100% T>MIC or bacteria with MIC>4 mg/L, however, the number of doses must be increased while maintaining the same daily dose for the 3-hour prolonged infusion regimen. Conclusion: A population pharmacokinetic model of imipenem was developed for Vietnamese adult patients with severe illness. By using Monte Carlo simulation, the appropriate dose has been suggested based on the bacterial MIC value and the targeted PK/PD goal.

20.
PLoS One ; 17(7): e0271567, 2022.
Article in English | MEDLINE | ID: mdl-35895665

ABSTRACT

BACKGROUND: Adolescents who are willing to perform first aid can help prevent injuries and ultimately death among themselves and others involved in accidents or injuries. This study aims to estimate the prevalence of students' willingness to perform first aid procedures and additionally examine associated factors among high school students in Hue, Vietnam. METHODS: A cross-sectional study utilizing multi-stage stratified random sampling was conducted between April to July 2020 by investigating 798 high school students in Hue, Vietnam. Participants were invited to complete a self-reported questionnaire pertaining to individual demographic characteristics, personal perception of self-efficacy, and willingness to perform first aid. To better interpret these findings, both multivariable linear and Poisson regression models were fitted to evaluate the association between individual student characteristics and the willingness to perform first aid. RESULTS: The prevalence of having willingness to perform first aid (defined as ≥4 points out of 5 to all three questions) was 49.9% (95%CI:28.6-71.2%). The major reported barriers in performing first aid were fear of making mistakes and hurting victims (34.4%, 95%CI:31.9-37.0%), no prior first aid training (29.8%, 95%CI:25.9-33.9%), and forgetting first aid steps (23.0%, 95%CI:15.8-32.2%). By employing the multivariable linear regression model, it was identified that students with high (ß = 0.614, 95%CI:0.009-1.219) or very high (ß = 1.64, 95%CI:0.857-2.422) levels of self-efficacy appeared to be more willing to perform first aid. Similarly, in the Poisson regression models, compared to neutral students, students who reported high (PR = 1.214, 95%CI:1.048-1.407) or very high (PR = 1.871, 95%CI:1.049-3.337) levels of self-efficacy were more willing to perform first aid. CONCLUSIONS: The level of willingness to perform first aid among high school students in this study population was found to be moderate. Therefore, integrating activities to promote self-efficacy in first aid training could be considered a progressive step towards improving a student's willingness to provide such life-saving procedures.


Subject(s)
First Aid , Students , Adolescent , Cross-Sectional Studies , Humans , Self Efficacy , Surveys and Questionnaires , Vietnam/epidemiology
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