Development of a computer-based tool to obtain a family health history in Vietnam.

Background: Family health history (FHH) is central to human genomic profiling construction; however, there is no protocol for documenting FHH in a pedigree format in Vietnam.Aim: A "Gia Su Suc Khoe" (GSSK) tool was developed to create a user-friendly interface for collecting FHH and offering diseases' risk assessment.Results: A tool was described (https://giasusuckhoe.vn/) with good feedback from genetic counselors and family-medicine doctors. Among 20 surveys, 100% of respondents noted that the report accurately reflected their FHH and were satisfied with the tool's display. About 74% of familial conditions were covered. Overall, all constructive feedback has been adapted into the updated version.Conclusion: Gia Su Suc Khoe has the potential to significantly improve healthcare delivery and outcomes in Vietnam.

[Box: see text].

Class II Correction and Crowding Treatment Using In-House Direct Printed Clear Aligners: A Literature Review and Case Report.

Clear aligner therapy has significantly improved orthodontic treatment by offering patients a more aesthetically pleasing option compared to traditional braces. This literature review and case report specifically focus on the effectiveness of directly printed clear aligners in treating Class II malocclusions and crowding. Class II malocclusions are characterized by excessive overjet, which often results from skeletal or dental discrepancies between the upper and lower jaws. Crowding refers to the lack of space for teeth within the dental arch, leading to misalignment and potential functional issues. The review and case report highlight the increasing importance of directly printed clear aligners in modern orthodontics and provide clinicians with a valuable tool to effectively address complex malocclusions and crowding while also meeting patient needs for discretion and comfort. Further research is necessary to validate the long-term stability and outcomes of directly printed clear aligner therapy in various orthodontic cases. A detailed case report demonstrates the successful treatment of a patient with Class II malocclusion and mild crowding using directly printed clear aligners. Treatment outcomes include improvements in dental alignment, occlusion, and facial aesthetics, showcasing the effectiveness of this innovative approach.

A multidisciplinary approach to managing severe gummy smile using 3D simulation and digital surgical guide: a case report.

A smile that reveals >4 mm of gum tissue is called a gummy smile (GS), offering negative impacts on people's self-confidence and aesthetic appearance. The treatment for GS should be planned according to underlying causes such as altered passive eruption of teeth, dentoalveolar extrusion, vertical maxillary excess, and short or hyperactive lip muscles. In this case report, a patient with severe GS received orthodontic and gingivoplasty treatment, aided by digital tools such as 3D simulation, smile design, and 3D printed guides. The treatment yielded remarkable and satisfactory results, without the need for extensive surgery. Our findings suggest that gingivoplasty is a minimally invasive, time- and cost-effective alternative to more extensive procedures for correcting severe gum recession.

Correction of a severe post-surgical iatrogenic class II anterior open bite with lingual appliances and mini-screws: a case report.

An iatrogenic open bite after orthognathic surgery is an uncommon malocclusion, with only one documented case reported in the literature. However, the open bite in this case report was not a true open bite, as it resulted from the interferences between the maxillary second molars and mandibular retromolar bones. This case report aims to present the management of a true iatrogenic open bite with posterior teeth in centric occlusion, occurring after mandibular setback surgery. The anterior open bite accompanied a severe class II malocclusion and increased lower anterior facial height. The patient was treated with fixed lingual appliances and mini-screws to distalize the entire maxillary arch and close the open bite. After treatment, a positive overbite and dental class I relationship was achieved. The treatment outcomes were stable at the 2-year follow-up. Lingual appliances combined with mini-screws may offer effective non-surgical management of iatrogenic open bite after orthognathic surgery. Clinical and Surgical Implications: Iatrogenic open bites can develop from various causes that include surgical options such as orthognathic surgery or in patients treated with occlusal splint therapy. These may be treated with the help of skeletal anchorage options such as orthodontic mini-screws.

Management of a severe skeletal open bite case using temporary anchorage devices and multiloop edgewise arch wire technique.

The primary cause of complex AOB malocclusion is typically a combination of dental, skeletal, functional, and habitual factors. Open bite correction is a challenging treatment due to its complexity and the requirement for long-term stability, therefore, multidisciplinary treatment is often the best option for achieving stable esthetic outcomes.

Transfer of natural radionuclides from soil to water spinach (Ipomoea aquatica Forssk) under flooded and unflooded conditions in Hanoi, Vietnam.

Transfer of natural radionuclides from soil to water spinach (Ipomoea aquatica Forssk) in Hanoi, Vietnam have been investigated using a low background gamma spectrometer with an HPGe detector (Model-GC5019). Twenty pairs of soil and water spinach samples in two environmental conditions, i.e., flooded and unflooded, were collected for measuring the activity concentrations and determining the soil-to-plant transfer factors (TFs) of natural radionuclides. For water spinach, stems and leaves were collected as the main parts for human consumption and livestock food. The TF of 40K is within the range of 0.32-2.49, which is greater than that of 228Ra (0.01-0.17) and 226Ra (0.01-0.13). The geometric means (geometric standard deviations) of the TFs are 1.17(1.89), 0.05(2.41) and 0.04(1.88) for flooded sites, and 0.89(1.73), 0.03(2.12) and 0.03(1.82) for unflooded sites, respectively. Comparing between the flooded and unflooded sites, the TFs are all greater at the flooded sites.

A comprehensive analysis of the immune system in healthy Vietnamese people.

Lifestyle, diet, socioeconomic status and genetics all contribute to heterogeneity in immune responses. Vietnam is plagued with a variety of health problems, but there are no available data on immune system values in the Vietnamese population. This study aimed to establish reference intervals for immune cell parameters specific to the healthy Vietnamese population by utilizing multi-color flow cytometry (MCFC). We provide a comprehensive analysis of total leukocyte count, quantitative and qualitative shifts within lymphocyte subsets, serum and cytokine and chemokine levels and functional attributes of key immune cells including B cells, T cells, natural killer (NK) cells and their respective subpopulations. By establishing these reference values for the Vietnamese population, these data contribute significantly to our understanding of the human immune system variations across diverse populations. These data will be of substantial comparative value and be instrumental in developing personalized medical approaches and optimizing diagnostic strategies for individuals based on their unique immune profiles.

A novel network-based method identifies a cuproplasia-related pan-cancer gene signature to predict patient outcome.

Copper is a vital micronutrient involved in many biological processes and is an essential component of tumour cell growth and migration. Copper influences tumour growth through a process called cuproplasia, defined as abnormal copper-dependent cell-growth and proliferation. Copper-chelation therapy targeting this process has demonstrated efficacy in several clinical trials against cancer. While the molecular pathways associated with cuproplasia are partially known, genetic heterogeneity across different cancer types has limited the understanding of how cuproplasia impacts patient survival. Utilising RNA-sequencing data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets, we generated gene regulatory networks to identify the critical cuproplasia-related genes across 23 different cancer types. From this, we identified a novel 8-gene cuproplasia-related gene signature associated with pan-cancer survival, and a 6-gene prognostic risk score model in low grade glioma. These findings highlight the use of gene regulatory networks to identify cuproplasia-related gene signatures that could be used to generate risk score models. This can potentially identify patients who could benefit from copper-chelation therapy and identifies novel targeted therapeutic strategies.

Digitally planned surgical crown lengthening: a novel bone reduction strategy to correct a gummy smile.

This report describes the bone reduction guide which was digitally obtained to improve diagnosis, treatment outcome and follow-up. Treatment of gingival smiles due to altered passive eruption should include interdisciplinary planning and smile design to facilitate the prediction of treatment outcome. Crown lengthening surgery can be supported by digital tools to improve surgical planning and follow-up. A 30-year-old female patient was referred to a private dental clinic seeking solutions for her gingival smile. Based on the anatomical crown length, a smile design was created, and the patient was presented with a simulated smile before treatment. In the surgical phase, a full-thickness flap was raised in the upper jaw to achieve the desired outcome. Using cone-beam computed tomography to determine cementoenamel junction for smile design and treatment planning brings many benefits. Patients and clinicians can foresee treatment results. From there, appropriate changes can be made. The bone reduction guide is designed to rest on the bone to help the clinician cut the bone accurately and thoroughly follow the established plan.

Use of surgical grafting as a part of multidisciplinary treatment for a patient treated with fixed orthodontic therapy to improve treatment outcomes.

Key Clinical Abstract: Multidisciplinary treatment options can help provide good clinical outcomes if these are appropriately sequenced and carried out correctly. This case exemplifies interdisciplinary involvement to ensure the patient received an improved esthetic outcome. Abstract: The presence of anterior diastemas may compromise the esthetics of a patient's smile, causing mental, and social trauma in many patients. After careful evaluation Periodontal, surgical, and prosthodontic treatments are sometimes required to ensure successful treatment outcomes using a multidisciplinary staged treatment approach. These approaches must be carefully planned to ensure timely treatment progress. Surgical intervention must be planned at the right point in treatment to ensure adequate healing before placement of esthetic restorations.

Antimicrobial Resistance Patterns of Common Gram-Negative Microorganisms Isolated from Patients with Lower Respiratory Tract Infections in a Teaching Hospital in Vietnam.

This cross-sectional study investigated the antimicrobial resistance (AMR) patterns of gram-negative pathogens isolated from 4,789 hospitalized patients with lower respiratory tract infections (LRTIs). Of the collected specimens, 1,325 (27.7%) tested positive for gram-negative bacteria. Acinetobacter baumannii (38.6%), Pseudomonas aeruginosa (33.5%), Klebsiella pneumoniae (18.7%), Escherichia coli (5.6%), and Klebsiella aerogenes (3.5%) were the most prevalent isolates. AMR analysis revealed high resistance rates (79.9%-100%) of A. baumannii isolates to multiple classes of antibiotics except amikacin, trimethoprim/sulfamethoxazole, and colistin. P. aeruginosa displayed low resistance to colistin (< 10%) but high resistance to other antibiotics. K. pneumoniae displayed high resistance rates of 90.0%-100.0% to most penicillins, whereas resistance rates were notably lower for colistin (7.1%) and amikacin (16.7%). K. aerogenes exhibited high resistance to various antibiotics and sensitivity to amikacin (95.1%), ampicillin (100.0%), and colistin (100.0%). E. coli isolates exhibited resistance to ampicillin (96.9%) and maximum sensitivity to several antibiotics. Our study identified significant AMR trends and highlighted the prevalence of multidrug-resistant strains (93.6% for K. aerogenes and 69.1%-92.4% for other isolates). These findings emphasize the urgent need for appropriate antibiotic management practices to combat AMR in gram-negative pathogens associated with LRTIs.

Comparison and summary of in silico prediction tools for CYP450-mediated drug metabolism.

The cytochrome P450 (CYP450) enzyme system is responsible for the metabolism of more than two-thirds of xenobiotics. This review summarizes reports of a series of in silico tools for CYP450 enzyme-drug interaction predictions, including the prediction of sites of metabolism (SOM) of a drug and the identification of inhibitor/substrates for CYP subtypes. We also evaluated four prediction tools to identify CYP inhibitors utilizing 52 of the most frequently prescribed drugs. ADMET Predictor and CYPlebrity demonstrated the best performance. We hope that this review provides guidance for choosing appropriate enzyme prediction tools from a variety of in silico platforms to meet individual needs. Such predictions are useful for medicinal chemists to prioritize their designed compounds for further drug discovery.

Unpolarized laser method for infrared spectrum calculation of amide I CO bonds in proteins using molecular dynamics simulation.

The investigation of the strong infrared (IR)-active amide I modes of peptides and proteins has received considerable attention because a wealth of detailed information on hydrogen bonding, dipole-dipole interactions, and the conformations of the peptide backbone can be derived from the amide I bands. The interpretation of experimental spectra typically requires substantial theoretical support, such as direct ab-initio molecular dynamics simulation or mixed quantum-classical description. However, considering the difficulties associated with these theoretical methods and their applications are limited in small peptides, it is highly desirable to develop a simple yet efficient approach for simulating the amide I modes of any large proteins in solution. In this work, we proposed a comprehensive computational method that extends the well-established molecular dynamics (MD) simulation method to include an unpolarized IR laser for exciting the CO bonds of proteins. We showed the amide I frequency corresponding to the frequency of the laser pulse which resonated with the CO bond vibration. At this frequency, the protein energy and the CO bond length fluctuation were maximized. Overall, the amide I bands of various single proteins and amyloids agreed well with experimental data. The method has been implemented into the AMBER simulation package, making it widely available to the scientific community. Additionally, the application of the method to simulate the transient amide I bands of amyloid fibrils during the IR laser-induced disassembly process was discussed in details.

Development and test of highly accurate endpoint free energy methods. 2: Prediction of logarithm of n-octanol-water partition coefficient (logP) for druglike molecules using MM-PBSA method.

The logarithm of n-octanol-water partition coefficient (logP) is frequently used as an indicator of lipophilicity in drug discovery, which has substantial impacts on the absorption, distribution, metabolism, excretion, and toxicity of a drug candidate. Considering that the experimental measurement of the property is costly and time-consuming, it is of great importance to develop reliable prediction models for logP. In this study, we developed a transfer free energy-based logP prediction model-FElogP. FElogP is based on the simple principle that logP is determined by the free energy change of transferring a molecule from water to n-octanol. The underlying physical method to calculate transfer free energy is the molecular mechanics-Poisson Boltzmann surface area (MM-PBSA), thus this method is named as free energy-based logP (FElogP). The superiority of FElogP model was validated by a large set of 707 structurally diverse molecules in the ZINC database for which the measurement was of high quality. Encouragingly, FElogP outperformed several commonly-used QSPR or machine learning-based logP models, as well as some continuum solvation model-based methods. The root-mean-square error (RMSE) and Pearson correlation coefficient (R) between the predicted and measured values are 0.91 log units and 0.71, respectively, while the runner-up, the logP model implemented in OpenBabel had an RMSE of 1.13 log units and R of 0.67. Given the fact that FElogP was not parameterized against experimental logP directly, its excellent performance is likely to be expanded to arbitrary organic molecules covered by the general AMBER force fields.

Phosphorylation at Ser289 Enhances the Oligomerization of Tau Repeat R2.

In tauopathies such as Alzheimer's disease (AD), aberrant phosphorylation causes the dissociation of tau proteins from microtubules. The dissociated tau then aggregates into sequent forms from soluble oligomers to paired helical filaments and insoluble neurofibrillary tangles (NFTs). NFTs is a hallmark of AD, while oligomers are found to be the most toxic form of the tau aggregates. Therefore, understanding tau oligomerization with regard to abnormal phosphorylation is important for the therapeutic development of AD. In this study, we investigated the impact of phosphorylated Ser289, one of the 40 aberrant phosphorylation sites of full-length tau proteins, on monomeric and dimeric structures of tau repeat R2 peptides. We carried out intensive replica exchange molecular dynamics simulation with a total simulation time of up to 0.1 ms. Our result showed that the phosphorylation significantly affected the structures of both the monomer and the dimer. For the monomer, the phosphorylation enhanced ordered-disordered structural transition and intramolecular interaction, leading to more compactness of the phosphorylated R2 compared to the wild-type one. As to the dimer, the phosphorylation increased intermolecular interaction and ß-sheet formation, which can accelerate the oligomerization of R2 peptides. This result suggests that the phosphorylation at Ser289 is likely to promote tau aggregation. We also observed a phosphorylated Ser289-Na+-phosphorylated Ser289 bridge in the phosphorylated R2 dimer, suggesting an important role of cation ions in tau aggregation. Our findings suggest that phosphorylation at Ser289 should be taken into account in the inhibitor screening of tau oligomerization.

Phosphorylation of Tau R2 Repeat Destabilizes Its Binding to Microtubules: A Molecular Dynamics Simulation Study.

Phosphorylation, the most popular post-translational modification of tau protein, plays an important role in regulating tau physiological functions. However, aberrant phosphorylation attenuates the binding affinity of tau to a microtubule (MT), resulting in MT destabilization followed by accumulation of neurofibrillary tangles in the brain. There are in total 85 potential phosphorylation sites in a full-length tau protein, and about half of them are abnormal as they occur in tau of Alzheimer's disease (AD) brain only. In this work, we investigated the impact of abnormal Ser289, Ser293, and Ser289/Ser293 phosphorylation on tau R2-MT binding and the conformation of tau R2 using molecular dynamics simulation. We found that the phosphorylation significantly affected R2-MT interaction and reduced the binding affinity of tau R2 peptides to MTs. Free energy decomposition analysis suggested that the post-translational modified residues themselves made a significant contribution to destabilize tau repeat R2-MT binding. Therefore, the phosphorylation may attenuate the binding affinity of tau to MTs. Additionally, the phosphorylation also enhanced helix-coil transition of monomeric R2 peptides, which may result in the acceleration of tau aggregation. Since these phosphorylated sites have not been examined in previous experimental studies, our finding through all-atom molecular dynamics simulations and free energy analysis can inspire experimental scientists to investigate the impact of the phosphorylation on MT binding and aggregation of full-length tau and the pathological roles of the phosphorylation at those sites in AD development through in vitro/in vivo assays.

Investigation of the Structure of Full-Length Tau Proteins with Coarse-Grained and All-Atom Molecular Dynamics Simulations.

Tau proteins not only have many important biological functions but also are associated with several neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease (AD). However, it is still a challenge to identify the atomic structure of full-length tau proteins due to their lengthy and disordered characteristics and the factor that there are no crystal structures of full-length tau proteins available. We performed multi- and large-scale molecular dynamics simulations of the full-length tau monomer (the 2N4R isoform and 441 residues) in aqueous solution under biological conditions with coarse-grained and all-atom force fields. The obtained atomic structures produced radii of gyration and chemical shifts that are in excellent agreement with those of experiment. The generated monomer structure ensemble would be very useful for further studying the oligomerization mechanism and discovering tau oligomerization inhibitors, which are important events in AD drug development.

Molecular dynamics simulation of cancer cell membrane perforated by shockwave induced bubble collapse.

It has been widely accepted that cancer cells are softer than their normal counterparts. This motivates us to propose, as a proof-of-concept, a method for the efficient delivery of therapeutic agents into cancer cells, while normal cells are less affected. The basic idea of this method is to use a water jet generated by the collapse of the bubble under shockwaves to perforate pores in the cell membrane. Given a combination of shockwave and bubble parameters, the cancer membrane is more susceptible to bending, stretching, and perforating than the normal membrane because the bending modulus of the cancer cell membrane is smaller than that of the normal cell membrane. Therefore, the therapeutic agent delivery into cancer cells is easier than in normal cells. Adopting two well-studied models of the normal and cancer membranes, we perform shockwave induced bubble collapse molecular dynamics simulations to investigate the difference in the response of two membranes over a range of shockwave impulse 15-30 mPa s and bubble diameter 4-10 nm. The simulation shows that the presence of bubbles is essential for generating a water jet, which is required for perforation; otherwise, pores are not formed. Given a set of shockwave impulse and bubble parameters, the pore area in the cancer membrane is always larger than that in the normal membrane. However, a too strong shockwave and/or too large bubble results in too fast disruption of membranes, and pore areas are similar between two membrane types. The pore closure time in the cancer membrane is slower than that in the normal membrane. The implications of our results for applications in real cells are discussed in some details. Our simulation may be useful for encouraging future experimental work on novel approaches for cancer treatment.

Stable Cavitation Interferes with Aß16-22 Oligomerization.

Ultrasound and microbubbles are used for many medical applications nowadays. Scanning ultrasound can remove amyloid-ß (Aß) aggregates in the mouse brain and restores memory in an Alzheimer's disease mouse model. In vitro studies showed that amyloid fibrils are fragmented due to the ultrasound-induced bubble inertial cavitation, and ultrasonic pulses accelerate the depolymerization of Aß fibrils into monomers at 1 µM of concentration. Under applied ultrasound, microbubbles can be in a stable oscillating state or unstable inertial cavitation state. The latter occurs when ultrasound causes a dramatic change of bubble sizes above a certain acoustic pressure. We have developed and implemented a nonequilibrium molecular dynamics simulation algorithm to the AMBER package, to facilitate the investigation of the molecular mechanism of Aß oligomerization under stable cavitation. Our results indicated that stable cavitation not only inhibited oligomeric formation, but also prevented the formation of ß-rich oligomers. The network analysis of state transitions revealed that stable cavitation altered the oligomerization pathways of Aß16-22 peptides. Our simulation tool may be applied to optimize the experimental conditions to achieve the best therapeutical effect.

Joint Computational/Cell-Based Approach for Screening Inhibitors of Tau Oligomerization: A Proof-of-Concept Study.

BACKGROUND: Tau assembly produces soluble oligomers and insoluble neurofibrillary tangles, which are neurotoxic to the brain and associated with Alzheimer's and Parkinson's diseases. Therefore, preventing tau aggregation is a promising therapy for those neurodegenerative disorders. OBJECTIVE: The aim of this study was to develop a joint computational/cell-based oligomerization protocol for screening inhibitors of tau assembly. METHODS: Virtual oligomerization inhibition (VOI) experiment using molecular dynamics simulation was performed to screen potential oligomerization inhibitors of PHF6 hexapeptide. Tau seeding assay, which is directly related to the outcome of therapeutic intervention, was carried out to confirm a ligand's ability in inhibiting tau assembly formation. RESULTS: Our protocol was tested on two known compounds, EGCG and Blarcamesine. EGCG inhibited both the aggregation of PHF6 peptide in VOI and tau assembly in tau seeding assay, while Blarcamesine was not a good inhibitor at the two tasks. We also pointed out that good binding affinity to tau aggregates is needed, but not sufficient for a ligand to become a good inhibitor of tau oligomerization. CONCLUSION: VOI goes beyond traditional computational inhibitor screening of amyloid aggregation by directly examining the inhibitory ability of a ligand to tau oligomerization. Comparing with the traditional biochemical assays, tau seeding activities in cells is a better indicator for the outcome of a therapeutic intervention. Our hybrid protocol has been successfully validated. It can effectively and efficiently identify the inhibitors of amyloid oligomerization/aggregation processes, thus, facilitate to the drug development of tau-related neurodegenerative diseases.