The Mutation Spectrum and Two Novel Point Mutations in the APC Gene in Vietnamese Patients with Familial Adenomatous Polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary disorder primarily caused by germline mutations in the APC gene. The most common type of mutation in the APC gene is point mutation, while deletion mutation is much less frequent. The current study was conducted to investigate the mutation spectrum of the APC gene in Vietnamese FAP patients. METHODS: Patients with the clinical diagnosis of FAP on colorectal endoscopy were screened for mutations in the APC gene using Sanger sequencing. Those who exhibited no point mutation subsequently underwent MLPA assay to detect deletion and duplication mutations. Besides, the relatives of patients with mutated APC genes were recruited for detecting carrier status. RESULTS: Sixty-three patients with clinical colorectal polyposis were recruited. Mutations in the APC gene were detected in 26/63 patients (41.3%). Genetic analysis of 105 asymptomatic relatives of these 26 patients found mutations in the APC gene in 55 individuals (52.4%). CONCLUSION: We successfully established the APC gene mutation spectrum in Vietnamese FAP patients for the first time. Of importance, we discovered two novel point mutations in the APC gene. The high prevalence of carrier status in asymptomatic family members of patients with mutation emphasizes the crucial role of appropriate genetic screening for early diagnosis, surveillance, and preventive measurements.

Quality of Life and Factors Affecting It: A Study Among People Living Near a Solid Waste Management Facility.

Background: The amount of waste generated has been increasing over the years. Meanwhile, the capacity of solid waste management facilities (SWMFs) for waste disposal does not meet the needs, resulting in adverse consequences on the natural environment and health of residents living near these plants, which can significantly degrade their quality of life (QoL). This study aims to evaluate the QoL of residents living near an SWMF and the potential impacts it has on the residents. Methods: A cross-sectional descriptive study was conducted involving 801 subjects, aged 18 and above, who live near the SWMF of Hue City, Vietnam. The QoL of the subjects was quantitatively assessed using the WHO QoL assessment scale (WHOQOL-BREF). The general, health, and environmental factors influencing QoL were identified using bivariate and multivariate logistic regression analyses. Results: About 22.6% of the subjects had a good QoL. In particular, the proportions for good psychological health (6.9%) and environment (13.6%) were low, indicating an influence of the SWMF. Significant factors that degraded the QoL of residents were less education defined by not graduating from high school (odds ratio, OR = 2.78; 95% CI = 1.09-7.06), poor health status (OR = 2.50; 95% CI: 1.56-4.01), dissatisfaction with water quality (OR = 2.41; 95% CI: 1.10-5.25), and unacceptance of the SWMF presence (OR = 1.70; 95% CI: 1.11-2.60). Moreover, subjects living within 2 km of the plant had dermatological diseases and digestive disorders more frequently than those who lived away from the plant. They also reported more complaints regarding water, air, and soil quality, which were likely due to the operation of the SWMF. Conclusions: Burying and disposing of solid waste at the SWMF might lead to the degradation of the surrounding water and soil environments, and its collection and transportation are considered to cause odor and dust. The efforts of responsible authorities to strictly supervise and inspect these activities at the SWMF are essential, not only to protect the surrounding environment but also to improve the QoL of those who live nearby these plants.

Health vs. privacy? The risk-risk tradeoff in using COVID-19 contact-tracing apps.

In the midst of the COVID-19 pandemic, contact-tracing apps have emerged as reliable tools for public health communication and the promotion of preventative health. However, to function properly, contact-tracing apps require users to provide sensitive information, which has raised concerns about data disclosure, misuse and social surveillance. Little is known about how different types of risk perception simultaneously hinder and motivate individuals' engagement in mobile health apps, particularly in the context of a pandemic. Based on the privacy calculus theory and the risk-risk tradeoff concept, this study examined the risk-risk tradeoff model to enhance the understanding of COVID-19 contact-tracing app users' decision from the perspective of risk minimization. Findings from PLS-SEM and fsQCA revealed that users engage in health risk-privacy risk tradeoff when evaluating and deciding to use the apps. The focal study therefore contributes to the research on privacy calculus theory and calls for a balanced managerial solution to mitigate this tradeoff dilemma.

Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for inhibiting amyloid beta formation: in silico and in vitro study.

Combining Lipinski's rule with the docking and steered molecular dynamics simulations and using the PubChem data base of about 1.4 million compounds, we have obtained DNA dyes Hoechst 34580 and Hoechst 33342 as top-leads for the Alzheimer's disease. The binding properties of these ligands to amyloid beta (Aß) fibril were thoroughly studied by in silico and in vitro experiments. Hoechst 34580 and Hoechst 33342 prefer to locate near hydrophobic regions with binding affinity mainly governed by the van der Waals interaction. By the Thioflavin T assay, it was found that the inhibition constant IC50 ≈ 0.86 and 0.68 µM for Hoechst 34580 and Hoechst 33342, respectively. This result qualitatively agrees with the binding free energy estimated using the molecular mechanic-Poisson Boltzmann surface area method and all-atom simulations with the AMBER-f99SB-ILDN force field and water model TIP3P. In addition, DNA dyes have the high capability to cross the blood brain barrier. Thus, both in silico and in vitro experiments have shown that Hoechst 34580 and 33342 are good candidates for treating the Alzheimer's disease by inhibiting Aß formation.

Ligand binding to anti-cancer target CD44 investigated by molecular simulations.

CD44 is a cell-surface glycoprotein and receptor for hyaluronan, one of the major components of the tumor extracellular matrix. There is evidence that the interaction between CD44 and hyaluronan promotes breast cancer metastasis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated the mechanism and energetics of F-19848A binding to CD44 using molecular simulation. Using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method, we obtained the binding free energy and inhibition constant of the complex. The van der Waals (vdW) interaction and the extended portion of F-19848A play key roles in the binding affinity. We screened natural products from a traditional Chinese medicine database to search for CD44 inhibitors. From combining pharmaceutical requirements with docking and molecular dynamics simulations, we found ten compounds that are potentially better or equal to the F-19848A ligand at binding to CD44 receptor. Therefore, we have identified new candidates of CD44 inhibitors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer.

A New Method for Navigating Optimal Direction for Pulling Ligand from Binding Pocket: Application to Ranking Binding Affinity by Steered Molecular Dynamics.

In this paper we present a new method for finding the optimal path for pulling a ligand from the binding pocket using steered molecular dynamics (SMD). Scoring function is defined as the steric hindrance caused by a receptor to ligand movement. Then the optimal path corresponds to the minimum of this scoring function. We call the new method MSH (Minimal Steric Hindrance). Contrary to existing navigation methods, our approach takes into account the geometry of the ligand while other methods including CAVER only consider the ligand as a sphere with a given radius. Using three different target + receptor sets, we have shown that the rupture force Fmax and nonequilibrium work Wpull obtained based on the MSH method show a much higher correlation with experimental data on binding free energies compared to CAVER. Furthermore, Wpull was found to be a better indicator for binding affinity than Fmax. Thus, the new MSH method is a reliable tool for obtaining the best direction for ligand exiting from the binding site. Its combination with the standard SMD technique can provide reasonable results for ranking binding affinities using Wpull as a scoring function.