Reducing Self-Assembly by Increasing Net Charge: Effect on Biological Activity of Mastoparan C.

The ability of amphipathic peptides to arrange themselves in aqueous solutions, known as self-assembly, has been found to reduce the effectiveness of these peptides in interacting with cell membranes. Therefore, minimizing their tendency to self-assemble could be a potential strategy for enhancing the pharmacological properties of antimicrobial peptides (AMPs). To explore this idea, this study prepared a series of natural peptides mastoparan C (MPC) with increased net charge and hydrophilicity via alanine-to-lysine substitution and investigated the impact on the biological activity. The preliminary data suggested the influence of both the overall positive charge and the position of a lysine residue on the self-assembly of MPC and its derivatives. Besides, the analogue MPC-A5K,A8K displayed higher anticancer activity and comparable antimicrobial activity with significantly lower hemolysis than MPC. Hence, reducing self-assembly by expanding the cationic area could be a promising approach for developing potent and selective AMPs.

HCV RNA Quantification by a Domestic Commercial Assay: A Case Study among People Who Inject Drugs in Vietnam.

The desired performance of nucleic acid testing (NAT) may vary if used for disease diagnosis or for the evaluation of the therapeutic efficacy of a treatment, although in most cases, the same assay is used. However, these tests may not be affordable in many situations including in low/middle income countries that in response have developed domestic assays. Given the example of HCV NAT among people who inject drugs in Vietnam, we aimed at evaluating a domestic assay versus an FDA- and CE-approved assay. This cross-evaluation revealed that (i) the domestic assay had a poorer sensitivity with a threshold of detection above 104 IU/mL, and (ii) the FDA-approved assay had a percentage of false negative results close to 1%. Together, in the present study, the domestic assay had a performance compatible with diagnosis purposes (given that this population was 70% HCV seropositive) but not compatible with HCV treatment monitoring (given that treatment failures are rare and the observed viremia frequently below the threshold of detection). This study highlights the need for a proper evaluation of HCV RNA domestic assays in order to efficiently contribute to the WHO HCV elimination target by 2030.

Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs.

People who inject drugs (PWID) are a population exposed to many genotoxicants and with a high prevalence of HCV infection. Direct-acting antiviral (DAA) regimens are now widely used to treat chronic HCV infection. Although side effects to treatment are currently rare, the long-term effects such as suspicions of de novo hepatocellular carcinoma (HCC) occurrence or HCC recurrence and cardiac defects are still up for debate. Given the structure of DAAs, the molecules have a potential mitochondrial DNA (mtDNA) genotoxicity. We have previously reported acute mtDNA toxicity of three DAA regimens among PWID with a strong impact on the rate of mtDNA deletion, less on the quantity of mtDNA copy per cell at sustained viral response at 12 weeks (SVR12). Herein, we report the mtDNA parameters nine months after drug discontinuation. We observed that the percentage of the deleted mtDNA genome increased over time. No exposure to any other genotoxicants during this period was associated with a high deletion percentage, suggesting that the replicative advantage of the deleted molecules outweighed their elimination processes. Such observation calls for longer-term follow-up and may contribute to the molecular basis of subclinical side effects of DAA treatments.

Applicability of a Novel Wearable Wireless Electrocardiogram Monitoring Device (Spyder) for Arrhythmia Detection in Patients with Suspected Cardiac Arrhythmias.

INTRODUCTION: In clinical practice, many cardiovascular symptoms can be caused by arrhythmias that are not detected by electrocardiography (ECG) or 24-48 h Holter ECG monitoring. AIMS: To describe the efficacy and applicability of a new device (Spyder) in detecting cardiac arrhythmias with midterm ECG monitoring. METHODS: A descriptive, prospective study was performed on 26 consecutive patients who underwent midterm ECG monitoring with the novel ECG patch device (Spyder). The study was conducted over a 6-month period from August 2020 to February 2021. RESULTS: Twenty-six patients (mean age, 57.8 ± 12.5 years; men, 77%) wearing a Spyder wireless ECG-monitoring device were recruited. The mean wearing time was 84 hours. The main indications for using the device were detection of recurrent atrial fibrillation after radiofrequency ablation (30.7%) and screening for atrial fibrillation after cryptogenic stroke (23.1%). All ECG monitor recordings obtained during the study period were of good quality. The device detected 12 episodes of atrial fibrillation in eight patients, one episode of ventricular tachycardia, one supraventricular tachycardia event, one case of paroxysmal third-degree atrioventricular block, and five cases of frequent premature ventricular contraction. The time to detection of the first episodes of atrial fibrillation and ventricular and supraventricular tachycardia was 28.8 and 47 hours, respectively. CONCLUSIONS: The new wearable wireless ECG-monitoring device (Spyder) is a feasible and effective method for the detection of cardiac arrhythmias.

Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs.

Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. This study aims to explore the impact of direct-acting antiviral (DAA) treatments on mtDNA among PWID. A total of 470 actively injecting heroin users were included. We used quantitative PCR on whole blood to determine the mitochondrial copy number per cell (MCN) and the proportion of mitochondrial DNA deletion (MDD). These parameters were assessed before and after DAA treatment. MDD was significantly increased after HCV treatment, while MCN did not differ. MDD was even greater when subjects were cotreated with ARV. In multivariate analysis, we identified that poly-exposure to DAA and daily heroin injection or regular consumption of methamphetamines were positively associated with high MCN loss while DAA and ARV treatments or methadone use were identified as risk factors for having mtDNA deletion. These observations deserve attention since they were previously associated with premature cell ageing or cell transformation and therefore call for a long-term follow-up.

Computational insights into structural, electronic, and optical properties of Janus GeSO monolayer.

Although O is an element of chalcogen group, the study of two-dimensional (2D) O-based Janus dichalcogenides/monochalcogenides, especially their 1T-phase, has not been given sufficient attention. In this work, we systematically investigate the structural, electronic, and optical properties of 1T Janus GeSO monolayer by using the density functional theory. Via the analysis of phonon spectrum and evaluation of elastic constants, the GeSO monolayer is confirmed to be dynamically and mechanically stable. Calculated results for the elastic constants demonstrate that the Janus GeSO monolayer is much mechanically flexible than other 2D materials due to its small Young's modulus. At the ground state, while both GeS2 and GeO2 monolayers are indirect semiconductors, the Janus GeSO monolayer is found to be a direct band gap semiconductor. Further, effective masses of both electrons and holes are predicted to be directionally isotropic. The Janus GeSO monolayer has a broad absorption spectrum, which is activated from the visible light region and its absorption intensity is very high in the near-ultraviolet region. The calculated results not only systematically provide the fundamental physical properties of GeSO monolayer, but also stimulate scientists to further studying its importance both theoretically and experimentally.

A Case of Streptococcus thoraltensis Bacteremia and Prosthetic Valve Endocarditis in a 68-Year-Old Vietnamese Man.

BACKGROUND Streptococcus thoraltensis is a rare cause of human disease. This report describes a patient with infective endocarditis caused by S. thoraltensis and complicated by ischemic stroke. CASE REPORT A 68-year-old man was admitted for a 12-day duration of fever. He had a history of severe aortic valve stenosis, for which he underwent prosthetic valve replacement, and type 2 diabetes mellitus. Echocardiography revealed vegetation attached to the right coronary cusp of the prosthetic aortic valve and rupture of the sinus of Valsalva into the right ventricle. Blood cultures were positive for S. thoraltensis. He experienced an ischemic stroke involving the vegetation of the aortic valve and died of acute heart failure. CONCLUSIONS S. thoraltensis may be considered an emerging pathogen in patients with infective endocarditis.

Rapid UV/Vis Spectroscopic Dye Authentication Assay for the Determination and Classification of Reactive Dyes, Monascus Pigments, and Natural Dyes in Coloring Foodstuff.

Food authenticity in the field of food dyes can be interpreted as the correctness of the coloring ingredients indicated. The Rapid UV/vis Spectroscopic Dye Authentication Assay (RaSDAY) presented in this work was used to verify the authenticity of water-soluble reddish colorings for food use. RaSDAY includes the processing of samples under different experimental conditions with pH variations and heat exposure. The absorbances measured are analyzed by principal component analysis and a k-nearest neighbors algorithm. As a result, classification of anthocyanins, betalains, and carmine and the detection of Monascus pigments, undeclared artificial food dyes, and reactive textile azo dyes can be performed by utilizing a rapid screening method. In 17 out of 20 samples of coloring food additives that were included in this work, reactive dyes, unpermitted Monascus pigments, and artificial food dyes were detected using the developed method. "Reactive Red 120", "Reactive Red 195", and "Reactive Red 198" were identified by subsequent 1H NMR spectroscopy in eight of those samples.

Emerging Role of Circulating Tumor Cells in Gastric Cancer.

With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

Ongoing strategies to improve the management of upper respiratory tract infections and reduce inappropriate antibiotic use particularly among lower and middle-income countries: findings and implications for the future.

Introduction: Antibiotics are indispensable to maintaining human health; however, their overuse has resulted in resistant organisms, increasing morbidity, mortality and costs. Increasing antimicrobial resistance (AMR) is a major public health threat, resulting in multiple campaigns across countries to improve appropriate antimicrobial use. This includes addressing the overuse of antimicrobials for self-limiting infections, such as upper respiratory tract infections (URTIs), particularly in lower- and middle-income countries (LMICs) where there is the greatest inappropriate use and where antibiotic utilization has increased the most in recent years. Consequently, there is a need to document current practices and successful initiatives in LMICs to improve future antimicrobial use.Methodology: Documentation of current epidemiology and management of URTIs, particularly in LMICs, as well as campaigns to improve future antimicrobial use and their influence where known.Results: Much concern remains regarding the prescribing and dispensing of antibiotics for URTIs among LMICs. This includes considerable self-purchasing, up to 100% of pharmacies in some LMICs. However, multiple activities are now ongoing to improve future use. These incorporate educational initiatives among all key stakeholder groups, as well as legislation and other activities to reduce self-purchasing as part of National Action Plans (NAPs). Further activities are still needed however. These include increased physician and pharmacist education, starting in medical and pharmacy schools; greater monitoring of prescribing and dispensing practices, including the development of pertinent quality indicators; and targeted patient information and health education campaigns. It is recognized that such activities are more challenging in LMICs given more limited resources and a lack of healthcare professionals.Conclusion: Initiatives will grow across LMICs to reduce inappropriate prescribing and dispensing of antimicrobials for URTIs as part of NAPs and other activities, and these will be monitored.

Trends in prediabetes and diabetes prevalence and associated risk factors in Vietnamese adults / 한국역학회지

OBJECTIVES@#The prevalence of diabetes mellitus is rapidly increasing in Vietnam, particularly among adults aged over 45 years. This study estimated trends in diabetes and prediabetes prevalence and determined risk factors in Vietnamese adults (over 45 years). @*METHODS@#A cross-sectional study was conducted based on data from an annual diabetes screening program among people aged 45-69 years in an urban city in central Vietnam (Da Nang). Joinpoint regression analyses were performed to calculate the annual percentage change and ptrend-values. Multinomial logistic regression analysis was used to determine risk factors. @*RESULTS@#In total, 3,765 men and 9,149 women were included in this analysis. The age-adjusted prevalence of diabetes and prediabetes in 2017 was 11.4% and 52.9%, respectively. The prevalence of diabetes was higher in men (15.1%) than in women (10.3%), but that of prediabetes was similar in both genders (53.4% vs. 52.8%). The prevalence of prediabetes significantly increased during the study period, whereas no upward or downward trend for diabetes was observed. The prevalence of obesity, abdominal obesity, hypertension, and dyslipidemia showed no obvious trend. Obesity, a high waist-to-hip ratio, hypertension, more severe abdominal obesity, and dyslipidemia were significantly associated with a higher risk of diabetes and prediabetes. @*CONCLUSIONS@#Diabetes and prediabetes were more prevalent among people aged over 45 years than in the general population. Da Nang has experienced a marked increase in the prevalence of prediabetes. These findings have significant implications regarding the need for nationwide public health interventions and management aiming at diabetes prevention and control.

Trends in prediabetes and diabetes prevalence and associated risk factors in Vietnamese adults / 한국역학회지

OBJECTIVES@#The prevalence of diabetes mellitus is rapidly increasing in Vietnam, particularly among adults aged over 45 years. This study estimated trends in diabetes and prediabetes prevalence and determined risk factors in Vietnamese adults (over 45 years). @*METHODS@#A cross-sectional study was conducted based on data from an annual diabetes screening program among people aged 45-69 years in an urban city in central Vietnam (Da Nang). Joinpoint regression analyses were performed to calculate the annual percentage change and ptrend-values. Multinomial logistic regression analysis was used to determine risk factors. @*RESULTS@#In total, 3,765 men and 9,149 women were included in this analysis. The age-adjusted prevalence of diabetes and prediabetes in 2017 was 11.4% and 52.9%, respectively. The prevalence of diabetes was higher in men (15.1%) than in women (10.3%), but that of prediabetes was similar in both genders (53.4% vs. 52.8%). The prevalence of prediabetes significantly increased during the study period, whereas no upward or downward trend for diabetes was observed. The prevalence of obesity, abdominal obesity, hypertension, and dyslipidemia showed no obvious trend. Obesity, a high waist-to-hip ratio, hypertension, more severe abdominal obesity, and dyslipidemia were significantly associated with a higher risk of diabetes and prediabetes. @*CONCLUSIONS@#Diabetes and prediabetes were more prevalent among people aged over 45 years than in the general population. Da Nang has experienced a marked increase in the prevalence of prediabetes. These findings have significant implications regarding the need for nationwide public health interventions and management aiming at diabetes prevention and control.