Study on the clinical and electrophysiological characteristics of nerve function in myasthenia gravis patients in Vietnam.

Background: In Vietnam, there is limited research on the role of nerve conduction in myasthenia gravis and its association with clinical features. Objective: This study aims to describe the electrophysiological features in patients with myasthenia gravis. Methods: This descriptive study was conducted from September 2019 to December 2021. The study included 33 myasthenia gravis patients who sought medical consultation or received inpatient treatment during this period. The Myasthenia Gravis Foundation of America classifies myasthenia gravis into five groups: I, IIa, IIb, IIIa, IIIb, IVa, IVb, and V. Notably, Group I involves pure ocular weakness, whereas Group a primarily impacts limb and axial muscles, and Group b mainly affects bulbar and respiratory muscles. Results: The study revealed that motor and sensory nerve conduction in the upper and lower limbs were within normal limits for the patient group under evaluation. Repetitive nerve stimulation testing at a frequency of 3 Hz showed positive results in 66.7% of myasthenia gravis patients. Myasthenia gravis patients displayed distinct clinical symptoms, with ptosis being the most common (87.9%). Myasthenia Gravis Foundation of America classification indicated the highest proportion in subgroup IIa (24.2%), with myasthenia gravis predominating in limb and axial muscles (Group a) observed in 51.5% of cases. Needle electromyography showed no abnormalities in myasthenia gravis patients. There was an association between acetylcholine receptor antibody titers and the results of the 3 Hz repetitive nerve stimulation test in myasthenia gravis patients, with a significance of p = 0.002. Conclusion: Nerve conduction studies should be performed in patients with suspected neuromuscular disorders to aid in differential diagnosis and definitive diagnosis of myasthenia gravis.

Recent strides toward transforming lignin into plastics and aqueous electrolytes for flow batteries.

Lignin is an abundant polyaromatic polymer with a wide range of potential future uses. However, the conversion of lignin into valuable products comes at a cost, and medium- to high-value applications are thus appropriate. Two examples of these are polymers (e.g., as fibers, plasticizers, or additives) and flow batteries (e.g., as redox species). Both of these areas would benefit from lignin-derived molecules with potentially low molecular weight and high (electro)chemical functionality. A promising route to obtain these molecules is oxidative lignin depolymerization, as it enables the formation of targeted compounds with multiple functionalities. An application with high potential in the production of plastics is the synthesis of new sustainable polymers. Employing organic molecules, such as quinones and heterocycles, would constitute an important step toward the sustainability of aqueous flow batteries, and lignin and its derivatives are emerging as redox species, mainly due to their low cost and renewability.

A Cross-Sectional Study Investigating Clinical Features, Brain Imaging, and Treatment Efficacy in Patients with Cerebral Venous Thrombosis in the Mekong Delta, Vietnam.

Background: Cerebral venous thrombosis (CVT) is a challenging condition with potential long-term consequences, but it is also a treatable disorder that offers the possibility of complete recovery. This study was conducted to comprehensively investigate the clinical features, brain imaging findings, and treatment outcomes of patients diagnosed with cerebral venous thrombosis. Materials and Methods: Conducted as a cross-sectional descriptive study, patients diagnosed with cerebral venous thrombosis were enrolled at Can Tho Central General Hospital between January 2021 and June 2022. Results: Notably, a substantial proportion of patients (83.4%) exhibited signs of brain damage, with intracranial hemorrhage (50%), brain infarction (30.9%), subarachnoid hemorrhage (16.6%), and hemorrhagic infarct (4.7%) being the predominant findings. Thrombosis primarily affected the superior sagittal sinus (85.7%), transverse sinus (52.4%), and sigmoid sinus (42.8%). All patients received anticoagulation treatment, resulting in a favorable recovery upon hospital discharge for the majority (90.5%), while a small percentage (9.5%) experienced critical illness or death. Conclusion: Our study on cerebral venous thrombosis found diverse clinical presentations, primarily headache. Intracranial hemorrhage was common, affecting superior sagittal, transverse, and sigmoid sinuses. Most patients achieved favorable recoveries with anticoagulation treatment, emphasizing early intervention's importance.

PheWAS analysis on large-scale biobank data with PheTK.

Summary: With the rapid growth of genetic data linked to electronic health record data in huge cohorts, large-scale phenome-wide association study (PheWAS), have become powerful discovery tools in biomedical research. PheWAS is an analysis method to study phenotype associations utilizing longitudinal electronic health record (EHR) data. Previous PheWAS packages were developed mostly in the days of smaller biobanks and with earlier PheWAS approaches. PheTK was designed to simplify analysis and efficiently handle biobank-scale data. PheTK uses multithreading and supports a full PheWAS workflow including extraction of data from OMOP databases and Hail matrix tables as well as PheWAS analysis for both phecode version 1.2 and phecodeX. Benchmarking results showed PheTK took 64% less time than the R PheWAS package to complete the same workflow. PheTK can be run locally or on cloud platforms such as the All of Us Researcher Workbench ( All of Us ) or the UK Biobank (UKB) Research Analysis Platform (RAP). Availability and implementation: The PheTK package is freely available on the Python Package Index (PyPi) and on GitHub under GNU Public License (GPL-3) at https://github.com/nhgritctran/PheTK . It is implemented in Python and platform independent. The demonstration workspace for All of Us will be made available in the future as a featured workspace. Contact: PheTK@mail.nih.gov.

Mitigating Wildlife Spillover in the Clinical Setting: How Physicians and Veterinarians Can Help Prevent Future Disease Outbreaks.

Introduction: The transmission of pathogens from wildlife to humans is a major global health threat that has been highlighted by the proposed origins of the COVID-19 pandemic. Numerous barriers impede pathogen spillover events from ensuing widespread human transmission, but human activity has accelerated the frequency of spillovers and subsequent disease outbreaks, in part through a booming wildlife trade whose impacts on health are not well understood. Methods: A literature review was conducted to examine the risk that the wildlife trade poses to public health and the degree to which these risks are recognized and addressed in clinical practice and medical and veterinary education. Results: The illicit aspects of the wildlife trade challenge efforts to understand its impacts on health. The U.S. and Europe play a leading role in the global wildlife trade that often goes unacknowledged. In particular, the consumption of wild meat and ownership of exotic pets poses public health risks. The potential role of clinicians is underutilized, both in the clinical setting and in clinical education. Discussion: Physicians and veterinarians have the unique opportunity to utilize their clinical roles to address these knowledge gaps and mitigate future outbreaks. We outline a multifaceted approach that includes increasing clinical knowledge about the ecology of zoonotic diseases, leveraging opportunities for mitigation during patient/client-clinician interactions, and incorporating One Health core competencies into medical and veterinary school curricula.

Multilevel and multicomponent intervention to promote colorectal cancer screening among underserved Vietnamese Americans: A cluster randomized trial.

Purpose: The fecal immunochemical test (FIT) is a non-invasive method for colorectal cancer (CRC) screening, particularly effective in underserved Vietnamese American communities with low screening rates. This study reports on a culturally tailored multilevel intervention, incorporating FIT, aimed at increasing CRC screening among these populations aged 50 or above in the Greater Philadelphia metropolitan area. Methods: From 2017 to 2020, we conducted a two-arm cluster randomized controlled trial to test the efficacy of a culturally tailored, multicomponent multilevel intervention aimed at increasing CRC screening uptake via enhanced self-awareness and self-efficacy, improved access to care, and changes in social norms and removal of stigma. The intervention group received multicomponent, multilevel CRC intervention including provision of a FIT self-sampling kit, with intervention approaches informed by the Centers for Disease Control's Clinical Preventive Services (CPS) Guidelines for adults 50+. The control group received only the CPS education. Results: The study sample consisted of 746 eligible Vietnamese American participants recruited from 20 community-based organizations, with 95% having limited English proficiency. At 12-month follow-up, the intervention group showed substantially higher rates of FIT completion (89.56% vs. 7.59%, p < .001) and any CRC testing (91.48% vs. 42.41%, p < .001) compared to the control group. Conclusion: The results suggest that the community-based, culturally-tailored multilevel intervention, which incorporates with FIT self-testing, effectively enhances CRC screening among low-income Vietnamese Americans. Additionally, these results underscore the significance of community-oriented strategies, like collaborating with relevant community-based organizations, in achieving CRC screening targets.

Point-of-care image-based quantitative urinalysis with commercial reagent strips: Design and clinical evaluation.

Urinalysis is a useful test as an indicator of health or disease and as such, is a part of routine health screening. Urinalysis can be undertaken in many ways, one of which is reagent strips used in the general evaluation of health and to aid in the diagnosis and monitoring of kidney disease. To be effective, the test must be performed properly, and the results interpreted correctly. However, different light conditions and colour perception can vary between users leading to ambiguous readings. This has led to camera devices being used to capture and generate the estimated biomarker concentrations, but image colour can be affected by variations in illumination and inbuilt image processing. Therefore, a new portable device with embedded image processing techniques is presented in this study to provide quantitative measurements that are invariant to changes in illumination. The device includes a novel calibration process and uses the ratio of RGB values to compensate for variations in illumination across an image and improve the accuracy of quantitative measurements. Results show that the proposed calibration method gives consistent homogeneous illumination across the whole image. Comparisons against other existing methods and clinical results show good performance with a correlation to the clinical values. The proposed device can be used for point-of-care testing to provide reliable results consistent with clinical values.

Cyclotides derived from Viola dalatensis Gagnep: A novel approach for enrichment and evaluation of antimicrobial activity.

Cyclotides, plant-derived cysteine-rich peptides, exhibit a wide range of beneficial biological activities and possess exceptional structural stability. Cyclotides are commonly distributed throughout the Violaceae family. Viola dalatensis Gagnep, a Vietnamese species, has not been well studied, especially for cyclotides. This pioneering research explores cyclotides from V. dalatensis as antimicrobials. This study used a novel approach to enhance cyclotides after extraction. The approach combined 30% ammonium sulfate salt precipitation and RP-HPLC. A comprehensive analysis was performed to ascertain the overall protein content, flavonoids content, polyphenol content, and free radical scavenging capacity of compounds derived from V. dalatensis. Six known cyclotides were sequenced utilizing MS tandem. Semi-purified cyclotide mixtures (M1, M2, and M3) exhibited antibacterial efficacy against Bacillus subtilis (inhibitory diameters: 19.67-23.50 mm), Pseudomonas aeruginosa (22.17-23.50 mm), and Aspergillus flavus (14.67-21.33 mm). The enriched cyclotide precipitate from the stem extract demonstrated a minimum inhibitory concentration (MIC) of 0.08 mg/mL against P. aeruginosa, showcasing significant antibacterial effectiveness compared to the stem extract (MIC: 12.50 mg/mL). Considerable advancements have been achieved in the realm of cyclotides, specifically in their application as antimicrobial agents.

Antibiotic resistance monitoring in wastewater in the Nordic countries: A systematic review.

The Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have effectively kept lower antibiotic-resistant bacterial (ARB) pathogen rates than many other countries. However, in recent years, these five countries have encountered a rise in ARB cases and challenges in treating infections due to the growing prevalence of ARB pathogens. Wastewater-based surveillance (WBS) is a valuable supplement to clinical methods for ARB surveillance, but there is a lack of comprehensive understanding of WBS application for ARB in the Nordic countries. This review aims to compile the latest state-of-the-art developments in WBS for ARB monitoring in the Nordic countries and compare them with clinical surveillance practices. After reviewing 1480 papers from the primary search, 54 were found relevant, and 15 additional WBS-related papers were included. Among 69 studies analyzed, 42 dedicated clinical epidemiology, while 27 focused on wastewater monitoring. The PRISMA review of the literature revealed that Nordic countries focus on four major WBS objectives of ARB: assessing ARB in the human population, identifying ARB evading wastewater treatment, quantifying removal rates, and evaluating potential ARB evolution during the treatment process. In both clinical and wastewater contexts, the most studied targets were pathogens producing carbapenemase and extended-spectrum beta-lactamase (ESBL), primarily Escherichia coli and Klebsiella spp. However, vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have received more attention in clinical epidemiology than in wastewater studies, probably due to their lower detection rates in wastewater. Clinical surveillance has mostly used culturing, antibiotic susceptibility testing, and genotyping, but WBS employed PCR-based and metagenomics alongside culture-based techniques. Imported cases resulting from international travel and hospitalization abroad appear to have frequently contributed to the rise in ARB pathogen cases in these countries. The many similarities between the Nordic countries (e.g., knowledge exchange practices, antibiotic usage patterns, and the current ARB landscape) could facilitate collaborative efforts in developing and implementing WBS for ARB in population-level screening.

Comparison of phenomic profiles in the All of Us Research Program against the US general population and the UK Biobank.

IMPORTANCE: Knowledge gained from cohort studies has dramatically advanced both public and precision health. The All of Us Research Program seeks to enroll 1 million diverse participants who share multiple sources of data, providing unique opportunities for research. It is important to understand the phenomic profiles of its participants to conduct research in this cohort. OBJECTIVES: More than 280 000 participants have shared their electronic health records (EHRs) in the All of Us Research Program. We aim to understand the phenomic profiles of this cohort through comparisons with those in the US general population and a well-established nation-wide cohort, UK Biobank, and to test whether association results of selected commonly studied diseases in the All of Us cohort were comparable to those in UK Biobank. MATERIALS AND METHODS: We included participants with EHRs in All of Us and participants with health records from UK Biobank. The estimates of prevalence of diseases in the US general population were obtained from the Global Burden of Diseases (GBD) study. We conducted phenome-wide association studies (PheWAS) of 9 commonly studied diseases in both cohorts. RESULTS: This study included 287 012 participants from the All of Us EHR cohort and 502 477 participants from the UK Biobank. A total of 314 diseases curated by the GBD were evaluated in All of Us, 80.9% (N = 254) of which were more common in All of Us than in the US general population [prevalence ratio (PR) >1.1, P < 2 × 10-5]. Among 2515 diseases and phenotypes evaluated in both All of Us and UK Biobank, 85.6% (N = 2152) were more common in All of Us (PR >1.1, P < 2 × 10-5). The Pearson correlation coefficients of effect sizes from PheWAS between All of Us and UK Biobank were 0.61, 0.50, 0.60, 0.57, 0.40, 0.53, 0.46, 0.47, and 0.24 for ischemic heart diseases, lung cancer, chronic obstructive pulmonary disease, dementia, colorectal cancer, lower back pain, multiple sclerosis, lupus, and cystic fibrosis, respectively. DISCUSSION: Despite the differences in prevalence of diseases in All of Us compared to the US general population or the UK Biobank, our study supports that All of Us can facilitate rapid investigation of a broad range of diseases. CONCLUSION: Most diseases were more common in All of Us than in the general US population or the UK Biobank. Results of disease-disease association tests from All of Us are comparable to those estimated in another well-studied national cohort.

A pilot study of dietary fibres on pathogen growth in an ex vivo colonic model reveals their potential ability to limit vancomycin-resistant Enterococcus expansion.

Aim: Dietary fibre is important for shaping gut microbiota. The aim of this pilot study was to investigate the impact of dietary fibres on pathogen performance in the presence of gut microbiota. Methods: In an ex vivo gut model, pooled faecal samples were spiked with a cocktail of representative gastrointestinal pathogens and fermented with yeast ß-glucan for 24 hours, after which 16S rRNA amplicon sequencing and short-chain and branched-chain fatty acid (SCFA and BCFA) analyses were performed. In addition, oat ß-glucan, arabinoxylan, yeast ß-glucan, and galactooligosaccharides were each tested against individual representative pathogens and pathogen growth was assessed via qPCR. Glucose served as a control carbon source. Results: Based on 16S rRNA amplicon sequencing, yeast ß-glucan selected for higher proportions of Bacteroides (P = 0.0005, ~6 fold) and Clostridia (P = 0.005, ~3.6 fold) while species of Escherichia/Shigella (P = 0.021, ~2.8 fold) and Lactobacillus (P = 0.007, ~ 15.7-fold) were higher in glucose. Pathogen relative abundance did not differ between glucose and yeast ß-glucan. In the absence of pathogens, higher production of BCFAs (P = 0.002) and SCFAs (P = 0.002) fatty acids was observed for fibre group(s). For individual pathogens, yeast ß-glucan increased growth of Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes (P < 0.05), arabinoxylan increased S. typhimurium (P < 0.05). Tested fibres decreased vancomycin-resistant Enterococcus faecium (P < 0.05), with yeast ß-glucan causing a 1-log reduction (P < 0.01), while galactooligosaccharides decreased L. monocytogenes (P < 0.05). Conclusion: Tested fibres differentially influenced the growth of pathogens, but yeast ß-glucan could represent a dietary strategy to help limit vancomycin-resistant enterococci (VRE) expansion in the gut.

Systematic replication of smoking disease associations using survey responses and EHR data in the All of Us Research Program.

OBJECTIVE: The All of Us Research Program (All of Us) aims to recruit over a million participants to further precision medicine. Essential to the verification of biobanks is a replication of known associations to establish validity. Here, we evaluated how well All of Us data replicated known cigarette smoking associations. MATERIALS AND METHODS: We defined smoking exposure as follows: (1) an EHR Smoking exposure that used International Classification of Disease codes; (2) participant provided information (PPI) Ever Smoking; and, (3) PPI Current Smoking, both from the lifestyle survey. We performed a phenome-wide association study (PheWAS) for each smoking exposure measurement type. For each, we compared the effect sizes derived from the PheWAS to published meta-analyses that studied cigarette smoking from PubMed. We defined two levels of replication of meta-analyses: (1) nominally replicated: which required agreement of direction of effect size, and (2) fully replicated: which required overlap of confidence intervals. RESULTS: PheWASes with EHR Smoking, PPI Ever Smoking, and PPI Current Smoking revealed 736, 492, and 639 phenome-wide significant associations, respectively. We identified 165 meta-analyses representing 99 distinct phenotypes that could be matched to EHR phenotypes. At P < .05, 74 were nominally replicated and 55 were fully replicated. At P < 2.68 × 10-5 (Bonferroni threshold), 58 were nominally replicated and 40 were fully replicated. DISCUSSION: Most phenotypes found in published meta-analyses associated with smoking were nominally replicated in All of Us. Both survey and EHR definitions for smoking produced similar results. CONCLUSION: This study demonstrated the feasibility of studying common exposures using All of Us data.

Knowledge of common cancers among new-entry health science students in Japan and Vietnam.

BACKGROUND: The incidence and mortality rates of cancer are rapidly increasing worldwide. This study aimed to assess the knowledge of common cancers among new-entry health science students in Japan and Vietnam, thereby providing insights for implementing appropriate medical educational interventions. METHODS: This cross-sectional study was conducted among new-entry health science students at Hiroshima University, Japan, and the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. A printed predesigned questionnaire consisting of eleven questions was distributed to the participants during the freshmen health screening at the beginning of the academic year to assess their knowledge of cancer. RESULTS: A total of 2,748 new-entry health science students participated in the study, including 394 (14.3%) Japanese students and 2,354 (85.7%) Vietnamese students. Most cancer knowledge levels in Japanese students were significantly higher than those in Vietnamese students (p < 0.001), except for human papillomavirus (HPV) infection awareness. For this understanding, only 14.8% of Japanese students selected the correct answer, which was significantly lower than the 22.4% of Vietnamese students (p = 0.001). Both the Japanese and Vietnamese students had limited knowledge regarding the connection between HPV infection and cancer and the link between estrogen-progestogen menopausal therapy and breast cancer. Additionally, female students had better knowledge about breast, skin, and endometrial cancers than male students. CONCLUSIONS: Japanese students generally exhibited higher levels of cancer knowledge than Vietnamese students, except for HPV infection recognition. Both groups had limited knowledge regarding the connection between HPV infection and cancer and the relationship between estrogen-progestogen menopausal therapy and breast cancer.

Association of mental health conditions and functional gastrointestinal disorders among Vietnamese new-entry medical students.

BACKGROUND: Functional gastrointestinal disorders (FGIDs), also known as disorders of gut-brain interaction, occur not only in the elderly but also in young adults. This study aimed to evaluate the association between mental health conditions and FGIDs among Vietnamese new-entry medical students. METHODS: This cross-sectional study was conducted in February 2022 among new-entry medical students in Ho Chi Minh City, Vietnam. A printed questionnaire was distributed to all students on the day of freshmen health screening. Their urine samples were collected to screen for Helicobacter pylori infection using rapid urinary test. FGIDs were diagnosed using ROME IV criteria. Gastroesophageal reflux disease (GERD) was defined as the presence of typical reflux symptoms at least twice a week. Mental health conditions, including generalized anxiety disorder (GAD) and major depressive disorder (MDD), were identified using Generalized Anxiety Disorder Assessment-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. RESULTS: Among 400 new-entry medical students who participated in the study, the overall prevalence of FGIDs was 10.3% (functional dyspepsia 6.5%, irritable bowel disease 5.5%). The overlap syndrome (OS) of GERD-FGIDs or different FGIDs was present in 3.0% of participants. The prevalences of GAD and MDD were 6.8% and 10.2%, respectively. The urinary test was positive in 180 (45.0%) participants. In the multivariable logistic regression analysis, MDD was significantly associated with not only the risk of FGIDs (OR = 5.599, 95%CI: 2.173-14.430, p<0.001) but also the risk of OS (OR = 10.076, 95CI%: 2.243-45.266, p = 0.003). CONCLUSIONS: MDD is associated with FGIDs and OS among new-entry medical students.

Large-scale analysis of putative plasmids in clinical multidrug-resistant Escherichia coli isolates from Vietnamese patients.

Introduction: In the past decades, extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Escherichia coli isolates have been detected in Vietnamese hospitals. The transfer of antimicrobial resistance (AMR) genes carried on plasmids is mainly responsible for the emergence of multidrug-resistant E. coli strains and the spread of AMR genes through horizontal gene transfer. Therefore, it is important to thoroughly study the characteristics of AMR gene-harboring plasmids in clinical multidrug-resistant bacterial isolates. Methods: The profiles of plasmid assemblies were determined by analyzing previously published whole-genome sequencing data of 751 multidrug-resistant E. coli isolates from Vietnamese hospitals in order to identify the risk of AMR gene horizontal transfer and dissemination. Results: The number of putative plasmids in isolates was independent of the sequencing coverage. These putative plasmids originated from various bacterial species, but mostly from the Escherichia genus, particularly E. coli species. Many different AMR genes were detected in plasmid contigs of the studied isolates, and their number was higher in CR isolates than in ESBL-producing isolates. Similarly, the blaKPC-2, blaNDM-5, blaOXA-1, blaOXA-48, and blaOXA-181 ß-lactamase genes, associated with resistance to carbapenems, were more frequent in CR strains. Sequence similarity network and genome annotation analyses revealed high conservation of the ß-lactamase gene clusters in plasmid contigs that carried the same AMR genes. Discussion: Our study provides evidence of horizontal gene transfer in multidrug-resistant E. coli isolates via conjugative plasmids, thus rapidly accelerating the emergence of resistant bacteria. Besides reducing antibiotic misuse, prevention of plasmid transmission also is essential to limit antibiotic resistance.

Bromotyrosine-Derived Metabolites from a Marine Sponge Inhibit Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the antibiofilm properties of sponge-derived natural products ianthelliformisamines A-C and their combinations with clinically used antibiotics. Wild-type P. aeruginosa strain and its isogenic exopolysaccharide-deficient mutants were employed to determine the interference of the compounds with biofilm matrix components. We identified that ianthelliformisamines A and B worked synergistically with ciprofloxacin to kill planktonic and biofilm cells. Ianthelliformisamines A and B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin to 1/3 and 1/4 MICs, respectively. In contrast, ianthelliformisamine C (MIC = 53.1 µg/mL) alone exhibited bactericidal effects dose-dependently on both free-living and biofilm populations of wild-type PAO1, PAO1ΔpslA (Psl deficient), PDO300 (alginate overproducing and mimicking clinical isolates), and PDO300Δalg8 (alginate deficient). Interestingly, the biofilm of the clinically relevant mucoid variant PDO300 was more susceptible to ianthelliformisamine C than strains with impaired polysaccharide synthesis. Ianthelliformisamines exhibited low cytotoxicity towards HEK293 cells in the resazurin viability assay. Mechanism of action studies showed that ianthelliformisamine C inhibited the efflux pump of P. aeruginosa. Metabolic stability analyses indicated that ianthelliformisamine C is stable and ianthelliformisamines A and B are rapidly degraded. Overall, these findings suggest that the ianthelliformisamine chemotype could be a promising candidate for the treatment of P. aeruginosa biofilms.

Potential selection and maintenance of manure-originated multi-drug resistant plasmids at sub-clinical concentrations for tetracycline family antibiotics.

The goal of this study was to (a) determine the minimum selection concentrations of tetracycline family antibiotics necessary to maintain plasmids carrying tetracycline-resistant genes and (b) correlate these results to environmental hotspot concentrations reported in previous studies. This study used two plasmids (pT295A and pT413A) originating from dairy manure in a surrogate Escherichia coli host CV601. The minimum selection concentrations of antibiotics tested in nutrient-rich medium were determined as follows: 0.1 mg/L for oxytetracycline, 0.45 mg/L for chlortetracycline, and 0.13-0.25 mg/L for tetracycline. Mixing oxytetracycline and chlortetracycline had minimum selection concentration values increased 2-fold compared to those in single antibiotic tests. Minimum selection concentrations found in this study were lower than reported environmental hotspot concentrations, suggesting that tetracycline family antibiotics were likely to be the driver for the selection and maintenance of these plasmids. Relatively high plasmid loss rates (>90%) were observed when culturing a strain carrying a tetracycline-resistant plasmid in antibiotic-free nutrient-rich and nutrient-defined media. Overall, results suggested that these plasmids can be maintained at concentrations environmentally relevant in wastewater treatment plants, sewage, manure, and manured soil; however, they are unstable and easily lost in the absence of antibiotics.

Drug-Induced Liver Injury with Commonly Used Antibiotics in the All of Us Research Program.

Antibiotics are a known cause of idiosyncratic drug-induced liver injury (DILI). According to the Centers for Disease Control and Prevention, the five most commonly prescribed antibiotics in the United States are azithromycin, ciprofloxacin, cephalexin, amoxicillin, and amoxicillin-clavulanate. We quantified the frequency of acute DILI for these common antibiotics in the All of Us Research Program, one of the largest electronic health record (EHR)-linked research cohorts in the United States. Retrospective analyses were conducted applying a standardized phenotyping algorithm to de-identified clinical data available in the All of Us database for 318,598 study participants. Between February 1984 and December 2022, more than 30% of All of Us participants (n = 119,812 individuals) had been exposed to at least 1 of our 5 study drugs. Initial screening identified 591 potential case patients that met our preselected laboratory-based phenotyping criteria. Because DILI is a diagnosis of exclusion, we then used phenome scanning to narrow the case counts by (i) scanning all EHRs to identify all alternative diagnostic explanations for the laboratory abnormalities, and (ii) leveraging International Classification of Disease 9th revision (ICD)-9 and ICD 10th revision (ICD)-10 codes as exclusion criteria to eliminate misclassification. Our final case counts were 30 DILI cases with amoxicillin-clavulanate, 24 cases with azithromycin, 24 cases with ciprofloxacin, 22 cases with amoxicillin alone, and < 20 cases with cephalexin. These findings demonstrate that data from EHR-linked research cohorts can be efficiently mined to identify DILI cases related to the use of common antibiotics.

Hydrogel-Film-Fabricated Fluorescent Biosensors with Aggregation-Induced Emission for Albumin Detection through the Real-Time Modulation of a Vortex Fluidic Device.

Hydrogels have various promising prospects as a successful platform for detecting biomarkers, and human serum albumin (HSA) is an important biomarker in the diagnosis of kidney diseases. However, the difficult-to-control passive diffusion kinetics of hydrogels is a major factor affecting detection performance. This study focuses on using hydrogels embedded with aggregation-induced emission (AIE) fluorescent probe TC426 to detect HSA in real time. The vortex fluidic device (VFD) technology is used as a rotation strategy to control the reaction kinetics and micromixing during measurement. The results show that the introduction of VFD could significantly accelerate its fluorescence response and effectively improve the diffusion coefficient, while VFD processing could regulate passive diffusion into active diffusion, offering a new method for future sensing research.