RESUMEN
An individual's likelihood of developing non-communicable diseases is often influenced by the types, intensities and duration of exposures at work. Job exposure matrices provide exposure estimates associated with different occupations. However, due to their time-consuming expert curation process, job exposure matrices currently cover only a subset of possible workplace exposures and may not be regularly updated. Scientific literature articles describing exposure studies provide important supporting evidence for developing and updating job exposure matrices, since they report on exposures in a variety of occupational scenarios. However, the constant growth of scientific literature is increasing the challenges of efficiently identifying relevant articles and important content within them. Natural language processing methods emulate the human process of reading and understanding texts, but in a fraction of the time. Such methods can increase the efficiency of both finding relevant documents and pinpointing specific information within them, which could streamline the process of developing and updating job exposure matrices. Named entity recognition is a fundamental natural language processing method for language understanding, which automatically identifies mentions of domain-specific concepts (named entities) in documents, e.g., exposures, occupations and job tasks. State-of-the-art machine learning models typically use evidence from an annotated corpus, i.e., a set of documents in which named entities are manually marked up (annotated) by experts, to learn how to detect named entities automatically in new documents. We have developed a novel annotated corpus of scientific articles to support machine learning based named entity recognition relevant to occupational substance exposures. Through incremental refinements to the annotation process, we demonstrate that expert annotators can attain high levels of agreement, and that the corpus can be used to train high-performance named entity recognition models. The corpus thus constitutes an important foundation for the wider development of natural language processing tools to support the study of occupational exposures.
Asunto(s)
Procesamiento de Lenguaje Natural , Exposición Profesional , Humanos , Exposición Profesional/efectos adversos , Exposoma , OcupacionesRESUMEN
BACKGROUND: There are no clinical practice guidelines addressing the treatment of tobacco-cannabis co-use and a dearth of studies to inform treatment for co-use. This narrative review aims to (1) summarize promising intervention components used in published co-use treatment studies, (2) describe key gaps and emerging issues in co-use, and (3) provide recommendations and considerations in the development and evaluation of co-use interventions. METHODS: We conducted a literature search in June 2024 across several databases to update previous reviews on tobacco-cannabis co-use treatment. We found 9 published intervention studies that specifically addressed treatment for both substances. Data from these studies were manually extracted and summarized. RESULTS: Most of the 9 included studies (1) focused on acceptability and/or feasibility, (2) provided both psychosocial/behavioral and pharmacotherapy intervention components, (3) were conducted in adults, and (4) were delivered in-person, with some having digital asynchronous components, for a 5-to-12-week duration. The most common psychosocial/behavioral strategies used were Cognitive Behavioral Therapy, Motivational Interviewing, and Contingency Management; while the most common pharmacotherapy was Nicotine Replacement Therapy. There was no evidence of compensatory use of tobacco or cannabis when providing simultaneous treatment for both substances. CONCLUSIONS: The literature to date provides support for well-integrated multi-component interventions of psychosocial/behavioral and pharmacotherapy strategies for co-use treatment. This review reinforces an urgent need for treatments targeting tobacco and cannabis co-use. Future interventions should address key gaps, including co-use of vaporized products among youth and young adults, tailored interventions for priority populations, and digital applications to increase reach and advance health equity.
RESUMEN
Small molecules that exhibit broad-spectrum enteroviral inhibitory activity by targeting viral replication proteins are highly desired in antiviral drug discovery studies. To discover new human rhinovirus (hRV) inhibitors, we performed a high-throughput screening of 100,000 compounds from the Korea Chemical Bank library. This search led to identification of two phosphatidylinositol-4-kinase IIIß (PI4KIIIß) inhibitors having the pyrazolo-pyrimidine core structure, which display moderate anti-rhinoviral activity along with mild cytotoxicity. The results of a study aimed at optimizing the activity of the hit compounds showed that the pyrazolo-pyrimidine derivative 6f exhibits the highest activity (EC50 = 0.044, 0.066, and 0.083 µM for hRV-B14, hRV-A16, and hRV-A21, respectively) and moderate toxicity (CC50 = 31.38 µM). Furthermore, 6f has broad-spectrum activities against various hRVs, coxsackieviruses and other enteroviruses, such as EV-A71, EV-D68. An assessment of kinase inhibition potencies demonstrated that 6f possesses a high and selective kinase inhibition activity against PI4KIIIß (IC50 value of 0.057 µM) and not against PI4KIIIα (>10 µM). Moreover, 6f exhibits modest hepatic stability (46.9 and 55.3 % remaining after 30 min in mouse and human liver microsomes, respectively). Finally, an in vivo study demonstrated that 6f possesses a desirable pharmacokinetic profile reflected in low systemic clearance (0.48 Lâh-1 kg-1) and modest oral bioavailability (52.4 %). Hence, 6f (KR-26549) appears to be an ideal lead for the development of new antiviral drugs.
Asunto(s)
Antivirales , Pirimidinas , Rhinovirus , Replicación Viral , Humanos , Rhinovirus/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Replicación Viral/efectos de los fármacos , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/síntesis química , Animales , Relación Estructura-Actividad , Estructura Molecular , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Ratones , Relación Dosis-Respuesta a Droga , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Pruebas de Sensibilidad Microbiana , Fosfotransferasas (Aceptor de Grupo Alcohol)RESUMEN
Use of both cannabis and tobacco has surpassed use of tobacco alone among young adults in California. To better understand why, we collected data with 32 young adults ages 18-30 in Northern California who regularly used cigarettes and cannabis and had diverse sexual, gender, racial, and ethnic identities. Geographically-explicit ecological momentary assessment (EMA; 30 days) was integrated with qualitative mapping interviews. We found contrasting situations of use for cannabis (e.g., around other people) versus cigarettes (e.g., recent discrimination) and different reasons for why participants chose one substance over the other (e.g., enhancing experiences vs. stepping away). Understanding when and why diverse young adults choose cannabis versus cigarettes as they navigate everyday environments helps explain how cannabis and tobacco retail markets shape substance use disparities over time.
RESUMEN
Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children's Hospital from January 2022 to June 2023. The median age was 85 (range: 2-188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2-7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39-4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63-6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 109/L) (OR 2.18, 95% CI 1.29-3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38-4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28-4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 109/L) (OR 2.48, 95% CI 1.10-5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22-5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12-4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.
Asunto(s)
COVID-19 , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , Masculino , Femenino , Niño , COVID-19/epidemiología , COVID-19/diagnóstico , COVID-19/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Vietnam/epidemiología , Preescolar , Adolescente , Lactante , SARS-CoV-2/aislamiento & purificación , Pronóstico , Recuento de Linfocitos , Unidades de Cuidado Intensivo Pediátrico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismoRESUMEN
Importance: Little is known about whether concurrent use of tobacco and cannabis is associated with higher or lower levels of mental health problems than use of either substance alone among youths. Objective: To examine the association between concurrent use of tobacco and cannabis and mental health problems in a national sample of US youths. Design, Setting, and Participants: This cross-sectional study analyzed publicly available wave 6 data within the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative cohort study of US youths aged 14 to 17 years, collected from March to November 2021. This analysis used wave 6 single-wave weights to obtain statistically valid estimates for cross-sectional analyses generalizable to the wave 4 cohort sample. Data were analyzed from November 15, 2023, to April 20, 2024. Exposure: Past 30-day use of any tobacco and cannabis products was self-reported and categorized into 4 exclusive patterns: concurrent, tobacco only, cannabis only, and nonuse. Main Outcomes and Measures: Self-reported past-year internalizing and externalizing mental health problems were measured using the modified version of the Global Appraisal of Individual Needs-Short Screener and separately categorized into 3 levels: low (0-1 symptoms), moderate (2-3 symptoms), and high (≥4 symptoms). Results: A total of 5585 youths were included in the study, with a weighted proportion of 51.3% being male and 72.5% aged 15 to 17 years. In terms of race and ethnicity, 1606 youths (25.7%) were Hispanic, 626 (12.7%) were non-Hispanic Black, 2481 (50.5%) were non-Hispanic White, and 555 (11.0%) were non-Hispanic other. The prevalence of concurrent use (3.4% [95% CI, 2.9%-4.0%]) was comparable to tobacco-only use (3.9% [95% CI, 3.2%-4.6%]), but greater than cannabis-only use (2.5% [95% CI, 2.1%-2.9%]). High levels of internalizing and externalizing problems were most common for the concurrent use group (internalizing: 47.4% [95% CI, 39.2%-55.9%]; externalizing: 61.6% [95% CI, 54.1%-68.7%]), followed by the cannabis-only use group (internalizing: 44.8% [95% CI, 35.7%-54.1%]; externalizing: 48.5% [95% CI, 39.1%-57.9%]), the tobacco-only use group (internalizing: 41.4% [95% CI, 33.7%-49.5%]; externalizing: 46.3% [95% CI, 38.3%-54.5%]), and the nonuse group (internalizing: 22.4% [95% CI, 21.1%-23.8%]; externalizing: 30.4% [95% CI, 28.9%-31.9%]). After controlling for covariates in ordinal logistic regression models, concurrent use of tobacco and cannabis was associated with greater odds of reporting higher levels of externalizing problems compared with tobacco-only use (adjusted odds ratio [AOR], 1.83 [95% CI, 1.15-2.91]) and cannabis-only use (AOR, 1.85 [95% CI, 1.11-3.06]). However, there were no statistically significant differences in the odds of internalizing problems between concurrent use and use of tobacco or cannabis alone. Conclusions and Relevance: In this cross-sectional study of the PATH Study wave 6 youth data, concurrent use of tobacco and cannabis was linked to higher levels of externalizing mental health problems than use of single substances, indicating a potential need to combine mental health support with tobacco and cannabis cessation interventions for youths.
Asunto(s)
Trastornos Mentales , Humanos , Adolescente , Masculino , Femenino , Estudios Transversales , Estados Unidos/epidemiología , Trastornos Mentales/epidemiología , Estudios de CohortesRESUMEN
BACKGROUND: CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood. METHODS: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.gov: NCT04089423), people living with HIV of ≥18 years old were prospectively recruited in seven countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine a CD4 ≤200 cells/µl were evaluated. RESULTS: Among 1604 participants, the median flow cytometry CD4 was 367 (IQR 128-626) cells/µl and 521 (32.5%) had a CD4 ≤200 cells/µl. VISITECT sensitivity was 92.7% (483/521, 95% CI 90.1-94.7%) and specificity was 61.4% (665/1083, 95% CI 58.4-64.3%). For participants with a CD4 between 0-100, 101-200, 201-300, 301-500, and >500 cells/µl, VISITECT misclassified 4.5% (95% CI 2.5-7.2%), 12.5 (95% CI 8.0-18.2%), 74.1% (95% CI 67.0-80.5%), 48.0% (95% CI 42.5-53.6%), and 22.6% (95% CI 19.3-26.3%), respectively. CONCLUSIONS: VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT´s utility as CD4 triage test should be investigated.
RESUMEN
Thoracic endovascular aortic repair (TEVAR) is a minimally invasive procedure involving the placement of an endograft inside the dissection or an aneurysm to direct blood flow and prevent rupture. A significant challenge in endovascular surgery is the geometrical mismatch between the endograft and the artery, which can lead to endoleak formation, a condition where blood leaks between the endograft and the vessel wall. This study uses computational modeling to investigate the effects of artery curvature and endograft oversizing, the selection of an endograft with a larger diameter than the artery, on endoleak creation. Finite element analysis is employed to simulate the deployment of endografts in arteries with varying curvature and diameter. Numerical simulations are conducted to assess the seal zone and to quantify the potential endoleak volume as a function of curvature and oversizing. A theoretical framework is developed to explain the mechanisms of endoleak formation along with proof-of-concept experiments. Two main mechanisms of endoleak creation are identified: local buckling due to diameter mismatch and global buckling due to centerline curvature mismatch. Local buckling, characterized by excess graft material buckling and wrinkle formation, increases with higher levels of oversizing, leading to a larger potential endoleak volume. Global buckling, where the endograft bends or deforms to conform to the centerline curvature of the artery, is observed to require a certain degree of oversizing to bridge the curvature mismatch. This study highlights the importance of considering both curvature and diameter mismatch in the design and clinical use of endografts. Understanding the mechanisms of endoleak formation can provide valuable insights for optimizing endograft design and surgical planning, leading to improved clinical outcomes in endovascular aortic procedures.
Asunto(s)
Procedimientos Endovasculares , Modelos Cardiovasculares , Humanos , Procedimientos Endovasculares/métodos , Endofuga , Prótesis Vascular , Simulación por Computador , Análisis de Elementos Finitos , Implantación de Prótesis Vascular , Aorta Torácica/cirugía , Reparación Endovascular de AneurismasRESUMEN
Objectives: To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources. Methods: A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR). Results: Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases. Conclusions: These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible.
RESUMEN
Nonlinear biomolecular interactions on membranes drive membrane remodeling crucial for biological processes including chemotaxis, cytokinesis, and endocytosis. The complexity of biomolecular interactions, their redundancy, and the importance of spatiotemporal context in membrane organization impede understanding of the physical principles governing membrane mechanics. Developing a minimal in vitro system that mimics molecular signaling and membrane remodeling while maintaining physiological fidelity poses a major challenge. Inspired by chemotaxis, we reconstructed chemically regulated actin polymerization inside vesicles, guiding membrane self-organization. An external, undirected chemical input induced directed actin polymerization and membrane deformation uncorrelated with upstream biochemical cues, suggesting symmetry breaking. A biophysical model incorporating actin dynamics and membrane mechanics proposes that uneven actin distributions cause nonlinear membrane deformations, consistent with experimental findings. This protocellular system illuminates the interplay between actin dynamics and membrane shape during symmetry breaking, offering insights into chemotaxis and other cell biological processes.
Asunto(s)
Actinas , Células Artificiales , Membrana Celular , Polimerizacion , Actinas/metabolismo , Células Artificiales/metabolismo , Células Artificiales/química , Membrana Celular/metabolismo , Quimiotaxis , Modelos BiológicosRESUMEN
The human aorta undergoes complex morphologic changes that indicate the evolution of disease. Finite element analysis enables the prediction of aortic pathologic states, but the absence of a biomechanical understanding hinders the applicability of this computational tool. We incorporate geometric information from computed tomography angiography (CTA) imaging scans into finite element analysis (FEA) to predict a trajectory of future geometries for four aortic disease patients. Through defining a geometric correspondence between two patient scans separated in time, a patient-specific FEA model can recreate the deformation of the aorta between the two time points, showing pathologic growth drives morphologic heterogeneity. A shape-size geometric feature space plotting the variance of the shape index versus the inverse square root of aortic surface area (δð® vs. ) quantitatively demonstrates the simulated breakdown in aortic shape. An increase in δð® closely parallels the true geometric progression of aortic disease patients.
RESUMEN
BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro-regenerative local milieu and re-establish proper oligodendrocyte functions may be beneficial. EXPERIMENTAL APPROACH: Here, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein-coupled receptor 17 (GPR17) and of cysteinyl-leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1G93A ALS mouse model. We chronically treated SOD1G93A mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches. KEY RESULTS: Oral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1G93A mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1G93A mice, suggesting enhanced pro-regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex-based difference in the protective activity of MTK. CONCLUSIONS AND IMPLICATIONS: Our results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti-asthmatic drug, may be a promising sex-specific strategy for personalized ALS treatment.
Asunto(s)
Acetatos , Esclerosis Amiotrófica Lateral , Ciclopropanos , Ratones Transgénicos , Oligodendroglía , Quinolinas , Sulfuros , Animales , Femenino , Ciclopropanos/farmacología , Quinolinas/farmacología , Acetatos/farmacología , Acetatos/uso terapéutico , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Oligodendroglía/patología , Sulfuros/farmacología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Ratones , Masculino , Receptores de Leucotrienos/metabolismo , Receptores de Leucotrienos/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Proteínas del Tejido NerviosoRESUMEN
Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Femenino , Masculino , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Inmunogenicidad Vacunal , Adulto Joven , Eficacia de las Vacunas , Vietnam , Adolescente , Vacunas de ARNm , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/administración & dosificaciónRESUMEN
There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54·4% (95% CI: 48·7-60·0), overall specificity was 85·2% (83·2-87·0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%-38·0%) to 73·2% (60·4%-83·0%), and 75·0 (65·0%-82·9%) to 96·5 (92·1%-98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).
Asunto(s)
Infecciones por VIH , Tuberculosis , Humanos , Femenino , Masculino , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Estudios Prospectivos , Tuberculosis/diagnóstico , Persona de Mediana Edad , Sensibilidad y Especificidad , Mycobacterium tuberculosis/aislamiento & purificación , Lipopolisacáridos/orina , Esputo/microbiologíaRESUMEN
Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown. Objectives: In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB triage test. Methods/Measurements: Consecutive outpatient adults with cough ≥2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating characteristic (ROC) regression model. Results: Among 2904 participants, of whom 613 (21%) had microbiologically-confirmed TB, CRP sensitivity was 84% (95% CI: 81-87%) and specificity was 61% (95% CI: 59-63%). CRP accuracy varied geographically, with higher sensitivity in African countries (≥91%) than Asian countries (64-82%). Sensitivity was higher among men than women (87% vs. 79%, difference +8%, 95% CI: 1-15%) and specificity was higher among people without HIV than PWH (64% vs. 45%, difference +19%, 95% CI: 13-25%). ROC regression identified country and measures of TB disease severity as predictors of CRP performance. Conclusions: Overall, CRP did not achieve the minimum accuracy targets and its performance varied by setting and in some sub-groups, likely reflecting population differences in mycobacterial load.
RESUMEN
Nanoplastics are anticipated to be ubiquitous in various environmental compartments. However, challenges in analytical methods hinder our understanding of risks related to specific nanplastics characteristics such as size and chemical compositions, and interactions between nanoplastics and microorganisms. In this study, we applied fit-for-purpose analytical methods and techniques to understand how nanoplastic chemical composition influences their interaction with bacteria collected from activated sludge. When exposed to polystyrene (PS) and polyvinyl chloride (PVC) nanoplastics for 5 days, the nanoplastics attached to the bacteria. Specifically, on day 1, there was a significant predominance of PS nanoplastics over PVC ones of similar size and shape, possibly due to differences in their chemical composition. After 5 days, there is a substantial decrease in nanoplastics attached to bacteria, suggesting bacterial defence mechanisms may reduce particles attachment over time. The overall bacterial community structure demonstrated a high degree of resilience. This resilience highlights the ability of microbial communities to maintain their structure despite nanoplastic stressors, as evidenced by consistent alpha diversity, PCoA, and PERMANOVA results. Understanding these mechanisms is crucial for assessing nanoplastic fate and thus environmental impacts.
RESUMEN
AIM: This study aimed to investigate awareness of having hypertension, diabetes and dyslipidaemia and their associated factors among US adults. METHODS: Data from the National Health and Nutrition Examination Survey, including 21,399 adults aged ⩾20 years (pregnant women excluded) collected between 2011 and 2018, were used. Blood pressure was measured using a Baumanometer calibrated mercury true gravity wall model sphygmomanometer. Serum total cholesterol levels were measured using enzymatic assays. The percentage of haemoglobin A1C (HbA1c), which reflects long-term blood glucose levels, was measured and used to identify diabetes. Participants self-reported whether they were told by a doctor that they have hypertension, dyslipidaemia and diabetes. Awareness was defined as alignment between objective and self-reported measures for having the conditions. Sampling weights and the Taylor series linearisation variance estimation method were used in the analyses. RESULTS: The findings showed that 64.06% of people with hypertension, 54.71% of those with dyslipidaemia and 78.40% of those with diabetes were aware of having the respective condition. Age, sex and health insurance were associated with awareness of having all three conditions, but marital status was not associated with any outcome. Weight status was associated with awareness of having hypertension and dyslipidaemia, whereas ethnicity was associated with awareness of having hypertension and diabetes. Relative family income was only associated with awareness of having hypertension. CONCLUSIONS: Large proportions of US adults with hypertension, dyslipidaemia and diabetes are not aware of having the conditions. Interventions targeting groups at higher risk of being unaware of these conditions are needed.
RESUMEN
Objective: We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam's two largest cities, Hanoi and Ho Chi Minh city. Methods: All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization's catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis. Results: 233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3-20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %. Conclusions: Drug resistance among most MDR-TB strains in Vietnam's two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis.
RESUMEN
INTRODUCTION: Cigarettes are frequently co-used with alcohol and cannabis. However, definitions of co-use vary and the extent to which cigarette use changes on days with different patterns of co-use is unclear. We compared the number of cigarettes smoked on different days based on co-use patterns of cigarettes and alcohol or cannabis. METHODS: This study analyzed 2408 smoking days collected in a 30-day smartphone-based daily diary study among 146 young adults (aged 18-26) with an oversample from sexual minority groups. Two separate multilevel models were estimated: one for cigarette and alcohol co-use and the other for cigarette and cannabis co-use. Both models examined day-level associations between the number of cigarettes smoked and 3 different types of days (smoking-only days, same-occasion co-use days, different-occasion co-use days), controlling for demographic characteristics. RESULTS: More cigarettes were smoked on same-occasion co-use days compared to cigarette-smoking-only days for both alcohol (b=1.474, SE=0.136, t=10.8, p<.001) and cannabis (b=0.822, SE=0.209, t=3.9, p<.001). There were no significant differences in cigarettes smoked on days with co-use on the same day, but on different occasions, compared to days with smoking only. CONCLUSIONS: Compared to days with cigarette smoking only, more cigarettes are smoked on days when cigarettes are co-used with alcohol or cannabis on the same occasion, while the same is not true for days with co-use on different occasions. Conflating different definitions of co-use may impact findings on associations between co-use and smoking behavior.
Asunto(s)
Consumo de Bebidas Alcohólicas , Fumar Cigarrillos , Fumar Marihuana , Humanos , Masculino , Femenino , Adulto Joven , Consumo de Bebidas Alcohólicas/epidemiología , Adulto , Adolescente , Fumar Cigarrillos/epidemiología , Fumar Marihuana/epidemiología , Fumar/epidemiología , Teléfono InteligenteRESUMEN
OBJECTIVE: Social media platforms are promising to provide smoking cessation support. This study aimed to identify baseline factors associated with cigarette smoking abstinence among young adult smokers enrolled in a real-world social media-based smoking cessation program. AIMS AND METHODS: We analyzed data from young adult smokers (aged 18-30 years) participating in a publicly available Facebook-based smoking cessation program serving the San Francisco Bay Area. The analytic sample consisted of 248 participants who completed both the baseline and follow-up surveys at 3 months. Multivariable logistic regression analysis determined baseline factors significantly associated with self-reported 7-day cigarette smoking abstinence at 3 months. RESULTS: Participants were race/ethnically diverse, well-educated, and 47.6% reported LGBâ +â sexual identity. Those who reported dual use of cigarettes and e-cigarettes in the past 30 days (vs. cigarette use only), current alcohol users (vs. non-users), and those aged 25-30 years (vs. 18-24 years) were significantly less likely to report 7-day abstinence at 3 months. Non-daily smokers (vs. daily smokers) and those with high desire to quit smoking (vs. low to moderate desire) were more likely to report abstinence. Results also showed reduction in the percentage of e-cigarette and other tobacco product use among participants. CONCLUSIONS: Social media interventions may be more effective for young adult non-daily smokers and those with high desire to quit smoking. Smoking cessation programs may help reduce use of other tobacco products among treatment-seeking smokers. Smoking cessation interventions for young adults need to explicitly address dual use of cigarettes and e-cigarettes and use of alcohol. IMPLICATIONS: Findings of this study highlight the need for future interventions to address dual use of cigarettes and e-cigarettes and use of alcohol to improve cigarette smoking abstinence outcomes. The reduction in the use of other tobacco products among program participants indicates that social media smoking cessation programs may exert a broader positive influence on overall tobacco consumption. The large number of LGB+ smokers participating in the program suggests social media is a promising cessation channel for this hard-to-reach group, warranting further study.