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The pervasive presence of microplastics has emerged as a pressing global environmental concern, posing threats to food security and human health upon infiltrating agricultural soils. These microplastics primarily originate from agricultural activities, including fertilizer inputs, compost-based soil remediation, irrigation, and atmospheric deposition. Their remarkable durability and resistance to biodegradation contribute to their persistent presence in the environment. Microplastics within agricultural soils have prompted concerns regarding their potential impacts on agricultural practices. Functioning as significant pollutants and carriers of microcontaminants within agricultural ecosystems, microplastics and their accompanying contaminants represent ongoing challenges. Within these soil ecosystems, the fate and transportation of microplastics can detrimentally affect plant growth, microbial communities, and, subsequently, human health via the food chain. Specifically, microplastics interact with soil factors, impacting soil health and functionality. Their high adsorption capacity for hazardous microcontaminants exacerbates soil contamination, leading to increased adverse effects on organisms and human health. Due to their tiny size, microplastic debris is easily ingested by soil organisms and can transfer through the food chain, causing physiological and/or mechanical damage. Additionally, microplastics can affect plant growth and have the potential to accumulate and be transported within plants. Efforts to mitigate these impacts are crucial to safeguarding agricultural sustainability and environmental health. Future research should delve into the long-term impacts of environmental aging processes on microplastic debris within agricultural soil ecosystems from various sources, primarily focusing on food security and human beings.
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Heavy metals such as cadmium (Cd), arsenic (As), and lead (Pb) pose significant health risks, particularly in Asia, where rice is a staple for nearly three billion people. Despite their known dangers and environmental prevalence, studies addressing their concentrations in rice across different regions and the associated health implications remain insufficient. This review systematically examines the occurrence and impact of these toxic elements, filling a critical gap in the literature. Data from seven countries indicate mean concentrations in the order of Pb > As>Cd, with values of 0.255 ± 0.013, 0.236 ± 0.317, and 0.136 ± 0.150 mg/kg, respectively. Uncertainty analysis shows extensive variability, especially for Cd, with a 95% confidence interval range from 0.220 to 0.992 mg/kg. The typical daily intake of heavy metals through rice consumption, in the order of As>Cd > Pb, frequently exceeds safe limits. Generally, data obtained from various studies showed that children were more prone to heavy metal contamination through rice consumption than adults. This review is fundamental for ongoing monitoring, future research, and management strategies to reduce heavy metal contamination in rice.
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This study investigates the presence of microplastics (MPs) in seawater, sediments, and organisms along the coastal areas of Da Nang, Vietnam. The results obtained revealed MP concentrations ranging from 111 to 304 MPs/L in seawater and 2267 to 4600 MPs/kg in sediment. In organisms such as oysters, mussels, crabs, snails, and fish, MP levels ranged from 1.8 to 17.3 MPs/g (wet weight). Fiber MPs were found to be predominant across seawater, sediment, and organisms. The study identified eight, ten, and eleven types of MPs in seawater, sediment, and organisms, respectively, with Nylon, Polytetrafluoroethylene (PTFE), and Ethylene vinyl alcohol (EVOH) being the most prevalent. Notably, MP concentrations were significantly higher in benthic organisms such as oysters, mussels, and crabs compared to fish (t-test, p < 0.05), suggesting habitat dependency. Similar concentrations, shapes, and types of MPs in seawater, sediments, and organisms demonstrate a tendency for MP accumulation in aquatic organisms within the marine environment.
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Organismos Aquáticos , Monitoramento Ambiental , Microplásticos , Água do Mar , Poluentes Químicos da Água , Animais , Vietnã , Poluentes Químicos da Água/análise , Água do Mar/química , Microplásticos/análise , Sedimentos Geológicos/química , Braquiúros , Peixes , Bivalves , Ostreidae , CaramujosRESUMO
PURPOSE: Fluoropyrimidine-related toxicity and mortality risk increases significantly in patients carrying certain DPYD genetic variants with standard dosing. We implemented DPYD genotyping at a multisite cancer center and evaluated its impact on dosing, toxicity, and hospitalization. METHODS: In this prospective observational study, patients receiving (reactive) or planning to receive (pretreatment) fluoropyrimidine-based chemotherapy were genotyped for five DPYD variants as standard practice per provider discretion. The primary end point was the proportion of variant carriers receiving fluoropyrimidine modifications. Secondary end points included mean relative dose intensity, fluoropyrimidine-related grade 3+ toxicities, and hospitalizations. Fisher's exact test compared toxicity and hospitalization rates between pretreatment carriers, reactive carriers, and wild-type patients. Univariable and multivariable logistic regression identified factors associated with toxicity and hospitalization risk. Kaplan-Meier methods estimated time to event of first grade 3+ toxicity and hospitalization. RESULTS: Of the 757 patients who received DPYD genotyping (median age 63, 54% male, 74% White, 19% Black, 88% GI malignancy), 45 (5.9%) were heterozygous carriers. Fluoropyrimidine was modified in 93% of carriers who started treatment. In 442 patients with 3-month follow-up, 64%, 31%, and 30% of reactive carriers, pretreatment carriers, and wild-type patients had grade 3+ toxicity, respectively (P = .085); 64%, 25%, and 13% were hospitalized (P < .001). Reactive carriers had 10-fold higher odds of hospitalization compared with wild-type patients (P = .001), whereas no significant difference was noted between pretreatment carriers and wild-type patients. Time-to-event of toxicity and hospitalization were significantly different between genotype groups (P < .001), with reactive carriers having the earliest onset and highest incidence. CONCLUSION: DPYD genotyping prompted fluoropyrimidine modifications in most carriers. Pretreatment testing reduced toxicities and hospitalizations compared with reactive testing, thus normalizing the risk to that of wild-type patients, and should be considered standard practice.
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Di-Hidrouracila Desidrogenase (NADP) , Genótipo , Hospitalização , Humanos , Masculino , Feminino , Di-Hidrouracila Desidrogenase (NADP)/genética , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Estudos Prospectivos , Idoso , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Institutos de Câncer , AdultoRESUMO
The COVID-19 pandemic was caused by the SARS-CoV-2 virus, marking one of the most catastrophic global health crises of the 21st century. Throughout this period, widespread use and improper disposal of personal protective equipment (PPE) emerged as a pressing environmental issue, significantly impacting various life forms. During the COVID-19 pandemic, there was a high rate of PEP disposal. An alarming 1.6 × 106 tons of plastic waste each day has been generated since the onset of the outbreak, predominantly from the inadequate disposal of PPE. The mismanagement and subsequent degradation of discarded PPE significantly contribute to increased non-biodegradable micro(nano)plastic (MNP) waste. This pollution has had profound adverse effects on terrestrial, marine, and aquatic ecosystems, which have been extensively of concern recently. Accumulated MNPs within aquatic organisms could serve as a potential route for human exposure when consuming seafood. This review presents a novel aspect concerning the pollution caused by MNPs, particularly remarking on their role during the pandemic and their detrimental effects on human health. These microplastic particles, through the process of fragmentation, transform into nanoparticles, persisting in the environment and posing potential hazards. The prevalence of MNP from PPE, notably masks, raises concerns about their plausible health risks, warranting global attention and comprehensive exploration. Conducting a comprehensive evaluation of the long-term effects of these processes and implementing effective management strategies is essential.
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COVID-19 , Equipamento de Proteção Individual , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Poluição Ambiental/prevenção & controle , Microplásticos/análise , SARS-CoV-2 , Plásticos , NanopartículasRESUMO
BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.
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Fluoropyrimidine chemotherapy is a primary component of many solid tumor treatment regimens, particularly those for gastrointestinal malignancies. Approximately one-third of patients receiving fluoropyrimidine-based chemotherapies experience serious adverse effects. This risk is substantially higher in patients carrying DPYD genetic variants, which cause reduced fluoropyrimidine metabolism and inactivation (ie, dihydropyridine dehydrogenase [DPD] deficiency). Despite the known relationship between DPD deficiency and severe toxicity risk, including drug-related fatalities, pretreatment DPYD testing is not standard of care in the United States. We developed an in-house DPYD genotyping test that detects 5 clinically actionable variants associated with DPD deficiency, and genotyped 827 patients receiving fluoropyrimidines, of which 49 (6%) were identified as heterozygous carriers. We highlight 3 unique cases: (1) a patient with a false-negative result from a commercial laboratory that only tested for the c.1905 + 1G>A (*2A) variant, (2) a White patient in whom the c.557A>G variant (typically observed in people of African ancestry) was detected, and (3) a patient with the rare c.1679T>G (*13) variant. Lastly, we evaluated which DPYD variants are detected by commercial laboratories offering DPYD genotyping in the United States and found 6 of 13 (46%) did not test for all 5 variants included on our panel. We estimated that 20.4% to 81.6% of DPYD heterozygous carriers identified on our panel would have had a false-negative result if tested by 1 of these 6 laboratories. The sensitivity and negative predictive value of the diagnostic tests from these laboratories ranged from 18.4% to 79.6% and 95.1% to 98.7%, respectively. These cases underscore the importance of comprehensive DPYD genotyping to accurately identify patients with DPD deficiency who may require lower fluoropyrimidine doses to mitigate severe toxicities and hospitalizations. Clinicians should be aware of test limitations and variability in variant detection by commercial laboratories, and seek assistance by pharmacogenetic experts or available resources for test selection and result interpretation.
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Deficiência da Di-Hidropirimidina Desidrogenase , Di-Hidrouracila Desidrogenase (NADP) , Genótipo , Humanos , Di-Hidrouracila Desidrogenase (NADP)/genética , Masculino , Feminino , Pessoa de Meia-Idade , Deficiência da Di-Hidropirimidina Desidrogenase/diagnóstico , Deficiência da Di-Hidropirimidina Desidrogenase/genética , Idoso , Técnicas de Genotipagem/métodos , Adulto , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêuticoRESUMO
PURPOSE: It is unclear which triceps tendon repair constructs and techniques produce the strongest biomechanical performance while minimizing the risk of gap formation and repair failure. We aimed to determine associations of construct and technique variables with the biomechanical strength of triceps tendon repairs. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for peer-reviewed studies on biomechanical strength of triceps tendon repairs in human cadavers. 6 articles met the search criteria. Meta-regression was performed on the pooled dataset (123 specimens). Outcomes of interest included gap formation, failure mode, and ultimate failure load. Covariates were fixation type; number of implants; and number of sutures. Stratification by covariates was performed. We found no association between fixation type and ultimate failure load; however, suture anchor fixation was associated with less gap formation compared with transosseous direct repair (ß = - 1.1; 95% confidence interval [CI]:- 2.2, - 0.04). A greater number of implants was associated with smaller gap formation (ß = - 0.77; 95% CI: - 1.3, - 0.28) while a greater number of sutures was associated with higher ultimate failure load ( ß= 3; 95% CI: 21, 125). In human cadaveric models, the number of sutures used in triceps tendon repairs may be more important than the fixation type or number of implants for overall strength. If using a transosseous direct repair approach to repair triceps tendon tears, surgeons may choose to use more sutures in their repair in order to balance the risk of larger gap formation when compared to indirect repair techniques. LEVEL OF EVIDENCE: Level III.
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Cadáver , Técnicas de Sutura , Traumatismos dos Tendões , Humanos , Fenômenos Biomecânicos , Âncoras de Sutura , Traumatismos dos Tendões/cirurgia , Tendões/cirurgiaRESUMO
Water pollution remains a pressing environmental issue, with diverse pollutants such as heavy metals, pharmaceuticals, dyes, and aromatic hydrocarbon compounds posing a significant threat to clean water access. Historically, biomass-derived activated carbons (ACs) have served as effective adsorbents for water treatment, owing to their inherent porosity and expansive surface area. Nanocomposites have emerged as a means to enhance the absorption properties of ACs, surpassing conventional AC performance. Biomass-based activated carbon nanocomposites (ACNCs) hold promise due to their high surface area and cost-effectiveness. This review explores recent advancements in biomass-based ACNCs, emphasizing their remarkable adsorption efficiencies and paving the way for future research in developing efficient and affordable ACNCs. Leveraging real-time communication for ACNC applications presents a viable approach to addressing cost concerns.
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Carvão Vegetal , Frutas , Nanocompostos , Verduras , Purificação da Água , Nanocompostos/química , Carvão Vegetal/química , Purificação da Água/métodos , Frutas/química , Adsorção , Verduras/química , Poluentes Químicos da Água/química , BiomassaRESUMO
INTRODUCTION: This systematic review aims to evaluate the use of machine learning and artificial intelligence in hernia surgery. METHODS: The PRISMA guidelines were followed throughout this systematic review. The ROBINS-I and Rob 2 tools were used to perform qualitative assessment of all studies included in this review. Recommendations were then summarized for the following pre-defined key items: protocol, research question, search strategy, study eligibility, data extraction, study design, risk of bias, publication bias, and statistical analysis. RESULTS: A total of 13 articles were ultimately included for this review, describing the use of machine learning and deep learning for hernia surgery. All studies were published from 2020 to 2023. Articles varied regarding the population studied, type of machine learning or Deep Learning Model (DLM) used, and hernia type. Of the thirteen included studies, all included either inguinal, ventral, or incisional hernias. Four studies evaluated recognition of surgical steps during inguinal hernia repair videos. Two studies predicted outcomes using image-based DMLs. Seven studies developed and validated deep learning algorithms to predict outcomes and identify factors associated with postoperative complications. CONCLUSION: The use of ML for abdominal wall reconstruction has been shown to be a promising tool for predicting outcomes and identifying factors that could lead to postoperative complications.
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Aprendizado Profundo , Herniorrafia , Aprendizado de Máquina , HumanosRESUMO
The development of advanced materials for efficient photocatalytic H2 production and CO2 reduction is highly recommended for addressing environmental issues and producing clean energy sources. Specifically, MXenes have emerged as two-dimensional (2D) materials extensively used as high-performance cocatalysts in photocatalyst systems owing to their outstanding features of structure and properties such as high conductivity, large specific surface area, and abundant active sites. Nevertheless, there is a lack of deep and systematic studies concerning the application of these emerging materials for CO2 reduction reaction (CRR) and H2 production (HER). This review first outlines the essential features of MXenes, encompassing the synthesis methods, composition, surface terminations, and electronic properties, which make them highly active as cocatalysts. It then examines the recent progress in MXene-based photocatalysts, emphasizing the synergy achieved by coupling MXenes as co-catalysts with semiconductors, utilizing MXenes as a support for the consistent growth of photocatalysts, leading to finely dispersed nanoparticles, and exploiting MXene as exceptional precursors for creating MXene/metal oxide photocomposite. The roles of engineering surface terminations of MXene cocatalysts, MXene quantum dots (QDs), and distinctive morphologies in MXenes-based photocatalyst systems to enhance photocatalytic activity for both HER and CRR have been explored both experimentally and theoretically using DFT calculations. Challenges and prospects for MXene-based photocatalysts are also addressed. Finally, suggestions for further research and development of effective and economical MXenes/semiconductors strategies are proposed. This comprehensive review article serves as a valuable reference for researchers for applying MXenes in photocatalysis.
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The predominant use of intravenous catheters as primary access type in the pediatric hemodialysis population is associated with an increased risk of catheter related blood stream infections. While strict adherence to catheter placement and long-term care guidelines have helped to decrease the incidence of these infections, blood stream infections remain an infection burden in pediatric patients with long term hemodialysis catheters. The formation of biofilms on the surfaces of these catheters has been shown to be a source of microbes causing blood stream infections. One of the strategies for preventing bacterial colonization, inhibiting microbial multiplication, and suppressing the seeding of these microbes from biofilms upon maturation, has been the use of antibiotic-based lock solutions in-between dialysis treatments. Although clinical guidelines for the use of antibiotic lock solutions are yet to be developed, available evidence suggests a beneficial role of antibiotic lock solutions in the management of catheter related blood stream infections. Additionally, a clear understanding of how biofilms are formed and their role in the pathogenesis of catheter related bloodstream infection will facilitate the development of solutions that can prevent biofilm formation and inhibit their multiplication, maturation and seeding into the bloodstream.
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Environmental pollution of heavy metal(loid)s (HMs) caused adverse impacts, has become one of the emerging concerns and challenges worldwide. Metal(loid)s can pose significant threats to living organisms even when present in trace levels within environmental matrices. Extended exposure to these substances can lead to adverse health consequences in humans. Removing HM-contaminated water and moving toward sustainable development goals (SDGs) is critical. In this mission, biochar has recently gained attention in the environmental sector as a green and alternative material for wastewater removal. This work provides a comprehensive analysis of the remediation of typical HMs by biochars, associated with an understanding of remediation mechanisms, and gives practical solutions for ecologically sustainable. Applying engineered biochar in various fields, especially with nanoscale biochar-aided wastewater treatment approaches, can eliminate hazardous metal(loid) contaminants, highlighting an environmentally friendly and low-cost method. Surface modification of engineered biochar with nanomaterials is a potential strategy that positively influences its sorption capacity to remove contaminants. The research findings highlighted the biochars' ability to adsorb HM ions based on increased specific surface area (SSA), heightened porosity, and forming inner-sphere complexes with oxygen-rich groups. Utilizing biochar modification emerged as a viable approach for addressing lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and chromium (Cr) pollution in aqueous environments. Most biochars investigated demonstrated a removal efficiency >90 % (Cd, As, Hg) and can reach an impressive 99 % (Pb and Cr). Furthermore, biochar and advanced engineered applications are also considered alternative solutions based on the circular economy.
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Arsênio , Mercúrio , Metais Pesados , Humanos , Águas Residuárias , Cádmio/análise , Desenvolvimento Sustentável , Chumbo/análise , Metais Pesados/análise , Carvão Vegetal , Arsênio/análise , Mercúrio/análise , Cromo/análise , Poluição da Água/análise , SoloRESUMO
OBJECTIVES: To assess the experience of subjects with olfactory disorders in their daily life and medical management, and their expectations and proposals for improvement. MATERIAL AND METHODS: A cross-sectional observational study was conducted over the period January 2020 to December 2021, with 300 subjects with olfactory disorders: 222 female, 78 male; mean age 46±15 years. In total, 126 were patients consulting in ENT, and 174 were members of the Anosmie.org patients' association. Participants filled out a questionnaire; free texts were analyzed thematically and coded for various qualitative variables. RESULTS: Olfactory disorders considerably impacted health, safety and quality of life. Non-COVID-19 acute etiologies (non-COVID-19 viral infection, cranial trauma) showed particularly high risk of psychological, social, safety-related and nutritional consequences. Almost all patients (94%) were dissatisfied with their medical management: 28% had received little explanation, and 23% felt their dysosmia was completely neglected, with no exploration and no etiology suggested. Patients wished above all to have follow-up and accompaniment. CONCLUSION: Despite significant impact on health and quality of life, olfactory disorders are neglected by the medical community. Patients should be given an ENT assessment with olfactometry, to establish diagnosis and prognosis. Global multidisciplinary management is necessary, including therapeutic education, and psychological, social and nutritional follow-up.
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Transtornos do Olfato , Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Estudos Transversais , França , Adulto , Idoso , Satisfação do Paciente , Inquéritos e QuestionáriosRESUMO
Viral nervous necrosis (viral encephalopathy and retinopathy) is caused by piscine nodavirus (Nodaviridae, Betanodavirus). Since 1986, this highly infectious virus has caused mass mortalities of up to 100% in farmed saltwater and freshwater fish around the world (with the exception of South America and Antarctica), affecting >60 species across 10 orders. The Atlantic blue marlin (Makaira nigricans Lacépède, 1802) is a top-level predator found throughout the tropical waters of the Atlantic and Indo-Pacific oceans. Despite their popularity as a sportfish, relatively little is known about the Atlantic blue marlin and other billfish. We describe here chronic betanodavirus infection in a juvenile Atlantic blue marlin, which is, to our knowledge, the first report of disease in M. nigricans.
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Doenças dos Peixes , Meningoencefalite , Nodaviridae , Animais , Doenças dos Peixes/virologia , Doenças dos Peixes/patologia , Meningoencefalite/veterinária , Meningoencefalite/virologia , Meningoencefalite/patologia , Infecções por Mononegavirales/veterinária , Infecções por Mononegavirales/virologia , Infecções por Mononegavirales/patologia , Nodaviridae/isolamento & purificação , Perciformes/virologiaRESUMO
In today's era, nanoparticles (NPs) have become an integral part of human life, finding extensive applications in various fields of science, pharmacy, medicine, industry, electronics, and communication. The increasing popularity of NP usage worldwide is a testament to their tremendous potential. However, the widespread deployment of NPs unavoidably leads to their release into the environmental matrices, resulting in persistence in ecosystems and bioaccumulation in organisms. Understanding the environmental behavior of NPs poses a significant challenge due to their nanoscale size. Given the current environmental releases of NPs, known negative consequences, and the limited knowledge available for risk management, comprehending the toxicity of NPs in ecosystems is both awaiting and crucial. The present review aims to unravel the potential environmental influences of nano-scaled materials, and provides in-depth inferences of the current knowledge and understanding in this field. The review comprehensively summarizes the sources, fate, transport, toxicity, health risks, and remediation solutions associated with NP pollution in aquatic and soil ecosystems. Furthermore, it addresses the knowledge gaps and outlines further investigation priorities for the sustainable control of NP pollution in these environments. By gaining a holistic understanding of these aspects, we can work toward ensuring the responsible and sustainable use of NPs in today's fast-growing world.
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Ecossistema , Nanopartículas , Humanos , Nanopartículas/toxicidade , Solo , Poluição Ambiental , Gestão de RiscosRESUMO
Background: New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections. Methods: We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression. Results: In a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO2 <60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved Cmax/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects. Conclusion: The rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia.
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Pneumonia , Infecções por Pseudomonas , Humanos , Animais , Coelhos , Meropeném/uso terapêutico , Pseudomonas aeruginosa , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Tobramicina/farmacologia , Tobramicina/uso terapêutico , Pneumonia/tratamento farmacológico , Desenvolvimento de MedicamentosRESUMO
Methylene blue (MB) is hazardous in natural water because this dye causes serious diseases that endangers public health and ecosystems. Photocatalytic degradation is a prominent technique for achieving the effective elimination of dye pollutants from wastewater and contribute vitally to ecology and environmental safety. Herein, Cu2+-substituted ZnFe2O4 nanomaterials (CuxZn1-xFe2O4; x = 0, 0.1, 0.2, 0.3, 0.4, 0.6) were synthesized, characterized, and applied for the photocatalytic degradation of MB dye beneath visible light with the assistance of hydrogen peroxide (H2O2). The feature of the photo-catalysts was determined by XRD, EDX, FTIR, DRS, BET, SEM, and TEM techniques. Incorporation of Cu2+ ions changed the crystalline phase, particle size, morphology, and surface area. The photocatalysis condition was optimized with the following major factors, the amout of doping Cu2+ ions, H2O2 concentration, adsorbent dosage, and MB concentration. As a result, the photocatalytic MB degradation efficiency by Cu0.6Zn0.4Fe2O4 catalyst was 99.83% within 90 min under LED light (λ ≥ 420 nm), which was around 4 folds higher than that of pure ZnFe2O4. The photo-Fenton kinetics were in accordance with the pseudo-first-order kinetic model (R2 = 0.981), giving the highes rate constant of 0.034 min-1. It can be, therefore, concluded that Cu2+ substitution considerably boosted the photocatalytic activity of CuxZn1-xFe2O4 ZnFe2O4, suggesting a bright prospect of Cu0.6Zn0.4Fe2O4 as a photo-catalyst in the dyes wastewater treatment.
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OBJECTIVE: The study aims to assess the seroprevalence of Toxocariasis and its associated risk factors among individuals attending the outpatient department at Tra Vinh University Hospital, Vietnam, in 2022. SUBJECTS AND METHODS: A cross-sectional survey was conducted among outpatients of Tra Vinh University Hospital. Toxocariasis diagnosis was based on the Enzyme-Linked Immunosorbent Assay (ELISA) performed at the hospital's laboratory department. We assessed the seroprevalence of Toxocariasis and evaluated associated risk factors, including demographics and certain behaviors. RESULTS: Of the 249 participants surveyed, 165 tested positive for Toxocariasis, yielding a seroprevalence of 66.3% (95% CI: 60.4-72.1). Multivariate analysis revealed that age groups up to 30 and 30-60 years had higher odds of Toxocariasis infection, with adjusted odds ratios (aOR) of 2.52 (95% CI: 1.04-6.11) and 3.21 (95% CI: 1.44-7.15) respectively. Additionally, individuals residing in rural areas and those in contact with dogs or cats had increased risks, with aORs of 2.21 (95% CI: 1.21-4.01) and 2.04 (95% CI: 1.10-3.79), respectively. Notably, hand washing before eating emerged as a protective factor against Toxocariasis, presenting an aOR of 0.38 (95% CI: 0.19-0.76). CONCLUSIONS: Our findings underscore a significant seroprevalence (66.3%) of Toxocara spp. among outpatients at Tra Vinh University Hospital. Proactive measures, including hand hygiene before meals and after pet interactions, are advocated. There is a pronounced need for community-level epidemiological surveillance for human Toxocariasis.