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1.
Am J Hum Genet ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39419028

RESUMO

Vitiligo is a common autoimmune disease characterized by patches of depigmented skin and overlying hair due to destruction of melanocytes in the involved regions. We investigated the relationship between vitiligo risk and vitiligo age of onset (AOO) using a vitiligo polygenic risk score that incorporated the most significant SNPs from genome-wide association studies. We find that vitiligo genetic risk and AOO are strongly inversely correlated; subjects with higher common-variant polygenic risk tend to develop vitiligo at an earlier age. Nevertheless, the correlation is not simple. In individuals who carry a single high-risk major histocompatibility complex class II haplotype, the effect of additional polygenic risk on vitiligo AOO is reduced. Particularly among those with early-AOO vitiligo (onset ≤12 years of age), genetic risk can reflect contributions from high common-variant burden but also rare variants of high effect and sometimes both. While the heritability of vitiligo is relatively high, and we here show that genetic risk factors predict vitiligo AOO, vitiligo is never congenital, and thus environmental triggers also play an important role in disease onset.

2.
J Allergy Clin Immunol ; 154(4): 847-860, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39181455

RESUMO

Indoor air pollution is a growing public health concern globally and is associated with increased respiratory symptoms and morbidity. Individuals spend most of their time indoors, and pollutant-related health effects are often driven by the indoor environment. Understanding effective interventions to improve indoor air quality and their impact on respiratory outcomes is key to decreasing the burden of air pollution for high-risk populations across the life-span. This review applies a hierarchy of interventions framework specific to respiratory health effects and focuses on recent studies of interventions to improve indoor air quality among high-risk populations with chronic respiratory disease published in the past 3 years. While policy and source control interventions are likely the most effective and equitable approaches to improve indoor air quality and benefit population health, these were less extensively investigated. Engineering interventions, such as air cleaner interventions, were the most widely studied. Several studies, including those focused on asthma and chronic obstructive pulmonary disease, demonstrated improvement in symptoms and medication receipt with interventions in both home- and school-based settings. Combined multilevel interventions with engineering and behavioral interventions led to improved respiratory outcomes in some, but not all, studies. Placing the recent work in the context of the broader literature, we identify gaps in research. Further research is needed to understand intervention effectiveness over time and an increased focus on policy and source control interventions that can mitigate risk in vulnerable populations.


Assuntos
Poluição do Ar em Ambientes Fechados , Humanos , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/prevenção & controle , Doenças Respiratórias/prevenção & controle , Doenças Respiratórias/etiologia
3.
Annu Rev Entomol ; 69: 551-576, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-37827173

RESUMO

Bees are essential pollinators of many crops and wild plants, and pesticide exposure is one of the key environmental stressors affecting their health in anthropogenically modified landscapes. Until recently, almost all information on routes and impacts of pesticide exposure came from honey bees, at least partially because they were the only model species required for environmental risk assessments (ERAs) for insect pollinators. Recently, there has been a surge in research activity focusing on pesticide exposure and effects for non-Apis bees, including other social bees (bumble bees and stingless bees) and solitary bees. These taxa vary substantially from honey bees and one another in several important ecological traits, including spatial and temporal activity patterns, foraging and nesting requirements, and degree of sociality. In this article, we review the current evidence base about pesticide exposure pathways and the consequences of exposure for non-Apis bees. We find that the insights into non-Apis bee pesticide exposure and resulting impacts across biological organizations, landscapes, mixtures, and multiple stressors are still in their infancy. The good news is that there are many promising approaches that could be used to advance our understanding, with priority given to informing exposure pathways, extrapolating effects, and determining how well our current insights (limited to very few species and mostly neonicotinoid insecticides under unrealistic conditions) can be generalized to the diversity of species and lifestyles in the global bee community. We conclude that future research to expand our knowledge would also be beneficial for ERAs and wider policy decisions concerning pollinator conservation and pesticide regulation.


Assuntos
Inseticidas , Praguicidas , Abelhas , Animais
4.
Kidney Int ; 106(2): 214-225, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38797324

RESUMO

Environmental pollution significantly impacts global disease burden. However, the contribution of environmental pollution to kidney disease is often overlooked in nephrology. This review examines the growing body of research demonstrating the significant impacts of environmental pollutants, with a focus on air pollution as a primary factor, and acknowledges the roles of other pollutants, such as heavy metals, in the development and progression of kidney diseases. Short-term exposure to air pollution is linked with an increased risk of kidney disease-related events, including hospital admissions, and death, predominantly occurring in vulnerable populations. In contrast, long-term exposure, even at low to moderate levels, may lead to progressive pathophysiological changes, such as chronic systemic inflammation and oxidative stress, that contribute to the development of kidney disease. In addition, air pollution may exacerbate traditional kidney disease risk factors such as hypertension and diabetes, thereby accelerating disease progression. The review also explores how climate change may interact with various pollutants, including air pollution, influencing kidney disease indirectly. The examined evidence underscores the urgent need for an interdisciplinary approach to research further into environmental kidney disease. Environmental health policies could play a crucial role in the prevention, intervention, and improvement of kidney health worldwide.


Assuntos
Poluição do Ar , Mudança Climática , Exposição Ambiental , Nefropatias , Humanos , Fatores de Risco , Exposição Ambiental/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Nefropatias/etiologia , Poluição do Ar/efeitos adversos , Progressão da Doença , Poluentes Atmosféricos/efeitos adversos , Poluição Ambiental/efeitos adversos
5.
Cancer Invest ; 42(6): 478-490, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38845533

RESUMO

Biliary dysbiosis is associated with gallbladder cancer (GBC). We aimed to look for biliary bacteria specifically detected in GBC patients. We used 16S rRNA-based metagenomic analysis to elucidate biliary microbiota in 30 GBC and 30 gallstones-associated chronic cholecystitis patients. Relative abundance of five genera, Streptococcus, Enterococcus, Halomonas, Escherichia and Caulobacter was significantly associated with GBC. Of 15-species, 7 were detected significantly higher in GBC, Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius, Actinomyces bowdenii, Actinomyces israelii, Actinomyces gerencseriae, and Escherichia fergusonii were biosafety level-2 infectious bacteria; other 8 species were biosafety level-1 bacteria. These bacterial species may be involved in pathogenesis of GBC.


Assuntos
Colecistite , Neoplasias da Vesícula Biliar , Cálculos Biliares , Metagenômica , Humanos , Neoplasias da Vesícula Biliar/microbiologia , Colecistite/microbiologia , Cálculos Biliares/microbiologia , Feminino , Masculino , Metagenômica/métodos , Pessoa de Meia-Idade , Idoso , RNA Ribossômico 16S/genética , Doença Crônica , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Microbiota , Adulto , Disbiose/microbiologia
6.
Cytotherapy ; 26(7): 686-699, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38713109

RESUMO

Gene therapy is a fast-growing field showing great potential to treat genetic diseases and cancer. With accelerating gene therapy development and approval, their environment risk assessment (ERA) becomes increasingly important. An ERA is an assessment of the risks to human health and the environment upon exposure to a medicinal product as the result of its release during clinical development or after entering the market. Because ERA is an important component of regulatory submission, drug developers must perform a robust assessment to ensure the safety of unintended persons, animal, plants, microorganisms and environment at large. Global regulations on gene therapy ERA continue to evolve. Gene therapy ERAs are carried out according to general principles as provided in regulatory guidelines for application of clinical trials and marketing authorizations. The current review intends to summarize regulations and content requirements on gene therapy ERA in European Union, the USA and Japan. The approved gene therapy products by EMA and US Food and Drug Administration are analyzed for the critical aspects of their ERAs to provide the current status and practice of gene therapy ERAs by drug developers. For this purpose, the main contents of these gene therapy ERAs are summarized. Critical safety factors of gene therapy ERAs are described. With more experience and knowledge to be accumulated, gene therapy ERAs are expected to be less challenging with commonly used viral vectors.


Assuntos
Terapia Genética , Terapia Genética/métodos , Terapia Genética/efeitos adversos , Humanos , Medição de Risco , Animais , Estados Unidos , União Europeia
7.
Psychol Sci ; 35(5): 489-503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513051

RESUMO

Executive functioning (EF) has been shown to relate to academic achievement and well-being. Independent bodies of work have aimed to understand what environmental or personal attributes influence EF ability. However, most research has not considered how constellations of risk factors create distinct patterns of influence on EF ability. The current study tested a sample of children aged 9 to 10 years from the United States (N = 10,323, 48.06% female, Mage = 9.9 years, age range = 8.9-11.08 years) using a latent profile analysis (LPA) to detect subgroups that varied in their combinations of various risk factors. Six distinct groups of risk factors for children emerged, which in turn related to different average EF abilities. We found that family socioeconomic measures related to a subgroup having above- or below-average EF ability, but we also found an effect on EF across different risk factors. These results inform our understanding of individual variations in EF ability and highlight the idea that EF interventions should consider risk holistically.


Assuntos
Função Executiva , Humanos , Criança , Feminino , Função Executiva/fisiologia , Masculino , Fatores de Risco , Estados Unidos , Fatores Socioeconômicos , Sucesso Acadêmico
8.
BMC Cancer ; 24(1): 668, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824512

RESUMO

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.


Assuntos
Neoplasias Gastrointestinais , Humanos , Espanha/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Adulto , Idade de Início , Estilo de Vida , Adenocarcinoma/epidemiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Microambiente Tumoral , Qualidade de Vida , Incidência , Biomarcadores Tumorais , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia
9.
Psychol Med ; 54(9): 2162-2171, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38425272

RESUMO

BACKGROUND: Shared genetic risk between schizophrenia (SCZ) and bipolar disorder (BD) is well-established, yet the extent to which they share environmental risk factors remains unclear. We compare the associations between environmental exposures during childhood/prior to disorder onset with the risk of developing SCZ and BD. METHODS: We conducted a Swedish register-based nested case-control study using 4184 SCZ cases and 18 681 BD cases diagnosed 1988-2013. Cases were matched to five controls by birth year, birth region, and sex. Conditional logistic regression was used to estimate incidence rate ratios (IRR) for SCZ and BD for each exposure (severe childhood infections, adverse childhood experiences (ACEs), substance use disorders (SUDs), urban birth/longest residence). RESULTS: All SUD types were associated with very high risk (IRR 4.9-25.5), and all forms of ACEs with higher risk (IRR 1.5-4.3) for both disorders. In the mutually adjusted models, ACEs demonstrated slightly higher risk for BD (SCZ IRR 1.30, 1.19-1.42; BD IRR 1.49, 1.44-1.55), while for SUD, risk was higher for SCZ (SCZ IRR 9.43, 8.15-10.92; BD IRR 5.50, 5.15-5.88). Infections were associated with increased risk of BD (IRR 1.21, 1.17-1.26) but not SCZ. Urban birth and urban longest residence were associated with higher risk of SCZ (IRR 1.19, 1.03-1.37), while only the combination of urban birth and rural longest residence showed higher risk for BD (IRR 1.24, 1.13-1.35). CONCLUSIONS: There were both shared and unique environmental risk factors: SUDs and ACEs were risk factors for both disorders, while infections were more strongly associated with BD and urbanicity with SCZ.


Assuntos
Experiências Adversas da Infância , Transtorno Bipolar , Esquizofrenia , Humanos , Suécia/epidemiologia , Estudos de Casos e Controles , Feminino , Masculino , Fatores de Risco , Esquizofrenia/epidemiologia , Esquizofrenia/etiologia , Transtorno Bipolar/epidemiologia , Adulto , Experiências Adversas da Infância/estatística & dados numéricos , Criança , Adolescente , Sistema de Registros/estatística & dados numéricos , Adulto Jovem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Pessoa de Meia-Idade
10.
Psychol Med ; 54(10): 2435-2443, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38505954

RESUMO

BACKGROUND: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). METHODS: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. RESULTS: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. CONCLUSIONS: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Masculino , Feminino , Transtornos Psicóticos/genética , Esquizofrenia/genética , Adulto , Adulto Jovem , Funcionamento Psicossocial , Fatores de Risco , Adolescente
11.
Transgenic Res ; 33(4): 243-254, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38902591

RESUMO

Insect-protected soybean (SIP) that produces the Cry1A.105 and Cry2Ab2 insecticidal crystal proteins has been developed to provide protection from feeding damage caused by targeted lepidopteran insect pests. Typically, as part of environmental risk assessment (ERA), plant characterization is conducted, and the data submitted to regulatory agencies prior to commercialization of genetically modified (GM) crops. The objectives of this research were to: (a) compare soybean with and without the SIP trait in plant characterization field trials designed to fulfill requirements for submissions to global regulatory agencies and address China-specific considerations and (b) compare risk assessment conclusions across regions and the methodologies used in the field trials. The soybean with and without the SIP trait in temperate, tropical, and subtropical germplasm were planted in replicated multi-location trials in the USA (in 2012 and 2018) and Brazil (in 2013/2014 and 2017/2018). Agronomic, phenotypic, plant competitiveness, and survival characteristics were assessed for soybean entries with and without the SIP trait. Regardless of genetic background, growing region, season, or testing methodology, the risk assessment conclusions were the same: the evaluated insect-protected soybean did not differ from conventional soybean in evaluated agronomic, phenotypic, competitiveness, and survival characteristics indicating no change in plant pest/weed potential. These results reinforce the concept of data transportability across global regions, different seasons, germplasm, and methodologies that should be considered when assessing environmental risks of GM crops.


Assuntos
Glycine max , Plantas Geneticamente Modificadas , Glycine max/genética , Glycine max/parasitologia , Glycine max/crescimento & desenvolvimento , Animais , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Endotoxinas/genética , Brasil , Controle Biológico de Vetores , Proteínas Hemolisinas/genética , Produtos Agrícolas/genética , Insetos/genética , Insetos/patogenicidade , Lepidópteros/patogenicidade , Lepidópteros/genética , Proteínas de Bactérias/genética , Toxinas de Bacillus thuringiensis/genética
12.
Transgenic Res ; 33(3): 75-88, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38578501

RESUMO

Genetically engineered (GE) cotton event MON 88702, producing Mpp51Aa2 (previously mCry51Aa2) from Bacillus thuringiensis (Bt), controls sucking pests, such as Lygus spp. (Hemiptera: Miridae) and thrips (Thysanoptera). Ingesting high doses of the insecticidal protein resulted in adverse effects on life table parameters of beneficial, predatory Orius spp. (Hemiptera: Anthocoridae). This triggered laboratory studies with more realistic food treatments, including different combinations of prey types with and without Bt protein to further characterize risks to this important group of non-target organisms. In this work, exclusive feeding of frozen spider mites (Tetranychus urticae, Acari: Tetranychidae) from Bt cotton confirmed adverse effects on longevity and fecundity of O. majusculus adults. Alternate feeding of Bt protein-containing spider mites and Bt-free Ephestia kuehniella (Lepidoptera: Pyralidae) eggs mitigated effects on longevity, but not on fecundity. When living larvae of Spodoptera littoralis (Lepidoptera: Noctuidae) from Bt cotton were fed to the predators, however, no effects on longevity and reproduction of female O. majusculus were observed, despite the fact that Bt protein concentrations in larvae were almost as high as concentrations in spider mites. When a diverse mix of prey species with various Bt protein concentrations is consumed in the field, it is unlikely that exposure of Orius spp. to Mpp51Aa2 is high enough to exert adverse effects on predator populations. MON 88702 cotton may thus be a valuable tool for integrated management of sucking pests.


Assuntos
Bacillus thuringiensis , Gossypium , Longevidade , Controle Biológico de Vetores , Plantas Geneticamente Modificadas , Reprodução , Animais , Gossypium/genética , Gossypium/parasitologia , Gossypium/crescimento & desenvolvimento , Gossypium/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/parasitologia , Bacillus thuringiensis/genética , Reprodução/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Comportamento Predatório , Fertilidade/genética , Spodoptera/crescimento & desenvolvimento , Spodoptera/fisiologia , Spodoptera/genética , Larva/crescimento & desenvolvimento , Larva/genética , Toxinas de Bacillus thuringiensis/genética , Endotoxinas/genética , Endotoxinas/metabolismo , Heterópteros/genética , Heterópteros/fisiologia , Heterópteros/crescimento & desenvolvimento , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Tetranychidae/genética , Feminino
13.
Environ Sci Technol ; 58(29): 13056-13064, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38900493

RESUMO

Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.


Assuntos
Chuva , Borracha , Cidades , Poluentes Químicos da Água/análise , Monitoramento Ambiental , China
14.
Brain ; 146(5): 1745-1757, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36918362

RESUMO

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. The only established epidemiological risk factors for ALS are male sex and increasing age. The role of physical activity has been debated as an environmental risk factor. Over the last decade multiple studies have attempted to delineate the architecture of ALS. These have not yet established definite risk factors, often due to low-powered studies, lack of focus on at-risk genotypes and sub-optimal methodology. We have conducted a review of all the studies published between 2009 and December 2021. The free text search terms were [(motor neuron disease) OR (MND) OR (Amyotrophic Lateral Sclerosis) OR (ALS)] AND [(Exercise) or (Physical Activity) or (PA) or (sport)]. We identified common themes, for example soccer, head injury and the physiological mechanisms that differ in ALS patients. We have analysed the relevant, available studies (n = 93), highlighting the underlying reasons for any reported discrepancies. Overall, we have found that the more highly powered studies using validated exposure methodologies, linked strenuous, anaerobic physical activity as a risk factor for ALS. Future large-scale studies focusing on specific at-risk genotypes and physical activity should be conducted to confirm this finding. This will strengthen the evidence already surrounding strenuous physical activity as an environmental risk factor for ALS and allow advice to be given to at-risk family members. Increasing our understanding of the genetic-environmental interactions in the pathophysiology of ALS will allow for the possibility of developing preventative therapeutic approaches.


Assuntos
Esclerose Lateral Amiotrófica , Doença dos Neurônios Motores , Humanos , Masculino , Feminino , Esclerose Lateral Amiotrófica/tratamento farmacológico , Doença dos Neurônios Motores/tratamento farmacológico , Exercício Físico , Fatores de Risco
15.
Environ Res ; 243: 117833, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056612

RESUMO

Advanced oxidation processes such as thermal plasma activation and UV-C/H2O2 treatment are considered as applications for the degradation of pharmaceutical residues in wastewater complementary to conventional wastewater treatment. It is supposed that direct oxidative treatment can lower the toxicity of hospital sewage water (HSW). The aim of this study was to predict the ecotoxicity for three aquatic species before and after oxidative treatment of 10 quantified pharmaceuticals in hospital sewage water. With the application of oxidative chemistry, pharmaceuticals are degraded into transformation products before reaching complete mineralization. To estimate the potential ecotoxicity for fish, Daphnia and green algae ECOSAR quantitative structure-activity relationship software was used. Structure information from pristine pharmaceuticals and their oxidative transformation products were calculated separately and in a mixture computed to determine the risk quotient (RQ). Calculated mixture toxicities for 10 compounds found in untreated HSW resulted in moderate-high RQ predictions for all three aquatic species. Compared to untreated HSW, 30-min treatment with thermal plasma activation or UV-C/H2O2 resulted in lowered RQs. For the expected transformation products originating from fluoxetine, cyclophosphamide and acetaminophen increased RQs were predicted. Prolongation of thermal plasma oxidation up to 120 min predicted low-moderate toxicity in all target species. It is anticipated that further degradation of oxidative transformation products will end in less toxic aliphatic and carboxylic acid products. Predicted RQs after UV-C/H2O2 treatment turned out to be still moderate-high. In conclusion, in silico extrapolation of experimental findings can provide useful predicted estimates of mixture toxicity. However due to the complex composition of wastewater this in silico approach is a first step to screen for ecotoxicity. It is recommendable to confirm these predictions with ecotoxic bioassays.


Assuntos
Gases em Plasma , Poluentes Químicos da Água , Animais , Águas Residuárias/toxicidade , Esgotos , Peróxido de Hidrogênio/química , Água , Estresse Oxidativo , Preparações Farmacêuticas , Poluentes Químicos da Água/análise
16.
Environ Res ; 263(Pt 2): 120132, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39389202

RESUMO

Municipal wastewater treatment plants (WWTPs) are crucial for maintaining good quality of surface water, limiting environmental pollution. However, during wet-weather events, WWTPs become an important point-source discharge due to the activation of the bypass, which releases a mix of untreated wastewater and stormwater. This work aims to assess how the WWTP discharges (effluent and bypass) impact on the receiving surface water body during dry- and wet-weather, monitoring 78 pollutants (7 conventional pollutants, 19 heavy metals, and 52 micropollutants) in each stream (effluent during dry-weather, effluent and bypass during wet-weather), including the influent in dry-weather for comparison. The occurrence, concentration levels and variability, and environmental risk were addressed, with a specific focus on high-resolution (up to 20-min) sampling of the bypass, based on the expected relevant temporal dynamicity. A wider range of pollutants occurred in the bypass, included undetected compounds in the dry-weather influent. Besides, a greater inter-events variability in bypass concentrations was observed, but smaller intra-event variability, with only some pollutants exhibiting a distinct first-flush effect. To address the challenge of a cost-effective bypass monitoring, we explored the applicability of readily measurable water quality parameters (total suspended solids and electrical conductivity) as proxies for micropollutants. Correlations between these parameters and specific pollutant groups suggest a promising path for further investigation and broader application. The magnitude of the rain event also affected concentration levels, with event volume clearly affecting pollutants dilution. The environmental risk assessment revealed a significantly higher risk associated to bypass discharge compared to the effluent, especially for conventional pollutants, metals, and terbutryn, highlighting the urgency of improved bypass management strategies. Overall, this study highlights the contribution of wet-weather discharges from WWTPs, emphasizing the importance of high-frequency bypass monitoring to capture peak pollutant concentrations and accurately assess the environmental risk.

17.
Environ Res ; 262(Pt 1): 119811, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39159775

RESUMO

BACKGROUND: Health impact assessment studies quantifying the impact of the chemical exposome on children's health generally consider a small fraction of the exposome. Synthetizing available dose-response relationships is an essential step to fill this gap. We reviewed the literature for dose-response relationships relating the chemical exposome with children health. METHOD: We focused on 78 substance-outcome pairs for which the level of evidence had previously been classified as 'likely' or 'very likely'. We searched for dose-response relationships for these pairs from meta-analyses and, if none was available, from single epidemiological studies, from which we conducted meta-analyses whenever possible. RESULTS: We identified dose-response relationships for 50 of the 78 prioritized substance-outcome pairs (64%). Dose-response relationships stemmed from meta-analyses for 21 pairs, from de novo meta-analyses for 1 pair and single studies for 28 pairs. Dose-response relationships were available for tobacco (fetal and infant death, congenital heart defects, birth outcomes, orofacial clefts, respiratory health), lead (asthma, cognition, delayed puberty onset and iron deficiency anaemia), polychlorobiphenyls (PCBs) (cognition, respiratory infections and birth outcomes), bisphenol A (cognition), hexachlorobenzene (HCB) (respiratory health), Polybrominated diphenyl ethers (neurodevelopment), DDT (hypospadias, cryptorchidism, miscarriage), pesticides (neurodevelopment), methylmercury (cognition), PFAS (immune system, birth weight, behavior, miscarriage), arsenic (cognition, birth weight, death, respiratory health), cadmium (cognition, birth weight), manganese (behavior), sodium (blood pressure) and thallium (birth weight). For 28 of the 78 substance-outcome pairs (36%), no dose-response relationship was available from epidemiological studies in children. CONCLUSIONS: We identified dose-response relationships for 50 substance-outcome pairs, corresponding to 20 chemicals and 17 health outcomes. These can be used to perform more comprehensive quantitative health impact assessment of the exposome on child health. We also identified 28 substance-outcome pairs corresponding to 'likely' or 'very likely' effects for which research generating dose-response functions in children would be relevant.

18.
Environ Res ; 262(Pt 1): 119880, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39214491

RESUMO

Increasingly rigorous data quality (DQ) evaluations and/or screening practices are being applied to environmental and ecotoxicological datasets. DQ is predominantly evaluated by scoring given data against preselected criteria. This study provides the first examination on the effectiveness of score-based DQ evaluation in providing statistically meaningful differentiation of measurements using fish bioconcentration factor (BCF) dataset as an illustration. This is achieved by inspecting how log BCF differs with the built-in overall-DQ and specific-DQ evaluations, and how it is influenced by interactive effects and hierarchy of DQ criteria. Approximately 80-90% of analyzable chemicals show no statistical difference in log BCF between low-quality (LQ) and high-quality (HQ) measurements in overall evaluation (n = 183) or in individual evaluation of 6 DQ criteria (n = 53 to 101). Further examination shows that log BCF may/may not change with different combinations or total number of criteria violations. Tree analysis and nodal structures of deviation in log BCF also reveal the absence of common structural dependence on the criteria violated. Finally, simple averaging of all measurements without DQ differentiation yields comparable log BCFs as those derived using strictly HQ data with ≤0.5 log unit difference in over 93% of the chemicals (n = 158) and no dependence on number of measurements, fraction of LQ measurements, or bioaccumulation potential of the chemicals. For accurate log BCF, DQ appears no more important than having more independent measurements irrespective of their individual DQ statuses. This work concludes by calling for: (i) re-documentation of experimental details in legacy environmental and ecotoxicological datasets, (ii) examination of other DQ-categorized datasets using the tests and tools applied here, and (ii) a thorough and systematic reflection on how DQ should be assessed for modeling, benchmarking, and other data-based analyses or applications.

19.
Environ Res ; 252(Pt 3): 119045, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704014

RESUMO

Endocrine disrupting compounds (EDCs) pose a significant ecological risk, particularly in aquatic ecosystems. EDCs have become a focal point in ecotoxicology, and their identification and regulation have become a priority. Zooplankton have gained global recognition as bioindicators, benefiting from rigorous standardization and regulatory validation processes. This review aims to provide a comprehensive summary of zooplankton-based adverse outcome pathways (AOPs) with a focus on EDCs as toxicants and the utilisation of freshwater zooplankton as bioindicators in ecotoxicological assessments. This review presents case studies in which zooplankton have been used in the development of AOPs, emphasizing the identification of molecular initiating events (MIEs) and key events (KEs) specific to zooplankton exposed to EDCs. Zooplankton-based AOPs may become an important resource for understanding the intricate processes by which EDCs impair the endocrine system. Furthermore, the data sources, experimental approaches, advantages, and challenges associated with zooplankton-based AOPs are discussed. Zooplankton-based AOPs framework can provide vital tools for consolidating toxicological knowledge into a structured toxicity pathway of EDCs, offering a transformative platform for facilitating enhanced risk assessment and chemical regulation.


Assuntos
Rotas de Resultados Adversos , Disruptores Endócrinos , Poluentes Químicos da Água , Zooplâncton , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/análise , Zooplâncton/efeitos dos fármacos , Animais , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos
20.
Environ Res ; 244: 117934, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109957

RESUMO

Florfenicol, as a replacement for chloramphenicol, can tightly bind to the A site of the 23S rRNA in the 50S subunit of the 70S ribosome, thereby inhibiting protein synthesis and bacterial proliferation. Due to the widespread use in aquaculture and veterinary medicine, florfenicol has been detected in the aquatic environment worldwide. Concerns over the effects and health risks of florfenicol on target and non-target organisms have been raised in recent years. Although the ecotoxicity of florfenicol has been widely reported in different species, no attempt has been made to review the current research progress of florfenicol toxicity, hormesis, and its health risks posed to biota. In this study, a comprehensive literature review was conducted to summarize the effects of florfenicol on various organisms including bacteria, algae, invertebrates, fishes, birds, and mammals. The generation of antibiotic resistant bacteria and spread antibiotic resistant genes, closely associated with hormesis, are pressing environmental health issues stemming from overuse or misuse of antibiotics including florfenicol. Exposure to florfenicol at µg/L-mg/L induced hormetic effects in several algal species, and chromoplasts might serve as a target for florfenicol-induced effects; however, the underlying molecular mechanisms are completely lacking. Exposure to high levels (mg/L) of florfenicol modified the xenobiotic metabolism, antioxidant systems, and energy metabolism, resulting in hepatotoxicity, renal toxicity, immunotoxicity, developmental toxicity, reproductive toxicity, obesogenic effects, and hormesis in different animal species. Mitochondria and the associated energy metabolism are suggested to be the primary targets for florfenicol toxicity in animals, albeit further in-depth investigations are warranted for revealing the long-term effects (e.g., whole-life-cycle impacts, multigenerational effects) of florfenicol, especially at environmental levels, and the underlying mechanisms. This will facilitate the evaluation of potential hormetic effects and construction of adverse outcome pathways for environmental risk assessment and regulation of florfenicol.


Assuntos
Antibacterianos , Tianfenicol , Tianfenicol/análogos & derivados , Animais , Antibacterianos/toxicidade , Tianfenicol/toxicidade , Cloranfenicol/farmacologia , Bactérias , Mamíferos
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