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Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.
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Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10â¯% v/v low impact groundwater, and (iii) 0.01â¯%, 0.1â¯%, 1â¯%, and 10â¯% high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.
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Circulación Cerebrovascular , Agua Subterránea , Hipocampo , Trastornos de la Memoria , Ratas Sprague-Dawley , Contaminantes Químicos del Agua , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Agua Subterránea/química , Masculino , Femenino , Contaminantes Químicos del Agua/toxicidad , Ratas , Trastornos de la Memoria/inducido químicamente , Circulación Cerebrovascular/efectos de los fármacos , Serotonina/metabolismo , Síndromes de Neurotoxicidad/fisiopatología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/patología , Reconocimiento en Psicología/efectos de los fármacosRESUMEN
The nursing profession has witnessed its share of challenging and trying times including toxic or unhealthy work environments, unsustainable workloads, an aging workforce, inadequate staffing, nurse burnout, staff retention, inadequately trained staff, an increase in workplace violence, and several pandemics. Both individually and collectively, these thorny issues have placed a heavy burden on nurses. Unfortunately, many capable and competent nurses have left the profession altogether, which further compounds an already problematic situation. This article highlights several important strategies for recruiting, retaining, and supporting a high functioning nursing workforce in challenging and trying times.
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Agotamiento Profesional , Reorganización del Personal , Humanos , Lugar de Trabajo/psicología , Personal de Enfermería en Hospital/psicología , Carga de Trabajo , Satisfacción en el Trabajo , Admisión y Programación de PersonalRESUMEN
BACKGROUND: As disease-modifying Alzheimer's (AD) treatments are becoming available, concerns have been raised that even high-income countries lack the diagnostic capacity to accurately identify eligible patients in a timely manner. OBJECTIVES: We analyze how much NHS England would have to invest in capacity for AD specialists, biomarker testing with PET scans or CSF testing and MRI scans to reach G7 average levels and estimate the effect on wait times in the diagnostic process. DESIGN: Desk research and expert interviews for cost and capacity data. Markov model to estimate wait times. SETTING: NHS England. MEASUREMENTS: AD specialists, and PET and MRI scanners per capita in G7 countries and wait times in England under different investment scenarios. RESULTS: England has the lowest number of PET and MRI scanners and the second-lowest of AD specialists per capita among the G7 countries. An investment of GBP 14 billion over ten years would be needed to reach G7 average levels, of which 31%, 22%, 10%, 37% would be devoted to capacity for memory assessment services, PET scanning, CSF analysis, and MRI scanning, respectively. This investment would reduce estimated average wait times by around 87% between 2023 and 2032. CONCLUSIONS: The NHS England has large gaps in diagnostic capacity for AD. Without substantial investments, AD patients in England would experience substantial wait times and avoidable disease progression.
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Enfermedad de Alzheimer , Tomografía de Emisión de Positrones , Humanos , Enfermedad de Alzheimer/diagnóstico , Inglaterra , Imagen por Resonancia Magnética , Medicina Estatal , Inversiones en Salud , Listas de Espera , Cadenas de MarkovRESUMEN
The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.
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Ozono Estratosférico , Rayos Ultravioleta , Humanos , Ozono Estratosférico/análisis , Rayos Ultravioleta/efectos adversos , Ozono/química , Cambio ClimáticoRESUMEN
INTRODUCTION: As treatments for secondary prevention of Alzheimer's disease (AD) are being studied, concerns about their value for money have appeared. We estimate cost-effectiveness of a hypothetical screening and prevention program. METHODS: We use a Markov model to project cost-effectiveness of a treatment that reduces progression to symptomatic AD by 50% with either chronic treatment until progression to mild cognitive impairment or treatment for one year followed by monitoring with AD blood tests and retreatment with one dose in case of amyloid re-accumulation. Diagnoses would be made with an AD blood test with sensitivity and specificity of 80%, and inconclusive results in 20%. Individuals testing negative would be re-tested in five years and those with inconclusive results in one. RESULTS: The program would generate per-person value of $53,721 from a payer (reduction of direct cost and patient QALY gains) and $69,861 from a societal perspective (adding valuation of reduced caregiver burden). With chronic treatment, it would be cost-effective up to annual drug prices of $7,000 and $10,300, respectively. Time-limited treatment would be cost-effective at annual drug prices of $54,257 and $78,458 from a payer and societal perspective, respectively. Higher specificity of the blood test would decrease cost per person with similar value generation DISCUSSION: A hypothetical prevention treatment for AD could be economically viable from a payer and societal perspective.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Disfunción Cognitiva/prevención & controlRESUMEN
Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. Here, we characterized the function and evolution of the Diptericin antimicrobial peptide family of Diptera. Using mutations affecting the two Diptericins (Dpt) of Drosophila melanogaster, we reveal the specific role of DptA for the pathogen Providencia rettgeri and DptB for the gut mutualist Acetobacter. The presence of DptA- or DptB-like genes across Diptera correlates with the presence of Providencia and Acetobacter in their environment. Moreover, DptA- and DptB-like sequences predict host resistance against infection by these bacteria across the genus Drosophila. Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family and reveals how the host immune repertoire adapts to changing microbial environments.
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Acetobacter , Péptidos Antimicrobianos , Proteínas de Drosophila , Drosophila melanogaster , Interacciones Huésped-Patógeno , Microbiota , Providencia , Animales , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/metabolismo , Drosophila melanogaster/inmunología , Drosophila melanogaster/microbiología , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Evolución Molecular , Interacciones Huésped-Patógeno/inmunologíaRESUMEN
Photographic identification catalogs of individual killer whales (Orcinus orca) over time provide a tool for remote health assessment. We retrospectively examined digital photographs of Southern Resident killer whales in the Salish Sea to characterize skin changes and to determine if they could be an indicator of individual, pod, or population health. Using photographs collected from 2004 through 2016 from 18,697 individual whale sightings, we identified six lesions (cephalopod, erosions, gray patches, gray targets, orange on gray, and pinpoint black discoloration). Of 141 whales that were alive at some point during the study, 99% had photographic evidence of skin lesions. Using a multivariate model including age, sex, pod, and matriline across time, the point prevalence of the two most prevalent lesions, gray patches and gray targets, varied between pods and between years and showed small differences between stage classes. Despite minor differences, we document a strong increase in point prevalence of both lesion types in all three pods from 2004 through 2016. The health significance of this is not clear, but the possible relationship between these lesions and decreasing body condition and immunocompetence in an endangered, non-recovering population is a concern. Understanding the etiology and pathogenesis of these lesions is important to better understand the health significance of these skin changes that are increasing in prevalence.
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Orca , Animales , Estudios RetrospectivosRESUMEN
In cooperative species, human-induced rapid environmental change may threaten cost-benefit tradeoffs of group behavioral strategies that evolved in past environments. Capacity for behavioral flexibility can increase population viability in novel environments. Whether the partitioning of individual responsibilities within social groups is fixed or flexible across populations is poorly understood, despite its relevance for predicting responses to global change at the population and species levels and designing successful conservation programs. We leveraged bio-logging data from two populations of fish-eating killer whales (Orcinus orca) to quantify patterns of fine-scale foraging movements and their relationships with demography. We reveal striking interpopulation differences in patterns of individual foraging behavior. Females from the endangered Southern Resident (SRKW) population captured less prey and spent less time pursuing prey than SRKW males or Northern Resident (NRKW) females, whereas NRKW females captured more prey than NRKW males. The presence of a calf (≤3 years) reduced the number of prey captured by adult females from both populations, but disproportionately so for SRKW. SRKW adult males with a living mother captured more prey than those whose mother had died, whereas the opposite was true for NRKW adult males. Across populations, males foraged in deeper areas than females, and SRKW captured prey deeper than NRKW. These population-level differences in patterns of individual foraging behavior challenge the existing paradigm that females are the disproportionate foragers in gregarious resident killer whales, and demonstrate considerable variation in the foraging strategies across populations of an apex marine predator experiencing different environmental stressors.
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Understanding the factors that cause endangered populations to either grow or decline is crucial for preserving biodiversity. Conservation efforts often address extrinsic threats, such as environmental degradation and overexploitation, that can limit the recovery of endangered populations. Genetic factors such as inbreeding depression can also affect population dynamics but these effects are rarely measured in the wild and thus often neglected in conservation efforts. Here we show that inbreeding depression strongly influences the population dynamics of an endangered killer whale population, despite genomic signatures of purging of deleterious alleles via natural selection. We find that the 'Southern Residents', which are currently endangered despite nearly 50 years of conservation efforts, exhibit strong inbreeding depression for survival. Our population models suggest that this inbreeding depression limits population growth and predict further decline if the population remains genetically isolated and typical environmental conditions continue. The Southern Residents also had more inferred homozygous deleterious alleles than three other, growing, populations, further suggesting that inbreeding depression affects population fitness. These results demonstrate that inbreeding depression can substantially limit the recovery of endangered populations. Conservation actions focused only on extrinsic threats may therefore fail to account for key intrinsic genetic factors that also limit population growth.
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Depresión Endogámica , Orca , Animales , Endogamia , Orca/genética , Dinámica Poblacional , Selección GenéticaRESUMEN
Epigenetic approaches for estimating the age of living organisms are revolutionizing studies of long-lived species. Molecular biomarkers that allow age estimates from small tissue biopsies promise to enhance studies of long-lived whales, addressing a fundamental and challenging parameter in wildlife management. DNA methylation (DNAm) can affect gene expression, and strong correlations between DNAm patterns and age have been documented in humans and nonhuman vertebrates and used to construct "epigenetic clocks". We present several epigenetic clocks for skin samples from two of the longest-lived cetaceans, killer whales and bowhead whales. Applying the mammalian methylation array to genomic DNA from skin samples we validate four different clocks with median errors of 2.3-3.7 years. These epigenetic clocks demonstrate the validity of using cytosine methylation data to estimate the age of long-lived cetaceans and have broad applications supporting the conservation and management of long-lived cetaceans using genomic DNA from remote tissue biopsies.
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Envejecimiento , Metilación de ADN , Humanos , Animales , Envejecimiento/genética , Mamíferos , Biomarcadores , ADN , Epigénesis GenéticaRESUMEN
We attempted to characterize zooplankton community response following spills of the unconventional crude oil, diluted bitumen (dilbit), into 10-m diameter, ~ 100 m3, ~ 1.5-m deep boreal lake limnocorrals, including two controls and seven dilbit treatments ranging from 1.5 to 180 L (1:100,000 to 1:1,000 v/v, dilbit:water). Community composition and abundances were monitored weekly to bi-weekly over three months. Total zooplankton biomass and abundance seemingly collapsed in all limnocorrals, regardless of treatment, though some rotifer species persisted. As a result, it was not possible to determine the impacts of dilbit. We theorize several potential non-oil-related reasons for the sudden community collapse - including elevated zinc levels, fish grazing pressures, and sampling biases - and provide guidance for future work using in-lake enclosures.
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Petróleo , Contaminantes Químicos del Agua , Animales , Lagos , Zooplancton , Contaminantes Químicos del Agua/análisis , HidrocarburosRESUMEN
Complex mixtures of unknown contaminants present a challenge to identify toxicological risks without using large numbers of animals and labor-intensive screens of all organs. This study examined soil extracts from a legacy-contaminated pesticide packaging and blending site. HepG2 cytotoxicity was used as an initial screen of 18 soil samples; then, three extracts (A, B and C) from different locations at the study site were used for testing in animals. The first two extracts were identified as the most toxic in vitro, and the latter extract obtained from a location further from these two toxic sampling sites. Then, target organ toxicities were identified following biweekly oral gavage for one month of three soil extracts (0.1% in polyethylene glycol or PEG) compared to vehicle control in male Sprague-Dawley rats (n = 9-10/group). Exposure to extract A significantly increased neutrophils and lymphocytes compared to control. In contrast, all extracts increased plasma α-2 macroglobulin and caused mild-to-moderate lymphocytic proliferation within the spleen white pulp, all indicative of inflammation. Rats exposed to all soil extracts exhibited acute tubular necrosis. Cholinesterase activity was significantly reduced in plasma, but not brain, after exposure to extract A compared to control. Increased hepatic ethoxyresorufin-o-deethylase activity compared to control was observed following exposure to extracts A and B. Exposure to soil extract C in rats showed a prolonged QTc interval in electrocardiography as well as increased brain lipid peroxidation. Candidate contaminants are organochlorine, organophosphate/carbamate pesticides or metabolites. Overall, HepG2 cytotoxicity did not successfully predict the neurotoxicity and cardiotoxicity observed with extract C but was more successful with suspected hydrocarbon toxicities in extracts A and B. Caution should be taken when extrapolating the observation of no effects from in vitro cell culture to in vivo toxicity, and better cell culture lines or assays should be explored.
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Hígado , Suelo , Ratas , Masculino , Animales , Ratas Sprague-DawleyRESUMEN
AIMS: A whole systems approach to tackling obesity has been recommended by Public Health England for several years. This qualitative study aimed to investigate whether systems thinking is reflected in local authority plans and strategies to tackle obesity, using the leverage points for intervention in a complex system, as a framework. METHOD: We sought to identify obesity strategies/plans for Southampton and 19 other local authority comparators (based on children's services and Office for National Statistics data). A healthy weight strategy was available for 10 local authorities and a qualitative document analysis was undertaken. The policy actions proposed in the plans were coded against the leverage points for intervention in a complex system and themes were developed to characterise interventions in each category. RESULTS: A majority of actions included in the plans were categorised as 'Numbers, Constants and Parameters' which reflect downstream measures. However, there were examples of actions that could act on higher leverage points. In addition, some local authority plans included interventions that could act on 10 of the 12 leverage points suggesting incorporation of systems thinking. CONCLUSIONS: Some local authority plans to tackle obesity do reflect systems thinking when viewed through the lens of the leverage points for intervention in a complex system. Interventions at higher leverage points should be prioritised by public health decision-makers, especially in a climate of competing agendas and limited resources.
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Obesidad , Salud Pública , Niño , Humanos , Obesidad/prevención & control , Inglaterra , Políticas , Análisis de SistemasRESUMEN
Antimicrobial peptides (AMPs) are key to defence against infection in plants and animals. Use of AMP mutations in Drosophila has now revealed that AMPs can additively or synergistically contribute to defence in vivo. However, these studies also revealed high specificity, wherein just one AMP contributes an outsized role in combatting a specific pathogen. Here, we show the Drosocin locus (CG10816) is more complex than previously described. In addition to its namesake peptide 'Drosocin', it encodes a second mature peptide from a precursor via furin cleavage. This peptide corresponds to the previously uncharacterized 'Immune-induced Molecule 7'. A polymorphism (Thr52Ala) in the Drosocin precursor protein previously masked the identification of this peptide, which we name 'Buletin'. Using mutations differently affecting Drosocin and Buletin, we show that only Drosocin contributes to Drosocin gene-mediated defence against Enterobacter cloacae. Strikingly, we observed that Buletin, but not Drosocin, contributes to the Drosocin gene-mediated defence against Providencia burhodogranariea, including an importance of the Thr52Ala polymorphism for survival. Our study reveals that the Drosocin gene encodes two prominent host defence peptides with different specificity against distinct pathogens. This finding emphasizes the complexity of the Drosophila humoral response and demonstrates how natural polymorphisms can affect host susceptibility.
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Péptidos Catiónicos Antimicrobianos , Drosophila , Animales , Secuencia de Aminoácidos , Péptidos Catiónicos Antimicrobianos/genética , Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Glicopéptidos , Inmunidad InnataRESUMEN
Opportunities to assess odontocete health are restricted due to their limited time at the surface, relatively quick movements and large geographic ranges. For endangered populations such as the southern resident killer whales (SKRWs) of the northeast Pacific Ocean, taking advantage of non-invasive samples such as expelled mucus and exhaled breath is appealing. Over the past 12 years, such samples were collected, providing a chance to analyse and assess their bacterial microbiomes using amplicon sequencing. Based on operational taxonomic units, microbiome communities from SRKW and transient killer whales showed little overlap between mucus, breath and seawater from SRKW habitats and six bacterial phyla were prominent in expelled mucus but not in seawater. Mollicutes and Fusobacteria were common and abundant in mucus, but not in breath or seawater, suggesting these bacterial classes may be normal constituents of the SRKW microbiome. Out of 134 bacterial families detected, 24 were unique to breath and mucus, including higher abundances of Burkholderiaceae, Moraxellaceae and Chitinophagaceae. Although there were multiple bacterial genera in breath or mucus that include pathogenic species (e.g. Campylobacter, Hemophilus, Treponema), the presence of these bacteria is not necessarily evidence of disease or infection. Future emphasis on genotyping mucus samples to the individual animal will allow further assessment in the context of that animal's history, including body condition index and prior contaminants burden. This study is the first to examine expelled mucus from cetaceans for microbiomes and demonstrates the value of analysing these types of non-invasive samples.
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The atmospheric microbiome is one of the least studied microbiomes of our planet. One of the most abundant, diverse and impactful parts of this microbiome is arguably fungal spores. They can be very potent outdoor aeroallergens and pathogens, causing an enormous socio-economic burden on health services and annual damages to crops costing billions of Euros. We find through hypothesis testing that an expected warmer and drier climate has a dramatic impact on the atmospheric microbiome, conceivably through alteration of the hydrological cycle impacting agricultural systems, with significant differences in leaf wetness between years (p-value <0.05). The data were measured via high-throughput sequencing analysis using the DNA barcode marker, ITS2. This was complemented by remote sensing analysis of land cover and dry matter productivity based on the Sentinel satellites, on-site detection of atmospheric and vegetation variables, GIS analysis, harvesting analysis and footprint modelling on trajectory clusters using the atmospheric transport model HYSPLIT. We find the seasonal spore composition varies between rural and urban zones reflecting both human activities (e.g. harvest), type and status of the vegetation and the prevailing climate rather than mesoscale atmospheric transport. We find that crop harvesting governs the composition of the atmospheric microbiome through a clear distinction between harvest and post-harvest beta-diversity by PERMANOVA on Bray-Curtis dissimilarity (p-value <0.05). Land cover impacted significantly by two-way ANOVA (p-value <0.05), while there was minimal impact from air mass transport over the 3 years. The hypothesis suggests that the fungal spore composition will change dramatically due to climate change, an until now unforeseen effect affecting both food security, human health and the atmospheric hydrological cycle. Consequently the management of crop diseases and impact on human health through aeroallergen exposure need to consider the timing of crop treatments and land management, including post harvest, to minimize exposure of aeroallergens and pathogens.
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Cambio Climático , Microbiota , Agricultura , Hongos , Humanos , Esporas FúngicasRESUMEN
Thiamethoxam is a neonicotinoid insecticide widely applied in the Canadian Prairies. It has been detected in surface waters of agro-ecosystems, including wetlands, but the potential effects on non-target invertebrate communities in these wetlands have not been well characterized. In an effort to understand better the fate of thiamethoxam in wetlands and the response of invertebrates (zooplankton and emergent insects), model systems were used to mimic wetland flooding into planted fields. Outdoor mesocosms were treated with a single application of thiamethoxam-treated canola seeds at three treatment levels based on a recommended seeding rate (i.e., 6 kg/ha; 1×, 10×, and 100× seeding rate) and monitored over ten weeks. The mean half-life of thiamethoxam in the water column was 6.2 d. There was no ecologically meaningful impact on zooplankton abundances or community structure among treatments. Statistically significant differences were observed in aquatic insect abundance between control mesocosms and the two greatest thiamethoxam treatments (10× and 100× seeding rate). The observed results indicate exposure to thiamethoxam at environmentally relevant concentrations likely does not represent a significant ecological risk to abundance and community structure of wetland zooplankton and emergent insects.
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Insecticidas , Tiametoxam , Contaminantes Químicos del Agua , Animales , Canadá , Ecosistema , Insecticidas/análisis , Insecticidas/toxicidad , Invertebrados , Neonicotinoides/toxicidad , Nitrocompuestos/toxicidad , Dinámica Poblacional , Tiametoxam/análisis , Tiametoxam/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
Diluted bitumens (dilbits) are produced by mixing highly viscous bitumen with lighter petroleum products to facilitate transport. The unique physical and chemical properties of dilbit may affect the environmental fate and effects of dilbit-derived chemical compounds when spilled. To further explore this, we monitored experimental spills of Cold Lake Winter Blend (CLWB) dilbit for 70 days in limnocorrals installed in a freshwater boreal lake. A regression design with 2 controls and 7 treatments was used to assess the fate and behaviour of polycyclic aromatic compounds (PACs) as they partitioned from the dilbit into the air, water column and sediments. Treatments ranged from 1.5 to 180 L of CLWB, resulting in oil:water ratios ranging between 1:71000 to 1:500 (v:v). We began to detect elevated concentrations of PACs as early as 6 h post-addition in the air, 12 h post-addition in the water column, and 15-28 d post-addition in the sediments. By the end of the experiment, concentrations of PACs had largely declined in the water column but remained elevated in the sediments. Our results demonstrate that under conditions typical of temperate boreal lakes, only a small proportion of PACs from dilbit enters the aquatic system, but even so, may produce concentrations of ecotoxicological concern, especially in the sediments, which is the ultimate sink for dilbit-derived PACs.
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Hidrocarburos Policíclicos Aromáticos , Compuestos Policíclicos , Contaminantes Químicos del Agua , Hidrocarburos , Lagos/química , Contaminantes Químicos del Agua/análisisRESUMEN
Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human Methylation EPIC array, we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women's Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p ≤ 6.45×10-8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195 g (95%CI: -241, -149 g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin-releasing hormone-binding protein (CRHBP). Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p = 1.37×10-255), maternal smoking (7.71%, p = 1.50 x 10-57) and maternal plasma folate levels during pregnancy (0.33%, p = 0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.