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2.
Sci Rep ; 12(1): 22072, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627291

RESUMEN

Firefighters suffer an increased risk of cancer from exposures to chemicals released from fires. Our earlier research has found that fire toxicants not only remain on firefighters' PPE, but are also tracked back to fire stations. The UK Firefighter Contamination Survey assesses firefighters' risk of developing cancer due to occupational exposure to fire toxins. Over 4% of surveyed firefighters were found to have a cancer diagnosis, with the age-specific cancer rate up to 323% higher (35-39 year olds) than that of the general population. Firefighters who had served ≥ 15 years were 1.7 times more likely to develop cancer than those who had served less time. Firefighters were at least twice as likely to be diagnosed with cancer if they noticed soot in their nose/throat (odds ratio (OR) = 2.0, 1.1-3.5), or remained in their PPE for more than four hours after attending a fire incident (OR = 2.3, 1.1-5.2). Also associated with an increased likelihood of cancer was: eating while wearing PPE (OR = 1.8, 1.2-2.7); failing to store clean/dirty PPE separately (OR = 1.3, 1.0-1.7); working in a station that smells of fire (OR = 1.3, 1.0-1.8) or not having designated (separated) clean and dirty areas (OR = 1.4, 1.1-1.7); using an on-site washing machine to launder fire hoods (OR = 1.3, 1.0-1.7); feeling that cleaning is not taken seriously at work (OR = 1.5, 1.2-2.0).


Asunto(s)
Bomberos , Neoplasias , Exposición Profesional , Humanos , Incidencia , Exposición Profesional/efectos adversos , Neoplasias/epidemiología , Neoplasias/etiología , Reino Unido/epidemiología
3.
Sci Rep ; 13(1): 97, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627294

RESUMEN

Firefighters are exposed to toxic chemicals not only from the fire incidents they attend, but also from their contaminated station and/or personal protective equipment (PPE). Little is currently known about firefighters' awareness, attitudes, and behaviours towards contaminants which was assessed in the UK firefighter contamination survey. Results revealed that lack of training on fire effluents and their health outcomes are strongly associated with increased fire smoke/contaminant exposure. Notably, untrained firefighters were at least twice as likely to: never clean personal protective equipment (PPE) (Crude Odds Ratio, OR 2.0, 1.5-2.7), infrequently send their PPE for professional cleaning (OR 2.0, 1.6-2.4), remain in the workwear (t-shirt etc.) worn while attending a fire incident (OR up to 3.6, 2.3-5.6), and indicate that cleaning at fire stations is not taken seriously (OR 2.4, 2.2-2.6). Firefighters personally viewing contamination as a "badge of honour" (BoH) were at least twice as likely to: remain in contaminated PPE after fire incidents (OR 2.3, 1.4-3.9), eat with sooty hands (OR 2.2, 1.9-2.5), notice soot in the nose/throat (OR 3.7, 2.7-5.2), and smell fire smoke on the body for more than a day after incidents (OR 2.0, 1.6-2.4). They were also more likely to indicate that cleaning at fire stations is not taken seriously (OR 2.5, 2.2-2.9) and that fire stations smell of smoke always/most of the time (OR 2.3, 2.0-2.6). Strong links were also found between belief in the BoH and never cleaning PPE (OR 1.9, 1.4-2.7), and eating while wearing contaminated PPE (OR 1.8, 1.5-2.2).


Asunto(s)
Bomberos , Exposición Profesional , Salud Laboral , Humanos , Humo/efectos adversos , Reino Unido
4.
Sci Rep ; 13(1): 65, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627304

RESUMEN

Firefighters' personal protective equipment (PPE) is a potential source of chronic exposure to toxic contaminants commonly released from fires. These contaminants have also been found in fire stations. However, little research characterises the routes via which fire contaminants travel back to fire stations. The UK Firefighter Contamination Survey provides information on firefighters' PPE provision, decontamination, and storage practices. All serving UK firefighters were eligible to take part in the survey, which comprised 64 questions. A total of 10,649 responses were included for analysis, accounting for roughly 24% of the UK's firefighting workforce. Results revealed that most firefighters (84%) de-robe contaminated PPE/workwear after re-entering the appliance cab. There was a significant decreasing tendency to send PPE for cleaning after every incident with increasing seniority of role, length of service, and fire attendance frequency. Around one third of firefighters cleaned PPE after every incident. A number of issues were linked to external professional cleaning services, e.g. shrinkage, fit, turn-around time, and stock of reserve/pooled PPE. PPE storage was found to be a potential source of cross contamination, with almost half of firefighters (45%) indicating clean and dirty PPE is not stored separately. More than half of firefighters (57%) stored fire gloves (an item sent for professional decontamination by only 19% of firefighters, and never cleaned by 20%) within other items of PPE such as helmets, boots and tunic/trouser pockets. The survey's results can be used to target gaps in decontamination measures within UK Fire and Rescue Services.


Asunto(s)
Bomberos , Exposición Profesional , Humanos , Exposición Profesional/prevención & control , Exposición Profesional/análisis , Equipo de Protección Personal , Lugar de Trabajo , Reino Unido
5.
Sci Rep ; 13(1): 62, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627314

RESUMEN

Exposure to trauma, high-stress situations, and disrupted sleep are well known risk factors affecting firefighters' mental health. Little is known about the association between firefighters' exposure to fire contaminants and mental health disorders. The UK Firefighter Contamination Survey assessed firefighters' health and capacity for occupational exposure to contaminants. Participants were invited to anonymously complete its 64 questions online. Logistic regression analyses assessed the associations between self-reported mental health disorders and proxies of contaminant exposure. Results found that firefighters who notice soot in their nose/throat for more than a day after attending fires (Odds Ratio (OR) = 1.8, 1.4-2.4), and those who remain in their personal protective equipment (PPE) for over 4 h after fires (OR = 1.9, 1.2-3.1), were nearly twice as likely to report mental health disorders. Significantly increased odds ratios for all three outcomes of interest (anxiety, depression and/or any mental health disorders) were also found among firefighters who take PPE home to clean. Sleeping problems were reported by 61% of firefighters. These firefighters were 4.2 times more likely to report any mental health disorder (OR = 4.2, 3.7-4.9), 2.9 times more likely to report anxiety (OR = 2.9, 2.4-3.5) and 2.3 times more likely to report depression (OR = 2.3, 1.9-2.8) when compared to firefighters who did not report sleep issues. Effective decontamination measures within UK Fire and Rescue Services, together with firefighters' wellness, may play a crucial role in protecting firefighters' mental health.


Asunto(s)
Bomberos , Incendios , Exposición Profesional , Humanos , Salud Mental , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Equipo de Protección Personal , Reino Unido/epidemiología
6.
Folia Morphol (Warsz) ; 82(1): 198-204, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34845717

RESUMEN

Most variations of the abdominal blood supply are related to branching of the coeliac trunk and superior mesenteric artery. This case details a remarkable variation in the branching pattern of the left colic artery (LCA) observed during routine cadaveric dissection of an 84-year-old male donor. An anomalous common trunk, originating from the common hepatic artery, gave rise to three branches: 1) an accessory posterior pancreaticoduodenal artery to the head of the pancreas and adjacent duodenum, 2) the dorsal pancreatic artery anastomosing with branches of the splenic artery, and 3) the LCA. The LCA descended between the splenic vein and superior mesenteric artery to supply the left colic flexure and form a collateral route with the middle colic artery by contributing to the marginal artery of Drummond. Knowledge of this variation is clinically relevant for surgical and radiological procedures in the abdomen.


Asunto(s)
Arteria Mesentérica Inferior , Páncreas , Masculino , Humanos , Anciano de 80 o más Años , Arteria Celíaca , Arteria Hepática/anomalías , Arteria Mesentérica Superior/anomalías
7.
Arch Environ Contam Toxicol ; 82(4): 520-538, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35441861

RESUMEN

The effects of multigenerational Cu exposure on the freshwater gastropod Isidorella newcombi were investigated. Snails were exposed to a range of treatment-specific Cu concentrations in the parental to F2 generations, and a common Cu concentration in the F3 generation. In the parental to F2 generations, some general responses to 3 days Cu exposures included reduced survival and feeding in snails exposed to higher Cu concentrations. This suggested that the snails exposed to the high Cu concentration were experiencing Cu-induced stress that may apply selection pressure. In the F3 generation, when all treatments were exposed to a common Cu concentration, increased survival was correlated with the pre-exposure Cu concentration history. Snails that had been pre-exposed to Cu also displayed reduced stress at a sub-lethal level, indicated by lower lysosomal destabilisation (LD). Mortality and LD responses in the F3 generation were not related to Cu tissue concentrations, indicating increased tolerance and reduced stress were not related to changes in Cu bioaccumulation. Total antioxidant capacity increased in the higher Cu concentration pre-exposure treatments which could be associated with lower Cu-induced stress, however, this is not supported by the oxidative damage marker lipid peroxidation, which also increased. While Cu tissue concentrations and oxidative stress markers were assessed to determine underlying reasons for increased tolerance in snails from a population with a multi-generational exposure history to Cu, the results were not conclusive. Despite this, it was demonstrated through increased survival and reduced LD that Cu tolerance can develop over a short evolutionary time scale.


Asunto(s)
Cobre , Contaminantes Químicos del Agua , Animales , Biomarcadores , Cobre/análisis , Cobre/toxicidad , Agua Dulce , Estrés Oxidativo , Caracoles , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
8.
Respir Med Case Rep ; 34: 101533, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34745870

RESUMEN

We present two cases of acute hypercapnic respiratory failure due to diaphragmatic dysfunction secondary to bilateral phrenic nerve paralysis, in patients who were receiving immunotherapy for melanoma. Bilateral diaphragmatic paralysis is an uncommon cause of acute or sub-acute hypercapnic respiratory failure which causes severe breathlessness, orthopnoea and potentially death. Immune checkpoint inhibitors are now standard of care in several solid organ malignancies. However, their use is associated with a risk of developing autoimmune toxicities, which includes mononeuritis. Our two cases demonstrate the potential difficulties in recognising acute hypercapnic respiratory failure and diagnosis of the rare disorder of bilateral diaphragmatic dysfunction, with consequent delays in appropriate management. The occurrence of this rare condition in association with checkpoint inhibitor immunotherapy suggests a possible autoimmune mechanism. Awareness that this rare cause of respiratory failure may occur in patients receiving checkpoint inhibitor therapy might facilitate earlier diagnosis and treatment.

9.
Transl Psychiatry ; 11(1): 376, 2021 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-34226517

RESUMEN

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD's association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised ß: -0.201; 95% CI: [-0.36, -0.04]; pFDR = 0.022) and processing speed (-0.222; [-0.40, -0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD's association with greater decline in general cognitive ability remained significant, prior to FDR correction (-0.222; [-0.39, -0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Anciano , Anciano de 80 o más Años , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Niño , Cognición , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria
10.
Mol Psychiatry ; 26(6): 2651-2662, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33398085

RESUMEN

Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the eighth decade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1376 MRI scans. Volumetric changes among cortical regions of interest (ROIs) were more strongly correlated (average r = 0.805, SD = 0.252) than were cross-sectional volumes of the same ROIs (average r = 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r = 0.431, p < 0.001) and in the domains of visuospatial ability (r = 0.415, p = 0.002), processing speed (r = 0.383, p < 0.001) and memory (r = 0.372, p < 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.


Asunto(s)
Disfunción Cognitiva , Anciano , Envejecimiento , Encéfalo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Estudios Transversales , Humanos
11.
Arch Environ Contam Toxicol ; 79(4): 391-405, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33090264

RESUMEN

The native freshwater gastropod Isidorella newcombi attacks the roots of developing rice plants in southern Australia and is controlled using copper sulphate. The apparent tolerance of this species to moderate levels of copper (Cu) exposure led us to investigate its potential usefulness as a biomonitor species. To assess its response to chronic Cu exposure, adult I. newcombi were exposed to 0-120 µg L-1 of Cu for 28 days. Lethal and sublethal responses were investigated. The relationships between subcellular biomarkers and life history traits also were explored. At exposure concentrations of 60 µg L-1 Cu and above, 100% mortality was observed during the 28-day exposure period. In these treatments, there was an exposure concentration dependent decrease in the time that the snails survived. In the surviving snails, there was an exposure concentration-dependent increase in tissue Cu concentration. In the snails exposed to Cu concentrations above 15 µg L-1, no eggs were produced during the final week of copper exposure, indicating that populations would not persist at Cu concentrations above 15 µg L-1. The general stress biomarker lysosomal membrane destabilisation (LD) indicated organisms exposed to 10 µg L-1 Cu and above were experiencing Cu induced stress. This suggests that LD could act as an early warning system for responses at higher levels of biological organisation in I. newcombi exposed to copper.


Asunto(s)
Cobre/toxicidad , Caracoles/fisiología , Contaminantes Químicos del Agua/toxicidad , Animales , Biomarcadores , Cobre/análisis , Sulfato de Cobre , Agua Dulce , Reproducción , Pruebas de Toxicidad Crónica , Contaminantes Químicos del Agua/análisis
12.
Genes (Basel) ; 11(6)2020 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-32517221

RESUMEN

Pneumonia is the sixth largest cause of death in the UK. It is usually caused by Streptococcus pneumoniae, which healthy individuals can carry in their nose without symptoms of disease. Antimicrobial resistance further increases mortality and morbidity associated with pneumococcal infection, although few studies have analysed resistance in naturally circulating pneumococcal isolates in adult populations. Here, we report on the resistome and associated mobile genetic elements within circulating pneumococcus isolated from adult volunteers enrolled in the experimental human pneumococcal colonisation (EHPC) research program at the Liverpool School of Tropical Medicine, UK. Pneumococcal isolates collected from 30 healthy asymptomatic adults who had volunteered to take part in clinical research were screened for antibiotic susceptibility to erythromycin and tetracycline, and whole-genome sequenced. The genetic context of resistance to one or both antibiotics in four isolates was characterised bioinformatically, and any association of the resistance genes with mobile genetic elements was determined. Tetracycline and macrolide resistance genes [tet(M), erm(B), mef(A), msr(D)] were detected on known Tn916-like integrative and conjugative elements, namely Tn6002 and Tn2010, and tet(32) was found for the first time in S. pneumoniae located on a novel 50 kb genomic island. The widespread use of pneumococcal conjugate vaccines impacts on serotype prevalence and transmission within the community. It is therefore important to continue to monitor antimicrobial resistance (AMR) genes present in both vaccine types and non-vaccine types in response to contemporary antimicrobial therapies and characterise the genetic context of acquired resistance genes to continually optimise antibiotic therapies.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Islas Genómicas/genética , Infecciones Neumocócicas/tratamiento farmacológico , Streptococcus pneumoniae/genética , Eritromicina/uso terapéutico , Islas Genómicas/efectos de los fármacos , Humanos , Macrólidos/farmacología , Infecciones Neumocócicas/genética , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/uso terapéutico , Serogrupo , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/patogenicidad , Tetraciclina/uso terapéutico , Reino Unido/epidemiología
13.
Toxicol Sci ; 175(1): 35-49, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32096866

RESUMEN

Systematic evidence mapping offers a robust and transparent methodology for facilitating evidence-based approaches to decision-making in chemicals policy and wider environmental health (EH). Interest in the methodology is growing; however, its application in EH is still novel. To facilitate the production of effective systematic evidence maps for EH use cases, we survey the successful application of evidence mapping in other fields where the methodology is more established. Focusing on issues of "data storage technology," "data integrity," "data accessibility," and "transparency," we characterize current evidence mapping practice and critically review its potential value for EH contexts. We note that rigid, flat data tables and schema-first approaches dominate current mapping methods and highlight how this practice is ill-suited to the highly connected, heterogeneous, and complex nature of EH data. We propose this challenge is overcome by storing and structuring data as "knowledge graphs." Knowledge graphs offer a flexible, schemaless, and scalable model for systematically mapping the EH literature. Associated technologies, such as ontologies, are well-suited to the long-term goals of systematic mapping methodology in promoting resource-efficient access to the wider EH evidence base. Several graph storage implementations are readily available, with a variety of proven use cases in other fields. Thus, developing and adapting systematic evidence mapping for EH should utilize these graph-based resources to ensure the production of scalable, interoperable, and robust maps to aid decision-making processes in chemicals policy and wider EH.


Asunto(s)
Manejo de Datos , Técnicas de Apoyo para la Decisión , Salud Ambiental , Gestión del Conocimiento , Toxicología , Exactitud de los Datos , Bases de Datos Factuales , Toma de Decisiones , Práctica Clínica Basada en la Evidencia , Humanos , Almacenamiento y Recuperación de la Información
14.
Environ Int ; 130: 104851, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31284092

RESUMEN

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) confer waterproof, greaseproof, and non-stick properties when added to consumer products. They are also used for industrial purposes including in aqueous film forming foams for firefighting. PFAS are ubiquitous in the environment, are widely detected in human biomonitoring studies, and are of growing regulatory concern across federal, state, and local governments. Regulators, scientists, and citizens need to stay informed on the growing health and toxicology literature related to PFAS. OBJECTIVES: The goal of this systematic evidence map is to identify and organize the available health and toxicology related literature on a set of 29 PFAS of emerging and growing concern. SEARCH AND STUDY ELIGIBILITY: We will search the electronic database PubMed for health or toxicological studies on 29 PFAS of emerging concern. Eligible studies must contain primary research investigating the link between one or more of the PFAS of interest and a health effect, toxicological, or biological mechanistic endpoint. STUDY APPRAISAL AND SYNTHESIS METHODS: Title and abstract screening and full text review will require a single reviewer for inclusion to the next level and two independent reviewers for exclusion. Study quality will not be conducted for this evidence mapping. Study characteristics will be extracted and coded from the included studies and checked for accuracy by a second reviewer. The extracted and coded information will be visualized in a publicly available, interactive database hosted on Tableau Public. Results of the evidence mapping will be published in a narrative summary.


Asunto(s)
Fluorocarburos/toxicidad , Animales , Bases de Datos Factuales , Estado de Salud , Humanos
15.
Environ Int ; 130: 104871, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31254867

RESUMEN

BACKGROUND: While systematic review (SR) methods are gaining traction as a method for providing a reliable summary of existing evidence for health risks posed by exposure to chemical substances, it is becoming clear that their value is restricted to a specific range of risk management scenarios - in particular, those which can be addressed with tightly focused questions and can accommodate the time and resource requirements of a systematic evidence synthesis. METHODS: The concept of a systematic evidence map (SEM) is defined and contrasted to the function and limitations of systematic review (SR) in the context of risk management decision-making. The potential for SEMs to facilitate evidence-based decision-making are explored using a hypothetical example in risk management priority-setting. The potential role of SEMs in reference to broader risk management workflows is characterised. RESULTS: SEMs are databases of systematically gathered research which characterise broad features of the evidence base. Although not intended to substitute for the evidence synthesis element of systematic reviews, SEMs provide a comprehensive, queryable summary of a large body of policy relevant research. They provide an evidence-based approach to characterising the extent of available evidence and support forward looking predictions or trendspotting in the chemical risk sciences. In particular, SEMs facilitate the identification of related bodies of decision critical chemical risk information which could be further analysed using SR methods, and highlight gaps in the evidence which could be addressed with additional primary studies to reduce uncertainties in decision-making. CONCLUSIONS: SEMs have strong and growing potential as a high value tool in resource efficient use of existing research in chemical risk management. They can be used as a critical precursor to efficient deployment of high quality SR methods for characterising chemical health risks. Furthermore, SEMs have potential, at a large scale, to support the sort of evidence summarisation and surveillance methods which would greatly increase the resource efficiency, transparency and effectiveness of regulatory initiatives such as EU REACH and US TSCA.


Asunto(s)
Toma de Decisiones , Medición de Riesgo , Sustancias Peligrosas , Humanos , Política Pública , Proyectos de Investigación
16.
Osteoarthritis Cartilage ; 27(8): 1244-1251, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31022456

RESUMEN

OBJECTIVE: Alkaptonuria (AKU) is a rare, inherited disorder of tyrosine metabolism, where patients are unable to breakdown homogentisic acid (HGA), which increases systemically over time. It presents with a clinical triad of features; HGA in urine, ochronosis of collagenous tissues, and the subsequent ochronotic arthritis of these tissues. In recent years the advance in the understanding of the disease and the potential treatment of the disorder looks promising with the data on the efficacy of nitisinone. However, there are limited methods for the detection and monitoring of ochronosis in vivo, or for treatment monitoring. The study aim was to test the hypothesis that Raman spectra would identify a distinct chemical fingerprint for the non-ochronotic, compared to ochronotic cartilage. DESIGN: Ochronotic and non-ochronotic cartilage from human hips and ears were analysed using Raman spectroscopy. RESULTS: Non-ochronotic cartilage spectra were similar and reproducible and typical of normal articular cartilage. Conversely, the ochronotic cartilage samples were highly fluorescent and displayed limited or no discernible Raman peaks in the spectra, in stark contrast to their non-ochronotic pairs. Interestingly, a novel peak was observed associated with the polymer of HGA in the ochronotic cartilage that was confirmed by analysis of pigment derived from synthetic HGA. CONCLUSION: This technique reveals novel data on the chemical differences in ochronotic compared with non-ochronotic cartilage, these differences are detectable by a technique that is already generating in vivo data and demonstrates the first possible procedure to monitor the progression of ochronosis in tissues of patients with AKU.


Asunto(s)
Alcaptonuria/patología , Cartílago Articular/patología , Cartílago Auricular/patología , Articulación de la Cadera/patología , Ocronosis/patología , Espectrometría Raman , Adolescente , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
17.
Vet Parasitol ; 259: 53-60, 2018 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-30056984

RESUMEN

Equine strongyle parasites are ubiquitous in grazing equids across the world. Anthelmintic resistance is widely developed in cyathostomin populations, but very few surveys have evaluated anthelmintic efficacy in equine populations in the United States, and most of these are over 15 years old. The present study was carried out as part of the National Animal Health Monitoring Systems (NAHMS) Equine 2015-2016 study. The aims were to investigate anthelmintic treatment efficacy by means of the fecal egg count reduction test (FECRT) and identify parameters associated with decreased efficacy. Data were collected from equine operations in 28 states via questionnaires and fecal samples submitted for fecal egg count analysis. Participants were instructed to collect samples from six equids at the day of anthelmintic treatments and 14 days later, and they were asked to include an empty syringe with a legible label of the anthelmintic product used in the shipment. Overall, dewormer treatment was effective for 76.3% of operations (84.6% of animals). Macrocyclic lactone use was effective for 88.7% of operations (95.0% of animals) while pyrimidine/benzimidazole use was effective for 21.4% of operations (43.5% of animals). Univariate analysis revealed that overall, macrocyclic lactones exhibited significantly higher efficacy than the pyrimidine and benzimidazole drug classes (p < 0.0001). There were no statistically significant differences observed between geographic regions (West, South Central, North East, and Southeast). Body weight (p = 0.0355), amount of anthelmintic administered (p = 0.0119), and operation size (p = 0.0162) were statistically associated with anthelmintic efficacy, while anthelmintic treatment frequency in the previous 12 months was not (p = 0.7081). Multiple, mixed-effect logistic regression revealed that anthelmintic drug class (p < 0.0001) was the most impactful factor in predicting anthelmintic efficacy, after accounting for operation size, region and clustering of equids at the operation level. Pasture rotation (p = 0.0129) also demonstrated a significant effect using this model. These data document widespread occurrence of reduced anthelmintic efficacy of benzimidazole and pyrimidine products against strongyle infections in equids in the United States. Anthelmintic efficacy patterns were relatively uniform between the four studied regions, and some epidemiological factors were identified to be associated with anthelmintic efficacy against strongyle infections. This information can be useful in devising sustainable parasite control strategies in the future.


Asunto(s)
Antihelmínticos/efectos adversos , Recuento de Huevos de Parásitos/veterinaria , Infecciones Equinas por Strongyloidea/tratamiento farmacológico , Strongyloidea/efectos de los fármacos , Animales , Antihelmínticos/uso terapéutico , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/estadística & datos numéricos , Resistencia a Medicamentos , Heces/parasitología , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/parasitología , Caballos/parasitología , Ivermectina/efectos adversos , Ivermectina/uso terapéutico , Recuento de Huevos de Parásitos/métodos , Recuento de Huevos de Parásitos/estadística & datos numéricos , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Infecciones Equinas por Strongyloidea/epidemiología , Infecciones Equinas por Strongyloidea/parasitología , Encuestas y Cuestionarios , Resultado del Tratamiento , Estados Unidos/epidemiología
18.
Vet Parasitol ; 257: 58-68, 2018 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-29773232

RESUMEN

Equine strongyle parasites are considered ubiquitous in grazing equids across the world, and cyathostomin parasites are known pathogens causing well-described disease complexes in horses. Decades of intensive anthelmintic treatments have led to anthelmintic resistance in cyathostomins, and current recommendations are to lower treatment intensity and base control strategies on fecal egg count surveillance. Little is known about risk factors associated with strongyle parasite egg shedding patterns in the United States equine population, as the most recent national survey was conducted 20 years ago. The present study was carried out as part of the National Animal Health Monitoring Systems (NAHMS) Equine 2015-2016 study. The aims were to describe strongyle parasite egg shedding patterns in the United States equine population and identify risk factors associated with prevalence and egg count magnitude. Data were collected from equine operations in 28 states via questionnaires and fecal samples submitted to a parasitology research laboratory for fecal egg count analysis and the data gathered underwent comprehensive statistical analyses. Though region and season were related, overall, the summer months and the fall in the southeast tended to have the greatest odds of presence of strongyles eggs on a FEC. Generally, equids resident in the Western region (Arizona, California, Colorado, Montana, Oregon, and Wyoming) had significantly lower strongyle prevalence, no matter the season, as well as a markedly different distribution between strongyle egg shedding levels (p = 0.0005). Overall, egg counts were over-dispersed with about 27% of equids (95% Confidence Interval (CI): 20-34%) contributing 80% of the egg output. Pasture history was significantly associated with strongyle egg prevalence (p = 0.0003) and egg shedding levels (p = 0.0063) with daily access in the previous 30 days being associated with higher odds of presence and greater median egg count levels. Equid gender was significantly associated with strongylid presence (p = 0.0081) and egg count level (p = 0.0008), with male equids having significantly lower odds and median egg counts than female equids, and age was significantly negatively associated with strongylid prevalence (p < 0.0001). Time since last deworming was significantly positively associated with prevalence of strongyle eggs, and this was dependent on the class of dewormer used (p = 0.0086), with equids treated with macrocyclic lactone class of drugs having lower odds of strongyle egg presence at 120 days since the last deworming. These data provide useful insights into strongylid egg shedding patterns in the United States equine population, and they can help refine parasite control recommendations depending on region, pasture access, and age distribution.


Asunto(s)
Antinematodos/farmacología , Recuento de Huevos de Parásitos/veterinaria , Infecciones Equinas por Strongyloidea/epidemiología , Strongyloidea/aislamiento & purificación , Factores de Edad , Animales , Heces/parasitología , Femenino , Caballos , Masculino , Densidad de Población , Prevalencia , Factores de Riesgo , Estaciones del Año , Factores Sexuales , Infecciones Equinas por Strongyloidea/parasitología , Infecciones Equinas por Strongyloidea/prevención & control , Strongyloidea/efectos de los fármacos , Estados Unidos/epidemiología
19.
Vet Parasitol ; 250: 45-51, 2018 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-29329623

RESUMEN

The widespread occurrence of anthelmintic resistance in equine parasites across the world has led to recommendations of fecal egg count-based parasite programs to reduce treatment intensity and thereby delay further development of resistance as much as possible. The most recent study describing equine parasite control in the United States was conducted 20 years ago, and little is known about current strategies employed. This study was part of the National Animal Health Monitoring Systems (NAHMS) Equine 2015 Study, and aimed to describe equine parasite control strategies in the U.S. and evaluate to which extent respondents were in compliance with current guidelines. The study was carried out in 28 states, representing 70.9% of all equine operations with at least five equids present. Two questionnaires were administered, either by mail or delivered in person by veterinary medical officers. Participants provided specific details of their operation and were asked questions about strategies for anthelmintic therapy and diagnostic testing. A total of 380 operations provided data regarding their parasite control practices. Most respondents dewormed 2-3 times a year with ivermectin being the most commonly used anthelmintic. About 22% of respondents used fecal egg counts (FEC) in some form, with less than 10% using them on a regular basis. Less than 5% made use of fecal egg count reduction tests (FECRT). These results suggest little change since the last nationwide survey was conducted in 1998, as the majority of respondents did not report using FECs. This is in stark contrast to recent European surveys, where 50-60% of respondents were using FECs routinely. However, the anthelmintic treatment intensity appears to have been lowered compared to 1998. Taken together, these results suggest a continuing need for education and outreach regarding sustainable parasite control.


Asunto(s)
Crianza de Animales Domésticos/estadística & datos numéricos , Control de Enfermedades Transmisibles/estadística & datos numéricos , Enfermedades de los Caballos/prevención & control , Enfermedades de los Caballos/parasitología , Ivermectina/uso terapéutico , Crianza de Animales Domésticos/tendencias , Animales , Antihelmínticos/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológico , Caballos , Recuento de Huevos de Parásitos/veterinaria , Encuestas y Cuestionarios , Estados Unidos
20.
Eur J Med Genet ; 61(5): 284-287, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29288088

RESUMEN

Ataxia Telangiectasia (AT) is named after the two key clinical features that characterize its classical phenotype, namely a progressive cerebellar gait disorder (ataxia) and vascular anomalies (telangiectasias) visible in the conjunctivae and skin. AT is an autosomal recessively inherited disorder, caused by mutations in the ATM gene that encodes the ATM protein. While the ataxia is subject of many publications, the telangiectasias are under emphasised. We here describe the observation that the absence or presence of ATM protein and the level of residual ATM kinase activity are related to the occurrence of telangiectasias and describe the clinical consequences of these vascular malformations. Finally, we hypothesize that ATM dysfunction dysregulates angiogenesis.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/deficiencia , Ataxia Telangiectasia/diagnóstico , Adolescente , Adulto , Ataxia Telangiectasia/genética , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Fisiológica , Fenotipo
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