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1.
Mol Psychiatry ; 26(6): 2651-2662, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33398085

RESUMO

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.


Assuntos
Disfunção Cognitiva , Idoso , Envelhecimento , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Estudos Transversais , Humanos
2.
Arch Environ Contam Toxicol ; 82(4): 520-538, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35441861

RESUMO

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.


Assuntos
Cobre , Poluentes Químicos da Água , Animais , Biomarcadores , Cobre/análise , Cobre/toxicidade , Água Doce , Estresse Oxidativo , Caramujos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
3.
Arch Environ Contam Toxicol ; 79(4): 391-405, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33090264

RESUMO

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.


Assuntos
Cobre/toxicidade , Caramujos/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores , Cobre/análise , Sulfato de Cobre , Água Doce , Reprodução , Testes de Toxicidade Crônica , Poluentes Químicos da Água/análise
4.
Osteoarthritis Cartilage ; 27(8): 1244-1251, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31022456

RESUMO

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.


Assuntos
Alcaptonúria/patologia , Cartilagem Articular/patologia , Cartilagem da Orelha/patologia , Articulação do Quadril/patologia , Ocronose/patologia , Análise Espectral Raman , Adolescente , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Clin Genet ; 90(2): 105-17, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26662178

RESUMO

Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder with immunodeficiency and an increased risk of developing cancer, caused by mutations in the ataxia-telangiectasia mutated (ATM) gene. Logically, blood relatives may also carry a pathogenic ATM mutation. Female carriers of such a mutation have an increased risk of breast cancer. Other health risks for carriers are suspected but have never been studied systematically. Consequently, evidence-based guidelines for carriers are not available yet. We systematically analyzed all literature and found that ATM mutation carriers have a reduced life expectancy because of mortality from cancer and ischemic heart diseases (RR 1.7, 95% CI 1.2-2.4) and an increased risk of developing cancer (RR 1.5, 95% CI 0.9-2.4), in particular breast cancer (RRwomen 3.0, 95% CI 2.1-4.5), and cancers of the digestive tract. Associations between ATM heterozygosity and other health risks have been suggested, but clear evidence is lacking. Based on these results, we propose that all female carriers of 40-50 years of age and female ATM c.7271T>G mutation carriers from 25 years of age onwards be offered intensified surveillance programs for breast cancer. Furthermore, all carriers should be made aware of lifestyle factors that contribute to the development of cardiovascular diseases and diabetes.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Ataxia Telangiectasia/genética , Neoplasias da Mama/genética , Neoplasias Gastrointestinais/genética , Mutação , Isquemia Miocárdica/genética , Adulto , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Medicina Baseada em Evidências , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/patologia , Expressão Gênica , Aconselhamento Genético , Predisposição Genética para Doença , Heterozigoto , Humanos , Expectativa de Vida , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/patologia , Guias de Prática Clínica como Assunto , Fatores de Risco
7.
Opt Express ; 24(3): 2542-61, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26906828

RESUMO

This paper describes the development and application of a novel optical technique for the measurement of liquid film thickness formed on surfaces during the impingement of automotive fuel sprays. The technique makes use of the change of the light scattering characteristics of a metal surface with known roughness, when liquid is deposited. Important advantages of the technique over previously established methods are the ability to measure the time-dependent spatial distribution of the liquid film without a need to add a fluorescent tracer to the liquid, while the measurement principle is not influenced by changes of the pressure and temperature of the liquid or the surrounding gas phase. Also, there is no need for non-fluorescing surrogate fuels. However, an in situ calibration of the dependence of signal intensity on liquid film thickness is required. The developed method can be applied to measure the time-dependent and two-dimensional distribution of the liquid fuel film thickness on the piston or the liner of gasoline direct injection (GDI) engines. The applicability of this technique was evaluated with impinging sprays of several linear alkanes and alcohols with different thermo-physical properties. The surface temperature of the impingement plate was controlled to simulate the range of piston surface temperatures inside a GDI engine. Two sets of liquid film thickness measurements were obtained. During the first set, the surface temperature of the plate was kept constant, while the spray of different fuels interacted with the surface. In the second set, the plate temperature was adjusted to match the boiling temperature of each fuel. In this way, the influence of the surface temperature on the liquid film created by the spray of different fuels and their evaporation characteristics could be demonstrated.

8.
Ultrasound Obstet Gynecol ; 48(1): 92-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26183321

RESUMO

OBJECTIVE: To evaluate the diagnostic yield of postmortem magnetic resonance imaging (PM-MRI) compared with conventional autopsy in fetuses of early gestational age and low body weight. METHODS: Fetuses of < 31 weeks' gestation that underwent 1.5-T PM-MRI and conventional autopsy were included. The findings of PM-MRI and conventional autopsy were reported blinded to each other. The reports of conventional autopsy and PM-MRI for each organ system (cardiovascular, neurological, abdominal, non-cardiac thoracic and musculoskeletal) were classified as either diagnostic or non-diagnostic. The likelihood of a non-diagnostic examination by PM-MRI was calculated according to fetal gestational age and body weight. RESULTS: Full datasets were examined of 204 fetuses, with mean gestational age of 20.95 ± 3.82 weeks (range, 12.0-30.7 weeks) and body-weight range of 15.9-1872 g. Body weight was the most significant predictor of diagnostic yield of PM-MRI. There was 95% confidence that 90% of fetuses will show diagnostic images by PM-MRI for all five organ systems when fetal body weight is ≥ 535 g, but < 50% of fetuses will have all five systems diagnostic on PM-MRI when body weight is < 122 g. CONCLUSION: PM-MRI is highly likely to provide adequate diagnostic images for fetuses with a body weight > 500 g. Below this weight, the diagnostic yield of standard 1.5-T PM-MRI decreases significantly. These data should help inform parents and clinicians on the suitability of performing PM-MRI in fetuses with low body weight. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Autopsia , Peso Corporal , Imageamento por Ressonância Magnética , Natimorto , Adulto , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos
9.
BMC Med Imaging ; 16: 34, 2016 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-27121379

RESUMO

BACKGROUND: Post mortem imaging is playing an increasingly important role in perinatal autopsy, and correct interpretation of imaging changes is paramount. This is particularly important following intra-uterine fetal death, where there may be fetal maceration. The aim of this study was to investigate whether any changes seen on a whole body fetal post mortem magnetic resonance imaging (PMMR) correspond to maceration at conventional autopsy. METHODS: We performed pre-autopsy PMMR in 75 fetuses using a 1.5 Tesla Siemens Avanto MR scanner (Erlangen, Germany). PMMR images were reported blinded to the clinical history and autopsy data using a numerical severity scale (0 = no maceration changes to 2 = severe maceration changes) for 6 different visceral organs (total 12). The degree of maceration at autopsy was categorized according to severity on a numerical scale (1 = no maceration to 4 = severe maceration). We also generated quantitative maps to measure the liver and lung T2. RESULTS: The mean PMMR maceration score correlated well with the autopsy maceration score (R(2) = 0.93). A PMMR score of ≥4.5 had a sensitivity of 91%, specificity of 64%, for detecting moderate or severe maceration at autopsy. Liver and lung T2 were increased in fetuses with maceration scores of 3-4 in comparison to those with 1-2 (liver p = 0.03, lung p = 0.02). CONCLUSIONS: There was a good correlation between PMMR maceration score and the extent of maceration seen at conventional autopsy. This score may be useful in interpretation of fetal PMMR.


Assuntos
Feto/patologia , Imageamento por Ressonância Magnética/métodos , Autopsia , Morte Fetal , Humanos , Fígado/patologia , Pulmão/patologia , Imageamento por Ressonância Magnética/instrumentação
10.
Clin Genet ; 87(3): 199-208, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25040471

RESUMO

Ataxia telangiectasia (A-T) is a rare recessively inherited disorder resulting in a progressive neurological decline. It is caused by biallelic mutation of the ATM gene that encodes a 370 kDa serine/threonine protein kinase responsible for phosphorylating many target proteins. ATM is activated by auto(trans)phosphorylation in response to DNA double strand breaks and leads to the activation of cell cycle checkpoints and either DNA repair or apoptosis as part of the cellular response to DNA damage. The allelic heterogeneity in A-T is striking. While the majority of mutations are truncating, leading to instability and loss of the ATM protein from the allele, a significant proportion of patients carry one of a small number of mutations that are either missense or leaky splice site mutations resulting in retention of some ATM with activity. The allelic heterogeneity in ATM, therefore, results in an equally striking clinical heterogeneity. There is also locus heterogeneity because mutation of the MRE11 gene can cause an obvious A-T like disorder both clinically and also at the cellular level and mutation of the RNF168 gene results in a much milder clinical phenotype, neurologically, with the major clinical feature being an immunological defect.


Assuntos
Ataxia Telangiectasia/diagnóstico , Idade de Início , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/epidemiologia , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/deficiência , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas de Ligação a DNA/genética , Progressão da Doença , Ativação Enzimática , Heterogeneidade Genética , Humanos , Proteína Homóloga a MRE11 , Mutação , Neoplasias/etiologia , Fenótipo , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética
11.
Clin Radiol ; 70(8): 872-80, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26050535

RESUMO

AIM: To compare the diagnostic accuracy of non-invasive cerebral post-mortem magnetic resonance imaging (PMMRI) specifically for cerebral and neurological abnormalities in a series of fetuses and children, compared to conventional autopsy. MATERIALS AND METHODS: Institutional ethics approval and parental consent was obtained. Pre-autopsy cerebral PMMRI was performed in a sequential prospective cohort (n = 400) of fetuses (n = 277; 185 ≤ 24 weeks and 92 > 24 weeks gestation) and children <16 years (n = 123) of age. PMMRI and conventional autopsy findings were reported blinded and independently of each other. RESULTS: Cerebral PMMRI had sensitivities and specificities (95% confidence interval) of 88.4% (75.5 to 94.9), and 95.2% (92.1 to 97.1), respectively, for cerebral malformations; 100% (83.9 to 100), and 99.1% (97.2 to 99.7) for major intracranial bleeds; and 87.5% (80.1 to 92.4) and 74.1% (68 to 79.4) for overall brain pathology. Formal neuropathological examination was non-diagnostic due to maceration/autolysis in 43/277 (16%) fetuses; of these, cerebral PMMRI imaging provided clinically important information in 23 (53%). The sensitivity of PMMRI for detecting significant ante-mortem ischaemic injury was only 68% (48.4 to 82.8) overall. CONCLUSIONS: PMMRI is an accurate investigational technique for identifying significant neuropathology in fetuses and children, and may provide important information even in cases where autolysis prevents formal neuropathological examination; however, PMMRI is less sensitive at detecting hypoxic-ischaemic brain injury, and may not detect rarer disorders not encountered in this study.


Assuntos
Autopsia/métodos , Encefalopatias/diagnóstico , Encéfalo/anormalidades , Feto/anormalidades , Imageamento por Ressonância Magnética/métodos , Adolescente , Criança , Pré-Escolar , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Lactente , Recém-Nascido , Hemorragias Intracranianas/diagnóstico , Estudos Prospectivos , Sensibilidade e Especificidade
12.
Appl Opt ; 54(14): 4566-79, 2015 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-25967518

RESUMO

Schlieren [Schlieren and Shadowgraphy Techniques (McGraw-Hill, 2001); Optics of Flames (Butterworths, 1963)] is a non-intrusive technique that can be used to detect density variations in a medium, and thus, under constant pressure and mixture concentration conditions, measure whole-field temperature distributions. The objective of the current work was to design a schlieren system to measure line-of-sight (LOS)-averaged temperature distribution with the final aim to determine the temperature distribution inside the cylinder of internal combustion (IC) engines. In a preliminary step, we assess theoretically the errors arising from the data reduction used to determine temperature from a schlieren measurement and find that the total error, random and systematic, is less than 3% for typical conditions encountered in the present experiments. A Z-type, curved-mirror schlieren system was used to measure the temperature distribution from a hot air jet in an open air environment in order to evaluate the method. Using the Abel transform, the radial distribution of the temperature was reconstructed from the LOS measurements. There was good agreement in the peak temperature between the reconstructed schlieren and thermocouple measurements. Experiments were then conducted in a four-stroke, single-cylinder, optical spark ignition engine with a four-valve, pentroof-type cylinder head to measure the temperature distribution of the reaction zone of an iso-octane-air mixture. The engine optical windows were designed to produce parallel rays and allow accurate application of the technique. The feasibility of the method to measure temperature distributions in IC engines was evaluated with simulations of the deflection angle combined with equilibrium chemistry calculations that estimated the temperature of the reaction zone at the position of maximum ray deflection as recorded in a schlieren image. Further simulations showed that the effects of exhaust gas recirculation and air-to-fuel ratio on the schlieren images were minimal under engine conditions compared to the temperature effect. At 20 crank angle degrees before top dead center (i.e., 20 crank angle degrees after ignition timing), the measured temperature of the flame front was in agreement with the simulations (730-1320 K depending on the shape of the flame front). Furthermore, the schlieren images identified the presence of hot gases ahead of the reaction zone due to diffusion and showed that there were no hot spots in the unburned mixture.

13.
Br J Anaesth ; 112(5): 816-23, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24638234

RESUMO

There is wide variation in how pain is managed in the UK. Patients often find themselves caught in a sea of referrals while continuing to suffer with poorly relieved symptoms. The British Pain Society's (BPS) Initial Assessment and Management of Pain care pathway (one of the five new BPS care pathways published by the Map of Medicine(®)) sets out how best to initially manage persistent pain. Patient education and supported self-management is recommended from an early stage. This pathway focuses on the start of the journey of a patient with pain, where a full diagnostic work-up is not yet complete. The pathway covers diverse recommendations such as appropriate content of a pain consultation, the use of clinical decision management tools to aid stratification of care, and resources to support patients to make informed decisions. Recommendations for monitoring of therapeutic effect are also included. Early identification of people at high risk of chronic disability may allow more intensive management, better use of resources, and reduction in disability. Implementation poses significant challenges; more research is needed to determine the most effective interventions. This article highlights practice points for the non-specialist, discusses areas of controversy, and examines the challenges of implementation.


Assuntos
Dor Crônica/diagnóstico , Dor Crônica/terapia , Manejo da Dor/métodos , Medição da Dor/métodos , Humanos , Educação de Pacientes como Assunto/métodos , Sociedades Médicas , Reino Unido
14.
Prenat Diagn ; 33(4): 307-12, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23457031

RESUMO

BACKGROUND: Perinatal autopsy provides essential clinical information, including cause of death; yet, autopsy rates have steadily declined because of parental refusal. Technology now enables less invasive alternatives to traditional autopsy and may increase the acceptability of post-mortem examination. OBJECTIVE: This study aimed to examine the relative acceptability among healthcare professionals of a minimally invasive autopsy (MIA; magnetic resonance imaging and laparoscopic-guided tissue sampling), compared with standard autopsy. METHODS: This study was questionnaire-based survey of healthcare professionals working in clinical settings where paediatric and perinatal deaths occur. RESULTS: Of 250 questionnaires distributed, 224 were returned (90% response rate). Autopsy was generally perceived as acceptable. Demographic factors affecting acceptability included ethnicity and religion but not professional role. MIA compared favourably with traditional autopsy, 50% of respondents reporting both equally acceptable, 40% reporting MIA more acceptable and 10% less acceptable. Healthcare professionals agreed that having a MIA option would make it easier to discuss autopsy with parents (P < 0.001). CONCLUSION: Less invasive autopsy appears an acceptable alternative to traditional autopsy for most respondents. Healthcare professionals should be aware that ethnic and religious opinions influence their own views on autopsy decisions and should be mindful of this when discussing autopsy with parents. Further research is needed to determine parental opinions.


Assuntos
Autopsia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/psicologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Anaesthesia ; 68(2): 142-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23121470

RESUMO

We compared the McGrath® Series 5 videolaryngoscope with the Macintosh laryngoscope in a simulated difficult airway, using manual in-line stabilisation in 88 anaesthestised patients of ASA physical status 1-2. The primary outcome was laryngoscopic view. Secondary outcomes included rates of successful tracheal intubation and complications. A Cormack and Lehane grade-1 or -2 view was found in all patients when using the McGrath compared with 45 (51%, p < 0.0001) using the Macintosh laryngoscopes. The mean (SD) percentage of glottic opening was 82 (23)% using the McGrath compared with 13 (23)% using the Macintosh (p < 0.0001). In 66 out of 88 patients (75%), the McGrath improved the glottic view by one to three grades compared with the Macintosh (p < 0.001). Intubation of the trachea was successful in all patients using the McGrath, while the Macintosh was successful in 26 (59%, p < 0.001). There was no significant difference in the complication rates between the devices.


Assuntos
Intubação Intratraqueal/instrumentação , Laringoscópios , Laringoscopia/instrumentação , Obstrução das Vias Respiratórias , Análise de Variância , Desenho de Equipamento , Feminino , Humanos , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Masculino , Pessoa de Meia-Idade , Gravação em Vídeo
16.
Nat Genet ; 13(3): 350-3, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8673136

RESUMO

Ataxia telangiectasia (AT) is characterized by neurological deterioration, immunodeficiency, spontaneous chromosomal instability, hypersensitivity to ionizing radiation, predisposition to cancer, particularly T cell leukaemia and lymphoma, and premature ageing. The most commonly observed defect affecting telomeres in humans is telomeric fusions, particularly in T lymphocytes in AT patients. Rarely, some tumour cells, like senescent cells, have dicentric chromosomes that may arise as a result of telomeric sequence loss. We show that the AT mutation in the homozygous state confers a predisposition to accelerated telomere shortening with increasing age in peripheral blood lymphocytes (PBLs), which may be linked to premature senescence. We also show that telomeric fusions are associated with large (> 90%) preleukaemic translocation clones in T cells. We propose that these fusions may result from a compound effect of accelerated telomere shortening, together with a growth advantage of cells in large clones which leads to further telomere loss. Fusions are not observed in leukaemic cells in these patients. There is no evidence that either accelerated telomere loss per se or telomeric fusions are important in tumourigenesis. Telomerase is present in both normal and AT lymphocytes and so neither telomere shortening nor telomeric fusions can be explained by the absence of telomerase.


Assuntos
Ataxia Telangiectasia/genética , Telômero/ultraestrutura , Adolescente , Adulto , Fatores Etários , Sequência de Bases , Criança , Aberrações Cromossômicas , Células Clonais , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Fragmento de Restrição , Linfócitos T/fisiologia , Telomerase/metabolismo , Telômero/fisiologia
17.
Folia Morphol (Warsz) ; 82(1): 198-204, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34845717

RESUMO

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.


Assuntos
Artéria Mesentérica Inferior , Pâncreas , Masculino , Humanos , Idoso de 80 Anos ou mais , Artéria Celíaca , Artéria Hepática/anormalidades , Artéria Mesentérica Superior/anormalidades
18.
Sci Rep ; 13(1): 65, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627304

RESUMO

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.


Assuntos
Bombeiros , Exposição Ocupacional , Humanos , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/análise , Equipamento de Proteção Individual , Local de Trabalho , Reino Unido
19.
Sci Rep ; 13(1): 62, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627314

RESUMO

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.


Assuntos
Bombeiros , Incêndios , Exposição Ocupacional , Humanos , Saúde Mental , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Equipamento de Proteção Individual , Reino Unido/epidemiologia
20.
Sci Rep ; 12(1): 22072, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627291

RESUMO

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).


Assuntos
Bombeiros , Neoplasias , Exposição Ocupacional , Humanos , Incidência , Exposição Ocupacional/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Reino Unido/epidemiologia
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