RESUMO
The global distribution of primary production and consumption by humans (fisheries) is well-documented, but we have no map linking the central ecological process of consumption within food webs to temperature and other ecological drivers. Using standardized assays that span 105° of latitude on four continents, we show that rates of bait consumption by generalist predators in shallow marine ecosystems are tightly linked to both temperature and the composition of consumer assemblages. Unexpectedly, rates of consumption peaked at midlatitudes (25 to 35°) in both Northern and Southern Hemispheres across both seagrass and unvegetated sediment habitats. This pattern contrasts with terrestrial systems, where biotic interactions reportedly weaken away from the equator, but it parallels an emerging pattern of a subtropical peak in marine biodiversity. The higher consumption at midlatitudes was closely related to the type of consumers present, which explained rates of consumption better than consumer density, biomass, species diversity, or habitat. Indeed, the apparent effect of temperature on consumption was mostly driven by temperature-associated turnover in consumer community composition. Our findings reinforce the key influence of climate warming on altered species composition and highlight its implications for the functioning of Earth's ecosystems.
Assuntos
Biodiversidade , Clima , Pesqueiros , Cadeia Alimentar , Alismatales , Animais , Biomassa , Feminino , Peixes , Geografia , Aquecimento Global , Humanos , MasculinoRESUMO
Cryptosporidiosis remains the leading protozoan induced cause of diarrhoea-associated mortality worldwide. Cryptosporidium hominis, the anthroponotically transmitted species within the Cryptosporidium genus, contributes significantly to the global burden of infection, accounting for the majority of clinical cases in many countries. This study applied high resolution melting analysis, a post-real-time PCR application, to the differentiation of six globally prevalent C. hominisgp60-subtypes. This novel method targeted three microsatellite, tandem repeat containing genetic markers, gp60, the genetic marker upon which current Cryptosporidium subtype nomenclature is based, MSB, and MSE, by which to differentiate between C. hominis isolates. This multi-locus approach successfully differentiated between all six C. hominisgp60-subtypes studied, some of which, such as IbA10G2, are known to exhibit global ubiquity. Thus, this method has the potential to be universally employed as a sensitive, cost effective and highly reproducible means to rapidly differentiate between C. hominisgp60-subtypes. Such a method would be of particular utility in epidemiological studies and outbreak scenarios, providing cost effective, clinically accessible alternative to DNA sequencing. The success of this preliminary study also supports further analysis of an expanded C. hominisgp60-subtype range and the potential expansion of the multi-locus panel in order to improve the discriminatory power of this approach.
Assuntos
Cryptosporidium/genética , Parasitologia/métodos , Criptosporidiose/parasitologia , Cryptosporidium/classificação , Cryptosporidium/isolamento & purificação , DNA de Protozoário/genética , Fezes/parasitologia , Marcadores Genéticos , Genótipo , Humanos , Tipagem de Sequências Multilocus , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNARESUMO
Reported incidence rates of cryptosporidiosis in Ireland are consistently among the highest in Europe. Despite the national prevalence of this enteric parasite and the compulsory nature of incidence surveillance and reporting, in-depth analyses seeking to genotype clinical isolates of Cryptosporidium on an intra-species level are rarely undertaken in Ireland. This molecular epidemiology study of 163 clinical Cryptosporidium isolates was conducted in Southern Ireland, from 2015 to 2018, in order to ascertain population subtype heterogeneity. Analysis was conducted via real-time PCR amplification and gp60 gene sequencing, which successfully determined the subtype designation of 149 of the 163 (91.4%) tested isolates. Overall, 12 C. parvum and five C. hominis subtypes were identified, with the incidence of the regionally predominant C. parvum species found to primarily occur during springtime months, while C. hominis incidence was largely confined to late summer and autumnal months. Additionally, one C. parvum and four C. hominis subtypes were newly reported by this study, having not been previously identified in clinical or livestock infection in Ireland. Overall, these data give insight into the diversification of the Cryptosporidium population and emergent subtypes, while also allowing comparisons to be made with clinical epidemiological profiles reported previously in Ireland and elsewhere.
Assuntos
Criptosporidiose/parasitologia , Cryptosporidium/classificação , Zoonoses/parasitologia , Animais , Criptosporidiose/epidemiologia , Cryptosporidium/genética , Cryptosporidium/isolamento & purificação , Cryptosporidium parvum/classificação , Cryptosporidium parvum/genética , Cryptosporidium parvum/isolamento & purificação , DNA de Protozoário/isolamento & purificação , Fezes/parasitologia , Gastroenterite/parasitologia , Glicoproteínas/química , Glicoproteínas/genética , Humanos , Incidência , Irlanda/epidemiologia , Estudos Longitudinais , Prevalência , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , RNA Ribossômico 18S/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Estações do Ano , Alinhamento de SequênciaRESUMO
The ocean plays a critical role in supporting human well-being, from providing food, livelihoods and recreational opportunities to regulating the global climate. Sustainable management aimed at maintaining the flow of a broad range of benefits from the ocean requires a comprehensive and quantitative method to measure and monitor the health of coupled humanocean systems. We created an index comprising ten diverse public goals for a healthy coupled humanocean system and calculated the index for every coastal country. Globally, the overall index score was 60 out of 100 (range 3686), with developed countries generally performing better than developing countries, but with notable exceptions. Only 5% of countries scored higher than 70, whereas 32% scored lower than 50. The index provides a powerful tool to raise public awareness, direct resource management, improve policy and prioritize scientific research.
Assuntos
Conservação dos Recursos Naturais/estatística & dados numéricos , Ecossistema , Monitoramento Ambiental/métodos , Internacionalidade , Biologia Marinha/métodos , Oceanografia/métodos , Água do Mar , Animais , Política Ambiental , Pesqueiros , Geografia , Atividades Humanas/normas , Atividades Humanas/estatística & dados numéricos , Oceanos e Mares , Recreação , Poluição da Água/análiseRESUMO
The risk of global extinction of reef-building coral species is increasing. We evaluated extinction risk using a biological trait-based resiliency index that was compared with Caribbean extinction during the Plio-Pleistocene, and with extinction risk determined by the International Union for Conservation of Nature (IUCN). Through the Plio-Pleistocene, the Caribbean supported more diverse coral assemblages than today and shared considerable overlap with contemporary Indo-Pacific reefs. A clear association was found between extant Plio-Pleistocene coral genera and our positive resilience scores. Regional extinction in the past and vulnerability in the present suggests that Pocillopora, Stylophora and foliose Pavona are among the most susceptible taxa to local and regional isolation. These same taxa were among the most abundant corals in the Caribbean Pliocene. Therefore, a widespread distribution did not equate with immunity to regional extinction. The strong relationship between past and present vulnerability suggests that regional extinction events are trait-based and not merely random episodes. We found several inconsistencies between our data and the IUCN scores, which suggest a need to critically re-examine what constitutes coral vulnerability.
Assuntos
Antozoários/fisiologia , Biodiversidade , Conservação dos Recursos Naturais/métodos , Recifes de Corais , Espécies em Perigo de Extinção , Extinção Biológica , Fósseis , Animais , Teorema de Bayes , Região do Caribe , Simulação por Computador , História Antiga , Funções Verossimilhança , Modelos Logísticos , Modelos Teóricos , Medição de Risco , Especificidade da Espécie , Isótopos de Estrôncio/análiseRESUMO
Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis that is executed in animals by immunization with myelin Ag in adjuvant. The SJL/J autoimmune-prone strain of mouse has been used to model relapsing-remitting multiple sclerosis. However, significant variations in peak scores, timing of onset, and incidence are observed among laboratories, with the postacute (relapse) phase of the disease exhibiting significant inconsistency. We characterized two substrains of SJL/J mice that exhibit profoundly different EAE disease parameters. Induction of EAE in the first SJL/J substrain resulted in many cases of chronic EAE that was dominated by an aggressive B cell response to the immunizing Ag and to endogenous CNS Ags. In contrast, the other SJL/J substrain exhibited a relapsing-remitting form of EAE concomitant with an elevated number of cytokine-producing CD4(+) T cells in the CNS. Exploiting these interstrain differences, we performed a genome-wide copy number analysis on the two disparate SJL/J substrains and discovered numerous gene-dosage differences. In particular, one inflammation-associated gene, Naip1, was present at a higher copy number in the SJL/J substrain that exhibited relapsing-remitting EAE. These results demonstrate that substrain differences, perhaps at the level of genomic copy number, can account for variability in the postacute phase of EAE and may drive chronic versus relapsing disease.
Assuntos
Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Predisposição Genética para Doença , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/imunologia , Doença Aguda , Adjuvantes Imunológicos/administração & dosagem , Animais , Linhagem Celular Tumoral , Células Cultivadas , Variações do Número de Cópias de DNA/imunologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/fisiopatologia , Feminino , Camundongos , Camundongos Endogâmicos , Mycobacterium tuberculosis/imunologia , Proteína Proteolipídica de Mielina/administração & dosagem , Proteína Proteolipídica de Mielina/imunologia , Proteína Inibidora de Apoptose Neuronal/biossíntese , Proteína Inibidora de Apoptose Neuronal/genética , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/imunologia , Fenótipo , Índice de Gravidade de Doença , Especificidade da Espécie , Redução de Peso/genética , Redução de Peso/imunologiaRESUMO
PURPOSE: School is a primary setting for pediatric occupational therapy practice, yet little is known about the provision of school-based occupational therapy in many countries internationally. The purpose of this study was to explore current school-based occupational therapy practice for the first time in Ireland to gain insight into current and potential service provision and to identify new directions and potential pathways for development. METHODS: This descriptive quantitative study utilized a cross-sectional online survey to gain the perspectives of the population of pediatric occupational therapists working regularly in schools across Ireland. Respondents were recruited through convenience and snowball sampling. Data were analysed through qualitative content analysis and descriptive statistics. RESULTS: The survey elicited 35 responses, yielding a 21.2% estimated response rate. Findings demonstrated that respondents provided therapy services in schools most commonly on a weekly (28.6%) or monthly (34.3%) basis, with only 5.0% working in the same school on a weekly or fortnightly basis. The majority of respondents (54.3%) used a direct therapy approach with a child, rather than coaching or modelling, to primarily address sensory, hand function, or daily living needs. None used a whole class or whole school (universal or tiered) approach. While respondents (54.3%) generally viewed collaborative practice as a strength of school-based practice, they also identified barriers to collaboration in schools. A core barrier is related to how services are constructed across health and education, with differing philosophies of service provision. The majority of respondents (75.0%) reported that they had not received any training to deliver evidence-based practice in therapy provision specific to school-based practice. Implications for Practice. This study indicates that therapists require continual education on evidence-based school practice as it applies in an Irish context. Furthermore, clarification of school therapy roles and service delivery models are required in order to determine how they contrast with traditional clinic roles. This will enable therapists to strengthen the coordination of service delivery between health and educational services to maximize the outcomes of school-based practice.
Assuntos
Terapia Ocupacional , Criança , Estudos Transversais , Humanos , Irlanda , Terapeutas Ocupacionais , Instituições AcadêmicasRESUMO
The protozoan parasite Cryptosporidium has emerged as a leading cause of diarrhoeal illness worldwide, posing a significant threat to young children and immunocompromised patients. While endemic in the vast majority of developing countries, Cryptosporidium also has the potential to cause waterborne epidemics and large scale outbreaks in both developing and developed nations. Anthroponontic and zoonotic transmission routes are well defined, with the ingestion of faecally contaminated food and water supplies a common source of infection. Microscopy, the current diagnostic mainstay, is considered by many to be suboptimal. This has prompted a shift towards alternative diagnostic techniques in the advent of the molecular era. Molecular methods, particularly PCR, are gaining traction in a diagnostic capacity over microscopy in the diagnosis of cryptosporidiosis, given the laborious and often tedious nature of the latter. Until now, developments in the field of Cryptosporidium detection and research have been somewhat hampered by the intractable nature of this parasite. However, recent advances in the field have taken the tentative first steps towards bringing Cryptosporidium research into the 21st century. Herein, we provide a review of these advances.
RESUMO
This study employed the post-real-time PCR application, high resolution melting (HRM) analysis, in order to differentiate between characterised clinical and reference Cryptosporidium parvum samples obtained from Cork University Hospital (Cork, Ireland) and the Cryptosporidium Reference Unit (Swansea, Wales). A sample set composed of 18 distinct C. parvum gp60-subtypes of the IIa gp60-subtype family (an allele family accounting for over 80% of all cryptosporidiosis cases in Ireland) was employed. HRM analysis-based interrogation of the gp60, MM5 and MS9-Mallon tandem repeat loci was found to completely differentiate between 10 of the 18 studied gp60-subtypes. The remaining eight gp60-subtypes were differentiated into three distinct groupings, with the designations within these groupings resolved to two to three potential gp60-subtypes. The current study aimed to develop a novel, reproducible, real-time PCR based multi-locus genotyping method to distinguish between C. parvum gp60-subtypes. These preliminary results support the further expansion of the multi-locus panel in order to increase the discriminatory capabilities of this novel method.
Assuntos
Cryptosporidium parvum/classificação , Cryptosporidium parvum/genética , Técnicas de Genotipagem/métodos , Reação em Cadeia da Polimerase em Tempo Real , Especificidade da EspécieRESUMO
Removal of predators can have strong indirect effects on primary producers through trophic cascades. Crustose coralline algae (CCA) are major primary producers worldwide that may be influenced by predator removal through changes in grazer composition and biomass. CCA have been most widely studied in Caribbean and temperate reefs, where cover increases with increasing grazer biomass due to removal of competitive fleshy algae. However, each of these systems has one dominant grazer type, herbivorous fishes or sea urchins, which may not be functionally equivalent. Where fishes and sea urchins co-occur, fishing can result in a phase shift in the grazing community with subsequent effects on CCA and other substrata. Kenyan reefs have herbivorous fishes and sea urchins, providing an opportunity to determine the relative impacts of each grazer type and evaluate potential human-induced trophic cascades. We hypothesized that fish benefit CCA, abundant sea urchins erode CCA, and that fishing indirectly reduces CCA cover by removing sea urchin predators. We used closures and fished reefs as a large-scale, long-term natural experiment to assess how fishing and resultant changes in communities affect CCA abundance. We used a short-term caging experiment to directly test the effects of grazing on CCA. CCA cover declined with increasing fish and sea urchin abundance, but the negative impact of sea urchin grazing was much stronger than that of fishes. Abundant sea urchins reduced the CCA growth rate to almost zero and prevented CCA accumulation. A warming event (El Niño Southern Oscillation, ENSO) occurred during the 18-year study and had a strong but short-term positive effect on CCA cover. However, the effect of the ENSO on CCA was lower in magnitude than the effect of sea urchin grazing. We compare our results with worldwide literature on bioerosion by fishes and sea urchins. Grazer influence depends on whether benefits of fleshy algae removal outweigh costs of grazer-induced bioerosion. However, the cost-benefit ratio for CCA appears to change with grazer type, grazer abundance, and environment. In Kenya, predator removal leads to a trophic cascade that is expected to reduce net calcification of reefs and therefore reduce reef stability, growth, and resilience.
Assuntos
Recifes de Corais , Comportamento Alimentar , Peixes , Cadeia Alimentar , Rodófitas , Ouriços-do-Mar , Animais , Fatores de TempoRESUMO
Cryptosporidium species subtypes are generally identified via DNA sequencing of the gp60 gene tandem repeat motif region. Due to the immunogenic nature of its glycoprotein products, gp60 is subject to host selective pressures, genetic recombination and evolutionary processes that drive extensive polymorphism at this locus. The elucidation of the polymorphic nature of this gene has led to the current mainstay in Cryptosporidium subtyping nomenclature. This study aimed to develop a real-time polymerase chain reaction based method utilising a post-PCR application, high resolution melting (HRM) analysis, in conjunction with the abovementioned gp60 nomenclature system, in order to differentiate between Cryptosporidium parvum gp60 subtypes. Subtype differentiation is based on the difference between the melting temperatures of individual subtypes conferred by variations in the polymorphic region of gp60. ⢠Nested gp60 primers were designed to amplify a target region of <200 base pairs for effective HRM analysis ⢠This method presents a rapid, sensitive, cost effective alternative to conventional sequencing. ⢠This method is highly flexible and may be applied to other loci in order to facilitate multi-locus analysis and improve the discriminative abilities of the method.
RESUMO
Cryptosporidium is a leading cause of gastroenteritis (cryptosporidiosis), with significant morbidity and mortality worldwide. Irish cryptosporidiosis incidence rates are consistently the highest reported in Europe. A retrospective, longitudinal study of clinical Cryptosporidium isolates was conducted from 2015 to 2018 in Cork, southern Ireland. Overall, 86.5% of cases were attributed to C. parvum, while the remaining 13.5% were caused by C. hominis Despite the widespread implications of this protozoan parasite in sporadic and outbreak-related illness in Ireland, the current dearth of species-level epidemiological surveillance and clinical studies needs to be addressed in order to elucidate the national impact of this enteric pathogen.
Assuntos
Criptosporidiose/epidemiologia , Cryptosporidium/isolamento & purificação , Gastroenterite/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Criptosporidiose/parasitologia , Cryptosporidium/genética , Monitoramento Epidemiológico , Fezes/parasitologia , Feminino , Gastroenterite/parasitologia , Humanos , Irlanda/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Adulto JovemRESUMO
Kelp forest ecosystems dominate 150,000 km of global temperate coastline, rivalling the coastal occurrence of coral reefs. Despite the astounding biological diversity and productive ecological communities associated with kelp forests, patterns of species richness and composition are difficult to monitor and compare. Crustose coralline algae are a critically important substrate for propagule settlement for a range of kelp forest species. Coralline-covered cobbles are home to hundreds of species of benthic animals and algae and form a replicable unit for ecological assays. Here, we use DNA metabarcoding of bulk DNA extracts sampled from cobbles to explore patterns of species diversity in kelp forests of the central California coast. The data from 97 cobbles within kelp forest ecosystems at three sites in Central California show the presence of 752 molecular operational taxonomic units (MOTUs) and 53 MOTUs assigned up to the species level with >95% similarity to current databases. We are able to detect spatial patterns of important management targets such as abalone recruits, and localized abundance of sea stars in 2012. Comparison of classic ecological surveys of these sites reveals large differences in species targets for these two approaches. In order to make such comparisons more quantitative, we use Presence/Absence Metabarcoding, using the fraction of replicate cobbles showing a species as a measure of its local abundance. This approach provides a fast and repeatable survey method that can be applied for biodiversity assessments across systems to shed light on the impact of different ecological disturbances and the role played by marine protected areas.
Assuntos
Biota/genética , DNA/genética , Kelp/genética , Animais , Biodiversidade , California , Recifes de Corais , Ecologia/métodos , Ecossistema , Cadeia Alimentar , FlorestasRESUMO
Dietary intervention with anthocyanins may confer benefits in brain function, including vision. Research to date indicates that animals have only a limited capacity to absorb anthocyanins, compared to other types of flavonoids. Pigs, which are a suitable model for human digestive absorption, were used to examine the deposition of anthocyanins in tissues including the liver, eye, and brain tissue. Pigs were fed diets supplemented with 0, 1, 2, or 4% w/w blueberries ( Vaccinium corymbosum L. 'Jersey') for 4 weeks. Prior to euthanasia, pigs were fasted for 18-21 h. Although no anthocyanins were detected in the plasma or urine of the fasted animals, intact anthocyanins were detected in all tissues where they were sought. LC-MS/MS results are presented for the relative concentration of 11 intact anthocyanins in the liver, eye, cortex, and cerebellum. The results suggest that anthocyanins can accumulate in tissues, including tissues beyond the blood-brain barrier.
Assuntos
Antocianinas/análise , Mirtilos Azuis (Planta)/química , Química Encefálica , Olho/química , Fígado/química , Suínos/metabolismo , Animais , Antocianinas/administração & dosagem , Antocianinas/farmacocinética , Cerebelo/química , Córtex Cerebral/química , Dieta , Frutas/química , MasculinoRESUMO
Atrial fibrillation (AF) is the main cause of morbidity among patients over 40 years of age with atrial septal defect (ASD). The closure of ASD in older patients does not decrease the occurrence of AF.(1-3) However, percutaneous ASD closure devices eliminate the possibility of a transseptal approach for future catheter-based procedures such as AF ablation. Epicardial pulmonary vein isolation with a bipolar radiofrequency clamp has been shown to be a safe and effective practice in surgical treatment of AF.(4,5) More recently, this technology has been utilized in a minimally invasive approach through bilateral thoracotomies. We present the case of a thoracoscopic-assisted pulmonary vein isolation on a patient with an atrial septal occlusion device.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Comunicação Interatrial/terapia , Veias Pulmonares/cirurgia , Cirurgia Torácica Vídeoassistida , Fibrilação Atrial/patologia , Procedimentos Cirúrgicos Cardíacos/instrumentação , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Veias Pulmonares/patologia , Cirurgia Torácica Vídeoassistida/métodosRESUMO
Ocean acidification (OA) increasingly threatens marine systems, and is especially harmful to calcifying organisms. One important question is whether OA will alter species interactions. Crustose coralline algae (CCA) provide space and chemical cues for larval settlement. CCA have shown strongly negative responses to OA in previous studies, including disruption of settlement cues to corals. In California, CCA provide cues for seven species of harvested, threatened, and endangered abalone. We exposed four common CCA genera and a crustose calcifying red algae, Peyssonnelia (collectively CCRA) from California to three pCO2 levels ranging from 419-2,013 µatm for four months. We then evaluated abalone (Haliotis rufescens) settlement under ambient conditions among the CCRA and non-algal controls that had been previously exposed to the pCO2 treatments. Abalone settlement and metamorphosis increased from 11% in the absence of CCRA to 45-69% when CCRA were present, with minor variation among CCRA genera. Though all CCRA genera reduced growth during exposure to increased pCO2, abalone settlement was unaffected by prior CCRA exposure to increased pCO2. Thus, we find no impacts of OA exposure history on CCRA provision of settlement cues. Additionally, there appears to be functional redundancy in genera of CCRA providing cues to abalone, which may further buffer OA effects.
Assuntos
Antozoários/fisiologia , Recifes de Corais , Gastrópodes/fisiologia , Rodófitas/fisiologia , Ácidos/química , Animais , California , Dióxido de Carbono/metabolismo , Dióxido de Carbono/farmacologia , Sinais (Psicologia) , Ecossistema , Gastrópodes/classificação , Gastrópodes/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Larva/crescimento & desenvolvimento , Larva/fisiologia , Metamorfose Biológica/efeitos dos fármacos , Oceanos e Mares , Água do Mar/químicaRESUMO
INTRODUCTION: The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) is a multidisciplinary, collaborative framework for the investigation of familial breast cancer. Based in Australia, the primary aim of kConFab is to facilitate high-quality research by amassing a large and comprehensive resource of epidemiological and clinical data with biospecimens from individuals at high risk of breast and/or ovarian cancer, and from their close relatives. METHODS: Epidemiological, family history and lifestyle data, as well as biospecimens, are collected from multiple-case breast cancer families ascertained through family cancer clinics in Australia and New Zealand. We used the Tyrer-Cuzick algorithms to assess the prospective risk of breast cancer in women in the kConFab cohort who were unaffected with breast cancer at the time of enrolment in the study. RESULTS: Of kConFab's first 822 families, 518 families had multiple cases of female breast cancer alone, 239 had cases of female breast and ovarian cancer, 37 had cases of female and male breast cancer, and 14 had both ovarian cancer as well as male and female breast cancer. Data are currently held for 11,422 people and germline DNAs for 7,389. Among the 812 families with at least one germline sample collected, the mean number of germline DNA samples collected per family is nine. Of the 747 families that have undergone some form of mutation screening, 229 (31%) carry a pathogenic or splice-site mutation in BRCA1 or BRCA2. Germline DNAs and data are stored from 773 proven carriers of BRCA1 or BRCA1 mutations. kConFab's fresh tissue bank includes 253 specimens of breast or ovarian tissue--both normal and malignant--including 126 from carriers of BRCA1 or BRCA2 mutations. CONCLUSION: These kConFab resources are available to researchers anywhere in the world, who may apply to kConFab for biospecimens and data for use in ethically approved, peer-reviewed projects. A high calculated risk from the Tyrer-Cuzick algorithms correlated closely with the subsequent occurrence of breast cancer in BRCA1 and BRCA2 mutation positive families, but this was less evident in families in which no pathogenic BRCA1 or BRCA2 mutation has been detected.
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Neoplasias Ovarianas/genética , Bancos de Tecidos , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Austrália , Estudos de Coortes , Análise Mutacional de DNA , Coleta de Dados , Estudos Epidemiológicos , Feminino , Mutação em Linhagem Germinativa , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Nova Zelândia , Linhagem , Pesquisa/organização & administração , Fatores de Risco , Manejo de EspécimesRESUMO
BACKGROUND: Germline mutations in the genes BRCA1 and BRCA2 account for only a proportion of hereditary breast cancer, suggesting that additional genes contribute to hereditary breast cancer. Recently a heterozygous variant in the ataxia-telangiectasia mutated (ATM) gene, IVS10-6T-->G, was reported by an Australian multiple-case breast cancer family cohort study (the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer) to confer a substantial breast cancer risk. Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial. METHODS: We determined the frequency of ATM IVS10-6T-->G variants in a cohort of individuals affected by breast and/or ovarian cancer who underwent BRCA1 and BRCA2 genetic testing at four major Australian familial cancer clinics. RESULTS: Seven of 495 patients (1.4%) were heterozygous for the IVS10-6T-->G variant; the carrier rate in unselected Australian women with no family history of breast cancer is reported to be 6 of 725 (0.83%) (P = 0.4). Two of the seven probands also harboured a pathogenic BRCA1 mutation and one patient had a BRCA1 unclassified variant of uncertain significance. CONCLUSION: These findings indicate that the ATM IVS10-6T-->G variant does not seem to occur at a significantly higher frequency in affected individuals from high-risk families than in the general population. A role for this variant as a low-penetrance allele or as a modifying gene in association with other genes (such as BRCA1) remains possible. Routine testing for ATM IVS10-6T-->G is not warranted in mutation screening of affected individuals from high-risk families.
Assuntos
Neoplasias da Mama Masculina/genética , Neoplasias da Mama/genética , Frequência do Gene/genética , Mutação em Linhagem Germinativa/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia , Austrália/epidemiologia , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Feminino , Genes BRCA1 , Genes BRCA2 , Triagem de Portadores Genéticos , Testes Genéticos , Humanos , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Estudos Retrospectivos , Proteínas Supressoras de TumorRESUMO
Laryngeal edema is a relatively rare yet serious postoperative complication for those patients undergoing general anesthesia. Maintenance of airway and breathing are always the first priority of perioperative patient care. Medical-surgical nurses working in postoperative settings must be familiar with the signs, symptoms, and necessary prompt treatment for this life-threatening condition.
Assuntos
Edema Laríngeo/enfermagem , Enfermagem Perioperatória/métodos , Complicações Pós-Operatórias/enfermagem , Adulto , Anestesia Geral/efeitos adversos , Humanos , Intubação Intratraqueal/efeitos adversos , Edema Laríngeo/etiologia , Máscaras Laríngeas , Laringoscopia , Avaliação em Enfermagem/métodos , Assistência Perioperatória/métodos , Assistência Perioperatória/enfermagem , Complicações Pós-Operatórias/etiologia , Fatores de RiscoRESUMO
Rare exonic, non-truncating variants in known cancer susceptibility genes such as BRCA1 and BRCA2 are problematic for genetic counseling and clinical management of relevant families. This study used multifactorial likelihood analysis and/or bioinformatically-directed mRNA assays to assess pathogenicity of 19 BRCA1 or BRCA2 variants identified following patient referral to clinical genetic services. Two variants were considered to be pathogenic (Class 5). BRCA1:c.4484G> C(p.Arg1495Thr) was shown to result in aberrant mRNA transcripts predicted to encode truncated proteins. The BRCA1:c.122A>G(p.His41Arg) RING-domain variant was found from multifactorial likelihood analysis to have a posterior probability of pathogenicity of 0.995, a result consistent with existing protein functional assay data indicating lost BARD1 binding and ubiquitin ligase activity. Of the remaining variants, seven were determined to be not clinically significant (Class 1), nine were likely not pathogenic (Class 2), and one was uncertain (Class 3).These results have implications for genetic counseling and medical management of families carrying these specific variants. They also provide additional multifactorial likelihood variant classifications as reference to evaluate the sensitivity and specificity of bioinformatic prediction tools and/or functional assay data in future studies.