RESUMO
Understanding how dispersal and gene flow link geographically separated the populations over evolutionary history is challenging, particularly in migratory marine species. In southern right whales (SRWs, Eubalaena australis), patterns of genetic diversity are likely influenced by the glacial climate cycle and recent history of whaling. Here we use a dataset of mitochondrial DNA (mtDNA) sequences (n = 1327) and nuclear markers (17 microsatellite loci, n = 222) from major wintering grounds to investigate circumpolar population structure, historical demography and effective population size. Analyses of nuclear genetic variation identify two population clusters that correspond to the South Atlantic and Indo-Pacific ocean basins that have similar effective breeder estimates. In contrast, all wintering grounds show significant differentiation for mtDNA, but no sex-biased dispersal was detected using the microsatellite genotypes. An approximate Bayesian computation (ABC) approach with microsatellite markers compared the scenarios with gene flow through time, or isolation and secondary contact between ocean basins, while modelling declines in abundance linked to whaling. Secondary-contact scenarios yield the highest posterior probabilities, implying that populations in different ocean basins were largely isolated and came into secondary contact within the last 25,000 years, but the role of whaling in changes in genetic diversity and gene flow over recent generations could not be resolved. We hypothesise that these findings are driven by factors that promote isolation, such as female philopatry, and factors that could promote dispersal, such as oceanographic changes. These findings highlight the application of ABC approaches to infer the connectivity in mobile species with complex population histories and, currently, low levels of differentiation.
Assuntos
Evolução Molecular , Variação Genética/genética , Genética Populacional , Baleias/genética , Animais , Clima , DNA Mitocondrial/genética , Fluxo Gênico/genética , Genótipo , Haplótipos/genética , Repetições de Microssatélites/genética , Oceano Pacífico , Filogenia , Densidade Demográfica , Baleias/fisiologiaRESUMO
BACKGROUND: Few clinical trials have evaluated long-term treatment of nail psoriasis with biologics. OBJECTIVE: Safety and efficacy of adalimumab [ADA; Humira AbbVie Inc, North Chicago, IL, USA)] long-term treatment (52 weeks) was evaluated in a phase-3, randomized trial in patients with moderate-to-severe plaque psoriasis and concomitant moderate-to-severe fingernail psoriasis. Results from the first 26 weeks (Period A) have been reported. METHODS: Patients receiving 40 mg ADA every other week or placebo in Period A, continued with or switched to 40 mg ADA every-other-week treatment in the subsequent 26-week open-label extension (OLE) period. Main efficacy evaluations were ≥75% improvement in total-fingernail modified Nail Psoriasis Severity Index (mNAPSI 75) and achievement of Physician's Global Assessment for Fingernail Psoriasis of clear or minimal disease (PGA-F 0/1) with a ≥2-grade improvement from baseline, across the trial for patients who continued ADA from Period A through the OLE (Continuous-ADA Population). Safety was evaluated during the OLE and for patients receiving ADA at any time during the study (All-ADA Population). RESULTS: Of the 217 patients initially randomized in Period A, 188 (86.6%; 94 in each treatment group) entered the OLE after completion of or early escape from Period A. For the Continuous-ADA Population (N = 109), endpoint achievement rates improved from OLE entry (Week 26) to Week 52, including total-fingernail mNAPSI 75 (47.4-54.5%); PGA-F 0/1 (51.1-55.6%) and total-fingernail mNAPSI = 0 (6.6-17.9%). Serious adverse event and serious infection rates for the All-ADA Population (N = 203) were 6.9% and 3.4%, respectively. CONCLUSIONS: In this population of psoriasis patients with concomitant, moderate-to-severe nail psoriasis, long-term efficacy and improvement in signs and symptoms of nail disease were demonstrated after every-other-week ADA treatment, including incremental improvements in rate of total clearance of nail disease. No new safety risks were identified for patients receiving at least one ADA dose across 52 weeks.
Assuntos
Adalimumab/uso terapêutico , Doenças da Unha/tratamento farmacológico , Psoríase/tratamento farmacológico , Adalimumab/efeitos adversos , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/complicações , Psoríase/complicações , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Understanding the genetic structure of a population is essential to its conservation and management. We report the level of genetic diversity and determine the population structure of a cryptic deep ocean cetacean, the Gray's beaked whale (Mesoplodon grayi). We analysed 530 bp of mitochondrial control region and 12 microsatellite loci from 94 individuals stranded around New Zealand and Australia. The samples cover a large area of the species distribution (~6000 km) and were collected over a 22-year period. We show high genetic diversity (h=0.933-0.987, π=0.763-0.996% and Rs=4.22-4.37, He=0.624-0.675), and, in contrast to other cetaceans, we found a complete lack of genetic structure in both maternally and biparentally inherited markers. The oceanic habitats around New Zealand are diverse with extremely deep waters, seamounts and submarine canyons that are suitable for Gray's beaked whales and their prey. We propose that the abundance of this rich habitat has promoted genetic homogeneity in this species. Furthermore, it has been suggested that the lack of beaked whale sightings is the result of their low abundance, but this is in contrast to our estimates of female effective population size based on mitochondrial data. In conclusion, the high diversity and lack of genetic structure can be explained by a historically large population size, in combination with no known exploitation, few apparent behavioural barriers and abundant habitat.
Assuntos
Variação Genética , Genética Populacional , Baleias/genética , Animais , Austrália , Conservação dos Recursos Naturais , DNA Mitocondrial/genética , Ecossistema , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Padrões de Herança , Masculino , Repetições de Microssatélites , Nova Zelândia , Densidade Demográfica , Análise de Sequência de DNARESUMO
BACKGROUND: Psoriatic arthritis commonly develops in psoriasis patients and, if undiagnosed, can lead to potentially avoidable joint damage and an increased risk of comorbidity and mortality. Increased awareness of PsA symptoms among dermatologists provides an opportunity for earlier diagnosis, more timely therapy and prevention of disability. OBJECTIVE: To provide Australian epidemiological data on the frequency of undiagnosed PsA among psoriasis patients in dermatology practice, and to investigate the impact of psoriasis on quality of life and work productivity. METHODS: Nine tertiary centre dermatology practices enrolled patients presenting with plaque psoriasis and no prior rheumatologist-confirmed PsA diagnosis. Patients were screened using the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire and were referred to a rheumatologist for assessment of PsA status using CASPAR criteria if they had a PASE score ≥44. RESULTS: Based on the composite and sequential application of PASE and CASPAR criteria, undiagnosed PsA among psoriasis patients in this study is 9% [95% CI: 6, 12]. The PPV of PASE in this setting is 26% [95% CI: 19, 34]. Nail involvement and chronic large plaque psoriasis were identified as independent positive predictors of PsA, whereas scalp psoriasis was an independent negative predictor of PsA. Patients with moderate-to-severe psoriasis (PASI ≥15) had lower quality of life scores than patients with less severe psoriasis. CONCLUSION: In this study, the frequency of undiagnosed PsA in Australian dermatology practice was 9% among plaque psoriasis patients with no prior PsA diagnosis. Compared with psoriasis alone, the impact of undiagnosed PsA on health-related quality of life of psoriasis patients is substantial.
Assuntos
Artrite Psoriásica/epidemiologia , Qualidade de Vida , Absenteísmo , Adulto , Artrite Psoriásica/diagnóstico , Austrália/epidemiologia , Dermatologia/estatística & dados numéricos , Eficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Unhas , Presenteísmo , Prevalência , Psoríase/epidemiologia , Psoríase/patologia , Fatores de Risco , Dermatoses do Couro Cabeludo/epidemiologia , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Superpopulation capture-recapture models are useful for estimating the abundance of long-lived, migratory species because they are able to account for the fluid nature of annual residency at migratory destinations. Here we extend the superpopulation POPAN model to explicitly account for heterogeneity in capture probability linked to reproductive cycles (POPAN-tau). This extension has potential application to a range of species that have temporally variable life stages (e.g., non-annual breeders such as albatrosses and baleen whales) and results in a significant reduction in bias over the standard POPAN model. We demonstrate the utility of this model in simultaneously estimating abundance and annual population growth rate (lamda) in the New Zealand (NZ) southern right whale (Eubalaena australis) from 1995 to 2009. DNA profiles were constructed for the individual identification of more than 700 whales, sampled during two sets of winter expeditions in 1995-1998 and 2006-2009. Due to differences in recapture rates between sexes, only sex-specific models were considered. The POPAN-tau models, which explicitly account for a decrease in capture probability in non-calving years, fit the female data set significantly better than do standard superpopulation models (deltaAIC > 25). The best POPAN-tau model (AIC) gave a super-population estimate of 1162 females for 1995-2009 (95% CL 921, 1467) and an estimated annual increase of 5% (95% CL--2%, 13%). The best model (AIC) gave a superpopulation estimate of 1007 males (95% CL 794, 1276) and an estimated annual increase of 7% (95% CL 5%, 9%) for 1995-2009. Combined, the total superpopulation estimate for 1995-2009 was 2169 whales (95% CL 1836, 2563). Simulations suggest that failure to account for the effect of reproductive status on the capture probability would result in a substantial positive bias (+19%) in female abundance estimates.
Assuntos
Reprodução/fisiologia , Baleias/fisiologia , Animais , Feminino , Genótipo , Masculino , Modelos Biológicos , Densidade Demográfica , Baleias/genéticaRESUMO
Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.
Assuntos
Metilação de DNA , Epigênese Genética , Humanos , Camundongos , Animais , Metilação de DNA/genética , Envelhecimento/genética , Longevidade/genética , Mamíferos/genéticaRESUMO
Glucocorticoids are regularly used as biomarkers of relative health for individuals and populations. Around the Western Antarctic Peninsula (WAP), baleen whales have and continue to experience threats, including commercial harvest, prey limitations and habitat change driven by rapid warming, and increased human presence via ecotourism. Here, we measured demographic variation and differences across the foraging season in blubber cortisol levels of humpback whales (Megaptera novaeangliae) over two years around the WAP. Cortisol concentrations were determined from 305 biopsy samples of unique individuals. We found no significant difference in the cortisol concentration between male and female whales. However, we observed significant differences across demographic groups of females and a significant decrease in the population across the feeding season. We also assessed whether COVID-19-related reductions in tourism in 2021 along the WAP correlated with lower cortisol levels across the population. The decline in vessel presence in 2021 was associated with a significant decrease in humpback whale blubber cortisol concentrations at the population level. Our findings provide critical contextual data on how these hormones vary naturally in a population over time, show direct associations between cortisol levels and human presence, and will enable comparisons among species experiencing different levels of human disturbance.
Assuntos
COVID-19 , Jubarte , Humanos , Animais , Masculino , Feminino , Hidrocortisona , Regiões Antárticas , Estações do AnoRESUMO
Antarctic minke whales (Balaenoptera bonaerensis, AMW) are an abundant, ice-dependent species susceptible to rapid climatic changes occurring in parts of the Antarctic. Here, we used remote biopsy samples and estimates of length derived from unoccupied aircraft system (UAS) to characterize for the first time the sex ratio, maturity, and pregnancy rates of AMWs around the Western Antarctic Peninsula (WAP). DNA profiling of 82 biopsy samples (2013-2020) identified 29 individual males and 40 individual females. Blubber progesterone levels indicated 59% of all sampled females were pregnant, irrespective of maturity. When corrected for sexual maturity, the median pregnancy rate was 92.3%, indicating that most mature females become pregnant each year. We measured 68 individuals by UAS (mean = 8.04 m) and estimated that 66.5% of females were mature. This study provides the first data on the demography of AMWs along the WAP and represents the first use of non-lethal approaches to studying this species. Furthermore, these results provide baselines against which future changes in population status can be assessed in this rapidly changing marine ecosystem.
RESUMO
Baleen whales are the largest animals that have ever lived. To develop an improved estimation of substitution rate for nuclear and mitochondrial DNA for this taxon, we implemented a relaxed-clock phylogenetic approach using three fossil calibration dates: the divergence between odontocetes and mysticetes approximately 34 million years ago (Ma), between the balaenids and balaenopterids approximately 28 Ma, and the time to most recent common ancestor within the Balaenopteridae approximately 12 Ma. We examined seven mitochondrial genomes, a large number of mitochondrial control region sequences (219 haplotypes for 465 bp) and nine nuclear introns representing five species of whales, within which multiple species-specific alleles were sequenced to account for within-species diversity (1-15 for each locus). The total data set represents >1.65 Mbp of mitogenome and nuclear genomic sequence. The estimated substitution rate for the humpback whale control region (3.9%/million years, My) was higher than previous estimates for baleen whales but slow relative to other mammal species with similar generation times (e.g., human-chimp mean rate > 20%/My). The mitogenomic third codon position rate was also slow relative to other mammals (mean estimate 1%/My compared with a mammalian average of 9.8%/My for the cytochrome b gene). The mean nuclear genomic substitution rate (0.05%/My) was substantially slower than average synonymous estimates for other mammals (0.21-0.37%/My across a range of studies). The nuclear and mitogenome rate estimates for baleen whales were thus roughly consistent with an 8- to 10-fold slowing due to a combination of large body size and long generation times. Surprisingly, despite the large data set of nuclear intron sequences, there was only weak and conflicting support for alternate hypotheses about the phylogeny of balaenopterid whales, suggesting that interspecies introgressions or a rapid radiation has obscured species relationships in the nuclear genome.
Assuntos
Evolução Molecular , Filogenia , Baleias/classificação , Baleias/genética , Animais , Humanos , Fatores de TempoRESUMO
Bottlenose dolphins (Tursiops truncatus) and Guiana dolphin (Sotalia guianensis) live in sympatry along the Caribbean Coast of Central and South America and social interactions between these species have been described in the Caribbean Coast of Costa Rica, including sexual encounters. Here we examine and document the only known hybridization event between a male Guiana dolphin and a female bottlenose dolphin, in captivity at Oceanario Islas del Rosario (Colombian Caribbean), using photographic and genetic evidence from mitochondrial DNA markers and nuclear autosomal introns.
Assuntos
Animais de Zoológico/genética , Golfinho Nariz-de-Garrafa/genética , Golfinhos/genética , Animais , Animais de Zoológico/anatomia & histologia , Golfinho Nariz-de-Garrafa/anatomia & histologia , DNA Mitocondrial , Golfinhos/anatomia & histologia , Feminino , Genes Mitocondriais , Hibridização Genética , MasculinoRESUMO
The complementarity of historical and contemporary processes contributes to understanding the genetic structure of continuously distributed marine species with high dispersal capabilities. Cephalorhynchus eutropia, has a continuous coastal distribution with strong genetic differentiation identified by nuclear DNA markers. We explored the historical dimension of this genetic differentiation between northern and southern populations to evaluate phylogeographic structure. Additionally, we conducted mtDNA and microsatellite analyses to detect past and recent demographic changes. The southern population was characterized by lower genetic diversity with a signal of population expansion, likely associated with ice retreat and habitat extension after the Last Glacial Maximum (LGM). In contrast, structure within the northern population was more consistent with stable historical population size. Approximate Bayesian Computation analyses suggested that during the LGM, C. eutropia persisted in the northern area; while the south was colonized by dispersal ~11,000 years ago followed by population expansion. This study shows that Chilean dolphin population structure is consistent with predictions from the Expansion-Contraction biogeographic model, with a poleward post-glacial shift revealed in current genetic structure. The results also confirm the validity of the population units previously identified, demonstrating their historical origin and highlighting the utility of integrating genetic markers with different temporal scale resolutions.
Assuntos
DNA Mitocondrial/genética , Golfinhos/genética , Ecossistema , Repetições de Microssatélites/genética , Modelos Biológicos , Animais , Chile , Evolução Molecular , Especiação Genética , Variação Genética , Genética Populacional , Periodicidade , Filogenia , FilogeografiaRESUMO
Juvenile survival and recruitment can be more sensitive to environmental, ecological and anthropogenic factors than adult survival, influencing population-level processes like recruitment and growth rate in long-lived, iteroparous species such as southern right whales. Conventionally, Southern right whales are individually identified using callosity patterns, which do not stabilise until 6-12 months, by which time the whale has left its natal wintering grounds. Here we use DNA profiling of skin biopsy samples to identify individual Southern right whales from year of birth and document their return to the species' primary wintering ground in New Zealand waters, the Subantarctic Auckland Islands. We find evidence of natal fidelity to the New Zealand wintering ground by the recapture of 15 of 57 whales, first sampled in year of birth and available for subsequent recapture, during winter surveys to the Auckland Islands in 1995-1998 and 2006-2009. Four individuals were recaptured at the ages of 9 to 11, including two females first sampled as calves in 1998 and subsequently resampled as cows with calves in 2007. Using these capture-recapture records of known-age individuals, we estimate changes in survival with age using Cormack-Jolly-Seber models. Survival is modelled using discrete age classes and as a continuous function of age. Using a bootstrap method to account for uncertainty in model selection and fitting, we provide the first direct estimate of juvenile survival for this population. Our analyses indicate a high annual apparent survival for juveniles at between 0.87 (standard error (SE) 0.17, to age 1) and 0.95 (SE 0.05: ages 2-8). Individual identification by DNA profiling is an effective method for long-term demographic and genetic monitoring, particularly in animals that change identifiable features as they develop or experience tag loss over time.
Assuntos
Migração Animal , Baleias/fisiologia , Animais , Biópsia , Feminino , Variação Genética , Genótipo , Geografia , Masculino , Nova Zelândia , Densidade Demográfica , Dinâmica Populacional , Estações do Ano , Análise de Sequência de DNA , Pele , Baleias/crescimento & desenvolvimentoRESUMO
PURPOSE: Cost-utility analyses (CUAs) present the value of an intervention as the ratio of its incremental cost divided by its incremental survival benefit, with survival weighted by utilities to produce quality-adjusted life years (QALYs). We critically reviewed the CUA literature and its role in informing clinical oncology practice, research priorities, and policy. METHODS: The English-language literature was searched between 1975 and1997 for CUAs. Two readers abstracted from each article descriptions of the clinical situation and patients, the methods used, study perspective, the measures of effectiveness, costs included, discounting, and whether sensitivity analyses were performed. The readers then made subjective quality assessments. We also extracted utility values from the reviewed papers, along with information on how and from whom utilities were measured. RESULTS: Our search yielded 40 studies, which described 263 health states and presented 89 cost-utility ratios. Both the number and quality of studies increased over time. However, many studies are at variance with current standards. Only 20% of studies took a societal perspective, more than a third failed to discount both the costs and QALYs, and utilities were often simply estimates from the investigators or other physicians. CONCLUSION: The cost-utility literature in oncology is not large but is rapidly expanding. There remains much room for improvement in the methodological rigor with which utilities are measured. Considering quality-of-life effects by incorporating utilities into economic studies is particularly important in oncology, where many therapies obtain modest improvements in response or survival at the expense of nontrivial toxicity.
Assuntos
Oncologia/economia , Neoplasias/economia , Ensaios Clínicos como Assunto/economia , Análise Custo-Benefício/estatística & dados numéricos , Custos de Cuidados de Saúde/normas , Humanos , Oncologia/estatística & dados numéricos , PublicaçõesRESUMO
OBJECTIVES: This study was designed to investigate the organ and disease specificity of antiheart antibodies in patients with dilated cardiomyopathy. BACKGROUND: Autoimmune disease is characterized by the presence of circulating autoantibodies, and autoimmune mechanisms may play a role in the pathogenesis of dilated cardiomyopathy. METHODS: An SDS-PAGE (sodium dodecylsulfate polyacrylamide gel electrophoresis) procedure followed by Western blotting was used to screen serum samples for antiheart antibodies of two immunoglobulin classes, IgM and IgG, from 52 patients with dilated cardiomyopathy and 48 patients with ischemic heart disease as control subjects. Use of two-dimensional gel electrophoresis followed by Western blotting and protein sequencing enabled us to identify the protein bands against which antiheart antibodies were produced in both groups of patients. RESULTS: Strong IgG antiheart antibodies against myocardial proteins, cross-reacting with skeletal muscle proteins, were detected in significantly more patients with dilated cardiomyopathy (n = 24 [46%]) than with ischemic heart disease (n = 8 [17%]) (p = 0.001). Patients with dilated cardiomyopathy showed a significantly greater frequency and reactivity of IgG antiheart antibodies against six myocardial proteins (molecular weight 30, 35, 40, 60, 85 and 200 kD) than did patients with ischemic heart disease. These were identified as myosin light chain 1, tropomyosin, actin, heat shock protein (HSP)-60, an unidentified protein and myosin heavy chain, respectively. CONCLUSIONS: We detected strong IgG antiheart antibodies in significantly more patients with dilated cardiomyopathy than with ischemic heart disease. The most immunogenic band was that corresponding to HSP-60. Antibodies against HSP-60 were found in 85% and 42% of patients with dilated cardiomyopathy and ischemic heart disease, respectively, confirming our hypothesis of an immune involvement in dilated cardiomyopathy.
Assuntos
Autoanticorpos/sangue , Cardiomiopatia Dilatada/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Isquemia Miocárdica/sangue , Miocárdio/imunologia , Actinas/química , Actinas/imunologia , Adolescente , Adulto , Sequência de Aminoácidos , Autoanticorpos/imunologia , Western Blotting , Cardiomiopatia Dilatada/epidemiologia , Cardiomiopatia Dilatada/imunologia , Estudos de Casos e Controles , Chaperonina 60 , Reações Cruzadas , Eletroforese em Gel de Poliacrilamida , Feminino , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/imunologia , Humanos , Masculino , Dados de Sequência Molecular , Peso Molecular , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/imunologia , Quinase de Cadeia Leve de Miosina/química , Quinase de Cadeia Leve de Miosina/imunologia , Miosinas/química , Miosinas/imunologia , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Tropomiosina/química , Tropomiosina/imunologiaRESUMO
BACKGROUND: Studies have demonstrated economic and clinical effectiveness using troponin as a risk stratification tool in chest pain patients. Those with a positive result are investigated invasively, whilst those with a negative result and ECG are promptly mobilized, facilitating discharge. AIM: To determine whether our use of troponin I (cTnI) in routine clinical practice conforms to ideal standards. DESIGN: Audit study. METHODS: Data were collected from 93 laboratory request forms for cTnI measurement on 72 patients with matched available patient records. RESULTS: Eighty requests had no information regarding timing of blood sample in relation to the clinical event; 39% gave no clinical indication. Only 71% of results were available within 12 h. An admission diagnosis of acute coronary syndrome (ACS) was made in 25%. Fifteen had typical cardiac chest pain with a negative cTnI: 6 of these had an exercise treadmill test before discharge. Nine had a positive cTnI, but only two had coronary angiography. Of patients with negative cTnI and possible ACS, 84% were in hospital for >4 days. DISCUSSION: The introduction of troponin assays into widespread use requires careful assessment. cTnI requests and subsequent patient management remain below expected standards. Ideally, the laboratory should provide an accurate result within a reasonable time frame, while physicians need to request cTnI at a suitable time-point and use the result appropriately. Lessons from the introduction of cTnI measurement may be useful for the introduction of future new tests in other areas of cardiology and medicine.
Assuntos
Dor no Peito/diagnóstico , Doença das Coronárias/diagnóstico , Troponina I/sangue , Biomarcadores/sangue , Diagnóstico Diferencial , Humanos , Valor Preditivo dos Testes , Medição de Risco , SíndromeRESUMO
BACKGROUND: The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown. METHODS: We conducted a prospective cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis (CVD) compared with a matched group without AF (n = 26,753), randomly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF. Stroke rates were also determined in another cohort free of CVD (n = 14,267). Total medical costs after hospitalization were available from a 1991 cohort. Cumulative mortality, stroke rates, and costs following index admission were adjusted by multivariate and proportional hazard regression analyses. RESULTS: Mortality rates were high in individuals with CVD, ranging from 19.0% to 52.1% in 1 year. Adjusted relative mortality risk was approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P < .05). Incidence of stroke was high in individuals with CVD, 6.2% to 15.4% in 1 year, with and without AF, and was at least 5-fold higher than in individuals without CVD. In those with CVD, stroke rates were approximately 25% higher in women with AF (P < .05) but only 10% higher in men. Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men, and 9.8- to 11.2-fold greater in women with AF (P < .05). Second- and third-year costs were increased as well. CONCLUSION: Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs.
Assuntos
Fibrilação Atrial/complicações , Fibrilação Atrial/economia , Fibrilação Atrial/mortalidade , Transtornos Cerebrovasculares/etiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/terapia , Humanos , Análise dos Mínimos Quadrados , Medicare , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Distribuição por Sexo , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVES: Nitric oxide (NO) has complex effects on myocardial function particularly following ischaemia-reperfusion. The goal of this study was to examine the result of repetitive myocardial stunning on myocardial NO release and expression of inducible (iNOS) and constitutive (eNOS) NO synthases. METHODS AND RESULTS: Propofol anaesthetised pigs underwent ten, 2-min episodes of circumflex artery occlusion (n = 6) or acted as sham operated controls (n = 4). Measurements of segment shortening demonstrated a fall in function in the ischaemic territory to 52.5 +/- 7.3% (mean +/- S.E.M.) of baseline shortening 30 min after the stunning stimulus, recovering to 92 +/- 8.7% 5.5 h later. Function remained stable in sham controls. The change in venous-arterial [NO] between baseline and 6 h reperfusion was found to be significantly different between the two groups (0.2 +/- 0.7 in stunned vs. -4.3 +/- 1.6 microM in shams; P < 0.02). Western blotting and band optical density used to compare tissue from stunned territory (S), non-stunned territory (IC) and sham control animals (SC) demonstrated this was associated with an increase in the expression of both iNOS (S: 93 +/- 13.4, IC: 37 +/- 2.4 and SC: 25 +/- 4 [arbitrary units], P < 0.01 and P = 0.031) and eNOS (S: 104 +/- 7.4, IC; 62.5 +/- 7.4 and SC; 75.7 +/- 0.6, P < 0.03 and P < 0.01) in stunned myocardium. Immunocytochemistry localised iNOS reactivity to vascular smooth muscle cells and cardiomyocytes in stunned tissue and eNOS reactivity to endothelial cells. CONCLUSION: Recovery from repetitive myocardial stunning is associated with the increased expression of both iNOS and eNOS and would be compatible with a protective role for both these enzymes. This finding has possible relevance for both the late window of ischaemic preconditioning and myocardial hibernation.
Assuntos
Miocárdio Atordoado/enzimologia , Miocárdio/enzimologia , Óxido Nítrico Sintase/metabolismo , Animais , Western Blotting , Densitometria , Endotélio Vascular/enzimologia , Feminino , Imuno-Histoquímica , Masculino , Músculo Liso Vascular/enzimologia , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Recidiva , SuínosRESUMO
Fidelity to migratory destinations is an important driver of connectivity in marine and avian species. Here we assess the role of maternally directed learning of migratory habitats, or migratory culture, on the population structure of the endangered Australian and New Zealand southern right whale. Using DNA profiles, comprising mitochondrial DNA (mtDNA) haplotypes (500 bp), microsatellite genotypes (17 loci) and sex from 128 individually-identified whales, we find significant differentiation among winter calving grounds based on both mtDNA haplotype (FST = 0.048, ΦST = 0.109, p < 0.01) and microsatellite allele frequencies (FST = 0.008, p < 0.01), consistent with long-term fidelity to calving areas. However, most genetic comparisons of calving grounds and migratory corridors were not significant, supporting the idea that whales from different calving grounds mix in migratory corridors. Furthermore, we find a significant relationship between δ(13)C stable isotope profiles of 66 Australian southern right whales, a proxy for feeding ground location, and both mtDNA haplotypes and kinship inferred from microsatellite-based estimators of relatedness. This indicates migratory culture may influence genetic structure on feeding grounds. This fidelity to migratory destinations is likely to influence population recovery, as long-term estimates of historical abundance derived from estimates of genetic diversity indicate the South Pacific calving grounds remain at <10% of pre-whaling abundance.
Assuntos
Migração Animal , Variação Genética , Genética Populacional , Baleias/genética , Animais , Austrália , DNA Mitocondrial/genética , Haplótipos , Nova ZelândiaRESUMO
Human leukocyte antigen (HLA) associations have been reported in Amerindian patients with actinic prurigo. To determine if similar associations are present in the British Caucasoid population with actinic prurigo, 26 patients underwent serological typing for HLC Class I and II antigens. DNA analysis by both sequence-specific priming and group-specific amplification with single-stranded oligonucleotide probe hybridization was used to confirm the DR and DQ typing and to perform DR4 subtyping. All patients were DR4 positive, and 25 of 26 patients were DQ7 positive. DR4 subtyping revealed 12 of 20 patients tested to be DRB1*0407. A nonsignificant association was also found with HLA B55 that is in linkage disequilibrium with DRB1*0407. No HLA associations were found in 25 British Caucasoid patients with polymorphic light eruption. DRB1*0407 is rare in European Caucasoids without actinic prurigo, and HLA-DR4 may have an important role in determining expression of this disease.