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PURPOSE: Accurate discrimination of benign and pathogenic rare variation remains a priority for clinical genome interpretation. State-of-the-art machine learning variant prioritization tools are imprecise and ignore important parameters defining gene-disease relationships, e.g., distinct consequences of gain-of-function versus loss-of-function variants. We hypothesized that incorporating disease-specific information would improve tool performance. METHODS: We developed a disease-specific variant classifier, CardioBoost, that estimates the probability of pathogenicity for rare missense variants in inherited cardiomyopathies and arrhythmias. We assessed CardioBoost's ability to discriminate known pathogenic from benign variants, prioritize disease-associated variants, and stratify patient outcomes. RESULTS: CardioBoost has high global discrimination accuracy (precision recall area under the curve [AUC] 0.91 for cardiomyopathies; 0.96 for arrhythmias), outperforming existing tools (4-24% improvement). CardioBoost obtains excellent accuracy (cardiomyopathies 90.2%; arrhythmias 91.9%) for variants classified with >90% confidence, and increases the proportion of variants classified with high confidence more than twofold compared with existing tools. Variants classified as disease-causing are associated with both disease status and clinical severity, including a 21% increased risk (95% confidence interval [CI] 11-29%) of severe adverse outcomes by age 60 in patients with hypertrophic cardiomyopathy. CONCLUSIONS: A disease-specific variant classifier outperforms state-of-the-art genome-wide tools for rare missense variants in inherited cardiac conditions ( https://www.cardiodb.org/cardioboost/ ), highlighting broad opportunities for improved pathogenicity prediction through disease specificity.
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Cardiomiopatías , Mutación Missense , Algoritmos , Área Bajo la Curva , Cardiomiopatías/diagnóstico , Cardiomiopatías/genética , Humanos , Persona de Mediana Edad , Mutación Missense/genética , VirulenciaRESUMEN
This paper is a case report of a 22 year old, previously healthy woman that presented comatose to the Emergency Room at Landspitali University Hospital Iceland. A CT image of the head on admission revealed a large right cerebellar infarct with oedema compressing the fourth ventricle. A CT angiogram on admission was suspicious for a dissection of the left vertebral artery (confirmed during endovascular treatment) and a total occlusion of the distal third of the basilar artery. Thrombolytic therapy with t-PA was initiated followed by thrombectomy with good recanalization. The following day the patient underwent suboccipital craniotomy for malignant cerebellar infarction. She made a good clinical recovery to a modified Ranking scale of 1 at 90 days after discharge from the hospital. Following the case is a literature review on the clinical aspects of occlusion of the vertebrobasilar system, use and utility of imaging and treatment with (anticoagulation, IV and IA thrombolysis) modalities that have been tried. Finally, the evidence regarding thrombectomy and the role of craniotomy for malignant stroke are reviewed.
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Infarto Cerebral/terapia , Fibrinolíticos/administración & dosificación , Trombectomía , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/etiología , Craneotomía , Femenino , Humanos , Resultado del Tratamiento , Insuficiencia Vertebrobasilar/complicaciones , Insuficiencia Vertebrobasilar/diagnóstico por imagen , Insuficiencia Vertebrobasilar/terapia , Adulto JovenAsunto(s)
Hipertensión , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: The geographic isolation and homogeneous population of Iceland are ideally suited to ascertain clinical and genetic characteristics of hypertrophic cardiomyopathy (HCM) at the population level. METHODS AND RESULTS: Medical records and cardiac imaging studies obtained between 1997 and 2010 were reviewed to identify Icelandic patients with HCM. Surviving patients were recruited for clinical and genetic studies. A previously identified Icelandic mutation, MYBPC3 c.927-2A>G, was genotyped, and mutation-negative samples were sequenced for HCM genes and other hypertrophic genes. Record review identified 180 patients with HCM. Genetic analyses of 151 patients defined pathogenic mutations in 101 (67%), including MYBPC3 c.927-2A>G (88 patients, 58%), 4 other MYBPC3 or MYH7 mutations (5 patients, 3.3%), and 2 GLA mutations (8 patients, 5.3%). Haplotype and genetic genealogical data defined MYBPC3 c.927-2A>G as a founder mutation, introduced into the Icelandic population in the 15th century, with a current population prevalence of 0.36%. MYBPC3 c.927-2A>G mutation carriers exhibited phenotypic diversity but were younger at diagnosis (42 versus 49 years; P=0.001) and sustained more adverse events (15% versus 2%; P=0.02) than mutation-negative patients. All-cause mortality for patients with HCM was similar to that of an age-matched Icelandic population (hazard ratio, 0.98; P=0.9). HCM-related mortality (0.78%/y) occurred at a mean age of 68 compared with 81 years for non-HCM-related mortality (P=0.02). CONCLUSIONS: A founder MYBPC3 mutation that arose >550 years ago is the predominant cause of HCM in Iceland. The MYBPC3 c.927-2A>G mutation is associated with low adverse event rates but earlier cardiovascular mortality, illustrating the impact of genotype on outcomes in HCM.
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Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/mortalidad , Proteínas Portadoras/genética , Efecto Fundador , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Haplotipos , Humanos , Islandia/epidemiología , Masculino , Persona de Mediana Edad , Fenotipo , Prevalencia , Adulto JovenRESUMEN
Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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Antivirales/farmacología , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/virología , Mutación Missense , Neuraminidasa/aislamiento & purificación , Oseltamivir/farmacología , Proteínas Virales/aislamiento & purificación , Sustitución de Aminoácidos , Animales , Patos , Heces/virología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Proteínas Mutantes/genética , Neuraminidasa/genética , Selección Genética , Proteínas Virales/genéticaRESUMEN
Harvesting geothermal energy often leads to a pressure drop in reservoirs, decreasing their profitability and promoting the formation of steam caps. While steam caps are valuable energy resources, they also alter the reservoir thermodynamics. Accurately measuring the steam fraction in reservoirs is essential for both operational and economic perspectives. However, steam content estimations are very limited both in space and time since current methods rely on direct measurements within production wells. Besides, these estimations normally present large uncertainties. Here, we present a pioneering method for indirectly sampling the steam content in the subsurface using the ever-present seismic background noise. We observe a consistent annual velocity drop in the Hengill geothermal field (Iceland) and establish a correlation between the velocity drop and steam buildup using in-situ borehole data. This application opens new avenues to track the evolution of any gas reservoir in the crust with a surface-based and cost-effective method.
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BACKGROUND: Current treatment of herpes labialis is usually with topical antiviral drugs and early drug administration is required for effectiveness. Monocaprin, a 1-monoglyceride of capric acid, has high microbicidal activity in vitro and efficiently inactivates herpes simplex virus. Tetracyclines are inhibitors of matrix metalloproteinases that are part of the inflammatory response and contribute to the breakdown of tissue in ulcers. The study objective was to investigate the antiviral and wound-healing effect of a hydrogel containing either monocaprin or a combination of monocaprin and a low dose of doxycycline in vivo against herpes labialis. METHODS: Subjects were divided into two groups: (i) with prodromal symptoms of herpes labialis; (ii) with a vesicle. Both groups applied the hydrogel five times a day for five days. Test formulations were: (i) hydrogel containing monocaprin and doxycycline (MCD), (ii) hydrogel containing only monocaprin and (iii) placebo hydrogel. Formulations were distributed randomly to subjects within each group. Subjects recorded treatment results in a 6-day diary and a 7-day follow-up diary. RESULTS: For the MCD group the mean time to healing was 5.5 days (prodromal) and 5.3 days (vesicles/ulceration) or significantly shorter than for the placebo groups (7.25 and 7.5 days respectively; P < 0.05). Pain relief was significantly more with MCD (combining both the prodromal and vesicle groups) than with the monocaprin and placebo groups (P = 0.0114). CONCLUSION: Combining monocaprin with low-dose doxycycline offers an effective treatment for herpes labialiss, significantly reducing time to healing and pain compared with the placebo and monocaprin alone.
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Antivirales/uso terapéutico , Doxiciclina/uso terapéutico , Glicéridos/uso terapéutico , Herpes Labial/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antivirales/administración & dosificación , Vesícula/tratamiento farmacológico , Método Doble Ciego , Doxiciclina/administración & dosificación , Portadores de Fármacos , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Glicéridos/administración & dosificación , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato , Masculino , Inhibidores de la Metaloproteinasa de la Matriz , Registros Médicos , Persona de Mediana Edad , Dimensión del Dolor , Placebos , Simplexvirus/efectos de los fármacos , Estomatitis Aftosa/tratamiento farmacológico , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacos , Adulto JovenRESUMEN
OBJECTIVES: To study the association between Medicare's wage index adjustment and the differential use of labor-intensive surgical procedures and medical device-intensive minimally invasive clinical procedures across the United States. STUDY DESIGN: We combine a conceptual model and an empirical investigation of its predictions, applied to aortic valve replacement, to study the relationship between variation in Medicare wage index payment adjustment across hospital referral regions (HRRs) and the utilization of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in these areas. METHODS: Using detailed individual Medicare claims data for 2013-2018 and a novel geographical crosswalk to nest information on Medicare's wage index and utilization of TAVR and SAVR, we estimate a mixed effects Poisson regression model across HRRs to test our hypotheses. RESULTS: We find regional variation in Medicare wage index adjustment levels to be correlated with differential TAVR and SAVR utilization and growth over time. In particular, in HRRs where the wage index is half the national mean there is a 35% decline in the rate of TAVR use and in HRRs where the wage index is 50% higher than the national mean there is a 52% increase in the rate of TAVR use. CONCLUSIONS: Consistent with our framework and hypothesis, our results highlight the importance of adjusting Medicare hospital inpatient payments for device-intensive procedures. Absent such adjustment, access to appropriate interventions may be reduced in areas with low wage index, and lower reimbursement, when driven by wage index adjustment, may influence the treatment approach selected.
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Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Estenosis de la Válvula Aórtica/cirugía , Hospitales , Humanos , Medicare , Factores de Riesgo , Resultado del Tratamiento , Estados UnidosRESUMEN
Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.
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Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Mieloma Múltiple/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Islandia/epidemiología , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/epidemiología , Mieloma Múltiple/epidemiología , Mieloma Múltiple/prevención & control , Factores de RiesgoRESUMEN
Objective: The myosin-binding protein C (MYBPC3) c.927-2A>G founder mutation accounts for >90% of sarcomeric hypertrophic cardiomyopathy (HCM) in Iceland. This cross-sectional observational study explored the penetrance and phenotypic burden among carriers of this single, prevalent founder mutation. Methods: We studied 60 probands with HCM caused by MYBPC3 c.927-2A>G and 225 first-degree relatives. All participants underwent comprehensive clinical evaluation and relatives were genotyped. Results: Genetic and clinical evaluation of relatives identified 49 genotype-positive (G+) relatives with left ventricular hypertrophy (G+/LVH+), 59 G+without LVH (G+/LVH-) and 117 genotype-negative relatives (unaffected). Compared with HCM probands, G+/LVH+ relatives were older at HCM diagnosis, had less LVH, a less prevalent diastolic dysfunction, fewer ECG abnormalities, lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I levels, and fewer symptoms. The penetrance of HCM was influenced by age and sex; specifically, LVH was present in 39% of G+males but only 9% of G+females under age 40 years (p=0.015), versus 86% and 83%, respectively, after age 60 (p=0.89). G+/LVH- subjects had normal wall thicknesses, diastolic function and NT-proBNP levels, but subtle changes in LV geometry and more ECG abnormalities than their unaffected relatives. Conclusions: Phenotypic expression of the Icelandic MYBPC3 founder mutation varies by age, sex and proband status. Men are more likely to have LVH at a younger age, and disease manifestations were more prominent in probands than in relatives identified via family screening. G+/LVH- individuals had subtle clinical differences from unaffected relatives well into adulthood, indicating subclinical phenotypic expression of the pathogenic mutation.
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Cardiomiopatía Hipertrófica/genética , Proteínas Portadoras/genética , Efecto Fundador , Heterocigoto , Mutación , Sarcómeros/genética , Función Ventricular Izquierda/genética , Remodelación Ventricular/genética , Adulto , Edad de Inicio , Anciano , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Hemodinámica/genética , Herencia , Humanos , Islandia , Masculino , Persona de Mediana Edad , Linaje , Penetrancia , Fenotipo , Factores de RiesgoRESUMEN
The natural reservoir of influenza A virus is waterfowl, particularly dabbling ducks (genus Anas). Although it has long been assumed that waterfowl are asymptomatic carriers of the virus, a recent study found that low-pathogenic avian influenza (LPAI) infection in Bewick's swans (Cygnus columbianus bewickii) negatively affected stopover time, body mass and feeding behaviour. In the present study, we investigated whether LPAI infection incurred ecological or physiological costs to migratory mallards (Anas platyrhynchos) in terms of body mass loss and staging time, and whether such costs could influence the likelihood for long-distance dispersal of the avian influenza virus by individual ducks. During the autumn migrations of 2002-2007, we collected faecal samples (n=10918) and biometric data from mallards captured and banded at Ottenby, a major staging site in a flyway connecting breeding and wintering areas of European waterfowl. Body mass was significantly lower in infected ducks than in uninfected ducks (mean difference almost 20 g over all groups), and the amount of virus shed by infected juveniles was negatively correlated with body mass. There was no general effect of infection on staging time, except for juveniles in September, in which birds that shed fewer viruses stayed shorter than birds that shed more viruses. LPAI infection did not affect speed or distance of subsequent migration. The data from recaptured individuals showed that the maximum duration of infection was on average 8.3 days (s.e. 0.5), with a mean minimum duration of virus shedding of only 3.1 days (s.e. 0.1). Shedding time decreased during the season, suggesting that mallards acquire transient immunity for LPAI infection. In conclusion, deteriorated body mass following infection was detected, but it remains to be seen whether this has more long-term fitness effects. The short virus shedding time suggests that individual mallards are less likely to spread the virus at continental or intercontinental scales.
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Migración Animal , Patos , Virus de la Influenza A , Gripe Aviar/virología , Animales , Gripe Aviar/epidemiología , Prevalencia , Factores de Tiempo , Esparcimiento de VirusRESUMEN
Commitment to the melanocyte lineage is characterized by the onset of expression of the microphthalmia-associated transcription factor (Mitf). This transcription factor plays a fundamental role in melanocyte development and maintenance and seems to be crucial for the survival of malignant melanocytes. Furthermore, Mitf has been shown to be involved in cell cycle regulation and to play important functions in self-renewal and maintenance of melanocyte stem cells. Although little is known about how Mitf regulates these various processes, one possibility is that Mitf interacts with other regulators. Here we show that Mitf can interact directly with beta-catenin, the key mediator of the canonical Wnt signaling pathway. The Wnt signaling pathway plays a critical role in melanocyte development and is intimately involved in triggering melanocyte stem cell proliferation. Significantly, constitutive activation of this pathway is a feature of a number of cancers including malignant melanoma. Here we show that Mitf can redirect beta-catenin transcriptional activity away from canonical Wnt signaling-regulated genes toward Mitf-specific target promoters to activate transcription. Thus, by a feedback mechanism, Mitf can diversify the output of canonical Wnt signaling to enhance the repertoire of genes regulated by beta-catenin. Our results reveal a novel mechanism by which Wnt signaling and beta-catenin activate gene expression, with significant implications for our understanding of both melanocyte development and melanoma.
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Expresión Génica , Factor de Transcripción Asociado a Microftalmía/metabolismo , beta Catenina/metabolismo , Secuencia de Aminoácidos , Animales , Células COS , Línea Celular , Linaje de la Célula , Proliferación Celular , Chlorocebus aethiops , Genes Reporteros , Glutatión Transferasa/metabolismo , Proteínas Fluorescentes Verdes/genética , Humanos , Luciferasas/análisis , Luciferasas/metabolismo , Melanocitos/metabolismo , Factor de Transcripción Asociado a Microftalmía/química , Factor de Transcripción Asociado a Microftalmía/genética , Modelos Biológicos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/metabolismo , Homología de Secuencia de Aminoácido , Transducción de Señal , Transcripción Genética , Transfección , Proteínas Wnt/metabolismo , beta Catenina/químicaAsunto(s)
Ligamiento Genético , Programas Informáticos , Marcadores Genéticos/genética , Humanos , LinajeRESUMEN
Global measures of biodiversity indicate consistent decline, but trends reported for local communities are more varied. Therefore, we need better understanding of mechanisms that drive changes in diversity of local communities and of differences in temporal trends between components of local diversity, such as species richness and species turnover rate. Freshwater ecosystems are vulnerable to multiple stressors, and severe impacts on their biodiversity have been documented. We studied species richness and composition of local boreal waterbird communities in 1990/1991 and 2016 at 58 lakes distributed over six regions in Finland and Sweden. The study lakes represented not only local trophic gradients but also a latitudinal gradient in the boreal biome. While species richness tended to be lower in 2016 than in 1990/1991, species turnover was relatively high. Within foraging guilds, local species richness of diving ducks and surface feeding waterbirds decreased, whereas that of large herbivores increased. The number of species gained in local communities was higher in lakes with rich vegetation than in lakes with sparse vegetation. Conservation of boreal freshwater ecosystems would benefit from recognizing that large-scale environmental changes can affect local diversity via processes operating at finer scales.
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Biodiversidad , Aves , Ecosistema , Lagos , Animales , Ambiente , Finlandia , Modelos Teóricos , Suecia , Factores de TiempoRESUMEN
BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B). METHODS AND RESULTS: Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, α-galactosidase A (α-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations. CONCLUSIONS: Men with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities.
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Cardiomiopatía Hipertrófica/diagnóstico , Enfermedad de Fabry/diagnóstico , Adolescente , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/genética , Niño , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/genética , Femenino , Genotipo , Heterocigoto , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico , Enfermedades de Inicio Tardío , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Fenotipo , Adulto Joven , alfa-Galactosidasa/genéticaRESUMEN
INTRODUCTION: ST-segment Elevation Myocardial Infarction (STEMI) is a life-threatening disease and good outcome depends on early restoration of coronary blood flow. Primary percutaneous coronary intervention (PPCI) is the treatment of choice if performed within 120 minutes of first medical contact (FMC) but in case of anticipated long transport or delays, pre-hospital fibrinolysis is indicated. The aim was to study transport times and adherence to clinical guidelines in patients with STEMI transported from outside of the Reykjavik area to Landspitali University Hospital in Iceland. MATERIALS AND METHODS: Retrospective chart review was conducted of all patients diagnosed with STEMI outside of the Reykjavik area and transported to Landspitali University Hospital in Reykjavik in 2011-2012. Descriptive statistical analysis and hypothesis testing was applied. RESULTS: Eighty-six patients had signs of STEMI on electrocardiogram (ECG) at FMC. In southern Iceland nine patients (21%) underwent PPCI within 120 minutes (median 157 minutes) and no patient received fibrinolysis. In northern Iceland and The Vestman Islands, where long transport times are expected, 96% of patients eligible for fibrinolysis (n=31) received appropriate therapy in a median time of 57 minutes. Significantly fewer patients received appropriate anticoagulation treatment with clopidogrel and enoxaparin in southern Iceland compared to the northern part. Mortality rate was 7% and median length of stay in hospital was 6 days. CONCLUSIONS: Time from FMC to PPCI is longer than 120 minutes in the majority of cases. Pre-hospital fibrinolysis should be considered as first line treatment in all parts of Iceland outside of the Reykjavik area. Directly electronically transmitted ECGs and contact with cardiologist could hasten diagnosis and decrease risk of unnecessary interhospital transfer. A STEMI database should be established in Iceland to facilitate quality control.
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Atención a la Salud/organización & administración , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea , Servicios de Salud Rural/organización & administración , Tiempo de Tratamiento/organización & administración , Transporte de Pacientes/organización & administración , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Electrocardiografía , Servicios Médicos de Urgencia/organización & administración , Femenino , Adhesión a Directriz , Hospitales Universitarios , Humanos , Islandia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Terapia Trombolítica , Factores de Tiempo , Resultado del TratamientoRESUMEN
The last decade has seen a surge in research on avian influenza A viruses (IAVs), in part fuelled by the emergence, spread and potential zoonotic importance of highly pathogenic virus subtypes. The mallard (Anas platyrhynchos) is the most numerous and widespread dabbling duck in the world, and one of the most important natural hosts for studying IAV transmission dynamics. In order to predict the likelihood of IAV transmission between individual ducks and to other hosts, as well as between geographical regions, it is important to understand how IAV infection affects the host. In this study, we analysed the movements of 40 mallards equipped with GPS transmitters and three-dimensional accelerometers, of which 20 were naturally infected with low pathogenic avian influenza virus (LPAIV), at a major stopover site in the Northwest European flyway. Movements differed substantially between day and night, as well as between mallards returning to the capture site and those feeding in natural habitats. However, movement patterns did not differ between LPAIV infected and uninfected birds. Hence, LPAIV infection probably does not affect mallard movements during stopover, with high possibility of virus spread along the migration route as a consequence.
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BACKGROUND: Acute bacterial cellulitis is a potentially serious infection that commonly recurs. The identification of preventable risk factors could reduce infection-related morbidity and cost and improve patient management. The aim of this study was to identify the risk factors associated with lower-limb cellulitis, including both analysis of risk factors associated with cellulitis in either limb and risk factors in a single limb associated with cellulitis in the same limb. We placed particular emphasis on dermatophytic infections of the foot and bacterial infection and colonization of the toe webs. METHODS: We conducted a prospective case-control study of 100 subjects with cellulitis and 200 control subjects, matched for age and sex, who were admitted to a university hospital during the period October 2000-February 2004. Data were obtained with a questionnaire and from examination of lower limbs and microbiological analyses of samples from the feet. RESULTS: The median age of the participants was 66.5 years (interquartile range, 48.8-77.0). The following risk factors were strongly and independently associated with cellulitis: previous history of cellulitis (OR, 31.04; 95% CI, 4.15-232.20), the presence of Staphylococcus aureus and/or beta -hemolytic streptococci in the toe webs (OR, 28.97; 95% CI, 5.47-153.48), presence of leg erosions or ulcers (OR, 11.80; 95% CI, 2.47-56.33), and prior saphenectomy (OR, 8.49; 95% CI, 1.62-44.52). Tinea pedis interdigitalis was associated with cellulitis only when toe web bacteria were excluded from the analysis (OR, 3.86; 95% CI, 1.32-11.27). CONCLUSIONS: Risk factors for acute bacterial cellulitis in hospitalized patients include predisposing factors and the presence of sites of pathogen entry on legs and toe webs. These findings indicate that improved awareness and management of toe web intertrigo, which may harbor bacterial pathogens, and other skin lesions might reduce the incidence of cellulitis.