Most causal variants of Mendelian diseases are exonic. Whole‐exome sequencing (WES) has become the diagnostic gold standard, but causative variant prioritization constitutes a bottleneck. Here we ...assessed an in‐house sample‐to‐sequence pipeline and benchmarked free prioritization tools for germline causal variants from WES data. WES of 61 unselected patients with a known genetic disease cause was obtained. Variant prioritizations were performed by diverse tools and recorded to obtain a diagnostic yield when the causal variant was present in the first, fifth, and 10th top rankings. A fraction of causal variants was not captured by WES (8.2%) or did not pass the quality control criteria (13.1%). Most of the applications inspected were unavailable or had technical limitations, leaving nine tools for complete evaluation. Exomiser performed best in the top first rankings, while LIRICAL led in the top fifth rankings. Based on the more conservative top 10th rankings, Xrare had the highest diagnostic yield, followed by a three‐way tie among Exomiser, LIRICAL, and PhenIX, then followed by AMELIE, TAPES, Phen‐Gen, AIVar, and VarNote‐PAT. Xrare, Exomiser, LIRICAL, and PhenIX are the most efficient options for variant prioritization in real patient WES data.
Terrestrial gamma absorbed dose rates as well as spatial distribution of gamma-emitting radionuclides 40K, 226Ra and 232Th and 137Cs in soils, are provided in detail for the first time in the Western ...Canary Islands.
The distribution of terrestrial gamma absorbed dose rates and the activity concentrations of 40K, 226Ra and 232Th are discussed with respect to the main lithologies and geological features of each island. The average terrestrial absorbed dose rate (71.4 nGy·h−1) reported here was slightly higher to previously reported values for the Eastern islands of this archipelago (43 nGy·h−1) and close to the world's average (59 nGy·h−1).
Relatively high 137Cs activity concentrations, up to 100 Bq·kg−1, were measured in some of the collected samples. To understand the origin of these activities, we compared the results from two different field surveys performed in 1991 and in 2013. The activity concentrations were found to be rather similar despite the 22 years gap between the measurements. Complementary radiometric data from aerosol samples collected at this site show that there are additional contributions of 137Cs to this site produced by the deposition of dust particles brought by Saharan dust storms.
In terms of radiological risk, the gamma absorbed doses reported (external exposure) pose no risk to the local population. However, the contribution of the soil 137Cs activity concentrations to the gamma absorbed dose were as high as 50% in some few locations.
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•The spatial distribution of gamma radionuclides in 4 volcanic islands was determined.•Natural radionuclides in soils were compared against the main geological features.•137Cs in collected soil samples was compared with other sites in Europe.•137Cs has not decreased in a period of 22 years due to African dust intrusions.•Absorbed doses were linked with the concentrations of gamma radionuclides in soils.
Complete mitogenome in a population sample from Cameroon Olaechea-Lázaro, Sonia; García, Óscar; González-Montelongo, Rafaela ...
Forensic science international : genetics,
November 2021, 2021-11-00, 20211101, Letnik:
55
Journal Article
Hereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. ...Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis. Consequently, a delay in the diagnosis, and inaccurate or incomplete diagnosis and treatment of hereditary angioedema are common.
In agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of Hereditary Angioedema, to facilitate the clinical diagnosis and adapt it to the paradigm of precision medicine and next-generation sequencing-based genetic tests, we aimed to develop a genetic annotation tool, termed Hereditary Angioedema Database Annotation (HADA).
HADA is built on top of a database of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics.
HADA is provided as a freely accessible, user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can also be incorporated into automated command-line stand-alone annotation tools.
HADA can achieve the rapid detection of variants affecting function for different hereditary angioedema types, and further integrates useful information to reduce the diagnosis odyssey and improve its delay.
From February 22 to 24, 2020, an intense dust storm affected the Spanish archipelago of the Canary Islands. Here we assess the radiological impact on the Canary Islands population of several natural ...and artificial radionuclides (40K, 137Cs, 210Pb, 7Be), and other radiological parameters (gross alpha and gross beta activity concentrations) measured in atmospheric aerosols before, during and after the dust storm.
Total Suspended Matter highly correlated with PM10 (Pearson's correlation coefficient, ro = 0.98), showed increments ranging from 849% to 1778% against the background average levels, reaching levels of >3000 μg m−3.
40K and 137Cs radionuclides showed activity values over the minimum detection activity from January to March 2020, coupled with dust intrusion episodes during the study. This finding supports the use of these radionuclides as radiotracers for African low altitude dust intrusions occurring particularly during winter months over the Canary Islands.
A high correlation between gross beta and 210Pb activities suggests that the latter is the main source for gross beta emitters in aerosol samples collected in the study region. 210Pb and 7Be showed a moderate positive correlation and did not show any significant change during the storm, suggesting a similar dynamics of alpha and beta emitters in the low atmosphere.
A Principal Component Analysis of these observations showed two components representing a Saharan component (based on 40K, 137Cs, gross alpha, and PM10) and a heterogeneous component representing North Atlantic and Europe air masses (based on 7Be, 210Pb, and gross beta).
In addition, a K-means cluster analysis helped to disentangle the origin of air masses arriving at the archipelago. Three different clusters were identified: a continental cluster (based on gross beta, 210Pb, and 7Be activity concentrations); an oceanic cluster (with low values of PM10 air concentrations, gross beta, gross alpha, and 210Pb, and 7Be and 40K activity concentrations), reflecting the Atlantic air contributions with lower radionuclide activity and microparticulate matter; and a dust intrusion cluster (with high PM10 values and 137Cs, 40K and gross alpha activity concentrations) representing dust intrusion episodes observed in Tenerife Island. These studies allow the detection and monitoring of radioactive elements, estimating the potential radiological risk to the population associated with mineral dust intrusions.
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•On February 2020, an intense dust storm struck the Canary Islands archipelago.•PM10 air concentration reached levels of >3000 μg m−3.•Gross alpha, 137Cs and 40K showed higher values during such a dust storm.•PCA identified two main components that explain 81% of the total variance.•Three clusters are identified with Oceanic, Continental and Saharan origins.
Several variants of concern (VOCs) explain most of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic waves in Europe. We aimed to dissect the spread of the SARS-CoV-2 VOCs in ...the Canary Islands (Spain) between December 2020 and September 2021 at a micro-geographical level. We sequenced the viral genome of 8,224 respiratory samples collected in the archipelago. We observed that Alpha (B.1.1.7) and Delta (B.1.617.2 and sublineages) were ubiquitously present in the islands, while Beta (B.1.351) and Gamma (P.1/P.1.1) had a heterogeneous distribution and were responsible for fewer and more controlled outbreaks. This work represents the largest effort for viral genomic surveillance in the Canary Islands so far, helping the public health bodies in decision-making throughout the pandemic.
RESUMEN Se presenta la segunda parte de las recomendaciones latinoamericanas para el manejo de la Hipertensión Arterial (HTA) en adultos. En una primera fase se han descripto los aspectos más ...relevantes de la epidemiología, aspectos fisiopatológicos, cómo hacer diagnóstico, pautas terapéuticas, urgencias y emergencias hipertensivas, poblaciones especiales, hipertensión refractaria y la aplicación de las guías en la vida real. En esta segunda parte, se emiten recomendaciones respondiendo a preguntas específicas para prevención primaria, secundaria, terciaria y cuaternaria. En general pocas recomendaciones al respecto del manejo de la hipertensión arterial surgen desde la clínica médica/ medicina interna, a pesar de dos situaciones: la mayoría de los pacientes con hipertensión arterial son evaluados y manejados por los clínicos, y la clínica médica es la especialidad que permite la mirada holística e integrada de los problemas de salud del adulto, permitiendo agregar el enfoque biográfico al biológico, comprender e interpretar no solo el problema de salud sino sus causas y consecuencias (que muchas veces suelen corresponder a diferentes parénquimas, lo cual en el modelo fragmentado haría transitar al paciente por distintas especialidades). El bajo porcentaje de pacientes hipertensos controlados obliga a todos los profesionales involucrados en el manejo de los mismos a optimizar recursos y detectar problemas que se asocien a un control deficitario como la sub utilización del tratamiento farmacológico, baja tasa de pacientes tratados con estrategia combinada (la mayoría de los pacientes actualmente recibe monoterapia), falta de prescripción adecuada de los cambios en el estilo de vida, baja adherencia terapéutica e inercia clínica. En la presente publicación se presentan recomendaciones efectuadas por especialistas en clínica médica / medicina interna para el manejo de la hipertensión arterial en adultos, respondiendo preguntas de prevención primaria, secundaria, terciaria, y cuaternaria.
Cardiovascular diseases (CVD), mainly ischemic heart disease and stroke, is the main cause of death worldwide and each year more people die from CVD than from any other cause. These data call for a ...paradigm shift, where health promotion and cardiovascular prevention will acquire a central role in health policies. From this perspective, dedicating time during the consultation to promoting the acquisition of heart-healthy habits would be indicated in all individuals, regardless of cardiovascular risk classification, the role of the internist being fundamental. This position document from the International Forum of Internal Medicine (FIMI) presents the main indications regarding changes in lifestyle and acquisition of healthy habits to prevent CVD. The different sections will address topics including: nutrition, physical activity, sedentary lifestyle, obesity, smoking, alcohol consumption, sleep, stress, environmental problems related to CVD and specific conditions in women. A section is included about starting CVD promotion and prevention measures at an early age, childhood and adolescence, also mentioning epigenetic aspects related to CVD. Social determinants in CVD are also taken into account, since some of these aspects, such as low socioeconomic level, modify cardiovascular risk and should be taken into account.
Cardiovascular diseases (CVD), mainly ischemic heart disease and stroke, is the main cause of death worldwide and each year more people die from CVD than from any other cause. These data call for a ...paradigm shift, where health promotion and cardiovascular prevention will acquire a central role in health policies. From this perspective, dedicating time during the consultation to promoting the acquisition of heart-healthy habits would be indicated in all individuals, regardless of cardiovascular risk classification, the role of the internist being fundamental. This position document from the International Forum of Internal Medicine (FIMI) presents the main indications regarding changes in lifestyle and acquisition of healthy habits to prevent CVD. The different sections will address topics including: nutrition, physical activity, sedentary lifestyle, obesity, smoking, alcohol consumption, sleep, stress, environmental problems related to CVD and specific conditions in women. A section is included about starting CVD promotion and prevention measures at an early age, childhood and adolescence, also mentioning epigenetic aspects related to CVD. Social determinants in CVD are also taken into account, since some of these aspects, such as low socioeconomic level, modify cardiovascular risk and should be taken into account.
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