Familial hypercholesterolemia: Molecular characterization of possible cases from the Azores Islands (Portugal)

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of the cholesterol metabolism, which constitutes a risk factor for coronary arterial disease (CAD). In the Azores Islands (Portugal), where mortality from CAD doubles its rate comparatively to the rest of the country and where a high frequency of dyslipidemia has been reported, the prevalence and distribution of FH remain unknown. The molecular characterization of a group of 33 possible cases of FH of Azorean background was undertaken in this study. A DNA array was initially used to search mutations in the LDLR, APOB and PCSK9 loci in 10 unrelated possible cases of FH. No mutations were detected in the array; after sequencing the full LDLR gene, 18 variants were identified, corresponding to two missense (c.806G > A; c.1171G > A) and sixteen synonymous alterations. Six of the synonymous variants which are consistently described in the literature as associated with altered cholesterol levels were used to build haplotypes. The most frequent haplotype corresponded to TTCGCC (45%), a "risk" haplotype, formed exclusively by alleles that were reported to increase cholesterol levels. Some of the variants detected in the full sequencing of the LDLR gene fell within the ligand-binding domain of this gene, defined by exons 2 to 6. To add information as to the role of such variants, these exons were sequenced in the remaining 23 possible FH cases. Two missense alterations (c.185C > T; c.806G > A) were found in this subset of possible FH cases. The missense alteration c.185C > T, identified in one individual, is novel for the Portuguese population. In silico analysis was not conclusive for this alteration, whose role will have to be further investigated. This study represents the first approach to the establishment of the mutational profile of FH in the Azores Islands.This work was supported by the project entitled “High prevalence pathologies in the Azores: genetic and biochemical markers” with reference (M2.1.2/I/026/2008) funded by SRCTE. M. R. receives a PhD fellowship (M3.1.2/F/006/2011) from Fundo Regional para a Ciência. T.C. receives a post-doctoral fellowships from Fundação para a Ciência e a Tecnologia (SFRH/BPD/38659/ 2007) and N. K. (M3.1.7/F/002/2008) and A. R. (M3.1.7/F/031/2011) both receives post-doctoral fellowships from Fundo Regional para a Ciência

A Partial African Ancestry for the Creole Cattle Populations of the Caribbean

Seventy-eight cattle samples from three Creole Caribbean islands and one Brazilian breed were analyzed for sequence variation in the hypervariable segment of the mitochondrial DNA control region. Seventy-three samples displayed Bos taurus haplotypes, and five samples exhibited haplotypes that were of Bos indicus ancestry. Phylogenetic analysis revealed that all sampled B. taurus sequences fell into two distinct clusters with separate African and European origins. European sequences were encountered in each population; however, the distribution of African haplotypes was uneven, with the highest proportion of African influence found in the Guadeloupe Creole. The reduced levels of African haplotypic variation within the Caribbean and Brazilian are consistent with prior founder effects. Additionally, genetic variation at three microsatellite loci illustrated African influence uniquely in the Guadeloupe Creole. Collectively, the data suggest that this African influence is, at least in part, attributable to the historical importation of African cattle to the Americas. Furthermore, alleles of B. indicus ancestry were detected at appreciable frequencies in all Caribbean Creole populations and may reflect zebu introgressions from either West Africa or the Indian subcontinen

A Quasi-Exclusive European Ancestry in the Senepol Tropical Cattle Breed Highlights the Importance of the slick Locus in Tropical Adaptation

Background: The Senepol cattle breed (SEN) was created in the early XXth century from a presumed cross between a European (EUT) breed (Red Poll) and a West African taurine (AFT) breed (N'Dama). Well adapted to tropical conditions, it is also believed trypanotolerant according to its putative AFT ancestry. However, such origins needed to be verified to define relevant husbandry practices and the genetic background underlying such adaptation needed to be characterized. Methodology/Principal Findings: We genotyped 153 SEN individuals on 47,365 SNPs and combined the resulting data with those available on 18 other populations representative of EUT, AFT and Zebu (ZEB) cattle. We found on average 89% EUT, 10.4% ZEB and 0.6% AFT ancestries in the SEN genome. We further looked for footprints of recent selection using standard tests based on the extent of haplotype homozygosity. We underlined i) three footprints on chromosome (BTA) 01, two of which are within or close to the polled locus underlying the absence of horns and ii) one footprint on BTA20 within the slick hair coat locus, involved in thermotolerance. Annotation of these regions allowed us to propose three candidate genes to explain the observed signals (TIAM1, GRIK1 and RAI14). Conclusions/Significance: Our results do not support the accepted concept about the AFT origin of SEN breed. Initial AFT ancestry (if any) might have been counter-selected in early generations due to breeding objectives oriented in particular toward meat production and hornless phenotype. Therefore, SEN animals are likely susceptible to African trypanosomes which questions the importation of SEN within the West African tsetse belt, as promoted by some breeding societies. Besides, our results revealed that SEN breed is predominantly a EUT breed well adapted to tropical conditions and confirmed the importance in thermotolerance of the slick locus. (Résumé d'auteur

Lymnaea schirazensis, an Overlooked Snail Distorting Fascioliasis Data: Genotype, Phenotype, Ecology, Worldwide Spread, Susceptibility, Applicability

BACKGROUND: Lymnaeid snails transmit medical and veterinary important trematodiases, mainly fascioliasis. Vector specificity of fasciolid parasites defines disease distribution and characteristics. Different lymnaeid species appear linked to different transmission and epidemiological patterns. Pronounced susceptibility differences to absolute resistance have been described among lymnaeid populations. When assessing disease characteristics in different endemic areas, unexpected results were obtained in studies on lymnaeid susceptibility to Fasciola. We undertook studies to understand this disease transmission heterogeneity. METHODOLOGY/PRINCIPAL FINDINGS: A ten-year study in Iran, Egypt, Spain, the Dominican Republic, Mexico, Venezuela, Ecuador and Peru, demonstrated that such heterogeneity is not due to susceptibility differences, but to a hitherto overlooked cryptic species, Lymnaea schirazensis, confused with the main vector Galba truncatula and/or other Galba/Fossaria vectors. Nuclear rDNA and mtDNA sequences and phylogenetic reconstruction highlighted an old evolutionary divergence from other Galba/Fossaria species, and a low intraspecific variability suggesting a recent spread from one geographical source. Morphometry, anatomy and egg cluster analyses allowed for phenotypic differentiation. Selfing, egg laying, and habitat characteristics indicated a migration capacity by passive transport. Studies showed that it is not a vector species (n = 8572 field collected, 20 populations): snail finding and penetration by F. hepatica miracidium occur but never lead to cercarial production (n = 338 experimentally infected). CONCLUSIONS/SIGNIFICANCE: This species has been distorting fasciolid specificity/susceptibility and fascioliasis geographical distribution data. Hence, a large body of literature on G. truncatula should be revised. Its existence has henceforth to be considered in research. Genetic data on livestock, archeology and history along the 10,000-year post-domestication period explain its wide spread from the Neolithic Fertile Crescent. It is an efficient biomarker for the follow-up of livestock movements, a crucial aspect in fascioliasis emergence. It offers an outstanding laboratory model for genetic studies on susceptibility/resistance in F. hepatica/lymnaeid interaction, a field of applied research with disease control perspectives

Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts

Background: Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients. Methods: This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days. Results: The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death. Conclusion: The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

A partial african ancestry for the Creole cattle populations of the Caribbean

Seventy-eight cattle samples from three Creole Caribbean islands and one Brazilian breed were analyzed for sequence variation in the hypervariable segment of the mitochondrial DNA control region. Seventy-three samples displayed Bos taurus haplotypes, and five samples exhibited haplotypes that were of Bos indicus ancestry. Phylogenetic analysis revealed that all sampled B. taurus sequences fell into two distinct clusters with separate African and European origins. European sequences were encountered in each population; however, the distribution of African haplotypes was uneven, with the highest proportion of African influence found in the Guadeloupe Creole. The reduced levels of African haplotypic variation within the Caribbean and Brazilian are consistent with prior founder effects. Additionally, genetic variation at three microsatellite loci illustrated African influence uniquely in the Guadeloupe Creole. Collectively, the data suggest that this African influence is, at least in part, attributable to the historical importation of African cattle to the Americas. Furthermore, alleles of B. indicus ancestry were detected at appreciable frequencies in all Caribbean Creole populations and may reflect zebu introgressions from either West Africa or the Indian subcontinent. (Résumé d'auteur

African and European mitochondrial haplotypes in South American Creole cattle

South American Creole cattle are direct descendants of the animals brought to the New World by the Spanish and Portuguese during the 16th century. A portion of the mitochondrial D-loop was sequenced in 36 animals from five Creole cattle populations in Argentina and four in Bolivia. Individuals belonging to the potentially ancestral Spanish breed Retinta were also analysed. Sequence comparisons revealed three main groups: two with the characteristics of European breeds and a third showing the transitions representative of the African taurine breeds. The African sequences were found in two populations from Argentina and three populations from Bolivia, whose only connections go back to colonial times. The most probable explanation for the finding is that animals could have been moved from Africa to Spain during the long-lasting Arabian occupation that started in the seventh century, and from the Iberian Peninsula to America eight centuries later. However, since African haplotypes were not found in the Spanish sample, the possibility of cattle transported directly from Africa cannot be disregarded.Fil: Mirol, Patricia Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Investigaciones en Genética Básica y Aplicada; ArgentinaFil: Giovambattista, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Investigaciones en Genética Básica y Aplicada; ArgentinaFil: Liron, Juan Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Investigaciones en Genética Básica y Aplicada; ArgentinaFil: Dulout, Fernando Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Centro de Investigaciones en Genética Básica y Aplicada; Argentin