Publications by authors named "Isabel Alvarez"

59 Publications

Functional characterization of Copy Number Variations regions in Djallonké sheep.

J Anim Breed Genet 2021 Mar 8. Epub 2021 Mar 8.

Área de Genética y Reproducción Animal, SERIDA, Gijón, Spain.

A total of 184 Djallonké (West African Dwarf) sheep of Burkina Faso were analysed for Copy Number Variations (CNV) using Ovine 50 K SNP BeadChip genotyping data and two different CNV calling platforms: PennCNV and QuantiSNP. Analyses allowed to identify a total of 63 candidate Copy Number Variations Regions (CNVR) on 11 different ovine chromosomes covering about 82.5 Mb of the sheep genome. Gene-annotation enrichment analysis allowed to identify a total of 751 potential candidate ovine genes located in the candidate CNVR bounds. Functional annotation allowed to identify five statistically significant Functional Clusters (FC; enrichment factor > 1.3) involving 61 candidate genes. All genes forming significantly enriched FC were located on ovine chromosome (OAR) 21. FC1 (22 genes including PAG4 and PAG6) and FC5 (three genes: CTSC, CTSW and CTSF), coding proteases (peptidases and cathepsins, respectively), were involved in reproductive performance and modulation of gestation. Both FC3 and FC4 were involved in inflammatory and immunologic response through coding serum amyloid A and B-box-type zinc finger proteins, respectively. Finally, FC2 consisted of 27 genes (including OR10G6 and OR8B8) involved in olfactory receptor activity, key for animals adapting to new food resources. CNVR identified on at least 15% of individuals were considered CNVR hotspots and further overlapped with previously reported quantitative trait loci (QTL). CNVR hotspots spanning genes putatively involved with lipid metabolism (SKP1, TCF7, JADE2, UBE2B and SAR1B) and differential expression in mammary gland (SEC24A and CDKN2AIPNL) on OAR5 and dairy traits (CCDC198 and SLC35F4) on OAR7 overlapped with QTL associated with lipid metabolism, milk protein yield and milk fat percentage. Information obtained from local sheep populations naturally adapted to harsh environments contributes to increase our understanding of the genomic importance of CNV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jbg.12542DOI Listing
March 2021

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi.

J Clin Oncol 2021 Apr 12;39(11):1214-1222. Epub 2021 Feb 12.

Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy.

Purpose: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL).

Methods: We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050).

Results: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases.

Conclusion: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.02465DOI Listing
April 2021

Population Structure Assessed Using Microsatellite and SNP Data: An Empirical Comparison in West African Cattle.

Animals (Basel) 2021 Jan 11;11(1). Epub 2021 Jan 11.

Servicio Regional de Investigación y Desarrollo Agroalimentario, E-33394 Gijón, Spain.

A sample of 185 West African cattle belonging to nine different taurine, sanga, and zebu populations was typed using a set of 33 microsatellites and the BovineHD BeadChip of Illumina. The information provided by each type of marker was summarized via clustering methods and principal component analyses (PCA). The aim was to assess differences in performance between both marker types for the identification of population structure and the projection of genetic variability on geographical maps. In general, both microsatellites and Single Nucleotide Polymorphism (SNP) allowed us to differentiate taurine cattle from zebu and sanga cattle, which, in turn, would form a single population. Pearson and Spearman correlation coefficients computed among the admixture coefficients (fitting K = 2) and the eigenvectors corresponding to the first two factors identified using PCA on both microsatellite and SNP data were statistically significant (most of them having < 0.0001) and high. However, SNP data allowed for a better fine-scale identification of population structure within taurine cattle: Lagunaire cattle from Benin were separated from two different N'Dama cattle samples. Furthermore, when clustering analyses assumed the existence of two parental populations only (K = 2), the SNPs could differentiate a different genetic background in Lagunaire and N'Dama cattle. Although the two N'Dama cattle populations had very different breeding histories, the microsatellite set could not separate the two N'Dama cattle populations. Classic bidimensional dispersion plots constructed using factors identified via PCA gave different shapes for microsatellites and SNPs: plots constructed using microsatellite polymorphism would suggest the existence of weakly differentiated, highly intermingled, subpopulations. However, the projection of the factors identified on synthetic maps gave comparable images. This would suggest that results on population structuring must be interpreted with caution. The geographic projection of genetic variation on synthetic maps avoids interpretations that go beyond the results obtained, particularly when previous information on the analyzed populations is scant. Factors influencing the performance of the projection of genetic parameters on geographic maps, together with restrictions that may affect the election of a given type of markers, are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani11010151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827059PMC
January 2021

Ancient Homozygosity Segments in West African Djallonké Sheep Inform on the Genomic Impact of Livestock Adaptation to the Environment.

Animals (Basel) 2020 Jul 12;10(7). Epub 2020 Jul 12.

Servicio Regional de Investigación y Desarrollo Agroalimentario, E-33394 Gijón, Spain.

A sample of Burkina Faso Djallonké (West African Dwarf) sheep was analyzed to identify stretches of homozygous segments (runs of homozygosity; ROH) overlapping with ancient homozygosity-by-descent (HBD) segments. HBD segments were considered ancient if they were likely to be inherited from ancestors living from 1024 to 2048 generations ago, roughly coinciding with the time in which sheep entered into West Africa. It is hypothesized that such homozygous segments can inform on the effect of the sheep genome of human-mediated selection for adaptation to this harsh environment. PLINK analyses allowed to identify a total of 510 ROH segments in 127 different individuals that could be summarized into 124 different ROH. A total of 32,968 HBD segments were identified on 119 individuals using the software ZooRoH. HBD segments inherited from ancestors living 1024 and 2048 generations ago were identified on 61 individuals. The overlap between consensus ROH identified using PLINK and HBD fragments putatively assigned to generations 1024 and 2048 gave 108 genomic areas located on 17 different ovine chromosomes which were considered candidate regions for gene-annotation enrichment analyses. Functional annotation allowed to identify six statistically significant functional clusters involving 50 candidate genes. Cluster 1 was involved in homeostasis and coagulation; functional clusters 2, 3, and 6 were associated to innate immunity, defense against infections, and white blood cells proliferation and migration, respectively; cluster 4 was involved in parasite resistance; and functional cluster 5, formed by 20 genes, was involved in response to stress. The current analysis confirms the importance of genomic areas associated to immunity, disease resistance, and response to stress for adaptation of sheep to the challenging environment of humid Sub-Saharan West Africa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani10071178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401600PMC
July 2020

The Perceptions of Professional Values among Students at a Spanish Nursing School.

Healthcare (Basel) 2020 Mar 26;8(2). Epub 2020 Mar 26.

Nursing Faculty Gimbernat, Autonomous University of Barcelona, Sant Cugat del Vallès 08174, Spain.

(1) Background: This study aims to reflect student nurses' perceptions of professional values across the four training years. (2) Methods: This study was designed as a cross-sectional study; data were collected using the Nurses' Professional Values Scale-Revised, adapted by Basurto-Hoyuelos. A total of 315 student nurses participated from a Nursing Faculty in Spain representing each of the four academic years. (3) Results Students' perceptions of professional values were significantly correlated with their academic year. Overall, students' scores were higher in the ethics dimension. The two highest scores were for for years 1 and 2 (4.77 and 4.68, respectively) and for years 3 and 4 (4.95 and 4.98, respectively). Lower scores were observed in the professional expertise dimension across all years, and corresponded to a single item (3.51, 3.38, 3.98, and 3.26, respectively). (4) Conclusions: This study is relevant as it highlights how nursing students' perceptions of professional values change overtime, even during the four years of their training. The ethics dimension was the most highly regarded across all academic years. However, the professional expertise dimension requires greater attention throughout the degree as students regarded it as less important for their immediate future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/healthcare8020074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348720PMC
March 2020

Genomic scan of selective sweeps in Djallonké (West African Dwarf) sheep shed light on adaptation to harsh environments.

Sci Rep 2020 02 18;10(1):2824. Epub 2020 Feb 18.

Servicio Regional de Investigación y Desarrollo Agroalimentario, E-33394, Gijón, Spain.

The Djallonké (West African Dwarf) sheep is a small-sized haired sheep resulting from a costly evolutionary process of natural adaptation to the harsh environment of West Africa including trypanosome challenge. However, genomic studies carried out in this sheep are scant. In this research, genomic data of 184 Djallonké sheep (and 12 Burkina-Sahel sheep as an outgroup) generated using medium-density SNP Chips were analyzed. Three different statistics (iHS, XP-EHH and nSL) were applied to identify candidate selection sweep regions spanning genes putatively associated with adaptation of sheep to the West African environment. A total of 207 candidate selection sweep regions were defined. Gene-annotation enrichment and functional annotation analyses allowed to identify three statistically significant functional clusters involving 12 candidate genes. Genes included in Functional Clusters associated to selection signatures were mainly related to metabolic response to stress, including regulation of oxidative and metabolic stress and thermotolerance. The bovine chromosomal areas carrying QTLs for cattle trypanotolerance were compared with the regions on which the orthologous functional candidate cattle genes were located. The importance of cattle BTA4 for trypanotolerant response might have been conserved between species. The current research provides new insights on the genomic basis for adaptation and highlights the importance of obtaining information from non-cosmopolite livestock populations managed in harsh environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-59839-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028950PMC
February 2020

Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer.

J Clin Med 2019 Dec 11;8(12). Epub 2019 Dec 11.

Girona Biomedical Research Institute (IDIBGI), Girona 17190, Spain.

The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (≥20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status ( = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm ( = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm ( = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8122180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947627PMC
December 2019

Contextualizing pertuzumab approval in the treatment of HER2-positive breast cancer patients.

Cancer Treat Rev 2020 Feb 29;83:101944. Epub 2019 Nov 29.

Hospital Arnau Vilanova, Valencia, and Universidad Católica de Valencia, Spain.

The use of adjuvant pertuzumab in HER2-positive early-stage breast cancer has recently been approved by the EMA on the basis of data from the APHINITY trial. Accordingly, we have produced this opinion article with the aim of putting the study data in perspective against other add-on therapeutic strategies, to clarify methodological or statistical doubts about the study, and to define the population of high-risk patients with hormone receptor-negative breast cancer that we agree, in general, should be treated. With this approval, physicians must be well prepared to place the APHINITY study data in context. It is now up to each country to ratify the EMA-approved indications and to agree on reimbursement, and doctors must optimize their use based on knowledge and discussion with patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2019.101944DOI Listing
February 2020

Identification of genomic regions and candidate genes of functional importance for gastrointestinal parasite resistance traits in Djallonké sheep of Burkina Faso.

Arch Anim Breed 2019 5;62(1):313-323. Epub 2019 Jun 5.

SERIDA Deva., Camino de Rioseco 1225, 33394 Gijón (Asturias), Spain.

A total of 184 Djallonké lambs from Burkina Faso with phenotypes for packed-cell volume (PCV), log-transformed fecal egg count (lnFEC), and FAffa MAlan CHArt (FAMACHA©) eye scores were typed with the OvineSNP50 BeadChip of Illumina to contribute to the knowledge of the genetic basis of gastrointestinal (GIN) parasite resistance in sheep. Association analysis identified a total of 22 single-nucleotide polymorphisms (SNPs) related with PCV (6 SNPs), lnFEC (7), and FAMACHA scores (9) distributed among 14 chromosomes (OAR). The identified SNPs accounted for 18.76 % of the phenotypic variance for PCV, 21.24 % for lnFEC, and 34.38 % for FAMACHA scores. Analyses pointed out the importance of OAR2 for PCV, OAR3 for FAMACHA scores, and OAR6 for lnFEC. The 125 kb regions surrounding the identified SNPs overlapped with seven previously reported quantitative trait loci (QTLs) for the traits analyzed in the current work. The only chromosome harboring markers associated with the three traits studied was OAR2. In agreement with the literature, two different chromosomal areas on OAR2 can play a major role in the traits studied. Gene-annotation enrichment analysis allowed us to identify a total of 34 potential candidate genes for PCV (6 genes), lnFEC (4), and FAMACHA scores (24). Annotation analysis allowed us to identify one functional term cluster with a significant enrichment score (1.302). The cluster included five genes (, , , , and ) involved in immunity-related and cell-proliferation processes. Furthermore, this research suggests that the gene can underlie a previously reported QTL for immunoglobulin A levels on OAR22 and confirms the importance of genes involved in growth and size (such as the gene on OAR18) for GIN resistance traits. Since association studies for the ascertainment of the genetic basis of GIN resistance may be affected by genotype-environment interactions, obtaining information from local sheep populations managed in harsh environments contributes to the identification of novel genomic areas of functional importance for GIN resistance for that trait.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5194/aab-62-313-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853132PMC
June 2019

Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study.

Breast Cancer Res Treat 2019 Aug 31;177(1):115-125. Epub 2019 May 31.

Medical Oncology Department, Instituto de Investigación Sanitaria H. U. Gregorio Marañon, Universidad Complutense, CIBERONC, C/Dr. Esquerdo 46, 28009, Madrid, Spain.

Purpose: GEICAM/2006-10 compared anastrozole (A) versus fulvestrant plus anastrozole (A + F) to test the hypothesis of whether a complete oestrogen blockade is superior to aromatase inhibitors alone in breast cancer patients receiving hormone adjuvant therapy.

Methods: Multicenter, open label, phase III study. HR+/HER2- EBC postmenopausal patients were randomized 1:1 to adjuvant A (5 years [year]) or A + F (A plus F 250 mg/4 weeks for 3 year followed by 2 year of A). Stratification factors: prior chemotherapy (yes/no); number of positive lymph nodes (0/1-3/≥ 4); HR status (both positive/one positive) and site.

Primary Objective: disease-free survival (DFS). Planned sample size: 2852 patients.

Results: The study has an early stop due to the financer decision with 870 patients (437 randomized to A and 433 to A + F). Patient characteristics were well balanced. After a median follow-up of 6.24y and 111 DFS events (62 in A and 49 in A + F) the Hazard Ratio for DFS (combination vs. anastrozole) was 0.84 (95% CI 0.58-1.22; p = 0.352). The proportion of patients disease-free in arms A and A + F at 5 year and 7 year were 90.8% versus 91% and 83.6% versus 86.7%, respectively. Most relevant G2-4 toxicities (≥ 5% in either arm) with A versus A + F were joint pain (14.7%; 13.7%), fatigue (2.5%; 7.2%), bone pain (3%; 6.5%), hot flushes (3.5%; 5%) and muscle pain (2.8%; 5.1%).

Conclusions: The GEICAM/2006-10 study did not show a statistically significant increase in DFS by adding adjuvant F to A, though no firm conclusions can be drawn because of the limited sample size due to the early stop of the trial. ClinicalTrials.gov: NCT00543127.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-019-05296-8DOI Listing
August 2019

Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients.

Aging (Albany NY) 2019 05;11(9):2874-2888

Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.

Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the "drug plus diet" approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients. A panel of 11 serum metabolites including markers of mitochondrial function and intermediates/products of folate-dependent one-carbon metabolism were measured in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. Metabolite profiles revealed a significant increase of the ketone body β-hydroxybutyrate and of the TCA intermediate α-ketoglutarate in the metformin-containing arm. A significant relationship was found between the follow-up levels of homocysteine and the ability of treatment arms to achieve a pathological complete response (pCR). In the metformin-containing arm, patients with significant elevations of homocysteine tended to have a higher probability of pCR. The addition of metformin to an established anti-cancer therapeutic regimen causes a fasting-mimicking modification of systemic host metabolism. Circulating homocysteine could be explored as a clinical pharmacodynamic biomarker linking the antifolate-like activity of metformin and biological tumor response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.101960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535060PMC
May 2019

The Allele of rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin.

Front Oncol 2019 28;9:193. Epub 2019 Mar 28.

Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.

The minor allele () of the single-nucleotide polymorphism (SNP) , located near the () gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes. We herein investigated whether the same SNP would predict clinical response to neoadjuvant metformin in women with early breast cancer (BC). DNA was collected from 79 patients included in the intention-to-treat population of the METTEN study, a phase 2 clinical trial of HER2-positive BC patients randomized to receive either metformin combined with anthracycline/taxane-based chemotherapy and trastuzumab or equivalent regimen without metformin, before surgery. SNP genotyping was assessed using allelic discrimination by quantitative polymerase chain reaction. Logistic regression analyses revealed a significant relationship between the genotype and the ability of treatment arms to achieve a pathological complete response (pCR) in patients (odds ratio [OR] = 10.33, 95% confidence interval [CI]: 1.29-82.89, = 0.028). In the metformin-containing arm, patients bearing the allele had a significantly higher probability of pCR (OR = 7.94, 95%CI: 1.60-39.42, = 0.011). Conversely, no association was found between and clinical response in the reference arm (OR = 0.77, 95%CI: 0.20-2.92, = 0.700). After controlling for tumor size and hormone receptor status, the allele remained a significant predictor of pCR solely in the metformin-containing arm. If reproducible, the allele might warrant consideration as a predictive clinical biomarker to inform the personalized use of metformin in BC patients. EU Clinical Trials Register, EudraCT number 2011-000490-30. Registered 28 February 2011, https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000490-30/ES.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447648PMC
March 2019

Legacies of domestication, trade and herder mobility shape extant male zebu cattle diversity in South Asia and Africa.

Sci Rep 2018 12 21;8(1):18027. Epub 2018 Dec 21.

Servicio Regional de Investigación y Desarrollo Agroalimentario, E-33394, Gijón, Spain.

All tropically adapted humped cattle (Bos indicus or "zebu"), descend from a domestication process that took place >8,000 years ago in South Asia. Here we present an intercontinental survey of Y-chromosome diversity and a comprehensive reconstruction of male-lineage zebu cattle history and diversity patterns. Phylogenetic analysis revealed that all the zebu Y-chromosome haplotypes in our dataset group within three different lineages: Y3, the most predominant and cosmopolitan lineage; Y3, only observed in West Africa; and Y3, predominant in South and Northeast India. The divergence times estimated for these three Zebu-specific lineages predate domestication. Coalescent demographic models support either de novo domestication of genetically divergent paternal lineages or more complex process including gene flow between wild and domestic animals. Our data suggest export of varied zebu lineages from domestication centres through time. The almost exclusive presence of Y3 haplotypes in East Africa is consistent with recent cattle restocking in this area. The cryptic presence of Y3 haplotypes in West Africa, found nowhere else, suggests that these haplotypes might represent the oldest zebu lineage introduced to Africa ca. 3,000 B.P. and subsequently replaced in most of the world. The informative ability of Interspersed Multilocus Microsatellites and Y-specific microsatellites to identify genetic structuring in cattle populations is confirmed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-36444-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303292PMC
December 2018

TUSARC: Prognostic Value of High-Sensitivity Cardiac Troponin T Assay in Asymptomatic Patients with High Cardiovascular Risk.

Am J Med 2019 05 15;132(5):631-638. Epub 2018 Dec 15.

Clinical testing laboratory, Hospital Santos Reyes Aranda de Duero Burgos, Spain.

Background: Prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) assays have been assessed in selected populations in different studies and in registries of members of the general population with low cardiovascular risk. The aim of this study was to determine the prognostic value of hs-cTnT in an asymptomatic very-high cardiovascular risk Spanish population.

Methods: From a previous prospective cohort of the TUSARC (troponina T UltraSensible en pacientes Asintomáticos de alto Riesgo Cardiovascular) registry, follow-up was conducted in 602 patients (93.18%). The association of high hs-cTnT (≥99th percentile value) and incidence of primary event was studied. A primary event was defined as a combined major cardiovascular event (incidence of cardiovascular death, decompensated heart failure, non-fatal cerebrovascular event, non-fatal myocardial infarction, or coronary revascularization). The association between high hs-cTnT and incidence of secondary events was studied as well.

Results: In patients with high hs-cTnT, the incidence of primary event during follow-up was significantly higher (18.30% vs 3.67% P < .001): heart failure (6.25% vs 0.73% P < .001), cardiovascular death (7.29% vs 0.00% P < .001), and death from any cause (7.81% vs 0.98% P < .001).

Conclusions: In an asymptomatic very-high cardiovascular risk Spanish population, elevated hs-cTnT was significantly associated with incident major cardiovascular combined end point and incidence of heart failure, cardiovascular death, and death from any cause.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2018.11.035DOI Listing
May 2019

A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study.

Oncotarget 2018 Nov 2;9(86):35687-35704. Epub 2018 Nov 2.

Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain.

The METTEN study assessed the efficacy, tolerability, and safety of adding metformin to neoadjuvant chemotherapy plus trastuzumab in early HER2-positive breast cancer (BC). Women with primary, non-metastatic HER2-positive BC were randomized (1:1) to receive metformin (850 mg twice-daily) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of 3-weekly FE75C plus trastuzumab (arm A), or equivalent regimen without metformin (arm B), followed by surgery. Primary endpoint was the rate of pathological complete response (pCR) in the per-protocol efficacy population. pCR rate was numerically higher in the metformin-containing arm A (19 of 29 patients [65.5%, 95% CI: 47.3-80.1]) than in arm B (17 of 29 patients [58.6%, 95% CI: 40.7-74.5]; OR 1.34 [95% CI: 0.46-3.89], = 0.589). The rate of breast-conserving surgery was 79.3% and 58.6% in arm A and B ( = 0.089), respectively. Blood metformin concentrations (6.2 μmol/L, 95% CI: 3.6-8.8) were within the therapeutic range. Seventy-six percent of patients completed the metformin-containing regimen; 13% of patients in arm A dropped out because of metformin-related gastrointestinal symptoms. The most common adverse events (AEs) of grade ≥3 were neutropenia in both arms and diarrhea in arm A. None of the serious AEs was deemed to be metformin-related. Addition of anti-diabetic doses of metformin to a complex neoadjuvant regimen was well tolerated and safe. Because the study was underpowered relative to its primary endpoint, the efficacy data should be interpreted with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.26286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235018PMC
November 2018

Feasibility of a Post-Auricle Wireless Power System for Pediatric Mechanical Circulatory Support Pumps.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:1514-1517

Heart failure (HF) affects approximately 12,000-35,000 children each year in the United States. The development of blood pumps has provided circulatory support for many adults suffering with HF until they receive a heart transplant. However, while the development of blood pumps for adults has led to fullyimplantable continuous flow devices, blood pump technology for children has lagged significantly behind. One area for improving blood pump implantability in children is the use of wireless powering transfer systems (WPTS). These systems eliminate the power cord connecting the implanted blood pump to the external power supply. In adults, WPTS have decreased the number of power cord-related infections and have improved patient outcomes after pump implantation. Unfortunately, the components of these wireless systems are too large for children. In this paper we describe the preliminary work to develop a fully implantable WPTS specifically designed to power the Jarvik 2000 Child. Specifically, we design planar coils 36 um in thickness to be implanted in behind-the-ear fashion. An amplifier and rectifier circuit were also built to provide 15.7V and 0.5A of voltage and current to the pump.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC.2018.8512576DOI Listing
July 2018

Efficacy of bendamustine and rituximab in splenic marginal zone lymphoma: results from the phase II BRISMA/IELSG36 study.

Br J Haematol 2018 12 8;183(5):755-765. Epub 2018 Nov 8.

APHP, Saint-Louis Hospital, Haemato-oncology- Paris Diderot University, Paris, France.

Splenectomy in addition to immunotherapy with rituximab can provide quick and sometimes durable disease control in patients with splenic marginal zone lymphoma (SMZL). However, systemic chemotherapy is ultimately required in many cases. The BRISMA (Bendamustine-rituximab as first-line treatment of splenic marginal zone lymphoma)/IELSG (International Extranodal Lymphoma Study Group)36 trial is an open-label, single arm phase II study designed by the IELSG in cooperation with the Fondazione Italiana Linfomi and the lymphoma Study Association according to Simon's two-stage method. The primary endpoint was complete response rate. Fifty-six patients with SMZL diagnosis confirmed on central revision were treated with bendamustine (90 mg/m  days 1, 2) and rituximab (375 mg/m  day 1) every 28 days for six cycles (B-R). The overall response and CR rates were 91% and 73%, respectively. Duration of response, progression-free survival and overall survival at 3 years were 93% (95% confidence interval [CI] 81-98), 90% (95% CI 77-96) and 96% (95% CI 84-98), respectively. Toxicity was mostly haematological. Neutropenia grade ≥3 was recorded in 43% of patients; infections and febrile neutropenia in 5·4% and 3·6%. Overall, 14 patients (25%) experienced serious adverse events. Five patients (9%) went off-study because of toxicity and one patient died from infection. In conclusion, B-R resulted in a very effective first-line regimen for SMZL. Based on the results achieved in the BRISMA trial, B-R should be considered when a chemotherapy combination with rituximab is deemed necessary for symptomatic SMZL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.15641DOI Listing
December 2018

Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial: A Randomized Phase 3 Clinical Trial.

JAMA Oncol 2018 Mar;4(3):302-308

Department of Medical Oncology, Hospital del Mar, Barcelona, Spain.

Importance: Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial.

Objective: To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting.

Design, Setting, And Participants: In this multicenter, open-label study, in collaboration with Grupo Español de Investigación en Cáncer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90 mg/m2 (349 patients), or nab-paclitaxel, 125 mg/m2 (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice.

Main Outcomes And Measures: The primary end point was the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens.

Results: From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P = .19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively.

Conclusions And Relevance: The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome.

Trial Registration: clinicaltrials.gov Identifier: NCT01822314.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2017.4612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885830PMC
March 2018

Differential distribution of Y-chromosome haplotypes in Swiss and Southern European goat breeds.

Sci Rep 2017 11 23;7(1):16161. Epub 2017 Nov 23.

Departament de Ciència Animal i dels Aliments, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.

The analysis of Y-chromosome variation has provided valuable clues about the paternal history of domestic animal populations. The main goal of the current work was to characterize Y-chromosome diversity in 31 goat populations from Central Eastern (Switzerland and Romania) and Southern Europe (Spain and Italy) as well as in reference populations from Africa and the Near East. Towards this end, we have genotyped seven single nucleotide polymorphisms (SNPs), mapping to the SRY, ZFY, AMELY and DDX3Y Y-linked loci, in 275 bucks from 31 populations. We have observed a low level of variability in the goat Y-chromosome, with just five haplotypes segregating in the whole set of populations. We have also found that Swiss bucks carry exclusively Y1 haplotypes (Y1A: 24%, Y1B1: 15%, Y1B2: 43% and Y1C: 18%), while in Italian and Spanish bucks Y2A is the most abundant haplotype (77%). Interestingly, in Carpathian goats from Romania the Y2A haplotype is also frequent (42%). The high Y-chromosome differentiation between Swiss and Italian/Spanish breeds might be due to the post-domestication spread of two different Near Eastern genetic stocks through the Danubian and Mediterranean corridors. Historical gene flow between Southern European and Northern African goats might have also contributed to generate such pattern of genetic differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-15593-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701018PMC
November 2017

Using root metaphors to analyze communication between nurses and patients: a qualitative study.

BMC Med Educ 2017 Nov 16;17(1):216. Epub 2017 Nov 16.

Pedagogy, University of Lleida, Lleida, Spain.

Background: Metaphors in communication can serve to convey individuals' backgrounds, contexts, experiences, and worldviews. Metaphors used in a health care setting can help achieve consensual communication in professional-patient relationships. Patients use metaphors to describe symptoms, or how disease affects them. Health professionals draw on shared understanding of such metaphors to better comprehend and meet patient needs, and to communicate information that patients can more easily integrate into their lives. This study incorporated a theoretical framework based on four worldviews, each with an underlying foundational metaphor (root metaphor). The use of these root metaphors (formism, mechanism, contextualism, and organicism) can have an explanatory function and serve to impart new meanings, as each type of metaphor can lead to a particular interpretation. The study aimed to extract and discuss the root metaphors, with a view to analyzing the communication between health professionals and patients.

Methods: In a case study in Spain over a six-month period, we analyzed the content of recorded, transcribed interviews conducted by one nurse with 32 patients who had chronic illnesses. We inductively extracted five categories that emerged from the interviews: blood sugar, cholesterol, exercise, blood pressure, and diet. We then examined these categories from the standpoint of each of the four root metaphors using two approaches: A series (deductive) and an emergent (inductive) approach.

Results: The results show that the nurse tended to primarily use two worldviews: mechanism and formism. In contrast, patients tended to favor mechanism when discussing cholesterol, blood pressure, and blood sugar levels, whereas contextualism was predominant when the category was diet or exercise.

Conclusions: This study adds to the existing literature on health professionals and patients' communication. It shows how the use of Pepper's root metaphors help to analyze the communication between the nurse and patients. Furthermore, it shows they are both using different root metaphors when they are talking about illness and treatments especially regarding blood sugar, cholesterol, exercise, blood pressure, and diet. Further qualitative and quantitative studies are needed to solidly these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12909-017-1059-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689157PMC
November 2017

Long-Term Follow-Up of the Intergroup Exemestane Study.

J Clin Oncol 2017 Aug 3;35(22):2507-2514. Epub 2017 May 3.

James P. Morden, Lucy Kilburn, Claire Snowdon, and Judith M. Bliss, The Institute of Cancer Research; Hanna Nicholas, Cancer Research UK; R. Charles Coombes, Imperial College London, London; Gianfilippo Bertelli, Singleton Hospital, Swansea; Robert Coleman, Weston Park Hospital, Sheffield; Lesley Fallowfield, University of Sussex, Brighton; David Dodwell, St James Hospital, Leeds, United Kingdom; Isabel Alvarez, Hospital Donostia, GEICAM Spanish Breast Cancer Group, San Sebastian, Spain; Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Stephen Jones, US Oncology Research, The Woodlands, TX; Per E. Lønning, University of Bergen and Haukeland University Hospital, Bergen, Norway; Olaf Ortmann, University Medical Center Regensburg, Regensburg, Germany; Cornelis van de Velde, Leiden University Medical Centre, Leiden, the Netherlands; Jørn Andersen, Aarhus University Hospital, Aarhus, Denmark; Lucia Del Mastro, IRCCS Azienda Ospedaliera Universitaria San Martino IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; Stig Holmberg, Sahlgrenska Universitetssjukhuset, Goteborg, Sweden; and Robert Paridaens, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.

Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy. Given the large number of non-breast cancer-related deaths now reported, breast cancer-free survival (BCFS), with censorship of intercurrent deaths, was the primary survival end point of interest. Analyses focus on patients with estrogen receptor-positive or unknown tumors (n = 4,599). Results At the time of the data snapshot, median follow-up was 120 months. In the population that was estrogen receptor positive or had unknown estrogen receptor status, 1,111 BCFS events were observed with 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group. The data corresponded to an absolute difference (between exemestane and tamoxifen) at 10 years of 4.0% (95% CI, 1.2% to 6.7%), and the hazard ratio (HR) of 0.81 (95% CI, 0.72 to 0.92) favored exemestane. This difference remained in multivariable analysis that was adjusted for nodal status, prior use of hormone replacement therapy, and prior chemotherapy (HR, 0.80; 95% CI, 0.71 to 0.90; P < .001). A modest improvement in overall survival was seen with exemestane; the absolute difference (between exemestane and tamoxifen) at 10 years in the population that was estrogen receptor positive or had unknown estrogen receptor status was 2.1% (95% CI, -0.5% to 4.6%), and the HR was 0.89 (95% CI, 0.78 to 1.01; P = .08). For the intention-to-treat population, the absolute difference was 1.6% (95% CI, -0.9% to 4.1%); the HR was 0.91 (95% CI, 0.80 to 1.03, P = .15). No statistically significant difference was observed in the proportion of patients who reported a fracture event in the post-treatment period. Conclusion The Intergroup Exemestane Study and contemporaneous studies have established that a strategy of switching to an aromatase inhibitor after 2 to 3 years of tamoxifen can lead to sustained benefits in terms of reduction of disease recurrence and breast cancer mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2016.70.5640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175047PMC
August 2017

High-sensitivity Troponin T Assay in Asymptomatic High Cardiovascular Risk Patients. The TUSARC Registry.

Rev Esp Cardiol (Engl Ed) 2017 Apr 22;70(4):261-266. Epub 2016 Dec 22.

Servicio de Cardiología, Hospital Santos Reyes, Aranda de Duero, Burgos, Spain. Electronic address:

Introduction And Objectives: High-sensitivity troponin T assays (Hs-TnT) have been carried out in selected populations in clinical trials and in registries of the general population with low cardiovascular risk (CVR). The aim of this study was to determine the proportion of individuals with detectable Hs-TnT and the proportion of individuals with elevated Hs-TnT in a Spanish population of asymptomatic individuals with very high CVR, as well as the parameters associated with Hs-TnT elevation.

Methods: The study included 690 patients. Hs-TnT detection and Hs-TnT elevation (≥99th percentile value), as well the association of elevated Hs-TnT and clinical, analytical, and treatment data were analyzed.

Results: Hs-TnT was analyzed in 646 patients and was detected in 645. Elevated TnT was detected in 212 patients (32.9%). On multivariate analysis, elevated TnT was independently associated with male sex (OR, 2.81; 95%CI, 1.67-4.73; P < .001), older age (OR, 1.06; 95%CI, 1.04-1.09; P < .001), a higher body mass index (OR, 1.07; 95%CI, 1.02-1.12; P < .002), insulin therapy (OR, 1.99; 95%CI, 1.15-3.46; P = .01), history of heart failure (OR, 3.92; 95%CI, 1.24-12.39; P = .02), and estimated glomerular filtration rate calculated by CKD-EPI (OR, 0.96; 95%CI, 0.95-0.97; P < .001).

Conclusions: In a Spanish population of asymptomatic individuals at very high CVR, Hs-TnT was associated with older age, male sex, higher body mass index, insulin therapy, history of heart failure, and lower glomerular filtration rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rec.2016.11.018DOI Listing
April 2017

A Multicenter Phase II Study of Twice-Weekly Bortezomib plus Rituximab in Patients with Relapsed Follicular Lymphoma: Long-Term Follow-Up.

Acta Haematol 2017 4;137(1):7-14. Epub 2016 Nov 4.

Program of Innovative Therapy in Oncology and Hematology, Department of Diagnostic, Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy.

Single-agent bortezomib (B) has shown activity in heavily pretreated patients with relapsed/refractory indolent lymphoma. On the basis of these findings, we performed a phase II study of B combined with rituximab (R) in patients with relapsed follicular lymphoma (FL). Forty-five patients with fairly good prognostic profiles were enrolled from 2007 to 2011 and received a total of 6 cycles of the B+R combination. The endpoints were the overall response rate (ORR), progression-free survival (PFS), duration of remission (DoR), overall survival (OS), and toxicity evaluation. When considering all the enrolled patients the ORR was 64%. At 5 years, the estimated PFS, DoR, and OS were 34, 49, and 70%, respectively. After excluding the 7 R-naïve patients, the ORR was 58%, with a PFS of 19 months. The most common grade >2 toxicities were thrombocytopenia (18%), peripheral neuropathy (13%), and neutropenia (2%). Our study shows the feasibility, long-term efficacy, and excellent tolerability of the B+R combination. We are aware that our study has specific limitations, such as the small sample size consisting of patients with a relatively good prognostic profile. However, because FL patients will be treated with subsequent chemotherapy regimens, a well-tolerated and effective chemotherapy-free therapy could be considered an additional tool for long-term disease control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000449052DOI Listing
February 2017

Assessing performance of single-sample molecular genetic methods to estimate effective population size: empirical evidence from the endangered Gochu Asturcelta pig breed.

Ecol Evol 2016 Jul 23;6(14):4971-80. Epub 2016 Jun 23.

SERIDA-Deva Camino de Rioseco 1225 Gijón Asturias 33394 Spain.

Estimating effective population size (N e ) using linkage disequilibrium (LD) information (N e( LD ) ) has the operational advantage of using a single sample. However, N e( LD ) estimates assume discrete generations and its performance are constrained by demographic issues. However, such concerns have received little empirical attention so far. The pedigree of the endangered Gochu Asturcelta pig breed includes individuals classified into discrete filial generations and individuals with generations overlap. Up to 780 individuals were typed with a set of 17 microsatellites. Performance of N e( LD ) was compared with N e estimates obtained using genealogical information, molecular coancestry (N e(M) ) and a temporal (two-sample) method (N e( JR ) ). Molecular-based estimates of N e exceeded those obtained using pedigree data. Estimates of N e( LD ) for filial generations F3 and F4 (17.0 and 17.3, respectively) were lower and steadier than those obtained using yearly or biannual samplings. N e( LD ) estimated for samples including generations overlap could only be compared with those obtained for the discrete filial generations when sampling span approached a generation interval and demographic correction for bias was applied. Single-sample N e(M) estimates were lower than their N e( LD ) counterparts. N e(M) estimates are likely to partially reflect the number of founders rather than population size. In any case, estimates of LD and molecular coancestry tend to covary and, therefore, N e(M) and N e( LD ) can hardly be considered independent. Demographically adjusted estimates of N e( JR ) and N e( LD ) took comparable values when: (1) the two samples used for the former were separated by one equivalent to discrete generations in the pedigree and (2) sampling span used for the latter approached a generation interval. Overall, the empirical evidence given in this study suggested that the advantage of using single-sample methods to obtain molecular-based estimates of N e is not clear in operational terms. Estimates of N e obtained using methods based in molecular information should be interpreted with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.2240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979721PMC
July 2016

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication.

Curr Biol 2016 06 26;26(12):1577-1584. Epub 2016 May 26.

US Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA.

Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089372PMC
http://dx.doi.org/10.1016/j.cub.2016.04.038DOI Listing
June 2016

Lack of specific alleles for the bovine chemokine (C-X-C) receptor type 4 (CXCR4) gene in West African cattle questions its role as a candidate for trypanotolerance.

Infect Genet Evol 2016 08 24;42:30-3. Epub 2016 Apr 24.

Área de Genética y Reproducción Animal, SERIDA, Camino de los Claveles 604, 33203 Gijón, Spain. Electronic address:

A panel of 81 Asian, African and European cattle (Bos taurus and B. indicus) was analysed for the whole sequence of the CXCR4 gene (3844bp), a strong candidate for cattle trypanotolerance. Thirty-one polymorphic sites identified gave 31 different haplotypes. Neutrality tests rejected the hypothesis of either positive or purifying selection. Bayesian phylogenetic tree showed differentiation of haplotypes into two clades gathering genetic variability predating domestication. Related with clades definition, linkage disequilibrium analyses suggested the existence of one only linkage block on the CXCR4 gene. Two tag SNPs identified on exon 2 captured 50% of variability. Whatever the analysis carried out, no clear separation between cattle groups was identified. Most haplotypes identified in West African taurine cattle were also found in European cattle and in Asian and West African zebu. West African taurine samples did not carry unique variants on the CXCR4 gene sequence. The current analysis failed in identifying a causal mutation on the CXCR4 gene underlying a previously reported QTL for cattle trypanotolerance on BTA2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2016.04.029DOI Listing
August 2016

Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study.

Breast Cancer Res Treat 2016 Feb 24;156(1):81-9. Epub 2016 Feb 24.

Department of Medical Oncology, Elche University General Hospital, Elche, Spain.

There are several prognostic multigene-based tests for managing breast cancer (BC), but limited data comparing them in the same cohort. We compared the prognostic performance of the EndoPredict (EP) test (standardized for pathology laboratory) with the research-based PAM50 non-standardized qRT-PCR assay in node-positive estrogen receptor-positive (ER+) and HER2-negative (HER2-) BC patients receiving adjuvant chemotherapy followed by endocrine therapy (ET) in the GEICAM/9906 trial. EP and PAM50 risk of recurrence (ROR) scores [based on subtype (ROR-S) and on subtype and proliferation (ROR-P)] were compared in 536 ER+/HER2- patients. Scores combined with clinical information were evaluated: ROR-T (ROR-S, tumor size), ROR-PT (ROR-P, tumor size), and EPclin (EP, tumor size, nodal status). Patients were assigned to risk-categories according to prespecified cutoffs. Distant metastasis-free survival (MFS) was analyzed by Kaplan-Meier. ROR-S, ROR-P, and EP scores identified a low-risk group with a relative better outcome (10-year MFS: ROR-S 87 %; ROR-P 89 %; EP 93 %). There was no significant difference between tests. Predictors including clinical information showed superior prognostic performance compared to molecular scores alone (10-year MFS, low-risk group: ROR-T 88 %; ROR-PT 92 %; EPclin 100 %). The EPclin-based risk stratification achieved a significantly improved prediction of MFS compared to ROR-T, but not ROR-PT. All signatures added prognostic information to common clinical parameters. EPclin provided independent prognostic information beyond ROR-T and ROR-PT. ROR and EP can reliably predict risk of distant metastasis in node-positive ER+/HER2- BC patients treated with chemotherapy and ET. Addition of clinical parameters into risk scores improves their prognostic ability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-016-3725-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788691PMC
February 2016

African Cattle do not Carry Unique Mutations on the Exon 9 of the ARHGAP15 Gene.

Anim Biotechnol 2016 ;27(1):9-12

a Área de Genética y Reproducción Animal , SERIDA, Camino de los Claveles , Gijón , Spain.

A panel of 81 Asian, African and European cattle (Bos taurus and B. indicus) was sequenced for the exon 9 of the ARHGAP15, a strong candidate for cattle trypanotolerance on BTA2. The analyses provided five different haplotypes defined by four (two nonsynonymous) mutations. Neutrality tests suggest a recent sweep in the studied bovine sequences. The two most frequent haplotypes (H1 and H3) gathered 88% of the chromosomes analyzed and were present in all the cattle groups analyzed, including Asian zebu and European cattle. The current results question the sole association of the polymorphism identified, including mutation c.53317501A > C, with the trypanotolerant response in West African cattle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10495398.2015.1053606DOI Listing
July 2016

Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile.

Curr Cancer Drug Targets 2016 ;16(5):415-28

Medical Oncology Department, MD Anderson Cancer Center, Madrid, C/ Arturo Soria, 270, 28033 - Madrid. Spain.

Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone-independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel. Nab-paclitaxel can be administered to all patients for whom the treatment choice is a taxane. In this review, 6 patient profiles for which nabpaclitaxel may be particularly useful are described and analyzed: (i) as first-line treatment of MBC, (ii) as second-line treatment of MBC after oral chemotherapy, (iii) after a standard taxane, (iv) as third-line treatment after a standard taxane and oral chemotherapy, (v) for patients with HER2-positive MBC and (vi) for patients with intolerance to standard taxanes. Nab-paclitaxel is a rational treatment choice for patients with MBC in different settings, as well as for those with prior exposure to a standard taxane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568009615666150817121731DOI Listing
October 2017

Geographical assessment of body measurements and qualitative traits in West African cattle.

Trop Anim Health Prod 2015 Dec 30;47(8):1505-13. Epub 2015 Jul 30.

SERIDA-Deva, Camino de Rioseco 1225, E-33394, Deva-Gijón, Asturias, Spain.

A total of 1015 adult cows belonging to nine West African cattle breeds were assessed for 16 body measurements and 18 qualitative traits to ascertain the existence of geographical patterns of variation. Sampling was carried out in 29 different provinces of Mali, Burkina Faso and Benin. For body measurements, taurine breeds took lower average values than the zebu breeds. Sanga cattle took intermediate values. Qualitative traits did not allow to differentiate among cattle groups (taurine, zebu or sanga) or breeds. Principal component analysis identified two factors explaining 56.4 and 9.2 % of the variance for body measurements, respectively. Two correspondence analysis dimensions computed on qualitative traits explained a small proportion of the variability (20.8 and 13.5 %, respectively). Contour plots were constructed using the eigenvalues computed for each individual and either factor or dimension identified; confidence regions calculated confirmed that body measurements clearly differentiated zebu and taurine cattle breeds while qualitative traits did not. Factor 1 was projected on a geographical map, using provinces as nodes, to assess breed-free variation for body measurements. A pattern of continuous variation from the Sahel area southwards was identified. Probably, breeding decisions promoting the crosses between zebu-like and taurine cattle are underlying this geographical pattern of variation. The implementation of selection strategies aiming at the increase of the productivity of native West African taurine cattle breeds while avoiding looses in trypanotolerant ability would be highly advisable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11250-015-0891-7DOI Listing
December 2015