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1.
Phys Rev Lett ; 132(4): 041001, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38335333

RESUMEN

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

2.
J Autoimmun ; 135: 102990, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36621176

RESUMEN

OBJECTIVES: To characterize the splicing machinery (SM) of leukocytes from primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome with lupus (APS + SLE) patients, and to assess its clinical involvement. METHODS: Monocytes, lymphocytes and neutrophils from 80 patients (22 APS, 35 SLE and 23 APS + SLE) and 50 HD were purified, and 45 selected SM components were evaluated by qPCR-microfluidic array. Relationship with clinical features and underlying regulatory mechanisms were assessed. RESULTS: APS, SLE and APS + SLE leukocytes displayed significant and specific alterations in SM-components (SMC), associated with clinical features [autoimmune profiles, disease activity, lupus nephritis (LN), and CV-risk markers]. A remarkable relationship among dysregulated SMC in monocytes and the presence of LN in SLE was highlighted, revealing a novel pathological mechanism, which was further explored. Immunohistology analysis of renal biopsies highlighted the pathological role of the myeloid compartment in LN. Transcriptomic analysis of monocytes from SLE-LN(+) vs SLE-LN(-) identified 271 genes differentially expressed, mainly involved in inflammation and IFN-signaling. Levels of IFN-related genes correlated with those of SMC in SLE-LN(+). These results were validated in two external SLE-LN(+) datasets of whole-blood and kidney biopsies. In vitro, SLE-LN(+)-serum promoted a concomitant dysregulation of both, the IFN signature and several SMC, further reversed by JAKinibs treatment. Interestingly, IFNs, key inflammatory cytokines in SLE pathology, also altered SMC. Lastly, the over/down-expression of selected SMC in SLE-monocytes reduced the release of inflammatory cytokines and their adhesion capacity. CONCLUSION: Overall, we have identified, for the first time, a specific alteration of SMC in leukocytes from APS, SLE and APS + SLE patients that would be responsible for the development of distinctive clinical profiles.


Asunto(s)
Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Inflamación , Citocinas
3.
Phys Rev Lett ; 130(6): 062501, 2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36827565

RESUMEN

The Majorana Demonstrator searched for neutrinoless double-ß decay (0νßß) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to ∼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q_{ßß} (0.12%), we set a half-life limit of 0νßß in ^{76}Ge at T_{1/2}>8.3×10^{25} yr (90% C.L.). This provides a range of upper limits on m_{ßß} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.

4.
Phys Rev Lett ; 131(15): 152501, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37897780

RESUMEN

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.

6.
Epilepsy Behav ; 144: 109253, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37192579

RESUMEN

OBJECTIVE: This study aims to assess the prevalence of Interictal Dysphoric Disorder (IDD) in drug-resistant epilepsy (DRE) and to describe its clinical and psychopathological profile, including personality, as well as its impact on quality of life (QOL). METHOD: A retrospective cross-sectional study from an Epilepsy Unit from January 2007 to December 2017. All patients were diagnosed with DRE. Patients underwent a battery of tests (HADS, SCL-90R, PDQ-4+, QOLIE-31) and a psychiatrist assessed the presence of Axis-I disorders and IDD. Statistical procedures were carried out using R-4.0.1 software. RESULTS: A total of 282 patients were included. A statistically significant association was found between IDD and mood and anxiety disorders (p < 0.001 and p < 0.05 respectively), and between IDD and higher scores in all HADS and SCL-90-R items compared to subjects without IDD (p < 0.001). A statistically significant association was also found between IDD and obsessive-compulsive, borderline and depressive personality disorder (p < 0.05). Scores in all QOLIE-31 items except for 'medication effects' were significantly lower in subjects with IDD compared with subjects without IDD (p < 0.001). CONCLUSIONS: In DRE, IDD subjects show differences in the psychopathological profile and QOL scores compared to subjects without a diagnosis of IDD. An early diagnosis of IDD could facilitate prompt interventions which might positively impact QOL.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Humanos , Calidad de Vida , Epilepsia/epidemiología , Estudios Transversales , Relevancia Clínica , Estudios Retrospectivos
7.
Phys Rev Lett ; 129(8): 080401, 2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36053678

RESUMEN

The Majorana Demonstrator neutrinoless double-beta decay experiment comprises a 44 kg (30 kg enriched in ^{76}Ge) array of p-type, point-contact germanium detectors. With its unprecedented energy resolution and ultralow backgrounds, Majorana also searches for rare event signatures from beyond standard model physics in the low energy region below 100 keV. In this Letter, we test the continuous spontaneous localization (CSL) model, one of the mathematically well-motivated wave function collapse models aimed at solving the long-standing unresolved quantum mechanical measurement problem. While the CSL predicts the existence of a detectable radiation signature in the x-ray domain, we find no evidence of such radiation in the 19-100 keV range in a 37.5 kg-y enriched germanium exposure collected between December 31, 2015, and November 27, 2019, with the Demonstrator. We explored both the non-mass-proportional (n-m-p) and the mass-proportional (m-p) versions of the CSL with two different assumptions: that only the quasifree electrons can emit the x-ray radiation and that the nucleus can coherently emit an amplified radiation. In all cases, we set the most stringent upper limit to date for the white CSL model on the collapse rate, λ, providing a factor of 40-100 improvement in sensitivity over comparable searches. Our limit is the most stringent for large parts of the allowed parameter space. If the result is interpreted in terms of the Diòsi-Penrose gravitational wave function collapse model, the lower bound with a 95% confidence level is almost an order of magnitude improvement over the previous best limit.

8.
Phys Rev Lett ; 129(8): 081803, 2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36053699

RESUMEN

Axions were originally proposed to explain the strong-CP problem in QCD. Through axion-photon coupling, the Sun could be a major source of axions, which could be measured in solid state detection experiments with enhancements due to coherent Primakoff-Bragg scattering. The Majorana Demonstrator experiment has searched for solar axions with a set of ^{76}Ge-enriched high purity germanium detectors using a 33 kg-yr exposure collected between January, 2017 and November, 2019. A temporal-energy analysis gives a new limit on the axion-photon coupling as g_{aγ}<1.45×10^{-9} GeV^{-1} (95% confidence level) for axions with mass up to 100 eV/c^{2}. This improves laboratory-based limits between about 1 eV/c^{2} and 100 eV/c^{2}.

9.
Neurologia ; 35(9): 621-627, 2020.
Artículo en Español | MEDLINE | ID: mdl-38620654

RESUMEN

Introduction: We analysed the neurological complications of patients with severe SARS-CoV-2 infection who required intensive care unit (ICU) admission. Patients and methods: We conducted a retrospective, observational, descriptive study of consecutive patients admitted to the ICU due to severe respiratory symptoms secondary to SARS-CoV-2 infection between 1 April and 1 June 2020. Results: We included 30 patients with neurological symptoms; 21 were men (72.40%), and mean age (standard deviation [SD]) was 57.41 years (11.61). The mean duration of ICU stay was 18.83 days (14.33). The neurological conditions recorded were acute confusional syndrome in 28 patients (93.33%), neuromuscular disease in 15 (50%), headache in 5 (16.66%), cerebrovascular disease in 4 (13.33%), and encephalopathies/encephalitis in 4 (13.33%). CSF analysis results were normal in 6 patients (20%). Brain MRI or head CT showed alterations in 20 patients (66.6%). EEG was performed in all patients (100%), with 8 (26.66%) showing abnormal findings. In 5 of the 15 patients with clinical myopathy, diagnosis was confirmed with electroneuromyography. We found a correlation between older age and duration of ICU stay (P = .002; 95% CI: 4.032-6.022; OR: 3,594). Conclusions: Severe COVID-19 mainly affects men, as observed in other series. Half of our patients presented acute myopathy, and almost all patients left the ICU with acute confusional syndrome, which fully resolved; no correlation was found with EEG or neuroimaging findings. Older age is associated with longer ICU stay.

10.
Int J Biometeorol ; 62(4): 513-523, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28988310

RESUMEN

This study focused on phenological timing and spatial patterns in 30 Poaceae species flowering in spring in different types of plant cover (scrub, riverbank and pasture). Grass community composition was studied, and the influence of species and plant cover on the start date and duration of flowering was assessed from March to June in both 2014 and 2015. Twenty-nine sampling sites were selected for phenological monitoring using the BBCH scale. Data were subjected to GLMM analyses. Binary discriminant analysis revealed differences in grass community composition as a function of plant cover type; scrub cover comprised a considerably larger number of species than those in riverbank and pasture. Moreover, more species diversity was observed in 2014 than in 2015 with a drier and stressed pre-flowering period. Differences on phenology were also recorded between plant cover types and study years. Species in pasture and riverbank flowered before (113.4 days; 116.1 days) than species in scrub (120.9 days), being these species with shorter flowering length because they are more exposed to the characteristic of the Mediterranean region during the summer. In general, flowering onset occurred later in 2014 (118.2 days) than in 2015 (115.8 days), probably attributable to precipitation occurring during March. On the other hand, spatial autocorrelation within some cover types has been observed, showing spatial patterns exist at a smaller scale. The findings of this study contribute to a better understanding of grass phenology in different environments.


Asunto(s)
Flores/crecimiento & desarrollo , Poaceae/crecimiento & desarrollo , Estaciones del Año , Lluvia , España , Temperatura
11.
J Food Sci Technol ; 55(9): 3739-3748, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30150834

RESUMEN

This study considered the effect of the nopal mucilage (NM) fraction on the physical, barrier and mechanical properties of citric pectin-based (CP) films. Pectin aqueous dispersion 75 mL (2.0 g/100 g water) were mixed with 5 mL of glycerol and 20 mL of NM aqueous dispersions at different concentrations; namely, 5, 10, 12, 14 16, 18 and 20 g/100 g water. Films containing the highest NM content (20 g/100 g water) exhibited improved thermal stability. The addition of NM at relatively low concentration (0-10 g/100 g water) led to important modifications of mechanical properties, including elongation to break, tensile strength, and elasticity. Microstructural analysis showed that films containing between 14 and 20 g/100 g water of NM presented rough and fractured surfaces. As mucilage concentration in films was increased, the vapor water permeability decreased as result of better internal cohesiveness of components. The modification of the physical properties in CP films resulted from molecular and physical interaction of its components. In general, the combination of NM and CP for forming edible films led to enhanced thermal stability and higher water vapor permeability, which are prescribed properties for applications as food packaging.

12.
J Food Sci Technol ; 55(3): 935-943, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29487435

RESUMEN

Freeze-dried faba bean (Vicia faba L.) protein adsorption isotherms were determined at 25, 35 and 40 °C and fitted with the Guggenheim-Anderson-de Boer model. The pore radius of protein was in the range of 0.87-6.44 nm, so that they were considered as micropores and mesopores. The minimum integral entropy ranged between 4.33 and 4.44 kg H2O/100 kg d.s., was regarded as the point of maximum of stability. The glass transition temperature of the protein equilibrated at the different conditions of storage was determined, showing that the protein remained in glassy state for all cases. The protein showed compact and rigid structures, evidenced by microscopy analysis.

13.
Clin Genet ; 91(3): 453-457, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27649371

RESUMEN

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by a high genetic heterogeneity with several related genes recently described, including BMPR2,TBX4 and KCNK3. The association between KCNK3 and PAH has been recently identified, but the prognosis and phenotype associated with these mutations have been poorly described. We studied a series of 136 idiopathic and hereditary PAH Spanish patients for BMPR2, TBX4 and KCNK3 mutations. We report the results of KCNK3 in which we were able to describe two new mutations (p.Gly106Arg and p.Leu214Arg) in three patients. The first one was found in a patient belonging to a consanguineous Romani family, who carried a homozygous mutation in KCNK3 and developed a severe and early form of the disease. To the best of our knowledge, this is the first time that a homozygous mutation in KCNK3 is reported in a PAH patient. The second one was found in a patient who presented at the young adult age a severe form of the disease. The present report supports the contribution of KCNK3 mutations to the genetic etiology of PAH and strongly suggests that mutations in KCNK3 follow incomplete dominance with worsening of the clinical features in homozygous patients.


Asunto(s)
Hipertensión Pulmonar Primaria Familiar/genética , Predisposición Genética a la Enfermedad , Mutación , Proteínas del Tejido Nervioso/genética , Canales de Potasio de Dominio Poro en Tándem/genética , Adulto , Niño , Preescolar , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Femenino , Homocigoto , Humanos , Masculino , Linaje , Fenotipo
14.
J Environ Manage ; 172: 129-35, 2016 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-26934641

RESUMEN

Some methods to design water networks with minimum fresh water consumption are based on the selection of a key contaminant. In most of these "single contaminant methods", a maximum allowable concentration of contaminants must be established in water demands and water sources. Turbidity is not a contaminant concentration but is a property that represents the "sum" of other contaminants, with the advantage that it can be cheaper and easily measured than biological oxygen demand, chemical oxygen demand, suspended solids, dissolved solids, among others. The objective of this paper is to demonstrate that turbidity can be used directly in the design of water networks just like any other contaminant concentration. A mathematical demonstration is presented and in order to validate the mathematical results, the design of a water network for a guava fudge production process is performed. The material recovery pinch diagram and nearest neighbors algorithm were used for the design of the water network. Nevertheless, this water network could be designed using other single contaminant methodologies. The maximum error between the expected and the real turbidity values in the water network was 3.3%. These results corroborate the usefulness of turbidity in the design of water networks.


Asunto(s)
Hidrología/métodos , Contaminantes Químicos del Agua/química , Algoritmos , Análisis de la Demanda Biológica de Oxígeno , Agua Dulce/química , Modelos Teóricos , Reproducibilidad de los Resultados , Agua , Contaminantes Químicos del Agua/análisis
15.
Cancer Metastasis Rev ; 33(1): 353-9, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24390486

RESUMEN

This paper summarizes the current understanding of the biology of somatostatin receptor (sst), role of immunotherapy in neuroendocrine tumor (NET), new agents for PPRT, and methods to assess response and clinical benefit in NET. One of the most interesting aspects of sst biology is the recent discovery of truncated variants of the sst5 receptor subtype with unique tissue distribution and response to somatostatin (SST). These truncated receptors are associated with bad patient prognosis, decreased response to SST analogs, and may be new targets for diagnoses and treatment. IFN remains a cost-effective agent, particularly in classic mid gut carcinoids, and there is interest to continue examining immunotherapy's in this disease. PRRT remains a key strategy for treatment and imaging. In addition to the classic agents, there are a series of new agents targeting other receptors such as the incretin receptors (GLP-1R; GIPR) and other G-protein coupled receptors with great potential. With regards to therapy monitoring, the most commonly used criteria are Response Criteria Evaluation in Solid Tumors (RECIST). However, for different reasons, these criteria are not very useful in NET. Incorporation of other criteria such as Choi as well as functional imaging assessment with PET would be of great interest in this area.


Asunto(s)
Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Diagnóstico por Imagen/métodos , Neoplasias Gastrointestinales/metabolismo , Humanos , Inmunoterapia/métodos , Tumores Neuroendocrinos/metabolismo , Receptores de Somatostatina/metabolismo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Resultado del Tratamiento
16.
Hum Reprod ; 30(6): 1491-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25779698

RESUMEN

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association. STUDY FUNDING/COMPETING INTERESTS: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest.


Asunto(s)
Complicaciones de la Diabetes , Menopausia , Adulto , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Humanos , Persona de Mediana Edad
17.
Ann Oncol ; 25(7): 1422-1428, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24718887

RESUMEN

BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.


Asunto(s)
Neoplasias de la Mama/sangre , Posmenopausia , Premenopausia , Prolactina/sangre , Neoplasias de la Mama/etiología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Factores de Riesgo
18.
Stem Cell Res Ther ; 14(1): 366, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38093328

RESUMEN

BACKGROUND: Induced pluripotent stem cell (iPSC)-derived cell therapies are an interesting new area in the field of regenerative medicine. One of the approaches to decrease the costs of iPSC-derived therapies is the use of allogenic homozygous human leukocyte antigen (HLA)-matched donors to generate iPSC lines and to build a clinical-grade iPSC bank covering a high percentage of the Spanish population. METHODS: The Spanish Stem Cell Transplantation Registry was screened for cord blood units (CBUs) homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes. Seven donors were selected with haplotypes covering 21.37% of the haplotypes of the Spanish population. CD34-positive hematopoietic progenitors were isolated from the mononuclear cell fraction of frozen cord blood units from each donor by density gradient centrifugation and further by immune magnetic labeling and separation using purification columns. Purified CD34 + cells were reprogrammed to iPSCs by transduction with the CTS CytoTune-iPS 2.1 Sendai Reprogramming Kit. RESULTS: The iPSCs generated from the 7 donors were expanded, characterized, banked and registered. Master cell banks (MCBs) and working cell banks (WCBs) from the iPSCs of each donor were produced under GMP conditions in qualified clean rooms. CONCLUSIONS: Here, we present the first clinical-grade, iPSC haplobank in Spain made from CD34 + cells from seven cord blood units homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes within the Spanish population. We describe their generation by transduction with Sendai viral vectors and their GMP-compliant expansion and banking. These haplolines will constitute starting materials for advanced therapy medicinal product development (ATMP).


Asunto(s)
Células Madre Pluripotentes Inducidas , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Cadenas HLA-DRB1/metabolismo , Antígenos HLA/metabolismo , Antígenos HLA-B/metabolismo , Antígenos HLA-A/metabolismo
19.
Rev Mal Respir ; 40(9-10): 838-852, 2023.
Artículo en Francés | MEDLINE | ID: mdl-37923650

RESUMEN

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.


Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Asesoramiento Genético/métodos , Hipertensión Arterial Pulmonar/genética , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/terapia , Mutación , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/genética , Pruebas Genéticas/métodos , Predisposición Genética a la Enfermedad
20.
Heliyon ; 9(10): e20903, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37886767

RESUMEN

•Depressive/anxious disorders and cognitive impairment are frequent comorbidities in epilepsy and have a more deleterious effect in DRE.•Studies concerning the relationship between anxiety and depression and cognitive performance in DRE are scarce.•Higher scores in HADS are associated with lower QOLIE-31 scores and might be considered as predictors of QOL in DRE.•A relationship between anxious and depressive symptoms -measured with HADS and SCL-90R- and cognition might not exist.•There remains an unexplored study area regarding this relationship which requires more attention to improve the assessment of DRE.

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