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Oceanic islands have been recognized as natural laboratories in which to study a great variety of evolutionary processes. One such process is evolutionary radiations, the diversification of a single ancestor into a number of species that inhabit different environments and differ in the traits that allow them to exploit those environments. The factors that drive evolutionary radiations have been studied for decades in charismatic organisms such as birds or lizards, but are lacking in lichen-forming fungi, despite recent reports of some lineages showing diversification patterns congruent with radiation. Here we propose the Ramalina decipiens group as a model system in which to carry out such studies. This group is currently thought to be comprised of five saxicolous species, all of them endemic to the Macaronesian region (the Azores, Madeira, Selvagens, Canary and Cape Verde islands). Three species are single-island endemics (a rare geographic distribution pattern in lichens), whereas two are widespread and show extreme morphological variation. The latter are suspected to harbor unrecognized species-level lineages. In order to use the Ramalina decipiens group as a model system it is necessary to resolve the group's phylogeny and to clarify its species boundaries. In this study we attempt to do so following an integrative taxonomy approach. We constructed a phylogenetic tree based on six molecular markers, four of which are newly developed and generated competing species hypotheses based on molecular (species discovery strategies based on both single locus and multilocus datasets) and phenotypic data (unsupervised clustering algorithms based on morphology, secondary chemistry and geographic origin). We found that taxonomic diversity in the Ramalina decipiens group has been highly underestimated in previous studies. In consequence, we describe six new species, most of them single-island endemics and provide a key to the group. Phylogenetic relationships among species have been reconstructed with almost full support which, coupled with the endemic character of the group, makes it an excellent system for the study of island radiations in lichen-forming fungi. Citation: Blázquez M, Pérez-Vargas I, Garrido-Benavent I, et al. 2024. Endless forms most frustrating: disentangling species boundaries in the Ramalina decipiens group (Lecanoromycetes, Ascomycota), with the description of six new species and a key to the group. Persoonia 52: 44-93. https://doi.org/10.3767/persoonia.2024.52.03 .
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Nails are a keratinized matrix that has been proposed as an alternative to hair to evaluate long-term and retrospective consumption of drugs of abuse and pharmaceuticals. This matrix has been gaining interest in recent years, with new studies focusing on the analysis of fingernails and/or toenails for different substances. However, nails and hair present differences in structure, growth, and incorporation pathways that may affect drug incorporation and analysis and complicate the interpretation of the results. To better understand the results in nail samples, a comparison of concentrations found in hair, fingernails, and toenails has been described in the literature for some drugs. This review unifies the results found in the literature, with special interest on studies that report paired samples from the same individuals. Differences between fingernail and toenail samples, as well as proposed cut-offs in nails, are also discussed. Definite conclusions can be reached for some drugs, but, in general, more standardized studies are needed to better understand nail results.
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The Variational Monte Carlo (VMC) method has recently seen important advances through the use of neural network quantum states. While more and more sophisticated ansatze have been designed to tackle a wide variety of quantum many-body problems, modest progress has been made on the associated optimization algorithms. In this work, we revisit the Kronecker-Factored Approximate Curvature (KFAC), an optimizer that has been used extensively in a variety of simulations. We suggest improvements in the scaling and the direction of this optimizer and find that they substantially increase its performance at a negligible additional cost. We also reformulate the VMC approach in a game theory framework, to propose a novel optimizer based on decision geometry. We find that on a practical test case for continuous systems, this new optimizer consistently outperforms any of the KFAC improvements in terms of stability, accuracy and speed of convergence. Beyond VMC, the versatility of this approach suggests that decision geometry could provide a solid foundation for accelerating a broad class of machine learning algorithms. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.
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OBJECTIVE: Vitiligo is a common systemic, idiopathic autoimmune disease. The aim of this study was to analyze the frequency of variants of the superoxide dismutase 1 (SOD1) gene (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) and circulating plasma protein levels through in-silico analysis. PATIENTS AND METHODS: Blood samples were collected from adult patients of both sexes with a clinical diagnosis of vitiligo. ELISA tests for SOD and analysis of gene variants by qPCR were compared to a disease-free reference group. RESULTS: The population analyzed was young people between 29 and 37 years old, with a higher percentage of women. The population was found in the Hardy-Weinberg equilibrium (HWE). The 50 bp Ins/Del, rs4817415, and rs2070424 variants showed no significant difference between groups (p > 0.05). Although, in the dominant model, the CT and CTTT genotypes of the rs1041740 and rs17880135 variants showed an association with susceptibility to vitiligo compared to the control. Plasma SOD levels showed significant differences between the groups, and when stratified according to the genotypes of each variant, there was a significant difference, except with the rs17880135 variant. The haplotypes InsCGTC and InsAGCC are shown to be risk factors for susceptibility to vitiligo. The in-silico analysis demonstrated that the rs4817415, rs2070424, rs1041740, and rs17880135 variants of the SOD1 gene participate in the modification of selected regulatory elements for differentiating the protein, transcription factors, and long non-coding RNA. CONCLUSIONS: Information regarding the pathogenesis of vitiligo helps recognize risk factors and identify the relationship of diagnostic markers of cell damage inherent to the disease. This will help improve aspects of prevention and the choice of treatment alternatives appropriate to each case.
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Vitíligo , Masculino , Adulto , Humanos , Femenino , Adolescente , Superóxido Dismutasa-1/genética , Vitíligo/genética , Genotipo , Factores de Riesgo , Proteínas Sanguíneas/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.
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Dieta Mediterránea , Gases de Efecto Invernadero , Humanos , Dieta , Ambiente , Recolección de DatosRESUMEN
OBJECTIVE: The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as well as to perform in silico assessments of the variants' potential impact. PATIENTS AND METHODS: We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR. RESULTS: The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs). CONCLUSIONS: The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.
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Neoplasias de la Mama , Superóxido Dismutasa , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple , Factores de Riesgo , ARN Circular , Superóxido Dismutasa/genética , Factores de Transcripción/genéticaRESUMEN
OBJECTIVES: We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults. DESIGN: Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial. SETTING: Community-dwelling, free-living participants in PREDIMED-Plus trial. PARTICIPANTS: 6,874 Spanish older adults (55-75 years, 49% women) with overweight/obesity and metabolic syndrome. INTERVENTION: Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations. MEASUREMENTS: COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk. RESULTS: Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12)). CONCLUSIONS: There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks.
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COVID-19 , Enfermedades Cardiovasculares , Dieta Mediterránea , Síndrome Metabólico , Humanos , Femenino , Anciano , Masculino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/prevención & control , Síndrome Metabólico/complicaciones , Sobrepeso/complicaciones , Estudios Prospectivos , Enfermedades Cardiovasculares/etiología , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/complicaciones , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/terapia , Estilo de Vida , Pérdida de PesoRESUMEN
Glial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRα1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRα1 complex also supports synaptic cell adhesion independently of RET. Here, we describe the structure of a decameric GDNF-GFRα1 assembly determined by crystallography and electron microscopy, revealing two GFRα1 pentamers bridged by five GDNF dimers. We reconsitituted the assembly between adhering liposomes and used cryo-electron tomography to visualize how the complex fulfils its membrane adhesion function. The GFRα1:GFRα1 pentameric interface was further validated both in vitro by native PAGE and in cellulo by cell-clustering and dendritic spine assays. Finally, we provide biochemical and cell-based evidence that RET and heparan sulfate cooperate to prevent assembly of the adhesion complex by competing for the adhesion interface. Our results provide a mechanistic framework to understand GDNF-driven cell adhesion, its relationship to trophic signalling, and the central role played by GFRα1.
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Factor Neurotrófico Derivado de la Línea Celular Glial , Proteínas Proto-Oncogénicas c-ret , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas c-ret/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: To describe patients hospitalized in internal medicine in terms of malnutrition and sarcopenia, depending on the presence or absence of type 2 diabetes mellitus (DM2), as well as to evaluate short- and long-term mortality related to both. METHODS: Cross-sectional, single-center study, which included consecutive patients admitted to internal medicine in May and October 2021. Malnutrition was determined using the Mini Nutritional Assessment-Short Form (MNA-SF) and sarcopenia using SARC-F and handgrip strength. Patients hospitalized for more than 48â¯h are excluded. RESULTS: 511 patients were analyzed, 49.1% male, mean age 75.2 +/- 15 years, 210 (41.1%) DM2. 6 groups (2â¯×â¯3 design) are generated based on the presence of DM2 and the nutritional status according to the result of the MNA-SF: 12-14 points, without risk; MNA-SF 8-12 points, high risk; MNA-SF 0-7 points, malnourished. Malnourished patients with DM2 had significantly higher sarcopenia, comorbidity, inflammation, and pressure ulcers. The main determinants of in-hospital mortality were sarcopenia (OR 1.27, 95%CI 1.06-1.54, pâ¯=â¯0.01), comorbidity (OR 1.27, 95%CI 1,08-1,49, pâ¯=â¯0.003) and inflammation (OR 1.01, 95%CI 1.00-1.02, pâ¯=â¯0.02). The 120-day prognosis was worse among malnourished patients (pâ¯=â¯0.042). CONCLUSION: Patients admitted with DM2 have a similar degree of malnutrition than the rest, but with greater sarcopenia. This sarcopenia, together with inflammation and comorbidity determine a worse prognosis. The active and early identification of malnutrition and sarcopenia and their subsequent approach could improve the prognosis of patients.
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Diabetes Mellitus Tipo 2 , Desnutrición , Sarcopenia , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Sarcopenia/diagnóstico , Fuerza de la Mano , Estudios Transversales , Desnutrición/complicaciones , Pronóstico , Inflamación , Medicina Interna , Evaluación GeriátricaRESUMEN
BACKGROUND AND OBJECTIVES: There are no clinical guidelines on the management of dysplastic nevus (DN). The aims of this study were to determine the percentage of dermatologists in the center-Spain section of the Spanish Academy of Dermatology and Venereology (AEDV) who would manage a histologically confirmed DN with a watch-and-wait approach or with wider surgical margins and to investigate whether their attitudes would vary depending on whether or not the patient had a personal and/or family history of melanoma. MATERIAL AND METHODS: We collected data from an anonymous survey sent to 738 dermatologists between June 15 and July 31, 2022. The independent variables were degree of dysplasia (low vs. high), margin status (positive vs. negative), and a personal or family history of melanoma (yes vs. no in both cases). The dependent variables were attitude towards management (watch-and-wait vs. re-excision with a surgical margin of 1 to 4mm or re-excision with a surgical margin of 5 to 10mm). RESULTS: We obtained 86 responses to the questionnaire. When pathology indicated a low-grade DN, 60.5% of dermatologists stated they would obtain a surgical margin of 1 to 4mm if the first margins were positive, and 97.7% would watch and wait if the report described negative margins. For high-grade DNs, 1.2% of dermatologists would watch and wait to manage DN with positive margins; 68.8% would use this approach for negative margins. A family or personal history of melanoma had no influence on most of the dermatologists' attitudes. CONCLUSIONS: Management strategies for DN among dermatologists from the center-Spain section of the AEDV varied, particularly when faced with low-grade DN with positive margins and high-grade DN with negative margins. A family or personal history of melanoma did not influence clinical attitudes in most cases.
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Dermatología , Síndrome del Nevo Displásico , Melanoma , Neoplasias Cutáneas , Venereología , Humanos , Síndrome del Nevo Displásico/cirugía , Síndrome del Nevo Displásico/patología , Márgenes de Escisión , España , Dermatólogos , Melanoma/cirugía , Melanoma/patología , Encuestas y Cuestionarios , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC. DESIGN AND METHODS: Type of study: National multicenter longitudinal analytical observational study. STUDY POPULATION: Patients with FPTMC. STUDY GROUPS: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). STUDY VARIABLES: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. STATISTICAL ANALYSIS: Cox regression analysis and survival analysis. RESULTS: Ninety-four patients were included, 44% (n = 41) with unicentric FPTMC and 56% (n = 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%; p = 0.003), lymph node dissection (41 vs. 15%; p = 0.005) and therapy with radioactive iodine (96 vs. 73%; p = 0.002). Tumor stage was similar in both groups (p = 0.237), with a higher number of T3 cases in the group B (24 vs. 5%; p = 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%; p = 0.337), disease recurrence rate (21 vs. 8%; p = 0.159) and disease-free survival (p = 0.075). CONCLUSIONS: Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.
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Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/patología , Radioisótopos de Yodo/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma Papilar/patología , Pronóstico , Tiroidectomía/métodos , Estudios RetrospectivosRESUMEN
The nuclear shell model is one of the prime many-body methods to study the structure of atomic nuclei, but it is hampered by an exponential scaling on the basis size as the number of particles increases. We present a shell-model quantum circuit design strategy to find nuclear ground states by exploiting an adaptive variational quantum eigensolver algorithm. Our circuit implementation is in excellent agreement with classical shell-model simulations for a dozen of light and medium-mass nuclei, including neon and calcium isotopes. We quantify the circuit depth, width and number of gates to encode realistic shell-model wavefunctions. Our strategy also addresses explicitly energy measurements and the required number of circuits to perform them. Our simulated circuits approach the benchmark results exponentially with a polynomial scaling in quantum resources for each nucleus. This work paves the way for quantum computing shell-model studies across the nuclear chart and our quantum resource quantification may be used in configuration-interaction calculations of other fermionic systems.
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PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.
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Linfoma , Neoplasias de la Tiroides , Tiroiditis , Humanos , Estudios RetrospectivosRESUMEN
Ionic liquids (ILs) are widely applied in many bioprocesses involving microorganisms due to their unique properties. In this work, the toxicity of imidazolium and pyrrolidinium ionic liquids towards E. coli., a bacterium for which there are limited toxicity data in the literature, was determined. For its simplicity, the nephelometry method was used to estimate ionic liquid toxicity values. The influence of the cation and the alkyl chain length of the cation and anion was analysed. Pyrrolidinium cations were seen to be less toxic than imidazolium cations, while an increase in the alkyl chain length of both pyrrolidinium and imidazolium cations increased the toxicity. Among the anions studied, dimethylphosphate ([Me2PO4]) was the less toxic, while the EC50 for the ionic liquid 1-butyl-3-methylpyrrolidinium dimethylphosphate ([C1C4Pyr][Me2PO4]) was close to 200 mM. Furthermore, a dicationic ionic liquid based on imidazolium and pyrrolidinium cations was synthetized and its toxicity toward E. coli was analysed, maintaining a growth rate of 100 % in the range 0-0.76 mM. The methodology used in this work allows to easily find the less toxic ionic liquids that are biocompatible with E. coli to be used in new bioprocesses.
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Líquidos Iónicos , Líquidos Iónicos/toxicidad , Escherichia coli , CationesRESUMEN
BACKGROUND: Understanding the perception of the risks associated with xenotransplant, especially among professionals who will contribute to the care of the animals, is important for xenotransplant to become a clinical reality. The objective of this study was to analyze opinions regarding the risks of organ xenotransplant among veterinary university students in Spain. METHODS: The study population was 2683 veterinary students from different courses and universities in Spain. Instrument valuation: Validated self-administered questionnaire completed anonymously (PCID-XENOTx-Ríos). Consent to collaborate in the study was requested. Variables for the study: attitude toward xenotransplant and risks (infectious, immunologic, ethical/moral, philosophical, religious, other unspecified risks). STATISTICS: descriptive analysis, Student t test, χ2 test, and Fisher exact test. RESULTS: Of the total number of respondents, 2646 students answered this question, with a completion rate of 98.6%. They considered immunologic risk 78.4% (n = 2074), infectious risk 48.6% (n = 1286), ethical/moral risk 10.7% (n = 284), philosophical risk 5.2% (n = 137), religious risk 1.5% (n = 40), and other risks 3.9% (n = 104). Significant relationships were observed between immunologic risks (P < .001), ethical/moral risks (P < .001), and other risks (P = .002). CONCLUSIONS: Despite the consideration of different types of risks, the favorable attitude toward xenotransplant among veterinary students at Spanish universities is highly prevalent, and evidence-based information campaigns on the different risks associated with xenotransplant are important.
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Trasplante de Órganos , Obtención de Tejidos y Órganos , Animales , Humanos , Trasplante Heterólogo/efectos adversos , Universidades , Actitud , España , Encuestas y Cuestionarios , Estudiantes , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Background and Purpose: Verapamil, a drug widely used in certain cardiac pathologies, exert its therapeutic effect mainly through the blockade of cardiac L-type calcium channels. However, we also know that both voltage-dependent and certain potassium channels are blocked by verapamil. Because sympathetic neurons of the superior cervical ganglion (SCG) are known to express a good variety of potassium currents, and to finely tune cardiac activity, we speculated that the effect of verapamil on these SCG potassium channels could explain part of the therapeutic action of this drug. To address this question, we decided to study, the effects of verapamil on three different potassium currents observed in SCG neurons: delayed rectifier, A-type and TREK (a subfamily of K2P channels) currents. We also investigated the effect of verapamil on the electrical behavior of sympathetic SCG neurons. Experimental Approach: We employed the Patch-Clamp technique to mouse SCG neurons in culture. Key Results: We found that verapamil depolarizes of the resting membrane potential of SCG neurons. Moreover, we demonstrated that this drug also inhibits A-type potassium currents. Finally, and most importantly, we revealed that the current driven through TREK channels is also inhibited in the presence of verapamil. Conclusion and Implications: We have shown that verapamil causes a clear alteration of excitability in sympathetic nerve cells. This fact undoubtedly leads to an alteration of the sympathetic-parasympathetic balance which may affect cardiac function. Therefore, we propose that these possible peripheral alterations in the autonomic system should be taken into consideration in the prescription of this drug.
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PURPOSE: Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain. METHODS: Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence). RESULTS: Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210-5.473; p = 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638-1000; p < 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405-333.333; p < 0.001). CONCLUSION: FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA.