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FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.
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Leucemia Mieloide Aguda , Mutação , Proteínas Nucleares , Nucleofosmina , Tirosina Quinase 3 Semelhante a fms , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Idoso , Masculino , Feminino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Proteínas Nucleares/genética , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagem , Adulto , Taxa de SobrevidaRESUMO
Plant-based beverages (PBB) market is largely growing. In this study, 136 beverages made of soy, oat, almond, rice, tigernut, and others (mixtures of various plant materials), from the Spanish market were evaluated through labelling information. Energy value and fat content were intermediate between skimmed and whole cow milk; while fatty acids profile was quite different. Carbohydrate content was usually higher than cow milk, and highly dependent on the addition of sugars. All products provided some dietary fibre. With the exception of soy-based drinks, samples presented lower protein and calcium content than milk (1/3 samples studied were Ca-fortified), and 23% were vitamin D enriched. The claim "No added sugars" was in more than 50% samples. A right labelling and nutritional education of consumers is essential to make adequate choices, since the appearing of many claims is not always indicative of a better-quality product. Plant-based beverages cannot be considered as an alternative to milk, but as a different product, with their own nutritional and functional entity. Their inclusion in a diversified balanced diet can provide interesting functional components, such as soluble fibre or unsaturated fatty acids (mainly soybean and almond drink), which can help improve the health status of the population.
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Rotulagem de Alimentos , Leite , Feminino , Animais , Bovinos , Bebidas , Vitaminas , AçúcaresRESUMO
Germplasm banks are the most significant repository for plant genetic resources for food and agriculture (PGRFA) worldwide. Despite their strategic importance, national germplasm banks of tropical megadiverse developing countries such as Colombia have extremely limited funds. Therefore, making strategic decisions about research investment is essential. Here, we designed a data-driven approach to build an index that sorts Colombian PGRFA into three groups: high, medium, or low priority, based on four pillars of information from open-access databases and aligned with the sustainable goals of no poverty and zero hunger: Geographic origin, vulnerability status, economic benefits, and food security importance. We analyzed 345 PGRFA using the index, separating them into two groups, 275 already conserved in the Colombian germplasm bank (BGVCOL group) and 70 not currently conserved in the BGVCOL (NCB group). We used fuzzy logic to classify each PGRFA by each pillar and integrate it to obtain a priority index. Missing data for native crops were frequent in the BGVCOL group. Therefore we adopted an imputation strategy to fill the gaps and calculated the uncertainty. After applying the index, PGRFA with higher priority were 24 (8.72%) from the BGVCOL (i.e., 15 potatoes, three tomatoes, two tree tomatoes, pineapple, cocoa, papaya, and yacon) and one from NCB (i.e., coffee). We concluded that this methodology successfully prioritized PGRFA in Colombia and shows the big holes of knowledge for future research and alternatives to improve this index. The versatility of this methodology could be helpful in other genebanks with budget limitations for research investment. Supplementary Information: The online version contains supplementary material available at 10.1007/s10531-023-02599-7.
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There is an increasing trend today towards plant-based diets in western society, often resulting in milk restriction. In the case of very young children, the direct substitution of milk by other foods, without proper nutritional advice, may lead to a lack of nutrients and hence to growth and development alterations. This study focuses on the nutritional assessment of various commercially available plant-based drinks, to determine their adequacy as alternatives to ruminant milk, in relation to the nutritional requirements of toddlers (1-3 years old), and to establish whether other sources of nutrient supplementation may be needed, as well as any other possible positive and /or negative health effects associated to their consumption. A sample of 179 commercial plant-based drinks (almond, coconut, hemp, oat, rice, soy, tigernut) were chosen and their nutrient contents were compared to the EFSA nutrient reference values for toddlers. The scientific literature on the presence of bioactive and/or undesirable compounds was reviewed. None of the plant-based drinks studied should be considered as a milk substitute, since they are different food products with a different composition. However, from the results obtained, the best choice for toddlers who do not consume milk would be to consume at least 250 mL/day of fortified soy drink (for its higher amount and quality of protein, polyunsaturated fatty acids and phytosterols), and always in the context of a carefully-balanced diet. Almond, hemp or oat drinks are other alternatives that can be used in combination or for soy-allergic toddlers. The key nutrients that should be fortified in plant-based drinks are: vitamins A and B12, calcium, zinc and iodine, as they represent the most significant nutritional differences with milk; vitamin D would also be desirable. Of these, vitamins A, B12, D and calcium, are easily found in many commercial plant-based drinks on the Spanish market (most frequently in soy drinks), unlike iodine and zinc, which were not added to any. Given the fish restriction in vegetarians/vegans and the fact that plant-based drinks provide high amounts of phytates and tannins, which act as antinutrients, a good strategy for the industry would be to fortify plant-based drinks with iodine and zinc to improve the nutritional value of products aimed to vegetarians/vegans.
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Iodo , Veganos , Animais , Cálcio , Humanos , Avaliação Nutricional , Vegetarianos , Vitaminas , ZincoRESUMO
ABSTRACT The pathologies caused by microbial groups generate health risks in domestic dogs and cats; showing a zoonotic potential and producing affections in humans. According to that background, the purpose of this study was to establish the main microorganisms causing clinical pathologies in domestic dogs and cats by reviewing medical records in a veterinary clinic in Valledupar, Colombia. In order to do that, a retrospective study was conducted with clinical histories of dogs and cats admitted during 2017 and 2018 to the veterinary clinic "Mis Mejores Amigos", located in the city of Valledupar, Colombia. Based on the information, a descriptive, explanatory and statistical analysis was applied, the latter by means of a Sperman correlation to evaluate the relationship between race, sex, age, microbial group and pathology-pathogen. From a total of 462 reports of canines and felines admitted to the clinic, a total of 273 diagnoses were obtained. 4% of the felines and 24% of the canines were affected by some microbial group. The most prevalent microorganisms in canines were Ancylostoma spp. (9 %) Entamoeba histolytica (5%) Ehrlichia spp. (5%), and Isospora sp. (5%) while in felines were Haemobartonella felis (20%) and Haemobartonella spp. (17%). It was determined that there is only correlation between the age of felines and the microbial group that affects them, in addition to the pathology presented with the pathogen. It was observed a high percentage of Ancylostoma sp. (9%) in canines of mongrel and French Poodle breeds whilst in felines was found the bacterium Haemobartonella felis in 20% of the mongrel breeds.
RESUMEN Las patologías causadas por grupos microbianos generan riesgos en la salud de perros y gatos domésticos, lo que tiene un potencial zoonótico y produce afecciones en seres humanos. De acuerdo con lo anterior, el objetivo de este estudio fue establecer los principales microorganismos causantes de patologías clínicas en perros y gatos domésticos mediante la revisión de historias clínicas en una clínica veterinaria de Valledupar, Colombia. Se realizó un estudio retrospectivo con historias clínicas de perros y gatos ingresados durante 2017 y 2018 a la clínica veterinaria "Mis mejores amigos", ubicada en la ciudad de Valledupar, Colombia. Con base en la información se aplicó un análisis descriptivo, explicativo y estadístico, este último mediante una correlación de Sperman para evaluar relación entre raza, sexo, edad, grupo microbiano y patología-patógeno. De un total 462 reportes de caninos y felinos ingresados a la clínica, se obtuvieron 273 diagnósticos. El 4% de los felinos y el 24 % de los caninos presentaban afecciones por algún grupo microbiano. Los microorganismos más prevalentes en caninos fueron Ancylostoma spp. (9%) Entamoeba histolytica (5%) Ehrlichia spp. (5%) e Isospora sp. (5%), mientras que en felinos fueron Haemobartonella felis (20%) y Haemobartonella spp. (17%). Se determinó que solo existe correlación entre la edad de felinos y el grupo microbiano que los afecta, además de la patología presentada con el patógeno. Se observó un alto porcentaje de Ancylostoma sp. (9%) en caninos de las razas mestiza y French Poodle, y, por otro lado, en felinos se identificó la bacteria Haemobartonella felis en 20% de los sujetos de raza mestiza.
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Animais , Gatos , Cães , Parasitos , Patologia , Bactérias , Zoonoses , Diagnóstico , Animais de Estimação , Estudos Retrospectivos , Felidae , Cães , Entamoeba histolyticaRESUMO
RESUMEN La parasitosis intestinal en mamíferos silvestres es una de las principales complicaciones debido a las condiciones exógenas del cautiverio; predisponen al animal a complicaciones fisiológicas o infecciones secundarias que impiden su rehabilitación y reintroducción. El objetivo de esta investigación fue determinar la presencia de parásitos gastrointestinales en mamíferos silvestres del Centro de Atención y Valoración de Fauna silvestre del Centro de Educación Ambiental San Emigdio, San Emigdio, Palmira (Colombia). Se tomaron muestras fecales de 25 animales cautivos en el Centro de Atención y Valoración y fueron analizadas mediante dos técnicas: a) montaje con solución salina al 0,85 % y solución de lugol al 1% y b) técnica de flotación por solución saturada (Sheather) con densidad de 1.28g/ml, encontrando un 36% de positividad. Se encontró Enterobius vermicularis, Fasciola sp., Entamoeba sp. y Ancylostoma sp. El grupo de primates no humanos presentó cargas parasitarias más altas con respecto a felinos, caninos y demás mamíferos del estudio. Los microorganismos identificados son reconocidos como parásitos causantes de complicaciones en animales cautivos y en libertad; al igual, son catalogados como posibles riesgos zoonóticos.
ABSTRACT Intestinal parasitosis in wild mammals is one of the main complications due to the exogenous conditions of captivity. They predispose the animal to physiological complications or secondary infections that prevent its rehabilitation and reintroduction. The objective is to determine the presence of gastrointestinal parasites in wild mammals from the Wildlife Care and Valuation Center of the San Emigdio Environmental Education Center, San Emigdio, Palmira (Colombia). Fecal samples were taken from 25 captive animals in Care and Valuation Center being analyzed using two techniques: a) assembly with 0.85% saline solution and 1% lugol solution and b) saturated solution flotation technique (Sheather) with a density of 1.28g/ml, with a 36% of positivity. Enterobius vermicularis, Fasciola sp., Entamoeba sp. and Ancylostoma sp. were found. The group of non-human primates had higher parasitic intensity compared to felines, canines and other mammals in the study. The identified microorganisms are recognized as parasites causing complications in captive animals and in free life; likewise, they are classified as possible zoonotic risks.
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Animais , Parasitos , Trematódeos , Zoonoses , Meio Selvagem , Infecções , Mamíferos , Nematoides , Doenças Parasitárias , Toxoplasma , Sarcocystis , Entamoeba , Fasciola , IsosporaRESUMO
All organisms live in close association with a variety of microorganisms called microbiota. Furthermore, several studies support a fundamental role of the microbiota on the host health and homeostasis. In this context, the aim of this work was to determine the structure and diversity of the microbiota associated with the scallop Argopecten purpuratus, and to assess changes in community composition and diversity during the host immune response. To do this, adult scallops were immune challenged and sampled after 24 and 48â¯h. Activation of the immune response was established by transcript overexpression of several scallop immune response genes in hemocytes and gills, and confirmed by protein detection of the antimicrobial peptide big defensin in gills of Vibrio-injected scallops at 24â¯h post-challenge. Then, the major bacterial community profile present in individual scallops was assessed by denaturing gradient gel electrophoresis (DGGE) of 16S rDNA genes and dendrogram analyses, which indicated a clear clade differentiation of the bacterial communities noticeable at 48â¯h post-challenge. Finally, the microbiota structure and diversity from pools of scallops were characterized using 16S deep amplicon sequencing. The results revealed an overall modulation of the microbiota abundance and diversity according to scallop immune status, allowing for prediction of some changes in the functional potential of the microbial community. Overall, the present study showed that changes in the structure and diversity of bacterial communities associated with the scallop A. purpuratus are detected after the activation of the host immune response. Now, the relevance of microbial balance disruption in the immune capacity of the scallop remains to be elucidated.
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Imunidade Inata , Microbiota , Pectinidae/imunologia , Vibrio/fisiologia , Animais , DNA Bacteriano/análise , Eletroforese em Gel de Gradiente Desnaturante , Pectinidae/microbiologia , RNA Ribossômico 16S/análise , Análise de Sequência de RNARESUMO
Robot-mediated neurorehabilitation is a growing field that seeks to incorporate advances in robotics combined with neuroscience and rehabilitation to define new methods for treating problems related with neurological diseases. In this paper, a systematic literature review is conducted to identify the contribution of robotics for upper limb neurorehabilitation, highlighting its relation with the rehabilitation cycle, and to clarify the prospective research directions in the development of more autonomous rehabilitation processes. With this aim, first, a study and definition of a general rehabilitation process are made, and then, it is particularized for the case of neurorehabilitation, identifying the components involved in the cycle and their degree of interaction between them. Next, this generic process is compared with the current literature in robotics focused on upper limb treatment, analyzing which components of this rehabilitation cycle are being investigated. Finally, the challenges and opportunities to obtain more autonomous rehabilitation processes are discussed. In addition, based on this study, a series of technical requirements that should be taken into account when designing and implementing autonomous robotic systems for rehabilitation is presented and discussed.
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Reabilitação Neurológica/instrumentação , Robótica/instrumentação , Reabilitação do Acidente Vascular Cerebral/instrumentação , Extremidade Superior/fisiopatologia , Humanos , Doenças do Sistema Nervoso , Estudos Prospectivos , Recuperação de Função FisiológicaRESUMO
Small RNA and chaperone proteins form synergistic duos that play pivotal roles in controlling gene expression in bacteria. This is the case for Hfq, a highly pleiotropic pretranslational modulator of general protein expression, which responds to harsh environmental conditions and influences fitness and virulence in a wide range of pathogenic Enterobacteria. Given this relevancy, we evaluated the presence and potential role of Hfq in the fish pathogen Piscirickettsia salmonis, a Gram-negative bacterium that threatens the sustainability of Chilean salmon production. Using bioinformatics tools were identified and characterized two variants of Hfq, which share the consensus RNA-binding domains and the active sites described functional Hfq other bacteria. Additionally, we demonstrated that hfq-1 and hfq-2 were transcriptionally active when growing in cell-free media and in infected susceptible fish cell line. Expression of both genes differed under different growth conditions and under stress, suggesting that their roles might be independent and different, depending on the bacterial physiological status. In conclusion, we demonstrate the existence of two different and functional ORF coding for the hfq marker in marine bacteria and a preliminary analysis indicating that these two novel proteins might have relevant roles in the biology and pathogenic potential of P. salmonis.
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Fator Proteico 1 do Hospedeiro/genética , Oncorhynchus mykiss , Piscirickettsia/isolamento & purificação , Infecções por Piscirickettsiaceae/veterinária , Salmo salar , Sequência de Aminoácidos , Animais , Linhagem Celular , Chile , Doenças dos Peixes/microbiologia , Fator Proteico 1 do Hospedeiro/metabolismo , Infecções por Piscirickettsiaceae/microbiologia , Alinhamento de SequênciaRESUMO
STUDY QUESTION: Are there intracellular Ca2+ ([Ca2+]i) oscillations correlated with flagellar beating in human sperm? SUMMARY ANSWER: The results reveal statistically significant [Ca2+]i oscillations that are correlated with the human sperm flagellar beating frequency, when measured in three-dimensions (3D). WHAT IS KNOWN ALREADY: Fast [Ca2+]i oscillations that are correlated to the beating flagellar frequency of cells swimming in a restricted volume have been detected in hamster sperm. To date, such findings have not been confirmed in any other mammalian sperm species. An important question that has remained regarding these observations is whether the fast [Ca2+]i oscillations are real or might they be due to remaining defocusing effects of the Z component arising from the 3D beating of the flagella. STUDY DESIGN, SIZE, DURATION: Healthy donors whose semen samples fulfill the WHO criteria between the age of 18-28 were selected. Cells from at least six different donors were utilized for analysis. Approximately the same number of experimental and control cells were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Motile cells were obtained by the swim-up technique and were loaded with Fluo-4 (Ca2+ sensitive dye) or with Calcein (Ca2+ insensitive dye). Ni2+ was used as a non-specific plasma membrane Ca2+ channel blocker. Fluorescence data and flagella position were acquired in 3D. Each cell was recorded for up to 5.6 s within a depth of 16 microns with a high speed camera (coupled to an image intensifier) acquiring at a rate of 3000 frames per second, while an oscillating objective vibrated at 90 Hz via a piezoelectric device. From these samples, eight experimental and nine control sperm cells were analyzed in both 2D and 3D. MAIN RESULTS AND THE ROLE OF CHANCE: We have implemented a new system that allows [Ca2+]i measurements of the human sperm flagellum beating in 3D. These measurements reveal statistically significant [Ca2+]i oscillations that correlate with the flagellar beating frequency. These oscillations may arise from intracellular sources and/or Ca2+ transporters, as they were insensitive to external Ni2+, a non-specific plasma membrane Ca2+ channel blocker. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Analysis in 3D needs a very fast image acquisition rate to correctly sample a volume containing swimming sperm. This condition requires a very short exposure time per image making it necessary to use an image intensifier which also increases noise. The lengthy analysis time required to obtain reliable results limited the number of cells that could be analyzed. WIDER IMPLICATIONS OF THE FINDINGS: The possibility of recording flagellar [Ca2+]i oscillations described here may open a new avenue to better understand ciliary and flagellar beating that are fundamental for mucociliary clearance, oocyte transport, fertilization, cerebrospinal fluid pressure regulation and developmental left-right symmetry breaking in the embryonic node. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACyT) (grants 253952 to G.C.; 156667 to F.M.M. and Fronteras 71 39908-Q to A.D. and Post-doctoral scholarships 366844 to P.H.-H. and 291028 to F.M.) and the Dirección General de Asuntos del Personal Académico of the Universidad Nacional Autónoma de México (DGAPA-UNAM) (grants CJIC/CTIC/4898/2016 to F.M. and IN205516 to A.D.). There are no conflicts of interest to declare.
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Canais de Cálcio/fisiologia , Cálcio/metabolismo , Imageamento Tridimensional/métodos , Motilidade dos Espermatozoides/fisiologia , Cauda do Espermatozoide/fisiologia , Espermatozoides/fisiologia , Adolescente , Adulto , Compostos de Anilina/química , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Fluoresceínas/química , Corantes Fluorescentes/química , Humanos , Imageamento Tridimensional/instrumentação , Masculino , Níquel/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Cauda do Espermatozoide/efeitos dos fármacos , Cauda do Espermatozoide/ultraestrutura , Espermatozoides/efeitos dos fármacos , Espermatozoides/ultraestrutura , Gravação em Vídeo , Xantenos/químicaRESUMO
Despite the significant advances in the development of automated image analysis algorithms for the detection and extraction of neuronal structures, current software tools still have numerous limitations when it comes to the detection and analysis of dendritic spines. The problem is especially challenging in in vivo imaging, where the difficulty of extracting morphometric properties of spines is compounded by lower image resolution and contrast levels native to two-photon laser microscopy. To address this challenge, we introduce a new computational framework for the automated detection and quantitative analysis of dendritic spines in vivo multi-photon imaging. This framework includes: (i) a novel preprocessing algorithm enhancing spines in a way that they are included in the binarized volume produced during the segmentation of foreground from background; (ii) the mathematical foundation of this algorithm, and (iii) an algorithm for the detection of spine locations in reference to centerline trace and separating them from the branches to whom spines are attached to. This framework enables the computation of a wide range of geometric features such as spine length, spatial distribution and spine volume in a high-throughput fashion. We illustrate our approach for the automated extraction of dendritic spine features in time-series multi-photon images of layer 5 cortical excitatory neurons from the mouse visual cortex.
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Algoritmos , Espinhas Dendríticas/ultraestrutura , Imageamento Tridimensional/métodos , Animais , Processamento de Imagem Assistida por Computador/métodos , Masculino , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neurônios/ultraestrutura , Córtex Visual/citologiaRESUMO
For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients. Cumulative incidence of neutrophil engraftment was 97% in the Haplo-Cord and 100% in the PTCY-haplo group, achieved in a median of 12 and 17 days, respectively (P=0.01). Grade II-IV acute GvHD rate was significantly higher in the PTCY-haplo group (9.8% vs 29%, P=0.02) as well as chronic GvHD rates (20% vs 38%, P=0.03). With a median follow-up of 61 months for the Haplo-Cord group and 26 months for the PTCY-haplo cohort, overall survival at 2 years was 55% and 59% (P=0.66), event-free survival was 45% vs 56% (P=0.46), relapse rate was 27% vs 21% (P=0.79), and non-relapse mortality was 17% vs 23% (P=0.54), respectively. In this multicenter experience, Haplo-Cord and PTCY-haplo HSCT offer valid alternatives for patients with AML. Neutrophil engraftment was faster in the Haplo-Cord cohort, with similar survival rates, with higher GvHD rates after haploidentical HSCT.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Ciclofosfamida/uso terapêutico , Leucemia Mieloide Aguda/terapia , Transplante Haploidêntico/métodos , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
The different forms of diabetes mellitus differ in their pathogenesis but, ultimately, they are all characterized by progressive islet ß-cell loss. Restoring the ß-cell mass is therefore a major goal for future therapeutic approaches. The number of ß-cells found at birth is determined by proliferation and differentiation of pancreatic progenitor cells, and it has been considered to remain mostly unchanged throughout adult life. Recent studies in mice have revealed an unexpected plasticity in islet endocrine cells in response to stress; under certain conditions, islet non-ß-cells have the potential to reprogram into insulin producers, thus contributing to restore the ß-cell mass. Here, we discuss the latest findings on pancreas and islet cell plasticity upon physiological, pathological and experimental conditions of stress. Understanding the mechanisms involved in cell reprogramming in these models will allow the development of new strategies for the treatment of diabetes, by exploiting the intrinsic regeneration capacity of the pancreas.
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Plasticidade Celular , Reprogramação Celular , Células Secretoras de Insulina/citologia , Estresse Fisiológico , Animais , Diabetes Mellitus , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/fisiologia , Camundongos , Regeneração , Células-TroncoRESUMO
Relapsed or refractory Hodgkin lymphoma (advanced HL) still remains a therapeutic challenge. Recently, unmanipulated haploidentical related donor transplant with reduced conditioning regimen (HAPLO-RIC) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has became a promising rescue strategy potentially available to almost every patient. This paper reports our multicenter experience using an IV busulfan-based HAPLO-RIC regimen and PT-Cy in the treatment of 43 patients with advanced HL. Engraftment occurred in 42 patients (97.5%), with a median time to neutrophil and platelet recovery of 18 and 26 days. Cumulative incidences of grades II-IV acute GvHD and chronic GvHD were 39% and 19%, respectively. With a median follow-up of 25.5 months for survivors, 27 patients are alive, with 22 of them disease free. Cumulative incidences of 1-year non-relapse mortality and relapse at 2 years were 21% and 24%, respectively. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 48% and 58%, respectively. CR prior to HAPLO-RIC correlated with better EFS (78.5% vs 33.5%; P=0.015) and OS (86% vs 46%; P=0.044). Our findings further confirm prior reports using HAPLO-RIC in advanced HL in a multicenter approach employing an IV busulfan-based conditioning regimen.
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Bussulfano/uso terapêutico , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença de Hodgkin/complicações , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Espanha , Análise de Sobrevida , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
We report the first case of recently characterized species M. monacense associated with chronic nodular vasculitis, infecting a young woman. This case represents the first isolation of M. monacense from Ecuador. The isolate was identified by conventional and molecular techniques.
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Inhibitors of nuclear factor kappa B (IκBs) are major control components of the Rel/NF-κB signaling pathway, a key regulator in the modulation of the expression of immune-related genes in vertebrates and invertebrates. The activation of the Rel/NF-κB signaling pathway depends largely in the degradation of IκB proteins and thus, IκBs are a main target for the identification of genes whose expression is controlled by Rel/NF-κB pathway. In order to identify such regulation in bivalve mollusks, the cDNA sequence encoding an IκB protein was characterized in the scallop Argopecten purpuratus, ApIκB. The cDNA sequence of ApIκB is comprised of 1480 nucleotides with a 1086 bp open reading frame encoding for 362 amino acids. Bioinformatics analysis showed that ApIκB displays the conserved features of IκB proteins. The deduced amino acid sequence consists of a 39.7 kDa protein, which has an N-terminal degradation motif, six ankyrin repeats and a C-terminal phosphorylation site motif. Phylogenetic analysis revealed a high degree of identity between ApIκB and other IκBs from mollusks, but also to arthropod cactus proteins and vertebrate IκBs. Tissue expression analysis indicated that ApIκB is expressed in all examined tissues and it is upregulated in circulating hemocytes from scallops challenged with the pathogenic Gram-negative bacterium Vibrio splendidus. After inhibiting ApIκB gene expression using the RNA interference technology, the gene expression of the antimicrobial peptide big defensin was upregulated in hemocytes from non-challenged scallops. Results suggest that ApIκB may control the expression of antimicrobial effectors such as big defensin via a putative Rel/NF-κB signaling pathway. This first evidence will help to deepen the knowledge of the Rel/NF-κB conserved pathway in scallops.
Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Expressão Gênica , NF-kappa B/antagonistas & inibidores , Pectinidae/genética , Pectinidae/imunologia , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Proteínas I-kappa B/química , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Especificidade de Órgãos , Moléculas com Motivos Associados a Patógenos/farmacologia , Pectinidae/metabolismo , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Homologia Estrutural de ProteínaRESUMO
Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble intercellular adhesion molecule 1 (ICAM-1) and VCAM-1, von Willebrand factor (vWF), and high-sensitivity C-reactive protein (hs-CRP) in 228 biomass-exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56 years (s.d. = 13), average BMI was 26.5 kg/m(2) (s.d. = 4.4), 48% were male, 59.4% completed high school, and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302 ng/ml; P < 0.001), soluble VCAM-1 (403 vs. 362 ng/ml; P < 0.001), and E-selectin (54.2 vs. 52.7 ng/ml; P = 0.05) were increased in biomass-exposed vs. non-exposed participants, respectively, whereas serum levels of vWF (1148 vs. 1311 mU/ml; P < 0.001) and hs-CRP (2.56 vs. 3.12 mg/l; P < 0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (P = 0.03) and VCAM-1 (P = 0.05) and E-selectin (P = 0.05), and remained negatively associated with serum levels of vWF (P = 0.02) and hs-CRP (P < 0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed.
Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Biocombustíveis/toxicidade , Exposição Ambiental/efeitos adversos , Fumaça/efeitos adversos , Biomarcadores/sangue , Biomassa , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Selectina E/sangue , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Peru , Fatores de Risco , Proteína Amiloide A Sérica/análise , Molécula 1 de Adesão de Célula Vascular/sangue , Fator de von Willebrand/análiseRESUMO
Sperm commonly compete within females to fertilize ova, but research has focused on short-term sperm storage: sperm that are maintained in a female for only a few days or weeks before use. In nature, females of many species store sperm for months or years, often during periods of environmental stress, such as cold winters. Here we examine the outcome of sperm competition in the fruit fly Drosophila pseudoobscura, simulating the conditions in which females survive winter. We mated females to two males and then stored the female for up to 120 days at 4°C. We found that the outcome of sperm competition was consistent when sperm from two males was stored for 0, 1 or 30 days, with the last male to mate fathering most of the offspring. However, when females were stored in the cold for 120 days, the last male to mate fathered less than 5% of the offspring. Moreover, when sperm were stored long term the first male fathered almost all offspring even when he carried a meiotic driving sex chromosome that drastically reduces sperm competitive success under short-term storage conditions. This suggests that long-term sperm storage can radically alter the outcome of sperm competition.
Assuntos
Temperatura Baixa , Drosophila/fisiologia , Hibernação/fisiologia , Estações do Ano , Animais , Feminino , Masculino , Reprodução , Comportamento Sexual Animal , Espermatozoides/fisiologia , Fatores de TempoRESUMO
MOTIVATION: PAR-CLIP, a CLIP-seq protocol, derives a transcriptome wide set of binding sites for RNA-binding proteins. Even though the protocol uses stringent washing to remove experimental noise, some of it remains. A recent study measured three sets of non-specific RNA backgrounds which are present in several PAR-CLIP datasets. However, a tool to identify the presence of common background in PAR-CLIP datasets is not yet available. RESULTS: We used the measured sets of non-specific RNA backgrounds to build a common background set. Each element from the common background set has a score that reflects its presence in several PAR-CLIP datasets. We present a tool that uses this score to identify the amount of common backgrounds present in a PAR-CLIP dataset, and we provide the user the option to use or remove it. We used the proposed strategy in 30 PAR-CLIP datasets from nine proteins. It is possible to identify the presence of common backgrounds in a dataset and identify differences in datasets for the same protein. This method is the first step in the process of completely removing such backgrounds. AVAILABILITY: The tool was implemented in python. The common background set and the supplementary data are available at https://github.com/phrh/BackCLIP. CONTACT: phreyes@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Reagentes de Ligações Cruzadas/química , Bases de Dados Genéticas , Imunoprecipitação/métodos , Software , Raios Ultravioleta , Proteínas de Ligação a RNA/metabolismoRESUMO
BACKGROUND: The Pfeffer Functional Activities Questionnaire (PFAQ) is a validated instrument used in Chile to diagnose dependency in older people. AIM: To suggest a shorter and easier version of the PFAQ, with appropriate levels of sensitivity and specificity, which may be applied to the general older population. MATERIAL AND METHODS: Three Chilean surveys applied to older people were used, namely the Survey of Life Events of the Elderly, (n = 1,371) and the 2010 and 2013 National Surveys of Quality of Life of Older People (n = 1,954 and 2,644 respectively). To evaluate the instrument, we performed correlation analysis between items and principal components analysis. We calculated internal consistency using Cronbach alpha, we computed sensitivity and specificity indicators, and analyzed convergent and predictive validity. RESULTS: After constructing different scales, the one that gave more information and had the best balance between sensitivity and specificity was chosen. Items with less weight factor and greater gender bias were eliminated, keeping seven questions from the original PFAQ. Reliability was verified using Cronbach alpha's coefficient and from correlations between the new instrument and key variables. CONCLUSIONS: According to our goals, the proposed scale is solely conformed by items that do not have gender bias. It discriminates in the general population adequately, allowing the design of a shorter test, of easier implementation.