RESUMEN
Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).
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Envejecimiento , Bases de Datos Genéticas , Genómica , Animales , Humanos , Envejecimiento/genética , Senescencia Celular , Longevidad/genéticaRESUMEN
Gene co-expression analysis has emerged as a powerful method to provide insights into gene function and regulation. The rapid growth of publicly available RNA-sequencing (RNA-seq) data has created opportunities for researchers to employ this abundant data to help decipher the complexity and biology of genomes. Co-expression networks have proven effective for inferring the relationship between the genes, for gene prioritization and for assigning function to poorly annotated genes based on their co-expressed partners. To facilitate such analyses we created previously an online co-expression tool for humans and mice entitled GeneFriends. To continue providing a valuable tool to the scientific community, we have now updated the GeneFriends database and website. Here, we present the new version of GeneFriends, which includes gene and transcript co-expression networks based on RNA-seq data from 46 475 human and 34 322 mouse samples. The new database also encompasses tissue-specific gene co-expression networks for 20 human and 21 mouse tissues, dataset-specific gene co-expression maps based on TCGA and GTEx projects and gene co-expression networks for additional seven model organisms (fruit fly, zebrafish, worm, rat, yeast, cow and chicken). GeneFriends is freely available at http://www.genefriends.org/.
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Bases de Datos Genéticas , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Animales , Humanos , ARN , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: Artificial intelligence (AI) has the potential to increase the affordability and accessibility of eye disease screening, especially with the recent approval of AI-based diabetic retinopathy (DR) screening programs in several countries. METHODS: This study investigated the performance, feasibility, and user experience of a seamless hardware and software solution for screening chronic eye diseases in a real-world clinical environment in Germany. The solution integrated AI grading for DR, age-related macular degeneration (AMD), and glaucoma, along with specialist auditing and patient referral decision. The study comprised several components: (1) evaluating the entire system solution from recruitment to eye image capture and AI grading for DR, AMD, and glaucoma; (2) comparing specialist's grading results with AI grading results; (3) gathering user feedback on the solution. RESULTS: A total of 231 patients were recruited, and their consent forms were obtained. The sensitivity, specificity, and area under the curve for DR grading were 100.00%, 80.10%, and 90.00%, respectively. For AMD grading, the values were 90.91%, 78.79%, and 85.00%, and for glaucoma grading, the values were 93.26%, 76.76%, and 85.00%. The analysis of all false positive cases across the three diseases and their comparison with the final referral decisions revealed that only 17 patients were falsely referred among the 231 patients. The efficacy analysis of the system demonstrated the effectiveness of the AI grading process in the study's testing environment. Clinical staff involved in using the system provided positive feedback on the disease screening process, particularly praising the seamless workflow from patient registration to image transmission and obtaining the final result. Results from a questionnaire completed by 12 participants indicated that most found the system easy, quick, and highly satisfactory. The study also revealed room for improvement in the AMD model, suggesting the need to enhance its training data. Furthermore, the performance of the glaucoma model grading could be improved by incorporating additional measures such as intraocular pressure. CONCLUSIONS: The implementation of the AI-based approach for screening three chronic eye diseases proved effective in real-world settings, earning positive feedback on the usability of the integrated platform from both the screening staff and auditors. The auditing function has proven valuable for obtaining efficient second opinions from experts, pointing to its potential for enhancing remote screening capabilities. TRIAL REGISTRATION: Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2021-10574-BO-ff.
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Retinopatía Diabética , Glaucoma , Degeneración Macular , Humanos , Inteligencia Artificial , Retinopatía Diabética/diagnóstico , Tamizaje Masivo/métodos , Programas Informáticos , Degeneración Macular/diagnóstico , Glaucoma/diagnósticoRESUMEN
Mycoses are one of the major causes of morbidity/mortality among immunocompromised individuals. Considering the importance of these infections, the World Health Organization (WHO) defined a priority list of fungi for health in 2022 that include Candida albicans as belonging to the critical priority group and Pichia kudriavzevii (Candida krusei) to the medium priority group. The existence of few available antifungal drugs, their high toxicity, the acquired fungal resistance, and the appearance of new species with a broader spectrum of resistance, points out the need for searching for new antifungals, preferably with new and multiple mechanisms of action. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 was previously tested against several fungi and revealed an interesting activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans. The main objective of the present work was to deeply understand the mechanisms involved in its antifungal activity. The effects of the cyclam salt on yeast metabolic viability (resazurin reduction assay), yeast mitochondrial function (JC-1 probe), production of reactive oxygen species (DCFH-DA probe) and on intracellular ATP levels (luciferin/luciferase assay) were evaluated. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 induced a significant decrease in the metabolic activity of both C. albicans and C. krusei, an increase in Reactive Oxygen Species (ROS) production, and an impaired mitochondrial function. The latter was observed by the depolarization of the mitochondrial membrane and decrease in ATP intracellular levels, mechanisms that seems to be involved in the antifungal activity of H4[H2(4-CF3PhCH2)2Cyclam]Cl4. The interference of the cyclam salt with human cells revealed a CC50 value against HEK-293 embryonic kidney cells of 1.1 µg/mL and a HC10 value against human red blood cells of 0.8 µg/mL.
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Antifúngicos , Candida albicans , Candida , Pruebas de Sensibilidad Microbiana , Especies Reactivas de Oxígeno , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Candida/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , PichiaRESUMEN
Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel "ape-specific" enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.
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Hominidae , Longevidad , Animales , Evolución Molecular , Hominidae/genética , Longevidad/genética , Primates/genética , Secuencias Reguladoras de Ácidos NucleicosRESUMEN
Linking records could serve as a useful tool for scientific research and as a facilitator for local policymaking. This article examines the challenges and opportunities for researchers to lawfully link routinely collected health and education data with cohort data of children when using it as a tool for scientific research in Portugal. Such linking can be lawfully conducted in Portugal if three requirements are met. First, data processing pursues a legitimate purpose, such as scientific research. Secondly, data linking complies with the legal obligations of research entities and researchers, acting as data controllers or processors, and it respects the rights of children as data subjects. Finally, data linking is based on the explicit written consent of those with parental responsibility for the child. So far, the implementation of the General Data Protection Regulation in Portugal has not facilitated record linkage. It is argued that further harmonised implementation of that Regulation across European Union and European Economic Area Member States, establishing a minimum shared denominator for record linkage in scientific research for the common good, including without explicit consent, is needed.
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Unión Europea , Humanos , Niño , PortugalRESUMEN
While mucosal inflammation is a major source of stress during enteropathogen infection, it remains to be fully elucidated how the host benefits from this environment to clear the pathogen. Here, we show that host stress induced by different stimuli mimicking inflammatory conditions strongly reduces the binding of Shigella flexneri to epithelial cells. Mechanistically, stress activates acid sphingomyelinase leading to host membrane remodeling. Consequently, knockdown or pharmacological inhibition of the acid sphingomyelinase blunts the stress-dependent inhibition of Shigella binding to host cells. Interestingly, stress caused by intracellular Shigella replication also results in remodeling of the host cell membrane, in vitro and in vivo, which precludes re-infection by this and other non-motile pathogens. In contrast, Salmonella Typhimurium overcomes the shortage of permissive entry sites by gathering effectively at the remaining platforms through its flagellar motility. Overall, our findings reveal host membrane remodeling as a novel stress-responsive cell-autonomous defense mechanism that protects epithelial cells from infection by non-motile bacterial pathogens.
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Membrana Celular/inmunología , Disentería Bacilar/inmunología , Células Epiteliales/inmunología , Inmunidad Innata , Infecciones por Salmonella/inmunología , Salmonella typhimurium/inmunología , Shigella flexneri/inmunología , Estrés Fisiológico/inmunología , Animales , Membrana Celular/patología , Disentería Bacilar/patología , Células Epiteliales/patología , Cobayas , Infecciones por Salmonella/patologíaRESUMEN
BACKGROUND: Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of patients with allergic diseases. Although the pain caused by the administration of subcutaneous immunotherapy with allergens (SCITA) is considered to be minimal, no studies assessing that pain for the treatment of only pediatric patients have been reported. Objectives: This research aimed to evaluate the pain associated with SCITA for pediatric patients followed at our Immunoallergology Department. METHODS: During four consecutive weeks, the nurse who administered the injection completed a questionnaire recording the child's assessment of the pain associated with SCITA; these questionnaires were randomized before any analyses were done. Two different pain evaluation scales were used, with the choice of scale being determined based on the child's age: the self-reporting faces scale (score: 0-10; 5 to 8 years old) and the numeric scale (score: 0-10; >8 years old). Demographic and clinical data, as well as any adverse reactions, were documented. RESULTS: We included 46 pediatric patients (mean age: 12.3 ± 2.6 years; 69.5% male), most of whom were suffering from rhinitis/rhinoconjunctivitis and undergoing subcutaneous immunotherapy with mites. Seven local adverse reactions were recorded, and all were mild. Ten patients did not mention any pain associated with SCITA. Of the 36 patients who mentioned some pain, 33 mentioned mild pain (scores between 1 and 3); only three mentioned moderate pain (scores between 4 and 6). For both scales, the median score obtained was 1. The maximum pain reported had a score of 6. No significant differences were observed between different groups of patients. CONCLUSIONS: In this study, SCITA was shown to be a mildly painful procedure that is associated with only a few local reactions. Therefore, SCITA should be considered as a safe option for the treatment of most pediatric patients suffering from allergies.
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Alérgenos/administración & dosificación , Desensibilización Inmunológica/estadística & datos numéricos , Dolor Asociado a Procedimientos Médicos/epidemiología , Adolescente , Alérgenos/efectos adversos , Niño , Desensibilización Inmunológica/efectos adversos , Femenino , Humanos , Hipersensibilidad/terapia , Inyecciones Subcutáneas , Masculino , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/etiologíaRESUMEN
Traffic is a main source of air pollutants in urban areas and consequently daily peak exposures tend to occur during commuting. Personal exposure to particulate matter (PM) was monitored while cycling and travelling by bus, car and metro along an assigned route in Lisbon (Portugal), focusing on PM2.5 and PM10 (PM with aerodynamic diameter <2.5 and 10 µm, respectively) mass concentrations and their chemical composition. In vehicles, the indoor-outdoor interplay was also evaluated. The PM2.5 mean concentrations were 28 ± 5, 31 ± 9, 34 ± 9 and 38 ± 21 µg/m3 for bus, bicycle, car and metro modes, respectively. Black carbon concentrations when travelling by car were 1.4 to 2.0 times higher than in the other transport modes due to the closer proximity to exhaust emissions. There are marked differences in PM chemical composition depending on transport mode. In particular, Fe was the most abundant component of metro PM, derived from abrasion of rail-wheel-brake interfaces. Enhanced concentrations of Zn and Cu in cars and buses were related with brake and tyre wear particles, which can penetrate into the vehicles. In the motorised transport modes, Fe, Zn, Cu, Ni and K were correlated, evidencing their common traffic-related source. On average, the highest inhaled dose of PM2.5 was observed while cycling (55 µg), and the lowest in car travels (17 µg). Cyclists inhaled higher doses of PM2.5 due to both higher inhalation rates and longer journey times, with a clear enrichment in mineral elements. The presented results evidence the importance of considering the transport mode in exposure assessment studies.
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Contaminantes Atmosféricos , Material Particulado , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Tamaño de la Partícula , Material Particulado/análisis , Portugal , Emisiones de Vehículos/análisisRESUMEN
Selective breeding of the domestic dog (Canis lupus familiaris) rigidly retains desirable features, and could inadvertently fix disease-causing variants within a breed. We combine phenotypic data from > 72,000 dogs with a large genotypic dataset to search for genes associated with cancer mortality and longevity in pedigree dog breeds. We validated previous findings that breeds with higher average body weight have higher cancer mortality rates and lower life expectancy. We identified a significant positive correlation between life span and cancer mortality residuals corrected for body weight, implying that long-lived breeds die more frequently from cancer compared to short-lived breeds. We replicated a number of known genetic associations with body weight (IGF1, GHR, CD36, SMAD2 and IGF2BP2). Subsequently, we identified five genetic variants in known cancer-related genes (located within SIPA1, ADCY7 and ARNT2) that could be associated with cancer mortality residuals corrected for confounding factors. One putative genetic variant was marginally significantly associated with longevity residuals that had been corrected for the effects of body weight; this genetic variant is located within PRDX1, a peroxiredoxin that belongs to an emerging class of pro-longevity associated genes. This research should be considered as an exploratory analysis to uncover associations between genes and longevity/cancer mortality.
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Enfermedades de los Perros/genética , Enfermedades de los Perros/mortalidad , Predisposición Genética a la Enfermedad , Longevidad/genética , Neoplasias/veterinaria , Alelos , Animales , Biomarcadores , Peso Corporal , Cruzamiento , Perros , Estudios de Asociación Genética , Variación Genética , Genotipo , Linaje , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVES: To identify serum sphingolipids that could act as candidate biomarkers in RA. METHODS: We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient groups with the control group through multiple-regression analyses controlling for age at diagnosis, gender and medication (cDMARDs and corticoids). RESULTS: Established RA patients had significantly increased levels of sphingosine, monohexosylceramide and ceramide compared with controls, when controlling for age and gender. Monohexosylceramide levels remained significantly increased when additionally controlling for medication. On the contrary, SpA patients had significantly decreased levels of ceramide, in both analyses. CONCLUSION: We observed a detectable increase in the levels of certain sphingolipids in the serum of established RA patients when compared with controls, in line with previous observations in the synovial fluid. Such findings provide further evidence that sphingolipids may play a key role in the pathophysiology of RA.
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Artritis Reumatoide/sangre , Cerebrósidos/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Ceramidas/sangre , Femenino , Humanos , Lipidómica , Masculino , Persona de Mediana Edad , Factores Sexuales , Esfingosina/sangreRESUMEN
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally modulate gene expression and orchestrate a wide range of biological and pathological processes. The use of high-throughput screening technologies, in particular microscopy-based screenings (also known as high-content screenings), coupled with genome-wide libraries for modulation of miRNA levels, allow for comprehensive functional analysis of each member of the miRNome in different phenotypic cell-based assays. The wealth of information obtained from such screenings spans across various fields of research, including cancer, cardiovascular, cell reprogramming, and infection biology. Here, we provide an overview of the rationale for performing screenings using synthetic libraries of miRNA mimics and inhibitors, and of the microscopy-based miRNA screenings performed to date. Moreover, a list of resources available for such endeavor is provided. Finally, we describe a detailed procedure for a case study where microscopy-based screening using a library of miRNA mimics was performed to identify miRNAs that control infection of epithelial cells by the bacterial pathogen Salmonella. The methodologies described here can be easily adapted for screenings addressing other biological questions.
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MicroARNs/fisiología , Infecciones por Salmonella/genética , Células Epiteliales/microbiología , Regulación de la Expresión Génica , Humanos , Salmonella , Transfección/métodosRESUMEN
BACKGROUND: Very-low-birth-weight (VLBW) preterm neonates are vulnerable to patent ductus arteriosus (PDA), which might be related to high-resistance flow in the superior mesenteric artery (SMA), with decreased diastolic flow in situations of marked intestinal hypoperfusion. No previous studies have evaluated the portal vein and superior mesenteric vein (SMV) parameters to assess the PDA hemodynamic repercussions. OBJECTIVE: To assess mesenteric and portal flow in VLBW preterm neonates with or without PDA using serial Doppler ultrasonography (US). MATERIALS AND METHODS: We conducted a prospective longitudinal study on 61 VLBW preterm neonates submitted to 161 Doppler US exams, from 2 days to 20 days of age. RESULTS: All infants exhibited a progressive daily increase in the mean of the SMA diameter and systolic velocity, the portal vein diameter, the peak velocity, the mean velocity and the flow volume and of SMV diameter (P<0.05). The incidence of PDA was 37.7% (n=23) and infants with the disease revealed a smaller diameter, greater systolic velocity, lower diastolic velocity, and higher resistivity and pulsatility indices on SMA compared to those without PDA (P<0.05). Additionally, 47.8% (n=11) of infants with PDA exhibited absent or reversed end-diastolic flow in the SMA, and its resolution was seen among 54.5% (n=6) of these. Infants with PDA also exhibited lower values of portal vein diameter and flow volume and of SMV diameter (P<0.01). CONCLUSION: Doppler US enhances the understanding of mesenteric and portal flow, including the effects of PDA. The study of SMV and portal vein flow is proposed as a new parameter in PDA evaluation.
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Conducto Arterioso Permeable/diagnóstico por imagen , Conducto Arterioso Permeable/fisiopatología , Enfermedades del Prematuro/diagnóstico por imagen , Enfermedades del Prematuro/fisiopatología , Arteria Mesentérica Superior/diagnóstico por imagen , Vena Porta/diagnóstico por imagen , Ultrasonografía Doppler , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Estudios Longitudinales , Masculino , Estudios ProspectivosRESUMEN
Glioblastoma (GBM) is a deadly and therapy resistant malignant brain tumour, characterized by an aggressive and diffuse growth pattern, which prevents complete surgical resection. Despite advances in the identification of genomic and molecular alterations that fuel the tumour, average patient survival post-diagnosis remains very low (â¼14.6-months). In addition to being highly heterogeneous, GBM tumour cells exhibit high adaptive capacity to targeted molecular therapies owing to an established network of signalling cascades with functional redundancy, which provides them with robust compensatory survival mechanisms. Here, we investigated whether a multimodal strategy combining multitargeted tyrosine kinase inhibitors (MTKIs) and microRNA (miRNA) modulation could overcome the signalling pathway redundancy in GBM and, hence, promote tumour cell death. By performing a high-throughput screening, we identified a myriad of miRNAs, including those belonging to the miR-302-3p/372-3p/373-3p/520-3p family, which coordinately act with the MTKI sunitinib to decrease GBM cell viability. Two members of this family, hsa-miRNA-302a-3p and hsa-miRNA-520 b, were found to modulate the expression of receptor tyrosine kinase mediators (including AKT1, PIK3CA and SOS1) in U87 and DBTRG human GBM cells. Importantly, administration of mimics of these miRNAs with sunitinib or axitinib resulted in decreased tumour cell proliferation and enhanced cell death, whereas no significant effect was observed when coupling miRNA modulation with temozolomide, the first-line drug for GBM therapy. Overall, our results provide evidence that combining the 'horizontal' inhibition of signalling pathways promoted by MTKIs with the 'vertical' inhibition of the downstream signalling cascade promoted by hsa-miR-302a-3p and hsa-miR-520 b constitutes a promising approach towards GBM treatment.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Glioblastoma/genética , Glioblastoma/terapia , MicroARNs/genética , Inhibidores de Proteínas Quinasas/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Terapia Combinada , Predisposición Genética a la Enfermedad , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , MicroARNs/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , TransfecciónRESUMEN
BACKGROUND: Seagrasses are foundation species in estuarine and lagoon systems, providing a wide array of services for the ecosystem and the human population. Understanding the dynamics of their stands is essential in order to better assess natural and anthropogenic impacts. It is usually considered that healthy seagrasses aim to maximize their stand biomass (g DW m-2) which may be constrained by resource availability i.e., the local environment sets a carrying capacity. Recently, this paradigm has been tested and reassessed, and it is believed that seagrasses actually maximize their efficiency of space occupation-i.e., aim to reach an interspecific boundary line (IBL)-as quick as possible. This requires that they simultaneously grow in biomass and iterate new shoots to increase density. However, this strategy depresses their biomass potential. RESULTS: to comply with this new paradigm, we developed a seagrass growth model that updates the carrying capacities for biomass and shoot density from the seagrass IBL at each time step. The use of a joint biomass and density growth rates enabled parameter estimation with twice the sample sizes and made the model less sensitive to episodic error in either of the variables. The use of instantaneous growth rates enabled the model to be calibrated with data sampled at widely different time intervals. We used data from 24 studies of six seagrass species scattered worldwide. The forecasted allometric biomass-density growth trajectories fit these observations well. Maximum growth and decay rates were found consistently for each species. The growth rates varied seasonally, matching previous observations. CONCLUSIONS: State-of-art models predicting both biomass and shoot density in seagrass have not previously incorporated our observation across many seagrass species that dynamics depend on current state relative to IBL. Our model better simulates the biomass-density dynamics of seagrass stands while shedding light on its intricacies. However, it is only valid for established patches where dynamics involve space-filling, not for colonization of new areas.
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Alismatales/fisiología , Biomasa , Conservación de los Recursos Naturales , Modelos Biológicos , Densidad de Población , Dinámica PoblacionalRESUMEN
Objectives: The main goal of this work was to analyse how treatment intervention with tofacitinib prevents the early disturbances of bone structure and mechanics in the rat model of adjuvant-induced arthritis. This is the first study to access the impact of tofacitinib on the skeletal bone effects of inflammation. Methods: Fifty Wistar rats with adjuvant-induced arthritis were randomly housed in experimental groups, as follows: non-arthritic healthy group (n = 20); arthritic non-treated group (n = 20); and 10 animals undergoing tofacitinib treatment. Rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for comparison. After 22 days of disease progression, rats were killed and bone samples collected for histology, micro-CT, three-point bending and nanoindentation analysis. Blood samples were also collected for quantification of bone turnover markers and systemic cytokines. Results: At the tissue level, measured by nanoindentation, tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and three-point bending tests revealed that tofacitinib did not reverse the effects of arthritis on the cortical and trabecular bone structure and on mechanical properties. Conclusion: Possible reasons for these observations might be related to the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or to the kinetics of its bone effects, which might need longer exposure.
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Artritis/tratamiento farmacológico , Remodelación Ósea/efectos de los fármacos , Resorción Ósea/tratamiento farmacológico , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Adyuvantes Inmunológicos/toxicidad , Animales , Artritis/inducido químicamente , Artritis/complicaciones , Resorción Ósea/diagnóstico , Resorción Ósea/etiología , Huesos/metabolismo , Huesos/patología , Modelos Animales de Enfermedad , Femenino , Osteocalcina/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Ratas , Ratas Wistar , Resultado del Tratamiento , Microtomografía por Rayos XRESUMEN
BACKGROUND: Biomass-density relations have been at the centre of a search for an index which describes the health of seagrass meadows. However, this search has been complicated by the intricacy of seagrass demographics and their complex biomass-density relations, a consequence mainly of their modular growth and clonality. Concomitantly, biomass-density upper boundaries have been determined for terrestrial plants and algae, reflecting their asymptotic maximum efficiencies of space occupation. Each stand's distance to its respective biomass-density upper boundary reflects its effective efficiency in packing biomass, which has proved a reliable ecological indicator in order to discriminate between taxonomic groups, functional groups and clonal vs. non-clonal growth. RESULTS: We gathered data from 32 studies on 10 seagrass species distributed worldwide and demonstrated that seagrasses are limited by their own boundary line, placed below the boundaries previously determined for algae and terrestrial plants. Then, we applied a new metric-dgrass: each stand's perpendicular distance to the seagrass boundary-and used this parameter to review fundamental aspects such as clonal growth patterns, depth distribution, seasonality, interspecific competition, and the effects of light, temperature and nutrients. CONCLUSIONS: Seagrasses occupy space less efficiently than algae and terrestrial plants. Using only their biomass and density data we established a new and efficient tool to describe space occupation by seagrasses. This was used with success to evaluate their meadows as an ecological indicator for the health of coastal ecosystems.
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Alismatales/fisiología , Biomasa , Especies Centinela/fisiología , Metadatos , Densidad de PoblaciónRESUMEN
AIM: This systematic review and meta-analysis presents an overview of the efficacy of suit therapy on functioning in children and adolescents with cerebral palsy (CP). METHOD: A systematic review with meta-analysis was conducted. A comprehensive search of peer-reviewed articles was performed on electronic databases, from their inception to May 2014. Studies included were rated for methodological quality using the Physiotherapy Evidence Database scale. Effects of suit therapy on functioning were assessed using meta-analytic techniques. RESULTS: From the 46 identified studies, four met the inclusion criteria and were included in the meta-analysis. Small, pooled effect sizes were found for gross motor function at post-treatment (g=0.46, 95% confidence interval [CI] 0.10-0.82) and follow-up (g=0.47, 95% CI 0.03-0.90). INTERPRETATION: The small number of studies, the variability between them, and the low sample sizes are limitations of this review. Findings suggest that to weigh and balance benefits against harms, clinicians, patients, and families need better evidence to examine and prove the effects of short intensive treatment such as suit therapy on gross motor function in children and adolescents with CP. Therefore, more research based on high-quality studies focusing on functioning in all dimensions of the International Classification of Functioning, Disability and Health perspective is necessary to clarify the impact of suit therapy.
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Parálisis Cerebral/rehabilitación , Terapia por Ejercicio/instrumentación , Evaluación de Resultado en la Atención de Salud , Adolescente , Niño , Terapia por Ejercicio/métodos , HumanosRESUMEN
The purpose of this study was to evaluate the validity and the reliability of the European Portuguese version of the EAT-10 (P-EAT-10). This research was conducted in three phases: (i) cultural and linguistic adaptation; (ii) feasibility and reliability test; and (iii) validity tests. The final sample was formed by a cohort of 520 subjects. The P-EAT-10 index was compared for socio-demographic and clinic variables. It was also compared for both dysphagic and non-dysphagic groups as well as for the results of the 3Oz wst. Lastly, the P-EAT-10 scores were correlated with the EuroQol Group Portuguese EQ-5D index. The Cronbach's α obtained for the P-EAT-10 scale was 0.952 and it remained excellent even if any item was deleted. The item-total and the intraclass correlation coefficients were very good. The P-EAT-10 mean of the non-dysphagic cohort was 0.56 and that of the dysphagic cohort was 14.26, the mean comparison between the 3Oz wst groups and the P-EAT-10 scores were significant. A significant higher perception of QoL was also found among the non-dysphagic subjects. P-EAT-10 is a valid and reliable measure that may be used to document dysphagia which makes it useful both for screening in clinical practice and in research.