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Huanglongbing, also known as citrus greening, is currently the most devastating citrus disease with limited success in prevention and mitigation. A promising strategy for Huanglongbing control is the use of antimicrobials fused to a carrier protein (phloem protein of 16 kDa or PP16) that targets vascular tissues. This study investigated the effects of genetically modified citrus trees expressing Citrus sinensis PP16 (CsPP16) fused to human lysozyme and ß-defensin-2 on the soil microbiome diversity using 16S amplicon analysis. The results indicated that there were no significant alterations in alpha diversity, beta diversity, phylogenetic diversity, differential abundance, or functional prediction between the antimicrobial phloem-overexpressing plants and the control group, suggesting minimal impact on microbial community structure. However, microbiota diversity analysis revealed distinct bacterial assemblages between the rhizosphere soil and root environments. This study helps to understand the ecological implications of crops expressing phloem-targeted antimicrobials for vascular disease management, with minimal impact on soil microbiota.
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Bacterias , Citrus , Microbiota , Floema , Enfermedades de las Plantas , Rizosfera , Microbiología del Suelo , Floema/microbiología , Floema/metabolismo , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Enfermedades de las Plantas/microbiología , Citrus/microbiología , Plantas Modificadas Genéticamente/microbiología , Plantas Modificadas Genéticamente/genética , Filogenia , Metagenómica , Muramidasa/metabolismo , Muramidasa/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , beta-Defensinas/genética , ARN Ribosómico 16S/genética , Antiinfecciosos/farmacología , Antiinfecciosos/metabolismo , Citrus sinensis/microbiología , Raíces de Plantas/microbiologíaRESUMEN
Dietary polyphenols have beneficial effects in situations of impaired cognition in acute models of neurodegeneration. The possibility that they may have a direct effect on the electrical activity of neuronal populations has not been tested. We explored the electrophysiological action of protocatechuic acid (PCA) on CA1 pyramidal cells ex vivo and network activity in anesthetized female rats using pathway-specific field potential (FP) generators obtained from laminar FPs in cortex and hippocampus. Whole-cell recordings from CA1 pyramidal cells revealed increased synaptic potentials, particularly in response to basal dendritic excitation, while the associated evoked firing was significantly reduced. This counterintuitive result was attributed to a marked increase of the rheobase and voltage threshold, indicating a decreased ability to generate spikes in response to depolarizing current. Systemic administration of PCA only slightly altered the ongoing activity of some FP generators, although it produced a striking disengagement of infraslow activities between the cortex and hippocampus on a scale of minutes. To our knowledge, this is the first report showing the direct action of a dietary polyphenol on electrical activity, performing neuromodulatory roles at both the cellular and network levels.
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Hipocampo , Neuronas , Ratas , Femenino , Animales , Potenciales de Acción/fisiología , Hipocampo/fisiología , Neuronas/fisiología , Células Piramidales/fisiologíaRESUMEN
Agave tequilana stems store fructan polymers, the main carbon source for tequila production. This crop takes six or more years for industrial maturity. In conducive conditions, agave wilt disease increases the incidence of dead plants after the fourth year. Plant susceptibility induced for limited photosynthates for defense is recognized in many crops and is known as "sink-induced loss of resistance". To establish whether A. tequilana is more prone to agave wilt as it ages, because the reduction of water-soluble carbohydrates in roots, as a consequence of greater assembly of highly polymerized fructans, were quantified roots sucrose, fructose, and glucose, as well as fructans in stems of agave plants of different ages. The damage induced by inoculation with Fusarium solani or F. oxysporum in the roots or xylem bundles, respectively, was recorded. As the agave plant accumulated fructans in the stem as the main sink, the amount of these hexoses diminished in the roots of older plants, and root rot severity increased when plants were inoculated with F. solani, as evidence of more susceptibility. This knowledge could help to structure disease management that reduces the dispersion of agave wilt, dead plants, and economic losses at the end of agave's long crop cycle.
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Agave , Fructanos , Fusarium , Enfermedades de las Plantas , Raíces de Plantas , Agave/microbiología , Agave/metabolismo , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Fructanos/metabolismo , Enfermedades de las Plantas/microbiología , Fusarium/patogenicidad , Hexosas/metabolismo , Tallos de la Planta/microbiología , Tallos de la Planta/metabolismoRESUMEN
Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.
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Alzheimer's disease (AD) is associated with senile plaques of beta-amyloid (Aß) that affect the function of neurons and astrocytes. Brain activity results from the coordinated function of neurons and astrocytes in astroglial-neuronal networks. However, the effects of Aß on astroglial and neuronal network function remains unknown. Simultaneously monitoring astrocyte calcium and electric neuronal activities, we quantified the impact of Aß on sensory-evoked cortical activity in a mouse model of AD. At rest, cortical astrocytes displayed spontaneous hyperactivity that was related to Aß density. Sensory-evoked astrocyte responsiveness was diminished in AD mice, depending on the density and distance of Aß, and the responses showed altered calcium dynamics. Hence, astrocytes were spontaneously hyperactive but hypo-responsive to sensory stimulation. Finally, AD mice showed sensory-evoked electrical cortical hyperresponsiveness associated with altered astrocyte-neuronal network interplay. Our findings suggest dysfunction of astrocyte networks in AD mice may dysregulate cortical electrical activity and contribute to cognitive decline.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides/farmacología , Animales , Astrocitos , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Neuronas , Placa AmiloideRESUMEN
INTRODUCTION: Parvalbumin (PV)-positive cells are strategic elements of neuronal networks capable of influencing memory and learning processes. However, it is not known whether pituitary hormones may be related to PV expression in the hippocampus - a part of the limbic system with important functions in learning and memory. OBJECTIVE: Since previous studies indicate that prolactin (PRL) plays a significant role in hippocampal-dependent learning and synaptic plasticity, we hypothesized that a rise in PRL levels can modify PV expression in the hippocampus. METHODS: We employed biochemical, immunohistochemistry, and densitometry techniques - as well as a behavioural assay - in a hyperprolactinemia model using subcutaneous osmotic pumps in female mice. RESULTS: PRL treatment via osmotic pump induced an increase in PRL receptor (PRLR) expression in most regions of the hippocampus analysed by Western blotting and immunohistochemistry methods. Fluorescent densitometry analysis revealed that PV expression decreases in the same layers in the hippocampus following PRL treatment, while double labelling immunostaining indicated close localization of PV and PRLR in PV-positive interneurons. In addition, we found that PRL induced a reduction in the ß2/3 subunit of GABAA receptor (GABAAR) expression that was linearly correlated with the reduction in PV expression. This reduction in the ß2/3 subunit of GABAAR expression was maintained in trained animals in which PRL treatment improved the learning of a spatial memory task. CONCLUSIONS: These data show, for the first time, that an increase in PRL level is associated with changes in key constituent elements of inhibitory circuits in the hippocampus and may be of relevance for the alterations in cognitive function reported in hyperprolactinemia.
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Hipocampo , Hiperprolactinemia , Parvalbúminas , Prolactina , Receptores de GABA-A , Animales , Femenino , Hipocampo/metabolismo , Ratones , Parvalbúminas/metabolismo , Prolactina/farmacología , Receptores de GABA-A/metabolismo , Receptores de Prolactina/metabolismoRESUMEN
PURPOSE: We aim to evaluate the effects of myofascial induction therapy (MIT) on the sequelae suffered by the survivors of HNC (sHNC). METHODS: We enrolled 46 sHNC in a randomized controlled trial (RCT), of whom 20 received a MIT protocol and 23 were placed on a waitlist while receiving the recommended treatment for 6 weeks. The MIT protocol included a total of 18 sessions, 3 days a week on alternate days for 6 weeks. Maximal mouth opening, the presence of temporomandibular dysfunction, cervical endurance, active range of motion (AROM), shoulder AROM, handgrip strength, and perceived physical fitness were assessed. RESULTS: Maximal mouth opening, temporomandibular dysfunction, cervical endurance, and AROM, affected shoulder abduction and unaffected shoulder flexion and external rotation significantly improved (p < .05) after an MIT protocol, but only cervical AROM and affected shoulder abduction changes were clinically meaningful. No statistically significant changes were observed in the other shoulder AROM, handgrip strength, or physical fitness perception (p > .05). CONCLUSION: A 6-week MIT protocol improves mouth opening, TMD, cervical function (endurance and AROM), affected shoulder abduction and unaffected shoulder flexion, and external rotation AROM in the sHNC. However, no changes were observed in most of the shoulder AROM, muscular strength, or perceived physical fitness. Future studies should perform longer follow-up designs, increase the sample size, and include multimodal treatments to address these sequelae in the sHNC.
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Neoplasias de Cabeza y Cuello , Quimioterapia de Inducción , Humanos , Hombro , Rango del Movimiento Articular , Neoplasias de Cabeza y Cuello/terapia , SobrevivientesRESUMEN
Chitinase chi18-5 is an enzyme able to hydrolyze chitin and chitosan producing chitooligosaccharides (COS) of potential technological interest. chi18-5 is produced naturally by the fungus Trichoderma atroviride. It belongs to the glycosyl hydrolase (GH) family 18 of the Carbohydrate Active Enzyme (CAZy) database and it has 83% identity compared to the well-characterized chi42 of Trichoderma harzianum. Several efforts have been made to characterize the biochemical activity of the enzyme and its structure. Here, we studied the biophysical properties of recombinant chi18-5. In order to gain insight into its structure and stability, we studied thermal denaturation by Circular Dichroism (CD), Intrinsic Fluorescence (FL), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FT-IR) at several pH between 3 and 8. We observed that the conformation of chi18-5 changes near its pI, and the transitions as a function of the temperature involved an increment in ß-sheet secondary structure at the expenses of âº-helix. We also performed amide hydrogen exchange dynamics in selected conditions. At pH ≤ 6, the proportion of fast exchanging residues are larger than at pH ≥ 6. Our results suggest that at pH below pI, chi18-5 is in a less compact structure which may have influence in the interaction with substrate and enzyme activity. KEY POINTS: ⢠Characterization of enzyme behavior is critical for their wide applications ⢠We produced and characterized biophysically a chitinase as a function of pH ⢠The pH of optimum activity correlates with a less compact structure of chi18-5.
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Quitinasas , Quitina , Quitinasas/genética , Quitinasas/metabolismo , Concentración de Iones de Hidrógeno , Estructura Secundaria de Proteína , Espectroscopía Infrarroja por Transformada de Fourier , TemperaturaRESUMEN
The South Brazilian grasslands (Campos Sulinos) form the dominant vegetation in southern Brazil. They are species-rich ecosystems that occur under distinct geomorphological and climatic conditions but spatial variation of plant species diversity remains understudied. Here, we present a detailed description of plant communities across the region. Our data were obtained in 1080 plots, representing well-preserved grasslands in different ecological systems. Apart from describing alpha and beta diversity, we investigated the relations of plant communities with environmental features. We identified 759 plant species and found clear differences in community composition across the region. Northern and Southern highland grasslands, humid and dry coastal grasslands and the mesic Pampa grassland were clearly distinct, related to climatic and edaphic features. While species abundance distribution was markedly uneven, local species richness was high, above 20 species/m2, especially in the highlands and in mesic Pampa sites, on shallow soils. The predominant component of beta diversity was species turnover, which suggests that a network of well-conserved grasslands distributed across the region would be the best strategy to protect plant diversity. Our results establish regionalized reference values for richness and diversity that can be useful for initiatives of restoration and conservation of these grasslands.
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Ecosistema , Pradera , Biodiversidad , Brasil , Plantas , Valores de ReferenciaRESUMEN
Dynamic signaling between the endocrine system (ES) and the nervous system (NS) is essential for brain and body homeostasis. In particular, reciprocal interaction occurs during pregnancy and motherhood that may involve changes in some brain plasticity processes. Prolactin (PRL), a hormone with pleiotropic effects on the NS, promotes maternal behavior and has been linked to modifications in brain circuits during motherhood; however, it is unclear whether PRL may regulate synaptic plasticity. Therefore, the main aim of the present work was to determine the cellular and molecular mechanisms triggered by PRL that regulate synaptic plasticity in the hippocampus. By analyzing extracellular recordings in CA3-CA1 synapses of hippocampal slices, we report that PRL modifies short and long-term synaptic plasticity in female mice of reproductive age, but not in sexually immature females or adult males. This effect is carried out through mechanisms that include participation of GABAA receptors and activation of the JAK2-mediated signaling pathway. These findings show for the first time how PRL enhances the synaptic strength in hippocampal circuits and that this effect is sexually dimorphic, which would influence complex brain processes in physiological conditions like pregnancy and lactation.
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Plasticidad Neuronal , Prolactina , Animales , Femenino , Hipocampo/fisiología , Potenciación a Largo Plazo/fisiología , Masculino , Ratones , Plasticidad Neuronal/fisiología , Receptores de GABA-A , Sinapsis/fisiología , Transmisión Sináptica/fisiologíaRESUMEN
The Program for Biodiversity Research (PPBio) is an innovative program designed to integrate all biodiversity research stakeholders. Operating since 2004, it has installed long-term ecological research sites throughout Brazil and its logic has been applied in some other southern-hemisphere countries. The program supports all aspects of research necessary to understand biodiversity and the processes that affect it. There are presently 161 sampling sites (see some of them at Supplementary Appendix), most of which use a standardized methodology that allows comparisons across biomes and through time. To date, there are about 1200 publications associated with PPBio that cover topics ranging from natural history to genetics and species distributions. Most of the field data and metadata are available through PPBio web sites or DataONE. Metadata is available for researchers that intend to explore the different faces of Brazilian biodiversity spatio-temporal variation, as well as for managers intending to improve conservation strategies. The Program also fostered, directly and indirectly, local technical capacity building, and supported the training of hundreds of undergraduate and graduate students. The main challenge is maintaining the long-term funding necessary to understand biodiversity patterns and processes under pressure from global environmental changes.
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Biodiversidad , Ecosistema , Brasil , Conservación de los Recursos Naturales , Humanos , ConocimientoRESUMEN
AIM: This manuscript aims to evaluate, through a scoping review, current knowledge of the biomechanical behavior, materials, preparations, and limitations of occlusal veneers. BACKGROUND: Occlusal veneers are a minimally invasive alternative for the additive restoration of posterior teeth with significant loss of the occlusal structure. This type of restoration has been emerged in recent years as an alternative to invasive treatment, which in the same way seeks to restore the structure of the posterior teeth. All this is because in recent years restorative dentistry has focused a large part of its objectives on conservative therapies. REVIEW RESULTS: Five electronic databases-PubMed, Cochrane, LILACS, EMBASE, and Google Scholar-were searched. Title and abstracts were independently screened by three reviewers, followed by a full-text review. A total of 42 articles met our inclusion criteria; most of these studies were in vitro (n = 35) and other studies were clinical studies (n = 7). These in vitro studies included 21 studies that analyzed the type of preparation and 6 studies that evaluated the limitations of occlusal veneers. CONCLUSION: Thicknesses between 0.7 and 1.0 mm are recommended for ceramic materials; in addition, thicknesses less than 0.7 mm are recommended to use polymeric materials. The materials used for this type of restoration are plastic- and ceramic-based materials, whose load resistance values were found to exceed 2000 N in most studies. It is recommended to carry out a minimally invasive preparation or not to carry out a dental preparation, as long as there is a peripheral enamel to make an external bevel that redirects the eccentric forces to the axis of the tooth. CLINICAL SIGNIFICANCE: Restorative dentistry has moved toward conservative treatments with the least amount of dental tissue being removed. Occlusal veneers appear to be a conservative option in the reconstruction of tooth tissues lost due to tooth wear and in cases where it is necessary to restore or increase the vertical dimension.
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Coronas con Frente Estético , Desgaste de los Dientes , Cerámica , HumanosRESUMEN
Dopaminergic afferents innervate spiny projection neurons (SPNs) in the striatum, maintaining basal ganglia activity. The loss of striatal innervation is the hallmark of Parkinson's disease (PD), which is characterized by dopaminergic denervation. A lack of dopamine in the dorsal striatum induces plasticity changes in SPNs. However, PD-associated denervation is progressive, and how plasticity is modified in partially innervated areas is poorly understood. The most studied models of PD are based on the use of neurotoxins that induce an almost complete striatal denervation. To investigate the impact of partial dopamine (DA) innervation in striatal plasticity, we use a genetic model of PD, Aphakia (Ak) mice, whose striatum presents an increasing dorso-ventral gradient of dopamine innervation. We studied SPNs in three different areas (dorsal, middle and ventral, with low, moderate and high innervation by tyrosine hydroxylase TH-positive axons, respectively) using fast scan cyclic voltammetry, microiontophoresis, immunohistochemistry and patch clamp techniques. Our data show an increasing dorso-ventral gradient of extracellular DA levels, overlapping with the gradient of TH innervation. Interestingly, spine loss in both direct (d-SPN) and indirect SPNs (i-SPN) decreases from dorsal to ventral in the parkinsonian striatum of Ak mice, following the decrease in DA levels. However, their dendritic trees and the number of nodes are only reduced in the poorly innervated dorsal areas and remain unaltered in moderate and highly innervated areas. The firing rate of direct SPNs does not change in either moderate or highly innervated areas, but increases in poorly innervated areas. In contrast, action potential frequency of indirect SPNs does not change along the dorso-ventral innervation gradient. Our findings indicate that spine density in d-SPNs and i-SPNs varies in a dopamine concentration-dependent manner, indicating that both d- and i-SPN are similarly innervated by DA.
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Cuerpo Estriado , Espinas Dendríticas , Dopamina/metabolismo , Plasticidad Neuronal/fisiología , Neuronas Aferentes , Animales , Cuerpo Estriado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patologíaRESUMEN
BACKGROUND: Numerous studies indicate an association between neurodegenerative and metabolic diseases. Although still a matter of debate, growing evidence from epidemiological and animal studies indicate that preexisting diabetes increases the risk to develop Parkinson's disease. However, the mechanisms of such an association are unknown. OBJECTIVES: We investigated whether diabetes alters striatal dopamine neurotransmission and assessed the vulnerability of nigrostriatal neurons to neurodegeneration. METHODS: We used streptozotocin-treated and genetically diabetic db/db mice. Expression of oxidative stress and nigrostriatal neuronal markers and levels of dopamine and its metabolites were monitored. Dopamine release and uptake were assessed using fast-scan cyclic voltammetry. 6-Hydroxydopamine was unilaterally injected into the striatum using stereotaxic surgery. Motor performance was scored using specific tests. RESULTS: Diabetes resulted in oxidative stress and decreased levels of dopamine and its metabolites in the striatum. Levels of proteins regulating dopamine release and uptake, including the dopamine transporter, the Girk2 potassium channel, the vesicular monoamine transporter 2, and the presynaptic vesicle protein synaptobrevin-2, were decreased in diabetic mice. Electrically evoked levels of extracellular dopamine in the striatum were enhanced, and altered dopamine uptake was observed. Striatal microinjections of a subthreshold dose of the neurotoxin 6-hydroxydopamine in diabetic mice, insufficient to cause motor alterations in nondiabetic animals, resulted in motor impairment, higher loss of striatal dopaminergic axons, and decreased neuronal cell bodies in the substantia nigra. CONCLUSIONS: Our results indicate that diabetes promotes striatal oxidative stress, alters dopamine neurotransmission, and increases vulnerability to neurodegenerative damage leading to motor impairment. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Diabetes Mellitus Experimental , Dopamina , Animales , Cuerpo Estriado/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Ratones , Sustancia Negra/metabolismo , Transmisión SinápticaRESUMEN
OBJECTIVES: The purpose of this study was to investigate the short-term effects of myofascial induction on mechanosensitivity of upper limb nerves. METHODS: In this secondary analysis of a randomized, single-blind, placebo-controlled crossover study, 21 breast cancer survivors with stage I-IIIA cancer were randomly allocated to an experimental group (30 minutes of myofascial induction session) or placebo control group (unplugged pulsed 30 minutes of shortwave therapy), with a 4-week washout period between sessions that occurred in a physical therapy laboratory in the Health Science Faculty (University of Granada, Spain). Range of motion (universal goniometry), structural differentiation, symptoms (yes/no), and pressure pain thresholds (electronic algometry) were assessed during neurodynamic tests and attitude toward massage scale as covariate. RESULTS: An analysis of covariance revealed significant timeâ¯×â¯group interactions for range of motion in affected upper limb nerves (median, P < .001; radial, Pâ¯=â¯.036; ulnar, Pâ¯=â¯.002), but not for nonaffected upper limb nerves (median, Pâ¯=â¯.083; radial, Pâ¯=â¯.072; ulnar, Pâ¯=â¯.796). A χ2 or Fisher exact test, as appropriate, also revealed a significant difference (Pâ¯=â¯.044) in sensitivity for the affected upper limb ulnar nerve in the experimental group, whereas the rest of the assessed nerves (affected and nonaffected upper limb nerves) showed no significant changes in either the experimental or control groups (P > .05). An analysis of covariance revealed no significant interactions on pressure pain thresholds over the nerves for affected (all P > .05) and nonaffected (all P > .05) upper limb nerves. CONCLUSION: A single myofascial induction session may partially improve mechanosensitivity of median, radial, and ulnar nerves and yield positive effects on symptom mechanosensitivity, especially regarding the ulnar nerve in breast cancer survivors.
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Neoplasias de la Mama/rehabilitación , Supervivientes de Cáncer/estadística & datos numéricos , Dolor de Cuello/rehabilitación , Rango del Movimiento Articular/fisiología , Dolor de Hombro/rehabilitación , Tratamiento de Tejidos Blandos/métodos , Adulto , Neoplasias de la Mama/complicaciones , Estudios Cruzados , Femenino , Humanos , Masculino , Manipulación Espinal/métodos , Mecanorreceptores/fisiología , Persona de Mediana Edad , Dolor de Cuello/etiología , Conducción Nerviosa/fisiología , Método Simple Ciego , España , Nervio Cubital/fisiologíaRESUMEN
Extrapulmonary tuberculosis (TB) represents approximately 15% of all TB infections. It is difficult to diagnose on the basis of imaging characteristics and clinical symptoms, and biopsy is required in many cases. Radiologists must be aware of the imaging findings of extrapulmonary TB to identify the condition in high-risk patients, even in the absence of active pulmonary infection. In extrapulmonary TB, the lymphatic system is most frequently affected. The presence of necrotic lymph nodes and other organ-specific imaging features increases the diagnostic probability of extrapulmonary TB. Disseminated infection and central nervous system involvement are the most frequent manifestations in immunosuppressed patients. Renal disease can occur in immunocompetent patients with very long latency periods between the primary pulmonary infection and genitourinary involvement. In several cases, gastrointestinal, solid-organ, and peritoneal TB show nonspecific imaging findings. Tuberculous spondylitis is the most frequent musculoskeletal manifestation. It is usually diagnosed late and affects multiple vertebral segments with extensive paraspinal abscess. Articular disease is the second most frequent musculoskeletal manifestation, and synovitis is its predominant imaging finding.©RSNA, 2019.
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Imagen por Resonancia Magnética/métodos , Tuberculosis/diagnóstico por imagen , Absceso/diagnóstico por imagen , Absceso/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Enfermedades Musculares/diagnóstico por imagen , Enfermedades Musculares/fisiopatología , Riesgo , Tuberculoma/diagnóstico por imagen , Tuberculosis/fisiopatología , Tuberculosis del Sistema Nervioso Central/diagnóstico por imagen , Tuberculosis del Sistema Nervioso Central/fisiopatología , Tuberculosis Ganglionar/diagnóstico por imagen , Tuberculosis Ganglionar/fisiopatología , Tuberculosis Meníngea/diagnóstico por imagen , Tuberculosis Meníngea/fisiopatología , Tuberculosis Osteoarticular/diagnóstico por imagen , Tuberculosis Osteoarticular/fisiopatología , Tuberculosis Urogenital/diagnóstico por imagen , Tuberculosis Urogenital/fisiopatologíaRESUMEN
BACKGROUND: Accumulation of senescent cells has been associated with pro-inflammatory effects with deleterious consequences in different human diseases. The purpose of this study was to analyze cell senescence in human synovial tissues (ST), and its impact on the pro-inflammatory function of synovial fibroblasts (SF). RESULTS: The expression of the senescence marker p16INK4a (p16) was analyzed by immunohistochemistry in rheumatoid arthritis (RA), osteoarthritis (OA), and normal ST from variably aged donors. The proportion of p16(+) senescent cells in normal ST from older donors was higher than from younger ones. Although older RA and OA ST showed proportions of senescent cells similar to older normal ST, senescence was increased in younger RA ST compared to age-matched normal ST. The percentage of senescent SA-ß-gal(+) SF after 14 days in culture positively correlated with donor's age. Initial exposure to H2O2 or TNFα enhanced SF senescence and increased mRNA expression of IL6, CXCL8, CCL2 and MMP3 and proteins secretion. Senescent SF show a heightened IL6, CXCL8 and MMP3 mRNA and IL-6 and IL-8 protein expression response upon further challenge with TNFα. Treatment of senescent SF with the senolytic drug fenofibrate normalized IL6, CXCL8 and CCL2 mRNA expression. CONCLUSIONS: Accumulation of senescent cells in ST increases in normal aging and prematurely in RA patients. Senescence of cultured SF is accelerated upon exposure to TNFα or oxidative stress and may contribute to the pathogenesis of synovitis by increasing the production of pro-inflammatory mediators.
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Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies.
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Transformación Celular Neoplásica/metabolismo , Progresión de la Enfermedad , Proteínas de Choque Térmico/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Animales , Transformación Celular Neoplásica/patología , Humanos , Modelos Biológicos , Transducción de SeñalRESUMEN
In this paper, a first approach to the design of a portable device for non-contact monitoring of respiratory rate by capacitive sensing is presented. The sensing system is integrated into a smart vest for an untethered, low-cost and comfortable breathing monitoring of Chronic Obstructive Pulmonary Disease (COPD) patients during the rest period between respiratory rehabilitation exercises at home. To provide an extensible solution to the remote monitoring using this sensor and other devices, the design and preliminary development of an e-Health platform based on the Internet of Medical Things (IoMT) paradigm is also presented. In order to validate the proposed solution, two quasi-experimental studies have been developed, comparing the estimations with respect to the golden standard. In a first study with healthy subjects, the mean value of the respiratory rate error, the standard deviation of the error and the correlation coefficient were 0.01 breaths per minute (bpm), 0.97 bpm and 0.995 (p < 0.00001), respectively. In a second study with COPD patients, the values were −0.14 bpm, 0.28 bpm and 0.9988 (p < 0.0000001), respectively. The results for the rest period show the technical and functional feasibility of the prototype and serve as a preliminary validation of the device for respiratory rate monitoring of patients with COPD.
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Capacidad Eléctrica , Monitoreo Fisiológico/instrumentación , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Frecuencia Respiratoria , Dispositivos Electrónicos Vestibles , Adulto , Femenino , Humanos , Internet , MasculinoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) can affect the lungs in different manners, with interstitial lung disease (ILD) as the most serious manifestation. Although lung and joint compromise could be thought to evolve in parallel, there are data suggesting the opposite. In this study, we evaluated the relationship between lung and joint involvement in RA ILD. METHODS: An observational cross-sectional study of RA ILD patients evaluated from January 2015 to February 2017. Joint disease assessment included number of tender and swollen joints, patient's global assessment of disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein, and disease activity score (DAS28). Lung disease assessment included forced vital capacity, diffusion capacity (DLCO), and Goh high-resolution computed tomography (HRCT) score for total extent, ground glass, and reticular pattern. We studied the correlation between both components of the disease. RESULTS: We included 46 patients, 14 (30.4%) men, with a mean (SD) of the age of 59.9 years (11.89). 12 (26.09) patients were in remission or had low disease activity measured with DAS28. The HRCT showed usual interstitial pneumonia (UIP) pattern in 10 (21.7%), possible UIP in 18 (39.1%), and inconsistent with UIP in 18 (39.1%). We found a good correlation between the ESR and the ground glass score in the HRCT (r = 0.39; p = 0.03). However, we found no correlation between lung function tests or HRCT scores and the other components of the DAS28. CONCLUSIONS: We only found a good correlation between ESR and ground glass score. It is possible that different pathways of the immune response mediate damage in lungs and joints.