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There are no established maintenance protocols for cutaneous lymphomas. We aim to determine patient treatments and outcomes during the COVID-19 pandemic in order to uncover the most effective maintenance protocols for cutaneous lymphomas and impact of treatment interruption. Data was collected retrospectively from nine international institutions, including 149 patients. Younger patients had earlier stages of disease and were most frequently treated with skin-directed therapies including topical steroids, mechlorethamine gel, and phototherapy. Treatment interruption varied by treatment type and stage, with patients on topical therapies and earlier stages of disease being least likely to experience interruption. Treatment interruption was significantly associated with progression of disease and worse outcomes, with twice as many patients progressing who had interruption compared to those without interruption. This study may demonstrate the significance of continuous maintenance therapies, even in younger patients with early stages of disease.
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The caridoid or "tail flip" escape behavior of decapod crustaceans is a model system in neurobiology, but many aspects of its biomechanics are not well understood. To understand how the freshwater virile crayfish Faxonius virilis interacts with the substrate during the tail flip, we studied tail-flip hydrodynamics and force generation for free-moving animals standing on substrate, as well as tethered animals held at different distances from the substrate. We found no significant differences in force generation when distance from substrate was varied. Particle image velocimetry revealed that vortex formation was similar at all distances, but there were notable differences in interactions between shed vortices and substrate at different distances. Negative vorticity (clockwise flow of water) was observed in tethered animals interacting with the substrate but was largely absent in free-swimming animals. We found no evidence of ground effects enhancing tail flip performance in either tethered or free-swimming individuals, as peak force generation occurred before vortex shedding. This study contributes to our understanding of the crayfish escape response and highlights the need for more work that incorporates free-swimming animals and complex environments in the study of crustacean biomechanics.
La reacción de escape caridoide de los crustáceos decápodos, o "coletazo," es un sistema modelo en la neurobiología. Múltiples aspectos de su biomecánica siguen sin explicación. Para entender como el cangrejo de río de agua dulce Faxonius virilis interacciona con el substrato durante el coletazo, hemos estudiado la hidrodinámica y la generación de fuerza del coletazo en animales de movimiento libre parados sobre el substrato, al igual que en animales restringidos a varias distancias por encima del substrato. No hemos detectado ninguna diferencia significativa en la generación de fuerza cuando la distancia del substrato es variada. La velocimetría por imagen de partículas (PIV) ha revelado que la formación de vórtices es similar a todas las distancias, pero existen diferencias notables en las interacciones entre vórtices desprendidos y substrato a diferentes distancias. Hemos observado una vorticidad negativa en animales restringidos interactuando con el substrato, pero no en animales con libre movimiento. No hemos detectado que efectos relacionados al suelo aumenten el rendimiento del coletazo en individuos libres o restringidos, ya que la generación de fuerza máxima ocurrió antes del desprendimiento de los vórtices. Este estudio contribuye al entendimiento de la reacción de escape de los cangrejos de río, y destaca también la necesidad de estudios adicionales que incorporen animales con capacidad de movimiento libre y en ambientes complejos para el estudio de la biomecánica de los crustáceos.
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Objectives were to determine the effect of corn silage inclusion within dry-rolled corn (DRC) or steam-flaked corn (SFC) finishing diets on cattle growth performance and carcass characteristics. The experiment used British and continental crossbred steers (nâ =â 480; initial body weight [BW]â =â 389â ±â 17 kg) in a 4â ×â 2 factorial arrangement of treatments with six replications per treatment. Treatments consist of four inclusions of corn silage (0%, 15%, 30%, or 45%; dry matter [DM] basis) within either a DRC or SFC diet. A corn silage by corn processing interaction was observed for dry-matter intake (DMI; Pâ =â 0.05). As corn silage inclusion increased in the diet, DMI increased linearly (Pâ <â 0.01) for both corn processing methods. DM intake was not different between SFC and DRC-fed cattle at 0% (Pâ =â 0.33), 30% (Pâ =â 0.90), or 45% (Pâ =â 0.31) corn silage inclusion. The interaction was due to the DMI of cattle fed 15% silage, as cattle-fed DRC consumed 0.5 kg/d less (Pâ <â 0.01) than cattle on the SFC diet. Quadratic effects were observed for final BW, hot carcass weight (HCW), average daily gain (ADG), feed efficiency (G:F), marbling, and fat depth (Pâ <â 0.01), regardless of corn processing. Cattle fed 15% or 30% corn silage gained faster (Pâ <â 0.01) than those fed 0% or 45% corn silage. Feed efficiency decreased quadratically (Pâ <â 0.01) as silage inclusion increased in the diet with G:F similar for cattle fed 0% and 15% silage and decreased curvilinearly for cattle fed 30% and 45% silage. The incidence of liver abscesses was greater (Pâ =â 0.03) in cattle fed 0% corn silage than for steers fed 15%, 30%, or 45% corn silage. Corn processing method, independent of silage, had no effect (Pâ =â 0.42) on liver abscess incidence. Feeding SFC increased (Pâ <â 0.01) steer final BW and HCW when compared to cattle-fed DRC, regardless of silage inclusion. Corn silage inclusion had similar effects on performance in both DRC diets and SFC diets except for DMI. As corn silage inclusion increased in the diet, feed efficiency decreased linearly (Pâ <â 0.01). Cattle-fed SFC gained 7.9% more (Pâ <â 0.01) and were 6.7% more efficient (Pâ <â 0.01) than cattle-fed DRC. In diets containing either DRC or SFC, corn silage can be included at up to 30% of the diet without negative impacts on ADG or HCW.
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Background: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy. Objectives: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide. Material and methods: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating. Results: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing. Conclusion: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study's hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.
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Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies.
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Imunidade Inata , Neoplasias , Masculino , Humanos , Camundongos , Animais , Citocinas , Interleucina-33 , Linfócitos , Neoplasias/terapiaRESUMO
Polar lakes harbour a unique biogeochemistry that reflects the implications of climatic fluctuations against a susceptible yet extreme environment. In addition to polar, Store Saltsø (Kangerlussuaq, southwestern Greenland) is an endorheic lake with alkaline and oligotrophic waters that host a distinctive ecology adapted to live in such particular physico-chemical and environmental conditions. By exploring the sedimentary record of Store Saltsø at a molecular and compound-specific isotopic level, we were able to understand its ecology and biogeochemical evolution upon climate change. We employed lipid biomarkers to identify biological sources and metabolic traits in different environmental samples (shore terrace, sediment core, and white precipitates at the shore), and their succession over time to reconstruct the lake paleobiology. Different molecular ratios and geochemical proxies provided further insights toward the evolution of environmental conditions in the frame of the deglaciation history of Kangerlussuaq. The relative abundance of terrestrial (i.e., plant derived) biomarkers (odd long-chain n-alkanes, even long-chain n-alkanols, and phytosterols) in the upper half of the shore terrace versus the relatively more present aquatic biomarkers (botryococcenes and long-chain alkenones) in its lower half revealed higher lake water levels in the past. Moreover, the virtual absence of organics in the deepest section of the sediment core (32-29 cm depth) suggested that the lake did not yet exist at the northwestern shore of Store Saltsø â¼5100 years ago. According to the relative abundance of lipid biomarkers detected in the adjacent section above (29-25 cm depth), we hypothesize that the northwestern shore of Store Saltsø formed â¼4900 years ago. By combining the molecular and compound-specific isotopic analysis of lipids in a â¼360 cm sedimentary sequence, we recreated the paleobiology and evolution of an extreme lacustrine environment suitable for the study of the limits of life and the effects of climate warming.
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Monitoramento Ambiental , Lagos , Groenlândia , Lagos/química , Biomarcadores , Lipídeos/análise , Sedimentos Geológicos/químicaRESUMO
In recent years, SGLT2 inhibitors have become an integral part of heart failure therapy, and several mechanisms contributing to cardiorenal protection have been identified. In this study, we place special emphasis on the atria and investigate acute electrophysiological effects of dapagliflozin to assess the antiarrhythmic potential of SGLT2 inhibitors. Direct electrophysiological effects of dapagliflozin were investigated in patch clamp experiments on isolated atrial cardiomyocytes. Acute treatment with elevated-dose dapagliflozin caused a significant reduction of the action potential inducibility, the amplitude and maximum upstroke velocity. The inhibitory effects were reproduced in human induced pluripotent stem cell-derived cardiomyocytes, and were more pronounced in atrial compared to ventricular cells. Hypothesizing that dapagliflozin directly affects the depolarization phase of atrial action potentials, we examined fast inward sodium currents in human atrial cardiomyocytes and found a significant decrease of peak sodium current densities by dapagliflozin, accompanied by a moderate inhibition of the transient outward potassium current. Translating these findings into a porcine large animal model, acute elevated-dose dapagliflozin treatment caused an atrial-dominant reduction of myocardial conduction velocity in vivo. This could be utilized for both, acute cardioversion of paroxysmal atrial fibrillation episodes and rhythm control of persistent atrial fibrillation. In this study, we show that dapagliflozin alters the excitability of atrial cardiomyocytes by direct inhibition of peak sodium currents. In vivo, dapagliflozin exerts antiarrhythmic effects, revealing a potential new additional role of SGLT2 inhibitors in the treatment of atrial arrhythmias.
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Fibrilação Atrial , Compostos Benzidrílicos , Glucosídeos , Células-Tronco Pluripotentes Induzidas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Animais , Suínos , Miócitos Cardíacos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Potenciais de Ação , SódioRESUMO
Type 2 innate lymphoid cells (ILC2s) perform vital functions in orchestrating humoral immune responses, facilitating tissue remodelling, and ensuring tissue homeostasis. Additionally, in a role that has garnered considerably less attention, ILC2s can also enhance Th1-related cytolytic T lymphocyte immune responses against tumours. Studies have thus far generally failed to address the mystery of how one ILC2 cell-type can participate in a multiplicity of functions. Here we utilized single cell RNA sequencing analysis to create the first comprehensive atlas of naïve and tumour-associated lung ILC2s and discover multiple unique subtypes of ILC2s equipped with developmental gene programs that become skewed during tumour expansion favouring inflammation, antigen processing, immunological memory and Th1-related anti-tumour CTL responses. The discovery of these new subtypes of ILC2s challenges current paradigms of ILC2 biology and provides an explanation for their diversity of function.
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Imunidade Inata , Neoplasias , Humanos , Linfócitos , Pulmão/patologia , Inflamação/patologia , Neoplasias/genética , Neoplasias/patologiaRESUMO
BACKGROUND: Atipamezole, an α-2 adrenergic receptor antagonist, reverses the α-2 agonist anesthetic effects. There is a dearth of information on the physiological effects of these drugs in cynomolgus macaques (Macaca fascicularis). We assessed atipamezole's physiologic effects. We hypothesized atipamezole administration would alter anesthetic parameters. METHODS: Five cynomolgus macaques were sedated with ketamine/dexmedetomidine intramuscularly, followed 45 min later with atipamezole (0.5 mg/kg). Anesthetic parameters (heart rate, blood pressure [systolic (SAP), diastolic (DAP), and mean (MAP) blood pressure], body temperature, respiratory rate, and %SpO2) were monitored prior to and every 10 min (through 60 min) post atipamezole injection. RESULTS: While heart rate was significantly increased for 60 min; SAP, DAP, MAP, and temperature were significantly decreased at 10 min. CONCLUSIONS: This study indicates subcutaneous atipamezole results in increased heart rate and transient blood pressure decrease. These findings are clinically important to ensure anesthetist awareness to properly support and treat patients as needed.
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Anestésicos , Ketamina , Animais , Macaca fascicularis , Imidazóis/farmacologia , Ketamina/farmacologia , Anestésicos/farmacologia , Frequência CardíacaRESUMO
The objective was to evaluate ocular changes based on sex in steroid-induced glaucoma models in rats comparing healthy controls, over 24 weeks follow-up. Eighty-nine Long-Evans rats (38 males and 51 females) with steroid-induced glaucoma were analysed. Two steroid-induced glaucoma models were generated by injecting poly-co-lactic-glycolic acid microspheres loaded with dexamethasone (MMDEX model) and dexamethasone-fibronectin (MMDEXAFIBRO model) into the ocular anterior chamber. Intraocular pressure was measured by rebound tonometer Tonolab®. Neuroretinal function was analysed using dark- and light-adapted electroretinography (Roland consult® RETIanimal ERG), and structure was analysed using optical coherence tomography (OCT Spectralis, Heidelberg® Engineering) using Retina Posterior Pole, Retinal Nerve Fibre Layer and Ganglion Cell Layer protocols over 24 weeks. Males showed statistically (p < 0.05) higher intraocular pressure measurements. In both sexes and models neuroretinal thickness tended to decrease over time. In the MMDEX model, males showed higher IOP values and greatest percentage thickness loss in the Ganglion Cell Layer (p = 0.015). Females receiving MMDEXAFIBRO experienced large fluctuations in thickness, a higher percentage loss (on average) in Retina Posterior Pole (p = 0.035), Retinal Nerve Fibre Layer and Ganglion Cell Layer than aged-matched males, and the highest thickness loss rate by mmHg. Although no difference was found by sex in dark- and light-adapted electroretinography, increased amplitude in photopic negative response was found in MMDEX males and MMDEXAFIBRO females at 12 weeks. Although both glaucoma models used dexamethasone, different intraocular pressure and neuroretinal changes were observed depending on sex and other influential cofactors (fibronectin). Both sex and the induced glaucoma model influenced neuroretinal degeneration.
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Fibronectinas , Glaucoma , Masculino , Feminino , Ratos , Animais , Seguimentos , Células Ganglionares da Retina , Ratos Long-Evans , Pressão Intraocular , Tomografia de Coerência Óptica/métodos , Dexametasona/toxicidadeRESUMO
(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lymphoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analyzed patient records (1984-2016) from 27 clinical sites in Europe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS) and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. The median (range) times from the start of first-line therapy to the first R/R MF and from the first to the second R/R MF were 11.2 (0.3-166.5) and 13.5 (0.0-174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radiotherapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). The median (95% confidence interval [CI]) OS from the diagnosis of the first R/R MF was 11.5 (6.5-not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); the estimated median PFS (95% CI) from the time of the first R/R MF was 1.3 (1.0-2.1) years. (4) Conclusions: High rates of R/R disease were observed after second- and third-line treatments in this real-world cohort, with longer median OS in patients receiving non-chemotherapy treatment versus chemotherapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.
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Introduction: This study analysed the psychometric properties of the Reward Probability Index (RPI) in an online Colombian sample with 1129 participants. Method: To conduct a cross-validation study, the sample was randomly divided into two subsamples. An exploratory factor analysis was conducted with the first subsample yielding a two-factor structure. Then, the fit of this two-factor model was tested on the second subsample by conducting a confirmatory factor analysis. Results: This model obtained a good fit to the data and measurement invariance across gender was observed. The RPI also showed good internal consistency according to both Cronbach's alpha and McDonald's omega, scoring .88 in both cases. The RPI demonstrated convergent construct validity given its correlations with other related measures such as the Environmental Reward Observation Scale (r = .81), and the full version of the Behavioral Activation Scale for Depression (r = .71). Conclusions: The RPI showed good psychometric properties in this Colombian sample.
Introducción: Este artículo tuvo como objetivo analizar las propiedades psicométricas del Índice de Probabilidad de Recompensa (RPI) en una muestra colombiana en línea con 1129 participantes. Método: Para realizar un estudio de validación cruzada, la muestra se dividió aleatoriamente en dos submuestras. Se realizó un análisis factorial exploratorio con la primera submuestra que arrojó una estructura de dos factores. Luego, se probó el ajuste de este modelo de dos factores en la segunda submuestra mediante la realización de un análisis factorial confirmatorio. Resultados: Este modelo obtuvo un buen ajuste a los datos y se observó invarianza de medida entre sexos. El RPI también mostró buena consistencia interna según el alfa de Cronbach y el omega de McDonald (.88 en ambos casos) y validez de constructo convergente dadas las correlaciones con otras medidas relacionadas como la Escala de Observación de Recompensa Ambiental (r = .81), y la versión de la Escala de Activación Conductual para la Depresión (r = .71). Conclusiones: el RPI mostró buenas propiedades psicométricas en esta muestra colombiana.
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Humanos , Depressão , ComportamentoRESUMO
Adherence to antidepressants is essential for good outcomes when treating depressive disorders.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Venlafaxina/efeitos adversos , PacientesRESUMO
TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 (mGluR5). Under neuroinflammatory conditions, mGluR5 activation in astrocytes can be neuroprotective or have the opposite effect. In the current study, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP decreases the secreted levels of pro-inflammatory cytokines (IL-6 and IL-8) following short rTNF-α stimulation, although this effect subsides with time. Additionally, CTEP enhances synaptoneurosome phagocytosis by astrocytes in both non-stimulated and rTNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation augment the expression of the reactivity marker SERPINA3 and reduces the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockade may have beneficial and detrimental effects under inflammatory conditions.
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Astrócitos , Células-Tronco Pluripotentes Induzidas , Fagocitose , Receptor de Glutamato Metabotrópico 5 , Humanos , Astrócitos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.
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Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Síndrome de Sézary/terapia , Síndrome de Sézary/patologia , Consenso , Qualidade de Vida , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Fatores Imunológicos/uso terapêuticoRESUMO
Little is currently known about how climate modulates the relationship between plant diversity and soil organic carbon and the mechanisms involved. Yet, this knowledge is of crucial importance in times of climate change and biodiversity loss. Here, we show that plant diversity is positively correlated with soil carbon content and soil carbon-to-nitrogen ratio across 84 grasslands on six continents that span wide climate gradients. The relationships between plant diversity and soil carbon as well as plant diversity and soil organic matter quality (carbon-to-nitrogen ratio) are particularly strong in warm and arid climates. While plant biomass is positively correlated with soil carbon, plant biomass is not significantly correlated with plant diversity. Our results indicate that plant diversity influences soil carbon storage not via the quantity of organic matter (plant biomass) inputs to soil, but through the quality of organic matter. The study implies that ecosystem management that restores plant diversity likely enhances soil carbon sequestration, particularly in warm and arid climates.
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Ecossistema , Solo , Carbono , Biodiversidade , Biomassa , Plantas , NitrogênioRESUMO
Introducción. La adherencia a los antidepresivos es fundamental para obtener buenos resultados en el tratamiento de la depresión. El objetivo del actual estudio fue evaluar la adherencia, aceptabilidad y tolerabilidad de venlafaxina XR a dosis de 300 mg/día, administrada en uno o dos comprimidos, tras un periodo de tratamiento de 6 ± 2 meses en pacientes con trastorno depresivo mayor (TDM). Metodología. Estudio observacional, transversal, de práctica clínica habitual en el que participaron 590 pacientes con TDM que asistían a consultas de centros públicos o privados de toda España, de los cuales 361 y 229 recibieron uno (300 mg) o dos comprimidos (150+150 mg o 225+75 mg) de venlafaxina XR, respectivamente. Los datos del estudio se obtuvieron de la entrevista con el paciente, de la historia clínica y de cuestionarios validados. Resultados. El método Haynes-Sackett y el cuestionario de Morisky-Green revelaron que la adherencia al tratamiento fue similar en ambos grupos. Los pacientes que recibieron la dosis de venlafaxina XR en un comprimido mostraron mayor satisfacción con el tratamiento según el cuestionario TSQM9. La escala MADRS reveló que en el 23% de los pacientes el TDM había remitido, y solo en el 9% se mantenía grave, en el 26% era moderado y en el 42% leve. Igual resultado se obtuvo con el cuestionario PHQ-9. En general, los pacientes mostraron buena tolerabilidad a la venlafaxina XR a dosis altas con las dos pautas de administración, y los efectos adversos más comunes fueron la disfunción sexual, sudoración y estreñimiento. Conclusiones. La adherencia al tratamiento con venlafaxina XR de 300 mg/día en uno o dos comprimidos fue similar. Los pacientes que recibieron un solo comprimido mostraron mayor satisfacción con el tratamiento. El perfil de seguridad de venlafaxina XR 300 mg fue favorable. No se produjeron abandonos, ni elevaciones clínicamente significativas de la presión arterial que condicionaran la pauta de uso. (AU)
Background. Adherence to antidepressants is essential for good outcomes when treating depressive disorders. The objective of the current study was to evaluate the adherence, acceptability and tolerability of venlafaxine XR at a dose of 300 mg/day, administered in one or two tablets, after a treatment period of 6 ± 2 months in patients with major depressive disorder (MDD). Subjects and methods. Observational, cross-sectional study of routine clinical practice in 590 outpatients with MDD who attended at public or private centers all over country, of whom 361 and 229 received one (300 mg) or two tablets (150+150 mg o 225+75 mg) of venlafaxine XR, respectively. The study data were obtained from the interview with the patient, the clinical history and validated questionnaires. Results. The Haynes-Sackett method and the MoriskyGreen questionnaire revealed that adherence to treatment was similar in both groups. The patients who received the dose of venlafaxine XR in one tablet showed greater satisfaction with the treatment according to the TSQM-9 questionnaire. The MADRS scale revealed that in 23% of the patients the MDD had remitted, and only in 9% it remained severe, in 26% it was moderate and in 42% mild. The same result was obtained with the PHQ-9 questionnaire. In general, the patients showed good tolerability to high doses of venlafaxine XR with both dosing regimens, and the most common adverse effects were sexual dysfunction, sweating and constipation. Conclusions. Adherence to treatment with venlafaxine XR 300 mg/day in one or two tablets was similar. Patients who received a single tablet showed greater satisfaction with the treatment. The safety profile of high dose venlafaxine was favorable and there was dropouts or clinically significant elevations that affected the dosing regimen. (AU)
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Humanos , Cooperação e Adesão ao Tratamento , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/terapia , Tolerância a MedicamentosRESUMO
60-year-old woman referring visual disability. She presented bone spicule pigmentation and retinal atrophy in all peripheral retina, as well as macular retinal flecks. Multimodal imaging showed typical findings of both inherited retinal dystrophies (IRD). Electroretinogram confirmed rod dysfunction. Biallelic mutations were found in ABCA4 and CNGA1 genes. Although not common, different IRDs may be present in a same patient at the same time. This is the first reported case of the combination of RP with late-onset Stargardt's disease. We propose the name 'Stargardt's pigmentosa' for this novel clinical entity.
Assuntos
Degeneração Macular , Distrofias Retinianas , Feminino , Humanos , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/genética , Retina , Distrofias Retinianas/diagnóstico por imagem , Distrofias Retinianas/genética , Eletrorretinografia , Transportadores de Cassetes de Ligação de ATP/genéticaRESUMO
N-Nitrosodimethylamine (NDMA, ONN(CH3)2) is a highly potent carcinogenic investigated by health authorities in some countries. In this manuscript, density functional theory (DFT) is applied to study the NDMA molecular and dissociative adsorption on a Ni8 nanocluster. Molecular adsorption is two times stronger than the NDMA adsorption on the Ni{111} surface. NDMA dissociative adsorption is found more stable than molecular adsorption by ≈1 eV. To dissociate the NDMA molecule into O and NN(CH3)2 fragments, an activation energy is calculated in 0.954 and 0.810 eV from the two most stable molecular configurations. However, to dissociate the NDMA molecule into ON and N(CH3)2 fragments, a smaller activation energy of 0.654 eV is calculated. With the inclusion of the London dispersion forces (optB88-vdW functional), NDMA molecular interactions are a bit stronger. However, the activation energies are slightly smaller. Meta-GGA functional SCAN has also, been applied. The inclusion of the implicit solvation model displays a NDMA weaker interaction with the Ni8 nanocluster. Dissociative adsorption is more stable than molecular adsorption, but the energy difference is a bit smaller, ≈0.850 eV. Present results show that the Ni8 nanoclusters are promising catalysts to NDMA elimination from water.