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Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS-MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS-MDS accurately predicted overall survival (OS) and leukaemia-free survival (LFS), outperforming the Revised-IPSS score. Similarly, in the Taiwanese cohort, the AIPSS-MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS-MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision-making in CMML enables clinicians to identify high-risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS-MDS to further refine risk stratification in CMML and improve patient outcomes.
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Leucemia Mielomonocítica Crônica , Leucemia , Síndromes Mielodisplásicas , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Prognóstico , Inteligência Artificial , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/tratamento farmacológico , Medição de RiscoRESUMO
BACKGROUND: Ruxolitinib is approved for patients with polycythemia vera (PV) who are resistant/intolerant to hydroxyurea, but its impact on preventing thrombosis or disease-progression is unknown. METHODS: A retrospective, real-world analysis was performed on the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to subsequent treatment with ruxolitinib (n = 105) or the best available therapy (BAT; n = 272). Survival probabilities and rates of thrombosis, hemorrhage, acute myeloid leukemia, myelofibrosis, and second primary cancers were calculated according to treatment. To minimize biases in treatment allocation, all results were adjusted by a propensity score for receiving ruxolitinib or BAT. RESULTS: Patients receiving ruxolitinib had a significantly lower rate of arterial thrombosis than those on BAT (0.4% vs 2.3% per year; P = .03), and this persisted as a trend after adjustment for the propensity to have received the drug (incidence rate ratio, 0.18; 95% confidence interval, 0.02-1.3; P = .09). There were no significant differences in the rates of venous thrombosis (0.8% and 1.1% for ruxolitinib and BAT, respectively; P = .7) and major bleeding (0.8% and 0.9%, respectively; P = .9). Ruxolitinib exposure was not associated with a higher rate of second primary cancers, including all types of neoplasia, noncutaneous cancers, and nonmelanoma skin cancers. After a median follow-up of 3.5 years, there were no differences in survival or progression to acute leukemia or myelofibrosis between the 2 groups. CONCLUSIONS: The results suggest that ruxolitinib treatment for PV patients with resistance/intolerance to hydroxyurea may reduce the incidence of arterial thrombosis. LAY SUMMARY: Ruxolitinib is better than other available therapies in achieving hematocrit control and symptom relief in patients with polycythemia vera who are resistant/intolerant to hydroxyurea, but we still do not know whether ruxolitinib provides an additional benefit in preventing thrombosis or disease progression. We retrospectively studied the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to whether they subsequently received ruxolitinib (n = 105) or the best available therapy (n = 272). Our findings suggest that ruxolitinib could reduce the incidence of arterial thrombosis, but a disease-modifying effect could not be demonstrated for ruxolitinib in this patient population.
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Leucemia Mieloide Aguda , Segunda Neoplasia Primária , Policitemia Vera , Mielofibrose Primária , Trombose , Hemorragia/induzido quimicamente , Humanos , Hidroxiureia/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Nitrilas , Policitemia Vera/tratamento farmacológico , Mielofibrose Primária/tratamento farmacológico , Pirazóis , Pirimidinas , Estudos Retrospectivos , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Trombose/prevenção & controleRESUMO
MAIN CONCLUSION: Drought alone and drought plus warming will change the nutrient requirements and biomass distributions of Stylosanthes capitata, while warming will be advantageous only under well-watered condition for the next decades. Climate change effects on natural and managed ecosystems are difficult to predict due to its multi-factor nature. However, most studies that investigate the impacts of climate change factors on plants, such as warming or drought, were conducted under one single stress and controlled environments. In this study, we evaluated the effects of elevated temperature (+ 2 °C) (T) under different conditions of soil water availability (W) to understand the interactive effects of both factors on leaf, stem, and inflorescence macro and micronutrients concentration and biomass allocation of a tropical forage species, Stylosanthes capitata Vogel under field conditions. Temperature control was performed by a temperature free-air controlled enhancement (T-FACE) system. We observed that warming changed nutrient concentrations and plant growth depending on soil moisture levels, but the responses were specific for each plant organ. In general, we found that warming under well-watered conditions greatly improved nutrient concentration and biomass production, whilst the opposite effect was observed under non-irrigated and non-warmed conditions. However, under warmed and non-irrigated conditions, leaf biomass and leaf nutrient concentration were greatly reduced when compared to non-warmed and irrigated plants. Our findings suggest that warming (2 °C above ambient temperature) and drought, as well as both combined stresses, will change the nutrient requirements and biomass distributions between plant aerial organs of S. capitata in tropical ecosystems, which may impact animal feeding in the future.
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Secas , Fabaceae , Animais , Biomassa , Dióxido de Carbono , Mudança Climática , Ecossistema , Estado Nutricional , Solo , ÁguaRESUMO
- Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most destructive diseases affecting banana crops worldwide. Therefore, the development of resistant cultivars is a promising alternative to mitigate the effects of the disease on banana plantations. The objectives of this study were to induce somaclonal variation in banana cultivars of the Silk and Cavendish types and to select somaclones resistant to subtropical race 4, thereby enabling the production of fruit in areas where this race is present. Shoot clump apexes of the Grand Naine and Maçã (Silk) cultivars were grown in MS medium. The cultures were subcultured four times. They were then challenged with fusaric acid (FA) in an experiment consisting of four treatments with different concentrations (0.1, 0.2, 0.3, and 0.4 mM) and five repetitions, each consisting of a Petri dish containing seven multiple shoot clumps in MS culture medium supplemented with 2.5 mg/L benzylamine purine. Multiple shoot clumps without the addition of FA were also used in the experiment, and were subcultured three times and maintained in a dark room. The multiple shoot clumps that survived the treatment with FA were transferred to MS medium and maintained in the growth chamber in the presence of light. The regenerated plants were later planted in tanks containing soil infested with an isolate classified as Foc subtropical race 4 (Foc STR4), and were evaluated for resistance to the pathogen at 90 days after inoculation (d.a.i.). Pathogen structures were confirmed by root clarification and root staining technique. All somaclones of the Maçã (Silk) cultivar were susceptible to Fusarium wilt and two somaclones of the Grand Naine cultivar were selected as resistant. The addition of FA as a selective agent was effective in the selection of somaclones among plants of the Grand Naine cultivar, as shown by the selection of two somaclones resistant to Foc STR4. The next step will consist of the agronomic and market potential validation of the selected somaclones, aiming to confirm their potential use by producers.
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Temperature and soil water availability play important roles in the biogeochemical cycles of essential elements for plant growth, such as carbon (C), nitrogen (N), and phosphorus (P). In this study, we investigated how drought and warming impact C:N:P stoichiometric ratios of different plant organs (leaves, inflorescences, and stems), and biomass allocation and production of a field-grown pasture of Stylosanthes capitata, a tropical forage legume. We evaluated the effects of elevated temperature (+2 °C above ambient temperature) under two conditions of soil water availability, irrigated, and non-irrigated. In general, we observed that different functional plant organs showed distinct responses to drought and warming demonstrating how important is to evaluate different functional plant organs to unravel crop nutrient dynamics. In addition, interactive effects between warming and drought were observed in many situations, highlighting the importance of multifactorial studies. Our data showed that warming produced plants with more inflorescences, decreasing leaf:inflorescence ratio. However, only warming under well-watered conditions improved biomass production (in 38%). Warmed and irrigated plants showed higher stoichiometric homeostasis compared to other treatments. In an opposite direction, drought decreased P concentration and increased N:P ratios in different organs, reducing the stoichiometric homeostasis under both conditions of temperature. We have concluded that warm and well-watered conditions without restrictions in soil nutrient availability can enhance plant production, presumably due to a higher level of stoichiometric homeostasis.
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Fabaceae , Solo , Ar , Biomassa , Nitrogênio , Folhas de Planta , Temperatura , ÁguaRESUMO
Plant responses to nitrogen supply are dependent on auxin signaling, but much still remains to be elucidated regarding N deficiency in tomato. Thus, the objective of this work was to evaluate how low auxin sensitivity regulates the responses of tomato plants to N deficiency. For this purpose, we used the tomato diageotropica mutant, with low auxin sensitivity, and a near isogenic line cv. Micro-Tom grown in nutrient solutions under absence and presence of nitrogen. Plant height, stem diameter, root and shoot dry mass, area and root density, number of lateral roots, leaf area, chlorophylls and carotenoids content, nitrogen accumulation and nitrogen use efficiency were evaluated. We observed a clear interaction between the tomato genotype and nitrogen. When the plants were grown with nitrogen, 'Micro-Tom' showed higher growth than the diageotropica mutant. Under nitrogen deficiency condition, the mutant showed improved growth, nitrogen use efficiency and higher contents of pigments. In general, the low sensitivity to auxin in diageotropica caused reduced growth in both shoot and root. However, the diageotropica tomato showed a positive regulation of the nitrogen use efficiency under nitrogen deficiency. In general, our data revealed that the reduced sensitivity to auxin increased the adaptive capacity to the nitrogen deficiency.
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Ácidos Indolacéticos , Solanum lycopersicum , Ácidos Indolacéticos/farmacologia , Solanum lycopersicum/genética , Nitrogênio , Folhas de Planta , Raízes de PlantasRESUMO
BACKGROUND: Preservation of the periareolar dermis, after de-epithelization in reduction mammaplasty, may result in reduced nipple-areola complex (NAC) mobility. Consequently, distortion in shape and difficulty correcting the areola position can occur. OBJECTIVES: The aim of this study was to evaluate NAC viability and sensitivity resulting from periareolar dermis section after de-epithelization in patients who underwent reduction mammaplasty surgery. METHODS: This study was a randomized, controlled double-blind clinical trial. A total of 41 patients (82 breasts) were randomly allocated into 2 groups and underwent reduction mammaplasty-involving the superior pedicle-with a final inverted T-shaped scar. A sectioning of the periareolar dermis was performed on the breasts in the experimental group. Semmes-Weinstein monofilaments were used to evaluate NAC sensitivity at the preoperative evaluation, and 3, 6, and 52 weeks after surgery. RESULTS: No cases of partial or total NAC necrosis were noted in either group. The comparison between the groups did not show significant differences regarding NAC sensitivity. However, a statistically significant difference was noted when sensitivity levels at the preoperative evaluation and 3 weeks after surgery were compared in the experimental group. A significant difference was noted when the scores of the sensitivity 3 weeks after surgery were compared between the control and the experiment groups. Nevertheless, after 1 year, no statistical differences were observed in the experimental group or between both groups. CONCLUSIONS: The sectioning of the periareolar dermis does not affect the viability or the pressure sensitivity of the NAC.
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Mamoplastia , Mamilos , Cicatriz/etiologia , Derme , Feminino , Humanos , Mamilos/cirurgia , Cuidados Pré-OperatóriosRESUMO
OBJECTIVES: Gastrointestinal (GI) inflammation and GI integrity deficits are common comorbidities of neuropsychiatric disorders. Ongoing research suggests that these aberrations may be contributing to heightened immune signals that have the potential to disrupt neuronal homeostasis and exacerbate behavioural deficits. The current study aimed to determine whether the well-characterized animal model of neuropsychopathology, the maternal immune activation (MIA) model, produced GI inflammation and integrity disruptions in association with anxiety-like behaviour. METHODS: Pregnant Wistar rats were exposed to the viral mimetic polyriboinosinic:polyribocytidilic acid (polyI:C) on gestational days (GD) 10 and 19. Evidence of ANS activation, GI inflammation, and GI barrier integrity was assessed in both neonatal (postnatal day, P7) and adult (P84) offspring. Anxiety-like behaviour was assessed at P100. RESULTS: Neonatal MIA offspring exhibited an altered intestinal inflammatory profile and evidence of an increase in lymphoid aggregates. MIA neonates also displayed disruptions to GI barrier tight junction protein mRNA. In addition, adult MIA offspring exhibited an increase in anxiety-like behaviours. CONCLUSION: These results indicate that the MIA rat model, which is well documented to produce behavioural, neurochemical, and neuroanatomical abnormalities, also produces GI inflammation and integrity disruptions. We suggest that this model may be a useful tool to elucidate biological pathways associated with neuropsychiatric disorders.
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Ansiedade/induzido quimicamente , Ansiedade/imunologia , Trato Gastrointestinal/imunologia , Mediadores da Inflamação/imunologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/imunologia , Animais , Ansiedade/metabolismo , Modelos Animais de Doenças , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Poli I-C/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos WistarRESUMO
Maternal exposure to infectious agents during gestation has been identified as a significant risk factor for schizophrenia. Using a mouse model, past work has demonstrated that the gestational timing of the immune-activating event can impact the behavioural phenotype and expression of dopaminergic and glutamatergic neurotransmission markers in the offspring. In order to determine the inter-species generality of this effect to rats, another commonly used model species, the current study investigated the impact of a viral mimetic Poly (I:C) at either an early (gestational day 10) or late (gestational day 19) time-point on schizophrenia-related behaviour and neurotransmitter receptor expression in rat offspring. Exposure to Poly (I:C) in late, but not early, gestation resulted in transient impairments in working memory. In addition, male rats exposed to maternal immune activation (MIA) in either early or late gestation exhibited sensorimotor gating deficits. Conversely, neither early nor late MIA exposure altered locomotor responses to MK-801 or amphetamine. In addition, increased dopamine 1 receptor mRNA levels were found in the nucleus accumbens of male rats exposed to early gestational MIA. The findings from this study diverge somewhat from previous findings in mice with MIA exposure, which were often found to exhibit a more comprehensive spectrum of schizophrenia-like phenotypes in both males and females, indicating potential differences in the neurodevelopmental vulnerability to MIA exposure in the rat with regards to schizophrenia related changes.
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Efeitos Tardios da Exposição Pré-Natal/imunologia , Esquizofrenia/imunologia , Animais , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Feminino , Masculino , Exposição Materna , Memória de Curto Prazo/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Poli I-C/farmacologia , Gravidez , Ratos , Ratos Wistar , Reflexo de Sobressalto/efeitos dos fármacos , Esquizofrenia/etiologiaRESUMO
BACKGROUND AND AIM: To compare the efficacy and tolerability of a low-volume (2-L) polyethylene glycol (PEG) regimen for colonoscopy compared to single (4-L) or split-dose (2-L + 2-L) regimens. METHODS: In-hospital patients who were candidates for colonoscopy were randomly assigned to: group 1 single-dose (PEG 4 L the day before the study, n = 60); group 2: split-dose (2 L the day before and 2 L on the day of the procedure, n = 61); and group 3: low-volume 2-L PEG solution (the day of the procedure, n = 59). A blinded evaluation of the quality of colonic preparation was assessed by the Boston bowel preparation scale. RESULTS: Satisfactory bowel preparation of the right colon was more frequently reported for group 3 than for group 1 (70% vs 53%, P = 0.045), in the transverse colon it was 82% versus 69% (P = 0.032), and on the left side of the colon it was 80% versus 67.7% (P = 0.028). Compared to group 2, satisfactory bowel preparation in group 3 was similar in the transverse colon and left colon. Nausea, vomiting, and abdominal discomfort were less frequent in patients of group 3. Patients in group 3 had fewer sleep disorders and fewer hours of sleep loss compared to patients in the other groups. CONCLUSIONS: Preparation with 2 L caused less abdominal discomfort and fewer sleep disorders. The split dose had a better quality of preparation in the right colon. Both preparations were clearly better than the 4-L preparation.
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Catárticos/administração & dosagem , Colonoscopia , Polietilenoglicóis/administração & dosagem , Irrigação Terapêutica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Chicory is a food with high nutritional. The use of beneficial elements in plants, such as sodium (Na) and silicon (Si), may be important to mitigate nutritional disorders, such as potassium (K) deficiency, but research is lacking on this topic. The objective was to evaluate the effects of sodium and nano-silicon on the nutritional, physiological, growth, and quality parameters of chicory under K deficiency and sufficiency. We used a concentration for sufficient K (3.0 mmol L-1), K-deficiency (1.5 mmol L-1), combined with the lack or presence of Na (2.0 mmol L-1) and Si (2.0 mmol L-1). The experiment was carried out in a greenhouse with six treatments corresponding to K sufficiency, K-sufficiency with Na, K-sufficiency with Si, K deficiency, K-deficiency with Na, and K-deficiency with Si, with six replications. The following growth variables were evaluated: (i) plant height, (ii) stem diameter, (iii) number of leaves, (iv) leaf area, and (v) plant biomass. Potassium and Si contents in the above ground part and K utilization efficiency were assessed, and the accumulation of K, Na, and Si was calculated. The efficiency of the quantum yield of photosystem II (Fv/Fm) and the photosynthetic pigments was determined. Electrolyte leakage index and relative water content, as well as phenolic compounds, ascorbic acid, and leaf firmness index were also determined. We found that supplying nano-Si and Na to a K-deficient nutrient solution increased K accumulation by 60% and 50% and K use efficiency by 79% and 62% compared to plants without supply of those elements. Nano-Si reduced electrolyte leakage, being 41% less than Na in K-deficient chicory. However, when Na was added to a nutrient solution with sufficient potassium, the K use efficiency decreased by 48% compared to sufficient potassium without Na. Under the same condition of sufficient supply of potassium and Na, K accumulation decreased by 20% in chicory compared to sufficient potassium without Na, and the photosynthetic pigments-total chlorophyll and carotenoids-were reduced by 5% and 10%, respectively. Our findings contribute to improve cultivation systems with low supply of K as the supply of Na and nano-Si mitigates the damage caused to the metabolism of chicory under K deficiency.
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Cichorium intybus , Potássio , Silício , Sódio , Silício/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Cichorium intybus/metabolismo , Fotossíntese , Deficiência de Potássio/metabolismo , Folhas de Planta/metabolismo , Clorofila/metabolismoRESUMO
The prediction of semiconductor device performance is a persistent challenge in materials science, and the ability to anticipate useful specifications prior to construction is crucial for enhancing the overall efficiency. In this study, we investigate the constituents of a solar cell by employing scanning tunneling microscopy (STM) and spectroscopy (STS). Through our observations, we identify a spatial distribution of the dopant type in thin films of materials that were designed to present major p-doping for germanium sulfide (GeS) and dominant n-doping for tin disulfide (SnS2). By generating separate STS maps for each semiconductor film and conducting a statistical analysis of the gap and doping distribution, we determine intrinsic limitations for the solar cell efficiency that must be understood prior to processing. Subsequently, we fabricate a solar cell utilizing these materials (GeS and SnS2) via vapor phase deposition and carry out a characterization using standard J-V curves under both dark/illuminated irradiance conditions. Our devices corroborate the expected reduced efficiency due to doping fluctuation but exhibit stable photocurrent responses. As originally planned, quantum efficiency measurements reveal that the peak efficiency of our solar cell coincides with the range where the standard silicon solar cells sharply decline. Our STS method is suggested as a prequel to device development in novel material junctions or deposition processes where fluctuations of doping levels are retrieved due to intrinsic material characteristics such as the occurrence of defects, roughness, local chemical segregation, and faceting or step bunching.
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The discovery of ferroelectricity in two-dimensional van der Waals materials has sparked enormous interest from the scientific community, due to its possible applications in next-generation nanoelectronic devices, such as random-access memory devices, digital signal processors, and solar cells, among others. In the present study, we used vapor phase deposition to synthesize ultrathin germanium sulfide nano-flakes on a highly oriented pyrolytic graphite substrate. Nanostructures of variable thicknesses were characterized using scanning tunneling microscopy and spectroscopy. Tunneling currents under forward and backward biases were measured as a function of nano-flake thickness. Remarkably, we clearly observed a hysteresis pattern, which we attributed to surface ferroelectric behavior, consistent with the screening conditions of polarization charges. The effect increases as the number of layers is reduced. This experimental result may be directly applicable to miniaturized memory devices, given the two-dimensional nature of this effect.
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PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.
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Neoplasias Encefálicas , Radioterapia (Especialidade) , Humanos , Estudos Retrospectivos , Neoplasias Encefálicas/radioterapia , Irradiação Craniana , MorteRESUMO
Myelodysplastic neoplasms (MDS) are a heterogeneous group of hematological stem cell disorders characterized by dysplasia, cytopenias, and increased risk of acute leukemia. As prognosis differs widely between patients, and treatment options vary from observation to allogeneic stem cell transplantation, accurate and precise disease risk prognostication is critical for decision making. With this aim, we retrieved registry data from MDS patients from 90 Spanish institutions. A total of 7202 patients were included, which were divided into a training (80%) and a test (20%) set. A machine learning technique (random survival forests) was used to model overall survival (OS) and leukemia-free survival (LFS). The optimal model was based on 8 variables (age, gender, hemoglobin, leukocyte count, platelet count, neutrophil percentage, bone marrow blast, and cytogenetic risk group). This model achieved high accuracy in predicting OS (c-indexes; 0.759 and 0.776) and LFS (c-indexes; 0.812 and 0.845). Importantly, the model was superior to the revised International Prognostic Scoring System (IPSS-R) and the age-adjusted IPSS-R. This difference persisted in different age ranges and in all evaluated disease subgroups. Finally, we validated our results in an external cohort, confirming the superiority of the Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS) over the IPSS-R, and achieving a similar performance as the molecular IPSS. In conclusion, the AIPSS-MDS score is a new prognostic model based exclusively on traditional clinical, hematological, and cytogenetic variables. AIPSS-MDS has a high prognostic accuracy in predicting survival in MDS patients, outperforming other well-established risk-scoring systems.
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BACKGROUND: Psychological stress, particularly in chronic form, can lead to mood and cognitive dysfunction and is a major risk factor in the development of depressive states. How stress affects the brain to cause psychopathologies is incompletely understood. We sought to characterise potential depression related mechanisms by analysing gene expression and molecular pathways in the infralimbic medial prefrontal cortex (ILmPFC), following a repeated psychological stress paradigm. The ILmPFC is thought to be involved in the processing of emotionally contextual information and in orchestrating the related autonomic responses, and it is one of the brain regions implicated in both stress responses and depression. RESULTS: Genome-wide microarray analysis of gene expression showed sub-chronic restraint stress resulted predominantly in a reduction in transcripts 24 hours after the last stress episode, with 239 genes significantly decreased, while just 24 genes had increased transcript abundance. Molecular pathway analysis using DAVID identified 8 pathways that were significantly enriched in the differentially expressed gene list, with genes belonging to the brain-derived neurotrophic factor - neurotrophin receptor tyrosine kinase 2 (BDNF-Ntrk2) pathway most enriched. Of the three intracellular signalling pathways that are downstream of Ntrk2, real-time quantitative PCR confirmed that only the PI3K-AKT-GSK3B and MAPK/ERK pathways were affected by sub-chronic stress, with the PLCγ pathway unaffected. Interestingly, chronic antidepressant treatment with the selective serotonin reuptake inhibitor, fluoxetine, prevented the stress-induced Ntrk2 and PI3K pathway changes, but it had no effect on the MAPK/ERK pathway. CONCLUSIONS: These findings indicate that abnormal BDNF-Ntrk2 signalling may manifest at a relatively early time point, and is consistent with a molecular signature of depression developing well before depression-like behaviours occur. Targeting this pathway prophylactically, particularly in depression-susceptible individuals, may be of therapeutic benefit.
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Antidepressivos de Segunda Geração/farmacologia , Fluoxetina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Sistema Límbico/metabolismo , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/patologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Sistema Límbico/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Córtex Pré-Frontal/efeitos dos fármacos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor trkC/genética , Receptor trkC/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
The decrease in the use of K fertilizers may be relevant for developing countries that depend on imports, as well as for specific groups such as patients with chronic kidney disease, who have restricted K in their diets. However, the decrease in the use of K affects plant yield, requiring the study of alternatives to mitigate nutritional stress. Sodium is a beneficial element that can mitigate K deficiency, but studies on kale plants are lacking. We investigated the role of Na in kale grown with and without K in nutrient feed solution. Four treatments were used: abundant K, abundant K plus Na, deficient K, and deficient K plus Na. Low Na (2 mmol L-1) attenuated the symptoms of K deficiency in kale by minimizing leaf water loss and increasing pigment content, leaf area, and plant dry mass. The synergism between K and Na negatively affected the growth of kale plants.
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Brassica , Fertilizantes , Humanos , Folhas de Planta , Sódio , ÁguaRESUMO
INTRODUCTION: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. METHODS: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. RESULTS: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. CONCLUSIONS: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management.
Assuntos
Síndrome Torácica Aguda , Anemia Falciforme , Síndrome Torácica Aguda/diagnóstico , Síndrome Torácica Aguda/epidemiologia , Síndrome Torácica Aguda/etiologia , Analgésicos Opioides , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/terapia , Humanos , Recém-Nascido , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
The availability of information about population minorities, in this case, the LGBTQIA+ population (Lesbians, Gays, Bisexual, Transvestite/Transsexual, Queer, Intersex, and Asexual), and the possible intersections with other variables on population bases is essential for understanding the similarities and specificities of the reality experienced by these groups, and the establishment of focused public policies. In this sense, this paper aims to reflect on the problems related to research about the sex and gender orientations/performances and, consequently, the lack of information on this topic available in population databases. From the inclusion of the question about sexual orientation in the 2019 National Health Survey database, despite the limitations, this paper presents possible opportunities for investigations on the topic from different perspectives.
A disponibilidade de informações a respeito das minorias populacionais, nesse caso, da população LGBTQIA+ (Lésbicas, Gays, Bissexuais, Travestis e Transexuais, Queers, Intersexuais e Assexuais) e a possibilidade de cruzamentos com demais variáveis em bases populacionais é imprescindível para a compreensão das similaridades e especificidades da realidade vivenciada por estes grupos, bem como para a criação de políticas públicas focalizadas. Nesse sentido, buscamos refletir nesse artigo sobre os problemas relativos à investigação sobre as orientações/performances de sexo e gênero e, por consequência, a falta de informação sobre tal temática disponível nas bases de dados populacionais. A partir da inclusão da pergunta sobre orientação sexual na base de dados da Pesquisa Nacional de Saúde (PNS), de 2019, apesar das limitações, apresentamos algumas das possíveis oportunidades de investigações sobre o tema a partir de diferentes óticas.
Assuntos
Homossexualidade Feminina , Minorias Sexuais e de Gênero , Bissexualidade , Feminino , Identidade de Gênero , Humanos , Masculino , Comportamento SexualRESUMO
Background: Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractory stage, patients are no longer responsive to therapy and management of weight loss is no longer possible. It is therefore critical to detect cachexia as early as possible. In this study we applied a metabolomics approach to search for early biomarkers of cachexia. Methods: Multi-platform metabolomics analyses were applied to the murine Colon-26 (C26) model of cachexia. Tumor bearing mice (n = 5) were sacrificed every other day over the 14-day time course and control mice (n = 5) were sacrificed every fourth day starting at day 2. Linear regression modeling of the data yielded metabolic trajectories that were compared with the trajectories of body weight and skeletal muscle loss to look for early biomarkers of cachexia. Results: Weight loss in the tumor-bearing mice became significant at day 9 as did the loss of tibialis muscle. The loss of muscle in the gastrocnemius and quadriceps was significant at day 7. Reductions in amino acids were among the earliest metabolic biomarkers of cachexia. The earliest change was in methionine at day 4. Significant alterations in acylcarnitines and lipoproteins were also detected several days prior to weight loss. Conclusion: The results of this study demonstrate that metabolic alterations appear well in advance of observable weight loss. The earliest and most significant alterations were found in amino acids and lipoproteins. Validation of these results in other models of cachexia and in clinical studies will pave the way for a clinical diagnostic panel for the early detection of cachexia. Such a panel would provide a tremendous advance in cachectic patient management and in the design of clinical trials for new therapeutic interventions.