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FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.
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Leucemia Mieloide Aguda , Mutação , Proteínas Nucleares , Nucleofosmina , Tirosina Quinase 3 Semelhante a fms , Idoso , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Proteínas Nucleares/genética , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagemRESUMO
Salmonella enterica can survive in surface waters (SuWa), and the role of nonhost environments in its transmission has acquired increasing relevance. In this study, we conducted comparative genomic analyses of 172 S. enterica isolates collected from SuWa across 3 months in six states of central Mexico during 2019. S. enterica transmission dynamics were assessed using 87 experimental and 112 public isolates from Mexico collected during 2002 through 2019. We also studied genetic relatedness between SuWa isolates and human clinical strains collected in North America during 2005 through 2020. Among experimental isolates, we identified 41 S. enterica serovars and 56 multilocus sequence types (STs). Predominant serovars were Senftenberg (n = 13), Meleagridis, Agona, and Newport (n = 12 each), Give (n = 10), Anatum (n = 8), Adelaide (n = 7), and Infantis, Mbandaka, Ohio, and Typhimurium (n = 6 each). We observed a high genetic diversity in the sample under study, as well as clonal dissemination of strains across distant regions. Some of these strains are epidemiologically important (ST14, ST45, ST118, ST132, ST198, and ST213) and were genotypically close to those involved in clinical cases in North America. Transmission network analysis suggests that SuWa are a relevant source of S. enterica (0.7 source/hub ratio) and contribute to its dissemination as isolates from varied sources and clinical cases have SuWa isolates as common ancestors. Overall, the study shows that SuWa act as reservoirs of various S. enterica serovars of public health significance. Further research is needed to better understand the mechanisms involved in SuWa contamination by S. enterica, as well as to develop interventions to contain its dissemination in food production settings. IMPORTANCE Surface waters are heavily used in food production worldwide. Several human pathogens can survive in these waters for long periods and disseminate to food production environments, contaminating our food supply. One of these pathogens is Salmonella enterica, a leading cause of foodborne infections, hospitalizations, and deaths in many countries. This research demonstrates the role of surface waters as a vehicle for the transmission of Salmonella along food production chains. It also shows that some strains circulating in surface waters are very similar to those implicated in human infections and harbor genes that confer resistance to multiple antibiotics, posing a risk to public health. This study contributes to expand our current knowledge on the ecology and epidemiology of Salmonella in surface waters.
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Salmonella enterica , Agricultura , Aquicultura , Genômica , Humanos , México/epidemiologia , Salmonella enterica/genéticaRESUMO
We report experimental results that show the interplay between visibility, distinguishability, and the degree of polarization, as ruled by a recent extension of the polarization coherence theorem (PCT). Theorems of this kind address duality in both quantum and classical scenarios. We particularly focus on the inherent vector nature of the polarization degree of freedom and display various effects that lie beyond the scope of the original PCT. Our results exhibit features that can be shared by quantum and classical phenomena, whenever these phenomena reflect some hidden or exposed coherence.
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Huntington's disease (HD) is a hereditary neurodegenerative disease, with peripheral consequences that negatively contribute to quality of life. Circulating microRNAs (cmiRNAs) are being explored for their roles in intercellular communication and gene expression regulation, which allows gaining insight into the regulation of crosstalk between neuronal and peripheral tissues. Here, we explore the cmiRNA profile of plasma samples from fifteen symptomatic patients, with 40-45 CAG repeats in the HTT gene, and seven healthy matched controls. Isolated miRNAs from plasma samples were run against human miRNome panels, which have sequences for 752 human mature miRNAs. We found that 168 cmiRNAs are altered in symptomatic patients. Considering Bonferroni's correction, miR-877-5p, miR-223-3p, miR-223-5p, miR-30d-5p, miR-128, miR-22-5p, miR-222-3p, miR-338-3p, miR-130b-3p, miR-425-5p, miR-628-3p, miR-361-5p, miR-942 are significantly increased in HD patients as compared with controls. Moreover, after patient's organization according to approved HD scales, miR-122-5p is significantly decreased in HD patients with Unified Huntington's Disease Rating Scale >24, whereas an increase in miR-100-5p levels and a decrease in miR-641 and miR-330-3p levels were recorded when patients were rearranged by Total Functional Capacity. These results suggest that cmiRNA profile could be further modified by disease progression, making cmiRNAs useful as monitoring biomarkers. Analysis of target genes indicated a general overexpression of cmiRNAs implicated in metabolism regulation. Profiling cmiRNA of HD subjects opens the possibility of personalized therapies for different groups of HD patients, based on disease modifiers: regulation of altered pathways might contribute to not only alleviate disease symptoms, but also influence HD progression.
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MicroRNA Circulante/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Doença de Huntington/genética , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , MicroRNA Circulante/sangue , MicroRNA Circulante/metabolismo , Progressão da Doença , Humanos , Doença de Huntington/sangue , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Masculino , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
The feasibility of anaerobic co-digestion in semicontinuous mode of two major urban biowaste, food waste (FW) and garden and park waste (GPW) (75 % FW and 25 % GPW) as well as the co-digestion of FW with the process water originated from the hydrothermal carbonization of GPW (95 % FW and 5 % process water), both on a COD basis, has been assessed. The effect of varying organic loading rate (OLR) from 1.5 to 3.5 g COD/L·d on methane yield, gross energy recovery, and microbiome population was evaluated. For comparison, anaerobic digestion of FW was also conducted to determine the best strategy for sustainable biowaste management. This study showed an optimal OLR of 2.5 g COD/L·d. Acetic and propionic acid content increased as OLR raised for each condition studied, while methane yield decreased at the highest OLR tested indicating overloading of the system. The anaerobic co-digestion of FW and process water showed a 10 % increase on methane production compared to anaerobic digestion of FW (324 vs. 294 mL CH4 STP/L·d). Moreover, it enhances the process due to a greater abundance and diversity of hydrolytic and acidogenic bacteria belonging to Bacterioidota, Firmicutes, and Chloroflexi phyla, as well as promotes the hydrogenotrophic pathway under higher propionic concentrations which is not usually favoured for methane production. The integration of hydrothermal carbonization of GPW with the anaerobic co-digestion of 95 % FW and 5 % of process water results in the highest potential energy recovery and could be a good strategy for sustainable management of urban biowaste.
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Alimentos , Eliminação de Resíduos , Anaerobiose , Reatores Biológicos , Perda e Desperdício de Alimentos , Metano/análise , Digestão , ÁguaRESUMO
Vascular endothelial cells have important tissue-specific functions in fibrosis and regeneration. In the salivary gland, endothelial cells are required for proper development, but their roles within adult glands are largely unknown. To identify ligand-receptor interactions between endothelial cells and other cell types that may be important during fibrosis and regeneration, we used a reversible ductal ligation injury. To induce injury, a clip was applied to the primary ducts for 14 d, and to induce a regenerative response, the clip was subsequently removed for 5 d. To identify endothelial cell-produced factors, we used single-cell RNA sequencing of stromal-enriched cells from adult female submandibular and sublingual salivary glands. Transcriptional profiles of homeostatic salivary gland endothelial cells were compared to endothelial cells of other organs. Salivary gland endothelial cells expressed many unique genes and displayed the highest overlap in gene expression with other fenestrated endothelial cells from the colon, small intestine, and kidney. Comparison of the 14-d ligated, mock-ligated, and 5-d deligated stromal-enriched transcripts and lineage tracing revealed that endothelial cells retain their identity following ligation and recovery from injury. CellChat and NATMI were used to predict changes in ligand-receptor interactions from endothelial cells to other cells in response to ligation and deligation. CellChat and NATMI predicted that after ligation, interactions with fibroblasts, epithelial cells, and glial cells were increased, and following deligation, interactions with pericyte, glia, fibroblasts, and immune cells were increased. Some of the highest-ranked interactions predicted in ligated compared to mock endothelial cells were between glial cells via Col4a2-Cd93 and Jag2-Notch1, as well as epithelial cells via Pecam1-Cd38, while in deligated compared to ligated endothelial cells, the top interactions were between fibroblasts via Ntf3-Ntrk2, glial cells via Hspg2-Itgb1, and pericytes via Jam2-F11r. Understanding salivary gland endothelial cell signaling will inform future endothelial cell-based regenerative therapies.
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Células Endoteliais , Glândulas Salivares , Adulto , Humanos , Feminino , Ligantes , Fibrose , Perfilação da Expressão GênicaRESUMO
Inhibition of telomerase is proposed to limit the growth of cancer cells by triggering telomere shortening and cell death. Telomere maintenance by telomerase is sufficient, in some cell types, to allow immortal growth. Telomerase has been shown to cooperate with oncogenes in transforming cultured primary human cells into neoplastic cells, suggesting that telomerase activation contributes to malignant transformation. Moreover, telomerase inhibition in human tumour cell lines using dominant-negative versions of TERT leads to telomere shortening and cell death. These findings have led to the proposition that telomerase inhibition may result in cessation of tumour growth. The absence of telomerase from most normal cells supports the potential efficacy of anti-telomerase drugs for tumour therapy, as its inhibition is unlikely to have toxic effects. Mice deficient for Terc RNA (encoding telomerase) lack telomerase activity, and constitute a model for evaluating the role of telomerase and telomeres in tumourigenesis. Late-generation Terc-/- mice show defects in proliferative tissues and a moderate increase in the incidence of spontaneous tumours in highly proliferative cell types (lymphomas, teratocarcinomas). The appearance of these tumours is thought to be a consequence of chromosomal instability in these mice. These observations have challenged the expected effectiveness of anti-telomerase-based cancer therapies. Different cell types may nonetheless vary in their sensitivity to the chromosomal instability produced by telomere loss or to the activation of telomere-rescue mechanisms. Here we show that late-generation Terc-/- mice, which have short telomeres and are telomerase-deficient, are resistant to tumour development in multi-stage skin carcinogenesis. Our results predict that an anti-telomerase-based tumour therapy may be effective in epithelial tumours.
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Neoplasias Cutâneas/genética , Telomerase/deficiência , Telômero/patologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Carcinógenos , Citometria de Fluxo , Imunidade Inata/genética , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Queratinócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Papiloma/induzido quimicamente , Papiloma/genética , Papiloma/metabolismo , Papiloma/patologia , Proteínas Proto-Oncogênicas p21(ras)/biossíntese , Pele/metabolismo , Pele/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Acetato de Tetradecanoilforbol , Fatores de Tempo , Proteína Supressora de Tumor p53/biossínteseRESUMO
Public spaces are considered areas that promote users' physical and mental health. The role of these people in public spaces makes it necessary to evaluate such areas. In this study, 12 urban parks on the island of Tenerife were evaluated, combining the assessment of a trained observer and the perception of users, to analyse and categorise the environmental quality of the parks. The findings of this study conclude that users are good evaluators of public spaces; that the Public Space Characteristics Observation Questionnaire (PSCOQ) tool allows the classification of public spaces and that physical order is capable of predicting the environmental quality and the restorative capacity of spaces, as perceived by users. The PSCOQ observation tool makes it possible to detect the strengths and weaknesses of public spaces so they can be improved and adapted to the needs of users.
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PURPOSE: There are still many challenges for modelling a thrombus migration process in aneurysms. The main novelty of the present research lies in the modelling of aneurysm clot migration process in a realistic cerebral aneurysm, and the analysis of forces suffered by clots inside an aneurysm, through transient FSI simulations. METHODS: The blood flow has been modelled using a Womersley velocity profile, and following the Carreau viscosity model. Hyperelastic Ogden model has been used for clot and isotropic linear elastic model for the artery walls. The FSI coupled model was implemented in ANSYS® software. The hemodynamic forces suffered by the clot have been quantified using eight different clot sizes and positions inside a real aneurysm. RESULTS: The obtained results have shown that it is almost impossible for clots adjacent to aneurysm walls, to leave the aneurysm. Nevertheless, in clots positioned in the centre of the aneurysm, there is a real risk of clot migration. The risk of migration of a typical post-coiling intervention clot in an aneurysm, in contact with the wall and occupying a significant percentage of its volume is very low in the case studied, even in the presence of abnormally intense events, associated with sneezes or impacts. CONCLUSIONS: The proposed methodology allows evaluating the clot migration risk, vital for evaluating the progress after endovascular interventions, it is a step forward in the personalized medicine, patient follow-up, and helping the medical team deciding the optimal treatment.
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Aneurisma Intracraniano , Trombose , Humanos , Hemodinâmica , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Trombose/diagnóstico por imagem , Trombose/etiologiaRESUMO
Late-onset neutropaenia is defined as an absolute neutrophil count of <1.5×103cells/µL starting>4 weeks after the last dose of rituximab, in the absence of other identifiable causes. Late-onset neutropaenia is a rare adverse reaction to rituximab (observed in approximately 5% of patients). Rheumatic diseases constitute the main indication for rituximab; in these patients, neutropaenia appears after a mean of>28 days. Ocrelizumab is another monoclonal antibody that binds to CD20 (a glycosylated phosphoprotein mainly expressed on the membranes of B-lymphocytes); in January 2018, it was approved for the treatment of relapsing-remitting and primary progressive multiple sclerosis. We present a case of neutropaenia following intravenous infusion of ocrelizumab in a patient with primary progressive multiple sclerosis who presented with neutropaenic fever, herpetic stomatitis, and ecthyma gangrenosum only 20 days after infusion.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Neutropenia , Humanos , Esclerose Múltipla/tratamento farmacológico , Rituximab/efeitos adversosRESUMO
The optic discs of dogs exhibit considerable size, shape, and colour variations, depending on the degree of myelination. This variability makes the interpretation of lesions difficult, owing to the lack of reference patterns. This study aimed to compare optic nerve head (ONH) parameters determined by digital planimetry (DP) in two pure-bred dogs, Spanish Greyhound (SG) and Spanish Water Dog (SWD). The vertical and horizontal diameters, area, circularity, and the proportion of the ONH at the tapetal or non-tapetal zone (top height and bottom height) were calculated using image treatment software and compared between breeds. Significant between-breed differences were detected for all parameters, with SWD exhibiting greater height, width, area, top height, and lower circularity of the ONH than SG. Linear regression revealed that age significantly influenced mean disc height (R2 = 0.310; p = 0.0001), mean disc width (R2 = 0.280; p = 0.0001), mean disc area (R2 = 0.281; p = 0.0001), and circularity (R2 = 0.243; p = 0.0001). The multiple regression model significantly predicted mean disc height, width, and area [(S) (R2 = 0.715; p = 0.001), (R2 = 0.742; p = 0.001), and (S) (R2 = 0.736; p = 0.001), respectively], based on age and breed. Excellent concordance was observed between the measurements of experienced and novice researchers, and there were no differences between the parameters measured by the researcher and those obtained by the software. Planimetric ONH measurements can be easily performed by novice operators using a portable fundus camera and digital computer software. These results may be of considerable clinical value, but further studies are required because of the great variability of the ONH in dogs.
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Disco Óptico , Cães , Animais , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologia , SoftwareRESUMO
Multigenerational toxicity testing is a valuable tool for understanding the long-term effects of contaminants on aquatic organisms. This review focuses on the use of multigenerational tests with Daphnia, a widely used model organism in aquatic toxicological studies. The review highlights the importance of studying multiple generations to assess Daphnia spp. reproductive, growth, and physiological responses to various contaminants. We discuss the outcomes of multigenerational tests involving different contaminants, including nanoparticles, pesticides, and pharmaceuticals. The results reveal that multigenerational exposure can lead to transgenerational effects, where the impacts of contaminants are observed in subsequent generations even after the initial exposure has ceased. These transgenerational effects often manifest as reproduction, growth, and development alterations. Furthermore, we emphasize the need for standardized protocols in multigenerational testing to ensure comparability and reproducibility of results across studies. We also discuss the implications of multigenerational testing for ecological risk assessment, as it provides a more realistic representation of the long-term effects of contaminants on populations and ecosystems. Overall, this review highlights the significance of multigenerational tests with Daphnia in advancing our understanding of the ecological impacts of contaminants. Such tests provide valuable insights into the potential risks associated with long-term exposure to pollutants and contribute to the development of effective mitigation strategies for aquatic ecosystems.
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Ecossistema , Poluentes Químicos da Água , Animais , Daphnia , Reprodutibilidade dos Testes , Poluentes Químicos da Água/toxicidade , Meio Ambiente , ReproduçãoRESUMO
Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatment.
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Epilepsias Mioclônicas , Canal de Sódio Disparado por Voltagem NAV1.1 , Animais , Camundongos , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/terapia , Convulsões/terapia , Convulsões/genética , Estimulação Magnética Transcraniana , Modelos Animais de Doenças , Fenômenos MagnéticosRESUMO
Hollow nanospheres of molybdenum disulfide have been synthesized by a novel solvothermal method under low temperature (180 degrees C). These nanomaterials were characterized by X-ray diffraction (XRD), Fourier transformation infra-red spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM, HRTEM) and X-ray Photoelectron Spectroscopy (XPS). A mechanism for the synthesis reaction is tentatively proposed and discussed.
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BACKGROUND: Malignant melanoma (MM) is a very aggressive tumour. Although surgical excision of MM in the early stages has a very good prognosis, it often fails to completely inhibit tumour progression. Methylene blue photodynamic therapy (MB-PDT) is a technique that induces tissue damage by reactive oxygen species (ROS). AIM: To investigate the efficacy of and potential use of MB-PDT in restraining the aggressiveness of MM by analysing levels of proliferating cell nuclear antigen (PCNA) and heparanase (HPSE, a molecular marker of cell invasion) in a mouse model. METHODS: Expression of PCNA and two HPSE isoforms were analysed using immunohistochemistry (IHC) after MB-PDT in mice. Tumour volume and weight were also measured. RESULTS: Two treatments with MB-PDT promoted a decrease of 99% decrease in tumour volume and 75% in tumour weight compared with untreated mice (P < 0.05). Using IHC, a decrease in expression of 75% for PCNA and 95% for both HPSE isoforms (P < 0.05) was found. CONCLUSION: MB-PDT is a cheap and efficient method of decreasing MM volume and thus disease progression. This reduction is mediated by downregulation of PCNA and heparanases.
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Glucuronidase/metabolismo , Melanoma Experimental/tratamento farmacológico , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Animais , Biomarcadores Tumorais/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/uso terapêutico , Feminino , Imuno-Histoquímica , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Nus , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
OBJECTIVE: Falls from heights are a major preventable cause of morbidity and mortality in children. The aims of this study are to describe the evolution and long-term prognosis of such patients, to identify the pediatric population at greatest risk of falling from heights in our setting, and to define the variables at admission capable of predicting mortality. DESIGN: A retrospective patient cohort review was carried out. SETTING: Pediatric patients. POPULATION: Pediatric patients admitted to the pediatric intensive care unit following a fall from a height of over two meters, in the last 10 years. RESULTS: Ninety-two percent of the patients fell from buildings. Out of a total of 54 patients suffering falls, 51% were preschoolers. Fifty percent of the adolescents cases corresponded to attempted suicide. Fifty-two percent of the children were immigrants. Head injuries were the most common type of traumatism. The mortality rate was 12%. Eighty-two percent of the patients with a follow-up period of two years were leading an independent life. The independent predictors of mortality were the height of the fall, the Glasgow coma score and pediatric trauma index score upon admission, the presence of anemia, acidosis and hypotension upon admission, the need for vasoactive drugs, and the presence of severe head injury with the development of intracranial hypertension. CONCLUSIONS: Falls from heights occur mainly in unsupervised preschool children and teenagers attempting suicide. These patients have a high number of injuries, a high mortality rate, and important care needs. Most survivors are able to lead an independent life over the long term. Preventive measures should be implemented in risk populations.
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Acidentes por Quedas/estatística & dados numéricos , Traumatismos Craniocerebrais/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To identify early prognostic factors that lead to an increased risk of unfavorable prognosis. DESIGN: Observational cohort study from October 2002 to October 2017. SETTING AND PATIENTS: Patients with severe TBI admitted to intensive care were included. VARIABLES AND INTERVENTIONS: Epidemiological, clinical, analytical and therapeutic variables were collected. The functional capacity of the patient was assessed at 6 months using the Glasgow Outcome Scale (GOS). An unfavorable prognosis was considered a GOS less than or equal to 3. A univariate analysis was performed to compare the groups with good and bad prognosis and their relationship with the different variables. A multivariate analysis was performed to predict the patient's prognosis. RESULTS: 98 patients were included, 61.2% males, median age 6.4 years (IQR 2.49-11.23). 84.7% were treated by the out-of-hospital emergency services. At 6 months, 51% presented satisfactory recovery, 26.5% moderate sequelae, 6.1% severe sequelae, and 2% vegetative state. 14.3% died. Statistical significance was found between the score on the prehospital Glasgow coma scale, pupillary reactivity, arterial hypotension, hypoxia, certain analytical and radiological alterations, such as compression of the basal cisterns, with an unfavorable prognosis. The multivariate analysis showed that it is possible to make predictive models of the evolution of the patients. CONCLUSIONS: it is possible to identify prognostic factors of poor evolution in the first 24 h after trauma. Knowledge of them can help clinical decision-making as well as offer better information to families.
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Lesões Encefálicas Traumáticas , Traumatismo Múltiplo , Lesões Encefálicas Traumáticas/complicações , Criança , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Morbidade , Traumatismo Múltiplo/complicações , PrognósticoRESUMO
BACKGROUND AND OBJECTIVE: The attainment of a methodology to simulate the hemodynamic in patient-specific cerebral vessels with aneurysms is still a challenge. The novelty of this work is focused on the effect of coil embolization in a realistic cerebral aneurysm, according to the vessel wall thickness and aneurysm thickness, through transient FSI simulations. METHODS: The quality of the mesh for simulations was checked with a specific mesh convergence study; and the numerical methodology was validated using numerical research data of the literature. The model was implemented in ANSYS® software. The total deformation and equivalent stress evolution in the studied cases, before and after coil embolization, were compared. More than 20 different models were employed due to different arterial wall thickness and aneurysm wall thickness combinations. RESULTS: The obtained results have showed that deformation and stress values are highly influenced with the sac thickness. The thinner sac aneurysm thickness is, the greater deformation and stress are. The results after coil embolization process have highlighted that considering typical values of arterial wall thickness and aneurysm thickness 0.3 mm and 0.15 mm respectively, a deformation reduction around 50% and a stress reduction around 70% can be achieved. CONCLUSIONS: The proposed methodology is a step forward in the personalized medicine, quantifying the aneurysm rupture risk reduction, and helping the medical team in the preoperative planning, or to deciding the optimal treatment.
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Aneurisma Intracraniano , Modelos Cardiovasculares , Artérias , Hemodinâmica , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapiaRESUMO
RANK signaling in mouse mammary tumor cells exerts an immunosuppressive environment by promoting the infiltration of pro-tumorigenic neutrophils and preventing CD8 T cell recruitment. Single-agent denosumab led to an increased tumor immune infiltration by lymphocytes and CD8 + T cells in breast cancer patients, supporting the immunomodulatory role of RANK signaling.
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Neoplasias da Mama , Animais , Neoplasias da Mama/tratamento farmacológico , Denosumab , Feminino , Humanos , Imunoterapia , Camundongos , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-BRESUMO
OBJECTIVE: To identify early prognostic factors that lead to an increased risk of unfavorable prognosis. DESIGN: Observational cohort study from October 2002 to October 2017. SETTING AND PATIENTS: Patients with severe TBI admitted to intensive care were included. VARIABLES AND INTERVENTIONS: Epidemiological, clinical, analytical and therapeutic variables were collected. The functional capacity of the patient was assessed at 6 months using the Glasgow Outcome Scale (GOS). An unfavorable prognosis was considered a GOS ≤3. A univariate analysis was performed to compare the groups with good and bad prognosis and their relationship with the different variables. A multivariate analysis was performed to predict the patient's prognosis. RESULTS: A total of 98 patients were included, 61.2% males, median age 6.4years (IQR 2.49-11.23). 84.7% were treated by the out-of-hospital emergency services. At 6 months, 51% presented satisfactory recovery, 26.5% moderate sequelae, 6.1% severe sequelae, and 2% vegetative state. 14.3% died. Statistical significance was found between the score on the prehospital Glasgow coma scale, pupillary reactivity, arterial hypotension, hypoxia, certain analytical and radiological alterations, such as compression of the basal cisterns, with an unfavorable prognosis. The multivariate analysis showed that it is possible to make predictive models of the evolution of the patients. CONCLUSIONS: It is possible to identify prognostic factors of poor evolution in the first 24hours after trauma. Knowledge of them can help clinical decision-making as well as offer better information to families.