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OBJECTIVE: The objective of this study was to describe the outcomes of outpatient oncological neurosurgery (OON) in a European clinical setting and to compare them with the conventional inpatient protocol. METHODS: Patients who had undergone OON (either tumor removal or biopsy) at the authors' center since 2019 were analyzed. A matched cohort of patients was selected from patients undergoing tumor surgery in the same period. Collected data included patient demographics, postoperative progress, specific location of the target lesion, and the procedure performed. RESULTS: There were 18 patients in the case group and 59 patients in the control group. The outpatient surgeries had a same-day discharge rate of 89%, and all ambulatory patients successfully completed the Enhanced Recovery After Surgery program within 6.24 hours of the procedure. All ambulatory patients underwent Hospital-at-Home postoperative follow-up for an average of 4.12 days. Radiological complications were present in 11% of the case group and 8% of the control group. Postoperative neurological deficit occurred in 6% of the same-day discharge group and 3% of the control group. Among the patients in the control group, 3% suffered from postoperative seizures, whereas no seizures were observed in the case group. These differences were not statistically significant. General anesthesia-related complications were not observed in any of the patients. CONCLUSIONS: The authors' findings demonstrate that Enhanced Recovery After Surgery protocols and same-day discharge craniotomy for tumor resection and image-guided biopsy under general anesthesia, when patients are carefully selected, can be safely performed with excellent outcomes in a European clinical setting. The OON program proved to be a viable alternative to conventional hospitalization, showing comparable safety records and offering advantages in terms of patient recovery.
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Neoplasias Encefálicas , Alta do Paciente , Humanos , Seguimentos , Anestesia Geral/métodos , Hospitais , Neoplasias Encefálicas/cirurgia , Complicações Pós-OperatóriasRESUMO
OBJECTIVE: Despite growing evidence on the benefits of outpatient oncological neurosurgery (OON), it is only performed in a few specialized centers and there are no previous descriptions of established OON programs in Europe. Moreover, increasing application of telemedicine strategies, especially after the start of the coronavirus disease 2019 (COVID-19) pandemic, is drastically changing neurosurgical management, particularly in the case of vulnerable populations such as neuro-oncological patients. In this context, the authors implemented an OON program in their hospital with telematic follow-up. Herein, they describe the protocol and qualitatively analyze the barriers and facilitators of the development process. METHODS: An OON program was developed through the following steps: assessment of hospital needs, specific OON training, multidisciplinary team organization, and OON protocol design. In addition, the implementation phase included training sessions, a pilot study, and continuous improvement sessions. Finally, barriers and facilitators of the protocol's implementation were identified from the feedback of all participants. RESULTS: An OON protocol was successfully designed and implemented for resection or biopsy of supratentorial lesions up to 3 cm in diameter. The protocol included the patient's admission to the day surgery unit, noninvasive anesthetic monitoring, same-day discharge, and admission to the hospital-at-home (HaH) unit for telematic and on-site postoperative care. After a pilot study including 10 procedures in 9 patients, the main barriers identified were healthcare provider resistance to change, lack of experience in outpatient neurosurgery, patient reluctance, and limitations in the recruitment of patients. Key facilitators of the process were the patient education program, the multidisciplinary team approach, and the HaH-based telematic postoperative care. CONCLUSIONS: Initiating an OON program with telematic follow-up in a European clinical setting is feasible. Nevertheless, it poses several barriers that can be overcome by identifying and maximizing key facilitators of the process. Among them, patient education, a multidisciplinary team approach, and HaH-based postoperative care were crucial to the success of the program. Future studies should investigate the cost-effectiveness of telemedicine to assess potential cost savings, from reduced travel and wait times, and the impact on patient satisfaction.
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Neoplasias Encefálicas , COVID-19 , Telemedicina , Neoplasias Encefálicas/cirurgia , Humanos , Pacientes Ambulatoriais , Projetos PilotoRESUMO
Background: Glioblastoma (GBM) remains a major clinical challenge due to its invasive capacity, resistance to treatment, and recurrence. We have previously shown that ODZ1 contributes to glioblastoma invasion and that ODZ1 mRNA levels can be upregulated by epigenetic mechanisms in response to hypoxia. Herein, we have further studied the transcriptional regulation of ODZ1 in GBM stem cells (GSCs) under hypoxic conditions and analyzed whether HIF2α has any role in this regulation. Methods: We performed the experiments in three primary GSC cell lines established from tumor specimens. GSCs were cultured under hypoxia, treated with HIF regulators (DMOG, chetomin), or transfected with specific siRNAs, and the expression levels of ODZ1 and HIF2α were analyzed. In addition, the response of the ODZ1 promoter cloned into a luciferase reporter plasmid to the activation of HIF was also studied. Results: The upregulation of both mRNA and protein levels of HIF2α under hypoxia conditions correlated with the expression of ODZ1 mRNA. Moreover, the knockdown of HIF2α by siRNAs downregulated the expression of ODZ1. We found, in the ODZ1 promoter, a HIF consensus binding site (GCGTG) 1358 bp from the transcription start site (TSS) and a HIF-like site (CCGTG) 826 bp from the TSS. Luciferase assays revealed that the stabilization of HIF by DMOG resulted in the increased activity of the ODZ1 promoter. Conclusions: Our data indicate that the HIF2α-mediated upregulation of ODZ1 helps strengthen the transcriptional control of this migration factor under hypoxia in glioblastoma stem cells. The discovery of this novel transcriptional pathway identifies new targets to develop strategies that may avoid GBM tumor invasion and recurrence.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/etiologia , Glioblastoma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas do Tecido Nervoso/genética , Tenascina/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia Celular , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Glioblastoma/patologia , Humanos , Células-Tronco Neoplásicas/patologia , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/genética , Tenascina/metabolismoRESUMO
BACKGROUND: COVID-19 high-titer CCP selection is a concern, because neutralizing antibody (nAb) testing requires sophisticated labs and methods. Surrogate tests are an alternative for measuring nAb levels in plasma bags, including those that are pathogen-reduced. STUDY DESIGN/METHODS: We studied a panel consisting of 191 samples from convalescent donors tested by nAb (CPE-VNT), obtained from 180 CCP donations (collection: March 20-January 21) and 11 negative controls, with a total of 80 and 111 serum and plasma samples (71 amotosalen/UV treated), with nAb titers ranging from negative to 10,240. Samples were blindly tested for several surrogates: one anti-RBD, two anti-spike, and four anti-nucleocapsid tests, either isolated or combined to improve their positive predictive values as predictors of the presence of high-titer nAbs, defined as those with titers ≥160. RESULTS: Except for combined and anti-IgA/M tests, all isolated surrogate tests showed excellent performance for nAb detection: sensitivity (98.3%-100%), specificity (85.7%-100%), PPV (98.9%-100%), NPV (81.3%-100%), and AUC (0.93-0.96), with a variable decrease in sensitivity and considerably lower specificity when using FDA authorization and concomitant nAb titers ≥160. All surrogates had AUCs that were statistically different from CPE-VNT if nAb≥160, including when using combined, orthogonal approaches. CONCLUSIONS: Surrogate tests (isolated or in combination) have an indirect good performance in detecting the presence of nAb, with lower sensitivity and specificity when high nAb titer samples are used, possibly accepting a considerable number of donors whose nAb titers are actually low, which should be evaluated by each laboratory responsible for CCP collection.
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Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , Doadores de Sangue , Humanos , Imunização Passiva , SARS-CoV-2 , Soroterapia para COVID-19RESUMO
OBJECTIVE: The functional importance of the superior temporal lobe at the level of Heschl's gyrus is well known. However, the organization and function of these cortical areas and the underlying fiber tracts connecting them remain unclear. The goal of this study was to analyze the area formed by the organization of the intersection of Heschl's gyrus-related fiber tracts, which the authors have termed the "Heschl's gyrus fiber intersection area" (HGFIA). METHODS: The subcortical connectivity of Heschl's gyrus tracts was analyzed by white matter fiber dissection and by diffusion tensor imaging tractography. The white matter tracts organized in relation to Heschl's gyrus were isolated in 8 human hemispheres from cadaveric specimens and in 8 MRI studies in 4 healthy volunteers. In addition, these tracts and their functions were described in the surgical cases of left temporal gliomas next to the HGFIA in 6 patients who were awake during surgery and underwent intraoperative electrical stimulation mapping. RESULTS: Five tracts were observed to pass through the HGFIA: the anterior segment of the arcuate fasciculus, the middle longitudinal fasciculus, the acoustic radiation, the inferior fronto-occipital fasciculus, and the optic radiation. In addition, U fibers originating at the level of Heschl's gyrus and heading toward the middle temporal gyrus were identified. CONCLUSIONS: This investigation of the HGFIA, a region where 5 fiber tracts intersect in a relationship with the primary auditory area, provides new insights into the subcortical organization of Wernicke's area. This information is valuable when a temporal surgical approach is planned, in order to assess the surgical risk related to language disturbances.
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Córtex Auditivo/diagnóstico por imagem , Córtex Auditivo/fisiologia , Vias Auditivas/diagnóstico por imagem , Vias Auditivas/fisiologia , Percepção Auditiva/fisiologia , Idioma , Adulto , Idoso , Idoso de 80 Anos ou mais , Córtex Auditivo/anatomia & histologia , Vias Auditivas/anatomia & histologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/fisiologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologiaRESUMO
The original version of this article, published on 15 October 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The name of Mariano Amo-Salas and the affiliation of Ismael Herruzo were presented incorrectly.
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OBJECTIVES: We wished to determine whether tumor morphology descriptors obtained from pretreatment magnetic resonance images and clinical variables could predict survival for glioblastoma patients. METHODS: A cohort of 404 glioblastoma patients (311 discoveries and 93 validations) was used in the study. Pretreatment volumetric postcontrast T1-weighted magnetic resonance images were segmented to obtain the relevant morphological measures. Kaplan-Meier, Cox proportional hazards, correlations, and Harrell's concordance indexes (c-indexes) were used for the statistical analysis. RESULTS: A linear prognostic model based on the outstanding variables (age, contrast-enhanced (CE) rim width, and surface regularity) identified a group of patients with significantly better survival (p < 0.001, HR = 2.57) with high accuracy (discovery c-index = 0.74; validation c-index = 0.77). A similar model applied to totally resected patients was also able to predict survival (p < 0.001, HR = 3.43) with high predictive value (discovery c-index = 0.81; validation c-index = 0.92). Biopsied patients with better survival were well identified (p < 0.001, HR = 7.25) by a model including age and CE volume (c-index = 0.87). CONCLUSIONS: Simple linear models based on small sets of meaningful MRI-based pretreatment morphological features and age predicted survival of glioblastoma patients to a high degree of accuracy. The partition of the population using the extent of resection improved the prognostic value of those measures. KEY POINTS: ⢠A combination of two MRI-based morphological features (CE rim width and surface regularity) and patients' age outperformed previous prognosis scores for glioblastoma. ⢠Prognosis models for homogeneous surgical procedure groups led to even more accurate survival prediction based on Kaplan-Meier analysis and concordance indexes.
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Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
Throughout history, many scientists have wondered about the reason for neural pathway decussation in the CNS resulting in contralateral forebrain organization. Hitherto, one of the most accepted theories is the one described by the renowned Spanish physician, Santiago Rámon y Cajal at the end of the 19th century. This Nobel Prize winner, among his many contributions to science, gave us the answer to this question: the key lies in the optic chiasm. Based on the fact that the ocular lenses invert the image formed in the retina, Cajal explained how the decussation of the fibers in the optic chiasm is necessary to obtain a continuous image of the outside in the brain. The crossing of the tactile and motor pathways occurred posteriorly as a compensatory mechanism to allow the cortical integration of the sensory, motor, and visual functions. This theory had a great influence on the scientific community of his time, and maintains its importance today, in which none of the theories formulated to date has managed to entirely refute Cajal's. In addition, the decussation of neural pathways plays a significant role in different diseases, especially in the recovery process after a hemispheric lesion and in several congenital pathologies. The advantages of cerebral lateralization have also recently been published, although the evolutionary connection between fiber decussation and cortical function lateralization remains a mystery to be solved. A better understanding of the molecular and genetic substrates of the midline crossing processes might result in significant clinical advances in brain plasticity and repair.
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Lateralidade Funcional , Neuroanatomia/história , Quiasma Óptico , Médicos/história , História do Século XVII , História do Século XVIII , História do Século XIX , Humanos , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Quiasma Óptico/anatomia & histologia , Quiasma Óptico/fisiologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/fisiologiaRESUMO
Purpose To evaluate the prognostic and predictive value of surface-derived imaging biomarkers obtained from contrast material-enhanced volumetric T1-weighted pretreatment magnetic resonance (MR) imaging sequences in patients with glioblastoma multiforme. Materials and Methods A discovery cohort from five local institutions (165 patients; mean age, 62 years ± 12 [standard deviation]; 43% women and 57% men) and an independent validation cohort (51 patients; mean age, 60 years ± 12; 39% women and 61% men) from The Cancer Imaging Archive with volumetric T1-weighted pretreatment contrast-enhanced MR imaging sequences were included in the study. Clinical variables such as age, treatment, and survival were collected. After tumor segmentation and image processing, tumor surface regularity, measuring how much the tumor surface deviates from a sphere of the same volume, was obtained. Kaplan-Meier, Cox proportional hazards, correlations, and concordance indexes were used to compare variables and patient subgroups. Results Surface regularity was a powerful predictor of survival in the discovery (P = .005, hazard ratio [HR] = 1.61) and validation groups (P = .05, HR = 1.84). Multivariate analysis selected age and surface regularity as significant variables in a combined prognostic model (P < .001, HR = 3.05). The model achieved concordance indexes of 0.76 and 0.74 for the discovery and validation cohorts, respectively. Tumor surface regularity was a predictor of survival for patients who underwent complete resection (P = .01, HR = 1.90). Tumors with irregular surfaces did not benefit from total over subtotal resections (P = .57, HR = 1.17), but those with regular surfaces did (P = .004, HR = 2.07). Conclusion The surface regularity obtained from high-resolution contrast-enhanced pretreatment volumetric T1-weighted MR images is a predictor of survival in patients with glioblastoma. It may help in classifying patients for surgery.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Sobrevida , Resultado do TratamentoRESUMO
Parietal lobe functions include somesthesia, language, calculation, self-motion perception, and visuospatial awareness. In this video, the authors show the intraoperative mapping of a left parietal lobe for a low-grade glioma resection. Standard sensory and language mapping were performed. Interestingly, by using the "Line Bisection" task, subcortical stimulation of the gyrus angularis was repeatedly associated with ipsilateral spatial neglect, often described in the right parietal lobe. In a similar way, subcortical stimulation in a more posterior point elicited episodes of vertigo, probably due to stimulation of the superior longitudinal fasciculus. Both findings were useful to define the functional limit of the resection. The video can be found here: https://youtu.be/qgGDRW_6u0A .
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Mapeamento Encefálico/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Percepção de Movimento/fisiologia , Lobo Parietal/diagnóstico por imagem , Percepção Espacial/fisiologia , Adulto , Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Humanos , Masculino , Lobo Parietal/cirurgiaRESUMO
OBJECTIVE: International collaborations between high-income (HICs) and low- and middle-income countries (LMICs) have been developed as an attempt to reduce the inequalities in surgical care around the world. In this paper the authors review different models for international surgical education and describe projects developed by the Division of Neurosurgery at the University of Toronto in this field. METHODS: The authors conducted a review of models of international surgical education reported in the literature in the last 15 years. Previous publications on global neurosurgery reported by the Division of Neurosurgery at the University of Toronto were reviewed to exemplify the applications and challenges of international surgical collaborations. RESULTS: The most common models for international surgical education and collaboration include international surgical missions, long-term international partnerships, fellowship training models, and online surgical education. Development of such collaborations involves different challenges, including limited time availability, scarce funding/resources, sociocultural barriers, ethical challenges, and lack of organizational support. Of note, evaluation of outcomes of international surgical projects remains limited, and the development and application of assessment tools, such as the recently proposed Framework for the Assessment of International Surgical Success (FAIRNeSS), is encouraged. CONCLUSIONS: Actions to reduce inequality in surgical care should be implemented around the world. Different models can be used for bilateral exchange of knowledge and improvement of surgical care delivery in regions where there is poor access to surgical care. Implementation of global neurosurgery initiatives faces multiple limitations that can be ameliorated if systematic changes occur, such as the development of academic positions in global surgery, careful selection of participant centers, governmental and nongovernmental financial support, and routine application of outcome evaluation for international surgical collaborations.
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Intercâmbio Educacional Internacional , Modelos Educacionais , Neurocirurgia/educação , Países em Desenvolvimento , Saúde Global , Disparidades em Assistência à Saúde , Humanos , Ontário , Faculdades de MedicinaRESUMO
BACKGROUND: The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. METHODS: A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. RESULTS: Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). CONCLUSION: Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. KEY POINTS: ⢠Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. ⢠Patients with small width of contrast enhancing areas have better prognosis. ⢠The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Meios de Contraste , Feminino , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Carga TumoralRESUMO
BACKGROUND: The aim of this study was to enhance the visual feedback of surgeons, during robotic surgeries, by designing and developing an actuated 2D imaging probe, which is used in conjunction with the traditional stereoscopic camera of the da Vinci surgical system. The probe provides the surgeon with additional visual cues, overcoming visualization constraints encountered during certain scenarios of robot-assisted minimally invasive surgery. METHODS: The actuated imaging probe is implemented as a master-slave tele-manipulated system, and it is designed to be compatible with the da Vinci surgical system. The detachable probe design enables it to be mounted on any of the EndoWrist(®) instruments of the robot and is controlled by the surgeon using a custom-made pedal system. The image from the 2D probe is rendered along with the stereoscopic view on the surgeon's console. RESULTS: The experimental results demonstrate the effectiveness of the proposed actuated imaging probe when used as an additional visualization channel and in surgical scenarios presenting visual problems due to tissue occlusion. CONCLUSION: The study shows the potential benefits of an additional actuated imaging probe when used in conjunction with traditional surgical instruments to perform surgical tasks requiring visualization from multiple orientations and workspaces.
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Retroalimentação , Procedimentos Cirúrgicos Robóticos/instrumentação , Cirurgia Assistida por Computador/instrumentação , Percepção de Profundidade , Desenho de Equipamento , Humanos , Curva de AprendizadoRESUMO
Arca zebra is a mollusk of commercial value and a major socioeconomic fishery in Northeastern Venezuela. The present study aimed to evaluate the reproductive effort (RE), fattening index (FI) and yield (Y) in different size groups of A. zebra from the morro Chacopata, Venezuela. For this, monthly samplings from June 2008 and June 2009, were undertaken, and the bivalves obtained were distributed in three length groups: I (30.1 to 50.0 mm), II (50.1 to 70.0 mm) and III (> 70.0 mm). Monthly RE, FI and Y were determined based on bivalve changes in volume of fresh meat (VFM), intervalvar volume (IV), dry gonad biomass (DW), dry biomass of the organism without gonad (DWs), fresh biomass of meat (FBM) and total biomass including shell (TBIS). Besides, environmental variables such as temperature, salinity, dissolved oxygen, total organic and inorganic seston and chlorophyll a were measured monthly. There was great variation in the DW between length groups (relevant for II and III): increased from June until late September 2008, was followed by a marked decrease in October 2008, recovered in the following months, and decreased in January 2009, with a slight increase until May 2009; these changes were associated with variations in sea temperature. The weight of the gonad (DW) influenced the RE, FI and Y, as these reached their peaks in the months where there was higher gonadal production, indicating the influence of temperature on A. zebra reproduction.
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Arcidae/fisiologia , Animais , Aquicultura , Arcidae/crescimento & desenvolvimento , Meio Ambiente , Reprodução/fisiologia , Estações do Ano , Temperatura , Venezuela , Aumento de Peso/fisiologiaRESUMO
We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodeling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through the activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by the binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here, we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analyzed the levels of the EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express the EGFR and found that EGFR-expressing cells responded to the EGF ligand by increasing ODZ1 at the mRNA and protein levels. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway, or Additionally, the siRNA-mediated knockdown of MAPK11 (p38ß MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signaling pathway through p38ß MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.
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Fator de Crescimento Epidérmico , Receptores ErbB , Glioblastoma , Tenascina , Regulação para Cima , Humanos , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Tenascina/genética , Tenascina/metabolismoRESUMO
OBJECTIVES: The objective of this study was to explore the factors and outcomes associated with gestational syphilis in Peru. METHODS: Women from the miscarriage, vaginal delivery, and C-section wards from a large maternity hospital in Lima with or without syphilis diagnosis were enrolled and their pregnancy outcomes compared. Maternal syphilis status using maternal blood and child serostatus using cord blood were determined by rapid plasma reagin (RPR) and rapid syphilis tests. The newborns' clinical records were used to determine congenital syphilis. RESULTS: A total of 340 women were enrolled, 197 were positive and 143 were negative for RPR/rapid syphilis tests. Antibody titers in sera from cord and maternal blood were comparable with RPR titers and were highly correlated (rho = 0.82, P <0.001). Young age (P = 0.009) and lower birth weight (P = 0.029) were associated with gestational syphilis. Of the women with gestational syphilis, 76% had received proper treatment. Mothers of all newborns with congenital syphilis also received appropriate treatment. Treatment of their sexual partners was not documented. CONCLUSIONS: Syphilis during pregnancy remains a major cause of the fetal loss and devastating effects of congenital syphilis in newborns.
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Complicações Infecciosas na Gravidez , Sífilis Congênita , Sífilis , Humanos , Feminino , Gravidez , Peru/epidemiologia , Sífilis Congênita/epidemiologia , Sífilis Congênita/diagnóstico , Adulto , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/microbiologia , Estudos Prospectivos , Recém-Nascido , Sífilis/epidemiologia , Sífilis/diagnóstico , Adulto Jovem , Resultado da Gravidez/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Sorodiagnóstico da Sífilis , Adolescente , Sangue FetalRESUMO
PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer that could potentially be surrounded by healthy arteries or veins that a surgeon would have to avoid during treatment. A realistic 3D liver model is an unmet need for HCC preoperative planning. METHODS: This paper presents a method to create a soft phantom model of the human liver with the help of a 3D-printed mold, silicone, ballistic gel, and a blender. RESULTS: For silicone, the elastic modulus of seven different ratios of base silicone and silicone hardener are tested; while for ballistic gel, a model using 20% gelatin and 10% gelatin is created for the tumor and the rest of the liver, respectively. It is found that the silicone modulus of elasticity matches with the real liver modulus of elasticity. It is also found that the 10% gelatin part of the ballistic gel model is an excellent emulation of a healthy human liver. CONCLUSION: The 3D flexible liver phantom made from a 10% gelatin-to-water mixture demonstrates decent fidelity to real liver tissue in terms of texture and elasticity. It holds significant potential for improving medical training, preoperative planning, and surgical research. We believe that continued development and validation of such models could further enhance their utility and impact in the field of hepatobiliary treatment planning and education.
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Magnesium (Mg) is a promising material for bone tissue engineering applications due to it having similar mechanical properties to bones, biocompatibility, and biodegradability. The primary goal of this study is to investigate the potential of using solvent-casted polylactic acid (PLA) loaded Mg (WE43) composites as filament feedstock for fused deposition modeling (FDM) 3D Printing. Four PLA/Magnesium (WE43) compositions (5, 10, 15, 20 wt%) are synthesized and produced into filaments, then used to print test samples on an FDM 3D printer. Assessments are made on how Mg incorporation affected PLA's thermal, physicochemical, and printability characteristics. The SEM study of the films shows that the Mg particles are uniformly distributed in all the compositions. The FTIR results indicate that the Mg particles blend well with the polymer matrix and there is no chemical reaction between the PLA and the Mg particles during the blending process. The thermal studies show that the addition of Mg leads to a small increase in the melting peak reaching a maximum of 172.8 °C for 20% Mg samples. However, there are no dramatic variations in the degree of crystallinity among the Mg-loaded samples. The filament cross-section images show that the distribution of Mg particles is uniform up to a concentration of 15% Mg. Beyond that, non-uniform distribution and an increase in pores in the vicinity of the Mg particles is shown to affect their printability. Overall, 5% and 10% Mg composite filaments were printable and have the potential to be used as composite biomaterials for 3D-printed bone implants.
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INTRODUCTION: Cortical and subcortical motor mapping has advanced the notion of maximal safe resection of intra-axial brain tumours, thereby preserving neurological functions as well as improving survival. Despite being an age-old and established neurosurgical procedure across the world, the strategy and techniques involved in motor mapping have a gamut of variation due to a lack of defined standard protocols. METHODS: We disseminated a structured survey among focused group of neurosurgeons with established practices involving brain mapping. It consisted of 40 questions, split into five sections assessing the practice description, general approach for motor mapping, preference for asleep versus awake mapping, operative techniques and approach to representative tumor cases. Practice-patterns during primary motor mapping for brain tumours were analysed from responses of 51 neurosurgeons. RESULTS: 60.8 % felt that any lesion even near (without infiltration) was suffice to define "involvement" of the cortical/subcortical motor pathways. 82.4 % felt that motor mapping was necessary for brain tumours involving motor pathways, irrespective of the tumor histology or patient age. 90.2 % opined that tumor location was the predominant factor affecting their choice between awake or asleep mapping. 31.4 % believed that all cases should be performed awake unless patient-related medical, psychological, or anaesthetic contraindications exist, whereas 45.1 % felt that all cases should be performed asleep unless language mapping is required. MRI, DTI-based tractography and intra-operative fluorescence were the most commonly employed surgical adjuncts. CONCLUSIONS: The data from this survey may serve as a preliminary foundation for a more standardized approach to patient selection and the approach to motor mapping for brain tumors.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Procedimentos Neurocirúrgicos/métodos , Imageamento por Ressonância Magnética , Seleção de Pacientes , Mapeamento Encefálico/métodos , Vigília/fisiologiaRESUMO
Sugar beet pulp, a byproduct from sugar beet refining, is used by farmers as fertilizer or sold as animal feed. Both options underestimate the potential of sugar beet pulp as a platform to produce specialty and bulky chemicals as a promising pathway for sustainable biochemicals - mind the pulp. This study proposes a biorefinery concept to produce food additives (pectin-derived oligosaccharides) and bulky chemicals (terephthalic acid). Since the biorefinery has a low technology readiness level (TRL = 1), it is relevant to evaluate the feasibility of this biorefinery concept to provide guidance (at an early stage) on the environmental and economic advantages and limitations. For this purpose, the life cycle assessment and techno-economic assessment frameworks are used to assess the environmental impact and economic performance of the biobased terephthalic acid, respectively. Moreover, environmental impacts are accounted for in economic terms using different monetary valuation methods (environmental prices, Ecovalue12, and Ecotax). The environmental impact of biobased terephthalic acid was higher in most impact categories than the fossil counterpart, depending on the selected allocation approach (mass vs economic). The economic feasibility of the proposed biorefinery is highly dependent on the pectin-derived oligosaccharides market price and the valorization of byproducts (humins and levulinic acid). The selection of the monetary valuation method is critical for monetizing environmental impacts when comparing biobased against fossil-based alternatives.