Asociación entre comportamientos de riesgo y sobrepeso en adolescentes: análisis de clases latentes / Association between risk behaviors and overweight in adolescents: a latent classes analysis / Associação entre comportamentosde risco e excesso de peso em adolescentes: análise de classes latentes

RESUMEN Este estudio tuvo como objetivo describir la agregación de comportamientos del estilo de vida en adolescentes brasileños e identificar la asociación de estas agregaciones con el exceso de peso. Se ha utilizado información sobre el consumo alimentario, tiempo frente a la televisión y práctica de actividad física de una muestra compuesta por 14141 adolescentes, de ambos sexos, con edades entre 11 y 17 años, procedente de la Encuesta Nacional de Salud del Escolar (2015), que fueron divididos en tres clases: físicamente activos (FA), comportamiento de riesgo (CR) e inactivos físicamente con alimentación saludable (IA). Los resultados mostraron que las niñas y adolescentes mayores tienen menos probabilidades de desarrollar exceso de peso en comparación con los niños y adolescentes más jóvenes, así como los sujetos pertenecientes a la clase CR, que tienen menos probabilidades de presentar exceso de peso, mientras que los adolescentes de clase IA tienen más probabilidades en comparación con la FA. Se puede concluir que la adopción de hábitos saludables parece ejercer una influencia importante en cuanto al resultado de sobrepeso, ya que, no obstante, la adopción de alimentación "no saludable" es prevalente en la clase CR, los niveles de actividad física se asemejan a la clase FA, que puede mitigar los efectos de los comportamientos negativos relacionados con la alimentación.

ABSTRACT This study aimed to describe the cluster of lifestyle behaviors among Brazilian adolescents and to identify the association of these clusters with overweight. Information related to food consumption, TV time and physical activity were used, from a sample of 14141 adolescents of both sexes, aged between 11 and 17 years, from the National School Health Survey (2015), who were split into three classes: physically active (FA), risky behavior (CR), and physically inactive with healthy eating (AI). Results showed that girls and older adolescents have less chances to be overweight when compared to boys and younger adolescents, respectively. Moreover, subjects classified as CR have less chances of being overweight, whereas those classified as AI are more prone to be overweight compared to those belonging to FA class. We conclude that the adoption of healthy habits seems to be of relevance in the expression of overweight, because although the high prevalence of "unhealthy" diet among subjects from the CR class, their physical activity levels are similar to their peers from the FA class, which may mitigate the impacts unhealthy behaviors associated with food consumption.

RESUMO Este estudo teve como objetivo descrever a agregação de comportamentos de estilo de vida em adolescentes brasileiros e identificar a associação dessas agregações com o excesso de peso. Informações sobre consumo alimentar, tempo em frente à televisão e prática de atividade física de uma amostra composta por 14141 adolescentes, de ambos os sexos, com idade entre 11 e 17 anos, da Pesquisa Nacional de Saúde do Escolar (2015), que foram divididos em três classes: fisicamente ativo (AF), comportamento de risco (CR) e fisicamente inativo com alimentação saudável (IA). Os resultados mostraram que meninas e adolescentes mais velhos são menos propensos a desenvolver excesso de peso em comparação com crianças e adolescentes mais novos, assim como os sujeitos pertencentes à classe CR, que são menos propensos ao excesso de peso, enquanto os adolescentes da classe IA são mais propensos em relação aos AF. Pode-se concluir que a adoção de hábitos saudáveis parece ter influência importante no resultado do excesso de peso, pois, no entanto, a adoção de dietas "não saudáveis" é prevalente na classe CR, os níveis de atividade física são semelhantes aos da classe AF, o que pode atenuar os efeitos de comportamentos negativos relacionados à alimentação.

MiR-200c-based metabolic modulation in glioblastoma cells as a strategy to overcome tumor chemoresistance.

Glioblastoma (GB) is the most aggressive and common form of primary brain tumor characterized by fast proliferation, high invasion and resistance to current standard treatment. The average survival rate post-diagnosis is 14.6 months, despite the aggressive standard post-surgery radiotherapy concomitant with chemotherapy with temozolomide (TMZ). Currently, efforts are being endowed to develop new and more efficient therapeutic approaches capable to overcome chemoresistance, inhibit tumor progression and improve overall patient survival rate. Abnormal microRNA (miRNA) expression has been correlated with chemoresistance, proliferation and resistance to apoptosis, which result from their master regulatory role of gene expression. Altered cell metabolism, favoring glycolysis, was identified as an emerging cancer hallmark and has been described in GB, thus offering a new target for innovative GB therapies. In this work, we hypothesized that a gene therapy-based strategy consisting of the overexpression of a miRNA downregulated in GB and predicted to target crucial metabolic enzymes might promote a shift of GB cell metabolism, decreasing the glycolytic dependence of tumor cells and contributing to their sensitization to chemotherapy with TMZ. The increase of miR-200c levels in DBTRG cells resulted in downregulation of messenger RNA of enzymes involved in bioenergetics pathways and impaired cell metabolism and mobility. In addition, miR-200c overexpression prior to DBTRG cell exposure to TMZ resulted in cell cycle arrest. Overall, our results show that miR-200c overexpression could offer a way to overcome chemoresistance developed by GB cells in response to current standard chemotherapy, providing an improvement to current GB standard treatment, with benefit for patient outcome.

Downregulation of long non-protein coding RNA MVIH impairs glioblastoma cell proliferation and invasion through an miR-302a-dependent mechanism.

Glioblastoma (GB) is the most frequent and malignant type of brain tumor, for which no effective therapy exists. The high proliferative and invasive nature of GB, as well as its acquired resistance to chemotherapy, makes this type of cancer extremely lethal shortly after diagnosis. Long non-protein coding RNAs (lncRNA) are a class of regulatory RNAs whose levels can be dysregulated in the context of diseases, unbalancing several physiological processes. The lncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA-MVIH), overexpressed in several cancers, was described to co-precipitate with phosphoglycerate kinase 1 (PGK1), preventing secretion of this enzyme to the extracellular environment and promoting cell migration and invasion. We hypothesized that, by silencing the expression of lncRNA-MVIH, the secretion of PGK1 would increase, reducing GB cell migration and invasion capabilities. We observed that lncRNA-MVIH silencing in human GB cells significantly decreased glycolysis, cell growth, migration, and invasion and sensitized GB cells to cediranib. However, no increase in extracellular PGK1 was observed as a consequence of lncRNA-MVIH silencing, and therefore, we investigated the possibility of a mechanism of miRNA sponge of lncRNA-MVIH being in place. We found that the levels of miR-302a loaded onto RISC increased in GB cells after lncRNA-MVIH silencing, with the consequent downregulation of several miR-302a molecular targets. Our findings suggest a new mechanism of action of lncRNA-MVIH as a sponge of miR-302a. We suggest that lncRNA-MVIH knockdown may be a promising strategy to address GB invasiveness and chemoresistance, holding potential towards its future application in a clinical context.

World Health Organization Grade III Meningiomas: A Retrospective Study at an Academic Medical Center.

BACKGROUND: Meningiomas are the most common primary brain tumors and are generally considered benign. However, a rare subgroup of meningiomas, classified as World Health Organization (WHO) grade III meningiomas, can show extremely aggressive behavior and high rates of recurrence. Despite ongoing research, data on the clinical outcome of this subgroup of meningiomas are still limited. METHODS: Medical records of patients with WHO grade III meningiomas diagnosed between 2000 and 2018 at the Coimbra University Hospital Center were retrospectively reviewed and several variables of interest and their relation to patients' survival were analyzed. RESULTS: Of the 26 patients included in the final analysis, 23 had anaplastic meningiomas, 2 had papillary meningiomas, and 1 had a rhabdoid meningioma. Median overall survival and median progression-free survival were 2.45 and 1.22 years, respectively. Overall survival at 1, 2 and 5 years was 73%, 57%, and 35%, respectively. Adjuvant radiotherapy correlated with improved survival for subtotally resected meningiomas but not for gross totally resected meningiomas. There was a trend toward improved overall survival with gross total resection versus subtotal resection, but this difference failed to reach statistical significance. CONCLUSIONS: This study provides insight into the clinical outcomes of WHO grade III meningiomas and suggests that adjuvant radiotherapy may not be beneficial for patients who underwent gross total resection. This rare subset of meningiomas still portends a devastating prognosis and the impact of extent of resection and adjuvant therapies in these patients needs further clarification.

Ultra-Early Versus Early Aneurysm Surgery After Subarachnoid Hemorrhage: A Retrospective Outcome Analysis

Object The timing of definitive management of ruptured intracranial aneurysms has been the subject of considerable debate, although the benefits of early surgery (until 72 hours postictus) are widely accepted. The aim of the present study is to evaluate the potential benefit of ultra-early surgery (until 24 hours) when compared with early surgery, in those patients who were treated by surgical clipping at the Neurosurgery Department of the Coimbra Hospital and University Centre. Methods A 17-year database of consecutive ruptured and surgically treated intracranial aneurysms was analyzed. Outcome was measured by the Glasgow Outcome Scale (GOS). Baseline characteristics were analyzed by the Fisher exact test, the chi-squared and Mann-Whitney tests. Logistic regression was used to assess the impact of good grade according to the World Federation of Neurological Surgeons (WFNS) scale and ultra-early surgery in a good GOS outcome. Results 343 patients who were submitted to surgical clipping in the first 72 hours postictus were included, 165 of whom have undergone ultra-early surgery. Demographics and preoperative characteristics of ultra-early and early surgery patients were similar. Goodgrade patients according to the WFNS scale submitted to ultra-early surgery demonstrated an improvedGOS at discharge and at 6months. Poor-grade patients according to theWFNS scale submitted to ultra-early surgery demonstrated an improved GOS at discharge. Conclusions Ultra-early surgery for aneurysmal subarachnoid hemorrhage patients improves outcome mainly on good-grade patients. Efforts should be made on the logistics of emergency departments to consider achieving treatment on this timeframe as a standard of care.

Management and Outcome of Solitary Spinal Amyloidoma-A Systematic Literature Review.

BACKGROUND: Solitary spinal amyloidoma (SSA) is a rare and poorly characterized disease. There are few cases described, and the knowledge of this neoplasm is limited. A more accurate description of demographics, clinical findings, and outcomes may be useful for a better understanding of this pathology, as well as therapeutic intervention, adding value to the research of localized amyloidosis. METHODS: A systematic search was carried out from when registries began until February 2020. We also include a case diagnosed and treated in our department. Descriptive statistics were used to evaluate data, demographics, clinical findings, diagnostic modalities, therapeutics, and finally neurologic outcomes. The Kaplan-Meier method was used to assess overall survival and progression-free survival. RESULTS: The final cohort comprises 35 patients. The mean age at diagnosis was 61.97 years, and 68.60% of the patients were male. SSA developed more frequently in the thoracic spine (48.60%), followed by the cervical spine (17.10%). Intradural lesions were rare, and the average neoplastic score for spinal instability was 9.5 points. The most common symptoms were impaired motor function (74.29%) and axial back pain (65.70%). After surgery, neurologic recovery was reported in 82.90% of cases. Mean progression-free survival and mean overall survival were 47.26 and 156.66 months. CONCLUSIONS: SSA is a rare subgroup of localized amyloidosis, usually being diagnosed in male patients between the sixth and eighth decades. The gold standard treatment seems to be surgical resection. SSA patients have excellent long-term survival and a low rate of local recurrence.

A New R Program for Flow-Log Analysis of Single Holes (FLASH-R).

A new version of the computer program FLASH (Flow-Log Analysis of Single Holes) is presented for the analysis of borehole vertical flow logs to estimate fracture (or layer) transmissivities and far-field hydraulic heads. The program is written in R, an open-source environment. All previous features have been retained and new features incorporated including more rigorous parameter estimation, uncertainty analysis, and improved data import. The program has a dynamic user interface compatible with most operating systems.

MiR-144 overexpression as a promising therapeutic strategy to overcome glioblastoma cell invasiveness and resistance to chemotherapy.

Glioblastoma (GB) is the most aggressive and common form of primary brain tumor, characterized by fast proliferation, high invasion, and resistance to current standard treatment. The average survival rate post-diagnosis is only of 14.6 months, despite the aggressive standard post-surgery treatment approaches of radiotherapy concomitant with chemotherapy with temozolomide. Altered cell metabolism has been identified as an emerging cancer hallmark, including in GB, thus offering a new target for cancer therapies. On the other hand, abnormal expression levels of miRNAs, key regulators of multiple molecular pathways, have been correlated with pathological manifestations of cancer, such as chemoresistance, proliferation, and resistance to apoptosis. In this work, we hypothesized that gene therapy based on modulation of a miRNA with aberrant expression in GB and predicted to target crucial metabolic enzymes might impair tumor cell metabolism. We found that the increase of miR-144 levels, shown to be downregulated in U87 and DBTRG human GB cell lines, as well as in GB tumor samples, promoted the downregulation of mRNA of enzymes involved in bioenergetic pathways, with consequent alterations in cell metabolism, impairment of migratory capacity, and sensitization of DBTRG cells to a chemotherapeutic drug, the dichloroacetate (DCA). Taken together, our findings provide evidence that the miR-144 plus DCA combined therapy holds promise to overcome GB-acquired chemoresistance, therefore deserving to be explored toward its potential application as a complementary therapeutic approach to the current treatment options for this type of brain tumor.

Effect of chronic methylphenidate treatment on hippocampal neurovascular unit and memory performance in late adolescent rats.

Methylphenidate (MPH) is the classic treatment for attention deficit hyperactivity disorder (ADHD) among children and adults. Despite its beneficial effects, non-medical use of MPH is nowadays a problem with high impact on society. Thus, our goal was to uncover the neurovascular and cognitive effects of MPH chronic use during a critical period of development in control conditions. For that, male Wistar Kyoto rats were treated with MPH (1.5 or 5 mg/kg/day at weekdays, per os) from P28 to P55. We concluded that the higher dose of MPH caused hippocampal blood-brain barrier (BBB) hyperpermeability by vesicular transport (transcytosis) concomitantly with the presence of peripheral immune cells in the brain parenchyma. These observations were confirmed by in vitro studies, in which the knockdown of caveolin-1 in human brain endothelial cells prevented the increased permeability and leukocytes transmigration triggered by MPH (100 µM, 24 h). Furthermore, MPH led to astrocytic atrophy and to a decrease in the levels of several synaptic proteins and impairment of AKT/CREB signaling, together with working memory deficit assessed in the Y-maze test. On the contrary, we verified that the lower dose of MPH (1.5 mg/kg/day) increased astrocytic processes and upregulated several neuronal proteins as well as signaling pathways involved in synaptic plasticity culminating in working memory improvement. In conclusion, the present study reveals that a lower dose of MPH in normal rats improves memory performance being associated with the modulation of astrocytic morphology and synaptic machinery. However, a higher dose of MPH leads to BBB dysfunction and memory impairment.

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles.

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.

Nucleolin is expressed in patient-derived samples and glioblastoma cells, enabling improved intracellular drug delivery and cytotoxicity.

One of the major challenges in Glioblastoma (GBM) therapy relates with the existence of glioma stem-like cells (GSCs), known to be chemo- and radio-resistant. GSCs and non-stem GBM cells have the ability to interchange, emphasizing the importance of identifying common molecular targets among those cell sub-populations. Nucleolin overexpression has been recently associated with breast cancer sub-populations with different stem-like phenotype. The goal of this work was to evaluate the potential of cell surface nucleolin as a target in GBM cells. Different levels of nucleolin expression resulted in a 3.4-fold higher association of liposomes targeting nucleolin (functionalized with the nucleolin-binding F3 peptide) in U87, relative to GBM11 glioblastoma cells. Moreover, nucleolin was suggested as a potential marker in OCT4-, NANOG-positive GSC, and in the corresponding non-stem GBM cells, as well as in SOX2-positive GSC. Doxorubicin delivered by liposomes targeting nucleolin enabled a level of cytotoxicity that was 2.5- or 4.6-fold higher compared to the non-targeted counterparts. Importantly, an overexpression of nucleolin was also observed in cells of patient-derived samples, as compared with normal brain. Overall, these results suggested nucleolin as a therapeutic target in GBM.

Tophaceous gout of the lumbar spine mimicking a spinal meningioma.

PURPOSE: Although gout is a common metabolic disorder, it usually affects distal joints of the appendicular skeleton. Axial spine involvement is rare, with only 131 cases reported in the literature. The authors report a rare case of lumbar spinal gout mimicking a spinal meningioma. METHODS: A 77-year-old man with a history of gout presented with chronic low back pain and progressive paraparesis. Imaging revealed a lumbar spine compressive mass lesion with a dural tail signal. The differential diagnosis was thought to be straightforward favoring a spinal meningioma. Tophaceous gout was never considered. The presence of a dural tail associated with the lesion is an interesting detail of this case, that strongly misguided it and to the best of our knowledge it is the first one reported in the literature. RESULTS: The patient underwent surgery and intra-operative findings were surprisingly different from those expected, revealing a chalky white mass lesion firmly adherent and compressing the dural sac. It was completely excised, leaving the dura intact. Histopathology confirmed the diagnosis of tophaceous gout. The patient was sent to physical therapy and had a complete remission of pain and neurological deficit, regaining his walking capacity. CONCLUSION: Although spinal gout is rare, it should be considered in the differential diagnosis for patients presenting with symptoms of spinal stenosis, a suspicion of neoplastic lesion of the spine, and a previous history of gout. Early diagnosis can ensure proper and timely medical management, perhaps avoiding neurological compromise and the need for surgery.

"Eu queria mudar": a psicanálise face à adolescência pobre e sem lugar / "I wanted to change": psychoanalysis in the face of the impoverished adolescence with no place / "Yo quisiera cambiar": el psicoanálisis frente a la adolescencia pobre y sin lugar / «Je voulais changer¼: la psychanalyse face à l'adolescence pauvre et pas de place

O presente artigo tem por objetivo, a partir da articulação de interrogantes que emergem da condução de um caso clínico, refletir acerca das possibilidades de intervenção da Psicanálise e das políticas públicas no caso de adolescências que se constituem em contexto de "ralé". Partimos de uma breve problematização das políticas públicas direcionadas aos adolescentes para desdobrar, posteriormente, ao modo de estudo clínico, questões e proposições sobre a adolescência e seus contextos, bem como as possibilidades de intervenção no cenário da socioeducação. Discutindo o caso, apontamos como direção de trabalho, nesta situação de adolescência sem lugar, a construção de ancoragens possíveis para a sustentação do sujeito e seu desejo em sua relação com o Outro.

This article aims to reflect on the possibilities of Psychoanalysis and public policies in the work with adolescents that are in the context of "rabble", starting with the questions that emerge from a clinical case. We start from a brief questioning of public policies directed to adolescents. Later we unfold questions and propositions about adolescence and its contexts, from the mode of a clinical study. We also develop some possibilities of intervention in the scene of socioeducation.The direction of work is pointed by the case discussion of adolescence without place. We propose, as a clinical directon, the construction of possible anchorages to support the subject and his desire in its relation with the Other.

El presente artículo tiene como objetivo reflexionar, a partir de interrogaciones que surgen de la conducción de un caso clínico con adolescencias que se constituyen en contextos de 'ralé'/miséria, sobre la posibilidad intervenciones del Psicoanálisis y de las políticas públicas, . Partimos de una breve problematización de las políticas públicas dirigidas los adolescentes para después despegar, en la modalidad de estudio clínico, propuestas sobre la adolescencia e sus contextos. Igualmente discutimos las posibilidades de intervenciones en el escenario de la socioeducación. Al discutir el caso proponemos, como dirección del trabajo en esta situación de adolescencia sin lugar, la construcción de posibles anclajes para el sustento del sujeto y de su deseo en la relación con el Otro.

Cet article a l'objectif de réfléchir sur les possibilités d'intervention psychanalytique e des politiques publiques auprès des adolescents qui se constituent dans des contextes de 'ralé'. Cette réflexion a lieu a partir des interrogations qui émergent d'un cas clinique. Nous partons d'une brève problématisation des politiques publiques dirigées aux adolescentes, et, après, en utilisant le méthode d'étude clinique, nous nous penchons sur des questions et des propositions à propos de l'adolescent et ses contextes, et aussi les possibilités d'intervention dans la scène de la socio-éducation. À partir de la discussion du cas, nous proposons une direction de travail auprès de cet adolescent qui n'a pas un lieu social, c'est la construction des fondements possibles pour la sustentation du sujet et son désir par rapport à l'Autre.

"Caiu, tchau e bença": os sentimentos, comportamentos e soluções de idosos após a queda em residências unipessoais / "If you fell, bye and God bless": elderly' feelings, behaviour and the found solutions after a fall at home where they live alone / "Ha caído, adiós y bendecir": los sentimientos, comportamientos y soluciones de ancianos después de caer en viviendas

Este artigo objetiva apresentar uma análise dos sentimentos e comportamentos de idosos que residem sozinhos pós-queda em casa e as soluções dadas por eles para evitar novos acidentes. Realizou-se uma pesquisa qualitativa com técnicas de observação participante, entrevistas e documentação em caderno de anotações, fotos, áudio e vídeos. A amostra é composta por dez idosos (quatro homens e seis mulheres)com idade entre 65 e 85 anos, residentes em domicílios unipessoais, que sofreram queda na residência nosúltimos cinco anos. Cinco dos dez indivíduos entrevistados alteraram a configuração espacial da residência(adaptações e pequenas reformas) e os outros cinco declararam ter deixado de realizar a atividade que oslevaram à queda. Todos destacaram um bom grau de autonomia na realização das atividades da vida diária(AVD), mas consideram a queda como um fenômeno inevitável e possuem conhecimentos sobre os riscos, aperda da autonomia e a possibilidade de não residir mais sozinhos foram citados como elementos de medo.(AU

This paper presents an analysis of the feelings and behaviors of elderly who live alone in a post-fall eventand their solutions to prevent further accidents. A qualitative research was carried out using techniquesof participant observation, interviews and documentation in notebook, photos, audio and videos. Thesample is comprised of ten individuals (four men and six women) aged between 65 and 85 years residingin single-person households, who suffered a fall inside their home in the last five years. Five of the 10individuals interviewed changed the spatial configuration of the residence (adaptations and minor reforms)and the other five declared that they are avoiding to carry out the activity that led them to fall. All stresseda good degree of autonomy in the activities of daily living (ADL), but considered the fall as an inevitablephenomenon and, they know about risks. The loss of autonomy and the possibility of not residing aloneanymore were cited as elements of fear.

Este artículo tiene como objetivo presentar un análisis de los sentimientos y comportamientos de ancianosque residen solos post-caída en casa y las soluciones dadas por ellos para evitar nuevos accidentes. Serealizó una investigación cualitativa con técnicas de observación participante, entrevistas y documentaciónen cuaderno de notas, fotos, audio y vídeos. La muestra está compuesta por diez ancianos (cuatro hombresy seis mujeres) con edad entre 65 y 85 años, residentes en domicilios unipersonales, que sufrieron caída enla residencia en los últimos cinco años. Cinco de los diez individuos entrevistados alteraron la configuraciónespacial de la residencia (adaptaciones y pequeñas reformas) y los otros cinco declararon haber dejadode realizar la actividad que los llevaron a la caída. Todos destacaron un buen grado de autonomía en larealización de las actividades de la vida diaria (AVD), pero consideran la caída como un fenómeno inevitabley tienen conocimientos sobre los riesgos, la pérdida de la autonomía y la posibilidad de no residir más solos fueron citados como elementos de miedo.

The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells.

Glioblastoma (GBM) is the most malignant primary brain tumor, with an average survival rate of 15 months. GBM is highly refractory to therapy, and such unresponsiveness is due, primarily, but not exclusively, to the glioma stem-like cells (GSCs). This subpopulation express stem-like cell markers and is responsible for the heterogeneity of GBM, generating multiple differentiated cell phenotypes. However, how GBMs maintain the balance between stem and non-stem populations is still poorly understood. We investigated the GBM ability to interconvert between stem and non-stem states through the evaluation of the expression of specific stem cell markers as well as cell communication proteins. We evaluated the molecular and phenotypic characteristics of GSCs derived from differentiated GBM cell lines by comparing their stem-like cell properties and expression of connexins. We showed that non-GSCs as well as GSCs can undergo successive cycles of gain and loss of stem properties, demonstrating a bidirectional cellular plasticity model that is accompanied by changes on connexins expression. Our findings indicate that the interconversion between non-GSCs and GSCs can be modulated by extracellular factors culminating on differential expression of stem-like cell markers and cell-cell communication proteins. Ultimately, we observed that stem markers are mostly expressed on GBMs rather than on low-grade astrocytomas, suggesting that the presence of GSCs is a feature of high-grade gliomas. Together, our data demonstrate the utmost importance of the understanding of stem cell plasticity properties in a way to a step closer to new strategic approaches to potentially eliminate GSCs and, hopefully, prevent tumor recurrence.

Chordoid Glioma of the Third Ventricle, a Rare Tumor with an Unexpected Outcome

Chordoid glioma is a rare tumor of the third ventricle whose imaging features are difficult to distinguish from other more common lesions in this location. There are only 83 cases described so far in the literature. Although gross total resection (GTR) is the treatment of choice, immediate postoperative mortality with this approach can be as high as 29%, and morbidity among survivors can reach 67%. We report a case of a male patient of advanced age, with a third ventricle mass lesion, who presented with a progressive right temporal hemianopia. Imaging was compatible with craniopharyngioma, meningioma or even metastasis. Chordoid glioma was not considered in the differential diagnosis. The patient underwent surgery and GTR was achieved. There were no postoperative complications, and the patient was discharged from the hospital three weeks later. Unexpectedly, two days afterwards, he suffered a major brainstem hemorrhagic stroke and, unfortunately, died.

O glioma cordoide é um tumor raro do terceiro ventrículo, e as suas características imagiológicas são difíceis de distinguir de outras lesões mais comuns nesta localização. Até a data presente, existem apenas 83 casos de gliomas cordoides descritos na literatura. A remoção macroscópica total destes tumores deve ser o tratamento de escolha; no entanto, a mortalidade pós-operatória imediata pode chegar aos 29%, e a morbilidade pode atingir os 67% entre os sobreviventes. Nós descrevemos o caso de um homem idoso com uma lesão tumoral no terceiro ventrículo, que se manifestou com uma hemianopsia temporal direita progressiva. Os exames de imagem eram compatíveis com craniofaringioma, meningioma ou até metástase. O glioma cordoide não foi considerado como uma das hipóteses no diagnóstico diferencial inicial. O paciente foi submetido a cirurgia, tendo-se obtido a remoção macroscópica total. Não houve qualquer complicação no período pós-operatório, e o paciente teve alta hospitalar após três semanas. Inesperadamente, dois dias após a alta clínica, o paciente sofreu um AVC hemorrágico do tronco cerebral, e acabou por falecer.

Subcutaneous Dissemination in Highly Aggressive Intracranial Glioblastoma: Case Report and Literature Review

Glioblastoma (GBM) is a highly invasive and incurable primary central nervous system (CNS) tumor. Despite its aggressive behavior, extracranial metastases are rare, with an estimated incidence of less than 2%. In our literature review, we found only 21 reported cases of skin and soft tissue dissemination. We report a case of an early (two and a half months) postoperative skin and muscle flap-associated dissemination of a temporal glioblastoma. The particular aspect of this case, besides its rarity, is that the clinical presentation, the image reports and even the surgical findings were always in favor of a postoperative subdural empyema and epicranial abscesses. The diagnosis of soft tissue dissemination was only possible after negative microbiological cultures and histopathological confirmation of muscle and skin invasion by the tumor. This case illustrates the rare but potential risk of myocutaneous flap tumor dissemination through the durotomy/craniotomy site that can mimic a much more common, post-surgical infection.

O glioblastoma é um tumor do sistema nervoso central extremamente invasivo e incurável. Apesar do comportamento agressivo desses tumores, a metastização extracraniana é rara, apresentando uma incidência inferior a 2%. A nossa revisão da literatura revelou apenas 21 casos descritos de disseminação de glioblastoma para a pele e tecidos moles. Nós descrevemos um caso de disseminação precoce de um glioblastoma temporal para o retalho miocutâneo associado à cirurgia, cerca de 2 meses e meio após a intervenção. Além da raridade, este caso é peculiar, uma vez que tanto a forma de apresentação clínica quanto a descrição imagiológica e os achados intraoperatórios foram sempre muito sugestivos de um empiema subdural e de abcessos epicranianos. O diagnóstico definitivo de disseminação tumoral para os tecidos moles apenas foi possível após o resultado negativo das culturas microbiológicas e a confirmação histológica de invasão do músculo e da pele pelo tumor. Este caso ilustra o raro, mas potencial risco de disseminação tumoral de um glioblastoma através do retalho miocutâneo de acesso cirúrgico e do local de craniotomia/durotomia, que se pode facilmente confundir com uma situação mais frequente de infecção após cirurgia.

Contamination by intestinal parasites in vegetables marketed in an area of Jequitinhonha Valley, Minas Gerais, Brazil / Contaminação por parasitas intestinais em hortaliças comercializadas em uma área do Vale do Jequitinhonha, Minas Gerais, Brasil

ABSTRACT Objective: The present study aimed to evaluate the presence of helminthes and intestinal protozoa in vegetables commercialized in Diamantina, a municipality located at Jequitinhonha Valley, one of the poorest regions of the world. Methods: A total of 108 specimens, including lettuce, green onion and rocket, were monthly collected from the most popular open street market, green grocery and supermarket of the municipality. The samples were processed by a concentration method and evaluated by light microscopy for parasitological identification. Results: The percentage of contamination was 50.9% (55/108), with predominance of nematode larvae (36.5%), cysts of Entamoeba coli (26.0%) and eggs of hookworms/Strongyloides spp. (12.9%). Lettuce showed greater contamination rate (61.1%) and samples from the open street market were more contaminated (77.8%). Information collected at each point of sale pointed the field cultivation as the critical step for such contaminations. Conclusion: Vegetables marketed in Diamantina presents a wide variety of intestinal parasites, which may represent a potential risk to the health of consumers of fresh vegetables.

RESUMO Objetivo: O presente estudo teve como objetivo avaliar a presença de helmintos e protozoários intestinais em hortaliças comercializados em Diamantina, um município localizado no Vale do Jequitinhonha, uma das regiões mais pobres do mundo. Métodos: Cento e oito exemplares, incluindo alface, cebolinha e rúcula, foram mensalmente coletados em uma feira livre, uma quitanda e um supermercado do município. As amostras foram processadas por um método de concentração e avaliadas por microscopia óptica para pesquisa de estruturas parasitárias. Resultados: O percentual global de contaminação foi de 50,9% (55/108), com predominância de larvas de nematódeos (36,5%), cistos de Entamoeba coli e ovos de ancilostomídeos/Strongyloides spp. (12,9%). A alface demonstrou a maior taxa de contaminação (61,1%) e as amostras da feira livre foram as mais contaminadas (77,8%). Informações coletadas em cada ponto de venda apontaram o cultivo em campo como a etapa crítica para a contaminação. Conclusão: Hortaliças comercializadas em Diamantina apresentam uma ampla variedade de parasitas intestinais, o que representa um risco potencial à saúde dos consumidores da área.

Methylphenidate-triggered ROS generation promotes caveolae-mediated transcytosis via Rac1 signaling and c-Src-dependent caveolin-1 phosphorylation in human brain endothelial cells.

Methylphenidate (MPH) is an amphetamine-like stimulant commonly prescribed for attention deficit hyperactivity disorder. Despite its widespread use, the cellular/molecular effects of MPH remain elusive. Here, we report a novel direct role of MPH on the regulation of macromolecular flux through human brain endothelial cells (ECs). MPH significantly increased caveolae-mediated transcytosis of horseradish peroxidase through ECs without affecting paracellular permeability. Using FRET-based live cell imaging, together with pharmacological inhibitors and lentiviral-mediated shRNA knockdown, we demonstrate that MPH promoted ROS generation via activation of Rac1-dependent NADPH oxidase (NOX) and c-Src activation at the plasma membrane. c-Src in turn was shown to mediate the phosphorylation of caveolin-1 (Cav1) on Tyr14 leading to enhanced caveolae formation and transendothelial transport. Accordingly, the inhibition of Cav1 phosphorylation by overexpression of a phosphodefective Cav1Y14F mutant or knocking down Cav1 expression abrogated MPH-induced transcytosis. In addition, both vitamin C and inhibition of NOX blocked MPH-triggered vesicular transport. This study, therefore, identifies Rac1/NOX/c-Src-dependent signaling in MPH-induced increase in transendothelial permeability of brain endothelial cell monolayers via caveolae-mediated transcytosis.

Experimental design of a liposomal lipid system: A potential strategy for paclitaxel-based breast cancer treatment.

Paclitaxel (PTX) is widely used as a first-line treatment for patients with metastatic breast cancer; however, its poor water solubility represents a major challenge for parenteral administration. The encapsulation of the PTX in drug-delivery systems with high affinity for tumor sites could improve the uptake and increase its therapeutic efficacy. In this work, long-circulating and pH-sensitive PEG-coated (SpHL-PTX) and PEG-folate-coated liposomes containing PTX (SpHL-FT-PTX) were prepared, and the physicochemical properties and in vitro cytotoxic activity were evaluated. Both formulations presented adequate physicochemical properties, including a mean diameter smaller than 200 nm, zeta potential values near the neutral range, and an encapsulation percentage higher than 93%. Moreover, SpHL-FT-PTX showed a good stability after storage for 100 days at 4 °C. The viability studies on breast cancer cell lines (MDA-MB-231 and MCF-7) demonstrated cytotoxic activity more pronounced for SpHL-FT-PTX than for SpHL-PTX or free drug for both tumor cell lines. This activity was reduced to a rate comparable to SpHL-PTX when the cells were previously treated with folic acid in order to saturate the receptors. In contrast, in the normal cell line (L929), cell viability was decreased only by free or liposomal PTX in the highest concentrations. A significantly higher selectivity index was obtained after SpHL-FT-PTX treatment compared to SpHL-PTX and free PTX. Therefore, the results of the present work suggest that SpHL-FT-PTX can be a promising formulation for the treatment of metastatic breast cancer.