Extracellular vesicles throughout development: A potential roadmap for emerging glioblastoma therapies.

Extracellular vesicles (EVs) are membrane-delimited vesicular bodies carrying different molecules, classified according to their size, density, cargo, and origin. Research on this topic has been actively growing through the years, as EVs are associated with critical pathological processes such as neurodegenerative diseases and cancer. Despite that, studies exploring the physiological functions of EVs are sparse, with particular emphasis on their role in organismal development, initial cell differentiation, and morphogenesis. In this review, we explore the topic of EVs from a developmental perspective, discussing their role in the earliest cell-fate decisions and neural tissue morphogenesis. We focus on the function of EVs through development to highlight possible conserved or novel processes that can impact disease progression. Specifically, we take advantage of what was learned about their role in development so far to discuss EVs impact on glioblastoma, a particular brain tumor of stem-cell origin and poor prognosis, and how their function can be hijacked to improve current therapies.

Assessing the efficacy of oral Tranexamic Acid as adjuvant of Topic Triple Combination Cream Therapy in Melasma: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Melasma is a skin pigmentation disorder that lacks consistent treatment success despite various methods used. Tranexamic Acid (TXA) has shown hypopigmentation properties, but whether TXA administration should be combined with standard treatment or not, is still not clarified. We aimed to perform an investigation of oral TXA effectiveness and safety as an adjuvant of Triple Combination Cream (TCC) Therapy in melasma. METHODS: We searched PubMed, EMBASE and Cochrane Central for studies comparing TCC plus adjuvant TXA to TCC therapy alone in patients with melasma. Outcomes of interest included change from the baseline of Melasma Area Severity Index (MASI) score, recurrence of melasma and adverse events. Statistical analysis was performed using R Studio 4.3.2. RESULTS: Four trials, involving 480 patients were included. In the pooled analysis, the decrease from baseline in the MASI score (mean difference [MD] -3.10; 95% confidence interval [CI] -5.85 to -0.35) was significantly higher in patients treated with oral tranexamic acid as an adjuvant to TCC compared to TCC alone. Melasma recurrence (RR 0.28; 95% CI 0.16-0.49) was significantly lower in the group treated with TCC and TXA. Regarding erythema (RR 0.63; 95% CI 0.34-1.17) and burning (RR 0.59; 95% CI 0.30-1.17), there was no significant difference. CONCLUSION: This meta-analysis demonstrated statistically significant benefits of TCC plus TXA combination treatment compared with TCC alone. Furthermore, the results suggest that the addition of TXA to TCC therapy may reduce melasma recurrence.

Assessment and characterization of biofilm formation among human isolates of Streptococcus dysgalactiae subsp. equisimilis.

The capacity to form biofilm is considered a protective mechanism that allows the bacteria to survive and proliferate in hostile environments, facilitating the maintenance of the infectious process. Recently, biofilm has become a topic of interest in the study of the human pathogen group A Streptococcus (GAS). Although GAS has not been associated with infection on medical implants, the presence of microcolonies embedded in an extracellular matrix on infected tissues has been reported. Despite the similarity between GAS and Streptococcus dysgalactiae subspecies equisimilis (SDSE), there are no studies in the literature describing the production of biofilm by SDSE. In this work, we assessed and characterized biofilm development among SDSE human isolates of group C. The in vitro data showed that 59.3% of the 118 isolates tested were able to form acid-induced biofilm on glass, and 28% formed it on polystyrene surfaces. More importantly, biofilm was also formed in a foreign body model in mice. The biofilm structure was analyzed by confocal laser scanning microscopy, transmission electron microscopy, and scanning electron microscopy. Long fibrillar-like structures were observed by scanning electron microscopy. Additionally, the expression of a pilus associated gene of SDSE was increased for in vitro sessile cells compared with planktonics, and when sessile cells were collected from biofilms formed in the animal model compared with that of in vitro model. Results obtained from the immunofluorescence microscopy indicated the biofilm was immunogenic. Our data also suggested a role for proteins, exopolysaccharide and extracellular DNA in the formation and accumulation of biofilm by SDSE.

Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression.

Non-canonical secretion pathways, collectively known as unconventional protein secretion (UPS), are alternative secretory mechanisms usually associated with stress-inducing conditions. UPS allows proteins that lack a signal peptide to be secreted, avoiding the conventional endoplasmic reticulum-Golgi complex secretory pathway. Molecules that generally rely on the canonical pathway to be secreted may also use the Golgi bypass, one of the unconventional routes, to reach the extracellular space. UPS studies have been increasingly growing in the literature, including its implication in the biology of several diseases. Intercellular communication between brain tumor cells and the tumor microenvironment is orchestrated by various molecules, including canonical and non-canonical secreted proteins that modulate tumor growth, proliferation, and invasion. Adult brain tumors such as gliomas, which are aggressive and fatal cancers with a dismal prognosis, could exploit UPS mechanisms to communicate with their microenvironment. Herein, we provide functional insights into the UPS machinery in the context of tumor biology, with a particular focus on the secreted proteins by alternative routes as key regulators in the maintenance of brain tumors.

Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma.

Tumor cells can employ epithelial-mesenchymal transition (EMT) or autophagy in reaction to microenvironmental stress. Importantly, EMT and autophagy negatively regulate each other, are able to interconvert, and both have been shown to contribute to drug-resistance in glioblastoma (GBM). EMT has been considered one of the mechanisms that confer invasive properties to GBM cells. Autophagy, on the other hand, may show dual roles as either a GBM-promoter or GBM-suppressor, depending on microenvironmental cues. The Wingless (WNT) signaling pathway regulates a plethora of developmental and biological processes such as cellular proliferation, adhesion and motility. As such, GBM demonstrates deregulation of WNT signaling in favor of tumor initiation, proliferation and invasion. In EMT, WNT signaling promotes induction and stabilization of different EMT activators. WNT activity also represses autophagy, while nutrient deprivation induces ß-catenin degradation via autophagic machinery. Due to the importance of the WNT pathway to GBM, and the role of WNT signaling in EMT and autophagy, in this review we highlight the effects of the WNT signaling in the regulation of both processes in GBM, and discuss how the crosstalk between EMT and autophagy may ultimately affect tumor biology.

[Utilization of parenteral drugs in vials at a pediatric unit of a university hospital]. / Utilização de medicamentos parenterais em frascos-ampola em uma unidade pediátrica de um hospital universitário.

This observational study aimed to determine the frequency of utilization of vials containing parenteral medications in a pediatric unit, and to identify nursing team actions related to their preparation and administration. Data were collected from prescription forms and by checking these drugs in the refrigerator and stocks at the unit. Vials were prescribed to 30.8% of patients. Aspects such as: reconstitution, storage, temperature and drug label were observed. Only 6.8% of the drugs had all the information researched in order to evaluate the process of preparation and administration. The correct identification of vials is important for the safe use of medication. Training programs for the healthcare team and the adoption of intravenous therapy guidelines are essential tools to optimize the utilization of parenteral medication.

Adverse Drug Reactions in Patients Receiving Systemic Antifungal Therapy at a High-Complexity Hospital.

The aim of the present study was to determine the frequency of adverse drug reactions (ADRs) associated with the use of systemic antifungal drugs in patients hospitalized at a high-complexity hospital. In addition, factors associated with ADRs were investigated. This cross-sectional retrospective study involved the investigation of 183 medical records of patients receiving systemic antifungal therapy. Antifungal drugs were classified using the fourth level of the Anatomical Therapeutic Chemical System. ADR causality was classified using the Naranjo algorithm. Drug interactions were assessed using DRUG-REAX software. Data were analyzed with descriptive statistics and univariate and multivariate logistic regression. A total of 53 patients (29.0%) had at least 1 ADR involving antifungals. Ninety-six ADRs were detected. The main ADRs observed were an infusion reaction in 24 patients (25.0%), hypokalemia in 22 (22.9%), nephrotoxicity in 18 (18.7%), and hepatotoxicity in 15 (15.6%). Amphotericin B and voriconazole were associated with ADRs of major clinical impact. Eleven of the ADRs (11.4%) were related to drug interactions. The following 3 factors were contributors to the multivariate model for the occurrence of ADRs caused by antifungal drug use: neoplasm diagnosis (odds ratio [OR], 3.9; 1.9-7.9), length of hospital stay (OR, 2.2; 1.1-4.5), and the use of ≥13 drugs (OR, 3.4; 1.6-7.2). Our study revealed positive associations between the occurrence of ADRs and diagnosis of a neoplasm, the length of stay, and the use of multiple drugs concomitant with antifungals. These risk factors should be considered in antifungal stewardship, among other actions, to promote the rational use of antifungal agents.

Drug utilization study of systemic antifungal agents in a Brazilian tertiary care hospital.

Background The inappropriate use of systemic antifungal agents can result in unnecessary exposure, adverse events, increased microbial resistance and increased costs. Aim This study analysed the use of systemic antifungal agents and adherence to treatment guidelines for fungal infections. Setting A Brazilian tertiary hospital. Methods This cross-sectional study investigated 183 patients who were treated with systemic antifungals. Antifungal drugs were classified according to the fourth level of the Anatomical Therapeutic Chemical classification system. The appropriateness of treatments was analysed with respect to the indication, dose and potential drug-drug interactions. Descriptive and univariate statistical analyses were performed. The main outcome measure was the frequency of adherence to treatment guidelines for fungal infections. Results The number of established treatments was 320, with 163 (50.9 %) pre-emptive, 63 (19.7 %) targeted, 56 (17.5 %) empirical and 38 (11.9 %) prophylactic treatments. The overall adherence to the treatment guidelines was 29.4 %. The proportion of appropriate treatment considering indication, dosage and drug-drug interactions was 84.1, 67.8 and 47.2 %, respectively. The most commonly prescribed systemic antifungal agents were fluconazole in 170 (53.1 %), voriconazole in 43 (13.4 %) and amphotericin B deoxycholate in 36 (11.3 %) cases. Conclusion The study showed a low proportion of appropriate antifungal drug use; the dosage and drug-drug interactions criteria were the determining factors for the high percentage of non-adherence to treatment guidelines in the hospital. The profile of antifungal agents used showed the predominance of fluconazole as well as the use of new antifungal drugs.

Psicologia e políticas públicas de enfrentamento à violência contra mulheres: experiências de universitárias / Psychology and public policies to cope with violence against women: university student experiences / Psicología y políticas públicas para combatir la violencia contra las mujeres: experiencias de universitarias

O estudo investigou as experiências de universitárias do curso de Psicologia junto às políticas públicas de enfrentamento à violência contra mulheres (VCM) em um município do sudoeste goiano. Foi realizada pesquisa de campo, com metodologia qualitativa, partindo das premissas da Psicologia Sócio-histórica. A amostra foi composta por 10 estudantes de psicologia. Os dados foram obtidos por meio de entrevistas. Foi desenvolvida análise dos dados por meio dos núcleos de significação. Os dados deram origem a três eixos de análise: Conceito de gênero e VCM; Políticas Públicas: práticas, atuações e intervenções no enfrentamento da VCM; Formação em psicologia e VCM. Verificou-se dificuldades em identificar as categorias gênero, VCM e políticas públicas, assim como precário conhecimento sobre a rede intersetorial de atendimento às mulheres. Percebeu-se fragilidades no processo de formação profissional para o enfrentamento da VCM. Exceto pelas atuações no campo da justiça, notou-se práticas insipientes nas demais políticas. Notou-se muitos obstáculos ideológicos, políticos, institucionais, sociais e econômicos em relação às práticas sobre a VCM por parte das participantes, elementos que dificultam a atuação frente aos problemas de gênero.

The study investigated the experiences of psychology course university students in terms of public policies to cope with violence against women (VCM) in a municipality in southwest Goiás. Field research was carried out, with a qualitative methodology, based in Socio-historical Psychology. The sample consisted of 10 psychology students. The data was obtained through interviews. Data analysis was developed through the meaning nuclei. The data gave rise to three axes of analysis: Concept of gender and VCM; Public Policies: practices, actions and interventions in confronting VCM; Training in psychology and VCM. There were difficulties in identifying the categories gender, VCM and public policies, as well as precarious knowledge about the intersectoral network of care for women. There were perceived weaknesses in the process of professional training to confront VCM. Policies in the justice field are quite active, but policies from other fields are still developing.. There were many ideological, political, institutional, social and economic obstacles to participants' practices in terms of VCM , which made it difficult to deal with gender issues.

Este estudio investigó las experiencias de universitarias del curso de Psicología, así como las políticas públicas de combate a la violencia contra las mujeres (VCM) en un municipio del suroeste Goiano. Se realizó una investigación de campo, con metodología cualitativa, partiendo desde las premisas de la Psicología Socio-histórica. La muestra fue compuesta por 10 estudiantes de psicología. Los datos fueron obtenidos por medio de entrevistas. El análisis de los datos fue realizado a través de los núcleos de significación. Los datos dieron origen a tres ejes de análisis: Concepto de género y VCM; Políticas Públicas: prácticas, actuaciones e intervenciones en el combate de la VCM; Formación en psicología y VCM. Fue verificado dificultades en identificar las categorías género, VCM y políticas públicas, así como el precario conocimiento sobre la red intersectorial de atención a las mujeres. Se percibió fragilidades en el proceso de formación profesional para el combate de la VCM. Excepto por las actuaciones en el campo de la justicia, se notó prácticas insípidas en las demás políticas. Se notaron muchos obstáculos ideológicos, políticos, institucionales, sociales y económicos en relación a las prácticas sobre la VCM por parte de las participantes, elementos que dificultan la actuación frente a los problemas de género.

Utilização de medicamentos parenterais em frascos-ampola em uma unidade pediátrica de um hospital universitário / Utilization of parenteral drugs in vials at a pediatric unit of a university hospital / Uso de medicamentos parenterales en frascos-ampolla en un servicio pediátrica de un hospital universitario

Este estudo observacional determinou a freqüência de utilização de medicamentos parenterais em frascos-ampola em uma unidade pediátrica, e identificou as ações da equipe de enfermagem associadas ao preparo e administração desses medicamentos. Os dados foram coletados por meio da prescrição médica e observação direta dos medicamentos nas geladeiras e armários da unidade. A apresentação em frascos-ampola foi prescrita para 30,8 por cento dos pacientes. Foram observados aspectos quanto à reconstituição, ao armazenamento, à temperatura e à rotulagem dos medicamentos, fatores importantes para utilização segura dos mesmos. As informações pesquisadas para avaliar o processo de preparo e de administração estavam todas presentes em apenas 6,8 por cento dos medicamentos. A identificação correta dos frascos-ampola é importante para o uso seguro dos medicamentos. O treinamento da equipe de saúde e a adoção de diretrizes de terapia endovenosa são instrumentos essenciais para otimizar o processo de utilização de medicamentos parenterais.

This observational study aimed to determine the frequency of utilization of vials containing parenteral medications in a pediatric unit, and to identify nursing team actions related to their preparation and administration. Data were collected from prescription forms and by checking these drugs in the refrigerator and stocks at the unit. Vials were prescribed to 30.8 percent of patients. Aspects such as: reconstitution, storage, temperature and drug label were observed. Only 6.8 percent of the drugs had all the information researched in order to evaluate the process of preparation and administration. The correct identification of vials is important for the safe use of medication. Training programs for the healthcare team and the adoption of intravenous therapy guidelines are essential tools to optimize the utilization of parenteral medication.

Este estudio de observación determinó la frecuencia para utilizar medicamentos parenterales en frascos-ampolla en una unidad pediátrica, identificando las acciones del equipo de enfermería con respecto a su preparación y administración. Para la recolección de datos se utilizó la prescripción médica y la observación directa de los medicamentos en los frigideres y estantes del servicio. La presentación en frascos-ampolla fue prescripta en 30.8 por ciento de los pacientes. Se observó la reconstitución, el almacenamiento, la temperatura y los rótulos de los medicamentos, factores importantes para asegurar su administración. Las informaciones investigadas para evaluar el proceso de preparación y administración estuvieron presentes en apenas 6.8 por ciento de los medicamentos. La correcta identificación de los frascos-ampolla es importante para su administración. El entrenamiento del equipo de salud y la adopción de directrices sobre tratamiento endovenoso son instrumentos esenciales para optimizar la utilización del medicamento parenteral.

Estudo de utilização de medicamentos parenterais em uma unidade de internação pediátrica de um hospital universitário / Study utilization of parenteral medications in pediatric unit of universitary hospital

A administração de medicamentos parenterais tem grande importância na assistência pediátrica e no risco para aquisição de infecções hospitalares. Este estudo observacional transversal visoudescrever a utilização de medicamentos em uma unidade de internação pediátrica. Elaborou-se um instrumento de coleta de dados, as variáveis relativas à farmacoterapia foram coletadas da prescrição médica e a análise estatística descritiva foi realizada no SPSS. A amostra foi constituída de 75 pacientes pediátricos, sendo 56,0 % do sexo masculino; apresentando como predominante a faixa etária de lactentes. O tempo de internação mais frequente foi maior que 20 dias (24,0%) seguida de 6 a 10 dias (21,3%) e menos de 3 dias (17,3%). A via parenteral foi prescrita para 56 pacientes (74,7%) e 19 (25,3%) utilizaram outras vias ou não utilizaram medicamentos; sendo que a via parenteral endovenosa foi utilizada por 52 (92,9%) dos pacientes. O número de medicamentos parenterais prescritos abrangeu 47 fármacos. A média do número de medicamentos por paciente foi quatro, o que implica em exigência de maior tempo da equipe de enfermagem em atividades relacionadas à administração de medicamentos. O número elevado de medicamentos prescritos desperta preocupações em relação à segurança. O farmacêutico deve estimular a conversão da via de administração parenteral para a oral.

Parenteral drug administration has clinical relevance in pediatric care and the risk of acquire nosocomial infection. The purpose of this observational crosssectional study was to describe the utilization of parenteral drugs in a pediatric unit. A research questionnaire was created. The variables about pharmacotherapy were collect in prescriptions. The descriptive statistical analysis was performed using SPSSA total of 75 patients were admitted, 56% were male. The age range most frequently was the infants. The length of hospitalization was over 20 days (24.0%), 6 to 10 days (21.3%) and less than 3 days (17.3%). Parenteral route was used to 56 (74.7%) patients, so 19 (25.3%) used other routes or did not use medicine. Intravenous route was used to 52 (92.9%) patients. Overall, 47 different parenteral drugs were prescribed. The average of 4 drugs per patient requires more time of nursing team in activities related with drug administration. The high number of drug prescribed per patient raise concern about safety. The pharmacist should stimulate conversion from parenteralto oral administration.

Mirror visual feedback: elaboração de protocolo para aplicação em pacientes com hanseníase / Mirror visual feedback: elaboration of protocol for application in patients with leprosy

Os primeiros estudos acerca da técnica Mirror visual feedback, técnica essa introduzida por Ramachandran e conhecida como terapia do espelho, foram em pacientes com amputação dos membros superiores e inferiores, na busca por respostas sobre a origem da dor no membro fantasma. Após o êxito em sua aplicação relativa às dores fantasmas começou a ser também testada em outras patologias. Uma doença que desperta curiosidade para métodos alternativos de tratamento é a hanseníase, que compromete pele e nervos periféricos, podendo causar hipersensibilidade do nervo, edema, déficit motor, sensitivo e dor intensa interferindo na funcionalidade e estabilidade emocional, social e produtiva. O objetivo deste trabalho foi elaborar um protocolo terapêutico com foco na futura aplicação do Mirror Visual Feedback em pacientes atingidos pela hanseníase que apresentam dor neuropática e dor fantasma, através do levantamento de conhecimentos acerca da técnica na literatura nacional e internacional.

Rotinas e cuidados de vigilância na sala de recuperaçäo anestésica / Routine and care in the anesthesia recovery period

Este trabalho procura estabelecer rotinas e cuidados de vigilância dados ao paciente submetido à anestesia geral e bloqueios, com o objetivo de detectar e/ou previnir complicaçöes anestésicas, basendo-se em dados estatísticos levantados pelas autoras, no período de fevereiro de 1988 a março de 1990, na sala de recuperaçäo anestésica da Faculdade de Medicina de Botucatu (UNESP). Os dados coletados foram dispostos em tabelas, apresentando os ítens das complicaçöes com as 10 maiores incidências para anestesias gerais e as cinco maiores incidências para bloqueios e suas respectivas causas, rotinas e cuidados, visando um planejamento de assistência individualizada.