Satisfaction and perception of chronic pain patients about an online and face-to-face pain neuroscience education program: cross-sectional study / Satisfação e percepção de indivíduos com dor crônica sobre um programa de educação em neurociência da dor online e presencial: estudo observacional transversal

ABSTRACT BACKGROUND AND OBJECTIVES: The complexity of chronic musculoskeletal pain requires the need to know the treatment strategies from the perspective of the service user. The objective of this study was to analyze the satisfaction and perception of individuals with chronic musculoskeletal pain participating in a pain neuroscience education program in the online and face-to-face modalities. METHODS: This is a cross-sectional observational study, composed of 26 participants, of which 13 individuals participated in 10 meetings of face-to-face pain education (FG), and the other 13 in the online modality (OG). The satisfaction assessment consisted of 10 questions from the MedRisk Instrument for Measuring Patient Satisfaction With Physical Therapy Care, and the perception assessment was obtained by means of seven questions developed by the researchers, specific about the pain education program. For statistical analysis, Mann-Whitnney and chi square tests, Biostat software and significance level (0.05) were used. RESULTS: Of the 17 questions, there was a difference between the groups in only 5 questions. The FG reported greater satisfaction and perception in the questions of "explanation about the treatment received" (Chi2=6.19; p=0.05), "ways to avoid future problems" (Chi2=4.727; p=0.03), "return to future services" (Chi2=4.727; p=0.03), "relationship with other people" (10 vs 8; p=0.03) and "increased level of physical activity" (9 vs 8; p=0.03). CONCLUSION: There was good satisfaction and perception of individuals with chronic musculoskeletal pain participating in a pain neuroscience education program both in the online and face-to-face modality. Some differences were observed between both, especially in issues that seem to involve face-to-face contact with a professional, with more positive results in the FG.

RESUMO JUSTIFICATIVA E OBJETIVOS: A complexidade da dor musculoesquelética crônica exige a necessidade de conhecer as estratégias de tratamento sob a perspectiva do usuário do serviço. O objetivo deste estudo foi analisar a satisfação e a percepção de indivíduos com dor musculoesquelética crônica sobre um programa de educação em neurociência dor nas modalidades online e presencial. MÉTODOS: Trata-se de um estudo observacional do tipo transversal, composto por 26 participantes, dos quais 13 indivíduos participaram de 10 encontros de educação em dor presencial (GP), e os outros 13 na modalidade online (GO). A avaliação da satisfação consistiu em 10 questões do MedRisk Instrument for Measuring Patient Satisfaction With Physical Therapy Care, e a avaliação da percepção foi obtida por meio de sete perguntas desenvolvidas pelos pesquisadores, específicas sobre o programa de educação em dor. Para análise estatística, foram utilizados os testes de Mann-Whitney e Qui-quadrado, software Biostat e nível de significância ≤0,05. RESULTADOS: Das 17 questões, houve diferença entre os grupos apenas em 5 questões. O GP relatou maior satisfação e percepção nas questões que se referem a "explicação sobre o tratamento recebido" (Qui2=6,19; p=0,05), "formas de evitar futuros problemas" (Qui2=4,727; p=0,03), "retorno para futuros serviços" (Qui2=4,727; p=0,03), "relacionamento com outras pessoas" (10 vs 8; p=0,03) e "aumento do nível de atividade física" (9 vs 8; p=0,03). CONCLUSÃO: Indivíduos com dor musculoesquelética crônica mostraram boa satisfação e percepção de um programa de educação em neurociência da dor tanto na modalidade online quanto na presencial. Algumas diferenças foram observadas entre ambas, sobretudo nas questões que parecem envolver contato face-a-face com um profissional, com resultados mais positivos quando o programa é oferecido de forma presencial.

Burnout Syndrome and Consumption of Alcohol and Illicit Substances in University Students / Síndrome de Burnout e Consumo de Álcool e Substâncias Ilícitas em Universitários / Síndrome de Burnout y Consumo de Alcohol y de Sustancias Ilícitas por Universitarios

Abstract The consumption of alcohol and illicit substances has shown alarming levels among young university students, and its use may be associated with the coping strategy of academic burnout. This review aimed to synthesize the scientific evidence related to the consumption of alcohol and illicit substances associated with burnout syndrome in university students. Searches were carried out in: Biblioteca Virtual em Saúde, PubMed, Web of Science, PsycNet and Scopus databases, with no year limitation and based on the PRISMA guideline. Among the 2.269 articles identified, 16 met the inclusion criteria. All studies evaluated students in the health area, 12 studies found an association between the variables, with alcohol and illicit substances consumption strongly related to burnout syndrome. It was concluded that there is an association between the studied variables, indicating that the presence of burnout syndrome in university students can result in the use of negative strategies as a coping measure.

Resumo O consumo de álcool e substâncias ilícita tem apresentado níveis alarmantes entre jovens universitários, e seu uso pode estar associado à estratégia de enfrentamento do burnout acadêmico. Esta revisão teve por objetivo sintetizar as evidências científicas relacionadas ao consumo de álcool e substâncias ilícitas associadas a síndrome de burnout em estudantes universitários. Foram realizadas buscas nas bases: Biblioteca Virtual em Saúde, PubMed, Web of Science, PsycNet e Scopus, sem limitação de ano e baseado na guia PRISMA. Entre os 2.269 artigos identificados, 16 atenderam aos critérios de inclusão. Todos os estudos avaliaram estudantes da área da saúde, 12 estudos encontraram associação entre as variáveis, sendo o consumo de álcool e substâncias ilícitas fortemente relacionado à sindrome de burnout. Concluiu-se que há associação entre as variáveis estudadas, indicando que a presença da síndrome de burnout em universitários pode resultar no uso de estratégias negativas como medida de enfrentamento.

Resumen El consumo de alcohol y de sustancias ilícitas ha mostrado niveles alarmantes entre los jóvenes universitarios, y su uso puede estar asociado con estrategias de enfrentamiento del burnout académico. Esta revisión tuvo como objetivo sintetizar la evidencia científica relacionada con el consumo de alcohol y de sustancias ilícitas asociadas al síndrome de burnout en estudiantes universitarios. Las búsquedas se realizaron en las bases Biblioteca Virtual en Salud, PubMed, Web of Science, PsycNet y Scopus, sin limitación de año y basándose en la guía PRISMA. De los 2.269 artículos encontrados, 16 cumplieron los criterios de inclusión. Todos los estudios evaluaron estudiantes del área de salud y 12 estudios encontraron asociación entre las variables, entre los que el consumo de alcohol y de sustancias ilícitas estuvo fuertemente relacionado con el síndrome de burnout. Se concluyó que existe asociación entre las variables estudiadas, indicando que la presencia de síndrome de burnout en estudiantes universitarios puede resultar en el uso de estrategias negativas como medida de enfrentamiento.

Loss of postnatal quiescence of neural stem cells through mTOR activation upon genetic removal of cysteine string protein-α.

Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.

Model Driven Development Applied to Complex Event Processing for Near Real-Time Open Data.

Nowadays, data are being produced like never before because the use of the Internet of Things, social networks, and communication in general are increasing exponentially. Many of these data, especially those from public administrations, are freely offered using the open data concept where data are published to improve their reutilisation and transparency. Initially, the data involved information that is not updated continuously such as budgets, tourist information, office information, pharmacy information, etc. This kind of information does not change during large periods of time, such as days, weeks or months. However, when open data are produced near to real-time such as air quality sensors or people counters, suitable methodologies and tools are lacking to identify, consume, and analyse them. This work presents a methodology to tackle the analysis of open data sources using Model-Driven Development (MDD) and Complex Event Processing (CEP), which help users to raise the abstraction level utilised to manage and analyse open data sources. That means that users can manage heterogeneous and complex technology by using domain concepts defined by a model that could be used to generate specific code. Thus, this methodology is supported by a domain-specific language (DSL) called OpenData2CEP, which includes a metamodel, a graphical concrete syntax, and a model-to-text transformation to specific platforms, such as complex event processing engines. Finally, the methodology and the DSL have been applied to two near real-time contexts: the analysis of air quality for citizens' proposals and the analysis of earthquake data.

Multiscale socio-ecological networks in the age of information.

Interactions between people and ecological systems, through leisure or tourism activities, form a complex socio-ecological spatial network. The analysis of the benefits people derive from their interactions with nature-also referred to as cultural ecosystem services (CES)-enables a better understanding of these socio-ecological systems. In the age of information, the increasing availability of large social media databases enables a better understanding of complex socio-ecological interactions at an unprecedented spatio-temporal resolution. Within this context, we model and analyze these interactions based on information extracted from geotagged photographs embedded into a multiscale socio-ecological network. We apply this approach to 16 case study sites in Europe using a social media database (Flickr) containing more than 150,000 validated and classified photographs. After evaluating the representativeness of the network, we investigate the impact of visitors' origin on the distribution of socio-ecological interactions at different scales. First at a global scale, we develop a spatial measure of attractiveness and use this to identify four groups of sites. Then, at a local scale, we explore how the distance traveled by the users to reach a site affects the way they interact with this site in space and time. The approach developed here, integrating social media data into a network-based framework, offers a new way of visualizing and modeling interactions between humans and landscapes. Results provide valuable insights for understanding relationships between social demands for CES and the places of their realization, thus allowing for the development of more efficient conservation and planning strategies.

Neural crest derived progenitor cells contribute to tumor stroma and aggressiveness in stage 4/M neuroblastoma.

Pediatric tumors arise upon oncogenic transformation of stem/progenitor cells during embryonic development. Given this scenario, the existence of non-tumorigenic stem cells included within the aberrant tumoral niche, with a potential role in tumor biology, is an intriguing and unstudied possibility. Here, we describe the presence and function of non-tumorigenic neural crest-derived progenitor cells in aggressive neuroblastoma (NB) tumors. These cells differentiate into neural crest typical mesectodermal derivatives, giving rise to tumor stroma and promoting proliferation and tumor aggressiveness. Furthermore, an analysis of gene expression profiles in stage 4/M NB revealed a neural crest stem cell (NCSC) gene signature that was associated to stromal phenotype and high probability of relapse. Thus, this NCSC gene expression signature could be used in prognosis to improve stratification of stage 4/M NB tumors. Our results might facilitate the design of new therapies by targeting NCSCs and their contribution to tumor stroma.

Gene Expression Profiling Supports the Neural Crest Origin of Adult Rodent Carotid Body Stem Cells and Identifies CD10 as a Marker for Mesectoderm-Committed Progenitors.

Neural stem cells (NSCs) are promising tools for understanding nervous system plasticity and repair, but their use is hampered by the lack of markers suitable for their prospective isolation and characterization. The carotid body (CB) contains a population of peripheral NSCs, which support organ growth during acclimatization to hypoxia. We have set up CB neurosphere (NS) cultures enriched in differentiated neuronal (glomus) cells versus undifferentiated progenitors to investigate molecular hallmarks of cell classes within the CB stem cell (CBSC) niche. Microarray gene expression analysis in NS is compatible with CBSCs being neural crest derived-multipotent progenitor cells able to sustain CB growth upon exposure to hypoxia. Moreover, we have identified CD10 as a marker suitable for isolation of a population of CB mesectoderm-committed progenitor cells. CD10 + cells are resting in normoxia, and during hypoxia they are activated to proliferate and to eventually complete maturation into mesectodermal cells, thus participating in the angiogenesis necessary for CB growth. Our results shed light into the molecular and cellular mechanisms involved in CBSC fate choice, favoring a potential use of these cells for cell therapy. Stem Cells 2016;34:1637-1650.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones.

KEY POINTS: Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin-phospholipid interaction. ABSTRACT: Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB.

Anti-tumor effects of Ganoderma lucidum (reishi) in inflammatory breast cancer in in vivo and in vitro models.

The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.

Motorneurons require cysteine string protein-α to maintain the readily releasable vesicular pool and synaptic vesicle recycling.

Cysteine string protein-α (CSP-α) is a synaptic vesicle protein that prevents activity-dependent neurodegeneration by poorly understood mechanisms. We have studied the synaptic vesicle cycle at the motor nerve terminals of CSP-α knock-out mice expressing the synaptopHluorin transgene. Mutant nerve terminals fail to sustain prolonged release and the number of vesicles available to be released decreases. Strikingly, the SNARE protein SNAP-25 is dramatically reduced. In addition, endocytosis during the stimulus fails to maintain the size of the recycling synaptic vesicle pool during prolonged stimulation. Upon depolarization, the styryl dye FM 2-10 becomes trapped and poorly releasable. Consistently with the functional results, electron microscopy analysis revealed characteristic features of impaired synaptic vesicle recycling. The unexpected defect in vesicle recycling in CSP-α knock-out mice provides insights into understanding molecular mechanisms of degeneration in motor nerve terminals.

Cysteine string protein-alpha prevents activity-dependent degeneration in GABAergic synapses.

The continuous release of neurotransmitter could be seen to place a persistent burden on presynaptic proteins, one that could compromise nerve terminal function. This supposition and the molecular mechanisms that might protect highly active synapses merit investigation. In hippocampal cultures from knock-out mice lacking the presynaptic cochaperone cysteine string protein-alpha (CSP-alpha), we observe progressive degeneration of highly active synaptotagmin 2 (Syt2)-expressing GABAergic synapses, but surprisingly not of glutamatergic terminals. In CSP-alpha knock-out mice, synaptic degeneration of basket cell terminals occurs in vivo in the presence of normal glutamatergic synapses onto dentate gyrus granule cells. Consistent with this, in hippocampal cultures from these mice, the frequency of miniature IPSCs, caused by spontaneous GABA release, progressively declines, whereas the frequency of miniature excitatory AMPA receptor-mediated currents (mEPSCs), caused by spontaneous release of glutamate, is normal. However, the mEPSC amplitude progressively decreases. Remarkably, long-term block of glutamatergic transmission in cultures lacking CSP-alpha substantially rescues Syt2-expressing GABAergic synapses from neurodegeneration. These findings demonstrate that elevated neural activity increases synapse vulnerability and that CSP-alpha is essential to maintain presynaptic function under a physiologically high-activity regimen.

The global impact of endoscopic ultrasound (EUS) regarding the survival of a pancreatic adenocarcinoma in a tertiary hospital.

BACKGROUND: Pancreatic ductal adenocarcinoma is a type of neoplasm with a high mortality rate. There are a number of different procedures that may be followed in the study of the pancreas; one such procedure is endoscopic ultrasonography (EUS). OBJECTIVE: This study aimed to retrospectively evaluate the impact on patient survival of a biliopancreatic EUS performed 2 months prior to the first treatment session of the pancreatic ductal adenocarcinoma. MATERIAL AND METHODS: We carried out a retrospective evaluation of the medical case histories of our patients who had been diagnosed with pancreatic ductal adenocarcinoma over a period of 10 years (1 Jan 1999-31 Dec 2008), combining the computer archives of our Pathological Anatomy (biopsy and cytology) Dept. and those of the Digestive Department's Endoscopic Ultrasonography Unit in order to exclude any pancreatic neoplasms derived from other origins. Information regarding the patients' age, sex, tumor location, and various diagnostic tests (EUS, EUS-fine-needle aspiration (FNA), helical computed tomography (CT), multidetector-row CT (MDCT)) were recorded, along with the different treatments that had been followed in each case. RESULT: When the survival rates of patients diagnosed with and without EUS were compared, evaluating the average survival rate and the survival rate after 1, 3, and 5 years, respectively, the differences in the results proved to be statistically significant (p = 0.014) in favor of the diagnosis with EUS. However, no significant differences were found when using other diagnostic imaging methods, such as EUS-FNA (p = 0.271), helical CT (p = 0.843), or MDCT (p = 0.738). To evaluate other influencing survival factors, a study was undertaken to record data depending on the sex of the patients. Results showed a higher survival rate in the female patients with a median of 6.57 months compared to that of the male patients with a median of 4.7 months (p = 0.014). Variables, which had resulted significant prior to treatment, were included in a multivariate Cox regression model, after which only the sex and EUS remained significant. CONCLUSION: A biliopancreatic EUS carried out during the 2 months prior to the start of the treatment of the pancreatic ductal adenocarcinoma has a statistically significant impact on the patient survival rate. We believe that this is due to the possibility of a very-early-stage diagnosis of the adenocarcinoma permitted by the use of this technique.

Clear-cell adenocarcinoma of vesical origin: a case study of metastatic disease treated with chemotherapy.

Vesical clear cell adenocarcinoma is an uncommon tumour. The description of nearly all published cases focuses on histological issues, providing few clinical particulars and limited followup. The treatment choice is resection. No publications have been found regarding systemic treatments for advanced disease. We present a case of metastatic clear cell adenocarcinoma of the bladder treated with chemotherapy.

Monitoring synaptic function at the neuromuscular junction of a mouse expressing synaptopHluorin.

We monitored presynaptic exocytosis and vesicle recycling at neuromuscular junctions of transgenic mice expressing synaptopHluorin (spH), using simultaneous optical and electrophysiological recordings. Synaptic transmission was indistinguishable from that in wild-type controls. Fluorescence rose during and decayed monotonically after stimulus trains to the nerve, with amplitudes and decay times increasing with the amount of stimulation. The relatively large size of synaptic terminals allowed us to examine the spatial profile of fluorescence changes. We identified hot spots of exocytosis, which were stable with repeated trains. Photobleach experiments showed that spH freshly exposed by nerve stimulation was not preferentially retrieved by compensatory endocytosis; instead, most retrieved spH preexisted in the surface membrane. Finally, we compared fluorescence and electrical [summed end-plate potentials (EPPs)] estimates of exocytosis, which diverged during repeated trains, as fluorescence exceeded summed EPPs, although the average amplitude of miniature EPPs was unchanged. This might reflect exocytosis of spH-containing, acetylcholine-free ("empty") vesicles or other organelles during intense stimulation.