Cancer stem cells in prostate cancer: implications for targeted therapy

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies include surgery, radiation, hormonal ablation, and chemotherapy. Despite increasing efforts, these therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. The cancer stem cell (CSC) hypothesis is an emerging model that explains many of the molecular characteristics of oncological disease as well as the tendency of cancers to relapse, metastasize, and develop resistance to conventional therapies. CSCs are a reservoir of cancer cells that exhibit properties of self-renewal and the ability to reestablish the heterogeneous tumor cell population. The existence of PCa stem cells offers a theoretical explanation for many uncertainties regarding PCa and also for treatment resistance and disease progression once clinical cure is achieved. Therapies targeting CSCs might therefore lead to more effective cancer treatments, divergent from a traditional anti-proliferative approach, based on tumor bulk reduction accompanied by CSC-specific inhibition. Here, we focus on reviewing the historical perspective as well as concepts regarding stem cells and CSCs in PCa. In addition, we will report possible strategies and new clinical approaches that address the CSC-based concept of tumorigenesis in PCa. (C) 2017 S. Karger AG, Base

El Sujeto y el habla en psicopatología : aportes sobre la forclusión

Neste trabalho apresentamos uma contribuição ao estudo da especificidade da escuta psicanalítica na prática clínica. Iniciamos com uma análise histórica do termo foraclusão e da leitura que Lacan fez da concepção freudiana do processo de Verwerfung. Interessa mostrar a aproximação entre o sujeito foracluído da ciência, a constituição do sujeito na fala e o modelo topológico do corte. Trata-se de indagar sobre a estrutura na qual o sujeito está simbolicamente representado, e na qual, ao mesmo tempo, ele faz parte. Nesse sentido, o termo indiscriminado sujet responde tanto ao uso gramatical quanto ao topológico. Trabalhamos através de um caso clínico a diferença entre uma clínica do fenômeno e uma clínica da escuta, cujo efeito é um sujeito.In this work we present a contribution to the study of the specificity of the psychoanalytical listening in clinical practice. We begin with a historical analysis of the term "forclusion" [rejection] and Lacan's interpretation of the freudian concept of the process of Verwerfung. This article deals with the relation among the rejected subject of the science, the constitution of the subject in speech and the topological model of the cut. We inquire about the structure in which the subject is symbolically represented and, at the same time, it is part of. In this way, the indiscriminate term sujet recovers both the grammatical and topological use. Through a clinical case we work the differences between a clinical practice of the phenomenon and a clinical practice of listening whose effect is a subject.En este trabajo presentamos una contribución al estudio de la especificidad de la escucha psicoanalítica en la práctica clínica. Iniciamos con un análisis histórico del término forclusión y de la lectura que hace Lacan de la concepción freudiana del proceso de Verwerfung. Nos interesa mostrar la aproximación entre el sujeto forcluído de la ciencia, la constitución del sujeto en el habla y el modelo topológico del corte. Tratamos de indagar sobre la estructura en la que el sujeto se encuentra simbólicamente representado y, de la que, al mismo tiempo, es parte. En este sentido, el término indiscriminado sujet responde tanto al uso gramatical como al topológico. Trabajamos a través de un caso clínico, la diferencia entre una clínica del fenómeno y una clínica de la escucha, cuyo efecto es el sujeto

Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2008/54953-0, 2008/04618-0, 2009/50113-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Spatial and temporal dynamics of the abundance of crustose calcareous algae on the southernmost coral reefs of the western Atlantic (Abrolhos Bank, Brazil)

Crustose calcareous algae (CCA) constitute one of the main reef builders on the Abrolhos Bank, Brazil. Once CCA taxonomy is locally understood, differences in growth-forms may be useful for the delimitation of taxa using characteristics such as the presence or absence of surface protuberances. Here, growth-forms were used to identify and quantify the most common CCA taxa on the shallow reefs (3-10 m) of the Abrolhos Bank to determine possible changes in the CCA community over a period of 10 years, and the ecological significance of CCA to local reefs was interpreted. The CCA assemblages were surveyed from 2006-2015 by using fixed photoquadrats at four sites in the inner (10-20 km from the mainland) and mid-shelf reefs (40-75 km from the mainland). The five most common CCA taxa were Pneophyllum conicum, the Lithophyllum kaiserii / Lithophyllum sp. complex, Melyvonnea erubescens, the Hydrolithon boergesenii / Porolithon onkodes complex and Peyssonelia sp. The overall mean CCA cover on the reefs was 20%. A comparison with a previous monitoring study in the same region indicated that the CCA cover nearly doubled from 2003-2008 to 2006-2015. This study reveals that the coral-killing species P. conicum dominated CCA flora on the shallow Abrolhos reefs in the last decade, and the local specific abundance of CCA slightly fluctuated over time and was species-and site-specific. The information obtained in this study contributes to the understanding of the ecology of the key calcifying components of the Abrolhos reefs and provides a useful baseline for exploring the responses of CCA to future environmental changes.PELDMudancas Climaticas scientific programmes of the Brazilian National Science Agency (CNPq)Brazilian IODP Program (CAPES/MEC)P&D Program ANP/BrasoilFAPERJDiretoria Pesquisa Cient, Inst Pesquisas, Jardim Bot Rio De Janeiro, Rua Pacheco Leao 915, BR-22460030 Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Inst Biol, BR-21941599 Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Dept Oceanog, Ave Fernando Ferrari 514, BR-29090600 Vitoria, ES, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilUniv Fed Paraiba, Ctr Ciencias Aplicadas & Educ, Campus 4 Litoral Norte, BR-58297000 Rio Tinto, PB, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilANP/Brasoil: 48610.011015/2014-55Web of Scienc

Mesophotic reef fish assemblages of the remote St. Peter and St. Paul's Archipelago, Mid-Atlantic Ridge, Brazil

Mesophotic reef fish assemblages (30-90 m depth) of the small and remote St. Peter and St. Paul's Archipelago (SPSPA), Mid-Atlantic Ridge, Brazil, were characterized using remotely operated vehicles. Ordination analyses identified distinct fish assemblages in the upper (30-50 m) and lower (50-90 m) mesophotic zones, the former characterized by high abundances of species that are also abundant at euphotic reefs (Caranx lugubris, Melichthys niger, Stegastes sanctipauli and Chromis multilineata) and the latter dominated by two mesophotic specialists (Prognathodes obliquus and Chromis enchrysura). Planktivores dominated fish assemblages, particularly in the upper mesophotic zone, possibly due to a greater availability of zooplankton coming from the colder Equatorial Undercurrent in mesophotic depths of the SPSPA. Turf algae, fleshy macroalgae and scleractinian corals dominated benthic assemblages between 30 and 40 m depth, while bryozoans, black corals and sponges dominated between 40 and 90 m depth. Canonical correspondence analysis explained 74 % of the relationship between environmental characteristics (depth, benthic cover and complexity) and structure of fish assemblages, with depth as the most important independent variable. Juveniles of Bodianus insularis and adults of P. obliquus and C. enchrysura were clearly associated with branching black corals (Tanacetipathes spp.), suggesting that black corals play key ecological roles in lower mesophotic reefs of the SPSPA. Results from this study add to the global database about mesophotic reef ecosystems (MREs) and provide a baseline for future evaluations of possible anthropogenic and natural disturbances on MREs of the SPSPA.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPqCNPqFundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Univ Sao Paulo, Inst Oceanog, Programa Posgrad Oceanog Biol, BR-05508120 Sao Paulo, SP, BrazilUniv Fed Paraiba, Programa Posgrad Ciencias Biol Zool, BR-58059900 Joao Pessoa, PB, BrazilUniv Fed Paraiba, Programa Posgrad Ecol & Monitoramento Ambiental, BR-58297000 Rio Tinto, PB, BrazilUniv Estadual Paraiba, Programa Posgrad Ecol & Conservac, BR-58109753 Campina Grande, PB, BrazilUniv Fed Pernambuco, Dept Oceanog, Ctr Tecnol & Geociencias, BR-50670901 Recife, PE, BrazilUniv Fed Paraiba, Ctr Ciencias Exatas & Nat, Dept Sistemat & Ecol, BR-58051900 Joao Pessoa, PB, BrazilInst Pesquisas Jardim Bot Rio De Janeiro, Rio De Janeiro, RJ, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilUniv Fed Rio de Janeiro, Inst Biol, BR-21944970 Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, SAGE COPPE, BR-21944970 Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Inst Oceanog, Dept Oceanog Biol, BR-05508120 Sao Paulo, SP, BrazilUniv Fed Paraiba, Dept Engn & Meio Ambiente, BR-58297000 Rio Tinto, PB, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilCNPq: 557185/09-2CNPq: 484875/2011-6Web of Scienc

Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections : a prospective multicentre study (WISS Study)

Background: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. Methods: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. Results: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p <0.0001). The multivariate logistic regression model was highly significant (p <0.0001, R-2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. Conclusions: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.Peer reviewe

Physiological parameters for Prognosis in Abdominal Sepsis (PIPAS) Study : a WSES observational study

BackgroundTiming and adequacy of peritoneal source control are the most important pillars in the management of patients with acute peritonitis. Therefore, early prognostic evaluation of acute peritonitis is paramount to assess the severity and establish a prompt and appropriate treatment. The objectives of this study were to identify clinical and laboratory predictors for in-hospital mortality in patients with acute peritonitis and to develop a warning score system, based on easily recognizable and assessable variables, globally accepted.MethodsThis worldwide multicentre observational study included 153 surgical departments across 56 countries over a 4-month study period between February 1, 2018, and May 31, 2018.ResultsA total of 3137 patients were included, with 1815 (57.9%) men and 1322 (42.1%) women, with a median age of 47years (interquartile range [IQR] 28-66). The overall in-hospital mortality rate was 8.9%, with a median length of stay of 6days (IQR 4-10). Using multivariable logistic regression, independent variables associated with in-hospital mortality were identified: age > 80years, malignancy, severe cardiovascular disease, severe chronic kidney disease, respiratory rate >= 22 breaths/min, systolic blood pressure 4mmol/l. These variables were used to create the PIPAS Severity Score, a bedside early warning score for patients with acute peritonitis. The overall mortality was 2.9% for patients who had scores of 0-1, 22.7% for those who had scores of 2-3, 46.8% for those who had scores of 4-5, and 86.7% for those who have scores of 7-8.ConclusionsThe simple PIPAS Severity Score can be used on a global level and can help clinicians to identify patients at high risk for treatment failure and mortality.Peer reviewe

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firing

Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two shor