Combining Wake-Up-Back-to-Bed with Cognitive Induction Techniques: Does Earlier Sleep Interruption Reduce Lucid Dream Induction Rate?

Lucid dreaming offers the chance to investigate dreams from within a dream and by real-time dialogue between experimenters and dreamers during REM sleep. This state of consciousness opens a new experimental venue for dream research. However, laboratory study in this field is limited due to the rarity of lucid dreamers. In a previous study, we were able to induce in 50% of the participants a lucid dream in a single sleep laboratory night by combining a wake-up-back-to-bed (WBTB) sleep routine and a mnemonic method (Mnemonic Induction of Lucid Dreams, MILD). In three experiments, we tried to replicate our earlier findings while we adapted our procedure in shortening (Exp1–3: 4.5 vs. 6 h of uninterrupted sleep in the first half of the night), simplifying (Exp2: time-based wakening vs. REM wakening in the second half of the night), and applying another induction technique (Exp3: reality testing vs. MILD). In the three conditions, four out of 15 (26%), zero out of 20 (0%), and three out of 15 (20%) participants reported a lucid dream. Compared to the original study, the earlier sleep interruption seems to reduce the lucid dream induction rate. Furthermore, without REM awakenings in the morning, lucid dream induction failed, whereas reality testing showed a lower success rate compared to MILD. Further systematic sleep laboratory studies are needed to develop reliable techniques for lucid dream research

Short-course combination treatment for experimental chronic Chagas disease

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality. Current treatment options, benznidazole (BNZ) and nifurtimox, offer limited efficacy and often lead to adverse side effects because of long treatment durations. Better treatment options are therefore urgently required. Here, we describe a pyrrolopyrimidine series, identified through phenotypic screening, that offers an opportunity to improve on current treatments. In vitro cell-based washout assays demonstrate that compounds in the series are incapable of killing all parasites; however, combining these pyrrolopyrimidines with a subefficacious dose of BNZ can clear all parasites in vitro after 5 days. These findings were replicated in a clinically predictive in vivo model of chronic Chagas disease, where 5 days of treatment with the combination was sufficient to prevent parasite relapse. Comprehensive mechanism of action studies, supported by ligand-structure modeling, show that compounds from this pyrrolopyrimidine series inhibit the Qi active site of T. cruzi cytochrome b, part of the cytochrome bc1 complex of the electron transport chain. Knowledge of the molecular target enabled a cascade of assays to be assembled to evaluate selectivity over the human cytochrome b homolog. As a result, a highly selective and efficacious lead compound was identified. The combination of our lead compound with BNZ rapidly clears T. cruzi parasites, both in vitro and in vivo, and shows great potential to overcome key issues associated with currently available treatments.</p

Short-course combination treatment for experimental chronic Chagas disease

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality. Current treatment options, benznidazole (BNZ) and nifurtimox, offer limited efficacy and often lead to adverse side effects because of long treatment durations. Better treatment options are therefore urgently required. Here, we describe a pyrrolopyrimidine series, identified through phenotypic screening, that offers an opportunity to improve on current treatments. In vitro cell-based washout assays demonstrate that compounds in the series are incapable of killing all parasites; however, combining these pyrrolopyrimidines with a subefficacious dose of BNZ can clear all parasites in vitro after 5 days. These findings were replicated in a clinically predictive in vivo model of chronic Chagas disease, where 5 days of treatment with the combination was sufficient to prevent parasite relapse. Comprehensive mechanism of action studies, supported by ligand-structure modeling, show that compounds from this pyrrolopyrimidine series inhibit the Qi active site of T. cruzi cytochrome b, part of the cytochrome bc1 complex of the electron transport chain. Knowledge of the molecular target enabled a cascade of assays to be assembled to evaluate selectivity over the human cytochrome b homolog. As a result, a highly selective and efficacious lead compound was identified. The combination of our lead compound with BNZ rapidly clears T. cruzi parasites, both in vitro and in vivo, and shows great potential to overcome key issues associated with currently available treatments.</p

Short-course combination treatment for experimental chronic Chagas disease.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality. Current treatment options, benznidazole (BNZ) and nifurtimox, offer limited efficacy and often lead to adverse side effects because of long treatment durations. Better treatment options are therefore urgently required. Here, we describe a pyrrolopyrimidine series, identified through phenotypic screening, that offers an opportunity to improve on current treatments. In vitro cell-based washout assays demonstrate that compounds in the series are incapable of killing all parasites; however, combining these pyrrolopyrimidines with a subefficacious dose of BNZ can clear all parasites in vitro after 5 days. These findings were replicated in a clinically predictive in vivo model of chronic Chagas disease, where 5 days of treatment with the combination was sufficient to prevent parasite relapse. Comprehensive mechanism of action studies, supported by ligand-structure modeling, show that compounds from this pyrrolopyrimidine series inhibit the Qi active site of T. cruzi cytochrome b, part of the cytochrome bc1 complex of the electron transport chain. Knowledge of the molecular target enabled a cascade of assays to be assembled to evaluate selectivity over the human cytochrome b homolog. As a result, a highly selective and efficacious lead compound was identified. The combination of our lead compound with BNZ rapidly clears T. cruzi parasites, both in vitro and in vivo, and shows great potential to overcome key issues associated with currently available treatments

História versus teoria? A historiografia de Hobbes na teoria das relacoes internacionais

Uma dificuldade crucial no estudo das relações internacionais é unir investigação teórica com investigação histórica. O objetivo deste artigo é analisar como Hobbes enfrentou este problema, bem como em que medida a solução que apresentou influenciou a teoria das relações internacionais e permite ainda hoje resolver dificuldades desta disciplina. A primeira parte examina como Hobbes justifica seu método de pensar histórica e teoricamente ao mesmo tempo. A segunda parte mostra como Hobbes é recuperado no pós-Segunda Guerra tanto pela revisão do programa idealista como pelo emergente realismo, em ambos os casos a fim de criticar o idealismo do entreguerras. A terceira parte, tendo em vista o debate contemporâneo em relações internacionais, mostra como o neo-realismo, concentrando-se em tecnologias de poder, perde o interesse pela investigação histórica presente no realismo clássico; e o normativismo que se fortalece a partir dos anos 90, formulando uma justificada crítica à ausência de reflexão ética no neorealismo, recai muitas vezes em variantes do idealismo utópico. Em ambos há um déficit de investigação histórica, o que não permite analisar a contingência das relações sociais. Se o caráter predominantemente antropológico da historiografia de Hobbes, bem como o caráter predominantemente institucionalista de sua teoria do Estado e do Direito não podem mais ser aceitos, é seu modo de pensar ao mesmo tempo teórica e historicamente o legado e o desafio que nos deixa

Right out of the box: How to situate metaphysics of science in relation to other metaphysical approaches

Several advocates of the lively field of "metaphysics of science" have recently argued that a naturalistic metaphysics should be based solely on current science, and that it should replace more traditional, intuition-based, forms of metaphysics. The aim of the present paper is to assess that claim by examining the relations between metaphysics of science and general metaphysics. We show that the current metaphysical battlefield is richer and more complex than a simple dichotomy between "metaphysics of science" and "traditional metaphysics", and that it should instead be understood as a three dimensional "box", with one axis distinguishing "descriptive metaphysics" from "revisionary metaphysics," a second axis distinguishing a priori from a posteriori metaphysics, and a third axis distinguishing "commonsense metaphysics", "traditional metaphysics" and "metaphysics of science." We use this three-dimensional figure to shed light on the project of current metaphysics of science, and to demonstrate that, in many instances, the target of that project is not defined with enough precision and clarity