Depuis le début de la guerre contre le narcotrafic, des millions de personnes ont disparu au Mexique. Tandis que leurs familles ne cessent de les chercher, l’État s’obstine dans un récit manichéen ...qui minimise ou revictimise leur douleur. Une « dispute mémorielle » agite donc le pays, où les familles, organisées en collectifs, luttent pour obtenir justice et dignité. Dans l’État du Nuevo León, le FUNDENL (Fuerzas Unidas por Nuestros Desaparecidos en Nuevo León), l’un des collectifs les plus actifs, a choisi l’appropriation de l’espace public et l’installation d’un anti-monument afin de forcer l’État à reconnaître sa présence et ses revendications. Mais outre la reconnaissance officielle de la part de l’État, ces collectifs cherchent à solidariser le reste de la société civile à leur cause, afin que leur douleur soit vue comme un « trauma culturel ». Dans ce contexte, l’espace digital est un outil crucial dans l’activisme et la politisation citoyenne actuelle. L’artiviste Zahara Gómez Lucini crée donc avec le FUNDENL un dispositif de communication digitale afin d’établir des ponts entre les familles de victimes et le reste de la société civile. À travers l’émotion, l’empathie et l’identification permises par le dispositif musical du Cancionero para no olvidar, l’objectif est d’encourager les citoyens à se politiser et à agir autour des disparitions forcées, afin qu’elles soient reconnues comme un problème social et collectif.
Abstract
Study Objectives
Precision medicine for obstructive sleep apnea (OSA) requires noninvasive estimates of each patient’s pathophysiological “traits.” Here, we provide the first automated ...technique to quantify the respiratory arousal threshold—defined as the level of ventilatory drive triggering arousal from sleep—using diagnostic polysomnographic signals in patients with OSA.
Methods
Ventilatory drive preceding clinically scored arousals was estimated from polysomnographic studies by fitting a respiratory control model (Terrill et al.) to the pattern of ventilation during spontaneous respiratory events. Conceptually, the magnitude of the airflow signal immediately after arousal onset reveals information on the underlying ventilatory drive that triggered the arousal. Polysomnographic arousal threshold measures were compared with gold standard values taken from esophageal pressure and intraoesophageal diaphragm electromyography recorded simultaneously (N = 29). Comparisons were also made to arousal threshold measures using continuous positive airway pressure (CPAP) dial-downs (N = 28). The validity of using (linearized) nasal pressure rather than pneumotachograph ventilation was also assessed (N = 11).
Results
Polysomnographic arousal threshold values were correlated with those measured using esophageal pressure and diaphragm EMG (R = 0.79, p < .0001; R = 0.73, p = .0001), as well as CPAP manipulation (R = 0.73, p < .0001). Arousal threshold estimates were similar using nasal pressure and pneumotachograph ventilation (R = 0.96, p < .0001).
Conclusions
The arousal threshold in patients with OSA can be estimated using polysomnographic signals and may enable more personalized therapeutic interventions for patients with a low arousal threshold.
A possible precision-medicine approach to treating obstructive sleep apnoea (OSA) involves targeting ventilatory instability (elevated loop gain) using supplemental inspired oxygen in selected ...patients. Here we test whether elevated loop gain and three key endophenotypic traits (collapsibility, compensation and arousability), quantified using clinical polysomnography, can predict the effect of supplemental oxygen on OSA severity.36 patients (apnoea-hypopnoea index (AHI) >20 events·h
) completed two overnight polysomnographic studies (single-blinded randomised-controlled crossover) on supplemental oxygen (40% inspired)
sham (air). OSA traits were quantified from the air-night polysomnography. Responders were defined by a ≥50% reduction in AHI (supine non-rapid eye movement). Secondary outcomes included blood pressure and self-reported sleep quality.Nine of 36 patients (25%) responded to supplemental oxygen (ΔAHI=72±5%). Elevated loop gain was not a significant univariate predictor of responder/non-responder status (primary analysis). In
analysis, a logistic regression model based on elevated loop gain and other traits (better collapsibility and compensation; cross-validated) had 83% accuracy (89% before cross-validation); predicted responders exhibited an improvement in OSA severity (ΔAHI 59±6%
12±7% in predicted non-responders, p=0.0001) plus lowered morning blood pressure and "better" self-reported sleep.Patients whose OSA responds to supplemental oxygen can be identified by measuring their endophenotypic traits using diagnostic polysomnography.
Obstructive sleep apnoea (OSA) is characterised by pharyngeal obstruction occurring at different sites. Endoscopic studies reveal that epiglottic collapse renders patients at higher risk of failed ...oral appliance therapy or accentuated collapse on continuous positive airway pressure. Diagnosing epiglottic collapse currently requires invasive studies (imaging and endoscopy). As an alternative, we propose that epiglottic collapse can be detected from the distinct airflow patterns it produces during sleep.23 OSA patients underwent natural sleep endoscopy. 1232 breaths were scored as epiglottic/nonepiglottic collapse. Several flow characteristics were determined from the flow signal (recorded simultaneously with endoscopy) and used to build a predictive model to distinguish epiglottic from nonepiglottic collapse. Additionally, 10 OSA patients were studied to validate the pneumotachograph flow features using nasal pressure signals.Epiglottic collapse was characterised by a rapid fall(s) in the inspiratory flow, more variable inspiratory and expiratory flow and reduced tidal volume. The cross-validated accuracy was 84%. Predictive features obtained from pneumotachograph flow and nasal pressure were strongly correlated.This study demonstrates that epiglottic collapse can be identified from the airflow signal measured during a sleep study. This method may enable clinicians to use clinically collected data to characterise underlying physiology and improve treatment decisions.
β-Lapachone is an ortho-naphthoquinone originally isolated from the heartwood of Handroanthus impetiginosus and can be obtained through synthesis from lapachol, naphthoquinones, and other aromatic ...compounds. β-Lapachone is well known to inhibit topoisomerase I and to induce NAD(P)H: quinone oxidoreductase 1. Currently, phase II clinical trials are being conducted for the treatment of pancreatic cancer. In view of ever-increasing scientific interest in this naphthoquinone, herein, the authors present a review of the synthesis, physicochemical properties, biological activities, and toxicity of β-lapachone. This natural compound has shown activity against several types of malignant tumors, such as lung and pancreatic cancers and melanoma. Furthermore, this ortho-naphthoquinone has antifungal and antibacterial activities, underscoring its action against resistant microorganisms and providing anti-inflammatory, antiobesity, antioxidant, neuroprotective, nephroprotective, and wound-healing properties. β-Lapachone presents low toxicity, with no signs of toxicity against alveolar macrophages, dermal fibroblast cells, hepatocytes, or kidney cells.
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•The formation of ROS is the primary mechanism of β-lapachone against cancer cells.•The β-lapachone has shown antiviral, antiparasitic and antimicrobial effects.•Anti-inflammatory activities of β-lapachone may be due to synergistic mechanisms.•β-lapachone has potential therapeutic effects on obesity by the fat-browning effect.•β-Lapachone is able to suppress metastasis in vivo by several mechanisms.
Graphene oxide (GO) has been evaluated for application in environmental remediation and pollution control strategies. However, the side effects caused by the interactions of GO with classical ...pollutants in aquatic environments are still largely unknown. In this work, the ecotoxicological effects of GO, cadmium, zinc and the interactions between GO and these trace elements (co-exposure) were evaluated through acute toxicity tests and routine metabolism (i.e., oxygen consumption and ammonia excretion) in Palaemon pandaliformis (shrimp). After 96 h of exposure, GO did not present acute ecotoxicity at concentrations up to 5.0 mg L−1. However, the association of GO with Cd or Zn increased the toxicity of these trace elements as demonstrated by the decrease in LC50 values. The 96 h LC50 of Cd associated with GO was 1.7 times less than the 96 h LC50 of Cd alone. Similarly, the 96 h LC50 of Zn associated with GO was 1.8 times less than the 96 h LC50 of Zn alone. Additionally, the co-exposure of GO with trace elements impaired the routine metabolism of P. pandaliformis. Finally, the GO potentiated the ecotoxicological effects of Cd and Zn in the shrimp model. Future research on this emerging nanomaterial should focus on its use and disposal in aquatic ecosystems.
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•The impact of graphene oxide co-exposure with trace elements were studied for the first time in P. pandaliformis (shrimp).•Combined exposure of GO with Cd or Zn increased the acute lethal toxicity of these trace elements.•Routine metabolism (Oxygen and Ammonia) is a key bioindicator of sub-lethal toxicity effects.
The objective of the study was to assess the biological and mechanical characteristics of chitosan‐based scaffolds enriched by mineral phases and biomineralized in simulated body fluid (SBF) as a ...possible biomaterial for dentin regeneration. Thus, porous chitosan scaffolds were prepared by the mineral‐induced bubbling‐effect technique and subjected to biomineralization to create biomimetic scaffolds for dentin tissue engineering. Suspensions containing calcium hydroxide, nanohydroxyapatite, or β‐tricalcium phosphate were added to the chitosan (CH) solution and subjected to gradual freezing and freeze‐drying to obtain CHCa, CHnHA, and CHβTCP porous scaffolds, respectively, by the bubbling effect. Then, scaffolds were incubated in SBF for 5 days at 37°C, under constant stirring, to promote calcium‐phosphate (CaP) biomineralization. Scanning electron microscopy revealed increased pore size and porosity degree on mineral‐containing scaffolds, with CHCa and CHnHA presenting as round, well‐distributed, and with an interconnected pore network. Nevertheless, incubation in SBF disrupted the porous architecture, except for CHCaSBF, leading to the deposition of CaP coverage, confirmed by Fourier Transform Infrared Spectroscopy analyses. All mineral‐containing and SBF‐treated formulations presented controlled degradation profiles and released calcium throughout 28 days. When human dental pulp cells (HDPCs) were seeded onto scaffold structures, the porous and interconnected architecture of CHCa, CHnHA, and CHCaSBF allowed cells to infiltrate and spread throughout the scaffold structure, whereas in other formulations cells were dispersed or agglomerated. It was possible to determine a positive effect on cell proliferation and odontogenic differentiation for mineral‐containing formulations, intensely improved by biomineralization. A significant increase in mineralized matrix deposition (by 8.4 to 18.9 times) was observed for CHCaSBF, CHnHASBF, and CHβTCPSBF in comparison with plain CH. The bioactive effect on odontoblastic marker expression (ALP activity and mineralized matrix) was also observed for HDPCs continuously cultivated with conditioned medium obtained from scaffolds. Therefore, biomineralization of chitosan scaffolds containing different mineral phases was responsible for increasing the capacity for mineralized matrix deposition by pulpal cells, with potential for use in dentin tissue engineering.
Hydrothermal carbonization (HTC) is a thermochemical process carried out in an aqueous medium. It is capable of converting biomass into a solid, carbon-rich material (hydrochar), and producing a ...liquid phase (process water) which contains the unreactive feedstock and/or chemical intermediates from the carbonization reaction. The aim of this study was to evaluate the characteristics of process water generated by HTC from vinasse and sugarcane bagasse produced by sugarcane industry and to evaluate its toxicity to both marine (using
Artemia salina
as a model organism) and the terrestrial environment (through seed germination studies of maize, lettuce, and tomato). The experiments showed that concentrated process water completely inhibited germination of maize, lettuce, and tomato seeds. On the other hand, diluted process water was able to stimulate seedlings of maize and tomato and enhance root and shoot growth. For
Artemia
, the LC
50
indicated that the process water is practically non-toxic; however, morphological changes, especially damages to the digestive tube and antennas of
Artemia
, were observed for the concentration of 1000 mg C L
−1
.
Most chronic and acute lung diseases have no cure, leaving lung transplantation as the only option. Recent work has improved our understanding of the endogenous regenerative capacity of the lung and ...has helped identification of different progenitor cell populations, as well as exploration into inducing endogenous regeneration through pharmaceutical or biological therapies. Additionally, alternative approaches that aim at replacing lung progenitor cells and their progeny through cell therapy, or whole lung tissue through bioengineering approaches, have gained increasing attention. Although impressive progress has been made, efforts at regenerating functional lung tissue are still ineffective. Chronic and acute lung diseases are most prevalent in the elderly and alterations in progenitor cells with ageing, along with an increased inflammatory milieu, present major roadblocks for regeneration. Multiple cellular mechanisms, such as cellular senescence and mitochondrial dysfunction, are aberrantly regulated in the aged and diseased lung, which impairs regeneration. Existing as well as new human
in vitro
models are being developed, improved and adapted in order to study potential mechanisms of lung regeneration in different contexts. This review summarises recent advances in understanding endogenous as well as exogenous regeneration and the development of
in vitro
models for studying regenerative mechanisms.
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Benznidazole (BNZ), the only commercialized antichagasic drug, and the antifungal compound posaconazole (PCZ) have shown synergistic action in the therapy of Chagas disease, however ...both active pharmaceutical ingredients (APIs) exhibit low aqueous solubility potentially limiting their bioavailability and therapeutic efficacy. In this paper, we report for the first time the formation of a eutectic mixture as well as an amorphous solid solution of PCZ and BNZ (at the same characteristic ratio of 80:20wt%), which provided enhanced solubility and dissolution rate for both APIs. This eutectic system was characterized by DSC and the melting points obtained were used for the construction of a phase diagram. The preservation of the characteristic PXRD patterns and the IR spectra of the parent APIs, and the visualization of a characteristic eutectic lamellar crystalline microstructure using Confocal Raman Microscopy confirm this system as a true eutectic mixture. The PXRD result also confirms the amorphous nature of the prepared solid solution. Theoretical chemical analyses indicate the predominance of π-stacking interactions in the amorphous solid solution, whereas an electrostatic interaction between the APIs is responsible for maintaining the alternating lamellar crystalline microstructure in the eutectic mixture. Both the eutectic mixture and the amorphous solid solution happen to have a characteristic PCZ to BNZ ratio similar to that of their pharmacological doses for treating Chagas disease, thus providing a unique therapeutic combination dose with enhanced apparent solubility and dissolution rate.
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