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Exosomes are promising therapeutics for tissue repair and regeneration to induce and guide appropriate immune responses in dystrophic pathologies. However, manipulating exosomes to control their biodistribution and targeting them in vivo to achieve adequate therapeutic benefits still poses a major challenge. Here we overcome this limitation by developing an externally controlled delivery system for primed annexin A1 myo-exosomes (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes to achieve controlled delivery and localization of Exomyo to skeletal muscles by systemic injection using an external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo from these ferromagnetic nanotubes in vivo to synergistically promote beneficial muscle responses in a murine animal model of Duchenne muscular dystrophy. Our findings provide insights into the development of exosome-based therapies for muscle diseases and, in general, highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.

Background: Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the pre-hospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage. Methods: Intracerebral hemorrhage was produced by stereotaxic injection of collagenase in Wistar rats. A randomized non-inferiority trial design was used to assign rats to HDT15° or flat position (n=64). HDT15° was applied for 1 hour during the time window of hematoma expansion. The primary outcome was hematoma volume at 24 hours. Secondary outcomes were mass effect, mortality and functional deficit in the main study and acute changes of intracranial pressure, hematoma growth and cardiorespiratory parameters in separate sets of randomized animals (n=32). Results: HDT15° achieved the specified criteria of non-inferiority for hematoma volume at 24 hours. Mass effect, mortality and functional deficit at 24 hours showed no difference in the two groups. HDT15° induced a mild increase in intracranial pressure with respect to the pre-treatment values (+ 2.91 +/- 1.76 mmHg). HDT15° had a neutral effect on MRI-based analysis of hematoma growth and cardiorespiratory parameters. Conclusions: Application of HDT15° in the hyperacute phase of experimental intracerebral hemorrhage does not worsen early outcome. Further research is needed to implement HDT15° as an emergency collateral therapeutic for acute stroke.

[PT] O uso de coagulantes naturais no tratamento de água é alternativo ao de sintéticos, possíveis causadores de toxicidade. Este trabalho avaliou a viabilidade do uso de extrato de babosa (Aloe arborescens) como coagulante para remoção de cor aparente e turbidez no tratamento convencional. Os ensaios foram realizados em jar test, com água bruta do rio São Tomás, estado de Goiás, Brasil, abrangendo os intervalos de 6.0 a 8.0 unidades de pH e de 0.025 a 10.0 mL L-1 de coagulante. Elaboraram-se diagramas de coagulação com as eficiências obtidas de cada um dos 72 pares de valores pH versus dose de coagulante e obtiveram-se remoções na água decantada de 36% para turbidez e 52% para cor aparente e na água filtrada de 68% para turbidez e 70% para cor aparente. As eficiências obtidas não foram suficientes para atender às exigências do padrão de potabilidade brasileiro para os parâmetros analisados., [EN] The use of natural coagulants in water treatment is an alternative to synthetic that can cause toxicity. This research evaluated the viability of utilizing Aloe arborescens as a coagulant for the removal of color and turbidity in conventional water treatment. The assays were performed in a jar test with water from the São Tomás River, State of Goiás, Brazil, which covers a pH range of 6.0 to 8.0, with coagulant concentrations of 0.025 to 10.0 mL L-1. The authors elaborated coagulation diagrams with the efficiencies obtained from each of the 72 pH values versus the coagulant doses and obtained a 36% reduction in turbidity and 52% reduction in apparent color with the decanted water and a 68% reduction in turbidity and 70% reduction in apparent color with the filtered water. The efficiencies for the parameters analyzed were not sufficient to meet the requirements of the Brazilian Potability Standard.