Elastase, a serine proteinase released by activated human neutrophils, can degrade a wide variety of biomacromolecules including elastin, and is considered a marker of inflammatory diseases. As the logical strategy to protect tissue is to inhibit excessive elastase activity, experimental and clinical researches have concentrated on trying to find efficient elastase inhibitors. As thymol, one of the major components of thyme oil with a phenolic structure, has been credited with a series of pharmacological properties, that include antimicrobial and antioxidant effects, the aim of this study was to explore whether it can also interfere with the release of elastase by human neutrophils stimulated with the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). After the neutrophils were incubated with increasing amounts of thymol (2.5, 5, 10, 20 µg/ml), elastase release was initiated by fMLP and measured using MeO-Suc-Ala-Ala-Pro-Val-MCA. The results showed that thymol inhibited fMLP-induced elastase release in a concentration-dependent manner, with the effects of 10 and 20 µg/ml being statistically significant. The behavior of cytosolic calcium mobilization revealed by fura-2 closely resembled that of elastase, thus suggesting that they may be related. The hydrophobic nature of thymol means that it can approach ion channel proteins through the lipid phase of the membrane, alter the local environment of calcium channels and thus inhibit capacitative calcium entry. In brief, thymol inactivates calcium channels machinery, thus triggering a corresponding reduction in elastase. The antibacterial and antimycotic activity of thymol is already well known, but our findings that it inhibits elastase extend our knowledge of the anti-inflammatory activity of this interesting molecule that is already credited with antioxidant activity. These two latter characteristics make thymol a molecule that can have helpful effects in controlling the inflammatory processes present in many infections.

Las posibilidades que ofrecen las tecnologías son muchas, sin embargo, las personas mayores son a menudo incapaces de disfrutar de ellas plenamente, sintiéndose desanimadas o intimidadas por estos nuevos dispositivos. Esto les lleva a un progresivo aislamiento en una sociedad donde es esencial conocer las distintas formas de comunicación a través de Internet y las TIC. En este trabajo presentamos un estudio realizado durante el proyecto Nacodeal, cuyo objetivo es ofrecer una solución tecnológica para proporcionar autonomía y una mejor calidad de vida para las personas mayores durante sus actividades diarias mediante la integración de las TIC. Para lograr este objetivo se ha desarrollado tecnología puntera en realidad aumentada (RA), así como servicios de Internet e interfaces para dispositivos móviles especialmente diseñados para personas mayores. Estas tecnologías emplean la infraestructura presente en la mayoría de casas y centros de cuidados de mayores. Presentamos un prototipo de sistema compuesto por una tableta y un dispositivo de RA portátil, así como el análisis del impacto social en la interacción con usuarios y la valoración de la aceptación y usabilidad. Esta evaluación se llevó a cabo a través de grupos focales y pruebas piloto individuales con 48 participantes: ancianos, cuidadores y expertos. Sus comentarios concluyen que existen fuertes beneficios e intereses por parte de las personas mayores en las TIC asistenciales basadas en RA, especialmente en los aspectos relacionados con la comunicación y autonomíaModern technology offers many facilities, but elderly people are often unable to enjoy them fully because they feel discouraged or intimidated by modern devices, and thus become progressively isolated in a society where Internet communication and ICT knowledge are essential. In this paper we present a study performed during the Nacodeal Project, which aims to offer a technological solution that may improve elderly people’s every day autonomy and life quality through the integration of ICTs. In order to achieve this goal, state-of-art Augmented Reality technology was developed along with carefully designed Internet services and interfaces for mobile devices. Such technology only requires the infrastructure which already exists in most residences and healthcare centres. We present the design of a prototypical system consisting of a tablet and a wearable AR system, and the evaluation of its impact on the social interaction of its users as well its acceptance and usability. This evaluation was performed, through focus groups and individual pilot tests, on 48 participants that included elderly people, caregivers and experts. Their feedback leads us to the conclusion that there are significant benefits to be gained and much interest among the elderly in assistive AR-based ICTs, particularly in relation to the communication and autonomy that they may provid

The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg•kg −1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO 3 , 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.

Lactate's role in the brain is understood as a contributor to brain energy metabolism, but it may also regulate the cerebral microcirculation. The purpose of this systematic review was to evaluate evidence of lactate as a physiological effector within the normal cerebral microcirculation in reports ranging from in vitro experiments to in vivo studies in animals and humans. Following pre‐registration of a review protocol, we systematically searched the PubMed, EMBASE , and Cochrane databases for literature covering themes of ‘lactate’, ‘the brain’, and ‘microcirculation’. Abstracts were screened, and data extracted independently by two individuals. We excluded studies evaluating lactate in disease models. Twenty‐eight papers were identified, 18 of which were in vivo animal experiments (65%), four on human studies (14%), and six on in vitro or ex vivo experiments (21%). Approximately half of the papers identified lactate as an augmenter of the hyperemic response to functional activation by a visual stimulus or as an instigator of hyperemia in a dose‐dependent manner, without external stimulation. The mechanisms are likely to be coupled to NAD + / NADH redox state influencing the production of nitric oxide. Unfortunately, only 38% of these studies demonstrated any control for bias, which makes reliable generalizations of the conclusions insecure. This systematic review identifies that lactate may act as a dose‐dependent regulator of cerebral microcirculation by augmenting the hyperemic response to functional activation below 5 mmol/kg, and by initiating a hyperemic response above 5 mmol/kg. Open Science Badges This article has received a badge for * Pre‐registration * because it made the data publicly available. The data can be accessed at www.radboudumc.nl/getmedia/53625326-d1df-432c-980f-27c7c80d1a90/THollyer_lactate_protocol.aspx . The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/ .

Intracranial hypertension (IH) is a common feature of many pathologies, including brain edema. In the brain, the extended network of capillaries ensures blood flow to meet local metabolic demands. Capillary circulation may be severely affected by IH, but no studies have quantified the effect of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) on capillary perfusion during the development of brain edema. We used optical coherence tomography angiography to quantify relative changes of fractional perfused volume (FPV) in cortical capillaries and simultaneously monitored ICP and blood pressure (BP) in anesthetized male C57Bl/6NTac mice during development of brain edema induced by water intoxication (WI) within 30 min. WI induced severe IH and brain herniation. ICP and CPP reached 90.2 mm Hg and 38.4 mm Hg, respectively. FPV was significantly affected already at normal ICP (ICP <15 mm Hg, slope & -1.46, p < 0.001) and, at the onset of IH (ICP = 20-22 mm Hg), FPV was 17.9 -13.3% lower than baseline. A decreasing trend was observed until the ICP peak (D%FPV = -43.6 -19.2%). In the ICP range of 7-42 mm Hg, relative changes in FPV were significantly correlated with ICP, BP, and CPP ( p < 0.001), with ICP and CPP being the best predictors. In conclusion, elevated ICP induces a gradual collapse of the cerebral microvasculature, which is initiated before the clinical threshold of IH. In summary, the estimate of capillary perfusion might be essential in patients with IH to assess the state of the brain microcirculation and to improve the availability of oxygen and nutrients to the brain.