Quantitative analysis of Tr1 lymphocytes in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is usually accompanied by a low-grade inflammatory phenomenon, which participates in the pathogenesis of different complications of this condition. The inflammatory response is under the regulation of different mechanisms, including T regulatory (Treg) lymphocytes. However, the possible role of type 1 T regulatory (Tr1) cells in T2DM has not been explored so far. AIM: To carry out a quantitative analysis of Tr1 lymphocytes and other immune cell subsets in patients with T2DM and correlate these results with clinical findings and treatments. MATERIALS AND METHODS: Sixty patients with T2DM and twenty-three healthy controls were included in the study. Biochemical and anthropometric variables were evaluated, and Tr1 lymphocytes (CD4+CD49+LAG-3+IL-10+) and other cell subsets (Th17, Th22 and Foxp3 + Treg cells) were analyzed in peripheral blood samples by multiparametric flow cytometry. RESULTS: Significant increased levels of Tr1 cells were detected in patients with severe and mild disease, compared to healthy controls. In addition, CD4+IL-10+ lymphocytes were also increased in patients with T2DM. In contrast, similar levels of Foxp3+ Treg cells, Th17 and Th22 lymphocytes were observed in patients and controls. Likewise, no significant associations were detected between Tr1 cell levels and different clinical and laboratory parameters. However, those patients receiving glucagon-like peptide-1 receptor agonists (GLP-1-RA) showed similar levels of Tr1 cells than healthy controls, and significant lower numbers than untreated patients. CONCLUSION: We observed an increase in Tr1 and CD4+IL10+ lymphocyte levels in T2DM. Moreover, GLP1-RA treatment was significantly associated with normalization of the Tr1 levels. This highlights another potential immune dysfunction in patients with T2DM, which could participate in the pathogenesis of this condition.

Characterization of the Clogging Transition in Vibrated Granular Media.

The existence of a transition from a clogged to an unclogged state has been recently proposed for the flow of macroscopic particles through bottlenecks in systems as diverse as colloidal suspensions, granular matter, or live beings. Here, we experimentally demonstrate that, for vibrated granular media, such a transition genuinely exists, and we characterize it as a function of the outlet size and vibration intensity. We confirm the suitability of the "flowing parameter" as the order parameter, and we find out that the rescaled maximum acceleration of the system should be replaced as the control parameter by a dimensionless velocity that can be seen as the square root of the ratio between kinetic and potential energy. In all the investigated scenarios, we observe that, for a critical value of this control parameter S_{c}, there seems to be a continuous transition to an unclogged state. The data can be rescaled with this critical value, which, as expected, decreases with the orifice size D. This leads to a phase diagram in the S-D plane in which clogging appears as a concave surface.

Estimating density limits for walking pedestrians keeping a safe interpersonal distancing.

With people trying to keep a safe distance from others due to the COVID-19 outbreak, the way in which pedestrians walk has completely changed since the pandemic broke out1,2. In this work, laboratory experiments demonstrate the effect of several variables-such as the pedestrian density, the walking speed and the prescribed safety distance-on the interpersonal distance established when people move within relatively dense crowds. Notably, we observe that the density should not be higher than 0.16 pedestrians per square meter (around 6 m2 per pedestrian) in order to guarantee an interpersonal distance of 1 m. Although the extrapolation of our findings to other more realistic scenarios is not straightforward, they can be used as a first approach to establish density restrictions in urban and architectonic spaces based on scientific evidence.

Nonergodicity in silo unclogging: Broken and unbroken arches.

We report an experiment on the unclogging dynamics in a two-dimensional silo submitted to a sustained gentle vibration. We find that arches present a jerking motion where rearrangements in the positions of their beads are interspersed with quiescent periods. This behavior occurs for both arches that break down and those that withstand the external perturbation: Arches evolve until they either collapse or get trapped in a stable configuration. This evolution is described in terms of a scalar variable characterizing the arch shape that can be modeled as a continuous-time random walk. By studying the diffusivity of this variable, we show that the unclogging is a weakly nonergodic process. Remarkably, arches that do not collapse explore different configurations before settling in one of them and break ergodicity much in the same way than arches that break down.

An instrument for studying granular media in low-gravity environment.

A new experimental facility has been designed and constructed to study driven granular media in a low-gravity environment. This versatile instrument, fully automatized, with a modular design based on several interchangeable experimental cells, allows us to investigate research topics ranging from dilute to dense regimes of granular media such as granular gas, segregation, convection, sound propagation, jamming, and rheology-all without the disturbance by gravitational stresses active on Earth. Here, we present the main parameters, protocols, and performance characteristics of the instrument. The current scientific objectives are then briefly described and, as a proof of concept, some first selected results obtained in low gravity during parabolic flight campaigns are presented.

Can nonalcoholic beer, silicon and hops reduce the brain damage and behavioral changes induced by aluminum nitrate in young male Wistar rats?

Aluminum consumption has been associated with various neurodegenerative diseases. Previous studies suggest that regular beer intake reverses the pro-oxidant and inflammatory statuses induced by aluminum nitrate intoxication. This paper aims to evaluate the in vitro antioxidant capacity and acetylcholinesterase inhibitory activity of non-alcoholic beer (NABeer), silicon or hops, as well as their effect on animal behavior (e.g. curiosity, immobilization, rearing, grooming, swimming) and brain antioxidant enzyme (activity and gene expression) and anti-inflammatory status in aluminum nitrate intoxicated rats. Male Wistar rats were divided into five groups: 1) Control, 2) Aluminum nitrate (450 µg/kg/day), 3) Aluminum nitrate plus NABeer, 4) Aluminum nitrate plus hops, and 5) Aluminum nitrate plus silicon. Hops showed the highest in vitro antioxidant capacity and silicon the highest anticholinesterase activity. In the Aluminum group the brain aluminum/silicon ratio increased with impairment of brain antioxidant and inflammatory statuses. NABeer, silicon and hops block the negative effect on the in vivo antioxidant and inflammatory statuses induced by Aluminum nitrate and improve swimming and rearing behavioral tests. The various positive results suggest that NABeer is useful as a functional multi-target drink in the prevention of some neurodegenerative events caused by aluminum intoxication. More studies are required to conclude present results.

Effects of Fiber Purified Extract of Carob Fruit on Fat Digestion and Postprandial Lipemia in Healthy Rats.

Increased postprandial lipemia is a cardiovascular disease (CVD) risk factor. Carob fruit extract (CFE) contains condensed tannins, and their intake has been inversely related to CVD. The objective was to evaluate the in vitro pancreatic lipase activity in the presence of CFE and the in vivo effect of CFE on postprandial lipemia of healthy Wistar rats in acute and subchronic digestibility studies and to relate it with changes in fat digestion and absorption. CFE significantly reduced pancreatic lipase activity. A peak delay and a dose-dependent decrease in plasma triglyceride and cholesterol areas under the curve were observed, effects that increased after the subchronic treatment. The levels of nondigested, nonabsorbed triglycerides of the remaining intestinal lumen fat were significantly higher in the maximum dose of CFE administrated versus the control ( P < 0.05). This study demonstrates for the first time the hypolipemic properties of CFE from the first administration, modifying postprandial lipemia by reducing the extents of fat digestion and absorption.

Slow relaxation dynamics of clogs in a vibrated granular silo.

We experimentally explore the vibration-induced unclogging of arches halting the flow in a two-dimensional silo. The endurance of arches is determined by carrying out a survival analysis of their breaking times. By analyzing the dynamics of two morphological variables, we demonstrate that arches evolve toward less regular structures and it seems that there may exist a certain degree of irregularity that the arch reaches before collapsing. Moreover, we put forward that σ (the standard deviation of all angles between consecutive beads) describes faithfully the morphological evolution of the arch. Focusing on long-lasting arches, we study σ calculating its two-time autocorrelation function and its mean-squared displacement. In particular, the apparent logarithmic increase of the correlation and the decrease of the mean-squared displacement of σ when the waiting time is increased reveal a slowing down of the dynamics. This behavior is a clear hallmark of aging phenomena and confirms the lack of ergodicity in the unclogging dynamics. Our findings provide new insights on how an arch tends to destabilize and how the probability that it breaks with a long sustained vibration decreases with time.

Clogging Transition of Vibration-Driven Vehicles Passing through Constrictions.

We report experimental results on the competitive passage of elongated self-propelled vehicles rushing through a constriction. For the chosen experimental conditions, we observe the emergence of intermittencies similar to those reported previously for active matter passing through narrow doors. Noteworthy, we find that, when the number of individuals crowding in front of the bottleneck increases, there is a transition from an unclogged to a clogged state characterized by a lack of convergence of the mean clog duration as the measuring time increases. It is demonstrated that this transition-which was reported previously only for externally vibrated systems such as colloids or granulars-appears also for self-propelled agents. This suggests that the transition should also occur for the flow through constrictions of living agents (e.g., humans and sheep), an issue that has been elusive so far in experiments due to safety risks.

A comprehensive approach to formulation of seaweed-enriched meat products: From technological development to assessment of healthy properties.

Meat consumption is influenced by various kinds of factors, among them health implications. Different strategies can be effective in developing meat-based functional foods. These basically entail reducing the presence of compounds with negative health implications and enhancing the presence of beneficial compounds. This article reviews a comprehensive model for the development of meat-based functional foods based on a presentation of the research achieved in terms of the design and development of qualitatively and quantitatively modified meat products (frankfurters, patties and restructured steaks). These were reformulated to incorporate nutrients associated with three different seaweeds (wakame-Undaria pinnatifida; nori-Porphyra umbilicalis; and sea spaghetti-Himanthalia elongata) as sources of bioactive substances, while simultaneously reducing sodium and fat and improving fatty acid profiles. Those seaweeds were chosen, because in terms of composition and health implications, abundance on Spanish coasts, relatively widespread consumption, and suitability in terms of flavour and colour they are better suited than others for use as ingredients in new products. It also discusses the consequences of the use of this type of meat-based functional foods (combination of pork meat and 5% of each seaweed with or without hypercholesterolaemic agent included in the diets) on growing animals (Wistar male rats), and their effects on different aspects of lipoprotein metabolism, oxidative stress and liver structure. This article, then, reports a comprehensive approach to the production of seaweed-enriched meat products, considering aspects of technological development aimed at achieving the functional effect.

Pedestrian collective motion in competitive room evacuation.

When a sizable number of people evacuate a room, if the door is not large enough, an accumulation of pedestrians in front of the exit may take place. This is the cause of emerging collective phenomena where the density is believed to be the key variable determining the pedestrian dynamics. Here, we show that when sustained contact among the individuals exists, density is not enough to describe the evacuation, and propose that at least another variable -such as the kinetic stress- is required. We recorded evacuation drills with different degrees of competitiveness where the individuals are allowed to moderately push each other in their way out. We obtain the density, velocity and kinetic stress fields over time, showing that competitiveness strongly affects them and evidencing patterns which have been never observed in previous (low pressure) evacuation experiments. For the highest competitiveness scenario, we detect the development of sudden collective motions. These movements are related to a notable increase of the kinetic stress and a reduction of the velocity towards the door, but do not depend on the density.

Fiber purified extracts of carob fruit decrease carbohydrate absorption.

The postprandial state plays a central role in the development and setting of chronic diseases. Condensed tannins (CT) are polyphenols with a known ability to modify carbohydrate digestion and absorption. The high concentration of CT in the pulp of carob fruit suggests a potential antidiabetic effect. The aim of this work was to analyze the in vitro and in vivo effects of carob fruit extract (CFE) on the digestion and absorption of carbohydrates. α-Glucosidase activity and glucose diffusion were tested in vitro using 0.5, 1, 2 and 5 mg mL-1 CFE concentrations. Two in vivo absorption studies, acute and subchronic, were carried out in four groups of 6 two-month-old male Wistar rats (control and CFE 25, 50 and 150 mg per kg b.w.), administering 1 mL of olive oil and 0.5 g per kg b.w. of glucose solution by oral gavage. CFE significantly inhibited α-glucosidase activity, through a competitive mechanism, from 1 mg mL-1, and also reduced glucose diffusion in a dose-dependent manner. In the acute study, CFE (50 and 150 mg per kg b.w.) significantly reduced the area under the curve (AUC) of blood glucose. Subchronic CFE administration induced further AUC decreases; and CFE at 150 mg per kg b.w. reduced sodium-glucose-linked transporter-1 (SGLT1) levels in the duodenum. This study demonstrates the hypoglycemic properties of CFE, highlighting its potential role as a suitable nutritional strategy in diabetic patients.

Stability of clogging arches in a silo submitted to vertical vibrations.

We present experimental results on the endurance of arches that block the outlet of a two-dimensional silo when subjected to vertical vibration. In a recent paper [C. Lozano et al., Phys. Rev. Lett. 109, 068001 (2012)], it was shown that the arch resistance against vibrations is determined by the maximum angle among those formed between each particle in the bridge and its two neighbors: the larger the maximum angle is, the weaker the bridge. It has also been reported that the breaking time distribution shows a power-law tail with an exponent that depends on the outlet size, the vibration intensity, and the load [I. Zuriguel et al., Sci. Rep. 4, 7324 (2014)]. Here we connect these previous works, demonstrating the importance of the maximum angle in the arch on the exponent of the breaking time distribution. Besides, we find that the acceleration needed to break an arch does not depend on the ramp rate of the applied acceleration, but it does depend on the outlet size above which the arch is formed. We also show that high frequencies of vibration reveal a change in the behavior of the arches that endure very long times. These arches have been identified as a subset with special geometrical features. Therefore, arches that cannot be broken by means of a given external excitation might exist.

Granular segregation driven by particle interactions.

We report the results of an experimental study of particle-particle interactions in a horizontally shaken granular layer that undergoes a second order phase transition from a binary gas to a segregation liquid as the packing fraction C is increased. By focusing on the behavior of individual particles, the effect of C is studied on (1) the process of cluster formation, (2) cluster dynamics, and (3) cluster destruction. The outcomes indicate that the segregation is driven by two mechanisms: attraction between particles with the same properties and random motion with a characteristic length that is inversely proportional to C. All clusters investigated are found to be transient and the probability distribution functions of the separation times display a power law tail, indicating that the splitting probability decreases with time.

Flow and clogging of a sheep herd passing through a bottleneck.

We present an experimental study of a flock passing through a narrow door. Video monitoring of daily routines in a farm has enabled us to collect a sizable amount of data. By measuring the time lapse between the passage of consecutive animals, some features of the flow regime can be assessed. A quantitative definition of clogging is demonstrated based on the passage time statistics. These display broad tails, which can be fitted by power laws with a relatively large exponent. On the other hand, the distribution of burst sizes robustly evidences exponential behavior. Finally, borrowing concepts from granular physics and statistical mechanics, we evaluate the effect of increasing the door size and the performance of an obstacle placed in front of it. The success of these techniques opens new possibilities regarding their eventual extension to the management of human crowds.

Flow-rate fluctuations in the outpouring of grains from a two-dimensional silo.

We present experimental results obtained with a two-dimensional silo discharging under gravity through an orifice at the flat bottom. High-speed measurements provide enough time resolution to detect every single bead that goes out and this allows the measurement of the flow rate in short-time windows. Two different regimes are clearly distinguished: one for large orifices, which can be described by Gaussian fluctuations, and another for small orifices, in which extreme events appear. The frontier between those two regimes coincides with the outlet size below which jamming events are frequent. Moreover, it is shown that the power spectrum of the flow-rate oscillations is not dominated by any particular frequency.

Anomalous diffusion in silo drainage.

The silo discharge process is studied by molecular dynamics simulations. The development of the velocity profile and the probability density function for the displacements in the horizontal and vertical axis are obtained. The PDFs obtained at the beginning of the discharge reveal non-Gaussian statistics and superdiffusive behaviors. When the stationary flow is developed, the PDFs at shorter temporal scales are non-Gaussian too. For big orifices a well-defined transition between ballistic and diffusive regime is observed. In the case of a small outlet orifice, no well-defined transition is observed. We use a nonlinear diffusion equation introduced in the framework of non-extensive thermodynamics in order to describe the movements of the grains. The solution of this equation gives a well-defined relationship (gamma = 2/(3 - q)) between the anomalous diffusion exponent gamma and the entropic parameter q introduced by the non-extensive formalism to fit the PDF of the fluctuations.

Convective motion in a vibrated granular layer.

Velocity measurements are presented for a vertically shaken granular layer. For frequencies around 110 Hz and accelerations larger than gravity, the layer develops a convective motion in the form of one or more rolls. The velocity of the grains near the wall has been measured. It grows linearly with the acceleration, then the growth rate slows down. A rescaling with the amplitude of the wall velocity and the height of the granular layer makes all data collapse in a single curve.

Local marangoni number at the onset of hydrothermal waves

We report the results of an experiment in which a layer of fluid, placed in a container open to the air, is subjected to a horizontal temperature difference DeltaT. The fluid height h is kept constant and both the horizontal temperature difference and the horizontal dimensions of the fluid layer are changed. In this configuration, when DeltaT goes beyond a certain threshold, waves propagating from the cold to the hot side appear (hydrothermal waves) with a determined group velocity. We study the influence of the container geometry on these waves. Close to the threshold, they are spatially localized near the hot side and a local Marangoni number is defined to describe this behavior. If DeltaT is further increased, the waves fill the whole fluid layer. We also find an agreement between our experimental results and theoretical works and simulations.