A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread

The lymphatic network that transports interstitial fluid and antigens to lymph nodes constitutes a conduit system that can be hijacked by invading pathogens to achieve systemic spread unless dissemination is blocked in the lymph node itself. Here, we show that a network of diverse lymphoid cells (natural killer cells, γδ T cells, natural killer T cells, and innate-like CD8+ T cells) are spatially prepositioned close to lymphatic sinus-lining sentinel macrophages where they can rapidly and efficiently receive inflammasome-generated IL-18 and additional cytokine signals from the pathogen-sensing phagocytes. This leads to rapid IFNγ secretion by the strategically positioned innate lymphocytes, fostering antimicrobial resistance in the macrophage population. Interference with this innate immune response loop allows systemic spread of lymph-borne bacteria. These findings extend our understanding of the functional significance of cellular positioning and local intercellular communication within lymph nodes while emphasizing the role of these organs as highly active locations of innate host defense

Residues and dissipation kinetics of two imidacloprid nanoformulations on bean (Phaseolus vulgaris L.) under field conditions

The current study investigates the dissipation kinetics of two imidacloprid (IMI) nanoformulations (entitled: Nano-IMI and Nano-IMI/TiO2) on common bean (Phaseolus vulgaris) seeds under field conditions and compares them with 35% Suspension Concentrate (SC) commercial formulation. To do so, it sprays P. vulgaris plants at 30 and 60 g/ha within green bean stage, sampling them during the 14-day period after the treatment. Following extraction and quantification of IMI residues, dissipation data have been fitted to simple-first order kinetic model (SFOK) and to first-order double-exponential decay (FODED) models, with 50% and 90% dissipation times (DT50 and DT90, respectively) assessed along the pre-harvest interval (PHI). With the exception of Nano-IMI at 60 g/ha, other decline curves are best fitted to the FODED model. In general, dissipation is faster for Nano-IMI (at 30 g/ha: DT50 = 1.09 days, DT90 = 4.30 days, PHI = 1.23 days; at 60 g/ha: DT50 = 1.29 days, DT90 = 4.29 days, PHI = 2.95 days) and Nano-IMI/TiO2 (at 30 g/ha: DT50 = 1.15 days, DT90 = 4.40 days, PHI = 1.08 days; at 60 g/ha: DT50 = 0.86 days, DT90 = 4.92 days, PHI = 3.02 days), compared to 35% SC (at 30 g/ha: DT50 = 1.58, DT90 = 6.45, PHI = 1.93; at 60 g/ha: DT50 = 1.58 days, DT90 = 14.50 days, PHI = 5.37 days). These results suggest the suitability of Nano-IMI and Nano-IMI/TiO2 application at both rates in terms of their residues on P. vulgaris seeds

Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function inflammed tissues

Activated T cells must mediate effector responses sufficient to clear pathogens while avoiding excessive tissue damage. Here we have combined dynamic intravital microscopy with ex vivo assessments of T cell cytokine responses to generate a detailed spatiotemporal picture of CD4+ T cell effector regulation in the skin. In response to antigen, effector T cells arrested transiently on antigen presenting cells, briefly producing cytokine and then resuming migration. Antigen recognition led to PD-1 upregulation of the programmed death-1 (PD-1) glycoprotein by T cells and blocking its canonical ligand, programmed death-ligand 1 (PD-L1), lengthened the duration of migration arrest and cytokine production, showing that PD-1 interaction with PD-L1 is a major negative feedback regulator of antigen responsiveness. We speculate that the immune system employs a mechanism involving T cell recruitment, transient activation, and rapid desensitization, allowing the T cell response to rapidly adjust to changes in antigen presentation and minimize collateral injury to the host

The effect of zinc sulphate syrup on children's respiratory tract infections

BACKGROUND AND OBJECTIVE: After Iron, zinc is the second most abundant trace element in the body that is present in all organs, tissues and body fluids. It is a necessary component for maintaining immunological integrity antioxidant activity, and has critical role in the control and prevention of infection. The aim of this study was to investigate the effect of zinc sulphate syrup in treatment of children with respiratory tract infection. METHODS: In this randomized clinical trial study, one hundred and twenty four children with respiratory infection (62 in case and 62 in control group) from pediatric ward of Hajar hospital of Sharekord university enrolled. Both groups received standard treatment. In addition to, zinc sulphate syrup was given to case group and placebo to control group. Respiratory rate, bed and cough and fever duration were compared between the case and control groups (IRCT: 201103025951N1). FINDINGS: The mean duration of fever in the case group was 2.6±0.82 days and in the control group 4±1.5 days (p<0.001). The mean of bed duration in the case group was 4.7±1.5 days and in the control group 5±1.8 days (p=0.42). The mean of cough duration in the case and control groups was 3.4±1.3 and 4.7±1.6 days respectively (p=0.09). Respiratory rate in the case group was 28.3±4.3 and in the control 28.1±4.9 (p=0.77). CONCLUSION: The study showed that zinc supplementation has a beneficial effect in decreasing the fever duration in children with respiratory infection. But there was no significant effect on respiratory rate, duration of bed and cough

Spatial modeling of individual-level infectious disease transmission: Tuberculosis data in Manitoba, Canada

Geographically dependent individual level models (GD-ILMs) are a class of statistical models that can be used to study the spread of infectious disease through a population in discrete-time in which covariates can be measured both at individual and area levels. The typical ILMs to illustrate spatial data are based on the distance between susceptible and infectious individuals. A key feature of GD-ILMs is that they take into account the spatial location of the individuals in addition to the distance between susceptible and infectious individuals. As a motivation of this article, we consider tuberculosis (TB) data which is an infectious disease which can be transmitted through individuals. It is also known that certain areas/demographics/communities have higher prevalent of TB (see Section 4 for more details). It is also of interest of policy makers to identify those areas with higher infectivity rate of TB for possible preventions. Therefore, we need to analyze this data properly to address those concerns. In this article, the expectation conditional maximization algorithm is proposed for estimating the parameters of GD-ILMs to be able to predict the areas with the highest average infectivity rates of TB. We also evaluate the performance of our proposed approach through some simulations. Our simulation results indicate that the proposed method provides reliable estimates of parameters which confirms accuracy of the infectivity rates

Brazilian disk tests: Circular holes and size effects

Abstract Size effects related to circular notched samples imply that the strength of the structure decreases as the hole radius increases. In this framework, Brazilian disk tests are carried out on brittle samples containing a circular hole. By considering two different polymers, namely Polymethyl-methacrylate (PMMA) and General-purpose Polystyrene (GPPS), respectively, five different notch radii were machined and tested for each material, keeping low the hole to disk diameter ratio in order to reproduce an infinite geometry. Under this assumption, analytical relationship for the stress field and the stress intensity factor can be implemented without loss of accuracy. The coupled finite fracture mechanics (FFM) is then applied to catch the recorded failure stresses, allowing a complete description of the experimental size effects. On the contrary, the smallest radius leads to a locally negative geometry, opening the discussion on the stability of crack propagation in circularly notched plates under generic biaxial loadings

Using the equivalent material concept and the average strain energy density to analyse the fracture behaviour of structural materials

ABSTRACT: This paper provides a complete overview of the applicability of the Equivalent Material Concept in conjunction with the Average Strain Energy Density criterion, to provide predictions of fracture loads in structural materials containing U-notches. The Average Strain Density Criterion (ASED) has a linear-elastic nature, so in principle, it does not provide satisfactory predictions of fracture loads in those materials with nonlinear behaviour. However, the Equivalent Material Concept (EMC) is able to transform a physically nonlinear material into an equivalent linear-elastic one and, therefore, the combination of the ASED criterion with the EMC (EMC?ASED criterion) should provide good predictions of fracture loads in physically nonlinear materials. The EMC?ASED criterion is here applied to different types of materials (polymers, composites and metals) with different grades of nonlinearity, showing the accuracy of the corresponding fracture load predictions and revealing qualitatively the limitations of the methodology. It is shown how the EMC?ASED criterion provides good predictions of fracture loads in nonlinear materials as long as the nonlinear behaviour is mainly limited to the tensile behaviour, and how the accuracy decreases when the nonlinear behaviour is extended to the material behaviour in the presence of defectsFunding: This research was funded by the Spanish Ministry of Science, Innovation and Universities, grant number PGC2018-095400-B-I00 (MCIU/AEI/FEDER, UE)

Classical and delayed orthostatic hypotension in patients with unexplained syncope and severe orthostatic intolerance

Background: Orthostatic hypotension (OH) is a major sign of cardiovascular autonomic failure leading to orthostatic intolerance and syncope. Orthostatic hypotension is traditionally divided into classical OH (cOH) and delayed OH (dOH), but the differences between the two variants are not well-studied. We performed a systematic clinical and neuroendocrine characterization of OH patients in a tertiary syncope unit. Methods: Among 2,167 consecutive patients (1,316 women, 60.7%; age, 52.6 ± 21.0 years) evaluated for unexplained syncope and severe orthostatic intolerance with standardized cardiovascular autonomic tests including head-up tilt (HUT), we identified those with a definitive diagnosis of cOH and dOH. We analyzed patients' history, clinical characteristics, hemodynamic variables, and plasma levels of epinephrine, norepinephrine, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1, mid-regional-fragment of pro-atrial-natriuretic-peptide and pro-adrenomedullin in the supine position and at 3-min HUT. Results: We identified 248 cOH and 336 dOH patients (27% of the entire cohort); 111 cOH and 152 dOH had blood samples collected in the supine position and at 3-min HUT. Compared with dOH, cOH patients were older (68 vs. 60 years, p < 0.001), more often male (56.9 vs. 39.6%, p < 0.001), had higher systolic blood pressure (141 vs. 137 mmHg, p = 0.05), had lower estimated glomerular filtration rate (73 vs. 80 ml/min/1.73 m2, p = 0.003), more often pathologic Valsalva maneuver (86 vs. 49 patients, p < 0.001), pacemaker-treated arrhythmia (5 vs. 2%, p = 0.04), Parkinson's disease (5 vs. 1%, p = 0.008) and reported less palpitations before syncope (16 vs. 29%, p = 0.001). Supine and standing levels of CT-proAVP were higher in cOH (p = 0.022 and p < 0.001, respectively), whereas standing norepinephrine was higher in dOH (p = 0.001). After 3-min HUT, increases in epinephrine (p < 0.001) and CT-proAVP (p = 0.001) were greater in cOH, whereas norepinephrine increased more in dOH (p = 0.045). Conclusions: One-quarter of patients with unexplained syncope and severe orthostatic intolerance present orthostatic hypotension. Classical OH patients are older, more often have supine hypertension, pathologic Valsalva maneuver, Parkinson's disease, pacemaker-treated arrhythmia, and lower glomerular filtration rate. Classical OH is associated with increased vasopressin and epinephrine during HUT, but blunted increase in norepinephrine