The reaction to social stress in social phobia: discordance between physiological and subjective parameters.

Research on the biopsychological background of social phobia (SP) is scarce and inconsistent. We investigated endocrine and autonomic markers along with subjective responses to a standardized stress situation (Trier Social Stress Test, TSST) in SP patients and healthy controls (HC).We examined 88 patients with the primary diagnosis of SP as well as 78 age and sex comparable HCs with the TSST. Blood and saliva samples were obtained before and after the TSST for the assessment of salivary cortisol, plasma cortisol, salivary alpha-amylase (sAA), and prolactin. Heart rate (HR) and heart rate variability (HRV) were recorded continuously. Scalp-near hair samples were collected for the assessment of long-term cortisol secretion. The self-reported stress response was measured with different state and trait scales.While self-reported anxiety was elevated in SP before, during, immediately after, and one week after the TSST, no significant differences in biological stress responses were observed between SP and HC. There was a trend for SP to show higher baseline stress markers. Also long-term cortisol deposition in hair remained unaltered.Our results suggest that the excessive self-reported stress in SP is not reflected by a respective biological stress response. Patients with SP apparently show neither an extreme form of focused fear reactivity nor excessive defensive impairment

Pressure drop particle precipitation from a quasi-incompressible, ternary and liquid mixture

We found a quasi-incompressible and liquid mixture of ibuprofen, water and acetone, that enables the crystallization of ibuprofen particles by decreasing the pressure from 15MPa to ambient pressure (~0.1MPa). We measured the solubility of ibuprofen in the mixture as a function of the acetone/water-ratio for pressures of 0.1MPa, 5.5MPa and 15MPa and at 308K using the cloud point method. Based on the solubilities, binodal compositions of the ternary system were modelled using the NRTL-SAC model. The solubility of the drug in the mixture increases with increasing pressure at constant acetone/water-ratio. This pressure sensitive solubility can be exploited for the crystallization of ibuprofen particles via a pressure-drop approach. A pressure-drop from 15MPa to ambient pressure (~0.1MPa) can result in a supersaturation of up to 1.43.The project leading to this contribution has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under ERC Starting Grant agreement No. 637654 (Inhomogeneities). The ICTS “Nanbiosis”, more specifically U6 Unit, unit of the CIBER in Bioengineering, Biomaterials & Nanomedicne (CIBER-BBN), is also acknowledged for the experimental information provided. The authors acknowledge funding from the Generalitat de Catalunya through the Centres de Recerca de Catalunya (CERCA) programme and grant 2017-SGR-918, from the Ministry of Economy and Competitiveness (MINECO) of Spain through grant PID2019–105622RB-I00 (MOL4BIO).Peer reviewe

Mean (±SEM) hair cortisol concentrations of patients with social phobia (SP) and healthy controls (HC).

<p>Mean (±SEM) hair cortisol concentrations of patients with social phobia (SP) and healthy controls (HC).</p

Means (±SEM) of salivary cortisol responders and non-responders to the TSST for social phobia patients (SP) and healthy controls (HC).

<p>Means (±SEM) of salivary cortisol responders and non-responders to the TSST for social phobia patients (SP) and healthy controls (HC).</p

Group characteristics of patients with social phobia (SP) and healthy controls (HC).

<p><i>Notes</i>: <i>T</i> = T-Test, <i>p</i> = p-value; df = degrees of freedom, <i>M</i> = mean, <i>SD</i> = standard deviation; BMI  =  body mass index; LSAS  =  Liebowitz Social Anxiety Scale; SPAI  =  Social Phobia Anxiety Inventory; TPQ  =  Tridimensional Personality Questionnaire; BDI  =  Beck Depression Inventory; d = disorder.</p>1<p>N = 165 because of one missing value.</p>2<p>N = 143 because of missing values.</p><p>* = <i>p</i><.05,</p><p>** = <i>p</i><0.01,</p><p>*** = <i>p</i><.001.</p

Means (±SD) of self-reported responses to the Trier Social Stress Test (TSST) in patients with social phobia (SP) and healthy controls (HC).

<p><i>Notes</i>: <i>T</i> =  T-Test, <i>p</i> = p-value; df  =  degrees of freedom, <i>M</i> =  mean, <i>S D</i> =  standard deviation; Ti  =  main effect of time; SP  =  main effect of diagnosis of social phobia; TixSP  =  interaction of time and diagnosis; MDBF  =  multidimensional mental-state questionnaire; Stai-S  =  state version of the State-Trait Anxiety Inventory; PASA  =  Primary Appraisal Secondary Appraisal questionnaire; VAS  =  visual analogue scales; PEPQ  =  Post Event Processing Questionnaire.</p><p>* = <i>p</i><.05,</p><p>** = <i>p</i><0.01,</p><p>*** = <i>p</i><.001.</p

Pressure-responsive, surfactant-free CO2‑based nanostructured fluids

Microemulsions are extensively used in advanced material and chemical processing. However, considerable amounts of surfactant are needed for their formulation, which is a drawback due to both economic and ecological reasons. Here, we describe the nanostructuration of recently discovered surfactant-free, carbon dioxide (CO2)-based microemulsion-like systems in a water/organic-solvent/CO2 pressurized ternary mixture. “Water-rich” nanodomains embedded into a “water-depleted” matrix have been observed and characterized by the combination of Raman spectroscopy, molecular dynamics simulations, and small-angle neutron scattering. These single-phase fluids show a reversible, pressure-responsive nanostructuration; the “water-rich” nanodomains at a given pressure can be instantaneously degraded/expanded by increasing/decreasing the pressure, resulting in a reversible, rapid, and homogeneous mixing/demixing of their content. This pressure-triggered responsiveness, together with other inherent features of these fluids, such as the absence of any contaminant in the ternary mixture (e.g., surfactant), their spontaneous formation, and their solvation capability (enabling the dissolution of both hydrophobic and hydrophilic molecules), make them appealing complex fluid systems to be used in molecular material processing and in chemical engineering.N.G. acknowledges the European Commission (EC) (FP7-PEOPLE-2013-Initial Training Networks (ITN) “‘NANO2FUN’” project no. 607721) for her Postdoctoral contract. A.S.B. thanks funding from the European Research Council under ERC starting grant agreement no. 637654. The authors appreciate the economical support from DGI, MINECO, Spain (Grant MAT2016-80826-R and “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV- 2015-0496)), and the Instituto de Salud Carlos III, through “Acciones CIBER”. The ICTS “Nanbiosis”, more specifically U6 Unit, is also acknowledged since some of the studies here reported have been performed there. Neutron beam time at the Institut Laue-Langevin (ILL) Grenoble, France, is acknowledged together with Dr. Thomas Sottmann, who has kindly provided the high-pressure cell used for SANS measurements. The authors acknowledge the valuable support of Julian Jonathan Schuster from FAU with respect to the processing of Raman spectra and the valuable help of David Bowyer during experiments at ILL.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Humoral immune responses mediate the development of a restrictive phenotype of chronic lung allograft dysfunction

Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 → parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human RAS lungs. Gene expression profiling revealed differential humoral immune cell activation as a key feature of the RAS murine model, with significant B cell and plasma cell infiltration noted in the RAS lung allografts. B6D2F1/J lung allografts transplanted into μMt-/- (mature B cell deficient) or activation-induced cytidine deaminase (AID)/secretory μ-chain (μs) double-KO (AID-/-μs-/-) C57BL/6J mice demonstrated significantly decreased allograft fibrosis, indicating a key role for antibody secretion by B cells in mediating RAS pathology. Our study suggests that skewing of immune responses determines the diverse allograft remodeling patterns and highlights the need to develop targeted therapies for specific CLAD phenotypes

Interleukin 6 trans‐signaling is a critical driver of lung allograft fibrosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168372/1/ajt16417.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168372/2/ajt16417_am.pd

Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using 111In-tilmanocept

Abstract Background Atherosclerotic plaque phenotypes are classified based on the extent of macrophage infiltration into the lesions, and the presence of certain macrophage subsets might be a sign for plaque vulnerability. The mannose receptor (MR) is over-expressed in activated macrophages. Tilmanocept is a tracer that targets MR and is approved in Europe and the USA for the detection of sentinel lymph nodes. In this study, our aim was to evaluate the potential of 111In-labelled tilmanocept for the detection of MR-positive macrophages in atherosclerotic plaques of apolipoprotein E-knockout (ApoE-KO) mouse model. Methods Tilmanocept was labelled with 111In. The labelling stability and biodistribution of the tracer was first evaluated in control mice (n = 10) 1 h post injection (p.i.). For in vivo imaging studies, 111In-tilmanocept was injected into ApoE-KO (n = 8) and control (n = 8) mice intravenously (i.v.). The mice were scanned 90 min p.i. using a dedicated animal SPECT/CT. For testing the specificity of 111In-tilmanocept uptake in plaques, a group of ApoE-KO mice was co-injected with excess amount of non-labelled tilmanocept. For ex vivo imaging studies, the whole aortas (n = 9 from ApoE-KO and n = 4 from control mice) were harvested free from adventitial tissue for Sudan IV staining and autoradiography. Cryosections were prepared for immunohistochemistry (IHC). Results 111In radiolabelling of tilmanocept provided a yield of greater than 99%. After i.v. injection, 111In-tilmanocept accumulated in vivo in MR-expressing organs (i.e. liver and spleen) and showed only low residual blood signal 1 h p.i. MR-binding specificity in receptor-positive organs was demonstrated by a 1.5- to 3-fold reduced uptake of 111In-tilmanocept after co-injection of a blocking dose of non-labelled tilmanocept. Focal signal was detected in atherosclerotic plaques of ApoE-KO mice, whereas no signal was detected in the aortas of control mice. 111In-tilmanocept uptake was detected in atherosclerotic plaques on autoradiography correlating well with Sudan IV-positive areas and associating with subendothelial accumulations of MR-positive macrophages as demonstrated by IHC. Conclusions After i.v. injection, 111In-tilmanocept accumulated in MR-expressing organs and was associated with only low residual blood signal. In addition, 111In-tilmanocept uptake was detected in atherosclerotic plaques of mice containing MR-expressing macrophages suggesting that tilmanocept represents a promising tracer for the non-invasive detection of macrophages in atherosclerotic plaques