Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression.

BACKGROUND: Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. METHODS: 51 depressed participants (HDRS score > 13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. RESULTS: We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r = 0.28, p = 0.02), prefrontal cortex (r = 0.24, p = 0.04), and insular cortex (r = 0.24, p = 0.04), but not with the peripheral inflammatory markers: CRP levels (r = 0.07, p = 0.53), IL-6 (r = -0.08, p = 0.61), and TNF-α (r = -0.06, p = 0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r = 0.34, p = 0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. CONCLUSION: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component

Superhard CrN/MoN films with multilayer architecture

Main regularities of the formation of microstructure and properties ofmultilayer nanostructured CrN/MoN films with periodically changing architecture of layers were considered. Coatings were fabricated by vacuum-arc evaporation of the cathodes (Arc-PVD) in nitrogen atmosphere (pN was 0.4, 0.09 and 0.03 Pa). CrN and γ-Mo2N nitride phases with fcc lattices and a small volume of metastable MoNx cubic phase were formed in the films at pN = 0.4 Pa. The decrease of pN to 0.09 Pa causes the formation of β-Cr2N hexagonal phase. Preferential crystallographic orientation changes from [311] to [111] and [200] when bias voltage Ub is −20, −150 and −300 V respectively. The nanocrystallites size in coatings with bilayer thickness λ = 44 nm decreases to 5.8 nm. The microdeformation grows from 0.4 to 2.3% when Ub changes to −20 V. Coatings show high hardness of 38–42 GPa and H/E = 0.107. In a couple with results of tribological tests, coatings demonstrate strong wear resistance, which makes them appropriate and promising for industrial applications as protective ones. The effect of deposition conditions (pN, Ub, λ) on composition, structure, hardness, toughness and wear resistance was studied to achieve superior mechanical and physical properties of coatings with long lifetime in harsh environment.State budget programs of Ukraine, grant numbers 0116U002621, 0115U000682, 0116U006816; SFRH/BD/ 129614/2017; NORTE-01-0145-FEDER-022096info:eu-repo/semantics/publishedVersio

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy respons

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Analyzing the Throughput and QoS Performance of WiMAX Link in an Urban Environment

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Do weight bearing radiographs estimate the stability of an isolated distal fibula fracture?

Category: Trauma Introduction/Purpose: Differentiating stable isolated fibula fractures consistent with supination external rotation (SER) II ankle fractures from unstable SER IV fractures is essential in determining the need for surgical stabilisation. Stress radiographs are usually required to assess stability including gravity stress views (GSV) and external rotation views (ER). There is no clear consensus as to which modality is most useful to determine stability in a fracture clinic or emergency setting. In last, few years clinical uncertainty about the reliability has led researcher to focus on weight bearing radiographs (WB) .We aim to review recent literature regarding reliability of WB radiographs to estimate the stability of supination external rotation ankle fractures. Methods: A systematic review of the literature relating to radiological assessment of stability of supination external rotation ankle fractures was conducted according to PRISMA guidelines. The systematic review was prospectively registered with PROSPERO. It involved the following steps: Researching the question-Do weight bearing radiographs estimate the stability of an isolated distal fibula fracture? Setting inclusion and exclusion criteria-All English language articles published in the including any Randomised controlled trials (RCT’s) and cohort studies. Data collection)– A literature search of Medline (PubMed), the Cochrane Bone, Joint, and Muscle Trauma Group trial register, the Cochrane central register of controlled trials, Embase and CINAHL was undertaken. The grey literature was searched. Key terms ‘supination external rotation fracture’, ‘stability’. Other variations to the key words were ‘weight bearing’, “axial load”, ‘stress x-rays’, ‘systematic reviews’ and ‘meta-analysis’. Results: A total of six studies met the inclusion criteria including 601 patients. No previous systematic review on stress radiographs including weight bearing was published. All studies concluded weight bearing radiographs is an easy, pain-free, safe and reliable method to estimate stability of isolated distal fibula fractures. No serious concerns or complications were reported. Conclusion: The evidence base contained many methodological limitations and most of the evidence was either level III or IV, and so any conclusion drawn from the research must be done so with caution. The studies suggest that GSV overestimates the instability which should be assessed with studies should focus on randomized controlled trials with narrow range of clinically useful outcome measures

Modifications in surface, structural and mechanical properties of brass using laser induced Ni plasma as an ion source

Laser induced Ni plasma has been employed as source of ion implantation for surface, structural and mechanical properties of brass. Excimer laser (248 nm, 20 ns, 120mJ and 30 Hz) was used for the generation of Ni plasma. Thomson parabola technique was employed to estimate the energy of generated ions using CR39 as a detector. In response to stepwise increase in number of laser pulses from 3000 to 12000, the ion dose varies from 60 × 1013 to 84 × 1016 ions/cm2 with constant energy of 138 KeV. SEM analysis reveals the growth of nano/micro sized cavities, pores, pits, voids and cracks for the ion dose ranging from 60 × 1013 to 70 × 1015 ions/cm2. However, at maximum ion dose of 84 × 1016 ions/cm2 the granular morphology is observed. XRD analysis reveals that new phase of CuZnNi (200) is formed in the brass substrate after ion implantation. However, an anomalous trend in peak intensity, crystallite size, dislocation line density and induced stresses is observed in response to the implantation with various doses. The increase in ion dose causes to decrease the Yield Stress (YS), Ultimate Tensile Strength (UTS) and hardness. However, for the maximum ion dose the highest values of these mechanical properties are achieved. The variations in the mechanical properties are correlated with surface and crystallographical changes of ion implanted brass