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Rheumatoid Arthritis (RA) is a chronic inflammatory disorder where incidence and severity of myocardial infarction are increased. Data on the incidence and outcome of stroke are conflicting. Thus, we investigated outcome after Ischemia/Reperfusion (I/R) brain injury in a mouse model of RA and assessed for the role of the tumour necrosis factor-α (TNF-α) inhibitor Infliximab herein. We used a TNF-α reliant mouse model of RA. RA and wildtype (WT) animals were treated with vehicle (RA/WT) or Infliximab (RA Infliximab) for 4 weeks, before undergoing I/R brain injury. RA-animals displayed larger strokes and poorer neurological performance. Immunohistochemistry on brain sections revealed increased numbers of resident and peripheral innate immune cells (microglia and macrophages); increased Blood-Brain-Barrier (BBB)-disruption; decreased levels of the tight junction proteins (TJPs) claudin-5 and occludin; increased expression of matrix-metalloproteinases (MMP)-3 and -9 and enhanced lipid peroxidation. Treatment with Infliximab corrected these alterations. We show that RA associates to worse stroke-outcome via exacerbated BBB degradation by decrease of the TJPs claudin-5 and occludin. We identified MMPs-3 and -9 and increased oxidative stress as potential mediators thereof. Increased numbers of resident and peripheral innate immune cells (microglia and macrophages) may in turn contribute to all these effects. Infliximab-treatment restored the phenotype of RA-mice to baseline. Our data provide evidence clearly linking RA to adverse stroke-outcome in mice and indicate an approved TNF-α inhibitor as a potential strategy to reduce stroke-burden in this setting.

Conservation of historical buildings is an important issue and the environmental conditions seriously affect the monument’s stones. The protection of cultural heritage buildings and monuments by surface treatment with polymers is a common practice due to their ability to form a protective layer on the monument’s surface as well as to control the transport of different fluids from the surface to the monument’s interior. In this work, three different substrates were used: Carrara marble, Botticino limestone, and Angera stone. A commercially available Si-based resin (Alpha ® SI30) was used as protective agent to improve the hydrophobicity features of the different tested materials. The surface properties of the coating and the relative interaction with the adopted stones were studied using different techniques such as contact angle measurements, electron microscope coupled with an energy dispersive spectrometer, X-ray photoelectron spectroscopy, atomic force microscopy, and attenuated total reflection infrared spectroscopy.

High-pressure phase transformations between the polymorphic forms I, II, III, and IIIb of CaCO 3 were investigated by analytical in situ high-pressure high-temperature experiments on oriented single-crystal samples. All experiments at non-ambient conditions were carried out by means of Raman scattering, X-ray, and synchrotron diffraction techniques using diamond-anvil cells in the pressure range up to 6.5 GPa. The composite-gasket resistive heating technique was applied for all high-pressure investigations at temperatures up to 550 K. High-pressure Raman spectra reveal distinguishable characteristic spectral differences located in the wave number range of external modes with the occurrence of band splitting and shoulders due to subtle symmetry changes. Constraints from in situ observations suggest a stability field of CaCO 3 -IIIb at relatively low temperatures adjacent to the calcite-II field. Isothermal compression of calcite provides the sequence from I to II, IIIb, and finally, III, with all transformations showing volume discontinuities. Re-transformation at decreasing pressure from III oversteps the stability field of IIIb and demonstrates the pathway of pressure changes to determine the transition sequence. Clausius–Clapeyron slopes of the phase boundary lines were determined as: Δ P /Δ T  = −2.79 ± 0.28 × 10 −3  GPa K −1 (I–II); +1.87 ± 0.31 × 10 −3  GPa K −1 (II/III); +4.01 ± 0.5 × 10 −3  GPa K −1 (II/IIIb); −33.9 ± 0.4 × 10 −3  GPa K −1 (IIIb/III). The triple point between phases II, IIIb, and III was determined by intersection and is located at 2.01(7) GPa/338(5) K. The pathway of transition from I over II to IIIb can be interpreted by displacement with small shear involved (by 2.9° on I/II and by 8.2° on II/IIIb). The former triad of calcite-I corresponds to the [20-1] direction in the P 2 1 / c unit cell of phase II and to [101] in the pseudomonoclinic C 1 ¯ setting of phase IIIb. Crystal structure investigations of triclinic CaCO 3 -III at non-ambient pressure–temperature conditions confirm the reported structure, and the small changes associated with the variation in P and T explain the broad stability of this structure with respect to variations in P and T . PVT equation of state parameters was determined from experimental data points in the range of 2.20–6.50 GPa at 298–405 K providing K T 0  = 87.5(5.1) GPa, ( δK T / δT) P  = −0.21(0.23) GPa K −1 , α 0  = 0.8(21.4) × 10 −5  K −1 , and α 1  = 1.0(3.7) × 10 −7  K −1 using a second-order Birch–Murnaghan equation of state formalism.

In situ high-pressure investigations on norsethite, BaMg(CO 3 ) 2 , have been performed in sequence of diamond-anvil cell experiments by means of single-crystal X-ray and synchrotron diffraction and Raman spectroscopy. Isothermal hydrostatic compression at room temperature yields a high-pressure phase transition at P c  ≈ 2.32 ± 0.04 GPa, which is weakly first order in character and reveals significant elastic softening of the high-pressure form of norsethite. X-ray structure determination reveals C 2 /c symmetry (Z = 4; a  = 8.6522(14) Å, b  = 4.9774(13) Å, c  = 11.1542(9) Å, β  = 104.928(8)°, V  = 464.20(12) Å 3 at 3.00 GPa), and the structure refinement ( R 1  = 0.0763) confirms a distorted, but topologically similar crystal structure of the so-called γ-norsethite, with Ba in 12-fold and Mg in octahedral coordination. The CO 3 groups were found to get tilted off the ab- plane direction by ~16.5°. Positional shifts, in particular of the Ba atoms and the three crystallographically independent oxygen sites, give a higher flexibility for atomic displacements, from which both the relatively higher compressibility and the remarkable softening originate. The corresponding bulk moduli are K 0  = 66.2 ± 2.3 GPa and d K/ d P  = 2.0 ± 1.8 for α-norsethite and K 0  = 41.9 ± 0.4 GPa and d K/ d P  = 6.1 ± 0.3 for γ-norsethite, displaying a pronounced directional anisotropy (α: β a −1  = 444(53) GPa, β c −1  = 76(2) GPa; γ: β a −1  = 5.1(1.3) × 10 3  GPa, β b −1  = 193(6) GPa β c −1  = 53.4(0.4) GPa). High-pressure Raman spectra show a significant splitting of several modes, which were used to identify the transformation in high-pressure high-temperature experiments in the range up to 4 GPa and 542 K. Based on the experimental series of data points determined by XRD and Raman measurements, the phase boundary of the α-to-γ-transition was determined with a Clausius–Clapeyron slope of 9.8(7) × 10 −3  GPa K −1 . An in situ measurement of the X-ray intensities was taken at 1.5 GPa and 411 K in order to identify the nature of the structural variation on increased temperatures corresponding to the previously reported transformation from α- to β-norsethite at 343 K and 1 bar. The investigations revealed, in contrast to all X-ray diffraction data recorded at 298 K, the disappearance of the superstructure reflections and the observed reflection conditions confirm the anticipated R 3 ¯ m space-group symmetry. The same superstructure reflections, which disappear as temperature increases, were found to gain in intensity due to the positional shift of the Ba atoms in the γ-phase.

Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in β-amyloid plaques. Active immunization with ankG of arcAβ transgenic mice reduced brain β-amyloid pathology and increased brain levels of soluble Aβ 42 . AnkG immunization induced a reduction in β-amyloid pathology, also in Swedish transgenic mice . Anti-ankG monoclonal antibodies reduced Aβ-induced loss of dendritic spines in hippocampal ArcAβ organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain β-amyloid and its related neuropathology.

This work is devoted to the characterization of a suite of very rare, highly decorated and coloured glass vessels and beads from the VII to the IV century BC. The most serious difficulty in developing this study was that any sampling – even micro-sampling – was absolutely forbidden. As a consequence, the mineralogical and chemical nature of chromophores and opacifiers present in these Iron Age finds were identified by means of the following synchrotron-based, strictly non-destructive, techniques: micro X-ray fluorescence (μ-XRF), Fe  K -edge micro X-ray absorption near edge spectroscopy (μ-XANES) and X-ray powder diffraction (XRPD). The μ-XRF mapping evidenced high levels of Pb and Sb in the yellow decorations and the presence of only Sb in the white and light-blue ones. Purple and black glass show high amounts of Mn and Fe, respectively. The XRPD analyses confirmed the presence of lead and calcium antimonates in yellow, turquoise and white decorations. Fe  K -edge μ-XANES spectra were collected in different coloured parts of the finds, thus enabling the mapping of the oxidation state of these elements across the samples. In most of the samples iron is present in the reduced form Fe 2+ in the bulk glass of the vessels, and in the oxidized form Fe 3+ in the decorations, indicating that these glass artefacts were produced in at least two distinct processing steps under different furnace conditions.

Microscopic, prismatic single crystals of synchysite-(Ce) from Cuasso al Monte (typical average composition Ca1.01Ce0.37Nd0.20Y0.17La0.09Pr0.05Sm0.05Gd0.03Th0.03(CO3)2F0.72) have been investigated by a variety of techniques, including single-crystal X-ray diffraction, Raman spectroscopy, scanning and transmission electron microscopy, and precession-assisted three-dimensional electron diffraction. The synchysite crystals are affected by an extraordinary abundance of diverse defects, such as stacking faults (polytypic disorder), core–rim chemical zoning, fluid and solid (hematite) inclusions, and metamict damage. Notwithstanding these faults, reliable X-ray crystal structure refinements have been obtained, which may enrich the currently scarce database. On the other hand, electron diffraction data, while remaining within acceptable limits, evidenced some challenges in refinement, even applying dynamical theory, potentially due to the impact of defects on data quality at the nanometre scale or absorption effects in such dense compounds, even in thin foils. The apparent polytypic disorder affecting the studied synchysite actually disguises an ordered superstructure, suggesting a crystal growth by screw dislocation. The nanostructural relationships between inclusions and host suggest that the crystals trapped a large number of fluid inclusions during growth, while hematite inclusion formed later, filling voids or fractures. The studied crystals are chemically zoned, with the core enriched in Ce, La and Nd; the rim enriched in Y; and the outer rim enriched in Th. The latter, undergoing α decay, induced radiation damage to the outer rim structure of the crystals.

The purpose of the study was to investigate the effect of inhaling 1600 μg of salbutamol (SAL) on 30 m sprint before and after the Yo-Yo Intermittent Recovery test. In a randomised cross over single blind study 13 male non-asthmatic, football players volunteered (mean ± SD; age 18.1 ± 0.9 years; weight 69.5 ± 8.3 kg; height 1.78 ± 0.07 m). Participants completed two visits and were randomly assigned to either (SAL) or (PLA) treatment and performed a set of three sprints of 30 m before and after the Yo-Yo Intermittent Recovery Test (Yo-Yo IRT). Best sprint and mean sprint were analysed in addition to the distance covered during the Yo-Yo IRT; rating of perceived exertion and heart rate were collected at the end of each level completed. Repeated measures ANOVA were performed to investigate changes in performance between groups. Following the inhalation of supra-therapeutic salbutamol dose (1600 μg) neither 30 m sprint time (PLA 4.43 ± 0.14 s; SAL 4.44 ± 0.15 s, p = 0.76) nor distance covered in the Yo-Yo IRT test reported significant variation between PLA conditions (1660 ± 217 m) and SAL (1610 ± 229 m, p = 0.16). Moreover, lactate values, heart rate and RPE did not differ significantly between groups. The inhalation of 1600 μg salbutamol does not enhance 30 m sprint performance in non-fatigued and fatigue conditions. Our findings suggest when football players acutely inhale double the permitted dose of salbutamol, as indicated in the World Anti-Doping Agency List of Prohibited Substances and Methods, they will not experience improvements in sprint or endurance performance.

The CaSiO3 system exhibits notable structural complexity, featuring different polymorphs and polytypes across various pressure (P) and temperature (T) conditions compatible with Earth's environments. Among these, the pseudowollastonite and breyite structures are characterized by the presence of threefold tetrahedral rings. In this study, we conducted multianvil syntheses in the pressure and temperature range 4–5 GPa and 600–800 °C to stabilize crystals of a new high-pressure polymorph reported by Chatterjee et al. (1984) and obtain structural information. The structure was solved by combining 3D electron diffraction (ED) and synchrotron single-crystal X-ray diffraction (SC-XRD). The new high-pressure polymorph, here referred to as parabreyite, features threefold tetrahedral rings, with a different configuration compared to breyite. Parabreyite is triclinic, P1‾, with unit cell parameters a= 8.1911(10) Å, b= 9.3441(9) Å, c= 10.4604(10) Å, α= 73.901(8)°, β= 89.814(9)° and γ= 77.513(9)°. The bulk modulus, K0= 90.7(5) GPa, was determined by an in situ SC-XRD experiment using a diamond anvil cell (DAC) in the pressure interval 0–10 GPa. Thermal expansion was also determined by low- and high-temperature SC-XRD measurements and resulted in a larger value compared to breyite. Additionally, we performed in situ synchrotron SC-XRD on synthetic pseudowollastonite in the pressure interval 0–14 GPa and did not observe any structural phase transition in this ring-type polymorph. We also report the differences between the Raman spectra of parabreyite and breyite to help with the in situ identification of these polymorphs. The threefold ring topology of parabreyite suggests a new configuration for high-density tetrahedra structures, with significant implications for the prediction of high-pressure sp3 carbonates.

Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder with exocrine pancreatic insufficiency, bone marrow failure and skeletal abnormalities. Patients frequently present failure to thrive, susceptibility to infections and short stature. A persistent or intermittent neutropenia occurs in 88–100% of patients. Bone marrow biopsy usually reveals a hypoplastic specimen with varying degrees of hypoplasia and fat infiltration. Some patients may develop myeloblastic syndrome and acute myeloblastic leukemia. The genetic defect in SDS has been identified in 2002. The osteoporosis is increased in patients with SDS, and also, bone malformations are included among the primary characteristics of the syndrome. The severity and location change with age and sexes. The typical characteristics include the following: secondary ossification centers delayed appearance, metaphysis enlargement and irregularity (very common in childhood, particularly in coastal and femur), growth cartilage progressive thinning and irregularity (possibly asymmetric growth), generalized osteopenia with cortical thinning. We describe a clinical case regarding an SDS patient with severe bone abnormalities and treated surgically for corrective osteotomy. The persistent or intermittent neutropenia that characterized this disease and the consequent risk of infection is a contraindication for short stature correction and limbs lengthening.