A Potential Link to Skin Destruction and Metabolic Alterations

Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-α stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-α blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL- cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment

Using the Inelastic Background in Hard X-Ray Photoelectron Spectroscopy for a Depth-Resolved Analysis of the Cds / CU(In,GA)SE \u3c Inf \u3e 2 \u3c / Inf \u3e Interface

The inelastic background of hard x-ray photoelectron spectroscopy data is analyzed to paint a depth-resolved picture of the CdS/Cu(In,Ga)Se2 (CdS/CIGSe) layer structure. The CdS/CIGSe interface is the central component in next-generation chalcopyrite thin-film photovoltaic devices. By analyzing both, the (unscattered) core-level peaks and the inelastic background, and by varying the excitation photon energy from 2.1 up to 14 keV, we can derive photoemission information over a broad range of electron kinetic energies and, hence, sampling depths. With this complementary information, the CdS film thickness of a CdS/CIGSe interface can be accurately determined as a function of the CdS deposition time. For the thinner CdS films, the film thickness can be shown to vary laterally. Furthermore, small amounts of Se and process-related Rb can be detected in a thin (∼2 nm) surface layer of all investigated CdS films

Level-spacing distributions of the Gaussian unitary random matrix ensemble

Level-spacing distributions of the Gaussian Unitary Ensemble (GUE) of random matrix theory are expressed in terms of solutions of coupled differential equations. Series solutions up to order 50 in the level spacing are obtained, thus providing a very good description of the small-spacing part of the level-spacing distribution, which can be used to make comparisons with experimental or numerical data. The level-spacing distributions can be obtained by solving the system of differential equations numerically.Comment: The series expansions discussed in this paper are available as Mathematica code at http://mcs.open.ac.uk/ugg2/RMT/LevelSpacingGUE.m (16kB

Extracorporeal immune therapy with immobilized agonistic anti-Fas antibodies leads to transient reduction of circulating neutrophil numbers and limits tissue damage after hemorrhagic shock/resuscitation in a porcine model

Background: Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tissue damage after hemorrhagic shock/resuscitation. Methods: In a prospective controlled double-armed animal trial 24 Munich Mini Pigs (30.3 +/- 3.3 kg) were rapidly haemorrhaged to reach a mean arterial pressure (MAP) of 35 +/- 5 mmHg, maintained hypotensive for 45 minutes, and then were resuscitated with Ringer's solution to baseline MAP. With beginning of resuscitation 12 pigs underwent extracorporeal immune therapy for 3 hours (LIM group) and 12 pigs were resuscitated according to standard medical care (SMC). Haemodynamics, haematologic, metabolic, and organ specific damage parameters were monitored. Neutrophil infiltration was analyzed histologically after 48 and 72 hours. Lipid peroxidation, and apoptosis were specifically determined in lung, bowel, and liver. Results: In the LIM group, neutrophil counts were reduced versus SMC during extracorporeal immune therapy. After 72 hours, the haemodynamic parameters MAP and cardiac output (CO) were significantly better in the LIM group. Histological analyses showed reduction of shock-related neutrophil tissue infiltration in the LIM group, especially in the lungs. Lower amounts of apoptotic cells and lipid peroxidation were found in organs after LIM treatment. Conclusions: Transient Fas-directed extracorporeal immune therapy may protect from posthemorrhagic neutrophil tissue infiltration and tissue damage

Alkali treatments of Cu(In,Ga)Se2 thin‐film absorbers and their impact on transport barriers

We study the impact of different alkali post-deposition treatments by thermal admittance spectroscopy and temperature-dependent current-voltage (IVT) characteristics of high-efficiency Cu(In,Ga)Se2thin-film solar cells fabricated from low-temperature and high-temperature co-evaporated absorbers. Capacitance steps observed by admittance spectroscopy for all samples agree with the widely observed N1 signature and show a clear correlation to a transport barrier evident from IVT characteristics measured in the dark, indicating that defects are likely not responsible for these capacitance steps. Activation energies extracted from capacitance spectra and IVT characteristics vary considerably between different samples but show no concise correlation to the alkali species used in the post-deposition treatments. Numerical device simulations show that the transport barrier in our devices might be related to conduction band offsets in the absorber/buffer/window stack

Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa

BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors