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Background and Aims: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic. Methods: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel. Results: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age – 35.2 ± 13.5 years, disease duration – 7.1 (interquartile range: 3.7–13.9) years; Crohn’s disease – 94/118 (79.6%). Skin eruption induced by an anti–tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) – 31/46 (67.4%) and inflammatory alopecia (IA) – 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P = .09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P = NS). Conclusion: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab.

Ehlers–Danlos syndromes (EDS) are a group of connective tissue disorders caused by mutations in collagen and collagen-interacting genes. We delineate a novel form of EDS with vascular features through clinical and histopathological phenotyping and genetic studies of a three-generation pedigree, displaying an apparently autosomal dominant phenotype of joint hypermobility and frequent joint dislocations, atrophic scarring, prolonged bleeding time and age-related aortic dilatation and rupture. Coagulation tests as well as platelet counts and function were normal. Reticular dermis displayed highly disorganized collagen fibers and transmission electron microscopy (TEM) revealed abnormally shaped fibroblasts and endothelial cells, with high amount and irregular shape of extracellular matrix (ECM) substance, especially near blood vessels. Genetic analysis unraveled a heterozygous mutation in THBS2 (NM_003247.5:c.2686T>C, p.Cys896Arg). We generated CRISPR/Cas9 knock-in (KI) mice, bearing the heterozygous human mutation in the mouse ortholog. The KI mice demonstrated phenotypic traits correlating with those observed in the human subjects, as evidenced by morphologic, histologic, and TEM analyses, in conjunction with bleeding time assays. Our findings delineate a novel form of human EDS with classical-like elements combined with vascular features, caused by a heterozygous THBS2 missense mutation. We further demonstrate a similar phenotype in heterozygous THBS2Cys896Arg KI mice, in line with previous studies in Thbs2 homozygous null-mutant mice. Notably, THBS2 encodes Thrombospondin-2, a secreted homotrimeric matricellular protein that directly binds the ECM-shaping Matrix Metalloproteinase 2 (MMP2), mediating its clearance. THBS2 loss-of-function attenuates MMP2 clearance, enhancing MMP2-mediated proteoglycan cleavage, causing ECM abnormalities similar to those seen in the human and mouse disease we describe.

Background Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial β-oxidation. Methods We evaluated the ¹³C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and ¹³C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with ¹³C-OBT and ¹³C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). Results Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P < 0.05), using MBID but not ¹³C-octanoate. Conclusions OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.

Background Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial [beta]-oxidation. Methods We evaluated the .sup.13C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and .sup.13C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with .sup.13C-OBT and .sup.13C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). Results Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P < 0.05), using MBID but not .sup.13C-octanoate. Conclusions OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.

Power spectra of segmentation-cell length (a dominant length scale of EUV emission in the transition region) from full-disk He  ii extreme ultraviolet (EUV) images observed by the Extreme ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory (SOHO) and the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO) during periods of quiet-Sun conditions for a time interval from 1996 to 2015 were analyzed. The spatial power as a function of the spatial frequency from about 0.04 to 0.27 (EIT) or up to 0.48 (AIA) Mm −1 depends on the distribution of the observed segmentation-cell dimensions – a structure of the solar EUV network. The temporal variations of the spatial power reported by Didkovsky and Gurman ( Solar Phys. 289 , 153, 2014 ) were suggested as decreases at the mid-spatial frequencies for the compared spectra when the power curves at the highest spatial frequencies of 0.5 pix −1 were adjusted to match each other. This approach has been extended in this work to compare spectral ratios at high spatial frequencies expressed in the solar spatial frequency units of Mm −1 . A model of EIT and AIA spatial responses allowed us to directly compare spatial spectral ratios at high spatial frequencies for five years of joint operation of EIT and AIA, from 2010 to 2015. Based on this approach, we represent these ratio changes as a long-term network transformation that may be interpreted as a continuous dissipation of mid-size network structures to the smaller-size structures in the transition region. In contrast to expected cycling of the segmentation-cell dimension structures and associated spatial power in the spectra with the solar cycle, the spectra demonstrate a significant and steady change of the EUV network. The temporal trend across these structural spectra is not critically sensitive to any long-term instrumental changes, e.g. degradation of sensitivity, but to the change of the segmentation-cell dimensions of the EUV network structure.

Power spectra of segmentation-cell length (a dominant length scale of EUV emission in the transition region) from full-disk HeII extreme ultraviolet (EUV) images observed by the Extreme ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory (SOHO) and the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO) during periods of quiet Sun conditions for a time interval from 1996 to 2015 were analyzed. The spatial power as a function of the spatial frequency from about 0.04 to 0.27 (EIT) or up to 0.48 (AIA) 1/Mm depends on the distribution of the observed segmentation-cell dimensions, -- a structure of the solar EUV network. The temporal variations of the spatial power reported by Didkovsky and Gurman (Solar Phys., 289, 153) were suggested as decreases at the mid-spatial frequencies for the compared spectra when the power curves at the highest spatial frequencies of 0.5 1/pix were adjusted to match each other. That approach has been extended in this work to compare spectral ratios at high spatial frequencies expressed in the solar spatial frequency units of 1/Mm. Based on this approach we represent these ratio changes as a long-term network transformation which may be interpreted as a continuous dissipation of mid-size network structures to the smaller-size structures in the transition region. In contrast to expected cycling of the segmentation-cell dimension structures and associated spatial power in the spectra with the solar cycle, the spectra demonstrate a significant and steady change of the EUV network. The temporal trend across these structural spectra is not critically sensitive to any long-term instrumental changes, e.g. degradation of sensitivity, but to the change of the segmentation-cell dimensions of the EUV network structure.