Intracerebral hemorrhage is the most dangerous complication in tPA thrombolytic therapy for ischemic stroke, which occurs as a consequence of endothelial cell death at the blood brain barrier (BBB) during thrombolytic reperfusion. We have previously shown that cerebral ischemia induced rapid occludin degradation and BBB disruption. Here we demonstrated an important role of occludin degradation in facilitating the evolution of ischemic endothelial cells towards death. Cultured brain microvascular endothelial cells (bEnd.3 cells) were exposed to oxygen-glucose deprivation (OGD) or incubated with occludin siRNA or occludin AAV to achieve an occludin deficiency or overexpression status before exposing to reoxygenation (R) or TNF-α treatment. Cell death was assessed by measuring lactate dehydrogenase release, TUNEL staining and flow cytometry analysis. Inhibition of OGD-induced occludin degradation with SB-3CT or overexpression of occludin with occludin AAV both significantly attenuated OGD/R-induced apoptosis and pyroptosis in bEnd.3 cells. Consistently, knockdown of occludin with siRNA potentiated TNF-α-induced apoptosis, supporting an important role of occludin integrity in endothelial cell survival. Similar results were observed for pyroptosis, in which occludin knockdown with siRNA led to a significant augmentation of cytokines secretion, inflammasome activation and pyroptosis occurrence in TNF-α-treated bEnd.3 cells. Lastly, upregulation of c-Yes, PI3K/AKT and ERK concurrently occurred with occludin degradation after OGD/R or TNF-α treatment, and the level of these proteins were further increased when inhibition of occludin degradation or overexpression of occludin. These data indicate that occludin degradation inflicted during ischemia makes BBB endothelial cells more vulnerable to reperfusion-associated stress stimuli.Tuberculosis (TB) screening and eventual TB infection prophylaxis in case of screening positivity for latent TB infection (LTBI) are mandatory before starting a biologic treatment for psoriasis.1 Indeed, opportunistic infections reactivation, especially LTBI, is one the main risk during biologic therapy, in particular with tumour necrosis factor (TNF)-α inhibitors. It is already known that TNFα plays a major role in the initial and long-term control of TB.Aim To evaluate the accuracy of ultrasound examination (USE) for the detection of artificial bone defects in bovine mandibles in the absence of complete erosion of the cortical bone plate, and determine the minimum cortical thickness that constitutes a barrier for ultrasound waves. Methodology Sixty bovine mandibular anatomical blocks were harvested and uniformly distributed among six experimental groups. The negative control consisted of blocks with no intra-bony defects, whereas the positive control consisted of blocks with an artificial lesion of 2.0 mm diameter produced buccally perforating the cortical bone plate. Two experimental groups comprised blocks with small (2.0 mm) and large (5.0 mm) artificial defects created under a cortical plate thinned to varying thicknesses. Two additional groups had small (2.0 mm) and large (5.0 mm) artificial defects that did not involve the cortical plate. After USE, the scans were saved and submitted to three blinded examiners. Sensitivity, specificity, predictive valuhe thickness or presence of the cortical plate.Background The number of qualitative studies on eczema has increased rapidly in recent years. Systematically reviewing these can provide greater understandings of people’s perceptions of eczema and eczema treatments. Objectives We sought to systematically review and thematically synthesise qualitative studies exploring views and experiences of people with eczema and parents/carers of children with eczema. Methods We searched MEDLINE, PsycINFO, CINAHL and EMBASE from the earliest date available to February 2019. We selected papers focusing on views and experiences of eczema, eczema treatments, and barriers/facilitators to eczema self-management. We excluded papers focusing on health service provision models or health professionals’ views. Results We synthesised 39 papers (reporting 32 studies) from 13 countries. We developed four analytical themes 1) Eczema not viewed as long-term condition, 2) Significant psychosocial impact not acknowledged by others, 3) Hesitancy (patient/carer uncertainty) about eczema treatments and 4) Insufficient information and advice. Our findings suggest people with eczema and their carers experience frustration at having to manage a condition that is often seen by others as mundane but has significant psychosocial impact and is difficult to manage due to concerns about, and burden of, treatment. This frustration can be exacerbated by experiences of conflicting and/or insufficient information and advice from health professionals, family and others. Conclusions Effective self-management of eczema could be supported by addressing beliefs and concerns about treatments; seeking positive ways to promote a 'control not cure’ message; acknowledging psychosocial impacts of eczema and treatment burden; and providing clear consistent advice or signposting towards reliable information.Regeneration is a unique defense mechanism of liver tissue in response to functional cell loss induced by toxic chemicals or surgical resection. In this study, we found that Islet-cell autoantigen 69 (Ica69) accelerates liver regeneration in mice. Following 70% partial hepatectomy, both Ica69 mRNA and protein are significantly upregulated in mouse hepatocytes at the early stage of liver regeneration. Compared with the wild-type mice, Ica69-deficient mice have more severe liver injury, delayed liver regeneration and high surgical accidental mortality following hepatectomy. Mechanistically, Ica69 interacts with Pick1 protein to regulate Tgfbr1 protein expression and Tgfβ-induced Smad2 phosphorylation. Our findings suggest that Ica69 in liver tissue is a new potential target for promoting liver regeneration.Background Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic. Objective Report three-year safety from three phase 3 trials of CZP in adults with plaque psoriasis (PSO). Methods Data were pooled from CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272), CIMPACT (NCT02346240). Included patients had moderate to severe PSO ≥6 months; were randomised to CZP 200 mg every two weeks (Q2W) (400 mg at Weeks 0, 2, 4) or CZP 400 mg Q2W; received ≥1 dose CZP with up to 144 weeks’ exposure. Treatment-emergent adverse events (TEAEs) were classified using MedDRAv18.1. Reported incidence rates (IRs) are incidence of new cases/100 patient-years (PY). Results Over 144 weeks, 995 patients received ≥1 dose CZP (exposure 2,231.3 PY); 731 and 728 received ≥1 dose CZP 200 mg Q2W (1,211.4 PY) and 400 mg Q2W (1,019.9 PY), respectively. IR (95% confidence interval [CI]) of TEAEs was 144.9 (135.3-155.0) for all patients; 134.1 (123.2-145.7) and 158.3 (145.5-171.9) for CZP 200 mg and 400 mg Q2W, respectively. IR of serious TEAEs for all patients was 7.5 (6.4-8.8); 6.7 (5.2-8.3) and 8.7 (6.9-10.8) for CZP 200 mg and 400 mg Q2W, respectively. 3.2% patients reported serious infections (2.2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was 1 case of active tuberculosis, 16 malignancies in 14 patients and 7 deaths (2 considered treatment-related). Cumulative IR of TEAEs did not increase over time. Conclusions No new safety signals were identified compared to previously reported data. Risk did not increase with longer or higher CZP exposure.Bullous pemphigoid (BP) is a serious, rare complication from immune checkpoint inhibitors (ICIs). While most dermatologic immune-related adverse events (irAEs) present early and are mild, ICI-induced BP (ICI-BP) manifests months into therapy and can prompt ICI discontinuation and severe immunosuppression. Following irAE management guidelines, providers rely on systemic corticosteroids – which, at high doses, may confer poorer oncologic outcomes for ICI patients. Our study aims to identify diagnostic and therapeutic differences between ICI-BP and idiopathic BP (iBP) to assist providers in prompt recognition and management of this skin toxicity.Thermoregulation of leaf temperature (Tleaf ) may foster metabolic homeostasis in plants, but the degree to which Tleaf is moderated, and under what environmental contexts, is a topic of debate. Isotopic studies inferred the temperature of photosynthetic carbon assimilation to be a constant value of ~20°C; in contrast leaf biophysical theory suggests a strong dependence of Tleaf on environmental drivers. Can this apparent disparity be reconciled? We continuously measured Tleaf and whole-crown net CO2 uptake for Eucalyptus parramattensis trees growing in field conditions in whole-tree chambers at ambient and +3 °C warming, and calculated assimilation-weighted leaf temperature (TL-AW ) across 265 days varying in air temperature (Tair ) from -1 to 45°C. We compared these data to TL-AW derived from wood cellulose δ18 O. Tleaf exhibited substantial variation driven by Tair , light intensity, and vapor pressure deficit, and Tleaf was strongly linearly correlated with Tair with a slope of ~1.0. TL-AW calculated from cellulose δ18 O vs. crown fluxes were remarkably consistent; both varied seasonally and in response to the warming treatment, tracking variation in Tair . The leaves studied here were nearly poikilothermic, with no evidence of thermoregulation of Tleaf towards a homeostatic value. Importantly, this work supports the use of cellulose δ18 O to infer TL-AW , but does not support the concept of strong homeothermic regulation of Tleaf.Purpose Glomus tumors are rare vascular pathologies characterized by a triad of symptoms tenderness, pain and cold intolerance. In the hand they are highly concentrated under the nail bed. In this retrospective study, we aimed to present a topographic map of the location of glomus tumors in the nail bed and a map-based surgical approach algorithm to the subungual glomus tumors. Methods We prepared a nail bed map with 6 zones and named these zones as ulnar distal, ulnar proximal, central distal, central proximal, radial distal and radial proximal. With respect to the tumor location and the used surgical approach we retrospectively evaluated the intraoperative photos and the hospital records of patients who were operated between 2008-2019 and had the pathological diagnosis of glomus tumor. The examination records of the postoperative first year were evaluated for each patient retrospectively. A descriptive statistical analysis was performed. In addition we analyzed the described surgical approaches to excise a glomus tumor in the nail bed. The described approaches and the approaches used by us were matched with the localisation of the tumors in this study developing an algorithm for the surgical approach depending on the localisation of the nail bed glomus tumor. Results Finally 44 patients had inclusion criteria. The distribution of the glomus tumor was as follows 2 were on ulnar distal (4.5 %), 9 on ulnar proximal (20.5 %), 1 on central distal (2.3 %), 18 on central proximal (40.9 %), 4 on radial distal (9.1 %) and 10 were on the radial proximal zones (22.7 %). 4 lateral approaches, 1 nail sparing and 39 transungual approaches were performed. We had one recurrence in a male patient operated by transungual approach. Conclusion Glomus tumors are mostly located on the central proximal part of the nail bed. Our glomus map and the algorithm we described might be helpful for the selection of the surgical approach for the glomus tumor.