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  • Leach posted an update 8 months, 4 weeks ago

    At this time point, 2-mercaptoethanol in the HgCl2 + 2-mercaptoethanol group reversed the effects of HgCl2 as compared to the HgCl2 group. Present study showed the expression and immunolocalisation of AQP3 in human spermatozoa and the potential role of AQPs in the sperm motility and MMP. © 2020 Blackwell Verlag GmbH.AIMS Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies by boosting immune-mediated destruction of neoplastic cells, but course with side effects stemming from generalized immune system activation against normal tissues. Checkpoint ligand expression in non-tumoral cells of tissues affected by immune-related adverse effects has been described in ICI-associated hypophysitis, myocarditis, and acute interstitial nephritis. We aimed to investigate the tissue expression of the immune checkpoint receptor PD-1 and its ligand, PD-L1, in PD-1 inhibitor-associated colitis. METHODS AND RESULTS PD-1 and PD-L1 immunohistochemical expression was analyzed in 15 cases of PD-1 inhibitor-associated colitis and potential mimics – infectious colitis and inflammatory bowel disease (IBD). Increased epithelial expression of PD-L1 was observed in PD1i-colitis when compared to normal colon and infectious colitis, but that was lower than expression in IBD. Conversely, PD-1 expression in inflammatory cells was higher in infectious colitis, intermediate in IBD and minimal or absent in normal colon and in patients receiving PD-1 inhibitors. CONCLUSIONS Although our results do not allow the use of PD-L1 as a discriminatory marker of PD1i-colitis against other entities within the differential diagnosis, they support the concept that ICI-colitis and IBD share similar pathogenetic mechanisms. They also highlight that PD-L1 epithelial overexpression is a commonly used mechanism of the gastrointestinal tract mucosa to protect itself from inflammatory-mediated damage from different etiologies, which likely underpins the high incidence of gastrointestinal IRAEs in patients receiving ICI therapies in which such mechanism is disrupted. This article is protected by copyright. All rights reserved.WHAT IS KNOWN AND THE OBJECTIVE De novo Crohn’s disease (CD) is an increasingly reported diagnosis after ileal pouch anal anastomosis (IPAA). Currently, no consensus exists on the best treatment strategy. CASE SUMMARY This report details the case of a 5-year-old child with early-onset ulcerative colitis (UC) who developed findings compatible with CD 12 months after IPAA. Thalidomide therapy led to clinical and endoscopic remission without side effects at 6 months. WHAT IS NEW AND CONCLUSION To our knowledge, this is the first report of thalidomide for treatment of de novo CD. Thalidomide therapy could be considered in patients with de novo CD, with similar indications of CD. © 2020 John Wiley & Sons Ltd.KEY POINTS Cutaneous reflexes were tested to examine the neuronal mechanisms contributing to muscle spasms in humans with chronic spinal cord injury (SCI). Specifically, we tested the effect of Achilles and tibialis anterior tendon vibration on the early and late components of the cutaneous reflex and reciprocal Ia inhibition in the soleus and tibialis anterior muscles in humans with chronic SCI. We found that tendon vibration reduced the amplitude of later but not earlier cutaneous reflex activity in the antagonist but not agonist muscle relative to the location of the vibration. In addition, reciprocal Ia inhibition between antagonist ankle muscles increased with tendon vibration and participants with a larger suppression of later cutaneous reflex activity had stronger reciprocal Ia inhibition from the antagonistic muscle. Histone Methyltransferase inhibitor Our study is the first to provide evidence that tendon vibration attenuates late cutaneous spasm-like reflex activity likely via reciprocal inhibitory mechanisms, and may represent a metherior tendon was vibrated. Notably, tendon vibration at 80 Hz increased reciprocal Ia inhibition between antagonistic ankle muscles and vibratory-induced increases in reciprocal Ia inhibition were correlated with decreases in LLR, suggesting that participants with a larger suppression of later cutaneous reflex activity had stronger reciprocal Ia inhibition from the antagonistic muscle. Our study is the first to provide evidence that tendon vibration suppresses late spasm-like activity in antagonist but not agonist muscles, likely via reciprocal inhibitory mechanisms, in humans with chronic SCI. We argue that targeted vibration of antagonistic tendons might help to control spasms after SCI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND The long term performance of the Riata family of leads has recently come under increasing scrutiny. We aimed to determine the long term performance of the Riata 1580 leads compared with Endotak 0158 leads. METHODS All patients with Riata 1580 or Endotak 0158 leads implanted from 2003-2008 at the Heart Hospital, UCLH were analysed. Significant electrical changes were threshold increase >1V at a set pulse width between pacing checks, persistent R wave fall to 400Ω over 12 months. RESULTS 333 Riata and 356 Endotak leads were implanted. Median follow up time + interquartile range, after exclusion of censored events including loss to follow up Riata 3652 + 655 days, Endotak 3730 + 810 days. A total of 51 (15.9%) Riata leads and 21 (6.3%) Endotak leads were affected. A greater risk of failure was found for the Riata lead compared with the Endotak lead (p = 0.0001). An additional time-dependent effect was found, with the Riata lead 1.9 times more likely to fail in the first 6 years following lead implantation and 5.3 times more likely to fail after 6 years. CONCLUSIONS Riata leads have a higher risk of failure compared to Endotak leads over time. The importance of careful ongoing performance surveillance late in the leads’ lifetime is reflected in this ten year follow up study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND The objectives of this study were to characterize the risk of death (1) from the primary cancer vs competing cause of death; and (2) from various causes of death vs the general poplation. The relative risk of death after a pediatric cancer diagnosis versus the general population and the risk of death from a primary cancer diagnosis versus competing causes of death. METHODS This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database (1980-2015) and included patients aged 0 to 19 years at the time of diagnosis. Observed deaths were calculated; the risk of death versus the general population was assessed with standardized mortality ratios (SMRs). Competing risk models for the cause of death were performed. RESULTS There were 58,356 patients who were diagnosed, and the mortality rate was 22.8%. To assess causes of death, 6996 patients who died during the study period were included (45,580 total person-years at risk) 5128 (73%) died of their primary cancer, and 1868 (27%) died of a competing cause.

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