Gisselfog5955

Human papillomavirus (HPV) testing is very sensitive for primary cervical screening but has low specificity. Triage tests that improve specificity but maintain high sensitivity are needed. Women enrolled in the experimental arm of Phase 2 of the New Technologies for Cervical Cancer randomized controlled cervical screening trial were tested for high-risk HPV (hrHPV) and referred to colposcopy if positive. hrHPV-positive women also had HPV genotyping (by polymerase chain reaction with GP5+/GP6+ primers and reverse line blotting), immunostaining for p16 overexpression and cytology. We computed sensitivity, specificity and positive predictive value (PPV) for different combinations of tests and determined potential hierarchical ordering of triage tests. A number of 1,091 HPV-positive women had valid tests for cytology, p16 and genotyping. Ninety-two of them had cervical intraepithelial neoplasia grade 2+ (CIN2+) histology and 40 of them had CIN grade 3+ (CIN3+) histology. The PPV for CIN2+ was >10% in hrHPV-positive women with positive high-grade squamous intraepithelial lesion (61.3%), positive low-grade squamous intraepithelial lesion (LSIL+) (18.3%) and positive atypical squamous cells of undetermined significance (14.8%) cytology, p16 positive (16.7%) and, hierarchically, for infections by HPV33, 16, 35, 59, 31 and 52 (in decreasing order). Referral of women positive for either p16 or LSIL+ cytology had 97.8% sensitivity for CIN2+ and women negative for both of these had a 3-year CIN3+ risk of 0.2%. Similar results were seen for women being either p16 or HPV16/33 positive. hrHPV-positive women who were negative for p16 and cytology (LSIL threshold) had a very low CIN3+ rate in the following 3 years. Recalling them after that interval and referring those positive for either test to immediate colposcopy seem to be an efficient triage strategy. The same applies to p16 and HPV16. © 2020 UICC.INTRODUCTION The immuno-microenvironment of injured nerves adversely affects mesenchymal stem cell (MSC) therapy for neurotmesis. Magnetic resonance imaging (MRI) can be used to non-invasively monitor nerve degeneration and regeneration. The aim of this study was to investigate nerve repair following MSC transplantation combined with microenvironment immunomodulation in neurotmesis by using multiparametric MRI. METHODS Rats with sciatic nerve transection and surgical coaptation were treated with MSCs combined with immunomodulation or MSCs alone. Serial multiparametric MRI examinations were performed over an 8-week period after surgery. RESULTS Nerves treated with MSCs combined with immunomodulation showed better functional recovery, rapid recovery of nerve T2, fractional anisotropy and radial diffusivity values, and more rapid restoration of the fiber tracks than nerves treated with MSCs alone. DISCUSSION Transplantation of MSCs in combination with immunomodulation can exert a synergistic repair effect on neurotmesis, which can be monitored by multiparametric MRI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.INTRODUCTION Shear wave elastography (SWE) shows promise in peripheral neuropathy evaluation but has potential limitations due to tissue size and heterogeneity. We tested SWE sensitivity to elasticity change and the effect of probe position in a median nerve cadaver model. OD36 METHODS Ten specimens were used to measure median nerve elasticity under increasing loads using SWE and indentation. Measurements were compared using repeated-measures ANOVA. RESULTS Indentation and SWE-based longitudinal nerve elasticity increased with tensile loading (p less then 0.01), showing a similar relationship. Acquisition in a transverse plane showed lower values compared to longitudinal measurements, mostly under higher loads (p=0.03), as did post-dissection elasticity (p=0.02). Elasticity did not change when measured proximal to the carpal tunnel. DISCUSSION Longitudinal SWE is sensitive to changes in median nerve elasticity. Measuring elasticity of peripheral nerves noninvasively could elucidate intra-neural pathology related to compression neuropathies, and proof to be of added value as a diagnostic or prognostic tool. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Cl- has long been known as a micronutrient for oxygenic photosynthetic resulting from its role an essential cofactor for Photosystem II (PSII). Evidence on the in vivo Cl- distribution in Spinacia oleracea leaves and chloroplasts show that sufficient Cl- is present for the involvement in PSII function, as indicated by in vitro studies on, among other organisms, S. oleracea PsII There is also sufficient Cl- to function, with K+ , of parsing the H+ electrochemical potential difference (proton motive force) across the illuminated thylakoid membrane into electrical potential difference and pH difference components. However, recent in vitro work on PSII from S. oleracea shows that oxygen evolving complex (OEC) synthesis, and re-synthesis after photodamage, requires significantly higher Cl- concentrations than satisfy the function of assembled PSII O2 evolution of the synthesised PSII with OEC. The low Cl- affinity of OEC (re-)assembly could be a component of limiting the rate of OEC (re-) assembly. This article is protected by copyright. All rights reserved.Zileuton is an orally active inhibitor of leukotriene synthesis for maintenance treatment of asthma, for which clinical usage has been associated with idiosyncratic liver injury. Mechanistic understanding of zileuton toxicity is hampered by the rarity of the cases and lack of an animal model. A promising model for mechanistic study of rare liver injury is the Diversity Outbred (JDO) mouse population, with genetic variation similar to that found in humans. In this study, female DO mice were administered zileuton or vehicle i.g. daily for seven days. Serum liver enzymes were elevated in the zileuton group, with marked interindividual variability in response. Zileuton treatment-induced findings in susceptible DO mice included microvesicular fatty change, hepatocellular mitosis, and hepatocellular necrosis. Inducible nitric oxide synthase (iNOS) and nitrotyrosine abundance were increased in livers of animals with necrosis and those with fatty change, implicating nitrosative stress as a possible injury mechanism. Conversely, DO mice lacking adverse liver pathology following zileuton exposure experienced decreased hepatic concentrations of resistin and increased concentrations of insulin and leptin, providing potential clues into mechanisms of toxicity resistance.