Handbergmullen0824

AIMS/INTRODUCTION Pancreatic islets are heterogenous. To clarify the relationship between islet heterogeneity and incretin action in the islets, we studied gene expression and metabolic profiles of non-large and enlarged islets of the ZFDM rat, an obese diabetes model, as well as incretin-induced insulin secretion (IIIS) in these islets. MATERIALS AND METHODS Pancreatic islets of control (fa/+) and fatty (fa/fa) rats at 8 and 12 weeks of age were isolated. The islets of fa/fa rats at 12 weeks of age were separated into non-large islets (≤ 200 μm in diameter) and enlarged islets (> 300 μm in diameter). Morphological analyses, insulin secretion experiments, transcriptome analysis, metabolome analysis, and oxygen consumption analysis were performed on these islets. RESULTS The number of enlarged islets was increased with age in fatty rats and IIIS was significantly reduced in the enlarged islets. Markers for β-cell differentiation were markedly decreased in the enlarged islets, but those for cell proliferation were increased. Glycolysis was enhanced in the enlarged islets while the TCA cycle was suppressed. Oxygen consumption rate under glucose stimulation was reduced in the enlarged islets. Production of glutamate, a key signal for IIIS, was decreased in the enlarged islets. CONCLUSIONS The enlarged islets of ZFDM rats, which are defective for IIIS, exhibit tumor cell-like metabolic features including a dedifferentiated state, accelerated aerobic glycolysis, and impaired mitochondrial function. The age-dependent increase in such islets could contribute to the pathophysiology of obese diabetes. This article is protected by copyright. NVP-BGT226 clinical trial All rights reserved.OBJECTIVE Establish the prevalence of high grade CIN (CIN2+) in women referred to colposcopy with persistent hrHPV cytology negative screening sample according to hrHPV genotype, age at referral and colposcopic performance DESIGN Prospective cohort study SETTING Single colposcopy clinic linked to a population based screening programme POPULATION Women referred with persistent hrHPV cytology negative routine screening samples METHODS Prospective study with descriptive statistics from a single colposcopy unit between June 2014 and July 2019 MAIN OUTCOME MEASURES Prevalence of hrHPV genotypes and CIN2+, positive predictive value for colposcopic impression, inadequate colposcopic examinations RESULTS 3107 women were referred. Prevalence of CIN2+ was highest for persistent HPV16 infections (10.7%) compared with HPV18 (3.6%) or HPVO (4.7%). Prevalence of CIN2+ declined with age (25-34yrs 14.2% to 55-64yrs 1.1%) whereas the percentage of women with an inadequate colposcopic examination increased (25-34yrs 0.9% to 55-64yrs 29.5%). High grade colposcopic impression fell over time during the study from 16.1% to 5.1%. The PPV for colposcopic impression of CIN2+ was affected by hrHPV genotype (57.3% for HPV16 vs 32.1% for nonHPV16). The adjunctive use of electrical impedance spectroscopy detected an extra 42 cases of CIN2+ which was irrespective of hrHPV genotype. CONCLUSIONS Primary hrHPV cervical screening increases detection of CIN2+, however, low specificity results in more women being referred to colposcopy with a low prevalence of CIN2+. Colposcopy performs poorly in some groups, particularly with HPVO infections and women over 50 years. An appropriate threshold for referral to colposcopy in primary hrHPV screening has not been established. This article is protected by copyright. All rights reserved.IMPORTANCE The epidemiology of episcleritis and scleritis in Australia is largely unknown. BACKGROUND To determine incidence, prevalence and clinical characteristics of episcleritis and scleritis in Melbourne. DESIGN Retrospective longitudinal study. PARTICIPANTS Patients aged ≥18 years with episcleritis or scleritis seen at the Royal Victorian Eye and Ear Hospital from November 2014 to October 2015. METHODS Medical record review confirmed clinical diagnosis and characteristics. Incidence and prevalence were calculated using estimates of the adult population in areas of Melbourne with ≥30 ocular presentations/year to the emergency department. MAIN OUTCOME MEASURES Diagnosis of active episcleritis or scleritis, aetiology, ocular complications and treatments. RESULTS From a general population of 3 408 068, we confirmed 149 new and 23 pre-existing cases of active episcleritis, and 35 new and 23 pre-existing cases of active scleritis. Incidence per 100 000 person-years was 4.4 (CI 3.7-5.1) for episcleritis and 1.0 (CI 0.7-1.4) for scleritis, while 12-month prevalence was 5.1 (CI 4.3-5.9) and 1.7 (1.3-2.2) per 100 000 persons, respectively. Systemic disease was associated with 10% of episcleritis compared with 34% of scleritis (P  less then  0.001). Ocular complications were seen in 3% (6/184) of episcleritis eyes and 44% (32/72) of scleritis eyes, with the commonest being anterior uveitis (12/72) and ocular hypertension (14/72). At presentation, scleritis patients were commonly treated with oral non-steroidal anti-inflammatory drugs (60%) and prednisolone (19%). By 12 months, 24% of scleritis patients required immunosuppressants. CONCLUSION AND RELAVANCE Rates of episcleritis and scleritis in our single-centre Australian study were low. Episcleritis was usually benign, whereas scleritis had increased ocular complications and systemic disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Sertoli cells are crucial for spermatogenesis in the seminiferous epithelium because their actin cytoskeleton supports vesicular transport, cell junction formation, protein anchoring, and spermiation. Here, we show that a junction-mediating and actin-regulatory protein (JMY) affects the blood-tissue barrier (BTB) function through remodeling of the Sertoli cell junctional integrity and it also contributes to controlling endocytic vesicle trafficking. These functions are critical for the maintenance of sperm fertility since loss of Sertoli cell-specific Jmy function induced male subfertility in mice. Specifically, these mice have (a) impaired BTB integrity and spermatid adhesion in the seminiferous tubules; (b) high incidence of sperm structural deformity; and (c) reduced sperm count and poor sperm motility. Moreover, the cytoskeletal integrity was compromised along with endocytic vesicular trafficking. These effects impaired junctional protein recycling and reduced Sertoli cell BTB junctional integrity. In addition, JMY interaction with actin-binding protein candidates α-actinin1 and sorbin and SH3 domain containing protein 2 was related to JMY activity, and in turn, actin cytoskeletal organization.