Background: Blue Light Imaging (BLI) is a new imaging technology that enhances mucosal surface and vessel patterns. A specific BLI classification was recently developed to enable better characterisation of colorectal polyps (BLI Adenoma Serrated International Classification (BASIC)). The aim of this study was to validate the diagnostic performance of BASIC in predicting polyp histology in experienced and trainee endoscopists. Methods: Five experienced and five trainee endoscopists evaluated high-definition white light (HDWL) and BLI images from 45 small polyps to assess baseline accuracy, sensitivity, specificity, and positive and negative predictive values (NPVs) of polyp histology. Each endoscopist was trained with the BLI classification before repeating the exercise. Results were compared pre-and post-training. Results: The overall pre-training accuracy improved from 87% to 94%. The sensitivity and NPV of adenoma diagnosis also improved significantly from 79% to 96% and 81% to 95% with BASIC training. This improvement was noted in both groups. The interobserver level of agreement was very good (K ¼ 0.90) in the experienced cohort and good (K ¼ 0.66) in the trainee group post-training. Conclusions: BLI is a useful tool for optical diagnosis, and the use of BASIC with adequate training can significantly improve the accuracy, sensitivity and NPV of adenoma diagnosis.
Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.
Background Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. Methods The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion. Immunofluorescent staining was also conducted to analyse the expression of cardiac FKBPL. Cardiac spheroids were generated using human cardiac fibroblasts and human coronary artery endothelial cells and treated with patient plasma from normotensive controls, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE); n = 3. FKBPL and CD31 expression was quantified by immunofluorescent labelling. Results The RUPP procedure induced significant increases in blood pressure (p < 0.001), collagen deposition (p < 0.001) and cardiac BNP45 (p < 0.05). It also induced a significant increase in cardiac FKBPL mRNA (p < 0.05) and protein expression (p < 0.01). RUPP placentae also exhibited increased collagen deposition and decreased Flt1 mRNA expression (p < 0.05). RUPP kidneys revealed an increase in average glomerular size (p < 0.05). Cardiac spheroids showed a significant increase in FKBPL expression when treated with LOPE plasma (p < 0.05) and a trend towards increased FKBPL expression following treatment with EOPE plasma (p = 0.06). Conclusions The rat RUPP model induced cardiac, renal and placental features reflective of preeclampsia. FKBPL was increased in the hearts of RUPP rats and cardiac spheroids treated with plasma from women with preeclampsia, perhaps reflective of restricted angiogenesis and inflammation in this disorder. Elucidation of these novel FKBPL mechanisms in cardiac health in preeclampsia could be key in preventing future CVD.
Ten-day sequential therapy was significantly better than 7-day triple therapy in a clinical setting with low rates of clarithromycin and dual resistance. Concomitant therapy was significantly better than standard triple therapy in the subgroup of patients with clarithromycin-resistant strains.
In the NCSP, CRC was found in 6.2% of those participants attending colonoscopy, with 81.3% of carcinomas found in the left colon. A localized clinical stage was found in 70.2% participants. In 22.8% of CRC patients, cancer was cured with endoscopic resection only.
The main idea of this research was to evaluate the efficacy of canine demodicosis conventional treatments using mathematical analyses. All available papers published between 1980 and 2014 were used in this study. One hundred six clinical trials enrolling 3414 cases of generalized demodicosis in dogs are studied. Dogs entered in the analysis were only the ones in which the disease occurred naturally, excluding the studies in which transplantation of Demodex canis mites was done from other animals. In conventional acaricide treatments, sorted according to active substances (moxidectin, amitraz, doramectin, ivermectin, and milbemycin oxime), the way of application (spot-on, dips, orally, or subcutaneous), concentration, and interval of application were used as input parameters in mathematical modeling. Data of interest were the treatment outcome, the number of dogs that went into remission, the number of animals not responding to treatment microscopically, the average duration of therapy, the follow-up period, the number of patients with disease recurrence, the number of adverse effects, and the number of animals with side effects. Dogs lost to follow-up or when the treatment was discontinued, due to various reasons not in connection with the therapy protocol, were not considered. Statistical and mathematical analyses were applied for prediction of the drugs' effectiveness. Developed mathematical models showed satisfactorily r (2), higher than 0.87. Good evidence for recommending the use of milbemycin oxime PO (0.5 mg/kg, daily) and moxidectin spot-on (Advocate®, Bayer) weekly is found. A bit less effective therapies were based on ivermectin PO (0.5 mg/kg, daily), moxidectin PO (0.35 mg/kg, daily), and amitraz dips (0.05 % solution, weekly), respectively. It is important to keep in mind that Advocate® is recommended by the manufacturer for use in milder cases.
The previous cesarean section is an important risk factor for the development of placental complications.
Background: Optical diagnosis of colorectal polyps (CRPs) remains challenging. Imaging enhancement techniques such as narrow band imaging and blue light imaging (BLI) can improve optical diagnosis. We developed and prospectively validated a computer-aided diagnosis system (CADx) using high definition white light (HDWL) and BLI images, and compared it with the optical diagnosis of expert and novice endoscopists. Methods: The CADx characterized CRPs by exploiting artificial neural networks. Six experts and thirteen novices optically diagnosed 60 CRPs based on intuition. After a washout period of four weeks, the same set of CRPs was permuted and optically diagnosed using BASIC (BLI Adenoma Serrated International Classification). Results: The CADx had a diagnostic accuracy of 88.3% using HDWL images and 86.7% using BLI images. The overall diagnostic accuracy, combining HDWL and BLI (multimodal imaging), was 95.0% and significantly higher compared to experts (81.7%, p=0.031) and novices (66.5%, p<0.001). Sensitivity (95.6% vs. 61.1% and 55.4%) was also higher for CADx, while specificity was higher for experts compared to CADx and novices (94.1% vs 93.3% and 92.1%). For endoscopists, diagnostic accuracy did not increase using BASIC, neither for experts (Intuition 79.5% vs BASIC 81.7%, p=0.140) nor for novices (Intuition 66.7% vs BASIC 66.5%, p=0.953). Conclusion: The CADx had a significantly higher diagnostic accuracy than experts and novices for the optical diagnosis of CRPs. Multimodal imaging, incorporating both HDWL and BLI, improved the diagnostic accuracy of the CADx. BASIC did not increase the diagnostic accuracy of endoscopists compared to intuitive optical diagnosis.
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