Spatio-temporal image correlation (STIC) in evaluation of advanced neuroendocrine tumours

Introduction: 4D Ultrasound technology merging the Power Doppler option called High-Definition Flow (HDF) with Spatio-Temporal Image Correlation (STIC) is used in gynaecology and obstetrics. It seems to be a promising tool in assessing tissue vascularisation. The aim of the paper was to assess whether HDF STIC technique could be a useful tool for the evaluation of gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN) advancement. Material and methods: Forty-eight patients [mean age 57.7 ± 10.3 years; male 40.9% (n = 18)] diagnosed with metastatic GEP-NENs were included in the analysis. All subjects were enrolled in the Department of Endocrinology and Neuroendocrine Tumours, Medical University of Silesia, Katowice. We analysed liver metastases. Patients with G3 grading or faintly vascularised lesions were excluded. HDF STIC volumes were acquired during USG examination. 4D indices [volumetric pulsatility index (vPI) and volumetric systolic/diastolic index (vS/D)] were calculated using dedicated software. Results: There were no correlations between vS/D and Ki-67 [p = 0.67; r = –0.19; (–0.28–0.19)], CgA [p = 0.47; r = –0.11; (–0.38–0,19)], 5-HIAA [p = 0.52; r = –0.09 (–0.37–0.2)], serotonin [p = 0.83; r = –0.03 (–0.32–0.26)], and VCAM-1 (p = 0.62; r = 0.09 (–03–0.47)]. The were no correlations between vPI and Ki-67 [p = 0.29; r = –0.16 (–0.45–0.14)], CgA (p = 0.46; r = –0.11 (–0.39–0.19)], 5-HIAA [p = 0.52; r = –0.09 (–0.37–0.2)], serotonin [p = 0.82; r = –0.03 (–0.32–0.26)], and VCAM-1 (p = 0.62; r = –0.09 (–03–0.47)]. There was no significant difference between carcinoid versus non-carcinoid patients if compared by vS/D and vPI (p = 0.62, p = 0.61, respectively). Conclusions: HDF STIC seems not to be an efficient marker to assess advancement of NENs, due to lack of correlation with widely used and approved markers of progression.

Effects of infection-induced migration delays on the epidemiology of avian influenza in wild mallard populations

Wild waterfowl populations form a natural reservoir of Avian Influenza (AI) virus, and fears exist that these birds may contribute to an AI pandemic by spreading the virus along their migratory flyways. Observational studies suggest that individuals infected with AI virus may delay departure from migratory staging sites. Here, we explore the epidemiological dynamics of avian influenza virus in a migrating mallard (Anas platyrhynchos) population with a specific view to understanding the role of infection-induced migration delays on the spread of virus strains of differing transmissibility. We develop a host-pathogen model that combines the transmission dynamics of influenza with the migration, reproduction and mortality of the host bird species. Our modeling predicts that delayed migration of individuals influences both the timing and size of outbreaks of AI virus. We find that (1) delayed migration leads to a lower total number of cases of infection each year than in the absence of migration delay, (2) when the transmission rate of a strain is high, the outbreak starts at the staging sites at which birds arrive in the early part of the fall migration, (3) when the transmission rate is low, infection predominantly occurs later in the season, which is further delayed when there is a migration delay. As such, the rise of more virulent AI strains in waterfowl could lead to a higher prevalence of infection later in the year, which could change the exposure risk for farmed poultry. A sensitivity analysis shows the importance of generation time and loss of immunity for the effect of migration delays. Thus, we demonstrate, in contrast to many current transmission risk models solely using empirical information on bird movements to assess the potential for transmission, that a consideration of infection-induced delays is critical to understanding the dynamics of AI infection along the entire flyway.<br /

Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity

Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p&nbsp;&lt;.001. Over 24&nbsp;months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10&nbsp;ml/min/1.73&nbsp;m2 decrease), that was most notable in patients with eGFR &lt;30&nbsp;ml/min/1.73&nbsp;m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90&nbsp;ml/min/1.73&nbsp;m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P &lt;.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Intracellular protein determination using droplet-based immunoassays

This paper describes the implementation of a sensitive, on-chip immunoassay for the analysis of intracellular proteins, developed using microdroplet technology. The system offers a number of analytical functionalities, enabling the lysis of low cell numbers, as well as protein detection and quantification, integrated within a single process flow. Cells were introduced into the device in suspension and were electrically lysed in situ. The cell lysate was subsequently encapsulated together with antibody-functionalized beads into stable, water-in-oil droplets, which were stored on-chip. The binding of intracellular proteins to the beads was monitored fluorescently. By analyzing many individual droplets and quantifying the data obtained against standard additions, we measured the level of two intracellular proteins, namely, HRas-mCitrine, expressed within HEK-293 cells, and actin-EGFP, expressed within MCF-7 cells. We determined the concentrations of these proteins over 5 orders of magnitude, from 50 pM to 1 μM. The results from this semiautomated method were compared to those for determinations made using Western blots, and were found not only to be faster, but required a smaller number of cells

Republika nie jest dana raz na zawsze. Ronald J. Oakerson o dziedzictwie myśli Vincenta Ostroma

The republic can never be taken for granted. Democratic republics face two perennial problems: one is maintaining the openness of the public realm to the whole public and the independence of the public realm from government; the other is keeping the process of governance firmly embedded in the public realm, where it is visible to the public, rather than allowing it to disappear inside the walls of government. The U.S. is challenged on both fronts today.Republika nigdy nie może być traktowana jako oczywistość. Demokratyczne rządy republikańskie borykają się z dwoma odwiecznymi problemami: jednym z nich jest utrzymanie otwartości sfery publicznej na ogół społeczeństwa oraz niezależności sfery publicznej od rządu; drugim jest utrzymanie procesu rządzenia mocno osadzonego w sferze publicznej, gdzie jest on widoczny dla opinii publicznej, a nie pozwalanie, by zniknął on za murami instytucji państwowych. Stany Zjednoczone stykają się dzisiaj z problemami na obu frontach

Effect of type 4 resistant starch on colour and rheological properties of tomato ketchup

Celem pracy była ocena przydatności technologicznej skrobi opornej typu RS4, różnego pochodzenia botanicznego, jako zagęstnika do sosów typu keczup. Materiał do badań stanowiły naturalne skrobie: ziemniaczana, kukurydziana oraz kukurydziana woskowa, modyfikowane za pomocą czynnika sieciującego, zawierającego bezwodnik adypinowy i octowy. Wykonano badania: reologiczne, tekstury, barwy oraz kwasowości gotowego wyrobu. Stwierdzono, że wszystkie sosy pod względem reologicznym stanowiły płyny pseudoplastyczne z granicą płynięcia. Największą lepkością pozorną cechował się keczup z dodatkiem skrobi kukurydzianej woskowej, następnie: ze skrobią ziemniaczaną oraz kukurydzianą. Parametry profilu tekstury badanych sosów różniły się nieznacznie od parametrów keczupów handlowych, a największe różnice wystąpiły w zakresie twardości i adhezyjności. Zastosowanie preparatów skrobi opornej do produkcji sosów wpłynęło pozytywnie na ich barwę. Pochodzenie botaniczne skrobi nie miało wpływu na pH badanych produktów. Stwierdzono przydatność skrobi opornej typu RS4, zwłaszcza ziemniaczanej i kukurydzianej woskowej, do zagęszczania sosów typu keczup.The objective of the research study was to asses the usefulness of a technological RS4 type resistant starch of different botanical origin used as a thickener in ketchup sauces. The research material consisted of natural starches: potato starch, maize starch, and waxy maize starch, which were modified by the use of a cross-linking agent containing an adipic and acetic anhydride. The following research was performed: rheological analysis, texture analysis, colour and acidity analysis of the end product. It was found that, from the rheological point of view, all the sauces were pseudo-plastic fluids with a yield point. The highest apparent viscosity was recorded for the ketchup with the addition of the waxy maize, then, for the ketchup with the potato starch added, and with the maize starch added. The parameters of the texture profile of the ketchups analyzed slightly differed from the parameters of commercial ketchups, and the largest differences appeared in the range of hardness and adhesiveness. The application of the resistant starch preparations as a thickening agent to the production of the ketchup sauces has a positive effect on their colour. The botanical origin did not have any effect on the pH level of the analyzed products. The usefulness was confirmed of the RS34 type resistant starch, in particular of the potato and waxy maize starch, when applied as a thickener in ketchup type sauces