Adaptive changes in transmembrane transport and metabolism of triiodothyronine in perfused livers of fed and fasted hypothyroid and hyperthyroid rats

The transport and subsequent metabolism of triiodothyronine (T3) were studied in isolated perfused livers of euthyroid, hypothyroid, and hyperthyroid rats, both fed and 48-hour-fasted. T3 kinetics (transport and metabolism) during perfusion were evaluated by a two-pool model, whereas the metabolism of T3 was also investigated by determination of T3 breakdown products by chromatography of medium and bile. For comparison of groups, metabolism was corrected for differences in transport. Transport parameters in fed hypothyroid livers were not significantly changed as compared with euthyroid livers, whereas metabolism was decreased. In fed hyperthyroid livers, fractional transfer rate constants for influx (k21) and efflux (k12) were decreased and metabolism, corrected for differences in intracellular mass transfer, was increased. Furthermore, for transport in hyperthyroid livers it was shown that only total mass transfer (TMT) into the metabolizing liver compartment (not into the nonmetabolizing liver compartment) was decreased. Transport and metabolic parameters in fasted hypothyroid livers were decreased as compared with euthyroid fed livers. In fasted hyperthyroid livers, transport and metabolism were not significantly different as compared with that in euthyroid fed livers, so transport was increased versus hyperthyroid fed livers. It appeared therefore that fasting normalized the effects of hyperthyroidism on both the transport and metabolic processes of T3 in the liver. The present study demonstrates normal transport and decreased metabolism in livers of hypothyroid fed rats and decreased transport and increased metabolism in livers of hyperthyroid fed rats. In livers of hypothyroid fasted rats transport and metabolism were decreased, whereas in livers of hyperthyroid fasted rats transport and metabolism were not significantly different from that in euthyroid fed livers. These changes might favor tissue euthyroidism despite the altered thyroid and nutritional state, and can therefore be seen as adaptation mechanisms to these altered states at the tissue level

Identification and Validation of the Predictive Capacity of Risk Factors and Models in Liver Transplantation Over Time

Background. Outcome after liver transplantation (LT) is determined by donor, transplant and recipient risk factors. These factors may have different impact on either patient or graft survival (outcome type). In the literature, there is wide variation in the use of outcome types and points in time (short term or long term). Objective of this study is to analyze the predictive capacity of risk factors and risk models in LT and how they vary over time and per outcome type. Methods. All LTs performed in the Netherlands from January 1, 2002, to December 31, 2011, were analyzed with multivariate analyses at 3-month, 1-year, and 5-year for patient and (non-)death-censored graft survival. The predictive capacity of the investigated risk models was compared with concordance indices. Results. Recipient age, model for end-stage liver disease sodium, ventilatory support, diabetes mellitus, hepatocellular carcinoma, previous malignancy, hepatitis C virus antibody, hepatitis B virus antibody, perfusion fluid, and Eurotransplant donor risk index (ET-DRI) had significant impact on outcome (graft or patient survival) at 1 or multiple points in time. Significant factors at 3-month patient survival (recipient age, model for end-stage liver disease sodium, ventilato

Presburger Modal Logic Is PSPACE-Complete

International audienceWe introduce a Presburger modal logic PML with regularity constraints and full Presburger constraints on the number of children thatgeneralize graded modalities, also known as number restrictions in description logics. We show that PML satisfiability is only PSPACE-complete by designing a Ladner-like algorithm that can be turned into an analytic proof system algorithm. This extends a well-known and non-trivial PSPACE upper bound for graded modal logic. Furthermore, we provide a detailed comparison with logics that contain Presburger constraints and that are dedicated to query XML documents. As an application, we show that satisfiability for Sheaves Logic SL is PSPACE-complete, improving significantly its best known upper bound

The National Immunisation Programme in the Netherlands: surveillance and developments in 2016-2017.

Surveillance and developments in 2016-2017 In 2016, about 760,000 children aged 0 to 19 years received a total of 2,140,000 vaccinations within the National Immunisation Programme (NIP). Participation in the NIP was high (more than 90% depending on the vaccine), but dropped by around 0.5% for newborns for the third consecutive year. The participation in vaccinations against human papillomavirus (HPV) declined from 61 to 53 per cent. The number of reports (1,483) of adverse events following immunisation (in total 3,665) in 2016 was comparable to the number of reports in 2015. NIP target diseases The number of reported cases of most NIP target diseases was again low. However, the number of cases of Haemophilus influenzae type b (Hib) disease in 2016 (n=44) was considerably higher than in the previous five years (22-34 cases), with the highest incidence occurring among children under five years of age. Pertussis incidence in 2016 fits within the usual fluctuations. However, six people died from pertussis in 2016.The incidence of cervical cancer cases increased in 2016 (9.3 per 100,000 compared with 7.7 per 100,000 in 2015). In 2017, two fully vaccinated employees were exposed to a wild poliovirus type 2 (WPV2). Due to strict isolation, no transmission was detected. Potential NIP target diseases An increase in the number of meningococcal (Men) disease was observed after more than two decades of decrease. An ongoing increase in the number of cases of MenW disease has been observed (9, 50 and 34, respectively, in 2015, 2016 and the first five months of 2017). Dutch Health Council recommendations The RIVM facilitate the Dutch Health Council with their recommendations on vaccinations and therefore has collected and structured relevant national and international information in background documents concerning rotavirus, meningococcal disease and HPV.The Health Council has advised earlier that maternal pertussis vaccination should be provided. The Ministry of Health, Welfare and Sport (VWS) has expressed a positive attitude towards the advice but still has to make a decision. In 2017, the Health Council also advised that all employees who are in close contact with young infants during work should be offered vaccination against pertussis. In addition, the Dutch Health Council advised in September 2017 positive on vaccination against rotavirus and the minister decided to vaccinate against MenACWY in 2018. (aut. ref.

Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5–11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4–17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions

Saccular Abdominal Aortic Aneurysms Patient Characteristics, Clinical Presentation, Treatment, and Outcomes in the Netherlands

Objective: The aim of this was to analyze differences between saccularshaped abdominal aortic aneurysms (SaAAAs) and fusiform abdominal aortic aneurysms (FuAAAs) regarding patient characteristics, treatment, and outcome, to advise a threshold for intervention for SaAAAs.Background: Based on the assumption that SaAAAs are more prone to rupture, guidelines suggest early elective treatment. However, little is known about the natural history of SaAAAs and the threshold for intervention is not substantiated.Methods: Observational study including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which the shape was registered, registered in the Dutch Surgical Aneurysm Audit (DSAA). Patients were stratified by urgency of surgery; elective versus acute (symptomatic/ruptured). Patient characteristics, treatment, and outcome were compared between SaAAAs and FuAAAs.Results: A total of 7659 primary AAA-patients were included, 6.1% (n = 471) SaAAAs and 93.9% (n = 7188) FuAAAs. There were 5945 elective patients (6.5% SaAAA) and 1714 acute (4.8% SaAAA). Acute SaAAApatients were more often female (28.9% vs 17.2%, P = 0.007) compared with acute FuAAA-patients. SaAAAs had smaller diameters than FuAAAs, in elective (53.0mm vs 61 mm, P = 0.000) and acute (68mm vs 75 mm, P = 0.002) patients, even after adjusting for sex. In addition, 25.2% of acute SaAAA-patients presented with diameters <55mm and 8.4% <45 mm, versus 8.1% and 0.6% of acute FuAAA-patients (P = 0.000). Postoperative outcomes did not significantly differ between shapes in both elective and acute patients.Conclusions: SaAAAs become acute at smaller diameters than FuAAAs in DSAA patients. This study therefore supports the current idea that SaAAAs should be electively treated at smaller diameters than FuAAAs. The exact diameter threshold for elective treatment of SaAAAs is difficult to determine, but a diameter of 45mm seems to be an acceptable threshold.Vascular Surger