Transcatheter aortic valve implantation (TAVI) is an alternative therapy for symptomatic severe aortic valve stenosis in high-risk patients with several co-morbidities. We evaluated the 1-year ...effects of TAVI on quality of life, exercise capacity, neurohormonal activation, and myocardial hypertrophy. From June 2008 to October 2009, consecutive patients aged ≥75 years with symptomatic severe aortic valve stenosis (area <1 cm2 ) and a logistic euroSCORE ≥15% or aged >60 years with additional specified risk factors underwent TAVI. An aortic valve prosthesis (CoreValve) was inserted in a retrograde fashion. Examinations were performed before and 30 days and 1 year after TAVI. An assessment of the quality of life (Minnesota Living with Heart Failure Questionnaire), a 6-minute walking test, measurement of B-type natriuretic peptide, and echocardiography were performed. In 51 patients (mean age 78 ± 6.6 years, mean left ventricular ejection fraction 58.4 ± 12.2%), the follow-up examinations were performed after TAVI. The 1-year follow-up visit after TAVI revealed significantly improved quality of life (baseline Minnesota Living with Heart Failure Questionnaire score 39.6 ± 19 vs 26.1 ± 18, p <0.001) and more distance covered in the 6-minute walking test (baseline 185 ± 106 vs 266 ± 118 m, p <0.001). The B-type natriuretic peptide level had decreased (baseline 642 ± 634 vs 323 ± 266 pg/ml, p <0.001), and the left ventricular mass index had decreased (156 ± 45 vs 130 ± 42 g/m2 , p <0.001). The left ventricular diameter and ejection fraction remained unchanged. In conclusion, TAVI leads to significantly reduced neurohormonal activation, regression of myocardial hypertrophy, and lasting enhancement of quality of life and exercise capacity in patients with symptomatic and severe aortic stenosis 1 year after intervention.
Based on the representative data collection of the German Environmental Survey on Children 2003-2006 (GerES IV) the Human Biomonitoring Commission of the German Federal Environment Agency has updated ...the reference values for a comprehensive number of environmental pollutants in blood and urine of children in Germany. Reference values are statistically derived values that indicate the upper margin of background exposure to a given pollutant in a given population at a given time. They can be used as criteria to classify the measured values of individuals or population groups as being “elevated” or “not elevated”. Since environmental conditions are changing, reference values are continuously checked and updated if new information becomes available. Therefore, the previously derived reference values for metabolites of pyrethroids (
cis-,
trans-Cl
2Ca and 3-PBA: 1, 2, and 2
μg/l), of PAH (1-hydroxypyrene: 0.5
μg/l), for arsenic in urine (15
μg/l), and for PCB 138, PCB 153, PCB 180 in whole blood (0.3, 0.4, 0.3
μg/l) and for DDE (western Germany) in whole blood (0.7
μg/l) were confirmed. The following reference values were lowered: lead in blood from 50 to 35
μg/l, cadmium in urine from 0.5 to 0.2
μg/l, mercury in whole blood from 1.0 to 0.8
μg/l, mercury in urine from 0.7 to 0.4
μg/l, ß-HCH in whole blood from 0.3 to 0.1
μg/l, HCB in whole blood from 0.3 to 0.2
μg/l, and DMP in urine from 135 to 75
μg/l, and DMTP in urine from 160 to 100
μg/l. Based on the extended data set of the GerES IV, the reference value for the sum of PCB 138+153+180 in whole blood of children aged 7 to 14 was raised from 0.9 to 1.0
μg/l. The reference value for DEP in urine of children aged 3 to 14 was raised from 16 to 30
μg/l. New reference values in urine of children aged 3 to 14 living in Germany were derived for antimony (0.3
μg/l), nickel (4.5
μg/l), thallium (0.6
μg/l), uranium (0.04
μg/l), metabolites of organophosphorous compounds (DMDTP, DETP: 10
μg/l, 10
μg/l) and metabolites of PAH (1-hydroxyphenanthrene: 0.6
μg/l; 2/9-hydroxyphenanthrene: 0.4
μg/l; 3-hydroxyphenanthrene: 0.5
μg/l; 4-hydroxyphenanthrene: 0.2
μg/l; ∑ hydroxyphenanthrene (1, 2/9, 3, 4): 1.5
μg/l) in urine and for DDE in blood of children aged 7 to 14 years living in eastern Germany (1.4
μg/l). If reliable and repeated measurements show a value above the reference value, an environmental hygiene-based search for the causes and sources of this exposure is recommended. After that, it should be checked whether the exposure can be decreased within reasonable bounds.
Intestinal transport and sensing processes and their interconnection to metabolism are relevant to pathologies such as malabsorption syndromes, inflammatory diseases, obesity and type 2 diabetes. ...Constituting a highly selective barrier, intestinal epithelial cells absorb, metabolize, and release nutrients into the circulation, hence serving as gatekeeper of nutrient availability and metabolic health for the whole organism. Next to nutrient transport and sensing functions, intestinal transporters including peptide transporter 1 (PEPT1) are involved in the absorption of drugs and prodrugs, including certain inhibitors of angiotensin-converting enzyme, protease inhibitors, antivirals, and peptidomimetics like β-lactam antibiotics. Here, we verify the applicability of 3D organoids for
in vitro
investigation of intestinal biochemical processes related to transport and metabolism of nutrients and drugs. Establishing a variety of methodologies including illustration of transporter-mediated nutrient and drug uptake and metabolomics approaches, we highlight intestinal organoids as robust and reliable tool in this field of research. Currently used
in vitro
models to study intestinal nutrient absorption, drug transport and enterocyte metabolism, such as Caco-2 cells or rodent explant models are of limited value due to their cancer and non-human origin, respectively. Particularly species differences result in poorly correlative data and findings obtained in these models cannot be extrapolated reliably to humans, as indicated by high failure rates in drug development pipelines. In contrast, human intestinal organoids represent a superior model of the intestinal epithelium and might help to implement the 3Rs (Reduction, Refinement and Replacement) principle in basic science as well as the preclinical and regulatory setup.
Clinically relevant extended-spectrum beta-lactamase (ESBL)-producing multi-resistant Escherichia coli have been on the rise for years. Initially restricted to mostly a clinical context, recent ...findings prove their prevalence in extraclinical settings independent of the original occurrence of antimicrobial resistance in the environment. To get further insights into the complex ecology of potentially clinically relevant ESBL-producing E. coli, 24 isolates from wild birds in Berlin, Germany, and 40 ESBL-producing human clinical E. coli isolates were comparatively analyzed. Isolates of ST410 occurred in both sample groups (six). In addition, three ESBL-producing E. coli isolates of ST410 from environmental dog feces and one clinical dog isolate were included. All 10 isolates were clonally analyzed showing almost identical macrorestriction patterns. They were chosen for whole-genome sequencing revealing that the whole-genome content of these 10 E. coli isolates showed a very high genetic similarity, differing by low numbers of single nucleotide polymorphisms only. This study gives initial evidence for a recent interspecies transmission of a new successful clone of ST410 E. coli between wildlife, humans, companion animals and the environment. The results underline the zoonotic potential of clinically relevant multi-resistant bacteria found in the environment as well as the mandatory nature of the ‘One Health’ approach.
A successful, multi-resistant ESBL-producing Escherichia coli clone of sequence type ST410 occurs in wildlife, humans and environmental dog feces, possibly indicating a recent transmission event.
Graphical Abstract Figure.
A successful, multi-resistant ESBL-producing Escherichia coli clone of sequence type ST410 occurs in wildlife, humans and environmental dog feces, possibly indicating a recent transmission event.
Assumed representative center‐of‐stand measurements are typical inputs to models that scale forest transpiration to stand and regional extents. These inputs do not consider gradients in transpiration ...at stand boundaries or along moisture gradients and therefore potentially bias the large‐scale estimates. We measured half‐hourly sap flux (JS) for 173 trees in a spatially explicit cyclic sampling design across a topographically controlled gradient between a forested wetland and upland forest in northern Wisconsin. Our analyses focused on three dominant species in the site: quaking aspen (Populus tremuloides Michx), speckled alder (Alnus incana (DuRoi) Spreng), and white cedar (Thuja occidentalis L.). Sapwood area (AS) was used to scale JS to whole tree transpiration (EC). Because spatial patterns imply underlying processes, geostatistical analyses were employed to quantify patterns of spatial autocorrelation across the site. A simple Jarvis type model parameterized using a Monte Carlo sampling approach was used to simulate EC (EC−SIM). EC−SIM was compared with observed EC(EC−OBS) and found to reproduce both the temporal trends and spatial variance of canopy transpiration. EC−SIM was then used to examine spatial autocorrelation as a function of environmental drivers. We found no spatial autocorrelation in JS across the gradient from forested wetland to forested upland. EC was spatially autocorrelated and this was attributed to spatial variation in AS which suggests species spatial patterns are important for understanding spatial estimates of transpiration. However, the range of autocorrelation in EC−SIM decreased linearly with increasing vapor pressure deficit, implying that consideration of spatial variation in the sensitivity of canopy stomatal conductance to D is also key to accurately scaling up transpiration in space.
Human activities, especially conversion and degradation of habitats, are causing global biodiversity declines. How local ecological assemblages are responding is less clear--a concern given their ...importance for many ecosystem functions and services. We analysed a terrestrial assemblage database of unprecedented geographic and taxonomic coverage to quantify local biodiversity responses to land use and related changes. Here we show that in the worst-affected habitats, these pressures reduce within-sample species richness by an average of 76.5%, total abundance by 39.5% and rarefaction-based richness by 40.3%. We estimate that, globally, these pressures have already slightly reduced average within-sample richness (by 13.6%), total abundance (10.7%) and rarefaction-based richness (8.1%), with changes showing marked spatial variation. Rapid further losses are predicted under a business-as-usual land-use scenario; within-sample richness is projected to fall by a further 3.4% globally by 2100, with losses concentrated in biodiverse but economically poor countries. Strong mitigation can deliver much more positive biodiversity changes (up to a 1.9% average increase) that are less strongly related to countries' socioeconomic status.
The use of extracorporeal membrane oxygenation (ECMO) is discussed to improve patients' outcome in severe COVID-19 with respiratory failure, but data on ECMO remains controversial. The aim of the ...study was to determine the characteristics of patients under invasive mechanical ventilation (IMV) with or without veno-venous ECMO support and to evaluate outcome parameters. Ventilated patients with COVID-19 with and without additional ECMO support were analyzed in a retrospective multicenter study regarding clinical characteristics, respiratory and laboratory parameters in day-to-day follow-up. Recruitment of patients was conducted during the first three COVID-19 waves at four German university hospitals of the Ruhr University Bochum, located in the Middle Ruhr Region. From March 1, 2020 to August 31, 2021, the charts of 149 patients who were ventilated for COVID-19 infection, were included (63.8% male, median age 67 years). Fifty patients (33.6%) received additional ECMO support. On average, ECMO therapy was initiated 15.6 ± 9.4 days after symptom onset, 10.6 ± 7.1 days after hospital admission, and 4.8 ± 6.4 days after the start of IMV. Male sex and higher SOFA and RESP scores were observed significantly more often in the high-volume ECMO center. Pre-medication with antidepressants was more often detected in survivors (22.0% vs. 6.5%; p = 0.006). ECMO patients were 14 years younger and presented a lower rate of concomitant cardiovascular diseases (18.0% vs. 47.5%; p = 0.0004). Additionally, cytokine-adsorption (46.0% vs. 13.1%; p < 0.0001) and renal replacement therapy (76.0% vs. 43.4%; p = 0.0001) were carried out more frequently; in ECMO patients thrombocytes were transfused 12-fold more often related to more than fourfold higher bleeding complications. Undulating C-reactive protein (CRP) and massive increase in bilirubin levels (at terminal stage) could be observed in deceased ECMO patients. In-hospital mortality was high (Overall: 72.5%, ECMO: 80.0%, ns). Regardless of ECMO therapy half of the study population deceased within 30 days after hospital admission. Despite being younger and with less comorbidities ECMO therapy did not improve survival in severely ill COVID-19 patients. Undulating CRP levels, a massive increase of bilirubin level and a high use of cytokine-adsorption were associated with worse outcomes. In conclusion, ECMO support might be helpful in selected severe cases of COVID-19.
Understanding how anthropogenic disturbance influences patterns of community composition and the reinforcing interactive processes that structure communities is important to mitigate threats to ...biodiversity. Competition is considered a primary reinforcing process, yet little is known concerning disturbance effects on competitive interaction networks. We examined how differences in ant community composition between undisturbed and disturbed Bornean rainforest, is potentially reflected by changes in competitive interactions over a food resource. Comparing 10 primary forest sites to 10 in selectively-logged forest, we found higher genus richness and diversity in the primary forest, with 18.5% and 13.0% of genera endemic to primary and logged respectively. From 180 hours of filming bait cards, we assessed ant-ant interactions, finding that despite considered aggression over food sources, the majority of ant interactions were neutral. Proportion of competitive interactions at bait cards did not differ between forest type, however, the rate and per capita number of competitive interactions was significantly lower in logged forest. Furthermore, the majority of genera showed large changes in aggression-score with often inverse relationships to their occupancy rank. This provides evidence of a shuffled competitive network, and these unexpected changes in aggressive relationships could be considered a type of competitive network re-wiring after disturbance.
Aims
This prospective study aimed to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) and aortic mean gradient patterns on outcome after transcatheter aortic valve ...implantation (TAVI).
Methods and results
From 2008 to 2011, 202 consecutive patients with severe symptomatic aortic valve stenosis (aortic valve area <1.0 cm2) were submitted to TAVI. Patients were divided into four groups according to LVEF (>50% vs. ≤50%) and aortic mean pressure gradient (>40 mmHg vs. ≤40 mmHg): group 1, preserved LVEF/high gradient (n = 86); group 2, preserved LVEF/low gradient (n = 27); group 3, reduced LVEF/high gradient (n = 45); and group 4, reduced LVEF/low gradient (n = 44). A CoreValve prosthesis (Medtronic, Minneapolis, MN, USA) was inserted retrogradely. Echocardiography was performed before and 1 year after TAVI. The primary study endpoint (1‐year all‐cause mortality) was reached in 47 patients (23%). All‐cause mortality was lowest in group 1 (14%), intermediate in group 2 (22%) and group 3 (27%), and highest in group 4 (39%) (P = 0.007). In survivors, aortic mean gradient decreased in all patients (baseline 48 ± 13 mmHg vs. 10 ± 4 mmHg at 1 year, P < 0.001). LVEF improved in group 3 and group 4 (baseline 42 ± 8% vs. 51 ± 11% at 1 year, P < 0.001).
Conclusion
Severe aortic stenosis with low gradient and/or reduced LVEF is associated with worse outcome after TAVI compared with aortic stenosis with preserved LVEF/high gradient. The evaluation of these haemodynamic parameters may help to improve risk stratification in patients undergoing TAVI.
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