The effect of catchment soils on heavy metal concentrations in a brook situated in the historic mining region of Braubach, Germany

Forest soils located in the region of Braubach (Rhineland-Palatinate, Germany) are characterized by elevated concentrations of cadmium (Cd), copper (Cu), and lead (Pb), resulting from local heavy metal emissions. The regional geomorphology is dominated by the low mountain range of the Rhenish Massif and the frequent occurrence of V-shaped valleys crossed by small tributaries of the Rhine River. The frequent occurrence of steep valley slopes should theoretically facilitate the influence of polluted forest soils on brooks of the valley bottoms by intensified processes of slope water influx and soil erosion. To investigate pollution state and soil-water interactions in a heavy metal enriched catchment, concentrations of Cd, Cu, and Pb were determined for catchment soils, sediment, suspended matter, and surface water of a brook situated close to a former smelter area. Heavy metal binding was characterized by BCR sequential extraction method. Total concentrations of Cd increased with the transition from catchment soils to brook sediments and suspended matter, while the proportions of the analyzed binding fractions partially changed. The concentrations of Cu and Pb in soils were marked by a higher heterogeneity and exceeded the concentrations found in sediments and suspended matter. For Pb, the proportions of binding fractions were relatively static, whereas the Cu binding fractions in suspended matter clearly differed in comparison with soils and sediments. For all studied heavy metals, an increase in the concentration of the respective dissolved fraction was found along the course of the brook

Zur Pyometra beim Hund

Im Rahmen der hier vorliegenden Arbeit wurde die aktuelle wissenschaftliche Literatur zur Pyometra der Hündin dargestellt. In zweiten Teil der Arbeit wurden zwei interaktive Lernfälle über die Pyometra erstellt und anschließend von Studenten der Tiermedizinischen Fakultät der Ludwig Maximilian Universität München bearbeitet und evaluiert. Zur Pathogenese der Pyometra gibt es nach wie vor keine einheitliche, in allen Einzelheiten übereinstimmende, wissenschaftliche Meinung. Einigkeit besteht darin, dass neben einer bakteriellen Infektion des Uterus auch hormonelle Einflussfaktoren für das Krankheitsgeschehen ursächlich sind. Ob im Vorfeld einer Pyometra zwingend eine glandulär-zystische Hyperplasie des Endometriums vorliegen muss, wird unterschiedlich diskutiert. Als gesichert wird dagegen angesehen, dass es durch den wiederholten Hormoneinfluss zu Veränderungen des Endometriums kommt, die wiederum die Manifestation der bakteriellen Infektion und somit die Entstehung einer Pyometra begünstigen. Die chirurgische Therapie der Pyometra ist nicht mehr die einzige Therapiemethode. Durch die Verabreichung von Progesteronrezeptorblockern ist eine erfolgreiche konservative Therapie sowohl der offenen als auch der geschlossenen Form der Pyometra möglich. Voraussetzung für den Therapieerfolg ist, dass die Patientinnen zum Zeitpunkt der Behandlung noch unter dem Einfluss der körpereigenen Progesterons stehen und die ovarielle Funktion ungestört ist. Der Einsatz der Progesteronrezeptorblocker in der Behandlung der Pyometra hat im Vergleich zu den bisher eingesetzten Prostaglandinen kaum Nebenwirkungen. Im zweiten Teil der hier vorliegenden Arbeit wurden zwei Lernfälle zum Thema Pyometra der Hündin mit dem Casus und Lern- und Autorensystem erstellt. Der inhaltliche Schwerpunkt des ersten Lernfalles ist die diagnostische Vorgehensweise im Falle der geschlossenen Form der Pyometra. Der zweite im Rahmen dieser Arbeit erstellte Lernfall beschäftigt sich in erster Linie mit der konservativen Therapie der offenen Pyometra. Nach der Bearbeitung wurden die beiden Lernfälle mittels eines Fragebogens von Studenten der Tiermedizinischen Fakultät der Ludwig Maximilian Universität München bewertet. Die Evaluierung ergab, dass die grosse Mehrheit der Studenten Freude an der Bearbeitung der Lernfälle hatte, diese als eine sinnvolle Ergänzung zur Vorlesung ansieht und Interesse daran hat, weitere derartige Lernfälle zur Verfügung gestellt zu bekommen. Die überwiegend positive Bewertung der Lernfälle durch die Studenten zeigt, dass solche E-Learning Programme in Zukunft eine sinnvolle Ergänzung zu den traditionellen Lehr- und Lernmethoden darstellen könnten. Die Frage nach dem tatsächlichen Lernerfolg, der mit der Bearbeitung der Fälle verbunden ist, muss durch weitere Untersuchungen geklärt werden

PAT concepts for chromatography: Real-time monitoring, real-time control, and cause of error diagnostics

In the recent years, the growing competition in the biopharmaceutical industry due to biosimilars combined with market fluctuations and increasing product pipelines have given rise to the evaluation of continuous processing. Advantages include smaller equipment that may be disposable, an overall process intensification as well as steady-state operation. As variability should be managed by the continuous process itself to insure a consistent product quality, the development of advanced Process Analytical Technology (PAT) concepts is one crucial aspect for the implementation of continuous processing. In chromatographic protein purification, process variability can lead to variations in retention volumes or peak shapes of the eluting species. If the contaminants are co-eluting with the product, a peak deconvolution is required to enable real-time process monitoring and control. In order to overcome this analytical bottleneck, a tool will be presented, which allows for real-time peak deconvolution and pooling decisions in chromatography [1]. The peak deconvolution is obtained by Partial Least Squares Regression (PLS) modelling with spectroscopic data. The applicability of the peak deconvolution tool for real-life applications was successfully demonstrated in a case study with co-eluting monoclonal antibody, its aggregates, and fragments as well as in case study with co-eluting serum proteins [2]. Aside from the detection of variations in elution profiles, a fast diagnostics of their causes is crucial for a comprehensive process understanding and control. The identification of causes for variations in chromatography processes requires however a mechanistic understanding. In this presentation, a case study will be shown, where the deconvoluted peaks of three co-eluting model-proteins of several linear gradient elutions were used for the calibration of a mechanistic chromatography model. Variations in the elution profiles of all proteins were subsequently induced by deliberately generated errors in the process parameters flow rate, salt concentration in loading buffer, and salt concentration in elution buffer. The individual elution profiles of all proteins were determined by the peak deconvolution tool. The peak deconvolution in combination with the mechanistic model allowed for a fast estimation of the actual values of the three process parameters by curve fitting. In summary, peak deconvolution by PLS modelling with spectroscopic data might enable real-time monitoring and control in future chromatographic processes. A combination of peak deconvolution with mechanistic modelling allows furthermore for a fast cause of error-diagnostics, which might contribute to better process understanding and control and might minimize lot rejections

Gelöste Schwermetallgehalte in Uferbereichen der Unteren Lahn und ihre räumliche Differenzierung in Abhängigkeit von Flussstauungen

Um Konzentrationsverhältnisse und Mobilitätsverhalten gelöster Schwermetalle während saisonalen Wasserstands- und Durchfeuchtungsänderungen zu analysieren, wurden in Bereichen der Unteren Lahn vier Auenböden untersucht. Im Fokus dieser vergleichenden Untersuchung stand die Berücksichtigung standortspezifischer bodenhydrologischer Unterschiede, die in ufernahen Böden theoretisch aus der Stauregulierung des Gewässers hervor gehen können. Um eine solche Beeinflussung in Umfang und Ausmaß einschätzen zu können, wurden Porenwässer der Auenböden über einen Zeitraum von zwei Jahren (2011-2013) regelmäßig entnommen und nach den darin gelösten Schwermetallgehalten untersucht

Cold steel versus impedance-dependent tissue sealer tonsillectomy - a study protocol for a randomised controlled trial

INTRODUCTION: Approximately 7,000 tonsillectomies are performed annually in Denmark on a benign basis. The cold steel surgical technique is the gold standard. The risk of post tonsillectomy bleeding (PTH) in a centre in Jutland is 7.9%. A new impedance-dependent tissue sealer (IDTS) device has been developed, with preliminary results showing a reduction in operation time, perioperative bleeding and post-operative risk of bleeding of 4.5%.METHODS: A randomised, controlled, double-blinded multicentre trial of cold steel tonsillectomy versus IDTS will be performed on 1,250 patients. The main endpoint is PTH, perioperative bleeding, operation time and post-operative pain. The secondary outcomes are days until return to work, food intake, activity and quality of life. Included in the study are patients with indication for surgery weighing ≥ 16 kg, and excluded are patients with malignancy, bleeding disorders and unwillingness to participate in the study.CONCLUSIONS: To our knowledge, the present study is the largest randomised controlled trial in ENT surgery in the Nordic countries. The study will potentially provide evidence on PTH regarding two tonsillectomy methods.FUNDING: The authors have no potential conflicts of interest to declare. The study is supplied with instruments from Medtronic needed for the surgical procedures. Furthermore, a minor part of the funding of the entire project is provided by the aforementioned company. The funding providers have no role in design or conduct of the study.CLINICALTRIALS: gov with the identification number NCT05270109.</p

trans-Dibromidobis(1-ethyl-3-methyl­imidazol-2-yl­idene)palladium(II)

The title compound, trans-[PdBr2(C6H10N2)2], was synthesized ionothermally in the ionic liquid solvent 1-ethyl-3-methyl­imidazolium bromide. In the crystal, the PdII atoms are square-planarly coordinated to two Br atoms and two neutral (C6H10N2) ligands. The PdII atom is located on an inversion centre

Nanostructure and magnetic anomaly of mechanosynthesized Ce1−x_{1-x}Yx_{x}O2−δ_{2-δ} (x ≤ 0.3) solid solutions

Electromagnetic properties of complex oxide solid solutions containing Ce and Y attract increasing interests due to their high application potential. Their properties are known to be dependent on many factors including grain size and crystal defects. Here we focus on unique features of nanocrystalline Ce$_{1-x}$Y$_{x}$O$_{2-δ}$ (x ≤ 0.3) solid solutions prepared via a mechanosynthesis. Mechanically activated CeO$_{2-δ}$ and mechanosynthesized Ce$_{1-x}$Y$_{x}$O$_{2-δ}$ exhibit room-temperature ferromagnetism. The saturation magnetization reaches maximum for the Ce$_{0.9}$Y$_{0.1}$O$_{2-δ}$ solid solution. XPS and Raman spectra show that Ce$^{Zahl}$4+s are partially reduced to Ce$^{3+}$, with simultaneous introduction of oxygen vacancies accumulated on surface of the solid solutions. An analysis of the experimental magnetization data and the determination of both the spin state and the concentration of magnetic carriers revealed that a small part of the Ce$^{3+}$ spins (<1%) is responsible for the magnetic state of the Ce$_{1-x}$Y$_{x}$O$_{2-δ}$ system. Existence of clusters with a short-range antiferromagnetic order is also suspected

Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7‐related osteopetrosis

Human induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three-step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. We observed continuous production of monocyte-like cells over a period of up to 9 weeks, generating sufficient material for several osteoclast differentiations. The analysis of stage-specific gene and surface marker expression proved mesodermal priming, the presence of monocyte-like cells, and of terminally differentiated multinucleated osteoclasts, able to form resorption pits and trenches on bone and dentine in vitro. In comparison to peripheral blood mononuclear cell (PBMC)-derived osteoclasts hiPSC-derived osteoclasts were larger and contained a higher number of nuclei. Detailed functional studies on the resorption behavior of hiPSC-osteoclasts indicated a trend towards forming more trenches than pits and an increase in pseudoresorption. We used hiPSCs from an autosomal recessive osteopetrosis (ARO) patient (BIHi002-A, ARO hiPSCs) with compound heterozygous missense mutations p.(G292E) and p.(R403Q) in CLCN7, coding for the Cl-/H+-exchanger ClC-7, for functional investigations. The patient's leading clinical feature was a brain malformation due to defective neuronal migration. Mutant ClC-7 displayed residual expression and retained lysosomal co-localization with OSTM1, the gene coding for the osteopetrosis-associated transmembrane protein 1, but only ClC-7 harboring the mutation p.(R403Q) gave strongly reduced ion currents. An increased autophagic flux in spite of unchanged lysosomal pH was evident in undifferentiated ARO hiPSCs. ARO hiPSC-derived osteoclasts showed an increased size compared to hiPSCs of healthy donors. They were not able to resorb bone, underlining a loss-of-function effect of the mutations. In summary, we developed a highly reproducible, straightforward hiPSC-osteoclast differentiation protocol. We demonstrated that osteoclasts differentiated from ARO hiPSCs can be used as a disease model for ARO and potentially also other osteoclast-related diseases. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

PIK3CA mutant tumors depend on oxoglutarate dehydrogenase

Oncogenic PIK3CA mutations are found in a significant fraction of human cancers, but therapeutic inhibition of PI3K has only shown limited success in clinical trials. To understand how mutant PIK3CA contributes to cancer cell proliferation, we used genome scale loss-of-function screening in a large number of genomically annotated cancer cell lines. As expected, we found that PIK3CA mutant cancer cells require PIK3CA but also require the expression of the TCA cycle enzyme 2-oxoglutarate dehydrogenase (OGDH). To understand the relationship between oncogenic PIK3CA and OGDH function, we interrogated metabolic requirements and found an increased reliance on glucose metabolism to sustain PIK3CA mutant cell proliferation. Functional metabolic studies revealed that OGDH suppression increased levels of the metabolite 2-oxoglutarate (2OG). We found that this increase in 2OG levels, either by OGDH suppression or exogenous 2OG treatment, resulted in aspartate depletion that was specifically manifested as auxotrophy within PIK3CA mutant cells. Reduced levels of aspartate deregulated the malate-aspartate shuttle, which is important for cytoplasmic NAD + regeneration that sustains rapid glucose breakdown through glycolysis. Consequently, because PIK3CA mutant cells exhibit a profound reliance on glucose metabolism, malate-aspartate shuttle deregulation leads to a specific proliferative block due to the inability to maintain NAD + /NADH homeostasis. Together these observations define a precise metabolic vulnerability imposed by a recurrently mutated oncogene. Keyword: PIK3CA; 2OG; OGDH; TCA cycle; glycolysisDamon Runyon Cancer Research Foundation (HHMI Fellowship

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research