LiLa-Klassifikation für Frakturen der langen Röhrenknochen im Wachstumsalter

Die Unfallchirurgie - Neben der AO-Klassifikation für Frakturen im Wachstumsalter (PCCF, ?Pediatric Comprehensive Classification of Long-Bone Fractures“) gibt es die...     

Gene control of tyrosine kinase TIE2 and vascular manifestations of infections

Ligands of the endothelial-enriched tunica interna endothelial cell kinase 2 (Tie2) are markedly imbalanced in severe infections associated with vascular leakage, yet regulation of the receptor itself has been understudied in this context. Here, we show that TIE2 gene expression may constitute a novel vascular barrier control mechanism in diverse infections. Tie2 expression declined rapidly in wide-ranging models of leak-associated infections, including anthrax, influenza, malaria, and sepsis. Forced Tie2 suppression sufficed to attenuate barrier function and sensitize endothelium to permeability mediators. Rapid reduction of pulmonary Tie2 in otherwise healthy animals attenuated downstream kinase signaling to the barrier effector vascular endothelial (VE)-cadherin and induced vascular leakage. Compared with wild-type littermates, mice possessing one allele of Tie2 suffered more severe vascular leakage and higher mortality in two different sepsis models. Common genetic variants that influence TIE2 expression were then sought in the HapMap3 cohort. Remarkably, each of the three strongest predicted cis-acting SNPs in HapMap3 was also associated with the risk of acute respiratory distress syndrome (ARDS) in an intensive care unit cohort of 1,614 subjects. The haplotype associated with the highest TIE2 expression conferred a 28% reduction in the risk of ARDS independent of other major clinical variables, including disease severity. In contrast, the most common haplotype was associated with both the lowest TIE2 expression and 31% higher ARDS risk. Together, the results implicate common genetic variation at the TIE2 locus as a determinant of vascular leak-related clinical outcomes from common infections, suggesting new tools to identify individuals at unusual risk for deleterious complications of infection.Among vascular-enriched receptor tyrosine kinases, Tie2 is unusual in at least two functional aspects. First, Tie2 phosphorylation is tightly controlled by the interplay of several proteins: a paralogous receptor, Tie1; a tyrosine phosphatase, vascular endothelial-protein tyrosine phosphatase (VE-PTP); and two secreted ligands, angiopoietin (Angpt)-1 and Angpt-2, the latter of which can act as an agonist, partial agonist, or antagonist depending upon context (1–6). Second, unlike classic growth factor receptors, Tie2 is heavily expressed and phosphorylated throughout the quiescent adult vasculature (7), suggesting that Tie2 signaling has one or more roles in vascular maintenance.Based largely on Angpt-1 overexpression studies, Tie2 has been implicated in vascular barrier defense (8, 9). However, adult-specific deletion of Angpt-1 does not appear to trigger vascular leakage (10). Moreover, Angpt-1 has repeatedly been ascribed functions that are independent of Tie2 (11–13). Finally, observational studies in humans suffering clinical manifestations of vascular leakage have consistently shown a marked imbalance in Tie2 ligands tilting in favor of Angpt-2 (reviewed in 14). Although decreased Tie2 activity has been inferred from these reports, the role of TIE2 gene expression has not been directly queried experimentally or in clinical settings.This question is important not only for understanding control mechanisms of the circulatory system but also to guide the development of strategies to predict, stratify, and treat patients affected by acute vascular leakage. If tonic Tie2 signaling is indeed necessary for vascular barrier maintenance, then reducing the pool of receptors could constitute a ligand-independent means to attenuate barrier-protective signaling in the endothelium. We therefore hypothesized that the level of Tie2 expression modulates the sensitivity of blood vessels, and thereby the entire organism, to noxious stimuli. Cellular, rodent, and human genetics studies were undertaken to test this concept.     

Topiramate‐induced nephrolithiasis

Nephrolithiasis is a less common side effect of the antiepileptic drug topiramate. We report the case of a 3‐year‐old boy who presented to the emergency department with abdominal pain; examinations revealed a large calcification in the left kidney. Regular ultrasound examinations are recommended in children using topiramate.     

Necessity of 3D visualization for the removal of lower wisdom teeth: required sample size to prove non-inferiority of panoramic radiography compared to CBCT

The availability of cone beam computed tomography (CBCT) and the numbers of CBCT scans rise constantly, increasing the radiation burden to the patient. A growing discussion is noticeable if a CBCT scan prior to the surgical removal of wisdom teeth may be indicated. We aimed to confirm non-inferiority with respect to damage of the inferior alveolar nerve in patients diagnosed by panoramic radiography compared to CBCT in a prospective randomized controlled multicentre trial. Sample size (number of required third molar removals) was calculated for the study and control groups as 183,474 comparing temporary and 649,036 comparing permanent neurosensory disturbances of the inferior alveolar nerve. Modifying parameter values resulted in sample sizes ranging from 39,584 to 245,724 respectively 140,024 to 869,250. To conduct a clinical study to prove a potential benefit from CBCT scans prior to surgical removal of lower wisdom teeth with respect to the most important parameter, i.e., nerval damage, is almost impossible due to the very large sample sizes required. This fact vice versa indicates that CBCT scans should only be performed in high risk wisdom tooth removals.     

On the symmetry of siblings: automated single-cell tracking to quantify the behavior of hematopoietic stem cells in a biomimetic setup

The interplay between hematopoietic stem and progenitor cells (HSPC) and their local microenvironment is a key mechanism for the organization of hematopoiesis. To quantitatively study this process, a time-resolved analysis of cellular dynamics at the single-cell level is an essential prerequisite. One way to generate sufficient amounts of appropriate data is automatic single-cell tracking using time-lapse video microscopy. We describe and apply newly developed computational algorithms that allow for an automated generation of high-content data of single-cell characteristics at high temporal and spatial resolution, together with the reconstruction and statistical evaluation of complete genealogical histories. This methodology has been applied to the particular example of purified primary human HSPCs in bioengineered culture conditions. The combination of genealogical information and dynamic profiles of cellular properties identified a marked symmetry between sibling HSPCs regarding cell cycle time, but also migration speed and growth kinetics. Furthermore, we demonstrate that this symmetry of HSPC siblings can be altered by exogenous cues of the local biomimetic microenvironment. Using the example of HSPC growth in biomimetic culture systems, we show that our approach provides a valuable tool for the quantitative analysis of dynamic single-cell features under defined in?vitro conditions, allowing for integration of functional and genealogical data. The efficiency and accuracy of our approach pave the way for new and intriguing insights into the organizational principles of developmental patterns and the respective influence of exogenous cues not limited to the study of primary HSPCs.     

Quantitative spatially resolved post-mortem analysis of lithium distribution and transition metal depositions on cycled electrodes via a laser ablation-inductively coupled plasma-optical emission spectrometry method

Diminishing the loss of performance of lithium ion batteries (LIBs) is a challenge that is yet to be fulfilled. Understanding of deterioration processes and mechanisms (i.e., so-called aging) requires analytically accurate examination of aged cells. Changes in the distribution of lithium or transition metals in the LIB cells can influence their cycle and calendar life significantly. As electrochemically treated cells and especially their electrodes do not age homogeneously and the local electrochemistry (e.g. deposition patterns) is strongly dependent on surface properties, bulk analysis is not a satisfactory investigation method. Therefore, a surface sensitive method, namely laser ablation-inductively coupled plasma-optical emission spectrometry (LA-ICP-OES) is presented. LIB cells with lithium metal oxide LiNi_1/3Co_1/3Mn_1/3O₂ (NCM111) as cathode material and graphite as anode material are investigated using a 213 nm Nd:YAG laser.

An LA-ICP-OES method was developed and applied to investigate the transition metal dissolution in lithium batteries as well as lithium deposition e.g. in case of short circuits.