Mitophagy-Related Cell Death Mediated by Vacquinol-1 and TRPM7 Blockade in Glioblastoma IV

Glioblastoma IV (GBM) is one of the deadliest malignant diseases in adults and is characterized by a high mutation rate and multiple traits to suppress inborn and acquired immunity. We here approached autophagy-related cell death in newly established GBM cell lines derived from individual tumor isolates. Treatment with a small molecule, termed Vacquinol-1 (Vac) exhibited 100% GBM cell death, which was related to mitochondrial dysfunction, calcium-induced endoplasmic reticulum (ER)-stress, and autophagy. The toxicity of Vac was significantly increased by the inhibition of transient receptor potential cation channel, subfamily M, member 7 (TRPM7). TRPM7 is overexpressed in GBM as well as in many other tumors and thus may be a potential target by the natural compound carvacrol. Of note, at higher concentrations, Vac also induced growth inhibition and cell death in non-transformed cell types. However, in the presence of the TRPM7 inhibitor carvacrol, the tumor-selective effect of Vac was very much increased. Results given in the present study are based on long-term video microscopy using IncuCyteZOOM®, calcium measurements, and 3D ultrastructural analysis using the cryofixed material

Immune phenotypes predict survival in patients with glioblastoma multiforme

Background: Glioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods: Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results: Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA) and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions: Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention

Design of the IoT weather station

Čtenář této práce je seznámen se základní myšlenkou iniciativy internetu věcí, je obeznámen se základní meteorologickou terminologií, s meteorologickými veličinami a s jejich vyhodnocováním. Rovněž se dočítá o možné variantě řešení návrhu IoT meteostanice zahrnující hardwarové a softwarové výstupy, návody a popisy vztažené k návrhu a celkové shrnutí problematiky.A reader of this thesis is introduced into basic think about Internet of Things initiation, is informed about elementary meteorologic terminology, about meteorologic units and about their processing. The reader will also read about possible variant of IoT weather station design solution including hardware and software outputs, including guidelines and descriptions related to the design and including final summary of the problematics.

Design of the IoT weather station

A reader of this thesis is introduced into basic think about Internet of Things initiation, is informed about elementary meteorologic terminology, about meteorologic units and about their processing. The reader will also read about possible variant of IoT weather station design solution including hardware and software outputs, including guidelines and descriptions related to the design and including final summary of the problematics

Die Epidemiologie und Prävention der Schädel-Hirn-Verletzung im Kindesalter

Das Schädel-Hirn-Trauma (SHT) stellt ein signifikantes medizinisches, soziales und wirtschaftliches Problem dar. Die Verletzung des Gehirns ist eine der häufigsten Todesursache in vielen Populationen unter 45 Jahren. Außerdem resultiert das SHT in dieser Altersgruppe oft in einer körperlichen und/oder geistigen Behinderung. Laut Ergebnissen des statischen Bundesamten steigen die Behandlungszahlen des SHTs besonders im Kindesalter. Die unterschiedlichen Altersgruppen und nicht einheitliche Definition der Einschluss- und Ausschlusskriterien erschweren erheblich die objektive Darstellung und den Vergleich der epidemiologischen Daten. Ziel dieser Arbeit ist die Darstellung der aktuellen Behandlungsdaten von Schädel-Hirn-Verletzungen im Kindesalter am Universitätsklinikum Ulm. Es wurden alle Kinder und junge Erwachsene im Alter zwischen 0 und 18 Jahren eingeschlossen, die zwischen dem 01.01.2010 und dem 31.12.2011 in der Klinik für Unfall-, Hand-, Plastische- und Wiederherstellungschirurgie, der Klinik für Neurochirurgie, der Sektion Kinderchirurgie und der Klinik für Kinder und Jugendmedizin des Universitätsklinikums Ulm mit der Diagnose Schädel-Hirn-Trauma (ICD 10; S06.0-9) stationär behandelt und überwacht wurden. Es wurden nur symptomatische Kinder eingeschlossen, die unter Übelkeit, Erbrechen und/oder Kopfschmerzen gelitten haben und/oder ein neues neurologisches Defizit nach einer Kopfverletzung aufwiesen. Berücksichtig wurde die interne Dokumentation wie Entlassungsberichte, Operationsberichte und Pflegedokumentation. Alle Daten wurden in einer Datenbank in Form einer Excel-Tabelle erfasst. Zur Datenanalyse wurde SPSS® (IBM Company, SPSS Inc. Chicago Illinois) verwendet. In Anwesenheit steigender Behandlungszahlen des SHTs im Kindesalter zeigt sich in dieser Arbeit kein Paradigmenwechsel. Das leichte SHT im Kindesalter überwiegt. Das männliche Geschlecht zusammen mit dem Alter zwischen 1 und 4 Jahren weisen ein hohes Risiko für ein SHT auf. Räderbetriebene Unfallmechanismen dominieren nicht. Die meisten Kinder erleiden ein SHT als Folge des Sturzes zu Hause. Mit dem Alter steigt die Anzahl der Verkehrsunfälle und die Anzahl der Stürze sinkt. Unter älteren Kindern und vor allem jungen Erwachsenen kommt ein SHT zwar nicht so häufig vor. Umso mehr ist jedoch eine längere stationäre Behandlung mit kompliziertem Verlauf und mehreren Begleitverletzungen nötig. Das resultiert auch in häufiger Anwendung einer Computertomographie oder Kernspintomographie. Das SHT im Kindesalter hat eine überwiegend gute Prognose und neurochirurgische Interventionen sind nur in wenigen Fällen notwendig. Die Kenntnisse der epidemiologischen Situation des Schädel-Hirn-Traumas im Kindesalter können zur weiteren Verbesserung der Prävention beitragen. Die Anpassung der gesamten Wohnumgebung unter Berücksichtigung der Sicherheitsmaßnahmen für das Kind durch die Eltern müssen klargemacht werden. Edukative Programme und bessere Informierung, besonders in jungen Familien ohne Erfahrung, tragen dazu bei, die Risiken für eine Verletzung des Kindes primär zu erkennen und zu vermeiden

The Impact of an Ultra-Early Postoperative MRI on Treatment of Lower Grade Glioma

The timing of MRI imaging after surgical resection may have an important role in assessing the extent of resection (EoR) and in determining further treatment. The aim of our study was to evaluate the time dependency of T2 and FLAIR changes after surgery for LGG. The Log-Glio database of patients treated at our hospital from 2016 to 2021 was searched for patients >18a and non-enhancing intra-axial lesion with complete MR-imaging protocol. A total of 16 patients matched the inclusion criteria and were thus selected for volumetric analysis. All patients received an intraoperative scan (iMRI) after complete tumor removal, an ultra-early postoperative scan after skin closure, an early MRI within 48 h and a late follow up MRI after 3–4 mo. Detailed volumetric analysis of FLAIR and T2 abnormalities was conducted. Demographic data and basic characteristics were also analyzed. An ultra-early postoperative MRI was performed within a median time of 30 min after skin closure and showed significantly lower FLAIR (p = 0.003) and T2 (p = 0.003) abnormalities when compared to early postoperative MRI (median 23.5 h), though no significant difference was found between ultra-early and late postoperative FLAIR (p = 0.422) and T2 (p = 0.575) images. A significant difference was calculated between early and late postoperative FLAIR (p = 0.005) and T2 (p = 0.019) MRI scans. Additionally, we found no significant difference between intraoperative and ultra-early FLAIR/T2 (p = 0.919 and 0.499), but we found a significant difference between iMRI and early MRI FLAIR/T2 (p = 0.027 and p = 0.035). Therefore, a postoperative MRI performed 24 h or 48 h might lead to false positive findings. An MRI scan in the first hour after surgery (ultra-early) correlated best with residual tumor at 3 months follow up. An iMRI with open skull, at the end of resection, was similar to an ultra-early MRI with regard to residual tumor

Epidermal to Mesenchymal Transition and Failure of EGFR-Targeted Therapy in Glioblastoma

Glioblastoma multiforme (GBM), the most common primary brain tumor in adults, is almost never curable with the current standard treatment consisting of surgical resection, irradiation and temozolomide. The prognosis remains poor despite undisputable advances in the understanding of this tumor’s molecular biology and pathophysiology, which unfortunately has so far failed to translate into a meaningful clinical benefit. Dysregulation and a resulting prominent pathophysiological role of the epidermal growth factor receptor (EGFR) have been identified in several different malignant tumor entities, GBM among them. The EGFR is overexpressed in about 40% of GBM cases, and half of these coexpress a mutant, constitutively activated subtype, EGFRvIII. Unfortunately, recent trials studying with therapeutic approaches targeted against the EGFR and EGFRvIII have failed to meet expectations, with only a minority of patients responding despite evidence of good <em>in vitro</em> and rodent model activity. Having potentially high relevance within this context, epithelial to mesenchymal transition (EMT) is a phenomenon associated with early stages of carcinogenesis, cancer invasion and recurrence. During EMT, epithelial cells lose many of their epithelial characteristics, prominently E-cadherin expression, and acquire properties that are typical for mesenchymal cells such as the expression of vimentin. Epithelial to mesenchymal transition has been specifically demonstrated in GBM. In this review, we summarize the evidence that EMT may precipitate GBM resistance to EGFR-targeted therapy, and may thus be among the principal factors contributing to the clinical failure of targeted therapy against EGFR and EGFRvIII

Management of pseudo-aneurysm combined with carotid-cavernous fistula after iatrogenic injury of internal carotid artery due to paranasal sinuses surgery – case report

Although infrequent, occurrences of internal carotid artery (ICA) injuries during transnasal procedures can potentially lead to severe neurological deficits or even prove fatal. We present a case of a 54 years old male patient who suffered an iatrogenic ICA lesion resulting in a pseudo-aneurysm and direct carotid-cavernous fistula after paranasal sinuses surgery. Successful multirdisciplinary treatment included flow diversion, transsphenoidal surgery and embolization of a carotid-cavernous fistula.A sealing of injured ICA wall and complete occlusion of carotid cavernous fistula led to the patient's discharged without any neurological deficits.ICA injury during transnasal surgery is a rare but dangerous and potentially life-threatening complication necessitating multidisciplinary approach and management in a specialized center