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Frameless Stereotaxy in Stereoelectroencephalography Using Intraoperative Computed Tomography
No full textAround one-third of all epilepsy patients are pharmacoresistant, often presenting with temporal lobe epilepsy (TLE), and 20% show extratemporal seizure onsets [1,2,3,4,5]. For carefully selected patients with focal pharmacoresistant epilepsy, resective surgery is a well-established and promising treatment option, showing excellent outcomes especially in TLE patients [4,6], but posing a greater challenge in extratemporal lobe epilepsy [7,8,9]. However, one major prerequisite for resective surgery is the clear and precise approximation of the epileptogenic zone (EZ). Especially in cases in which non-invasive multimodal diagnostics fail to accurately define the EZ due to inconclusive radiological, clinical, semiological, and neuropsychological findings, further invasive diagnostics utilizing intracranial electroencephalography (iEEG) might be useful [10,11].
The current common practice for performing iEEG is the so-called stereo EEG (SEEG), which is based on the implantation of depth electrodes. Following anatomo-electro-clinical hypotheses, SEEG allows for the identification of seizure origin and propagation and a definition of the EZ. SEEG depth electrode implantation can generally be performed using frame-based stereotaxy or frameless navigation, with or without robotic assistance [12,13,14,15]. Accuracy is crucial in determining the risk of intracranial complications and the likelihood of successful EEG recordings and localization of the epileptogenic zone [15], independent of the applied technique. Clinical accuracy is a multifactorial parameter. In stereotactic and navigational applications, overall or clinical accuracy, which is most important to the surgeon, can be roughly divided into application accuracy and intraoperative accuracy, and the surgeon tremendously depends on accuracy in every single step of the procedure. Application accuracy itself can be divided into three domains as follows: imaging, technical, and registration accuracy [16,17,18]. Imaging accuracy mainly concerns the precise and optimized multimodal planning of trajectories incorporating target and risk structures, and the modality also ensures geometrical accuracy. The technical accuracy of the navigational systems depends, e.g., on the technique used (frame-based vs. frameless); the intrinsic accuracy of the systems itself; or the tracking technique used, which is nowadays considered to be less than 3 mm in frameless systems and even less in frame-based stereotactic systems, aiming for submillimeter accuracy [16,19]. Especially in frameless setups, registration accuracy mainly influences the application accuracy, offering user-dependent methods for landmark- and surface-based techniques with mean target registration errors of up to 5 mm [20,21,22] or automated intraoperative imaging-based techniques with higher registration accuracy and with target registration errors (TREs) of less than 1 mm [18,23,24,25,26]. While the domains mentioned above are related to the presurgical phase, intraoperative events hamper overall accuracy during the course of surgery. Navigational accuracy is known to decrease over time, which is related to, e.g., the attachment of drapes, incision, trepanation/drilling, and the duration of the surgery itself. These impact the spatial relationship between the patient’s head and the reference unit (reference array vs. frame), affecting the non-linear deformations of the brain, which might be a minor issue compared to craniotomy cases.
Several methods for measuring accuracy have been introduced recently, and these are inconsistently used across different studies, dealing with the accuracy of depth electrodes in epilepsy patients. The most prominent ones are the Euclidean distance at the entry and target points, which describe the three-dimensional deviation between the planned and detected trajectory endpoints. However, especially in the case of the target points, the radial and depth errors can be considered instead, as the depth error, incorporated in the Euclidean distance, is surgeon-dependent, thereby not reflecting the accuracy of the used approach [15]. In addition to the radial error, the angular deviation between the planned and detected trajectory can also be considered. Another study suggested reporting the directional errors instead to assess the systematic error in the stereotactic system [27].
Despite a potential loss of implantation accuracy when using frameless implantation techniques instead of frame-based methods, this study aims to evaluate the effect of utilizing automated intraoperative imaging-based techniques for patient registration, which are known to offer higher accuracy, on the implantation accuracy of SEEG depth electrodes.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Gut–Brain Axis and Brain Microbiome Interactions from a Medical Perspective
No full textBackground: The gut microbiome directly impacts brain health and activity,
meaning the two are closely associated. This relationship suggests a link between microbial
imbalances and diseases such as Alzheimer’s, although multiple other contributing factors,
such as genetics, also play a part. Additionally, recent studies discovered that cerebrospinal
fluid has some microbial deoxyribonucleic acid (DNA), which can be interpreted to mean a
microbiome exists in the brain too. The vagus nerve and the central nervous and immune
systems are responsible for the connection between the brain and gut microbiome. Aims
and Objectives: The main aim of this systematic review is to analyze existing research on
the gut–brain axis and the brain microbiome to fill the current knowledge gap. Materials
and Methods: A search was conducted on the PubMed database based on a set of prede-
fined MeSH terms. Results: After the search, 2716 articles meeting the MeSH parameters
were found in PubMed. This list was then downloaded and analyzed according to the
inclusion/exclusion criteria, and 63 relevant papers were selected. Discussion: Bacteria
in the gut microbiome produce some substances that are considered neuroactive. These
compounds can directly or indirectly affect brain function through the gut–brain axis.
However, various knowledge gaps on the mechanisms involved in this connection need to
be addressed first.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Untersuchungen zur Darstellung von (mis-)match-Siloxankomplexen
No full textZiel dieser Arbeit war die Untersuchung von mismatch-Komplexen mit Liganden, welche eine
oder mehrere Siloxaneinheiten aufweisen. Dabei konnten diverse Liganden und Komplexe
realisiert werden, wobei die einzelnen Abschnitte hier separat zusammengefasst werden und
der kumulative Teil mit den unveröffentlichten Ergebnissen zusammengeführt wird.The aim of this thesis was the study of mismatch complexes with ligands containing one or
more siloxane units. Multiple ligands and complexes were sythesised whereby the individual
sections are seperatly summarized and the cumulative part is merged with the unpublished
results
Biological and experimental factors that define the effectiveness of microbial inoculation on plant traits: a meta-analysis
No full textBacterial and fungal microbiomes associated with plants can significantly affect the host’s phenotype. Inoculating plants with one or multiple bacterial and fungal species can affect specific plant traits, which is exploited in attempts to increase plant performance and stress tolerance by microbiome engineering. Currently, we lack a comprehensive synthesis on the generality of these effects related to different biological (e.g.plant models,plant traits,and microbial taxa) and experimental factors.In a meta-analysis,we showed that the plant trait under consideration and the microbial taxa used to inoculate plants significantly influenced the strength of the effect size. In a methodological context,experiments under sterilized conditions and short-term periods resulted in larger positive effects on plant traits than those of unsterilized and long-term experiments. We recommend that future studies should not only consider (short-term) laboratoryexperimentswithsterilizedplantsandsingleinoculantsbutalsoandmoreoften(long-term)fieldorgreenhouseexperiments with naturally occurring microbial communities associated with the plants and inoculated consortia including both bacteria and fungi.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Increased Myocardial MAO-A, Atrogin-1, and IL-1β Expression in Transgenic Mice with Pancreatic Carcinoma : Benefit of MAO-A Inhibition for Cardiac Cachexia
No full textCancer cachexia (CC) continues to challenge clinicians by massively impairing patients’
prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac
cachexia as characterized by atrophy, compromised metabolism, innervation and function of the
myocardium through factors awaiting clarification for therapeutic targeting. Because monoamine
oxidase-A (MAO-A) is a myocardial source of H2O2 and implicated in myofibrillar protein catabolism
and heart failure, we presently studied myocardial MAO-A expression, inflammatory cells, and
capillarization together with transcripts of pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic
signals (by qRT-PCR) in a 3x-transgenic (LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre) mouse model
of orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) mice. Moreover,
we evaluated the effect of MAO-A inhibition by application of harmine hydrochloride (HH, 8 weeks,
i.p., no sham control) on PDAC-related myocardial alterations. Myocardial MAO-A protein content
was significantly increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with
an increased percentage of atrogin-1+ (p < 0.001), IL-1β+ (p < 0.01), COX2+ (p < 0.001), and CD68+
(p > 0.05) cells and enhanced transcripts of pro-inflammatory IL-1β (2.47-fold), COX2 (1.53-fold), TNF
(1.87-fold), and SOCS3 (1.64-fold). Moreover, PDAC was associated with a reduction in capillary
density (−17%, p < 0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3.
Importantly, HH treatment largely reversed the PDAC-related increases in atrogin-1+, IL-1β+, and
TNF+ cell fraction as well as in COX2, IL-1β, TNF, and SOCS3 transcripts, whereas capillary density
and KDR transcripts failed to improve. In mice with PDAC, increased myocardial pro-atrophic/-
inflammatory signals are attributable to increased expression of MAO-A, because they are significantly
improved with MAO-A inhibition as a potential novel therapeutic option. The PDAC-related loss in
myocardial capillary density may be due to other mechanisms awaiting evaluation with consideration
of cardiomyocyte size, cardiac function and physical activity.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Utilization and Evaluation of Ethics Consultation Services in Neonatal Intensive Care
No full textBackground: The opportunities of perinatal medicine have improved, but this has also been accompanied by increasing ethical challenges. Clinical ethics consultation services (CEC) could support medical teams facing these. However, nothing is currently known about the availability, utilization and evaluation of CEC in German neonatology units. Methods: This study was designed as a national, descriptive, mixed quantitative–qualitative questionnaire study. The head physicians of the pediatric departments and the heads (medical and nursing) of the corresponding neonatal intensive care units of the 213 German perinatal centers were asked to participate. Results: Ninety percent of the respondents (responding rate 24.4–38.0%) stated that CEC are established and available. However, utilization is rather low [rarely N = 40 (54.1%), never N = 12, (16.2%), occasionally N = 19 (25.7%)], although it was rated as very helpful. There was a significant correlation between utilization and perceived general usefulness (r = 0.224, p = 0.033) and support (r = 0.41, p < 0.001); whereas evaluations differed significantly between professional groups (t = −2.298, p = 0.23, Cohen’s d = 0.42). Conclusions: The contradiction between the low utilization despite positive evaluations could be related to perceived hurdles. These and the different perceptions within the professional groups give rise to the consideration of whether alternative approaches, e.g., liaison services, would be preferable in neonatology.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Recommendations for the primary prevention of atherosclerotic cardiovascular disease in primary care: a systematic guideline review
No full textIntroduction: This study systematically reviews and synthesizes recommendations from national and international clinical practice guidelines (CPGs) regarding the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults in primary care settings.
Methods: CPGs were retrieved from MEDLINE, Trip, guideline repositories, and websites of guidelines-producing societies. Two reviewers independently screened the guidelines for eligibility, assessed their quality, and extracted study characteristics and relevant recommendations for further consistency analysis. Recommendations, with their strength and evidence level, were thematically coded and clustered around clinical questions using ATLAS.ti.
Results: We included 26 CPGs from which we extracted 581 recommendations on risk assessment, non-pharmacological, and pharmacological interventions. Twenty-one guidelines (81%) were rated as having “very good” methodological quality. We categorized the recommendations into 124 clusters. Forty-four clusters (35%) included consistent recommendations, but only four of them (3%) included highly consistent recommendations. These clusters emphasized avoiding routine prescriptions of nicotinic acid, aspirin, and fibrates for primary ASCVD prevention alone, and recommending 20 mg/day of atorvastatin for high-risk ASCVD patients. The recommendations also highlighted the importance of adhering to a Mediterranean-type diet, patient-centered counseling, and standardized risk assessment for patients over the age of 40.
Discussion: This review underscores the heterogeneity in primary ASCVD prevention recommendations and the importance of personalized strategies for at-risk individuals.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Implant-Derived S. aureus Isolates Drive Strain-Specific Invasion Dynamics and Bioenergetic Alterations in Osteoblasts
No full textBackground: Implants are integral to modern orthopedic surgery. The outcomes are good, but infections remain a serious issue. Staphylococcus aureus (S. aureus), along with Staphylococcus epidermidis, are predominant pathogens responsible for implant-associated infections, as conventional antibiotic treatments often fail due to biofilm formation or the pathogens’ ability to invade cells and to persist intracellularly. Objectives: This study therefore focused on interactions of S. aureus isolates from infected implants with MG63 and SaOS2 osteoblasts by investigating the adhesion, invasion, and the impact on the bioenergetics of osteoblasts. Methods and Results: We found that the ability of S. aureus to adhere to osteoblasts depends on the isolate and was not associated with a single gene or expression pattern of characteristic adhesion proteins, and further, was not correlated with invasion. However, analysis of invasion capabilities identified better invasion conditions for S. aureus isolates with the SaOS2 osteoblastic cells. Interestingly, metabolic activity of osteoblasts remained unaffected by S. aureus infection, indicating cell survival. In contrast, respiration assays revealed an altered mitochondrial bioenergetic turnover in infected cells. While basal as well as maximal respiration in MG63 osteoblasts were not influenced statistically by S. aureus infections, we found increased non-mitochondrial respiration and enhanced glycolytic activity in the osteoblasts, which was again, more pronounced in the SaOS2 osteoblastic cells. Conclusions: Our findings highlight the complexity of S. aureus-host interactions, where both the pathogen and the host cell contribute to intracellular persistence and survival, representing a major factor for therapeutic failures
Die Besucherbücher der Odenwaldschule (1910-1933)
No full textDie Besucherbücher der Odenwaldschule beginnen am 15. Mai 1910, also mit Gründung der Schule. Bis zum politischen Sieg der Nationalsozialisten im März 1933 waren sie auf 668 dichtbeschriebene Seiten angewachsen. Sieht man von den sicherlich auch vergessenen Eintragungen ab, so ist die Quelle vollständig, denn es gibt bis 1933 keine zeitlichen Lücken. Die eigenhändigen Einträge enthalten in der Regel Datum des Besuchs, Name und Vorname der Besucherinnen oder der Besucher. Hinzu kommen zumeist Angaben über Wohnort und akademische Titel (in Einzelfällen auch über den Beruf) sowie bei Ausländerinnen und Ausländern das Herkunftsland
Immunophenotyping of myelomonocytic cells in patients with COVID-19 disease
No full textDas neuartige Coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)
trat im Dezember 2019 erstmals in der chinesischen Stadt Wuhan auf und breitete sich seither
über den gesamten Globus aus, sodass die WHO am 11. März 2020 die durch das Coronavirus
hervorgerufene Erkrankung COVID-19 offiziell zu einer Pandemie erklärte. Das Krankheitsbild
variiert zwischen asymptomatischen Verläufen, milder Symptomatik bis hin zu schwersten
Verläufen, die eine Hospitalisierung oder sogar intensivmedizinische Behandlung erforderlich
machen. Dabei stellt insbesondere die schwere Pneumonie im Rahmen der COVID-19
Erkrankung mit Beatmungspflichtigkeit und nachfolgendem Lungenversagen (Acute
respiratory distress syndrome, ARDS) eine klinische Herausforderung dar. COVID-19
manifestiert sich zudem systemisch und kann mit einer dysregulierten Immunantwort
einhergehen, welche mit einer erhöhten Mortalität assoziiert ist. Ziel dieser Arbeit war, die
immunologischen Veränderungen von COVID-19 Patienten mittels durchflusszytometrischer
Analysieren zu erfassen und COVID-19 spezifische Merkmale von schweren
Krankheitsverläufen ausfindig zu machen, um eine frühzeitige Risikostratifizierung zu
ermöglichen und eine Grundlage für Therapieoptionen zu bieten.
Die Studienpopulation umfasste 25 Patienten, die im Zeitraum vom 19.03.2020 bis zum
17.06.2020 im Universitätsklinikum Marburg mit COVID-19 typischen Milchglasinfiltraten in der
Bildgebung stationär aufgenommen wurden. Dieses Patientenkollektiv wurde anhand des
Testergebnisses aus der RT-PCR in eine SARS-CoV-2 positive (N = 16) und eine SARS-CoV-
2 negative (N = 9) Population, sowie unabhängig vom Testergebnis in eine Intensiv- und eine
Nicht-Intensiv-Gruppe unterteilt. Die 18 intensivmedizinisch betreuten Patienten galten als
stellvertretend für einen schweren Verlauf und wurden auf mögliche COVID-19 spezifische
Marker, die einen schlechten Verlauf prognostizieren können, untersucht. Es wurden Receiver
Operating Characteristic (ROC)-Kurven angelegt, um Parameter auf ihr
Unterscheidungsvermögen zwischen SARS-CoV-2 positiven und -negativen Patienten zu
untersuchen. Des Weiteren wurde jeweils für die verschiedenen Zellreihen eine
Korrelationsmatrix nach Spearman erstellt, um nach COVID-19 spezifischen Parametern, die
innerhalb der Intensivgruppe mit einem schweren Krankheitsverlauf assoziiert sind, zu
ermitteln.
Unsere Ergebnisse zeigten bei den SARS-CoV-2 positiven Patienten nicht nur eine längere
mediane Aufenthaltsdauer im Krankenhaus sowie auf einer Intensivstation, sondern auch ein
deutlich häufiger auftretendes und schwerwiegenderes ARDS mit einer wesentlich längeren
invasiven Beatmungsdauer als bei den SARS-CoV-2 negativen Patienten. Ferner sind in der
SARS-CoV-2 positiven Gruppe im Vergleich zur negativen Kontrollgruppe mehr Patienten
verstorben, wobei der Großteil entlassen werden konnte.
Die durchflusszytometrischen Analysen der myeloischen Zellreihe ergaben, dass die
zirkulierenden neutrophilen Granulozyten eine deutlich geringere Granularität, gemessen am
SSC-Signal (Differenz ± SD; 1,11 ± 0,43 SSC-Quotient; p = 0,017), und Expression von CD15
(Differenz ± SD; 295,70 ± 117,50 MFI; p = 0,02) aufweisen, während im Monozyten
Kompartiment vermehrt nicht-klassische und intermediäre Monozyten bei Patienten mit
COVID-19 vorliegen. Zudem korrelierten eine niedrige CD16- (r = -0,72, p = 0,01, 95%-CI [-
0,92; -0,23]) und eine hohe CD64-Expression (r = 0,76, p = 0,01, 95%-CI [ 0,31; 0,93]) auf den
neutrophilen Granulozyten mit der Schwere des Gesundheitszustands und dem Sterberisiko
(ein hoher APACHE-II-Score), sowie eine erhöhte CD36 Expression mit einer
schwerwiegenderen Oxygenierungsstörung (Horowitz-Quotient) bei Patienten mit COVID-19
auf der Intensivstation (r = 0,66, p = 0,03, 95%-CI [0,07; 0,91]).
In dieser Arbeit konnte gezeigt werden, dass die durchflusszytometrische
Immunphänotypisierung zur Diagnostik und Prognoseabschätzung von COVID-19 Patienten
beitragen kann.The newly described coronavirus SARS-CoV-2 (severe acute respiratory syndrome
coronavirus type 2) first appeared in the Chinese city of Wuhan in December 2019 and has
since spread with enormous dynamics across the globe. On March 11, 2020, the WHO officially
declared the designated COVID-19 disease caused by SARS-CoV-2 as a pandemic. The
clinical appearance varies between asymptomatic cases, mild symptoms up to the most severe
courses that require hospitalization or even intensive medical treatment. In particular, severe
pneumonia in the context of COVID-19 disease with the need for ventilation and subsequent
lung failure (acute respiratory distress syndrome, ARDS) is a clinical challenge. COVID-19 also
shows systemic manifestations and can be accompanied by a dysregulated immune response,
which is associated with an increased mortality. As a result, the aim of this work was to record
the immunological changes in COVID-19 patients by means of flow cytometric analyzes and
to identify COVID-specific differences between mild and severe disease courses. The better
understanding should enable supportive diagnostics as well as early risk stratification to
optimize the therapy.
The study population comprised 25 patients who were admitted to Marburg University Hospital
between March 19, 2020 and June 17, 2020 with the COVID-typical ground-glass opacity in
imaging. Based on the test result from the RT-PCR, patients were divided into a SARS-CoV-2
positive (N = 16) and a SARS-CoV-2 negative (N = 9) population and, regardless of the test
result, into an intensive and a non-intensive group. The 18 ICU-patients were considered
representative of a severe course and were examined for possible COVID- 19 specific markers
that could predict disease severity. We used Receiver Operating Characteristic (ROC) analysis
to examine parameters for their ability to differentiate between SARS-CoV-2 positive and
SARS-CoV-2 negative patients. In addition, a correlation matrix according to Spearman was
created for various cell rows to determine COVID-specific parameters that are associated with
disease severity within the intensive group.
Our results showed that the patients with COVID-19 not only had a longer median length of
stay in hospital and longer time in an intensive care unit, but also had a significantly more
frequent and more serious lung failure (ARDS) with significantly longer invasive ventilation than
in the control group. Moreover, the death counts of the SARS-CoV-2 positive patients were
higher compared to the negative control group. However, the majority could be discharged.
The multiparameter flow cytometry analysis of the myeloid cell series showed that neutrophil
granulocytes with a low CD15 expression (difference ± SD; 295,70 ± 117,50 MFI; p = 0,02)
and diminished granularity (difference ± SD; 1,11 ± 0,43 side-scatter ratio; p = 0,02) were
characteristic of COVID-19 pneumonia, while non-classical and intermediate monocytes are
increasingly present in the monocyte compartment in patients with COVID-19. In addition, severe COVID-19 infection was correlated with a low CD16 expression (r = -0,72, p = 0,01,
95%-CI [-0,92; -0,23]) and high CD64 expression (r = 0,76, p = 0,01, 95%-CI [0,31; 0,93]) in
the neutrophil granulocytes, and ARDS was correlated with CD36 expression (r = 0,66, p =
0,03, 95%-CI [0,07; 0,91]).
In this work it was confirmed that the COVID-19 disease is related to characteristic changes in
the blood count, which are recorded by flow cytometry and can also be included in the
diagnosis of the COVID-19 disease to enable early risk stratification