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Identifikation wichtiger prognostischer Faktoren für die interventionelle Herzklappentherapie bei fortgeschrittener Herzinsuffizienz
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NeuroGame: neural mechanisms underlying cognitive improvement in video gamers
Get PDFThe video game market represents an influential and profitable industry. But concerns have been raised how video games impact on the human mind. There are reservations that video gaming may be addictive and foster aggressive behaviour. In contrast, a convincing body of research indicates that playing video games may improve cognitive processing. The exact mechanism thereof is not entirely understood. Most research suggests that video games train individuals in learning how to employ attentional control to focus on processing relevant information, while being able to suppress irrelevant information. Thus, video game players acquire the ability of being able to develop strategies to process information more efficiently. However, no algorithmic solution therefore has been provided yet. Thus, it is not clear which and how attentional control functions contribute to these effects. Moreover, neural mechanisms thereof are not well understood. We hypothesized that alterations in alpha power, i.e., modulations in brain oscillatory activity around 10 Hz, represent a promising neural substrate of video gaming effects. This was because, alpha activity represents an established neural correlate of attention processing given that its amplitude modulation corresponds to alterations in information processing. We investigated this by relating differential cognitive processing in video game players to changes in alpha power modulation. Moreover, we tried to imitate this effect using non-invasive brain stimulation. We were successful in achieving the former but not the latter. We provide a reasonable explanation for this. Thus, our results mostly support our hypothesis according to which altered alpha power may account for gaming effects
The immune-modulating effects of PFKFB3 inhibition in a syngeneic ovarian cancer model
Get PDFBackground: Despite significant advances in surgery and chemotherapy, ovarian cancer remains the leading cause of death among gynecological malignancies. In an effort to establish new therapies, the focus has shifted toward restricting cancer metabolism. A key regulatory enzyme, PFKFB3, is overexpressed in OC and plays an important role in promoting tumor cell growth. Targeting glycolysis via selective PFKFB3 inhibition has shown promising results in pre-clinical studies. Nevertheless, its effects on the hosts` ability to initiate a potent anti-tumor immune response remain unknown. In this study, we describe the effects of PFK-158, a novel selective molecule inhibitor of PFKFB3, on the immune profile of mice using a syngeneic ovarian cancer model.
Methods: We investigated the anti-cancer activity and immune-modulating effects of PFK-158 treatment in vitro, ex vivo, and in vivo. The focus of this study has been the adaptive immune system and more specifically, the T cell-mediated immune response, being the most relevant prognostic factor in OC survival. Proliferation and metabolomic analysis were performed on serous ovarian cancer mimicking STOSE cells as well as murine T cells purified from splenic tissue. T cell secretory function was assessed by flow cytometry. Lastly, a comparative analysis of tumor burden and immunologic parameters in plasma, spleens, and ascitic fluid was performed in the control and treatment groups.
Results: Our study showed that PFKFB3 inhibition decreased the proliferation of malignant cells by metabolic restriction in vitro and resulted in suppressed tumor growth in vivo. PFK-158 also inhibited T cell viability, proliferation, and function as measured by cytokine release ex vivo. However, the loss of function proved to be reversible following a drug-free rehabilitation phase. Most importantly, we observed, that i.p. administration of PFK-158 led to elevated concentration levels of the immune-activating cytokine IFN-ɣ, while the concentration of immune-suppressing anti-inflammatory cytokines IL-4 and IL-6 declined in vivo. Moreover, immunohistochemical examination of the tumor tissue samples revealed an increase in tumor-infiltrating CD8+ lymphocytes under PFK-158 treatment.
Conclusion: Our research demonstrates that direct PFKFB3 inhibition not only impairs tumor growth via metabolic restrain in OC but also leads to tipping the scales towards a more effective anti-tumor immune response
Neue Anwendungsmöglichkeiten der dreidimensionalen Oberflächenerfassung zum Vergleich der Akuttoxizität radioonkologischer Fraktionierungsschemata beim Mammakarzinom sowie zur Ganzkörperscan-gestützten Verlaufsdokumentation und volumetrischen Evaluation plastisch-chirurgischer Eingriffe der unteren Extremität
Get PDFGated 99mTc-tetrofosmin SPECT and gated 18F-FDG PET for the assessment of left ventricular myocardial dyssynchrony and its impact of the left ventricular function
Get PDFGlobally, cardiovascular disease (CVD) is the leading cause of mortality. Coronary artery disease (CAD) is one of the most prevalent types of CVD and annually accounts for around half of all CVD deaths. Therefore, CAD is one of the main contributors to massive health, and health-economic, burdens. A major factor in the morbidity and mortality of CAD is Left Ventricular Mechanical Dyssynchrony (LVMD). LVMD can also be used as a measure of disease burden and, potentially, clinical outcome Currently, the non-invasive standard test within nuclear medicine diagnostic imaging for patients with CAD is ECG-gated myocardial perfusion scintigraphy (MPS). Another well-recognized non-invasive imaging technique for myocardial metabolic imaging (MMI) is ECG-gated 18Ffluorodeoxyglucose PET (FDG-PET).
Several computer software packages are currently available to provide phase analysis of ECG-gated MPS imaging and also ECG-gated FDG PET for the evaluation of LVMD. For our analyses we used Quantitative Gated SPECT (QGS, Cedars-Sinai, Los Angeles, California). Phase analysis of LVMD in patients with heart failure (HF) provides an additional tool to select patients for cardiac resynchronization therapy (CRT). The results of LVMD phase analysis of MPS and FDG-PET leads to a better selection of patients for CRT improving both treatment efficacy and cost efficiency.
In our joint publication we investigated the performance of gated FDG PET phase analysis as compared to gated MPS as well as looked at possible cut-off values for FDG PET to define dyssynchrony. We analyzed the phase analysis parameters Bandwidth (BW), Phase Standard Deviation (Phase SD), and Entropy between SPECT and PET datasets. Based on the results we could only find moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony. The optimized cut-off value for Entropy was 63%.
In my first author publication we further investigated the relationship between LVMD and LV function. We were able to show that LVMD is linked to significantly higher end diastolic volume (EDV) and end systolic volume (ESV) as well as a significantly reduced left ventricular ejection fraction (LVEF) for MPS and gated FDG PET imaging. Additionally, we validated that the increasing severity of LVMD is associated with increasing EDV and ESV as well as a decreasing LVEF. The association was strongest for the dyssynchrony parameter Entropy. Both studies show that phase analysis results of QGS for gated MPS and gated FDG-PET not only assess LVMD but also demonstrate a good correlation with LV function. Furthermore, we demonstrated that the methods cannot be used interchangeably, even though in principle both measure the same parameters.
Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. There is, however, limitation for both studies. Neverteless, this novel approach of objective analysis of dyssynchrony, is a great way forward to dive deeper into the phase analysis of both imaging techniques and thus to expand the clinical efficiency of these methods