„Geographiedidaktische Forschungen“ 1977-2017 – ein Spiegel geographiedidaktischer Entwicklungen und Diskurse in Deutschland?

Der vorliegende Beitrag wirft anlässlich des vierzigjährigen Bestehens der Schriftenreihe „Geographiedidaktische Forschungen“ des Hochschulverbandes für Geographiedidaktik (HGD) einen Blick zurück auf die Entwicklung der Reihe und beleuchtet zugleich mit Blick nach vorne zukünftige Handlungsfelder. Dabei liegt der Fokus neben Informationen zur Zielstellung, zu den Gründungskontexten sowie zu formalen und personellen Veränderungen der Schriftenreihe auf einer Dokumentation der 67 bislang erschienenen Bände, ihrer thematischen Schwerpunkte und Beitragsformate. Im Rahmen des Beitrags soll zudem der Frage nachgegangen werden, inwiefern die Schriftenreihen einen Spiegel geographiedidaktischer Entwicklungen und Diskurse in Deutschland repräsentiert

Characterization of Anti-Cancer Activities of Violacein: Actions on Tumor Cells and the Tumor Microenvironment

Natural products have been shown to serve as promising starting points for novel anti cancer drugs. In this study, the anti-cancer activities of the purple compound violacein, initially isolated from Chromobacterium violaceum, were investigated. To highlight the crucial role of the tumor microenvironment on the effectiveness of cancer therapies, this study includes effects on macrophages as prototypic cells of the microenvironment in addition to the investigation of tumor-centric activities. Using 2D and 3D cell culture models, automated live-cell microscopy, and biochemical analyses, violacein was demonstrated to inhibit tumor cell proliferation and migration. The violacein-triggered tumor cell death was further associated with caspase 3-like activation and ATP release. Stimuli released from dead cells resulted in inflammatory activation of macrophages, as shown by NF-kB reporter cell assays, macrophage morphology, and gene expression analysis. Moreover, macrophages deficient in the inflammasome component Nlrp3 were found to be significantly less sensitive towards treatment with violacein and doxorubicin. Taken together, this study provides new insights into the biological activity of violacein against cancer. In addition, the in vitro data suggest immunogenic features of induced cell death, making violacein an interesting candidate for further studies investigating the compound as an inducer of immunogenic cell death

CSF Protein Concentration Shows No Correlation With Brain Volume Measures

Background: CSF protein concentrations vary greatly among individuals. Accounting for brain volume may lower the variance and increase the diagnostic value of CSF protein concentrations. Objective: To determine the relation between CSF protein concentrations and brain volume. Methods: Brain volumes (total intracranial, gray matter, white matter volumes) derived from brain MRI and CSF protein concentrations (total protein, albumin, albumin CSF/serum ratio) of 29 control patients and 497 patients with clinically isolated syndrome or multiple sclerosis were studied. Finding: We found significant positive correlations of CSF protein concentrations with intracranial, gray matter, and white matter volumes. None of the correlations remained significant after correction for age and sex. Conclusion: Accounting for brain volume derived from brain MRI is unlikely to improve the diagnostic value of protein concentrations in CSF

CNS demyelinating events in primary Sjogren's syndrome: A single-center case series on the clinical phenotype

ObjectiveThe study aimed to assess the prevalence, clinical characteristics, and therapeutic outcomes of the central nervous system (CNS) demyelinating disease in a large cohort of primary Sjogren's syndrome (pSS). MethodsThis is an explorative cross-sectional study of patients with pSS seen in the departments of rheumatology, otorhinolaryngology, or neurology of a tertiary university center between January 2015 and September 2021. ResultsIn a cohort of 194 pSS patients, 22 patients had a CNS manifestation. In this CNS group, 19 patients had a lesion pattern suggestive of demyelination. While there were no obvious differences in the patients' epidemiological disposition or rate of other extraglandular manifestations, the CNS group differed from the remaining patients with pSS by having less glandular manifestations but a higher seroprevalence for anti-SSA/Ro antibodies. Notably, patients with CNS manifestations were often diagnosed with multiple sclerosis (MS) and treated as such, although age and disease course were atypical of MS. Many first-line MS agents were ineffective in these MS look-alikes;however, the disease course was benign with B-cell-depleting agents. ConclusionNeurological symptoms of pSS are common and clinically manifest mainly as myelitis or optic neuritis. Notably, in the CNS, the pSS phenotype can overlap with MS. The prevailing disease is crucial since it has a major impact on the long-term clinical outcome and the choice of disease-modifying agents. Although our observations neither confirm pSS as a more appropriate diagnosis nor rule out simple comorbidity, physicians should consider pSS in the extended diagnostic workup of CNS autoimmune diseases

“Geographiedidaktische Forschungen” (GDF) from 1977 to 2017–A Possible Mirror of the Development and the Discourses on Geography Didactics in Germany Over the Past 40 Years?

Der vorliegende Beitrag wirft anlässlich des vierzigjährigen Bestehens der Schriftenreihe „Geo graphiedidaktische Forschungen“ des Hochschulverbandes für Geographiedidaktik (HGD) einen Blick zurück auf die Entwicklung der Reihe und beleuchtet zugleich mit Blick nach vorne zukünf tige Handlungsfelder. Dabei liegt der Fokus neben Informationen zur Zielstellung, zu den Grün dungskontexten sowie zu formalen und personellen Veränderungen der Schriftenreihe auf einer Dokumentation der 67 bislang erschienenen Bände, ihrer thematischen Schwerpunkte und Bei tragsformate. Im Rahmen des Beitrags soll zudem der Frage nachgegangen werden, inwiefern die Schriftenreihen einen Spiegel geographiedidaktischer Entwicklungen und Diskurse in Deutschland repräsentiert.In the occasion of the 40th anniversary of the publication series "Geographiedidaktische For schungen" by Hochschulverband für Geographiedidaktik (HGD) this article gives a look back at the development of the series and, at the same time, highlights on future areas of action. In addition to information on the objectives, founding contexts and formal and personal changes in the series, the focus is on the documentation of the 67 volumes published so far, their thematic focuses and contribution format

Combined Treatment With Pembrolizumab and Allogenic BK Virus-Specific T Cells in Progressive Multifocal Leukoencephalopathy A Case Report

Objective We report a combination of BK virus-specific T cells and pembrolizumab as a treatment option in progressive multifocal leukoencephalopathy (PML). Results A 57-year-old male patient diagnosed with PML presented a fast-progressing right hemiparesis, aphasia, and cognitive deficits. Brain MRI showed a severe leukoencephalopathy with diffusion restriction. The patient was treated with 10 doses of pembrolizumab (2 mg/kg body weight) in differing intervals and 2 partially human leukocyte antigen-matched allogenic BK virus-specific T cell transfusions after the fifth pembrolizumab treatment. Although pembrolizumab alone decreased the viral load but failed to control the virus, BK-specific T cell transfer further enhanced the decline of JC virus copies in the CSF. Moreover, the regression of leukoencephalopathy and disappearance of diffusion restriction in subsequent brain MRI were observed. The combined treatment resulted in a clinical stabilization with improvements of the cognitive and speech deficits. Discussion This case supports the hypothesis that pembrolizumab is more efficient in the presence of an appropriate number of functional antigen-specific T cells. Thus, the combined treatment of pembrolizumab and virus-specific T cells should be further evaluated as a treatment option for PML in future clinical trials

Gray matter atrophy in relapsing-remitting multiple sclerosis is associated with white matter lesions in connecting fibers

Background: Lesions of brain white matter (WM) and atrophy of brain gray matter (GM) are well-established surrogate parameters in multiple sclerosis (MS), but it is unclear how closely these parameters relate to each other. Objective: To assess across the whole cerebrum whether GM atrophy can be explained by lesions in connecting WM tracts. Methods: GM images of 600 patients with relapsing-remitting MS (women = 68%;median age = 33.0 years, median expanded disability status scale score = 1.5) were converted to atrophy maps by data from a healthy control cohort. An atlas of WM tracts from the Human Connectome Project and individual lesion maps were merged to identify potentially disconnected GM regions, leading to individual disconnectome maps. Across the whole cerebrum, GM atrophy and potentially disconnected GM were tested for association both cross-sectionally and longitudinally. Results: We found highly significant correlations between disconnection and atrophy across most of the cerebrum. Longitudinal analysis demonstrated a close temporal relation of WM lesion formation and GM atrophy in connecting fibers. Conclusion: GM atrophy is associated with WM lesions in connecting fibers. Caution is warranted when interpreting group differences in GM atrophy exclusively as differences in early neurodegeneration independent of WM lesion formation

Bioelectrical Impedance Analysis and Mid-Upper Arm Muscle Circumference Can Be Used to Detect Low Muscle Mass in Clinical Practice

Identification of low muscle mass becomes increasingly relevant due to its prognostic value in cancer patients. In clinical practice, mid-upper arm muscle circumference (MAMC) and bioelectrical impedance analysis (BIA) are often used to assess muscle mass. For muscle-mass assessment, computed tomography (CT) is considered as reference standard. We investigated concordance between CT, BIA, and MAMC, diagnostic accuracy of MAMC, and BIA to detect low muscle mass and their relation with the clinical outcome malnutrition provided with the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF). This cross-sectional study included adult patients with advanced esophageal and gastrointestinal cancer. BIA, MAMC, and PG-SGA-SF were performed. Routine CT-scans were used to quantify psoas muscle index (PMI) and skeletal muscle area. Good concordance was found between CT(PMI) and both BIA(FFMI (fat free mass index)) (ICC 0.73), and BIA(ASMI (appendicular skeletal muscle index)) (ICC 0.69) but not with MAMC (ICC 0.37). BIA(FFMI) (94%), BIA(ASMI) (86%), and MAMC (86%) showed high specificity but low sensitivity. PG-SGA-SF modestly correlated with all muscle-mass measures (ranging from −0.17 to −0.43). Of all patients with low muscle mass, 62% were also classified with a PG-SGA-SF score of ≥4 points. Although CT remains the first choice, since both BIA and MAMC are easy to perform by dieticians, they have the potential to be used to detect low muscle mass in clinical practice

Multiple sclerosis lesions and atrophy in the spinal cord: Distribution across vertebral levels and correlation with disability

Background: The vast majority of magnetic resonance imaging (MRI) studies on multiple sclerosis (MS) covered the spinal cord (SC), if at all, incompletely.Objective: To assess SC involvement in MS, as detectable by whole SC MRI, with regard to distribution across vertebral levels and relation to clinical phenotypes and disability.Methods: We investigated SC MRI with sagittal and axial coverage. Analyzed were brain and SC MRI scans of 17 healthy controls (HC) and of 370 patients with either clinically isolated syndrome (CIS, 27), relapsing remitting MS (RRMS, 303) or progressive MS (PMS, 40). Across vertebral levels, cross-sectional areas were semiautomatically segmented, and lesions manually delineated.Results: The frequency of SC lesions was highest at the level C3-4. The volume of SC lesions increased from CIS to RRMS, and from RRMS to PMS whereas lesion distribution across SC levels did not differ. SC atrophy was demonstrated in RRMS and, to a higher degree, in PMS;apart from an accentuation at the level C3-4, it was evenly distributed across SC levels. SC lesions and atrophy volume were not correlated with each other and were independently associated with disability.Conclusion: SC lesions and atrophy already exist at the stage of RRMS in the whole SC with an accentuation in the cervical enlargement;SC lesions and atrophy are more pronounced in the stage of PMS. Both contribute to the clinical picture but are largely independent