Search

Simple Summary: Folate receptors can serve to increase folate uptake in cancer cells through significant overexpression, which is ultimately critical for cell proliferation and tumor growth. Therefore, the characterization of folate receptor expression in cancer presents exciting opportunities in multiple dimensions. On the one hand, the folate receptor can be used as a target for selective transfer of therapeutic agents. On the other hand, it can be used for risk stratification. We found that in prostate cancer (PCa), activation and membrane integration by GPI–transamidase exhibit significant changes. By image analysis, we could demonstrate these differences to healthy control cells and tissues, and we expect high potential in this approach to identify biological subtypes and allow risk stratification based on these alterations in PCa. Due to the proliferation-induced high demand of cancer cells for folic acid (FA), significant overexpression of folate receptors 1 (FR1) is detected in most cancers. To our knowledge, a detailed characterization of FR1 expression and regulation regarding therapeutic and diagnostic feasibilities in prostate cancer (PCa) has not been described. In the present study, cell cultures, as well as tissue sections, were analyzed using Western blot, qRT-PCR and immunofluorescence. In addition, we utilized FA-functionalized lipoplexes to characterize the potential of FR1-targeted delivery into PCa cells. Interestingly, we detected a high level of FR1-mRNA in healthy prostate epithelial cells and healthy prostate tissue. However, we were able to show that PCa cells in vitro and PCa tissue showed a massively enhanced FR1 membrane localization where the receptor can finally gain its function. We were able to link these changes to the overexpression of GPI–transamidase (GPI-T) by image analysis. PCa cells in vitro and PCa tissue show the strongest overexpression of GPI-T and thereby induce FR1 membrane localization. Finally, we utilized FA-functionalized lipoplexes to selectively transfer pDNA into PCa cells and demonstrate the therapeutic potential of FR1. Thus, FR1 represents a very promising candidate for targeted therapeutic transfer pathways in PCa and in combination with GPI-T, may provide predictive imaging in addition to established diagnostics. [ABSTRACT FROM AUTHOR]

An ionization beam profile monitor relying on a supersonic gas-jet shaped into an extended, thin curtain is proposed for operation in an ultra high vacuum environment for very low perturbation on the accelerated beam, as requested for the in-ring profile monitoring at the Ultra low energy Storage Ring (USR) at the Facility for Low-energy Antiproton and Ion Research (FLAIR), in Darmstadt. In this paper, we describe the working principle of the monitor, as well as providing an analysis of sensitivity and resolution dependence on geometrical design and gas curtain thickness. [ABSTRACT FROM AUTHOR]

Purpose: Bacterial pneumonia, a major cause of respiratory tract infections (RTI), can be challenging to diagnose and to treat adequately, especially when seasonal viral pathogens co-circulate. The aim of this study was to give a real-world snapshot of the burden of respiratory disease and treatment choices in the emergency department (ED) of a tertiary care hospital in Germany in the fall of 2022. Methods: Anonymized analysis of a quality control initiative that prospectively documented all patients presenting to our ED with symptoms suggestive of RTI from Nov 7th to Dec 18th, 2022. Results: 243 patients were followed at the time of their ED attendance. Clinical, laboratory and radiographic examination was performed in 92% of patients (224/243). Microbiological work-up to identify causative pathogens including blood cultures, sputum or urine-antigen tests were performed in 55% of patients (n = 134). Detection of viral pathogens increased during the study period from 7 to 31 cases per week, while bacterial pneumonias, respiratory tract infections without detection of a viral pathogen and non-infectious etiologies remained stable. A high burden of bacterial and viral co-infections became apparent (16%, 38/243), and co-administration of antibiotic and antiviral treatments was observed (14%, n = 35/243). 17% of patients (41/243) received antibiotic coverage without a diagnosis of a bacterial etiology. Conclusion: During the fall of 2022, the burden of RTI caused by detectable viral pathogens increased unusually early. Rapid and unexpected changes in pathogen distribution highlight the need for targeted diagnostics to improve the quality of RTI management in the ED. [ABSTRACT FROM AUTHOR]

Colistin is a last resort drug for the treatment of multiple drug-resistant (MDR) Gram-negative bacterial infections. Rapid methods to detect resistance are highly desirable. Here, we evaluated the performance of a commercially available MALDI-TOF MS-based assay for colistin resistance testing in Escherichia coli at two different sites. Ninety clinical E. coli isolates were provided by France and tested in Germany and UK using a MALDI-TOF MS-based colistin resistance assay. Lipid A molecules of the bacterial cell membrane were extracted using the MBT Lipid Xtract Kit™ (RUO; Bruker Daltonics, Germany). Spectra acquisition and evaluation were performed by the MBT HT LipidART Module of MBT Compass HT (RUO; Bruker Daltonics) on a MALDI Biotyper® sirius system (Bruker Daltonics) in negative ion mode. Phenotypic colistin resistance was determined by broth microdilution (MICRONAUT MIC-Strip Colistin, Bruker Daltonics) and used as a reference. Comparing the results of the MALDI-TOF MS-based colistin resistance assay with the data of the phenotypic reference method for the UK, sensitivity and specificity for the detection of colistin resistance were 97.1% (33/34) and 96.4% (53/55), respectively. Germany showed 97.1% (33/34) sensitivity and 100% (55/55) specificity for the detection of colistin resistance by MALDI-TOF MS. Applying the MBT Lipid Xtract™ Kit in combination with MALDI-TOF MS and dedicated software showed excellent performances for E. coli. Analytical and clinical validation studies must be performed to demonstrate the performance of the method as a diagnostic tool. [ABSTRACT FROM AUTHOR]

Liassodites obsti gen. et sp. nov., an Early Jurassic member of Trachypachidae, is described from Western Pomerania (Germany). An epoxy resin transfer method is applied for the preparation of three-dimensionally preserved fossil. An annotated list of Palaeozoic and Mesozoic trachypachid genera was elaborated. For each trachypachid fossil member and erroneously placed genus, a short diagnosis or available arguments on systematic position are proposed. The relations of the subfamilies Eodromeinae and Coptoclaviscinae (Coptoclavidae) are discussed. The description of Liassodites obsti gen. et sp. nov. makes it possible to suppose that the currently recognised hiatus between families Carabidae and Trachypachidae is not great enough to regard them as two separate families. The genus Coptoclavisca should be regarded as a member of Trachypachidae or Carabidae (including Trachypachinae). The new genus Apermunda gen. nov. is proposed for Petrodromeus minor. Novunda nom. nov. is proposed for Unda and the following binominal names are changed: Novunda angulata comb. nov., N. cursoria comb. nov., N. microplata comb. nov., N. pachycephala comb. nov. and N. chifengensis comb. nov. A synonymy of Evertus and Fortiseode is established, with change of species name: Evertus pervalimand comb. nov. The taxa Beipiaocarabus, Leptopodocoleus (including Leptopodocoleidae), Praedodromeus, Procalosoma, Xinbinia, 'Eodromeus' viriosus, 'Unda' chonggezhuangensis and 'Unda' pandurata, 'Karadromeus' xiangfanggouensis are regarded as incertae sedis. [ABSTRACT FROM AUTHOR]

Small-group interventions allow for tailored instruction for students with learning difficulties. A crucial first step is the accurate identification of students who need such an intervention. This study investigated how teachers decide whether their students need a remedial reading intervention. To this end, 64 teachers of 697 third-grade students from Germany were asked to rate whether a reading intervention for their students was "not necessary," "potentially necessary," or "definitely necessary." Independent experimenters tested the students' reading and spelling abilities with standardized tests, and a subsample of 370 children participated in standardized tests of phonological awareness and vocabulary. Findings show that teachers' decisions with regard to students' needing a reading intervention overlapped more with results from standardized spelling assessments than from reading assessments. Hierarchical linear models indicated that students' spelling abilities, along with phonological awareness and vocabulary, explained variance in teachers' ratings over and above students' reading skills. Teachers thus relied on proximal cues such as spelling skills to reach their decision. These findings are discussed in relation to clinical standards and educational contexts. Findings indicate that the teachers' assignment of children to interventions might be underspecified, and starting points for specific teacher training programs are outlined. [ABSTRACT FROM AUTHOR]

Summary: Background: Epidemiology and management practices of invasive fungal diseases (IFD) after allogeneic haematopoietic stem cell transplantation (HSCT) are a subject of constant change. We investigated the contemporary incidence, diagnostics, antifungal management and outcome at a major paediatric transplant centre in Germany. Methods: The single‐centre retrospective observational study included all paediatric allogeneic HSCT patients (pts) transplanted between 2005 and 2015. Patient‐related data were assessed up to 365 days post‐transplant. The primary endpoint was the incidence of possible, probable and proven IFDs. Secondary endpoints included diagnostics and antifungal treatment; analysis of risk factors; and overall survival with the last follow‐up in January 2017. Results: A total of 221 first (196), second (21) or third (4) procedures were performed in 200 pts (median age: 9 years, range, 0.5‐22) for leukaemia/lymphoma (149) and non‐malignant disorders (72). Prophylaxis was administered in 208 HSCT procedures (94%; fluconazole, 116, mould‐active agents, 92). At least one computed tomography scan of the chest was performed in 146, and at least one galactomannan antigen assay in 60 procedures. There were 15 cases of proven (candidemia, 4; aspergillosis, 4) or probable (aspergillosis, 7) IFDs, accounting for an incidence rate of 6.8%. Overall mortality at last follow‐up was 30%; the occurrence of proven/probable IFDs was associated with a reduced survival probability (P <.001). Conclusion: Morbidity and mortality from IFDs at our institution were consistent with data reported from other centres. Utilisation of healthcare resources for prevention, diagnosis and management of IFDs was considerable. [ABSTRACT FROM AUTHOR]

Diagnosing Autism Spectrum Disorders (ASD) is important throughout the lifespan. The objective was to investigate the transcultural diagnostic validity of the Social Communication Questionnaire (SCQ) in a clinical sample of 451 adults with Intellectual Developmental Disorder (IDD) with and without ASD in Germany, the U.S.A. and Great Britain. Variables associated with higher SCQ sum-scores were higher levels of IDD, male gender, a diagnosis of ASD and the study site (Germany > U.S.A > G.B.). An ROC analysis revealed a cut-score of 13, which resulted in a sensitivity of 0.87 and a specificity of 0.58. It is recommended to adjust the cut-score according to level of IDD and gender. Further research is needed to align diagnostic assignment of ASD across different sites and countries. [ABSTRACT FROM AUTHOR]

With the increase in molecular genetic understanding of disease, diagnostic test development and availability are growing rapidly. This study investigated oncologists' decision making on using pharmacogenomic tests for cancer treatment and examined cross-cultural differences between the USA and Germany. Pilot studies revealed that the following cues play a role in decisions on pharmacogemonic tests: stage of cancer, availability of treatment options, cost of the treatment options, severity of side effects of the treatments, therapeutic consequence of the test, cost of the test and guideline recommendation specifying use of the test. All cues were used for designing the main study comprising nine scenarios, for each of which oncologists were asked to decide whether they would order a pharmacogenomic test. On average, US oncologists opted for the test in 6.5 out of the nine scenarios (SE = 0.2), and German oncologists in 5.4 scenarios (SE = 0.2). The majority of oncologists' decisions in both the USA (76.1%) and Germany (64%) were best explained by a simple sequential model (heuristical strategy). In the USA, the information about cost of the test was most influential on the decisions; in Germany it was the guideline recommendation of the test. When the side effects of therapy B were described as being more severe within the scenarios, choices in favour of a non-recommended test increased by about 20% within both samples. Both US and German oncologists were highly inclined to use pharmacogenomic tests, but differed in what information influenced their decisions - a difference possibly explained by the differences in the health insurance systems. Although many oncologists' heuristical decisions were based on the valid cue of a test's guideline recommendation, an alarming number abandoned it when a therapy had potentially severe side effects. [ABSTRACT FROM AUTHOR]

Background: Diagnosing dementia, a syndrome affecting 35.6 million people worldwide, can be challenging, especially in patients with a migrant background. Language barriers and language-based diagnostic tools, cultural differences in the perception of the syndrome as well as restricted access to healthcare can influence medical care. For the first time in Germany, this study investigates whether German general practitioners (GPs) feel prepared to meet the diagnostic needs of these patient groups and whether there are challenges and support needs. Methods: A cross-sectional study among a random sample of 982 general practitioners in Germany was conducted from October 2017 to January 2018 (response rate: 34.5%). A self-developed, written, standardised questionnaire was used. Descriptive statistics as well as multiple logistic regression analyses were performed using data of 326 GPs. Results: Ninety-six percent of GPs reported having experienced barriers at least once. Uncertainties in diagnosing dementia in patients with a migrant background were indicated by 70.9%. There was no significant association between uncertainties in diagnosing dementia and GPs' sociodemographic characteristics. The most frequently reported barriers were language barriers that affected or prevented diagnostics (89.3%) and information deficits in patients with a migrant background (59.2%). Shameful interaction or lack of acceptance of the syndrome was also common (55.5%). A demand for more information about the topic was expressed by 70.6% of GPs. Conclusions: Public health measures supporting GPs in their interaction with patients with a migrant background as well as information and services for dementia patients are needed. Efforts to facilitate access to interpreting services and to focus on people with a migrant background in healthcare are necessary. Trial registration: German Clinical Trials Register: DRKS00012503, date of registration: 05/09/2017 (German Institute of Medical Documentation and Information. German Clinical Trials Register (DRKS) 2017). Clinical register of the study coordination office of the University hospital of Bonn: ID530, date of registration: 05/09/2017 (Universitätsklinikum Bonn. Studienzentrum. UKB-Studienregister 2017). [ABSTRACT FROM AUTHOR]