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Human spatial encoding of three-dimensional navigable space was studied, using a virtual environment simulation. This allowed subjects to become familiar with a realistic scene by making simulated rotational and translational movements during training. Subsequent tests determined whether subjects could generalize their recognition ability by identifying novel-perspective views and topographic floor plans of the scene. Results from picture recognition tests showed that familiar direction views were most easily recognized, although significant generalization to novel views was observed. Topographic floor plans were also easily identified. In further experiments, novel-view performance diminished when active training was replaced by passive viewing of static images of the scene. However, the ability to make self-initiated movements, as opposed to watching dynamic movie sequences, had no effect on performance. These results suggest that representation of navigable space is view dependent and highlight the importance of spatial-temporal continuity during learning.

Byline: Sonja Fritsche (1), Theron S. Rumsey (1), Heinrich H. D. Meyer (2), Gabi Schmidt (3), H. Steinhart (3) Keywords: Key wordsaSteroid hormones; Anabolic implant; Steers; Beef Abstract: aProfiles of steroid hormones (androgens, estrogens, progestogens and corticoids), their precursors and metabolites were analyzed in nine beef samples obtained from steers which had received the anabolic implant Synovex-S (200mg progesterone plus 20mg estradiol benzoate) and in nine samples from control steers. Analysis of phenolic steroids was performed by enzyme immunoassay after separation by HPLC. Neutral steroids were determined by GC-MS. Concentrations of the hormones progesterone and 17[beta]-estradiol, of their precursors and metabolites (pregnenolone, 17[alpha]-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, epitestosterone, [alpha]-androsterone, 17[alpha]-estradiol, and estrone) and of the corticosteroids cortisone and hydrocortisone did not differ significantly between treatments (P&gt 0.05) but the ratio of 17[beta]-estradiol to its metabolites and the cortisone/hydrocortisone ratio were significantly higher in beef from treated steers (P&lt 0.01). Concentrations of testosterone and 5[alpha]-dihydrotestosterone were below the determination limits (10ng/kg and 20ng/kg, respectively) in both treated and control steers. Author Affiliation: (1) Growth Biology Laboratory, Livestock and Poultry Sciences Institute, Agricultural Research Service, U. S. Department of Agriculture, Beltsville, MD 20705-2350, USA e-mail: Fritsche@lpsi.barc.usda.gov e-mail: trumsey@lpsi.barc.usda.gov, US (2) Institut fur Physiologie, Forschungszentrum fur Milch und Lebensmittel, Technische Universitat Munchen, D-85350 Freising-Weihenstephan, Germany e-mail: physio@pollux.edv.agrar.tu-muenchen.de, DE (3) Institut fur Biochemie und Lebensmittelchemie, Universitat Hamburg, Grindelallee 117, D-20146 Hamburg, Germany e-mail: Gabi-Schmidt@public.uni-hamburg.de e-mail: fc6a070@lc.chemie.uni-hamburg.de, DE Article note: Received: 10 August 1998

Renal failure is common and comes with a steep increasing prevalence in older patients. It is a frequent aspect in multimorbidity and associated with polypharmacia. Based on available literature an overview is given concerning important drug-drug interactions and how to avoid or manage them. Among a large variety of possible interactions anticoagulation and diuretic therapy still represent the highest clinical relevance., (© 2024. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Pulmonary edema and its association with low flow times has been observed in postcardiac arrest patients. However, diagnosis of distinct types of lung pathology is difficult.The aim of this study was to investigate pulmonary edema by transpulmonary thermodilution (TPTD) after out-of-hospital cardiac arrest (OHCA), and the correlation to downtimes. In this retrospective single-center study consecutive patients with return of spontaneous circulation (ROSC) following OHCA, age ≥ 18, and applied TPTD were enrolled. According to downtimes, patients were divided into a short and a long no-flow-time group, and data of TPTD were analysed. We identified 45 patients (n = 25 short no-flow time; n = 20 long no-flow time) who met the inclusion criteria. 24 h after ROSC, the extra vascular lung water index (EVLWI) was found to be lower in the group with short no-flow time compared to the group with long no-flow time (10.7 ± 3.5 ml/kg vs. 12.8 ± 3.9 ml/kg; p = 0.08) and remained at a similar level 48 h (10.9 ± 4.3 ml/kg vs. 12.9 ± 4.9 ml/kg; p = 0.25) and 72 h (11.1 ± 5.0 ml/kg vs. 13.9 ± 7.7 ml/kg; p = 0.27) post-ROSC. We found a statistically significant and moderate correlation between no-flow duration and EVLWI 48 h (r = 0.51; p = 0.002) and 72 h (r = 0.54; p = 0.004) post-ROSC. Pulmonary vascular permeability index (PVPI) was not correlated with downtimes. Our observation underlines the presence of cardiac arrest-related lung edema by determination of EVLWI. The duration of no-flow times is a relevant factor for increased extravascular lung water index., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

In this paper, Graham Priest's understanding of dialetheism, the view that there exist true contradictions, is discussed, and various kinds of metaphysical dialetheism are distinguished between. An alternative to dialetheism is presented, namely a thesis called 'dimathematism'. It is pointed out that dimathematism enables one to escape a slippery slope argument for dialetheism that has been put forward by Priest. Moreover, dimathematism is presented as a thesis that is helpful in rejecting the claim that logic is a normative discipline., (© The Author(s) 2022.)

Objectives: The objective of this study was to determine the diagnostic performance of 15 O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA)., Background: 15 O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date., Methods: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15 O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15 O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15 O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15 O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15 O-water PET are both >60%., Conclusions: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15 O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies., Clinical Trial Registration Information: Clinical-Trials.gov (#NCT05134012)., (Copyright © 2023 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Key Message: A major QTL on chromosome 6DL corresponding to bunt resistance gene Bt11 was identified in four mapping populations generated through crosses with Bt11-carriers PI 166910 and M822123. Common bunt in wheat has witnessed a renaissance with the rise of organic agriculture that began in the 1980s. The abandonment of systemic fungicides in organic farming, together with a lack of resistant cultivars, has led to wide-spread problems due to common bunt infections. Knowledge about genetic sources for resistance is still scarce and only few of the known bunt resistance factors are currently used in breeding. We therefore aimed to map the resistance factor harboured by the Turkish landrace PI 166910, which is the resistance donor for the Bt11 bunt differential line. Four mapping populations (MPs) with 96-132 recombinant inbred lines (RILs) were phenotyped for common bunt resistance over 2, 3 or 4 years with one or two local bunt populations and genotyped with the 25K SNP array. A major bunt resistance locus on the distal end of chromosome 6D designated QBt.ifa-6DL was identified in all MPs and experiments. Additional QTL contributing to resistance were detected on chromosomes 4B, 1A, 1B, 2A and 7B. QBt.ifa-6DL mapped to a region overlapping with the Bt9-locus identified in previous studies, but results indicate that QBt.ifa-6DL is different from Bt9 and convincing evidence from haplotype comparisons suggests that it represents the Bt11 resistance allele. Markers for the distal region of chromosome 6D between 492.6 and 495.2 Mbp can be used to select for QBt.ifa-6DL. This resistance factor confers high and stable resistance against common bunt and should be integrated into organic and low-input wheat breeding programs., (© 2023. The Author(s).)

Purpose: To develop sonographic criteria for ranula that to allow rapid and precise diagnosis, differentiation between enoral (ER) and plunging ranula (PR), and differential diagnosis from other competing pathologies in this region., Methods: Patients who presented with or were referred with ranula between 2002 and 2022 were assessed in a retrospective study. After clinical investigation, ultrasound examinations were performed in all cases. Several sonographic parameters describing the echotexture, shape and size of ranulas, their relationship to important surrounding anatomical landmarks and the characteristic spreading pattern of ERs and PRs were elaborated and evaluated., Results: 207 ranulas were included (82.12% ERs and 17.87% PRs). The ranulas were all in close anatomical relationship to the sublingual gland (SLG) and mylohyoid muscle (MM). The echo texture was hypoechoic to anechoic in 97.6% of the lesions. In comparison with ERs, PRs were larger and irregular in shape significantly more often (P = 0.0001). There were significant differences between ERs and PRs in their exact location relative to the SLG (superficial, deep, anterior, each P = 0.0001; posterior, P = 0.03) and level of the MM (above, below, above and below, P = 0.0001 each). The exact extent and plunging pattern were depicted in all PRs, but naturally in none of the ERs., Conclusions: The ultrasound criteria developed in this study, confirming previously published results, indicate that ultrasound is an excellent diagnostic tool for diagnosing ranula and differentiating between ERs and PRs., (© 2022. The Author(s).)

In malignant melanoma, a highly aggressive form of skin cancer, many microRNAs are aberrantly expressed contributing to tumorigenesis and progression. Further, deregulation of microRNA processing enzymes, like the miRNA-binding protein Argonaute 2, significantly impacts microRNA function. This study characterizes a novel splice variant of Argonaut 2, AGO2-ex1/3. AGO2-ex1/3 is substantially expressed in different melanoma cell lines and patient-derived tissue samples. It is a mature mRNA, which is translated into an N-terminally truncated Argonaute 2 protein form. Molecular dynamics simulations show that the PAZ, MID, and PIWI domain largely retain their structure in AGO2-ex1/3 and that the truncation of the N-terminus leads to an increased interdomain flexibility. Expression of AGO2-ex1/3 provides a survival advantage for melanoma cells while the knockdown causes significantly reduced proliferation and increases apoptosis. RNA-sequencing revealed that in cells lacking AGO2-ex1/3 expression many miRNA target genes are deregulated, implicating a considerable role of AGO2-ex1/3 for miRNA function. This study inaugurates insights into an important role of a so far unknown splice variant of Argonaute 2 for the miRNA pathway as well as the mechanisms which drive growth and survival of melanoma cells. This knowledge provides the basis for potential new promising therapeutic targets focusing on small RNA-mediated gene regulation in melanoma., (© 2022. The Author(s).)

Purpose: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%)., Methods: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups., Results: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed., Conclusion: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Chest X-ray is one of the most widespread examinations of the human body. In interventional radiology, its use is frequently associated with the need to visualize various tube-like objects, such as puncture needles, guiding sheaths, wires, and catheters. Detection and precise localization of these tube-like objects in the X-ray images are, therefore, of utmost value, catalyzing the development of accurate target-specific segmentation algorithms. Similar to the other medical imaging tasks, the manual pixel-wise annotation of the tubes is a resource-consuming process., Methods: In this work, we aim to alleviate the lack of annotated images by using artificial data. Specifically, we present an approach for synthetic generation of the tube-shaped objects, with a generative adversarial network being regularized with a prior-shape constraint. Namely, our model uses Frangi-based regularization to draw synthetic tubes in the predefined fake mask regions and, then, uses the adversarial component to preserve the global realistic appearance of the synthesized image., Results: Our method eliminates the need for the paired image-mask data and requires only a weakly labeled dataset, with fine-tuning on a small paired sample (10-20 images) proving sufficient to reach the accuracy of the fully supervised models., Conclusion: We report the applicability of the approach for the task of segmenting tubes and catheters in the X-ray images, whereas the results should also hold for the other acquisition modalities and image computing applications that contain tubular objects., (© 2022. CARS.)

Skeletal muscle tissue engineering aims at generating biological substitutes that restore, maintain or improve normal muscle function; however, the quality of cells produced by current protocols remains insufficient. Here, we developed a multifactor-based protocol that combines adenovector (AdV)-mediated MYOD expression, small molecule inhibitor and growth factor treatment, and electrical pulse stimulation (EPS) to efficiently reprogram different types of human-derived multipotent stem cells into physiologically functional skeletal muscle cells (SMCs). The protocol was complemented through a novel in silico workflow that allows for in-depth estimation and potentially optimization of the quality of generated muscle tissue, based on the transcriptomes of transdifferentiated cells. We additionally patch-clamped phenotypic SMCs to associate their bioelectrical characteristics with their transcriptome reprogramming. Overall, we set up a comprehensive and dynamic approach at the nexus of viral vector-based technology, bioinformatics, and electrophysiology that facilitates production of high-quality skeletal muscle cells and can guide iterative cycles to improve myo-differentiation protocols., (© 2022. The Author(s).)

Infections with hepatitis B, C, and E virus (HBV, HCV, and HEV) can be transmitted via blood and cause severe acute or chronic liver infections. To ensure the safety of blood donations and protect recipients from virus transmissions, blood donations in Germany are tested for viral genomes using nucleic acid amplification techniques (NATs) as well as for viral antigens and antibodies by serological testing. This article describes the relevant regulations on the safety of blood and blood products in Germany and the various screening methods. The safety of blood products is assessed.Currently used NAT methods for detection of hepatitis viruses are based either on polymerase chain reaction (PCR) or isothermal methods such as transcription-mediated amplification (TMA), which enable a highly sensitive detection of viral infections and thereby contribute to the reduction of the diagnostic window. Antigen tests for the detection of viral surface protein of hepatitis B virus in blood donations were introduced in the 1970s in order to prevent potential transmissions. Since the introduction of mandatory testing for HCV-specific antibodies in 1992, HCV NAT testing in 1999, anti-HBc antibody testing in 2006, and the non-mandatory HBV NAT, which is voluntarily performed by most of the blood establishments, blood safety has increased tremendously. Only a few isolated cases of transfusion-transmitted infections in the early window period have been reported since. The success of the recent introduction of mandatory HEV NAT testing in 2020 will have to be assessed in the upcoming years. Besides blood donor screening, the system for blood safety in Germany is supplemented by additional measures for donor selection and pathogen inactivation., (© 2022. The Author(s).)

Non-motor symptoms like cognitive impairment are a huge burden for patients with Parkinson's disease. We examined conflict adaptation by using the congruency sequence effect as an index of adaptation in 17 patients with Parkinson's disease and 18 healthy controls with an Eriksen flanker task using functional magnet resonance imaging to reveal possible differences in executive function performance. We observed overall increased response times in patients with Parkinson's disease compared to healthy controls. A flanker interference effect and congruency sequence effect occurred in both groups. A significant interaction of current and previous trial type was revealed, but no effect of response sequence concerning left or right motor responses. Therefore, top-down conflict monitoring processes are likely the main contributors leading to the congruency sequence effect in our paradigm. In both groups incongruent flanker events elicited activation in the middle temporal gyrus, inferior parietal cortex, dorsolateral prefrontal cortex and the insula in contrast to congruent flanker events. A psychophysiological interactions analysis revealed increased functional connectivity of inferior parietal cortex as a seed to the left prefrontal thalamus during incongruent vs. congruent and neutral stimuli in patients with Parkinson's disease that may reflect compensatory facilitating action selection processes. We conclude that patients with Parkinson's disease exhibit conflict adaptation comparable to healthy controls when investigated while receiving their usual medication., (© 2021. The Author(s).)

Background: Recent advances in acute stroke therapy have been shown to improve clinical outcome and therefore reduce long-term disability. Acute therapy procedures in stroke have a limited time frame after onset of symptoms; thus, rapid emergency management is critical. The Tyrolean Stroke Pathway was developed to optimize the entire treatment pathway from stroke onset to outpatient rehabilitation., Objectives: The description of the Tyrolean Stroke Pathway as an example to optimize the entire treatment pathway of stroke patients in a central European alpine region with a focus on prehospital management., Materials and Methods: In four subprojects from the prehospital phase up to outpatient rehabilitation, the project optimized intersections between different phases of care and evaluated the care processes using quality assurance measures., Results: After implementation, thrombolysis rates doubled and functional outcome of stroke patients after 3 months improved and complications, e.g., pneumonia, declined. Access to rehabilitation improved, particularly because of the establishment of quality assured and funded outpatient rehabilitation., Conclusions: The project showed that a holistic standardized stroke pathway from acute management up to outpatient rehabilitation can be successfully implemented in clinical routine. The project improved the entire health care pathway of stroke patients. The Stroke Action Plan for Europe 2018-2030 recommends to have national plans for stroke that encompass the entire chain of care., (© The Author(s) 2022.)

Congenital myasthenic syndromes are rare hereditary disorders caused by mutations associated with proteins of the neuromuscular junction. Abnormal ''gain of function'' mutations result in prolonged nicotinic acetylcholine receptor channel open state causing a rare subtype of CMS, slow-channel CMS (SCCMS). Mutations in the delta subunit encoding the gene, CHRND, resulting in SCCMS are extremely rare. An important clue to the diagnosis of SCCMS is repetitive CMAP's. Fluoxetine, usually at high doses, is used to treat SCCMS. The mutation, recently described in one patient, was identified by whole exome sequencing and validated, and its segregation with the disease was ascertained by Sanger sequencing. Here, we describe clinical and genetic findings of an early onset SCCMS patient carrying a very rare missense mutation c.880C > T in CHRND causing a highly conserved leucine to phenylalanine substitution in the M2 domain of CHRND. The patient had no repetitive CMAP. He had a dramatic response to fluoxetine at low-moderate doses (40 mg/day), increasing over months: Being wheelchair bound, he could walk independently after treatment. Rare cases may offer insight into the pathological gating mechanism leading to CMS. SCCMS should be suspected even without a repetitive CMAP. Fluoxetine at relatively low doses can be a very effective treatment., (© 2020. Belgian Neurological Society.)