The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

Measurement of charge carrier mobilities in thin films on metal substrates by reflection time resolved terahertz spectroscopy.

We show that charge carrier mobilities can be measured by reflection time resolved THz spectroscopy (R-TRTS) even for thin films on metal contacts, such as polycrystalline Cu2SnZnSe4 grown on molybdenum. In the measurement a reduced THz reflection upon photo-excitation is observed in contrast to increased THz reflection commonly observed on insulating substrates, and which excludes standard analytic R-TRTS analyses. Instead, a numerical transfer matrix method is used to model the THz reflection from which we derive carrier mobilities of 100 cm2/Vs consistent with literature. We show that R-TRTS on metal substrates is ~100x less sensitive compared to measurements on insulating substrates. These sensitivity of these R-TRTS measurements can be increased by using lower substrate refractive indices, lower substrate conductivities, thicker sample layers or higher THz probe frequencies.

Higher agreement between readers with deep learning CAD software for reporting pulmonary nodules on CT.

Purpose: The aim was to evaluate the impact of CAD software on the pulmonary nodule management recommendations of radiologists in a cohort of patients with incidentally detected nodules on CT. Methods: For this retrospective study, two radiologists independently assessed 50 chest CT cases for pulmonary nodules to determine the appropriate management recommendation, twice, unaided and aided by CAD with a 6-month washout period. Management recommendations were given in a 4-point grade based on the BTS guidelines. Both reading sessions were recorded to determine the reading times per case. A reduction in reading times per session was tested with a one-tailed paired t-test, and a linear weighted kappa was calculated to assess interobserver agreement. Results: The mean age of the included patients was 65.0 ± 10.9. Twenty patients were male (40 %). For both readers 1 and 2, a significant reduction of reading time was observed of 33.4 % and 42.6 % (p < 0.001, p < 0.001). The linear weighted kappa between readers unaided was 0.61. Readers showed a better agreement with the aid of CAD, namely by a kappa of 0.84. The mean reading time per case was 226.4 ± 113.2 and 320.8 ± 164.2 s unaided and 150.8 ± 74.2 and 184.2 ± 125.3 s aided by CAD software for readers 1 and 2, respectively. Conclusion: A dedicated CAD system for aiding in pulmonary nodule reporting may help improve the uniformity of management recommendations in clinical practice.

Environmental risk assessment of veterinary pharmaceuticals: development of a standard laboratory test with the dung beetle Aphodius constans.

The environmental risk assessment of veterinary pharmaceuticals for dung beetles is required if the substance is an anti-parasiticide for the treatment of pasture animals. However, the demonstration of the environmental safety of those substances for dung fauna is hampered by the fact that no standardized laboratory test system is currently available. Here a test system using the temperate dung beetle species Aphodius (Agrilinus) constans (Scarabaeidae: Aphodiinae) Duftschmidt is described. The survival of first instar larvae of A. constans exposed to a model substance, dimethoate, spiked into formulated (i.e. dried, formulated and re-wetted) or fresh dung was measured over a period of three weeks. Larvae performed better in formulated dung which also proved to be more suitable for mixing-in test substances homogenously. Dimethoate caused significant larval mortality with LC50 values within a range of 1.3-2.8 mg a.s./kg dung (d.w.), depending on the dung type. Based on the data presented here, it is recommended to incorporate this new test system in the risk assessment process for veterinary pharmaceuticals. However, an international ringtest should to be performed beforehand to ensure adequate validation of the method.

Osteointegration of hydroxyapatite-titanium implants coated with nonglycosylated recombinant human bone morphogenetic protein-2 (BMP-2) in aged sheep.

Osteointegration of metal implants into aged organisms can be severely compromised due to reduced healing capacity of bone, lack of precursor cells for new bone formation, or osteoporosis. Here, we report on successful implant healing in a novel model of aged sheep in the presence of nonglycosylated bone morphogenetic protein 2 (BMP-2). Ewes of 8 to 12 years with significant radiologic and histologic signs of osteoporosis and adipocytic bone marrow received a cylindrical hydroxyapatite-titanium implant of 12 x 10 mm. BMP-2 has been produced as a bacterial recombinant fusion protein with maltose-binding protein and in vitro generation of mature BMP-2 by renaturation and proteolytic cleavage. A BMP-2 inhibition ELISA was developed to measure the in vitro release kinetics of bioactive human BMP-2 from immersed solid implant materials by using Escherichia coli expressed and biotinylated recombinant human BMP-2 receptor IA extracellular domain (ALK-3 ECD). The implants were placed laterally below both tibial plateaus, with the left leg implant carrying 380 microg BMP-2. Both implant types became integrated within the following 20 weeks. The control implant only integrated at the cortical bone, and little new bone formation was found within the pre-existing trabecular bone or the marrow cavity. Marrow fat tissue was partially replaced by unspecific connective tissue. In contrast, BMP-2-coated implants initiated significant new bone formation, initially in trabecular arrangements to be replaced by cortical-like bone after 20 weeks. The new bone was oriented towards the cylinder. Highly viable bone marrow appeared and filled the lacunar structures of the new bone. In mechanical tests, the BMP-2-coated implants displayed in average 50% higher stability. This animal model provided first evidence that application of nonglycosylated BMP-2 coated on solid implants may foster bone healing and regeneration even in aged-compromised individuals.

[Long-term thymoleptic management of depressive states with special reference to retarded depression]. / Zur längerfristigen thymoleptischen Behandlung depressiver Zustände unter besonderer Berücksichtigung spätdepressiver Erkrankungen.

Attention is drawn to the importance of long-term thymoleptic treatment by describing the progress of 39 patients who were continually adjusted to a thymoleptic maintenance dose for a mean duration of two years following a depressive reaction. Apart from having a direct thymoleptic effect on insufficiency phenomena lasting longer than particular phases this led to the conclusion that treatment should be related strictly to phase due to the particular proneness of such patients to relapse during postdepressive insufficiency syndromes. Special mention is made of typological features characterising the course of depressive reactions.

[Study instrument for psychopathology in computer-assisted analysis of findings (Structured Psychopathologic Detection System)]. / Untersuchungsinstrument für die Psychopathologie zur rechnergestützten Befundanalyse (SPES-RB).

With the Structured Psychopathological Evaluation-System (SPES) an instrument existed for employment of objective criteria. This study was designed to present an evaluation system based on new scientific results, that is applying on the strength of a reduced catalogue of symptoms (94 compared with 198 Items at SPES-A) to clinical routine. Additional findings differentiated by this system be able to classify by the help of an operational decision system.

[Frequency pattern of alpha waves in the early stages of cerebrovascular circulation disorders]. / Uber das Frequenzverhalten der Alpha-Grundaktivität im Frühstadium zerebraler Durchblutungsstörungen

In this study 201 EEG curves are interpreted belonging to patients suffering from incipient disturbances of the cerebral circulation. The patients were divided into 3 groups according to age (group I, 30-40 years; group II, 40-50 years; group III, 50 years and over). In group I there prevailed a rate of 11-12 alpha waves per sec., and a slower rate was hardly ever found; in group III the frequency pattern was quite different. This decreased frequency of the waves could be confirmed by statistics. We believe a direct link can be assumed to exist between a decrease in frequency and the beginning of disturbed cerebral circulation.

Rapid conversion of Histoplasma capsulatum, Blastomyces dermatitidis and sporothrix schenckii in tissue culture.

A simple method for positive identification of Histoplasma capsulatum, Blastomyces dermatitidis, and Sporothrix schenckii is given. Primary tissue cultures of guinea pig peritoneal macrophage were inoculated with the mycelial phase of each organism and after 24 h the cells were stained and observed microscopically. The characteristic yeast phase could then be observed allowing for positive identification.

Pathogenicity of the basidiospores of Filobasidiella neoformans.

The pathogenicity of the purified basidiospores of Filosbasidiella neoformans was determined. The basidiospores were purified by successive filtration and inoculated into white Swiss female mice via the intracranial and intravenous route. At autopsy, infection was seen with as few as fifty inoculated cells. The brain, liver and spleen were examined culturally and histologically to prove the pathogenicity of the purified basidiospores .

Technique for the purification of the hyphae of Filobasidiella neoformans.

A technique for the purification of the hyphae of Filobasidiella neoformans is described. Cultural conditions and strains for maximal hyphal production were determined. Blastospores were separated from hyphae by sonification of mycelial suspensions. Following this, the initial density ranges of all cell types were determined by isopycnic centrifugation, using Renografin-60 as a supporting medium. Based on these data, rate centrifugation with different density ranges was used to obtain cell separation. The final percentage of non-hyphal cells to total population was 0.007%. These were determined to be still viable at the end of separation.

[Principles of computer-assisted classification in psychiatry]. / Grundlagen eines rechnergestützten Klassifikators in der Psychiatrie.

The use of computer based diagnostic decision and artificial intelligence are discussed in relation to the problems of validity and reliability of psychiatric diagnoses. The authors suggest a definition of a computer aided classificator as an existent decision system for an automatically analysis of findings.

Toward the development of operational criteria of differentiated mental states.

The purpose of this paper is to discuss possibilities for developing operational criteria in psychopathological states and to identify the parameters that differentiate psychotic patients. Statistical analysis was performed in the first step with the aid of factor analysis with extraction of syndromatic characteristics of so-called psychopathological basis syndromes. By cluster analysis in the second step we found out more approaches to a differentiated definition of psychotic states. The classification of individuals into 'natural' and not preestablished groups enabled the construction of descriptive psychopathological algorithms to determine ICD-9 diagnosis within the limitations of descriptive psychiatry.

Pathogenicity of the hyphae of Filobasidiella neoformans.

The pathogenicity of the purified hyphae of Filobasidiella neoformans was determined. The hyphal particles were inoculated into white Swiss female mice via the intracranial and intravenous route. Upon autopsy, infection was seen with as few as 25 hyphal elements. The brain, liver, and spleen were examined culturally and the brain examined histologically to prove the pathogenicity of the purified hyphae.

Deep penetrating naevus: clinicopathological study of 31 cases with further delineation of histological features allowing distinction from other pigmented benign melanocytic lesions and melanoma.

AIMS: To examine a series of deep penetrating naevus (DPN) and discuss the differential diagnosis of pigmented, deep penetrating melanocytic lesions and their biological potential. DPN has been described as a variant of common acquired intradermal melanocytic naevus. DPN remains poorly recognized by pathologists, partly attributable to its relatively rare occurrence. METHODS AND RESULTS: Thirty-one cases of deeply pigmented lesions were studied. The patients included 17 females and 14 males with an age range between 3 and 56 years (mean 25.8, median 23). The common clinical sites were face (n = 10) back (n = 6) and lower extremity (n = 7). The clinical diagnoses included various benign melanocytic naevi, and malignant melanoma, as well as non-melanocytic lesions. Histologically, all cases presented as wedge-shaped lesions composed of fusiform cells but also epithelioid melanocytes, with pale cytoplasm and oval nuclei. Pigment was identified in melanophages but also within lesional melanocytic cells. Nine cases contained mitotic figures. Nine cases showed the coexistence of 'ordinary' common acquired naevocytes, and seven lesions showed overlapping features with either ordinary blue naevus or Spitz naevus. In 13 lesions there was at least one feature that may cause concern as to the biological nature of the tumour. These include asymmetry, cytological atypia, inflammation, or an 'expansile' advancing margin. Each tumour was treated by simple excision; one lesion recurred after 1 year. No tumour metastasized. CONCLUSIONS: DPN is a distinct variant of melanocytic naevus. In some cases the histological features overlap with other benign melanocytic lesions. Criteria for recognizing malignant examples remain unclear, but cytological atypia and low mitotic activity do not necessarily portend a sinister outcome.

Interactions between Histoplasma capsulatum and macrophages from normal and treated mice: comparison of the mycelial and yeast phases in alveolar and peritoneal macrophages.

Interactions between macrophages (alveolar and peritoneal) from normal, vaccinated (with heat-killed yeast cells), and Mycobacterium bovis BCG-treated mice and the mycelial and yeast phases of Histoplasma capsulatum were observed. Phagocytosis of microconidia, small hyphal fragments, and yeast cells occurred 4 to 6 h after the infection of macrophage cultures. Conversion to the yeast phase began at 6 to 7 h and was complete after a 72-h incubation at 37 degrees C. Macrophages surrounded and adhered to macroconidia and large hyphal elements. More macrophages (65 to 68%) from BCG-treated mice contained fungi at 24 h than did macrophages from normal or vaccinated mice. Although there was no increase in the number of fungi in macrophages from vaccinated mice, only the macrophages from BCG-treated mice contained fewer fungi after 48 h of infection with the mycelial phase of H. capsulatum. Fungal growth was not inhibited in any of the macrophage cultures when infected with the yeast phase. The macrophages infected with yeast cells were destroyed after 48 to 72 h in the culture. Only BCG-treated macrophages survived infection with the mycelial phase, whereas macrophages from normal and vaccinated mice were destroyed by the infection.

Effects of time lapse between sputum collection and culturing on isolation of clinically significant fungi.

A retrospective study of 34,314 sputum specimens received by a reference laboratory over a 10-year period demonstrated that clinically significant fungi could be isolated even after long periods of delay between collecting and culturing. As a result of this study, it should be stressed that although immediate culturing for fungi is the ideal, specimens should not be rejected because of delays in transport.

Evaluation of the p-nitro-alpha-acetylamino-beta-hydroxypropiophenone differential test for identification of Mycobacterium tuberculosis complex.

The p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) differential test for the identification of Mycobacterium tuberculosis recovered from clinical specimens was evaluated by two laboratories and found to be a rapid and accurate procedure with a specificity exceeding 99%.