[Bed capacity management in times of the COVID-19 pandemic : A simulation-based prognosis of normal and intensive care beds using the descriptive data of the University Hospital Augsburg]. / Bettenkapazitätssteuerung in Zeiten der COVID-19-Pandemie : Eine simulationsbasierte Prognose der Normal- und Intensivstationsbetten anhand der deskriptiven Daten des Universitätsklinikums Augsburg.

BACKGROUND: Following the regional outbreak in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world, presenting the healthcare systems with huge challenges worldwide. In Germany the coronavirus diseases 2019 (COVID-19) pandemic has resulted in a slowly growing demand for health care with a sudden occurrence of regional hotspots. This leads to an unpredictable situation for many hospitals, leaving the question of how many bed resources are needed to cope with the surge of COVID-19 patients. OBJECTIVE: In this study we created a simulation-based prognostic tool that provides the management of the University Hospital of Augsburg and the civil protection services with the necessary information to plan and guide the disaster response to the ongoing pandemic. Especially the number of beds needed on isolation wards and intensive care units (ICU) are the biggest concerns. The focus should lie not only on the confirmed cases as the patients with suspected COVID-19 are in need of the same resources. MATERIAL AND METHODS: For the input we used the latest information provided by governmental institutions about the spreading of the disease, with a special focus on the growth rate of the cumulative number of cases. Due to the dynamics of the current situation, these data can be highly variable. To minimize the influence of this variance, we designed distribution functions for the parameters growth rate, length of stay in hospital and the proportion of infected people who need to be hospitalized in our area of responsibility. Using this input, we started a Monte Carlo simulation with 10,000 runs to predict the range of the number of hospital beds needed within the coming days and compared it with the available resources. RESULTS: Since 2 February 2020 a total of 306 patients were treated with suspected or confirmed COVID-19 at this university hospital. Of these 84 needed treatment on the ICU. With the help of several simulation-based forecasts, the required ICU and normal bed capacity at Augsburg University Hospital and the Augsburg ambulance service in the period from 28 March 2020 to 8 June 2020 could be predicted with a high degree of reliability. Simulations that were run before the impact of the restrictions in daily life showed that we would have run out of ICU bed capacity within approximately 1 month. CONCLUSION: Our simulation-based prognosis of the health care capacities needed helps the management of the hospital and the civil protection service to make reasonable decisions and adapt the disaster response to the realistic needs. At the same time the forecasts create the possibility to plan the strategic response days and weeks in advance. The tool presented in this study is, as far as we know, the only one accounting not only for confirmed COVID-19 cases but also for suspected COVID-19 patients. Additionally, the few input parameters used are easy to access and can be easily adapted to other healthcare systems.

Capitate glandular trichomes in Aldama discolor (Heliantheae - Asteraceae): morphology, metabolite profile and sesquiterpene biosynthesis.

The capitate glandular trichome is the most common type described in Asteraceae species. It is known for its ability to produce various plant metabolites of ecological and economic importance, among which sesquiterpene lactones are predominant. In this paper, we applied microscopy, phytochemical and molecular genetics techniques to characterise the capitate glandular trichome in Aldama discolor, a native Brazilian species of Asteraceae, with pharmacological potential. It was found that formation of trichomes on leaf primordia of germinating seeds starts between 24 h and 48 h after radicle growth indicates germination. The start of metabolic activity of trichomes was indicated by separation of the cuticle from the cell wall of secretory cells at the trichome tip after 72 h. This coincided with the accumulation of budlein A, the major sesquiterpene lactone of A. discolor capitate glandular trichomes, in extracts of leaf primordia after 96 h. In the same timeframe of 72-96 h post-germination, gene expression studies showed up-regulation of the putative germacrene A synthase (pGAS2) and putative germacrene A oxidase (pGAO) of A. discolor in the transcriptome of these samples, indicating the start of sesquiterpene lactone biosynthesis. Sequencing of the two genes revealed high similarity to HaGAS and HaGAO from sunflower, which shows that key steps of this pathway are highly conserved. The processes of trichome differentiation, metabolic activity and genetic regulation in A. discolor and in sunflower appear to be typical for other species of the subtribe Helianthinae.

First Report of Pustula tragopogonis, the Cause of White Rust on Cultivated Sunflower in Southern Germany.

Pustula tragopogonis (Pers.) Thines (2), formerly known as Albugo tragopogonis (Pers.) Gray, causes white rust on some members of the Asteraceae. It has been reported to attack cultivated sunflower in several parts of the world, for example, North America (1) and South Africa (3), but has not been previously reported on sunflower in Germany. During June 2003, the first diseased plants were observed in a sunflower field near Stuttgart, where sunflowers were grown as ornamentals. During 2004, P. tragopogonis was found in several ornamental sunflower fields in southern Germany. In some cases, P. tragopogonis co-occurred with Plasmopara halstedii (Farlow) Berl. & De Toni on the same plants. After a cold winter, the first diseased plants for 2005 were observed during June in the area around Stuttgart. The percentage of affected plants in the sunflower fields varied considerably, ranging from 20 to 80%. Only small lesions with oospores could be found on petioles and stems of infected plants. The typical spots with white blisters were observed mostly on leaves in the upper half of the plants, but also occurred on the bracteoles of the flower heads. Spots were chlorotic on the upper side of the leaf and exhibited whitish pustules on the lower side of the leaf. Pustules were concentrated around the margins of the leaves, but also were observed scattered on the whole lower surface. Light and scanning electron microscopy, as well as polymerase chain reaction and internal transcribed spacer sequencing were applied to identify the attacking pathogen as P. tragopogonis. Infection tests under laboratory conditions also proved the pathogenicity of the attacking agent to oilseed sunflower. Since the pathogen has survived the harsh winter months of early 2005 and appeared in three consecutive seasons, the disease seems now to be established in southern Germany and is expected to spread into other regions. References: (1) T. J. Gulya et al. Plant Dis. 86:559, 2002. (2) M. Thines and O. Spring. Mycotaxon 92:443, 2005. (3) P. S. van Wyk et al. Helia 22:83, 1995.

Cytological development and sesquiterpene lactone secretion in capitate glandular trichomes of sunflower.

The secretion of sesquiterpene lactones (STL) in capitate glandular trichomes from the anther appendages of Helianthus annuus L. (Asteraceae) was observed by light and fluorescence microscopy and HPLC analysis. Disk flowers within the sunflower capitulum showed the known ontogenetic progression from the centre to the margin. During development of the florets, the trichomes in the anther appendages secreted their metabolites into the subcuticular secretion storage space in front of the two apical cells. All stages of forming the cuticular globe, from the pre-secretory to the post-secretory phase, could be observed microscopically and secretory activity was simultaneously monitored. Six germacrolides and heliangolides of known structure were selected for quantitative analysis. The increase in STL content during extension of the subcuticular space was monitored by HPLC analysis. Thereby, the start and termination of STL biosynthesis was defined in relation to other developmental stages of floret ontogenesis, particularly, the pollen formation. Part of the secreted material showed autofluorescence which could be attributed to a hydroxy-trimethoxy-flavone, as determined by NMR and mass spectroscopy. The anther trichomes were cytologically and chemically similar to foliar glandular trichomes of sunflower and represent the multicellular capitate glandular trichome type common to many Asteraceae. The ease with which anther trichomes of H. annuus can be harvested and analyzed suggests that they can provide a valuable model system for investigation of STL and flavonoid metabolism in Asteraceae.

Sesquiterpene lactones and a myoinositol from glandular trichomes of Viguiera quinqueremis (Heliantheae; Asteraceae).

The extract of the floral parts of Viguiera quinqueremis afforded, in addition to known compounds, six new sesquiterpene lactones as well as a new myoinositol derivative. All compounds were detected in glandular trichomes which were collected micromechanically from the anther appendages and were analyzed by HPLC. Structure identification was performed by 1H NMR measurements including LC NMR and LC MS experiments.

Sesquiterpene lactones in Viguiera eriophora and Viguiera puruana (Heliantheae; Asteraceae).

Extracts of the aerial parts of Viguiera eriophora ssp. eriophora and Viguiera puruana afforded, in addition to known compounds, six new heliangolides and a germacrolide, whose structures were determined by spectral analysis. HPLC analysis and LC NMR experiments revealed the natural occurrence of the compounds in glandular trichomes. The taxonomic relevance of the results is briefly discussed.

Studies on Securigera securidacea (L.) Deg. et Dörfl. (Fabaceae) seeds, an antidiabetic Egyptian folk medicine.

A new cardenolide(-)-14-methoxy-rcanoside (1) was isolated from the aqueous extract of the seeds of Securigera securidacea (L.) Deg. et Dörfl. (Fabaceae) together with five new dihydrobenzofuran derivatives named securigran I-V (2-6). Kaempferol and astragalin were also isolated from the aqueous extract of the flowers. (-)-14-Methoxyhyrcanoside and the total aqueous extract of the seeds showed marked chronotropic activity. The total aqueous extract also showed a marked diuretic and severe hypokalemic effects on the K(+)-level in serum. The hypoglycemic effect of the seeds was also confirmed.

Sesquiterpene lactones and other constituents from Hymenoxys richardsonii and H. subintegra.

Two Hymenoxys species afforded, in addition to known compounds, three new pseudoguaianoloides, a new sesquiterpene glucoside and a new butyrolactone. This is the first report of an eudesmane from the genus Hymenoxys. The structures were elucidated by high-field NMR and chemical transformations.

Sunflower allergy. On the constituents of the trichomes of Helianthus annuus L. (Compositae).

Sesquiterpene lactones (STL) of the sunflower, occurring in fragile multicellular capitate glandular hairs, have been shown to display a remarkable sensitizing capacity when investigated by experimental sensitization in guinea pigs. The strongest response was induced by the hemiketal form of 1-O-methyl-4,5-dihydroniveusin A. The STL content of 50 capitate glands was sufficient to elicit a remarkable response in the guinea pigs. Thus, touching a sunflower plant (with up to 1000 capitate glands per cm2) may lead to the release of sufficient STL to sensitize humans, and these substances can be considered to be responsible for the cases of allergic contact dermatitis described in sunflower growers since 1906.

Biological activities of sesquiterpene lactones from Helianthus annuus: antimicrobial and cytotoxic properties; influence on DNA, RNA, and protein synthesis.

Sesquiterpene lactones, produced in light and capable of inhibiting auxin-induced elongation growth of coleoptile and hypocotyl segments, were isolated from young leaves of Helianthus annuus (Spring and Hager, Planta in press, 1982). These compounds have an antibiotic effect on gram-negative and gram-positive bacteria as well as on some fungi. The minimal inhibiting concentration (MIC) of compound II (15-hydroxy-3-dehydrodesoxyfruticin, Fig. 1), for example, is 15 micrograms/ml for Bacillus brevis, and 95 micrograms/ml for the fungus Eremothecium ashbyi. In addition, cytotoxic effects on mouse myeloma cells (NS-1) were also shown. Compound II causes a 50% inhibition of cell proliferation (ED50) at a concentration of 170 nM, compound I (niveusin C, Fig. 1) at 220 nM. The LD50-values were 0.15 micrograms II/ml and 1.24 micrograms I/ml, respectively. By measuring 14C-labelled thymidine, uridine and leucine incorporation into murine cells of the ascitic form of Ehrlich carcinoma (EAC) it could be shown that compounds I and II inhibit DNA and RNA synthesis, but do not affect the translation processes involved in protein synthesis. Furthermore, it could be shown that the exocyclic methylene group in the molecules of I and II plays an important role in triggering the described inhibitory effects.

Inhibition of elongation growth by two sesquiterpene lactones isolated from Helianthus annuus L. : Possible molecular mechanism.

Two sesquiterpene lactones belonging to the germacranolides were isolated from the leaves and stems of Helianthus annuus L. Their formation in the plant is light-dependent. Both sesquiterpene lactones (SL) strongly inhibit indole-3-acetic acid (IAA)-induced elongation growth of Avena sativa L. coleoptile segments and Helianthus annuus L. hypocotyl segments. Both SL do not, however, inhibit acid-induced growth nor growth triggered by fusicoccin at all. In the presence of dithiothreitol (DTT), the inhibitory effect of SL in the Avena-segment-test can be completely neutralized. This can be attributed to the binding of DTT to both SL. Using thin-layer-chromatography it could be shown that the inhibitors build adducts with SH-rich compounds, e.g., cysteine, glutathione, mercapto-ethanol, and DTT, whose Rf-value significantly differs from those of the primary substances. If the coleoptile segments are first treated with an inhibitor and the inhibitor is subsequently washed out, close to normal elongation growth can be induced by adding an IAA-solution. If the segments are simultaneously treated with inhibitor and IAA, no notable growth can be initiated for an extended amount of time, after the removal of both substances and the anewed addition of IAA. Fusicoccin, however, can immediately neutralize the induced growth inhibition. The same irreversible inhibition is observed when 2,4-dichlorophenoxyacetic acid (2,4-D) is used: If coleoptile segments are treated with an inhibitor plus 2,4-D or an inhibitor plus 3,5-dichlorophenoxyacetic acid (3,5-D), respectively, IAA-induced growth after removal of the substances can only be observed by those coleoptiles which had previously been treated with the non-auxin, 3,5-D plus an inhibitor. Based on these results, a possible mechanism describing how the inhibitor functions is discussed. The binding of an auxin to an auxin receptor sets a SH-group free (possibly due to a change in the conformation of the receptor); a site is given to which the inhibitor can bind irreversibly (via a S-bond). The IAA-receptor-inhibitor-complex is then no longer able to initiate elongation growth. If auxin is not present, no lasting bond between the inhibitor and the receptor can occur, since the essential SH-group remains masked. The inhibitor can be washed out again. Consequently, the SL's have to be able to intervene at the beginning of the IAA-induced reaction sequence, while the following steps remain uninfluenced, i.e. namely, the active excretion of protons into the cell wall compartments, which is directly induced by fusicoccin and causes elongation growth.