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Purpose: The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has caused substantial mortality worldwide. We investigated clinical and demographic features of COVID-19-related deaths that occurred between March 2020 and January 2022 in Regensburg, Germany. Methods: We compared data across four consecutive time periods: March 2020 to September 2020 (period 1), October 2020 to February 2021 (period 2), March 2021 to August 2021 (period 3), and September 2021 to January 2022 (period 4). Results: Overall, 405 deaths in relation to COVID-19 were reported. The raw case fatality ratio (CFR) was 0.92. In periods 1 to 4, the CFRs were 1.70%, 2.67%, 1.06%, and 0.36%. The age-specific CFR and mortality were highest in persons aged ≥ 80 years in period 2 while mortality in younger cases increased with time. The median age at death was 84 years and it varied slightly across periods. Around 50% of cases of death were previously hospitalized. In all time periods, the cause of death was mostly attributed to COVID-19. Over the four periods, we did not find significant changes in the distribution of sex and risk factors for severe disease. The most frequent risk factor was cardio-circulatory disease. Conclusion: In conclusion, the CFR decreased over time, most prominently for period 4. Mortality was considerable and younger cases were increasingly at risk. [ABSTRACT FROM AUTHOR]

Background: The importance of emergency rooms (ERs) as everyday healthcare suppliers is growing. Due to increasing patient flows, hospitals are forced to raise physicians' and caregivers' headcount continuously to meet the new demand of patients seeing the ER as primary point of contact in non-emergency situations. Patients from various cultural and educational backgrounds approach the ER for different reasons. Detailed understanding of these reasons and their roots is key to be able to offer guidance for patients as well as planning and staffing of hospitals in the future. Aim: This study examines motivation for the entrance to the medical system via the ER in Germany via an anonymized patient survey. Evaluation in regard to socioeconomic and medical reasons is taken into account. Materials and methods: Over the course of 210 h in the ER, a total of 235 patients were interviewed in the surgical emergency room of Klinikum rechts der Isar in the year 2016. Focus was set on standard cases to allow for facilitated comparability. Heavily injured patients were excluded from the study. Results: The main reasons for patients entering the ER were immediate help (45.9%) and treatment by a specialist (35.4%). Furthermore, the location/good accessibility (47.9%) and prior positive experience with the emergency room (20.7%) were decisive reasons for choosing the hospital over the outpatient sector. Analysis of demands of patients in relation to their migration background and their religious confession showed no significant difference between groups. Conclusion: Younger patients tend to more often access the ER instead of an outpatient clinic or doctor in private practice. As a survey suits the less urgent patients, our research describes this population in detail. The need for better information of patients regarding treatment options becomes apparent. The study's outcomes aim to teach physicians as well as operators how to influence resource management in the healthcare system by meaningful information of patients. Further research may evaluate long-term results of information measures. [ABSTRACT FROM AUTHOR]

Purpose: Selective hypoglossal nerve stimulation has proven to be a successful treatment option in patients with obstructive sleep apnea. The aim of this pilot study was to investigate if there is a cross-innervation of the hypoglossal nerve in humans and if patients with this phenotype show a different response to hypoglossal nerve stimulation compared to those with ipsilateral-only innervation Methods: Nineteen patients who previously received a selective hypoglossal nerve stimulation system (Inspire Medical Systems, Golden Valley, USA) were implanted with a nerve integrity system placing electrodes on both sides of the tongue. Tongue motions were recorded one and two months after surgery from transoral and transnasal views. Polysomnography (PSG) was also performed at two months. Electromyogram (EMG) signals and tongue motions after activation were compared with PSG findings. Results: Cross-innervation showed significant correlation with bilateral tongue movement and bilateral tongue base opening, which were associated with better PSG outcomes. Conclusion: Cross motor innervation of the hypoglossal nerve occurs in approximately 50% of humans, which is associated with a positive effect on PSG outcomes. Bilateral stimulation of the hypoglossal nerve may be a solution for non-responding patients with pronounced collapse at the soft palate during drug-induced sleep endoscopy. [ABSTRACT FROM AUTHOR]

Hintergrund: Die obstruktive Schlafapnoe ist eine häufige Erkrankung, bei der es im Schlaf auf unterschiedlichen Ebenen im Bereich der oberen Atemwege zu massiven Einschränkungen bis zum kompletten Sistieren des Atemluftstroms kommen kann. Für die individualisierte Therapie hat sich in den letzten Jahren die Schlafendoskopie unter medikamentöser Sedierung als wichtiges Diagnostikum etabliert.Ziel der Arbeit: Diese Arbeit soll einen Überblick über die pharmakologischen Eigenschaften der Sedativa zur Schlafendoskopie geben.Material und Methoden: Übersichtsarbeit/ReviewErgebnisse: Zur Durchführung einer Schlafendoskopie ist eine medikamentöse Sedierung unabdingbar. Aktuell werden hierfür vor allem Propofol, Midazolam und in klinischen Studien Dexmedetomidin verwendet. Für Midazolam besteht die meiste Erfahrung. Aufgrund seiner pharmakologischen Eigenschaften ist die Dosierung individuell sehr variabel. Es ist mit einer langen Wirkdauer zu rechnen, die relevante Überwachungszeiten nach sich zieht. Propofol ist sehr kurzwirksam und kann bei Verwendung neuer Infusionssysteme wie TCI („target-controlled infusion“) zu einer besseren Vergleichbarkeit führen. Bei höheren Dosierungen besteht allerdings im Vergleich zu Midazolam die Gefahr einer Apnoe und Kardiodepression. Die neuere Substanz Dexmedetomidin scheint einen schlafähnlicheren Zustand als Propofol und Midazolam zu erzeugen. Allerdings sind für Dexmedetomidin die Erfahrungen im Bereich prozeduraler Sedierungen noch gering.Diskussion: Für die Schlafendoskopie stehen mehrere Medikamente mit charakteristischen pharmakologischen Eigenschaften zur Verfügung. Kenntnisse über Pharmakologie und eine Erfahrung im Umgang mit diesen Medikamenten sind für eine sichere und zielführende Diagnostik unabdingbar. [ABSTRACT FROM AUTHOR]

In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA. [ABSTRACT FROM AUTHOR]

Background: Drug-induced sleep endoscopy (DISE) has become an important diagnostic examination tool in the treatment decision process for surgical therapies in the treatment of obstructive sleep apnea (OSA). Currently, there is a variety of regimes for the performance of DISE, which renders comparison and assessment across results difficult. It remains unclear how the different regimes influence the findings of the examination and the resulting conclusions and treatment recommendations. This study aimed to investigate the correlation between increasing levels of sedation (i.e., light, medium, and deep) induced by propofol using a target-controlled infusion (TCI) pump, with the obstruction patterns at the levels of the velum, oropharynx, tongue base, and epiglottis (i.e., VOTE classification). A second goal was the establishment of a sufficient sedation level to enable a reliable decision regarding treatment recommendations. Material and methods: Forty-three patients with OSA underwent a DISE procedure using propofol TCI. Three levels of sedation were defined, depending on entropy levels and assessment of sedation: light sedation, medium sedation, and deep sedation. The evaluation of the upper airway at each level, with increasing sedation, was documented using the VOTE classification. The elapsed time at which each assessment was performed was recorded. Results: Upper airway changes occurred and were measured throughout the DISE procedure. Clinically useful determinations of airway closure occurred at medium sedation; this level of sedation was most probably achieved with a blood propofol concentration of 3.2 μg/ml. In all 43 patients, definite treatment decisions could be made at medium sedation level. Increasing sedation did not result in changes in the treatment decision. Conclusions: Changes in upper airway collapse during DISE with propofol TCI occur at levels of medium sedation. Decisions regarding surgical treatment could be made at this level of sedation. Clinical trial name: Upper Airway Collapse in Patients with Obstructive Sleep Apnea Syndrome by Drug Induced Sleep Endoscopy (URL: ) Registration number: NCT02588300 [ABSTRACT FROM AUTHOR]

We present a strategic model to solve the long-term staffing problem of physicians in hospitals using flexible shifts. The objective is to minimize the total number of staff subject to several labor agreements. A wide range of legal restrictions and facility-specific staffing policies are considered. In general, the model is capable to incorporate different experience levels. In the simplest version the model decides about the number of staff for two experience levels, i.e. the number of residents (low experience) versus specialists (high experience). Shifts are constructed implicitly by the model and may have different starting times and several lengths. This allows more flexibility in the scheduling process. We formulate the problem as a mixed-integer program and solve it applying a column generation based heuristic. Using data provided by an anesthesia department of an 1100-bed hospital, computational results demonstrate the usage of the model as decision supporting tool when staffing decision are made by hospital management. [ABSTRACT FROM AUTHOR]

Fission yeast, Schizosaccharomyces pombe, is a natural inositol auxotroph. We show here that the amount of exogenous inositol added to the medium is critical for the control of its life cycle. Above growth-limiting concentrations inositol stimulates mating and sporulation in minimal medium. The effect of inositol is also observed on yeast-extract-medium plates. We selected a mutant, IM49, which mates and sporulates only poorly and show that it is defective in inositol transport. Its defect is in a gene ( itr2) coding for a putative 12 membrane-spanning protein. The polypeptide contains the two sugar-transport motifs typical for hexose transporters and shows good homology to the two Saccharomyces cerevisiae inositol transporters. The itr2 gene is essential for cell growth and its mRNA level is repressed by glucose. Mutant IM49 is also complemented by a multicopy suppressor gene ( itr1) which codes for a putative hexose transporter with unknown substrate specifity. [ABSTRACT FROM AUTHOR]

A mutant ( plc1-1) of Schizosacharomyces pombe unable to grow on a minimal medium containing high amounts of phosphate was selected. On yeast-extract agar its growth is temperature sensitive. Tests in liquid synthetic medium show that growth of the mutant is partially restored by lowering the phosphate and inositol concentrations in the growth medium. The growth defect is fully suppressed by a plasmid encoding a putative protein having the structural features of phosphoinositide-specific phospholipases C (PI-PLC). This protein, of 899 amino-acids, contains the characteristic X and Y domains found in all PI-PLCs of higher and lower eucaryotes and reveals, in addition, an EF-hand motif (putative Ca-binding site). Like the corresponding enzyme from Saccharomyces cerevisiae, the S. pombe PI-PLC is most similar to the δ form of PI-PLC isoenzymes. The cloned gene integrates at the plc1 site indicating that plc1 codes for a putative PI-PLC. Plc1 physically maps on the left arm of chromosome II between rad11 and mei3. [ABSTRACT FROM AUTHOR]

Expression of pho1-encodd acid phosphatase of Schizosaccharomyces pombe has been reported to be regulated by phosphate. In this communication we show that it is also regulated by adenine. Starving adenine auxotrophic strains for adenine leads to a drastic increase of the enzymatic activity while adenine represses this activity. Full repression by adenine only occurs when phosphate is not growth limiting and vice versa. Regulation occurs at the level of mRNA. We isolated adenine non-repressible mutants. They define four genes ( anr1, anr2, anr3, and anr5) which are involved in adenine-dependent pho1 expression. All anr mutants are also phosphate nonrepressible. These results indicate that the generation and/or transduction of the intracellular signal responsible for pho1 repression is simultaneously dependent on both adenine and phosphate. [ABSTRACT FROM AUTHOR]

We have investigated the thiamine metabolism in Schizosaccharomyces pombe and shown that: (1) Thiamine-repressible acid phosphate, coded for by the gene pho4, dephosphorylates thiamine phosphates indicating that the enzyme acts as a thiamine phosphate phosphatase. (2) In vivo synthesized thiamine is present intracellulary mainly as thiamine diphosphate. Starving cells for glucose decreases the intracellular thiamine pool. (3) The genes thi2, thi3 and thi4 control thiamine biosynthesis and probably code for thiamine biosynthetic enzymes. Thi3, which is involved in the synthesis of the pyrimidine moiety of the thiamine molecule, is allelic to the thiamine repressible gene nmt1. (4) Thiamine uptake is a thiamine regulated process, probably occurs by active transport and is controlled by the gene ptr1. [ABSTRACT FROM AUTHOR]

Nutritional conditions regulate mating of the fission yeast S. pombe. To investigate how nutritional signals are monitored by the cell and translated into appropriate mating behaviour, effects of unique and specific growth factors would be desirable. We show that thiamin can inhibit sexual agglutination and zygote formation in S. pombe. A concentration of 50 nM thiamin in the culture medium is required for full growth of a thiamin auxotrophic strain. At this concentration thiamin starts to inhibit mating of wild-type cells of opposite heterothallic mating type and at a 1μM concentration zygote formation is inhibited by more than 95%. Growth conditions modulate the inhibitory effect of thiamin. Thiamin acts only for a restricted period of time and seems to inhibit commitment to zygote formation rather than the cell aggregation and fusion process itself. Pyrithiamin, a thiamin antagonist, inhibits growth as well as mating. [ABSTRACT FROM AUTHOR]