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We investigate the possible formation of a Bose-Einstein condensed phase of pions in the early Universe at nonvanishing values of lepton flavor asymmetries. A hadron resonance gas model with pion interactions, based on first-principle lattice QCD simulations at nonzero isospin density, is used to evaluate cosmic trajectories at various values of electron, muon, and tau lepton asymmetries that satisfy the available constraints on the total lepton asymmetry. The cosmic trajectory can pass through the pion condensed phase if the combined electron and muon asymmetry is sufficiently large: |le+lμ|≳0.1, with little sensitivity to the difference le−lμ between the individual flavor asymmetries. Future constraints on the values of the individual lepton flavor asymmetries will thus be able to either confirm or rule out the condensation of pions during the cosmic QCD epoch. We demonstrate that the pion condensed phase leaves an imprint both on the spectrum of primordial gravitational waves and on the mass distribution of primordial black holes at the QCD scale, e.g., the black hole binary of recent LIGO event GW190521 can be formed in that phase.
Hintergrund: Die chirurgische Facharztweiterbildung erfordert neben dem Erlernen theoretischen Wissens ebenfalls den Erwerb praktisch-chirurgischer Kompetenzen. Eine Alternative zur Aus- und Weiterbildung am Patienten stellen simulationsbasierte Lehrkonzepte dar. Ziel der vorliegenden Studie ist die Analyse der Verteilung und des Einsatzes chirurgischer Simulatoren in deutschen Kliniken.
Methoden: Die Datenanalyse erfolgte auf Basis eines individuellen Onlinefragebogens mit insgesamt 19 standardisierten Fragen. Dieser wurde über die E‑Mail-Verteiler der deutschen chirurgischen Fachgesellschaften an die leitenden chirurgischen Klinikärzte versendet.
Ergebnisse: Insgesamt 267 vollständige Antwortdatensätze wurden analysiert (Rücklaufquote 12,0 %). 84,0 % der Teilnehmer gaben ihre Tätigkeit an einem Lehrkrankenhaus an. Zum Zeitpunkt der Untersuchung waren 143 chirurgische Simulatoren an 35,0 % der in die Auswertung eingeschlossenen Kliniken vorhanden. Regional zeigten sich deutliche Unterschiede zwischen den einzelnen Bundesländern. 21,1 % der Teilnehmer, an deren Klinik kein Simulator zur Verfügung steht, planten eine Neubeschaffung. Studierende (41,1 %) und Ärzte in Weiterbildung (ÄiW, 32,5 %) nutzten das Simulationstraining am häufigsten. Eine Integration in die chirurgische Weiterbildung bestand zu 81,8 % nicht. 94,0 % der beteiligten Kliniken zeigten Interesse an einer zukünftigen Integration in die chirurgische Facharztweiterbildung.
Schlussfolgerung: Die vorliegenden Ergebnisse bestätigen die besondere Bedeutung des simulationsbasierten Trainings für die chirurgische Weiterbildung an deutschen Kliniken. Gleichzeitig bestehen deutliche Informationsdefizite über das Nutzungsverhalten sowie eine defizitär empfundene Integration des Simulationstrainings in die chirurgische Weiterbildung.
Thermally stable and highly conductive SAMs on Ag substrate — the impact of the anchoring group
(2021)
Self-assembled monolayers (SAMs) on metal substrates are an important part of modern interfacial chemistry and nanotechnology. The robustness of SAMs strongly depends on their thermal stability, which, together with electric conductivity, crucial for their applications in molecular/organic electronics. In this context, using a multidisciplinary approach, the structure, stability, and conductivity properties of conjugated aromatic SAMs featuring the naphthalene backbone and S, Se, or COO group, mediating bonding to the Ag substrate are addressed. Whereas thermal stability of these SAMs exhibits a strong dependence on anchoring group, their conductivity is similar, which is rationalized by tentative model considering redistribution of charge density along the molecular framework. The thermal stability of model naphthalenethiol SAM, emphasized by desorption energy of ≈1.69 eV, is better than that of typical N-heterocyclic carbene (NHC) monolayers considered currently as the most stable SAMs on metal substrates. However, in contrast to NHC SAMs, which are highly insulating, the naphtalene-based SAM, with S, Se or COO anchoring groups, are highly conductive, even in comparison with analogous oligophenyl SAMs (by a factor of 10). A unique combination of the ultimate thermal stability and superior conductivity for the naphthalenethiol SAM on Ag makes it highly attractive for applications.
The Born cross sections and effective form factors for process 𝑒+𝑒−→Ξ−¯Ξ+ are measured at eight center-of-mass energies between 2.644 and 3.080 GeV, using a total integrated luminosity of 363.9 pb−1 𝑒+𝑒− collision data collected with the BESIII detector at BEPCII. After performing a fit to the Born cross section of 𝑒+𝑒−→Ξ−¯Ξ+, no significant threshold effect is observed.
The present study aims to report the currently available epidemiology of focal onset seizures in children aged >1 month to 4 years with the help of a literature review. The terms ‘seizure*’ OR ‘epilepsy’ combined with pediatric and epidemiology terms were used to search Embase, PubMed, and Web of Science up to November 16, 2021. Due to the scarcity of epidemiology data on focal onset seizures, the incidence and prevalence were estimated using the proportion of focal onset seizures in epilepsy patients from the most recently published articles. The estimated annual incidence per 100,000 children of focal onset seizures in children of 0–4 years of age ranged from 25.1 (95 % confidence interval [CI] 18.9–32.7) in the United Kingdom to 111.8 in the United States. The estimated period prevalence of focal onset seizures in children 0–4 years of age ranged from 0.15 % (99 % CI 0.13–0.18) in Canada to 0.61 % in the United States. Neurodevelopmental outcomes and psychiatric disorders were the most commonly reported comorbidities in children with epilepsy of age 0–4 years. Presence of focal onset seizures in children with different epilepsy syndromes needs to be thoroughly considered in the treatment planning of this population of interest.
Background: Multiple studies have focused on medical and pharmacological treatments and outcome predictors of patients with status epilepticus (SE). However, a sufficient understanding of recurrent episodes of SE is lacking. Therefore, we reviewed recurrent SE episodes to investigate their clinical characteristics and outcomes in patients with relapses.
Methods: In this retrospective, multicenter study, we reviewed recurrent SE patient data covering 2011 to 2017 from the university hospitals of Frankfurt and Marburg, Germany. Clinical characteristics and outcome variables were compared among the first and subsequent SE episodes using a standardized form for data collection.
Results: We identified 120 recurrent SE episodes in 80 patients (10.2% of all 1177 episodes). The mean age at the first SE episode was 62.2 years (median 66.5; SD 19.3; range 21–91), and 42 of these patients were male (52.5%). A mean of 262.4 days passed between the first and the second episode. Tonic–clonic seizure semiology and a cerebrovascular disease etiology were predominant in initial and recurrent episodes. After subsequent episodes, patients showed increased disability as indicated by the modified Rankin Scale (mRS), and 9 out of 80 patients died during the second episode (11.3%). Increases in refractory and super-refractory SE (RSE and SRSE, respectively) were noted during the second episode, and the occurrence of a non-refractory SE (NRSE) during the first SE episode did not necessarily provide a protective marker for subsequent non-refractory episodes. An increase in the use of intravenous-available anti-seizure medication (ASM) was observed in the treatment of SE patients. Patients were discharged from hospital with a mean of 2.8 ± 1.0 ASMs after the second SE episode and 2.1 ± 1.2 ASMs after the first episode. Levetiracetam was the most common ASM used before admission and on discharge for SE patients.
Conclusions: This retrospective, multicenter study used the mRS to demonstrate worsened outcomes of patients at consecutive SE episodes. ASM accumulations after subsequent SE episodes were registered over the study period. The study results underline the necessity for improved clinical follow-ups and outpatient care to reduce the health care burden from recurrent SE episodes.
Highlights
• German patients with LGS identified using most specific algorithm to date.
• Prevalence of probable LGS with epilepsy diagnosis before age 6 was 6.5 per 100,000.
• High healthcare costs of €22,787 PPY; mostly due to inpatient and home nursing care.
• Costs were greater in patients prescribed rescue medications.
• Over 10 years, LGS patients had significant mortality vs. controls (2.88 vs. 0.01%).
Abstract
Objective: This retrospective study examined patients with probable Lennox-Gastaut syndrome (LGS) identified from German healthcare data.
Methods: This 10-year study (2007–2016) assessed healthcare insurance claims information from the Vilua Healthcare research database. A selection algorithm considering diagnoses and drug prescriptions identified patients with probable LGS. To increase the sensitivity of the identification algorithm, two populations were defined: all patients with probable LGS (broadly defined) and only those with a documented epilepsy diagnosis before 6 years of age (narrowly defined). This specific criterion was used as LGS typically has a peak seizure onset between age 3 and 5 years. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, hospitalization rate and length of stay (LOS), medication use, and mortality.
Results: In the final year of the study, 545 patients with broadly defined probable LGS (mean [range] age: 31.4 [2–89] years; male: 53%) were identified. Using the narrowly defined probable LGS definition, the number of patients was reduced to 102 (mean [range] age: 7.4 [2–14] years; male: 52%). Prevalence of broadly defined and narrowly defined probable LGS was 39.2 and 6.5 per 100,000 people. During the 10-year study, 208 patients with narrowly defined probable LGS were identified and followed up for 1379 patient-years. The mean annual cost of healthcare was €22,787 per patient-year (PPY); greatest costs were attributable to inpatient care (33%), home nursing care (13%), and medication (10%). Mean annual healthcare costs were significantly greater for those with prescribed rescue medication (45% of patient-years) versus those without (€33,872 vs. €13,785 PPY, p < 0.001). Mean (standard deviation [SD]) annual hospitalization rate was 1.6 (2.0) PPY with mean (SD) annual LOS of 22.7 (46.0) days. Annual hospitalization rate was significantly greater in those who were prescribed rescue medication versus those who were not (2.2 [2.3] vs. 1.1 [1.6] PPY, p < 0.001). The mean (SD) number of different medications prescribed was 11.3 (7.3) PPY and 33.8 (17.0) over the entire observable time per patient (OET); antiepileptic drugs only accounted for 2.1 (1.1) of the medications prescribed PPY and 3.8 (2.0) OET. Over the 10-year study period, mortality in patients with narrowly defined probable LGS was significantly higher than the matched control population (six events [2.88%] vs. one event [0.01%], p < 0.001).
Conclusion: Annual healthcare costs incurred by patients with probable LGS in Germany were substantial, and mostly attributable to inpatient care, home nursing care, and medication. Patients prescribed with rescue medication incurred significantly greater costs than those who were not. Patients with narrowly defined probable LGS had a higher mortality rate versus control populations.
Highlights
• Prevalence of probable DS identified from German healthcare data: 4.7 per 100,000.
• Healthcare costs: €11,048 per patient-year, mostly inpatient care 47%, medication 26%.
• Costs and hospitalizations greater in patients with rescue medication than without.
• Mean (SD) of 5.0 (2.5) different ASMs prescribed per patient over study period.
• Patients with probable DS had significantly higher mortality risk vs. controls (11.88% vs. 1.19%).
Abstract
Objective: Ten-year retrospective study to assess burden of illness in patients with probable Dravet syndrome (DS) identified from German healthcare data.
Methods: In the absence of an International Classification of Diseases code, patients with probable DS were identified using a selection algorithm considering diagnoses and drug prescriptions. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, annual hospitalization rate (AHR) and length of stay (LOS), medication use, and mortality.
Results: In the final study year, 64 patients with probable DS (mean [range] age: 33.2 [3–82] years; male: 48%) were identified. Prevalence: 4.7 per 100,000 people. During the study, 160 patients with probable DS were identified and followed up for 1,261 patient-years. Mean cost of healthcare was €11,048 per patient-year (PPY), mostly attributable to inpatient care (47%), medication (26%), and services and devices (19%). Annual healthcare costs were significantly greater for those with prescribed rescue medication (15% of patient-years) vs. without (€16,123 vs. €10,125 PPY, p < 0.001). Mean (standard deviation [SD]) AHR and LOS were 1.1 (1.7) and 17.5 (33.5) days PPY. AHR was significantly greater in patients with prescribed rescue medication vs. without (1.6 [2.0] vs. 1.0 [1.6] PPY, p < 0.001). Mean (SD) number of antiseizure medications prescribed was 2.6 (1.2) PPY and 5.0 (2.5) over the entire observable time for each patient. Mortality rate was significantly higher for probable DS vs. matched controls (11.88% [19 events] vs. 1.19% [172 events], p < 0.001).
Conclusion: Probable DS is associated with substantial healthcare costs in Germany.
An important goal is to identify the direct activation domain (AD)-interacting components of the transcriptional machinery within the context of native complexes. Toward this end, we first demonstrate that the multisubunit TFIID, SAGA, mediator, and Swi/Snf coactivator complexes from transcriptionally competent whole-cell yeast extracts were all capable of specifically interacting with the prototypic acidic ADs of Gal4 and VP16. We then used hexahistidine tags as genetically introduced activation domain-localized cross-linking receptors. In combination with immunological reagents against all subunits of TFIID and SAGA, we systematically identified the direct AD-interacting subunits within the AD-TFIID and AD-SAGA coactivator complexes enriched from whole-cell extracts and confirmed these results using purified TFIID and partially purified SAGA. Both ADs directly cross-linked to TBP and to a subset of TFIID and SAGA subunits that carry histone-fold motifs.
Mnemonic but not contextual feedback signals defy dedifferentiation in the aging early visual cortex
(2024)
Perception is an intricate interplay between feedforward visual input and internally generated feedback signals that comprise concurrent contextual and time-distant mnemonic (episodic and semantic) information. Yet, an unresolved question is how the composition of feedback signals changes across the lifespan and to what extent feedback signals undergo age-related dedifferentiation, that is, a decline in neural specificity. Previous research on this topic has focused on feedforward perceptual representation and episodic memory reinstatement, suggesting reduced fidelity of neural representations at the item and category levels. In this fMRI study, we combined an occlusion paradigm that filters feedforward input to the visual cortex and multivariate analysis techniques to investigate the information content in cortical feedback, focusing on age-related differences in its composition. We further asked to what extent differentiation in feedback signals (in the occluded region) is correlated to differentiation in feedforward signals. Comparing younger (18–30 years) and older female and male adults (65–75 years), we found that contextual but not mnemonic feedback was prone to age-related dedifferentiation. Semantic feedback signals were even better differentiated in older adults, highlighting the growing importance of generalized knowledge across ages. We also found that differentiation in feedforward signals was correlated with differentiation in episodic but not semantic feedback signals. Our results provide evidence for age-related adjustments in the composition of feedback signals and underscore the importance of examining dedifferentiation in aging for both feedforward and feedback processing.
Highlights
• Short- and long-delay memory consolidation is less robust in children than in young adults.
• Short-delay brain profile comprised of hippocampal, cerebellar, and neocortical brain regions.
• Long-delay brain profile comprised of neocortical and selected hippocampal brain regions.
• Brain profiles differ between children and young adults.
Abstract
From early to middle childhood, brain regions that underlie memory consolidation undergo profound maturational changes. However, there is little empirical investigation that directly relates age-related differences in brain structural measures to memory consolidation processes. The present study examined memory consolidation of intentionally studied object-location associations after one night of sleep (short delay) and after two weeks (long delay) in normally developing 5-to-7-year-old children (n = 50) and young adults (n = 39). Behavioural differences in memory retention rate were related to structural brain measures. Our results showed that children, in comparison to young adults, retained correctly learnt object-location associations less robustly over short and long delay. Moreover, using partial least squares correlation method, a unique multivariate profile comprised of specific neocortical (prefrontal, parietal, and occipital), cerebellar, and hippocampal head and subfield structures in the body was found to be associated with variation in short-delay memory retention. A different multivariate profile comprised of a reduced set of brain structures, mainly consisting of neocortical (prefrontal, parietal, and occipital), hippocampal head, and selective hippocampal subfield structures (CA1–2 and subiculum) was associated with variation in long-delay memory retention. Taken together, the results suggest that multivariate structural pattern of unique sets of brain regions are related to variations in short- and long-delay memory consolidation across children and young adults.
Childhood is a period when memory consolidation and knowledge base undergo rapid changes. The present study examined short-delay (overnight) and long-delay (after a 2-week period) consolidation of new information either congruent or incongruent with prior knowledge in typically developing 6- to 8-year-old children (n = 32), 9- to 11-year-old children (n = 33), and 18- to 30-year-old young adults (YA; n = 39). Both memory accessibility (cued recall of objects) and precision (precision of object placement) of initially well-learned object–scene pairs were measured. Our results showed that overnight, memory accessibility declined similarly in all age groups; memory precision improved more in younger children (YC) compared to older children (OC) and even declined in YA. After a 2-week period, both memory accessibility and precision became worse. Specifically, while age groups showed similar decline in memory accessibility, precision decline was less in YC than in OC and YA. The accessibility and precision of congruent and incongruent information changed similarly with consolidation in all age groups. Taken together, our results showed that, for initially well-learned information, YC have robust memory consolidation, despite their overall lower mnemonic performance compared to OC and YA, which is potentially crucial for stable and precise knowledge accumulation early on in development.
Preparing auditory task switching in a task with overlapping and non-overlapping response sets
(2023)
We used a variant of cued auditory task switching to investigate task preparation and its relation to response-set overlap. Previous studies found increased interference with overlapping response sets across tasks relative to non-overlapping motor response sets. In the present experiments, participants classified either pitch or loudness of a simple tone as low or high, hence, both tasks were constructed around common underlying integrated semantic categories ranging from low to high. Manual responses overlapped in both category and modality for both tasks in Experiment 1A, whereas each task was related to a specific response category and response modality (manual vs. vocal) in Experiment 1B. Focusing on the manual responses in both experiments, the data showed that non-overlapping response sets (Experiment 1B) resulted in a decreased congruency effect, suggesting reduced response-based crosstalk and thus better task shielding, but at the same time switch costs were increased, suggesting less efficient switching between task sets. Moreover, varying preparation time (cue-stimulus interval, CSI) showed that long CSI led to better performance overall. Our results thus suggest that when non-overlapping response sets share common semantic categories across tasks, there is no general benefit over overlapping response sets.
The role of response set overlap for flexibility and cognitive control in auditory multitasking
(2022)
Highlights
• We introduced a new variant of auditory task-switching.
• Motor response set overlap was varied systematically across two experiments.
• Switch costs and congruency effects were similar for manual and vocal responses.
• Switch costs were not reduced with reduced motor response set overlap.
• We dissociated effects of motor response modality from motor response set overlap.
Abstract
We developed a new variant of auditory task-switching in order to systematically investigate shifting and cognitive control in auditory task-switching and their relation to motor response overlap in a comprehensive way. In two experiments, participants classified either pitch or loudness of a simple tone as either low or high, hence, both tasks were constructed around a common underlying dimension ranging from low to high. In Experiment 1, response sets overlapped in both category and motor modality (both manual), whereas each task was related to a specific response category and motor response modality (manual vs. vocal) in Experiment 2. The data revealed reliable switch costs that were, contrary to our expectations, not reduced with reduced response set overlap. In addition, we found reliable congruency effects and their sequential modulation in both experiments with manual as well as vocal responses, and in the absence of competing motor activation (i.e., without motor response overlap). Congruency effects after auditory task switches were smaller when response sets did not overlap. Our data thus provides an important empirical generalization of known effects to auditory stimuli as well as with both manual and vocal responses. In addition, we demonstrated that reduced congruency effects after switches for non-overlapping response sets were due to the extent of overlap between different response sets in task-switching.
The Board of Directors of the German Society of Epileptology and the committee on epilepsy and syncope of the German Society of Neurology have reviewed the current data on vaccination to prevent coronavirus disease 2019 (COVID-19) and vaccination prioritization in people with epilepsy and provide a summary and recommendations.
100 Jahre Dieter Janz
(2020)
The 20 April 2020 marks the centenary of Dieter Janz’s birth. This issue of Zeitschrift für Epileptologie is published in his honor with the aim of tracing the work of Dieter Janz over the last five decades and summarizing new findings on the Janz syndrome (Juvenile Myoclonic Epilepsy), which is named after him.
The paper presents the findings of two recent books on the financial history of the Frankfurt School: Jeanette Erazo-Heufelder, Der argentinische Krösus: Kleine Wirtschaftsgeschichte der Frankfurter Schule, 2017, and Bertus Mulder, Sophie Louisa Kwaak und das Kapital der Unternehmerfamilie Weil. Ein Beitrag zur Wirtschaftsgeschichte der Frankfurter Schule, 2021 (Dutch original 2015). In contrast to the “court histories” of the school, the two authors tell the story of the money that brought the school to life and secured its existence throughout a turbulent period of history. At the center of the books are individuals who have been sidelined until now or even completely ignored by the literature on the Frankfurt School: on the one hand, Felix Weil, who founded and financed the Institute of Social Research and, on the other hand, Erich A. Nadel and Sophie L. Kwaak, two employees of the holding company who managed the accounts of the Weil family and the Institute’s foundations and were responsible for protecting the assets from being seized by Nazis. The books’ thick descriptions induced the author of the present paper to consider an alternative perspective on the Frankfurt School by contemplating Max Horkheimer and Friedrich Pollock as playing confidential games with Weil and others.
Hintergrund: Mit der im Jahr 2020 aktualisierten AWMF-Leitlinie zur Versorgung mit einem Cochleaimplantat (CI) wurde erstmals der gesamte Prozess einer CI-Versorgung definiert. In der vorliegenden Studie wurden die Machbarkeit und die Ergebnisse einer sehr frühen Rehabilitationsmaßnahme (Reha) untersucht.
Methodik: Es wurden 54 Patienten in die Interventionsgruppe (IG) eingeschlossen, bei der die Reha innerhalb von 14 (maximal 28) Tagen nach der Implantation eingeleitet wurde. In eine Kontrollgruppe (KG, n = 21) wurden Patienten mit deutlich längerer Wartezeit eingeschlossen. Neben dem Beginn und der Dauer der Reha wurde das mit CI erreichte Sprachverstehen zu verschiedenen Zeitpunkten innerhalb von 12 Monaten erfasst. Zusätzlich wurde mit Fragebögen der Aufwand der Anpassung des CI-Prozessors und die Zufriedenheit der Patienten mit dem Ergebnis sowie dem Zeitpunkt des Beginns der Reha ermittelt.
Ergebnisse: Die Wartezeit zwischen Implantation und Beginn der Reha lag in der IG bei 14 Tagen und in der KG bei 106 Tagen (Mediane). Es konnten 92,6 % der Patienten der IG die Reha innerhalb von 14 Tagen antreten. Der Effekt der Reha lag in der IG bei 35 und in der KG bei 25 Prozentpunkten (Freiburger Einsilbertest). Nach 6 und 12 Monaten (M) CI-Nutzung zeigten beide Gruppen sowohl in der Testbedingung in Ruhe (IG/KG 6M: 70 %/70 %; 12M: 70 %/60 %, Freiburger Einsilbertest) als auch im Störgeräusch (IG/KG 6M: −1,1 dB SNR/–0,85 dB SNR; 12M: −0,65 dB SNR/+0,3 dB SNR, Oldenburger Satztest) vergleichbare Ergebnisse. Die mittels des Fragebogens Speech, Spatial and Qualities of Hearing Scale (SSQ) erfassten Ergebnisse für die Einschätzung der Hörqualität zeigten nach 6 Monaten eine bessere Bewertung in der IG, die sich nach 12 Monaten an die Ergebnisse der KG anglich. Die IG war mit dem Zeitpunkt des Beginns der Reha deutlich zufriedener als die KG. Alle anderen aus Fragebögen ermittelten Daten zeigten keine Unterschiede zwischen den beiden Gruppen.
Schlussfolgerung: Der sehr frühe Beginn einer stationären Reha nach Cochleaimplantation ist erfolgreich umsetzbar. Die Reha konnte innerhalb von 7 Wochen nach der Implantation abgeschlossen werden. Der Vergleich der Ergebnisse der Tests des Sprachverstehens vor und nach der Reha zeigte eine deutliche Steigerung. Somit ist ein deutlicher Reha-Effekt nachweisbar. Die Aufnahme der CI-Rehabilitation in den Katalog der Anschlussheilbehandlungen ist somit wissenschaftlich begründet und damit dringend zu empfehlen.
Background: The Association of the Scientific Medical Societies in Germany (AWMF) clinical practice guideline on cochlear implant (CI) treatment, which was updated in 2020, defined the entire process of CI care for the first time. In the present study, the feasibility and results of very early rehabilitation were examined.
Materials and methods: The intervention group (IG) comprised 54 patients in whom rehabilitation was initiated within 14 (maximally 28) days after implantation. Patients with a significantly longer waiting time were included in the control group (CG, n = 21). In addition to the start and duration of rehabilitation, the speech intelligibility achieved with CI was recorded at different timepoints within a 12-month period. In addition, questionnaires were used to assess the effort of fitting the CI processor and the patients’ satisfaction with the outcome as well as the timing of the start of rehabilitation.
Results: Median waiting time between implantation and start of rehabilitation was 14 days in the IG and 106 days in the CG; 92.6% of IG patients were able to start rehabilitation within 14 days. The effect of rehabilitation in the IG was 35 and in the CG 25 percentage points (Freiburg monosyllabic test). After 6 and 12 months of CI use, both groups showed comparable results in the test condition in quiet (IG/CG 6 months: 70%/70%; 12 months: 70%/60%, Freiburg monosyllabic test) and in noise (IG/CG 6 months: −1.1 dB SNR/–0.85 dB SNR; 12 months: −0.65 dB SNR/+0.3 dB SNR, Oldenburg sentence test). Hearing quality assessment scores collected by SSQ (Speech, Spatial and Qualities of Hearing Scale) questionnaire showed better scores in the IG at 6 months, which converged to CG scores at 12 months. The IG was significantly more satisfied with the timing of the start of rehab than the CG. All other data obtained from questionnaires showed no differences between the two groups.
Conclusion: A very early start of inpatient rehabilitation after cochlear implantation was successfully implemented. The rehabilitation was completed within 7 weeks of CI surgery. Comparison of speech recognition test results before and after rehabilitation showed a significant improvement. A clear rehabilitation effect can therefore be demonstrated. Inclusion of CI rehabilitation in the German catalog of follow-up treatments is thus scientifically justified and therefore strongly recommended.
Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs rapidly associated with translating ribosomes in the cytoplasm and that this incorporation was independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (following oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing neuronal synapses a rapid means to regulate local protein synthesis.
Protein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, and by the cellular environment (Dörrbaum et al., 2018). Here, we advanced our experimental approach to quantify changes in protein synthesis and degradation, as well as the resulting changes in protein turnover or abundance in rat primary hippocampal cultures during homeostatic scaling. Our data demonstrate that a large fraction of the neuronal proteome shows changes in protein synthesis and/or degradation during homeostatic up- and down-scaling. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.
The genus Legua Walker, 1870 comprises only two known species from Central America and Brazil, with a notable scarcity of collected specimens. Herein, we provide a new contribution to our knowledge of the distribution of Legua rosea Amédégnato and Poulain, 1986 (Romaleinae: Leguini), that has a restricted distribution in Brazil, based on entomological collection data and social media information. Our records emphasize the importance of natural history collections and new tools for biodiversity studies.
ZooBank registration. urn:lsid:zoobank.org:pub:17E0802B-A389-4983-AC74-21B51197F557
A new species of Paranthrene Hübner (Lepidoptera: Sesiidae) from the northern midwest United States
(2024)
A clearwing moth species, Paranthrene sogaardi Taft and Smith, 2024, new species, is described from Michigan and Minnesota. The recognition of this new species is based on a phylogeny estimated from mitochondrial cytochrome oxidase I and wingless DNA sequences of 25 specimens representing all Paranthrene Hübner species including individuals from various locations. Paranthrene sogaardi new species was monophyletic and differed from Paranthrene tabaniformis Rottenburg, 1775 by a mean of 7.6% COI pairwise “p” distance, coloration, and genitalic morphology.
ZooBank registration. urn:lsid:zoobank.org:pub:8B9ED6CE-4DEB-4CB2-9235-3CA593F4D9DB
Hurd (1952) separated Pepsis cerberus Lucas from P. elegans Lepeletier (Hymenoptera: Pompilidae: Pepsinae: Pepsini) based on external morphology and biogeography. Vardy (2005) synonymized the familiar and historically well-documented P. cerberus and P. elegans, combining these Nearctic taxa with several Neotropical variants in an extremely broad definition of P. menechma Lepeletier. In doing so, Vardy (2005) breached the principle of nomenclatural stability. He ignored the prevailing usage and clearly violated articles 23.2, 23.3 and 23.9.1.2 of the ICZN (1999). Morphological differences, ecological divergence, and narrow sympatric geographic distribution of P. cerberus and P. elegans contradict Vardy (2005) and justify full species status (Kurczewski 2023a). Furthermore, we propose the removal of the two species from the P. menechma list of synonyms and recommend full species reinstatement as Pepsis cerberus, restored status and Pepsis elegans, restored status. Pepsis menechma becomes a senior synonym of P. elegans. Morphometric re-examination and statistical analysis of P. cerberus and P. elegans structural features strongly support their reinstatement. Quantitative measurement of 10 parasitoid-related morphological characteristics of the females revealed the two species differ significantly in frons width/head width, head length/head width, vertex length/head width, vertex length/head length, flagellomere 1 length/flagellomere 1 width, forewing length/mesosoma width, and hind tibial inner spur length/hind basitarsus length. Pepsis cerberus and P. elegans females are structurally and statistically similar in gena-postgena corner radius, fore femur width/mesosoma width, and number of hind tibial serrations.
ZooBank registation. urn:lsid:zoobank.org:pub:D22EC64F-7C55-4071-9290-4661CA377B24
The geographic distributions of three large wasps, Sphecius speciosus (Drury), Stictia carolina Fabricius and Stizus brevipennis Walsh (Hymenoptera: Crabronidae), occurring in Arkansas are defined using museum specimens and three internet-based data platforms. The internet-based data platforms generally provided more county location records than museum records. Using data from internet sources for easily identified species can better serve to illustrate the known distributions for some species thus making for a powerful tool elucidating distributional patterns and conservation planning.
ZooBank registration. urn:lsid:zoobank.org:pub:DCAE9192-1765-40CD-952B-0A094F413991
Corrections and additions to the Hydnocerina (Coleoptera: Cleridae: Clerinae: Hydnocerini) of Mexico
(2024)
Corrections, additions and remarks are made with respect to the recent checklist of the Cleridae (Coleoptera) of Mexico (Araujo-Castillo et al. 2024). Current valid names, synonymies, clarifications of taxonomic problems, and omitted taxa are reviewed. This work is intended to serve as a supplement to the “Hydnocerinae” section of the checklist.
ZooBank registration. urn:lsid:zoobank.org:pub:EF3E45B5-6EA6-41AB-B92F-DB4ABF9D8215
The exclusively New World velvet ant genus Timulla Ashmead, 1899 (Hymenoptera: Mutillidae: Mutillinae: Trogaspidiini) contains 180 species and ten subspecies. Most of these species are known from a single sex, and the validity of the subspecies has not been evaluated since their original description in 1937 and 1938. The Timulla fauna of the United States of America includes thirty species and eight subspecies, and the fauna of Canada includes three species. The faunas of these two countries were critically studied with the following results. Out of the eight total subspecies, seven were found to be structurally identical to and sympatric with the nominate subspecies. The subspecific differences were limited to cuticle and/or setal coloration in males and intergrades between them were found in several cases. With the senior synonym listed first, seven subspecies-level synonymies are proposed, which include: Timulla barbigera (Bradley, 1916) = T. barbigera rohweri Mickel, 1937, new synonym; T. dubitata (Smith, 1855) = T. dubitata fugitiva Mickel, 1937, new synonym; T. hollensis (Melander, 1903) = T. hollensis melanderi Mickel, 1937, new synonym; T. ocellaria Mickel, 1937 = T. ocellaria rufidorsa Mickel, 1937, new synonym; T. suspensa (Gerstaecker, 1874) = T. suspensa jonesi Mickel, 1937, new synonym, = T. suspensa sonora Mickel, 1937, new synonym; T. vagans (Fabricius, 1798) = T. vagans rufinota Mickel, 1937, new synonym. The final remaining subspecies, Timulla navasota coahuila Krombein, 1951, is raised to a full species, Timulla coahuila Krombein, 1951, new status, based on its unique female morphology. Also, four new sex associations are proposed, which include: Timulla barbata (Fox, 1899) = T. wileyae Mickel, 1937, new synonym; T. euterpe (Blake, 1879) = T. compressicornis Mickel, 1937, new synonym; T. neobule Mickel, 1937 = T. nicholi Mickel, 1937, new synonym; T. subhyalina Mickel, 1937 = T. dubitatiformis Mickel, 1937, new synonym. The former species, T. dubitatiformis, which was previously known only from females, is here recognized as being a morphologically-conservative complex of species; its synonymy with T. subhyalina effectively associates the remaining male-based members of the Timulla ocellaria species-group with it as well, which includes Timulla hollensis (Melander, 1903), T. kansana Mickel, 1937, T. ocellaria Mickel, 1937, T. rufosignata (Bradley, 1916), T. sayi (Blake, 1871), T. subhyalina Mickel, 1937, and T. tolerata Mickel, 1937. Further, two species-level synonymies are proposed, which include: Timulla dubitata (Smith, 1855) = T. murcia Mickel, 1938, new synonym; T. vagans (Fabricius, 1798) = T. huntleyensis Mickel, 1937, new synonym. Finally, Timulla cyllene (Cameron, 1894) is newly recorded in the United States of America from the state of Arizona.
ZooBank registration. urn:lsid:zoobank.org:pub:891E0C92-B8BF-4487-84D4-42EB2254AF4A
Viruses that carry a positive-sense, single-stranded (+ssRNA) RNA translate their genomes soon after entering the host cell to produce viral proteins, with the exception of retroviruses. A distinguishing feature of retroviruses is reverse transcription, where the +ssRNA genome serves as a template to synthesize a double-stranded DNA copy that subsequently integrates into the host genome. As retroviral RNAs are produced by the host cell transcriptional machinery and are largely indistinguishable from cellular mRNAs, we investigated the potential of incoming retroviral genomes to directly express proteins. Here we show through multiple, complementary methods that retroviral genomes are translated after entry. Our findings challenge the notion that retroviruses require reverse transcription to produce viral proteins. Synthesis of retroviral proteins in the absence of productive infection has significant implications for basic retrovirology, immune responses and gene therapy applications.
We examined the feedback between the major protein degradation pathway, the ubiquitin-proteasome system (UPS), and protein synthesis in rat and mouse neurons. When protein degradation was inhibited, we observed a coordinate dramatic reduction in nascent protein synthesis in neuronal cell bodies and dendrites. The mechanism for translation inhibition involved the phosphorylation of eIF2α, surprisingly mediated by eIF2α kinase 1, or heme-regulated kinase inhibitor (HRI). Under basal conditions, neuronal expression of HRI is barely detectable. Following proteasome inhibition, HRI protein levels increase owing to stabilization of HRI and enhanced translation, likely via the increased availability of tRNAs for its rare codons. Once expressed, HRI is constitutively active in neurons because endogenous heme levels are so low; HRI activity results in eIF2α phosphorylation and the resulting inhibition of translation. These data demonstrate a novel role for neuronal HRI that senses and responds to compromised function of the proteasome to restore proteostasis.
The nine genera of Malagasy spittlebug are revised, with the addition of new characters, facilitating the identification of the species. Nesaulax Jacobi, 1917, is synonymized with Amberana Distant, 1908, leading to a new combination for Amberana vittipennis (Bergroth, 1894). A new endemic genus Soulierana Bucher & Bouteille gen. nov. is proposed for two species originally placed in Literna Stål, 1866, based on morphological characters of the head, tegmina and male genitalia. Also, three new species are described in this genus: Soulierana bigidea Bucher gen. et sp. nov., Soulierana claudinae Bouteille gen. et sp. nov. and Soulierana kelymena Le Cesne gen. et sp. nov. Pictures of species and drawings of the male genitalia for all genera, with the exception of Rhinaulax Amyot & Serville, 1843, Alluaudensia Lallemand, 1920 and Literna, are included. An identification key is available in both a dichotomous format and an interactive format (Xper3).
Systematics of the Sierra Nevada endemic earwig: Eulithinus analis (Forficulidae, Dermaptera)
(2024)
Since the description of Eulithinus analis (Rambur, 1838) the taxonomic position of this Sierra Nevada endemic earwig has been controversial. It has been subdivided in different taxa, assigned to various genera or transferred to different subfamilies. With the aim of clarifying its systematics, we performed a mitochondrial phylogeographic analysis using specimens from different localities of Sierra Nevada representing the diverse phenotypes treated as differentiated taxa until now, and a phylogenetic analysis including representatives of apparently distant, but morphologically close, relatives. The phylogenetic and phylogeographic results obtained using mitochondrial (cytb, cox1) and nuclear (ITS2) markers and the study of morphological characters, indicate that the Sierra Nevada Mountain Range harbors a single species of the genus Eulithinus. Based on these molecular data, the morphological characters used to date in the internal taxonomy of this group of earwigs, especially size and shape of the cerci, lack diagnostic validity and show a large inter- and intra-populational variability. These results imply the synonymy of Eulithinus montanus (Steinmann, 1981) with Eulithinus analis (Rambur, 1838) syn. nov. and the reconsideration of Eulithinus analis outside the subfamily Allodahliinae. We established the synonymy between Eulithinus analis (Rambur, 1838) and Forficula brevis Rambur, 1838 syn. nov., a name that must be removed from the synonymy of Forficula decipiens Gené, 1832.
Wir berichten über die Erfahrungen beim Aufbau einer Abteilung für die präoperative Eigenblutentnahme im Verantwortungsbereich des Institutes für Laboratoriumsmedizin der Städtischen Kliniken Frankfurt am Main-Höchst, einem Krankenhaus der Maximalversorgung mit 1150 Betten bzw. Tagesklinikplätzen. Die Herstellung von Eigenblutkonserven erfolgt nach § 13 des Arzneimittelgesetzes. Die Planung erfordert eine genaue Analyse des zu erwartenden Umfanges, der gegebenen Strukturen und betrieblichen Kapazitäten. Unsere Erfahrungen zeigen, daß mit der Entnahme von ca. 1200 autologen Blutkonserven pro Jahr und deren weiteren Bearbeitung eine Medizinisch-technische Assistentin ganztags und ein Arzt halbtags beschäftigt sind. Aus Gründen der Produktqualität und -Sicherheit sollte eine Trennung in die Komponenten Erythrozytenkonzentrat und Gefrorenes Frischplasma erfolgen und ein Qualitätssicherungssystem etabliert werden, das dem der Herstellung von homologen Blutkonserven entspricht. Dies bedeutet, bei jeder Entnahme die in den Richtlinien zur Blutgruppenbestimmung und Bluttransfusionen (Hämotherapie) in § 3.2.5 angegebenen Parameter zu testen (Glutamat-Pyruvattransaminase, Hepatitis B surfaceAntigen sowie Antikörper gegen Humanes Immundefizienz-Virus 1/2, Hepatitis-C-Virus und Treponema pallidum). Zusätzlich bestimmen wir C-reaktiyes Protein, ThromboplastinzeiL .Partielle Thromboplastinzeit, Leukozyten, Thrombozyten und Gesamteiweiß. Eine PC -gestützte Erfassung von Spender- und Spendedaten gewährleistet eine einfache statistische Auswertung der Entnahme Vorgänge. Die ebenfalls EDV-unterstützte Vergabe der Konservennummern und .BarcodeEtikettierung erleichtem es, die Eigenblutkonserven in der allgemeinen Blutbank-EDV zu verwalten. Durch eine fachübergreifende Zusammenarbeit, z.B. im Rahmen einer Transfusionskommission, müssen die Ablaufe aller fremdblutsparenden Maßnahmen vorgestellt und fortwährend optimiert werden, um Qualität, Akzeptanz und Wirtschaftlichkeit der autologen Blutentnahme zu erhalten.
Die Rate von positiven Blutkulturen wird in der Literatur mit 6,4% bis 18% angegeben. Hierbei wird nicht zwischen Einsendungen zur Bestätigung des Verdachts auf eine Sepsis bzw. zum Ausschluß einer Sepsis unterschieden. In einer prospektiven Untersuchung bei 315 Patienten mit Verdacht auf Sepsis, bei denen Blutkulturen beimpft wurden, konnte bei 199 (63%) ein ätiologischer Nachweis erbracht werden.
Ein Krankenhauslabor und ein Einsendelabor, das mehrere Krankenhäuser versorgt, haben prospektiv 3.907 Blutkulturflaschen für das BACTEC™ 9000–System (BDDiagnostics, Heidelberg, Germany) untersucht. Dabei wurden 1.888 aerobe Flaschen, 1.880 anaerobe Flaschen und 139 pädiatrische Blutkulturflaschen verarbeitet. Es wurden der Zeitpunkt der Beimpfung und der Zeitpunkt des Einlesens der Kulturen in das Gera ̈t dokumentiert. Neben den Medientypen und dem Blutvolumen wurden folgende Daten erhoben: Die Zeit vom Einlesen in das Gerät bis zum positiven Signal (Detektionszeit), die Identifizierung des Erregers bis zur Species, die Antibiotikatherapie und die Wiederfindungsrate verglichen mit der terminalen Subkultur. Die mittlere Transportdauer betrug 21,4 h, die mittlere Detektionszeit 21,5 h. 27 Flaschen waren falsch negativ und sechs Flaschen falsch positiv. Bei sieben der falschnegativen Flaschen hatte die Partnerflasche ein positives Signal gegeben (Staphylococcus aureus, Enterobactercloacae, Enterococcus faecalis, Candida albicans, Burkholderia cepacia, zwei Pseudomonas aeruginosa-Stämme). Davon waren vier Isolate strikte Aerobier, die nichtin der anaeroben Flasche wuchsen, fünf Patienten standen unter Antibiotikatherapie und eine Flasche hatte eine Transportzeit)48 h und ist in dieser Gruppe ebenfalls aufgeführt. 15/27 falsch negative Flaschen hatten eine Transportzeit)48 h, 11 Patienten bekamen in dieser Gruppe eine Antibiotikatherapie. 6/27 falsch negative Flaschen hatten eine Transportzeit-48 h, davon wurden zwei Patienten antibiotisch behandelt. Einmal handelte es sich um C. glabrata, die nicht in der anaeroben Flaschewuchs. Der klinisch relevante Anteil der falsch negativen Blutkulturen (Isolat nicht in der Begleitflasche nachgewiesen), der innerhalb von 48 h in das BACTEC™ 9000-Gerät eingelesen wurde, betrug 0,15%.
Chromaktiviert die Wirkung von Insulin. Bei Typ-1- undTyp-2-Diabetikern reflektierten verminderte Chromgehalte in Leukozyten eine verminderte Chromversorgung. Je schlechter die Diabeteseinstellung, umso niedriger ward er Chromstatus bei Typ-2-Diabetikern. Daher sollte bei diesen Patienten – besonders bei Typ-2-Diabetikern mit schlechter Einstellbarkeit – eine Chromsupplementation erwogen werden, wenn eine sichere Bestimmung der Chromversorgung nicht gewährleistet ist. Kupferionenbesitzen anti- und auch prooxidative Eigenschaften. Hohe Kupferplasmawerte korrelieren mit der Entstehung einer Arteriosklerose. Die Kupferkonzentrationen im Plasma waren bei beiden Diabetikergruppen erhöht, weitererhöhte Werte zeigten Typ-2-Diabetiker mit Hyperlipidämie oder diabetischen Folgeerkrankungen. Um das Risiko für Mikro- und Makroangiopathie oder Nephropathie zu vermindern, sollten Diabetiker eine hohe Kupferzufuhr vermeiden. Selen wirkt antioxidativ, immunstimulierend und antiatherogen. Der Selengehalt im Plasma reflektiert die Selenzufuhr. Die Selenplasmawerte waren bei beiden Diabetesgruppen geringfügig vermindert und auffällig vermindert bei Patienten mit Folgeerkrankungen. Eine selenreiche Ernährung oder Selengaben zur Prävention von Spätfolgen könnten bei Diabetikern daher sinnvoll sein. Patienten mit Nephropathie und eingeschränkter Zufuhr an tierischem, selen- und zinkreichem Protein profitieren möglicherweise von einer Selensupplementation. Zink ist an der Wundheilung, der Immunfunktion und der Aktivierung und Speicherung von Insulin beteiligt. Der Elementgehalt war beiTyp-1-Diabetikern in Leukozyten, dem bestem Indikator der Zinkversorgung, vermindert. Bei Patienten mit Nephropathie, Mikroangiopathie oder Neuropathie war das Zinkdefizit noch deutlicher ausgeprägt. Eine hochwertige, proteinreiche Ernährung könnte die Versorgungslage ver-bessern, auch eine Zinksupplementation wäre möglicherweise von Nutzen.
A comparison of different APTT-reagents, heparin-sensitivity and detection of mild coagulopathies
(1992)
The activated partial thromboplastin time (aPTT) is widely used to detect coagulation abnormalities or to monitor heparin treatment.
Many commercial aPTT-reagents are available which contain different phospholipid reagents and activators. In the present study 3 aPTT-reagents (aPTT-D, Instrumentation Laboratory, Neothromtin, Behring, PTTa, Boehringer) were compared using a computerized centrifugal analyzer. One aPTT-reagent (Pathromtin, Behring) was tested on a semiautomated coagulometer. Instrument precision was evaluated using aPTT-D as reagent.
Comparative tests were performed on plasma samples of 40 healthy donors, 3 patients with mild von Willebrand's disease (vWd), W patients with heaemophilia or subhaemophilia A, 1 patient with subhaemophilia A and vWd, 8 patients treated with subcutaneous injection of unfractionated heparin (UFH) and 14 patients treated with subcutaneous injection of a low molecular weight heparin (LMWH).
aPTT-D was the most sensitive reagent to detect mild vWd while Pathromtin detected none of these defects. In patients with heamophilia A and subhaemophilia A aPTT-D, Neothromtin and PTTa detected the abnormality in nearly all tested samples while Pathromtin was less sensitive.
Patients treated with subcutaneously applied UFH or LMWH often had a prolonged aPTTt especially when aPTT-D and Neothromtin were used as reagents.
Die Zytomegafie ist eine meist lebenslänglich latent bleibende vertikale und horizontale Herpesvirusinfektion mit gelegentlich schweren Krankheitsbildern, auch als Ursache oder Folge von Immunstörungen. Dem Virus wird ein onkogenes Potential zugeschrieben, zuletzt diskutiert bei AIDS und M. Kaposi. Für die Labordiagnose verfügen wir über die Mikroskopie (Zellkerneinschlüsse) und Elektronenmikroskopie, Nachweis der Virusinfektiosität auf Zellkulturen, DNA- und Polypeptidanalyse zur Virusstammidentifikation, direkte DNA- und Antigennachweise aus Patientenmaterial, immunhistologische Methoden (z.B. Immunperoxydase- Technik). Die Untersuchung der Immunzellen erfolgt bei der Zytomegalie quantitativ (T-ZellQuotient) und qualitativ (Lymphozytenstimulierung, neuerdings auch mit Vollblut). Am leichtesten gelingt die Labordiagnose serologisch, d.h. über den Antikörpernachweis. Dafür sind eine Vielzahl „liquid" und „solid phase"-Assays entwickelt worden. Am meisten haben sich heute neben der KB R (und P H A) Immunofluororeszenz und ELISA durchgesetzt, wobei einerseits unterschiedliche Antigene („early", „late antigens") und Antigenpräparationen (z. B. Viruskapsid, -envelope) zum Einsatz kommen, andererseits verschiedene Ig- Klassen und -Subklassen getestet werden, um die primäre und sekundäre Zytomegalie zu diagnostizieren und zu differenzieren. Speziell für den Ig M -Nachweis wurden viele Testmodifikationen etabliert; Rheumafaktorinterferenz und IgG-Kompetition lassen sich am besten durch IgG-Präzipitation ausschalten. Die neuen Methoden haben nicht nur die Aufklärung vieler interessanter Krankheitsfälle, sondern auch exakte epidemiologische Studien bei Risikogruppen ermöglicht (Blutspender: 47[0], schwangere Frauen 56[13], Patienten mit Hämophilie: 69[0], nach NTPL: 90[24], nach Herz-OP: 87[1], Prostituierte: 90[1]% CMV-IgG[(IgM)- Antikörperträger].
Acht kommerzielle Enzymimmunoassay (ELISA)-Testsysteme und ein in.houseHSV-1- und HSV-2-Western blot wurden anhand von 176 mittels Virusisolierung und -typisierung aus korrespondierenden Abstrichen gut charakterisierten Seren auf ihre Eignung zum Nachweis typenspezifischer Antikörper gegen Herpes simplex-Virus (HSV) Typ l und Typ 2 untersucht. Es zeigte sich, daß die auf Vollvirus-Antigenen basierenden ELISAs eine sehr unterschiedliche Sensitivität (85-100% für HSV-1, 35-100% für HSV-2) bei meist nur unzureichender Spezifität (57-93% für HSV-1, 48-91% für HSV-2) erreichen. Hingegen verbindet der einzige ELISA, der das als typspezifisch bekannte HSV-2-Glykoprotein gG-2 als Antigen verwendet, maximale Spezifität (100%) mit mangelnder Sensitivität (52%), wobei insbesondere HSV-l/-2-Koinfektionen nicht erkannt werden. Modifikationen der cut off-Werte konnten die Leistungscharakteristika nicht wesentlich verbessern. Im Western blot ließ sich kein einzelnes HSV-1- bzw. HSV-2-Antigen als optimaler Marker identifizieren, jedoch war bei allen Seren eine eindeutige Zuordnung aufgrund der Reaktivitäts-(Banden-)Muster möglich. Bei Untersuchung von potentiell falsch-positiven „tricky sera"'konnte eine ausreichende Spezifität der acht getesteten IgM-ELISAs lediglich durch Vorbehandlung mit Rheumafaktor-Absorbens erreicht werden. Die Auswertung von 3527 im Rahmen der Routinediagnostik durchgeführten Testungen auf Antikörper gegen HSV-1 und HSV-2 ergab Seroprävalenzraten von durchschnittlich 76,4% für anti-HSV-1 und 12,1% für anti-HSV-2 bei jeweils deutlichem Anstieg mit zunehmendem Alter.
Background: Hundreds of West African healthcare workers (HCW) have become ill with Ebola virus disease (EVD) and died during the recent outbreak. The occurrence of occupational infections in laboratories could be due to the lack of use of personal protective equipment, the failure to implement specific regulations about the use of equipment and how to work with hazardous materials. Our study attempted to assess the information as well as training level of HCW of a German high level isolation unit and their concern over an occupationally acquired EVD.
Methods: During the recent Ebola virus outbreak a survey was conducted among HCWs, using an anonymous questionnaire.
Results: Although 70% of our total study population stated that they have all the information needed to care for Ebola patients, only 18.2% of laboratory workers and 29.4% of the HCW of the virology department felt sufficiently trained. The HCW rated the Internet (64.3%) and the daily press (54.3%) as the most important sources of information. Medical literature (45.7%) and official institutions (40.4%) were rated less often.
Conclusions: Formulated pointedly, the HCW turned to popular science to get the information they need to feel safe. Further in house training regarding practical skills and reference to scientific literature would be a better solution to ensure workplace safety.
Für eine rasche Labordiagnose der Herpes simplex Virus (HSV) Infektion ist ein schneller Erregernachweis von entscheidender Bedeutung. In der vorliegenden Arbeit wird eine schnelle, modifizierte Virusisolierung über den Nachweis von Virusstrukturproteinen mit Hilfe typenspezifischer monoklonaler Antikörper innerhalb von 36 Stunden (IPF-HSV) beschrieben. Es wurden insgesamt 560 Proben aus der Routinediagnostik vergleichend mit der konventionellen Virusisolierung über einen cytopathischen Effekt (CPE) und anschließender Typisierung (ZK-IFT) in infizierten Vero-Zellen und humanen Vorhautfibroblasten (HFF) untersucht. Die Sensitivität des IPF-HSV für HSV-1, bezogen auf den ZK-IFT (Vero-Zellen), betrug 96,8%. Für HSV-2 wurde eine Sensitivität von 93,9% ermittelt. Die Spezifität des IPF-HSV
lag für beide Virustypen über 99% (HSV-1: 99,4%, HSV-2: 99,1%). Bezogen auf die konventionelle Virusisolierung im erweiterten Referenzstandard (Vero-Zellen und HFF) zeigte der IPF-HSV etwas geringere Werte für die Sensitivität (91,4% für HSV-1; 91,6% für HSV-2). Unter den im Referenzstandard negativen Proben fanden sich mittels IPF-HSV eine HSV-1- und drei HSV-2-positive Proben. Die Spezifität lag für beide HSV-Typen über 99% (99,8% für HSV-1, 99,4% für HSV-2). Bezogen auf den Referenzstandard ergab sich für den IPF-HSV ein positiv prädiktiver Wert von 97,0% (HSV-1) bzw. 91,7% (HSV-2); der negative prädiktive Wert des Tests lag jeweils bei 99,4%. Die Ergebnisse unserer Studie zeigen, daß der IPF-HSV eine sinnvolle Alternative zur konventionellen Virusisolierung darstellt, da der Erregernachweis bereits nach 36 Stunden möglich ist. Der Testaufbau ist unter Verwendung geeigneter mojioklonaler Antikörper und Zelltypen auch zur Schnelldiagnose respiratorischer Viruserkrankungen, der Zytomegalie, dem kongenitalen Rötelnsyndrom und ggf. Rotavirusinfektionen geeignet.
Herpes simplex virus type 2 (HSV-2) is the main cause of herpes genitalis, a recurrent sexually transmitted disease. By the use of routine Serologie methods (complement fixation test, enzyme immunoassay), virus carriers are difficult to identify because of strong antibody cross reactions with antigens of HSV-1 which is ubiquitously spread throughout the population. We introduce a microtechnique Western blot system loaded with HSV-1 and HSV-2 type-specific and common antigens on separated nitrocellulose strips. By the simultaneous evaluation of Immunologie reactions with both strips, the occurrence of HSV-2 specific antibodies can be sensitively detected in serum specimens containing antibodies to HSV-1. A total of 158 serum specimens were analyzed and the results obtained by Western blot were compared to those of a screening ELISA and virus isolation performed with smears of herpes lesions.
An agreement of 97.9 % was assessed between Western blot and virus isolation to detect an HSV-1 and HSV-2 infection. Less specific serologic results were produced by the screening ELISA on HSV-2 antibodies which correlated in 85.4 % (41/48) with virus isolation and typing. Concerning HSV-2 antibody testing, Western blot and ELISA showed an overall agreement in 89.8 % of the sera investigated.
As shown by our data, the HSV type specific Western blot proved to be a specific, reproducible and standardized technique. It can be utilized for both sero-epidemiological surveys and determination of the HSV immune status.
In der internationalen Norm DIN EN ISO 15189 (kurz ISO 15189) sind für medizinische Laboratorien besondere Anforderungen an die Qualität und Kompetenz festgelegt. Die ISO 15189 gilt für alle medizinischen Laboratorien. Sie wurde für den Bereich der Virologie durch eine gemeinsame Arbeitsgruppe der Gesellschaft für Virologie (GfV) und der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) in Form von fachspezifischen Checklisten konkretisiert.
Viele medizinische Laboratorien lassen sich im Rahmen einer Akkreditierung bestätigen, dass sie die Anforderungen der ISO 15189 erfüllen. Wesentlicher Bestandteil der Akkreditierung ist eine Begutachtung in den Laboratorien. Die Begutachtungen in der Virologie werden von Experten durchgeführt, die von der GfV benannt werden.
Gründe der Laboratorien für eine Akkreditierung können sehr unterschiedlich sein. Sie reichen von der Verbesserung der internen Abläufe und Ermittlung sicherer/richtiger Untersuchungsergebnisse bis zu einer besseren Positionierung am Markt.
Der Artikel stellt die Anforderungen und Probleme virusdiagnostisch tätiger Laboratorien, basierend auf der ISO 15189, als Erfahrungsbericht vor. Dabei wird auf die Infektionsserologie, die molekularbiologische Diagnostik und die Virusisolierung auf Zellkulturen eingegangen.
Trotz der Spenderauswahl, des serologischen Screenings der Blutspenden auf antiHIV-1, anti-HIV-2, anti-HCV und HBsAg, Inaktivierungs- und Eliminierungsverfahren bleibt ein Restrisiko für hämatogen übertragbare Viren bei Plasmapools und den daraus hergestellten Präparaten. Als zusätzliche Screeningmethode zur Erhöhung der Virussicherheit wird inzwischen die Testung der Einzelspende bzw. von Minipools auf HCV-RNA verlangt. In der vorliegenden Arbeit wurden 142 HBsAg, anti-HCV- und anti-HIV-11-2 negative Plasmapools, sowie Plasmapräparate (Immunglobulinpräparat und F IX Präparat), welche zum Teil aus für HGV-RNA PCR-positiven Ausgangspools hergestellt worden waren, mittels PCR auf das Vorhandensein von HGV-Nukleinsäure untersucht. Alle untersuchten Pools bzw. Plasmapräparate stammten von Spenden zwischen 1994 und 1996, also vor der Einführung der genannten Pflichttestung auf HCV-RNA. HGV-RNA wurde in 117 der 142 Plasmapools (82,4%) amplifiziert. Allerdings war HGV-RNA nur in einer (6,3%) von 16 IgG-Chargen aus für HGV-Nukleinsäure positiven Kryoüberständen nachweisbar. In 2 (6,5%) von 31 unselektierten Immunglobulinpräparaten war eine HGV- Kontamination vorhanden. Eine routinemäßige Anwendung der PCR ist zur Zeit aus technischen sowie Kosten-Nutzen-Überlegungen für HGV nicht zu empfehlen, solange die klinische Relevanz nicht gesichert ist. Die Ergebnisse unterstreichen die Wichtigkeit der im Herstellungsprozeß integrierten Viruseliminierungsverfahren, denn bei der vorliegenden Studie konnte nur in einem geringen Anteil der Endproduktchargen HGV-Nukleinsäure nachgewiesen werden.
603 Seren aus dem Raum Frankfurt am Main wurden in 12 verschiedenen Einzelkollektiven mit einem "in house" IFT mit latenten Antigenen und einem rekombinanten Prototyp ELISA mit dem LANA und K8.1-Protein auf Antikörper gegen das Humane Herpesvirus Typ 8 (HHV-8) ± auch bekannt als Kaposi-Sarkom-assoziiertes Herpesvirus (KSHV) ±getestet. Untersucht wurden (Risiko)gruppen wie HIV-seropositive Männer und Frauen, HIV-seronegative homosexuelle bzw. bisexuelle Männer, Patienten mit Kaposi-Sarkom, Transplantationspatienten und Kinder mit Hämophilie. Zur Abschätzung von Kreuzreaktionenund anderen Störungen der Testsysteme wurden Patienten mit akuten bzw. abgelaufenen EBV-Infektionen,HHV-6-seropositive Patienten, Rheumafaktor-positive Probanden und Frauen mit primärer biliärer Zirrhose(PBC) untersucht. Dreiundfünfzig diskrepante Probenwurden mit kommerziellen IFTs mit latenten bzw. lyti-schen Antigenen nachgetestet.Hohe HHV-8-SeropraÈvalenzen wurden bei HIV-Infizierten ohne (15,7 % bei Frauen, 23,3 % bei Männern)und insbesondere mit Kaposi-Sarkomen (100 %) gefunden. Eine geschlechtsabhängige Verteilung der Seroprävalenz bei den HIV-seropositiven Patienten wurde nicht festgestellt. Bei Blutspendern wurde eine HHV-8-Durchseuchung von 3 % (im ¹in-house-IFTª), bei Hämophilen von 0 % und bei Transplantationspatienten von 9,1 % ermittelt. Kreuzreaktionen mit Antikörpern gegen andere Herpesviren wie EBV und HHV-6 schienen die Tests nicht zu beeinflussen, während sich tendenziell eine erhöhte Anzahl reaktiver Proben bei Patienten mit Autoimmunantikörpern (Rheumafaktor-positive Patienten und Patientinnen mit PBC) zeigte. Insgesamt stimmten die Ergebnisse des rekombinanten ELISA mit denen des "in house"-IFT im Gesamtkollektiv gut überein. Unterschiedliche Ergebnisse fanden sich in den Einzelkollektiven, insbesondere bei Rheumafaktor-positiven Patienten und solchen mit PBC.
Pharmazeutika, die aus humanem Ausgangsmaterialstammen (speziell Blut- und Plasmaprodukte), sind prinzipiell auf ein infektiöses Gefahrenpptential zu prüfen. Dies wurde in den letzten Jahren durch verschiedene Vorfälle auch in das Bewußtsein der Öffentlichkeit gebracht. Durch Blut und Blutprodukte können eine Reihe von Infektionserregern übertragen Werden. Aus virologischer Sicht sind relevant: Humanes Immundefizienz Virus (H^titis B \(irus.(]^ *™-virus B19, Humanes T-Zell-L^I/II, Huhiänes Cj^omegälieyirüs (HCMV).und das;Epstein Barr Virus (EBV). :E)iese Viren weisen sehr un-terschiedliche physikalisch-chemische; Eigenschaften auf, was auf ihre Inaktivierbarkeit einen erbebücheiiEinflußhat. - " , " "Der Gefahreriausschluß hängt iii;-hohem^^ Mäße da-von ab, inwieweit ctie Prödukiiöhsveifahreh in der Lagesind, potentiell vorhandene Viren zu eliminieren oderzu inaktivieren. Daneben soflen die sorgfältige Spendier-auswahl und das Screening gespendeter^ JBlut-Einheitenauf bekannte infektiöse Agenitien:;die Sicherheit einesphannazeutischen Produktes gewährleisten. :Entsprechende Forderungen und Regelungen sinddurch die Europäische Union bereits vor Jähren heraus-gegeben und imletzten Jähr durch bundesdeutsche Be-hörden auf nationaler Ebene in einigen Punkten ergänztbzw. weitergehend präzisiert worden. Dann wird u/a.gefordert, in sogenanntenValidierungsstudien einequain-,titative Abschätzung derGesamtvirusabreichenitigbzyy:-inaktivierung im Verlaufe von mehrstufigen Reini-gungs- und maktivierurigsyerfahren bei der Herstellungsolcher Produkte durchzuführen: Unter Einbeziehungbiometrischer Analysen und durch die Forderung nachKombination mehrerer zur Inaktivierung / Eliminierungvon Viren geeigneter Verfahrensschritte ist sicherzustel-len, daß insgesamt eine Reduktion der Infektiosität um ^[[200~mindestens Falctor l O10 für umhüllte Viren bzw. l O6 fürnicht^umhüllte Viren im Modellsystem gewährleistet unddamit in praxi die Virussicherheit von Blutproduktensichergestellt ist.
Activated blood coagulation factor (F) XIII (FXIIIa), a transglutaminase comprised of two A and two B subunits in a tetrameric structure (A2B2) of 320 kd, has a central role in the haemostatic system by cross-linking fibrin monomers in the final step of blood coagulation, thus stabilizing the fibrin clot and increasing its resistance to fibrinolysis. In addition, FXIIIa is implicated in the cross-linking of several other proteins, such as a-2-antiplasmin, fibronectin, and collagen. The impact of genetic variations of FXIII in thrombotic disorders has not been studied until recently, when a common polymorphism was described as a new candidate genetic factor influencing the risk of thrombotic diseases. This polymorphism results from a G to T transition in codon 34 of exon 2 of the catalytic FXIII A-subunit gene, leading to the substitution of leucine for valine (FXHIVal34Leu) close to the thrombin activation site. Genotype at this polymorphism is closely related to FXIII fibrin cross-linking activity, and FXIIILeu is associated with increased thrombin activation of FXIII with associated changes in fibrin structure. Initially, FXIII Val34Leu was shown to be significantly less common in British patients with a history of myocardial infarction than in controls, suggesting for the first time a new role for FXIII in a polygenic thrombotic disease. In addition to its proposed protective effect against thrombotic heart diseases, the Leu34 allele has also been correlated with protection against venous thromboembolism and thrombotic cerebral artery occlusion, whereas it seems to confer an increased risk for intracerebral haemorrhage. Because this genetic variation is associated with a higher activity of the enzyme, the mechanism accounting for the putative anti-thrombotic effect of FXIII Val34Leu is not well understood. However, it has been hypothesized that increased rates of FXIII activation could lead to ineffective cross-linking, or that the kinetics of the cross-linking reactions may be disrupted because of the effects of FXIIIa on other proteins. Previous s'tudies have demonstrated that the FXIII Val34Leu polymorphism is highly prevalent in ^[[200~several Caucasian populations, with reported Leu34 allele frequencies of around 0.25, whereas it is less prevalent in populations of African and Asian origin. The known significant ethnic heterogeneity linked to the FXIII Val34Leu polymorphism is of relevance when analyzing its role in vascular diseases. In summary, published studies indicate that blood coagulation FXIII is involved in the multifactorial pathogenesis of vascular diseases and suggest a contribution of FXIII Val34Leu in determining the risk of myocardial infarction, stroke and venous thromboembolism.