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Hintergrund: Patienten, die präoperativ an einer eisendefizitären Erythropoese (IDE) oder Anämie leiden, haben unabhängig von anderen Erkrankungen ein erhöhtes Risiko für postoperative Morbidität. Ein Eisenmangel ist der häufigste Grund für eine Anämie und kann, wenn er frühzeitig diagnostiziert wird, effizient mittels Eisensubstitution behandelt werden. Zink-Protoporphyrin (ZnPP) ist im Vergleich zu klassischen Parametern wie Ferritin ein vielversprechender Parameter, um eine IDE zu diagnostizieren. Bisher wurde der Parameter im Blut gemessen. Nun soll geprüft werden, ob eine nicht-invasive Messung valide Ergebnisse liefert.
Methoden: Von März 2017 bis April 2018 wurden am Universitätsklinikum Frankfurt Patienten, die für eine Operation mit einem erwarteten Blutverlust von >10% geplant waren, auf eine IDE untersucht. Die Messung von nicht-invasivem ZnPP (ZnPP-NI) wurde mit der ZnPP-Referenz-Messung des ZnPP/Häm-Verhältnisses mittels Hochleistungsflüssigchromatographie (ZnPP-HPLC) verglichen. Die analytische Performance beim Nachweis einer IDE wurde mit im Blut gemessenen klassischen Eisenstatusparameter (Ferritin, Transferrinsättigung [TSAT], löslicher Transferrinrezeptor [sTfR] und sTfR-Index [sTfR-F]) verglichen.
Ergebnis: In dieser prospektiven Studie konnten 285 chirurgische Patienten präoperativ untersucht werden. Die Limits of Agreement zwischen ZnPP-NI und ZnPP-HPLC betrugen 20,3 μmol/mol Häm (95% -Konfidenzintervall 18,0-21,3; Akzeptanzkriterien 24,4 μmol/mol Häm; absolute Bias -0,3 μmol/mol Häm). Die analytische Performance zum Nachweis einer IDE der im Blut gemessenen Parameter war: ZnPP-HPLC (0,95), sTfR (0,90), sTfR-F (0,89), ZnPP-NI (0,88), TSAT (0,87) und Ferritin (0,65).
Fazit: Beim Nachweis einer IDE ist ZnPP-NI besser geeignet als Ferritin und vergleichbar valide wie TSAT. Der Vergleich mit einem Multiparameter-Index-Test ergab, dass ZnPP-NI von ≤40 μmol/mol Häm den Ausschluss einer IDE ermöglicht und ein Wert von ≥65 μmol/mol Häm eine IDE wahrscheinlich macht. ZnPP-NI kann daher für eine schnelle Erstbewertung in der IDE-Diagnostik und im Anämie Management ohne Blutentnahme verwendet werden.
Objectives: Rising prevalence of multidrug-resistant organisms (MDRO) is a major health problem in patients with liver cirrhosis. The impact of MDRO colonization in liver transplantation (LT) candidates and recipients on mortality has not been determined in detail.
Methods: Patients consecutively evaluated and listed for LT in a tertiary German liver transplant center from 2008 to 2018 underwent screening for MDRO colonization including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria (MDRGN), and vancomycin-resistant enterococci (VRE). MDRO colonization and infection status were obtained at LT evaluation, planned and unplanned hospitalization, three months upon graft allocation, or at last follow-up on the waiting list.
Results: In total, 351 patients were listed for LT, of whom 164 (47%) underwent LT after a median of 249 (range 0–1662) days. Incidence of MDRO colonization increased during waiting time for LT, and MRDO colonization was associated with increased mortality on the waiting list (HR = 2.57, p<0.0001. One patients was colonized with a carbapenem-resistant strain at listing, 9 patients acquired carbapenem-resistant gram-negative bacteria (CRGN) on the waiting list, and 4 more after LT. In total, 10 of these 14 patients died.
Conclusions: Colonization with MDRO is associated with increased mortality on the waiting list, but not in short-term follow-up after LT. Moreover, colonization with CRGN seems associated with high mortality in liver transplant candidates and recipients.
The C-type lectin-like receptor NKG2D contributes to the immunosurveillance of virally infected and malignant cells by cytotoxic lymphocytes. A peculiar and puzzling feature of the NKG2D-based immunorecognition system is the high number of ligands for this single immunoreceptor. In humans, there are a total of eight NKG2D ligands (NKG2DL) comprising two members of the MIC (MICA, MICB) and six members of the ULBP family of glycoproteins (ULBP1 to ULBP6). While MICA has been extensively studied with regard to its biochemistry, cellular expression and function, very little is known about the NKG2DL ULBP4. This is, at least in part, due to its rather restricted expression by very few cell lines and tissues. Recently, constitutive ULBP4 expression by human monocytes was reported, questioning the view of tissue-restricted ULBP4 expression. Here, we scrutinized ULBP4 expression by human peripheral blood mononuclear cells and monocytes by analyzing ULBP4 transcripts and ULBP4 surface expression. In contrast to MICA, there was no ULBP4 expression detectable, neither by freshly isolated monocytes nor by PAMP-activated monocytes. However, a commercial antibody erroneously indicated surface ULBP4 on monocytes due to a non-ULBP4-specific binding activity, emphasizing the critical importance of validated reagents for life sciences. Collectively, our data show that ULBP4 is not expressed by monocytes, and likely also not by other peripheral blood immune cells, and therefore exhibits an expression pattern rather distinct from other human NKG2DL.
Meningioma surgery in patients ≥70 years of age: clinical outcome and validation of the SKALE score
(2021)
Along with increasing average life expectancy, the number of elderly meningioma patients has grown proportionally. Our aim was to evaluate whether these specific patients benefit from surgery and to investigate a previously published score for decision-making in meningioma patients (SKALE). Of 421 patients who underwent primary intracranial meningioma resection between 2009 and 2015, 71 patients were ≥70 years of age. We compared clinical data including World Health Organization (WHO) grade, MIB-1 proliferation index, Karnofsky Performance Status Scale (KPS), progression free survival (PFS) and mortality rate between elderly and all other meningioma patients. Preoperative SKALE scores (Sex, KPS, ASA score, location and edema) were determined for elderly patients. SKALE ≥8 was set for dichotomization to determine any association with outcome parameters. In 71 elderly patients (male/female 37/34) all data were available. Postoperative KPS was significantly lower in elderly patients (p < 0.0001). Pulmonary complications including pneumonia (10% vs. 3.2%; p = 0.0202) and pulmonary embolism (12.7% vs. 6%; p = 0.0209) occurred more frequently in our elderly cohort. Analyses of the Kaplan Meier curves revealed differences in three-month (5.6% vs. 0.3%; p = 0.0033), six-month (7% vs. 0.3%; p = 0.0006) and one-year mortality (8.5% vs. 0.3%; p < 0.0001) for elderly patients. Statistical analysis showed significant survival benefit in terms of one-year mortality for elderly patients with SKALE scores ≥8 (5.1 vs. 25%; p = 0.0479). According to our data, elderly meningioma patients face higher postoperative morbidity and mortality than younger patients. However, resection is reasonable for selected patients, particularly when reaching a SKALE score ≥ 8.
Inflammatory nontraumatic atlantoaxial rotatory subluxation (AAS) in children is an often-missed diagnosis, especially in the early stages of disease. Abscess formation and spinal cord compression are serious risks that call for immediate surgical attention. Neither radiographs nor non-enhanced computed tomography (CT) images sufficiently indicate inflammatory processes. Magnetic resonance imaging (MRI) allows a thorough evaluation of paraspinal soft tissues, joints, and ligaments. In addition, it can show evidence of vertebral distraction and spinal cord compression. After conducting a scoping review of the literature, along with scientific and practical considerations, we outlined a standardized pediatric MRI protocol for suspected inflammatory nontraumatic AAS. We recommend contrast-enhanced MRI as the primary diagnostic imaging modality in children with signs of torticollis in combination with nasopharyngeal inflammatory or ear nose and throat (ENT) surgical history.
Background: To evaluate the impact of time to castration resistance (TTCR) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies for mHSPC.
Material and Methods: Of 213 mHSPC patients diagnosed between 01/2013-12/2020 who subsequently developed metastatic castration resistant prostate cancer (mCRPC), 204 eligible patients were analyzed after having applied exclusion criteria. mHSPC patients were classified into TTCR <12, 12-18, 18-24, and >24 months and analyzed regarding OS. Moreover, further OS analyses were performed after having developed mCRPC status according to TTCR. Logistic regression models predicted the value of TTCR on OS.
Results: Median follow-up was 34 months. Among 204 mHSPC patients, 41.2% harbored TTCR <12 months, 18.1% for 12-18 months, 15.2% for 18-24 months, and 25.5% for >24 months. Median age was 67 years and median PSA at prostate cancer diagnosis was 61 ng/ml. No differences in patient characteristics were observed (all p>0.05). According to OS, TTCR <12 months patients had the worst OS, followed by TTCR 12-18 months, 18-24 months, and >24 months, in that order (p<0.001). After multivariable adjustment, a 4.07-, 3.31-, and 6.40-fold higher mortality was observed for TTCR 18-24 months, 12-18 months, and <12 months patients, relative to TTCR >24 months (all p<0.05). Conversely, OS after development of mCRPC was not influenced by TTCR stratification (all p>0.05).
Conclusion: Patients with TTCR <12 months are at the highest OS disadvantage in mHSPC. This OS disadvantage persisted even after multivariable adjustment. Interestingly, TTCR stratified analyses did not influence OS in mCRPC patients.
Background: The incidence of pyogenic spinal infection has increased in recent years. In addition to treatment of the spinal infection, early diagnosis and therapy of coexisting infections, especially of secondary brain infection, are important. The aim of this study is to elucidate the added value of routine cerebral imaging in the management of these patients.
Methods: This was a retrospective single-center study. Cerebral imaging consisting of cerebral magnetic resonance imaging (cMRI) was performed to detect brain infection in patients with a primary pyogenic spinal infection. Results: We analyzed a cohort of 61 patients undergoing cerebral imaging after diagnosis of primary pyogenic spinal infection. The mean age in this cohort was 68.7 years and the gender distribution consisted of 44 males and 17 females. Spinal epidural abscess was proven in 32 (52.4%) patients. Overall positive blood culture was obtained in 29 (47.5%) patients, infective endocarditis was detected in 23 (37.7%) patients and septic condition at admission was present in 12 (19.7%) Patients. Coexisting brain infection was detected in 2 (3.3%) patients. Both patients revealed clinical signs of severe sepsis, reduced level of consciousness (GCS score 3), were intubated, and died due to multi-organ failure. Conclusions: Brain infection in patients with spinal infection is very rare. Of 61 patients with pyogenic spinal infection, two patients had signs of cerebral infection shown by imaging, both of whom were in a coma (GCS 3), and sepsis.
The efficacy of statin-treatment in aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We aimed to investigate the effects of statin-treatment in non-aneurysmal (na)SAH in accordance with animal research data illustrating the pathophysiology of naSAH. We systematically searched PubMed using PRISMA-guidelines and selected experimental studies assessing the statin-effect on SAH. Detecting the accordance of the applied experimental models with the pathophysiology of naSAH, we analyzed our institutional database of naSAH patients between 1999 and 2018, regarding the effect of statin treatment in these patients and creating a translational concept. Patient characteristics such as statin-treatment (simvastatin 40 mg/d), the occurrence of cerebral vasospasm (CVS), delayed infarction (DI), delayed cerebral ischemia (DCI), and clinical outcome were recorded. In our systematic review of experimental studies, we found 13 studies among 18 titles using blood-injection-animal-models to assess the statin-effect in accordance with the pathophysiology of naSAH. All selected studies differ on study-setting concerning drug-administration, evaluation methods, and neurological tests. Patients from the Back to Bedside project, including 293 naSAH-patients and 51 patients with simvastatin-treatment, were recruited for this analysis. Patients under treatment were affected by a significantly lower risk of CVS (p < 0.01; OR 3.7), DI (p < 0.05; OR 2.6), and DCI (p < 0.05; OR 3). Furthermore, there was a significant association between simvastatin-treatment and favorable-outcome (p < 0.05; OR 3). However, dividing patients with statin-treatment in pre-SAH (n = 31) and post-SAH (n = 20) treatment groups, we only detected a tenuously significant higher chance for a favorable outcome (p < 0.05; OR 0.05) in the small group of 20 patients with statin post-SAH treatment. Using a multivariate-analysis, we detected female gender (55%; p < 0.001; OR 4.9), Hunt&Hess ≤III at admission (p < 0.002; OR 4), no anticoagulant-therapy (p < 0.0001; OR 0.16), and statin-treatment (p < 0.0001; OR 24.2) as the main factors improving the clinical outcome. In conclusion, we detected a significantly lower risk for CVS, DCI, and DI in naSAH patients under statin treatment. Additionally, a significant association between statin treatment and favorable outcome 6 months after naSAH onset could be confirmed. Nevertheless, unified animal experiments should be considered to create the basis for developing new therapeutic schemes.
Purpose: To evaluate the prevalence and treatment patterns of speech and language disorders in Germany.
Methods: A retrospective analysis of data collected from 32% of the German population, insured by the statutory German health insurance (AOK, Local Health Care Funds). We used The International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification (ICD-10 GM) codes for stuttering (F98.5), cluttering (F98.6), and developmental disorders of speech and language (F80) to identify prevalent and newly diagnosed cases each year. Prescription and speech therapy reimbursement data were used to evaluate treatment patterns.
Results: In 2017, 27,977 patients of all ages were diagnosed with stuttering (21,045 males, 75% and 6,932 females, 25%). Stuttering prevalence peaks at age 5 years (boys, 0.89% and girls, 0.40%). Cluttering was diagnosed in 1,800 patients of all ages (1,287 males, 71.5% and 513 females, 28.5%). Developmental disorders of speech and language were identified in 555,774 AOK-insurants (61.2% males and 38.8% females). Treatment data indicate a substantial proportion newly diagnosed stuttering individuals receive treatment (up to 45% of 6-year-old patients), with slightly fewer than 20 sessions per year, on average. We confirmed a previous study showing increased rates of atopic disorders and neurological and psychiatric comorbidities in individuals with stuttering, cluttering, and developmental disorders of speech and language.
Conclusion: This is the first nationwide study using health insurance data to analyze the prevalence and newly diagnosed cases of a speech and language disorder. Prevalence and gender ratio data were consistent with the international literature. The crude prevalence of developmental disorders of speech and language increased from 2015 to 2018, whereas the crude prevalence for stuttering remained stable. For cluttering, the numbers were too low to draw reliable conclusions. Proportional treatment allocation for stuttering peaked at 6 years of age, which is the school entrance year, and is later than the prevalence peak of stuttering.
Clinical speech perception tests with simple presentation conditions often overestimate the impact of signal preprocessing on speech perception in complex listening environments. A new procedure was developed to assess speech perception in interleaved acoustic environments of different complexity that allows investigation of the impact of an automatic scene classification (ASC) algorithm on speech perception. The procedure was applied in cohorts of normal hearing (NH) controls and uni- and bilateral cochlear implant (CI) users. Speech reception thresholds (SRTs) were measured by means of a matrix sentence test in five acoustic environments that included different noise conditions (amplitude modulated and continuous), two spatial configurations, and reverberation. The acoustic environments were encapsulated in a randomized, mixed order single experimental run. Acoustic room simulation was played back with a loudspeaker auralization setup with 128 loudspeakers. 18 NH, 16 unilateral, and 16 bilateral CI users participated. SRTs were evaluated for each individual acoustic environment and as mean-SRT. Mean-SRTs improved by 2.4 dB signal-to-noise ratio for unilateral and 1.3 dB signal-to-noise ratio for bilateral CI users with activated ASC. Without ASC, the mean-SRT of bilateral CI users was 3.7 dB better than the SRT of unilateral CI users. The mean-SRT indicated significant differences, with NH group performing best and unilateral CI users performing worse with a difference of up to 13 dB compared to NH. The proposed speech test procedure successfully demonstrated that speech perception and benefit with ASC depend on the acoustic environment.
Purpose: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.
Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.
Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups.
Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.
Transcription factors (TFs) guide effector proteins like chromatin-modifying or -remodeling enzymes to distinct sites in the genome and thereby fulfill important early steps in translating the genome’s sequence information into the production of proteins or functional RNAs. TFs of the same family are often highly conserved in evolution, raising the question of how proteins with seemingly similar structure and DNA-binding properties can exert physiologically distinct functions or respond to context-specific extracellular cues. A good example is the TALE superclass of homeodomain-containing proteins. All TALE-homeodomain proteins share a characteristic, 63-amino acid long homeodomain and bind to similar sequence motifs. Yet, they frequently fulfill non-redundant functions even in domains of co-expression and are subject to regulation by different signaling pathways. Here we provide an overview of posttranslational modifications that are associated with murine and human TALE-homeodomain proteins and discuss their possible importance for the biology of these TFs.
Das Mammakarzinom ist die häufigste Krebserkrankung der Frau. Aufgrund der zu ver-zeichnenden steigenden Erkrankungs- als auch Überlebensraten werden stetig mehr Frauen mit der Diagnose Brustkrebs und ihren Folgen konfrontiert. Seit den 1990er Jah-ren wird eine kognitive Dysfunktion von Patientinnen nach Krebstherapie in der For-schung diskutiert, wobei die Hintergründe und Zusammenhänge dieses Phänomens bis heute strittig sind. Ziel dieser Arbeit ist die Untersuchung der kognitiven Leistungsfä-higkeit mit einem Fokus auf Aufmerksamkeitsleistungen vor und nach einer adjuvanten Krebstherapie. In diesem Zusammenhang soll besonders der Einfluss von psychischem Stress auf die Aufmerksamkeit und ferner auch die subjektive kognitive Leistungsfähig-keit von Brustkrebspatientinnen beleuchtet werden.
Dazu wurde die Aufmerksamkeitsfähigkeit von 20 Patientinnen, die in der Klinik für Frauenheilkunde und Geburtshilfe des Universitätsklinikums Frankfurt am Main ange-bunden waren, zu jeweils zwei Messzeitpunkten anhand einer neuropsychologischen Testbatterie (Trail-Making Test, NeuroCogFX) untersucht. Die erste Messung erfolgte vor Therapieeinleitung, eine zweite Messung nach Beendigung einer adjuvanten Krebs-therapie. Gleichzeitig wurden Werte zu Depressivität, Angst, krankheitsbezogener Le-bensqualität und der kognitiven Funktionsfähigkeit mittels verschiedener Fragebögen (HADS, EORTC-QLQ C30, EORTC-QLQ BR23) erhoben. Eine Kontrollgruppe von gesunden Probandinnen (N=13) wurde nach den gleichen Vorgaben untersucht.
30% der Patientinnen hatten eine kombinierte Chemotherapie erhalten, eine Radiatio war bei 70% und eine antihormonelle Therapie bei 75% erfolgt. Die Testungen der Pati-entinnen fanden im Mittel 12 (SD 15,4) Tage nach OP statt. Die T2-Messungen erfolg-ten im Mittel 10,3 (SD: 3,2) Monate nach den T1-Messungen für Patientinnen und 7,3 (SD: 1,8) Monate für Kontrollprobandinnen. Alter, IQ und Bildungsniveau waren zwi-schen beiden Gruppen gleich, Unterschiede zeigten sich hinsichtlich der BMI- Werte und der sportlichen Aktivität. Es zeigten sich weder zum ersten noch zum zweiten Messzeitpunkt signifikante Unterschiede der Aufmerksamkeitsleistungen zwischen Pati-entinnen und der Kontrollgruppe. Unterschiede fanden sich lediglich zwischen beiden Zeitpunkten in der einfachen Reaktionszeit mit schlechteren Testleistungen während T2 sowie im TMT Teil B mit besseren Ergebnissen während T2 für beide Gruppen. Hoch-signifikant unterschieden sich dagegen Patientinnen von der Kontrollgruppe mit schlechteren Werten hinsichtlich Angst und Depression, der Lebensqualität sowie der empfundenen kognitiven Funktionen. Dabei war keine signifikante Veränderung der Werte zwischen T1 und T2 messbar. Eine Korrelation zwischen aufmerksamkeitsbezo-genen Testleistungen und psychischem Stress bestand nicht, weiterhin fand sich kein Zusammenhang zwischen subjektiver kognitiver Leistungsfähigkeit und objektiven Testergebnissen. Hochsignifikant korrelierten dagegen schlechtere Werte der subjektiven kognitiven Fähigkeiten mit erhöhten Werten für Angst und Depression.
Auf Grundlage dieser Arbeit lässt sich kein relevanter Einfluss einer adjuvanten Krebs-therapie auf die Aufmerksamkeitsleistungen ableiten. Die Ergebnisse belegen aber signi-fikant erhöhte Werte für Depression und Angst von Brustkrebspatientinnen und den Einfluss von erhöhtem psychischem Stress auf die subjektive kognitive Funktionsfähig-keit. Diesbezüglich sollten zukünftige Behandlungsstrategien auch die subjektive kogni-tive Funktionsfähigkeit und in diesem Zusammenhang auch die spezifische Therapie von psychischem Stress in den Fokus rücken.
Die afrikanische Schlafkrankheit (HAT), übertragen durch die Tsetse Fliege und ausgelöst durch den einzelligen Parasit Trypanosoma brucei, wird vor über 100 Jahren entdeckt. Diese unbehandelt immer tödlich verlaufende Erkrankung zählt zu den Neglected Tropical Diseases. Es existiert keine Impfung und die Behandlung ist nebenwirkungsreich. Das weltweite Forschungsaufkommen zu diesem Thema wird von 1900 bis 2016 anhand von Metadaten untersucht, die aus dem Web of Science Core Collection (Clarivate Analytics) extrahiert wurden. Die 5079 Publikationen werden mittels bibliometrischer Parameter ausgewertet. Diese umfassen chronologische Publikationsparameter, Analysen der Länder, Institutionen, Autoren, Fachzeitschriften, Fachbereiche, Kooperationen und Geschlechterparität. Die Analyse zeigt ein aufkommendes Forschungsinteresse der Kolonialmächte Anfang des 20. Jahrhunderts in den okkupierten Koloniegebieten Afrikas. Zu dem Zeitpunkt als der Erreger entdeckt wird, grassiert eine Epidemie der Ost-und Westafrikanischen Schlafkrankheit. Mit Beginn des Ersten Weltkrieges brechen die Publikationszahlen ein. Erst ab den 1970ern steigen die Artikelzahlen kontinuierlich. Die Vernachlässigung der Erkrankung resultiert in einer Epidemie mit geschätzt 300.000 Fällen (1998). In den letzten Jahren verringerte sich die Anzahl der Neuinfektionen erheblich, im Jahr 2016 werden 2184 Fälle gemeldet. Zwischen 1964 und 2013 kommt es zu einer mehr als 11-fachen Steigerung der Publikationen. Ab 1980 nehmen die Zitierungen sprunghaft zu, wahrscheinlich konnten viele neue Erkenntnisse aufgrund der hohen Prävalenz gewonnen werden. Der meistzitierte und produktivste Fachbereich ist die Biochemistry and Molecular Biology. Der Anteil Pharmacology and Pharmacy nimmt kontinuierlich zu. Die Popularität könnte auf 2 Faktoren zurückgeführt werden, den steigenden Bedarf an neuen Medikamenten und den Einfluss der WHO. 2009 wird NECT als Kombinationstherapie zugelassen, 2018 folgt Fexinidazole. Das durchschnittliche Literaturverzeichnis vergrößert sich, ebenso die Forschungsgruppen, denn die durchschnittliche Autorenzahl steigt von 2,5 (1975) auf 8,03 (2014). Die Zahl der internationalen Kooperationsartikel wird innerhalb der letzten 30 Jahre versechsfacht. Die publikationsstärkste Nation ist die USA, gefolgt von
Großbritannien, weiteren westeuropäischen Staaten sowie Kenia und Nigeria. 36% der 25 produktivsten Länder sind afrikanische. Gemessen an ihren ökonomischen Daten ist die Forschungsleistung extrem hoch. Unter den 15 produktivsten Institutionen ist als einziges afrikanisches das International Livestock Research Institut (Nairobi) vertreten. Diese Forschungseinrichtung wird durch Stiftungen wie Wellcome Trust finanziell unterstützt, welche bei mehreren hundert Publikationen als Funding Agency dient. Zwei weitere außeruniversitäre Institutionen zählen zu den produktivsten: Das Center of Infectious Disease Research (USA) sowie das Institute of Tropical Medicine Antwerp (Belgien). Die zehn produktivsten Länderkooperationen finden innereuropäisch oder mit den USA statt, darunter existiert eine europäisch-afrikanische Kollaboration (ITM Antwerp, Ministry for für Public Health (DR Kongo)). Bei Analyse der europäisch-afrikanischen Kooperationen fällt auf, dass diese mit der ehemaligen Kolonialpolitik korrelieren könnten. Die meisten afrikanischen Nationen publizieren in Kooperationen, eine Ausnahme bildet Nigeria. Sie veröffentlichen nur 18,7% der Artikel in Zusammenarbeit. Sie sind das Land mit dem höchsten BIP der ausgewerteten afrikanischen Nationen. Der produktivste Autor ist E. Pays der an der Université Libre de Bruxelles forscht. Der meistzitierte Autor G.A.M. Cross von der Rockefeller University ist Verfasser von zwei der meistzitierten Artikel. Die erfolgreichsten Wissenschaftler stehen eher am Ende ihrer Karriere und fungieren meist als Letztautoren und als Leiter einer Einrichtung. Obwohl in den letzten Jahren eine zunehmende Geschlechterparität auf dem Forschungsgebiet identifiziert werden konnte, ist die Chancengleichheit für Frauen abhängig vom Land. In Brasilien überwiegt als einzige Nation der Anteil weiblicher Autoren, während Japan den geringsten Frauenanteil besitzt. 11,2% der Artikel erscheinen in der Fachzeitschrift Molecular and Biochemical Parasitology und deckt somit die beiden meistzugewiesenen Themenfelder ab. Infektiöse Erkrankungen, die vor allem Drittweltländer mit geringen finanziellen Möglichkeiten betreffen, müssen im Interesse der Weltgemeinschaft weiter intensiv erforscht werden. Um dies zu ermöglichen ist eine Finanzierung und Stärkung der Wissenschaft in den betroffenen Ländern vor Ort nötig.
Chronic granulomatous disease (CGD) is a primary immunodeficiency, which is diagnosed in most patients between one and three years of age. Here we report on a boy who presented at birth with extensive skin lesions and lymphadenopathy which were caused by CGD. An analysis of the literature revealed 24 patients with CGD who became symptomatic during the first six weeks of life. Although pulmonary complications and skin lesions due to infection were the leading symptoms, clinical features were extremely heterogenous. As follow-up was not well specified in most patients, the long-term prognosis of children with very early onset of CGD remains unknown.
Aging is accompanied by unisensory decline. To compensate for this, two complementary strategies are potentially relied upon increasingly: first, older adults integrate more information from different sensory organs. Second, according to the predictive coding (PC) model, we form “templates” (internal models or “priors”) of the environment through our experiences. It is through increased life experience that older adults may rely more on these templates compared to younger adults. Multisensory integration and predictive coding would be effective strategies for the perception of near-threshold stimuli, which may however come at the cost of integrating irrelevant information. Both strategies can be studied in multisensory illusions because these require the integration of different sensory information, as well as an internal model of the world that can take precedence over sensory input. Here, we elicited a classic multisensory illusion, the sound-induced flash illusion, in younger (mean: 27 years, N = 25) and older (mean: 67 years, N = 28) adult participants while recording the magnetoencephalogram. Older adults perceived more illusions than younger adults. Older adults had increased pre-stimulus beta-band activity compared to younger adults as predicted by microcircuit theories of predictive coding, which suggest priors and predictions are linked to beta-band activity. Transfer entropy analysis and dynamic causal modeling of pre-stimulus magnetoencephalography data revealed a stronger illusion-related modulation of cross-modal connectivity from auditory to visual cortices in older compared to younger adults. We interpret this as the neural correlate of increased reliance on a cross-modal predictive template in older adults leading to the illusory percept.
Background: Polytraumatized patients undergo a strong immunological stress upon insult. Phagocytes (granulocytes and monocytes) play a substantial role in immunological defense against bacteria, fungi and yeast, and in the clearance of cellular debris after tissue injury. We have reported a reduced monocytes phagocytic activity early after porcine polytrauma before. However, it is unknown if both phagocyte types undergo those functional alterations, and if there is a pathogen-specific phagocytic behavior. We characterized the phagocytic activity and capacity of granulocytes and monocytes after polytrauma.
Methods: Eight pigs (Sus scrofa) underwent polytrauma consisting of lung contusion, liver laceration, tibial fracture and hemorrhagic shock with fluid resuscitation and fracture fixation with external fixator. Intensive care treatment including mechanical ventilation for 72 h followed. Phagocytic activity and capacity were investigated using an in vitro ex vivo whole blood stimulation phagocytosis assays before trauma, after surgery, 24, 48, and 72 h after trauma. Blood samples were stimulated with Phorbol-12-myristate-13-acetate and incubated with FITC-labeled E. coli, S. aureus or S. cerevisiae for phagocytosis assessment by flow cytometry.
Results: Early polytrauma-induced significant increase of granulocytes and monocytes declined to baseline values within 24 h. Percentage of E. coli-phagocytizing granulocytes significantly decreased after polytrauma and during further intensive care treatment, while their capacity significantly increased. Interestingly, both granulocytic phagocytic activity and capacity of S. aureus significantly decreased after trauma, although a recovery was observed after 24 h and yet was followed by another decrease. The percentage of S. cerevisiae-phagocytizing granulocytes significantly increased after 24 h, while their impaired capacity after surgery and 72 h later was detected. Monocytic E. coli-phagocytizing percentage did not change, while their capacity increased after 24–72 h. After a significant decrease in S. aureus-phagocytizing monocytes after surgery, a significant increase after 24 and 48 h was observed without capacity alterations. No significant changes in S. cerevisiae-phagocytizing monocytes occurred, but their capacity dropped 48 and 72 h.
Conclusion: Phagocytic activity and capacity of granulocytes and monocytes follow a different pattern and significantly change within 72 h after polytrauma. Both phagocytic activity and capacity show significantly different alterations depending on the pathogen strain, thus potentially indicating at certain and possibly more relevant infection causes after polytrauma.
The adult heart has a limited capacity to replace or regenerate damaged cardiac tissue following severe myocardial injury. Thus, therapies facilitating the induction of cardiac regeneration holds great promise for the treatment of end-stage heart failure, and for pathologies invoking severe cardiac dysfunction as a result of cardiomyocyte death. Recently, a number of studies have demonstrated that cardiac regeneration can be achieved through modulation and/or reprogramming of cardiomyocyte proliferation, differentiation, and survival signaling. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are reported to play critical roles in regulating key aspects of cardiomyocyte physiologic and pathologic signaling, including the regulation of cardiac regeneration both in vitro and in vivo. In this review, we will explore and detail the current understanding of ncRNA function in cardiac regeneration, and highlight established and novel strategies for the treatment of heart failure through modulation of ncRNAs-driven cardiac regeneration.
Background: In clinical practice range of motion (RoM) is usually assessed with low-cost devices such as a tape measure (TM) or a digital inclinometer (DI). However, the intra- and inter-rater reliability of typical RoM tests differ, which impairs the evaluation of therapy progress. More objective and reliable kinematic data can be obtained with the inertial motion capture system (IMC) by Xsens. The aim of this study was to obtain the intra- and inter-rater reliability of the TM, DI and IMC methods in five RoM tests: modified Thomas test (DI), shoulder test modified after Janda (DI), retroflexion of the trunk modified after Janda (DI), lateral inclination (TM) and fingertip-to-floor test (TM).
Methods: Two raters executed the RoM tests (TM or DI) in a randomized order on 22 healthy individuals while, simultaneously, the IMC data (Xsens MVN) was collected. After 15 warm-up repetitions, each rater recorded five measurements.
Findings: Intra-rater reliabilities were (almost) perfect for tests in all three devices (ICCs 0.886–0.996). Inter-rater reliability was substantial to (almost) perfect in the DI (ICCs 0.71–0.87) and the IMC methods (ICCs 0.61–0.993) and (almost) perfect in the TM methods (ICCs 0.923–0.961). The measurement error (ME) for the tests measured in degree (°) was 0.9–3.3° for the DI methods and 0.5–1.2° for the IMC approaches. In the tests measured in centimeters the ME was 0.5–1.3cm for the TM methods and 0.6–2.7cm for the IMC methods. Pearson correlations between the results of the DI or the TM respectively with the IMC results were significant in all tests except for the shoulder test on the right body side (r = 0.41–0.81).
Interpretation: Measurement repetitions of either one or multiple trained raters can be considered reliable in all three devices.
Three AKT serine/threonine kinase isoforms (AKT1/AKT2/AKT3) mediate proliferation, metabolism, differentiation and anti-apoptotic signals. AKT isoforms are activated down- stream of PI3-kinase and also by PI3-kinase independent mechanisms. Mutations in the lipid phosphatase PTEN and PI3-kinase that increase PIP3 levels increase AKT signaling in a large proportion of human cancers. AKT and other AGC kinases possess a regulatory mechanism that relies on a conserved hydrophobic motif (HM) C-terminal to the catalytic core. In AKT, the HM is contiguous to the serine 473 and two other newly discovered (serine 477 and tyrosine 479) regulatory phosphorylation sites. In AKT genes, this regulatory HM region is encoded in the final exon. We identified a splice variant of AKT2 (AKT2-13a), which contains an alternative final exon and lacks the HM regulatory site. We validated the presence of mRNA for this AKT2-13a splice variant in different tissues, and the presence of AKT2-13a protein in extracts from HEK293 cells. When overexpressed in HEK293 cells, AKT2-13a is phosphorylated at the activation loop and at the zipper/turn motif phosphoryla- tion sites but has reduced specific activity. Analysis of the human transcriptome correspond- ing to other AGC kinases revealed that all three AKT isoforms express alternative transcripts lacking the HM regulatory motif, which was not the case for SGK1-3, S6K1-2, and classical, novel and atypical PKC isoforms. The transcripts of splice variants of Akt1-3 excluding the HM regulatory region could lead to expression of deregulated forms of AKT.