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Institute
- Institut für Biochemie (26)
- Abteilung für Mikrobiologie und Molekularbiologie (23)
- Institut für Pharmazie (20)
- Kliniken und Polikliniken für Innere Medizin (20)
- Institut für Geographie und Geologie (18)
- Institut für Physik (14)
- Institut für Diagnostische Radiologie und Neuroradiologie (13)
- Zoologisches Institut und Museum (13)
- Institut für Botanik und Landschaftsökologie & Botanischer Garten (11)
- Institut für Pharmakologie (10)
- Interfakultäres Institut für Genetik und Funktionelle Genomforschung (MNF) (10)
- Klinik für Psychiatrie und Psychotherapie (10)
- Poliklinik für Kieferorthopädie, Präventive Zahnmedizin und Kinderzahnheilkunde (10)
- Institut für Klinische Chemie und Laboratoriumsmedizin (9)
- Institut für Psychologie (9)
- Klinik und Poliklinik für Kinder- und Jugendmedizin (9)
- Klinik und Poliklinik für Neurologie (9)
- Klinik und Poliklinik für Chirurgie Abt. für Viszeral-, Thorax- und Gefäßchirurgie (8)
- Institut für Med. Biochemie u. Molekularbiologie (7)
- Institut für Mikrobiologie - Abteilung für Genetik & Biochemie (7)
- Poliklinik für Zahnerhaltung, Parodontologie und Endodontologie (7)
- Institut für Community Medicine (6)
- Institut für Philosophie (6)
- Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie/Plastische Operationen (6)
- Institut für Hygiene und Umweltmedizin (5)
- Institut für Mathematik und Informatik (5)
- Klinik und Poliklinik für Hals-, Nasen-, Ohrenkrankheiten, Kopf- und Halschirurgie (5)
- Institut für Anatomie und Zellbiologie (4)
- Institut für Epidemiologie u. Sozialmedizin (4)
- Institut für Fennistik und Skandinavistik (4)
- Klinik und Poliklinik für Frauenheilkunde u. Geburtshilfe (4)
- Institut für Erziehungswissenschaft (3)
- Institut für Medizinische Psychologie (3)
- Institut für Pathologie (3)
- Klinik und Poliklinik für Hautkrankheiten (3)
- Klinik und Poliklinik für Innere Medizin Abt. Gastroenterologie, Endokrinologie und Ernährungsmedizin (3)
- Universitätsmedizin (3)
- Wirtschaftswissenschaften (3)
- Friedrich-Loeffler-Institut für Medizinische Mikrobiologie (2)
- Historisches Institut (2)
- Institut für Anglistik/Amerikanistik (2)
- Institut für Baltistik (2)
- Institut für Politik- und Kommunikationswissenschaft (2)
- Klinik für Anästhesiologie und Intensivmedizin (2)
- Klinik und Poliklinik für Augenheilkunde (2)
- Klinik und Poliklinik für Chirurgie Abt. für Unfall- und Wiederherstellungschirurgie (2)
- Klinik und Poliklinik für Innere Medizin Abt. Nephrologie, Hochdruckkrankheiten und Dialyse (2)
- Klinik und Poliklinik für Urologie (2)
- Institut für Ethik und Geschichte der Medizin (1)
- Institut für Immunologie u. Transfusionsmedizin - Abteilung Transfusionsmedizin (1)
- Institut für Physiologie (1)
- Klinik für Herz-, Thorax- und Gefäßchirurgie - Klinikum Karlsburg (1)
- Klinik und Poliklinik für Kinderchirurgie (1)
- Klinik und Poliklinik für Neurochirurgie (1)
- Klinik und Poliklinik für Orthopädie und Orthopädische Chirurgie (1)
- Mathematisch-Naturwissenschaftliche Fakultät (1)
- Philosophische Fakultät (1)
- Rechtswissenschaften (1)
- Theologie (1)
Publisher
- MDPI (53)
- Frontiers Media S.A. (29)
- S. Karger AG (20)
- Copernicus (12)
- SAGE Publications (11)
- De Gruyter (9)
- Wiley (9)
- Public Library of Science (PLoS) (7)
- BioMed Central (BMC) (4)
- Nature Publishing Group (4)
Vielfältig lässt sich die Bedeutung von Vorstrafen zeigen; jenseits ihrer gesellschaftlichen Wirkungen beschäftigen sie Straf-, Arbeits- und Zivilgerichte. Dieser Beitrag untersucht, welche Implikationen die Registrierung einer Verurteilung hat. Dabei soll aus strafrechtlicher wie auch aus grundrechtlicher Perspektive belegt werden, dass der Staat als Autor der Verurteilung alle ihre Folgen bedenken und bestimmten Konsequenzen gegebenenfalls entgegenwirken muss. Zur Einstimmung sollen fünf Fallskizzen Schlaglichter auf den Problemkreis werfen:
Kriminalgeschichten aus dem europäischen Norden, die unter dem Label Nordic Noir laufen, haben nun schon seit geraumer Zeit Hochkonjunktur, sei es in
visueller oder gedruckter Form. Somit widmete sich das Literaturwissenschaftliche Kolloquium des Nordischen Klangs im vergangenen Jahr auch einmal diesem Thema, und zwar aus einer überwiegend flmanalytischen Perspektive und
mit Fokus auf bekannte Fernsehserien aus Skandinavien und Island. Das Motto des Kolloquiums lautete jedoch nicht einfach „Nordic Noir“, sondern „Nordic
Schwarz/Weiß“. Warum diese spezielle Teilformulierung? Um diese zu erläutern,
muss ich zunächst beim Ausgangsbegrif ansetzen:
AbstractThis paper takes concepts from spatial theory and globalization discourse and uses them in order to analyze the narrative function of descriptions of nature in romantic Icelandic poetry from the beginning of the 19th century and an Icelandic TV-Series from 2015. In Iceland’s romantic poetry of the early 19th century, especially in poems written by Bjarni Thorarensen, sublime nature is described as a form of guardian against foreign influences that threaten the way of living on the peripheral island. This romantic concept of Icelandic nature is closely connected to narrative patterns in the process of the Icelandic Nation-Building, as it characterizes Icelanders as simultaneously defined and protected by the harsh conditions on the island. The paper takes a comparative look at the underlying narrative concepts of nature in two of Bjarni Thorarensen’s poems and a recent Icelandic TV series, Baltasar Kormákur’s Ófærð (2015), that presents a different concept of Icelandic nature in its relation to a (threatening) global influence. The series depicts a globalized world in which crime does not only affect remote communities as an evil from the outside but as a local evil connected to forces on global scale. Nature as a narrative device in the TV series thus does not protect Icelanders from global forces, as it did in Bjarni Thorarensens poems in the early 19th century, but instead functions a catalyst that reveals the evil from the outside and the evil from within.
Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test
(2019)
Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations
within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous,
multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to
demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study
was to establish a test that allows for an objective assessment of the pathological potential of NPC1
gene variants. Chinese hamster ovary cells defective in the NPC1 gene accumulate cholesterol in
lysosomal storage organelles. The cells were transfected with NPC1-GFP plasmid vectors carrying
distinct sequence variants. Filipin staining was used to test for complementation of the phenotype.
The known variant p.Ile1061Thr showed a significantly impaired cholesterol clearance after 12 and
24 h compared to the wild type. Among the investigated variants, p.Ser954Leu and p.Glu1273Lys
showed decelerated cholesterol clearance as well. The remaining variants p.Gln60His, p.Val494Met,
and p.Ile787Val showed a cholesterol clearance indistinguishable from wild type. Further, p.Ile1061Thr
acquired an enhanced clearance ability upon 25-hydroxycholesterol treatment. We conclude that the
variants that caused an abnormal clearance phenotype are highly likely to be of clinical relevance.
Moreover, we present a system that can be utilized to screen for new drugs.
GPR68 (OGR1) belongs to the proton-sensing G protein-coupled receptors that are involved
in cellular adaptations to pH changes during tumour development. Although expression of GPR68
has been described in many tumour cell lines, little is known about its presence in human tumour
entities. We characterised the novel rabbit monoclonal anti-human GPR68 antibody 16H23L16
using various cell lines and tissue specimens. The antibody was then applied to a large series of
formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. Antibody specificity
was demonstrated in a Western blot analysis of GPR68-expressing cells using specific siRNAs.
Immunocytochemical experiments revealed pH-dependent changes in subcellular localisation of the
receptor and internalisation after stimulation with lorazepam. In normal tissue, GPR68 was present in
glucagon-producing islet cells, neuroendocrine cells of the intestinal tract, gastric glands, granulocytes,
macrophages, muscle layers of arteries and arterioles, and capillaries. GPR68 was also expressed
in neuroendocrine tumours, where it may be a positive prognostic factor, in pheochromocytomas,
cervical adenocarcinomas, and endometrial cancer, as well as in paragangliomas, medullary thyroid
carcinomas, gastrointestinal stromal tumours, and pancreatic adenocarcinomas. Often, tumour
capillaries were also strongly GPR68-positive. The novel antibody 16H23L16 will be a valuable tool for
basic research and for identifying GPR68-expressing tumours during histopathological examinations.
Renal drug transporters such as the organic cation transporters (OCTs), organic anion
transporters (OATs) and multidrug resistance proteins (MRPs) play an important role in the tubular
secretion of many drugs influencing their efficacy and safety. However, only little is known about
the distinct protein abundance of these transporters in human kidneys, and about the impact of
age and gender as potential factors of inter-subject variability in their expression and function.
The aim of this study was to determine the protein abundance of MDR1, MRP1-4, BCRP, OAT1-3,
OCT2-3, MATE1, PEPT1/2, and ORCTL2 by liquid chromatography-tandem mass spectrometry-based
targeted proteomics in a set of 36 human cortex kidney samples (20 males, 16 females; median age
53 and 55 years, respectively). OAT1 and 3, OCT2 and ORCTL2 were found to be most abundant
renal SLC transporters while MDR1, MRP1 and MRP4 were the dominating ABC transporters.
Only the expression levels of MDR1 and ORCTL2 were significantly higher abundant in older donors.
Moreover, we found several significant correlations between different transporters, which may
indicate their functional interplay in renal vectorial transport processes. Our data may contribute to
a better understanding of the molecular processes determining renal excretion of drugs.
Salivary glands provide secretory functions, including secretion of xenobiotics and among
them drugs. However, there is no published information about protein abundance of drug transporters
measured using reliable protein quantification methods. Therefore, mRNA expression and absolute
protein content of clinically relevant ABC (n = 6) and SLC (n = 15) family member transporters in the
human parotid gland, using the qRT-PCR and liquid chromatography-tandem mass spectrometry
(LC−MS/MS) method, were studied. The abundance of nearly all measured proteins ranged between
0.04 and 0.45 pmol/mg (OCT3 > MRP1 > PEPT2 > MRP4 > MATE1 > BCRP). mRNAs of ABCB1,
ABCC2, ABCC3, SLC10A1, SLC10A2, SLC22A1, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLCO1A2,
SLCO1B1, SLCO1B3 and SLCO2B1 were not detected. The present study provides, for the first time,
information about the protein abundance of membrane transporters in the human parotid gland,
which could further be used to define salivary bidirectional transport (absorption and secretion)
mechanisms of endogenous compounds and xenobiotics.
Determining the effect of a changing climate on tree growth will ultimately depend on our understanding of wood formation processes and how they can be affected by environmental conditions. In this context, monitoring intra-annual radial growth with high temporal resolution through point dendrometers has often been used. Another widespread approach is the microcoring method to follow xylem and phloem formation at the cellular level. Although both register the same biological process (secondary growth), given the limitations of each method, each delivers specific insights that can be combined to obtain a better picture of the process as a whole. To explore the potential of visualizing combined dendrometer and histological monitoring data and scrutinize intra-annual growth data on both dimensions (dendrometer → continuous; microcoring → discrete), we developed DevX (Dendrometer vs. Xylogenesis), a visualization application using the “Shiny” package in the R programming language. The interactive visualization allows the display of dendrometer curves and the overlay of commonly used growth model fits (Gompertz and Weibull) as well as the calculation of wood phenology estimates based on these fits (growth onset, growth cessation, and duration). Furthermore, the growth curves have interactive points to show the corresponding histological section, where the amount and development stage of the tissues at that particular time point can be observed. This allows to see the agreement of dendrometer derived phenology and the development status at the cellular level, and by this help disentangle shrinkage and swelling due to water uptake from actual radial growth. We present a case study with monitoring data for Acer pseudoplatanus L., Fagus sylvatica L., and Quercus robur L. trees growing in a mixed stand in northeastern Germany. The presented application is an example of the innovative and easy to access use of programming languages as basis for data visualization, and can be further used as a learning tool in the topic of wood formation and its ecology. Combining continuous dendrometer data with the discrete information from histological-sections provides a tool to identify active periods of wood formation from dendrometer series (calibrate) and explore monitoring datasets.
Formation of singly and doubly charged Arq+ and Tiq+ (q = 1,2) and of molecular Ar 2 +, ArTi+, and Ti 2 + ions in a direct current magnetron sputtering discharge with a Ti cathode and argon as working gas was investigated with the help of energy-resolved mass spectrometry. Measured ion energy distributions consist of low-energy and high-energy components resembling different formation processes. Intensities of Ar 2 + and ArTi+ dimer ions strongly increase with increasing gas pressure. Addition of oxygen gas leads to the formation of positively charged O+, O2 +, and TiO+ and of negatively charged O− and O2 - ions.
Abstract
We propose a setup enabling electron energy loss spectroscopy to determine the density of the electrons accumulated by an electropositive dielectric in contact with a plasma. It is based on a two-layer structure inserted into a recess of the wall. Consisting of a plasma-facing film made out of the dielectric of interest and a substrate layer, the structure is designed to confine the plasma-induced surplus electrons to the region of the film. The charge fluctuations they give rise to can then be read out from the backside of the substrate by near specular electron reflection. To obtain in this scattering geometry a strong charge-sensitive reflection maximum due to the surplus electrons, the film has to be most probably pre-n-doped and sufficiently thin with the mechanical stability maintained by the substrate. Taking electronegative CaO as a substrate layer we demonstrate the feasibility of the proposal by calculating the loss spectra for Al2O3, SiO2, and ZnO films. In all three cases we find a reflection maximum strongly shifting with the density of the surplus electrons and suggest to use it for charge diagnostics.
Abstract
Reactive high power impulse magnetron sputtering (HiPIMS) of a cobalt cathode in pure argon gas and with different oxygen admixtures was investigated by time-resolved optical emission spectroscopy (OES) and time-integrated energy-resolved mass spectrometry. The HiPIMS discharge was operated with a bipolar pulsed power supply capable of providing a large negative voltage with a typical pulse width of 100 μs followed by a long positive pulse with a pulse width of about 350 μs. The HiPIMS plasma in pure argon is dominated by Co+ ions. With the addition of oxygen, O+ ions become the second most prominent positive ion species. OES reveals the presence of Ar I, Co I, O I, and Ar II emission lines. The transition from an Ar+ to a Co+ ion sputtering discharge is inferred from time-resolved OES. The enhanced intensity of excited Ar+* ions is explained by simultaneous excitation and ionisation induced by energetic secondary electrons from the cathode. The intensity of violet Ar I lines is drastically reduced during HiPIMS. Intensity of near-infrared Ar I lines resumes during the positive pulse indicating an additional heating mechanism.
Background: This study aimed to prospectively investigate patients’ satisfaction with briefings before computed tomography (CT) examinations, determine feasibility, and identify factors influencing patient satisfaction independent of patient and physician characteristics.
Methods: One hundred sixty patients received information by a radiologist prior to contrast-enhanced CT examinations in an open, prospective, two-center, cross-sectional study (including the introduction of the radiologist, procedure, radiation exposure, possible side effects, and alternatives). Afterwards, patients and radiologists evaluated the briefing using a standardized questionnaire. Additionally, factors such as age, socioeconomic status, inpatient/outpatient status, length of the radiologist’s professional experience, duration of the briefing, clarity of the radiologist’s explanations as perceived by patients, and the duration of communication were obtained in this questionnaire. Subsequently, three classes of influencing factors were defined and entered stepwise into a hierarchical regression.
Results: Patient satisfaction ratings differed significantly by type of hospitalization, perceived type of communication, and patient gender. Hierarchical regression analysis revealed that perceived clarity was the strongest predictor of patients’ satisfaction when controlling for the patient and physician characteristics.
Conclusions: Patients appeared to be satisfied with the briefing prior to CT examination. The mean briefing time (2 min 35 s) seemed feasible. Patients’ demographics influenced satisfaction. To improve patients’ satisfaction with briefings before contrast-enhanced CT, radiologists should aim to clarify their communication.
Keywords: Doctor-patient communication, Informed consent, Patients’ satisfaction, Contrast-enhancement
Environmental activism, defined as a range of difficult pro-environmental behaviors, is analyzed within the conceptual framework of Significance Quest Theory (SQT). In Study 1, 40 interviews were carried out on two groups of people in the European Union: Committed Actors for Nature (CANs, n = 25) versus Committed Actors for Society (CASs, n = 15). Results demonstrated that Significance Quest (SQ) motivates each group to be strongly committed to their chosen action and the main difference between them being in their ideology (pro-social vs. pro-environmental). In Study 2 (N = 131), the relationship between SQ and intention to enact difficult pro-environmental behaviors was assessed. Results suggested that the higher the SQ, the higher the tendency to enact difficult pro-environmental behaviors, but not average or easy ones. Moreover, the higher the pro-environmental ideology, the stronger the indirect effect of SQ on difficult behavior through willingness to sacrifice.
Up to now, indices like the mean dmft/DMFT and the SiC (Significant Caries Index) have been used to depict caries experience in populations with high prevalence. With the caries decline, particularly for populations with low caries levels, these indices reach their statistical limits. This paper aims to introduce a specific term, the Specific affected Caries Index (SaC) for the risk groups in populations with low caries prevalence and to illustrate its use based on the consecutive German National Oral Health Survey (GNOHS) in children. In groups with a caries prevalence less than one-third of the population, many caries-free children (DMFT = 0) are included in the SiC (risk group), which calls for a new way of illustration. Mean caries experience (DMFT), caries prevalence, the SiC and SaC were portrayed for 12-year-olds in the GNOHS from 1994/95 to 2016. The SaC describes the mean caries experience (DMFT) in the group presenting caries experience (DMFT > 0). In 12-year-old 6th graders in Germany, the mean caries experience decreased from 2.4 (1994/95) to 0.4 DMFT (2016), with a recent prevalence of 21.2% (DMFT > 0, 2016). In 2016, the mean number of affected teeth in children with DMFT > 0 (SaC) was 2.1, while the SiC including 12% DMFT-free children in the risk group was 1.3. The SiC fails to reflect the caries severity in children in a population with low caries prevalence. Therefore, the newly introduced term Specific affected Caries Index (SaC) may be used to describe accurately caries experience in caries risk children in populations presenting low caries prevalence.
Vitamin B6 deficiency during pregnancy translates into a severe vitamin B6 deficiency (plasma levels decreased by 97%) in new-born rats. Further, hallmarks are increased (+89%) concentrations of homocysteine, gross changes in gene methylation and expression, and metabolic alterations including lipid metabolism. This study focuses on determining the effects of vitamin B6-deficiency on cardiolipin composition and oxidative phosphorylation in liver. For this purpose, hepatic cardiolipin composition was analyzed by means of LC/MS/MS, and mitochondrial oxygen consumption was determined by using a Clark-type electrode in a rat model of vitamin B6 deficiency. Liver mitochondria from new-born rats with pre-term vitamin B6 deficiency responded with substantial alterations in cardiolipin composition that include the following changes in the amounts of cardiolipin incorporated fatty acids: increase in C16, decrease in C18, decrease in saturated fatty acid, as well as increase in amount of oxidized cardiolipin species. These changes were accompanied by significantly decreased capacity of oxidative phosphorylation. In conclusion, vitamin B6 deficiency in new born rats induces massive alterations of cardiolipin composition and function of liver mitochondria. These findings support the importance of sufficient periconceptional supply of vitamin B6 to prevent vitamin B6 deficiency.
Impact statement
Vitamin B6 (VitB6) is an active co-enzyme for more than 150 enzymes and is required for a great diversity of biosynthesis and metabolic reactions. There is an increased need for VitB6 during pregnancy and sufficient supply of VitB6 is crucial for the prevention of cleft palate and neural tube defects. We show that liver mitochondria from new-born rats with pre-term VitB6 deficiency respond with substantial alterations in cardiolipin (CL) composition and in the amount of oxidized CL species. These changes are associated with a decrease in the efficiency of oxidative phosphorylation. The results of this study support the significance of sufficient supply of VitB6 during pregnancy (and periconceptional) for diminishing the number of early abortions and minimizing malformation. The established link between VitB6 deficiency, CL composition, and mitochondrial respiration/energy production provides mechanistic insight as to how the VitB6 deficiency translates into the known pathophysiological and clinically relevant conditions.
The aim of the present study was to construct a biological age score reflecting one’s physiologic capability and aging condition with respect to tooth loss over 10 y. From the follow-up to the population-based Study of Health in Pomerania (i.e., SHIP-2), 2,049 participants were studied for their baseline biomarker measures 10 y before (i.e., in SHIP-0). Metabolic and periodontal data were regressed onto chronological age to construct a score designated as “biological age.” For either sex separately, the impact of this individualized score was used to predict tooth loss in the follow-up cohort in comparison with each participant’s chronological age. Outcome data after 10 y with respect to tooth loss, periodontitis, obesity, and inflammation were shown to be better for biologically younger subjects than as expected by their chronological age, whereas for the older subjects, data were worse. Especially for tooth loss, a striking increase was observed in subjects whose biological age at baseline appeared to be higher than their chronological age. Biological age produced significantly better tooth loss predictions than chronological age (P < 0.001). Areas under receiver operating characteristic curves for tooth loss of ≥3 teeth in men during follow-up were 0.811 and 0.745 for biological and chronological age, respectively. For women, these figures were 0.788 and 0.724. For total tooth loss, areas under the curve were 0.890 and 0.749 in men and 0.872 and 0.752 in women. Biological age combines various measures into a single score and allows identifying individuals at increased risk of tooth loss.
Evidence is limited regarding whether periodontal treatment improves hemoglobin A1c (HbA1c) among people with prediabetes and periodontal disease, and it is unknown whether improvement of metabolic status persists >3 mo. In an exploratory post hoc analysis of the multicenter randomized controlled trial “Antibiotika und Parodontitis” (Antibiotics and Periodontitis)—a prospective, stratified, double-blind study—we assessed whether nonsurgical periodontal treatment with or without an adjunctive systemic antibiotic treatment affects HbA1c and high-sensitivity C-reactive protein (hsCRP) levels among periodontitis patients with normal HbA1c (≤5.7%, n = 218), prediabetes (5.7% < HbA1c < 6.5%, n = 101), or unknown diabetes (HbA1c ≥ 6.5%, n = 8) over a period of 27.5 mo. Nonsurgical periodontal treatment reduced mean pocket probing depth by >1 mm in both groups. In the normal HbA1c group, HbA1c values remained unchanged at 5.0% (95% CI, 4.9% to 6.1%) during the observation period. Among periodontitis patients with prediabetes, HbA1c decreased from 5.9% (95% CI, 5.9% to 6.0%) to 5.4% (95% CI, 5.3% to 5.5%) at 15.5 mo and increased to 5.6% (95% CI, 5.4% to 5.7%) after 27.5 mo. At 27.5 mo, 46% of periodontitis patients with prediabetes had normal HbA1c levels, whereas 47.9% remained unchanged and 6.3% progressed to diabetes. Median hsCRP values were reduced in the normal HbA1c and prediabetes groups from 1.2 and 1.4 mg/L to 0.7 and 0.7 mg/L, respectively. Nonsurgical periodontal treatment may improve blood glucose values among periodontitis patients with prediabetes (ClinicalTrials.gov NCT00707369).
Periodontitis is one of the most prevalent oral diseases worldwide and is caused by multifactorial interactions between host and oral bacteria. Altered cellular metabolism of host and microbes releases a number of intermediary end products known as metabolites. There is an increasing interest in identifying metabolites from oral fluids such as saliva to widen the understanding of the complex pathogenesis of periodontitis. It is believed that some metabolites might serve as indicators toward early detection and screening of periodontitis and perhaps even for monitoring its prognosis in the future. Because contemporary periodontal screening methods are deficient, there is an urgent need for novel approaches in periodontal screening procedures. To this end, we associated oral parameters (clinical attachment level, periodontal probing depth, supragingival plaque, supragingival calculus, number of missing teeth, and removable denture) with a large set of salivary metabolites (n = 284) obtained by mass spectrometry among a subsample (n = 909) of nondiabetic participants from the Study of Health in Pomerania (SHIP-Trend-0). Linear regression analyses were performed in age-stratified groups and adjusted for potential confounders. A multifaceted image of associated metabolites (n = 107) was revealed with considerable differences according to age groups. In the young (20 to 39 y) and middle-aged (40 to 59 y) groups, metabolites were predominantly associated with periodontal variables, whereas among the older subjects (≥60 y), tooth loss was strongly associated with metabolite levels. Metabolites associated with periodontal variables were clearly linked to tissue destruction, host defense mechanisms, and bacterial metabolism. Across all age groups, the bacterial metabolite phenylacetate was significantly associated with periodontal variables. Our results revealed alterations of the salivary metabolome in association with age and oral health status. Among our comprehensive panel of metabolites, periodontitis was significantly associated with the bacterial metabolite phenylacetate, a promising substance for further biomarker research.
For the goal of individualized medicine, it is critical to have clinical phenotypes at hand which represent the individual pathophysiology. However, for most of the utilized phenotypes, two individuals with the same phenotype assignment may differ strongly in their underlying biological traits. In this paper, we propose a definition for individualization and a corresponding statistical operationalization, delivering thereby a statistical framework in which the usefulness of a variable in the meaningful differentiation of individuals with the same phenotype can be assessed. Based on this framework, we develop a statistical workflow to derive individualized phenotypes, demonstrating that under specific statistical constraints the prediction error of prediction scores contains information about hidden biological traits not represented in the modeled phenotype of interest, allowing thereby internal differentiation of individuals with the same assigned phenotypic manifestation. We applied our procedure to data of the population-based Study of Health in Pomerania to construct a refined definition of obesity, demonstrating the utility of the definition in prospective survival analyses. Summarizing, we propose a framework for the individualization of phenotypes aiding personalized medicine by shifting the focus in the assessment of prediction models from the model fit to the informational content of the prediction error.
BK polyomavirus-associated haemorrhagic cystitis (BKHC) is a complication after allogeneic stem cell transplantation, which can occur in 5–60% of the cases. BK viruria alone can also occur in up to 100%. BKHC can lead to severe morbidity in stem cell-transplanted patients, but data about this disease is limited. Consequently, we conducted a prospective unicentric non-interventional trial on BKHC as well as BK viruria after first adult allogeneic stem cell transplantation with a follow-up time of 1 year after inpatient treatment. Between November 2013 and December 2015, we were able to include 40 adult patients with a mean age of 52.8 years. Twenty-seven (67.5%) of these patients were male and 13 (32.5%) were female. Acute myeloid leukaemia was the most frequent underlying disease (n = 15; 37.5%). Only 1 patient developed BKHC during inpatient treatment (n = 1; 2.5%), but BK viruria was frequent (n = 11; 27.5%) during inpatient treatment as well as in the follow-up time (n = 14; 35%). Interestingly, BK viruria was significantly associated with mucositis (p = 0.038) and number of transfused platelet concentrates (p = 0.001). This unexpected association will be discussed and needs further investigation.
Prediction models learn patterns from available data (training) and are then validated on new data (testing). Prediction modeling is increasingly common in dental research. We aimed to evaluate how different model development and validation steps affect the predictive performance of tooth loss prediction models of patients with periodontitis. Two independent cohorts (627 patients, 11,651 teeth) were followed over a mean ± SD 18.2 ± 5.6 y (Kiel cohort) and 6.6 ± 2.9 y (Greifswald cohort). Tooth loss and 10 patient- and tooth-level predictors were recorded. The impact of different model development and validation steps was evaluated: 1) model complexity (logistic regression, recursive partitioning, random forest, extreme gradient boosting), 2) sample size (full data set or 10%, 25%, or 75% of cases dropped at random), 3) prediction periods (maximum 10, 15, or 20 y or uncensored), and 4) validation schemes (internal or external by centers/time). Tooth loss was generally a rare event (880 teeth were lost). All models showed limited sensitivity but high specificity. Patients’ age and tooth loss at baseline as well as probing pocket depths showed high variable importance. More complex models (random forest, extreme gradient boosting) had no consistent advantages over simpler ones (logistic regression, recursive partitioning). Internal validation (in sample) overestimated the predictive power (area under the curve up to 0.90), while external validation (out of sample) found lower areas under the curve (range 0.62 to 0.82). Reducing the sample size decreased the predictive power, particularly for more complex models. Censoring the prediction period had only limited impact. When the model was trained in one period and tested in another, model outcomes were similar to the base case, indicating temporal validation as a valid option. No model showed higher accuracy than the no-information rate. In conclusion, none of the developed models would be useful in a clinical setting, despite high accuracy. During modeling, rigorous development and external validation should be applied and reported accordingly.
A successful colonization of different compartments of the human host requires multifactorial contacts between bacterial surface proteins and host factors. Extracellular matrix proteins and matricellular proteins such as thrombospondin-1 play a pivotal role as adhesive substrates to ensure a strong interaction with pathobionts like the Gram-positive Streptococcus pneumoniae and Staphylococcus aureus. The human glycoprotein thrombospondin-1 is a component of the extracellular matrix and is highly abundant in the bloodstream during bacteremia. Human platelets secrete thrombospondin-1, which is then acquired by invading pathogens to facilitate colonization and immune evasion. Gram-positive bacteria express a broad spectrum of surface-exposed proteins, some of which also recognize thrombospondin-1. This review highlights the importance of thrombospondin-1 as an adhesion substrate to facilitate colonization, and we summarize the variety of thrombospondin-1-binding proteins of S. pneumoniae and S. aureus.
Biocatalytic Production of Amino Carbohydrates through Oxidoreductase and Transaminase Cascades
(2019)
Plant-derived carbohydrates are an abundant renewable re- source. Transformation of carbohydrates into new products, in- cluding amine-functionalized building blocks for biomaterials applications, can lower reliance on fossil resources. Herein, bio- catalytic production routes to amino carbohydrates, including oligosaccharides, are demonstrated. In each case, two-step bio- catalysis was performed to functionalize d-galactose-contain- ing carbohydrates by employing the galactose oxidase from Fusarium graminearum or a pyranose dehydrogenase from
Agaricus bisporus followed by the w-transaminase from Chro- mobacterium violaceum (Cvi-w-TA). Formation of 6-amino-6- deoxy-d-galactose, 2-amino-2-deoxy-d-galactose, and 2-amino- 2-deoxy-6-aldo-d-galactose was confirmed by mass spectrome- try. The activity of Cvi-w-TA was highest towards 6-aldo-d-gal- actose, for which the highest yield of 6-amino-6-deoxy-d-galac- tose (67%) was achieved in reactions permitting simultaneous oxidation of d-galactose and transamination of the resulting 6- aldo-d-galactose.
Die kraniomandibuläre Dysfunktion ist eine häufige Erkrankung die mit Beschwerden im Kiefergelenk und Kaumuskelbereich einhergehen. Zur Behandlung werden Aufbissschienen eingesetzt. Ziel der vorliegenden Arbeit war zu untersuchen, wie sich eine dreimonatige Therapie mit einer Unterkieferaufbissschiene vom DIR-Typ bei CMD Patienten auswirkt. Dreizehn Patienten mit kraniomandibulärer Dysfunktion und moderater Schmerzausprägung wurden zu Beginn der Therapie, nach zwei Wochen und zum Ende der Therapie (12 Wochen) mittels funktioneller Magnetresonanztomographie bei okklusalen Bewegungen mit und ohne eingesetzte DIR-Schiene untersucht. Zusätzlich wurden an den Messzeitpunkten jeweils eine kinematographische Messung des Kiefergelenks, sowie ein Elektromyogramm der Kiefergelenksmuskulatur durchgeführt. Über den kompletten Therapiezeitraum wurde die Schmerzausprägung von den Patienten in einem Schmerztagebuch (VAS Skala 0-100) dokumentiert.
Obwohl die Schmerzintensität nach der Therapie um fast 60% abnahm, konnten keine signifikanten Veränderungen bei den kinematographischen und elektromyographischen Daten festgestellt werden. Im Verlauf der Therapie wurde eine Abnahme der fMRT Aktivität im primären und sekundären somatomotorischen Kortex, sowie im Inselkortex beobachtet. Zudem korreliert eine fMRT Aktivitätsabnahme in der linken anterioren Insel und im zerebellaren Kortex mit einer Abnahme der Schmerzintensität während der Therapie. Des Weiteren wurde bei der Eingliederung der DIR-Schiene eine Ökonomisierung im primären motorischen Kortex und in der rechten anterioren Insel festgestellt.
Nach Berücksichtigung der Limitationen kann man aus dieser Studie schlussfolgern, dass es durch die DIR-Schienentherapie nicht nur zu einer Reduktion der Schmerzen kommt, sondern auch neuronale Prozesse stattfinden die sowohl diskriminative als auch affektive Areale der Schmerzverarbeitung beeinflussen und sich auf der Krankheitsverlauf positiv auswirken können.
Die Zahl der Menschen mit Demenz (MmD) nimmt auch in den Krankenhäusern zu. Die Stationen sind üblicherweise auf eine Akutbehandlung ausgelegt, dies macht das Eingehen auf MmD schwierig. Sich dadurch ergebende mögliche Konsequenzen erstrecken sich von einer ungeplanten Wiedereinweisung über eine Heimeinweisung bis hin zum Tod des Patienten.
Verschiedene Studien konzentrieren sich auf die kurzfristigen Folgen einer Hospitalisierung
von MmD. Nur einige Studien erfassten Langzeitfolgen. Diese Informationen sind jedoch
bedeutend, um die Versorgung von MmD zu verbessern.
In der vorliegenden systematischen Übersichtsarbeit und Metaanalyse wird ein Überblick zu
den Langzeitfolgen (ungeplante Wiedereinweisung, Institutionalisierung und Mortalität) einer Hospitalisierung von MmD gegeben. Es werden Prädiktoren erfasst, die mit negativen Folgen
eines Krankenhausaufenthaltes assoziiert sind. Um alle relevanten Publikationen zum Thema zu erfassen, wurde eine systematische Literaturrecherche in den Datenbanken PubMed, CENTRAL und ScienceDirect durchgeführt. Die Qualität der einzelnen relevanten Studien
wurde in einem Formular zu Bewertung der Studien dokumentiert. Die Ergebnisse wurden in
einer Tabelle zusammengefasst, die Metaanalyse wurde mittels Review Manager 5.3 der Cochrane Collaboration berechnet.
Die systematische Literaturrecherche führte zu 1108 Artikeln, hiervon erfüllten 20 Artikel die Einschlusskriterien. 10 Studien wurden mit einer Kontrollgruppe durchgeführt und demnach in die Metaanalysen eingeschlossen. Die Inzidenz und das Relative Risiko für die Mortalität von
MmD (RR: 1,74 [95 %-KI 1,50-2,05]) und die Institutionalisierung (RR: 2,16 [95 %-KI 1,31-
3,56]) waren signifikant erhöht im Vergleich zu Menschen ohne Demenz. Die Ergebnisse bezüglich der ungeplanten Wiedereinweisung waren nicht aussagekräftig. Wichtige Faktoren, welche mit diesen Folgen assoziiert waren, waren der Schweregrad der Demenz, die Anzahl der eingenommen Medikamente und der Umfang der benötigten Hilfe bei der Verrichtung der Aktivitäten des täglichen Lebens.
Die Ergebnisse dieser Arbeit sprechen dafür, dass eine umfassendere Betreuung von MmD sowohl im Akutkrankenhaus als auch in der Häuslichkeit nötig ist. Außerdem sollten alle Prozesse an den Schnittstellen dieser Bereiche, insbesondere das Krankenhausentlassungsmanagement, weiter intensiviert und verbessert werden.
Die Schädelsonographie ist eine nicht-invasive, kosteneffektive und strahlenfreie Bildgebung zur Detektion zerebraler Pathologien des Neugeborenen. Im Rahmen der populationsbasierten Geburtenkohortenstudie „Survey of Neonates in Pomerania“ wurde die Schädelsonographie unabhängig von Empfehlungen der internationalen Literatur durchgeführt. Dadurch konnten Schweregrad, Outcome und Prävalenz der zerebralen Pathologien von asymptomatischen, reifen Neugeborenen in der angehängten Publikation von Weise et al. analysiert werden[2]. Für diese Gruppe ist keine Assoziation von
Auffälligkeiten in der Schädelsonographie mit neurologischen Entwicklungsstörungen zu finden. Daher wird keine Erweiterung der aktuellen Richtlinien oder die Einführung eines zerebralen Ultraschallscreenings für Neugeborenen nicht empfohlen. Die Schädelsonographie ist zur frühzeitigen Detektion von zerebralen Anomalien bei Neugeborenen nach der „American Institute of Ultrasound in Medicine (AIUM) Practice Guideline for the Performance of Neurosonography in Neonates and Infants 2014“, Leijser et al.,
Ment et al. und Ballardini et al. indiziert:
1. Eine Schädelsonographie ist bei Neugeborenen ≤34 SSW zu empfehlen und sollte bei <30 SSW durchgeführt werden.
2. Die Indikationsparameter der AIUM Practice Guideline sind sinnvoll und sollten in eine offizielle Leitlinie integriert werden (siehe Tabelle 2.1).
3. Aufgrund ähnlicher kumulativer Inzidenzen für Schädelsonographiebefunde bei Neugeborenen mit oder ohne Indikation aber stationärer Aufnahme ist die Untersuchung von Neugeborenen bei Aufnahme auf eine Neonatologie zu empfehlen.
4. Die Durchführung der Untersuchung sollte anhand der Richtlinien von Riccabona et al. erfolgen.
5. Dies schließt nicht die reguläre Teilnahme an den U-Untersuchungen aus, welche zur frühzeitigen Detektion neurologischer Entwicklungsstörungen beiträgt.
Prothrombotic and Proinflammatory Activities of the β-Hemolytic Group B Streptococcal Pigment
(2019)
A prominent feature of severe streptococcal infections is the profound inflammatory response that contributes to systemic toxicity. In sepsis the dysregulated host response involves both immunological and nonimmunological pathways. Here, we report a fatal case of an immunocompetent healthy female presenting with toxic shock and purpura fulminans caused by group B streptococcus (GBS; serotype III, CC19). The strain (LUMC16) was pigmented and hyperhemolytic. Stimulation of human primary cells with hyperhemolytic LUMC16 and STSS/NF-HH strains and pigment toxin resulted in a release of proinflammatory mediators, including tumor necrosis factor, interleukin (IL)-1β, and IL-6. In addition, LUMC16 induced blood clotting and showed factor XII activity on its surface, which was linked to the presence of the pigment. The expression of pigment was not linked to a mutation within the CovR/S region. In conclusion, our study shows that the hemolytic lipid toxin contributes to the ability of GBS to cause systemic hyperinflammation and interferes with the coagulation system.
Introduction: Senior urology physicians represent a heterogeneous group covering various clinical priorities and career objectives. No reliable data on gender-specific variations among senior urology physicians are available concerning professional and personal aspects. Methods: The objective of this study was to analyze professional perspectives, professional and personal settings, and individual career goals. A Web-based survey containing 55 items was designed which was available for senior physicians at German urologic centers between February and April 2019. Gender-specific differences were evaluated using bootstrap-adjusted multivariate logistic regression models. Results: One hundred and ninety-two surveys were evaluable including 29 female senior physicians (15.1%). Ninety-five percent would choose urology again as their field of specialization – with no significant gender-specific difference. 81.2% of participants rate the position of senior physician as a desirable career goal (comparing sexes: p = 0.220). Based on multivariate models, male participants self-assessed themselves significantly more frequently autonomously safe performing laparoscopic, open, and endourologic surgery. Male senior physicians declared 7 times more often to run for the position of head of department/full professor. Conclusion: This first study on professional and personal aspects among senior urology physicians demonstrates gender-specific variations concerning self-assessment of surgical expertise and future career goals. The creation of well-orchestrated human resources development strategies especially adapted to the needs of female urologists seems advisable.
Introduction: Senior urology physicians represent a heterogeneous group covering various clinical priorities and career objectives. No reliable data on gender-specific variations among senior urology physicians are available concerning professional and personal aspects. Methods: The objective of this study was to analyze professional perspectives, professional and personal settings, and individual career goals. A Web-based survey containing 55 items was designed which was available for senior physicians at German urologic centers between February and April 2019. Gender-specific differences were evaluated using bootstrap-adjusted multivariate logistic regression models. Results: One hundred and ninety-two surveys were evaluable including 29 female senior physicians (15.1%). Ninety-five percent would choose urology again as their field of specialization – with no significant gender-specific difference. 81.2% of participants rate the position of senior physician as a desirable career goal (comparing sexes: p = 0.220). Based on multivariate models, male participants self-assessed themselves significantly more frequently autonomously safe performing laparoscopic, open, and endourologic surgery. Male senior physicians declared 7 times more often to run for the position of head of department/full professor. Conclusion: This first study on professional and personal aspects among senior urology physicians demonstrates gender-specific variations concerning self-assessment of surgical expertise and future career goals. The creation of well-orchestrated human resources development strategies especially adapted to the needs of female urologists seems advisable.
Zielsetzung: Cutibacterium (C.) acnes ist Teil des anaeroben Haut-Mikrobioms. Besonders in der Schulterchirurgie kommt es postoperativ häufig zu Infektionen mit C. acnes auf Grund der schwierigen Erreichbarkeit des Erregers durch das Hautantiseptikum in den Haarfollikeln der Haut.
Basierend auf der Hypothese, dass eine verlängerte Einwirkzeit des Hautantiseptikums in talgdrüsenreichen Arealen wie der Schulter das Eindringen in die Haarfollikel begünstigt und dadurch die antiseptische Wirksamkeit verbessert wird, sollte die Effektivität der derzeit üblichen Einwirkzeit von 2,5 min mit der Einwirkzeit von 30 min verglichen werden. Aufgrund der unterschiedlichen Eigenschaften von PVP-Iod und Chlorhexidindigluconat (CHG) sollten zwei handelsübliche alkoholische Hautantiseptika mit Gehalt an PVP-Iod bzw. CHG miteinander verglichen werden.
Methode: Im cross-over-Design wurde auf der Schulter von 16 gesunden, freiwilligen Probanden die Einwirkzeit von 2,5 min mit einer Einwirkzeit von 30 min jeweils mit einem PVP-I-haltigen Hautantiseptikum und einem CHG-haltigen Hautantiseptikum verglichen werden. Die Probenentnahmen erfolgten vor, direkt nach und 3h nach erfolgter Hautantiseptik. Analysiert wurde sowohl die aerobe als auch die anaerobe Hautflora.
Ergebnisse: Die aerobe residente Hautflora wurde durch beide Antiseptika bereits bei der kurzen Einwirkzeit effektiv eradiziert.
Die anaerobe residente Flora wurde hinsichtlich der Sofortwerte durch das PVP-I-haltige Antiseptikum sowohl bei der Einwirkungszeit von 2,5 min als auch von 30 min effektiver reduziert als durch das CHG-haltige Antiseptikum. Die nach 3 h erhobenen Werte zeigten dagegen nur die Tendenz der höheren Wirksamkeit bei der verlängerten Einwirkzeit des PVP-I-haltigen Antiseptikums. Die verlängerte Einwirkzeit hatte bei beiden Antiseptika keinen negativen Einfluss auf die intakte Haut, d.h. keiner der Probanden klagte über Hautirritationen oder Beschwerden.
Schlussfolgerung: Die alkoholische Zubereitung mit PVP-Iod ist dem CHG basierten Alkohol an Wirksamkeit gegen die anaerobe Flora im Sofortwert überlegen. Die klinische Relevanz dieser Studie sollte in einer randomisierten klinischen Studie mit dem Endpunkt SSI verifiziert werden.
Bei Diagnosestellung einer malignen Tumorerkrankung beeinflusst ein möglichst exaktes Staging sowohl des Tumors und der Lymphknoten, als auch von möglichen Fernmetastasen, maßgeblich das therapeutische Vorgehen und die Prognose des Patienten. Wegweisend für diesen Entscheidungsprozess sind, neben Therapiewunsch, Alter und Allgemeinzustand des Patienten, die Befunde der radiologischen Bildgebung.
In der vorliegenden retrospektiven Studie wurde die bildgebende Diagnostik bei Patienten mit Kopf – Hals – Tumoren hinsichtlich der Sensitivität, Spezifität und der Genauigkeit überprüft. Dazu wurden die Befunde der radiologischen Bildgebung sowie der postoperativen histologischen Untersuchung des Resektats von insgesamt 286 Patienten aus einem Zeitraum vom 01.01.2006 bis zum 01.09.2010 ausgewertet und miteinander verglichen. Zum Vergleich der Befunde wurde die Stadieneinteilung nach TNM in ihrer 7.Auflage verwendet. Eine Einteilung der Patienten in Gruppen erfolgte anhand der Tumorlokalisation. Unter Berücksichtigung der eingesetzten radiologischen Diagnostik (CT vs. MRT) wurde sowohl das Tumor- (T) als auch das Lymphknoten-Stadium (N) betrachtet. Ferner wurden auch die Befunde der „Ausbreitungsdiagnostik“ erfasst (M-Stadium). Die vorliegende Studie zeigte, dass die Sensitivität und Spezifität für das Tumor- und Nodalstaging auf vergleichbarem Niveau anderer Studien lag. Auch die Genauigkeit der Bildgebung, gemessen anhand des Quotienten aus richtig positiven + richtig negativen Befunden und der Gesamtheit der Befunde, lag auf einem hohen Niveau, jedoch war die Übereinstimmung der Tumor- und Nodalstadien der Bildgebung mit denen aus der histologischen Untersuchung gering.
Eine initiale Fernmetastasierung trat häufiger bei fortgeschrittenen Tumoren und metastatischem Lymphknotenbefall auf. Ebenso verhielt es sich mit späteren Metastasierungen und Rezidiven. Von den eingesetzten bildgebenden Verfahren zur Detektion von Fernmetastasen, konnten die Standardröntgenaufnahme des Thorax und die CT des Thorax ihren Stellenwert bei der Metastasensuche unterstreichen. Die Sklettszintigraphie und Röngtenzielaufnahme des Skeletts erbrachten keinen diagnostischen Nutzen bei der Metastasensuche.
Als Schlussfolgerung der Studie lässt sich ableiten, dass die Sensitivität und Spezifität der radiologischen Bildgebung für das Tumor- und Nodalstaging auf einem hohen Niveau liegen, das exakte Staging jedoch weiterhin eine diagnostische Herausforderung bleibt. Im Hinblick auf Therapiestrategie, Prognose und möglichem Auftreten von Rezidiven und Spätmetastsierungen kommt dem exakten Tumor- und Nodalstaging jedoch eine übergeordnete Rolle bei der Diagnostik zu. Die Metastasensuche stellt ebenso eine Herausforderung an die bildgebende Diagnostik dar, wobei konventionelle Verfahren nur einen limitierten Nutzen bei der Metastasensuche zu haben scheinen.
Die lungenprotektive Beatmung reduziert die Mortalität bei Patienten mit Acute Respiratory Distress Syndrom (ARDS). Um den beatmungsinduzierten Lungenschaden (Ventilator Induced Lung Injury (VILI)) zu minimieren, werden Tidalvolumina limitiert, hohe Plateaudrücke vermieden und ein positiv endexspiratorischer Druck entsprechend der Leitlinien angewandt. Doch der Einfluss spezifischer Beatmungsschemata auf den VILI ist nicht genau definiert.
Die Erhöhung der Inspirationszeit und somit des Verhältnisses zwischen Inspiration und Exspiration kann die Oxygenierung zwar verbessern, erhöht jedoch auch die Zeit der Einwirkung von Stress und Strain auf die Lunge. Die Hypothese dieser Arbeit ist, dass die Erhöhung der Inspirationszeit und damit des Verhältnisses von Inspiration zu Exspiration (I:E) sich besonders im ARDS schädlich auf die Lunge auswirkt und VILI weiter verstärkt.
VILI wurde im murinen Experimentalmodell durch Beatmung mit hohen Tidalvolumina (HVT: 34ml/kg) induziert. Die Beatmung mit niedrigen Tidalvolumina (LVT 9ml/kg) wurde als Kontrolle benutzt. In allen Gruppen erfolgte die Beatmung mit 50 % Sauerstoffkonzentration in der Einatemluft (FiO2) und einem PEEP von 2 cmH2O. HVT- und LVT-Mäuse wurden mit einer I:E-Ratio von 1:2 oder 1:1 für eine Gesamtdauer von 4 Stunden oder bis zum einem alternativen Endpunkt, definiert durch einen Blutdruckabfall unter 40mmHg, beatmet. Eine dynamische Hyperinflammation bedingt durch ein erhöhtes I:E-Verhältnis wurde in einer separaten Gruppe ausgeschlossen. Ausgewertet wurden das Überleben bei Beatmung über 4 Stunden, die Lungencompliance, Oxygenierung, sowie nach Versuchsende die pulmonale Permeabilität, die Konzentrationen gängiger Mediatoren der pulmonalen und der systemischen Inflammation (Leukozytendifferenzierung in Lunge und Blut; Messung von IL-6, IL1-ß, KC, MCP-1 in BAL und Blut) und histopathologische Veränderungen des Lungengewebes.
In den Kontrollgruppen mit protektiver Beatmung (LVT 1:2 und LVT 1:1) wurden keine VILI typischen Veränderungen festgestellt und alle Tiere überlebten die Beatmungsdauer. Die HVT 1:2-Gruppe zeigte im Vergleich eine verringerte Lungen-Compliance, eine vermehrte Expression von entzündungstypischen Zytokinen und Einwanderung von neutrophilen Granulozyten, sowie deutliche histologische Zeichen des Lungenschadens. Auch hier überlebten alle Tiere die Beatmung von 4 Stunden. Die Tiere der HVT 1:1-Gruppe zeigten eine signifikant schlechtere Oxygenierung, Lungen-Compliance und eine vermehrte Expression proinflammatorischer Zytokine, sowie eine erhöhte Anzahl neutrophiler Granulozyten in Blut und Lunge. In der HVT 1:1-Gruppe kam es zu einer signifikant höheren Mortalität aufgrund der mechanischen Beatmung.
Die Ergebnisse zeigen, dass die Erhöhung der Inspirationszeit und damit das I:E-Verhältnis den mit der maschinellen Beatmung assoziierten Lungenschaden bei Mäusen signifikant verschlimmert. Daraus lässt sich ableiten, dass das Produkt aus Stress/Strain und Inspirationszeit ein entscheidender Faktor in der Pathogenese des VILI im ARDS ist und somit so gering wie möglich gehalten werden sollte. Dementsprechend sollte jeder Anlass bei der Beatmung eines Patienten, die Inspirationszeit zu erhöhen, kritisch hinterfragt werden.
Eine Thrombose ist eine Gefäßerkrankung, bei der eine lokalisierte, intravasale Blutgerinnung zur Bildung eines Thrombus in einem Gefäß führt. Die Aktivierung der
Blutgerinnungskaskade und damit der Gerinnungsfaktoren führt zu einer Bildung sowie Quervernetzung von Fibrin und so zur Entstehung eines Thrombus. Dieser wird
physiologisch über die Fibrinolyse abgebaut. Die Serinprotease PAI-1 inhibiert diese und wirkt somit prothrombotisch. Jüngste Studien haben gezeigt, dass S1P als Schlüsselmolekül des Immunsystems und des Metabolismus auch das Gerinnungssystem beeinflusst und in einer wechselseitigen Beziehung mit dem Gerinnungsfaktor Thrombin und seinen PARs steht. Die S1P-Konzentration im Körper korreliert dabei eng mit dem BMI. Die vorliegende Arbeit beschreibt die Wirkung des Signallipids S1P auf die PAI-1-Expression von Fettzellen und damit die Stellung der Adipozyten bei S1P-vermittelten thrombotischen Ereignissen in vitro. Weiterhin wurde
erstmalig die Wechselwirkung von Thrombin und S1P bei der Produktion von PAI-1 in Fettzellen untersucht. Hierfür wurden 3T3-L1-Fibroblasten in Adipozyten differenziert
und mit S1P stimuliert. Es zeigte sich eine konzentrationsabhängige Steigerung der PAI-1-mRNA. Diese Ergebnisse wurden ebenfalls von anderen Arbeitsgruppen
bestätigt. Der S1P-Effekt ließ sich auch mittels Western Blot-Analyse auf Proteinebene darstellen. Dabei zeigte sich eine starke Steigerung der PAI-1-Expression und
Sekretion von 3T3-L1-Zellen. S1PR-2- und S1PR3-Inhibitoren senkten den S1Pvermittelten Anstieg, sodass S1P über eine S1PR-2- und, bisher in der Literatur noch
nicht beschrieben, auch über eine S1PR-3-Aktivierung einen prothrombotischen Einfluss ausübt. Weiterhin konnte nach Stimulation mit S1P erstmalig eine Expressionssteigerung von PAR-1 und damit eine Wechselwirkung zwischen dem Signalweg von Thrombin und S1P in Adipozyten beobachtet werden. Es wurde die
Hypothese aufgestellt, dass Thrombin über den PAR-1 die Aktivität der Enzyme des S1P-Metabolismus steigert und so über eine endogene S1P-Produktion zu einer zusätzlichen Steigerung von PAI-1 führt. Diese konnte bisher noch nicht bestätigt werden, da lediglich eine geringe, jedoch nicht signifikante Steigerung von PAI-1 nach Thrombin-Stimulation beobachtet werden konnte. Somit ist das Fettgewebe ein wichtiges Bindeglied zwischen dem inflammatorischen Lipid S1P sowie dem Enzym PAI-1 und damit als Gewebe ein bisher stark unterschätzter Einflussfaktor bei der Entstehung und Aufrechterhaltung thrombotischer Ereignisse.
Das in dieser Pilotstudie eingeschlossene Patientenkollektiv umfasste 50 Patienten des Institutes für Diagnostische Radiologie und Neuroradiologie der Universitätsmedizin Greifswald, bei denen eine Indikation zur CT-gestützten interventionellen Therapie mittels PRT oder Facetten-/ISG-Infiltration im Rahmen der Schmerztherapie bei Wirbelsäulenerkrankungen gestellt wurde.
Im Rahmen dieser Pilotstudie wurden nach Studieneinwilligung alle Patienten in einem ärztlichen Aufklärungsgespräch über die bevorstehende medizinische Intervention informiert. Bei 25 Patienten erfolgte diese Aufklärung auf dem bisher üblichen Weg unmittelbar von Angesicht zu Angesicht und bei den anderen 25 Patienten wurde dieses Gespräch mittels eines Videotelefonates innerhalb der Klinik durchgeführt. Aufklärungsinhalte sowie die Möglichkeit dem Arzt Fragen zu stellen oder Ängste zu äußern, waren in beiden Kommunikationswegen identisch. Die Akzeptanz gegenüber dem entsprechenden Aufklärungsmedium sowie die verstandenen Inhalte wurden 24 Stunden nach der durchgeführten Intervention telefonisch in Fragebögen erfasst.
In den Variablen der Akzeptanz „Gesprächsklima“, „Inhaltsübermittlung“, „Fragenbeantwortung“ und „Beziehung“ kann kein signifikanter Unterschied zwischen beiden Aufklärungsmedien nachgewiesen werden.
Die Anzahl an erinnerten Nebenwirkungen ist in der Gruppe „Videotelefonie“ verglichen mit der Gruppe „von Angesicht zu Angesicht“ schwach signifikant höher und die Häufigkeitsverteilung für „Ja“-und „Nein“-Antworten der Variable „Strahlenbelastung“ unterscheidet sich schwach signifikant zugunsten der Aufklärung per Videotelefonie. Es konnten keine signifikanten Unterschiede bezüglich der Häufigkeiten von „Ja“- oder „Nein“-Antworten in den Variablen „Behandlungsziel“ und „Fahrtüchtigkeit“ abhängig von der Aufklärungsart nachgewiesen werden.
In Anbetracht dieser Ergebnisse lässt sich feststellen, dass die Aufklärung per Videotelefonie jener von Angesicht zu Angesicht in den hier untersuchten Punkten nicht unterliegt und somit als gleichwertiges Medium für Aufklärungsgespräche genutzt werden könnte.
Helicobacter (H.) pylori is the most important cause for peptic ulcer disease and a risk factor for gastric carcinoma. How colonization with H. pylori affects the intestinal microbiota composition in humans is unknown. We investigated the association of H. pylori infection with intestinal microbiota composition in the population-based cohort Study-of-Health-in-pomerania (SHip)-tRenD. Anti-H. pylori serology and H. pylori stool antigen tests were used to determine the H. pylori infection status. the fecal microbiota composition of 212 H. pylori positive subjects and 212 matched negative control individuals was assessed using 16S rRNA gene sequencing. H. pylori infection was found to be significantly associated with fecal microbiota alterations and a general increase in fecal microbial diversity. in infected individuals, the H. pylori stool antigen load determined a larger portion of the microbial variation than age or sex. the highest H. pylori stool antigen loads were associated with a putatively harmful microbiota composition. this study demonstrates profound alterations in human fecal microbiota of H. pylori infected individuals. While the increased microbiota diversity associated with H. pylori infection as well as changes in abundance of specific genera could be considered to be beneficial, others may be associated with adverse health effects, reflecting the complex relationship between H. pylori and its human host.
The spatio-temporal reduction and oxidation of protein thiols is an essential mechanism in signal transduction inall kingdoms of life. Thioredoxin (Trx) family proteins efficiently catalyze thiol-disulfide exchange reactions andthe proteins are widely recognized for their importance in the operation of thiol switches. Trx family proteinshave a broad and at the same time very distinct substrate specificity–a prerequisite for redox switching. Despiteof multiple efforts, the true nature for this specificity is still under debate. Here, we comprehensively compare theclassification/clustering of various redoxins from all domains of life based on their similarity in amino acidsequence, tertiary structure, and their electrostatic properties. We correlate these similarities to the existence ofcommon interaction partners, identified in various previous studies and suggested by proteomic screenings. Theseanalyses confirm that primary and tertiary structure similarity, and thereby all common classification systems, donot correlate to the target specificity of the proteins as thiol-disulfide oxidoreductases. Instead, a number ofexamples clearly demonstrate the importance of electrostatic similarity for their target specificity, independent oftheir belonging to the Trx or glutaredoxin subfamilies
The deep-sea tubeworm Riftia pachyptila lacks a digestive system but completely relies on bacterial endosymbionts for nutrition. Although the symbiont has been studied in detail on the molecular level, such analyses were unavailable for the animal host, because sequence information was lacking. To identify host-symbiont interaction mechanisms, we therefore sequenced the Riftia transcriptome, which served as a basis for comparative metaproteomic analyses of symbiont-containing versus symbiont-free tissues, both under energy-rich and energy-limited conditions. Our results suggest that metabolic interactions include nutrient allocation from symbiont to host by symbiont digestion and substrate transfer to the symbiont by abundant host proteins. We furthermore propose that Riftia maintains its symbiont by protecting the bacteria from oxidative damage while also exerting symbiont population control. Eukaryote-like symbiont proteins might facilitate intracellular symbiont persistence. Energy limitation apparently leads to reduced symbiont biomass and increased symbiont digestion. Our study provides unprecedented insights into host-microbe interactions that shape this highly efficient symbiosis.
A 2-day workshop of ORCA and the IADR Cariology Research Group was organized to discuss and reach consensus on definitions of the most commonly used terms in cariology. The aims were to identify and to select the most commonly used terms of dental caries and dental caries management and to define them based on current concepts. Terms related to definition, diagnosis, risk assessment, and monitoring of dental caries were included. The Delphi process was used to establish terms to be considered using the nominal group method favored by consensus. Of 222 terms originally suggested by six cariologists from different countries, a total of 59 terms were reviewed after removing duplicates and unnecessary words. Sixteen experts in cariology took part in the process of reaching consensus about the definitions of the selected caries terms. Decisions were made following thorough “round table” discussions of each term and confirmed by secret electronic voting. Full agreement (100%) was reached on 17 terms, while the definitions of 6 terms were below the agreed 80% threshold of consensus. The suggested terminology is recommended for use in research, in public health, as well as in clinical practice.
A 2-day workshop of ORCA and the IADR Cariology Research Group was organized to discuss and reach consensus on definitions of the most commonly used terms in cariology. The aims were to identify and to select the most commonly used terms of dental caries and dental caries management and to define them based on current concepts. Terms related to definition, diagnosis, risk assessment, and monitoring of dental caries were included. The Delphi process was used to establish terms to be considered using the nominal group method favored by consensus. Of 222 terms originally suggested by six cariologists from different countries, a total of 59 terms were reviewed after removing duplicates and unnecessary words. Sixteen experts in cariology took part in the process of reaching consensus about the definitions of the selected caries terms. Decisions were made following thorough “round table” discussions of each term and confirmed by secret electronic voting. Full agreement (100%) was reached on 17 terms, while the definitions of 6 terms were below the agreed 80% threshold of consensus. The suggested terminology is recommended for use in research, in public health, as well as in clinical practice.
Background: Pancreatic exocrine insufficiency (PEI) is characterized by inadequate production, insufficient secretion, and/or inactivation of pancreatic enzymes, resulting in maldigestion. The aim of this review was to analyze the prevalence and pathophysiology of PEI resulting from gastrointestinal (GI) surgery and to examine the use of pancreatic enzyme replacement therapy (PERT) for effectively managing PEI. Summary: A targeted PubMed search was conducted for studies examining the prevalence and pathophysiology of PEI in patients following GI surgery and for studies assessing the effects of PERT in these patients. PEI is a common complication following GI surgery that can lead to nutritional deficiencies, which may contribute to morbidity and mortality in patients. Timely treatment of PEI with PERT can prevent malnutrition, increase quality of life, and possibly reduce the associated mortality. Treatment of PEI should aim not only to alleviate symptoms but also to achieve significant improvements in nutritional parameters. Dose optimization of PERT is required for effective management of PEI, in addition to regular assessment of nutritional status, appropriate patient education, and reassessment if symptoms return. Key Messages: Difficulties in detecting PEI following GI surgery can result in undiagnosed and untreated maldigestion, leading to metabolic complications and increased morbidity. Both are preventable by early administration and monitoring for optimal doses of PERT.
Background: Pancreatic exocrine insufficiency (PEI) is characterized by inadequate production, insufficient secretion, and/or inactivation of pancreatic enzymes, resulting in maldigestion. The aim of this review was to analyze the prevalence and pathophysiology of PEI resulting from gastrointestinal (GI) surgery and to examine the use of pancreatic enzyme replacement therapy (PERT) for effectively managing PEI. Summary: A targeted PubMed search was conducted for studies examining the prevalence and pathophysiology of PEI in patients following GI surgery and for studies assessing the effects of PERT in these patients. PEI is a common complication following GI surgery that can lead to nutritional deficiencies, which may contribute to morbidity and mortality in patients. Timely treatment of PEI with PERT can prevent malnutrition, increase quality of life, and possibly reduce the associated mortality. Treatment of PEI should aim not only to alleviate symptoms but also to achieve significant improvements in nutritional parameters. Dose optimization of PERT is required for effective management of PEI, in addition to regular assessment of nutritional status, appropriate patient education, and reassessment if symptoms return. Key Messages: Difficulties in detecting PEI following GI surgery can result in undiagnosed and untreated maldigestion, leading to metabolic complications and increased morbidity. Both are preventable by early administration and monitoring for optimal doses of PERT.
Abstract
This article compares the use of calques modelled on anglicisms in different European languages, especially Spanish and German, which do not only show structural differences (e.g. with regard to the use of noun-noun compounds, which are more common in German) but also reflect different attitudes towards English. Aspects covered range from the factors generally favouring the coinage of such replacive forms, to the reasons for the emergence of different types of calques, to variations in their use and challenges concerning their identification. To unravel the main patterns and trends in calquing, this study includes numerous examples from written and oral language, i.e. items of different register affiliation, age, length, and semantic transparency. On a theoretical level, the article incorporates findings from the fields of lexicology, contact linguistics and sociolinguistics.
Patient-reported outcomes (PROs) refer to any report coming directly from patients about how they function or feel in relation to a health condition or its therapy. PROs have been applied in medicine for the assessment of the impact of clinical phenomena. Self-report scales and procedures for assessing physical pain in adults have been developed and used in clinical trials. However, insufficient attention has been dedicated to the assessment of mental pain. The aim of this paper is to outline the implications that assessment of mental pain may entail in psychiatry and medicine, with particular reference to a clinimetric index. A simple 10-item self-rating questionnaire, the Mental Pain Questionnaire (MPQ), encompasses the specific clinical features of mental pain and shows good clinimetric properties (i.e., sensitivity, discriminant and incremental validity). The preliminary data suggest that the MPQ may qualify as a PRO measure to be included in clinical trials. Assessment of mental pain may have important clinical implications in intervention research, both in psychopharmacology and psychotherapy. The transdiagnostic features of mental pain are supported by its association with a number of psychiatric disorders, such as depression, anxiety, eating disorders, as well as borderline personality disorder. Further, addressing mental pain may be an important pathway to prevent and diminish the opioid epidemic. The data summarized here indicate that mental pain can be incorporated into current psychiatric assessment and included as a PRO measure in treatment outcome studies.
40-Year Longitudinal Caries Development in German Adolescents in the Light of New Caries Measures
(2019)
This study assessed the 40-year longitudinal caries development in German adolescents in the light of the sixth National Oral Health Survey in Children (NOHSC, 2016) employing initial DMFT (IDMFT), Significant Caries Index (SiC) and Specific Affected Caries Index (SaC). On the basis of the current NOHSC (randomized cluster selection using school list or regional community school surveys, 55,956 12-year-old sixth-graders examined by 482 calibrated community/study dentists) DMFT, SiC, a novel IDMFT including initial lesions (IT) and the recently introduced SaC were calculated and also recalculated for national and international surveys from the last 4 decades. In 2016, 78.8% of children were caries-free (DMFT = 0), 65.5% including IT lesions. The mean DMFT was 0.44 (single components: DT = 0.14, MT = 0.02, FT = 0.29, IT = 0.52) showing a clear association with the school type as marker for the socio-economic status. The mean number of affected teeth in children with DMFT >0 was 2.07 (SaC) in comparison to almost 9 teeth in the 1970s. The current care index on the tooth level was 66.3%, leaving only 7.7% of children with restorative treatment needs. Longitudinally, a continuous caries decline of more than 80%, including the risk groups (SiC/SaC), to an internationally extremely low level was observed. In conclusion, the National Oral Health Surveys reveal a continuous caries decline to a very low caries level in 12-year-old 6th-graders in Germany even if IT lesions are included (IDMFT). In spite of proportional reductions in the risk groups (SiC/SaC), the polarized caries distribution according to socio-economic parameters reveals the need for targeted preventive programmes.
Objectives: Performing proper toothbrushing is a complicated process for children. Therefore, the aim of this study was to investigate the effect of a smartphone app for improving manual toothbrushing via a gravitation sensor. Methods: In this prospective, controlled, single-blinded, randomized clinical trial, 49 children (mean age 5.1 ± 0.6 years, 27 female) were randomly assigned to test (n = 26) and control (n = 23) groups. All children were provided with manual toothbrushes with an integrated gravitation sensor and they received oral health instructions. Only the children of the test group got an additional smartphone app to visualize and reward proper brushing in form and time. At baseline and recalls after 6 and 12 weeks, plaque and gingival indices (QHI, PBI) were recorded for analysis between the two groups. Results: At baseline, there were no significant differences between the test and control group regarding plaque and gingival indices (QHI: 2.36 ± 0.7 and 2.42 ± 0.8; p = 0.94; PBI: 0.42 ± 0.2 and 0.47 ± 0.3; p = 0.59). At the 6- and 12-week recalls, the test group showed statistically significantly better oral health indices than the controls (6-week recall, QHI: 0.8 ±0.5 and 1.88 ± 0.9; p < 0.001; PBI: 0.08 ± 0.1 and 0.26 ± 0.2; p < 0.001; 12-week recall, QHI: 0.44 ± 0.5 and 1.49 ± 0.7; p < 0.001; PBI: 0.05 ± 0.18 and 0.21 ± 0.1; p < 0.001). Conclusion: The results highlight the enormous possibilities of a toothbrushing application via the smartphone, at least for medium-term oral hygiene improvement in preschool children and even after excluding the app. The long-term effect should also be investigated to exclude the expected novelty effect.
Long-term nationally representative caries data in the primary dentition are rare, but nonetheless central to assess needs in caries prevention and treatment. This study evaluated the prevalence and trends of caries levels in the primary dentition of 6- to 7-year-olds in Germany as a whole and its federal states individually. In 2016, employing a randomized cluster selection, 6- to 7-year-old first graders were included in the National German Oral Health Survey performed regularly since 1994/95. Children were examined by 482 calibrated dentists in all 17 German regions using the WHO criteria for the decayed, missing, and filled teeth (dmft) including the assessment of initial carious lesions (it). In total, 151,555 6- to 7-year-olds were examined. Caries prevalence in the primary dentition dropped from 65% in 1994 to 44% in 2016, while the mean caries experience dropped from 2.89 to 1.73 dmft (dt = 0.74, mt = 0.19, ft = 0.80). When initial lesions were included, the mean caries experience increased to idmft = 2.12 (it = 0.38). In 2016, 49.7% of the examined 6- to 7-year-olds were caries-free including initial lesions. The Care Index at the tooth level was 57.5%, and the Significant Caries Index was 4.84 dmft. Depending on the German region, the mean dmft varied considerably, ranging from 1.37 to 2.31. In conclusion, despite the overall caries decline in 6- to 7-year-olds in Germany, only minor caries reductions were observed over the last decade, with a still existing high proportion of untreated dental decay. This calls for more effective preventive and restorative efforts with focus on the primary dentition in Germany.
Background: Huntington’s disease (HD) is a progressive neurodegenerative disorder. The striatum is one of the first brain regions that show detectable atrophy in HD. Previous studies using functional magnetic resonance imaging (fMRI) at 3 tesla (3 T) revealed reduced functional connectivity between striatum and motor cortex in the prodromal period of HD. Neuroanatomical and neurophysiological studies have suggested segregated corticostriatal pathways with distinct loops involving different cortical regions, which may be investigated using fMRI at an ultra-high field (7 T) with enhanced sensitivity compared to lower fields. Objectives: We performed fMRI at 7 T to assess functional connectivity between the striatum and several chosen cortical areas including the motor and prefrontal cortex, in order to better understand brain changes in the striatum-cortical pathways. Method: 13 manifest subjects (age 51 ± 13 years, cytosine-adenine-guanine [CAG] repeat 45 ± 5, Unified Huntington’s Disease Rating Scale [UHDRS] motor score 32 ± 17), 8 subjects in the close-to-onset premanifest period (age 38 ± 10 years, CAG repeat 44 ± 2, UHDRS motor score 8 ± 2), 11 subjects in the far-from-onset premanifest period (age 38 ± 11 years, CAG repeat 42 ± 2, UHDRS motor score 1 ± 2), and 16 healthy controls (age 44 ± 15 years) were studied. The functional connectivity between the striatum and several cortical areas was measured by resting state fMRI at 7 T and analyzed in all participants. Results: Compared to controls, functional connectivity between striatum and premotor area, supplementary motor area, inferior frontal as well as middle frontal regions was altered in HD (all p values <0.001). Specifically, decreased striatum-motor connectivity but increased striatum-prefrontal connectivity were found in premanifest HD subjects. Altered functional connectivity correlated consistently with genetic burden, but not with clinical scores. Conclusions: Differential changes in functional connectivity of striatum-prefrontal and striatum-motor circuits can be found in early and premanifest HD. This may imply a compensatory mechanism, where additional cortical regions are recruited to subserve functions that have been impaired due to HD pathology. Our results suggest the potential value of functional connectivity as a marker for future clinical trials in HD.
Background: Huntington’s disease (HD) is a progressive neurodegenerative disorder. The striatum is one of the first brain regions that show detectable atrophy in HD. Previous studies using functional magnetic resonance imaging (fMRI) at 3 tesla (3 T) revealed reduced functional connectivity between striatum and motor cortex in the prodromal period of HD. Neuroanatomical and neurophysiological studies have suggested segregated corticostriatal pathways with distinct loops involving different cortical regions, which may be investigated using fMRI at an ultra-high field (7 T) with enhanced sensitivity compared to lower fields. Objectives: We performed fMRI at 7 T to assess functional connectivity between the striatum and several chosen cortical areas including the motor and prefrontal cortex, in order to better understand brain changes in the striatum-cortical pathways. Method: 13 manifest subjects (age 51 ± 13 years, cytosine-adenine-guanine [CAG] repeat 45 ± 5, Unified Huntington’s Disease Rating Scale [UHDRS] motor score 32 ± 17), 8 subjects in the close-to-onset premanifest period (age 38 ± 10 years, CAG repeat 44 ± 2, UHDRS motor score 8 ± 2), 11 subjects in the far-from-onset premanifest period (age 38 ± 11 years, CAG repeat 42 ± 2, UHDRS motor score 1 ± 2), and 16 healthy controls (age 44 ± 15 years) were studied. The functional connectivity between the striatum and several cortical areas was measured by resting state fMRI at 7 T and analyzed in all participants. Results: Compared to controls, functional connectivity between striatum and premotor area, supplementary motor area, inferior frontal as well as middle frontal regions was altered in HD (all p values <0.001). Specifically, decreased striatum-motor connectivity but increased striatum-prefrontal connectivity were found in premanifest HD subjects. Altered functional connectivity correlated consistently with genetic burden, but not with clinical scores. Conclusions: Differential changes in functional connectivity of striatum-prefrontal and striatum-motor circuits can be found in early and premanifest HD. This may imply a compensatory mechanism, where additional cortical regions are recruited to subserve functions that have been impaired due to HD pathology. Our results suggest the potential value of functional connectivity as a marker for future clinical trials in HD.
Die vorliegende Arbeit liefert ein Modell zur Erzeugung PI3K-mutierter Tumoren in der
Mausleber, je nach Mutationsart mit unterschiedlichem onkogenen Potenzial. Bekannte und
bisher unbekannte nachgeschaltete Ziele der PI3K konnten identifiziert werden. Diese
können im Rahmen von künftigen Target Therapien von Bedeutung sein.
Die in diesem Versuch verwendete Methode des hydrodynamischen Gentransfers bietet eine
zuverlässige Möglichkeit, ohne aufwendige Zucht von transgenen Mausstämmen,
verschiedene (Onko)Gene in der Mausleber langfristig zu exprimieren und ihre
Auswirkungen in vivo zu untersuchen.