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Eine Befragung von Kindern und Jugendlichen mit Epilepsie oder Asthma bronchiale über Einfluss und Auswirkungen der chronischen Erkrankung auf Geschwisterkinder und die Geschwisterbeziehung.
Get PDFWenn ein Kind chronisch krank ist, hat dies Einfluss auf das alltägliche Leben, die Familie und damit auch auf die Geschwisterkinder. In der Literatur sind sowohl positive als auch negative Effekte auf die gesunden Geschwisterkinder beschrieben worden. Das stellt behandelnde Ärztinnen und Ärzte vor die Herausforderung, dass sie individuell abschätzen und beurteilen müssen, in welchen Familien die Geschwisterkinder durch die chronische Erkrankung möglicherweise negativ beeinflusst sind. Manche Geschwisterkinder können informiert und für Notfallsituationen geschult werden, andere benötigen psychosoziale Unterstützung und Entlastung. Da sowohl die Patient*innen als auch deren Geschwisterkinder älter werden, sollten die Umstände über die Jahre der Erkrankung hinweg erneut beurteilt werden.
Die Ergebnisse der vorliegenden Arbeit werfen durch den Perspektivwechsel ein neues Licht auf die Geschwister chronisch kranker Kinder. Indem die kranken Kinder selbst befragt wurden, konnte die Situation aus Sicht der Patient*innen dargestellt werden. Hierbei zeigte sich, dass die meisten Geschwisterkinder in die Behandlung der chronischen Erkrankung eingebunden sind. Außerdem geht ein Großteil der Befragten davon aus, dass die Geschwisterkinder wegen der Erkrankung besorgt seien. Manche Patient*innen nehmen negative Auswirkungen wie Ängste und Einschränkungen bei ihren Geschwisterkinder wahr und können diese benennen. Die wenigsten Patient*innen beschreiben Veränderungen in der Geschwisterbeziehung, die durch die chronische Erkrankung entstanden sind.
Um die Ergebnisse, die ausschließlich auf der Sichtweise und den Aussagen der erkrankten Kinder und Jugendlichen beruhen, prüfen und objektivieren zu können, sollten im nächsten Schritt die gesunden Geschwisterkinder befragt werden. So ließe sich eruieren, ob die negativen Auswirkungen auf die Geschwisterkinder und die Geschwisterbeziehung geringer sind als vorangegangene Studien beschrieben, oder ob die Patient*innen diese nicht wahrnehmen oder möglicherweise verdrängen.
Das Bewusstsein für die Geschwisterkinder sollte zukünftig gestärkt werden. Sie sollten als Bestandteil der Familie und im Umgang mit einer chronischen Erkrankung wie Epilepsie oder Asthma bronchiale unbedingt bedacht und berücksichtigt werden
Choose Wisely: Great Variation among Genotypes of Promising Paludiculture Crop Phragmites australis
Get PDFMeasures mitigating the climate crisis, such as paludiculture, which is the agriculture on rewetted peatlands, are urgently needed. The cosmopolitan species Phragmites australis has the potential to be used in paludiculture worldwide but is known for its high intraspecific variation. This raises the questions of whether (i) P. australis genotypes differ even at a regional scale, making them differently well suited for paludiculture and (ii) P. australis performance can be predicted by linking the variation in genotypes to strategies in the plant economics spectrum. Five P. australis genotypes from Mecklenburg-Western Pomerania were cultivated in two 10-month mesocosm experiments along gradients of water level and nutrient addition. We compared growth, morphology (height, growing density), above- and belowground biomass, functional and ecophysiological traits (SLA, LDMC, SRL, RDMC, root porosity, photosynthetic rate) as well as gene expression. Our results demonstrate a high variability of P. australis genotypes even at a regional scale, revealing genotype-specific productivity, morphology, and gene expression and implying that the selection of suitable genotypes will be crucial for the success of a paludiculture. However, trait covariation did not indicate distinct plant economic strategies to predict genotype performance. Instead, large-scale genotype trials are needed to select suitable genotypes for paludiculture
Visual Tooth Color Determination with Different Reference Scales as an Exercise in Dental Students’ Education
Get PDFVisual color determination (VCD) requires color competence and individual training. The aim of this study was to evaluate the deviations in students’ VCD with two different reference scales. The research hypothesis was that none of the color references would provide a better result. Participants evaluated nine templates randomly using two reference scales (VITA-classical (VC) and 3D-Master-Toothguide (3DM_TG)). The color distance to the chosen color (ΔEab) was calculated in the CIELAB 2000. The sum’s changes in the parameters (LCh°) represented the target variable. Results were evaluated with non-parametric, rank-scaled methods, utilizing the median with a 25%-75% quartile. The significance level (α = 0.05) is determined using the Student’s t-test. The mean ± 95%CI (SD) was −1.27 ± −1.09 (3.18); the median ΔE00 was −1.49 (−1.97; 0.96) for dC3DM_TG. The determination with VC showed noticeable differences (dCVC), with a mean ΔE00 of 0.00 ± 0.00 (2.20) and a median ΔE00 of 0.00 (1.17; 1.71). The standard error was 0.19 for the dCVC and 0.27 for the dC3DM_TG. dC3DM_TG vs. dCVC showed significant differences at p < 0.001. The dental student’s VCD resulted in color deviations, regardless of the reference template used. The color deviations in hue and chroma were comparable, regardless of the reference scale. VCD’s early implementation in dental education is useful to avoid shade misjudgments and potentially expensive remakes of dentures
Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population
Get PDFThe aim of this study was to disentangle the effects of various genetic factors on hippocampal subfield volumes using three different approaches: a biologically driven candidate gene approach, a hypothesis-free GWAS approach, and a polygenic approach, where AD risk alleles are combined with a polygenic risk score (PRS). The impact of these genetic factors was investigated in a large dementia-free general population cohort from the Study of Health in Pomerania (SHIP, n = 1806). Analyses were performed using linear regression models adjusted for biological and environmental risk factors. Hippocampus subfield volume alterations were found for APOE ε4, BDNF Val, and 5-HTTLPR L allele carriers. In addition, we were able to replicate GWAS findings, especially for rs17178139 (MSRB3), rs1861979 (DPP4), rs7873551 (ASTN2), and rs572246240 (MAST4). Interaction analyses between the significant SNPs as well as the PRS for AD revealed no significant results. Our results confirm that hippocampal volume reductions are influenced by genetic variation, and that different variants reveal different association patterns that can be linked to biological processes in neurodegeneration. Thus, this study underlines the importance of specific genetic analyses in the quest for acquiring deeper insights into the biology of hippocampal volume loss, memory impairment, depression, and neurodegenerative diseases
Intragastric Carbon Dioxide Release Prolongs the Gastric Residence Time of Postprandially Administered Caffeine
Get PDFSparkling water is said to increase gastric motility by the release of carbon dioxide, thereby potentially affecting the pharmacokinetics of orally administered drugs. The hypothesis of the present work was that the induction of gastric motility by intragastric release of carbon dioxide from effervescent granules could promote the mixing of drugs into the chyme under postprandial conditions, resulting in a prolonged drug absorption. For this purpose, an effervescent and a non-effervescent granule formulation of caffeine as a marker for gastric emptying were developed. In a three-way crossover study with twelve healthy volunteers, the salivary caffeine pharmacokinetics, after administration of the effervescent granules with still water and the administration of the non-effervescent granules with still and sparkling water, were investigated after intake of a standard meal. While the administration of the effervescent granules with 240 mL of still water led to a significantly prolonged gastric residence of the substance compared to the administration of the non-effervescent granules with 240 mL still water, the application of the non-effervescent granules with 240 mL sparkling water did not prolong gastric residence via mixing into caloric chyme. Overall, the mixing of caffeine into the chyme following the administration of the effervescent granules did not seem to be a motility mediated process
Evaluation of Pharmacobezoar Formation from Suspensions of Spray-Dried Amorphous Solid Dispersions: An MRI Study in Rats
Get PDFSpray-dried amorphous solid dispersions of new chemical entities and pH-dependent soluble polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were found to form solid agglomerates in the gastrointestinal tract of rodents after oral administration. These agglomerates, referring to descriptions of intra-gastrointestinal aggregated oral dosage forms termed pharmacobezoars, represent a potential risk for animal welfare. Previously, we introduced an in vitro model to assess the agglomeration potential of amorphous solid dispersions from suspensions and how it can be reduced. In this work, we investigated if the in vitro effective approach of viscosity enhancement of the vehicle used to prepare suspensions of amorphous solid dispersions could reduce the pharmacobezoar formation potential following repeated daily oral dosing to rats as well. The dose level of 2400 mg/kg/day used in the main study was determined in a dose finding study carried out in advance. In the dose finding study, MRI investigations were carried out at short time intervals to gain insights into the process of pharmacobezoar formation. Whereas MRI investigations underlined the importance of the forestomach for the formation of pharmacobezoars, viscosity enhancement of the vehicle reduced the incidence of pharmacobezoars, delayed the onset of pharmacobezoar formation and reduced the overall mass of pharmacobezoars found at necropsy
Cold physical plasma treatment optimization for improved bone allograft processing
Get PDFIn musculoskeletal surgery, the treatment of large bone defects is challenging and can require the use of bone graft substitutes to restore mechanical stability and promote host-mediated regeneration. The use of bone allografts is well-established in many bone regenerative procedures, but is associated with low rates of ingrowth due to pre-therapeutic graft processing. Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen (O2) and nitrogen (N2) species, is suggested to be advantageous in biomedical implant processing. CPP is a promising tool in allograft processing for improving surface characteristics of bone allografts towards enhanced cellularization and osteoconduction. However, a preclinical assessment regarding the feasibility of pre-therapeutic processing of allogeneic bone grafts with CPP has not yet been performed. Thus, this pilot study aimed to analyze the bone morphology of CPP processed allografts using synchrotron radiation-based microcomputed tomography (SR-µCT) and to analyze the effects of CPP processing on human bone cell viability and function. The analyzes, including co-registration of pre- and post-treatment SR-µCT scans, revealed that the main bone morphological properties (total volume, mineralized volume, surface area, and porosity) remained unaffected by CPP treatment if compared to allografts not treated with CPP. Varying effects on cellular metabolic activity and alkaline phosphatase activity were found in response to different gas mixtures and treatment durations employed for CPP application. It was found that 3 min CPP treatment using a He + 0.1% N2 gas mixture led to the most favourable outcome regarding a significant increase in bone cell viability and alkaline phosphatase activity. This study highlights the promising potential of pre-therapeuthic bone allograft processing by CPP prior to intraoperative application and emphasizes the need for gas source and treatment time optimization for specific applications
TLR4 sensing of IsdB of Staphylococcus aureus induces a proinflammatory cytokine response via the NLRP3-caspase-1 inflammasome cascade
Get PDFThe iron-regulated surface determinant protein B (IsdB) of Staphylococcus aureus is involved in the acquisition of iron from hemoglobin. Moreover, IsdB elicits an adaptive immune response in mice and humans. Here, we show that IsdB also has impact on innate immunity. IsdB induces the release of proinflammatory cytokines, including IL-6 and IL-1β, in innate immune cells of humans and mice. In silico analysis and thermophoresis show that IsdB directly binds to TLR4 with high affinity. TLR4 sensing was essential for the IsdB-mediated production of IL-6, IL-1β, and other cytokines as it was abolished by blocking of TLR4-MyD88-IRAK1/4-NF-κB signaling. The release of IL-1β additionally required activation of the NLRP3 inflammasome. In human monocytes infected with live S. aureus, IsdB was necessary for maximal IL-1β release. Our studies identify S. aureus IsdB as a novel pathogen-associated molecular pattern that triggers innate immune defense mechanisms
How to quantify factors degrading DNA in the environment and predict degradation for effective sampling design
Get PDFExtra-organismal DNA (eoDNA) from material left behind by organisms (noninvasive DNA, e.g., feces, hair) or from environmental samples (eDNA, e.g., water, soil) is a valuable source of genetic information. However, the relatively low quality and quantity of eoDNA, which can be further degraded by environmental factors, results in reduced amplification and sequencing success. This is often compensated for through cost- and time-intensive replications of genotyping/sequencing procedures. Therefore, system- and site-specific quantifications of environmental degradation are needed to maximize sampling efficiency (e.g., fewer replicates, shorter sampling durations), and to improve species detection and abundance estimates. Using 10 environmentally diverse bat roosts as a case study, we developed a robust modeling pipeline to quantify the environmental factors degrading eoDNA, predict eoDNA quality, and estimate sampling-site-specific ideal exposure duration. Maximum humidity was the strongest eoDNA-degrading factor, followed by exposure duration and then maximum temperature. We also found a positive effect when hottest days occurred later. The strength of this effect fell between the strength of the effects of exposure duration and maximum temperature. With those predictors and information on sampling period (before or after offspring were born), we reliably predicted mean eoDNA quality per sampling visit at new sites with a mean squared error of 0.0349. Site-specific simulations revealed that reducing exposure duration to 2–8 days could substantially improve eoDNA quality for future sampling. Our pipeline identified high humidity and temperature as strong drivers of eoDNA degradation even in the absence of rain and direct sunlight. Furthermore, we outline the pipeline's utility for other systems and study goals, such as estimating sample age, improving eDNA-based species detection, and increasing the accuracy of abundance estimates
Spezifische ω-Transaminasen zur Herstellung von enantiomerenreinen β- und γ-Aminosäuren
Get PDFIn den letzten Jahren gewannen ω-Transaminasen zunehmend an Bedeutung. Ihr breites Substratspektrum, das sowohl Aminosäuren als auch Amine umfasst, macht sie interessant für biotechnologische Anwendungen. Im Gegensatz zu α-Aminotransferasen sind ω-Aminotransferasen nicht auf α-Aminosäuren als Aminodonor bzw. α-Ketosäuren als Aminoakzeptoren beschränkt. Auch sind einige ω-Transaminasen in der Lage, Aldehyde oder Ketone zu aminieren. Dadurch sind sie vielseitig einsetzbar. Seit ihrer Entdeckung wurden ω-Transaminasen in einer Vielzahl von Organismen nachgewiesen. Viele dieser Enzyme stammen aus Pilzen und Bakterien. Da es ständig Bedarf an neuen Transaminasen gibt, wurden verschiedene Organismen auf das Vorhandensein solcher Enzyme untersucht. Die Hefe Blastobotrys raffinosifermentans LS3 ist einer dieser Organismen. Für diese Hefe existiert bereits eine Vielzahl biotechnologischer Anwendungen, was unter anderem an ihren vielseitigen physiologischen Möglichkeiten liegt. Um das Spektrum dieses Stammes noch zu erweitern, wurde sein Genom auf ORFs gescannt. Die ermittelten ORFs wurden translatiert und die so erhaltenen, theoretischen Proteine in einer Proteindatenbank gespeichert. Die Einträge dieser Datenbank wurden einem „hmmerscan“ (hmm ist kurz für „hidden Markov model“) unterzogen. Dabei werden die Proteine in sogenannte Pfams, kurz für Proteinfamilien, eingeteilt. Drei Proteine wurden der Familie PF00202.21 zugeordnet. Das ist die sogenannte Aminotran_3 Familie. In dieser Familie befinden sich eukaryotische ω-Transaminasen. Die Gene brota1, brota2 und brota3 codieren für diese Enzyme. Jeweils eins der Gene wurde in den Vektor XPLOR®3 kloniert, damit die potentiellen ω-Transaminasen in B. raffinosifermentans G1212 [aleu2 atrp1:ALEU2] [1] überexprimiert werden können. Eine Besonderheit von BroTA1 ist, dass es neben der Aminotran_3 Domäne noch eine AAA Domäne aufweist. Deshalb ist es mit etwa 85 kDa auch deutlich größer als die meisten ω-Transaminasen, die meist zwischen 45 und 50 kDa liegen. BroTA2 und BroTA3 beinhalten nur die Aminotran_3 Domäne. Alle drei Enzyme zeigen niedrige Aktivität bei der kinetischen Auflösung racemischer β-Aminosäuren.
Neben den eukaryotischen ω-Transaminasen wurden auch einige bakterielle Enzyme untersucht. Literatursuche und das Screenen der Stammsammlung der Arbeitsgruppe Hefegenetik des Leibniz-Instituts für Pflanzengenetik und Kulturpflanzenforschung führten zu mehreren potentiellen bakteriellen ω-Transaminasen. Das zu Beginn dieser Arbeit noch als hypothetisches Protein bezeichnete Enzym von Variovorax boronicumulans hat sich als ω-Transaminase herausgestellt. Das Enzym wurde detailliert hinsichtlich des Substratspektrums und seiner biochemischen Eigenschaften charakterisiert. Es handelt sich hierbei um eine ω-Transaminase mit β-Aktivität. Diese Transaminase akzeptiert sowohl aromatische als auch aliphatische β-Aminosäuren als Substrat. Sequenzvergleiche dieses Enzyms mit anderen ω-Transaminasen, die nur aliphatische Aminosäuren akzeptieren, führten zu tieferen Einblicken in konservierte Bereiche dieser beiden Gruppen von ω-Transaminasen.
Der dritte Ansatz war das Anpassen einer bekannten ω-Transaminase des thermophilen Bakteriums Sphaerobacter thermophilus an ein potentielles Motiv für aromatische ω-Transaminasen. Dadurch sollte die Aktivität des Enzyms erhöht werden. Dieser Ansatz führte zu 7 Varianten des Enzyms mit höherer Aktivität als der Wildtyp. Durch diese Versuche wurden einige für die Transferaseaktivität wichtige Aminosäurereste offenbart. So hat sich zum Beispiel herausgestellt, dass N70 offenbar wichtig für den Umsatz von γ-Aminosäuren ist, da ein Austausch gegen Glutamat zu einer verminderten Aktivität mit γ-Aminopentansäure führte.In recent years, ω-transaminases have become increasingly important. Their wide range of substrates, which includes both amino acids and amines, makes them interesting for biotechnological applications. In contrast to α-aminotransferases, ω-aminotransferases are not limited to α-amino acids as amino donors or α-keto acids as amino acceptors. Some ω-transaminases are also able to aminate aldehydes or ketones. This makes them versatile. Since their discovery ω-transaminases have been identified in a variety of organisms. Many of these enzymes derive from fungi and bacteria. Since there is a constant need for new transaminases, various organisms have been examined for the presence of such enzymes. The yeast Blastobotrys raffinosifermentans is one of these organisms. A large number of biotechnological applications already exist for this yeast. To expand the spectrum of this strain, its genome was scanned for ORFs. The determined ORFs were translated and the theoretical proteins obtained in this way were stored in a protein data base. The entries in this data base were subjected to a hmmerscan (hmm is short for “hidden Markov model”). The proteins are assigned to so-called pfams, short for protein families. Three proteins have been assigned to family PF00202.21. This is the so-called Aminotran_3 family. In this family are eukaryotic ω-transaminases. The genes brota1, brota2 and brota3 code for these enzymes. One gene each was cloned into the vector XPLOR®3 so that the potential ω-transaminases in B. raffinosifermentans G1212 [aleu2 atrp1:ALEU2] [1] can be overexpressed. A special feature of BroTA1 is that it has a AAA domain in addition to the Aminotran_3 domain. Therefore, at about 85 kDa, it is also significantly larger than most ω-transaminases, which are usually between 45 and 50 kDa. BroTA2 and BroTA3 contain only the aminotran_3 domain. All three enzymes show low activity in the kinetic resolution of racemic β-amino acids.
In addition to the eukaryotic ω-transaminases, some bacterial enzymes have also been studied. A literature search and screening of the strain collection of the yeast genetics group of the Leibniz-institute for plant genetics and crop science led to several potential bacterial ω-transaminases. The enzyme from Variovorax boronicumulans, which was still described as a hypothetical protein at the beginning of this work, turned out to be an ω-transaminase. The enzyme was characterized in detail with regard to the substrate spectrum and its biochemical properties. It is an ω-transaminase with β-activity. This transaminase accepts both aromatic and aliphatic β-amino acids as a substrate. Sequence comparisons of this enzyme with other ω-transaminases that only accept aliphatic amino acids led to deeper insights into conserved regions of these two groups of ω-transaminases.
The third approach was the adaptation of a known ω-transaminase from the thermophilic bacterium Sphaerobacter thermophilus to a potential motif for aromatic ω-transaminases. This should increase the activity of the enzyme. This approach resulted in 7 variants of the enzyme with higher activity than the wild type. These experiments revealed some amino acid residues important for transferase activity. For example, it turned out that N70 is apparently important for the conversion of γ-amino acids, since replacing it with glutamate led to reduced activity with γ-aminopentanoic acid