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Im Rahmen dieser publikationsbasierten Dissertation wurden drei wissenschaftliche Arbeiten veröffentlicht. Als Erstautorenschaft wurde 2022 die Arbeit “Effectiveness of High-intensity Focused Ultrasound (HIFU) Therapy of Solid and Complex Benign Thyroid Nodules - A Long-term Follow up Two-center Study.” im Journal “Experimental and Clinical Endocrinology & Diabetes” veröffentlicht. Im Folgenden wird der Inhalt dieser Arbeit dargelegt. Ein kurzer Überblick über die Ergebnisse der anderen beiden mitpublizierten Arbeiten findet sich im Kapitel „Weitere Ergebnisse der Arbeitsgruppe“.
Durch die hohe Prävalenz benigner Schilddrüsenknoten sind deren Behandlungsalternativen von großem wissenschaftlichem Interesse. Dabei bildet die nebenwirkungsarme, minimalinvasive Thermoablation mittels high-intensity focused ultrasound (HIFU) eine attraktive Alternative zu herkömmlichen Verfahren wie der Schilddrüsenchirurgie oder der Radioiodtherapie. Bei der HIFU-Echotherapie werden die Schilddrüsenknoten auf 80 - 90 Grad Celsius erhitzt, sodass eine irreversible Koagulationsnekrose entsteht. Um den Therapieprozess und die Indikationsstellung von HIFU bei benignen Schilddrüsenknoten zu optimieren, ist es notwendig, genaue Studien durchzuführen.
Ziel der vorliegenden bizentrischen Langzeitstudie war, die Effektivität von HIFU-Echotherapien bei benignen Schilddrüsenknoten zu evaluieren und erstmalig den Einfluss der Knotenmorphologie auf den Therapieerfolg zu untersuchen. Vor der Therapie und in regelmäßigen Intervallen nach der Therapie wurden die Größe und die Morphologie der Schilddrüsenknoten mittels Ultraschall dokumentiert. In der retrospektiven Studie wurden Daten von 58 Patienten ausgewertet. Dabei wurde die Gesamtpopulation in eine Gruppe mit soliden und in eine Gruppe mit komplexen Knoten eingeteilt. Die durchschnittliche prozentuale Volumenreduktion in jeder Gruppe wurde mit dem Wilcoxon-Signed-Rank Test statistisch analysiert.
Die Gesamtpopulation zeigte eine Volumenreduktion der zuvor abladierten Knoten von 38.86 % nach 3 Monaten (Spannweite: 4.03 % - 91.16 %, p < 0.0001, n = 25), 42.7 % nach 6 Monaten (Spannweite: 7.36 % - 93.2 %, p < 0.0001, n = 18), 62.21 % nach 9 Monaten (Spannweite: 12.88 % - 93.2 %, p = 0.0078, n = 8) und 61.42 % nach 12 Monaten (Spannweite: 39.39 % - 93.2 %, p > 0.05, n = 4). Die soliden Knoten hatten eine Volumenreduktion von 49.98 % nach 3 Monaten (Spannweite: 4.03 % - 91.16 %, p = 0.0001, n = 15), 46.40 % nach 6 Monaten (Spannweite: 7.36 % - 93.2 %, p = 0.001, n = 11), 65.77 % nach 9 Monaten (Spannweite: 39.39 % - 93.2 %, p = 0.0156, n = 7) und 63.88 % nach 12 Monaten (Spannweite: 39.39 % - 93.2%, p > 0.05, n = 2). Komplexe Knoten hatten eine Volumenreduktion von 35.2 % nach 3 Monaten (Spannweite: 5.85 % - 68.63 %, p = 0.002, n = 10), 36.89 % nach 6 Monaten (Spannweite: 12.23 % - 68.63 %, p = 0.0156, n = 7) und 63.64 % nach 12 Monaten (Spannweite: 52,38 % - 73.91 %, p > 0.05, n = 2).
In der vorliegenden bizentrischen Langzeitstudie wurde deutlich, dass HIFU-Echotherapie eine effektive Behandlungsoption benigner Schilddrüsenknoten ist. Erstmalig gezeigt wurde der Trend, dass solide Knoten besser auf HIFU-Echotherapie ansprechen als komplexe Knoten.
Anhand der gewonnenen Ergebnisse und der neuen Erkenntnisse zum Einfluss der Knotenmorphologie auf die HIFU-Echotherapie benigner Schilddrüsenknoten kann HIFU als Therapieoption besser bewertet werden. Eine differenziertere Indikationsstellung in Bezug auf solide und komplexe Knoten wird ermöglicht und die HIFU-Echotherapie kann gegen andere thermoablative Verfahren abgewogen werden.
Highlights
• An airport can result in high particle concentrations in a distant residential area.
• The particle size distribution indicated the airport as the main source of particles.
• Lower air traffic during the COVID-19 pandemic lead to lower particle concentrations.
• The particle concentration showed high temporal variations.
Abstract
Exposure to ultrafine particles has a significant influence on human health. In regions with large commercial airports, air traffic and ground operations can represent a potential particle source. The particle number concentration was measured in a low-traffic residential area about 7 km from Frankfurt Airport with a Condensation Particle Counter in a long-term study. In addition, the particle number size distribution was determined using a Fast Mobility Particle Sizer.
The particle number concentrations showed high variations over the entire measuring period and even within a single day. A maximum 24 h-mean of 24,120 cm−3 was detected. Very high particle number concentrations were in particular measured when the wind came from the direction of the airport. In this case, the particle number size distribution showed a maximum in the particle size range between 5 and 15 nm. Particles produced by combustion in jet engines typically have this size range and a high potential to be deposited in the alveoli. During a period with high air traffic volume, significantly higher particle number concentrations could be measured than during a period with low air traffic volume, as in the COVID-19 pandemic.
A large commercial airport thus has the potential to lead to a high particle number concentration even in a distant residential area. Due to the high particle number concentrations, the critical particle size, and strong concentration fluctuations, long-term measurements are essential for a realistic exposure analysis.
Highlights
• Since there is only a low level of evidence, it is difficult to agree on state-of-the-art standards or to provide recommendations and guidelines.
• The value of combining several monitoring devices for dual or triple guidance must be challenged.
• The principle of fascial plane blocks is suitable to avoid traumatic needle-to-nerve contact. However, local toxicity must be regarded as a possible mechanism for nerve injuries.
• Block procedures might be conducted during sedation or general anesthesia when considering the individual patients' clinical situations and the expertise of the anesthesiologist.
• The quality of ultrasound equipment and education provided by the corresponding anesthesia department is highly relevant
• Mexican and German populations of L. sericata differ in their development times.
• Mexican L. sericata had a shorter development time at 20°C than German flies.
• At 30 °C, German L. sericata pupariated and eclosed earlier than the Mexican flies.
• Differences in study design make the comparison of developmental studies difficult.
Abstract
The cosmopolitan blow fly Lucilia sericata is often used in forensic case work for estimating the minimum postmortem interval (PMImin). For this, the age of immature specimens developing on the dead body is calculated by measuring the time taken to reach the sampled developmental stage at a given temperature. To test whether regional developmental data of L. sericata is valid on a global scale, the time taken to reach different developmental stages was compared between a population from Mexico and one from Germany at two different constant temperatures.
The German population of L. sericata was collected in Frankfurt/Main, while the Mexican population originated near Oaxaca de Juarez and was transported to Germany in the larval stage. Only the F1 generation was used to avoid adaption of the Mexican flies. Eggs were immediately placed at 20 °C and 30 °C. Five times 30 freshly eclosed larvae per replicate (n = 5) were then transferred to a cup of minced meat in separate containers. The larvae were checked every 8 h for migration, pupariation or emergence of adult flies. The time at which the first individual and 50 % of the specimens per container entered each of these stages, was recorded.
Significant differences in the time of development between the two populations were observed at both temperatures. At 20 °C, the first specimens of the Mexican population reached all developmental stages a little (< 1 day to < 2 days) earlier than the German L. sericata. At 30 °C, the Mexican flies also reached the post-feeding stage slightly earlier (0.2 days). However, at 30 °C, the German flies started pupariation significantly earlier (after 5 days) than the Mexican flies (6.9 days) and the adults from Germany also emerged earlier (10.5 days compared to 13.1 days). The same pattern was observed when looking at 50 % of the total number of specimens per container. A comparison with previously published developmental studies was difficult as the experimental design varied widely between studies. However, the results were within the range of most studies. Our study has shown that age estimation can vary widely depending on the population on which the reference data used for the calculations are based. This highlights the importance of using local and population-specific developmental data for estimating the age of blow flies in case work.
Marjan van den Akker, Gesundheitswissenschaftlerin und Epidemiologin : Goethe, Deine Forscher
(2024)
Highlights
• Out of the six edible pumpkin seeds found in Cameroonian C. sativus showed most potent anti-proliferative effects on prostate cells.
• Its oil conserved almost all the effects of raw seeds and prevented benign prostatic hyperplasia (BPH).
• It exhibited potent anti-inflammatory activities in rat with BPH.
Abstract
Pumpkin seeds are claimed to treat prostate tumour/cancer. The in vitro (ability to inhibit cell growth through MTT assay) and in vivo (ability to prevent testosterone-induced BPH in rats at the doses of 125, 250, 500 and 1000 mg/kg BW) of six edible pumpkin seeds found in Cameroonian were assessed. The endpoints were cell growth arrest, prostate mass and volume, prostatic epithelium height, prostatic proteins, prostate specific antigen (PSA) and inflammatory cytokines. In vitro, C. sativus seeds exhibited the most potent antiproliferative effects on DU145 and PC3 prostate cancer cells and its oil conserved almost all the effects of raw seeds. Further, it prevented the increased of prostate relative mass and volume, prostate epithelium height, PSA and testosterone dose-dependently compared to normal rats. This effect is thought to be mediated through antiandrogenic, estrogenic and anti-inflammatory activities, evidenced by a decreased in IL-1β, IL-6 and TNFα level. Overall, this results justify its traditional use.
Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Beyond well-established difficulties with working memory in individuals with attention deficit hyperactivity disorder (ADHD), evidence is emerging that other memory processes may also be affected. We investigated, first, which memory processes show differences in adults and adolescents with ADHD in comparison to control participants, focusing on working and short-term memory, initial learning, interference, delayed and recognition memory. Second, we investigated whether ADHD severity, co-occurring depressive symptoms, IQ and physical fitness are associated with the memory performance in the individuals with ADHD.
We assessed 205 participants with ADHD (mean age 25.8 years, SD 7.99) and 50 control participants (mean age 21.1 years, SD 5.07) on cognitive tasks including the digit span forward (DSF) and backward (DSB), the Rey Auditory Verbal Learning Test (RAVLT), and the vocabulary and matrix reasoning subtests of the Wechsler Abbreviated Scale of Intelligence. Participants with ADHD were additionally assessed on ADHD severity, depression symptoms and cardiorespiratory fitness. A series of regressions were run, with sensitivity analyses performed when variables were skewed.
ADHD-control comparisons were significant for DSF, DSB, delayed and recognition memory, with people with ADHD performing less well than the control participants. The result for recognition memory was no longer significant in sensitivity analysis. Memory performance was not associated with greater ADHD or depression symptoms severity. IQ was positively associated with all memory variables except DSF. Cardiorespiratory fitness was negatively associated with the majority of RAVLT variables.
Individuals with ADHD showed difficulties with working memory, short-term memory and delayed memory, as well as a potential difficulty with recognition memory, despite preserved initial learning.
Highlights
• High resolution profile of C. pipiens' sugar diet has been obtained using UHPLC-MS.
• Artificial feeding using ornamental plants provides similar sugar profiles as observed in field collected mosquitoes.
• Metabolomic profiling found secondary metabolites and pollutants of anthropogenic use.
Abstract: Culex pipiens (Linnaeus, 1758) mosquitoes search plant sources of sugars to cope with the energetic demand of various physiological processes. The crop as part of the digestive system is devoted to the storage of sugar-based meal obtained from various nectars sources. The profiling of sugars and metabolites in the Culex pipiens’ crop is scarce, and only few studies used Liquid Chromatography – Mass Spectrometry (LC-MS), which provides broad detection for biomonitoring environmental substances and even contaminants in the sugar diet of mosquitoes populations.
Therefore, sugar and metabolite profiling were performed on crops obtained from mosquitoes exposed to plant nectar under laboratory or natural conditions by Ultra High-Performance LC-MS (UHPLC-MS). This method allowed us a precise quantitative and qualitative identification of sugar diet and associated environmental compounds in the crop of the mosquito C. pipiens. Under laboratory condition, mosquitoes were allowed to feed on either glucose solution, commercially-available flowers or field collected flowers. In addition, we collected mosquitoes from the field to compare those crop metabolomes with metabolome patterns occurring after nectar feeding in the lab.
The sugar quantities and quality obtained from the crops of mosquitoes collected in the field were similar to those crops obtained from mosquitoes that fed on commercially-available flowers and from field collected flowers with a limit of detection of 10 μg/L for sucrose, glucose and sucrose. Next to sugar compounds, we identified 2 types of amino acids, 12 natural products, and 9 pesticides.
Next to the diversity of sugar compounds, we could confirm that secondary metabolites and environmental pollutants are typically up taken from floral nectar sources by C. pipiens. The in-depth knowledge on mosquito–plant interactions may inspire the development and further optimization of mosquito trap systems and arboviral surveillance systems.
The lipid content of skin plays a determinant role in its barrier function with a particularly important role attributed to linoleic acid and its derivatives. Here we explored the consequences of interfering with the soluble epoxide hydrolase (sEH) on skin homeostasis. sEH; which converts fatty acid epoxides generated by cytochrome P450 enzymes to their corresponding diols, was largely restricted to the epidermis which was enriched in sEH-generated diols. Global deletion of the sEH increased levels of epoxides, including the linoleic acid-derived epoxide; 12,13-epoxyoctadecenoic acid (12,13-EpOME), and increased basal keratinocyte proliferation. sEH deletion (sEH-/- mice) resulted in thicker differentiated spinous and corneocyte layers compared to wild-type mice, a hyperkeratosis phenotype that was reproduced in wild-type mice treated with a sEH inhibitor. sEH deletion made the skin sensitive to inflammation and sEH-/- mice developed thicker imiquimod-induced psoriasis plaques than the control group and were more prone to inflammation triggered by mechanical stress with pronounced infiltration and activation of neutrophils as well as vascular leak and increased 12,13-EpOME and leukotriene (LT) B4 levels. Topical treatment of LTB4 antagonist after stripping successfully inhibited inflammation and neutrophil infiltration both in wild type and sEH-/- skin. While 12,13-EpoME had no effect on the trans-endothelial migration of neutrophils, like LTB4, it effectively induced neutrophil adhesion and activation. These observations indicate that while the increased accumulation of neutrophils in sEH-deficient skin could be attributed to the increase in LTB4 levels, both 12,13-EpOME and LTB4 contribute to neutrophil activation. Our observations identify a protective role of the sEH in the skin and should be taken into account when designing future clinical trials with sEH inhibitors.