The 10 most recently published documents
Die Diagnose von Pankreaserkrankungen kann aufgrund der versteckten Lage des Organs im Körper und des Mangels an eindeutigen Symptomen und zuverlässigen Biomarkern mitunter sehr schwierig sein. Die dieser Arbeit zugrunde liegenden Publikationen, an denen der Autor dieser Arbeit mitgewirkt hat, zeigen, dass Pankreaserkrankungen die Konzentrationen einiger im Blut zirkulierender Stoffwechselprodukte auf typische Weise beeinflussen. Deshalb stellt Metabolomik einen vielversprechenden Ansatz zur Identifikation von Biomarkern zur Diagnose von Pankreaserkrankungen dar.
Bislang existiert kein blutbasierter Biomarker zur Diagnose von chronischer Pankreatitis. In der Publikation von Adam, Beyer, et al. (2021) wurde nun in Plasmaproben eine Biomarkersignatur aus 8 Metaboliten identifiziert, die mit hoher Genauigkeit Patienten mit chronischer Pankreatitis von Kontrollpatienten ohne pankreatische Erkrankungen differenziert. Die 8 Metabolite decken dabei verschiedene Charakteristika der pankreatischen Veränderungen ab, die zusammen genommen für chronische Pankreatitis typisch sind. Es handelt sich um die erste Publikation, in der ein solcher Biomarker nicht nur identifiziert, sondern auch in prospektiv gesammelten Proben unabhängiger, großer Kohorten validiert wurde. Die Klassifikation der Patienten durch den Biomarker war dabei in den Validierungskohorten ebenso zuverlässig wie in der Identifikationskohorte und zeigte sich auch bei einem Matrixwechsel in Serumproben als robust.
Bei Beschwerden, die auf eine Pankreaserkrankung hindeuten, zeigen sich in der medizinischen Bildgebung nicht selten unklare Raumforderungen, die durch ein Pankreaskarzinom oder chronische Pankreatitis bedingt sein könnten. Das Protein CA 19-9 ist ein blutbasierter Marker für Pankreaskarzinome und gilt als Goldstandard, allerdings liegen die Werte auch bei chronischer Pankreatitis oft erhöht vor. In der Publikation von Mahajan et al. (2022) wurde eine zuvor veröffentlichte Signatur zur Differenzierung dieser Erkrankungen abgeändert, um technisch leichter umsetzbar zu sein. Die 12 Metabolite der verbesserten Signatur können in einem einzigen analytischen Verfahren bestimmt werden. Die hohe Genauigkeit des Biomarkers konnte anhand einer Kohorte mit prospektiv gesammelten Proben bestätigt werden. Die Signatur besticht zudem durch Robustheit gegenüber typischen Störfaktoren und einer hohen Performance für Patienten, die genetisch bedingt kein CA 19-9 produzieren.
Die in Adam, Beyer, et al. (2021) und Mahajan et al. (2022) vorgestellten Signaturen stellen die Grundlagen für die Entwicklung diagnostischer Tests auf metabolomischer Basis dar. Mit diesen Tests wird man erstmals in der klinischen Routine anhand einer Blutprobe chronische Pankreatitis diagnostizieren beziehungsweise PDAC mit hoher Genauigkeit ausschließen können.
Weitere Studien zu blutbasierten Biomarkern in Patientengruppen mit erhöhtem Risiko für Pankreaskarzinom, wie zum Beispiel neu diagnostizierte Diabetiker über 60 Jahren, sind in Arbeit. Wenn sich bei dieser Fragestellung zuverlässige Biomarker identifizieren lassen, beziehungsweise die zuvor identifizierte Signatur validiert werden kann, könnte basierend darauf ein diagnostischer Test zum Screening dieser vergleichsweise großen Risikogruppe entwickelt werden.
Diese Beispiele zeigen, dass der Metabolomik ein hohes Potenzial zur Diagnose von Pankreaserkrankungen innewohnt. Dieses Potenzial ist auch bei anderen Erkrankungen gegeben, bei denen sich die diagnostische Qualität von bildgebenden Verfahren und anderen minimalinvasiven Untersuchungen als begrenzt erwiesen hat. Durch technischen Fortschritt und zunehmende Verbreitung werden massenspektrometrische Stoffwechseluntersuchungen in der klinischen Routine einsetzbar. Die hier vorgestellten Publikationen zeigen schon jetzt, dass das Potenzial der Metabolomik erkannt wurde und wie es in Zukunft genutzt werden kann.
Background: Proper tooth brushing is a complicated process for children.
Aim of the study: was to investigate the effect of home-based differential learning to improve daily tooth brushing in children.
Study Design: In this prospective, controlled, single-blinded, randomized clinical trial, 58 children (age: 5.7 ± 1.5 years; 29 female) were randomly assigned to test or control groups through the child's self-drawing of an unlabeled envelope from a box. All children received oral hygiene instructions and information in these sealed envelopes and were asked to follow the corresponding instructions at home for 28 days. Children in the test group received instructions with exercises using the differential learning method, whereas the children in the control group received the usual tooth brushing instructions. At baseline and planned follow-ups after 4 and 12 weeks, plaque and gingival indices (QHI, PBI) were recorded in both groups by 2 calibrated and blinded investigators.
Results: At baseline, there were no significant differences between the test and control groups regarding plaque and gingival indices (QHI: 4.1 ± 0.5 vs. 4.1 ± 0.4; p = 0.7; PBI: 0.6 ± 0.3 vs. 0.6 ± 0.3; p = 0.7). At the 1st and 2nd follow-up, both groups showed improved oral health indices, but there was an overall better improvement in the test group. While the difference in gingival indices was statistically significant in the 1st recall (PBI/test: 0.1 ± 0.2 vs. control: 0.3 ± 0.2; p < 0.001), the difference in plaque indices was not (QHI/test: 2.1 ± 0.9; control: 2.6 ± 0.9; p = 0.07). At the 2nd recall (mean week = 19.5 weeks), the test group showed statistically significant and clinically relevant better oral health indices than the control group (2nd recall, QHI/test: 2.1 ± 0.9 vs. control: 3.2 ± 1; p < 0.001; PBI/test: 0.1 ± 0.2 vs. control: 0.5 ± 0.2; p < 0.001).
Conclusion: In conclusion, differential learning leads to oral hygiene improvement in children with high caries risk and initially poor oral hygiene, which was superior to the conventional learning method through repetition in the medium term.
Introduction
Healthcare-acquired infections and overuse of antibiotics are a common problem. Rising emergence of antibiotic and antiseptic resistances requires new methods of microbial decontamination or decolonization as the use of far-UV-C radiation.
Methods
The microbicidal efficacy of UV-C radiation (222 nm, 233 nm, 254 nm) was determined in a quantitative carrier test and on 3D-epidermis models against Staphylococcus (S.) aureus, S. epidermidis, S. haemolyticus, S. lugdunensis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. To mimic realistic conditions, sodium chloride solution, mucin, albumin, artificial saliva, artificial wound exudate and artificial sweat were used.
Results
In sodium chloride solution, irradiation with a dose of 40 mJ/cm2 (233 nm) was sufficient to achieve 5 lg reduction independent of bacteria genus or species. In artificial sweat, albumin and artificial wound exudate, a reduction >3 lg was reached for most of the bacteria. Mucin and artificial saliva decreased the reduction to <2 lg. On 3D epidermis models, reduction was lower than in the carrier test.
Conclusion
UV-C radiation at 233 nm was proven to be efficient in bacteria inactivation independent of genus or species thus being a promising candidate for clinical use in the presence of humans and on skin/mucosa.
The initiation of spring leaf-out is a critical determinant of the growing season in trees, affecting primary production and species interactions in forest ecosystems. Variations in the timing of leaf-out among tree species are linked to their differential progression of bud dormancy. However, identifying reliable markers for bud dormancy has been challenging, leaving the connection between the timing of autumn leaf senescence, bud dormancy and spring leaf-out unclear. To test whether species initiating dormancy release earlier also exhibit earlier leaf senescence in autumn and earlier leaf-out in spring, we estimated the dates of peak dormancy depth (PDD), senescence timing and spring leaf-out across various species, locations and experimental conditions in Central Europe. PDD was defined as the date when the maximum thermal sum was required for leaf-out, whereas leaf senescence was assessed through the decrease in leaf greenness. Our findings reveal that PDD timing is a more accurate predictor of species-level differences in spring leaf-out dates than the timing of leaf senescence, the latter being a poor proxy for PDD. The observed temporal asynchrony between PDD and senescence was linked to dormancy induction showing species-specific sensitivity to temperature variations. Conversely, the timing of leaf senescence showed a consistent reaction to temperature changes across all species. These findings suggest that the physiological processes within buds and leaves during autumn are governed by distinct environmental cues, with the bud dormancy process serving as a more reliable predictor of spring phenological differences among forest tree species than does autumn leaf senescence.
Background
Child maltreatment (CM) is linked to obesity in adulthood. However, sex-differences and direct measurements of body fat have previously been insufficiently considered in this context.
Objective
To assess sex-specific associations of CM with anthropometric markers of overweight/obesity and direct measures of body fat.
Participants and setting
Analyses were conducted in 4006 adults from a population-based cohort in Northeastern Germany (SHIP-TREND-0).
Methods
CM was assessed using the Childhood Trauma Questionnaire (CTQ). Obesity-related traits included anthropometric indicators (i.e., height, weight, body mass index [BMI], waist [WC] and hip circumference [HC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), fat mass (FM) and fat-free mass (FFM) derived from bioelectrical impedance analysis (BIA), and subcutaneous (SAT) and visceral adipose tissue (VAT) ascertained using magnetic resonance imaging (MRI). Sex-stratified linear regression models predicting obesity-related traits from total CTQ scores were adjusted for age and education. Exploratory analyses investigated effects of CTQ subscales on obesity-related traits.
Results
In men, CM was positively associated with WHtR (β = 0.04; p = .030) and VAT (β = 0.02; p = .031) and inversely with body height (β = −0.05; p = .010). In women, CM-exposure was positively associated with body weight (β = 0.07; p = .018), BMI (β = 0.03; p = .013), WC (β = 0.07; p = .005), HC (β = 0.05; p = .046), WHR (β = 0.03; p = .015), WHtR (β = 0.04; p = .006), FM (β = 0.04; p = .006), and SAT (β = 0.06; p = .041). In both sexes, effects were mainly driven by exposure to emotional and physical abuse.
Conclusions
Results suggest that associations between CM-exposure and obesity-related traits in adulthood are primarily present in women. This may have implications for sex-specific obesity-related cardiometabolic risk after CM.
The nivicolous species of the genus Diderma are challenging to identify, and there are several competing views on their delimitation. We analyzed 102 accessions of nivicolous Diderma spp. that were sequenced for two or three unlinked genes to determine which of the current taxonomic treatments is better supported by molecular species delimitation methods. The results of a haplotype web analysis, Bayesian species delimitation under a multispecies coalescent model, and phylogenetic analyses on concatenated alignments support a splitting approach that distinguishes six taxa: Diderma alpinum, D. europaeum, D. kamchaticum, D. meyerae, D. microcarpum and D. niveum. The first two approaches also support the separation of Diderma alpinum into two species with allopatric distribution. An extended dataset of 800 specimens (mainly from Europe) that were barcoded with 18S rDNA revealed only barcode variants similar to those in the species characterized by the first data set, and showed an uneven distribution of these species in the Northern Hemisphere: Diderma microcarpum and D. alpinum were the only species found in all seven intensively sampled mountain regions. Partial 18S rDNA sequences serving as DNA barcodes provided clear signatures that allowed for unambiguous identification of the nivicolous Diderma spp., including two putative species in D. alpinum.
The intricate relationship between KCNQ channels and vascular diseases is
discernible across various pathological conditions, revealing noteworthy insights into
their impact. Various structurally diverse compounds have been synthesized to
selectively target Kv7 channels. In the realm of Kv7 modulation, specific compounds
have demonstrated potential therapeutic utility along with in vivo evidence supporting
their effects (Evseev A, 2013). This thesis delves into the vasorelaxant effects of
Flupirtine, PVRF (Oxylipins), KWU 176, and KWU 183 on mesenteric arteries,
specifically examining their modulation of KCNQ channels. The central hypothesis
posits KWU 176 and KWU 183 as potent activators of KCNQ4 and KCNQ5 channels,
surpassing established activators in efficacy. Through pharmacological and genetic
methodologies, findings reveal that Flupirtine and PVRF induce endothelium-
independent vasorelaxation, while KWU 176 exhibits a dual impact on KCNQ4 and
KCNQ5 channels with significant endothelium-dependent vasodilatation. In contrast,
KWU 183 selectively activates KCNQ5 channels with endothelium-independent
vasorelaxation. Genetic knockout models underscore the regulatory role of Kcnq4 and
Kcnq5 channels in vasomotor responses. Beyond unraveling the nuanced
mechanisms of these compounds, this study contributes valuable insights for
optimizing cardiovascular function and potential therapeutic interventions. Modulators
like KWU 176 and KWU 183 emerge as promising candidates for enhancing
cardiovascular health, presenting a compelling avenue for future clinical applications.
Zerebrale kavernöse Malformationen (CCMs) sind Läsionen im venös-kapillären Gefäßbett des zentralen Nervensystems, welche zu epileptischen Anfällen und schlaganfallähnlichen Symptomen führen können. Die familiäre Form wird auf eine heterozygote Loss-of-Function- Keimbahnvariante in einem der Gene CCM1, CCM2 oder CCM3 zurückgeführt und ist mit der Entstehung multipler Kavernome assoziiert. Die Therapiemöglichkeiten für symptomatische CCM-Patient*innen sind limitiert. Neben der neurochirurgischen Resektion stehen aktuell keine kausalen nichtinvasiven Behandlungsoptionen zur Verfügung.
Um die Entwicklung zielgerichteter pharmakologischer Therapien zu unterstützen, wurde ein CCM-Zellkulturmodell auf Grundlage von humanen induzierten pluripotenten Stammzellen (iPSCs) etabliert. Hierzu wurden für Aktin fluoreszenzmarkierte iPSC-Linien mit einer CRISPR/Cas9-vermittelten Inaktivierung von CCM1, CCM2 oder CCM3 generiert. Nach erfolgreicher Qualitätssicherung der generierten iPSC-Linien mittels Sequenzierung nach Sanger und Next-Generation Sequencing, Immunfluoreszenzanalyse wichtiger Stammzellmarker sowie Karyotypisierung wurden diese zu endothelzellähnlichen Zellen differenziert. Die CCM-defizienten endothelzellähnlichen Zellen zeigten die in der Pathogenese zerebraler Kavernome bekannten Veränderungen wie die Ausbildung von Aktinstressfasern und die klonale Expansion bei Kontakt mit wildtypischen Zellen. Weitergehende Untersuchungen der klonalen Expansion in fluoreszenzbasierten Kokultivierungsanalysen legen nahe, dass dieser für das initiale Wachstum von CCMs entscheidende Prozess sowohl durch den Genotyp als auch das verwendete Kulturmedium beeinflusst wird. Ferner zeigte sich in einem RNA-Sequenzierungsprojekt der Greifswalder Arbeitsgruppe, dass ein spezifisches Genexpressionsmuster erst mit Eintritt der CCM1- defizienten Zellen in das endotheliale Differenzierungsstadium und damit abhängig von einer spezifischen Mikroumgebung zu beobachten ist.
Schlussfolgernd wurde mit dieser Arbeit der Grundstein für ein neues fluoreszenz- und iPSC- basiertes CCM-Zellkulturmodell gelegt, welches sowohl zukünftigen pharmakologischen Hochdurchsatzscreening-Studien und Live-Cell-Untersuchungen zugänglich wird, als auch neue Einblicke in die CCM-Pathogenese ermöglicht.
Problem
A seizure is a challenging situation for children with epilepsy. Little is known regarding the experience of children who perceive in advance that they are about to have a seizure.
Methods
From September 2020 to February 2021, we invited children with focal epilepsies aged 6–18 years to participate in a semi-structured interview.
Results
Of 52 children with focal epilepsies, 22 (42 %) said they perceive in advance that they are about to experience a seizure [11 with self-limited epilepsy with centro-temporal spikes (SELECTs), 11 with other focal epilepsies]. All 22/22 (100 %) children described physical symptoms such as headache or a numb feeling in one half of the body. Of those children, 17/22 (77 %) stated they try to do something about the seizure. Those strategies were perceived as helpful by 0/11 (0 %) children with SELECTs and 9/11 (86 %) children with other focal epilepsies (p < 0.001). Of the children with SELECTs 5/11 (45 %), and of those with other focal epilepsies 9/11 (86 %) stated they would like to know in the morning if they are to experience a seizure that day (n.s.).
Conclusion
Children who perceive in advance that they are about to have a seizure are well able to describe their experience. Most children take measures to manage their seizures. Those measures were regarded as helpful by most children with other focal epilepsies, but by no child with SELECTs. Larger studies are necessary to determine the factors contributing to the child’s perception as well as the nature of the support that they require.
The use of 3D printing techniques such as fused deposition modelling (FDM) for the manufacturing of dosage forms has become an interesting research field in pharmaceutics. When using FDM 3D printing, there are usually two temperature events that can have influence on temperature-sensitive drugs and excipients. The aim of this work was to investigate the influence of various parameters on the stability of the active ingredient dexamethasone. For this purpose, active ingredient-containing filaments were produced by hot melt extrusion and the influence of temperature and the presence of antioxidants on drug stability were investigated. Vitamin C, vitamin E and butylated hydroxytoluene were used as antioxidants. If suitable filaments were obtained, these filaments were used to 3D print test objects. In addition to the presence of antioxidants, the influence of printing parameters such as printing temperature, printing speed and print bed temperature on the active ingredient content was investigated. The variation of the temperature during the extrusion process showed an influence on the degradation of dexamethasone. Furthermore, during the investigation of the 3D printed objects, the presence of the antioxidants did not show any positive influence on the drug stability. The printing temperature was identified as a critical process parameter during 3D printing of dexamethasone, while other printing settings like the temperature of the print bed and the printing speed had no detectable influence.