Scientific publications of the Saarland University
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Impact of HPV Testing Based on the 2020 Update of the German Cervical Cancer Screening Program—Data from a Retrospective Monocentric Study
Get PDFBackground/Objectives: Since 2020, Germany has replaced its annual cytological
screening for cervical cancer in women aged 35 and older with a combination screening
program. This updated protocol, conducted every three years, includes both a cervical
Pap smear and an HPV (human papillomavirus) test. In addition, the 2020 update of the
German Cervical Cancer Screening Program mandates a more timely follow-up for certain
abnormal findings compared to the previous approach. Methods: Results of cytologic,
colposcopic, and histologic examinations between 2018 and 2021 were retrospectively
retrieved from the electronic patient records of the Institute of Pathology Saarbrücken
Rastpfuhl in order to present relevant findings within the years 2018–2019 and 2020–2021.
The present study included all women who received appropriate follow-up based on the
corresponding underlying screening modality. Results: Our reporting considered data from
30,715 women in 2018/19 (prior screening modality group) and 25,924 women in 2020/21
(updated screening modality group). In 2018/19, a total of 93 histological examinations
were performed, compared to 237 in 2020/21. In 2018/19, 52 cases of CIN III and 12 cases
of CIN II were identified, while in 2020/21, 78 cases of CIN III and 31 cases of CIN II
were detected. In contrast, while women with negative cytological findings in 2018/19
were typically not referred for further colposcopic or histological evaluation, the updated
program enabled earlier detection and treatment of cases with diagnosed high-grade
dysplasia based solely on a positive HPV test. Notably, 31 women who were diagnosed at
an earlier stage based solely on a positive HPV test initially presented with a cytological Pap
I result (negative for intraepithelial lesion or malignancy; NILM). Conclusions: Additional
HPV co-testing within the updated German cervical cancer screening program resulted not only in high rates of high-grade dysplasia detection but also a rise in the number
of colposcopic procedures. While negative follow-up HPV findings regularly showed
remission of the original finding, incidence of high-grade dysplasia was usually linked to a
positive HPV test
Ein Ausbildungscurriculum über die ultraschall-gesteuerte Punktion der Vena Subclavia mittels Micro-Convex-Schallkopf
Get PDFMit der ultraschallgesteuerten Punktion der Vena subclavia (VSC) zur Etablierung eines zent-ralvenösen Katheters (ZVK) sind viele Ärzte oft nur wenig vertraut. An den Kliniken fehlt es an formalen Ausbildungsprogrammen zur Erlernung dieser Technik. Eine spezielle Microcon-vex-Sonde (MCS) bietet aufgrund ihrer kompakten konvexen Form zusätzliche Vorteile. Die Microconvex-Inplane-Subclavian-Puncture (MISP)-Technik führt die Vorteile der MCS und einer in-plane Punktion für ZVK-Anlagen in die VSC zusammen. Um ein unproblematisches, risikofreies Üben der Punktionstechnik zu ermöglichen, werden Phantome benötigt, die äußerst teuer und kaum verfügbar sind. Ein evaluiertes standardisiertes Curriculum zur Erlernung der MISP-Technik fehlte bis dato.
Das Ziel dieser Arbeit lag in der Entwicklung eines standardisierten simulationsbasierten Cur-riculums, welches nachweislich die theoretischen und praktischen Kompetenzen der Teilneh-mer im Umgang mit der MCS zur Punktion der VSC mittels MISP-Technik sowie grundlie-gende Kenntnisse über die Anwendung von ZVKs verbessern soll. Darüber hinaus sollte ge-zeigt werden, dass die MISP-Technik auch für unerfahrene ZVK-Anwender einfach zu erlernen ist. Am Universitätsklinikum des Saarlandes in Homburg wurden mehrere Kursveranstaltungen durchgeführt, wobei die Teilnehmer, größtenteils Anästhesisten, als Probanden für eine pros-pektive Beobachtungsstudie dienten. Der Kurs bestand aus einem theoretischen sowie einem praktischen Teil. Als Hauptzielgrößen wurden bei den Teilnehmern Ergebnisse in Wissenstests, Punktescores sowie benötigte Zeiten bei Schall- und Punktionsübungen vor und nach Kursab-solvierung erfasst. Als Nebenzielgröße wurden dabei Unterschiede zwischen den Ergebnissen erfahrener und unerfahrener ZVK-Anwendern betrachtet. Für die Punktionsübungen wurde ein anatomisches Phantom entwickelt, welches den Kursteilnehmern ein kostengünstiges und rea-litätsnahes Üben der Punktion von VSC mittels MCS ermöglichen sollte. Insgesamt wiesen die Probanden nach Absolvierung der jeweiligen Kursabschnitte signifikant verbesserte theoreti-sche Kenntnisse, einen verbesserten praktischen Umgang mit der MCS zur VSC-Punktion und bessere Punktionsfähigkeiten auf. Nach Kursabsolvierung fanden wir nahezu keinen signifi-kanten Unterschied zwischen erfahrenen und unerfahren ZVK-Anwendern. Die Ergebnisse deuten darauf hin, dass die Erlernung der MISP-Technik mit diesem Curriculum effektiv und auch für unerfahrene ZVK-Anwender geeignet ist.Many doctors are unfamiliar with ultrasound-guided puncture of the subclavian vein (SCV) to establish a central venous catheter (CVC). Hospitals lack formal training programmes for learn-ing this technique. A special microconvex probe (MCS) offers additional advantages due to its compact convex shape. The microconvex in-plane subclavian puncture (MISP) technique com-bines the advantages of the MCS and an in-plane puncture for CVC insertions in the SCV. In order to enable easy, risk-free practice of the puncture technique, phantoms are required, which are extremely expensive and rarely available. An evaluated standardised curriculum for learn-ing the MISP technique has been lacking to date.
The aim of this work was to develop a standardised simulation-based curriculum that would demonstrably improve the theoretical and practical skills of participants in handling the MCS for puncturing the SCV using the MISP technique as well as basic knowledge about the use of CVCs. In addition, the aim was to demonstrate that the MISP technique is easy to learn even for inexperienced CVC users. Several courses were held at the Saarland University Hospital in Homburg, with the participants, mostly anaesthetists, serving as subjects for a prospective ob-servational study. The course consisted of a theoretical and a practical part. The main outcome measures were the participants' results in knowledge tests, point scores and the time required for ultrasound and puncture exercises before and after completing the course. Differences be-tween the results of experienced and inexperienced CVC users were considered as a secondary objective. An anatomical phantom was developed for the puncture exercises to enable the course participants to practise the puncture of SCV using MCS in a cost-effective and realistic manner. Overall, the participants showed significantly improved theoretical knowledge, im-proved practical handling of the MCS for SCV puncture and better puncture skills after com-pleting the respective course sections. After completing the course, we found almost no signif-icant difference between experienced and inexperienced CVC users. The results indicate that learning the MISP technique with this curriculum is effective and also suitable for inexperi-enced doctors
Das Mondorfer Abkommen als ‚Labor‘ für die polizeiliche Zusammenarbeit in Europa?
Get PDFAusweislich seiner Präambel verfolgt das 1997 zwischen Frankreich und Deutschland abgeschlossene Mondorfer Abkommen das Ziel, „die Zusammenarbeit der Behörden und Dienststellen mit polizeilichen […] Aufgaben […] in den Grenzgebieten auszubauen“. Hierzu enthält es Regelungen zur polizeilichen Zusammenarbeit, die nicht bundes- bzw. landesweit, sondern lediglich in deutsch-französischen Grenzgebieten Anwendung finden. Dieser Beitrag untersucht, inwieweit diese grenzgebietsspezifischen Regelungen des zwischen zwei ‚Motoren‘ der europäischen Integration abgeschlossenen Mondorfer Abkommens prototypisch waren für die Fortentwicklung des europäischen Rechts der polizeilichen Zusammenarbeit. Dabei zeigt sich, dass durch das Mondorfer Abkommen Grenzgebiete zwar nur in geringem Umfang zu einem Laborraum für das Recht, aber möglicherweise weitreichend zu einem Laborraum für die polizeiliche Praxis der europäischen Zusammenarbeit wurden
Sex-specific differences of advanced glycation end products in diabetes
Get PDFAdvanced glycation end products (AGEs) are formed through non-enzymatic glycation reactions and accumulate in tissues,
particularly under pathological conditions such as diabetes mellitus. These compounds are linked to the progression of diabetic
complications, including nephropathy, retinopathy, and cardiovascular disease, through mechanisms such as oxidative stress and
chronic inflammation. Emerging evidence suggests significant sex-specific differences in AGE formation, accumulation, and their
biological effects, influenced by hormonal variations, dietary patterns, and metabolic differences. While the underlying
biochemistry of AGE formation, such as the Maillard reaction and dicarbonyl compound activity, is well-characterized, the
implications of these processes for clinical outcomes remain underexplored. This mini-review highlights the interplay between
molecular mechanisms and sex-specific factors in AGE-related pathophysiology. It further discusses potential therapeutic
approaches targeting AGE formation and receptor-mediated pathways, emphasizing the importance of integrating sex-specific
considerations into diabetes management. Bridging molecular insights with clinical practice could advance personalized treatment
strategies for diabetic complications
Considerations on the Haigis formula: Are better outcomes possible with tuning?
Get PDFAbstract
Purpose: To design a vergence-based lens power formula based on the classical
Haigis formula for better outcomes while retaining the original formula
architecture.
Methods: Four new formula variants (A–D) incorporating a sum of segments
correction for axial length, harmonic mean of corneal radii instead of
arithmetic mean (all variants), and differing combinations of lower keratometer
index (C, D) and an additional term (a3) representing the lens thickness in the
effective lens position (B, D) were assessed in an analysis based on four datasets
of IOLMaster 700 biometric data for eyes treated with the Hoya Vivinex
lens (dataset 1), Alcon SA60AT lens (2), Johnson & Johnson ZCB00 lens (3),
and the Bausch & Lomb MX60 lens (4). All parameters (formula constants
and keratometer index) were calculated by nonlinear iterative optimisation
techniques for minimising the root mean squared prediction error (RMSPE).
Performance was assessed in terms of the final RMSPE.
Results: All four variants showed reductions in RMSPE ranging from 2.8% to
12.6% over the original Haigis formula. For each of the four datasets, variants
B and D (with the additional a3 constant) performed better in this respect
than variants A and C. In all four cases, variants C and D (with the adjusted
keratometer index) performed slightly better than A and B, respectively.
Conclusion: Although not amenable to statistical analysis, the % improvements
in RMSPE would appear to be clinically relevant. However, the benefit has to
be proven in a prospective multicentric study with a large sample size
The Shuttling of Methyl Groups Between Folate and Choline Pathways
Get PDFMethyl groups can be obtained either from the diet (labile methyl groups) or produced en dogenously (methylneogenesis) via one-carbon (C1-) metabolism as S-adenosylmethionine
(SAM). The essential nutrients folate and choline (through betaine) are metabolically en twined to feed their methyl groups into C1-metabolism. A choline-deficient diet in rats
produces a 31–40% reduction in liver folate content, 50% lower hepatic SAM levels, and a
doubling of plasma homocysteine. Similarly, folate deficiency results in decreased total hep atic choline. Thus, sufficient intakes of both folate and choline (or betaine) contribute to safe guarding the methyl balance in the body. A significant amount of choline (as phosphatidyl choline) is produced in the liver via the SAM-dependent phosphatidylethanolamine methyl transferase. Experimental studies using diets deficient in several methyl donors have shown
that supplemental betaine was able to rescue not only plasma betaine but also plasma folate.
Fasting plasma homocysteine concentrations are mainly determined by folate intake or
status, while the effect of choline or betaine on fasting plasma homocysteine is minor. This
appears to contradict the finding that approximately 50% of cellular SAM is provided via
the betaine-homocysteine methyltransferase (BHMT) pathway, which uses dietary choline
(after oxidation to betaine) or betaine to convert homocysteine to methionine and then to
SAM. However, it has been shown that the relative contribution of choline and betaine to
cellular methylation is better reflected by measuring plasma homocysteine after a methio nine load test. Choline or betaine supplementation significantly lowers post-methionine
load homocysteine, whereas folate supplementation has a minor effect on post-methionine
load homocysteine concentrations. This review highlights the interactions between folate
and choline and the essentiality of choline as a key player in C1-metabolism. We further
address some areas of interest for future work
Heterobimetallic unsaturated silicon clusters (siliconoids) with transition metal-expanded scaffolds
Get PDFWe report a heterobimetallical unsaturated silicon cluster (siliconoid) with a formally anionic group 9 metal vertex (Ir) in close contact to the lithium counter-cation, thus constituting a rare example of transition metal–lithium interactions. The anionic cluster is obtained by reductive chloride elimination from the corresponding neutral siliconoid complex of iridium(I) chloride with lithium/naphthalene. The previously exohedral transition metal center is fully incorporated into the siliconoid cluster scaffold giving rise to an irida-heterosiliconoid reminiscent of the corresponding homonuclear Si7 species. Despite the formal negative charge at the iridium center, the nucleophilic site is on one of the adjacent silicon vertices judging from the reactivity toward group 4 metallocene dichlorides, Cp2MCl2 (M = Zr, Hf). Under elimination of LiCl, the Cp2MCl moieties in the heterobimetallic products are installed as pending functionalities under retention of the literally uncompromised iridasiliconoid core
Immunhistochemischer Nachweis von TRPC-6 in peripheren Nerven des Menschen
No full textSeit seiner Entdeckung wird TRPC-6 mit einer Vielzahl von physiologischen und pathophysiologischen Vorgängen in unterschiedlichen Geweben in Verbindung gebracht. Er fungiert als
nicht selektiver Kationenkanal und gehört zu der Gruppe der TRP-Kanäle. Zunehmend offenbart sich dabei auch seine Bedeutung in der Entstehung von Schmerzüberempfindlichkeit. Dieser Zustand konnte bereits mit einer erhöhten Expression von TRPC-6 in dorsalen Spinalganglien assoziiert werden. Abgesehen davon, dass die meisten Nachweise an Proben tierischen Ursprungs geführt wurden, bleibt weiterhin unklar, ob der Kanal auch abseits der dorsalen Spinalganglien in peripheren Nerven exprimiert wird. Ziel dieser Arbeit war es daher, periphere Nerven von menschlichen Proben auf TRPC-6 zu untersuchen. Dafür wurden sowohl Proben
von N. ischiadicus und N. ulnaris an insgesamt acht Körperspendern entnommen und mittels
Immunhistochemie analysiert. Dabei wurden sowohl Längsschnitte als auch Querschnitte aus
den Proben gewonnen und angefärbt. Insgesamt zeigte sich bei 43 von 48 histologischen Schnitten ein positives Farbsignal. Größere Differenzen zwischen N. ischiadicus und N. ulnaris im
Hinblick auf die Anfärbung ließen sich dabei nicht feststellen. Einen geringen Unterschied gab
es lediglich in der Anfärbung von Querschnitten und Längsschnitten. Dabei waren die Längsschnitte bei beiden Nerven durchweg etwas besser gefärbt. Stärker ausgeprägt waren hingegen
die interindividuellen Unterschiede zwischen den Spendern. Interessanterweise waren dabei die
Proben eines Spenders besonders stark gefärbt, der zu Lebzeiten unter einem chronischen
Schmerzsyndrom litt. Dies steht im Einklang mit der bisher größtenteils durch Tierversuche
gewonnenen Kenntnis, dass der Kanal eine vermehrte Expression bei Schmerzzuständen in dorsalen Spinalganglien zeigt. Zukünftig könnte TRPC-6 somit eine wichtige Rolle als Angriffspunkt in der Schmerztherapie spielen.Since its discovery, TRPC-6 has been associated with a variety of physiological and pathophysiological processes in different tissues. It functions as a non-selective cation channel and
belongs to the group of TRP channels. Its importance in the development of pain hypersensitivity is becoming increasingly apparent. This condition has already been associated with increased expression of TRPC-6 in dorsal root ganglia. Apart from the fact that most of the evidence was obtained from samples of animal origin, it remains unclear whether the channel is
also expressed in peripheral nerves outside the dorsal root ganglia. The aim of this work was therefore to examine peripheral nerves from human samples for TRPC-6. For this purpose,
samples of both the sciatic and ulnar nerves were taken from a total of eight body donors and
analyzed by immunohistochemistry. Both longitudinal and transverse sections were obtained
from the samples and stained. In total, 43 of 48 histological sections showed a positive color
signal. There were no major differences between the sciatic and ulnar nerve with regard to
staining. There was only a slight difference in the staining of transverse and longitudinal sections. The longitudinal sections of both nerves were consistently slightly better colored. However, the inter-individual differences between the donors were more pronounced. Interestingly,
the samples of a donor who suffered from chronic pain syndrome during his lifetime were particularly strongly stained. This is consistent with the knowledge gained to date, largely from
animal experiments, that the channel shows increased expression in pain conditions in dorsal
root ganglia. In the future, TRPC-6 could therefore play an important role as a target in pain
therapy
Hesitant Minds in Vulnerable Times: COVID-19 Vaccine Hesitancy Among University Students in Ukraine
Get PDFCOVID-19 vaccine hesitancy (VH), like attitudes towards other vaccines, is a critical global
public health concern. Despite numerous studies covering psychological, sociodemo graphic, and other determinants of vaccine acceptance, resistance, and hesitance, few
studies have reported these factors among students, particularly in politically unstable
settings like Ukraine. This cross-sectional, descriptive, and quantitative study assesses
hesitancy towards COVID-19 vaccines, utilizing the 5Cs Model. Among 936 respondents
surveyed in 2023, 64% received at least one shot of the COVID-19 vaccine (acceptant),
11% were still considering getting vaccinated (hesitant), and 25% refused vaccination (re sistant). Vaccination behavior is significantly associated with the 5Cs. Higher collective
responsibility significantly increased acceptance and reduced resistance, while higher con straints lowered the chances of being either acceptant or resistant. Confidence protected
against resistance. Complacency, counterintuitively, reduced odds of resistance, pointing
to differences between passive hesitancy and active refusal. Male gender and sources of
information and misinformation influenced confidence. Collective responsibility was posi tively associated with official sources and negatively with conspiracy beliefs. Complacency
increased with official sources, while constraints and calculation were least explained by
predictors. Practical barriers should be tackled through improved accessibility and foster ing collective responsibility via targeted communication strategies. These findings provide
actionable insights for policymakers, healthcare providers, and academic institutions to
enhance vaccine uptake among university students, particularly in crisis settings