In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography

The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The 18F-radiolabeled polyamides were prepared by oxime ligation between 4-[18F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring β-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability. In vivo imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies

Seroprevalence of Measles-, Mumps-, and Rubella-specific antibodies in the German adult population – cross-sectional analysis of the German Health Interview and Examination Survey for Adults (DEGS1)

Background: The WHO European Region targets the elimination of measles, rubella, and the congenital rubella syndrome and welcomes mumps elimination via the joint MMR vaccine. In a push towards this elimination goal, Germany introduced a recommendation on MMR vaccination for adults in 2010 to prevent increasing numbers of measles cases among adults and to strengthen herd immunity. Methods: The prevalence of anti-measles, -mumps, and -rubella IgG antibodies was analysed in 7,115 participants between the ages of 18 and 79 years in the German Health Interview and Examination Survey. Risk factors of seronegativity of adults born 1970 or later were determined. Findings: The seroprevalence of anti-measles IgG antibodies was more than 97% in adults born before 1965 and less than 90% in adults born afterwards. Prevalence and GMTs declined with later years of birth. Seronegativity was associated with two-sided migration background and region of residence in East Germany. For anti-mumps IgG antibodies, the seroprevalence was less than 90% in almost all age groups. Prevalence and GMTs declined with later years of birth. Seronegativity was not associated with any socio-demographic factor. Anti-rubella IgG seropositivity was found in more than 90% of adults born before 1985. GMTs declined in younger age groups. Seronegativity was associated with birth between 1980 and 1993 and male gender. High socio-economic status lowered the odds of being seronegative. Interpretation: These data reinforce the implementation of the vaccination recommendation for adults and provide the basis for further evaluation of this measure. Funding: The Federal Ministry of Health, Germany.Peer Reviewe

Nationally representative results on SARS-CoV-2 seroprevalence and testing in Germany at the end of 2020

Pre-vaccine SARS-CoV-2 seroprevalence data from Germany are scarce outside hotspots, and socioeconomic disparities remained largely unexplored. The nationwide representative RKI-SOEP study (15,122 participants, 18–99 years, 54% women) investigated seroprevalence and testing in a supplementary wave of the Socio-Economic-Panel conducted predominantly in October–November 2020. Self-collected oral-nasal swabs were PCR-positive in 0.4% and Euroimmun anti-SARS-CoV-2-S1-IgG ELISA from dry-capillary-blood antibody-positive in 1.3% (95% CI 0.9–1.7%, population-weighted, corrected for sensitivity = 0.811, specificity = 0.997). Seroprevalence was 1.7% (95% CI 1.2–2.3%) when additionally correcting for antibody decay. Overall infection prevalence including self-reports was 2.1%. We estimate 45% (95% CI 21–60%) undetected cases and lower detection in socioeconomically deprived districts. Prior SARS-CoV-2 testing was reported by 18% from the lower educational group vs. 25% and 26% from the medium and high educational group (p < 0.001, global test over three categories). Symptom-triggered test frequency was similar across educational groups. Routine testing was more common in low-educated adults, whereas travel-related testing and testing after contact with infected persons was more common in highly educated groups. This countrywide very low pre-vaccine seroprevalence in Germany at the end of 2020 can serve to evaluate the containment strategy. Our findings on social disparities indicate improvement potential in pandemic planning for people in socially disadvantaged circumstances

Reconsidering inequalities in COVID-19 vaccine uptake in Germany: a spatiotemporal analysis combining individual educational level and area-level socioeconomic deprivation

Combining the frameworks of fundamental causes theory and diffusion of innovation, scholars had anticipated a delayed COVID-19 vaccination uptake for people in lower socioeconomic position depending on the socioeconomic context. We qualify these propositions and analyze educational differences in COVID-19 vaccination status over the first ten months of Germany’s vaccination campaign in 2021. Data from the study “Corona Monitoring Nationwide” (RKI-SOEP-2), collected between November 2021 and February 2022, is linked with district-level data of the German Index of Socioeconomic Deprivation (GISD). We estimated the proportion of people with at least one vaccination dose stratified by educational groups and within different settings of regional socioeconomic deprivation at three time points. Logistic multilevel regression models were applied to adjust for multiple covariates and to test cross-level-interactions between educational levels and levels of area-level socioeconomic deprivation. Vaccination rates were lower among respondents with lower education. With increasing area-level socioeconomic deprivation, educational differences were larger due to particularly low vaccination rates in groups with low education levels. The analysis of vaccination timing reveals that educational gaps and gaps by area-level socioeconomic deprivation had appeared early in the vaccination campaign and did not close completely before the 4th wave of COVID-19 infections

Self‐limited HBV infection of the recipient does not reactivate after liver transplantation: Observations from a 30‐year liver transplant program

Background: A self-limited hepatitis B infection can reactivate in patients under immunosuppression or chemotherapy (reappearance of hepatitis B surface antigen (HBsAg) or HBV-DNA). Exact circumstances of HBV reactivation in patients undergoing liver transplantation (LT) for end-stage liver diseases (ESLD) unrelated to HBV are unknown, and recommendations on HBV prophylaxis remain unclear. Patients and methods: Among 1273 liver transplants, 168 patients with a self-limited HBV hepatitis B infection prior to LT were identified from our prospective liver transplant database. Patients with underlying chronic HBV infection and recipients of an anti-HBc-positive liver were not included in the analysis. Demographic, laboratory, serological, and virological data were analyzed retrospectively. Appearance of HBsAg or HBV-DNA was defined as reactivation. Results: The median follow-up after LT was 12.0 years (0.6-30.7 years). The rate of HBV reactivation was 0% independent of antiviral prophylaxis (n = 7; 4.2%), the etiology of ESLD, hepatitis C treatment, or the anti-HBs concentration. The overall patient survival with a history of a self-limited HBV infection before LT did not significantly differ from the rest of the cohort. Conclusion: Antiviral treatment with nucleos(t)ide analogues post-liver transplantation in order to prevent HBV reactivation in patients with a resolved self-limited hepatitis B infection prior to LT seems to be omittable since the main viral reservoir is removed by the hepatectomy. These findings may clarify the current uncertainty in the recommendations regarding the risk of HBV reactivation in patients with self-limited hepatitis B prior to LT

What is the health status of girls and boys in the COVID-19 pandemic? Selected results of the KIDA study

Background: It is well known that there are gender differences in the health behaviour and physical and mental health of children. The COVID-19 pandemic influenced the health and lifestyles of children and adolescents by changing their living conditions. The present work investigates whether gender differences in selected health indicators are evident more than two years after the onset of the pandemic. Methods: In the study Kindergesundheit in Deutschland aktuell (KIDA) (German Children’s Health Update), cross-sectional telephone surveys were conducted with parents of 3- to 15-year-olds (n=3,478). Parental information on the general and mental health of the child, on increased need for health care and mental health services, as well as on physical activity and utilisation of sports activities were queried in standardised manner. Gender differences were assessed using Chi2 tests. Results: A total of 91% of the girls and 92% of the boys had their general health assessed as being (very) good by their parents (difference not significant, n.s.). An increased need for care and support was indicated for 10.6% of the 3- to 15-year-olds (girls: 9%, boys: 12%, n.s.). Boys met the physical activity recommendations of the WHO significantly more often (60%) than girls (54%). Good to excellent mental health was reported for 93% of both boys and girls. When changes during the pandemic were reported, no differences were found in the responses for girls compared to boys. Conclusions: Gender differences were found for individual parameters and age groups. These differences must be assessed in the context of other social determinants of health, and need to be considered when planning preventive measures

Day care study showed no differences in long-term symptoms in children who were and were not infected during COVID-19 outbreaks

Peer Reviewe

PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides

Contains fulltext : 97195.pdf (publisher's version ) (Closed access)PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their (111)In-labelled counterparts. METHODS: A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)](2)) and a tetrameric (E{E[c(RGDfK)](2)}(2)) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with (68)Ga. In vitro alpha(v)beta(3)-binding characteristics were determined in a competitive binding assay. In vivo alpha(v)beta(3)-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. RESULTS: The IC(50) values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)](2) and DOTA-E{E[c(RGDfK)](2)}(2) were 23.9 +/- 1.22, 8.99 +/- 1.20 and 1.74 +/- 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 +/- 1.15, 3.34 +/- 1.16 and 1.80 +/- 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the (68)Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 +/- 0.30, 5.24 +/- 0.27 and 7.11 +/- 0.67%ID/g, respectively) was comparable to that of their (111)In-labelled counterparts (2.70 +/- 0.29, 5.61 +/- 0.85 and 7.32 +/- 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. CONCLUSION: The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The (68)Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of alpha(v)beta(3) expression with PET

Hepatitis-B-Virus-Infektionen und impfinduzierte Immunität: die Rolle von soziodemografischen Determinanten

Hintergrund und Ziel: Trotz niedriger Prävalenz der Hepatitis-B-Virus-(HBV-)Infektion in Deutschland ist es wichtig, vulnerable Gruppen und Ansatzpunkte für die Prävention zu identifizieren. In ersten Analysen der „Studie zur Gesundheit Erwachsener in Deutschland“ (DEGS1, 2008–2011) waren HBV-Infektion und -Impfung mit sozidemografischen Determinanten assoziiert. In dieser Arbeit werden die Ergebnisse im Detail untersucht. Material und Methoden: In DEGS1 lag für 7046 Teilnehmende (Alter: 18–79 Jahre) eine HBV-Serologie vor. Die stattgehabte HBV-Infektion war durch Antikörper gegen das Hepatitis-B-Core-Antigen (Anti-HBc) definiert, die impfinduzierte Immunität durch alleinigen Nachweis von Antikörpern gegen das Hepatitis-B-Surface-Antigen (Anti-HBs). Seroprävalenzen von HBV-Infektions- und -Impfstatus wurden geschlechtsstratifiziert geschätzt und Assoziationen mit Alter, Gemeindegröße, Einkommen, formaler Bildung, Krankenversicherung und Migrationsgeneration in logistischen Regressionen analysiert. Ergebnisse: Die HBV-Infektion war bei Männern und Frauen unabhängig mit den Altersgruppen 34–64 und ≥ 65 Jahre, erster Migrationsgeneration und Leben in größeren Gemeinden assoziiert, zudem bei Männern mit niedrigem Einkommen und bei Frauen mit niedriger Bildung. Die impfinduzierte Immunität war bei Männern und Frauen unabhängig mit den Altersgruppen 18–33 und 34–64 Jahre, mittlerer und hoher Bildung und hohem Einkommen assoziiert, darüber hinaus bei Männern mit mittlerem Einkommen und privater Krankenversicherung und bei Frauen mit fehlendem Migrationshintergrund. Diskussion: Die Berücksichtigung von Migrationsstatus, Einkommen und Bildung könnte zur zielgenauen Ausrichtung der HBV-Prävention beitragen.Background and objective: Even though the prevalence of hepatitis B virus (HBV) infection in Germany is low, it is important to identify vulnerable groups and targeted approaches for infection prevention. Previous analyses from the “German Health Interview and Examination Survey for Adults” (DEGS1, 2008–2011) have shown that HBV infections and vaccination are associated with sociodemographic determinants. This paper examines the results in detail. Materials and methods: In the DEGS1, HBV serology was available for 7046 participants aged 18–79 years. HBV infection was defined by antibodies to hepatitis B core antigen (anti-HBc), vaccine-induced immunity by antibodies to hepatitis B surface antigen (anti-HBs) in the absence of other markers. Seroprevalences of HBV infection and vaccine-induced immunity were estimated stratified by sex, and associations with age, municipality size, income, formal education, health insurance and migration generation were analysed by logistic regression. Results: In both sexes, HBV infection was independently associated with age groups 34–64 and ≥ 65 years, first migrant generation and living in larger municipalities as well as low income in men and low education in women. Vaccine-induced immunity was independently associated with age groups 18–33 and 34–64 years, middle and high education and high income in both sexes, middle income and private health insurance in men and having no migration background in women. Conclusions: HBV prevention measures should take into account migration status, income and education in order to focus prevention measures.Peer Reviewe

Partnership, parenthood, employment and self-rated health in Germany and the EU – Results from the European Health Interview Survey (EHIS) 2

Partnership, parenthood and employment constitute three main social roles that people adopt in middle adulthood. Against the background of the discussion about multiple roles and the reconciliation of family and work, this article analyses the association between the combination of social roles and self-rated health in Germany and the European Union (EU). The analysis is based on data from the second wave of the European Health Interview Survey (EHIS 2), which was conducted in all EU Member States between 2013 and 2015. The final sample included 62,111 women and 50,719 men aged between 25 and 59. Using logistic regression models, predictive margins for fair to very bad health in different family and employment constellations were calculated for the EU and Germany (in the case of men only for the EU in total). A difference was identified according to employment status in all family groups for women and men at the EU level: non-employed people rated their health as fair or bad more often, followed by part-time and full-time workers. Smaller differences by employment status were found for mothers with a partner in terms of the proportion of mothers who self-rated their health as bad compared to women in other family groups. No differences in health by employment status were found in Germany among mothers. This applies also to single parents. Different patterns of associations were identified between groups of EU Member States with diverse welfare systems