To study the possible transmission, to the next generation, of epigenetic defects associated with in vitro maturation (IVM) of human oocytes.
Case–control study using epigenetic data.
Two ...collaborating university departments.
Eleven IVM newborns and 19 controls, conceived by conventional assisted reproduction.
Chorionic villus and cord-blood sampling.
Using bisulfite pyrosequencing, we have measured average methylation levels of 6 imprinted (LIT1, MEG, MEST, NESPas, PEG3, and SNRPN), 5 tumor-suppressor (APC, ATM, BRCA1, RAD51C, and TP53), 2 pluripotency (NANOG and OCT4), and 2 metabolic (LEP and NR3C1) genes, as well as 2 repetitive elements (ALU and LINE1) in 2 tissues of IVM and control neonates. Using deep bisulfite sequencing, we have determined methylation patterns of many individual DNA molecules to detect rare RAD51C epimutations (allele methylation errors).
No statistically significant impact was found of IVM on chorionic villus and cord-blood DNA methylation at the studied developmentally important genes and interspersed repeats. The RAD51C epimutation rate was low (0.5% ± 0.1%) in all analyzed samples.
IVM-induced epigenetic changes in offspring, if any, are relatively small in magnitude and/or infrequent.
The 'positive list for equines' (Regulation (EC) No 1950/2006) was implemented in the European Union in 2006. The drugs listed are approved for use in slaughter equines under certain conditions, ...although those drugs are not approved for use in livestock and are not listed in Table 1 of the annex to Regulation (EU) No 37/2010. The usage of such drugs has to be documented in the equine passport and a withdrawal period of six months must be adhered to before the equine can be slaughtered for human consumption. Since the withdrawal period is long, correct documentation is particularly important. This study compared the results of two sub-studies. In sub-study 1, 116 veterinarians and nine equine clinics in Germany were surveyed about the methods and drugs used for castration of equine stallions. In sub-study 2, the documentational findings of 195 equine passports, belonging to 194 horses and one donkey, were analyzed. Regarding sub-study 1, the most commonly used method for castration was reported as 'laid down'. Drug combinations entailing at least one drug from the 'positive list' were used by 86.7% (91/105) of veterinarians castrating horse stallions 'laid down' and by 64.3% (36/56) of veterinarians utilizing this method on donkey stallions. Regarding sub-study 2, drug documentation was verified in the passports of 4.6% (9/195) of all equines and in just 12.0% (3/25) of those belonging to slaughter equine geldings. Anesthetics from the 'positive list' were documented in 4.0% (1/25) of equine passports belonging to slaughter geldings. Because of the high discrepancy of the drug combinations used by veterinarians and the documentation actually found in equine passports, we conclude that drug administration is very seldom documented in equine passports in Germany. This could result in drug residues in equine meat and poses a potential risk for consumers.
In Europe, equines destined for human consumption (hereafter called slaughter equines) are subject to the same restrictions of usage of veterinary drugs as other food-producing animals, with ...amendments regulated in the so-called 'positive list', Regulation (EC) No. 1950/2006. Due to the complex legal requirements for drug administration in slaughter equines, it might be that specific knowledge regarding the legislation of slaughter equines may be insufficient among veterinarians, equine owners, and equine keepers. To study this assumption, three target group-specific surveys were conducted in 2021. Answers from 153 equine treating veterinarians, 170 equine owners, and 70 equine keepers were included in the analysis. In total 68.4% (91/133) of the participating veterinarians, the regulations of the 'positive list', Regulation (EC) No. 1950/2006, were 'rather complicated' to 'complicated'. Among the participating veterinarians, 38.4% (58/151) did not or could not answer correctly how to proceed if a slaughter equine is scheduled to receive phenylbutazone, usage of which is prohibited in all livestock by Regulation (EU) No. 37/2010. Simultaneously, 56.2% (86/153) of the participating veterinarians named phenylbutazone as the, or one of the, most often used non-steroidal anti-inflammatory drugs. Altogether, 41.2% (70/170) of participating equine owners and 42.9% (30/70) of equine keepers did not know under which circumstances an equine can legally be slaughtered for human consumption. In total, 34.3% (24/70) of the equine keepers classified their knowledge of national regulations for animal keepers regarding the documentation of drug usage in equines as 'poor' to 'nonexistent'. This lack of knowledge in all three surveyed groups, combined with the complex legal regulations regarding the usage and documentation of drugs in slaughter equines, could result in missing and false documentation, treatment of slaughter equines with prohibited substances and therefore pose a risk factor for drug residues in equine meat.
The COVID-19 pandemic has led to a deepening of existing inequalities and a rollback of achievements made in gender equality. Women in Global Health (WGH) is a global movement that aims to achieve ...gender equality in health and increase female leadership in global health. Here, the aim was to understand how the pandemic affects the private and professional lives of women working in global health in different European countries. Suggestions for future pandemic preparedness including how gender perspectives should be integrated into pandemic preparedness and how a women's network such as WGH helped them to overcome the impact of the pandemic were explored.
Qualitative semi-structured interviews were conducted in September 2020 with a sample size of nine highly educated women with a mean age of 42.1 years from the different WGH European chapters. The participants were informed of the study and were formally asked for their consent. The interviews were held in English
an online videoconference platform and lasted 20-25 min each. The interviews were audio recorded and transcribed verbatim. Thematic analysis was conducted according to Mayring Qualitative Content Analysis using MAXQDA.
The pandemic has both positive and negative effects on the professional and private lives of women. It led to an increased workload and stress as well as pressure to publish on COVID-19-related themes. Increased childcare and household responsibilities represented a double burden. The available space was limited if other family members were also working from home. Positive aspects included more time for family or partners and reduced travel. The participants report on perceived gender differences in the experience of the pandemic. International cooperation is considered to be a key factor for future pandemic preparedness. Being part of a women's network such as WGH was perceived as being very supportive in difficult situations during the pandemic.
This study provides unique insights into the experiences of women working in global health in different European countries. The COVID-19 pandemic influences their professional and private lives. Perceived gender differences are reported and suggest the need for integrating gender perspectives in pandemic preparedness. Networks for women, such as WGH, can facilitate the exchange of information in crises and provide women with professional and personal support.
Autosomal dominant inherited Myotonic dystrophy type 1 and 2 (DM1 and DM2) are the most frequent muscle dystrophies in the European population and are caused by repeat expansion mutations. For ...Germany cumulative empiric evidence suggests an estimated prevalence of DM2 of roughly 9 in 100,000, therefore being as prevalent as DM1. In DM2, a (CCTG)
repeat tract located in the first intron of the
gene is expanded. The CCTG repeat tract is part of a complex repeat structure comprising not only CCTG tetraplets but also repeated TG dinucleotides and TCTG tetraplet elements as well as NCTG interruptions. Here, we provide the distribution of normal sized alleles in the German population, which was found to be highly similar to the Slovak population. Sequencing of 34 unexpanded healthy range alleles in DM2 positive patients (heterozygous for a full expansion) revealed that the CCTG repeat tract is usually interrupted by at least three tetraplets which according to current opinion is supposed to render it stable against expansion. Interestingly, only the largest analyzed normal allele had 23 uninterrupted CCTGs and consequently could represent an instable early premutation allele. In our diagnostic history of DM2 cases, a total of 18 premutations were detected in 16 independent cases. Here, we describe two premutation families, one with an expansion from a premutation allele and the other with a contraction of a full expansion down to a premutation allele. Our diagnostic results support the general assumption that the premutation range of unstable CCTG stretches lies obviously between 25 and 75 CCTGs. However, the clinical significance of premutation alleles is still unclear. In the light of the two described families we suggest incomplete penetrance. Thus, as it was proposed for other repeat expansion diseases (e.g., Huntington's disease), a fluid transition of penetrance is more likely rather than a clear cut CCTG number threshold.
Several advanced oxidation processes (AOPs) were investigated for the degradation of isoniazid (INH) and rifampicin (RIF) in aqueous solution: TiO2 and ZnO heterogeneous photocatalysis and ...homogeneous and heterogeneous UV-A photo-Fenton processes. Under optimized conditions (pH 6.0 and 500 mg L-1 of photocatalyst) the UV-A TiO2-photocatalysis removed approximately 90% of INH and 60% of RIF at 60 min. Under similar experimental conditions, the degradation efficiency of ZnO was significantly lower to INH. The low-cost UV-A homogeneous photo-Fenton process removed 70% of INH and 80% of RIF at 60 min. Photo-Fenton process using iron-immobilized in chitosan beads showed lower degradation efficiency (7% to INH and 50% to RIF) probably due to low iron availability in the catalyst surface. A radical scavenging assay was performed to investigate the effect of free radicals (hydroxyl radical (OH), electron vacancy (hole, h+), superoxide radical anions (O2-), and singlet oxygen (1O2)) on INH and RIF degradation during TiO2/UV-A photocatalysis. The two drugs have distinct degradation mechanisms, while RIF is degraded by h+, INH suffers influence of various active species. The TiO2/UV-A photocatalysis was employed to degrade INH/RIF residue.
Conducting polymers are, without question, outstanding materials. Their unique combination between metal-like, electrical, magnetic, and optical properties and the processability of polymeric ...materials consolidated their use in the electrochemical sciences over the past decades. However, the versatile character of these polymers combined with the advent of nanoscience has expanded their horizon of applications, now entering the fields of biomedicine and life science, as well as the environmental sciences. This review brings the latest advances on the use of conducting polymers micro and nanostructures in biomedical applications, such as controlled drug release, artificial muscles, and tissue engineering, where their stimuli responsiveness has shown new and exciting possibilities. Moreover, this review shows that the use of conducting polymers in effective extraction and pre-concentration of trace amount pollutants from complex matrices resulted in extraction capacities often superior to the materials currently commercialized. More than extracting contaminants, conducting polymers have shown further promissing results in the degradation of organic contaminants through photoelectrocatalysis. New features in the synthesis of these polymers are also addressed.
Zusammenfassung
Hintergrund
Jede Schwangerschaft bringt physische, psychische und soziale Veränderungen mit sich. Diese können zu Stress und ambivalenten Gefühlen bei Schwangeren führen, die einen ...starken Einfluss auf das Wohlbefinden und die Gesundheit von Mutter und Kind haben. Zur Förderung eines komplikationslosen Verlaufs der Schwangerschaft wird in der Forschungsliteratur die Stärkung der gesundheitlichen Ressourcen gefordert. Das Zürcher Ressourcen Modell (ZRM) ist ein ressourcenaktivierendes Selbstmanagementtraining, welches nach aktuellen Studienergebnissen die Gefühlsregulierung unterstützen und Stress reduzieren kann.
Methodik
Ziel dieser Studie war die erstmalige Wirksamkeitsprüfung des ZRM in der Schwangerschaft. Angenommen wurde, dass durch die Aktivierung der persönlichen Ressourcen der Schwangeren das Stresserleben reduziert und das subjektive Wohlbefinden gesteigert werden kann. Die Konstrukte „Stress“ und „Wohlbefinden“ wurden anhand von fünf psychometrischen Parametern operationalisiert. Durchgeführt wurde eine quasiexperimentelle unkontrollierte 6‑stündige Online-Interventionsstudie mit dem ZRM im Januar 2021 an
N
= 32 Schwangeren, basierend auf einem Prä-Post-Follow-up-Design. Zur Überprüfung der gebildeten Hypothesen wurden einfaktorielle Varianzanalysen (rmANOVAs) durchgeführt.
Ergebnisse
Die 1-faktoriellen rmANOVAs ergaben, dass die ZRM-Intervention das Stresserleben allgemein und schwangerschaftsspezifisch sowie das Angsterleben signifikant senken konnte. Handlungsorientierung nach Misserfolg und emotionales Wohlbefinden konnten signifikant gesteigert werden. Hinsichtlich der subjektiven Vitalität ließ sich lediglich deskriptiv eine Steigerung der Werte verzeichnen.
Schlussfolgerung
Die ZRM-Intervention erwies sich als wirksame Methode zur Optimierung der Stressbewältigung und Steigerung des Wohlbefindens während der Schwangerschaft. Es kann zielführend sein, das ZRM-Training als Ergänzung zur üblichen Geburtsvorbereitung einzusetzen. Zukünftige Forschungsarbeiten sollten v. a. die Übertragbarkeit der Ergebnisse unter Einbindung einer Kontrollgruppe sicherstellen.
Abstract
Background
Every pregnancy brings changes, which can lead to stress and ambivalent feelings for the pregnant person. These feelings can have a strong impact on the well-being and health of mother and the unborn child. To promote a healthy pregnancy outcome, the research literature recommends strengthening of mental and physical resources. The Zurich Resource Model (ZRM) is a resource-activating self-management training, which according to recent study results can support emotional regulation and reduce stress.
Methods
The aim of this study was to analyze the effects of the ZRM during first-time pregnancy. It was hypothesized that the pregnant person by activating their personal resources will reduce their stress level and the subjective well-being can be increased. The constructs “stress” and “subjective well-being” were operationalized using five different psychometric parameters. A quasi-experimental uncontrolled 6 h online intervention study with the ZRM in January 2021 was conducted with 32 pregnant women, based on a pre–post-follow-up design. For hypothesis testing, 1‑factorial analyses of variance (rmANOVAs) were performed
Results
1-factorial rmANOVAs showed that the ZRM-Intervention could reduce experiencing stress in general and pregnancy-related stress as well as experincing anxiety. The ability of action-orientation and emotional well-being was increased. An increase in subjecitve vitality was shown using descpritive statistics.
Conclusion
The ZRM intervention proved to be an effective method for optimizing stress management and increasing well-being during pregnancy. It can be used in addition to the usual childbirth preparation. Further research is needed, especially to ensure the transferability of the results including a control group.
To mimic post-ovulatory ageing, we have extended the in vitro maturation (IVM) phase to 48 h and examined effects on (i) developmental potential, (ii) expression of a panel of developmentally ...important genes and (iii) gene-specific epigenetic marks. Results were compared with the 24 h IVM protocol (control) usually employed for bovine oocytes. Cleavage rates and blastocyst yields were significantly reduced in oocytes after extended IVM. No significant differences were observed in the methylation of entire alleles in oocytes for the genes bH19, bSNRPN, bZAR1, bOct4 and bDNMT3A. However, we found differentially methylated CpG sites in the bDNMT3Ls locus in oocytes after extended IVM and in embryos derived from them compared with controls. Moreover, embryos derived from the 48 h matured oocyte group were significantly less methylated at CpG5 and CpG7 compared with the 24 h group. CpG7 was significantly hypermethylated in embryos produced from the control oocytes, but not in oocytes matured for 48 h. Furthermore, methylation for CpG5-CpG8 of bDNMT3Ls was significantly lower in oocytes of the 24 h group compared with embryos derived therefrom, whereas no such difference was found for oocytes and embryos of the in vitro aged group. Expression of most of the selected genes was not affected by duration of IVM. However, transcript abundance for the imprinted gene bIGF2R was significantly reduced in oocytes analyzed after extended IVM compared with control oocytes. Transcript levels for bPRDX1, bDNMT3A and bBCLXL were significantly reduced in 4- to 8-cell embryos derived from in vitro aged oocytes. These results indicate that extended IVM leads to ageing-like alterations and demonstrate that epigenetic mechanisms are critically involved in ageing of bovine oocytes, which warrants further studies into epigenetic mechanisms involved in ageing of female germ cells, including humans.
To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2‐mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter ...regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age‐matched controls. Methylation analysis of up to 50,000 individual DNA molecules per gene and sample allowed quantification of epimutations (alleles with >50% methylated CpGs), which are associated with epigenetic silencing. Compared to ESR1, which is representative for an average promoter, TS genes were characterized by a very low (< 1%) average methylation level and a very low mean epimutation rate (EMR; < 0.0001% to 0.1%). With exception of BRCA1, which showed an increased EMR in BC (0.31% vs. 0.06%), there was no significant difference between patients and controls. One of 36 HR BC patients exhibited a dramatically increased EMR (14.7%) in BRCA1, consistent with a disease‐causing epimutation. Approximately one third (15 of 44) EO BC patients exhibited increased rates of single CpG methylation errors in multiple TS genes. Both EO and HR BC patients exhibited global underexpression of blood TS genes. We propose that epigenetic abnormalities in normal body cells are indicative of disturbed mechanisms for maintaining low methylation and appropriate expression levels and may be associated with an increased BC risk.
What's new?
Cancer can change patterns of DNA methylation, with widespread loss of methylation but also localized increases in methylation. Here, the authors analyzed blood cells, looking for differences in methylation between breast cancer patients and healthy persons. They developed a deep bisulfite sequencing assay to specifically test the promoter regions of 8 tumor suppressor genes, plus the estrogen receptor gene, along with reduced tumor suppressor gene expression. They found that breast cancer patients showed increased methylation changes in multiple tumor suppressor genes, reduced tumor suppressor gene expression. Thus, epigenetic abnormalities could indicate disruptions in the mechanisms that maintain proper methylation, and could signal increased tumor risk.
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