The elimination of hepatitis D as a public health problem: Needs and challenges.

Infection with hepatitis D virus leads to liver disease and cancer most rapidly of all hepatitis viruses. However, knowledge about hepatitis D remains poor and the burden and impact are underestimated, even though some 12-15 million people mainly in low- and middle-income countries may be affected. Its epidemiology is changing, with increasing migration leading to increased risks of infection and disease. A recent Viral Hepatitis Prevention Board meeting reviewed the current epidemiological status, improvements in diagnostic testing, advances in the development of novel antiviral agents in phase III trials and the need for a greater public health response, such as new guidelines and recommended testing of all people newly identified as infected with hepatitis B virus for hepatitis D virus infection. It identified issues and needs for attention with regard to prevention, diagnosis and treatment.

The effect of human follicular fluid on bovine oocyte developmental competence and embryo quality.

In this study, the hypothesis that embryo development during routine IVF procedures is determined by the pre-ovulatory follicular fluid composition was tested. Follicular fluid from women with obesity ('obese') and a 'positive' or 'negative' IVF outcome was added during the in-vitro maturation of bovine oocytes. 'Negative' and 'obese' follicular fluid reduced bovine embryo development, compared with laboratory control embryo development (P < 0.05 or P < 0.1). The addition of follicular fluid also altered bovine blastocyst gene expression. Furthermore, LDHA and PPARGC1B gene expression differed between follicular fluid groups. Data suggest that pre-ovulatory follicular fluid can potentially affect oocyte developmental competence and embryo quality. Furthermore, the bovine model may be used as a screening tool.

Nutrition and maternal metabolic health in relation to oocyte and embryo quality: critical views on what we learned from the dairy cow model.

Although fragmented and sometimes inconsistent, the proof of a vital link between the importance of the physiological status of the mother and her subsequent reproductive success is building up. High-yielding dairy cows are suffering from a substantial decline in fertility outcome over past decades. For many years, this decrease in reproductive output has correctly been considered multifactorial, with factors including farm management, feed ratios, breed and genetics and, last, but not least, ever-rising milk production. Because the problem is complex and requires a multidisciplinary approach, it is hard to formulate straightforward conclusions leading to improvements on the 'work floor'. However, based on remarkable similarities on the preimplantation reproductive side between cattle and humans, there is a growing tendency to consider the dairy cow's negative energy balance and accompanying fat mobilisation as an interesting model to study the impact of maternal metabolic disorders on human fertility and, more specifically, on oocyte and preimplantation embryo quality. Considering the mutual interest of human and animal scientists studying common reproductive problems, this review has several aims. First, we briefly introduce the 'dairy cow case' by describing the state of the art of research into metabolic imbalances and their possible effects on dairy cow reproduction. Second, we try to define relevant in vitro models that can clarify certain mechanisms by which aberrant metabolite levels may influence embryonic health. We report on recent advances in the assessment of embryo metabolism and meantime critically elaborate on advantages and major limitations of in vitro models used so far. Finally, we discuss hurdles to be overcome to successfully translate the scientific data to the field.

Fatty acid composition of the follicular fluid of normal weight, overweight and obese women undergoing assisted reproductive treatment: a descriptive cross-sectional study.

BACKGROUND: It has been well documented that the maturing oocyte is very vulnerable to changes in its micro-environment, the follicular fluid (FF). Recent research has focused on different components within this FF, like hormones, growth factors and metabolites, and how their concentrations are altered by diet and the metabolic health of the mother. It has been proposed that fatty acids (FAs) are potential factors that influence oocyte maturation and subsequent embryo development. However, a thorough study of the specific FF FA composition per lipid fraction and how this may be affected by BMI is currently lacking. Therefore, we investigated the BMI-related concentration of FAs in the phospholipid (PL), cholesteryl-ester (CHE), triglyceride (TG) and non-esterified (NE) lipid fraction in the FF of women undergoing assisted reproductive treatment (ART). METHODS: In this descriptive cross-sectional study, the FF of normal weight (18.5 ≤ BMI < 25.0 kg/m(2), n = 10), overweight (25.0 ≤ BMI < 30.0 kg/m(2), n = 10) and obese (BMI ≥ 30.0 kg/m(2), n = 10) women, undergoing ART, was sampled and analyzed for 23 specific FAs in the PL, CHE, TG and NEFA fraction, using a gas chromatographic analysis method. Differences between BMI-groups were studied by means of univariate general linear models and post hoc Sheffé tests. RESULTS: Total FA concentrations in the PL and CHE fraction did not differ between BMI groups. Total TG concentrations tended to differ and total NEFA concentrations differed significantly between BMI groups. Interestingly, 42% and 34% of the total FAs was esterified in the PL and CHE fraction, respectively, while only 10% were present in both the TG and NEFA fraction. Only few individual FA concentrations differed in the PL, CHE and TG fraction between BMI groups, whereas abundant BMI-related differences were found in the NEFA fraction. CONCLUSIONS: Our data show that differences in BMI are associated with alterations in the FA composition of the FF, an effect most pronounced in the NEFA fraction. These BMI-related variations could possibly affect granulosa cell viability, oocyte developmental competence and subsequent embryo quality possibly explaining differences in oocyte quality in obese patients described by others.

The Vaccine Training Barometer: Assessing healthcare providers' confidence to answer vaccine-related questions and their training needs.

Healthcare providers (HCP) are seen by the public as the most trustworthy source of information about vaccination. While HCPs could be a valuable partner to increase vaccine confidence in general, it is not clear whether they feel confident themselves to address questions concerning vaccination. In the context of the EU Joint Action on Vaccination (EU-JAV), the Vaccine Training Barometer, an online survey tool, was developed to assess how frequently HCPs receive questions about vaccination, how confident they feel to answer these questions, and to what extent they are willing to follow extra training. After a pilot test in Flanders, Belgium, the Barometer was launched and completed by 833 HCPs in Flanders and 291 HCPs in the Spanish regions of Catalonia, Navarre and Valencian Community from November 2020 until January 2021, during the COVID-19 pandemic, just before and during the start of the first COVID-19 vaccination campaigns. In both countries, HCPs frequently received questions about vaccination (mostly on a daily or weekly basis), and about two thirds of them indicated that the frequency of questions had increased during the three months prior to completing the survey. Most questions were about the side effects and safety of vaccines. In both countries, a considerable proportion of HCPs did not feel confident to answer vaccine-related questions (31.5% felt confident in Flanders, 21.6% in Spain). A large proportion of HCPs received questions in the last three months before the survey that they could not answer (52.4% of respondents in Flemish sample, 41.5% in Spanish sample). Only 11.4% (Flanders) and 11.3% (Spain) of the respondents felt they gained sufficient knowledge through their standard education to be able to answer questions about vaccination. Almost all respondents were willing to follow extra training on vaccination (Flanders: 95.4%, Spain: 96.6%). The Vaccine Training Barometer is thus a useful tool to monitor HCPs' confidence to answer questions about vaccination and to capture their training needs.

Individual factors influencing COVID-19 vaccine acceptance in between and during pandemic waves (July-December 2020).

BACKGROUND: A year after the start of the COVID-19 outbreak, the global rollout of vaccines gives us hope of ending the pandemic. Lack of vaccine confidence, however, poses a threat to vaccination campaigns. This study aims at identifying individuals' characteristics that explain vaccine willingness in Flanders (Belgium), while also describing trends over time (July-December 2020). METHODS: The analysis included data of 10 survey waves of the Great Corona Survey, a large-scale online survey that was open to the general public and had 17,722-32,219 respondents per wave. Uni- and multivariable general additive models were fitted to associate vaccine willingness with socio-demographic and behavioral variables, while correcting for temporal and geographical variability. RESULTS: We found 84.2% of the respondents willing to be vaccinated, i.e., respondents answering that they were definitely (61.2%) or probably (23.0%) willing to get a COVID-19 vaccine, while 9.8% indicated maybe, 3.9% probably not and 2.2% definitely not. In Flanders, vaccine willingness was highest in July 2020 (90.0%), decreased over the summer period to 80.2% and started to increase again from late September, reaching 85.9% at the end of December 2020. Vaccine willingness was significantly associated with respondents' characteristics: previous survey participation, age, gender, province, educational attainment, household size, financial situation, employment sector, underlying medical conditions, mental well-being, government trust, knowing someone with severe COVID-19 symptoms and compliance with restrictive measures. These variables could explain much, but not all, variation in vaccine willingness. CONCLUSIONS: Both the timing and location of data collection influence vaccine willingness results, emphasizing that comparing data from different regions, countries and/or timepoints should be done with caution. To maximize COVID-19 vaccination coverage, vaccination campaigns should focus on (a combination of) subpopulations: aged 31-50, females, low educational attainment, large households, difficult financial situation, low mental well-being and labourers, unemployed and self-employed citizens.

Alzheimer's disease CSF biomarkers: clinical indications and rational use.

This review focusses on the validation and standardization of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers, as well as on the current clinical indications and rational use of CSF biomarkers in daily clinical practice. The validated AD CSF biomarkers, Aß1-42, T-tau, and P-tau181, have an added value in the (differential) diagnosis of AD and related disorders, including mixed pathologies, atypical presentations, and in case of ambiguous clinical dementia diagnosis. CSF biomarkers should not be routinely used in the diagnostic work-up of dementia and cannot be used to diagnose non-AD dementias. In cognitively healthy subjects, CSF biomarkers can only be applied for research purposes, e.g., to identify pre-clinical AD in the context of clinical trials with potentially disease-modifying drugs. Therefore, biomarker-based early diagnosis of AD offers great opportunities for preventive treatment development in the near future.

Elevated non-esterified fatty acid concentrations during in vitro murine follicle growth alter follicular physiology and reduce oocyte developmental competence.

OBJECTIVE: To study how long-term elevated non-esterified fatty acid (NEFA) concentrations, typical in metabolic disorders such as obesity or type 2 diabetes, affect murine follicular development, follicle quality, and subsequent oocyte developmental competence in vitro. DESIGN: Experimental study. SETTING: In vitro culture setting. ANIMAL(S): Female and male 13-day old, B6CBAF1 mice of proven fertility were sacrificed for harvesting ovaries and epididymal sperm, respectively. INTERVENTION(S): Early secondary murine follicles were cultured in vitro in the presence of NEFAs until the antral stage (12 days). Treatments consisted of one or a mixture of NEFAs (stearic acid [SA], palmitic acid [PA], oleic acid [OA]) in physiological (basal) or pathological (high SA, high OA, high NEFA) concentrations. MAIN OUTCOME MEASURE(S): Follicular development; follicle and oocyte diameters; secretion of progesterone, estradiol, and inhibin B; and luteinized granulosa cell gene expression patterns were investigated. Oocytes from NEFA-exposed follicles were fertilized in vitro, and presumptive zygotes were cultured until the blastocyst stage. RESULT(S): Exposure to high SA reduced follicle diameters and day-12 antrum formation. Elevated NEFA concentrations changed luteinized granulosa cell messenger-ribonucleic acid abundance of genes related to energy/fatty acid/steroid metabolism, apoptosis, and oxidative stress. High NEFA and high SA treatments increased progesterone synthesis, compared with high OA follicles. Oocyte developmental competence was substantially reduced in oocytes retrieved from high OA-, high SA-, and high NEFA-exposed follicles compared with basal-treated follicles. CONCLUSION(S): This study showed, for the first time, that lipolysis-linked, elevated NEFA concentrations can potentially impair fertility, by altering follicular physiology and reducing oocyte developmental competence.