Perspectives of European Patient Advocacy Groups on Volunteer Registries and Vaccine Trials: VACCELERATE Survey Study.

BACKGROUND: The VACCELERATE Pan-European Scientific network aims to strengthen the foundation of vaccine trial research across Europe by following the principles of equity, inclusion, and diversity. The VACCELERATE Volunteer Registry network provides access to vaccine trial sites across the European region and supports a sustainable volunteer platform for identifying potential participants for forthcoming vaccine clinical research. OBJECTIVE: The aim of this study was to approach members of patient advocacy groups (PAGs) across Europe to assess their willingness to register for the VACCELERATE Volunteer Registry and their perspectives related to participating in vaccine trials. METHODS: In an effort to understand how to increase recruitment for the VACCELERATE Volunteer Registry, a standardized survey was developed in English and translated into 8 different languages (Dutch, English, French, German, Greek, Italian, Spanish, and Swedish) by the respective National Coordinator team. The online, anonymous survey was circulated, from March 2022 to May 2022, to PAGs across 10 European countries (Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Spain, and Sweden) to share with their members. The questionnaire constituted of multiple choice and open-ended questions evaluating information regarding participants' perceptions on participating in vaccine trials and their willingness to become involved in the VACCELERATE Volunteer Registry. RESULTS: In total, 520 responses were collected and analyzed. The PAG members reported that the principal criteria influencing their decision to participate in clinical trials overall are (1) the risks involved, (2) the benefits that will be gained from their potential participation, and (3) the quality and quantity of information provided regarding the trial. The survey revealed that, out of the 520 respondents, 133 individuals across all age groups were "positive" toward registering in the VACCELERATE Volunteer Registry, with an additional 47 individuals reporting being "very positive." Respondents from Northern European countries were 1.725 (95% CI 1.206-2.468) times more likely to be willing to participate in the VACCELERATE Volunteer Registry than respondents from Southern European countries. CONCLUSIONS: Factors discouraging participants from joining vaccine trial registries or clinical trials primarily include concerns of the safety of novel vaccines and a lack of trust in those involved in vaccine development. These outcomes aid in identifying issues and setbacks in present registries, providing the VACCELERATE network with feedback on how to potentially increase participation and enrollment in trials across Europe. Development of European health communication strategies among diverse public communities, especially via PAGs, is the key for increasing patients' willingness to participate in clinical studies.

Aging of the adrenal gland and its impact on the stress response.

This article discusses the physiological and anatomical changes of adrenal gland with age and the effects this has overall on how the organ responds to stress. Physiological changes entail a decrease in adrenocorticoid hormone secretion however cortisol levels remain intact leading to a disruptive stress response. Additionally, loss of zonation of the organ also occurs. Both characteristics in combination with chronic stress affect overall health. Complex interplay between adrenal aging and stress responsiveness is confounded further by the impact they expel on other systems, such as the thyroid hormone. The body undergoes age-related transformations modifying rate of cellular growth, differentiation, senescence, and hormone production. Given the multiplicity and complexity of hormones, their production must be considered to develop appropriate interventions to mitigate its effect on age related diseases in health.

Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

The Challenges of Vaccine Trial Participation among Underserved and Hard-to-Reach Communities: An Internal Expert Consultation of the VACCELERATE Consortium.

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

Burnout and motivation to study medicine among students during the COVID-19 pandemic.

Aim: To investigate medical students' burnout and motivation levels in each of the six years of their studies during the COVID-19 pandemic and identify independent predictors of burnout and motivation. Methods: An anonymous cross-sectional survey was sent to the students of all six years within our school. Burnout was measured with the adapted Oldenburg Burnout Inventory questionnaire (OLBI-S) and motivation with the updated Strength of Motivation for Medical School (SMMS-R) questionnaire. Univariate analysis was performed with the Kruskal-Wallis test and Spearman's correlation, while multivariable analysis with linear regression models. Results: A total of 333 medical students (52% of student body) responded. Higher burnout levels correlated with lower motivation to study medicine (rho = -0.30, p < 0.001). Burnout levels differed between the six years of medical studies, peaking in years two and four whereas being the lowest in year one (p = 0.01). Motivation levels differed significantly as well, peaking in years one and four whereas being the lowest in years five and six (p = 0.012). In the multivariable linear regression models, being a female (b = 2.22, p = 0.016), studying in the fourth year vs. first year (b = 2.54, p = 0.049), having a perceived beginner/intermediate vs. advanced/expert technology level (b = 2.05, p = 0.032) and a perceived poor school support system (b = 6.35, p < 0.001) were independently associated with higher burnout levels. Furthermore, studying in the fifth year vs. first year (b = -5.17, p = 0.019) and a perceived poor school support system (b = -3.09, p = 0.01) were independently associated with a reduced motivation to study medicine. Conclusion: Our study highlighted potential areas for intervention to decrease the rate of burnout and low motivation among medical students. However, further research is needed to unravel the full effect of the pandemic on medical students.

Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit.

BACKGROUND: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. OBJECTIVE: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. METHODS: Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients' Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. RESULTS: This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. CONCLUSIONS: The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials.

Key genes expressed in mitochondria­endoplasmic reticulum contact sites in cancer (Review).

Cell fate is critically affected by mitochondrial activity, from ATP production to metabolism, Ca2+ homeostasis and signaling. These actions are regulated by proteins expressed in mitochondria (Mt)­endoplasmic reticulum contact sites (MERCSs). The literature supports the fact that disruption to the physiology of the Mt and/or MERCSs can be due to alterations in the Ca2+ influx/efflux, which further regulates autophagy and apoptosis activity. The current review presents the findings of numerous studies with regard to the involvement of proteins positioned in MERCSs and how they express anti­ and pro­apoptotic properties by adjusting Ca2+ across membranes. The review also explores the involvement of mitochondrial proteins as hot spots in cancer development, cell death and/or survival, and the method via which they can potentially be targeted as a therapeutic option.

VACCELERATE Volunteer Registry: A European study participant database to facilitate clinical trial enrolment.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. METHODS: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. RESULTS: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. CONCLUSIONS: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands).

Shift to emergency remote preclinical medical education amidst the Covid-19 pandemic: A single-institution study.

The Covid-19 pandemic disrupted medical education, shifting it towards emergency remote delivery. This cross-sectional study aimed to assess the impact of the pandemic on preclinical medical education and identify predictors of the virtual learning experience and perceived stress. An anonymous survey was delivered electronically to the students of the authors' medical school that attended either histology or pathology. This survey contained two scales, the virtual learning experience (VLE) and the perceived stress scale-10 (PSS-10). A total of 173/255 (68%) responded, showing a positive perception towards the remote delivery of both courses. An exploratory factor analysis was performed on the VLE scale items and four new dimensions were formed: "course quality and learning outcomes", "student motivation", virtual against F2F learning", and "virtual laboratory sessions". The following significant predictors of enhanced VLE, in at least one dimension, were identified: female gender, pathology course, final examination grade >80%, lower perceived stress levels, studying in home country, and holding of another degree before medical school. In addition, the following predictors were significantly associated with higher levels of student perceived stress: female gender, pathology course, studying away from home, and suboptimal internet connection. Notably, the quality of internet connection was significantly associated with the students' final examination performance. Concerning the best mode for future delivery of both courses, most students proposed a blended, rather than an entirely on-campus or online approach. In conclusion, despite its problems, a high-quality remote preclinical medical education was possible in the authors' school and offered tremendous opportunities for future improvement.

Clinical significance of P-class pumps in cancer.

P-class pumps are specific ion transporters involved in maintaining intracellular/extracellular ion homeostasis, gene transcription, and cell proliferation and migration in all eukaryotic cells. The present review aimed to evaluate the role of P-type pumps [Na+/K+ ATPase (NKA), H+/K+ ATPase (HKA) and Ca2+-ATPase] in cancer cells across three fronts, namely structure, function and genetic expression. It has been shown that administration of specific P-class pumps inhibitors can have different effects by: i) Altering pump function; ii) inhibiting cell proliferation; iii) inducing apoptosis; iv) modifying metabolic pathways; and v) induce sensitivity to chemotherapy and lead to antitumor effects. For example, the NKA ß2 subunit can be downregulated by gemcitabine, resulting in increased apoptosis of cancer cells. The sarcoendoplasmic reticulum calcium ATPase can be inhibited by thapsigargin resulting in decreased prostate tumor volume, whereas the HKA α subunit can be affected by proton pump inhibitors in gastric cancer cell lines, inducing apoptosis. In conclusion, the present review highlighted the central role of P-class pumps and their possible use and role as anticancer cellular targets for novel therapeutic chemical agents.