Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

Existential Loneliness Among Older People from the Perspective of Health Care Professionals: A European Multicenter Study.

Introduction: Health care professionals (HCPs) encounter different forms of loneliness in their work. It is essential that they have the courage, skills, and tools to deal with loneliness, in particular with existential loneliness (EL) which relates to meaning in life and the fundamentals of living and dying. Aim: The aim of this study was to investigate HCPs' views on loneliness among older people and their understanding, perception, and professional experience of EL in older people. Materials and Methods: In all, 139 HCPs from five European countries participated in audio-recorded focus group and individual interviews. The transcribed materials were locally analyzed using a predefined template. The participating countries' results were then translated, merged, and inductively analyzed using conventional content analysis. Results: Participants described different forms of loneliness - a negative form that is unwanted and causes suffering, and a positive form where solitude is desired and sought. The results showed that the HCPs' knowledge and understanding of EL varied. The HCPs mainly related EL to different types of loss, eg loss of autonomy, independence, hope, and faith, and to concern alienation, guilt, regret and remorse, and concerns about the future. Discussion and Conclusions: The HCPs expressed a need to improve their sensitivity and self-confidence to engage in existential conversations. They also stated the need to increase their knowledge and understanding of aging, death, and dying. Based on these results, a training program aimed to increase knowledge and understanding of older people's situation has been developed. The program includes practical training in conversations about emotional and existential aspects, based on recurrent reflections on the topics presented. The program is available at: www.aloneproject.eu.

Compromised vitamin D receptor signalling in malignant melanoma is associated with tumour progression and mitogen-activated protein kinase activity.

The aims of this study were to investigate, in cutaneous malignant melanoma (MM), the integrity of nuclear vitamin D receptor (VDR) signalling, as implied by VDR subcellular location; to investigate the relationship between VDR and tumour progression and the inhibitory effect on VDR by mitogen-activated protein kinase (MAPK) overactivity. Archived tissue from 34 benign melanocytic naevi, 149 MMs and 44 matched metastases were stained by immunohistochemistry for VDR and a subset of primary MMs were stained for phosphorylated-extracellular signal-regulated kinase as a marker of MAPK activity. MM cell lines were investigated to show the subcellular location of VDR and cell viability in response to ligand±MAPK inhibitor. Benign melanocytic naevi showed mainly a strong nuclear VDR staining in contrast to MM where decreased nuclear and emergent cytoplasmic VDRs were associated with malignant progression in terms of dermal invasion and metastasis. MMs that retained exclusive nuclear VDR at the tumour base did not metastasize, a potentially important prognostic indicator. Decreased nuclear VDR correlated with increased cytoplasmic staining, suggesting the failure of nuclear entry as a primary cause of defective VDR signalling in MM. The histological subset analysis and MM cell line studies confirmed the inhibitory effect of MAPK activity on VDR signalling, but the pattern of VDR subcellular localization suggested failure of VDR nuclear entry as a primary effect of MAPK activity rather than direct inhibition of VDR-regulated transcription. Furthermore, high MAPK activity in tumours expressing cytoplasmic VDR was associated with worsened prognosis.