Prevalence of High Resilience in Old Age and Association with Perceived Threat of COVID-19—Results from a Representative Survey

Little is known about resilience in old age and its manifestation during the COVID-19 pandemic. This study aims to estimate the prevalence of high resilience in the German old age population. We further examine the socio-demographic correlates and whether high resilience reflects on older adults’ perception of the threat posed by COVID-19. The data were derived from a representative telephone survey of n = 1005 older adults (≥65 years) during the first COVID-19 lockdown. Assessments included socio-demographic variables, the perceived threat of COVID-19, and high resilience (Brief Resilience Scale; cutoff: ≥4.31). The association between high resilience and threat from COVID-19 was analyzed using ordinal logistic regression. The study sample had a mean age (SD) of 75.5 (7.1) years, and n = 566 (56.3%) were female. The estimated prevalence of high resilience was 18.7% (95% CI = [16.3; 21.2]). High resilience was more prevalent in the younger age group and participants with higher education levels. High resilience was significantly associated with a lower perception of threat from COVID-19. The results of the representative survey in the German old age population showed that one out of five adults aged 65 years and older had high resilience. Older adults with high resilience tended to feel less threatened by COVID-19. Further research on resilience in old age is needed to support vulnerable groups in the context of care

Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing

Gut-associated lymphoid tissue (GALT) dendritic cells (DCs) display a unique ability to generate CCR9+α4β7+ gut-tropic CD8+ effector T cells. We demonstrate efficient induction of CCR9 and α4β7 on CD8+ T cells in mesenteric lymph nodes (MLNs) after oral but not intraperitoneal (i.p.) antigen administration indicating differential targeting of DCs via the oral route. In vitro, lamina propria (LP)–derived DCs were more potent than MLN or Peyer's patch DCs in their ability to generate CCR9+α4β7+ CD8+ T cells. The integrin α chain CD103 (αE) was expressed on almost all LP DCs, a subset of MLN DCs, but on few splenic DCs. CD103+ MLN DCs were reduced in number in CCR7−/− mice and, although CD8+ T cells proliferated in the MLNs of CCR7−/− mice after i.p. but not oral antigen administration, they failed to express CCR9 and had reduced levels of α4β7. Strikingly, although CD103+ and CD103− MLN DCs were equally potent at inducing CD8+ T cell proliferation and IFN-γ production, only CD103+ DCs were capable of generating gut-tropic CD8+ effector T cells in vitro. Collectively, these results demonstrate a unique function for LP-derived CD103+ MLN DCs in the generation of gut-tropic effector T cells

RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML

The Adhesion G Protein-Coupled Receptor GPR97/ADGRG3 Is Expressed in Human Granulocytes and Triggers Antimicrobial Effector Functions

The adhesion family of G protein-coupled receptors (aGPCRs) comprises 33 members in human, several of which are distinctly expressed and functionally involved in polymorphonuclear cells (PMNs). As former work indicated the possible presence of the aGPCR GPR97 in granulocytes, we studied its cellular distribution, molecular structure, signal transduction, and biological function in PMNs. RNA sequencing and mass-spectrometry revealed abundant RNA and protein expression of ADGRG3/GPR97 in granulocyte precursors and terminally differentiated neutrophilic, eosinophilic, and basophilic granulocytes. Using a newly generated GPR97-specific monoclonal antibody, we confirmed that endogenous GPR97 is a proteolytically processed, dichotomous, N-glycosylated receptor. GPR97 was detected in tissue-infiltrating PMNs and upregulated during systemic inflammation. Antibody ligation of GPR97 increased neutrophil reactive oxygen species production and proteolytic enzyme activity, which is accompanied by an increase in mitogen-activated protein kinases and IκBα phosphorylation. In-depth analysis of the GPR97 signaling cascade revealed a possible switch from basal Gαs/cAMP-mediated signal transduction to a Gαi-induced reduction in cAMP levels upon mutation-induced activation of the receptor, in combination with an increase in downstream effectors of Gβγ, such as SRE and NF-κB. Finally, ligation of GPR97 increased the bacteria uptake and killing activity of neutrophils. We conclude that the specific presence of GPR97 regulates antimicrobial activity in human granulocytes

Maintien à domicile de la personne âgée dépendante et prise en charge par des équipes multidisciplinaires / Caroline Kuhn

STRASBOURG ILLKIRCH-Pharmacie (672182101) / SudocSTRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

La Chine (enjeux économiques du marché dermo-cosmétique, exemple du lancement de la gamme Eau Thermale Avène)

STRASBOURG ILLKIRCH-Pharmacie (672182101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Adhesion GPCRs in Regulating Immune Responses and Inflammation

The adhesion family comprises one of the five major clades of G protein-coupled receptors (GPCRs). Unlike conventional GPCRs, adhesion GPCRs (aGPCRs) have extended ectodomains with various protein folds that facilitate protein-protein interactions and, hence, putative cellular adhesive functions. Juxtaposed to the seven-pass transmembrane domain is a GPCR autoproteolysis-inducing domain that enables autoproteolytic cleavage of the receptor, resulting in a bipartite structure of many aGPCRs. aGPCRs are widely distributed and play critical roles in many developmental processes; yet, the underlying mechanisms of activation and signal transduction have emerged only recently. About one-third of the 33 human aGPCRs are expressed in hematopoietic stem, progenitor, or mature cells, where they define distinct cellular populations. Recent studies have demonstrated roles of aGPCR in the control of innate effector functions and the susceptibility for and onset of (auto) inflammatory conditions. We here discuss the current knowledge about aGPCRs in the regulation of immune responses and inflammatio

Prevalence of High Resilience in Old Age and Association with Perceived Threat of COVID-19—Results from a Representative Survey

Little is known about resilience in old age and its manifestation during the COVID-19 pandemic. This study aims to estimate the prevalence of high resilience in the German old age population. We further examine the socio-demographic correlates and whether high resilience reflects on older adults’ perception of the threat posed by COVID-19. The data were derived from a representative telephone survey of n = 1005 older adults (≥65 years) during the first COVID-19 lockdown. Assessments included socio-demographic variables, the perceived threat of COVID-19, and high resilience (Brief Resilience Scale; cutoff: ≥4.31). The association between high resilience and threat from COVID-19 was analyzed using ordinal logistic regression. The study sample had a mean age (SD) of 75.5 (7.1) years, and n = 566 (56.3%) were female. The estimated prevalence of high resilience was 18.7% (95% CI = [16.3; 21.2]). High resilience was more prevalent in the younger age group and participants with higher education levels. High resilience was significantly associated with a lower perception of threat from COVID-19. The results of the representative survey in the German old age population showed that one out of five adults aged 65 years and older had high resilience. Older adults with high resilience tended to feel less threatened by COVID-19. Further research on resilience in old age is needed to support vulnerable groups in the context of care

Prevalence of high resilience in old age and association with perceived threat of covid-19—results from a representative survey

Little is known about resilience in old age and its manifestation during the COVID-19 pandemic. This study aims to estimate the prevalence of high resilience in the German old age population. We further examine the socio-demographic correlates and whether high resilience reflects on older adults’ perception of the threat posed by COVID-19. The data were derived from a representative telephone survey of n = 1005 older adults (≥65 years) during the first COVID-19 lockdown. Assessments included socio-demographic variables, the perceived threat of COVID-19, and high resilience (Brief Resilience Scale; cutoff: ≥4.31). The association between high resilience and threat from COVID-19 was analyzed using ordinal logistic regression. The study sample had a mean age (SD) of 75.5 (7.1) years, and n = 566 (56.3%) were female. The estimated prevalence of high resilience was 18.7% (95% CI = [16.3; 21.2]). High resilience was more prevalent in the younger age group and participants with higher education levels. High resilience was significantly associated with a lower perception of threat from COVID-19. The results of the representative survey in the German old age population showed that one out of five adults aged 65 years and older had high resilience. Older adults with high resilience tended to feel less threatened by COVID-19. Further research on resilience in old age is needed to support vulnerable groups in the context of care