Caring for Family Caregivers of Geriatric Patients: Results of a Participatory Health Research Project on Actual State and Needs of Hospital-Based Care Professionals.

Because of societal changes, family caregivers are becoming vital in long-term care provision for geriatric patients after discharge from hospital. Hospital-based geriatric care teams need tools to prepare and support family caregivers for their future caregiving role in the home environment. To explore the actual state and needs for implementing a suitable family caregiver support concept in a large geriatric hospital in Germany, a Participatory Health Research methodology was chosen. An academic investigator, assisted by a critical friend, facilitated all research steps. Geriatric care professionals joined as co-researchers and performed qualitative data collection using semi-structured interviews and focus group discussions. The entire co-research team took part in the thematic analyses. The existing family caregiver support was perceived as uncoordinated and incomplete, and a lack of knowledge about support programmes in the community was apparent. The needs regarding a comprehensive family caregiver support concept that acts on both individual caregiver as well as on system level, but also connects the two levels, were formulated. High grades of participation of hospital-based co-researchers could be achieved. A critical reflection on the research strategy revealed that the participatory methodology, although time-consuming, was perceived as a useful strategy within the hierarchically organized hospital.

The Role of Gelatinases in Campylobacter Jejuni Infection of Gnotobiotic Mice.

Matrix metalloproteinases (MMP)-2 and -9 (also referred to gelatinases-A and -B, respectively) are upregulated in the inflamed gut of mice and men. We recently demonstrated that synthetic gelatinase blockage reduced large intestinal pro-inflammatory immune responses and apoptosis following murine Campylobacter (C.) jejuni infection. In order to address which gelatinase mediates C. jejuni-induced immune responses, gnotobiotic MMP-2(-/-), MMP-9(-/-), and wildtype (WT) mice were generated by broadspectrum antibiotic treatment and perorally infected with C. jejuni strain 81-176. The pathogen stably colonized the murine intestinal tract irrespective of the genotype but did not translocate to extra-intestinal compartments. At days 8 and 14 postinfection (p.i.), less pronounced colonic histopathological changes were observed in infected MMP-2(-/-) mice, less distinct epithelial apoptosis, but more epithelial proliferation in both MMP-2(-/-) and MMP-9(-/-) mice, as compared to WT controls. Reduced immune responses in gelatinase-deficient mice were characterized by lower numbers of effector as well as innate and adaptive immune cells within the colonic mucosa and lamina propria. The expression of IL-22, IL-18, IL-17A, and IL-1ß mRNA was higher in the colon of MMP-2(-/-) as compared to WT mice. In conclusion, both MMP-2 and MMP-9 are differentially involved in mediating C. jejuni-induced intestinal immunopathology.

Matrix Metalloproteinase-2 Mediates Intestinal Immunopathogenesis in Campylobacter Jejuni-Infected Infant Mice.

Increased levels of the matrix metalloproteinases (MMPs)-2 and -9 (also referred to gelatinase-A and -B, respectively) can be detected in the inflamed gut. We have recently shown that synthetic gelatinase blockage reduces colonic apoptosis and pro-inflammatory immune responses following murine Campylobacter (C.) jejuni infection. In order to dissect whether MMP-2 and/or MMP-9 is involved in mediating C. jejuni-induced immune responses, infant MMP-2(-/-), MMP-9(-/-), and wildtype (WT) mice were perorally infected with the C. jejuni strain B2 immediately after weaning. Whereas, at day 2 postinfection (p.i.), fecal C. jejuni B2 loads were comparable in mice of either genotype, mice expelled the pathogen from the intestinal tract until day 4 p.i. Six days p.i., colonic MMP-2 but not MMP-9 mRNA was upregulated in WT mice. Remarkably, infected MMP-2(-/-) mice exhibited less frequent abundance of blood in feces, less distinct colonic histopathology and apoptosis, lower numbers of effector as well as innate and adaptive immune cells within the colonic mucosa, and higher colonic IL-22 mRNA levels as compared to infected WT mice. In conclusion, these results point towards an important role of MMP-2 in mediating C. jejuni-induced intestinal immunopathogenesis.

Perfluorocarbon particle size influences magnetic resonance signal and immunological properties of dendritic cells.

The development of cellular tracking by fluorine ((19)F) magnetic resonance imaging (MRI) has introduced a number of advantages for following immune cell therapies in vivo. These include improved signal selectivity and a possibility to correlate cells labeled with fluorine-rich particles with conventional anatomic proton ((1)H) imaging. While the optimization of the cellular labeling method is clearly important, the impact of labeling on cellular dynamics should be kept in mind. We show by (19)F MR spectroscopy (MRS) that the efficiency in labeling cells of the murine immune system (dendritic cells) by perfluoro-15-crown-5-ether (PFCE) particles increases with increasing particle size (560>365>245>130 nm). Dendritic cells (DC) are professional antigen presenting cells and with respect to impact of PFCE particles on DC function, we observed that markers of maturation for these cells (CD80, CD86) were also significantly elevated following labeling with larger PFCE particles (560 nm). When labeled with these larger particles that also gave an optimal signal in MRS, DC presented whole antigen more robustly to CD8+ T cells than control cells. Our data suggest that increasing particle size is one important feature for optimizing cell labeling by PFCE particles, but may also present possible pitfalls such as alteration of the immunological status of these cells. Therefore depending on the clinical scenario in which the (19)F-labeled cellular vaccines will be applied (cancer, autoimmune disease, transplantation), it will be interesting to monitor the fate of these cells in vivo in the relevant preclinical mouse models.