Upon viral infection, stressed or damaged cells can release alarmins like IL‐33 that act as endogenous danger signals alerting innate and adaptive immune cells. IL‐33 coming from nonhematopoietic cells has been identified as important factor triggering the expansion of antiviral CD8+ T cells. In LN the critical cellular source of IL‐33 is unknown, as is its potential cell‐intrinsic function as a chromatin‐associated factor. Using IL‐33‐GFP reporter mice, we identify fibroblastic reticular cells (FRC) and lymphatic endothelial cells (LEC) as the main IL‐33 source. In homeostasis, IL‐33 is dispensable as a transcriptional regulator in FRC, indicating it functions mainly as released cytokine. Early during infection with lymphocytic choriomeningitis virus (LCMV) clone 13, both FRC and LEC lose IL‐33 protein expression suggesting cytokine release, correlating timewise with IL‐33 receptor expression by reactive CD8+ T cells and their greatly augmented expansion in WT versus ll33−/− mice. Using mice lacking IL‐33 selectively in FRC versus LEC, we identify FRC as key IL‐33 source driving acute and chronic antiviral T‐cell responses. Collectively, these findings show that LN T‐zone FRC not only regulate the homeostasis of naïve T cells but also their expansion and differentiation several days into an antiviral response.

Introduction: Malnutrition and nutrition-related diseases are associated with hospital admissions, disability, institutionalization, and mortality in older people. Specialists in Geriatric Medicine and nutrition evaluate nutritional status as part of the comprehens ive geriatric assessment; however, malnutrition still remains under-recognized and undermanaged. Our survey explored nutrition assessment approaches used in daily clinical practice by geriatricians across Europe. Methods: A 19-item survey on methods and instruments for malnutrition assessment in geriatric settings, and details of any national guidelines, was sent to 40 postgraduate fellows of the European Academy of Medicine of Ageing (EAMA, 2017-2019 class).Results: Thirty-six of the 40 eligible EAMA participants, representing 14 European countries, responded. In clinical practice, MNA and MNA-SF were most frequently used for screening (44.1%, 52.9%, respectively) and diagnosing (45.7%, 40.0%) malnutrition. Weight loss (n=36, 100%), body mass index (n=30, 85.7%), and low energy/food intake (n=27, 77.1%) were the most frequent clinical variables considered. The absolute and relative amount of weight loss, and over what time period, varied widely. These routinely considered clinical factors contribute to validated GLIM, ASPEN-AND and ESPEN criteria for diagnosis of malnutrition, but these criteria were seldom used (GLIM=0%, ASPEN=0%; n=9, ESPEN=25.7%). National guidelines were available in 9 of the 14 countries, and generally recommended MNA and MNA-SF for community-dwelling and hospitalized older patients. Albumin was often suggested as a nutritional marker. HighlightsNutritional assessment performed by geriatricians in clinical practice varies widely across European countries.

Despite the improvement of aeronautical equipment and the quality of dental care, barodontalgias were still present in 2010 in the French military and in civilian aircrews. We recommend prevention programs be established in order to minimize the frequency of barodontalgias and their potential repercussions on flight safety.

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Complications following intravesical BCG therapy are rare but can be severe and fatal. Histology seems to be the method that contributes most in confirmation of the diagnosis. Antimycobacterial therapy is effective, and probably more efficient when combined with corticosteroids, but the regimen and duration of the treatment are not standardized.

Among the growing family of inhibitory receptors regulating immunity, sialic acid-binding immunoglobulin domain-containing lectins (Siglecs) have recently emerged as immunoregulatory receptors recognizing sialylated ligands on tumor cell surface. However, their role in the immunoregulation of bladder cancer (BCa) remains unknown. Here, we determined the presence of eight Siglec ligands (SLs) on bladder nontumor and tumor cell lines. S2L, S3L, and S6L were not expressed, and few bladder tumor cell lines expressed S5L and S14L. In contrast, S7L and S10L were upregulated on all bladder tumor cell lines. We found a discrepency in S9L expression by nontumor cell lines, which is however highly expressed by bladder tumor cell lines. Notably, expression of S5L, S6L, and S14L was increased upon bacillus Calmette-Guérin (BCG) infection. Furthermore, we analyzed the expression of Siglecs onTcells from healthy donors and BCa patients. Circulating Tcells only expressed Siglec-6, which is upregulated in non-muscle-invasive BCa patients. In addition, BCG therapy induced the overexpression of Siglec-6 by urinary CD8 + T cells. In vitro functional assays suggested that Siglecs may decrease cytotoxic functions of effector CD8 + T cells. Finally, analyses from two BCa datasets (The Cancer Genome Atlas and UROMOL cohorts) showed that Siglec-6 is associated with tumor progression and poor survival. Our findings indicate that Siglec-6 might be a new target for BCa treatments. Patient summary: We investigated the expression of Siglecs, a family of immunoregulatory receptors, in bladder cancer patients. We observed that the expression of Siglec-6 is increased on circulating and urinary T cells of non-muscle-invasive bladder cancer patients. We also showed that Siglec-6 is associated with lower survival in bladder cancer patients and might contribute to bladder cancer recurrence.

BACKGROUND Identifying vulnerable older patients admitted to an emergency department (ED) who are at increased risk for adverse events and require a comprehensive geriatric assessment remains a major challenge. The interRAI Emergency Department Screener (EDS) was developed for this specific purpose, but data regarding its validity are scarce. OBJECTIVES To determine (1) convergent validity of the EDS with results of a geriatricianʼs assessment in defining the need for prompt versus delayed/no further geriatric assessment and (2) predictive validity of the EDS for hospital admission, prolonged hospital length of stay (LOS), and 30‐day readmission. DESIGN Prospective observational study. SETTING ED of an academic hospital in Switzerland. PARTICIPANTS Older patients, aged 75 years or older (N = 202), who visited the ED over a 4‐month period. Patients with life‐threatening conditions were excluded. MEASUREMENTS Data for EDS were collected by two clinical nurses. A brief geriatric assessment was performed separately and interpreted by a geriatrician blinded to the EDS results. Orientation after ED discharge, hospital LOS, and 30‐day readmission were retrieved from the administrative database. RESULTS Participants were aged 83.2 ± 5.4 years, 56.9% were female, and 43.6% lived alone. Frequent findings at geriatric assessment were impairment in gait/balance (69.3%), polypharmacy (64.9%), cognitive impairment/delirium (48.2%), risk of malnutrition (46.0%), and mood impairment (38.1%). The proportions of participants who required prompt, delayed, and no further geriatric assessment, according to the EDS, were 27.2%, 29.2%, and 43.6%, respectively. The EDS had low sensitivity in predicting hospital admission (28.8%), prolonged LOS (26.3%), and 30‐day readmission (26.1%), with the Area Under the Receiver Operating Characteristics (AUROC) being 51.8%, 48.1%, and 49.4%, respectively. CONCLUSION The EDS performed poorly in both convergent and predictive validity analyses, precluding its use as a screening tool in this ED environment. Further efforts should be undertaken to better target interventions to reduce adverse health trajectories in the older ED population.

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