The ability to walk under normal and cognitive dual task conditions is essential for safe mobility in older adults. However, while assessments of gait provide important health information, they have been limited to laboratory settings. We aimed to create an easy-to-use smartphone App enabling remote dual task walking assessments, and to demonstrate its reliability and validity in relatively healthy younger and older adults. The iPhone-based App utilized multi-media instructions and the phone's internal motion sensors to record movements during normal walking and walking with simultaneous serial-subtractions, with the phone placed in the user's pants pocket. Fourteen younger and 12 older adults completed two lab visits, during which data were acquired by the App and GAITRite mat over multiple normal and dual task walking trials. Participants also used the App to complete assessments in their homes on three separate days. Outcomes included average stride time and the dual-task cost to stride time. Across all detected strides in laboratory trials, derived outcome measures from the App were highly correlated with those derived from the GAITRite mat (Stride Time: p<0.001, r2 =0.99. Dual-task cost: p<0.001, r2 =0.98). These correlations were unaffected by age group, walking condition, and pocket tightness. Moreover, across trials, gait metrics demonstrated excellent test-retest reliability, both within and between laboratory visits and home-based assessments (ICC: 0.79-0.90). These results suggest that dual task walking assessments are valid and can be reliably administered in remote settings in relatively healthy younger and older adults.

Patient portals (PPs), secure websites that allow patients to access their electronic health records and other health tools, can benefit older adults managing chronic conditions. However, studies have shown a lack of PP use in older adults. Little is known about the way they use PPs in community settings and specific challenges they encounter. The aim of this study was to examine the current state of PP use in older adults, employing baseline data (quantitative and qualitative) from an ongoing nationwide online trial. The dataset includes 272 older adults (mean age, 70.0 years [50-92]) with chronic conditions. Findings showed that the majority of participants (71.3%) were using one or more PPs, but in limited ways. Their comments revealed practical difficulties with managing PPs, perceived benefits, and suggestions for improvement. Further studies with different older adult groups (e.g., clinic patients) will help develop and disseminate more usable PPs for these individuals.

To test the hypothesis of whether strenuous physical exercise inhibits neutrophils that can get activated by hypobaric hypoxia, we analyzed the effects of both high altitude and strenuous exercise alone and in combination on potentially cytotoxic functions of granulocytes in healthy volunteers (n = 12 men; average age 27.6 yr; range 24-38 yr). To this end, a field study was prospectively performed with an open-labeled within-subject design comprising three protocols. Protocol I (high altitude) involved a helicopter ascent, overnight stay at 3,196 m, and descent on the following day. Protocol II (physical exercise) involved hiking below an altitude of 2,100 m with repetitive ascents amounting to a total ascent to that of protocol III. Protocol III (combination of physical exercise and high altitude) involved climbing from 1,416 to 3,196 m, stay overnight, and descent on the following day. In protocol I, number of granulocytes did not change, but potentially cytotoxic functions of cells (CD18 expression and superoxide production) were early and significantly upregulated. In protocol II, subjects developed granulocytosis, but functions of cells were inhibited. In protocol III, granulocytosis occurred at higher values than those observed under protocol II. Potentially cytotoxic functions of cells, however, were strongly inhibited again. In conclusion, high altitude alone, even moderate in extent, can activate potentially cytotoxic functions of circulating granulocytes. Strenuous physical exercise strongly inhibits this activation, which may give protection from an otherwise inflammatory injury.

Despite continuous improvement of immunosuppression, small bowel transplantation (SBT) is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need to uncover novel insights that will lead to strategies to achieve better control of ACR. We hypothesized that particular miRNAs provide critical regulation of the intragraft immune response. The aim of our study was to identify miRNAs involved in intestinal ACR. We examined 26 small intestinal mucosal biopsies (AR/NR group; 15/11) obtained from recipients after SBT or multivisceral transplantation. We investigated the expression of 384 mature human miRNAs and 280 mRNAs associated with immune, inflammation and apoptosis processes. We identified differentially expressed 28 miRNAs and 58 mRNAs that characterized intestinal ACR. We found a strong positive correlation between the intragraft expression levels of three miRNAs (miR-142-3p, miR-886-3p and miR-132) and 17 mRNAs including CTLA4 and GZMB. We visualized these miRNAs within cells expressing CD3 and CD14 proteins in explanted intestinal allografts with severe ACR. Our data suggested that miRNAs have a critical role in the activation of infiltrating cells during intestinal ACR. These differences in miRNA expression patterns can be used to identify novel biomarkers and therapeutic targets for immunosuppressive agents.

Summary Small bowel transplantation (SBT) is becoming a preferred treatment for patients with irreversible intestinal failure. Despite continuous improvement of immunosuppression, SBT is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need for reliable detection markers and novel immunosuppressive strategies that can achieve better control of ACR. We hypothesized that particular transcriptomes provide critical regulation of the intragraft immune response. The aim of our study was to detect potential molecular biomarkers for identifying ACR in minute mucosal biopsies. We examined 30 intestinal mucosal biopsies (AR/NR; 17/13) obtained from recipients after SBT or multivisceral transplantation. We utilized TaqMan® Gene Signature Arrays (immune, inflammation and apoptosis) and investigated the expression of 280 genes. As one of our validations, we performed immunohistochemistry for selected targets. We detected 252 mRNAs in total, 92 of which were found with significantly different expression levels between the AR and NR groups. Immunohistochemistry showed significantly increased staining for IL1R2, ICAM1, GZMB, and CCL3 (P < 0.05) during ACR. For the first time, we characterize the potential molecular changes that are associated with modulation of histological appearances of intestinal ACR. These differences in transcriptome patterns can be used to identify robust biomarkers and potential novel therapeutic targets for immunosuppressive agents.