Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.
Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC. 相似文献
Objective Evaluate the efficacy of a 12 month nursing case-management intervention over a period of 18 months, 6 months after the end of intervention, for families of children attention deficit hyperactivity disorder (ADHD). Methods Mother and child dyads were enrolled to participate in a randomized controlled clinical trial. Children were 4–18 years old. Data were collected at baseline, 6, 12, and 18 months or 6 months after the termination of direct intervention. Longitudinal analyses, using generalized estimating equations, were conducted to assess change in study outcomes relating to family function, maternal stress, and child behavior over the 18 month period. Results Compared to control families, some family function outcomes were moderately improved in the intervention group. In particular, intervention families demonstrated substantial improvement in implementing family behavior controls (p value?=?0.038) and improvement in family satisfaction (not statistically significant p?=?0.062). Although there was improvement in the overall family function measure there was not a statistically significant difference between groups. Maternal stress and child behavior outcomes were not significantly different between control and intervention groups by the end of the intervention. Conclusions for Practice Addressing ADHD is complex and requires the assessment of comorbidities that might exacerbate negative behavior. Our findings support the latest American Academy of Pediatrics guidelines to use behavioral therapy as the first line of treatment in young children. Nursing case-management interventions that provide direct family education and improve family function, especially with respect to providing structure and behavior control, may complement and facilitate behavioral therapy for treatment of ADHD and improving child behavior. 相似文献
Although assessing individual consumer preferences are an important first step in providing person-centered care, the purpose of this study was to identify the top 10 shared preferences that are important to a majority of consumers receiving long-term services and supports.
Design
A cross-sectional survey design was used.
Setting and participants
Preference assessment interviews were conducted with 255 nursing home (NH) residents and 528 older adults receiving home and community-based services (HCBS).
Measurements
The Preferences for Everyday Living Inventory (PELI) was used to collect consumer preference information. Two versions of the PELI were used—the PELI-NH for NH residents and the PELI-HC for clients receiving HCBS and analysis focused on 41 shared items between the 2 versions. All respondents answered PELI questions independently and rated the importance of psychosocial preference items on a scale from not at all to a lot/very important.
Results
Ten preferences were shared as being important or very important by NH residents and older adults receiving HCBS. Most notably, more than 90% of respondents in each group rated “having regular contact with family” as an important priority. Having privacy, choices about what to eat, when to bathe, and activity options also were important preferences for a majority (77%-93%) in both settings.
Conclusion
Providers seeking to incorporate preference-based care can utilize study results as a foundation to incorporating important preferences into the care delivery process at the organizational level across care settings. For example, assessing all consumers on this core set of 10 shared preferences can assist with relationship building, transitions in care, and quality improvement. However, preferences with aggregate low-rated levels of importance in this study should not be discredited or eliminated. It is important for providers to understand the unique preference inventory of each older adult, which can then be targeted toward meeting goals for preference fulfillment. This can aid in bringing preferences into practice to improve the quality of care and quality of life to best meet the psychosocial needs of each person. 相似文献