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Inflammatory organ injury and sepsis have profound impacts on the morbidity and mortality of surgical and critical care patients. MicroRNAs are small RNAs composed of 20-25 nucleotides that have a significant contribution to gene regulation. MicroRNA-147 (miR-147), in particular, has been shown to have an emerging role in different physiological functions such as cell cycle regulation and inflammatory responses. However, animal model systems to study tissue-specific functions of miR-147 during inflammatory conditions in vivo are lacking. In the present study, we characterize miR-147 expression in different organs and cell types. Next, we generated a transgenic mouse line with a floxed miR-147 gene. Subsequently, we used this mouse line to generate mice with whole-body deletion of miR-147 (miR-147 -/-) by crossing "floxed" miR-147 mice with transgenic mice expressing Cre recombinase in all tissues (CMVcre mice). Systematic analysis of miR-147 -/- mice demonstrates normal growth, development, and off-spring. In addition, deletion of the target gene in different organs was successful at baseline or during inflammation, including the heart, intestine, stomach, liver, spleen, bone marrow, lungs, kidneys, or stomach. Moreover, miR-147 -/- mice have identical baseline inflammatory gene expression compared to C57BL/6 mice, except elevated IL-6 expression in the spleen (7.5 fold, p less then 0.05). Taken together, our data show the successful development of a transgenic animal model for tissue and cell-specific deletion of miR-147 that can be used to study the functional roles of miR-147 during inflammatory organ injury.Periodontitis is a widespread human chronic inflammatory disease of the tooth-surrounding tissues, which induces the destruction of periodontium and pathologic loss of teeth among adults. It has been reported that interleukin (IL)-17 was significantly increased in periodontitis patients compared to controls, while galectin-1 (Gal-1) was lower. Interestingly, it is found that Gal-1 treatment reduced systemic IL-17 levels. Hence, the aim of the present study was to explore the effect of Gal-1 on periodontitis development and investigate its underlying mechanism. In this study, Gal-1 was poorly expressed in lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs), and Gal-1 overexpression attenuated the production of inflammatory cytokines induced by LPS. Moreover, Gal-1 overexpression alleviated LPS-induced cell autophagy and apoptosis and reduced the expressions of IL-17A and IL-17R. Interestingly, IL-17A reversed the effect of Gal-1 on cell autophagy, inflammation, and cell apoptosis induced by the LPS challenge. In conclusion, Gal-1 inhibited LPS-induced autophagy and apoptosis of hPDLSC via regulation of IL-17A expression. Therefore, Gal-1 may have promising potential in regenerating periodontium.Allergic asthma (AA) is a complex disorder with heterogeneous features of airway hyperresponsiveness, inflammation, and remodeling. The increase of airway smooth muscle (ASM) mass is a fundamental component of bronchial remodeling in AA, yet the pathophysiological mechanisms and clinical outcomes associated with ASM modulation are still elusive. The objective of this study is to compare the expression level of β-dystroglycan (β-DG) in ASM in AA subjects and a healthy control group and to investigate the relationship between eosinophils and β-DG in ASM in patients with AA. Thirteen AA patients and seven control subjects were analyzed for the ASM area and eosinophil cells. Bronchial biopsies were stained by β-DG and eosinophil cationic protein (ECP) using immunohistochemistry. The proportion of ASM with β-DG staining was greater in those with AA than in the healthy control group (mean (95% CI) (28.3% (23.8-32.7%) vs. 16.4% (14.1-18.5%), P less then 0.0001). The number of ECP positive cells was higher in patients with AA than in the control group (4056 (3819-4296) vs. 466 (395-537) cells/mm2 P less then 0.0001). In AA, the number of ECP positive cells was significantly correlated to the β-DG expression in ASM (r = 0.77, P = 0.002). There is an increased β-DG expression in ASM and a higher number of ECP positive cells in the bronchial biopsy of those with AA than those in the control group. The increased expression of β-DG in ASM in AA subjects correlates with the number of eosinophils, suggesting a role for this cell in airway remodeling in AA.Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy. We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital. Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (46.9 vs. selleck chemical 8.2 months, p = 0.038). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively. DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival.Our previous studies revealed that MYCN downregulates the expression of DKK3, activates the Wnt/β-catenin signalling pathway at the transcriptional level, and thereby promotes the development of B cell acute lymphocytic leukaemia (B-ALL) but does not affect the methylation of the DKK3 promoter. Some studies have shown that MYCN is associated with histone acetylation. We speculate that histone deacetylase inhibitors (HDACis) can inhibit the Wnt/β-catenin signalling pathway by inhibiting MYCN and increasing the expression of DKK3. Based on previous experiments, we tested this hypothesis by analysing the changes in MYCN, DKK3 and the Wnt/β-catenin signalling pathways in B-ALL cells after treatment with the selective HDACi chidamide. The in vitro and in vivo experiments confirmed that chidamide inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of histone deacetylase, and these effects resulted in inhibition of the Wnt/β-catenin signalling pathway and the proliferation of B-ALL cells. These findings indicate that chidamide might be used alone or in combination with other chemotherapy regimens for patients with B-ALL and thus provide a new approach to the treatment of B-ALL.The effect of voluntary health insurance on preventive health has received limited research attention in developing countries, even when they suffer immensely from easily preventable illnesses. This paper surveys households in rural south-western Uganda, which are geographically serviced by a voluntary Community-based health insurance scheme, and applied propensity score matching to assess the effect of enrolment on using mosquito nets and deworming under-five children. We find that enrolment in the scheme increased the probability of using a mosquito net by 26% and deworming by 18%. We postulate that these findings are partly mediated by information diffusion and social networks, financial protection, which gives households the capacity to save and use service more, especially curative services that are delivered alongside preventive services. This paper provides more insight into the broader effects of health insurance in developing countries, beyond financial protection and utilisation of hospital-based services.The population of the United States is aging and by 2045 it is projected that approximately 1 in every 6 Alaskans will be 65+. Delivering healthcare and meeting the needs of older Alaskans in their community is critical to supporting healthy aging and community sustainability. Alaska Native (AN) Elders are underserved with very few studies providing an emic perspective on their experience aging. This research opens the door and allows us a glimpse of the AN Elder experience of aging the values, beliefs, and behaviors that allow them to age well. This study highlights the characteristics and activities of AN Elders in the Aleutian and Pribilof Islands to further develop the model of AN successful aging. There are many theories of aging and this study explores a cross-cultural understanding of gerotranscendence - the personal and interpersonal changes that result from successful aging or achieving Eldership. This study interviewed Elders in two communities of the Aleutian and Pribilof Islands region. Using 22 sed in increased life satisfaction. Elders provided clear evidence that they experienced aspects of gerotranscendence, which Tornstam (Journal of Aging Studies, 11(2), 143-154, 1997) categorized as the cosmic dimension, the self, and social and personal relationships. Elders adapting to aging-related changes and embracing their role as an Elder provided the greatest evidence of gerotranscendence - they developed new perspectives on life, took on new roles within the community, and experienced a shift in mindset that reinforced the importance of culture, tradition, and the Native Way of Life. This research allowed AN Elders to share their experiences, define successful aging, and expand the concept of Eldership to include changes in mindset, values, and relationships with themselves and others. The study is a framework to help us better understand the experiences of AN Elders aging successfully and the wisdom they wish to impart to others to help them learn to live healthy and meaningful lives.
Oncology settings increasingly use patient experience data to evaluate clinical performance. Given that older patients with hematologic malignancies are a high-risk population, this study examined factors associated with patient-reported health care experiences during the first year of their cancer diagnosis.
Cross-sectional study using the 2000-2015 SEER-CAHPS® data to examine patient experiences of Medicare enrollees with a primary diagnosis of leukemia or lymphoma. The primary outcomes were three CAHPS assessments overall care, personal doctor, and health plan overall. We estimated case-mix adjusted and fully adjusted associations between factors (i.e., clinical and sociodemographic) and the CAHPS outcomes using bivariate statistical tests and multiple linear regression.
The final sample included 1,151 patients, with 431 diagnosed with leukemia and 720 diagnosed with lymphoma (median time from diagnosis to survey 6months). Patients who completed the survey further apart from the diagnosis date reported significantly higher adjusted ratings of care overall (β .
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