Bergmannbuus6749

To examine if Wnt/beta-catenin pathway drives TM-MSCs towards a DA fate, we treated them with the Wnt agonist (CHIR, 3 μM) and the Wnt antagonist (IWP-2, 3 μM). Our results showed that the expressions of Nurr-1 and MAP2, as well as the Wnt/beta-catenin target genes, c-Myc and Cyclin D1, were significantly increased in the CHIR-treated TM-MSCs, but significantly reduced in those treated with IWP-2. Altogether, we declare first a higher neural potency of TM-MSCs compared to the more commonly used MSCs, BMSCs and ADSCs, and second that Wnt/beta-catenin activation directs the neurally induced TM-MSCs towards a DA fate.Young children are at high risk of lead poisoning, which can damage early cognitive and behavioral development and have long-lasting impacts. Home environments are persistent sources of exposure for children in urban, low-income settings. Community-academic partnerships are essential for public health intervention strategies addressing residential household lead exposure, yet community organization staff and home visitors often experience strain and burnout. We describe Parenting and Lead Mitigation at Home, a multifaceted partnership project to (a) develop and implement a community-based, peer-delivered education program for parents of young children in neighborhoods at risk for home lead exposure and (b) support the home visitors delivering programming. We developed, delivered, and initially evaluated Lead 101, a lead-exposure prevention curriculum informed by the Community Organizing and Family Issues (COFI) model. The goals were to educate parents around lead exposure risks and empower parents to reduce their child's risk. We developed a novel Reflective Practice pilot curriculum designed to provide emotional support to peer educators and community organization staff who delivered home-based programming. We trained 11 peer educators who delivered Lead 101 to 62 families. We pilot-tested the Reflective Practice curriculum with five community organization staff. The implementation process and pilot evaluation data suggest increased parent knowledge and self-efficacy regarding mitigation of home-based lead hazards, and high satisfaction with reflective practice. Using this model to develop multifaceted partnerships among universities, community-based organizations, and focal communities may facilitate community-engaged program development for families and systematic support for individuals working directly with families, thereby indirectly promoting child health and well-being.

Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeutic targets.

Chemoresistance is frequently elicited by microRNA (miRNA) alterations and splicing deregulations. Indeed, several miRNAs, such as miR-29c, have been shown to exert oncogenic or oncosuppressive activity. Alterations in the splicing machinery might also be involved in chemoresistance. Moreover, the Notch signaling pathway, often deregulated in MMe, plays a key role in cancer stem cells formation and self-renewal, leading to drug resistance and relapses.

The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.

The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.Mesenchymal stem cell-derived conditioned medium (MSC-CM) improves cardiac function, which is partly attributed to the released paracrine factors. Since such cardioprotection is moderate and transient, it is essential that MSC-CM's effective components are optimized to alleviate myocardial injury. To optimize MSC-CM, MSCs were treated with or without lipopolysaccharides (LPSs) for 48 h (serum-free), and the supernatant was collected. Then, LPS-CM (MSC stimulated by LPS) was further treated with LPS remover (LPS Re-CM) or was concentrated with a 10 kDa cutoff filter (10 kDa-CM). Enzyme-linked immunosorbent assay showed that all the pretreatments increased the levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin growth factor (IGF) except LPS Re-CM; 10 kDa-CM was superior to the other CMs. Cell Counting Kit-8 displayed that the viability of injured H9c2 cells was enhanced with the increase in the MSC-CM concentration. We also found that the 10 kDa-CM significantly alleviated H9c2 hypoxia/reoxygenation (H/R) injury, as evidenced by the increased Bcl-2/Bax ratio, and decreased the levels of lactate dehydrogenase and cardiac troponin. Transmission electron microscopy (TEM), TdT-mediated dUTP nick-end labelling (TUNEL), and hematoxylin and eosin staining (H&E) confirmed that 10 kDa-CM inhibited H/R-induced H9c2 morphological changes. Proteomic analysis identified 41 differentially expressed proteins in 10 kDa-CM, among which anti-inflammation, proangiogenesis, and antiapoptosis were related to cardiac protection. This study indicates that 10 kDa-CM protects H9c2 cardiomyocytes from H/R injury by preserving most of the protective factors, such as VEGF, HGF, and IGF, in MSC-CM.

In April 2020, the Japanese government declared a state of emergency owing to the outbreak of the novel coronavirus disease (COVID-19) pandemic, which resulted in reduced workforce and job losses. Furthermore, income is one of the most consistent predictors of dental visits. Therefore, this study examined the association between income changes and dental clinic visits during the COVID-19 state of emergency in Japan.

An online, self-reported cross-sectional survey about health activities including dental visits during the first COVID-19 state of emergency was conducted in Osaka, Japan (June 23 to July 12, 2020). Among participants with toothaches, the assessment for the association between "refrained from visiting a dentist despite wanting treatment for toothache during the state of emergency (refrained treatment)" and income changes before and after the state of emergency using a multivariate Poisson regression model adjusted for sex, age, self-rated health, frequency of regular dental visits, and employmeased income owing to COVID-19 before and after the state of emergency showed significantly higher prevalence ratios for refraining from visiting a dentist despite wanting treatment for toothache. Delanzomib in vitro We believe that our study makes a significant contribution because it provides novel, basic data that economic damages related to the COVID-19 pandemic might expand to oral health inequalities.

Our study found that individuals with decreased income owing to COVID-19 before and after the state of emergency showed significantly higher prevalence ratios for refraining from visiting a dentist despite wanting treatment for toothache. We believe that our study makes a significant contribution because it provides novel, basic data that economic damages related to the COVID-19 pandemic might expand to oral health inequalities.HIV represents a significant health burden in the United States. In 2012, the Centers for Disease Control and Prevention (CDC) stopped recommending many once-promoted interventions as part of a shift from one HIV intervention policy, Diffusion of Effective Behavioral Interventions (DEBI), to another, High Impact Prevention (HIP). Twenty-nine staff members from 10 organizations were interviewed to explore how organizations reacted to this shift. Three major themes emerged (1) Personal experience, community assessment, and epidemiological evidence influenced organizations' perceptions of efficacy and preference for earlier interventions. (2) Organizations were concerned that HIP interventions were not a good fit for their priority populations. (3) Organizations were frustrated with the top-down approach by the CDC prioritizing HIP interventions over earlier interventions. These results indicate that organizations continue to see value in and provide DEBI interventions. In addition, a more participatory process incorporating qualitative evidence and organizations' experiences may be necessary to achieve widespread de-implementation of DEBI interventions.

To explore the role of clonal hematopoiesis (CH) in chimeric antigen receptor (CAR) T-cell therapy outcomes, we performed targeted deep sequencing on buffy coats collected during the 21 days before lymphodepleting chemotherapy from 114 large B-cell lymphoma patients treated with anti-CD19 CAR T cells. We detected CH in 42 (36.8%) pretreatment samples, most frequently in PPM1D (19/114) and TP53 (13/114) genes. Grade≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) incidence was higher in CH-positive patients than CH-negative patients (45.2% vs. 25.0%, P=0.038). Higher toxicities with CH were primarily associated with DNMT3A, TET2, and ASXL1 genes (DTA mutations). Grade≥3 ICANS (58.9% vs. 25%, P=0.02) and≥3 cytokine release syndrome (17.7% vs. 4.2%, P=0.08) incidences were higher in DTA-positive than in CH-negative patients. The estimated 24-month cumulative incidence of therapy-related myeloid neoplasms after CAR T-cell therapy was higher in CH-positive than CH-negative patients [19% (95% CI, 5.5-38.7) vs. 4.2% (95% CI, 0.3-18.4), P=0.028].

Our study reveals that CH mutations, especially those associated with inflammation (DNMT3A, TET2, and ASXL1), are associated with severe-grade neurotoxicities in lymphoma patients receiving anti-CD19 CAR T-cell therapy. Further studies to investigate the mechanisms and interventions to improve toxicities in the context of CH are warranted. See related content by Uslu and June, p. 382. This article is highlighted in the In This Issue feature, p. 369.

Our study reveals that CH mutations, especially those associated with inflammation (DNMT3A, TET2, and ASXL1), are associated with severe-grade neurotoxicities in lymphoma patients receiving anti-CD19 CAR T-cell therapy. Further studies to investigate the mechanisms and interventions to improve toxicities in the context of CH are warranted. See related content by Uslu and June, p. 382. This article is highlighted in the In This Issue feature, p. 369.

To systematically investigate the performance of the analytical anisotropic algorithm (AAA) within the extremes of small tumor volumes and near-minimum lung and tumor tissue densities in order to identify combinations of these parameters where the use of AAA could result in a therapeutically unacceptable loss of tumor coverage on an energy and fractionation-specific basis.

Clinically appropriate volumetric modulated arc therapy (VMAT) treatment plans were generated with AAA for 180 unique combinations of lung density (0.05-0.30g/cm

), tumor density (0.30-1.00g/cm

), tumor diameter (0.5-2.5cm), and beam energy (6 and 10MV) and recomputed using the AcurosXB algorithm. Regression analysis was used to identify the strongest predictors of a reduction in biologically effective dose at a clinically relevant level (100Gy BED10) for commonly utilized 1-5 fraction treatment regimens. Measurements were performed within a phantom mimicking the lower extremes of lung and tumor densities to validate AcurosXB as the approximate ground truth within these scenarios.