Kidney transplantation is the preferred renal replacement therapy available. Yet, long‐term transplant survival is unsatisfactory, partially due to insufficient possibilities of longitudinal ...monitoring and understanding of the biological processes after transplantation. Small urinary extracellular vesicles (suEVs) – as a non‐invasive source of information – were collected from 22 living donors and recipients. Unbiased proteomic analysis revealed temporal patterns of suEV protein signature and cellular processes involved in both early response and longer‐term graft adaptation. Complement activation was among the most dynamically regulated components. This unique atlas of the suEV proteome is provided through an online repository allowing dynamic interrogation by the user. Additionally, a correlative analysis identified putative prognostic markers of future allograft function. One of these markers – phosphoenol pyruvate carboxykinase (PCK2) – could be confirmed using targeted MS in an independent validation cohort of 22 additional patients. This study sheds light on the impact of kidney transplantation on urinary extracellular vesicle content and allows the first deduction of early molecular processes in transplant biology. Beyond that our data highlight the potential of suEVs as a source of biomarkers in this setting.
Implementation research infrequently addresses economic factors, despite the importance of understanding the costs of implementing evidence-based practices (EBPs). Though partnerships with health ...economists have the potential to increase attention to economic factors within implementation science, barriers to forming these collaborations have been noted. This study investigated the experiences of health economists and implementation researchers who have partnered across disciplines to inform strategies to increase such collaborations.
A purposeful sampling approach was used to identify eight health economists and eight implementation researchers with experience participating in cross-disciplinary research. We used semi-structured interviews to gather information about participants' experiences with collaborative research. Thematic analysis was conducted to identify core themes related to facilitators and barriers to collaborations.
Health economists and implementation researchers voiced different perspectives on collaborative research, highlighting the importance of increasing cross-disciplinary understanding. Implementation researchers described a need to measure costs in implementation studies, whereas many health economists described that they seek to collaborate on projects that extend beyond conducting cost analyses. Researchers in both disciplines articulated motivations for collaborative research and identified strategies that promote successful collaboration, with varying degrees of convergence across these themes. Shared motivations included improving methodological rigor of research and making a real-world impact. Strategies to improve collaboration included starting partnerships early in the study design period, having a shared interest, and including health economists in the larger scope of the research.
Health economists and implementation researchers both conduct research with significant policy implications and have the potential to inform one another's work in ways that might more rapidly advance the uptake of EBPs. Collaborative research between health economists and implementation science has the potential to advance the field; however, researchers will need to work to bridge disciplinary differences. By beginning to develop strong working relationships; increasing their understanding of one another's disciplinary culture, methodology, and language; and increasing the role economists have within research design and execution, both implementation researchers and health economists can support successful collaborations and robust and informative research.
This paper posits that a clinician's own anxious reaction to delivering specific evidence-based interventions (EBIs) should be better accounted for within implementation science frameworks. A key ...next step for implementation science is to delineate the causal processes most likely to influence successful implementation of evidence-based interventions (EBIs). This is critical for being able to develop tailored implementation strategies that specifically target mechanisms by which implementation succeeds or fails. First, we review the literature on specific EBIs that may act as negatively valenced stimuli for clinicians, leading to a process of clinician maladaptive anxious avoidance that can negatively impact EBI delivery. In the following sections, we argue that there are certain EBIs that can cause emotional distress or discomfort in a clinician, related to either: (1) a clinicians' fear of the real or predicted short-term distress the EBI can cause patients, or (2) fears that the clinician will inadvertently cause the patient harm and/or face liability. This distress experienced by the clinician can perpetuate a cycle of maladaptive anxious avoidance by the clinician, contributing to lack of or suboptimal EBI implementation. We illustrate how this cycle of maladaptive anxious avoidance can influence implementation by providing several examples from leading EBIs in the psychosocial literature. To conclude, we discuss how leveraging decades of treatment literature aimed at mitigating maladaptive anxious avoidance can inform the design of more tailored and effective implementation strategies for EBIs that are negatively valenced.
The long‐term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows ...determining their cell surface phenotype in greater detail. Mouse (Lin−Sca‐1+ CD49f+ Trop2high‐phenotype) and human (Lin− CD49f+ TROP2high) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti‐human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single‐cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f+/TROP2high phenotype of basal prostate progenitor cells and characterized by in vivo sandwich‐transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9+/CD24+/CD29+/CD44+/CD47+/CD49f+/CD104+/CD147+/CD326+/Trop2high of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan‐1 and stage‐specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f+ TROP2+ basal prostate progenitor cells. Transplantation experiments suggest that CD49f+ TROP2high SSEA‐4high human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f+ TROP2high or CD49f+ TROP2high SSEA‐4low cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA‐4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage.
The existence of stem cells in the adult nervous system is well recognized; however, the potential of these cells is still widely debated. We demonstrate that neural stem cells exist within the ...embryonic and adult cerebellum. Comparing the potential of neural stem cells derived from the forebrain and cerebellum, we find that progeny derived from each of these brain regions retain regional character in vitro as well as after homotopic transplantation. However, when ectopically transplanted, neurosphere-derived cells from either region are largely unable to generate neurons. With regard specifically to embryonic and adult cerebellar stem cells, we observe that they are able to give rise to neurons that resemble different select classes of cerebellar subclasses when grafted into the perinatal host cerebellum. Most notably, upon transplantation to the perinatal cerebellum, cerebellar stem cells from all ages are able to acquire the position and mature electrophysiological properties of cerebellar granule cells.
Abstract Objectives To evaluate CD24/CD44/CD47 cancer stem cell marker expressions in bladder cancer (BCa) and provide data on their prognostic significance for clinical outcome in patients ...undergoing radical cystectomy (RC). Material and methods Primary BCa tissue was used for xenograft studies. A tissue microarray was prepared using specimens from a cohort of 132 patients. All patients underwent RC for urothelial BCa between 2001 and 2010. Expression of CD24, CD44, and CD47 was examined in primary samples and xenografts by fluorescence-activated cell sorting. Populations of CD24low - and CD24high - expressing cells were sorted and evaluated for tumorigenicity in vivo. Tissue microarray was analyzed for CD24/CD44 staining intensity and tumor-specific vs. stromal cell staining. Associations with BCa survival, BCa stage, and lymph node status were evaluated by univariate and multivariate analyses. Results CD24 and CD44/CD47 expressions mark distinct cell populations within the normal urothelium as well as in BCa. CD24high/low expression was not sufficient to characterize CD24 as a BCa-initiating marker in in vivo primary xenotransplants. CD24 and CD44 expressions correlated with lower cancer-specific survival in patients. However, multivariate analyses of CD24 or CD44 did not demonstrate significantly increased hazards for cancer-specific death if analyzed together with stage, grade, and nodal status of patients. Conclusions Cancer stem cell markers CD24/CD44/CD47 are differentially expressed in cells of urothelial BCa in patients undergoing RC and influence cancer-specific survival of patients. Further evaluation of CD24/CD44/CD47 protein expression could be of high therapeutic value in BCa. However, both CD24 and CD44 expressions cannot be regarded as independent prognostic parameters for patients undergoing RC.
A neonatal intensive care unit (NICU) hospitalization can add significant stress to the postpartum period. Parents experience isolation and uncertainty, which can affect their capacity to bond with ...their new baby. Understanding how stress is shaped by and changes following a NICU experience will help in developing supports for these families. We examined patterns of parenting stress over the first year of life following a NICU stay to better understand changes in stress, differences in maternal and paternal stress, and how medical and developmental variables impact parent stress. Parents of infants (n = 51) who had experienced a NICU hospitalization and met criteria for California’s High-Risk Infant Follow-Up program completed assessments at 6, 9, and 12 months. A comparison group (n = 38) from a historic dataset included parents of infants born full term without medical complications. NICU parents reported higher levels of parenting stress at 6 months, but not 12 months, with mothers and fathers reporting similar stress levels. Parenting-related stress was found to be relatively stable and consistent over this period. Among NICU parents, lower developmental level at 12 months was associated with more distress in interacting with their child. These findings highlight the importance of monitoring parenting stress following discharge from the NICU and developing interventions for supporting parents of NICU graduates showing developmental delays.
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