Patients hospitalized with acute heart failure, worsening renal function, and persistent congestion are at high risk for adverse outcomes despite current medical therapy

INTRODUCTION: Approximately 1/3 of patients with acute decompensated heart failure (ADHF) are discharged with persistent congestion. Worsening renal function (WRF) occurs in approximately 50% of patients hospitalized for ADHF and the combination of WRF and persistent congestion are associated with higher risk of mortality and HF readmissions. METHODS: We designed a multicenter, prospective registry to describe current treatments and outcomes for patients hospitalized with ADHF complicated by WRF (defined as a creatinine increase ≥0.3 mg/dL) and persistent congestion at 96 h. Study participants were followed during the hospitalization and through 90-day post-discharge. Hospitalization costs were analyzed in an economic substudy. RESULTS: We enrolled 237 patients hospitalized with ADHF, who also had WRF and persistent congestion. Among these, the average age was 66 ± 13 years and 61% had a left ventricular ejection fraction (LVEF) ≤ 40%. Mean baseline creatinine was 1.7 ± 0.7 mg/dL. Patients with persistent congestion had a high burden of clinical events during the index hospitalization (7.6% intensive care unit transfer, 2.1% intubation, 1.7% left ventricular assist device implantation, and 0.8% dialysis). At 90-day follow-up, 33% of patients were readmitted for ADHF or died. Outcomes and costs were similar between patients with reduced and preserved LVEF. CONCLUSIONS: Many patients admitted with ADHF have WRF and persistent congestion despite diuresis and are at high risk for adverse events during hospitalization and early follow-up. Novel treatment strategies are urgently needed for this high-risk population

Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression.

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST

Intergroup anxiety in pain care: impact on treatment recommendations made by White providers for Black patients

Race disparities in pain care are well-documented. Given that most black patients are treated by white providers, patient-provider racial discordance is one hypothesized contributor to these disparities. Research and theory suggest that providers' trait-level intergroup anxiety impacts their state-level comfort while treating patients, which, in turn, impacts their pain treatment decisions. To test these hypothesized relationships, we conducted a planned secondary analysis of data from a randomized controlled trial of a perspective-taking intervention to reduce pain treatment disparities. Mediation analyses were conducted on treatment decision data from white providers for black virtual patients with chronic pain. Results indicated that white providers with higher trait-level intergroup anxiety reported lower state-level comfort treating black patients and were thereby more likely to recommend opioid (indirect effect = 0.76, 95% confidence interval [CI]: 0.21-1.51) and pain specialty (indirect effect = 0.91, 95% CI: 0.26-1.78) treatments and less likely to recommend nonopioid analgesics (indirect effect = -0.45, 95% CI: -0.94 to -0.12). Neither trait-level intergroup anxiety nor state-level comfort significantly influenced provider decisions for physical therapy. This study provides important new information about intrapersonal and interpersonal contributors to race disparities in chronic pain care. These findings suggest that intergroup anxiety and the resulting situational discomfort encroach on the clinical decision-making process by influencing white providers' decisions about which pain treatments to recommend to black patients. Should these findings be replicated in future studies, they would support interventions to help providers become more aware of their trait-level intergroup anxiety and manage their state-level reactions to patients who are racially/ethnically different from themselves

Overgeneralized autobiographical memory and future thinking in combat veterans with posttraumatic stress disorder

a b s t r a c t Background: Studies show that individuals with Posttraumatic Stress Disorder (PTSD) tend to recall autobiographical memories with decreased episodic specificity. A growing body of research has demonstrated that the mechanisms involved in recalling autobiographical memories overlap considerably with those involved in imagining the future. Although shared autobiographical deficits in remembering the past and imagining the future have been observed in other clinical populations, this has yet to be examined in PTSD. This study examined whether, compared to combat trauma-exposed individuals without PTSD, those with combat-related PTSD would be more likely to generate overgeneralized autobiographical memories and imagined future events. Method: Operation Enduring/Iraqi Freedom (OEF/OIF) veterans with and without PTSD were presented with neutral word cues and were instructed to generate memories or imagine future autobiographical events. Responses were digitally recorded and were coded for level of episodic specificity and content related to combat trauma. Results: Individuals with PTSD were more likely to generate overgeneral autobiographical memories and future events than individuals without PTSD, and were more likely to incorporate content associated with combat when remembering the past or thinking about the future. Limitation: Limitations of the study include a cross-sectional design, precluding causality; the lack of a non-trauma exposed group, relatively small sample, and almost all-male gender of participants, limiting the generalizability to other populations. Conclusion: These findings suggest that individuals with PTSD show similar deficits when generating personal past and future events, which may represent a previously unexamined mechanism involved in the maintenance of PTSD symptoms

Decoding visual information from high-density diffuse optical tomography neuroimaging data

BACKGROUND: Neural decoding could be useful in many ways, from serving as a neuroscience research tool to providing a means of augmented communication for patients with neurological conditions. However, applications of decoding are currently constrained by the limitations of traditional neuroimaging modalities. Electrocorticography requires invasive neurosurgery, magnetic resonance imaging (MRI) is too cumbersome for uses like daily communication, and alternatives like functional near-infrared spectroscopy (fNIRS) offer poor image quality. High-density diffuse optical tomography (HD-DOT) is an emerging modality that uses denser optode arrays than fNIRS to combine logistical advantages of optical neuroimaging with enhanced image quality. Despite the resulting promise of HD-DOT for facilitating field applications of neuroimaging, decoding of brain activity as measured by HD-DOT has yet to be evaluated. OBJECTIVE: To assess the feasibility and performance of decoding with HD-DOT in visual cortex. METHODS AND RESULTS: To establish the feasibility of decoding at the single-trial level with HD-DOT, a template matching strategy was used to decode visual stimulus position. A receiver operating characteristic (ROC) analysis was used to quantify the sensitivity, specificity, and reproducibility of binary visual decoding. Mean areas under the curve (AUCs) greater than 0.97 across 10 imaging sessions in a highly sampled participant were observed. ROC analyses of decoding across 5 participants established both reproducibility in multiple individuals and the feasibility of inter-individual decoding (mean AUCs \u3e 0.7), although decoding performance varied between individuals. Phase-encoded checkerboard stimuli were used to assess more complex, non-binary decoding with HD-DOT. Across 3 highly sampled participants, the phase of a 60° wide checkerboard wedge rotating 10° per second through 360° was decoded with a within-participant error of 25.8±24.7°. Decoding between participants was also feasible based on permutation-based significance testing. CONCLUSIONS: Visual stimulus information can be decoded accurately, reproducibly, and across a range of detail (for both binary and non-binary outcomes) at the single-trial level (without needing to block-average test data) using HD-DOT data. These results lay the foundation for future studies of more complex decoding with HD-DOT and applications in clinical populations

Older adult insights for age friendly environments, products and service Systems.

  The environments we grow old in present a challenge to be adaptive to our changing needs and limitations. Environments, in the context of this paper, are the spaces, products and product service systems that we engage with, alone or with others, within and outside the home. A design coalition (Manzini, 2015) was generated between a number of academic Institutions and ISAX (Ireland Smart Ageing Exchange) an ‘ageing think tank’ organisation in Ireland. The intention of this coalition was to generate awareness of needs requirements for age friendly environments and to provide an example of how participatory design research can inform innovation in business and policy development at a local and state level. A five-week study was conducted using design and ethnographic methods with twenty-two Older Adult participants (age range 69 – 80).  The themes of study were identified as: Mobility, Public Spaces, Safety, Social Engagement, Services & Facilities. Cultural probes, semi-structured interviews and user observation, by both researchers and older adult participants, were used as methods to identify the unmet needs of participants within the sample group. A Co-Design Symposium (http://info.isax.ie/national-co-design-symposium )was held during June 2016 as an opportunity to demonstrate to a wider stakeholder audience the needs identified from this study. This Symposium was attended by over 100 people of various backgrounds (town planners, architects, transport experts, retailers, builders, health and other service providers). The older adult participants and designers (staff and researchers from the School of Design at the University of Limerick, IT Carlow, Limerick Institute of Technology and Limerick School of Art & Design) were placed within a team of ten. The research was presented using audio/visual presentation as well as artefacts from the fieldwork, completed diaries, scrapbooks, storyboards etc. Solutions were worked on, and delivered at end of day. This Symposium has impacted positively whereby policy makers in local government have invited ISAX to further discuss research outcomes and needs of older adults as a means to develop access areas in and around Limerick City. This paper outlines in further detail the design research methods used and the benefits through design education Student/ Researcher /Stakeholder collaboration by application ‘in the ‘field’ and displays the effectiveness of design coalitions in influencing and affecting change and insight into policy. It highlights how Co-Design collaborations can impact and generate design solutions that improve day to day experiences. Keywords: Older Adults, Co-Design, Needs Identification, Collaborative Coalitions, Product Service Systems