Search

Place-based socio-economic and racial inequities contribute to health disparities among people with HIV (PWH). We used geographic ecological momentary assessment (GEMA) methodologies to explore the interplay between psychosocial outcomes in daily diaries and community spatial measures among PWH in New Orleans. PWH (N = 69) were recruited from a clinic-based cohort study. Micro-longitudinal data were collected via smartphone-based daily diaries and geospatial tracking over 14 days. First, correlations were run between diary derived outcomes (e.g., feeling safe in current location, stress), and spatial measures (e.g., violent crime, alcohol outlets, and vacant lots) within a half-mile buffer around each diary point to understand the real time associations between mood and space. Next, we fit multilevel models, controlling for between-person effects, to assess within-person associations between accumulative spatial daily violence exposure (50m, 100m and 200m buffers), and measures of daily mood and coping. Violent crime, alcohol outlets and vacant lots were inversely correlated with feeling safe and positively correlated with perceived ease of obtaining drugs. Vacant lots were positively associated with stress and inversely correlated with positive mood. Within individuals, higher daily accumulated violence exposure was associated with increased rumination at the 50m buffer level, decreased trust in oneself and others at the 100m buffer, and decreased ratio of positive/negative mood at all buffers. Our results emphasize the intricate interplay between mental wellness, coping mechanisms, and spatial measures in PWH. Future research and interventions for PWH should consider how spatial factors may influence PWH in terms of mental health and care engagement., (© 2024. The Author(s).)

ABSTRACT This study examines the relationship between coping self-efficacy, concurrent stress, and psychological distress (borderline/clinical anxiety, depression, and PTSD symptoms) among people living with HIV (PLWH). Using data from a cohort of PLWH living in a southern peri-urban area, logistic regression analyses were conducted to determine the effects of self-reported coping self-efficacy on psychological distress in a sample of 85 violence-affected PLWH. We also tested the moderating effect of coping self-efficacy on the concurrent stress-psychological distress relationships. In adjusted models, coping self-efficacy was significantly associated with symptoms of anxiety and PTSD, but not depressive symptoms. Findings indicate that high coping self-efficacy may reduce one's likelihood of anxiety and PTSD symptoms among PLWH.

Background: In 2020, Greater New Orleans, Louisiana, was home to 7048 people living with HIV-1083 per 100,000 residents, 2.85 times the US national rate. With Louisiana routinely ranked last in indexes of health equity, violent crime rates in Orleans Parish quintupling national averages, and in-care New Orleans people living with HIV surviving twice the US average of adverse childhood experiences, accessible, trauma-focused, evidence-based interventions (EBIs) for violence-affected people living with HIV are urgently needed., Objective: To meet this need, we adapted Living in the Face of Trauma, a well-established EBI tailored for people living with HIV, into NOLA GEM, a just-in-time adaptive mobile health (mHealth) intervention. This study aimed to culturally tailor and refine the NOLA GEM app and assess its acceptability; feasibility; and preliminary efficacy on care engagement, medication adherence, viral suppression, and mental well-being among in-care people living with HIV in Greater New Orleans., Methods: The development of NOLA GEM entailed identifying real-time tailoring variables via a geographic ecological momentary assessment (GEMA) study (n=49; aim 1) and place-based and user-centered tailoring, responsive to the unique cultural contexts of HIV survivorship in New Orleans, via formative interviews (n=12; aim 2). The iOS- and Android-enabled NOLA GEM app leverages twice-daily GEMA prompts to offer just-in-time, in-app recommendations for effective coping skills practice and app-delivered Living in the Face of Trauma session content. For aim 3, the pilot trial will enroll an analytic sample of 60 New Orleans people living with HIV individually randomized to parallel NOLA GEM (intervention) or GEMA-alone (control) arms at a 1:1 allocation for a 21-day period. Acceptability and feasibility will be assessed via enrollment, attrition, active daily use through paradata metrics, and prevalidated usability measures. At the postassessment time point, primary end points will be assessed via a range of well-validated, domain-specific scales. Care engagement and viral suppression will be assessed via past missed appointments and self-reported viral load at 30 and 90 days, respectively, and through well-demonstrated adherence self-efficacy measures., Results: Aims 1 and 2 have been achieved, NOLA GEM is in Beta, and all aim-3 methods have been reviewed and approved by the institutional review board of Tulane University. Recruitment was launched in July 2023, with a target date for follow-up assessment completion in December 2023., Conclusions: By leveraging user-centered development and embracing principles that elevate the lived expertise of New Orleans people living with HIV, mHealth-adapted EBIs can reflect community wisdom on posttraumatic resilience. Sustainable adoption of the NOLA GEM app and a promising early efficacy profile will support the feasibility of a future fully powered clinical trial and potential translation to new underserved settings in service of holistic survivorship and well-being of people living with HIV., Trial Registration: ClinicalTrials.gov NCT05784714; https://clinicaltrials.gov/ct2/show/NCT05784714., International Registered Report Identifier (irrid): PRR1-10.2196/47151., (©Simone J Skeen, Stephanie Tokarz, Rayna E Gasik, Chelsea McGettigan Solano, Ethan A Smith, Momi Binaifer Sagoe, Lauryn V Hudson, Kara Steele, Katherine P Theall, Gretchen A Clum. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.10.2023.)

Introduction: Emergency departments (EDs) have become the primary source of care for increasing number of patients, leading to treatment of nonemergent cases, which divert resources from true emergency situations and represent poor cost-effectiveness for treating such cases. There is evidence that suggests that patient navigation (PN) integrated into the ED and other case management techniques can help reduce the number of primary care-related ED visits and these navigation programs are more cost-effective than the ED visits themselves. The Greater New Orleans Community Health Connection Primary Care Capacity Project Quality Improvement Initiative (GNOPQii) is a pilot project aimed at improving the efficiency of PN for patients who have had avoidable ED encounters or inpatient readmissions through applied data and technology program., Methods: Partnering Federally Qualified Health Centers were equipped with actionable ED utilization data to integrate with their own patient clinical data to track patient ED activity. The pilot design also included the use of patient navigators to address the nonclinical cultural and behavioral barriers to care. As part of the overall evaluation, comparisons of data utilization and PN services pre- and post-GNOPQii were conducted., Results: A total of 337 referrals were made, and 145 patients were enrolled into the GNOPQii pilot program. The direct services needed the most by patients were transportation and medication resources. Of those who enrolled (N = 145), 63 patients graduated, meaning program compliance and 90 days without visits to the ED, resulting in a 43% success rate., Discussion: If an estimated $1898 savings for every nonemergency ED encounter replaced by an office-based encounter is applied to our results, the GNOPQii program contributed to a minimum of $119 574.00 savings even if only 1 deterred ED visit per graduate is assumed. Future research is needed to systematically test the efficacy of GNOPQii in reducing nonemergent ED visits.

Purpose: Oxytocin (OXT) is recognized as an ubiquitously acting nonapeptide hormone that is involved in processes ranging from parturition to neural development. Its effects are mediated by cell signaling that occurs as a result of oxytocin receptor (OXTR) activation. We sought to determine whether the OXT-OXTR signaling pathway is also expressed within the retina., Methods: Immunohistochemistry using cell-specific markers was used to localize OXT within the rhesus retina. Reverse transcriptase PCR and immunohistochemistry were used to assess the expression of OXTR in both human and rhesus retina. Single-cell RT-PCR and Western blot analyses were used to determine the expression of OXTR in cultured human fetal RPE (hfRPE) cells. Human fetal RPE cells loaded with FURA-2 AM were studied by ratiometric Ca(2+) imaging to assess transient mobilization of intracellular Ca(2+) ([Ca(2+)]i)., Results: Oxytocin was expressed in the cone photoreceptor extracellular matrix of the rhesus retina. Oxytocin mRNA and protein were expressed in the human and rhesus RPE. Oxytocin mRNA and protein expression were observed in cultured hfRPE cells, and exposure of these cells to 100 nM OXT induced a transient 79 ± 1.5 nM increase of [Ca(2+)]i., Conclusions: Oxytocin and OXTR are present in the posterior retina, and OXT induces an increase in hfRPE [Ca(2+)]i. These results suggest that the OXT-OXTR signaling pathway is active in the retina. We propose that OXT activation of the OXTR occurs in the posterior retina and that this may serve as a paracrine signaling pathway that contributes to communication between the cone photoreceptor and the RPE., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Snowflake Vitreoretinal Degeneration (SVD) is associated with the R162W mutation of the Kir7.1 inwardly-rectifying potassium channel. Kir7.1 is found at the apical membrane of Retinal Pigment Epithelial (RPE) cells, adjacent to the photoreceptor neurons. The SVD phenotype ranges from RPE degeneration to an abnormal b-wave to a liquid vitreous. We sought to determine how this mutation alters the structure and function of the human Kir7.1 channel. In this study, we expressed a Kir7.1 construct with the R162W mutation in CHO cells to evaluate function of the ion channel. Compared to the wild-type protein, the mutant protein exhibited a non-functional Kir channel that resulted in depolarization of the resting membrane potential. Upon co-expression with wild-type Kir7.1, R162W mutant showed a reduction of IKir7.1 and positive shift in '0' current potential. Homology modeling based on the structure of a bacterial Kir channel protein suggested that the effect of R162W mutation is a result of loss of hydrogen bonding by the regulatory lipid binding domain of the cytoplasmic structure.

Expression of the c-Myc oncoprotein is affected by conserved threonine 58 (T58) and serine 62 (S62) phosphorylation sites that help to regulate c-Myc protein stability, and altered ratios of T58 and S62 phosphorylation have been observed in human cancer. Here, we report the development of 3 unique c-myc knock-in mice that conditionally express either c-Myc(WT) or the c-Myc(T58A) or c-Myc(S62A) phosphorylation mutant from the constitutively active ROSA26 locus in response to Cre recombinase to study the role of these phosphorylation sites in vivo. Using a mammary-specific Cre model, we found that expression of c-Myc(WT) resulted in increased mammary gland density, but normal morphology and no tumors at the level expressed from the ROSA promoter. In contrast, c-Myc(T58A) expression yielded enhanced mammary gland density, hyperplastic foci, cellular dysplasia, and mammary carcinoma, associated with increased genomic instability and suppressed apoptosis relative to c-Myc(WT). Alternatively, c-Myc(S62A) expression reduced mammary gland density relative to control glands, and this was associated with increased genomic instability and normal apoptotic function. Our results indicate that specific activities of c-Myc are differentially affected by T58 and S62 phosphorylation. This model provides a robust platform to interrogate the role that these phosphorylation sites play in c-Myc function during development and tumorigenesis.

Expression of the c-Myc proto-oncoprotein is tightly regulated in normal cells. Phosphorylation at two conserved residues, threonine58 (T58) and serine62 (S62), regulates c-Myc protein stability. In cancer cells, c-Myc can become aberrantly stabilized associated with altered T58 and S62 phosphorylation. A complex signalling cascade involving GSK3beta kinase, the Pin1 prolyl isomerase, and the PP2A-B56alpha phosphatase controls phosphorylation at these sites. We report here a novel role for the tumour suppressor scaffold protein Axin1 in facilitating the formation of a degradation complex for c-Myc containing GSK3beta, Pin1, and PP2A-B56alpha. Although knockdown of Axin1 decreases the association of c-Myc with these proteins, reduces T58 and enhances S62 phosphorylation, and increases c-Myc stability, acute expression of Axin1 reduces c-Myc levels and suppresses c-Myc transcriptional activity. Moreover, the regulation of c-Myc by Axin1 is impaired in several tested cancer cell lines with known stabilization of c-Myc or loss of Axin1. This study provides critical insight into the regulation of c-Myc expression, how this can be disrupted in three cancer types, and adds to our knowledge of the tumour suppressor activity of Axin1.

The F box protein Grr1 is the substrate specificity-determinant of the SCF(Grr1) E3 ubiquitin ligase complex. Genetic analyses of Grr1 mutants have implicated Grr1 in glucose repression, specifically with regard to expression of the SUC2 transcript. To better understand Grr1, we screened for substrates using a mutant version of Grr1 that should not associate with the SCF complex. We identified Gis4 as a novel Grr1 substrate. Gis4 was originally isolated as a multi-copy suppressor of a Gal--phenotype in the triple mutant snf1 mig1 srb8. Here, we show that Gis4 binds Grr1 in vivo and that Grr1 protein levels positively affect the protein levels of Gis4. The Gis4 protein is stable in wild-type cells and in grr1Delta cells; however, Gis4 is ubiquitinated in a Grr1-dependent manner. Furthermore, we show that Gis4 interacts with Snf1 in a Grr1-dependent fashion, and that Gis4 is involved in de-repression of SUC2 and in transcription of other Snf1-dependent transcripts. Gis4 appears to connect the glucose repression and de-repression pathways. We suggest that Gis4 may explain the glucose repression defects in carbon source metabolism for the grr1 mutants.

The Skp2 oncoprotein belongs to the family of F-box proteins that function as substrate recognition factors for SCF (Skp1, cullin, F-box protein) E3 ubiquitin-ligase complexes. Binding of the substrate to the SCFSkp2 complex catalyzes the conjugation of ubiquitin molecules to the bound substrate, resulting in multi-ubiquitination and rapid degradation by the 26 S proteasome. Using Skp2 as bait in a yeast two-hybrid screen, we have identified UBP43 as a novel substrate for Skp2. UBP43 belongs to the family of ubiquitin isopeptidases and specifically cleaves ISG15, a ubiquitin-like molecule that is induced by cellular stresses, such as type 1 interferons (IFN), nephrotoxic damage, and bacterial infection. UBP43 was originally identified as an up-regulated gene in knock-in mice expressing an acute myelogenous leukemia fusion protein, AML1-ETO, as well as in melanoma cell lines treated with IFN-beta. The phenotype of UBP43 knockout mice includes shortened life span, hypersensitivity to IFN, and neuronal damage, suggesting that tight regulation of ISG15 conjugation is critical for normal cellular function. In this study, we demonstrate that UBP43 is ubiquitinated in vivo and accumulates in cells treated with proteasome inhibitors. We also show that Skp2 promotes UBP43 ubiquitination and degradation, resulting in higher levels of ISG15 conjugates. In Skp2-/- mouse cells, levels of UBP43 are consistently up-regulated, whereas levels of ISG15 conjugates are reduced. Our results demonstrate that the SCFSkp2 is involved in controlling UBP43 protein levels and may therefore play an important role in modulating type 1 IFN signaling.