Characterization of Telehealth Use in Veterans with Spinal Cord Injuries and Disorders

BACKGROUND: Individuals with spinal cord injuries and disorders (SCI/D) require frequent interdisciplinary health care to address impairments in mobility, autonomic functions, and secondary complications. Telehealth has the capacity to substantially transform healthcare delivery and improve care by increasing access and communication. However, relatively little is known about telehealth use in this specific population. Here, we attempt to fill part of this gap. OBJECTIVE: To investigate the frequency and characteristics associated with telehealth use in Veterans with SCI/D. DESIGN: Cross-sectional, descriptive project SETTING: Veterans Health Administration (VHA) facilities. Participants: 15,028 Veterans living with SCI/D whom received services from the VHA SCI/D System of Care. Intervention: Not applicable Outcome Measures: Frequency and characteristics associated with VHA telehealth utilization. Results: Of the 15,028 Veterans with SCI/D included in the evaluation, 17% used some form of telehealth in VHA Fiscal Year (FY)2017. Veterans over the age of 65 had lower odds (OR = 0.88, p \u3c 0.05, CI: 0.80-0.98) of using telehealth. Being Caucasian (OR = 1.29, p \u3c 0.01, CI: 1.09-1.52), living in rural areas (OR =1.16, p \u3c 0.01, CI: 1.05-1.28), living greater distances away from the VHA (p \u3c 0.01 for all distances), and being in priority group 8, meaning that Veterans have higher copayment requirements (OR=1.46, p \u3c 0.001, CI: 1.19-1.81), were all significantly associated with greater odds of telehealth use. The most frequent types of telehealth used were real-time clinical video and store-and-forward between a provider and patient within the same hub network. Conclusion: There are opportunities to increase telehealth adoption in the SCI/D arena. The findings from this project highlight which Veterans are currently using telehealth services, as well as gaps regarding telehealth adoption in this population

X-Box Binding Protein 1 Is Essential for Insulin Regulation of Pancreatic α-Cell Function

Patients with type 2 diabetes (T2D) often exhibit hyperglucagonemia despite hyperglycemia, implicating defective α-cell function. Although endoplasmic reticulum (ER) stress has been suggested to underlie β-cell dysfunction in T2D, its role in α-cell biology remains unclear. X-box binding protein 1 (XBP1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR), and its deficiency in β-cells has been reported to impair insulin secretion, leading to glucose intolerance. To evaluate the role of XBP1 in α-cells, we created complementary in vivo (α-cell–specific XBP1 knockout [αXBPKO] mice) and in vitro (stable XBP1 knockdown α-cell line [αXBPKD]) models. The αXBPKO mice exhibited glucose intolerance, mild insulin resistance, and an inability to suppress glucagon secretion after glucose stimulation. αXBPKD cells exhibited activation of inositol-requiring enzyme 1, an upstream activator of XBP1, leading to phosphorylation of Jun NH2-terminal kinase. Interestingly, insulin treatment of αXBPKD cells reduced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) (pY896) and phosphorylation of Akt while enhancing serine phosphorylation (pS307) of IRS1. Consequently, the αXBPKD cells exhibited blunted suppression of glucagon secretion after insulin treatment in the presence of high glucose. Together, these data indicate that XBP1 deficiency in pancreatic α-cells induces altered insulin signaling and dysfunctional glucagon secretion

How Do Patients with Mental Health Diagnoses Use Online Patient Portals? An Observational Analysis from the Veterans Health Administration

Online patient portals may be effective for engaging patients with mental health conditions in their own health care. This retrospective database analysis reports patient portal use among Veterans with mental health diagnoses. Unadjusted and adjusted odds of portal feature use was calculated using logistic regressions. Having experienced military sexual trauma or having an anxiety disorder, post-traumatic stress disorder, or depression were associated with increased odds of portal use; bipolar, substance use, psychotic and adjustment disorders were associated with decreased odds. Future research should examine factors that influence portal use to understand diagnosis-level differences and improve engagement with such tools

Supporting the Implementation of Connected Care Technologies in the Veterans Health Administration: Cross-Sectional Survey Findings from the Veterans Engagement with Technology Collaborative (VET-C) Cohort

BACKGROUND: Widespread adoption, use, and integration of patient-facing technologies into the workflow of health care systems has been slow, thus limiting the realization of their potential. A growing body of work has focused on how best to promote adoption and use of these technologies and measure their impacts on processes of care and outcomes. This body of work currently suffers from limitations (eg, cross-sectional analyses, limited patient-generated data linked with clinical records) and would benefit from institutional infrastructure to enhance available data and integrate the voice of the patient into implementation and evaluation efforts. OBJECTIVE: The Veterans Health Administration (VHA) has launched an initiative called the Veterans Engagement with Technology Collaborative cohort to directly address these challenges. This paper reports the process by which the cohort was developed and describes the baseline data being collected from cohort members. The overarching goal of the Veterans Engagement with Technology Collaborative cohort is to directly engage veterans in the evaluation of new VHA patient-facing technologies and in so doing, to create new infrastructure to support related quality improvement and evaluation activities. METHODS: Inclusion criteria for veterans to be eligible for membership in the cohort included being an active user of VHA health care services, having a mobile phone, and being an established user of existing VHA patient-facing technologies as represented by use of the secure messaging feature of VHA\u27s patient portal. Between 2017 and 2018, we recruited veterans who met these criteria and administered a survey to them over the telephone. RESULTS: The majority of participants (N=2727) were male (2268/2727, 83.2%), White (2226/2727, 81.6%), living in their own apartment or house (2519/2696, 93.4%), and had completed some college (1176/2701, 43.5%) or an advanced degree (1178/2701, 43.6%). Cohort members were 59.9 years old, on average. The majority self-reported their health status as being good (1055/2725, 38.7%) or very good (524/2725, 19.2%). Most cohort members owned a personal computer (2609/2725, 95.7%), tablet computer (1616/2716, 59.5%), and/or smartphone (2438/2722, 89.6%). CONCLUSIONS: The Veterans Engagement with Technology Collaborative cohort is an example of a VHA learning health care system initiative designed to support the data-driven implementation of patient-facing technologies into practice and measurement of their impacts. With this initiative, VHA is building capacity for future, rapid, rigorous evaluation and quality improvement efforts to enhance understanding of the adoption, use, and impact of patient-facing technologies

Leptin receptor signaling regulates protein synthesis pathways and neuronal differentiation in pluripotent stem cells

The role of leptin receptor (OB-R) signaling in linking pluripotency with growth and development and the consequences of dysfunctional leptin signaling on progression of metabolic disease is poorly understood. Using a global unbiased proteomics approach we report that embryonic fibroblasts (MEFs) carrying the db/db mutation exhibit metabolic abnormalities, while their reprogrammed induced pluripotent stem cells (iPSCs) show altered expression of proteins involved in embryonic development. An upregulation in expression of eukaryotic translation initiation factor 4e (Eif4e) and Stat3 binding to the Eif4e promoter was supported by enhanced protein synthesis in mutant iPSCs. Directed differentiation of db/db iPSCs toward the neuronal lineage showed defects. Gene editing to correct the point mutation in db/db iPSCs using CRISPR-Cas9, restored expression of neuronal markers and protein synthesis while reversing the metabolic defects. These data imply a direct role for OB-R in regulating metabolism in embryonic fibroblasts and key developmental pathways in iPSCs.publishedVersio

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo

Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in <i>RUNX1</i>, <i>GATA2</i>, and <i>DDX41</i>

Individuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Sloan Digital Sky Survey IV: mapping the Milky Way, nearby galaxies, and the distant universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median ). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July