VA Palo Alto Healthcare System

About: VA Palo Alto Healthcare System is a healthcare organization based out in Palo Alto, California, United States. It is known for research contribution in the topics: Population & Health care. The organization has 2548 authors who have published 4605 publications receiving 209938 citations.

Access, Utilization, and Interest in mHealth Applications Among Veterans Receiving Outpatient Care for PTSD

Abstract: Mobile health (mHealth) refers to the use of mobile technology (e.g., smartphones) and software (i.e., applications) to facilitate or enhance health care. Several mHealth programs act as either stand-alone aids for Veterans with post-traumatic stress disorder (PTSD) or adjuncts to conventional psychotherapy approaches. Veterans enrolled in a Veterans Affairs outpatient treatment program for PTSD (N = 188) completed anonymous questionnaires that assessed Veterans' access to mHealth-capable devices and their utilization of and interest in mHealth programs for PTSD. The majority of respondents (n = 142, 76%) reported having access to a cell phone or tablet capable of running applications, but only a small group (n = 18) reported use of existing mHealth programs for PTSD. Age significantly predicted ownership of mHealth devices, but not utilization or interest in mHealth applications among device owners. Around 56% to 76% of respondents with access indicated that they were interested in trying mHealth programs for such issues as anger management, sleep hygiene, and management of anxiety symptoms. Findings from this sample suggest that Veterans have adequate access to, and interest in, using mHealth applications to warrant continued development and evaluation of mobile applications for the treatment of PTSD and other mental health conditions.

Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.

Abstract: Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 × 10-6; IFNAR2, P = 9.8 × 10-11 and IL-10RB, P = 2.3 × 10-14) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.

Gene transfer via reversible plasmid condensation with cysteine-flanked, internally spaced arginine-rich peptides.

Abstract: Nonviral gene transfer offers biosafety, stability, and expense advantages over viruses; however, it has suffered from poor efficiency. Because arginine-rich peptides facilitate uptake of macromolecules such as proteins, liposomes, and iron nanoparticles, we explored their potential in enhancing plasmid DNA delivery. In their unmodified form, known protein transduction sequences, including hepta-arginine and Tat47-57, failed to support effective gene delivery. However, by flanking a core of consecutive arginines with amino- and carboxy-terminal cysteines in vitro gene transfer was observed. Furthermore, interspersing arginines with glycine and histidine residues achieved reversible plasmid condensation and dramatically increased transfection levels in a variety of cell types. Unlike most available cationic homopolymers that function only in vitro, these new peptides also increased gene expression in both murine and human tissue in vivo. Thus, cysteine-flanked, internally spaced arginine-rich (CFIS-R) pept...

BP180 gene delivery in junctional epidermolysis bullosa.

Abstract: Epidermolysis bullosa (EB) comprises a family of inherited blistering skin diseases for which current therapy is only palliative. Junctional EB (JEB) involves dissociation of the dermal-epidermal junction and results from mutations in a number of genes that encode vital structural proteins, including BP180 (type XVII collagen/BPAG2). In order to develop a model of corrective gene delivery for JEB, we produced a retroviral expression vector for wild-type human BP180 and used it to restore BP180 protein expression to primary keratinocytes from BP180-negative patients with generalized atrophic JEB. Restoration of full-length BP180 protein expression was associated with adhesion parameter normalization of primary JEB keratinocytes in vitro. These cells were then used to regenerate human skin on immune-deficient mice. BP180 gene-transduced tissue demonstrated restoration of BP180 gene expression at the dermal-epidermal junction in vivo while untransduced regenerated JEB skin entirely lacked BP180 expression. These findings provide a basis for future efforts to achieve gene delivery in human EB skin tissue.