Richard L. Roudebush VA Medical Center

This cross-sectional clinical study aimed to explore the untargeted metabolomic and lipidomic profiles in gingival crevicular fluid (GCF) obtained from healthy individuals and patients with periodontitis. GCF was collected from 17 periodontally healthy and 19 periodontitis patients. For the unbiased characterisation of positively and negatively charged polar metabolite and lipid compounds, we employed hydrophilic interaction and reversed-phase liquid chromatography/mass spectrometry platforms, followed by a semisupervised deep learning-based approach for metabolomic peak curation and data analysis. A total of 256 metabolites were identified with Metabolomics Standards Initiative (MSI) confidence Levels 1-3, including 198 elevated and 58 diminished compounds in periodontal lesions (q < 0.05, |log2-transformed Fold Change (FC)| > 1). Periodontitis samples exhibited a significant positive accumulation of purine degradation and ceramide metabolites, along with a negative regulation of oxy fatty acids metabolism. Additionally, we observed a significant increase in established periodontitis biomarkers, including N-acetylneuraminic acid, citrulline and 2-pyrrolidineacetic acid. The study also characterised distinct differences in bacterial and fungal metabolite profiles between the healthy and diseased samples. These findings suggest that untargeted metabolomic screening of GCF may significantly improve our understanding of biochemical changes between healthy tissue and periodontitis. This knowledge is pivotal for the development of a precision paradigm in periodontitis.

Kidney intratubular casts are frequently observed in the distal nephron segments of the kidney and have long been regarded as a sign of kidney disease. However, the composition and pathological significance of intratubular casts have remained understudied. We leveraged Hematoxylin and Eosin (H&E) staining to identify intratubular casts along with concurrent Co-detection by indexing (CODEX) multiplexed spatial protein imaging on human kidney biopsy sections from the Kidney Precision Medicine Project (KPMP). We also conducted immunoblotting of Prominin-1 (PROM1/CD133) in urine and assessed its levels from publicly available urinary proteomics datasets of the KPMP consortium. We analyzed 493 intratubular casts across 42 individuals with kidney disease or healthy controls. We identified PROM1 and insulin-like growth factor binding protein 7 (IGFBP7) as major constituents of casts (positive staining in 89.0% and 39.1%, respectively). Staining for uromodulin (UMOD), an established cast component, was present in 86.6%. These components showed variable patterns across disease states. Intratubular casts were predominantly detected in the distal nephron segments, and their presence was associated with a marked loss of sodium-chloride cotransporter (NCC) and aquaporin-2 (AQP2) expression in the cast-containing tubular epithelium, suggesting underlying injury. The loss of these transporters correlated with protein components within casts, and the presence of intra-cast PROM1 showed the strongest association, with an odds ratio of 26.7 (95% confidence interval: 13.1-54.7). Urinary PROM1 secretion was confirmed by immunoblotting and was greater in patients with acute kidney injury (AKI) compared to healthy controls (P = 0.01). We identified PROM1, a dedifferentiation and injury marker expressed in epithelial cells, as a novel major constituent of intratubular casts. Our studies suggest that protein composition signature within casts varies with disease state and is associated with tubular injury in distal nephron segments. Our study also suggests that urinary PROM1 may have potential as a biomarker for AKI.

BACKGROUND: Rapid qualitative assessment was used to describe early strategies to implement an evidence-based walking program for hospitalized older adults, assiSTed eaRly mobIlity for hospitalizeD older vEterans (STRIDE), mandated by a regional Department of Veterans Affairs health care system office (Veterans Integrated Service Network [VISN]). METHODS: Data were collected from 6 hospital sites via semistructured interviews with key informants, observations of telephone-based technical assistance, and review of VISN-requested program documents (eg, initial implementation plans). An overarching framework of actionable feedback for VISN leadership and specification of locally initiated implementation strategies, using the Expert Recommendations for Implementing Change (ERIC) compilation, was used. Actionable feedback was shared with VISN leadership 1 month after the initiative. RESULTS: ERIC implementation strategies identified were as follows: (1) promoting adaptability-4 sites had physical therapists/kinesiotherapists instead of assistants walk patients; (2) promoting network weaving-strengthening nursing and PT/KT partnership with regular communication opportunities or a point person was important for implementation; (3) distributing educational materials-2 sites distributed information about STRIDE via e-mail and in person; and (4) organizing clinician implementation team meetings-3 sites used interdisciplinary team meetings to communicate with the clinical staff about STRIDE. CONCLUSION: This qualitative study sheds light on early experiences with implementing STRIDE; the results have been instructive for ongoing implementation and future dissemination of STRIDE, and the approach can be applied across contexts to inform implementation of other programs.

Abstract Background Sexual and gender minority (SGM) Veterans are more likely to require home care services than non-SGM Veterans. However, fear of discrimination deters many from seeking these supports. This landscape analysis seeks to assess team readiness and experiences with older SGM veterans within the U.S. Department of Veterans Affairs’ (VA) Home Based Primary Care (HBPC) program. Methods Using a multi-method approach, we conducted a survey of VA HBPC staff nationwide and five focus groups with staff at select sites. Results Of approximately 10,000 HBPC staff invited to participate, 321 responded. Respondents included clinicians (44%; e.g., nurses and physicians), social workers (20%), and other staff (31%; e.g., nutritionists). Most reported minimal training on SGM care, with over half (54%) receiving less than three hours in the past five years; 12% received no training at all. Despite this, 43% strongly agreed they were aware of the unique challenges faced by SGM Veterans and 46% somewhat agreed. Regarding community resources for SGM Veterans, 71% endorsed confidence in finding facilities safe from discrimination, but only 61% endorsed confidence finding an affirming one. In focus groups, staff reported limited experience with SGM veterans and raised concerns about the inclusivity of community resources. They also noted a strong desire for training in SGM care. Conclusion Our landscape assessment found that HBPC staff had concerns about the inclusivity and affirming nature of both VA and external services. Further training and resources are needed to enable the VA to deliver exemplary, affirming care for older SGM Veterans.