Peripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system and its regulators are altered in the setting of PAD and to assess the relationship between NO bioavailability and oxidative stress. Sera from 35 patients with intermittent claudication (IC), 26 patients with critical limb ischemia (CLI), and 35 non-PAD controls were analyzed to determine levels of tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), nitrate/nitrite (nitric oxides, or NOx), arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the oxidative stress markers 8-Oxo-2′-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), advanced glycation end products (AGEs), and protein carbonyls. NOx was significantly lower in IC and CLI patients compared to controls in association with elevated oxidative stress, with the greatest NOx reductions observed in CLI. Compared with controls, IC and CLI patients had reduced BH4, elevated BH2, and a reduced BH4/BH2 ratio. SDMA, the arginine/SDMA ratio, and the arginine/ADMA ratio were significantly higher in CLI patients. The NO system and its regulators are significantly compromised in PAD. This dysregulation appears to be driven by increased oxidative stress and worsens as the disease progresses from claudication to CLI.

Work from our laboratory documents pathological events, including myofiber oxidative damage and degeneration, myofibrosis, micro-vessel (diameter = 50–150 μm) remodeling, and collagenous investment of terminal micro-vessels (diameter ≤ 15 µm) in the calf muscle of patients with Peripheral Artery Disease (PAD). In this study, we evaluate the hypothesis that the vascular pathology associated with the legs of PAD patients encompasses pathologic changes to the smallest micro-vessels in calf muscle. Biopsies were collected from the calf muscle of control subjects and patients with Fontaine Stage II and Stage IV PAD. Slide specimens were evaluated by Quantitative Multi-Spectral and Fluorescence Microscopy. Inter-myofiber collagen, stained with Masson Trichrome (MT), was increased in Stage II patients, and more substantially in Stage IV patients in association with collagenous thickening of terminal micro-vessel walls. Evaluation of the Basement Membrane (BM) of these vessels reveals increased thickness in Stage II patients, and increased thickness, diameter, and Collagen I deposition in Stage IV patients. Coverage of these micro-vessels with pericytes, key contributors to fibrosis and BM remodeling, was increased in Stage II patients, and was greatest in Stage IV patients. Vascular pathology of the legs of PAD patients extends beyond atherosclerotic main inflow arteries and affects the entire vascular tree—including the smallest micro-vessels.

Peripheral artery disease (PAD) is a common atherosclerotic disease characterized by narrowed or blocked arteries in the lower extremities. Circulating serum biomarkers can provide significant insight regarding the disease progression. Here, we explore the metabolomics signatures associated with different stages of PAD and investigate potential mechanisms of the disease. We compared the serum metabolites of a cohort of 26 PAD patients presenting with claudication and 26 PAD patients presenting with critical limb ischemia (CLI) to those of 26 non-PAD controls. A difference between the metabolite profiles of PAD patients from non-PAD controls was observed for several amino acids, acylcarnitines, ceramides, and cholesteryl esters. Furthermore, our data demonstrate that patients with CLI possess an altered metabolomic signature different from that of both claudicants and non-PAD controls. These findings provide new insight into the pathophysiology of PAD and may help develop future diagnostic procedures and therapies for PAD patients.

Objectives: This study aimed to evaluate the effectiveness of using 1 to 4 mobile or fixed automated video monitoring systems (AVMSs) to decrease the risk of unattended bed exits (UBEs) as antecedents to unassisted falls among patients at high risk for falls and fall-related injuries in 15 small rural hospitals. Methods: We compared UBE rates and fall rates during baseline (5 months in which patient movement was recorded but nurses did not receive alerts) and intervention phases (2 months in which nurses received alerts). We determined lead time (seconds elapsed from the first alert because of patient movement until 3 seconds after an UBE) during baseline and positive predictive value and sensitivity during intervention. Results: Age and fall risk were negatively associated with the baseline patient rate of UBEs/day. From baseline to intervention: in 9 hospitals primarily using mobile systems, UBEs/day decreased from 0.84 to 0.09 (89%); in 5 hospitals primarily using fixed systems, UBEs/day increased from 0.43 to 3.18 (649%) as patients at low risk for falls were observed safely exiting the bed; and among 13 hospitals with complete data, total falls/1000 admissions decreased from 8.83 to 5.53 (37%), and injurious falls/1000 admissions decreased from 2.52 to 0.55 (78%). The median lead time of the AVMS was 28.5 seconds, positive predictive value was nearly 60%, and sensitivity was 97.4%. Conclusions: Use of relatively few AVMSs may allow nurses to adaptively manage UBEs as antecedents to unassisted falls and fall-related injuries in small rural hospitals. Additional research is needed in larger hospitals to better understand the effectiveness of AVMSs.

We provide a study comparison between two-dimensional measurement and volumetric (3D) segmentation of the lateral ventricles and brain structures in fetuses with isolated and non-isolated ventriculomegaly with 3D virtual organ computer-aided analysis (VOCAL) ultrasonography vs. magnetic resonance imaging (MRI) analyzed with 3D-Slicer software. In this cross-sectional study, 40 fetuses between 20 and 38 gestational weeks with various degrees of ventriculomegaly were included. A total of 71 ventricles were measured with ultrasound (US) and with MRI. A total of 64 sonographic ventricular volumes, 80 ventricular and 40 fetal brain MR volumes were segmented and analyzed using both imaging modalities by three observers. Sizes and volumes of the ventricles and brain parenchyma were independently analyzed by two radiologists, and interobserver correlation of the results with 3D fetal ultrasound data was performed. The semiautomated rotational multiplanar 3D VOCAL technique was performed for ultrasound volumetric measurements. Results were compared to manually extracted ventricular and total brain volumes in 3D-Slicer. Segmentation of fetal brain structures (cerebral and cerebellar hemispheres, brainstem, ventricles) performed independently by two radiologists showed high interobserver agreement. An excellent agreement between VOCAL and MRI volumetric and two-dimensional measurements was established, taking into account the intraclass correlation coefficients (ICC), and a Bland–Altman plot was established. US and MRI are valuable tools for performing fetal brain and ventricular volumetry for clinical prognosis and patient counseling. Our datasets could provide the backbone for further construction of quantitative normative trajectories of fetal intracranial structures and support earlier detection of abnormal brain development and ventriculomegaly, its timing and progression during gestation.

Background: The COVID-19 pandemic exposed significant healthcare access disparities for migrant communities, with infection rates up to three times higher than the general population. While mobile health technology offers potential solutions for reaching vulnerable populations during public health emergencies, implementation barriers persist. This study evaluates how mobile health interventions can effectively serve migrant communities through analysis of a digital health program implemented in rural Nebraska. Results: Analysis of semi-structured interviews with migrant family members between February 2022 and June 2024 revealed three key elements driving program success: culturally congruent support through community navigators, immediate access to testing and results, and program adaptability to meet broader community needs. Community navigators proved essential, expanding beyond technical support to address social needs ranging from food insecurity to domestic issues. The combination of digital tools with human support enabled families to make timely decisions about work and school attendance while accessing crucial social services. Conclusions: Digital health interventions can effectively serve migrant communities when designed with cultural sensitivity and supported by community navigators. While public health systems should prioritize technological infrastructure for emergency response, success requires concurrent investment in culturally responsive human support systems. The integration of digital tools with adaptable community navigation provides a model for reaching vulnerable populations during future public health emergencies.