Publications by authors named "Stephen Black"

This study introduces novel cospray-dried (Co-SD) formulations of simvastatin, a Nrf2 activator ROCK inhibitor, with l-carnitine as molecular mixtures in various molar ratios for targeted pulmonary inhalation aerosol delivery in pulmonary hypertension, optimized for excipient-free dry powder inhalers (DPIs). The two components were spray-dried at various molar ratios by using different starting feed solution concentrations and process parameters. In addition to comprehensive physicochemical characterization, in vitro aerosol dispersion performance as DPIs using two FDA-approved DPI devices with different shear stress properties, in vitro viability as a function of dose on 2D human pulmonary cellular monolayers and on 3D small airway epithelia human primary cultures at the air-liquid interface (ALI), and in vitro transepithelial electrical resistance (TEER) at the ALI were conducted.

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Human immunodeficiency virus type-1 (HIV-1) associated comorbidities account for the majority of poor health outcomes in people living with HIV (PLWH) in the era of antiretroviral therapy. Lung-related comorbidities such as chronic obstructive pulmonary disease (COPD) and bacterial pneumonia are primarily responsible for increased morbidity and mortality in PLWH, even when compensated for smoking. Smokers and COPD patients demonstrate cilia shortening, attenuated ciliary beat frequency (CBF), dysfunctional ciliated cells along with goblet cell hyperplasia, and mucus hypersecretion.

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Complications after iliofemoral and inferior vena cava stenting are rare, and most can be managed effectively without significant long-term consequences for the patient. Nevertheless, the procedure is not without risk, and clinicians considering starting a venous practice must be aware of the range of complications that can occur, which range from minor access site bleeds to fatal arrhythmia from stent migration to the heart. Most complications can be avoided with appropriate patient selection, stent sizing, and careful access and deployment techniques.

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Background: Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.

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Co-spray dried inhalable powder formulations of fasudil monohydrochloride salt (FMCS) and inhalable lung surfactant-based nanocarriers composed of synthetic phospholipids, zwitterionic DPPC (1,2-palmitoyl--glycero-3-phosphocholine) and anionic DPPG (1,2-dipalmitoyl--glycero-3-[phosphor-rac-1-glycerol]) sodium salt, were designed and optimized using organic solution advanced spray drying. FMCS can potentially be used for the treatment of various complex pulmonary diseases with this current work focusing on pulmonary arterial hypertension. Comprehensive physicochemical characterization, electron and optical microscopy imaging, thermal analysis, molecular fingerprinting spectroscopy, in vitro aerosol dispersion performance with human dry powder inhaler (DPI) devices, in vitro membrane permeation and drug release, and in vitro human cellular studies were conducted.

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Article Synopsis
  • This study aimed to evaluate a new classification system for chronic venous obstruction (CVO) patients who have undergone successful medical procedures across 13 vascular centers from 2015 to 2019.
  • Researchers analyzed the data of 1,033 CVO patients, classifying them into five categories based on the severity and location of their condition, and assessed stent deployment and complications alongside follow-up outcomes.
  • Results showed that primary patency rates varied significantly among the classifications, with lower rates indicating more severe CVO, and identified key predictors of patency loss such as CVO type and the total number of stents used, suggesting the need for further validation of this classification system in future research.
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Background: Nutcracker syndrome (NCS) describes the symptomatic compression of the left renal vein between the aorta and superior mesenteric artery. Whereas asymptomatic compression is a common radiological finding, patients with NCS can report a range of symptoms. There are no specific diagnostic criteria and interventions include a range of open surgical and endovascular procedures.

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Previously, we have shown that endothelial nitric-oxide synthase (eNOS) dimer levels directly correlate with the interaction of eNOS with hsp90 (heat shock protein 90). Further, the disruption of eNOS dimerization correlates with its redistribution to the mitochondria. However, the causal link between these events has yet to be investigated and was the focus of this study.

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The Rho Kinase (ROCK) pathway is recognized to be involved in changes that lead to remodeling in pulmonary hypertension (PH), particularly cellular processes including signaling, contraction, migration, proliferation, differentiation, and apoptosis. Simvastatin (Sim) has a potent anti-proliferative and pro-apoptotic effect on vasculature smooth muscle cells through the inhibition of the synthesis of isoprenoids intermediates which are essential for the post-translational isoprenylation of Rho, Rac, and Ras family GTPases. Sim targets the underlying mechanism in vascular remodeling.

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Endothelial cAMP-specific phosphodiesterase PDE3A is one of the major negative regulators of the endothelial barrier function in acute lung injury models. However, the mechanisms underlying its regulation still need to be fully resolved. We show here that the PDE3A is a newly described client of the molecular chaperone heat shock protein 90 (hsp90).

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microRNAs have emerged as essential regulators of health and disease, attracting significant attention from researchers across diverse disciplines. Following their identification as noncoding oligonucleotides intricately involved in post-transcriptional regulation of protein expression, extensive efforts were devoted to elucidating and validating their roles in fundamental metabolic pathways and multiple pathologies. Viral infections are significant modifiers of the host microRNAome.

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Transforming Growth Factor Beta1 (TGF-β1) signaling is upregulated in Chronic Obstructive Pulmonary disease (COPD), smokers, and people living with HIV. Cigarette smoking and HIV are also independent risk factors for COPD. Chronic inflammation is a hallmark of COPD.

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Article Synopsis
  • This systematic review and meta-analysis evaluated stenting outcomes for patients with stenosis in veins like the superior vena cava, finding that initial patency rates were high.
  • Of 39 studies involving 1,539 patients, primary patency was 81.5% at one year, but decreased to 63.2% at 12-24 months, with secondary patency rates showing better outcomes after further interventions.
  • The analysis highlighted that patients with malignant stenosis had better primary patency compared to those with benign stenosis, though overall evidence quality was very low, indicating a need for more research.
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Objective: Iliofemoral venous obstructive disease can result in significant, potentially debilitating symptoms that can negatively affect quality of life. Unlike arterial disease, patients with deep venous disease have a significantly lower median age, therefore the need for long term stent patency becomes a matter of decades rather than years. Furthermore, iliofemoral lesions frequently require stent placement across the inguinal ligament.

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Higher levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a TLR4 agonist, are associated with poor clinical outcomes in sepsis-induced acute lung injury (ALI). Little is known regarding the mechanisms by which eNAMPT is involved in ALI. Our recent work has identified a crucial role for mitochondrial dysfunction in ALI.

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Sepsis continues to overwhelm hospital systems with its high mortality rate and prevalence. A strategy to reduce the strain of sepsis on hospital systems is to develop a diagnostic/prognostic measure that identifies patients who are more susceptible to septic death. Current biomarkers fail to achieve this outcome, as they only have moderate diagnostic power and limited prognostic capabilities.

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Catheter-directed interventions for acute iliofemoral deep venous thrombosis (DVT) have been increasingly used over the past 15 years to target severe symptomatology and prevention of post-thrombotic syndrome incidence or reduce its severity if it were to develop. Aside from successful thrombus removal, adjunctive stents are frequently required to treat an uncovered lesion or significant residual thrombus to ensure quality of life improvement besides retarding DVT recurrence and post-thrombotic syndrome. As the evidence is mounting, the need and role for stenting, as well as the principles of an optimal technique, in the acute DVT setting are now better understood.

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Objective: Interventional treatments for acute iliofemoral deep vein thrombosis (DVT) remain controversial after publication of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) study. Interventions have been shown to reduce post-thrombotic syndrome severity and improve quality of life in DVT patients, but have been accompanied by risk of major bleeding from thrombolytics. We describe thrombus removal using a novel combined basket-rotational thrombectomy device that minimizes the need for thrombolytics or repeat procedures.

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Purpose: To report 36-month outcomes and subgroup analysis of the ABRE study evaluating the safety and effectiveness of the Abre venous self-expanding stent system for the treatment of symptomatic iliofemoral venous outflow obstruction disease.

Methods: The ABRE study was a prospective, multicenter, nonrandomized study that enrolled and implanted Abre venous stents in 200 participants (mean age 51.5 years [SD ± 15.

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Once thought of in terms of bioenergetics, mitochondria are now widely accepted as both the orchestrator of cellular health and the gatekeeper of cell death. The pulmonary disease field has performed extensive efforts to explore the role of mitochondria in regulating inflammation, cellular metabolism, apoptosis, and oxidative stress. However, a critical component of these processes needs to be more studied: mitochondrial network dynamics.

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Venous thromboembolism (VTE), notably deep venous thrombosis (DVT), represents a significant cardiovascular disease with high morbidity from post-thrombotic syndrome (PTS). Recent advancements in early thrombus removal technologies have prompted randomized controlled trials (RCT) to assess their efficacy and safety, particularly for iliofemoral DVT (IF-DVT), which carries the greatest risk of developing PTS. This narrative review summarizes these trials and introduces upcoming innovations to evaluate acute intervention for IF-DVT.

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