Population Pharmacokinetic Evaluation of Amikacin Liposome Inhalation Suspension in Patients with Treatment-Refractory Nontuberculous Mycobacterial Lung Disease.

Background And Objectives: Use of parenteral amikacin to treat refractory nontuberculous mycobacterial (NTM) lung disease is limited by systemic toxicity. A population pharmacokinetic model was developed using data pooled from two randomized trials to evaluate the pharmacokinetic properties of once-daily amikacin liposome inhalation suspension (ALIS) in patients with treatment-refractory NTM lung disease.

Methods: In phase 2 (TR02-112) and phase 3 (CONVERT) studies, patients with sputum cultures positive for Mycobacterium avium complex (both studies) or M.

Circulating microparticles from subjects with active pulmonary tuberculosis infection modulate immune response.

Microparticles (MPs) which circulate within the plasma are elevated in patients with active pulmonary tuberculosis infection. Circulating MPs isolated from the plasma of patients with active pulmonary tuberculosis infection modulate the cytokine production of immune cells in vitro.

The Contribution of the Urokinase Plasminogen Activator and the Urokinase Receptor to Pleural and Parenchymal Lung Injury and Repair: A Narrative Review.

Pleural and parenchymal lung injury have long been characterized by acute inflammation and pathologic tissue reorganization, when severe. Although transitional matrix deposition is a normal part of the injury response, unresolved fibrin deposition can lead to pleural loculation and scarification of affected areas. Within this review, we present a brief discussion of the fibrinolytic pathway, its components, and their contribution to injury progression.

Factor VIIa induces extracellular vesicles from the endothelium: a potential mechanism for its hemostatic effect.

Recombinant factor FVIIa (rFVIIa) is used as a hemostatic agent to treat bleeding disorders in hemophilia patients with inhibitors and other groups of patients. Our recent studies showed that FVIIa binds endothelial cell protein C receptor (EPCR) and induces protease-activated receptor 1 (PAR1)-mediated biased signaling. The importance of FVIIa-EPCR-PAR1-mediated signaling in hemostasis is unknown.

NOX1 Promotes Mesothelial-Mesenchymal Transition through Modulation of Reactive Oxygen Species-mediated Signaling.

Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells (PMCs) may contribute to PF through acquisition of a profibrotic phenotype, mesothelial-mesenchymal transition (MesoMT), which is characterized by increased expression of α-SMA (α-smooth muscle actin) and other myofibroblast markers. Although MesoMT has been implicated in the pathogenesis of PF, the role of the reactive oxygen species and the NOX (nicotinamide adenine dinucleotide phosphate oxidase) family in pleural remodeling remains unclear.

Cisplatin combined with laser‑activated nanotherapy as an adjuvant therapy for head and neck cancer.

Head and neck cancers (HNCs), in general, have a poor prognosis with a worldwide 5‑year survival rate of <50%. Numerous HNC patients with locoregionally advanced, difficult‑to‑treat, inoperable, recurrent and drug‑resistant tumors may require additional treatment options when the standard of care surgery, chemotherapy and radiation are not viable. The poor outcomes justify exploring strategies to increase the efficacy of lower doses of drugs, such as cisplatin, by combining these drugs with other treatment modalities and manipulating the dosing schedule.

Influences of reopening businesses and social venues: COVID-19 incidence rate in East Texas county.

As the on-going severe acute respiratory syndrome coronavirus 2 pandemic, we aimed to understand whether economic reopening (EROP) significantly influenced coronavirus disease 2019 (COVID-19) incidence. COVID-19 data from Texas Health and Human Services between March and August 2020 were analysed. COVID-19 incidence rate (cases per 100 000 population) was compared to statewide for selected urban and rural counties.

Burnout and Anxiety Among Trauma Nursing Specialties in a Rural Level I Trauma Center.

Background: Burnout and anxiety compromise physical and mental well-being of nurses and jeopardize patient safety. Personal, professional, and workplace characteristics have been associated with burnout and anxiety across diverse practice settings, yet none in rural, community trauma centers. We sought to identify the severity and predictors of burnout and anxiety in the trauma nursing staff of a rural Level I trauma center.

Memory like NK cells display stem cell like properties after Zika virus infection.

NK cells have been shown to display adaptive traits such as memory formation akin to T and B lymphocytes. Here we show that Zika virus infection induces memory like NK cells that express CD27. Strikingly, these cells exhibit stem-like features that include expansion capacity, self-renewal pathway, differentiation into effector cells, longer telomeres and gene signature associated with hematopoietic stem cell (HSC) progenitors.

Amikacin Liposome Inhalation Suspension for Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial.

Patients with refractory complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population.

A Participatory, State-Community-Academic Model to Improve Pregnancy Outcomes in Texas: The Healthy Families Initiative.

Background: While the Texas infant mortality rate (IMR) is below the Healthy People 2020 objective (5.7 per 1,000 live births), stark differences in IMR are seen across Texas communities. Health indicators for the state suggest important missed opportunities for improving maternal and infant outcomes.

Trends in Abusive and Nonabusive Injury Hospitalizations in Young Children in Texas, 2004-2018.

Hospitalization data provide context to understanding abusive and non-abusive injuries and how these hospitalizations change over time. The purpose of this study was to utilize Texas inpatient hospitalization data to assess age-related differences among infants (<12 months of age) and toddlers (12-59 months of age) in injury trends and patterns of injury among abusive and non-abusive hospitalization encounters over a 15-year time period. For both age groups, pediatric hospitalizations for non-abusive injuries decreased significantly over time; however, hospitalizations for abusive injuries did not.

A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis.

Crohn's disease and ulcerative colitis are the two forms of disorders of the human inflammatory bowel disease with unknown etiologies. Endothelial cell protein C receptor (EPCR) is a multifunctional and multiligand receptor, which is expressed on the endothelium and other cell types, including epithelial cells. Here, we report that EPCR is expressed in the colon epithelial cells, CD11c, and CD21/CD35 myeloid cells surrounding the crypts in the colon mucosa.

The prenatal triad: The importance of provider-patient communication with expectant fathers throughout the prenatal care process.

Previous research has primarily focused on the relationship between providers and expectant mothers as a key element of quality prenatal care. Significantly less attention has been directed toward expectant fathers and the importance of their communication with prenatal care providers and involvement in the prenatal care process. Much of this limited existing literature emphasizes the health benefits including fathers would bring for mom and baby, but rarely is the potential benefit to fathers' health included in the conversation.

Enhanced RIPK3 kinase activity-dependent lytic cell death in M1 but not M2 macrophages.

Macrophages play a crucial role in host innate immune defense against infection and tissue injury. Macrophages are highly plastic cells and their subtypes have been characterized as M1 (also termed classically activated) and M2 (alternatively activated). Although the M1/M2 paradigm has been well documented, less is known regarding the role of macrophage activation/polarization in inflammation-associated necrotic cell death.

Oxidative Stress Product, 4-Hydroxy-2-Nonenal, Induces the Release of Tissue Factor-Positive Microvesicles From Perivascular Cells Into Circulation.

Objective: TF (Tissue factor) plays a key role in hemostasis, but an aberrant expression of TF leads to thrombosis. The objective of the present study is to investigate the effect of 4-hydroxy-2-nonenal (HNE), the most stable and major oxidant produced in various disease conditions, on the release of TF microvesicles into the circulation, identify the source of TF microvesicles origin, and assess their effect on intravascular coagulation and inflammation. Approach and Results: C57BL/6J mice were administered with HNE intraperitoneally, and the release of TF microvesicles into circulation was evaluated using coagulation assays and nanoparticle tracking analysis.

Actin R256 Mono-methylation Is a Conserved Post-translational Modification Involved in Transcription.

Nuclear actin has been elusive due to the lack of knowledge about molecular mechanisms. From actin-containing chromatin remodeling complexes, we discovered an arginine mono-methylation mark on an evolutionarily conserved R256 residue of actin (R256me1). Actin R256 mutations in yeast affect nuclear functions and cause diseases in human.

Modeling dynamics of fatal opioid overdose by state and across time.

Opioid overdose fatalities include deaths from natural opioids (morphine and codeine), semi-synthetic opioids (oxycodone, hydrocodone), synthetic opioids (prescription and illicit fentanyl, tramadol), methadone, and heroin. From 1999 to 2017, there were 702,568 drug overdose deaths in the U.S.

Perfluorochemical-facilitated plasminogen activator delivery to the airways: A novel treatment for inhalational smoke-induced acute lung injury.

Background: Effective clinical management of airway clot and fibrinous cast formation of severe inhalational smoke-induced acute lung injury (ISALI) is lacking. Aerosolized delivery of tissue plasminogen activator (tPA) is confounded by airway bleeding; single-chain urokinase plasminogen activator (scuPA) moderated this adverse effect and supported transient improvement in gas exchange and lung mechanics. However, neither aerosolized plasminogen activator (PA) yielded durable improvements in physiologic responses or reduction in cast burden.

TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis.

Background: Chronic tissue injury was shown to induce progressive scarring in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), while an array of repair/regeneration and stress responses come to equilibrium to determine the outcome of injury at the organ level. In the lung, type I alveolar epithelial (ATI) cells constitute the epithelial barrier, while type II alveolar epithelial (ATII) cells play a pivotal role in regenerating the injured distal lungs. It had been demonstrated that eukaryotic cells possess repair machinery that can quickly patch the damaged plasma membrane after injury, and our previous studies discovered the membrane-mending role of Tripartite motif containing 72 (TRIM72) that expresses in a limited number of tissues including the lung.

Therapeutic doses of recombinant factor VIIa in hemophilia generates thrombin in platelet-dependent and -independent mechanisms.

Background: In hemophilia bypass therapy, a platelet-dependent mechanism is believed to be primarily responsible for recombinant factor VIIa (rFVIIa)'s hemostatic effect. rFVIIa may also possibly interact with other cells through its binding to endothelial cell protein C receptor (EPCR) or cell surface phospholipids.

Objectives: We aim to investigate the relative contribution of platelet-dependent and platelet-independent mechanisms in rFVIIa-mediated thrombin generation in hemophilic conditions at the injury site.

EPCR deficiency or function-blocking antibody protects against joint bleeding-induced pathology in hemophilia mice.

We recently showed that clotting factor VIIa (FVIIa) binding to endothelial cell protein C receptor (EPCR) induces anti-inflammatory signaling and protects vascular barrier integrity. Inflammation and vascular permeability are thought to be major contributors to the development of hemophilic arthropathy following hemarthrosis. The present study was designed to investigate the potential influence of FVIIa interaction with EPCR in the pathogenesis of hemophilic arthropathy and its treatment with recombinant FVIIa (rFVIIa).

Microparticles in the pathogenesis of TB: Novel perspectives for diagnostic and therapy management of Mycobacterium tuberculosis infection.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, usually chronic and has a progressive clinical course. Despite the availability of effective chemotherapy, TB is a leading killer of young adults worldwide and the global multi-drug resistant TB is reaching epidemic proportions. Interrupt transmission through early detection and treatment of the patients is a main element of the drug-resistant TB control strategy.