Glycocalyx heparan sulfate cleavage promotes endothelial cell angiopoietin-2 expression by impairing shear stress-related AMPK/FoxO1 signaling.

Angiopoietin-2 (Ang-2) is a key mediator of vascular disease during sepsis, and elevated plasma levels of Ang-2 are associated with organ injury scores and poor clinical outcomes. We have previously observed that biomarkers of endothelial glycocalyx (EG) damage correlate with plasma Ang-2 levels, suggesting a potential mechanistic linkage between EG injury and Ang-2 expression during states of systemic inflammation. However, the cell signaling mechanisms regulating Ang-2 expression following EG damage are unknown.

Increased Plasma Hyaluronan Levels are Associated With Acute Traumatic Coagulopathy.

Introduction: Acute traumatic coagulopathy (ATC) is an endogenous impairment in hemostasis that often contributes to early mortality after trauma. Endothelial glycocalyx damage is associated with trauma-induced coagulation abnormalities; however, the specific relationship between hyaluronan (HA), a key glycocalyx constituent, and ATC has not been evaluated.

Methods: We performed a secondary analysis of prospectively collected data from a recent study in which trauma patients (>18 years) admitted to our Level I trauma center with an ABC Score≥2 were enrolled.

A short review of loop quantum gravity.

An outstanding open issue in our quest for physics beyond Einstein is the unification of general relativity (GR) and quantum physics. Loop quantum gravity (LQG) is a leading approach toward this goal. At its heart is the central lesson of GR: gravity is a manifestation of spacetime geometry.

Alleviating the Tension in the Cosmic Microwave Background Using Planck-Scale Physics.

Certain anomalies in the CMB bring out a tension between the six-parameter flat ΛCDM model and the CMB data. We revisit the PLANCK analysis with loop quantum cosmology (LQC) predictions and show that LQC alleviates both the large-scale power anomaly and the tension in the lensing amplitude. These differences arise because, in LQC, the primordial power spectrum is scale dependent for small k, with a specific power suppression.

Associations of Plasma Angiopoietins-1 and -2 and Angiopoietin-2/-1 Ratios With Measures of Organ Injury and Clinical Outcomes in Children With Sepsis: A Preliminary Report.

Objectives: Results from preclinical and adult sepsis studies suggest that the balance of circulating angiopoietin-1 and -2 levels, represented as angiopoietin-2/-1 ratios, plays a pivotal role in mediating vascular dysfunction and organ injury during sepsis. However, the relationship of plasma angiopoietins with organ injury and clinical outcomes in children with sepsis remains unknown. We sought to determine whether plasma angiopoietin-1 and -2 levels and angiopoietin-2/-1 ratios in the acute phase of sepsis correlated with measures of organ injury and clinical outcomes in children with sepsis.

Temporal Dysregulation of the Angiopoietin-2/-1 Ratio After Trauma and Associations With Injury Characteristics and Outcomes.

Traumatic injury and hemorrhagic shock result in endothelial cell activation and vascular dysfunction that, if not corrected, can propagate multiorgan failure. Angiopoietin-1 and angiopoietin-2 are important regulators of endothelial cell function, and the ratio of plasma angiopoietin-2-to-1 is a useful indicator of overall vascular health. We therefore characterized plasma angiopoietin-2/-1 ratios over time after trauma in adults in an effort to gain insight into the pathophysiology that may drive post-traumatic vasculopathy and organ injury.

Transdermal vitamin D supplementation-A potential vitamin D deficiency treatment.

Vitamin D deficiency has high prevalence worldwide. Vitamin D3, the active form of vitamin D, exhibits array of roles in body, from calcium homeostasis and bone mineralization to cancer, neurological disorders, immunomodulatory action, and cardiac health. Current approaches for supplementing vitamin D3 are restricted to oral and parenteral routes.

Quantum Transfiguration of Kruskal Black Holes.

We present a new effective description of macroscopic Kruskal black holes that incorporates corrections due to quantum geometry effects of loop quantum gravity. It encompasses both the "interior" region that contains classical singularities and the "exterior" asymptotic region. Singularities are naturally resolved by the quantum geometry effects of loop quantum gravity, and the resulting quantum extension of the full Kruskal space-time is free of all the known limitations of previous investigations of the Schwarzschild interior.

Matrix metalloproteinase-9 deficiency protects mice from severe influenza A viral infection.

Matrix metalloproteinase-9 (MMP-9) cleaves various proteins to regulate inflammatory and injury responses. However, MMP-9's activities during influenza A viral (IAV) infections are incompletely understood. Herein, plasma MMP-9 levels were increased in patients with pandemic H1N1 and seasonal IAV infections.

Influenza-mediated reduction of lung epithelial ion channel activity leads to dysregulated pulmonary fluid homeostasis.

Severe influenza (IAV) infection can develop into bronchopneumonia and edema, leading to acquired respiratory distress syndrome (ARDS) and pathophysiology. Underlying causes for pulmonary edema and aberrant fluid regulation largely remain unknown, particularly regarding the role of viral-mediated mechanisms. Herein, we show that distinct IAV strains reduced the functions of the epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane regulator (CFTR) in murine respiratory and alveolar epithelia in vivo, as assessed by measurements of nasal potential differences and single-cell electrophysiology.

Alterations in Sod2-Induced Oxidative Stress Affect Endocrine Cancer Progression.

Context: Although important advances have been made in understanding the genetics of endocrine tumors, cellular physiology is relatively understudied as a determinant of tumor behavior. Oxidative stress and reactive oxygen species are metabolic factors that may affect tumor behavior, and these are, in part, controlled by manganese-dependent superoxide dismutase (MnSod), the mitochondrial superoxide dismutase (encoded by SOD2).

Objective: We sought to understand the role of MnSod in the prognosis of aggressive human endocrine cancers and directly assessed the effect of MnSod under- or overexpression on tumor behavior, using established mouse thyroid cancer models.

Deletion of Rap1b, but not Rap1a or Epac1, Reduces Protein Kinase A-Mediated Thyroid Cancer.

Background: Thyroid cancer is an emerging health problem in the United States and worldwide. With incidence rates of thyroid cancer rapidly rising, the need to develop new treatment options is becoming a priority, and understanding the molecular mechanisms of this disease is crucial to furthering these efforts. Thyroid growth is driven by the TSH/cAMP/PKA signaling pathway, and it has previously been shown that activation of PKA through genetic ablation of the regulatory subunit Prkar1a (Prkar1a KO) is sufficient to cause follicular thyroid cancer in mouse models.

ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype.

Mutations in genes encoding enzymes in the tricarboxylic acid cycle (TCA, also known as the Krebs cycle) have been implicated as causative genetic lesions in a number of human cancers, including renal cell cancers, glioblastomas and pheochromocytomas. In recent studies, missense mutations in the succinate dehydrogenase (SDH) complex have also been proposed to cause differentiated thyroid cancer. In order to gain mechanistic insight into this process, we generated mice lacking the SDH subunit D (Sdhd) in the thyroid.

Implications of a positive cosmological constant for general relativity.

Most of the literature on general relativity over the last century assumes that the cosmological constant [Formula: see text] is zero. However, by now independent observations have led to a consensus that the dynamics of the universe is best described by Einstein's equations with a small but positive [Formula: see text]. Interestingly, this requires a drastic revision of conceptual frameworks commonly used in general relativity, no matter how small [Formula: see text] is.

Gravitational Waves from Isolated Systems: Surprising Consequences of a Positive Cosmological Constant.

There is a deep tension between the well-developed theory of gravitational waves from isolated systems and the presence of a positive cosmological constant Λ, however tiny. In particular a generalization of Einstein's 1918 quadrupole formula that would allow a positive Λ is not yet available. We first explain the principal difficulties and then show that it is possible to overcome them in the weak field limit.

Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model.

Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown.

Treatment of AVN Using Autologous BM Stem Cells and Activated Platelet-Derived Growth Factor Concentrates.

Background: Avascular Necrosis (AVN) of hip is a devastating condition seen in younger individuals. It is the ischemic death of the constituents of the bone cartilage of the hip. The femoral head (FH) is the most common site for AVN.

Efficacy of Activated 3X Platelet-Rich Plasma in the Treatment of Androgenic Alopecia.

Background: Platelet-rich plasma (PRP) has shown remarkable beneficial effects without any major adverse reactions in the treatment of androgenic alopecia .The growth factors in activated autologous PRP induces the proliferation of dermal papilla cells.

Objectives: To investigate the clinical efficacy of Platelet Rich Plasma prepared using Merisis One Step Gel Separation Technology in treatment of androgenic alopecia.

Platelet-Rich Plasma Growth Factor Concentrated Spray (Keratogrow®) as a Potential Treatment for Androgenic Alopecia.

The objective is to investigate the safety and clinical efficacy of Autologous Platelet Rich Plasma Concentrated Spray (Keratogrow®), for hair loss. Autologous -PRP spray, prepared from a small volume of blood, was applied on the selected patients' scalps at least twice daily. Three months treatments were given for each patient.

Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability.

Mouse models of thyroid cancer: A 2015 update.

Thyroid cancer is the most common endocrine neoplasm, and its rate is rising at an alarming pace. Thus, there is a compelling need to develop in vivo models which will not only enable the confirmation of the oncogenic potential of driver genes, but also point the way towards the development of new therapeutics. Over the past 20 years, techniques for the generation of mouse models of human diseases have progressed substantially, accompanied by parallel advances in the genetics and genomics of human tumors.

Dioxin Exposure Impairs BMP-2-Mediated Spinal Fusion in a Rat Arthrodesis Model.

Background: Cigarette smoking inhibits bone-healing and leads to increased rates of pseudarthrosis. However, the mechanisms behind these effects are controversial. Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin)--a cigarette smoke constituent and potent activator of the aryl hydrocarbon receptor (Ahr)--negatively impacts bone quality and osteoblast differentiation.

Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis.

Peptide amphiphile (PA) nanofibers formed by self-assembly can be customized for specific applications in regenerative medicine through the use of molecules that display bioactive signals on their surfaces. Here, the use of PA nanofibers with binding affinity for the bone promoting growth factor BMP-2 to create a gel scaffold for osteogenesis is reported. With the objective of reducing the amount of BMP-2 used clinically for successful arthrodesis in the spine, amounts of growth factor incorporated in the scaffolds that are 10 to 100 times lower than that those used clinically in collagen scaffolds are used.

A comparative evaluation of factors influencing osteoinductivity among scaffolds designed for bone regeneration.

Due to differing compositions, synthetic scaffolds developed for bone regeneration vary widely in efficacy. To quantify the impact of such differences on osteoinductivity, numerous parameters were examined. Absorbable collagen sponge (ACS), three ceramic-based carriers (#1-3) of varying compositions, mineralized allograft chips, and an experimental phosphoserine-rich nanofiber scaffold [S(P) gel] were compared in their ability to promote cell adhesion, proliferation/survival, growth factor binding/release, and osteogenic gene expression.

Quantum gravity extension of the inflationary scenario.

Since the standard inflationary paradigm is based on quantum field theory on classical space-times, it excludes the Planck era. Using techniques from loop quantum gravity, the paradigm is extended to a self-consistent theory from the Planck scale to the onset of slow roll inflation, covering some 11 orders of magnitude in energy density and curvature. This preinflationary dynamics also opens a small window for novel effects, e.