Unique infrared thermographic profiles and altered hypothalamic neurochemistry associated with mortality in endotoxic shock.

Neonatal sepsis results in significant morbidity and mortality, but early detection is clinically challenging. In a neonatal rat model of endotoxic shock, we characterised unique infrared thermographic (IRT) profiles in skin temperature that could identify risk of later mortality. Ten-day old rats were placed in a thermally stable isolette and IRT images of cranial (T), scapula (T) and rump (T) skin temperature were obtained continuously for 8 h following an intraperitoneal injection of lipopolysaccharide (LPS) or saline.

Culture Expansion Alters Human Bone Marrow-Derived Mesenchymal Stem Cell Production of Osteoarthritis-Relevant Cytokines and Growth Factors.

Purpose: The purposes of this study were to characterize the human bone marrow-derived mesenchymal stem cells (BM-MSCs) production of osteoarthritis-relevant cytokines and growth factors as they are purified and multiplied, a process termed culture expansion, and to compare the immunomodulatory potential of BM-MSCs based on source and medium used for culture expansion.

Methods: BM-MSCs were obtained from iliac crest bone marrow aspirates of 4 healthy donors. These 4 BM-MSC cell lines underwent 4 rounds, or "passages," of the institutional culture expansion protocol, using institutional culture media.

Differential effects of macrophage subtype-specific cytokines on fibroblast proliferation and endothelial cell function in co-culture system.

Macrophages are involved in several critical activities associated with tissue repair and regeneration. Current approaches in regenerative medicine are focusing on leveraging the innate immune response to accelerate tissue regeneration and improve long-term healing outcomes. Of particular interest in this regard are the currently known, four main M2 macrophage subtypes: M2, M2, M2, M2 (M2 → M2).

Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: Current practices and recommendations.

Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, is increasingly recognized as an important pathogen of the human lung, disproportionally affecting people with cystic fibrosis (CF) and other susceptible individuals with non-CF bronchiectasis and compromised immune functions. M. abscessus infections are extremely difficult to treat due to intrinsic resistance to many antibiotics, including most anti-tuberculous drugs.

Polymerized cyclodextrin microparticles for sustained antibiotic delivery in lung infections.

Pulmonary infections complicate chronic lung diseases requiring attention to both the pathophysiology and complexity associated with infection management. Patients with cystic fibrosis (CF) struggle with continuous bouts of pulmonary infections, contributing to lung destruction and eventual mortality. Additionally, CF patients struggle with airways that are highly viscous, with accumulated mucus creating optimal environments for bacteria colonization.

Diplomate in Medical Laboratory Immunology Certification Examination: A New Chapter for Medical Laboratory Immunology.

It is indeed a privilege to be an immunologist in what is arguably the golden age of immunology. From astounding advances in fundamental knowledge to groundbreaking immunotherapeutic offerings, immunology has carved out an enviable niche for itself in basic science and clinical medicine. The need and the vital importance of appropriate education, training, and certification in clinical immunology was recognized by the World Health Organization as far back as 1972.

Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the "First in Cystic Fibrosis" Phase I Clinical Trial (CEASE-CF).

Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function.

Update on Innate and Adaptive Immunity in Cystic Fibrosis.

Cystic fibrosis (CF) pathophysiology is hallmarked by excessive inflammation and the inability to resolve lung infections, contributing to morbidity and eventually mortality. Paradoxically, despite a robust inflammatory response, CF lungs fail to clear bacteria and are susceptible to chronic infections. Impaired mucociliary transport plays a critical role in chronic infection but the immune mechanisms contributing to the adaptation of bacteria to the lung microenvironment is not clear.

Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis.

Overwhelming neutrophilic inflammation is a leading cause of lung damage in many pulmonary diseases, including cystic fibrosis (CF). The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway mediates the resolution of inflammation and is defective in CF-affected macrophages (MΦs). Here, we provide evidence that systemic administration of PP-007, a CO releasing/O transfer agent, induces the expression of HO-1 in a myeloid differentiation factor 88 (MyD88) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)-dependent manner.

CFTR Modulators Restore Acidification of Autophago-Lysosomes and Bacterial Clearance in Cystic Fibrosis Macrophages.

Cystic fibrosis (CF) human and mouse macrophages are defective in their ability to clear bacteria such as . The autophagy process in CF (F508del) macrophages is halted, and the underlying mechanism remains unclear. Furthermore, the role of CFTR in maintaining the acidification of endosomal and lysosomal compartments in CF cells has been a subject of debate.

Optimization of Human Mesenchymal Stem Cells for Rheumatoid Arthritis: Implications for Improved Therapeutic Outcomes.

Objective: Seropositive rheumatoid arthritis (RA) is a chronic autoimmune disease that is rarely "cured." Human mesenchymal stem cells (hMSCs) are known to reduce inflammation and restore immune homeostasis. However, methods for predicting therapeutic hMSC potency have not been established.

Enhancing Cystic Fibrosis Immune Regulation.

In cystic fibrosis (CF), sustained infection and exuberant inflammation results in debilitating and often fatal lung disease. Advancement in CF therapeutics has provided successful treatment regimens for a variety of clinical consequences in CF; however effective means to treat the pulmonary infection and inflammation continues to be problematic. Even with the successful development of small molecule cystic fibrosis transmembrane conductance regulator (CFTR) correctors and potentiators, there is only a modest effect on established infection and inflammation in CF patients.

Donor-defined mesenchymal stem cell antimicrobial potency against nontuberculous mycobacterium.

Chronic nontuberculous mycobacterial infections with Mycobacterium avium and Mycobacterium intracellulare complicate bronchiectasis, chronic obstructive airway disease, and the health of aging individuals. These insidious intracellular pathogens cause considerable morbidity and eventual mortality in individuals colonized with these bacteria. Current treatment regimens with antibiotic macrolides are both toxic and often inefficient at providing infection resolution.

Heparin-mediated antibiotic delivery from an electrochemically-aligned collagen sheet.

Background: Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue.

Objective: To develop and evaluate a novel, biologic antimicrobial coating for medical implants.

Methods: Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per a protocol developed by our group.

Characterizing the endometrial fluid cytokine profile in women with endometriosis.

Purpose: To compare growth factor and cytokine profiles in the endometrial secretions of patients with and without endometriosis to determine whether a particular protein profile is predictive of the disease.

Methods: Patients undergoing laparoscopic gynecologic surgery for benign indications were recruited for this prospective cohort study. Prior to surgery, endometrial fluid was aspirated and multiplex immunoassay was used to quantify 7 cytokines and growth factors.

Adipokine Resistin Levels at Time of Pediatric Crohn Disease Diagnosis Predict Escalation to Biologic Therapy.

Background: Hypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD.

Insights into the l,d-Transpeptidases and d,d-Carboxypeptidase of Mycobacterium abscessus: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors.

is a highly drug-resistant nontuberculous mycobacterium (NTM). Efforts to discover new treatments for infections are accelerating, with a focus on cell wall synthesis proteins ( l,d-transpeptidases 1 to 5 [Ldt to Ldt] and d,d-carboxypeptidase) that are targeted by β-lactam antibiotics. A challenge to this approach is the presence of chromosomally encoded β-lactamase (Bla).

-Induced Bronchoalveolar Lavage Gene Expression Signature in Latent Tuberculosis Infection Is Dominated by Pleiotropic Effects of CD4 T Cell-Dependent IFN-γ Production despite the Presence of Polyfunctional T Cells within the Airways.

Tuberculosis (TB) remains a worldwide public health threat. Development of a more effective vaccination strategy to prevent pulmonary TB, the most common and contagious form of the disease, is a research priority for international TB control. A key to reaching this goal is improved understanding of the mechanisms of local immunity to , the causative organism of TB.

Optimization of In Vitro and Growth Assays for Therapeutic Development.

Infection with nontuberculous mycobacteria (NTM) is a complication of lung disease in immunocompromised patients, including those with human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). The most widespread, disease-causing NTM is complex (), which colonizes the lungs as a combination of , , and other mycobacterial species. While combination drug therapy exists for colonization, there is no cure.

Periostin levels in children without respiratory disease.

Background: Periostin is a protein that serves as a downstream marker of the T-helper type 2 (Th2) cell response. It may serve to identify drug-responsive inflammatory phenotypes, particularly in children with asthma and possibly bronchiolitis. There are no published levels of periostin in healthy children <2 years of age, limiting interpretation of periostin levels in disease.

Stratification of peanut allergic murine model into anaphylaxis severity risk groups using thermography.

Murine models are readily used to investigate mechanisms potentially involved in anaphylaxis. Determining successful sensitization with current methods remain potentially lethal, invasive, expensive and/or cumbersome. Here we describe the use of thermography to read intradermal testing to detect peanut allergic sensitization in the murine model and as a first time sensitive tool for anaphylaxis stratification.

A case series: Association of anaphylaxis with a significant decrease in platelet levels and possible secondary risk of thrombosis.

Introduction: Anaphylaxis is a life threatening systemic inflammatory process that share mediators involved in the coagulation cascade. Platelet activating factor, known to increase platelet aggregation, has also been implicated as an important mediator of anaphylaxis. Although other inflammatory reactions are associated with an increased risk of thrombosis, anaphylaxis is currently not reported as one of them.