Use of a Hollow Fiber Bioreactor to Collect Extracellular Vesicles from Cells in Culture.

Current approaches for collection of extracellular vesicles (EV) are based on classical cell culture media production. This involves collection from cells grown in flasks, and can require multiple rounds of centrifugation or filtration, followed by ultracentrifugation or density gradient centrifugation. There are several limitations of these approaches, for example, they require a large input volume, the yield and concentration is low, and the process is time consuming. Most cell cultures require the use of fetal bovine serum which contains a large amount of endogenous EV that can contaminate isolations of cell-derived EVs. The use of cell cultures within a hollow fiber bioreactor could address many of these limitations and produce a continuous source of highly concentrated EVs without contamination from serum EVs, and that are suitable for downstream applications.

Extracellular vesicle therapeutics for liver disease.

Extracellular vesicles (EVs) are endogenous nanoparticles that play important roles in intercellular communication. Unmodified and engineered EVs can be utilized for therapeutic purposes. For instance, mesenchymal stem cell (MSC)-derived EVs have shown promise for tissue repair, while drug-loaded EVs have the potential to be used for cancer treatment. The liver is an ideal target for EV therapy due to the intrinsic regenerative capacity of hepatic tissue and the tropism of systemically injected nanovesicles for this organ. This review will give an overview of the potential of EV therapeutics in liver disease. Specifically, the mechanisms by which MSC-EVs induce liver repair will be covered. Moreover, the use of drug-loaded EVs for the treatment of hepatocellular carcinoma will also be discussed. Although there are several challenges associated with the clinical translation of EVs, these biological nanoparticles represent a promising new therapeutic modality for liver disease.

Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury.

Hepatic ischemia/reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSCs) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from mesenchymal stem cells (MSC-EV) on tissue injury. The effects of systemically administered mouse bone marrow-derived MSC-EV were evaluated in an experimental murine model of hepatic IRI induced by cross-clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of up to 6 hours. Compared with controls, intravenous administration of MSC-EV 30 minutes prior to IRI dramatically reduced the extent of tissue necrosis, decreased caspase 3-positive and apoptotic cells, and reduced serum aminotransferase levels. MSC-EV increased hepatic messenger RNA (mRNA) expression of NACHT, LRR, and PYD domains-containing protein 12, and the chemokine (C-X-C motif) ligand 1, and reduced mRNA expression of several inflammatory cytokines such as interleukin 6 during IRI. MSC-EV increased cell viability and suppressed both oxidative injury and nuclear factor kappa B activity in murine hepatocytes in vitro. In conclusion, the administration of extracellular vesicles derived from bone marrow-derived MSCs may ameliorate hepatic IRI by reducing hepatic injury through modulation of the inflammatory response.Liver Transplantation 23 791-803 2017 AASLD.

European Summit on the Prevention and Self-Management of Chronic Respiratory Diseases: report of the European Union Parliament Summit (29 March 2017).

On March 29, 2017, a European Summit on the Prevention and Self-Management of Chronic Respiratory Diseases (CRD) was organized by the European Forum for Research and Education in Allergy and Airway Diseases. The event took place in the European Parliament of Brussels and was hosted by MEP David Borrelli and MEP Sirpa Pietikainen. The aim of the Summit was to correspond to the needs of the European Commission and of patients suffering from CRD to join forces in Europe for the prevention and self-management. Delegates of the European Rhinologic Society, European Respiratory Society, European Academy of Allergy and Clinical Immunology, European Academy of Paediatrics, and European Patients Organization EFA all lectured on their vision and action plan to join forces in achieving adequate prevention and self-management of CRD in the context of Precision Medicine. Recent data highlight the preventive capacity of education on optimal care pathways for CRD. Self-management and patient empowerment can be achieved by novel educational on-line materials and by novel mobile health tools enabling patients and doctors to monitor and optimally treat CRDs based on the level of control. This report summarizes the contributions of the representatives of different European academic stakeholders in the field of CRD.

25th anniversary article: CVD polymers: a new paradigm for surface modification and device fabrication.

Well-adhered, conformal, thin (<100 nm) coatings can easily be obtained by chemical vapor deposition (CVD) for a variety of technological applications. Room temperature modification with functional polymers can be achieved on virtually any substrate: organic, inorganic, rigid, flexible, planar, three-dimensional, dense, or porous. In CVD polymerization, the monomer(s) are delivered to the surface through the vapor phase and then undergo simultaneous polymerization and thin film formation. By eliminating the need to dissolve macromolecules, CVD enables insoluble polymers to be coated and prevents solvent damage to the substrate. CVD film growth proceeds from the substrate up, allowing for interfacial engineering, real-time monitoring, and thickness control. Initiated-CVD shows successful results in terms of rationally designed micro- and nanoengineered materials to control molecular interactions at material surfaces. The success of oxidative-CVD is mainly demonstrated for the deposition of organic conducting and semiconducting polymers.

Antidepressant discontinuation in bipolar depression: a Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) randomized clinical trial of long-term effectiveness and safety.

OBJECTIVE: To assess long-term effectiveness and safety of randomized antidepressant discontinuation after acute recovery from bipolar depression. METHOD: In the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, conducted between 2000 and 2007, 70 patients with DSM-IV-diagnosed bipolar disorder (72.5% non-rapid cycling, 70% type I) with acute major depression, initially responding to treatment with antidepressants plus mood stabilizers, and euthymic for 2 months, were openly randomly assigned to antidepressant continuation versus discontinuation for 1-3 years. Mood stabilizers were continued in both groups. RESULTS: The primary outcome was mean change on the depressive subscale of the STEP-BD Clinical Monitoring Form. Antidepressant continuation trended toward less severe depressive symptoms (mean difference in DSM-IV depression criteria = -1.84 [95% CI, -0.08 to 3.77]) and mildly delayed depressive episode relapse (HR = 2.13 [1.00-4.56]), without increased manic symptoms (mean difference in DSM-IV mania criteria = +0.23 [-0.73 to 1.20]). No benefits in prevalence or severity of new depressive or manic episodes, or overall time in remission, occurred. Type II bipolar disorder did not predict enhanced antidepressant response, but rapid-cycling course predicted 3 times more depressive episodes with antidepressant continuation (rapid cycling = 1.29 vs non-rapid cycling = 0.42 episodes/year, P = .04). CONCLUSIONS: This first randomized discontinuation study with modern antidepressants showed no statistically significant symptomatic benefit with those agents in the long-term treatment of bipolar disorder, along with neither robust depressive episode prevention benefit nor enhanced remission rates. Trends toward mild benefits, however, were found in subjects who continued antidepressants. This study also found, similar to studies of tricyclic antidepressants, that rapid-cycling patients had worsened outcomes with modern antidepressant continuation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00012558.

Preparation and structural analysis of carbon-supported Co core/Pt shell electrocatalysts using electroless deposition methods.

Cobalt core/platinum shell nanoparticles were prepared by the electroless deposition (ED) of Pt on carbon-supported cobalt catalyst (Co/C) and verified by HRTEM images. For a 2.0 wt % Co/C core, the ED technique permitted the Pt loading to be adjusted to obtain a series of bimetallic compositions with varying numbers of monolayers (ML). The tendency for corrosion of Co and the electrochemical (i.e., oxygen reduction reaction (ORR)) activity of the structures were measured. The results from temperature-programmed reduction (TPR) analysis suggest that a single Pt ML coverage is formed at a Pt weight loading between 0.5 and 0.7% on the 2.0% Co/C. HRTEM analysis indicates that the continuity of the Pt shell on the Co core depends on the precursor Co particle size, where "large" Co particles (>10 nm) favor noncontinuous, three-dimensional Pt structures and "small" Co particles (<6 nm) favor layer-by-layer growth. For these larger core-shell particles, Co was observed to quickly corrode in 0.3 M H(2)SO(4). Surface area specific ORR activity, measured by chemisorption techniques, revealed that the Pt-Co/C catalysts performed better than a commercial Pt/C catalyst; however, on a Pt mass basis, only the lower Pt:Co atomic ratio Pt-Co/C catalysts outperformed the Pt/C catalyst.

Short term effects of air pollution on hospitalizations for cardiovascular diseases in eight French cities: the PSAS program.

INTRODUCTION: Short term associations between air pollution indicators and hospitalizations for cardiovascular diseases have been suggested by epidemiological and clinical studies. The present study aims at estimating the association between particles with diameter <10 microm (PM(10)), nitrogen dioxide (NO(2)) and ozone and hospitalizations for cardiovascular diseases in eight French cities during the 1998-2003 period. METHODS: The daily number of hospitalizations in each city was extracted from the French hospital information system (PMSI) for cardiovascular diseases, cardiac diseases, ischemic heart diseases and stroke. Excess relative risks (ERRs) of hospitalization associated with a 10 microg/m(3) increase in pollutant levels were estimated in each city by fitting a Poisson regression model, controlling for well-known confounding factors and temporal trends. City-specific results were then combined by inverse variance weighting. RESULTS: Daily number of hospitalizations for cardiovascular diseases was associated with PM(10) levels (for a 10 microg/m(3) increase, ERR=0.8%, 95% CI: [0.2, 1.5]), with NO(2) (1.1%, [0.6, 1.6]) but not with ozone (0.1% [-0.2%, 0.5%]). Associations were stronger in people aged 65 years and over, and when only hospitalizations for ischemic heart diseases were considered. No association was found between strokes and air pollution levels. DISCUSSION: Our study suggests that the ambient levels of air pollutants currently experienced in the eight French cities, which are close to European air quality guidelines, are yet linked to a short term increase of hospitalizations for cardiovascular diseases. These results are consistent with epidemiological and toxicological data on the cardiovascular effects of air pollution.

The relationship between smoking and suicidal behavior, comorbidity, and course of illness in bipolar disorder.

OBJECTIVES: The rate of smoking in people with bipolar disorder is much greater than in the general population, but the implications of smoking for the course of bipolar disorder have not been well studied. The purpose of this retrospective study was to examine the relationship between smoking, severity of bipolar disorder, suicidal behavior, and psychiatric and substance use disorder comorbidity. METHOD: We evaluated 399 outpatients with bipolar disorder who were treated in a bipolar specialty clinic from December 1999 to October 2004. Diagnosis, mood state, course of illness, functioning, and psychiatric comorbidities were assessed using the Affective Disorders Evaluation and the Mini-International Neuropsychiatric Interview. RESULTS: Of the 399 patients evaluated, 155 (38.8%) had a history of daily smoking. Having ever smoked was associated with earlier age at onset of first depressive or manic episode, lower Global Assessment of Functioning scores, higher Clinical Global Impressions-Bipolar Disorder scale scores, lifetime history of a suicide attempt (47% for smokers vs. 25% for those who had never smoked), and lifetime comorbid disorders: anxiety disorders, alcohol abuse and dependence, and substance abuse and dependence. In a logistic regression model including these factors, suicide attempts and substance dependence were significantly associated with smoking in patients with bipolar disorder. CONCLUSIONS: Bipolar patients with lifetime smoking were more likely to have earlier age at onset of mood disorder, greater severity of symptoms, poorer functioning, history of a suicide attempt, and a lifetime history of comorbid anxiety and substance use disorders. Smoking may be independently associated with suicidal behavior in bipolar disorder.

The integration of measurement and management for the treatment of bipolar disorder: a STEP-BD model of collaborative care in psychiatry.

Patients with bipolar disorder are among the most challenging to treat. These patients frequently present with complex mood and other symptoms that change over time, complex psychiatric and medical comorbid conditions, and multiple medications. Clinicians rarely systematically assess or measure all of these factors and instead rely on memory and general impressions. It is imperative that clinicians systematically track and monitor these relevant variables to ensure treatment decisions are based on precise clinical data. By integrating measurement and management, clinicians and patients can collaborate to assess the effectiveness of treatments and to make joint decisions about critical points at which to adjust treatment. This method was shown to be successful in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).