Progenitor and stem cells for bone and cartilage regeneration

Research in regenerative medicine is developing at a significantly quick pace. Cell-based bone and cartilage replacement is an evolving therapy aiming at the treatment of patients who suffer from limb amputation, damaged tissues and various bone and cartilage-related disorders. Stem cells are undifferentiated cells with the capability to regenerate into one or more committed cell lineages. Stem cells isolated from multiple sources have been finding widespread use to advance the field of tissue repair. The present review gives a comprehensive overview of the developments in stem cells originating from different tissues and suggests future prospects for functional bone and cartilage tissue regeneration.The European Network of Excellence EXPERTISSUES (Project No. NMP3-CT-2004-500283), under which this work was carried out, is acknowledged

Implementing integrated care guidelines in asthma and COPD: it ain't easy!

ObjectiveTo evaluate the implementation of a guideline-based, integrated, standardised, personal approach in patients with Chronic Obstructive Pulmonary Disease (COPD) or Asthma in a real-life situation.MethodsPatients at the outpatient clinic of the department of pulmonary disease were included in a controlled cohort study, comparing the use of diagnostic items and ‘Personalised care plans' (PCPs) in patients with obstructive lung disease before (2013) and after (2015) implementation of a personalised diagnostic pathway. Results were compared with reference data (2016) from two control hospitals that used the same guidelines but did not implement this pathway.Results100 patients were selected for all three cohorts. After implementing the diagnostic pathway in 2015, 35 % of patients visited attended all pre-planned appointments, whereas 65 % of patients did not: they were diagnosed using usual care. Factors contributing to patients not attending the diagnostic care pathway were: the logistical complexity and intensity of the 2-day pathway, patients willingness to participate in a personalised pathway, and low social economic status or low literacy. After the implementation of the pathway, a significant improvement was seen in the number of PCPs (P ConclusionImplementing a standardised diagnostic pathway in a real-life population significantly improved the number of personalised care plans, demonstrating that the implementation of holistic care planning is feasible in this population. Nevertheless, the pathway needs further improvements to maximize the number of patients benefitting from it, including logistical streamlining, removing unnecessary diagnostic tools, and increasing the focus on low literacy. Additionally, we found that implementing existing guidelines in a real life context is complex. Therefore, it is required to prioritize the translation of current guidelines into every-day practice, before expanding existing guidelines and protocols.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Smoking status and anti-inflammatory macrophages in bronchoalveolar lavage and induced sputum in COPD

<p>Abstract</p> <p>Background</p> <p>Macrophages have been implicated in the pathogenesis of COPD. M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties. We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD. Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.</p> <p>Methods</p> <p>114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV₁63 ± 9% predicted, no steroids past 6 months). BAL was collected from 71 patients. CD163⁺macrophages were quantified in BAL and sputum cytospins. Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.</p> <p>Results</p> <p>Ex-smokers with COPD had a higher percentage, but lower number of CD163⁺macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×10⁴/ml, p = 0.001 respectively). The percentage CD163⁺M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001). BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163⁺BAL macrophages (Rs = 0.38, p = 0.003). No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.</p> <p>Conclusions</p> <p>Our data suggest that smoking cessation partially changes the macrophage polarization <it>in vivo </it>in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters.</p

Metabolic Engineering for Biocatalyst Robustness to Organic Inhibitors

Microbial production of biorenewable fuels and chemicals is often limited by inhibition of the biocatalyst, either by increasing concentrations of the product compound or by contaminant compounds in the biomass‐derived sugars. This inhibition can interfere with economically viable production. Here we discuss typical mechanisms of inhibition and methods for improving biocatalyst robustness. Inhibition often takes the form of inhibition of enzyme activity, depletion of cofactor pools, and membrane damage; methods are discussed for mitigating each of these types of inhibition. Various evolutionary schemes have been developed and implemented on a variety of inhibitory compounds, including butanol, acetic acid, furfural, and ethanol. Reverse engineering of these improved strains can provide insight into new metabolic engineering strategies

Methods for sputum induction and analysis of induced sputum: a method for assessing airway inflammation in asthma.

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Electrochemical Impedance Spectroscopy as a Performance Indicator of Water Dissociation in Bipolar Membranes

Using electrochemical impedance spectroscopy (EIS), we observed the rate of water dissociation decrease in the presence of salt ions while also observing the diffusion and migration of these salt ions, showing a clear link between the peaks observed in EIS and ion crossover. In addition, we show how EIS can be used to in-situ monitor the stability and ageing of a BPM, revealing that degradation of the BPM is more prominent in extreme pH electrolyte pairs compared to non-extreme electrolyte pairs. The in-situ monitoring of the WDR and stability of a BPM are vital methods for adequate and consistent comparison of novel designs of BPM-based systems, where EIS allows for discriminating BPM characteristics from other components even during operation. &lt;br&gt;</jats:p

Electrochemical impedance spectroscopy as a performance indicator of water dissociation in bipolar membranes

A bipolar membrane (BPM) can be used to maintain a pH difference in an electrolysis cell, which provides freedom to independently optimize the environments and catalysts used for paired redox reactions. A BPM consists of two physical layers, of which one is selective for the exchange of cations and the other for anions. The water dissociation reaction (WDR) splits water into protons and hydroxide ions under an electric field that concentrates at the interface of the two membrane layers. However, salt ions in commonly used electrolytes influence this WDR when they are present at the interface. Using electrochemical impedance spectroscopy (EIS), we observed the rate of water dissociation decrease in the presence of salt ions while also observing the diffusion and migration of these salt ions, showing a clear link between the peaks observed in EIS and ion crossover. In addition, we show how EIS can be used to in situ monitor the stability and ageing of a BPM, revealing that degradation of the BPM is more prominent in extreme pH electrolyte pairs compared to non-extreme electrolyte pairs. The in situ monitoring of the WDR and stability of a BPM are vital methods for adequate and consistent comparison of novel designs of BPM-based systems, where EIS allows for discriminating BPM characteristics from other components even during operation.</p