Multipotent mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) represent promising candidates for the development of future strategies in cellular therapy. To create a comprehensive protein expression profile for UCB-MSCs, one UCB unit from a full-term delivery was isolated from the unborn placenta, transferred into culture, and their whole-cell protein fraction was subjected to two-dimensional electrophoresis (2-DE). Unambiguous protein identification was achieved with peptide mass fingerprinting matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS), peptide sequencing (MALDI LIFT-TOF/TOF MS), as well as gel-matching with previously identified databases. In overall five replicate 2-DE runs, a total of 2037 +/- 437 protein spots were detected of which 205 were identified representing 145 different proteins and 60 isoforms or post-translational modifications. The identified proteins could be grouped into several functional categories, such as metabolism, folding, cytoskeleton, transcription, signal transduction, protein degradation, detoxification, vesicle/protein transport, cell cycle regulation, apoptosis, and calcium homeostasis. The acquired proteome map of nondifferentiated UCB-MSCs is a useful inventory which facilitates the identification of the normal proteomic pattern as well as its changes due to activated or suppressed pathways of cytosolic signal transduction which occur during proliferation, differentiation, or other experimental conditions.

Introduction: Chronic Hypersensitivity Pneumonitis (cHP) is a fibrotic interstitial lung disease (ILD) resulting from repeated exposure to an offending antigen. Prognostication in cHP remains challenging, and the relationship between comorbidities and survival has yet to be characterized. The aim of this study was to describe the relationship between comorbid conditions and survival in patients with cHP. Methods: The prospective database from a tertiary referral centre for ILD was reviewed for patient-reported comorbidities, their frequency, and relationship with survival in cHP patients. Comorbidities were assessed by direct questioning of the patient at the baseline visit and by a standardized questionnaire for the diagnosis of interstitial lung diseases. During the follow-up examinations, patients were asked about newly diagnosed comorbidities. Results: Two hundred eleven patients with cHP were identified (mean age 63 years, 53% male, mean FVC 73%), with mean follow-up of 32 months. The mean number of comorbidities was 3 (10% had 0, 59% 1-3 and 31% ≥4 comorbidities). Most frequent comorbidities groups were cardiovascular (65%) and respiratory (26%), most common comorbidities were hypertension (56%), gastro-esophageal reflux disease (GERD) (24%), diabetes (20%) and coronary heart disease (18%). In general, deceased patients had more comorbidities than survivors (p = 0.005), yet there was no association between the absolute number of comorbidities and survival. Pulmonary hypertension (30.8% versus 5.7%, p = 0.001;), diastolic dysfunction (26.9% versus 6.4%, p = 0.004) and cerebrovascular disease were more frequent in non-survivors (23.1% versus 7.6%, p = 0.026). Lung cancer was not observed, and neither GERD nor antacid drugs were associated with outcome (p = 0.357 and p = 0.961, respectively). Conclusions: Comorbidities are common in cHP are associated with survival. Further work should determine whether interventions for these specific comorbidities can positively affect survival.

Background: Transbronchial cryobiopsy (cTBB) may offer an alternative to surgical lung biopsy (SLB) for histopathological diagnosis of interstitial lung diseases (ILDs). However, real-life experience is limited, although case series are increasingly reported. Objectives: We aimed to evaluate the value of cTBB performed under real-life conditions in a tertiary care center for ILDs. Methods: Data on all patients undergoing a cTBB for evaluation of suspected ILD between October 2015 and January 2017 were included in this retrospective case series. Procedure details, complication rates, histopathological results, and diagnostic consensus reached by a multidisciplinary team (MDT) discussion were collated and evaluated. Results: A total of 109 patients (mean age 64 years, range 19–85; 66% male, 38% never smokers) referred to our center with features suggestive of ILD underwent cTBB. The mean FVC% predicted was 77% (range 41–131), with a mean DLCO of 51% (range 20–86), and a 6-min walking test (6MWT) of 402 m (range 100–642). On average, 4 samples were taken from each patient (range 1–8), with a mean biopsy diameter of 5 mm (range 2–12). Complications included pneumothorax (11.9%), all treated with chest drain. Moderate bleeding occurred in 28.4% (all resolved without active measures). No acute disease exacerbations and no deaths occurred. A histopathological pattern diagnosis was possible in 80 cases (73.4%), and 26.6% of cases were considered nonspecific. An MDT consensus diagnosis was reached in 83.5% of cases. Subsequent SLB was proposed in 13 cases and performed in 8 cases. Conclusions: In the real-world setting, cTBB has a meaningful diagnostic value in the context of a MDT approach and may enable histopathological assessment even in patients with more advanced disease unsuitable for SLB.

Postoperative cognitive dysfunction (POCD) is a known phenomenon occurring after anesthesia with volatile anesthetics (VA), such as isoflurane. Recent reports suggest that VA interact with neurodegenerative disease-associated proteins including compounds with pathogenic relevance in Alzheimer disease (AD) and induce processes that may be linked to AD neuropathology. Unfortunately, our present understanding of the exact anesthetics' molecular mechanisms of action, their side effects on the brain, and their catenation with AD pathology is still limited. The present study analyzes the differential proteome of the hippocampus immediately after and 3 days after a 3-hour 1 minimal alveolar concentration isoflurane anesthesia in rats. Differential 2-dimensional electrophoresis, mass spectrometry, and functional network mapping were used to identify and functionally classify 12 different hippocampal proteins, which were significantly regulated after isoflurane anesthesia (6 up-regulated, 11 down-regulated with P<0.01). Induction of differential expression ranged from 0.05 (25-fold down-regulation) to 4.4 (4.4-fold up-regulation). Ten proteins were regulated immediately after and 7 proteins 3 days after isoflurane exposure. The proteome displays isoflurane-responsive protein candidates, which have also been shown to play a role in AD. They were grouped according to their key biologic activities, which showed that isoflurane affects selected biologic processes including synaptic plasticity, stress response, detoxification, and cytoskeleton in early and late recovery phases after anesthesia. These processes are also affected in AD. Results are discussed in view of AD, the toxicity mechanisms of isoflurane as well as the implications for our present understanding and conduction of clinical anesthesia.