Methane production from syngas using a trickle-bed reactor setup.

Syngas from gasification of waste biomass is a mixture of carbon monoxide (CO), carbon dioxide (CO2), and hydrogen (H2), which can be utilized for the synthesis of biofuels such as methane (CH4). The aim of the study research work was to demonstrate how syngas could be methanated and upgraded to natural gas quality (biomethane) in a fed-batch trickle-bed reactor system using either manure - (AD-M) or sludge-based (AD-WW) inoculum as microbial basis. The methanated syngas had a high concentration of CO2 and did not fulfil the criteria for natural gas quality biomethane. Further upgrading of syngas to biomethane could be achieved simultaneously in the same reactors by addition of exogenous H2, resulting in CH4 concentrations up to 91.0 ± 3.5% (AD-WW) and 95.3 ± 1.0% (AD-M). Microbial analysis indicated that the communities differed between AD-M and AD-WW demonstrating functional redundancy among the microbial communities of different inocula.

Variable oxygen administration in surgical and medical wards evaluated by 30-day mortality-An observational study.

BACKGROUND: Several studies in surgery and initial management of critical illness have indicated harmful effects of short-term exposure to hyperoxia. Exposure to and consequences of excessive oxygen administration in hospital wards are sparsely investigated. The aim of this study was to investigate the association between excessive oxygen administration in patients admitted to surgical or medical wards and 30-day mortality. METHODS: We included patients in the Capital Region of Denmark who were admitted to hospital in 2014 for either myocardial infarction, acute exacerbation of chronic obstructive pulmonary disease (COPD), hip fracture or open abdominal surgery. We defined groups of inadequate, adequate or excessive oxygen administration based on peripheral oxygen saturation and oxygen administration values in the first 48 hours after admission. The primary outcome was mortality within 30 days, and data were analysed with multivariable logistic regression for age, gender and comorbidities. RESULTS: We retrieved data from 11 196 patients, of which 81% had adequate, 18% had excessive and 1.8% inadequate oxygen administration. Mortality at 30 days was 4.2%, 7.6% and 27%, respectively, OR 1.46 (95%CI 1.16-1.84), P = .001 for patients with excessive compared to adequate oxygen administration. The association was significant in subgroups of patients admitted for acute exacerbation of COPD (OR 1.67, 95%CI 1.19-2.34) and myocardial infarction (OR 3.50, 95%CI 1.55-7.89). CONCLUSION: Patients who received excessive oxygen administration in surgical and medical wards during the first 48 hours of admission had a higher mortality risk within 30 days compared to patients with adequate oxygen administration. However, inadequate oxygen therapy still renders highest mortality and should be avoided.

Dropout from mentalization-based group treatment for adolescents with borderline personality features: A qualitative study.

Objective: Premature termination, or dropout, is a major concern in psychotherapy in general and an issue of particular importance in treatments for borderline personality disorder (BPD). Yet few studies investigating dropout from therapy in adolescent BPD populations exist. This study investigates reasons for dropping out from group-based mentalization-based treatment (MBT-G) for BPD or borderline features in an adolescent population.Method: Ten semi-structured interviews were performed with female adolescents who had dropped out from group-based MBT for BPD. The data were analyzed qualitatively using Systematic Text Condensation.Results: The results point to the existence of a subgroup of adolescent BPD patients who do not perceive the treatment sufficiently helpful or worthwhile, who experienced treatment as emotionally demanding, time-consuming and connected with unpleasant experiences. Positive reasons for early termination were reported in the form of experienced improvement in condition. Dropping out became understood as a process of weighing perceived benefits against perceived costs of staying in treatment. This understanding of dropout as a process implies the existence of a window of time where intervention to prevent dropout is possible, presupposing the detection of at-risk patients.

Clerkship students' use of a video library for training the mental status examination.

Aim: Fewer patient encounters and diminished bedside teaching pose a challenge to medical students' opportunity to learn during clinical clerkships in psychiatry. Videos can be used for close examination of signs and symptoms and to increase engagement and recall. A video library holding recordings of psychiatric patients with mental status examinations were prepared. We explored the students' use of this library during their clerkships.Methods and materials: The video library was introduced to three rotations of medical students and made accessible on hospital computers. Four students volunteered as key informants and were followed daily throughout the clerkship by the first author, using the ethnographic method of participant observation. At the end of the clerkship, group interviews were conducted with each rotation of students, including the key informants. Twelve students participated in the study. Field notes taken during participant observation and the transcribed interviews were merged in a thematic analysis.Results: The analysis reveals the students' autonomous and arbitrary use of the video library. Creatively extending the use of the videos, they scheduled their video sessions according to their individual needs. The students furthermore blended experiences gained from the library and in the ward, thus coping in various ways with the shortcomings of the video library.Conclusions: The medical students felt they benefited from the simplified learning situation offered by the video library. Their frequent shortcuts through the videos during sessions highlighted weaknesses in the feedback and reflection processes occasioned by the library.

Hyperoxia and antioxidants during major non-cardiac surgery and risk of cardiovascular events: Protocol for a 2 × 2 factorial randomised clinical trial.

BACKGROUND: Myocardial injury after non-cardiac surgery occurs in a high number of patients, resulting in increased mortality in the post-operative period. The use of high inspiratory oxygen concentrations may cause hyperoxia, which is associated with impairment of coronary blood flow. Furthermore, the surgical stress response increases reactive oxygen species, which is involved in several perioperative complications including myocardial injury and death. Avoidance of hyperoxia and substitution of reactive oxygen species scavengers may be beneficial. Our primary objective is to examine the effect of oxygen and added antioxidants for prevention of myocardial injury assessed by area under the curve for troponin measurements during the first three post-operative days. METHODS: The VIXIE trial (VitamIn and oXygen Interventions and cardiovascular Events) is an investigator-initiated, blinded, 2 × 2 factorial multicentre clinical trial. We include 600 patients with cardiovascular risk factors undergoing major non-cardiac surgery. Participants are randomised to an inspiratory oxygen fraction of 0.80 or 0.30 during and for 2 hours after surgery and either an intravenous bolus of vitamin C and an infusion of N-acetylcysteine or matching placebo of both. The primary outcome is the area under the curve for high-sensitive cardiac troponin release during the first three post-operative days as a marker of the extent of myocardial injury. Secondary outcomes are mortality, non-fatal myocardial infarction and non-fatal serious adverse events within 30 days. PERSPECTIVE: The current trial will provide further evidence for clinicians on optimal administration of perioperative oxygen in surgical patients with cardiovascular risks and the clinical effects of two common antioxidants.

E-Library of Authentic Patient Videos Improves Medical Students' Mental Status Examination.

OBJECTIVE: During psychiatric rotation, clerkship students must learn the clinical skill of recording an accurate Mental Status Examination (MSE). The authors built a video e-library consisting of 23 authentic patient videos that were accessible on a secure website during the rotation period, aimed at assisting students' acquisition of MSE skills. METHODS: The authors conducted a prospective case comparison study investigating the impact of the video e-library as "add-on" intervention, on acquisition of MSE skills, as measured by a test consisting of three videos with adjoining forced choice questionnaires. Eighty-five clerkship students had instructions and access to the video e-library whereas 82 did not. A group of clinicians, unfamiliar with the video e-library, was also subjected to the new MSE skills test and they served as a reference group. Outcome was defined as scores of MSE skills measured by the purpose made MSE skills test and entailed evaluation questions on the students' use of the e-library. RESULTS: The MSE skill test score differed between the three groups, and the clinicians scored higher than both student groups (clinicians mean score (M) 12.6; p < 0.001). However, the students with video access scored higher compared to students without access (M 10.7 versus M 9.9, p = 0.04). The e-library was appreciated by the students as helpful (83.6%) and they used it not only for practicing the MSE but also for observation of interviewing techniques. CONCLUSION: The e-library with video vignettes of authentic patients strengthens MSE skills as "add-on" to the psychiatric rotation, and evaluations by the students were positive.

Tofacitinib and TPCA-1 exert chondroprotective effects on extracellular matrix turnover in bovine articular cartilage ex vivo.

OBJECTIVE: Currently, there are no disease-modifying osteoarthritis drugs (DMOADs) approved for osteoarthritis. It is hypothesized that a subtype of OA may be driven by inflammation and may benefit from treatment with anti-inflammatory small molecule inhibitors adopted from treatments of rheumatoid arthritis. This study aimed to investigate how small molecule inhibitors of intracellular signaling modulate cartilage degradation and formation as a pre-clinical model for structural effects. DESIGN: Bovine cartilage explants were cultured with oncostatin M (OSM) and tumour necrosis factor α (TNF-α) either alone or combined with the small molecule inhibitors: SB203580 (p38 inhibitor), R406 (Spleen tyrosine kinase (Syk) inhibitor), TPCA-1 (Inhibitor of κB kinase (Ikk) inhibitor), or Tofacitinib (Tofa) (Janus kinases (Jak) inhibitor). Cartilage turnover was assessed with the biomarkers of degradation (AGNx1 and C2M), and type II collagen formation (PRO-C2) using ELISA. Explant proteoglycan content was assessed by Safranin O/Fast Green staining. RESULTS: R406, TPCA-1 and Tofa reduced the cytokine-induced proteoglycan loss and decreased AGNx1 release 3.7-, 43- and 32-fold, respectively. SB203580 showed no effect. All inhibitors suppressed C2M at a concentration of 3 µM. TPCA-1 and Tofa increased the cytokine reduced PRO-C2 3.5 and 3.7-fold, respectively. CONCLUSION: Using a pre-clinical model we found that the inhibitors TPCA-1 and Tofa inhibited cartilage degradation and rescue formation of type II collagen under inflammatory conditions, while R406 and SB203580 only inhibited cartilage degradation, and SB203580 only partially. These pre-clinical data suggest that TPCA-1 and Tofa preserve and help maintain cartilage ECM under inflammatory conditions and could be investigated further as DMOADs for inflammation-driven osteoarthritis.

Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for treatment of RA that enter phase I trials are eventually registered by the Food and Drug Administration, there is an immediate need for translational tools to facilitate early decision-making in drug development. In this study, we aimed to determine if the inability of fostamatinib (a small molecule inhibitor of Syk) to demonstrate sufficient efficacy in phase III of a previous clinical study could have been predicted earlier in the development process. METHODS: Biomarkers of bone, cartilage, and interstitial matrix turnover (C-telopeptide of type I collagen [CTX-I], matrix metalloproteinase-derived types I, II, and III collagen neoepitopes [C1M, C2M, and C3M]) were measured in 450 serum samples from the Oral Syk Inhibition in Rheumatoid Arthritis 1 study (OSKIRA-1, a phase III clinical study of the efficacy of fostamatinib in RA) at baseline and follow-up. Additionally, the same biomarkers were subsequently measured in conditioned media from osteoclast, cartilage, and synovial membrane cultured with the active metabolite of fostamatinib, R406, to assess the level of suppression induced by the drug. RESULTS: In OSKIRA-1 serum samples and osteoclast and cartilage cultures, fostamatinib suppressed the levels of CTX-I and C2M. In OSKIRA-1 serum samples and synovial membrane cultures, fostamatinib did not mediate any clinical or preclinical effect on either C1M or C3M, which have previously been associated with disease response and efficacy. CONCLUSION: These data demonstrate that translational biomarkers are a potential tool for early assessment and decision-making in drug development for RA treatment.

Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis.

OBJECTIVE: Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a commonly measured biomarker in rheumatology. The aim was to investigate the association of activated MMP-3 (actMMP3) species with treatment response compared to cMMP-3. METHODS: The LITHE biomarker study (n=741) was a 1-year phase III, double-blind, placebo-controlled, parallel group study of TCZ in RA patients on stable methotrexate. cMMP-3 and actMMP-3 were assessed in fasting serum at baseline, week 4, 16, 24 and 52. Patients not achieving ACR20 remission at week 16 or 28 received rescue treatment (escapers). Spearman's correlation was analysed between biomarker baseline level or biomarker delta and clinical measures. Changes in biomarker levels were studied as a function of time and treatment. RESULTS: ActMMP-3 16-week change in treatment groups was predictive of 1-year radiographic progression; a small change in actMMP3 was equal to worsening radiographics. Baseline cMMP-3 was associated with 52-weeks' radiographic status and cMMP3 16-weeks' change was predictive of 1-year change in disease activity. ActMMP-3 was dose-dependently decreased by TCZ, and escapers decreased in actMMP-3 upon treatment. CONCLUSIONS: ActMMP-3 and cMMP-3 were found to be efficacy biomarkers of TCZ and actMMP-3 were able to differentiated doses. Moreover, the suppression of actMMP3, but not cMMP3 was associated with treatment response. This study illustrates that two biomarkers of the same protein may have different predictive capacities.

Sprifermin (rhFGF18) modulates extracellular matrix turnover in cartilage explants ex vivo.

BACKGROUND: Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix (ECM) production. To gain further insight into the process of sprifermin in the cartilage tissue, this study aimed at investigating the ECM turnover of articular cartilage explants in a longitudinal manner. METHODS: Bovine full-depth articular cartilage explants were stimulated with sprifermin or placebo at weekly intervals, similar to the dosing regimen used in clinical trials. Pre-culturing with oncostatin M and tumour necrosis factor-α, was also used to induce an inflammatory state before treatment. Metabolic activity was measured using AlamarBlue, and chondrocyte proliferation was visualized by immuno-histochemical detection of proliferating cell nuclear antigen. ECM turnover was quantified by biomarker ELISAs; ProC2 reflecting type II collagen formation, CS846 reflecting aggrecan formation, active MMP9, C2M and AGNx2 reflecting matrix metalloproteinase activity, and AGNx1 reflecting aggrecanase activity. RESULTS: Sprifermin was able to reach the chondrocytes through the extracellular matrix, as it increased cell proliferation and metabolic activity of explants. ProC2 and CS846 was dose-dependently increased (P < 0.05) by sprifermin compared to placebo, while C2M and AGNx2 were unaffected, active MMP9 was slightly decreased, and AGNx1 was slightly increased. Over the course of treatment, the temporal order of ECM turnover responses was AGNx1, then ProC2, followed by CS846 and MMP9. Pro-inflammatory activation of the explants diminished the ECM turnover responses otherwise observed under non-inflammatory conditions. CONCLUSIONS: The data suggest that sprifermin has chondrogenic effects on articular cartilage ex vivo, exerted through a sequential process of ECM turnover; aggrecan degradation seems to occur first, while type II collagen and aggrecan production increased at a later time point. In addition, it was observed that these chondrogenic effects are dependent on the inflammatory status of the cartilage prior to treatment.

[Constructive learning theories and clinical apprenticeship]. / Et læringsteoretisk perspektiv på klinisk mesterlære

The article introduces how constructive learning theories as Constructive Alignment, Situated Learning and Cognitive Apprenticeship can explain learning during medical students' clinical placements and points out why Cognitive Apprenticeship can be particularly applicable in clinical psychiatry. This results in a discussion of the time frame, the organization of the placement in psychiatry at University of Copenhagen.

Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis.

OBJECTIVE: Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. METHODS: Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. RESULTS: TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1ß also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs. CONCLUSION: The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model.

Biomarkers of cartilage and surrounding joint tissue.

The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of disease modification. Today, the vast amount of patients suffering from serious, chronic joint diseases can only be offered treatments aimed at improving symptoms, such as pain and acute inflammation, and are not aimed at protecting the joint tissue. This huge, unmet medical need has been the driver behind the development of improved analytical techniques allowing better and more efficient clinical trial design, implementation and analysis. With this review, we aim to provide a brief and general overview of biochemical markers of joint tissue, with special focus on neoepitopes. Furthermore, we highlight recent studies applying biochemical markers in joint degenerative diseases. These disorders, including osteoarthritis, rheumatoid arthritis and spondyloarthropathies, are the most predominant disorders in Europe and the USA, and have enormous socioeconomical impact.

Potts shunt in a child with end-stage pulmonary hypertension after late repair of ventricular septal defect.

We report on a 10-year-old boy with medically refractory pulmonary arterial hypertension (PAH) and end-stage right heart failure after closure of a ventricular septal defect. The boy was a candidate for lung transplantation (LTX), but an alternative option was to create an Eisenmenger physiology with right-to-left shunting. The shunt could be created either as an intracardiac or as an extracardiac shunt. We decided to create a Potts shunt, a direct anastomosis between the left pulmonary artery and the descending aorta. The Potts shunt functioned as a right-to-left shunt, thus reducing the afterload on the right ventricle. The boy's clinical condition improved markedly, so he was discharged two weeks after the procedure. The ultimate therapeutic option for medically refractory PAH is LTX or heart-lung transplantation, but because of the short life span after LTX, time was bought by postponing the time of transplantation.

Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.

Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo response to a cancer related tumor antigen, Balb/c or B6.Cg(CB)-Tg(HLA-A/H2-D)2Enge/J (HLA-A2 transgenic) mice were immunized with a non-glycosylated or GalNAc-glycosylated MUC1 derived peptide followed by comparison of T cell proliferation, IFN-γ release, and antibody induction. GalNAc-glycosylation promoted presentation of OVA-MUC1 fusion peptides by MHC class II molecules and the MUC1 antigen elicited specific Ab production and T cell proliferation in both Balb/c and HLA-A2 transgenic mice. In contrast, GalNAc-glycosylation inhibited the presentation of OVA-MUC1 fusion peptides by MHC class I and abolished MUC1 specific CD8+ T cell responses in HLA-A2 transgenic mice. GalNAc glycosylation of MUC1 antigen therefore facilitates uptake, MHC class II presentation, and antibody response but might block the antigen presentation to CD8+ T cells.