Evaluation of PD-1 T lymphocytes in bronchoalveolar lavage in lung cancer compared to benign lung diseases.

The expression of the programmed cell death protein 1 (PD-1) has been shown to be markedly increased in tumor-infiltrating lymphocytes. However, the proportion of PD-1 + T cells in the bronchoalveolar lavage (BAL) of lung cancer patients has not been sufficiently evaluated so far. In this prospective study, the proportion of PD-1 + CD4 + as well as PD-1 + CD8 + T cells in BAL samples, isolated from patients with lung cancer, asthma or interstitial lung disease (ILD), were determined via flow cytometry and compared for differences. Bronchoalveolar lavage was performed in 34 patients (14 patients with lung cancer, 10 patients with asthma, 10 patients with ILD). The highest median proportion of PD-1 + CD4 + or PD-1 + CD8 + T cells were found in patients with ILD (83.1% [IQR 72.1; 87.5] and 73.8% [IQR 60.3; 86.3]) followed by patients with lung cancer (66.4% [IQR 59; 69] and 77.1% [IQR 35.8; 82.3]) and patients with asthma (61.3% [IQR 57.4; 70.5] and 57.3% [IQR 46; 65]). Thereby, the difference in the proportion of PD-1 + CD3 + CD4 + BAL cells between ILD patients and asthmatics was significantly different (p = 0.04). The proportion of PD-1 + CD4 + and PD-1 + CD8 + T cells in the BAL of patients with lung cancer did not differ significantly to patients with benign lung diseases. The highest proportion was observed in ILD patients suggesting further research to evaluate the role of the PD-1/PD-L1 pathway in ILD patients.

Defibrillator charging before rhythm analysis causes peri-shock pauses exceeding guideline recommended maximum 5 s : A randomized simulation trial.

INTRODUCTION: Charging defibrillators prior to analyzing heart rhythms may decrease the no-flow time during rhythm check pauses while resuscitating in cardiac arrest. Although this anticipatory method is already used in some centers little is known about its safety. This study was carried out to confirm the safety and feasibility of the anticipatory method. It was hypothesized that this anticipatory method results in shorter total no-flow times, while other parameters of defibrillation efficacy including defibrillator safety and minimization of peri-shock pauses are unchanged. METHODS: This manikin study assigned 243 medical students randomly to study groups, 121 to the anticipatory method and 122 to the recommended European Resuscitation Council (ERC) algorithm. Of these 237 students ultimately underwent training (112 anticipatory method vs. 125 ERC algorithm). Participants were assessed and video recorded during a simulated cardiac arrest scenario which included three different heart rhythms (ventricular fibrillation [VF], pulseless ventricular tachycardia [pVT], asystole) in randomized order. Video and software analyses were performed. Defibrillation safety was assessed using a 17-item checklist defined beforehand. RESULTS: A total of 203 simulated cardiac arrests (75 anticipatory method and 128 ERC 2010 algorithm) were analyzed. The anticipatory method did not significantly reduce no-flow time (25.8 s, standard deviation, SD 7.4 s vs. 27.4 s SD 8.4 s, p = 0.19); however, peri-shock pauses were significantly longer in the anticipatory group compared to the ERC 2010 group (9.5 s SD 2.8 s vs. 3.3 s SD 1.9 s, p < 0.001). No significant difference concerning defibrillation safety between the groups was observed according to the 17-item checklist (14.6 SD 1.6 vs. 15.0 SD 1.4, p = 0.07). CONCLUSION: Charging defibrillators before rhythm analysis did not decrease total no-flow time in simulated cardiac arrests but resulted in significantly longer peri-shock pauses exceeding 5 s. No significant differences in defibrillation safety were observed between the groups.

Improving Running Economy by Transitioning to Minimalist Footwear: A Randomised Controlled Trial.

OBJECTIVES: Ongoing debates about benefits and risks of barefoot- and minimally-shod running have, to date, revealed no conclusive findings for long-term effects on physical performance. The purpose of this study was to examine the effects of an 8-week transition to minimalist footwear (MFW) on running economy (RE). DESIGN: Randomised controlled trial. METHODS: Thirty-two male, habitually-shod runners were assigned randomly to an 8-week training intervention either in minimalist (=intervention group) or conventional running shoes (=control group). The intervention consisted of a gradual increase in use of the new footwear by 5% of the individual weekly distance. Before and after the intervention, a VO2max test was followed by a submaximal RE test at 70% and 80% of vVO2max in both shoe conditions 7days later. RE was measured at the submaximal tests and expressed as caloric unit cost (kcalkg-1km-1) and oxygen consumption (mlkg-1km-1). RESULTS: RE improved in the intervention group over time compared to the control group with small to moderate effect sizes (ES) in both shoe conditions: Effects on RE (kcalkg-1km-1) in conventional running shoes: ES vVO270%: 0.68 (95% CI: -0.14 to 1.51), ES vVO280%: 0.78 (95% CI: 0-1.56). In minimalist footwear: ES vVO270%: 0.3 (95% CI: -0.54 to 1.14), ES vVO280%: 0.42 (95% CI: -0.41 to 1.25). These effects were not statistically significant (p>0.05). The repeated-measures ANOVA also showed no group by time interactions for all submaximal RE testing conditions (p>0.05). CONCLUSIONS: Although not reaching statistical significance, training in MFW compared to CRS resulted in small to moderate improvements in RE.

[Full-scale simulation in German medical schools and anesthesia residency programs : Status quo]. / Full-Scale-Simulation in der anästhesiologischen Lehre und Weiterbildung in Deutschland : Gegenwärtiger Stand.

BACKGROUND: Simulation has been increasingly used in medicine. In 2003 German university departments of anesthesiology were provided with a full-scale patient simulator, designated for use with medical students. Meanwhile simulation courses are also offered to physicians and nurses. Currently, the national model curriculum for residency programs in anesthesiology is being revised, possibly to include mandatory simulation training. OBJECTIVES: To assess the status quo of full-scale simulation training for medical school, residency and continuing medical education in German anesthesiology. METHODS: All 38 German university chairs for anesthesiology as well as five arbitrarily chosen non-university facilities were invited to complete an online questionnaire regarding their centers' infrastructure and courses held between 2010 and 2012. RESULTS: The overall return rate was 86 %. In university simulation centers seven non-student staff members, mainly physicians, were involved, adding up to a full-time equivalent of 1.2. All hours of work were paid by 61 % of the centers. The median center size was 100 m2 (range 20-500 m2), equipped with three patient simulators (1-32). Simulators of high or very high fidelity are available at 80 % of the centers. Scripted scenarios were used by 91 %, video debriefing by 69 %. Of the participating university centers, 97 % offered courses for medical students, 81 % for the department's employees, 43 % for other departments of their hospital, and 61 % for external participants. In 2012 the median center reached 46 % of eligible students (0-100), 39 % of the department's physicians (8-96) and 16 % of its nurses (0-56) once. For physicians and nurses from these departments that equals one simulation-based training every 2.6 and 6 years, respectively. 31 % made simulation training mandatory for their residents, 29 % for their nurses and 24 % for their attending physicians. The overall rates of staff ever exposed to simulation were 45 % of residents (8-90), and 30 % each of nurses (10-80) and attendings (0-100). Including external courses the average center trained 59 (4-271) professionals overall in 2012. No clear trend could be observed over the three years polled. The results for the non-university centers were comparable. CONCLUSIONS: Important first steps have been taken to implement full-scale simulation in Germany. In addition to programs for medical students courses for physicians and nurses are available today. To reach everyone clinically involved in German anesthesiology on a regular basis the current capacities need to be dramatically increased. The basis for that to happen will be new concepts for funding, possibly supported by external requirements such as the national model curriculum for residency in anesthesiology.

MicroRNA-155 modulates P2R signaling and Th2 priming of dendritic cells during allergic airway inflammation in mice.

BACKGROUND: Dendritic cells (DCs) are the professional antigen-presenting cells (APCs) in the lung. They are known to be key players in the induction and maintenance of allergic asthma by cross-linking innate and adaptive immune responses. MicroRNAs (miRNAs) are known to influence cell fate and function by translational suppression or induction of messenger RNA (mRNA) degradation. miR-155 has been shown to be a crucial regulator of the immune system. However, its function in the pathogenesis of allergic airway inflammation (AAI) is not completely elucidated yet. METHODS: Wild type (WT) and miR-155-deficient (miR-155(-/-) ) mice were used in ovalbumin (OVA) and house dust mite (HDM) models of AAI. Adoptive transfer of sensitized DCs to the lungs, migration, and T-cell priming assays were used to investigate the functional relevance of miR-155 in DCs. RESULTS: miR-155(-/-) mice showed reduced eosinophilic airway inflammation compared to WT mice in both models of AAI. Furthermore, miR-155(-/-) DCs showed limited Th2 priming capacity and failed to induce airway inflammation in allergen-exposed WT mice. miR-155 deficiency on DCs was also associated with impaired purinergic receptor signaling, as miR-155(-/-) DCs showed reduced chemotaxis and IL-1beta secretion upon stimulation with ATP, probably due to direct targeting of ectonucleoside triphosphate diphosphohydrolases (ENTPD) by miR-155. CONCLUSIONS: miR-155 deficiency alleviates AAI by diminishing Th2 priming capacity and ATP-/P2R-induced activation of DCs in mice, suggesting this miRNA as a potential therapeutic target of AAI.

Attenuated allergic airway inflammation in Cd39 null mice.

BACKGROUND: Extracellular Adenosine-5'-Triphosphate (ATP) is known to accumulate in the lung, following allergen challenge, and contributes via activation of purinergic receptors on dendritic cells (DC), to the development of allergic airway inflammation (AAI). Extracellular ATP levels in the airways are normally tightly regulated by CD39. This ectonucleotidase is highly expressed by DC purified from skin (Langerhans cells) and bone marrow, and has been shown to modulate DC adaptive/haptenic immune responses. In this study, we have evaluated the impact of Cd39 deletion and associated perturbation of purinergic signaling in AAI. METHODS: Standard ovalbumin (OVA)-alum and house dust mite (HDM) bone marrow-derived DC (BMDC)-dependent models of AAI were used to study effects of Cd39. Migration assays, time lapse microscopy, and T-cell priming assays were further used to determine functional relevance of Cd39 expression on BMDC in the setting of immune and Th2-mediated responses in these models. RESULTS: Cd39(-/-) mice exhibited marked increases in BALF ATP levels but paradoxically exhibited limited AAI in both OVA-alum and HDM models. These pathophysiological abnormalities were associated with decreased myeloid DC activation and chemotaxis toward ATP, and were linked to purinergic receptor desensitization responses. Further, Cd39(-/-) DCs exhibited limited capacity to both prime Th2 responses and form stable immune synaptic interactions with OVA-transgenic naïve T cells. CONCLUSIONS: Cd39-deficient DCs exhibit limited capacity to induce Th2 immunity in a DC-driven model of AAI in vivo. Our data demonstrate a role of CD39 and perturbed purinergic signaling in models of AAI.

Reliability and performance-dependent variations of muscle function variables during isometric knee extension.

Despite the common use of standardised methods analysing neuromuscular function during knee extension, there is a lack of test-retest reliability studies. Furthermore, for most of the investigated variables it is unknown which changes of values indicate an enhancement of performance. The aim of the present study was to investigate performance-dependent variations of muscle functions during isometric contraction of knee extensors and to examine test-retest reliability of their measurement methods. For test-retest reliability sports students completed three test sessions. Highly skilled athletes, sports students and untrained subjects were investigated to determine the performance-dependent variations. The following variables were analysed: maximal voluntary contraction (MVC), voluntary activation (VA), absolute muscle reaction time (AR), muscle endurance (ME), and EMG frequency analysis (MF) of m. vastus lateralis (VL), m. vastus medialis (VM) and m. rectus femoris (RF). RESULTS TEST-RETEST-RELIABILITY: A high reliability between session 1 vs. 2 and session 2 vs. 3 was shown for MVC (ICC=0.92 and .97), VA (0.92/0.95) and ME (0.87/0.95). ICC in AR (0.23) was low between the first and second session and moderate between the second and third session (0.74). MF of VL, VM and RF showed low ICC between sessions. PERFORMANCE DEPENDENT VARIATIONS: Significant differences in nearly all variables (except VA) were found between trained (athletes and sports students) and untrained subjects.