E-vapor aerosols do not compromise bone integrity relative to cigarette smoke after 6-month inhalation in an ApoE-/- mouse model.

Cigarette smoke (CS) exposure is one of the leading risk factors for human health. Nicotine-containing inhalable products, such as e-cigarettes, can effectively support tobacco harm reduction approaches. However, there are limited comparative data on the effects of the aerosols generated from electronic vapor products (e-vapor) and CS on bone. Here, we report the effects of e-vapor aerosols and CS on bone morphology, structure, and strength in a 6-month inhalation study. Eight-week-old ApoE-/- mice were exposed to aerosols from three different e-vapor formulations-CARRIER (propylene glycol and vegetable glycerol), BASE (CARRIER and nicotine), TEST (BASE and flavor)-to CS from 3R4F reference cigarettes at matched nicotine concentrations (35 µg/L) or to fresh air (Sham) (N = 10 per group). Tibiae were analyzed for bone morphology by µCT imaging, biomechanics by three-point bending, and by histological analysis. CS inhalation caused a significant decrease in cortical and total bone volume fraction and bone density relative to e-vapor aerosols. Additionally, CS exposure caused a decrease in ultimate load and stiffness. In contrast, bone structural and biomechanical parameters were not significantly affected by e-vapor aerosol or Sham exposure. At the dissection time point, there was no significant difference in body weight or tibia bone weight or length among the groups. Histological findings revealed microcracks in cortical bone areas among all exposed groups compared to Sham control. In conclusion, because of the bone-preserving effect of e-vapor aerosols relative to CS exposure, e-vapor products could potentially constitute less harmful alternatives to cigarettes in situations in which bone health is of importance.

Different coupling mechanisms for a novel modular plate in acetabular fractures-a comparison using a laparoscopic model.

Introduction: Acetabular fractures are among the most challenging injuries in traumatology. The complex anatomy usually requires extensive surgical approaches baring the risk for iatrogenic damage to surrounding neurovascular structures. As a viable alternative, minimally invasive endoscopic techniques have emerged during the recent years. This paper reports on the feasibility of different coupling mechanisms for a novel suprapectineal plate especially designed for minimally invasive acetabular surgery. Methods: A total number of 34 participants contributed to the present study, who differed in their arthroscopic and surgical experience. A laparoscopic model was used to compare four different coupling mechanisms by the number of failed attempts, the time required for plate fixation, the influence of surgical experience as well as the learning success for each individual coupling mechanism. Moreover, the feasibility of each mechanism was evaluated by a questionnaire. Results: The results demonstrate that plates employing grooved and pressure-sliding coupling mechanisms exhibit fewer failed attempts and reduce trial times, especially in contrast to sole sliding mechanisms. Furthermore, our study revealed that proficiency in endoscopic procedures significantly influenced the outcome. Notably, the subjective evaluation of the participants show that the pressure base and pressure-slide base plate designs are the most supportive and feasible designs. Conclusions: In summary, the present study evaluates for the first-time different plate and coupling designs for minimal-invasive surgery, indicating a superior feasibility for plates with a grooved and pressure-sliding mechanism.

"Floating Hip": Epidemiology and Quality of Care. / "Floating Hip": Epidemiologie und Qualität der Versorgung.

INTRODUCTION: The "floating hip" is a rare and complex fracture involving the pelvis and the ipsilateral femur and is therefore difficult to treat. Data and studies on this topic are still scarce. The optimal strategy for surgical treatment and thus the resulting quality of treatment are still being debated; a femur-first strategy is often the preferred treatment. METHODS: Retrospectively, patients with a pelvic fracture treated at the Level I Trauma Centre of the University of Tübingen between 2003 and 2017 were identified. Patients with an additional ipsilateral femur fracture were identified in this collective. We compared the quality of treatment of pelvic fractures between floating and non-floating hip injuries. RESULTS: Proximal femur fractures were more common with pelvic ring fractures (n = 16) than with acetabular fractures (n = 1). Floating hip injuries occur more frequently in younger polytraumatised male patients. Pelvic fractures in floating hip injuries are operated more frequently (62.8% vs. 39.1%; p = 0.003) and the clinical course is significantly longer (27.8 ± 19.3 vs. 19.9 ± 23.1 days; p < 0.001). However, the quality of treatment of pelvic fracture, exemplified by morbidity (18.6% vs. 14.6%; p = 0.610) and mortality (7.0% vs. 2.6%; p = 0.108), shows no differences. CONCLUSION: Injury severity and complexity of pelvic fracture is significantly higher in floating hip injuries, but without affecting the resulting quality of treatment. A "femur first" treatment strategy is preferable. Algorithms for emergency treatment and definitive care are proposed in a flowchart.

Evaluation of decision-making in the treatment of acetabular fractures.

Treatment of acetabular fractures is challenging and risky, especially when surgery is performed. Yet, stability and congruity of the hip joint need to be achieved to ensure early mobilization, painlessness, and good function. Therefore, coming up with an accurate decision, whether surgical treatment is indicated or not, is the key to successful therapy. Data from the German pelvic Trauma Registry (n = 4213) was evaluated retrospectively, especially regarding predictors for surgery. Furthermore, a logistic regression model with surgical treatment as the dependent variable was established. In total, 25.8% of all registered patients suffered from an acetabular fracture and 61.9% of them underwent surgery. The fracture classification is important for the indication of surgical therapy. Anterior wall fractures were treated surgically in 10.2%, and posterior column plus posterior wall fractures were operated on in 90.2%. Also, larger fracture gaps were treated surgically more often than fractures with smaller gaps (>3 mm 84.4%, <1 mm 20%). In total, 51.4% of women and 66.0% of men underwent surgery. Apart from the injury severity score (ISS), factors that characterize the overall picture of the injury were of no importance for the indication of a surgical therapy (isolated pelvic fracture: 62.0%, polytrauma: 58.8%). The most frequent reason for non-operative treatment was 'minimal displacement' in 42.2%. Besides fracture classification and fracture characteristics, no factors characterizing the overall injury, except for the ISS, and unexpectedly gender, are important for making a treatment decision. Further studies are needed to determine the relevance of these factors, and whether they should be used for the decision-making process, in particular surgeons with less experience in pelvic surgery, can orient themselves to.

Pararectus approach vs. Stoppa approach for the treatment of acetabular fractures - a comparison of approach-related complications and operative outcome parameters from the German Pelvic Registry.

PURPOSE: The Pararectus approach has been introduced as an alternative anterior approach to the Stoppa approach in acetabular surgery. There is no evidence which approach should be preferred, especially regarding approach-related complications. Therefore, aim of this registry study was to compare the Pararectus approach to the Stoppa approach regarding complications and quality of reduction. METHODS: Patients from the German Pelvic Registry with a surgically treated acetabular fracture, either through the Pararectus approach or the Stoppa approach, were analyzed or compared regarding demographic, clinical and operative parameters. RESULTS: In total, 384 patients with an acetabular fracture received a surgical procedure with either the Pararectus approach (n=120) or the Stoppa approach (n=264). There were no differences between the two groups regarding demographic parameters and fracture pattern. The overall complication rate (35.0% vs. 31.4%), the mortality rate (5.0% vs. 3.0%) and the osteosynthesis-associated complication rate (5.8% vs. 4.2%) tended to be higher in the Pararectus group with no statistical significance. There were significantly more anatomical reductions in the Pararectus group (56% vs. 43%; p=0.01). However, operation time was significantly longer in the Pararectus group (255±125 vs. 205±103 minutes; p<0.001). CONCLUSION: Despite a longer operation time, the Pararectus approach and the Stoppa approach are equivalently applicable for the treatment of acetabular fractures regarding complication rates and quality of reduction. LEVEL OF EVIDENCE: III, retrospective comparative study.

Asymptomatic and Unnoticed Intra-articular Screw Over 18 Years after Fracture of the Posterior Wall of the Acetabulum - a Question of Stability? / Asymptomatische und unbemerkte intraartikuläre Schraubenlage über 18 Jahre nach Wandfraktur des hinteren Azetabulums ­ eine Frage der Stabilität?

Fractures of the posterior wall of the acetabulum occur in a frequency of 25 - 30%. Multifragmentary fractures involving 40 - 50% of the acetabular surface, the quality of reduction as well as involvement of cartilage and acetabular labrum are considered to have an impact on the development of a reduced posterior stability of the hip joint. This results in a shift of the main weight bearing area with development of a posttraumatic osteoarthritis. In the presented case, a 42-year old male patient was operated on 18 years ago due to a posterior acetabular wall fracture. Retrospectively, one of the screws was located partially intraarticular. However, the patient was asymptomatic over the 18-year period. The first consultation was due to unspecific symptoms of osteoarthritis of the right hip joint especially during flexion and external rotation. Due to only mild radiological signs of osteoarthritis, we indicated only the removal of the intraarticular screw. The symptoms postoperatively switched to a feeling of instability, so a total hip arthroplasty was performed. Since the operation, the patient is asymptomatic regarding the hip joint. The intraarticular screw seemed to stabilize the hip joint. This case demonstrates the importance of a good posterior guidance for the stability of the hip joint on one hand. On the other hand, it demonstrates the minor stress load of the posterior acetabular region, especially after fracture of the posterior wall. Therefore, a good posterior guidance should be one major aim of treatment of posterior acetabular wall fractures.

Modeling of stringent-response reflects nutrient stress induced growth impairment and essential amino acids in different Staphylococcus aureus mutants.

Stapylococcus aureus colonises the nose of healthy individuals but can also cause a wide range of infections. Amino acid (AA) synthesis and their availability is crucial to adapt to conditions encountered in vivo. Most S. aureus genomes comprise all genes required for AA biosynthesis. Nevertheless, different strains require specific sets of AAs for growth. In this study we show that regulation inactivates pathways under certain conditions which result in these observed auxotrophies. We analyzed in vitro and modeled in silico in a Boolean semiquantitative model (195 nodes, 320 edges) the regulatory impact of stringent response (SR) on AA requirement in S. aureus HG001 (wild-type) and in mutant strains lacking the metabolic regulators RSH, CodY and CcpA, respectively. Growth in medium lacking single AAs was analyzed. Results correlated qualitatively to the in silico predictions of the final model in 92% and quantitatively in 81%. Remaining gaps in our knowledge are evaluated and discussed. This in silico model is made fully available and explains how integration of different inputs is achieved in SR and AA metabolism of S. aureus. The in vitro data and in silico modeling stress the role of SR and central regulators such as CodY for AA metabolisms in S. aureus.

Comparison of pelvic C-clamp and pelvic binder for emergency stabilization and bleeding control in type-C pelvic ring fractures.

Severe bleeding is the major cause of death in unstable pelvic ring fractures. Therefore, a quick and efficient emergency stabilization and bleeding control is inevitable. C-clamp and pelvic binder are efficient tools for temporary bleeding control, especially from the posterior pelvic ring. Yet the C-clamp requires more user knowledge, training and equipment. However, whether this makes up for a more efficient bleeding control, is still under debate. Patients with a type-C pelvic ring fracture were identified from the German Pelvic Registry (GPR) and divided into three groups of 40 patients (1. no emergency stabilization, 2. pelvic binder, 3. C-clamp). The matching occurred according to the parameters age, gender, initial RR and initial HB. Complication-and mortality rates were compared especially regarding bleeding control. Regarding ISS and fracture dislocation there was no difference. The use of the C-clamp resulted in more complications, a higher mortality rate due to severe bleeding and more blood transfusions were admitted. Moreover the pelvic binder was established noticeably faster. However, the C-clamp was more often rated as effective. There is no evidence of advantage comparing the C-clamp to the pelvic binder, regarding bleeding control in type-C pelvic ring fractures. In fact, using the pelvic binder even showed better results, as the time until established bleeding control was significantly shorter. Therefore, the pelvic binder should be the first choice. The C-clamp should remain a measure for selected cases only, if an adequate bleeding control cannot be achieved by the pelvic binder.

Mechanical catalysis on the centimetre scale.

Enzymes play important roles in catalysing biochemical transaction paths, acting as logical machines through the morphology of the processes. A key challenge in elucidating the nature of these systems, and for engineering manufacturing methods inspired by biochemical reactions, is to attain a comprehensive understanding of the stereochemical ground rules of enzymatic reactions. Here, we present a model of catalysis that can be performed magnetically by centimetre-sized passive floating units. The designed system, which is equipped with permanent magnets only, passively obeys the local causalities imposed by magnetic interactions, albeit it shows a spatial behaviour and an energy profile analogous to those of biochemical enzymes. In this process, the enzyme units trigger physical conformation changes of the target by levelling out the magnetic potential barrier (activation potential) to a funnel type and, thus, induce cascading conformation changes of the targeted substrate units reacting in parallel. The inhibitor units, conversely, suppress such changes by increasing the potential. Because the model is purely mechanical and established on a physics basis in the absence of turbulence, each performance can be explained by the morphology of the unit, extending the definition of catalysis to systems of alternative scales.

A semi-quantitative model of Quorum-Sensing in Staphylococcus aureus, approved by microarray meta-analyses and tested by mutation studies.

Staphylococcus aureus (SA) causes infections including severe sepsis by antibiotic-resistant strains. It forms biofilms to protect itself from the host and antibiotics. Biofilm and planktonic lifestyle are regulated by a complex quorum sensing system (QS) with the central regulator agr. To study biofilm formation and QS we set up a Boolean node interaction network (94 nodes, 184 edges) that included different two component systems such as agr, sae and arl. Proteins such as sar, rot and sigB were included. Each gene node represents the resulting activity of its gene products (mRNA and protein). Network consistency was tested according to previous knowledge and the literature. Regulator mutation combinations (agr-, sae-, sae-/agr-, sigB+, sigB+/sae-) were tested in silico in the model and compared regarding system changes and responses to experimental gene expression data. High connectivity served as a guide to identify master regulators, and their detailed behaviour was studied both in vitro and in the model. System analysis showed two stable states, biofilm forming versus planktonic, with clearly different sub-networks turned on. Predicted node activity changes from the in silico model were in line with microarray gene expression data of different knockout strains. Additional in silico predictions about node activity and biofilm formation were compared to new in vitro experiments (northern blots and biofilm adherence assays) which confirmed these. Further experiments in silico as well as in vitro showed the sae locus as the central modulator of biofilm production. Sae knockout strains showed stronger biofilms. Wild type phenotype was rescued by sae complementation. The in silico network provides a theoretical model that agrees well with the presented experimental data on how integration of different inputs is achieved in the QS of SA. It faithfully reproduces the behaviour of QS mutants and their biofilm forming ability and allows predictions about mutations and mutation combinations for any node in the network. The model and simulations allow us to study QS and biofilm formation in SA including behaviour of MRSA strains and mutants. The in vitro and in silico evidence stresses the role of sae and agr in fine-tuning biofilm repression and/or SA dissemination.