Search Results
Assessing agreement between preclinical magnetic resonance imaging and histology: An evaluation of their image qualities and quantitative results
2017, Elschner, Cindy, Korn, Paula, Hauptstock, Maria, Schulz, Matthias C., Range, Ursula, Jünger, Diana, Scheler, Ulrich
One consequence of demographic change is the increasing demand for biocompatible materials for use in implants and prostheses. This is accompanied by a growing number of experimental animals because the interactions between new biomaterials and its host tissue have to be investigated. To evaluate novel materials and engineered tissues the use of nondestructive imaging modalities have been identified as a strategic priority. This provides the opportunity for studying interactions repeatedly with individual animals, along with the advantages of reduced biological variability and decreased number of laboratory animals. However, histological techniques are still the golden standard in preclinical biomaterial research. The present article demonstrates a detailed method comparison between histology and magnetic resonance imaging. This includes the presentation of their image qualities as well as the detailed statistical analysis for assessing agreement between quantitative measures. Exemplarily, the bony ingrowth of tissue engineered bone substitutes for treatment of a cleft-like maxillary bone defect has been evaluated. By using a graphical concordance analysis the mean difference between MRI results and histomorphometrical measures has been examined. The analysis revealed a slightly but significant bias in the case of the bone volume ðbiasHisto MRI: Bonevolume = 2: 40 %, p < 0: 005) and a clearly significant deviation for the remaining defect width ðbiasHisto MRI: Defectwidth = 6: 73 %, p 0: 005Þ: But the study although showed a considerable effect of the analyzed section position to the quantitative result. It could be proven, that the bias of the data sets was less originated due to the imaging modalities, but mainly on the evaluation of different slice positions. The article demonstrated that method comparisons not always need the use of an independent animal study, additionally.
Guidance of mesenchymal stem cells on fibronectin structured hydrogel films
2014, Kasten, Annika, Naser, Tamara, Brüllhoff, Kristina, Fiedler, Jörg, Müller, Petra, Möller, Martin, Rychly, Joachim, Groll, Jürgen, Brenner, Rolf E., Engler, Adam J.
Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.
A network-based microfoundation of Granovetter’s threshold model for social tipping
2020, Wiedermann, Marc, Smith, E. Keith, Heitzig, Jobst, Donges, Jonathan F.
Social tipping, where minorities trigger larger populations to engage in collective action, has been suggested as one key aspect in addressing contemporary global challenges. Here, we refine Granovetter’s widely acknowledged theoretical threshold model of collective behavior as a numerical modelling tool for understanding social tipping processes and resolve issues that so far have hindered such applications. Based on real-world observations and social movement theory, we group the population into certain or potential actors, such that – in contrast to its original formulation – the model predicts non-trivial final shares of acting individuals. Then, we use a network cascade model to explain and analytically derive that previously hypothesized broad threshold distributions emerge if individuals become active via social interaction. Thus, through intuitive parameters and low dimensionality our refined model is adaptable to explain the likelihood of engaging in collective behavior where social-tipping-like processes emerge as saddle-node bifurcations and hysteresis. © 2020, The Author(s).
Effect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study
2017, Walker, Jochen, Mertens, Ulf Kai, Schmidt, Carsten Oliver, Chenot, Jean-François
Spinal manual therapy (SMT) is a popular treatment option for low back pain (LBP). The aim of our analysis was to evaluate the effects of manual therapy delivered by general practitioners and ambulatory orthopedic surgeons in routine care on follow up consultations, sick leave, health service utilization and costs for acute LBP compared to matched patients not receiving manual therapy. This is a propensity score matched cohort study based on health claims data. We identified a total of 113.652 adult patients with acute LBP and no coded red flags of whom 21.021 (18%) received SMT by physicians. In the final analysis 17.965 patients in each group could be matched. Balance on patients' coded characteristics, comorbidity and prior health service utilization was achieved. The provision of SMT for acute LBP had no relevant impact on follow up visits and days of sick leave for LBP in the index billing period and the following year. SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs. 23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by replacing other health services for LBP. SMT for acute non-specific LBP in routine care was not clinically meaningful effective to reduce sick leave and reconsultation rates compared to no SMT and did not lead to meaningful savings by replacing other health services from the perspective of health insurance. This does not imply that SMT is ineffective but might reflect a problem with selection of suitable patients and the quality and quantity of SMT in routine care. National Manual Medicine societies should state clearly that imaging is not routinely needed prior to SMT in patients with low suspicion of presence of red flags and monitor the quality of provided services.
The role of risk communication in public health interventions. An analysis of risk communication for a community quarantine in Germany to curb the SARS-CoV-2 pandemic
2021, Scholz, Juliane, Wetzker, Wibke, Licht, Annika, Heintzmann, Rainer, Scherag, André, Weis, Sebastian, Pletz, Mathias, Betsch, Cornelia, Bauer, Michael, Dickmann, Petra, Frey, Rosemary
Background: Separating ill or possibly infectious people from their healthy community is one of the core principles of non-pharmaceutical interventions. However, there is scarce evidence on how to successfully implement quarantine orders. We investigated a community quarantine for an entire village in Germany (Neustadt am Rennsteig, March 2020) with the aim of better understanding the successful implementation of quarantine measures. Methods: This cross-sectional survey was conducted in Neustadt am Rennsteig six weeks after the end of a 14-day mandatory community quarantine. The sample size consisted of 562 adults (64% of the community), and the response rate was 295 adults, or 52% (33% of the community). Findings: National television was reported as the most important channel of information. Contact with local authorities was very limited, and partners or spouses played a more important role in sharing information. Generally, the self-reported information level was judged to be good (211/289 [73.0%]). The majority of participants (212/289 [73.4%]) approved of the quarantine, and the reported compliance was 217/289 (75.1%). A self-reported higher level of concern as well as a higher level of information correlated positively with both a greater acceptance of quarantine and self-reported compliant behaviour. Interpretation: The community quarantine presented a rare opportunity to investigate a public health intervention for an entire community. In order to improve the implementation of public health interventions, public health risk communication activities should be intensified to increase both the information level (potentially leading to better compliance with community quarantine) and the communication level (to facilitate rapport and trust between public health authorities and their communities). © 2021 Scholz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model
2021, Lotz, Benedict, Bothe, Friederike, Deubel, Anne-Kathrin, Hesse, Eliane, Renz, Yvonne, Werner, Carsten, Schäfer, Simone, Böck, Thomas, Groll, Jürgen, von Rechenberg, Brigitte, Richter, Wiltrud, Hagmann, Sebastien
Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (μCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.
Global, regional, and national burden of mortality associated with non-optimal ambient temperatures from 2000 to 2019: a three-stage modelling study
2021, Zhao, Qi, Guo, Yuming, Ye, Tingting, Gasparrini, Antonio, Tong, Shilu, Overcenco, Ala, Urban, Aleš, Schneider, Alexandra, Entezari, Alireza, Vicedo-Cabrera, Ana Maria, Zanobetti, Antonella, Analitis, Antonis, Zeka, Ariana, Tobias, Aurelio, Nunes, Baltazar, Alahmad, Barrak, Armstrong, Ben, Forsberg, Bertil, Pan, Shih-Chun, Íñiguez, Carmen, Ameling, Caroline, De la Cruz Valencia, César, Åström, Christofer, Houthuijs, Danny, Dung, Do Van, Royé, Dominic, Indermitte, Ene, Lavigne, Eric, Mayvaneh, Fatemeh, Acquaotta, Fiorella, de'Donato, Francesca, Di Ruscio, Francesco, Sera, Francesco, Carrasco-Escobar, Gabriel, Kan, Haidong, Orru, Hans, Kim, Ho, Holobaca, Iulian-Horia, Kyselý, Jan, Madureira, Joana, Schwartz, Joel, Jaakkola, Jouni J. K., Katsouyanni, Klea, Hurtado Diaz, Magali, Ragettli, Martina S., Hashizume, Masahiro, Pascal, Mathilde, de Sousa Zanotti Stagliorio Coélho, Micheline, Valdés Ortega, Nicolás, Ryti, Niilo, Scovronick, Noah, Michelozzi, Paola, Matus Correa, Patricia, Goodman, Patrick, Nascimento Saldiva, Paulo Hilario, Abrutzky, Rosana, Osorio, Samuel, Rao, Shilpa, Fratianni, Simona, Dang, Tran Ngoc, Colistro, Valentina, Huber, Veronika, Lee, Whanhee, Seposo, Xerxes, Honda, Yasushi, Guo, Yue Leon, Bell, Michelle L., Li, Shanshan
Background: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures. Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature–mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature–mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division. Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967–5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58–11·07) of all deaths (8·52% [6·19–10·47] were cold-related and 0·91% [0·56–1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60–87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000–03 to 2016–19, the global cold-related excess death ratio changed by −0·51 percentage points (95% eCI −0·61 to −0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13–0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe. Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios. Funding: Australian Research Council and the Australian National Health and Medical Research Council. © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license