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Primary creep regeneration (PCR) is a phenomenon observed during stress-varying/cyclic creep loading conditions where a load reversal might clear the previous strain hardening memory and cause the regeneration of the primary creep regime (i.e. a period of high creep strain rate) upon reloading. In this study, in-situ and ex-situ microstructural examinations, including transmission electron microscopy (TEM), electron backscatter diffraction (EBSD), neutron and synchrotron X-ray diffraction were conducted to better understand the responsible mechanisms of PCR for a 10%Cr martensitic steel at 600 °C. Our experimental evidence indicated that the PCR phenomenon is related to the change of dislocation density due to activation of dislocation generation and recovery mechanisms, formation and relaxation of dislocation pile-ups, as well as bowing/unbowing of dislocation-lines during stress-varying creep loading conditions. These mechanisms could explain the observed creep strain accumulation in the steel during the examined stress-varying creep loading conditions reported in the current and previous studies. The presented mechanistic description of the PCR phenomenon and the reported experimental observations for the microstructural and mechanical parameters can provide a basis for the formulation of physically-based models to describe the creep behaviour of the steel under high-temperature stress-varying creep loading conditions.

Study Objective: To study the inter-rater reliability of an electronic complementary uterine diagram (electronic American Fertility Society [eAFS] freely available at https://bit.ly/eAFS-score) in comparison with the conventional American Fertility Society (cAFS) intrauterine adhesion (IUA) scoring system. As a secondary aim, we wanted to assess the intra-rater reliability of these tools., Design: This was an observational cross-over study with a nested test-retest design., Setting: Self-identified gynecologists who performed diagnostic hysteroscopy as part of their routine practice were asked to score IUA on 7 preselected videos using both cAFS and eAFS tools in 2 separate rounds. The order of use of tools was determined at random. Gynecologists who agreed to be involved in a third round were asked to use the tool they were allocated to in the first round to assess intra-rater variability., Patients: No patients were recruited for the purpose of this study., Measurements and Main Results: Inter-rater agreement between evaluators when using eAFS and cAFS for IUA scoring. Overall, the inter-rater agreement was fair (0.25; confidence interval [CI], 0.17-0.34) for cAFS and moderate (0.53; CI, 0.48-0.58) for the eAFS tool. The biggest difference between both tools was seen in the "extent of cavity involved" component, which was fair (0.28; CI, 0.21-0.35) vs substantial (0.71; CI, 0.64-0.78) for cAFS vs eAFS, respectively. Moreover, agreement coefficients were comparable among "expert" and "non-expert" evaluators with the use of the eAFS tool. In addition, intra-rater perfect agreement was higher with the use of eAFS than cAFS (38% vs 32.5%)., Conclusion: The current AFS IUA scoring system has fair inter-rater agreement. However, using a complementary electronic uterine diagram increased this agreement from fair to moderate overall and from fair to substantial in the "extent of adhesions" domain of the tool. The use of the electronic diagram also improved inter-rater agreement among non-experts making it comparable with that of experts., (Copyright © 2025 AAGL. Published by Elsevier Inc. All rights reserved.)

We developed an ex vivo model system to analyze the influence of relevant environmental and mechanical factors potentially affecting the integrity of fetal membranes during fetoscopic surgery. The set-up exposes amniochorion membranes to insufflation at predefined levels of gas pressure, flow, humidity, and temperature. Change in fetal membranes stiffness is quantified during the phase mimicking surgery through measurement of membranes' strain in response to cyclic overpressure. The trocar induced perforation creates a mechanical weakness whose stability is assessed by increasing the insufflation pressure until membrane rupture. Damage of the epithelial cells lining the amnion is assessed through live-dead staining. Initial experiments demonstrated the functionality of the new apparatus and the feasibility of the proposed protocols. Fetal membranes exposed to air with low humidity for approximately 1 h demonstrated significant embrittlement, while their mechanical integrity was maintained in case of gas insufflation at high humidity (air as well as CO 2 ). Under dry circumstances, there was a significant rate of epithelial cell death. Separation of amnion and chorion in the region of the trocar site was visible in all experiments. This new model is a versatile platform for analyzing the mechanical, histological, and biological implications of fetoscopic surgery on fetal membranes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aging leads to biochemical and biomechanical changes in skin, with biological and functional consequences. Despite extensive literature on skin aging, there is a lack of studies which investigate the maturation of the tissue and connect the microscopic changes in the skin to its macroscopic biomechanical behavior as it evolves over time. The present work addresses this knowledge gap using multiscale characterization of skin in a murine model considering newborn, adult and aged mice. Monotonic uniaxial loading, tension relaxation with change of bath, and loading to failure tests were performed on murine skin samples from different age groups, complemented by inflation experiments and atomic force microscopy indentation measurements. In parallel, skin samples were characterized using histological and biochemical techniques to assess tissue morphology, collagen organization, as well as collagen content and cross-linking. We show that 1-week-old skin differs across nearly all measured parameters from adult skin, showing reduced strain stiffening and tensile strength, a thinner dermis, lower collagen content and altered crosslinking patterns. Surprisingly, adult and aged skin were similar across most biomechanical parameters in the physiologic loading range, while aged skin had lower tensile strength and lower stiffening behavior at large force values. This correlates with altered collagen content and cross-links. Based on a computational model, differences in mechanocoupled stimuli in the skin of the different age groups were calculated, pointing to a potential biological significance of the age-induced biomechanical changes in regulating the local biophysical environment of dermal cells. STATEMENT OF SIGNIFICANCE: Skin microstructure and the emerging mechanical properties change with age, leading to biological, functional and health-related consequences. Despite extensive literature on skin aging, only very limited quantitative data are available on microstructural changes and the corresponding macroscopic biomechanical behavior as they evolve over time. This work provides a wide-range multiscale mechanical characterization of skin of newborn, adult and aged mice, and quantifies microstructural correlations in tissue morphology, collagen content, organization and cross-linking. Remarkably, aged skin retained normal hydration and normal biomechanical function in the physiological loading range but showed significantly reduced properties at super-physiological loading. Our data show that age-related microstructural differences have a profound effect not only on tissue-level properties but also on the cell-level biophysical environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The mechanical properties of the skin determine tissue function and regulate dermal cell behavior. Yet measuring these properties remains challenging, as evidenced by the large range of elastic moduli reported in the literature-from below one kPa to hundreds of MPa. Here, we reconcile these disparate results by dedicated experiments at both tissue and cellular length scales and by computational models considering the multiscale and multiphasic tissue structure. At the macroscopic tissue length scale, the collective behavior of the collagen fiber network under tension provides functional tissue stiffness, and its properties determine the corresponding elastic modulus (100-200 kPa). The compliant microscale environment (0.1-10 kPa), probed by atomic force microscopy, arises from the ground matrix without engaging the collagen fiber network. Our analysis indicates that indentation-based elasticity measurements, although probing tissue properties at the cell-relevant length scale, do not assess the deformation mechanisms activated by dermal cells when exerting traction forces on the extracellular matrix. Using dermal-equivalent collagen hydrogels, we demonstrate that indentation measurements of tissue stiffness do not correlate with the behavior of embedded dermal fibroblasts. These results provide a deeper understanding of tissue mechanics across length scales with important implications for skin mechanobiology and tissue engineering. STATEMENT OF SIGNIFICANCE: Measuring the mechanical properties of the skin is essential for understanding dermal cell mechanobiology and designing tissue-engineered skin substitutes. However, previous results reported for the elastic modulus of skin vary by six orders of magnitude. We show that two distinct deformation mechanisms, related to the tension-compression nonlinearity of the collagen fiber network, can explain the large variations in elastic moduli. Furthermore, we show that microscale indentation, which is frequently used to assess the stiffness perceived by cells, fails to engage the fiber network, and therefore cannot predict the behavior of dermal fibroblasts in stiffness-tunable fibrous hydrogels. This has important implications for how to measure and interpret the mechanical properties of soft tissues across length scales., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We report an uncommon, infratentorial localization of adult H3 K27M-altered diffuse midline glioma arising in a particularly rare site (medulla oblongata). In addition to this unusual presentation, the lesion exhibited a substantial contrast enhancement and size decrease after dexamethasone, generating diagnostic dilemmas. Histology, molecular details, advanced Magnetic Resonance imaging features and differential diagnoses are here described and discussed, as well as common misconceptions about steroid-sensitive mass lesions, and practical difficulties for clinicians involved in the process of making diagnosis., (© 2022 Published by Elsevier Inc. on behalf of University of Washington.)

Aging is associated with progressive skin fragility and a tendency to tear, which can lead to severe clinical complications. The transcription factor NRF2 is a key regulator of the cellular antioxidant response, and pharmacological NRF2 activation is a promising strategy for the prevention of age-related diseases. Using a combination of molecular and cellular biology, histology, imaging and biomechanical studies we show, however, that constitutive genetic activation of Nrf2 in fibroblasts of mice suppresses collagen and elastin expression, resulting in reduced skin strength as seen in aged mice. Mechanistically, the "aging matrisome" results in part from direct Nrf2-mediated overexpression of a network of microRNAs that target mRNAs of major skin collagens and other matrix components. Bioinformatics and functional studies revealed high NRF2 activity in aged human fibroblasts in 3D skin equivalents and human skin biopsies, highlighting the translational relevance of the functional mouse data. Together, these results identify activated NRF2 as a promoter of age-related molecular and biomechanical skin features., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The thoracic lymphadenectomy during an esophagectomy for esophageal cancer includes resection of the thoracic duct (TD) compartment containing the TD lymph nodes (TDLNs). The role of TD compartment resection is still a topic of debate since metastatic TDLNs have only been demonstrated in squamous cell carcinomas in Eastern esophageal cancer patients. Therefore, the aim of this study was to assess the presence and metastatic involvement of TDLNs in a Western population, in which adenocarcinoma is the predominant type of esophageal cancer., Methods: From July 2017 to May 2020, all consecutive patients undergoing an open or robot-assisted transthoracic esophagectomy with concurrent lymphadenectomy and resection of the TD compartment in the University Medical Center Utrecht in Utrecht, the Netherlands, and the Città della Salute e della Scienza University Hospital in Turin, Italy, were included. The TD compartment was resected en bloc and was separated in the operation room by the operating surgeon after which it was macroscopically and microscopically assessed for (metastatic) TDLNs by the pathologist., Results: A total of 117 patients with an adenocarcinoma (73%) or squamous cell carcinoma (27%) of the esophagus were included. In 61 (52%) patients, TDLNs were found, containing metastasis in 9 (15%) patients. No major complications related to TD compartment resection were observed., Conclusions: This study demonstrates the presence of metastatic TDLNs in adenocarcinomas of the esophagus. This result provides a valid argument to routinely extend the thoracic lymphadenectomy with resection of the TD compartment during an esophagectomy for esophageal cancer., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Older patients with metastatic pancreatic adenocarcinoma (MPDAC) are under-represented in clinical trials., Methods: Our single-center, retrospective study enrolled MPDAC patients ≥ 70 treated with chemotherapy RESULTS: 105 patients were divided in groups based on the received treatments: 44 gemcitabine or capecitabine monotherapy (A), 34 nabpaclitaxel-gemcitabine (B) 27 4-drugs combinations (gemcitabine, cisplatin, capecitabine plus either nab-paclitaxel or epirubicin or docetaxel) (C). Group A: median age was 78 (70-87) and Karnofsky performance status (KPS) ≥80 was found in 84% of patients; Group B: median age 77 (71-84) and KPS ≥ 80 in 88% of patients; Group C: median age 73 (70-78) and KPS ≥ 80 in 93% of patients. Median OS was 7.9, 11.7 and 14.2 months in group A, B and C respectively; 1 and 2-year OS were 27% and 8% in group A; 44% and 5% in group B; 52% and 22% in group C. When lung metastatic only patients were excluded, patients <75 and ≥ 75 had similar OS in group A (6.4 vs 5.6 months) and in group B (12.3 vs 11.1 months). In group B grade 3 thrombocytopenia, fatigue and peripheral neuropathy were more frequent in patients ≥ 75., Conclusions: In older patients, combination chemotherapy shows acceptable feasibility and promising efficacy., Competing Interests: Declaration of competing interest MR reports grants, personal fees, and non-financial support from Celgene; grants and personal fees from Baxalta; grants and personal fees from Merck Serono; grants from Helsinn; and personal fees from Lilly, Pfizer, AstraZeneca, NovoCure, Halozyme, Novartis, and Shire. LG reports personal fees from Roche, Pfizer, Boehringer Ingelheim, Celgene, Taiho Pharmaceutical, Synthon, AstraZeneca, Genomic Health, Merck Sharp & Dohme, Synaffix, Eli Lilly, Odonate Therapeutics, Sandoz, Onkaido, Oncolytics Biotech, ADC Therapeutics, and Seattle Genetics. All other authors declare no competing interests., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The active and passive mechanical behavior of a cosmetic tightening product for skin anti-aging is investigated based on a wide range of in vivo and in vitro measurements. The experimental data are used to inform a numerical model of the attained cosmetic effect, which is then implemented in a commercial finite-element framework and used to analyze the mechanisms that regulate the biomechanical interaction between the native tissue and the tightening film. Such a film reduces wrinkles and enhances skin consistency by increasing its stiffness by 48-107% and reducing inelastic, non-recoverable deformations (-47%). The substrate deformability influences both the extent of tightening and the reduction of wrinkle amplitude. The present findings allow, for the first time, to rationalize the mechanisms of action of cosmetic products with a tightening action and provide quantitative evidence for further optimization of this fascinating class of biomaterials., Competing Interests: Declaration of Competing Interest This work was conducted in the framework of a collaboration between ETH Zurich and L’Oréal Research & Innovation, which involved funding from L’Oréal Research & Innovation. The analyzed cosmetic product is developed by L’Oréal Research & Innovation and was provided to ETH Zurich as part of this scientific collaboration. Some of the authors are currently employed by L’Oréal Research & Innovation., (Copyright © 2020. Published by Elsevier Ltd.)

One of the greatest challenges in providing early effective treatment in mood disorders is the early differential diagnosis between major depression (MDD) and bipolar disorder (BD). A remarkable need exists to identify reliable biomarkers for these disorders. We integrate structural neuroimaging techniques (i.e. Tract-based Spatial Statistics, TBSS, and Voxel-based morphometry) in a multiple kernel learning procedure in order to define a predictive function of BD against MDD diagnosis in a sample of 148 patients. We achieved a balanced accuracy of 73.65% with a sensitivity for BD of 74.32% and specificity for MDD of 72.97%. Mass-univariates analyses showed reduced grey matter volume in right hippocampus, amygdala, parahippocampal, fusiform gyrus, insula, rolandic and frontal operculum and cerebellum, in BD compared to MDD. Volumes in these regions and in anterior cingulate cortex were also reduced in BD compared to healthy controls (n = 74). TBSS analyses revealed widespread significant effects of diagnosis on fractional anisotropy, axial, radial, and mean diffusivity in several white matter tracts, suggesting disruption of white matter microstructure in depressed patients compared to healthy controls, with worse pattern for MDD. To best of our knowledge, this is the first study combining grey matter and diffusion tensor imaging in predicting BD and MDD diagnosis. Our results prompt brain quantitative biomarkers and multiple kernel learning as promising tool for personalized treatment in mood disorders., Competing Interests: Competing interest All other authors declare that they have no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

In the present paper, the three-dimensional structure and macroscopic mechanical response of electrospun poly(L-lactide) membranes is predicted based only on the geometry and elasto-plastic mechanical properties of single fibres supplemented by measurements of membrane weight and volume, and the resulting computational models are used to study the non-affine micro-kinematics of electrospun networks. To this end, statistical parameters describing the in-plane fibre morphology are extracted from scanning electron micrographs of the membranes, and computational network models are generated by matching the porosity of the real mats. The virtual networks are compared against computed tomography scans in terms of structure, and against uniaxial tension tests with respect to their macroscopic mechanical response. The obtained virtual network structure agrees well with the fibre disposition in real networks, and the rigorous prediction of the mechanical response of two membranes with mean diameters of 1.10μm and 0.70μm captures the experimental behaviour qualitatively. Favourable quantitative agreement, however, is obtained only after lowering the Young's moduli, yield stresses and hardening slopes determined in single fibre tests, and after reducing the density of inter-fibre bonds in the model of the membrane with thinner fibres. The simulations thus demonstrate the validity and merits of the approach to study the multi-scale mechanics of electrospun networks, but also point to potential discrepancies between the properties of electrospun fibres within a network and those produced for single fibre characterisation, and highlight the existing uncertainty on the density and quality of bonds between fibres in electrospun networks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The objective evaluation of scar quality plays a crucial role in improving burn surgery and scar rehabilitation. Suction-based skin measurements were proposed as a method to objectively determine the mechanical properties of scars, yet their use is limited, in particular for paediatric burn care. A new device was developed which provides essential advantages for scar assessment. The aim of this study was to assess its reliability, intra- and interobserver variability., Methods: The new device, "Nimble", consists of a lightweight probe that measures the negative pressure needed to obtain a predefined tissue elevation, revealing information on the stiffness of the tissue. 29 former paediatric burn patients were included. Three observers measured the tissue stiffness of a predefined location on the scar and on healthy skin using the Nimble, and the established suction device, the Cutometer ® . The reliability of both instruments in distinguishing between healthy skin and scar was assessed by means of the intraclass correlation coefficient., Results: The Nimble successfully differentiated between scar tissue and healthy skin in 92%, the Cutometer in 80% of the patients (p<0.05). Inter- and intraobserver variability of the Nimble (ICCs) were excellent. For the majority of the calculated ICC values the Nimble exceeded the Cutometer ® ., Conclusion: The new device enables reliable and safe measurement of the stiffness of scars. Measurements are less susceptible to patient non-compliance and observer dependency. The Nimble might therefore constitute an easy to use tool for the systematic assessment of scars, thus supporting decision-making in paediatric burn care., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Background: Chylothorax is a treacherous complication after esophagectomy associated with significant morbidity. Early enteral nutrition after esophagectomy is important for recovery but increases the pressure in the lymphatic system owing to the absorption of triglycerides. To lower the incidence of chylothorax after esophagectomy, the use of low fat-containing tube feeding was evaluated as a standard of care after esophagectomy., Methods: All consecutive patients who underwent an esophagectomy with gastric tube reconstruction and placement of jejunostomy at the University Medical Center Utrecht between January 1, 2012, and December 31, 2017, were included. Tube feeding was started as standard of care on postoperative day 1 with a normal fat-containing formula in the period between 2012 and 2014 and with a low fat-containing formula between 2014 and 2017., Results: Between 2012 and 2017, 198 patients were included. The tube feeding formula contained normal fat in 86 (43.4%) and low fat in 112 (53.6%). Chylothorax, associated with triglyceride levels exceeding 1.24 mmol/L in 27 patients (61.4%) with a clinical diagnosis of chylothorax, was significantly less observed in the low fat-formula group (15 [13.4%] vs 29 [33%], p = 0.001). No difference was seen in drain output, triglyceride levels in the pleura fluid, treatment strategy, and hospital mortality. At multivariable analysis, the normal-fat formula was associated with a 5.1 odds (95% confidence interval, 2.1 to 12.1) for postoperative chylothorax. Other factors independently associated with chylothorax were transthoracic resection, anastomotic leakage, number of resected lymph nodes, and lower body mass index., Conclusions: Administration of low fat-containing tube feed after esophagectomy was associated with a lower incidence of chylothorax., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In contrast to homogeneous materials, the mechanical properties of fibrous substrates depend on the probing lengthscale. This suggests that cells feel very different mechanical cues than expected from the macroscale characterisation of the substrate materials. By means of multiscale computational analyses we study here the mechanical environment of cells adhering to typical electrospun networks used in biomedical applications, with comparable macroscopic stiffness but different fibre diameters. The stiffness evaluated at the level of focal adhesions varies significantly, and the overall magnitude is strongly affected by the fibre diameter. The microscopic stiffness evaluated at cell scale depends substantially on the network topology and is about one order of magnitude lower than the macroscopic stiffness of the substrate, and two to three orders of magnitude below the fibres' elastic modulus. Moreover, the translation of stiffness over the scales is modulated by global deformations of the scaffold. In particular, uniaxial or biaxial stretching of the substrate induces nonlinear microscopic stiffening. Finally, although electrospun networks allow long-range transmission of cell-induced deformations, the comparison between the range of forces measured in cell traction force microscopy and those required to markedly deform typical electrospun networks reveals an order of magnitude difference, suggesting that these scaffolds provide a rather rigid environment for cells. All these results underline that the achievement of mechanical biocompatibility at all relevant lengthscales, and over the whole range of physiological loading states is extremely challenging. At the same time, the study shows that the diameter, length and curvature of fibre segments might be tunable towards achieving this goal. STATEMENT OF SIGNIFICANCE: Electrospun fabrics have growing use as substrates and scaffolds in tissue engineering and other biomedical applications. Based on multiscale computational analyses, this study shows that substrates of comparable macroscopic stiffness can provide tremendously different mechanical micro-environments, and that cells adhering to fibrous substrates may thus experience by orders of magnitude different mechanical cues than it would be expected from macroscale material characterisation. The simulations further reveal that the transfer of stiffness over the length scales changes with macroscopic deformation, and identify some key parameters that govern the transfer ratio. We believe that such refined understanding of the multiscale aspects of mechanical biocompatibility is key to the development of successful scaffold materials., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

By 2030 70% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) will occur in older adults. Elderly patients, defined by the World Health Organization (WHO) as people older than 65 years, represent a heterogeneous group with different biological and functional characteristics that need personalized anticancer treatments. Since older patients are under-represented in randomized phase III trials, their management is mostly extrapolated from studies performed in younger patients, without robust evidence-based recommendations. However, data from retrospective studies and case-control series show that elderly may benefit from chemotherapy in both the adjuvant and advanced disease settings. Although with discordant results, gemcitabine-based treatment and dose-adapted fluorouracil combination regimens seem to be effective and well tolerated in this subset of patients. A proper balance of potential treatment benefits and side effects represent the crucial point for managing elderly patients with PDAC. Therefore an appropriate patient selection is essential to maximize the therapeutic benefit in the older population: randomized studies aiming to better standardizing fitness parameters and implementing the routine use of comprehensive geriatric assessments are strongly warranted. In this light, the detection of molecular prognostic markers able to detect patients who may benefit more from oncological treatments should be a primary endpoint of age-focused clinical trials. Altogether, the field of geriatric oncology will expand in the next years, and the clinical management of elderly patients affected by PDAC will become a major public health issue., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The development and application of nanofibres requires a thorough understanding of the mechanical properties on a single fibre level including respective modelling tools for precise fibre analysis. This work presents a mechanical and morphological study of poly-l-lactide nanofibres developed by needleless electrospinning. Atomic force microscopy (AFM) and micromechanical testing (MMT) were used to characterise the mechanical response of the fibres within a diameter range of 200-1400 nm. Young's moduli E determined by means of both methods are in sound agreement and show a strong increase for thinner fibres below a critical diameter of 800 nm. Similar increasing trends for yield stress and hardening modulus were measured by MMT. Finite element analyses show that the common practice of modelling three-point bending tests with either double supported or double clamped beams is prone to significant bias in the determined elastic properties, and that the latter is a good approximation only for small diameters. Therefore, an analytical formula based on intermediate boundary conditions is proposed that is valid for the whole tested range of fibre diameters, providing a consistently low error in axial Young's modulus below 10%. The analysis of fibre morphology by differential scanning calorimetry and 2D wide-angle X-ray scattering revealed increasing polymer chains alignment in the amorphous phase and higher crystallinity of fibres for decreasing diameter. The combination of these observations with the mechanical characterisation suggests a linear relationship between Young's modulus and both crystallinity and molecular orientation in the amorphous phase. STATEMENT OF SIGNIFICANCE: Fibrous membranes have rapidly growing use in various applications, each of which comes with specific property requirements. However, the development and production of nanofibre membranes with dedicated mechanical properties is challenging, in particular with techniques suitable for industrial scales such as needleless electrospinning. It is therefore a key step to understand the mechanical and structural characteristics of single nanofibres developed in this process, and to this end, the present work presents changes of internal fibre structure and mechanical properties with diameter, based on dedicated models. Special attention was given to the commonly used models for analyzing Young's modulus of single nanofibers in three-point bending tests, which are shown to be prone to large errors, and an improved robust approach is proposed., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Resection of the thoracic duct is part of the formal en bloc mediastinal esophagolymphadenectomy for cancer, although with the adaptation of minimally invasive techniques, some centers started to leave the thoracic duct compartment in situ. However, previous studies reported thoracic duct lymph nodes in this compartment that may contain metastasis. The aim of this study was to assess the presence and number of lymph nodes in the fatty tissue surrounding the thoracic duct., Methods: A right-sided thoracoscopic esophagectomy was performed on seven fresh-frozen human cadavers (male, n = 3; female, n = 4). The esophagus and lymph node stations 7, 8, and 9 were resected en bloc, followed by resection of the thoracic duct compartment consisting of the fatty tissue covering the aorta, the thoracic duct and thoracic duct lymph nodes. Lymph nodes were visualized by a hematoxylin and eosin stain and counted macroscopically and microscopically., Results: Thoracic duct lymph nodes were found in 6 of 7 cadavers (86%), with a median number of 1 (range, 0 to 6). Nodes were predominantly located in the area of the azygos vein. A median of 4 subcarinal nodes (range, 1 to 8) and 2 periesophageal nodes (range, 1 to 4) were present., Conclusions: This study shows that thoracic duct lymph nodes are located within the fatty tissue surrounding the thoracic duct. Resection of this compartment during an esophagectomy for cancer increases lymph node yield., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The facial tissue of 9 healthy volunteers (m/f; age: 23-60y) is characterized at three different locations using a procedure combining suction measurements and 18MHz ultrasound imaging. The time-dependent and multilayered nature of skin is accounted for by adopting multiple loading protocols which differ with respect to suction probe opening size and rate of tissue deformation. Over 700 suction measurements were conducted and analyzed according to location-specific mechanical and morphological characteristics. All corresponding data are reported and made available for facial tissue analysis and biomechanical modeling. Higher skin stiffness is measured at the forehead in comparison to jaw and parotid; these two regions are further characterized by lower creep deformation. Thicker tissue regions display a tendency towards a more compliant and less dissipative response. Comparison of superficial layer thickness and corresponding mechanical measurements suggests that connective tissue density determines the resistance to deformation in suction experiments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A systematic investigation of the factors affecting the suture retention test is performed. The specimen width w and the distance a of the suture bite from the specimen free edge emerge as the most influential geometrical parameters. A conservative approach for the quantification of suture retention strength is identified, based on the use of a camera to monitor the incipient failure and detect the instant of earliest crack propagation. The corresponding critical force, called break starting strength, is extremely robust against test parameter variations and its dependence on the specimen geometry becomes negligible when a≥ 2mm and w≥ 10mm. Comparison of suture retention and mode I crack opening tests reveals a linear correlation between break starting strength and tearing energy. This suggests that the defect created by the needle and the load applied by the suture thread lead to a fracture mechanics problem, which dominates the initiation of failure., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A multiscale mechanics approach to the characterization of murine excisional wounds subjected to uniaxial tensile loading is presented. Local strain analysis at a physiological level of tension uncovers the presence of two distinct regions within the wound: i) a very compliant peripheral cushion and ii) a core area undergoing modest deformation. Microstructural visualizations of stretched wound specimens show negligible engagement of the collagen located in the center of a 7-day old wound; fibers remain coiled despite the applied tension, confirming the existence of a mechanically isolated wound core. The compliant cushion located at the wound periphery appears to protect the newly-formed tissue from excessive deformation during the phase of new tissue formation. The early remodeling phase (day 14) is characterized by a restored mechanical connection between far field and wound center. The latter remains less deformable, a characteristic possibly required for cell activities during tissue remodeling. The distribution of fibrillary collagens at these two time points corresponds well to the identified heterogeneity of mechanical properties of the wound region. This novel approach provides new insight into the mechanical properties of wounded skin and will be applicable to the analysis of compound-treated wounds or wounds in genetically modified tissue., Statement of Significance: Biophysical characterization of healing wounds is crucial to assess the recovery of the skin barrier function and the associated mechanobiological processes. For the first time, we performed highly resolved local deformation analysis to identify mechanical characteristics of the wound and its periphery. Our results reveal the presence of a compliant cushion surrounding a stiffer wound core; we refer to this heterogeneous mechanical behavior as "mechanical fingerprint" of the wound. The mechanical response is shown to progress towards that of the intact skin as healing takes place. Histology and multiphoton microscopy suggest that wounded skin recovers its mechanical function via progressive reconnection of the newly-deposited collagen fibers with the surrounding intact matrix., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Electrospun meshes may be considered as substitutes to textile polypropylene implants. We compared the host response and biomechanical properties of the rat abdominal wall following reinforcement with either polycaprolactone (PCL) modified with ureidopyrimidinone-motifs (UPy) or polypropylene mesh., Methods: First we measured the response to cyclic uniaxial load within the physiological range both dry (room temperature) and wet (body temperature). 36 rats underwent primary repair of a full-thickness abdominal wall defect with a polypropylene suture (native tissue repair), or reinforced with either UPy-PCL or ultra-light weight polypropylene mesh (n = 12/group). Sacrifice was at 7 and 42 days. Outcomes were compliance of explants, mesh dimensions, graft related complications and semi-quantitative assessment of inflammatory cell (sub) types, neovascularization and remodeling., Results: Dry UPy-PCL implants are less stiff than polypropylene, both are more compliant in wet conditions. Polypropylene loses stiffness on cyclic loading. Both implant types were well incorporated without clinically obvious degradation or herniation. Exposure rates were similar (n = 2/12) as well as mesh contraction. There was no reinforcement at low loads, while, at higher tension, polypropylene explants were much stiffer than UPy-PCL. The latter was initially weaker yet by 42 days it had a compliance similar to native abdominal wall. There were eventually more foreign body giant cells around UPy-PCL fibers yet the amount of M1 subtype macrophages was higher than in polypropylene explants. There were less neovascularization and collagen deposition., Conclusion: Abdominal wall reconstruction with electrospun UPy-PCL mesh does not compromise physiologic tissue biomechanical properties, yet provokes a vivid inflammatory reaction., (Copyright © 2017. Published by Elsevier Ltd.)

The effect of the production factors yielding a functional dermal substitute was investigated by means of monotonic and cyclic uniaxial tensile tests, as well as electron microscopy visualizations. The role of (i) plastic compression, (ii) product incubation, and (iii) cell permanence in the collagenous matrix in order to achieve a skin-like behavior were characterized in terms of material and structural stiffness, in-plane kinematics, and cyclic response, as well as pore size and network density. The plastic compression resulted in a denser and stiffer material, while no corresponding change was observed in the behavior of the entire structure. This was related to the progressive reduction in product thickness and amount of excess water, rather than to formation of new crosslinks between fibers. Contrary, irrespective of the presence of human fibroblasts, the product incubation induced both material and structural stiffening, indicating the formation of a denser network. These results were confirmed by similar evolutions in the construct in-plane kinematics and cyclic stress reduction. Finally, comparison of constructs incubated in different culture media indicated a determinant contribution of the biochemical environment, rather than of the seeded cells, to the achieved mechanical properties. The observed features are relevant in terms of mechanical biocompatibility of the implant and might direct future optimizations of the production process in order to rapidly attain the desired mechanical properties., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Abnormalities of T cell-mediated immune activation, in the absence of active somatic immune diseases, have consistently been reported in mood disorders. Apart from being important players in the regulation of cells of the immune system, T cells are essential for normal brain development. We here report studies on the relationship between circulating levels of T helper cells and structural and functional brain imaging in depressed bipolar patients. Since the CCL20-CCR6 axis is an important entry to the brain we differentiated the various T helper cell subpopulations on the basis of their chemokine receptor expression., Methods: FACS staining was performed for Th1, Th2, Th17, Th22 and T regulatory cells on frozen leukocytes of 25 consecutively admitted inpatients affected by a major depressive episode, without psychotic features, in the course of Bipolar Disorder I and 21 healthy controls. The frequency of the T helper populations was associated with DTI and fMRI data acquired on a Philips 3.0 Tesla scanner. Tract based spatial statistic was used to obtain measures of white matter integrity (fractional anisotropy, axial, radial and mean diffusivity) from a standard DTI sequence with 35 directions. Patients were also studied for fMRI through a moral valence decision task were subjects had to decide whether morally tuned stimuli were positive or negative., Results: The percentage of circulating Th17 (CCR6 + CXCR3 neg CCR4 + CCR10 neg ) cells correlated positively with higher fractional anisotropy in fiber tracts contributing to the functional integrity of the brain both in patients and healthy controls, while the frequency of circulating T regulatory (CD4 + CD25 + FOXP3 + ) cells correlated positively with higher radial and mean diffusivity in patients. The frequency of circulating T regulatory cells also correlated to lower neuronal responses to negative versus positive morally tuned stimuli in the right dorsolateral prefrontal cortex of patients. Th1 cells correlated negatively with white matter integrity in several tracts (healthy controls), while the cells showed a positive correlation to the levels of pro-inflammatory cytokines (patients)., Conclusion: This study shows a new putative role for Th17 cells. Th17 cells are not only playing a role in inducing autoimmunity and auto-inflammation, but might also play a counter intuitive anabolic role in the maintenance of the functional and structural integrity of the brain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Necrosis of the humeral head, infections and non-unions are among the most dangerous and difficult-to-treat complications of proximal humeral fractures. The aim of this work was to analyse in detail non-unions and post-traumatic bone defects and to suggest an algorithm of care. Treatment options are based not only on the radiological frame, but also according to a detailed analysis of the patient, who is classified using a risk factor analysis. This method enables the surgeon to choose the most suitable treatment for the patient, thereby facilitating return of function in the shortest possible time. The treatment of such serious complications requires the surgeon to be knowledgeable about the following possible solutions: increased mechanical stability; biological stimulation; and reconstructive techniques in two steps, with application of biotechnologies and prosthetic substitution., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The commercial polydimethysiloxane elastomer Sylgard(®) 184 with mixing ratio 10:1 is in wide use for biomedical research or fundamental studies of mechanobiology. In this paper, a comprehensive study of the large strain mechanical behavior of this material under multiaxial monotonic and cyclic loads, and its change during the first 26 days after preparation is reported. The equibiaxial stress response studied in inflation experiments reveals a much stiffer and more nonlinear response compared to the uniaxial and pure shear characteristics. The polymer revealed remarkably elastic behavior, in particular, very little dependence on strain rates between 0.3%/s and 11%/s, and on the strain history in cyclic experiments. On the other hand, both the small-strain and large strain nonlinear mechanical characteristics of the elastomer are changing with sample age and the results suggest that this process has not ceased after 26 days. A recent re-interpretation of the well-known Ogden model for incompressible rubber-like materials was applied to rationalize the results and accurate agreement was obtained with the experimental data over all testing configurations and testing times. The change of a single parameter in this model is shown to govern the evolution of the nonlinear material characteristics with sample age, attributed to a continuation of the cross-linking process. Based on a kinetic relation to account for this process over time, the model provided successful predictions of the material behavior even after more than one year., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A discrete network model (DNM) to represent the mechanical behavior of the human amnion is proposed. The amnion is modeled as randomly distributed points interconnected with connector elements representing collagen crosslinks and fiber segments, respectively. This DNM is computationally efficient and allows simulations with large domains. A representative set of parameters has been selected to reproduce the uniaxial tension-stretch and kinematic responses of the amnion. Good agreement is found between the predicted and measured equibiaxial tension-stretch curves. Although the model represents the amnion phenomenologically, model parameters are physically motivated and their effect on the tension-stretch and in-plane kinematic responses is discussed. The model is used to investigate the local response in the near field of a circular hole, revealing that the kinematic response at the circular free boundaries leads to compaction and strong alignment of the network at the border of the defect., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Mismatch of mechanical properties between highly deformable biomedical materials and adjacent native tissue might lead to short and long term health impairment. The capability of implants to deform at the right level, i.e. similar to the macroscopic mechanical response of the surrounding biological materials, is often associated with dissimilar microstructural deformation mechanisms. This mismatch on smaller length scales might lead to micro-injuries, cell damage, inflammation, fibrosis or necrosis. Hence, the mechanical biocompatibility of soft implants depends not only on the properties and composition of the implant material, but also on its organization, distribution and motion at one or several length scales. The challenges related to the analysis and attainment of mechanical biocompatibility are illustrated with two examples: prosthetic meshes for hernia and pelvic repair and electrospun scaffolds for tissue engineering. For these material systems we describe existing methods for characterization and analysis of the non-linear response to uniaxial and multiaxial stress states, its time and history dependence, and the changes in deformation behavior associated with tissue in-growth and material resorption. We discuss the multi-scale deformation behavior of biomaterials and adjacent tissue, and indicate major interdisciplinary questions to be addressed in future research., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This Position Paper contains clinically oriented guidelines by the Italian Association for the Study of the Pancreas (AISP) for the diagnosis and treatment of severe acute pancreatitis. The statements were formulated by three working groups of experts who searched and analysed the most recent literature; a consensus process was then performed using a modified Delphi procedure. The statements provide recommendations on the most appropriate definition of the complications of severe acute pancreatitis, the diagnostic approach and the timing of conservative as well as interventional endoscopic, radiological and surgical treatments., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Characterizing the mechanical response of the human amnion is essential to understand and to eventually prevent premature rupture of fetal membranes. In this study, a large set of macroscopic and microscopic mechanical tests have been carried out on fresh unfixed amnion to gain insight into the time-dependent material response and the underlying mechanisms. Creep and relaxation responses of amnion were characterized in macroscopic uniaxial tension, biaxial tension and inflation configurations. For the first time, these experiments were complemented by microstructural information from nonlinear laser scanning microscopy performed during in situ uniaxial relaxation tests. The amnion showed large tension reduction during relaxation and small inelastic strain accumulation in creep. The short-term relaxation response was related to a concomitant in-plane and out-of-plane contraction, and was dependent on the testing configuration. The microscopic investigation revealed a large volume reduction at the beginning, but no change of volume was measured long-term during relaxation. Tension-strain curves normalized with respect to the maximum strain were highly repeatable in all configurations and allowed the quantification of corresponding characteristic parameters. The present data indicate that dissipative behavior of human amnion is related to two mechanisms: (i) volume reduction due to water outflow (up to ∼20 s) and (ii) long-term dissipative behavior without macroscopic deformation and no systematic global reorientation of collagen fibers., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

This study is aimed at a comprehensive and extensive characterization of the mechanical biocompatibility of mesh prostheses. A robust and simple experimental protocol and a set of parameters is proposed, addressing stiffness under uniaxial and biaxial loading conditions, anisotropy, influence of prior deformation history, local mismatch of deformation mechanisms, and changes in mechanical properties when embedded in a homogeneous matrix. These parameters can form the basis for comparison of different mesh types and for evaluation of their mechanical biocompatibility. Measurements were performed on nine mesh types used for hernia and/or pelvic repair, including heavier as well as lighter implants and covering a wide range of mechanical responses. A total of 93 experiments were performed and all parameters are represented for each mesh in a single diagram to facilitate the quantitative assessment of implant characteristics and their comparison. The mechanics of implants is a critical factor determining clinical performance which should be accounted for in mesh selection and for development of future implants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: The recent evolution of prosthesis technology has enabled the surgeon to replace entire limbs. These special prostheses, or megaprostheses, were developed for the treatment of severe oncological bone loss; however, the indications and applications of these devices have expanded to other orthopaedic and trauma situations. For some years, surgeons have been implanting megaprostheses in non-oncological conditions, such as acute trauma in severe bone loss and poor bone quality; post-traumatic failures, both aseptic and septic (represented by complex non-unions and critical size bone defects); major bone loss in prosthetic revision, both aseptic and septic; periprosthetic fractures with component mobilisation and poor bone stock condition. The purpose of this study was to evaluate retrospectively the complications during and after the implantation of megaprosthesis of the lower limb in post-traumatic and prosthetic bone loss, and to propose tips about how to avoid and manage such complications., Materials and Methods: All the complications and difficulties we have encountered during or after the implantation of megaprosthesis in non-oncology patients were evaluated retrospectively. A total of 72 patients were treated with large resection mono-and bi-articular prostheses between January 2008 and January 2014., Results: The main critical problems found in the study were: restoration of the correct length and rotation of the limb; reconstruction of the knee extensor mechanism; trochanteric reconstruction; stability/dislocation of the implant; mobility/range of motion (ROM) of the implant; skin cover; sepsis, and bone quality., Conclusion: Megaprosthesis in severe bone loss can be considered as an available solution for the orthopaedic surgeon in extreme, appropriately selected cases. This type of complex surgery must be performed in specialised centres where knowledge and technologies are present. Patients with severe bone loss should not be treated in the same way as oncology patients because life expectancy is definitely longer; therefore, the surgical technique and the system implantation must be extremely rigorous to ensure longevity of the prosthesis. The characteristics of the bone and soft tissue conditions in these patients are very different from those presented by oncology patients, which creates critical problems that the surgeon should be able to manage to avoid serious complications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: The development of new megaprosthesis for the treatment of large bone defects provides important options to orthopaedic oncologic surgeons for the replacement of skeletal segments, such as the long bones of the upper and lower limbs and the relative joints. We implanted megaprosthesis using either a one-step or two-step technique depending on the patient's condition. The aim of this study was to evaluate retrospectively both clinical and radiological outcomes in patients who underwent lower limb megaprosthesis implant., Materials and Methods: A total of 32 patients were treated with mono- and bi-articular megaprosthesis subdivided as follows: proximal femur, distal femur, proximal tibia and total femur. The mean follow-up of patients was about 18 months (range 3 months to 5 years). Clinical and serial radiographic evaluations were conducted using standard methods (X-ray at 45 days, 3, 6, 12, 18 and 24 months) and blood parameters of inflammation were monitored for at least 2 months., Results: Although the mean length of follow-up was only 18 months, the first patients to enter the study were monitored for 5 years and showed encouraging clinical results, with good articulation of the segments, no somato-sensory or motor deficit and acceptable functional recovery. During surgery and, more importantly, in pre-operative planning, much attention should be given to the evaluation of the extensor apparatus, preserving it and, when necessary, reinforcing it with tendon substitutes., Discussion: Megaprosthesis in extreme cases of severe bone loss and prosthetic failure is a potential solution for the orthopaedic surgeon. In oncological surgery, the opportunity to restore functionality to the patient (although not ad integrum) is important for both the patient and the surgeon. The high mortality associated with cancer precludes long-term patient follow-up; therefore, there is a lack of certainty about the survival of this type of prosthesis and any medium- to long-term complications that may occur. Nevertheless, patients should be considered as an oncologic patient, not because of the disease, but because of the limited therapeutic options available., Conclusions: Megaprosthesis provides a valuable opportunity to restore functionality to patients with highly disabling diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To determine the efficacy of core decompression (CD) technique combined with recombinant morphogenetic proteins, autologous mesenchymal stem cells (MSCs) and xenograft bone substitute into the necrotic lesion of the femoral head on clinical symptoms and on the progression of osteonecrosis of the femoral head., Patients and Methods: A total of 38 patients (40 hips) with early stage osteonecrosis of the femoral head were studied over a 4-year period., Results: CD technique combined with recombinant morphogenetic proteins, autologous MSCs and xenograft bone substitute was associated with a significant reduction in both pain and joint symptoms and reduced the incidence of fractural stages. At 36 months, 33 patients achieved clinical and radiographic healing., Conclusion: This long-term follow-up study confirmed that CD technique combined with recombinant morphogenetic proteins, autologous MSCs and xenograft bone substitute may be an effective treatment for patients with early stage osteonecrosis of the femoral head., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study is aimed at a comprehensive experimental analysis of the mechanical behavior of a prosthetic mesh considering different length scales. Uniaxial and biaxial protocols are developed to evaluate global mechanical phenomena of the dry mesh. Furthermore, procedures for local deformation analysis and evaluation of corresponding homogenized kinematic measures are described. The global mechanical response of the prosthetic mesh is characterized by anisotropy, a nonlinear force response, hysteresis and preconditioning effects. The local deformation analysis allows to identify mesh specific phenomena related to mechanisms at the unit cell level. The global and the local kinematic responses of the mesh are seen to be directly related to clinical observations and help to understand associated complications, such as wrinkle formation, dislocation or erosion. In that sense, this study contributes to the analysis of mechanical biocompatibility of mesh implants and proposes protocols for comprehensive mesh product descriptions., (© 2013 Elsevier Ltd. All rights reserved.)

The soft tissue aspiration experiment has been further developed for application during laparoscopic surgery. The new setup has been tested and validated under lab-conditions and came then to in vivo operation. It is to our knowledge the first time ever a mechanical experiment has been performed under laparoscopic conditions on the human, which enables determining corresponding constitutive model equations. As most important results, the feasibility of laparoscopic tissue aspiration has been demonstrated and, based on an ad hoc parameter for the tissue stiffness, the liver and the stomach gave significantly different responses. Furthermore, the determined constitutive behavior for one healthy human liver was in line with results obtained from tissue aspiration during open surgery. Eventually, laparoscopic tissue aspiration might qualify as minimally invasive testing method for tactile feedback systems. The presented results are preliminary and more research is required., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Insight into the microstructure of fetal membrane and its response to deformation is important for understanding causes of preterm premature rupture of the membrane. However, the microstructure of fetal membranes under deformation has not been visualized yet. Second harmonic generation microscopy, combined with an in-situ stretching device, can provide this valuable information., Methods: Eight fetal membranes were marked over the cervix with methylene blue during elective caesarean section. One sample per membrane of reflected tissue, between the placenta and the cervical region, was cyclically stretched with a custom built inflation device. Samples were mounted on an in-situ stretching device and imaged with a multiphoton microscope at different deformation levels. Microstructural parameters such as thickness and collagen orientation were determined. Image entropy was evaluated for the spongy layer., Results: The spongy layer consistently shows an altered collagen structure in the cervical and cycled tissue compared with the reflected membrane, corresponding to a significantly higher image entropy. An increased thickness of collagenous layers was found in cervical and stretched samples in comparison to the reflected tissue. Significant collagen fibre alignment was found to occur already at moderate deformation in all samples., Conclusions: For the first time, second harmonic generation microscopy has been used to visualize the microstructure of fetal membranes. Repeated mechanical loading was shown to affect the integrity of the amnion-chorion interface which might indicate an increased risk of premature rupture of fetal membrane. Moreover, mechanical loading might contribute to morphological alterations of the fetal membrane over the cervical region., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

An in-vivo measurement procedure is presented to characterize the mechanical behavior of human uterine cervix during pregnancy. Based on the aspiration method, a new instrument was developed to provide an inherently safe and easy-to-use mechanical testing technique. Initial measurements were performed on non-pregnant women to develop an appropriate measurement protocol. An inverse analysis was carried out to determine representative model equations for cervical tissue. This model was used in a FE based parametric study focusing on the uncertainties related to the experiment. On this basis, a novel procedure was established which enabled for the first time to conduct mechanical measurements on 50 pregnant women in over 600 applications during gestation. An inverse analysis of the average tissue response at each trimester was performed to determine representative model equations for the cervix in the course of pregnancy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding., Methods: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed., Results: Significant weight loss (∼20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day)., Conclusion: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding.

A simple model system using synthetic materials was developed to simulate the in vivo mechanical behavior of prosthetic meshes. Two types of prosthetic meshes, SPMM (heavy-weight) and Gynemesh M (light-weight, partly absorbable) were embedded in dry conditions in an elastomeric matrix. These composites were characterized using two different testing configurations, i.e., uniaxial and biaxial tension. Stiffness parameters were calculated from the non-linear membrane tension versus stretch curves at different levels of membrane tension. The present model system qualitatively reproduces and even clarifies - as it is not affected by biological scatter - the findings of an analogous animal study (full thickness abdominal wall defect rabbit model). Biaxial tangent moduli are higher for SPMM than for Gynemesh M. A ranking of meshes according to uniaxial tangent moduli depends on the load level. At low tensions SPMM is stiffer than Gynemesh M, at moderate levels SPMM is more compliant than Gynemesh M. Stiffness values of meshes ingrown in native rabbit abdominal wall tissue are quantitatively determined based on data from the present protocol. Experiments using mesh elastomer composites were qualified as an effective tool for a mechanical characterization of prosthetic meshes. They are useful for an engineering optimization of textile meshes before a final validation in animal studies., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To determinate the efficacy of "polytherapy", a surgical technique that utilize all the components of the diamond concept (mesenchymal stem cells, bone morphogenetic proteins and scaffold) versus a "monotherapy", a surgical technique that utilize only one component of the diamond conceptin the treatment of severe forearm non-unions., Methods: We studied a database of 52 patients with 52 forearm non-unions; we classified the patients with the NUSS SCORE and we divided the patients in two group according to the treatment received. So we distinguished a group of patients treated according to the principles of "monotherapy" (33 patients) and a group of patients treated according to the principles of "polytherapy" (19 patients). The minimum follow up was 12 months., Results: In the monotherapy group 21/33 non-unions (63.64%) went on to develop a radiographic and clinical healing within a period of 12 months, the calculated DASH SCORE showed a mean value of 55.15 points. In the polytherapy group 17/19 (89.47%) nonunions went on to develop clinical and radiographic healing within 12 months, and the average DASH score showed a mean value of 45.47 points., Conclusion: The polytherapy technique with the use of recombinant morphogenetic proteins, autologous MSCs and scaffold in the same surgical time appears to be an effective treatment for patients with severe forearm non-unions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Iatrogenic preterm prelabor rupture of membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. Here, the proteolytic stability of mussel-mimetic tissue adhesive (mussel glue) and its sealing behavior on punctured fetal membranes are evaluated. The proteolytic degradation of mussel glue and fibrin glue were compared in vitro. Critical pressures of punctured and sealed fetal membranes were determined under close to physiological conditions using a custom-made inflation device. An inverse finite element procedure was applied to estimate mechanical parameters of mussel glue. Mussel glue was insensitive whereas fibrin glue was sensitive towards proteolytic degradation. Mussel glue sealed 3.7mm fetal membrane defect up to 60mbar (45mmHg) when applied under wet conditions, whereas fibrin glue needed dry membrane surfaces for reliable sealing. The mussel glue can be represented by a neo-Hookean material model with elastic coefficient C(1)=9.63kPa. Ex-vivo-tested mussel glue sealed fetal membranes and resisted pressures achieved during uterine contractions. Together with good stability in proteolytic environments, this makes mussel glue a promising sealing material for future applications., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: The gold standard for restoring bone defects is still considered to be autologous bone grafting. However, clinical benefits are not guaranteed and donor-site complications and morbidity is not infrequent. Research is on-going for the development of alternative bone substitutes of both biological and synthetic origin. The purpose of this study was to evaluate the type of materials used and their efficacy for the treatment of large bone defects in traumatology and orthopaedic surgery., Materials and Method: A literature review was carried out of Embase and PubMed databases. Inclusion criteria were articles in English language focusing on the use of bone substitutes in trauma and orthopaedic surgery for the treatment of bone defects and included details on the structural, biological or biomechanical properties of the pure product. Furthermore, based on two clinical challenges, fracture non-union and impaction grafting we elaborated on the use of polytherapy for large bone defects as guided by the diamond concept., Results: All the products indicated in this manuscript possess osteoconductive activities but have different resorption times and biomechanical properties. Bone graft substitute materials are used for a wide range of clinical applications even when the level of clinical evidence is low. The size and location of the defect and the local biological and mechanical environment as well as the biomechanical characteristics of the material determine the type of device that can be implanted in a bone defect., Conclusion: Proper assessment of the biological and mechanical environment and accurate patient selection are necessary to judge the extent of therapy the injury warrants. A sound understanding of various aspects of biomaterial properties and their relation and influence towards bone healing is of utmost importance. We suggest the application of polytherapy for the treatment of large bone defects and advocate the use of the diamond concept as a guideline., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The incidence of long bone non-unions has been estimated to range between 5 and 10%. Autologous bone graft usually harvested from the iliac crest continues to be the gold standard for biological enhancement of atrophic non-unions. However, its use has been hampered by minor and major donor site complications. Moreover despite possessing the properties of osteogenecity, osteoconductivity and some osteoinductivity the overall results of treatment have not been consistent with disappointing success rates at times. The concept of polytherapy for the treatment of non-unions, namely the simultaneous application of the three fundamental elements of the diamond concept, osteoprogenitor cells, growth factor and osteoconductive scaffold, appears to be an attractive alternative but more studies are desirable to validate this strategy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A comprehensive review of the existing literature, related to treatment options and management principles of pilon fractures was performed, and its results are presented. The identified series advocate in favour of a number of different treatment strategies and fixation methods. Decision making was mostly dependent on the severity of the local injury, the fracture pattern, the condition of the soft tissues, patient's profile and surgical expertise. External fixation and conservative treatment did not provide sufficient articular congruence in many cases. Internal fixation allowed excellent restoration of joint congruity in Rüedi type I and II fractures. A staged approach, consisting of fibular plating and temporary bridging external fixation, later substituted by an internal minimal invasive osteosynthesis or by a definitive external fixation, was favourable for Rüedi type III fractures. Closed pilon fractures with bad soft tissue conditions (Tscherne ≥ 3) or open pilon fractures are regarded as contraindication of open reduction plate fixation. Anatomic reduction of the fracture, restoration of joint's congruence, reconstruction of the posterior column, with minimal soft tissue insult, were all highlighted as of paramount importance., (Copyright © 2010 Elsevier Ltd. All rights reserved.)