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Abstract Extracting longitudinal image quantitative data, known as delta-radiomics, has the potential to capture changes in a patient’s anatomy throughout the course of radiation treatment for prostate cancer. Some of the major challenges of delta-radiomics studies are contouring the structures for individual fractions and accruing patients’ data in an efficient manner. The manual contouring process is often time consuming and would limit the efficiency of accruing larger sample sizes for future studies. The problem is amplified because the contours are often made by highly trained radiation oncologists with limited time to dedicate to research studies of this nature. This work compares the use of automated prostate contours generated using a deformable image-based algorithm to make predictive models of genitourinary and changes in total international prostate symptom score in comparison to manually contours for a cohort of fifty patients. Area under the curve of manual and automated models were compared using the Delong test. This study demonstrated that the delta-radiomics models were similar for both automated and manual delta-radiomics models.

Abstract For prostate cancer (PCa) patients treated with definitive radiotherapy (RT), acute and late RT-related genitourinary (GU) toxicities adversely impact disease-specific quality of life. Early warning of potential RT toxicities can prompt interventions that may prevent or mitigate future adverse events. During intensity modulated RT (IMRT) of PCa, daily cone-beam computed tomography (CBCT) images are used to improve treatment accuracy through image guidance. This work investigated the performance of CBCT-based delta-radiomic features (DRF) models to predict acute and sub-acute International Prostate Symptom Scores (IPSS) and Common Terminology Criteria for Adverse Events (CTCAE) version 5 GU toxicity grades for 50 PCa patients treated with definitive RT. Delta-radiomics models were built using logistic regression, random forest for feature selection, and a 1000 iteration bootstrapping leave one analysis for cross validation. To our knowledge, no prior studies of PCa have used DRF models based on daily CBCT images. AUC of 0.83 for IPSS and greater than 0.7 for CTCAE grades were achieved as early as week 1 of treatment. DRF extracted from CBCT images showed promise for the development of models predictive of RT outcomes. Future studies will include using artificial intelligence and machine learning to expand CBCT sample sizes available for radiomics analysis.

Abstract Characterization and further development of underutilized/underexploited indigenous tropical seed oils are essential to supplement both nutritional and industrial needs of an ever-increasing African (and global) population. Before now and to our best knowledge, the previous research involved Canarium schweinfurthii Engl. fruit specific to Nigeria appear to have been more on the evaluation of seed, pulp, and essential oils (from the seed), but much less on the pulp oil. To supplement existing information, this current work has aimed to biochemically characterize the Soxhlet-extracted pulp oil of C. schweinfurthii fruit gathered from a community situated in the South-east of Nigeria. Specifically, the biochemical characterization comprised the determinations of proximate compositions, lipid peroxidation, fatty acid profile, as well as carotenoids, sterols, and tocopherols. Processing the fruit sample to pulp oil involved, among others, oven-drying, and grinding, prior to the Soxhlet extraction. Results of proximate components of C. schweinfurthii pulp oil showed the following trend: crude fat content (~ 49.32%) > carbohydrates (~ 37.93%) > moisture content (~ 8.62%) > ash content (~ 3.74%) > crude protein content (~ 0.39%) values. The lipid peroxidation attributes comprised acid (~ 23.60 mg KOH/g), peroxide (~ 33.91 mEq. O2/kg), iodine (~ 58.3 g/100 g), and saponification (~ 138.21 mg KOH/g) values. In addition to the free (~ 13.8%), saturated (~ 9.74%), and unsaturated (~ 90.26%) fatty acids, a total of fifteen (15) fatty acid methyl esters (FAMEs) spectral peaks were found, from caprylic acid (C8:0) to lignoceric acid (C24:0). Total tocopherol concentration amounted to ~ 73 mg/100 g, which comprised α, β, γ-tocopherol, and δ-tocotrienol, with fair concentrations of carotenoids and sterols. Overall, the C. schweinfurthii pulp oil—biochemically competitive with a high concentration of unsaturated fatty acid, tocopherol, and sterol, suggests strong industrial promise.

Abstract We report the photoelectrocatalysis of diclofenac sodium using a reactor consisting of Ag-BiVO4/BiOI anode and Ag-BiOI cathode. The electrodes were prepared through electrodeposition on FTO glass and modified with Ag nanoparticles through photodeposition. The structural and morphological studies were carried out using XRD, SEM, and EDS which confirmed the successful preparation of the materials. The optical properties as observed with UV-DRS revealed that the electrodes were visible light active and incorporation of metallic Ag particles on the surface increased the absorption in the visible light region. Presence of p-n heterojunction in the anode led to decrease in the spontaneous recombination of photoexcited electron–hole pairs as seen in the photocurrent response. The results from photoelectrocatalytic degradation experiments revealed that replacing platinum sheet with Ag-BiOI as counter electrode resulted in higher (92%) and faster removal of diclofenac sodium as evident in the values of apparent rate constants. The reaction mechanism further revealed that efficiently separated photogenerated holes played a major role in the degradation of the pharmaceutical. The prepared electrodes showed good stability and impressive reusability. The reports from this study revealed that the dual photoelectrodes system has a great potential in treating pharmaceutical polluted wastewater using visible light irradiation.

Abstract Pharmaceuticals have been classified as emerging water pollutants which are recalcitrant in nature. In the quest to find a suitable technique in removing them from contaminated water, photoelectrocatalytic oxidation method has attracted much attention in recent years. This report examined the feasibility of degrading ciprofloxacin and sulfamethoxazole through photoelectrocatalytic oxidation using FTO-BiVO4/Ag2S with p-n heterojunction as anode. BiVO4/Ag2S was prepared through electrodeposition and successive ionic layer adsorption/reaction on FTO glass. Structural and morphological studies using XRD, SEM, EDS and diffusive reflectance UV-Vis confirmed the successful construction of p-n heterojunction of BiVO4/Ag2S. Electrochemical techniques were used to investigate enhanced charge separation in the binary electrode. The FTO-BiVO4/Ag2S electrode exhibited the highest photocurrent response (1.194 mA/cm−2) and longest electron lifetime (0.40 ms) than both pristine BiVO4 and Ag2S electrodes which confirmed the reduction in recombination of charge carriers in the electrode. Upon application of the prepared FTO-BiVO4/Ag2S in photoelectrocatalytic removal of ciprofloxacin and sulfamethoxazole, percentage removal of 80% and 86% were achieved respectively with a low bias potential of 1.2 V (vs Ag/AgCl) within 120 min. The electrode possesses good stability and reusability. The results obtained revealed BiVO4/Ag2S as a suitable photoanode for removing recalcitrant pharmaceutical molecules in water.

Abstract Isl1 has been described as an embryonic master control gene expressed in the pericloacal mesenchyme. Deletion of Isl1 from the genital mesenchyme in mice leads to an ectopic urethral opening and epispadias-like phenotype. Using genome wide association methods, we identified ISL1 as the key susceptibility gene for classic bladder exstrophy (CBE), comprising epispadias and exstrophy of the urinary bladder. The most significant marker (rs6874700) identified in our recent GWAS meta-analysis achieved a p value of 1.48 × 10− 24 within the ISL1 region. In silico analysis of rs6874700 and all other genome-wide significant markers in Linkage Disequilibrium (LD) with rs6874700 (D’ = 1.0; R2 > 0.90) revealed marker rs2303751 (p value 8.12 × 10− 20) as the marker with the highest regulatory effect predicted. Here, we describe a novel 1.2 kb intragenic promoter residing between 6.2 and 7.4 kb downstream of the ISL1 transcription starting site, which is located in the reverse DNA strand and harbors a binding site for EZH2 at the exact region of marker rs2303751. We show, that EZH2 silencing in HEK cells reduces ISL1 expression. We show that ezh2 −/− knockout (KO) zebrafish larvae display tissues specificity of ISL1 regulation with reduced expression of Isl1 in the pronephric region of zebrafish larvae. In addition, a shorter and malformed nephric duct is observed in ezh2 −/− ko zebrafish Tg(wt1ß:eGFP) reporter lines. Our study shows, that Ezh2 is a key regulator of Isl1 during urinary tract formation and suggests tissue specific ISL1 dysregulation as an underlying mechanism for CBE formation.

Abstract Traumatic brain injury (TBI) is a ubiquitous, common sequela of accidents with an annual prevalence of several million cases worldwide. In forensic pathology, structural proteins of the cellular compartments of the CNS in serum and cerebrospinal fluid (CSF) have been predominantly used so far as markers of an acute trauma reaction for the biochemical assessment of neuropathological changes after TBI. The analysis of endogenous metabolites offers an innovative approach that has not yet been considered widely in the assessment of causes and circumstances of death, for example after TBI. The present study, therefore, addresses the question whether the detection of metabolites by liquid-chromatography-mass spectrometry (LC/MS) analysis in post mortem CSF is suitable to identify TBI and to distinguish it from acute cardiovascular control fatalities (CVF). Metabolite analysis of 60 CSF samples collected during autopsies was performed using high resolution (HR)-LC/MS. Subsequent statistical and graphical evaluation as well as the calculation of a TBI/CVF quotient yielded promising results: numerous metabolites were identified that showed significant concentration differences in the post mortem CSF for lethal acute TBI (survival times up to 90 min) compared to CVF. For the first time, this forensic study provides an evaluation of a new generation of biomarkers for diagnosing TBI in the differentiation to other causes of death, here CVF, as surrogate markers for the post mortem assessment of complex neuropathological processes in the CNS (“neuroforensomics”).

Abstract Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states. Analysing the structural integrity along different release paths via molecular dynamic simulations, we found substantial disintegration rates upon shock release, increasing with the on-Hugnoiot shock temperature. We also find that recrystallization can occur after the expansion and hence during the release, depending on subsequent cooling mechanisms. Our study suggests higher ND recovery rates from off-Hugoniot states, e.g., via double-shocks, due to faster cooling. Laser-driven shock compression experiments of polyethylene terephthalate (PET) samples with in situ X-ray probing at the simulated conditions found diamond signal that persists up to 11 ns after breakout. In the diffraction pattern, we observed peak shifts, which we attribute to thermal expansion of the NDs and thus a total release of pressure, which indicates the stability of the released NDs.

Abstract It has recently been shown that KAT8, a genome-wide association study candidate risk gene for Parkinson’s Disease, is involved in PINK1/Parkin-dependant mitophagy. The KAT8 gene encodes a lysine acetyltransferase and represents the catalytically active subunit of the non-specific lethal epigenetic remodelling complex. In the current study, we show that contrary to KAT5 inhibition, dual inhibition of KAT5 and KAT8 via the MG149 compound inhibits the initial steps of the PINK1-dependant mitophagy process. More specifically, our study shows that following mitochondrial depolarisation induced by mitochondrial toxins, MG149 treatment inhibits PINK1-dependant mitophagy initiation by impairing PINK1 activation, and subsequent phosphorylation of Parkin and ubiquitin. While this inhibitory effect of MG149 on PINK1-activation is potent, MG149 treatment in the absence of mitochondrial toxins is sufficient to depolarise the mitochondrial membrane, recruit PINK1 and promote partial downstream recruitment of the autophagy receptor p62, leading to an increase in mitochondrial delivery to the lysosomes. Altogether, our study provides additional support for KAT8 as a regulator of mitophagy and autophagy processes.

We report the photoelectrocatalysis of diclofenac sodium using a reactor consisting of Ag-BiVO4/BiOI anode and Ag-BiOI cathode. The electrodes were prepared through electrodeposition on FTO glass and modified with Ag nanoparticles through photodeposition. The structural and morphological studies were carried out using XRD, SEM, and EDS which confirmed the successful preparation of the materials. The optical properties as observed with UV-DRS revealed that the electrodes were visible light active and incorporation of metallic Ag particles on the surface increased the absorption in the visible light region. Presence of p-n heterojunction in the anode led to decrease in the spontaneous recombination of photoexcited electron–hole pairs as seen in the photocurrent response. The results from photoelectrocatalytic degradation experiments revealed that replacing platinum sheet with Ag-BiOI as counter electrode resulted in higher (92%) and faster removal of diclofenac sodium as evident in the values of apparent rate constants. The reaction mechanism further revealed that efficiently separated photogenerated holes played a major role in the degradation of the pharmaceutical. The prepared electrodes showed good stability and impressive reusability. The reports from this study revealed that the dual photoelectrodes system has a great potential in treating pharmaceutical polluted wastewater using visible light irradiation. [ABSTRACT FROM AUTHOR]

Abstract Elevated plasma numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL), predict diabetes risk by unclear mechanisms. Upregulation of the NLRP3 inflammasome/interleukin-1 beta (IL-1β) system in white adipose tissue (WAT) is implicated in type 2 diabetes (T2D); however, metabolic signals that stimulate it remain unexplored. We hypothesized that (1) subjects with high-apoB have higher WAT IL-1β-secretion than subjects with low-apoB, (2) WAT IL-1β-secretion is associated with T2D risk factors, and (3) LDL prime and/or activate the WAT NLRP3 inflammasome. Forty non-diabetic subjects were assessed for T2D risk factors related to systemic and WAT glucose and fat metabolism. Regulation of the NLRP3 inflammasome was explored using LDL without/with the inflammasome’s priming and activation controls (LPS and ATP). LDL induced IL1B-expression and IL-1β-secretion in the presence of ATP in WAT and macrophages. Subjects with high-apoB had higher WAT IL-1β-secretion independently of covariates. The direction of association of LDL-induced WAT IL-1β-secretion to T2D risk factors was consistently pathological in high-apoB subjects only. Adjustment for IL-1β-secretion eliminated the association of plasma apoB with T2D risk factors. In conclusion, subjects with high-apoB have higher WAT IL-1β-secretion that may explain their risk for T2D and may be related to LDL-induced priming of the NLRP3 inflammasome. ClinicalTrials.gov (NCT04496154): Omega-3 to Reduce Diabetes Risk in Subjects With High Number of Particles That Carry "Bad Cholesterol" in the Blood—Full Text View—ClinicalTrials.gov.

Abstract Fat is physiologically embedded within the interosseous ligaments in the posterior part of the sacroiliac joint (PSIJ). This composite of fat and ligaments is hypothesized to serve a shock-absorbing, stabilizing function for the sacroiliac joint and the lumbopelvic transition region. Using a novel Python-based software (VolSEQ), total PSIJ volume and fat volume were computed semi-automatically. Differences within the cohort and the viability of the program for the quantification of fat in routine computed tomography (CT) scans were assessed. In 37 CT scans of heathy individuals, the PSIJ were first manually segmented as a region of interest in OSIRIX. Within VolSEQ, ‘fat’ Hounsfield units (− 150 to − 50 HU) are selected and the DICOM file of the patient scan and associated region of interest file from OSIRIX were imported and the pixel sub volumes were then automatically computed. Volume comparisons were made between sexes, sides and ages (≤ 30, 31–64 and > 65 years). PSIJ volumes in both software (VolSeq vs. OSIRIX) were non-different (both 9.7 ± 2.8cm3; p = 0.9). Total PSIJ volume (p = 0.3) and fat volume (p = 0.7) between sexes were non-different. A significant difference in total PSIJ volume between sexes (p

Abstract To test causal relationships between complex gut microbiota (GM) and host outcomes, researchers frequently transfer GM between donor and recipient mice via embryo transfer (ET) rederivation, cross-fostering (CF), and co-housing. In this study, we assess the influence of the transfer method and the differences in baseline donor and recipient microbiota richness, on transfer efficiency. Additionally, recipient mice were subjected to DSS-induced chronic colitis to determine whether disease severity was affected by GM transfer efficiency or features within the GM. We found that the recipient’s genetic background, the baseline richness of donor and recipient GM, and the transfer method all influenced the GM transfer efficiency. Recipient genetic background and GM both had significant effects on DSS colitis severity and, unexpectedly, the transfer method was strongly associated with differential disease severity regardless of the other factors.

Abstract We aimed to compare the time-course effect of D-galactose (D-gal)-induced aging, obesity, and their combined effects on bone homeostasis. Male Wistar rats were fed with either a normal diet (ND; n = 24) or a high-fat diet (HFD; n = 24) for 12 weeks. All rats were then injected with either vehicle or 150 mg/kg/day of D-gal for 4 or 8 weeks. Blood was collected to measure metabolic, aging, oxidative stress, and bone turnover parameters. Bone oxidative stress and inflammatory markers, as well as bone histomorphometry were also evaluated. Additionally, RAW 264.7 cells were incubated with either D-gal, insulin, or D-gal plus insulin to identify osteoclast differentiation capacity under the stimulation of receptor activator of nuclear factor κB ligand. At week 4, D-gal-induced aging significantly elevated serum malondialdehyde level and decreased trabecular thickness in ND- and HFD-fed rats, when compared to the control group. At week 8, D-gal-induced aging further elevated advanced glycation end products, increased bone inflammation and resorption, and significantly impaired bone microarchitecture in HFD-fed rats. The osteoclast number in vitro were increased in the D-gal, insulin, and combined groups to a similar extent. These findings suggest that aging aggravates bone dyshomeostasis in the obese condition in a time-dependent manner.

Abstract Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.

Abstract It is unclear whether plantar and posterior heel spurs are truly pathological findings and whether they are stimulated by traction or compression forces. Previous histological investigations focused on either one of the two spur locations, thereby potentially overlooking common features that refer to a uniform developmental mechanism. In this study, 19 feet from 16 cadavers were X-ray scanned to preselect calcanei with either plantar or posterior spurs. Subsequently, seven plantar and posterior spurs were histologically assessed. Five spur-free Achilles tendon and three plantar fascia entheses served as controls. Plantar spurs were located either intra- or supra-fascial whereas all Achilles spurs were intra-fascial. Both spur types consistently presented a trabecular architecture without a particular pattern, fibrocartilage at the tendinous entheses and the orientation of the spur tips was in line with the course of the attached soft tissues. Spurs of both entities revealed tapered areas close to their bases with bulky tips. Achilles and plantar heel spurs seem to be non-pathological calcaneal exostoses, which are likely results of traction forces. Both spur types revealed commonalities such as their trabecular architecture or the tip direction in relation to the attached soft tissues. Morphologically, heel spurs seem poorly adapted to compressive loads.

Abstract Realistic biomechanical models of the human head should accurately reflect the mechanical properties of all neurocranial bones. Previous studies predominantly focused on static testing setups, males, restricted age ranges and scarcely investigated the temporal area. This given study determined the biomechanical properties of 64 human neurocranial samples (age range of 3 weeks to 94 years) using testing velocities of 2.5, 3.0 and 3.5 m/s in a three-point bending setup. Maximum forces were higher with increasing testing velocities (p ≤ 0.031) but bending strengths only revealed insignificant increases (p ≥ 0.052). The maximum force positively correlated with the sample thickness (p ≤ 0.012 at 2.0 m/s and 3.0 m/s) and bending strength negatively correlated with both age (p ≤ 0.041) and sample thickness (p ≤ 0.036). All parameters were independent of sex (p ≥ 0.120) apart from a higher bending strength of females (p = 0.040) for the 3.5 -m/s group. All parameters were independent of the post mortem interval (p ≥ 0.061). This study provides novel insights into the dynamic mechanical properties of distinct neurocranial bones over an age range spanning almost one century. It is concluded that the former are age-, site- and thickness-dependent, whereas sex dependence needs further investigation.

Abstract Detailed understanding of the innervation of the hip capsule (HC) helps inform surgeons’ and anaesthetists’ clinical practice. Post-interventional pain following radiofrequency nerve ablation (RFA) and dislocation following total hip arthroplasty (THA) remain poorly understood, highlighting the need for more knowledge on the topic. This systematic review and meta-analysis focuses on gross anatomical studies investigating HC innervation. The main outcomes were defined as the prevalence, course, density and distribution of the nerves innervating the HC and changes according to demographic variables. HC innervation is highly variable; its primary nerve supply seems to be from the nerve to quadratus femoris and obturator nerve. Many articular branches originated from muscular branches of the lumbosacral plexus. It remains unclear whether demographic or anthropometric variables may help predict potential differences in HC innervation. Consequently, primary targets for RFA should be the anterior inferomedial aspect of the HC. For THA performed on non-risk patients, the posterior approach with capsular repair appears to be most appropriate with the lowest risk of articular nerve damage. Care should also be taken to avoid damaging vessels and muscles of the hip joint. Further investigation is required to form a coherent map of HC innervation, utilizing combined gross and histological investigation.

Abstract With the rapid growth and increasing use of brain MRI, there is an interest in automated image classification to aid human interpretation and improve workflow. We aimed to train a deep convolutional neural network and assess its performance in identifying abnormal brain MRIs and critical intracranial findings including acute infarction, acute hemorrhage and mass effect. A total of 13,215 clinical brain MRI studies were categorized to training (74%), validation (9%), internal testing (8%) and external testing (8%) datasets. Up to eight contrasts were included from each brain MRI and each image volume was reformatted to common resolution to accommodate for differences between scanners. Following reviewing the radiology reports, three neuroradiologists assigned each study to abnormal vs normal, and identified three critical findings including acute infarction, acute hemorrhage, and mass effect. A deep convolutional neural network was constructed by a combination of localization feature extraction (LFE) modules and global classifiers to identify the presence of 4 variables in brain MRIs including abnormal, acute infarction, acute hemorrhage and mass effect. Training, validation and testing sets were randomly defined on a patient basis. Training was performed on 9845 studies using balanced sampling to address class imbalance. Receiver operating characteristic (ROC) analysis was performed. The ROC analysis of our models for 1050 studies within our internal test data showed AUC/sensitivity/specificity of 0.91/83%/86% for normal versus abnormal brain MRI, 0.95/92%/88% for acute infarction, 0.90/89%/81% for acute hemorrhage, and 0.93/93%/85% for mass effect. For 1072 studies within our external test data, it showed AUC/sensitivity/specificity of 0.88/80%/80% for normal versus abnormal brain MRI, 0.97/90%/97% for acute infarction, 0.83/72%/88% for acute hemorrhage, and 0.87/79%/81% for mass effect. Our proposed deep convolutional network can accurately identify abnormal and critical intracranial findings on individual brain MRIs, while addressing the fact that some MR contrasts might not be available in individual studies.

Abstract The site-dependent load-deformation behavior of the human neurocranium and the load dissipation within the three-layered composite is not well understood. This study mechanically investigated 257 human frontal, temporal, parietal and occipital neurocranial bone samples at an age range of 2 to 94 years, using three-point bending tests. Samples were tested as full-thickness three-layered composites, as well as separated with both diploë attached and removed. Right temporal samples were the thinnest samples of all tested regions (median 90 MPa, p

Abstract The human temporal muscle fascia (TMF) is used frequently as a graft material for duraplasty. Encompassing biomechanical analyses of TMF are lacking, impeding a well-grounded biomechanical comparison of the TMF to other graft materials used for duraplasty, including the dura mater itself. In this study, we investigated the biomechanical properties of 74 human TMF samples in comparison to an age-matched group of dura mater samples. The TMF showed an elastic modulus of 36 ± 19 MPa, an ultimate tensile strength of 3.6 ± 1.7 MPa, a maximum force of 16 ± 8 N, a maximum strain of 13 ± 4% and a strain at failure of 17 ± 6%. Post-mortem interval correlated weakly with elastic modulus (r = 0.255, p = 0.048) and the strain at failure (r = − 0.306, p = 0.022) for TMF. The age of the donors did not reveal significant correlations to the TMF mechanical parameters. Compared to the dura mater, the here investigated TMF showed a significantly lower elastic modulus and ultimate tensile strength, but a larger strain at failure. The human TMF with a post-mortem interval of up to 146 h may be considered a mechanically suitable graft material for duraplasty when stored at a temperature of 4 °C.

Abstract Highly regular aligned trabeculae are found in the superficial posterior and inferior calcaneus appearing to connect the Achilles tendon (AT) to the plantar fascia (PF) in a bridge-like manner. This provides a morphological basis for the stretching-based heel pain treatment. However, the continuity of collagen fibres between the AT and the PF remains debated controversially to date. The given study morphologically investigated the AT-calcaneus-PF complex using histology and plastination. Moreover, the AT-calcaneus-PF complex was biomechanically mapped based on 13 sub-regions with a total of 76 tested samples. Regular calcaneal trabeculae were surrounded by tendon-like collagen fibre bundles and adipocytes. The orientation of calcaneal trabeculae was further closely related to the course of the PF collagen fibre bundles. The pooled biomechanical analysis revealed low elastic moduli (minimum = 4 MPa) and ultimate tensile strengths of the decalcified calcaneal samples (minimum = 0.4 MPa) and the calcaneal periostea (minimum = 2 MPa) and high respective values (elastic modulus maximum of 144 MPa; ultimate tensile strength maximum of 29 MPa) for the PF samples compared to the other sub-regions. This study provides structural evidence for a morphological connection between the AT and PF via the highly aligned calcaneal trabeculae of the posterior calcaneus. The AT-calcaneus-PF complex was biomechanically mapped to allow for an assessment of its site-dependent mechanical characteristics.

Abstract We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis and metastasis was quantified histologically. Results and identified markers were verified using tissue samples of over 100 melanoma patients. Knockdown of CEACAM1 prolonged the animals’ survival by significantly reducing subcutaneous growth of MeWo tumors and spontaneous lung metastasis. Microarray analysis revealed a strong influence of CEACAM1 knockdown on the network of EMT associated genes in the xenograft tumors (e.g. downregulation of BRAF, FOSL1, NRAS and TWIST). IGFBP7 and Latexin (highest up- and downregulated expression in microarray analysis) were found to be associated with longer and shorter survival, respectively, of melanoma patients. High FOSL1 and altered TWIST1 expression were found to be correlated with shortened survival in the cohort of melanoma patients. After a stepwise selection procedure combining above markers, multivariate analysis revealed IGFBP7, Latexin and altered TWIST to be prognostic markers for death. CEACAM1 could be a target for melanoma therapy as an alternative to (or in combination with) immune checkpoint and BRAF inhibitors.