Targeting tumor initiating cells through inhibition of cancer testis antigens and notch signaling : A hypothesis

Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer

Painful knee joint after ACL reconstruction using biodegradable interference screws- SPECT/CT a valuable diagnostic tool? A case report

With the presented case we strive to introduce combined single photon emission computerized tomography and conventional computer tomography (SPECT/CT) as new diagnostic imaging modality and illustrate the possible clinical value in patients after ACL reconstruction. We report the case of a painful knee due to a foreign body reaction and delayed degradation of the biodegradable interference screws after ACL reconstruction. The MRI showed an intact ACL graft, a possible tibial cyclops lesion and a patella infera. There was no increased fluid collection within the bone tunnels. The 99mTc-HDP-SPECT/CT clearly identified a highly increased tracer uptake around and within the tibial and femoral tunnels and the patellofemoral joint. On 3D-CT out of the SPECT/CT data the femoral graft attachment was shallow (50% along the Blumensaat's line) and high in the notch. At revision arthroscopy a diffuse hypertrophy of the synovium, scarring of the Hoffa fat pad and a cyclops lesion of the former ACL graft was found. The interference screws were partially degraded and under palpation and pressure a grey fluid-like substance drained into the joint. The interference screws and the ACL graft were removed and an arthrolysis performed

Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01–0145-FEDER-000008:BrainHealth 2020, and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, I.P., under projects PTDC/SAU-NEU/104100/2008, EXPL/NEU-NMC/0541/2012 and UID/NEU/04539/2013. This work was also funded by Marie Curie Actions - International reintegration grant #249288, 7th Framework programme, EU. Partially funded by Prémios Santa Casa Neurociências - Prize Melo e Castro for Spinal Cord Injury Research; Portuguese Foundation for Science and Technology (IF Development Grant to A.J.S.); NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme; by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by national funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. The authors would also like to acknowledge Prof. J.E. Davies from the Institute of Biomaterials and Biomedical Engineering at the University of Toronto, Canada, for kindly providing some of the HUCPVCs lots used in the present workinfo:eu-repo/semantics/publishedVersio

Offshore wind turbine subjected to supershear earthquake ruptures

Supershear earthquakes, analogous to supersonic speeds of sounds, show the presence of a Mach front in the top view. This feature was observed in several past earthquakes, including the 1999 Izmit earthquake, 2001 Kokoxili earthquake, to name a few. The ground motion from supershear ruptures can be destructive to structures due to dominant fault-parallel components. In this study, we demonstrate the effect of supershear ruptures on wind turbines by modelling them in OpenSees. Earthquake ruptures are simulated using SPECFEM3D, another open-source software. By considering arrays at different offsets along strike and away from the strike, the distance effect on serviceability limit states of wind turbines is studied using supershear and subshear earthquakes. © The Author(s) 2022

The position and orientation of total knee replacement components : a comparison of conventional radiographs, transverse 2D-CT slices and 3D-CT reconstruction

We studied the intra- and interobserver reliability of measurements of the position of the components after total knee replacement (TKR) using a combination of radiographs and axial two-dimensional (2D) and three-dimensional (3D) reconstructed CT images to identify which method is best for this purpose. A total of 30 knees after primary TKR were assessed by two independent observers (an orthopaedic surgeon and a radiologist) using radiographs and CT scans. Plain radiographs were highly reliable at measuring the tibial slope, but showed wide variability for all other measurements; 2D-CT also showed wide variability. 3D-CT was highly reliable, even when measuring rotation of the femoral components, and significantly better than 2D-CT. Interobserver variability in the measurements on radiographs were good (intraclass correlation coefficient (ICC) 0.65 to 0.82), but rotational measurements on 2D-CT were poor (ICC 0.29). On 3D-CT they were near perfect (ICC 0.89 to 0.99), and significantly more reliable than 2D-CT (p > 0.001). 3D-reconstructed images are sufficiently reliable to enable reporting of the position and orientation of the components. Rotational measurements in particular should be performed on 3D-reconstructed CT images. When faced with a poorly functioning TKR with concerns over component positioning, we recommend 3D-CT as the investigation of choice

Intraosseous lipomas originating from simple bone cysts

PurposeFatty or part-fatty intraosseous lesions are occasionally encountered while imaging the skeletal system. A number of case reports have proposed involution of calcaneal bone cysts to intraosseous lipomas, but this has never been proven. This paper sets out to prove that simple bone cysts (SBCs) can involute to fatty lesions indistinguishable from intraosseous lipomas.Materials and methodsThe pathology and PACS databases at 2 specialist orthopedic hospitals were retrospectively interrogated for all cases of intraosseous lipomas or SBCs with cross-sectional imaging follow-up for SBCs and precursor or follow-up imaging for intraosseous lipomas, in the time period from August 2007 to December 2016. For intraosseous lipoma cases, these were only included if change in imaging appearances was observed.ResultsThere was no case of change in the appearance in intraosseous lipomas. Six cases of SBC with cross-sectional imaging follow-up were identified in one participating hospital and none in the other. The 6 cases were comprised of 4 male and 2 female patients. Two were located in the proximal humerus, one in the proximal tibia, and 3 in the os calcis. All cases demonstrated filling in of the cystic lesion with fat from the periphery, in 2 cases complete filling in, and in 4 cases partial fatty conversion.ConclusionSBCs can heal with fatty conversion of the cystic cavity, with partly cystic remnants. It is proposed that at least part of the so-called intraosseous lipomas are healed simple bone cysts

The impact of sex on ropporin expression in multiple myeloma patients

Background: Multiple myeloma (MM) is a cancer of plasma cells wherein aberrant cells accumulate in the bone marrow leading to bone damage and interference with normal blood cell production. Although MM remains incurable, it is treatable. As with most forms of cancer, early detection is the key to improving prognosis and avoiding permanent damage. Cancer Testis Antigens (CTAs) are a class of proteins that are expressed in male gametogenic tissue but generally not in the somatic tissue of healthy adults. However, a number of cancer types have been shown to produce these proteins, and their expression has been correlated with malignancy. Ropporin is a specific CTA shown to be associated with MM, and this protein represents a potential target for MM diagnosis as well as immunotherapy. In this study, we examine the impact of sex on the expression of Ropporin, in MM patients. Methods: The expression of this particular CTA in MM patients was analyzed using PCR, ELISA, and immunohistochemistry in a cohort of 59 MM patients (37 male and 22 female). Results: 61% of MM patients were positive for Ropporin expression. When the data were broken down by sex, it was revealed that Roporrin expression was 81.8% in females and 48.6% in males. Interestingly, 50% of female patients as well as 78% of males expressing Ropporin were deceased. In addition, 100% of the deceased subjects in the cohort were Ropporin positive. Conclusions: Our results provide indications that sex can shift the expression of CTA in multiple myeloma. Furthermore, the data indicate CTA expression may affect the prognosis in MM patients. Further studies in a large cohort of patients are warranted to validate the correlation of CTA/ropporin in MM patients and sex