Investigation and characterization of MP derived from media conditioned by various cancer cell lines and their effect on human umbilical vein endothelial cells (HUVECs) under static and flow conditions

Microparticles (MP) are procoagulant due to tissue factor and phospholipid exposure on the surface. MP are tumour-derived and can be a beneficial biomarker of cancer to recognize individuals who are susceptible to venous thrombosis. The aim of the presented work was to develop and validate an in vitro microfluidic system consisting of two distinct microfluidic biochips to enable the investigation of the relationship between tumour MP and endothelial cells in vitro. Firstly, a range of tumour cell lines were assessed for procoagulant activity (PCA) of the cells and also MP released into the media. Pancreatic AsPC-1, human glioma U87 ovarian ES-2 and SKOV-3, were found to have the highest PCA in both cell suspension and cell- free media, while pancreatic MIAPaCa-2 and ovarian A2780 had a lower PCA. Cell lines were then investigated as to whether or not they could form stable spheroids in 3D cell culture U87, AsPC-1 and ES-2 produced the most compact spheroids and had the fastest PCA. In contrast, PANC-1, MIAPaCa-2 and A2780 formed loose shaped spheroids and slower PCA. However, SKOV-3 showed small compact spheroid and slower PCA. Following the application of media flow, ES-2 and U87 were selected and transferred into the developed dual microfluidic biochips model. Labelled MP were quantified via flow cytometry and this showed MP concentration reduced over time suggesting attachment of tumour MP to HUVECs. This reduction in MP was further reflected with a loss of PCA associated with the media. The effect of Doxorubicin on tumour spheroids resulted in an increased PCA of an endothelial cell layer under flow condition. In conclusion, in this study a microfluidic two-chip dynamic model mimics the interstitial fluid flow showed that tumour MPs released from tumour spheroids attach to endothelial cells and potentially could be a mechanism of clot formation in cancer patients

Procoagulant tumor microvesicles attach to endothelial cells on biochips under microfluidic flow

Tumor patients are at a high risk of venous thromboembolism (VTE), and the mechanism by which this occurs may involve tumor-derived microvesicles (MVs). Previously, it has been shown that tumor MVs become attached to endothelial cells in static conditions. To investigate whether this process occurs under physiologically relevant flow rates, tumor MVs were perfused across a microfluidic device coated with growing human umbilical vein endothelial cells (HUVECs). Cell lines were screened for their ability to form tumor spheroids, and two cell lines, ES-2 and U87, were selected; spheroids formed were transferred to a microfluidic chip, and a second endothelial cell biochip was coated with HUVECs and the two chips were linked. Media flowed through the spheroid chip to the endothelial chip, and procoagulant activity (PCA) of the tumor media was determined by a one-stage prothrombin time assay. Tumor MVs were also quantified by flow cytometry before and after interaction with HUVECs. Confocal images showed that HUVECs acquired fluorescence from MV attachment. Labeled MVs were proportionally lost from MV rich media with time when flowed over HUVECs and were not observed on a control chip. The loss of MV was accompanied by a proportional reduction in PCA. Flow cytometry, confocal microscopy, and live flow imagery captured under pulsatile flow confirmed an association between tumor MVs and HUVECs. Tumor MVs attached to endothelial cells under physiological flow rates, which may be relevant to the VTE pathways in cancer patient

Doxorubicin Enhances Procoagulant Activity of Endothelial Cells after Exposure to Tumour Microparticles on Microfluidic Devices

The majority of cancer patients undergoing chemotherapy have a significantly increased risk of venous thromboembolism via a mechanism not yet fully elucidated but which most probably involves tumour microparticles (MP) combined with damaged/activated endothelium. Tumour cell lines (ES-2 and U87) were cultured as 3D spheroids and transferred to biochips connected through to a second chip precultured with an endothelial cell layer (human umbilical vein endothelial cells [HUVECs]). Media were introduced with and without doxorubicin (DOX) to the spheroids in parallel chips under constant flow conditions. Media samples collected pre- and post-flow through the biochip were analysed for tissue factor microparticles (TFMP) and procoagulant activity (PCA). HUVECs were also harvested and tested for PCA at a constant cell number. TFMP levels in media decreased after passing over HUVECs in both conditions over time and this was accompanied by a reduction in PCA (indicated by a slower coagulation time) of the media. The relationship between PCA and TFMP was correlated (r = −0.85) and consistent across experiments. Harvested HUVECs displayed increased PCA when exposed to tumour spheroid media containing TFMP, which was increased further after the addition of DOX, suggesting that the TFMP in the media had bound to HUVEC cell surfaces. The enhanced PCA of HUVECs associated with the DOX treatment was attributed to a loss of viability of these cells rather than additional MP binding. The data suggest that tumour MP interact with HUVECs through ligand-receptor binding. The model described is a robust and reproducible method to investigate cytotoxic agents on tumour spheroids and subsequent downstream interaction with endothelial cells

Foot Function Index for Arabic-speaking patients (FFI-Ar) : translation, cross-cultural adaptation and validation study

Background: Foot Function Index (FFI) is a valid and reliable outcome measure, which is widely used to measure the foot and ankle functional level and disorders. Until now, no validated Arabic version of the FFI is available. This study was conducted at a tertiary care hospital in Riyadh, Saudi Arabia. The purpose of this project was to translate and adapt the FFI into Arabic and to evaluate its psychometric properties of validity and reliability. Methods: The study consisted of two phases. The first phase was the translation and cultural adaptation of the FFI to Arabic. The next phase involved, testing the psychometric properties of the Arabic version of the FFI on a sample of 50 consecutive participants which included internal consistency, test–retest reliability, floor and ceiling effects and construct validity. Results: The mean age of the study participants was 38 ± 12.94 years. Both the genders were evenly enrolled with 50% of the participants as male and 50% as female. Majority of them complained of plantar fasciopathy (32%) followed by pes planus (22%) and ankle sprain (18%). The scores of FFI-Ar were normally distributed, confirmed by a significant Shapiro–Wilk test. The mean value of FFI-Ar total score was 47.73 ± 19.85. There were no floor or ceiling effects seen in any of the subscales and total score. The internal consistency was good with the Cronbach’s alpha value of 0.882, 0.936 and 0.850 for the pain, disability and activity limitation subscales, respectively. The reproducibility of the FFI-Ar was analysed by intra-class correlation coefficient which revealed good to excellent test–retest reliability. A significant correlation was found between FFI-Ar and SF-36 and numeric rating scale (NRS) confirming its construct validity. Conclusion: The FFI-Arabic version showed good validity and reliability in patients with foot and ankle problems. This tool can be used in usual practice and research for analysing foot and ankle disorders in Arabic-speaking people

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Prepatellar Bursal Infection Caused by Mycobacterium tuberculosis with an In Situ Total Knee Arthroplasty: A Case Report and Comprehensive Literature Review

Prepatellar bursal infection is a rare occurrence. The incidence of tuberculosis, including musculoskeletal type, is increasing. We present a case of isolated prepatellar bursal swelling associated with a discharging sinus; the condition developed in an elderly patient 4 years after total knee arthroplasty. Aspiration of the bursa revealed acid-fast bacilli on Ziehl–Neelsen staining, typical of Mycobacterium tuberculosis; this was confirmed later on culture. The patient was successfully treated with a 6-month course of antituberculous chemotherapy. To the best of our knowledge, only two previous cases of tuberculous prepatellar bursal infection have been reported in English literature. Our case illustrates the importance of considering tuberculous prepatellar bursal infection in the differential diagnosis of anterior knee swelling. All physicians treating patients with musculoskeletal disease should be aware of the possibility of this diagnosis and maintain a high index of suspicion; this is especially true in areas where tuberculosis is still endemic and in high-risk patients, such as the elderly

Cementless Metaphyseal Sleeve Fixation in Revision Knee Arthroplasty: Our Experience with an Arabic Population at the Midterm

Objective. Metaphyseal sleeve (MS) fixation in revision knee arthroplasty (RKA) among Western populations has been reported with very encouraging outcomes. The aim of this study was to report our experience with the use of MS in RKA among an Arabic population. Clinical and radiographic outcomes and implant survivorship were reported at a minimum follow-up of 2 years and a mean follow-up of 4.1 years. Methods. A retrospective analysis was conducted on prospectively collected data of patients who underwent RKA with a MS in combination with a cementless stem (femoral or tibial). Range of motion (ROM) and Knee Society Score (KSS) were obtained pre- and postoperatively. Complications, occurrence of stem-tip pain, and implant survival were documented. Knee radiographs were obtained to evaluate the alignment and osseointegration or loosening of the MS. Results. A total of 52 sleeves (27 tibial and 25 femoral) implanted in 27 RKAs (27 patients) were included. The mean follow-up period was 4.1 ± 1.8 (2–7.5) years. Postoperatively, the ROM improved from 89.3 ± 9.2 to 106.3 ± 11.4 (p = 0.19) and the KSS also significantly improved, from 102.9 ± 35.6 to 130.2 ± 33.7 (p < 0.001). One patient (3.7%) developed heterotopic ossification, and another one (3.7 %) had a stem-tip pain on the tibial side; both were managed conservatively. One patient (3.7 %) sustained a fracture and required reoperation. None of the sleeves showed progressive radiolucent lines, and none required revision. The aseptic survivorship and overall survivorship at a mean of 4.1 years were 100% and 96.3%, respectively. Conclusion. MS provided successful midterm outcomes that were maintained in obese patients with different levels of constraint. Our series supports their use as a viable option in RKA

Utilizing Employee Intellectual Capital through Enterprise Social Network: A Case Study on Saudi Airlines Aviation Company

This Research aims to clarify the fact of intellectual capital investment by using Enterprise Social Networks in organizations, as a study on the Saudi Airlines Aviation Company. In addition, this research aims to define the role which technology, social capital and organizational culture play it in the organization in this field. This research aims to define the obstacles of intellectual capital investment by using Enterprise Social Networks. The analytic method was used to achieve this goal, whereas this researcher is using questionnaire to collect raw data. The research community consists of organization&rsquo;s employees (14000 employees), a random sample was selected from community of study and it was about (1500 employee). This rustles show that, there are several positive indicators which reflects that, the factor of intellectual capital investment by using Enterprise Social Networks in Saudi Airlines Aviation Company is going well. In the other side, the research found that, there are several factors related to intellectual capital investment by using Enterprise Social Networks which need to be activated for the purpose of using these networks effectively to be able to play its role in documenting, sharing and dissemination of knowledge through it. The research also found that, the best way for Saudi Airlines Aviation Company to earn more benefits is by increasing the use of this network among employees generally and between middle and high management particularly, this shall also include all employees and retired employees to learn from their experience. The research also found that, the employees are not having the awareness or they weren't trained on using and browsing the social media networks, they also are not having the idea about its role or its importance in the company, they don't use it as a tool for training and developing the knowledge of employees. In addition, the company doesn't provide the support whether it physical or mental for the employees to share the knowledge generally or by using networks particularly. The results shown that there are no technology obstacles or frequent breakdowns and this factor is not considered obstacle to use it. One of the most important recommendations that the research found it, verbalizing the training and raise awareness of employee about the role of social media networks in intellectual capital investment, it recommends to increase the use Enterprise Social Networks by employee in the company and support them physically and mentally by using determined system and make an strategy and guideline to clarify the system and how to use the network of company.Finally, the researcher recommends that, more studies that relating to this subject shall be made because it is not available widely in Arabic society

The Reality Of Knowledge Sharing Using Enterprise Social Networks in Business Organizations : A Case Study of Saudi Airlines Aviation Company

The study aimed to explore the reality of using enterprise social networks (ESN) in knowledge sharing in private sector a case study&nbsp; of Saudi Airlines aviation company, furthermore the study aimed to identify the roles impact such as the organizational culture , intercultural capital ,social capital and technology role ,Also the research aims to identify the most serious obstacles in using ESN in knowledge sharing. To fulfill these objectives the descriptive analytical method is used in this study, where the researcher used the questionnaire to collect primary data through direct questions and inquiries. The study population consisted of Saudi Airlines aviation company reached (14000) employee, and researcher selected a simple random sample of the total overall society for the study size was (1202) employee of the total community individual. The study concluded that the results of the study concluded&nbsp; the knowledge sharing reality through the ESN &nbsp;is in positive condition and available in high degree, the study also pointed that the four factors&nbsp; mentioned above need to be taken in the confederation for ESN knowledge sharing development .The study also showed &nbsp;number of ESN user to reach to 75% of current employee and no current authorize access for&nbsp; retired employee&nbsp; ,Also found lack of staff awareness and workshop programs among company ESN and it is benefit in knowledge sharing .Also the research found no staff knowledge sharing awarding program and lack of using the ESN as training and education tool , The study results also &nbsp;revealed that the technologies obstacles is very low , Finally research found no intensive management engorgement among knowledge sharing in ESN. The main recommendations of&nbsp; the&nbsp; research that need to increase &nbsp;ESN number of users , knowledge sharing awarding program should be in place ,Higher and line&nbsp; managers should&nbsp; encourage all staff &nbsp;among ESN knowledge sharing , setting up company ESN strategy and user guide .and the research suggested the company to facilitate ESN access to retiree to utilize works experience , ESN need&nbsp; ,The researcher also &nbsp;recommended further studies on the subject as there is scarcity in such studies in Arabic

Clinical and Radiological Outcomes of Extracorporeal Shock Wave Therapy in Early-Stage Femoral Head Osteonecrosis

Objective. Femoral head osteonecrosis is a progressive clinical condition with significant morbidity and long-term disability. Several treatment modalities including both surgical and nonsurgical options have been used with variable levels of success. High-energy extracorporeal shock wave therapy is a nonoperative treatment option that has been described for early-stage disease. We aimed to assess the functional and radiological outcomes of extracorporeal shockwave therapy (ESWT) in the treatment of osteonecrosis of the femoral head (ONFH). Methods. Thirty-three hips of 21 patients were included in this study. Adult patients with ONFH of any etiology and in the precollapse stage were included. Clinical (visual analogue scale [VAS] and Harris hip score [HHS]) and radiological (plain radiographs and magnetic resonance imaging [MRI]) evaluations were performed before and after intervention. We used 3000–4500 pulses in a single session performed under general anesthesia. Results. At an average of 8 months after ESWT, pain scores and HHS were significantly improved compared with the preintervention scores (p<0.001). The overall clinical outcomes were improved in 21 hips (63.3%), unchanged in 5 hips (15.15%), and worsened in 7 hips (21.2%). A trend toward a decrease in the size of the ONFH was observed although not of clinical significance (p=0.235). MRI revealed significant resolution of bone marrow edema (p<0.003). Regression was observed in 9 lesions (42.9%) and progression in 1 lesion (4.7%); no change was observed in the remaining 23 lesions (52.4%). Conclusion. ESWT is a viable noninvasive treatment option for early-stage ONFH. It significantly improves clinical outcomes and may halt or delay the radiographic progression of the disease in the precollapse stage