Interferometric Investigation of Cell Stiffness and Morphology on Oxidative Stress- Induced Human Umbilical Vein Endothelial Cells (HUVEC)

Cell stiffness that can be measured accordingly elasticity modulus is an important biomechanical feature that plays a one-to-one role on the basic features of the cell, such as migration and proliferation, and this feature is significantly affected by the characteristic of the cytoskeleton. Reactive Oxygen Species (ROS) are side-products formed as a result of the cell's general metabolic activities. Cells have a very effective antioxidant defense to deactivate the toxic effect of ROS however, oxidative stress at abnormal levels significantly damages cellular balance. Many conditions such as inflammation, neurodegenerative and cardiovascular diseases and aging are associated with oxidative stress. Besides, oxidative stress is one of the parameters that affect the biomechanical behavior of the cell, but the mechanism of this effect still remains a mystery. In this study, oxidative stress was mimicked on Human Umbilical Vein Endothelial (HUVEC) cells by using H2O2 and the effect of this situation on cell stiffness and morphological structure was investigated interferometrically for the first time. The changes that occurred in the cell stiffness were determined by calculating the elasticity modules of the cells. Cells were exposed to H2O2 for 24 hours at 0.5 mM and 1 mM concentrations, and as a result, cell stiffness was shown to decrease due to increased H2O2 concentration

Holographic Cell Stiffness Mapping Using Acoustic Stimulation

Accurate assessment of stiffness distribution is essential due to thecritical role of single cell mechanobiology in the regulation of many vitalcellular processes such as proliferation, adhesion, migration, and motility.Cell stiffness is one of the fundamental mechanical properties of the cell andis greatly affected by the intracellular tensional forces, cytoskeletalprestress, and cytoskeleton structure. Herein, we propose a novel holographicsingle-cell stiffness measurement technique that can obtain the stiffnessdistribution over a cell membrane at high resolution and in real-time. Theproposed imaging method coupled with acoustic signals allows us to assess thecell stiffness distribution with a low error margin and label-free manner. Wedemonstrate the proposed technique on HCT116 (Human Colorectal Carcinoma) cellsand CTC-mimicked HCT116 cells by induction with transforming growth factor-beta(TGF-\b{eta}). Validation studies of the proposed approach were carried out oncertified polystyrene microbeads with known stiffness levels. Its performancewas evaluated in comparison with the AFM results obtained for the relevantcells. When the experimental results were examined, the proposed methodologyshows utmost performance over average cell stiffness values for HCT116, andCTC-mimicked HCT116 cells were found as 1.08 kPa, and 0.88 kPa, respectively.The results confirm that CTC-mimicked HCT116 cells lose their adhesion abilityto enter the vascular circulation and metastasize. They also exhibit a softerstiffness profile compared to adherent forms of the cancer cells. Hence, theproposed technique is a significant, reliable, and faster alternative forin-vitro cell stiffness characterization tools. It can be utilized for variousapplications where single-cell analysis is required, such as disease modeling,drug testing, diagnostics, and many more

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit