Impaired Liver Size and Compromised Neurobehavioral Activity are Elicited by Chitosan Nanoparticles in the Zebrafish Embryo Model

The use of chitosan nanoparticles (ChNPs) in various biological and environmental applications is attracting great interest. However, potential side effects related to ChNP toxicity remain the major limitation hampering their wide application. For the first time, we investigate the potential organ-specific (cardiac, hepatic, and neuromuscular) toxicity of ChNPs (size 100–150 nm) using the zebrafish embryo model. Our data highlight the absence of both acute and teratogenic toxic effects of ChNPs (~100% survival rate) even at the higher concentration employed (200 mg/L). Although no single sign of cardiotoxicity was observed upon exposure to 200 mg/L of ChNPs, as judged by heartbeat rate, the corrected QT interval (QTc, which measures the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle), maximum cardiac arrest, and ejection fraction assays, the same dosage elicited the impairment of both liver size (decreased liver size, but without steatosis and lipid yolk retention) and neurobehavioral activity (increased movement under different light conditions). Although the observed toxic effect failed to affect embryo survival, whether a prolonged ChNP treatment may induce other potentially harmful effects remains to be elucidated. By reporting new insights on their organ-specific toxicity, our results add novel and useful information into the available data concerning the in vivo effect of ChNPs.This work was supported by the NPRP grant [#9-254-2-120] from the Qatar National Research Fund, a Member of Qatar Foundation. The study was also partially supported by the grants [GCC-2017-001] given to G.K.N. and [QUCG-CHS-2018n2019-1] given to G.P

Far-Lateral Cervical Approach as a Minimally Invasive Technique for Excision of Upper Cervical Anterolateral and Anterior Meningiomas and Dumbbell Schwannomas: Technical Report and Case Series

Objective To demonstrate the details of the far-lateral approach (FLA) as a minimally invasive technique for the excision of the upper cervical anterolateral and anterior meningiomas and dumbbell schwannomas, and to assess the clinical and radiological outcomes. Methods In this technical report and case series we report the FLA technique and patients who underwent the FLA for C1-C4 anterolateral and anterior meningiomas and dumbbell schwannomas between June 2007 and June 2020. All patients’ relative preoperative demographic, clinical, radiographic, operative, histopathological, and perioperative complications and follow-up clinical and radiographic data were reported. Results A total of 19 patients including 12 females and 7 males with a mean age 56.7±17.6 years and mean duration of symptoms 12.8±12.3 months were reported. 9 patients with anterolateral meningiomas, 5 with anterior meningiomas, and 5 with dumbbell schwannomas underwent uneventful FLA procedures. Gross total resection of tumors was reported in 17 patients (89.5%). Preoperative JOA score was normal in ten, grade-I in five, and grade-II in 4 patients, while at the last follow-up it improved to normal in seventeen and grade-I in two patients. Reported postoperative JOA scores at 6 months and at the last follow-up showed that all patients improved at least one grade on JOA scores. There was CSF leak in three patients and superficial wound infection in one. Conclusion Our results advocate the far-lateral cervical approach as a minimally invasive technique in the resection of the upper cervical anterolateral and anterior meningiomas and dumbbell schwannomas as a safe and effective technique

A remark on the mean-field dynamics of many-body bosonic systems with random interactions

The mean-field limit for the dynamics of bosons with random interactions is rigorously studied. It is shown that, for interactions that are almost-surely bounded, the many-body quantum evolution can be replaced in the mean-field limit by a single particle nonlinear evolution that is described by the Hartree equation. This is an Egorov-type theorem for many-body quantum systems with random interactions.Comment: 6 page

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

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

Background 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

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

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

Stock exchange demutualization, self-listing and performance: The case of the Australian Stock Exchange

This paper examines the effects of the recent spate of financial exchange mutual-to-stock conversion phenomenon on the performance of listed exchanges and the quality of the stock market using the Australian Stock Exchange (ASX) as a case study. We find that the ASX stock significantly outperformed the stock index and the control group on a market-adjusted return basis. The stock market performance is driven by strong operating performance. The profitability ratios of the ASX have significantly improved in the five years following the demutualization and self-listing. The performance improvements remain significant even after controlling for growth in the Australian economy. From a market quality perspective, we document evidence of increased trading activity by foreign investors after ASX's demutualization and self-listing. Interestingly, we also find that bid-ask spreads of the stock market have narrowed in the post-conversion period. In particular, small-cap firms have become more liquid. The results show that stock exchange conversion from mutual to publicly traded exchange is not only value enhancing for the exchange and its shareholders, but it is also beneficial for the stock market as a whole

Fourth order torque prediction model in end milling

This study presents the development of mathematical models for torque in end-milling of AISI 618. Response Surface Method (RSM) was used to predict the effect of torque in the end-milling. The relationship between the manufacturing process factors including the cutting speed, feed rate, axial depth and radial depth with the torque can be developed. The effect of the factors can be investigated from the equation developed for first order to fourth order model. The acquired results show that the torque increases with decreases of the cutting speed and increases the feed rate, axial depth and radial depth. It found that the second order is more accurate based on the analysis of variance (ANOVA) and the predicted torque results is closely match with the experimental results. Third- and fourth-order model generated for the response to investigate the 3 and 4-way interaction between the factors. It’s found less significant for the variables