Oxidative stress contributes to cobalt oxide nanoparticles-induced cytotoxicity and DNA damage in human hepatocarcinoma cells.

BackgroundCobalt oxide nanoparticles (Co(3)O(4)NPs) are increasingly recognized for their utility in biological applications, magnetic resonance imaging, and drug delivery. However, little is known about the toxicity of Co(3)O(4)NPs in human cells.MethodsWe investigated the possible mechanisms of genotoxicity induced by Co(3)O(4)NPs in human hepatocarcinoma (HepG2) cells. Cell viability, reactive oxygen species (ROS), glutathione, thiobarbituric acid reactive substance, apoptosis, and DNA damage were assessed in HepG2 cells after Co(3)O(4)NPs and Co(2+) exposure.ResultsCo(3)O(4)NPs elicited a significant (P < 0.01) reduction in glutathione with a concomitant increase in lipid hydroperoxide, ROS generation, superoxide dismutase, and catalase activity after 24- and 48-hour exposure. Co(3)O(4)NPs had a mild cytotoxic effect in HepG2 cells; however, it induced ROS and oxidative stress, leading to DNA damage, a probable mechanism of genotoxicity. The comet assay showed a statistically significant (P < 0.01) dose- and time-related increase in DNA damage for Co(3)O(4)NPs, whereas Co(2+) induced less change than Co(3)O(4)NPs but significantly more than control.ConclusionOur results demonstrated that Co(3)O(4)NPs induced cytotoxicity and genotoxicity in HepG2 cells through ROS and oxidative stress

The Moderating Effect of an Audit Committee on the Relationship between Non-Audit Services and Corporate Performance

The corporate performance is very important issue in developing countries like Jordan. However, there is a lack of studies that investigated this issue in developing countries, particularly in Jordan. This paper investigated the effect of board diversity and non-audit services (NAS) on the corporate performance of Jordanian industrial firms listed on the Amman stock exchange. It also explored the moderating effect of the audit committee on the association between NAS and the performance of firm, which has not been fully investigated so far by other studies on Jordanian firms. In this study, performance was measured using (ROA) return on assets and (ROE) return on equity. This study covered 58 industry firms listed on the Amman Stock Exchange in 2011. The findings showed that NAS and board diversity were significantly related to corporate performance. The results also showed that an audit committee moderates the relationship between NAS and corporate performance for the two models (ROE and ROA). The findings of this study indicated that NAS negatively affected firm performance by confining the functions of an independence auditor, a situation that would lead ultimately to lower financial performance of firms. This study concludes that the existence of an audit committee in the firms contribute positively to improving their performance. Keywords: corporate performance, non-audit services, audit committee, Jordan, industrial firm

Robust Vehicular Communications Using the Fast-Frequency-Hopping-OFDM Technology and the MIMO Spatial Multiplexing

Vehicle-to-Vehicle communication is one of the more emerging technologies in the 21st century from either the comfortable transportation or safer transportation point of view. Vehicle-to-Vehicle communication has one crucial factor, which is the huge information to be shared among vehicles, such as the position, the road data. In such situation, the accurate information sharing process is the most important factor in order to make the vehicles operating in the most feasible way. This work proposes a more robust vehicle communication system to make the existing vehicle transportation system more efficient. In this paper, we propose a fast frequency hopping orthogonal frequency division multiplexing to mitigate the Doppler spread effect on our previously published clustering benchmark.  This benchmark contains both of a clustering weighting factor based stage and a multiparallel processing stage. This is in addition to modify the PHY layer of the existing IEEE 802.11p standard in order to impose Multiple Input Multiple Output for higher throughput purposes.The results show a noticeable stability compared to our previously published work. Furthermore, the results are almost exceeds the achieved results from the Lower-ID Distributed Clustering Algorithm (DCA) from both of the speed and communication range

Bilateral Carotid Artery Molecular Calcification Assessed by [18F] Fluoride PET/CT:Correlation with Cardiovascular and Thromboembolic Risk Factors

Atherosclerosis, a leading cause of mortality and morbidity worldwide, involves inflammatory processes that result in plaque formation and calcification. The early detection of the molecular changes underlying these processes is crucial for effective disease management. This study utilized positron emission tomography/computed tomography (PET/CT) with [18F] sodium fluoride (NaF) as a tracer to visualize active calcification and inflammation at the molecular level. Our aim was to investigate the association between cardiovascular risk factors and [18F] NaF uptake in the left and right common carotid arteries (LCC and RCC). A cohort of 102 subjects, comprising both at-risk individuals and healthy controls, underwent [18F] NaF PET/CT imaging. The results revealed significant correlations between [18F] NaF uptake and cardiovascular risk factors such as age (β = 0.005, 95% CI 0.003-0.008, p &lt; 0.01 in LCC and β = 0.006, 95% CI 0.004-0.009, p &lt; 0.01 in RCC), male gender (β = -0.08, 95% CI -0.173--0.002, p = 0.04 in LCC and β = -0.13, 95% CI -0.21--0.06, p &lt; 0.01 in RCC), BMI (β = 0.02, 95% CI 0.01-0.03, p &lt; 0.01 in LCC and β = 0.02, 95% CI 0.01-0.03, p &lt; 0.01 in RCC), fibrinogen (β = 0.006, 95% CI 0.0009-0.01, p = 0.02 in LCC and β = 0.005, 95% CI 0.001-0.01, p = 0.01), HDL cholesterol (β = 0.13, 95% CI 0.04-0.21, p &lt; 0.01 in RCC only), and CRP (β = -0.01, 95% CI -0.02-0.001, p = 0.03 in RCC only). Subjects at risk showed a higher [18F] NaF uptake compared to healthy controls (one-way ANOVA; p = 0.02 in LCC and p = 0.04 in RCC), and uptake increased with estimated cardiovascular risk (one-way ANOVA, p &lt; 0.01 in LCC only). These findings underscore the potential of [18F] NaF PET/CT as a sensitive tool for the early detection of atherosclerotic plaque, assessment of cardiovascular risk, and monitoring of disease progression. Further research is needed to validate the technique's predictive value and its potential impact on clinical outcomes.</p

Associations of subclinical microcalcification and inflammation with carotid atheroma development:a dual-tracer PET/CT study

Purpose: Carotid artery atherosclerosis, a significant manifestation of cardiovascular disease (CVD) and leading cause of stroke, develops through a gradual process of arterial inflammation and calcification. This study explores the relationship between arterial inflammation (18 F-FDG PET/CT) and vascular calcification (18 F-NaF PET/CT) in the left and right common carotid arteries (LCC/RCC) and their association with CVD and thromboembolic risk in patients with subclinical atherosclerosis. Methods: A cohort of 115 subjects (73 healthy volunteers, 42 at-risk for CVD) underwent 18 F-NaF and 18 F-FDG PET/CT imaging. Radiotracer uptake was quantitatively assessed by measuring the average blood-pool-corrected mean standardized uptake value (aSUVmean). Results: Relative to healthy volunteers, at-risk subjects had greater uptake of NaF and FDG (10–22% and 16–27% higher, respectively, in both arteries, p &lt; 0.05). On multivariate regression, NaF aSUVmean correlated with age and BMI (p &lt; 0.01), and FDG aSUVmean correlated with BMI (p ≤ 0.01), fibrinogen (p &lt; 0.01 in LCC only), and total cholesterol (p = 0.02 in RCC only). NaF aSUVmean increased with elevated 10-year CVD risk (p = 0.003 in LCC only), while no significant trend was seen for FDG. NaF and FDG aSUVmean increased with elevated thromboembolic risk in both arteries (p &lt; 0.05). No correlations between NaF and FDG aSUVmean were observed (p &gt; 0.05). Conclusion: 18 F-NaF PET/CT may serve as a prognostic tool for carotid microcalcification and subclinical atherosclerosis, while the utility of 18 F-FDG PET/CT remains uncertain. Clinical trial registration: “Cardiovascular Molecular Calcification Assessed by 18F-NaF PET CT (CAMONA)”, NCT01724749, https://clinicaltrials.gov/study/NCT01724749.</p

The Economic Impact of Optimizing a COVID-19 Management Protocol in Pre-Existing Cardiovascular Disease Patients

This study answers the question of whether the health care costs of managing COVID-19 in preexisting cardiovascular diseases (CVD) patients increased or decreased as a consequence of evidence-based efforts to optimize the initial COVID-19 management protocol in a CVD group of patients. A retrospective cohort study was conducted in preexisting CVD patients with COVID-19 in Hamad Medical Corporation, Qatar. From the health care perspective, only direct medical costs were considered, adjusted to their 2021 values. The impact of revising the protocol was a reduction in the overall costs in non-critically ill patients from QAR15,447 (USD 4243) to QAR4337 (USD 1191) per patient, with an economic benefit of QAR11,110 (USD 3051). In the critically ill patients, however, the cost increased from QAR202,094 (USD 55,505) to QAR292,856 (USD 80,433) per patient, with added cost of QAR90,762 (USD 24,928). Overall, regardless of critical care status, the optimization of the initial COVID-19 protocols in patients with preexisting CVD did not reduce overall health care costs, but increased it by QAR80,529 (USD 22,117) per patient

Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma

Background: Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC). Methods: This study is prospective single-arm, multicenter phase II trial adopting Simon's two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3-4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit. Results: 13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33-73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported. Conclusion: In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630term=NCT03503630draw=2rank=1. © 2020 The Author(s)

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma

Background: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. Methods: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. Discussion: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. Trial registration: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018. © 2020 The Author(s)

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04–117·73]) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57–38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67–104·02) for those with obesity in the highest risk category and OR 20·07 (12·73–31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron