Design, synthesis and cytotoxic evaluation of 2-amino-4- aryl-6-substituted pyridine-3,5-dicarbonitrile derivatives

Purpose: To synthesize novel pyridine derivatives and evaluate their efficiency as potent inhibitors of cyclin dependent kinase 2 (CDK2) enzyme for cancer therapy.Methods: Pyridine scaffold were synthesized using one-pot multicomponent condensation reaction of arylidine with different primary amines. The cytotoxic potential of the new compounds was assessed using various cell lines. Furthermore, molecular docking studies based on the crystal structure of CDK2 was carried out to determine the possible binding modes that influence the anticancer activities.Results: The results indicate that one-pot multicomponent reaction generated a series of functionalized pyridines with good yield. In vitro cytotoxicity study revealed superior cytotoxicity of the designed compounds against prostate and cervical cancer cell lines compared to 5-fluorouracil (standard anticancer compound) with half-maximal inhibitory concentration (IC50) values of 0.1 – 0.85 and 1.2 –74.1 μM, respectively. Finally, molecular modeling simulation of the newly synthesized compounds showed that they fit well and are stabilized into CDK2 active site via hydrogen bonding and hydrophobic interactions.Conclusion: The results indicate that the newly synthesized pyridine can exert potent anticancer activity presumably via inhibition of CDK2. However, this will need to be confirmed in in vivo studies

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

Iliofemoral stenting for chronic venous occlusive disease: Initial and mid-term outcomes in single institution

Aim of the work: To evaluate and report the initial and midterm outcomes of endovascular venous stenting in cases suffering from chronic venous insufficiency due to iliac and common femoral vein obstruction. Patients & methods: Patients with chronic venous insufficiency were referred to our institution during the period from January 2014 to October 2015. CT venography was performed to evaluate site and extent of proximal venous stenosis or obstruction. Then conventional venography and endovascular stenting were done. The patency of the stents was assessed at short and midterm follow-up examinations. Results: CT venography revealed proximal iliac vein obstruction in 9 cases and common femoral vein obstruction in 3 cases. All were post-thrombotic. Technical success was 67% (8/12) with no immediate major complications. Follow-up CT venography done 1 month post-procedure revealed no restenosis. After one year 8 patients showed overall improvement of symptoms with decrease in lower limb edema, swelling and pain. Conclusion: Stent implantation for symptomatic ilio-femoral venous obstruction is a safe and effective procedure to resolve venous disease symptoms. Despite the small number of patients, initial and mid-term outcome has been good

Energy-Efficient Proactive Scheduling Policies for Finite-Buffer Regular Service Guarantees

In this work, we study the energy saving merits of proactive scheduling for downlink multimedia streaming towards a finite-buffer receiver under Rayleigh fading. Three different threshold-based proactive scheduling policies are proposed, each with a different threshold structure on the queue/channel state space. The first two policies consider a single channel gain threshold per queue state, either with a fixed or variable cache amount, whereas the last policy imposes a set of thresholds on the channel gain, fixed on all queue states. We consider a time-causal system in which only the current and previous environment states are known. Required transmit power/signal-to-noise ratio (SNR) for the proposed policies is analytically derived, and numerically benchmarked against a non-proactive (reactive) transmission upper bound, as well as to a non-causal genie-aided lower bound with fully-observable future channel values. Numerical results show that proactive scheduling could save more than 50% of the transmission energy on average. 2022 IEEE.This work has been made possible by partial support from the Center for Energy Systems Research at Tennessee Technological University.Scopu

Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients’ Survival: A Randomized Controlled Trial

Background and Objectives: Diarrhea induced by chemotherapy may represent a life-threatening adverse effect in cancer patients receiving chemotherapy. FOLFOX, an effective treatment for colon cancer, has been associated with diarrhea with high severity, particularly with higher doses. Management of diarrhea is crucial to increase the survival of cancer patients and to improve the quality of life. Glutamine is an abundant protein peptide found in blood and has a crucial role in boosting immunity, increasing protein anabolism, and decreasing the inflammatory effects of chemotherapy on the mucosal membranes, including diarrhea. This study aimed to provide evidence that parenteral L-alanyl L-glutamine dipeptide may have a positive influence on the incidence of diarrhea, treatment response, and the overall survival in colon cancer patients treated with modified FOLFOX-6 (mFOLFOX-6). Materials and Methods: Forty-four stage II and III colon cancer patients were included in this study where they were treated with the standard colon cancer chemotherapy mFOLFOX-6 and were randomly allocated into glutamine group and placebo group, each of 22 patients. Results: L-alanyl L-glutamine dipeptide was found to be significantly effective in decreasing the frequency and severity of diarrhea when compared to the placebo group, particularly after four and six cycles of mFOLFOX-6. There was no significant difference between the studied groups regarding to the overall survival. Conclusion: L-alanyl L-glutamine dipeptide can be considered as an add-on with chemotherapy to improve the quality of life and the overall survival of colon cancer patients