Synthesis, anti-Infammatory, Analgesic, Molecular Modeling and ADMET Studies of Novel Diclofenac Derivatives Containing Alanyl Moiety

The present work aims to synthesize novel diclofenac derivatives containing L-alanine moiety. The synthesized compounds docked into the active site to discover validated inhibitors of cyclooxygenases (COX-1 and COX-2). The calculations in-silico were predicted that, the compound with lowest energy of docked poses was interacted with residues of active site, perhaps could be making them possible selective inhibitors against (COX-2) and physiologically  active. The binding score of compound compared with reference drug, and show extensive interactions with the targets, which may consider it a suitable selective inhibitor against   (COX-2). Keywords: Alanine, Diclofenac, COX, DOCKING, ADMET

ABO blood group system and placental malaria in an area of unstable malaria transmission in eastern Sudan

<p>Abstract</p> <p>Background</p> <p>Understanding the pathogenesis of malaria in pregnancy and its consequences for both the mother and the baby is fundamental for improving malaria control in pregnant women.</p> <p>Aim</p> <p>The study aimed to investigate the role of ABO blood groups on pregnancy outcomes in an area of unstable malaria transmission in eastern Sudan.</p> <p>Methods</p> <p>A total of 293 women delivering in New Half teaching hospital, eastern Sudan during the period October 2006–March 2007 have been analyzed. ABO blood groups were determined and placental histopathology examinations for malaria were performed. Birth and placental weight were recorded and maternal haemoglobin was measured.</p> <p>Results</p> <p>114 (39.7%), 61 (22.1%) and 118 (38.2%) women were primiparae, secundiparae and multiparae, respectively. The ABO blood group distribution was 82(A), 59 (B), 24 (AB) and 128 (O). Placental histopathology showed acute placental malaria infections in 6 (2%), chronic infections in 6 (2%), 82 (28.0%) of the placentae showed past infection and 199 (68.0%) showed no infection. There was no association between the age (OR = 1.02, 95% CI = 0.45–2.2; <it>P </it>= 0.9), parity (OR = 0.6, 95% CI = 0.3–1.2; <it>P </it>= 0.1) and placental malaria infections. In all parity blood group O was associated with a higher risk of past (OR = 1.9, 95% CI = 1.1–3.2; <it>P </it>= 0.01) placental malaria infection. This was also true when primiparae were considered separately (OR = 2.6, 95% CI = 1.05–6.5, <it>P </it>= 0.03).</p> <p>Among women with all placental infections/past placental infection, the mean haemoglobin was higher in women with the blood group O, but the mean birth weight, foeto-placental weight ratio was not different between these groups and the non-O group.</p> <p>Conclusion</p> <p>These results indicate that women of eastern Sudan are at risk for placental malaria infection irrespective to their age or parity. Those women with blood group O were at higher risk of past placental malaria infection.</p

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

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&nbsp;years; 78.2% included were male with a median age of 37&nbsp;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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Natural frequency and critical velocities of heated inclined pinned PP-R pipe conveying fluid

Purpose: The flow velocity and pressure of fluid flowing through a pipeline can cause the vibration of pipes, and consequently result in the modification in natural frequency via fluid-structure interaction. The value of the natural frequency of a component when approaches the excitation force to a certain degree, a severe resonance failure may occur. Hence, avoiding the resonance failure of a pipe subjected to complex conditions is an essential issue that requires to be solved urgently in the engineering field. This work treats the transverse vibration for flexible inclined heated pipe, made of polypropylene randomcopolymer (PP-R), conveying fluid assuming pinned connections at the ends. The pipe was placed at different support angles and subjected to variant temperatures. Design/methodology/approach: The inclined pipe is modelled as Euler-Bernoulli beam taking into account its self-weight, temperature variation, inclination angle, aspect ratio, and internal fluid velocity. The integral transforms method, which includes the finite Fourier sine and the Laplace transforms, was used to develop an analytic solution to the modified equation of motion and the analytical expressions for dual natural frequencies of the pipefluid interaction system were computed. Findings: The proposed solution technique via finite Fourier sine and Laplace transforms offers a more convenient alternative to calculate the dynamic characteristic of pipes conveying fluid. The obtained results showed that the dynamical behaviour of pipe–fluid system is strongly affected by fluid flow velocity, degree of inclination, temperature variation, and aspect ratio of the pipe in transverse modes. Research limitations/implications: This work focuses on fundamental (first) mode in the most discussions. Practical implications: It was revealed that the thermal effects in the pipe are a very important factor and more significant in comparison with the internal fluid velocity and the inclination angle has a larger impact on vibration characteristics at a higher aspect ratio. The findings can be useful for the design of engineering components. Originality/value: Determining the combining effect of inclination angle, aspect ratio, and thermal loading on vibration characteristic of the pipes conveying fluid by using an improved analytic solution to the modified equation of motion via mixed of finite Fourier sine and Laplace transforms

Buckling and bending properties of aluminium plate with multiple cracks

Purpose: In this paper, the bending strength and buckling stability of (AA 7075-T6) aluminium plate weakened by many transverse cracks, which located at different positions, subjected to concentrated loads applied at the ends were analysed. Design/methodology/approach: Numerical modelling and calculation by the finite element method (ANSYS Package), for the critical load of bending and compression panel were estimated. Findings: It found that the variation of the critical stress in bending and buckling is proportional to the crack conditions (no. of crack and location). In general, the critical load in bending and buckling decreases with increasing the crack number in structure. Research limitations/implications: For both bending and buckling, two transverse cracks on one face of plate is more stable than two transverse cracks on opposite faces. Practical implications: In addition, many experimental tests were carried out by using an INSTRON test machine to obtain the buckling critical loads, where the experimental results were compared with the ones of the finite element method. Furthermore, bending strength was calculated theoretically for the cracked panel. Originality/value: Comparison between the experimental and numerical (FE based model) data and between the theoretical and nu-merical (FE based model) data for buckling and bending strength respectively indicate the precise and the simplicity of the developed models to determine the critical loads in such cases