Novel 1,5-diaryl pyrazole-3-carboxamides as selective COX-2/sEH inhibitors with analgesic, anti-inflammatory, and lower cardiotoxicity effects

Funding Information: The authors extend their appreciation to the Deanship of Scientific Research at Jouf University for funding this work through research grant number (DSR2020-04-421 )Peer reviewedPostprin

Discovery of novel oxazole-based macrocycles as anti-coronaviral agents targeting SARS-CoV-2 main protease

Peer reviewedPostprin

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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

Heavy Metals Residues in Bivalve Mollusks in Fayoum Province and their Potential Health Hazards

    Bivalves Mollusks have a potential benefit which include protection from anemia due to its content of iron and vit B12 in addition they pose a threat in promoting the ability to be contaminated by different heavy metals residues as a result of mining, industrial production untreated sewage sludge. Hg, Pb, Cd, As and Cr are the main five toxic heavy metals that induce human poisoning. For evaluation of Hg, Pb, Cd, As and Cr residues in Bivalve Mollusks in Fayoum province and their potential hazards, a total of 64 random samples of Bivalve Mollusks (Callista Florida species) were collected from the fish markets of Fayoum City, (Wadi Elrayan), Egypt The results revealed that the mean residues of Hg, Pb, Cd, As and Cr were 0.75, 0.77, 0.089, 7.285 and 0.011 mg/kg/ww, respectively. All samples examined  for Hg and  As exceeded the PML while Pb and Cd lied with the PML The collected samples were subjected to soaking in running water for 30 minutes; soaking in 5% acetic acid solution for 30 minutes and boiling with 5% acetic acid solution for 15 minutes .The heights reduction % of heavy metals residual levels were recorded after treatment in boiling 5% acetic acid treatment with the following reduction %; Hg (80%), Pb (67.6%), Cd (77.5%), As (44.35%) and Cr (75.76%). The assessment of Hazard quotient (HQ) and hazard index (HI) value was exceeded 1 which indicates a potential risk to human health and TR was &gt; 1x10-4 which indicates a carcinogenic risk to the local consumers and will face high chronic risk if they consume Bivalve Mollusks on regular basis in their diet

A survey on forensic event reconstruction systems

Security related incidents such as unauthorised system access, data tampering and theft have been noticeably rising. Tools such as firewalls, intrusion detection systems and anti-virus software strive to prevent these incidents. Since these tools only prevent an attack, once an illegal intrusion occurs, they cease to provide useful information beyond this point. Consequently, system administrators are interested in identifying the vulnerability in order to: 1) avoid future exploitation; 2) recover corrupted data; 3) present the attacker to law enforcement where possible. As such, forensic event reconstruction systems are used to provide the administrators with possible information. We present a survey on the current approaches towards forensic event reconstruction systems proposed over the past few years. Technical details are discussed, as well as analysis to their effectiveness, advantages and limitations. The presented tools are compared and assessed based on the primary principles that a forensic technique is expected to follow

Location verification on the Internet: Towards enforcing location-aware access policies over Internet clients

Over the Internet, location-sensitive content/service providers are those that employ location-aware authentication or location-aware access policies in order to prevent fraud, comply with media streaming licencing, regulate online gambling/voting, etc. An adversary can configure its device to fake geolocation information, such as GPS coordinates, and send this information to the location-sensitive provider. IP-address based geolocation is circumvented when the adversary's device employs a nonlocal IP address, which is easily achievable through third party proxy and Virtual Private Network providers. To address the issue that existing Internet geolocation techniques were not designed with adversaries in mind, we propose Client Presence Verification (CPV), a delay-based verification technique designed to verify an assertion about a device's presence inside a prescribed triangular geographic region. CPV does not identify devices by their IP addresses, thus hiding the IP does n

Trimodality therapy for malignant pleural mesothelioma: Results from an EORTC phase II multicentre trial

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less). Induction chemotherapy consisted of three courses of cisplatin 75 mg·m -2 and pemetrexed 500 mg·m -2. Nonprogressing patients underwent extrapleural pneumonectomy followed by postoperative radiotherapy (54 Gy, 30 fractions). Our primary end-point was "success of treatment" and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects' median age was 57 yrs. The subjects' TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3-4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6-32.9) and median progression-free survival was 13.9 months (95% CI 10.9-17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36-1.00). Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary. Copyrigh

Efficacy of Massage on Pain Intensity in Post-Cesarean Women: a Systematic Review and Meta-Analysis

Background: Cesarean section is a common surgical procedure that may be considered a safe alternative to natural birth and helps to resolve numerous obstetric conditions. Still, the Cesarean section is painful; relieving pain after a Cesarean section is crucial, therefore analgesia is necessary for the postoperative period. However, analgesia is not free of complications and contraindications, so massage may be a cost-effective method for decreasing pain post-Cesarean. Our study aims to determine the massage role in pain intensity after Cesarean sections. Methods: We searched five electronic databases for relevant studies. Data were extracted from the included studies after screening procedures. We calculated the pooled mean difference (MD) and standardized mean difference (SMD) for our continuous outcomes, using random or fixed-effect meta-analysis according to heterogenicity status. Interventional studies were assessed for methodological quality using the Cochrane risk-of-bias assessment tool, while observational studies were assessed using the National Institutes of Health’s tools. Results: Our study included 10 RCTs and five observational studies conducted with over 1,595 post-Cesarean women. The pooled MDs for pain intensity considering baseline values either immediately or post 60-90 minutes were favoring the massage group over the control group as follows:(stand. MD = -2.64, 95% CI [-3.80, -1.48], p &gt; .00001; MD = -2.64, 95% CI [-3.80, -1.48], p &gt; .00001, respectively). While pooled MDs regarding post-intervention only either immediately or post 60-90 minutes were:(stand. MD = -2.04, 95% CI [-3.26, -0.82], p = .001; stand. MD = -2.62, 95% CI [-3.52, -1.72], p &gt; .00001, respectively). Conclusion: Our study found that using massage was superior to the control groups in decreasing pain intensity either when the pain was assessed immediately after or 60-90 minutes post-massage application