Design, synthesis, biological evaluation, and nitric-oxide release studies of a novel series of celecoxib prodrugs possessing a nitric-oxide donor moiety

A new group of hybrid nitric oxide-releasing anti-inflammatory drugs (NONO-coxibs), in which an O2 ‑acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate NO-donor moiety is attached directly to the carboxylic acid group of 1-(4-aminosulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids (6a–c), were synthesized. A low amount of NO was released from the diazen-1-ium-1,2-diolate compounds 6a–c upon incubation with phosphate buffer saline (PBS) at pH 7.4 (range: pH 7.97–8.51), whereas, the percentage of NO released was significantly higher (84.5%–85.05% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum. These incubation studies demonstrated that both NO and the anti-inflammatory 1-(4-aminosulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H‑pyrazol-3-carboxylic acid (4a–c) would be released from the parent NONO-coxib upon in vivo cleavage by non-specific serum esterases. The parent compounds 4a-c displayed good antiinflammatory effects (ID50=81.4–112.4 mg/kg p.o.) between those exhibited by the reference drugs, aspirin (ID50=114.3 mg/kg p.o.) and celecoxib (ID50=12.6 mg/kg p.o.). Hybrid ester anti-inflammatory/NO-donor prodrugs (NONO‑coxibs) offer a potential drug-design concept directed toward the development of antiinflammatory drugs that are lacking adverse ulcerogenic and/or cardiovascular effects

The Safety and Efficacy of Cervical Laminectomy and Fusion versus Cervical Laminoplasty Surgery in Degenerative Cervical Myelopathy: A Prospective Randomized Trial

BACKGROUND: There is a lack of evidence of whether degenerative cervical myelopathy (DCM) is best treated through cervical laminoplasty (CLP) or cervical laminectomy with lateral mass fusion due to the lack of prospective randomized studies that are well designed. We conducted the largest prospective randomized trial to date to determine the comparative effectiveness and safety of both approaches. METHODS: In this prospective, randomized trial, we randomly assigned patients who had symptoms or signs of DCM to undergo either cervical laminectomy and lateral mass fixation (CLF) or CLP. The primary outcome measures were the change in the Visual Analog Scale (VAS), neck disability index, modified Japanese Orthopedic Association (mJOA) score, and Nurick’s myelopathy grading 1 year after surgery. The secondary outcome measures were the intraoperative, post-operative complications, hospital stay, C2-7 Cobb’s angle, and Odom’s criteria. The follow-up period was at least 1 year. RESULTS: A total of 30 patients (mean age, 54.5 ± 5.5 years, 70% of men) underwent prospective randomization. There was a significantly greater improvement in neck pain (VAS) in the CLF group at 1 year (p < 0.05). The improvement in the mJOA and Nurick’s myelopathy grading showed insignificant improvement between both groups. Furthermore, there was no significant difference in the patient’s post-operative satisfaction (Odom’s criteria). The mean operative time was significantly longer in the CLF group (p < 0.001), with no significant difference in the post-operative complications, however, there was a higher rate of C5 palsy, dural tear and infection in the CLF, and a higher rate of instrumentation failure in the CLP. The mean hospital stay was significantly longer in the posterior group (p < 0.05). Finally, there was a significant better improvement in the C2-7 Cobb’s angle at 1 year in the CLF group (p < 0.05). CONCLUSION: Among patients with multilevel DCM, the CLF approach was significantly better regarding the post-operative pain and Cobb’s angle while the CLP was significantly better in terms of shorter hospital stay and operative time

Neurodegeneration and inflammation crosstalk: therapeutic targets and perspectives

Glia, which was formerly considered to exist just to connect neurons, now plays a key function in a wide range of physiological events, including formation of memory, learning, neuroplasticity, synaptic plasticity, energy consumption, and homeostasis of ions. Glial cells regulate the brain's immune responses and confers nutritional and structural aid to neurons, making them an important player in a broad range of neurological disorders. Alzheimer's, ALS, Parkinson's, frontotemporal dementia (FTD), and epilepsy are a few of the neurodegenerative diseases that have been linked to microglia and astroglia cells, in particular. Synapse growth is aided by glial cell activity, and this activity has an effect on neuronal signalling. Each glial malfunction in diverse neurodegenerative diseases is distinct, and we will discuss its significance in the progression of the illness, as well as its potential for future treatmen

Chitosan-Functionalized-Graphene Oxide (GO@CS) Beads as an Effective Adsorbent to Remove Cationic Dye from Wastewater

In this study, the preparation of graphene oxide@chitosan (GO@CS) composite beads was investigated via continuous dropping techniques to remove methylene blue (MB)-dye from an aqueous media. The prepared beads were characterized using various techniques before and after the adsorption of MB. The experimental results showed that the adsorption processes fit the kinetic pseudo-second-order and Langmuir isotherm models. Moreover, the GO@CS beads achieve maximum adsorption capacities of 23.26 mg g$^{−1}$, which was comparable with other adsorbents in the literature. An important advantage of our adsorbent is that the GO@CS can remove 82.1% of the real sample color within 135 min

A Novel P@SiO2 Nano-Composite as Effective Adsorbent to Remove Methylene Blue Dye from Aqueous Media

This work aims to prepare a novel phosphate-embedded silica nanoparticles (P@SiO2) nanocomposite as an effective adsorbent through a hydrothermal route. Firstly, a mixed solution of sodium silicate and sodium phosphate was passed through a strong acidic resin to convert it into hydrogen form. After that, the resultant solution was hydrothermally treated to yield P@SiO2 nanocomposite. Using kinetic studies, methylene blue (MB) dye was selected to study the removal behavior of the P@SiO2 nanocomposite. The obtained composite was characterized using several advanced techniques. The experimental results showed rapid kinetic adsorption where the equilibrium was reached within 100 s, and the pseudo-second-order fitted well with experimental data. Moreover, according to Langmuir, one gram of P@SiO2 nanocomposite can remove 76.92 mg of the methylene blue dye. The thermodynamic studies showed that the adsorption process was spontaneous, exothermic, and ordered at the solid/solution interface. Finally, the results indicated that the presence of NaCl did not impact the adsorption behavior of MB dye. Due to the significant efficiency and promising properties of the prepared P@SiO2 nanocomposite, it could be used as an effective adsorbent material to remove various cationic forms of pollutants from aqueous solutions in future works

Basic Life Support (BLS) Knowledge Among General Population; a Multinational Study in Nine Arab Countries

Introduction: Basic Life Support (BLS) is a medical treatment used in life-threatening emergencies until the sufferer can be properly cared for by a team of paramedics or in a hospital. This study aimed to assess the level of knowledge regarding BLS and the contributing factors among the Arab non-medical population. Methods: An online survey-based cross-sectional study was conducted among non-medical populations in nine Arab countries between April 13, 2022, and June 30, 2022. The utilized questionnaire consisted of two parts: part one included socio-demographic characteristics and part two measured knowledge of BLS through an online survey. Results: The research included a total of 4465 participants. 2540 (56.89%) of the participants were knowledgeable about BLS. The mean basic life support knowledge scores of participants who received training were higher than those who had not (20.11 ± 4.20 vs. 16.96 ± 5.27; p< 0.01). According to the nations, Yemen scored the highest, while Morocco had the lowest levels of BLS knowledge (19.86 ± 4.71 vs. 14.15 ± 5.10, respectively; p< 0.01). Additionally, individuals who resided in urban areas scored on average higher than those who did in rural areas (17.86 ± 5.19 vs. 17.13 ± 5.24, p= 0.032) in understanding basic life support. Age, information sources, and previous training with theoretical and practical classes were significant predictors of BLS knowledge. Conclusion: The level of BLS knowledge among non-medical people in Arab nations is moderate but insufficient to handle the urgent crises that we face everywhere. In addition to physicians being required to learn the BLS principles, non-medical people should also be knowledgeable of the necessary actions to take in emergency events

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

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

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication