Reactivity of β-enamino ester of benzo[f]chromene: One pot synthesis of isolated and heterocycle-fused derivatives of benzo[f] chromene

The formation of isolated and fused benzo[f]chromene derivatives was achieved via reacting ethyl 3-amino-1-phenyl-1H-benzo[f]chromene-2-carboxylate (1) with some selected reagents under basic conditions. The new compound, ethyl 3-(dimethylaminomethyleneamino)-1-phenyl-1H-benzo[f]chromene-2-carboxylate  (2) was prepared from compound 1 and N,N-dimethyl formamide in presence of phosphorus oxychloride under mild conditions in excellent yield using Vilsmeier reaction. Also, 10-amino-12-phenyl-9-sulfanyl-12H-benzo[f] chromeno[2,3-d]pyrimidine-11(10H)-one (12), 10-aryl-14-phenyl-14H-benzo[f]chromeno [2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidine-13-one (15), ethyl 3-(4-oxo-2-thioxothiazolidin-3-yl)-1-phenyl-1H-benzo[f]chromene-2-carboxylate (18), ethyl 3-(4-phenyl-2-thioxothiazol-3(2H)-yl)-1-phenyl-1H-benzo[f]chromene-2-carboxylate (20), ethyl 3-acetamido-1-phenyl-1H-benzo[f]chromene-2-carboxylate (21), and 10-amino-9-methyl-12-phenyl-12H-benzo[f] chromeno[2,3-d]pyrimidine-11(10H)-one (23) were prepared. The structures of these compounds were established by elemental analysis, IR, MS and NMR spectral analy­sis

Analysis of NPHS2 Gene Mutations in Egyptian Children with Nephrotic Syndrome

BACKGROUND: Mutations in the NPHS2 genes are the main aetiology of early-onset and familial steroid-resistant nephrotic syndrome (SRNS). The pathogenic NPHS2 mutation together with the p.R229Q variant has been less described among Egyptian children. AIM: This study aims to determine the mutation of NPHS2 in children with NS and discover the role of p.R229Q variant in SRNS METHODS: The study included 53 children with NS, and 53 healthy volunteers matched in age and sex controls. The median age at disease onset was 7.3 years. Among NS cases, 31 cases had steroid-sensitive nephrotic syndrome (SSNS) and 22 children with steroid-resistant nephrotic syndrome (SRNS). Polymerase chain reaction amplification of the whole coding region of NPHS2 gene was carried out for its mutational analysis. Restriction digestion testing was carried out after PCR to determine the presence of R229Q polymorphism. Randomly selected samples were re-genotyped by two independent technicians for assessment of Quality control RESULTS: NS patients showed a significant higher frequency of heterozygous genotype GA (89.5%) compared to control group (10.5%) with increased risk of NS (OR, 12.04; 95% CI, 2.61 to55.38; p < 0.0001). Moreover, SRNS showed a significant higher frequency of GA genotype (68.2%) than the SSNS group (6.5%). The GA genotype was associated with increased risk of SRNS (OR, 31.1; 95% CI, 5.73 to 168.48; P < 0.001) and the A allele was associated with increased risk of SRNS (OR, 15.52; 95% CI, 3.325 to 72.422; P < .001). CONCLUSION: R229Q polymorphisms are associated with SRNS, and any child with SRNS should be searched for mutations in the NPHS2 gene

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

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

Simple method for synthesis of isolated heterocyclic compounds incorporating 2-(2-bromoacetyl)isoindoline-1,3-dione and 2-(2-cyanoacetyl)isoindoline-1,3-dione

1194-12042-(2-Bromoacetyl)isoindoline-1,3-dione 2 and 2-(2-cyanoacetyl)isoindoline-1,3-dione 3 have been used as starting intermediates for synthesis of functionalized heterocyclic derivatives such as, 2-(2-aminothiazol-5-yl)isoindoline-1,3-dione 4, 2-(2-(benzylideneamino)thiazol-5-yl)isoindoline-1,3-dione 5, 2-(2-(3-chloro-2-oxo-4-phenylazetidin-1-yl)thiazol-5-yl)isoindoline-1,3-dione 6, 2-(2-(4-oxo-2-phenylthiazolidin-3-yl)thiazol-5-yl)isoindoline-1,3-dione 7, 2-(2-arylhydrazono)-2-bromo(cyano)acetyl)-isoindoline-1,3-dione 8, 6-bromo-5-(1,3-dioxoisoindolin-2-yl)-3-oxo-2-phenyl-2,3-dihydropyridazine- 4-carbonitrile 10a, 4-(1,3-dioxoisoindolin-2-yl)-6-oxo-1-phenyl-1,6-dihydropyridazine-3,5-dicarbonitrile 10b, 1-acetyl-3-(1,3-dioxoisoindolin-2-yl)-5-aryl-4,5-dihydro-1H-pyrazole-4-carbonitrile 12, 4-cyano-3-(1,3-dioxoisoindolin-2-yl)-5-aryl-4,5-dihydro-1H-pyrazole-1-carbothioamide 13, 3-(1,3-dioxoisoindolin-2-yl)-1-(4-oxo-4,5-dihydrothiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-4-carbonitrile 14, 3-(1,3-dioxoisoindolin-2-yl)-1-(5-(1,3-dioxoisoindolin-2-yl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-4-carbonitrile 15, 2-(3-amino-5-(phenylamino)-1H-pyrazole-4-carbonyl)isoindoline-1,3-dione 17, 2-(5,7-dimethyl-2-(phenyl-amino)pyrazolo[1,5-a]pyrimidine-3-carbonyl)isoindoline-1,3-dione 18 and 2-(7-phenyl-2-(phenyl-amino)pyrazolo[1,5-a]pyrimidine-3-carbonyl)isoindoline-1,3-dione 20. The synthesized compounds have been characterized by IR, MS, 1H NMR and 13C NMR spectral analy­sis. </span

The impact of methotrexate therapy with vitamin D supplementation on the cardiovascular risk factors among patients with psoriasis; a prospective randomized comparative study

Background Controlling psoriasis with various systemic treatments, including methotrexate, may significantly decrease associated cardiovascular risk problems. Objective To assess the value of vitamin D supplementation on clinical response as well as changes in cardiovascular risk parameters in psoriasis patients treated with methotrexate. Methods This prospective randomized comparative study included 30 patients with moderate to severe psoriasis divided randomly to receive either methotrexate alone (Mtx) or methotrexate plus intramuscular vitamin D (MtxD) for 3 months. Lipid profile, HsCRP, carotid intima-media thickness (CIMT) and blood pressure (BP) measurements were recorded before and after the therapy. Results At end of study period, significant clinical improvement in both groups was observed. CIMT and systolic BP decreased in both groups but only statistically significant in Mtx group. HsCRP decreased in both groups but didn’t reach statistical significance. We also observed, an increase in triglycerides and cholesterol levels in the Mtx group with the latter decreasing in the combined Mtx and vitamin D therapy group. Conclusion Treating psoriasis with methotrexate may decrease cardiovascular disease risk factors. Adding vitamin D supplementation to methotrexate may protect lipid homeostasis, specifically cholesterol and triglycerides

Acidified Biochar as a Soil Amendment to Drought Stressed (Vicia faba L.) Plants: Influences on Growth and Productivity, Nutrient Status, and Water Use Efficiency

Drought is one of the major threats to global food security. Biochar use in agriculture has received much attention and improving it through chemical modification offers a potential approach for enhancing crop productivity. There is still limited knowledge on how acidified biochar influences soil properties, and consequently its influences on the agricultural productivity of drought stressed plants. The water use efficiency (I-WUE) of drought stressed faba beans was investigated through the effects of acidified biochar (ACBio) (a 3:100 (w:w) combination of citric acid and biochar) on soil properties, growth, productivity, nutrient uptake, water productivity (WP), and irrigation. Two field experiments (2016/2017 and 2017/2018) were conducted in saline soil (ECe, 7.2 dS m−1) on faba been plants grown under three irrigation regimes (i.e., 100, 80, and 60% of crop evapotranspiration (ETc)) combined with three levels of ACBio (0, 5, and 10 t ha−1). Plants exposed to water stress presented a significant decrease in plant height, dry matter, leave area, chlorophyll content (SPAD), the quantum efficiency of photosystem II (Fv/Fm, Fv/F0, and PI), water status (membrane stability index and relative water content), and seed yield. Acidified biochar soil incorporation improved soil properties (chemical and physical), plant growth, physiological responses, WP, I-WUE, and contents of N, P, K, and Ca. Results revealed that the application of ACBio at 10 t ha−1 and 5 t ha−1 significantly increased seed yield by 38.7 and 25.8%, respectively, compared to the control. Therefore, ACBio incorporation may find application in the future as a potential soil amendment for improving growth and productivity of faba bean plants under deficit irrigation

Factors related to time of stroke onset versus time of hospital arrival: A SITS registry-based study in an Egyptian stroke center.

BackgroundHigh-quality data on time of stroke onset and time of hospital arrival is required for proper evaluation of points of delay that might hinder access to medical care after the onset of stroke symptoms.PurposeBased on (SITS Dataset) in Egyptian stroke patients, we aimed to explore factors related to time of onset versus time of hospital arrival for acute ischemic stroke (AIS).Material and methodsWe included 1,450 AIS patients from two stroke centers of Ain Shams University, Cairo, Egypt. We divided the day to four quarters and evaluated relationship between different factors and time of stroke onset and time of hospital arrival. The factors included: age, sex, duration from stroke onset to hospital arrival, type of management, type of stroke (TOAST classification), National Institute of Health Stroke Scale (NIHSS) on admission and favorable outcome modified Rankin Scale (mRS ≤2).ResultsPre-hospital: highest stroke incidence was in the first and fourth quarters. There was no significant difference in the mean age, sex, type of stroke in relation to time of onset. NIHSS was significantly less in onset in third quarter of the day. Percentage of patients who received thrombolytic therapy was higher with onset in the first 2 quarters of the day (p = ConclusionPre-hospital factors still need adjustment to improve percentage of thrombolysis, while in-hospital factors showed consistent performance