3-Acetyl-1-(3-methyl­phen­yl)-5-phenyl-1H-pyrazole-4-carbonitrile

In the title compound, C19H15N3O, the central pyrazole ring makes dihedral angles of 35.52 (12) and 62.21 (11)° with the attached phenyl and methyl-substituted phenyl rings, respectively. The corresponding angle between the phenyl and methyl-substituted phenyl rings is 62.90 (11)°. In the crystal, mol­ecules are connected by weak C—H⋯O hydrogen bonds, forming supra­molecular chains propagating along the a-axis direction

Generation of polyclonal antibody with high avidity to rosuvastatin and its use in development of highly sensitive ELISA for determination of rosuvastatin in plasma

In this study, a polyclonal antibody with high avidity and specificity to the potent hypocholesterolaemic agent rosuvastatin (ROS) has been prepared and used in the development of highly sensitive enzyme-linked immunosorbent assay (ELISA) for determination of ROS in plasma. ROS was coupled to keyhole limpt hemocyanin (KLH) and bovine serum albumin (BSA) using carbodiimide reagent. ROS-KLH conjugate was used for immunization of female 8-weeks old New Zealand white rabbits. The immune response of the rabbits was monitored by direct ELISA using ROS-BSA immobilized onto microwell plates as a solid phase. The rabbit that showed the highest antibody titer and avidity to ROS was scarified and its sera were collected. The IgG fraction was isolated and purified by avidity chromatography on protein A column. The purified antibody showed high avidity to ROS; IC50 = 0.4 ng/ml. The specificity of the antibody for ROS was evaluated by indirect ELISA using various competitors from the ROS-structural analogues and the therapeutic agents used with ROS in a combination therapy. The proposed ELISA involved a competitive binding reaction between ROS, in plasma sample, and the immobilized ROS-BSA for the binding sites on a limited amount of the anti-ROS antibody. The bound anti-ROS antibody was quantified with horseradish peroxidase-labeled second anti-rabbit IgG antibody (HRP-IgG) and 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate for the peroxidase enzyme. The concentration of ROS in the sample was quantified by its ability to inhibit the binding of the anti-ROS antibody to the immobilized ROS-BSA and subsequently the color intensity in the assay wells. The assay enabled the determination of ROS in plasma at concentrations as low as 40 pg/ml

Enhanced drug delivery and wound healing potential of berberine-loaded chitosan–alginate nanocomposite gel: characterization and in vivo assessment

Berberine–encapsulated polyelectrolyte nanocomposite (BR–PolyET–NC) gel was developed as a long-acting improved wound healing therapy. BR–PolyET–NC was developed using an ionic gelation/complexation method and thereafter loaded into Carbopol gel. Formulation was optimized using Design-Expert® software implementing a three-level, three-factor Box Behnken design (BBD). The concentrations of polymers, namely, chitosan and alginate, and calcium chloride were investigated based on particle size and %EE. Moreover, formulation characterized in vitro for biopharmaceutical performances and their wound healing potency was evaluated in vivo in adult BALB/c mice. The particle distribution analysis showed a nanocomposite size of 71 ± 3.5 nm, polydispersity index (PDI) of 0.45, ζ–potential of +22 mV, BR entrapment of 91 ± 1.6%, and loading efficiency of 12.5 ± 0.91%. Percentage drug release was recorded as 89.50 ± 6.9% with pH 6.8, thereby simulating the wound microenvironment. The in vitro investigation of the nanocomposite gel revealed uniform consistency, well spreadability, and extrudability, which are ideal for topical wound use. The analytical estimation executed using FT-IR, DSC, and X-ray diffraction (XRD) indicated successful formulation with no drug excipients and without the amorphous state. The colony count of microbes was greatly reduced in the BR–PolyET–NC treated group on the 15th day from up to 6 CFU compared to 20 CFU observed in the BR gel treated group. The numbers of monocytes and lymphocytes counts were significantly reduced following healing progression, which reached to a peak level and vanished on the 15th day. The observed experimental characterization and in vivo study indicated the effectiveness of the developed BR–PolyET–NC gel toward wound closure and healing process, and it was found that >99% of the wound closed by 15th day, stimulated via various anti-inflammatory and angiogenic factors

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Serum protein biomarkers relevant to hepatocellular carcinoma and their detection

Hepatocellular carcinoma (HCC) is one of the most recurrent and lethal cancers worldwide. The low survival rate of this particular strain of carcinoma is largely due to the late stages at which it is diagnosed. Tumorigenesis of hepatocellular carcinoma is most frequently detected through ultrasonography, magnetic resonance imaging and computerized tomography scans, however, these methods are poor for detection of early tumor development. This review presents alternative hepatocellular carcinoma detection techniques through the use of protein and enzyme/isozyme biomarkers. The detection methods used to determine the serum levels of α-fetoprotein (AFP), glypican-3 (GPC3), Golgi protein 73 (GP73), α-L-fucosidase (AFU), des-γ-carboxyprothrombin (DCP), γ-glutamyl transferase (GGT) and squamous cell carcinoma antigen (SCCA) are presented and each marker's respective validity in the diagnosis of hepatocellular carcinoma is evaluated

Combined effects of biosolarization and Brassica amendments on survival of biocontrol agents and inhibition of Fusarium oxysporum

Biocontrol agents (BCAs) added in the soil or applied to the seeds face many abiotic and biotic stress challenges. Only those BCAs that survive under harsh conditions perform well. Improving the survival of BCAs along with inhibiting the biotic stresses imposed by bacterial, fungal, and viral infections has been a major challenge in agriculture, especially in hot-arid climates. The present study aimed to evaluate the individual and combined effects of soil solarization and Brassica amendments on the survival of two biocontrol agents (BCAs), namely Trichoderma harzianum and Aspergillus versicolor, and on the reduction in a cumin wilt pathogen Fusarium oxysporum f. sp. cumini (Foc) in a field experiment conducted for two years under hot-arid climates. BCAs performed well in the solarized pots, it caused the maximum reduction in viable F. oxysporum propagules, significantly higher at 5 cm than at 15 cm of depth. Brassica amendment with BCAs caused a greater decrease in F. oxysporum propagules (95.7 to 96.7%) compared to a combination of BCAs and solarization (91.0 to 95.7%). Combining T. harzianum with A. versicolor increased the survival of T. harzianum, whereas integration with Brassica amendment could only improve the survival of T. harzianum at a depth of 5 cm and not at lower depths. The slightest decrease in A. versicolor population at high soil temperature was estimated when combined with T. harzianum. However, combining A. versicolor with Brassica amendment improved the survival of A. versicolor at high compared to low soil temperatures. Still, elevated soil temperature reduced the viable propagules. These studies demonstrate that both the native BCAs are compatible, and their integration with the Brassica amendment improves their survival and ability to reduce the population of cumin wilt pathogen. Thus, these BCAs with Brassica amendments can survive and perform well under hot-arid climates

Combined Effects of Biosolarization and Brassica Amendments on Survival of Biocontrol Agents and Inhibition of Fusarium oxysporum

Biocontrol agents (BCAs) added in the soil or applied to the seeds face many abiotic and biotic stress challenges. Only those BCAs that survive under harsh conditions perform well. Improving the survival of BCAs along with inhibiting the biotic stresses imposed by bacterial, fungal, and viral infections has been a major challenge in agriculture, especially in hot-arid climates. The present study aimed to evaluate the individual and combined effects of soil solarization and Brassica amendments on the survival of two biocontrol agents (BCAs), namely Trichoderma harzianum and Aspergillus versicolor, and on the reduction in a cumin wilt pathogen Fusarium oxysporum f. sp. cumini (Foc) in a field experiment conducted for two years under hot-arid climates. BCAs performed well in the solarized pots; it caused the maximum reduction in viable F. oxysporum propagules, significantly higher at 5 cm than at 15 cm of depth. Brassica amendment with BCAs caused a greater decrease in F. oxysporum propagules (95.7 to 96.7%) compared to a combination of BCAs and solarization (91.0 to 95.7%). Combining T. harzianum with A. versicolor increased the survival of T. harzianum, whereas integration with Brassica amendment could only improve the survival of T. harzianum at a depth of 5 cm and not at lower depths. The slightest decrease in A. versicolor population at high soil temperature was estimated when combined with T. harzianum. However, combining A. versicolor with Brassica amendment improved the survival of A. versicolor at high compared to low soil temperatures. Still, elevated soil temperature reduced the viable propagules. These studies demonstrate that both the native BCAs are compatible, and their integration with the Brassica amendment improves their survival and ability to reduce the population of cumin wilt pathogen. Thus, these BCAs with Brassica amendments can survive and perform well under hot-arid climates