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Background Antimicrobial resistance is a growing menace, claiming millions of lives all over the world. In this context, drug repurposing is one approach gaining interest as a suitable alternative to conventional drug discovery and development. Methods Whole-cell assays were used to screen FDA-approved drugs to identify novel antimicrobial agents active against bacterial pathogens. Following identification of nitazoxanide, its various characteristics, such as antimicrobial activity against MDR isolates, time–kill kinetics, ability to synergize with approved drugs, antibiofilm activity and ability to generate resistance in Staphylococcus aureus, were determined, followed by determination of its in vivo potential against MDR S. aureus. Results Nitazoxanide demonstrated a potent in vitro antistaphylococcal profile, including equipotent activity against clinical drug-resistant S. aureus and Enterococcus spp. Nitazoxanide exhibited concentration-dependent killing, significantly eradicated preformed S. aureus biofilm and S. aureus did not generate resistance to it. Nitazoxanide strongly synergized with linezolid both in vitro and in vivo against linezolid-susceptible and -resistant S. aureus, displaying superior activity to untreated control and drug-alone treatment groups. Conclusions Nitazoxanide can be utilized in combination with linezolid against infections caused by linezolid-resistant S. aureus as it exhibits strong synergism in vitro and in vivo.

A series of donor-acceptor pyranones (3a-m, 4a-h) were synthesized using α-oxo-ketene- S, S-acetal as the synthon for their application as emissive materials for energy-saving organic light-emitting devices (OLEDs). Among them, five pyranones 3f, 3g, 3h, 3m, and 4e exhibited highly bright fluorescence in the solid state and weak or no emission in the solution state. Photophysical analysis of these dyes revealed that only 3f and 3m showed aggregation-induced emission behavior in a THF/water mixture (0-99%) with varying water fractions ( fw) leading to bright fluorescence covering the entire visible region, while other derivatives 3g, 3h, and 4e did not show any fluorescence signal. The computational studies of the compounds revealed that the longer wavelength absorption originates from HOMO to LUMO electronic excitation. These dyes exhibited good thermal stability with 5% weight loss temperature in the range of 218-347 °C. The potential application of the donor-acceptor pyranone dyads was demonstrated by fabrication of solution-processed OLEDs. Remarkably, OLED devices prepared using highly emissive compounds 6-(anthracen-9-yl)-4-(methylthio)-2-oxo-2 H-pyran-3-carbonitrile (3m) and 6-(4-methoxyphenyl)-4-(methylthio)-2-oxo-2 H-pyran-3-carbonitrile (3f) displayed pure white emission with CIE coordinates of (0.29, 0.31) and (0.32, 0.32), respectively. Additionally, the resultant devices exhibited external quantum efficiencies of 1.9 and 1.2% at 100 cd m-2, respectively.

A new dual responsive "turn-on" and "ratiometric" aggregation-induced emission luminogen (AIEgen) 3-formyl-5-(piperidin-1-yl)biphenyl-4-carbonitrile 6 a (FPBC 6 a) for selective detection of hydrazine in solution as well as in vapour phase is described. At a low concentration of 2.5 μm, the probe FPBC 6 a is non-fluorescent (turn-off) but remarkably lights up (turn-on with blue emission) in the presence of hydrazine solution (0.25-25 μm). Interestingly, at higher concentrations, the nanoaggregates of FPBC 6 a (>25 μm, 99 % HEPES in DMSO) displayed ratiometric response in the presence of hydrazine with a remarkable hypsochromic shift from the green (500-550 nm) to blue regions (440-480 nm). Furthermore, a real application of FPBC 6 a was successfully demonstrated through the detection and visualization of hydrazine in live cervical cancer cells as well as using portable test strips.

Luminescent carbon quantum dots (CQDs) prepared from aqueous beetroot extract were developed as unique fluorescent nanomaterials for in vivo live animal imaging applications. Blue (B) and green (G) emitting environmentally benign CQDs (particle size of 5 nm and 8 nm, respectively) exhibited bright fluorescence in aqueous medium and were found to be biocompatible, photostable and non-toxic in animal models. The in vivo imaging and toxicity evaluation of both CQDs were performed for the first time in the Caenorhabditis elegans (C. elegans) model, which revealed consistent fluorescence in the gut tissues of the worms without exerting any sign of toxic effects on the nematodes. The in vivo bio-distribution of G-CQDs given by tail vein injection in live BALB/c mice showed optical signals in the lower abdominal regions, mainly in the intestine, and cleared from the body through faeces. The tremendous potential shown by these eco-friendly CQDs in the C. elegans and mice models advocates new hopes for greener CQD nanomaterials as diagnostic tools in the biomedical field.

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 μmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388. ispartof: CANADIAN MEDICAL ASSOCIATION JOURNAL vol:191 issue:9 pages:E247-E256 ispartof: location:Canada status: published

Background: Myxoid and round cell liposarcomas (RCL) are low and high-grade counterparts of a common subtype of liposarcomas (LPS), representing a histologic continuum. Aims: The aim was to study the cytomorphology of hypercellular RCL and to look for features that differentiate RCL from other sarcomas displaying round cells with myxoid change. Materials and Methods: Eight cases of hypercellular RCL were identified retrospectively in which round cell component constituted greater than 75% of the area. Cytomorphological features were studied in detail. Results: Four cases were predominantly composed of round cells, out of which 2 were entirely composed of round cells. Myxoid metachromatic stroma was absent in 2 cases, while it was present in ample amounts in the remaining 6 cases. Spindle cells were completely absent in 5 cases and lipoblasts were observed in a single case of RCL. Plexiform vascular capillaries were seen in 4 cases. Adherence of neoplastic round cells around thin capillaries (ANAC) was observed in 7 cases. Conclusions: Plexiform capillary plexus and ANAC should be separately evaluated. The latter feature is the most consistent one, and is an important clue to the adipocytic nature of the neoplasm when hypercellular round cell areas are aspirated. Confident diagnosis of hypercellular RCL can be made on the basis of this feature. Lipoblasts, although specific, are seen in few cases. The rest of the features are nonspecific and useful only in combination.

The diagnosis and prognosis of the disease associated with lipid irregularity are areas of extreme significance. In this direction, fluoranthene based yellow fluorescent probes (FLUN-550, FLUN-552, FLUN-547) were designed and synthesized by conjugating the ethanolamine headgroup of the phospholipid phosphatidyl-ethanolamine present in biological membranes. Owing to unique photophysical properties and aqueous compatibility, these probes were successfully employed for staining lipid droplets (LDs) in preadipocytes and Leishmania donovani promastigotes. Furthermore, using the fluorescent probes FLUN-550 and FLUN-552 we successfully imaged and quantitatively detected the excess accumulation of lipids in a liver section of Plasmodium yoelii MDR infected mice (3- to 4-fold) and the tissue sections of third stage human cervical cancer patients (1.5- to 2-fold) compared to normal tissues. To the best of our knowledge, this is the first report of yellow fluorescent probes for imaging and quantitative detection of LDs in human cervical cancer tissues. These new yellow fluorescent lipid probes (FLUN-550 and FLUN-552) showed great potential for diagnosis of cervical cancer patients.

Objectives: To compare the efficacy and tolerability of losartan, telmisartan, and olmesartan as antihypertensive agents and evaluate and compare their effects on lipid profile and blood glucose. Materials and Methods: This was a randomized, open-label, parallel-group, comparative study conducted in sixty patients of Stage I hypertension. The eligible patients were randomly allocated into three treatment groups: (1) Tablet olmesartan (20 mg), (2) Tablet telmisartan (40 mg), and (3) Tablet losartan (50 mg). Blood pressure (BP) was assessed at an interval of 2 weeks for 3 months. Fasting blood glucose (FBG) and lipid profile were estimated at baseline and then at 12 weeks. Results: Olmesartan and telmisartan were more efficacious than losartan in reducing diastolic BP (DBP). There was a statistically significant decrease in mean blood glucose level (P < 0.02) after 12 weeks of treatment in telmisartan group when compared to baseline. Serum total cholesterol, triglycerides, and low-density lipoproteins decreased significantly after 12-week treatment with olmesartan and telmisartan. Conclusions: The most efficacious drug in reducing BP is Olmesartan whereas telmisartan and losartan show equal efficacy. Telmisartan shows the most favorable effects on FBG and lipid profile.

Background Achieving and maintaining hemostasis in neurosurgical procedures is critical to the outcome and challenging especially in cases of coagulopathy with diffuse oozing. After trauma to the brain, a cascade of events initiated by tissue factor (TF) or thromboplastin results in a defective coagulation process that even may lead to disseminated intravascular coagulation (DIC). Fibrin glue is sealant made up of fibrinogen and thrombin used for dural defect repair at the base, convexity, anastomosis of the nerve and nerve graft, reinforcing microvascular anastomosis. This study was carried out to determine the hemostatic effect of human fibrin glue on bleeding surface of brain and compare the effect with conventional methods of hemostasis. Method Thirty (30) white rats (Rattus novergicus) were divided equally into study and control group. After craniotomy and dural opening a stab incision was made on right frontal region of brain. In case group the bleeding was controlled with fibrin glue (average 0.5 ml) and in control group conventional method of hemostasis (cautery, cottonoid patty, and saline wash, surgicel) was used. Both the groups were studied for bleeding time, seizure, neurological deficit, wound complications and mortality. Results Outcome was assessed as 1) Bleeding in both the groups 2) Complications in both the groups. It was observed that in study group the time taken in hemostasis was significantly less in comparison to the control, No significant difference in the post procedure clinical outcome and inflammatory reaction/gliosis reaction was found in both the groups. Conclusion Human fibrin glue is simple, easy and safe alternative to conventional methods of hemostasis.

Background Esthesioneuroblastoma (ENB) is a rare and aggressive malignant tumor arising from olfactory epithelium. Surgical excision in the form of craniofacial surgical resection (CFR) has shown encouraging results. The purpose of the study is to analyze the outcome of this disease when managed by non-craniofacial resection (NCFR) surgery in limited resources. Methods Between October 1998 and January 2004, eight patients with ENB were treated in the Department of Radiotherapy at KGMU, Lucknow. None of these eight patients underwent CFR surgery. All patients received six cycles of vincristine, adriamycin and cyclophosphamide (VAC) based chemotherapy followed by radiotherapy. Results All the patients registered during this period had undergone operative procedures in the form of NCFR surgery except two. Complete response was present in five (62.5%) patients and three (37.5%) patients had partial response. Locoregional relapse-free survival at 3 years was 62.5% and median survival time was 38 months. Disease-free survival and overall survival at 3 years was 72.9 and 71.4%, respectively, and median disease-free survival time was 43 months, while mean overall survival time was 40.7 months as median overall survival time was not reached. Conclusion Patients in developing countries often present with advanced stages and because of non-availability of technical advances and surgical expertise one tends to approach these patients with palliative intent. Most of the patients in our series were of stage C disease (75%) and still our response rate and survival were encouraging despite the fact that surgery was not optimal. This combination chemoradiotherapy schedule can be used outside the protocol setting where resources are limited.

Objective The aim of the present study was to define the prognostic impact of nodal density (ND) and total tumor volume along with many other tumor, treatment and patient related variables using the late chemo-intensification treatment regimen with conventionally fractionated radiotherapy (70 Gy/7 weeks). Methods A total of 74 patients with Stage III and IV biopsy proven squamous cell carcinoma of oropharynx, hypopharynx and larynx were treated with this regimen. ND and total tumor volume was measured on high resolution CT scans for all the patients. Chemotherapy consisted of continuous infusion of 5 FU at 350 mg/m(2)/day and cisplatin as 1 h infusion at 10 mg/m(2)/day on days 1-5 of week 6 and 7 of radiotherapy. Results Grade III mucositis was present in 48 (64.9%) patients. Overall complete response rate was 77%. At 28 months, locoregional relapse-free survival (LRFS), overall survival (OS) and distant metastases-free survival (DMFS) was 70.8%, 66.9% and 81.9%, respectively. In the final multivariate Cox-regression model tumor stage, ND, primary site and nodal stage were independent variables predicting for LRFS. Similarly AJCC group staging, ND and total treatment volume were found to have significant impact, independently over LRFS. Conclusions There is tremendous variation in terms of ND and total tumor volume within AJCC nodal staging and tumor staging, respectively. ND had significant impact over LRFS and OS. Future phase III trial may need stratification on the basis of these variables.

Gorlin-Goltz syndrome is a rare autosomal-dominant syndrome related to mutation in " Patched" tumour suppressor gene on chromosome 9. Basocellular carcinomas, odontogenic keratocysts, palmar and/or plantar pits and ectopic calcifications of the falx cerebri are its major features, along with more than 100 minor features. Odontogenic cysts, notorious for recurrence, can make endotracheal intubation difficult, requiring modification of the standard intubation technique. We report such a case managed successfully by awake fibreoptic intubation. Direct laryngoscopy under anaesthesia later confirmed that it was a good decision.

Partial exchange transfusion during cardiopulmonary bypass, while conducting cardiac surgery may be a useful technique in patients with high level of sickle hemoglobin. Along with this preoperative use of hydroxyurea and alternative analgesic modalities such as transcutaneous electrical nerve stimulation in postoperative period may be beneficial, in our opinion. A 16-year-old female of Turner's syndrome having sickle cell anemia scheduled for closure of arterial septal defect on cardiopulmonary bypass was managed with partial exchange transfusion and warm cardioplegia.

The hazards of hydrogen peroxide have been known for long time, but it is still widely used in our country for irrigation of wounds. We report a case of oxygen embolism when hydrogen peroxide was accidently infiltrated subcutaneously along with local anesthetic during spine surgery and was successfully managed. We discuss the possible mechanism for embolism and its management. We also want to emphasize on the importance of being vigilant and avoiding such mistakes.