Rationale and design of the TUXEDO-2 India study: Ultra-Thin strUt Supraflex Cruz versus XiencE in a Diabetic pOpulation with multi-vessel disease-2.

BACKGROUND: The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease. AIMS: The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events. METHODS: In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%. CONCLUSIONS: The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

Peer Learning Program Metrics: A Pediatric Neuroradiology Example.

BACKGROUND AND PURPOSE: The American College of Radiology is now offering an accreditation pathway for programs that use peer learning. Here, we share feasibility and outcome data from a pilot peer learning program in a pediatric neuroradiology section that, in its design, follows the American College of Radiology peer learning accreditation pathway criteria. MATERIALS AND METHODS: We retrospectively reviewed metrics from a peer learning program with 5 participating full-time pediatric neuroradiologists during 1 year: 1) number of cases submitted, 2) percentage of radiologists meeting targets, 3) monthly attendance, 4) number of cases reviewed, 5) learning points, and 6) improvement actions. In addition, a faculty survey was conducted and is reported here. RESULTS: Three hundred twenty-four cases were submitted (mean, 7 cases/faculty/month). The faculty never met the monthly submission target. Peer learning meeting attendance was 100%. One hundred seventy-nine cases were reviewed during the peer learning meetings. There were 22 learning points throughout the year and 30 documented improvement actions. The faculty survey yielded the highest ratings (4.8 of 5) for ease of meeting the 100% attendance requirement and for the learning value of the peer learning sessions. The lowest rating (4.2 of 5) was given for the effectiveness of improvements as a result of peer learning discussions. CONCLUSIONS: Implementing a peer learning program that follows the American College of Radiology peer learning accreditation pathway criteria is feasible. Program metric documentation can be time-consuming. Participant feedback led to meaningful program improvement, such as improving trust, expanding case submission categories, and delegating tasks to administrative staff. Effort to make peer learning operations more efficient and more effective is underway.

Salivary Flow Rate, pH, Buffering Capacity, Total Protein, Oxidative Stress and Antioxidant Capacity in Children with and without Dental Caries.

OBJECTIVES: To measure and compare the levels of salivary flow rate, pH, buffering capacity, total protein, malondialdehyde (MDA) and total antioxidant capacity (TAC) between caries active and caries free children and to study the correlation between the DMFS/dfs score and above salivary parameters in caries active children. STUDY DESIGN: 50 caries active (DMFS/dfs ≥ 5) and 50 caries free (DMFS/dfs = 0) children aged between 6 to 12 years were included in the study. From all the children, unstimulated, mid-morning saliva samples were collected and salivary flow rate was calculated. Salivary pH, buffering capacity, total protein, MDA and TAC were measured. RESULTS: The mean levels of salivary flow rate, pH, buffering capacity were significantly decreased (p < 0.05) and total protein, MDA and TAC were significantly increased (p < 0.05) in caries active children when compared to caries free controls. There was a proportionate decrease (p < 0.05) in salivary flow rate, pH and buffering capacity and proportionate increase (p > 0.05) in salivary total protein, MDA and TAC as DMFS/dfs score increased in caries active children. CONCLUSIONS: Significant alteration in the levels of salivary flow rate, pH, total proteins, MDA and TAC and their correlation with DMFS/dfs score in caries active children suggest, the levels of these physico-chemical properties of saliva can act as strong indicators of caries status in children.

Significance of micronuclei in buccal smears of mobile phone users: A comparative study.

AIMS AND OBJECTIVES: The present study was designed to evaluate the frequency of micronuclei (MN) in the buccal exfoliated cells of mobile phone users. In addition, comparison of MN frequency between high and low mobile phone users was also done. MATERIALS AND METHODS: A total of 30 male and 30 female participants between the age group of 20-28 years were selected from the Outpatient Department of Navodaya Dental College and Hospital, Raichur, Karnataka. The participants were divided into two groups: Group A - low mobile phone users and Group B - high mobile phone users. Cell sampling and preparation was done on the slide. All the slides were observed for a total of 1000 cells for the presence and number of MN in each cell. RESULTS: There was a significant increase in the mean MN count in Group B in comparison to the Group A. There was highly significant difference in the mean MN count of participants using (code division multiple access) CDMA than (global system for mobiles) GSM mobile phones. The MN mean count was found to be significantly increased in nonheadphone users in comparison to headphone users. In Group B, the MN count on the side of mobile phone use was found to be statistically significantly elevated in comparison to the opposite side. CONCLUSION: Mobile phone radiation even in the permissible range when used for longer duration can cause significant genotoxicity. The genotoxicity accentuates when mobile phones are frequently used on the same side which may be due to more amount of radiation and increase in the temperature. Headphone usage reduces the genotoxicity of mobile phone radiation to some extent.

Comparative Study of Probiotic Ice Cream and Probiotic Drink on Salivary Streptococcus mutans Levels in 6-12 Years Age Group Children.

BACKGROUND: Dental caries is one of the most common health problems in the world. Probiotics are one the various preventive methods to reduce dental caries. The aim of this study is to compare the effectiveness of probiotic ice cream and drink on salivary Streptococcus mutans levels in children of 6-12 years age group. MATERIALS AND METHODS: A three phase study was carried out in children (n = 50) of 6-12 years age with zero decayed missing filled teeth (dmft)/DMFT. They were randomly divided into two equal groups. Saliva samples were collected before the consumptions of probiotic ice cream and probiotic drink. Colony count obtained was recorded as baseline data. For both groups probiotic ice cream and drink was given randomly for 7 days and a washout period of 90 days were given and then the saliva samples were collected and colony counting was done. RESULTS: Statistical analysis was performed using Student's paired t-test and multiple comparisons by Tukey's honest significant difference test which showed, there is a significant reduction in salivary S. mutans level in both groups after 7 days period. However, after washout period only probiotic ice cream showed reduction whereas drink did not. Also, there was no significant difference between probiotic ice cream and drink. CONCLUSION: Probiotic organisms definitely have a role in reducing the salivary S. mutans level and ice cream would be a better choice than drink. However, the prolonged use of the agents and their effects on caries is still to be determined.

Sleeve gastrectomy for gastric band failures - a prospective study.

BACKGROUND: We prospectively evaluated the feasibility and efficacy of a strategy of performing concomitant laparoscopic band removal and sleeve gastrectomy on all-comers who had a failed laparoscopic adjustable gastric band (LABG) and analysed the impact of the reason for revision surgery on outcomes. METHODS: Over a two-year period, 23 patients who previously had LAGB insertion were referred for revision surgery. Of this cohort, three patients elected to undergo band removal alone. Of the remaining 20 patients, 10 presented with weight regain and 10 presented with pathological symptoms secondary to band migration (band complication group). All patients were listed for simultaneous LABG removal and sleeve gastrectomy and the outcomes of the two groups analysed. RESULTS: Simultaneous band removal and sleeve gastrectomy was achieved in all cases of weight regain and in 7 cases of band complications. There were no complications in the weight regain group and three major morbidities in the band complication group. At the time of revision, the mean body mass index was 40.3 ± 1.5; however at a mean follow-up period of 2.2 ± 0.28 years the mean BMI of the cohort had fallen to 35.9 ± 1.4. The mean BMI was significantly lower in the band complication group (p = 0.03). CONCLUSIONS: Gastric band removal and revision sleeve gastrectomy following failed LABG is feasible as a single-stage procedure with good outcomes. The optimum peri-operative results of this approach are seen in patients with weight regain whilst the longer term outcomes are superior in those with band complications.

Large Scale Solid Phase Synthesis of Peptide Drugs: Use of Commercial Anion Exchange Resin as Quenching Agent for Removal of Iodine during Disulphide Bond Formation.

The S-acetamidomethyl (Acm) or trityl (Trt) protecting groups are widely used in the chemical synthesis of peptides that contain one or more disulfide bonds. Treatment of peptides containing S-Acm protecting group with iodine results in simultaneous removal of the sulfhydryl protecting group and disulfide formation. However, the excess iodine needs to be quenched or adsorbed as quickly as possible after completion of the disulfide bond formation in order to minimize side reactions that are often associated with the iodination step. We report here a simple method for simultaneous quenching and removal of iodine and isolation of disulphide bridge peptides. The use of excess inexpensive anion exchange resin to the oxidized peptide from the aqueous acetic acid/methanol solution affords quantitative removal of iodine and other color impurities. This improves the resin life time of expensive chromatography media that is used in preparative HPLC column during the purification of peptide using preparative HPLC. Further, it is very useful for the conversion of TFA salt to acetate in situ. It was successfully applied commercially, to the large scale synthesis of various peptides including Desmopressin, Oxytocin, and Octreotide. This new approach offers significant advantages such as more simple utility, minimal side reactions, large scale synthesis of peptide drugs, and greater cost effectiveness.

Fluorescent dye encapsulated ZnO particles with cell-specific toxicity for potential use in biomedical applications.

Fluorescein isothiocyanate (FITC)-encapsulated SiO(2) core-shell particles with a nanoscale ZnO finishing layer have been synthesized for the first time as multifunctional "smart" nanostructures. Detailed characterization studies confirmed the formation of an outer ZnO layer on the SiO(2)-FITC core. These approximately 200 nm sized particles showed promise toward cell imaging and cellular uptake studies using the bacterium Escherichia coli and Jurkat cancer cells, respectively. The FITC encapsulated ZnO particles demonstrated excellent selectivity in preferentially killing Jurkat cancer cells with minimal toxicity to normal primary immune cells (18% and 75% viability remaining, respectively, after exposure to 60 microg/ml) and inhibited the growth of both gram-positive and gram-negative bacteria at concentrations > or =250-500 microg/ml (for Staphylococcus aureus and Escherichia coli, respectively). These results indicate that the novel FITC encapsulated multifunctional particles with nanoscale ZnO surface layer can be used as smart nanostructures for particle tracking, cell imaging, antibacterial treatments and cancer therapy.

Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles.

Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells ( approximately 28-35x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity.

Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems.

We report on the toxicity of ZnO nanoparticles (NPs) to gram-negative and gram-positive bacterial systems, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and primary human immune cells. ZnO NP (~13 nm) showed complete inhibition of E. coli growth at concentrations 3.4 mM, whereas growth of S. aureus was completely inhibited for 1 mM. Parallel experiments using flow cytometry based assays clearly demonstrated that growth inhibitory properties of ZnO NP were accompanied by a corresponding loss of cell viability. Identical ZnO NP had minimal effects on primary human T cell viability at concentrations toxic to both gram-negative and gram-positive bacteria. Collectively, these experiments demonstrate selectivity in the toxic nature of ZnO NP to different bacterial systems and human T lymphocytes. Developing selective toxicity to biological systems and controlling it by NP design could lead to biomedical and antibacterial applications.

Effect of Co doping on the structural, optical and magnetic properties of ZnO nanoparticles.

We report the results of a detailed investigation of sol-gel-synthesized nanoscale Zn(1-x)Co(x)O powders processed at 350 °C with 0≤x≤0.12 to understand how the structural, morphological, optical and magnetic properties of ZnO are modified by Co doping, in addition to searching for the theoretically predicted ferromagnetism. With x increasing to 0.03, both lattice parameters a and c of the hexagonal ZnO decreased, suggesting substitutional doping of Co at the tetrahedral Zn(2+) sites. For x>0.03, these trends reversed and the lattice showed a gradual expansion as x approached 0.12, probably due to additional interstitial incorporation of Co. Raman spectroscopy measurements showed a rapid change in the ZnO peak positions for x>0.03, suggesting significant disorder and changes in the ZnO structure, in support of additional interstitial Co doping possibility. Combined x-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance spectroscopy, photoluminescence spectroscopy and diffuse reflectance spectroscopy showed clear evidence for tetrahedrally coordinated high-spin Co(2+) ions occupying the lattice sites of ZnO host system, which became saturated for x>0.03. Magnetic measurements showed a paramagnetic behaviour in Zn(1-x)Co(x)O with increasing antiferromagnetic interactions as x increased to 0.10. Surprisingly, a weak ferromagnetic behaviour was observed for the sample with x = 0.12 with a characteristic hysteresis loop showing a coercivity H(c)∼350 Oe, 25% remanence M(r), a low saturation magnetization M(s)∼0.04 emu g(-1) and with a Curie temperature T(c)∼540 K. The XPS data collected from Zn(1-x)Co(x)O samples showed a gradual increase in the oxygen concentration, changing the oxygen-deficient undoped ZnO to an excess oxygen state for x = 0.12. This indicates that such high Co concentrations and appropriate oxygen stoichiometry may be needed to achieve adequate ferromagnetic exchange coupling between the incorporated Co(2+) ions.

Identification and evaluation of antioxidant, analgesic/anti-inflammatory activity of the most active ninhydrin-phenol adducts synthesized.

Treatment of phenols with ninhydrin in acidic medium afforded 2-hydroxy-2-(ortho-hydroxy-phenyl/naphthyl)-1,3-dioxoindanes, which being unstable were isolated in their hemiketal forms. These synthesized compounds were subjected to TLC screening for radical scavenging and in vitro lipoxgenase and cycloxygenase enzyme inhibition assays. The best compound was identified and studied in detail for steady-state and time-resolved free radical kinetics, viz., DPPH, ABTS(-), *OH and rate constants for these reactions were evaluated. The best compound was also subjected to in vivo anti-inflammatory and analgesic activities in which the compound showed good promise for further structural optimization.

Carrier-controlled ferromagnetism in transparent oxide semiconductors.

The search for an ideal magnetic semiconductor with tunable ferromagnetic behaviour over a wide range of doping or by electrical gating is being actively pursued as a major step towards realizing spin electronics. A magnetic semiconductor having a high Curie temperature, capable of independently controlled carrier density and magnetic doping, is crucial for developing spin-based multifunctional devices. Cr-doped In(2)O(3) is such a unique system, where the electrical and magnetic behaviour-from ferromagnetic metal-like to ferromagnetic semiconducting to paramagnetic insulator-can be controllably tuned by the defect concentration. An explicit dependence of magnetic interaction leading to ferromagnetism on the carrier density is shown. A carrier-density-dependent high Curie temperature of 850-930 K has been measured, in addition to the observation of clear magnetic domain structures in these films. Being optically transparent with the above optimal properties, Cr-doped In(2)O(3) emerges as a viable candidate for the development of spin electronics.

The facile flow-injection spectrophotometric detection of gold(III) in water and pharmaceutical samples using 3,5-dimethoxy-4-hydroxy-2-aminoacetophenone isonicotinoyl hydrazone (3,5-DMHAAINH).

A simple, sensitive and rapid flow-injection spectrophotometric method was developed for the determination of trace amounts of Au(III) in aqueous dimethylformamide (DMF). The method is based on formation of Au(III)-(3,5-DMHAAINH)3 complex. The optimum conditions for the chromogenic reaction of Au(III) with 3,5-DMHAAINH is studied and the colored (reddish brown) complex is selectively monitored at lambda(max) 490 nm at pH 6.0. The reaction and flow conditions of the full experimental design were optimized. The detection limit (2 s) of 0.1 microg l-1 Au(III) was obtained at a sampling rate of 15 samples h-1. Beer's law is obeyed over the range of 0.30-4.00 microg ml-1. The molar absorptivity and Sandell's sensitivity were 3.450x10(4) M and 0.0050 microg ml-1, respectively. Job's method of continuous variation and stability constants corresponding to these maxima was determined and found to be 9.3x10(15) (1:3, M:R) (M, metal; R, reagent). The detailed study of various interferences confirmed the high selectivity of the developed method. The method was successfully applied for the determination of trace amount of Au(III) in water and pharmaceutical samples. The results obtained were in agreement with the reported methods at the 95% confidence level.

Hyperplastic polyps and serrated adenomas: colonoscopic surveillance?

Hyperplastic polyps are not thought to carry a malignant potential. They are, therefore, not regularly screened by the majority of clinicians. We present two case reports of serrated adenomas that add to a small but expanding body of clinical and histological evidence that suggests a hyperplastic to neoplastic pathway. Regular colonoscopic surveillance may be indicated in at least some cases of hyperplastic polyposis

Production of biodegradable plastics from activated sludge generated from a food processing industrial wastewater treatment plant.

Most of the excess sludge from a wastewater treatment plant (60%) is disposed by landfill. As a resource utilization of excess sludge, the production of biodegradable plastics using the sludge has been proposed. Storage polymers in bacterial cells can be extracted and used as biodegradable plastics. However, widespread applications have been limited by high production cost. In the present study, activated sludge bacteria in a conventional wastewater treatment system were induced, by controlling the carbon: nitrogen ratio to accumulate storage polymers. Polymer yield increased to a maximum 33% of biomass (w/w) when the C/N ratio was increased from 24 to 144, where as specific growth yield decreased with increasing C/N ratio. The conditions which are required for the maximum polymer accumulation were optimized and are discussed.

Postoperative stay following colorectal surgery: a study of factors associated with prolonged hospital stay.

AIM: To study the factors that contribute to postoperative stay following colorectal surgery. DESIGN: A prospective observational study. SETTING: Three colorectal surgical units - a teaching hospital, a large district general hospital and a district general hospital. PARTICIPANTS: 350 patients undergoing colorectal surgery. MAIN OUTCOME MEASURES: 28 pre-, peri- and postoperative patient- and treatment-related factors. RESULTS: Stepwise regression analysis suggests that the factors that significantly lengthen postoperative stay include a low albumin on admission, stoma formation, operative blood loss, urinary and respiratory complications, wound infections, postoperative ventilation and social delay at the time of discharge. The postoperative stay was not affected by patient age or by the seniority of the surgical team. CONCLUSIONS: Factors have been identified that determine the postoperative length of stay. These data may allow better planning and treatment of patients undergoing colorectal surgery.

16(R)-hydroxyeicosatetraenoic acid, a novel cytochrome P450 product of arachidonic acid, suppresses activation of human polymorphonuclear leukocyte and reduces intracranial pressure in a rabbit model of thromboembolic stroke.

OBJECTIVE: Activated polymorphonuclear leukocytes (PMNs) have been suggested to contribute to the development of increased intracranial pressure (ICP). We recently demonstrated that human PMNs produce a novel cytochrome P450-derived arachidonic acid metabolite, 1 6(R)-hydroxyeicosatetraenoic acid [16(R)-HETE], that modulates their function. It was thus of interest to examine this novel mediator in an acute stroke model. METHODS: 16-HETE was assessed initially in a variety of human PMN and platelet in vitro assays and subsequently in an established rabbit model of thromboembolic stroke. A total of 50 rabbits completed a randomized, blinded, four-arm study, receiving 16(R)-HETE, tissue plasminogen activator, both, or neither. Experiments were completed 7 hours after autologous clot embolization. The primary end point for efficacy was the suppression of increased ICP. RESULTS: In in vitro assays, 16(R)-HETE selectively inhibited human PMN adhesion and aggregation and leukotriene B4 synthesis. In the thromboembolic stroke model, animals that received 16(R)-HETE demonstrated significant suppression of increased ICP (7.7 +/- 1.2 to 13.1 +/- 2.7 mm Hg, baseline versus final 7-h time point, mean +/- standard error), compared with either the vehicle-treated group (7.7 +/- 0.9 to 15.8 +/- 2.6 mm Hg) or the tissue plasminogen activator-treated group (7.6 +/- 0.6 to 13.7 +/- 2.1 mm Hg). The group that received the combination of 16(R)-HETE plus tissue plasminogen activator demonstrated no significant change in ICP for the duration of the protocol (8.6 +/- 0.6 to 11.1 +/- 1.2 mm Hg). CONCLUSION: 16(R)-HETE suppresses the development of increased ICP in a rabbit model of thromboembolic stroke and may serve as a novel therapeutic strategy in ischemic and inflammatory pathophysiological states.