Bicyclic (alkyl)(amino)carbene (BICAAC) as a metal-free catalyst for reduction of nitriles to amines.

Bicyclic (alkyl)(amino)carbene (BICAAC) is introduced as a metal-free catalyst for the reduction of various nitriles to the corresponding amine hydrochloride salts in the presence of pinacolborane. Mechanistic investigations combining experiments and DFT calculations suggest a B-H addition to the carbene center, which acts as a carrier of the hydride source.

Is the Management of Rectal Cancer Using a Watch and Wait Approach Feasible, Safe and Effective in a Publicly Funded General Hospital?

AIMS: Although there is emerging evidence to suggest equivalent oncological outcomes using a watch and wait approach compared with primary total mesorectal excision surgery, there is a paucity of evidence about the safety and efficacy of this approach in routine clinical practice. Here we report the long-term outcomes and quality of life from patients managed with watch and wait following a clinical complete response (cCR) to neoadjuvant therapy. MATERIALS AND METHODS: Patients with adenocarcinoma of the rectum with cCR following neoadjuvant therapy managed using watch and wait were retrospectively identified. Demographic data, performance status, pretreatment staging information, oncological and surgical outcomes were obtained from routinely collected clinical data. Quality of life was measured by trained clinicians during telephone interviews. RESULTS: Over a 7-year period, 506 patients were treated for rectal cancer, 276 had neoadjuvant therapy and 72 had a cCR (26.1%). Sixty-three were managed with watch and wait. Thirteen patients had mucosal regrowth. There was no significant difference in the incidence of metastatic disease between the surgical and watch and wait cohorts (P = 0.38). The 13 patients with mucosal regrowth underwent salvage surgery. Eleven of the patients who underwent surgical resection had R0 resections. There was also a statistically and clinically significant improvement in the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) trial outcome index (P = 0.022). CONCLUSION: This study shows that watch and wait is safe and effective outside of tertiary referral centres. It suggests that an opportunistic cCR is durable and when mucosal regrowth occurs it can be salvaged. Finally, we have shown that quality of life is probably improved if a watch and wait approach is adopted.

Bicyclic (alkyl)(amino)carbene stabilized zinc(0) complex with singlet biradicaloid ground state.

A storable bicyclic (alkyl)(amino)carbene (BICAAC) stabilized two coordinate zinc(0) complex [(BICAAC)2Zn] (2) was synthesized. DFT calculations reveal that BICAAC plays a decisive role in imparting the stability to 2. This complex activates the C(sp3)-Cl bond of trityl chloride generating the Gomberg's free radical with greater efficiency than metallic Zn powder.

A Bottleable Imidazole-Based Radical as a Single Electron Transfer Reagent.

Reduction of 1,3-bis(2,6-diisopropylphenyl)-2,4-diphenyl-1H-imidazol-3-ium chloride (1) resulted in the formation of the first structurally characterized imidazole-based radical 2. 2 was established as a single electron transfer reagent by treating it with an acceptor molecule tetracyanoethylene. Moreover, radical 2 was utilized as an organic electron donor in a number of organic transformations such as in activation of an aryl-halide bond, alkene hydrosilylation, and in catalytic reduction of CO2 to methoxyborane, all under ambient temperature and pressure.

Mandatory surveillance and outbreaks reporting of the WHO priority pathogens for research & discovery of new antibiotics in European countries.

OBJECTIVES: In 2017 the WHO published a global priority list of 12 antibiotic-resistant bacteria (ARB) in urgent need of new antibiotics. We aimed to identify and assess publicly accessible mandatory surveillance systems and outbreaks reporting for these pathogens in the 28 European Union and four European Free Trade Association member states. METHODS: Compulsory reporting was mapped by reviewing national documents without applying language restrictions and through expert consultation. Information on surveillance targets, indicators, metrics and dissemination modalities was extracted and a qualitative assessment was performed for open access systems only. RESULTS: Twenty-one countries (66%) had a mandate to survey at least one among the 12 WHO priority pathogens; 15 provided access to surveillance frameworks. These systems covered most frequently carbapenem-resistant Enterobacteriales (12; 38%), methicillin-resistant Staphylococcus aureus (12; 38%), and vancomycin-resistant enterococci (8; 25%). None of the European countries required reporting of resistance in Salmonella, Campylobacter, Helicobacter pylori and Neisseria gonorrhoeae. High heterogeneity was observed in data collection, reporting and dissemination among countries with clinical outcomes and risk factors being reported in less than half (22% and 25%). Only six countries (19%) implemented mandatory surveillance of outbreaks due to at least one WHO priority pathogen. CONCLUSIONS: Our review shows that despite the increasing burden of ARB on the European population, very few countries implemented mandatory surveillance and outbreak reporting of the WHO priority pathogens. International efforts are needed to define the effectiveness of implementing mandatory reporting of these pathogens and to assess their role in reducing the spread of ARB in health-care and community settings.

NHC-catalyzed silylative dehydration of primary amides to nitriles at room temperature.

Herein we report an abnormal N-heterocyclic carbene catalyzed dehydration of primary amides in the presence of a silane. This process bypasses the energy demanding 1,2-siloxane elimination step usually required for metal/silane catalyzed reactions. A detailed mechanistic cycle of this process has been proposed based on experimental evidence along with computational study.

Electrochemical behavior of polypyrrole/chitosan composite coating on Ti metal for biomedical applications.

In the present work, the corrosion resistance performance and biocompatibility of polypyrrole/chitosan (PPy/CHI) composite coated Ti was studied. The deposition of composite coating was carried out by electropolymerization method. The deposited PPy/CHI composite coatings were different in morphology, structural, surface roughness and wettability compared PPy coated Ti. The presence of composite coating was confirmed by solid 13C NMR. The PPy/CHI composite coating showed enhanced microhardness and adhesion strength compared to the PPy coating. The corrosion protection ability of PPy/CHI composite coatings at various applied potentials was analyzed by dynamic electrochemical impedance spectroscopy (DEIS), exhibited higher impedance in all the potentials compared to uncoated and PPy coated Ti. The lower corrosion current density obtained for PPy/CHI-2 composite coating from polarization studies revealed increased corrosion protection ability in SBF solution. The stability of composite coating was confirmed by immersion studies. PPy/CHI-2 composite coating immersed in SBF solution enhances hydroxyapatite (HAp) formation.

Purulent myositis of the thigh as a presentation of perforated low rectal cancer.

Purulent myositis is an acute, intramuscular bacterial infection involving abscess formation most commonly affecting the quadriceps, hamstring and gluteal muscles. We present a case of extensive purulent myositis of the thigh and lower leg caused by bowel perforation below the peritoneal reflection secondary to rectal cancer. Cases of lower limb and perineal purulent myositis should raise suspicion of rectal perforation and should prompt investigations to exclude rectal malignancy.

The methodology of surveillance for antimicrobial resistance and healthcare-associated infections in Europe (SUSPIRE): a systematic review of publicly available information.

OBJECTIVES: Surveillance is a key component of any control strategy for healthcare-associated infections (HAIs) and antimicrobial resistance (AMR), and public availability of methodologic aspects is crucial for the interpretation of the data. We sought to systematically review publicly available information for HAIs and/or AMR surveillance systems organized by public institutions or scientific societies in European countries. METHODS: A systematic review of scientific and grey literature following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed. Information on HAIs and/or AMR surveillance systems published until 31 October 2016 were included. RESULTS: A total of 112 surveillance systems were detected; 56 from 20 countries were finally included. Most exclusions were due to lack of publicly available information. Regarding AMR, the most frequent indicator was the proportion of resistant isolates (27 of 34 providing information, 79.42%); only 18 (52.9%) included incidence rates; the data were only laboratory based in 33 (78.5%) of the 42 providing this information. Regarding HAIs in intensive care units, all 22 of the systems providing data included central line-associated bloodstream infections, and 19 (86.3%) included ventilator-associated pneumonia and catheter-associated urinary tract infections; incidence density was the most frequent indicator. Regarding surgical site infections, the most frequent procedures included were hip prosthesis, colon surgery and caesarean section (21/22, 95.5%). CONCLUSIONS: Publicly available information about the methods and indicators of the surveillance system is frequently lacking. Despite the efforts of European Centre for Disease Control and Prevention (ECDC) and other organizations, wide heterogeneity in procedures and indicators still exists.

Review of antimicrobial resistance surveillance programmes in livestock and meat in EU with focus on humans.

OBJECTIVES: In this review, we describe surveillance programmes reporting antimicrobial resistance (AMR) and resistance genes in bacterial isolates from livestock and meat and compare them with those relevant for human health. METHODS: Publications on AMR in European countries were assessed. PubMed was reviewed and AMR monitoring programmes were identified from reports retrieved by Internet searches and by contacting national authorities in EU/European Economic Area (EEA) member states. RESULTS: Three types of systems were identified: EU programmes, industry-funded supranational programmes and national surveillance systems. The mandatory EU-financed programme has led to some harmonization in national monitoring and provides relevant information on AMR and extended-spectrum ß-lactamase/AmpC- and carbapenemase-producing bacteria. At the national level, AMR surveillance systems in livestock apply heterogeneous sampling, testing and reporting modalities, resulting in results that cannot be compared. Most reports are not publicly available or are written in a local language. The industry-funded monitoring systems undertaken by the Centre Européen d'Etudes pour la Santé Animale (CEESA) examines AMR in bacteria in food-producing animals. CONCLUSIONS: Characterization of AMR genes in livestock is applied heterogeneously among countries. Most antibiotics of human interest are included in animal surveillance, although results are difficult to compare as a result of lack of representativeness of animal samples. We suggest that EU/EEA countries provide better uniform AMR monitoring and reporting in livestock and link them better to surveillance systems in humans. Reducing the delay between data collection and publication is also important to allow prompt identification of new resistance patterns.

Natural Products Diversity of Marine Ascidians (Tunicates; Ascidiacea) and Successful Drugs in Clinical Development.

This present study reviewed the chemical diversity of marine ascidians and their pharmacological applications, challenges and recent developments in marine drug discovery reported during 1994-2014, highlighting the structural activity of compounds produced by these specimens. Till date only 5% of living ascidian species were studied from <3000 species, this study represented from family didemnidae (32%), polyclinidae (22%), styelidae and polycitoridae (11-12%) exhibiting the highest number of promising MNPs. Close to 580 compound structures are here discussed in terms of their occurrence, structural type and reported biological activity. Anti-cancer drugs are the main area of interest in the screening of MNPs from ascidians (64%), followed by anti-malarial (6%) and remaining others. FDA approved ascidian compounds mechanism of action along with other compounds status of clinical trials (phase 1 to phase 3) are discussed here in. This review highlights recent developments in the area of natural products chemistry and biotechnological approaches are emphasized.

A comparative assessment of the acute inhalation toxicity of vanadium compounds.

Vanadium compounds have become important in industrial processes, resulting in workplace exposure potential and are present in ambient air as a result of fossil fuel combustion. A series of acute nose-only inhalation toxicity studies was conducted in both rats and mice in order to obtain comparative data on the acute toxicity potential of compounds used commercially. V2O3, V2O4, and V2O5, which have different oxidation states (+3, +4, +5, respectively), were delivered as micronized powders; the highly water-soluble and hygroscopic VOSO4 (+4) could not be micronized and was instead delivered as a liquid aerosol from an aqueous solution. V2O5 was the most acutely toxic micronized powder in both species. Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO4 was more toxic than the V2O5 particles in mice, but not in rats. These data suggest that an interaction of characteristics, i.e., bioavailability, solubility and oxidation state, as well as species sensitivity, likely affect the toxicity potential of vanadium compounds. Based on clinical observations and gross necropsy findings, the lung appeared to be the target organ for all compounds. The level of hazard posed will depend on the specific chemical form of the vanadium. Future work to define the inhalation toxicity potential of vanadium compounds of various oxidation states after repeated exposures will be important in understanding how the physico-chemical and biological characteristics of specific vanadium compounds interact to affect toxicity potential and the potential risks posed to human health.

Bioprospects of Microbial Enzymes from Mangrove-Associated Fungi and Bacteria.

Mangroves ecosystem provides the unique habitat for the colonization of fungi and bacteria. Interestingly, the enzymes derived from mangroves associated microorganisms have enormous economic value in industries of agriculture, pulp, paper, medicine, sewage treatments, etc. Microbial enzyme activity is required for the metabolism of plants and animals. In addition, the enzymes are also involved in aquatic animal food cycle and degradation of mangroves detritus. However, the understanding of current status of mangroves associated microorganism-derived enzymes and its application is required to improve the future omics studies. Therefore, this chapter is summarizing the current reports and application on enzymes derived from mangroves associated bacteria and fungi.

Drug release characteristics of quercetin-loaded TiO2 nanotubes coated with chitosan.

TiO2 nanotubes formed by anodic oxidation of Ti-6Al-7Nb were loaded with quercetin (TNTQ) and chitosan was coated on the top of the quercetin (TNTQC) to various thicknesses. Field emission scanning electron microscopy (FESEM), 3D and 2D analyses were used to characterize the samples. The drug release studies of TNTQ and TNTQC were studied in Hanks' solution for 192h. The studies showed that the native oxide on the sample is substituted by self assembled nanotube arrays by anodisation. FESEM images of chitosan-loaded TNT samples showed that filling of chitosan takes place in inter-tubular space and pores. Drug release studies revealed that the release of drug into the local environment during that duration was constant. The local concentration of the drug can be controlled and tuned by controlling the thickness of the chitosan (0.6, 1 and 3µm) to fit into an optimal therapeutic window in order to treat postoperative infections, inflammation and for quick healing with better osseointegration of the titanium implants.

Simultaneous And Extended Delivery Of Stavudine, Lamivudine And Nevirapine In Fixed Dose Combination Using Sandwiched Osmotic Tablets For Hiv Therapy.

Current HIV-therapy recommends combination of stavudine, lamivudine and nevirapine. Stavudine and lamivudine are administered as fixed combination while nevirapine as separate dosage form which often results in poor compliance and adherence to therapy by patients and therefore, there is a need to develop dosage forms that can overcome the problems of currently available dosage forms for treatment of HIV infection. The present study developed a single unit osmotic system for simultaneous and extended delivery of stavudine, lamivudine and nevirapine that can ensure patients compliance and adherence to HIV-therapy. Sandwich osmotic pump tablets (SOPTs) of stavudine, lamivudine and nevirapine in fixed dose combination were designed and evaluated for the effect of variables such as PEO (polymer), KCl (osmogen), and orifice diameter on the physicochemical characteristics and the release behavior of the drugs. A 24 h zero order release of stavudine, lamivudine and nevirapine from the formulations was observed and the release rate of the drugs was found to be affected by PEO, KCl, and orifice diameter. The in vitro release data of SOPT correlated with in vivo predictions by super - position method. The results of the study propose that a single unit osmotic system (SOPT) of stavudine, lamivudine and nevirapine is beneficial to overcome the disadvantages of currently available dosage forms for effective control of HIV infection.

Electrochemical behavior and effect of heat treatment on morphology, crystalline structure of self-organized TiO2 nanotube arrays on Ti-6Al-7Nb for biomedical applications.

In the present work, we investigate the formation of self-organized titanium oxide nanotube layers by anodic oxidation on titanium alloy Ti-6Al-7Nb in electrolyte solution containing sulfuric acid and hydrofluoric acid. The anodized surface was characterized by micro-Raman, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDS). The corrosion behavior of the treated and untreated samples was investigated through electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization studies in simulated body fluid (Hanks' solution). The investigations show that the native oxide on the sample is replaced by self-assembled nanoarray by anodization. FESEM of samples annealed at 450 to 800 °C show tubular morphology whereas those annealed at 850 °C show collapse of nanotubes. Electrochemical impedance data of the substrate and 10 V anodized samples were fitted with a two-time constant equivalent circuit and that of anodized samples (20, 30 V) with a three-time constant equivalent circuit.

Electrochemical and in vitro bioactivity of polypyrrole/ceramic nanocomposite coatings on 316L SS bio-implants.

The present investigation describes the versatile fabrication and characterization of a novel composite coating that consists of polypyrrole (PPy) and Nb2O5 nanoparticles. Integration of the two materials is achieved by electrochemical deposition on 316L stainless steel (SS) from an aqueous solution of oxalic acid containing pyrrole and Nb2O5 nanoparticles. Fourier transform infrared spectral (FTIR) and X-ray diffraction (XRD) studies revealed that the existence of Nb2O5 nanoparticles in PPy matrix with hexagonal structure. Surface morphological analysis showed that the presence of Nb2O5 nanoparticles strongly influenced the surface nature of the nanocomposite coated 316L SS. Micro hardness results revealed the enhanced mechanical properties of PPy nanocomposite coated 316L SS due to the addition of Nb2O5 nanoparticles. The electrochemical studies were carried out using cyclic polarization and electrochemical impedance spectroscopy (EIS) measurements. In order to evaluate the biocompatibility, contact angle measurements and in vitro characterization were performed in simulated body fluid (SBF) and on MG63 osteoblast cells. The results showed that the nanocomposite coatings exhibit superior biocompatibility and enhanced corrosion protection performance over 316L SS than pure PPy coatings.

Evaluation of vermicompost maturity using scanning electron microscopy and paper chromatography analysis.

Vermicompost was produced from flower waste inoculated with biofertilizers using the earthworm Eisenia fetida. Principal component analysis (PCA) and cluster analysis (CA) were carried out on the basis of physicochemical parameters of vermicomposted samples. From the results of the PCA and CA, it was possible to classify two different groups of vermicompost samples in the following categories: E2 and E5; and E1, E3, E4, and control. Scanning electron microscopy and biodynamic circular paper chromatography analysis were used to investigate the changes in surface morphology and functional groups in the control and vermicompost products. SEM analysis of E1-E5 shows more fragment and pores than the control. Chromatographic analysis of vermicompost indicated the mature condition of the compost materials.

Effect of Sr on the bioactivity and corrosion resistance of nanoporous niobium oxide coating for orthopaedic applications.

In this study, strontium incorporated Nb2O5 was synthesized in two different proportions by sol-gel methodology and was deposited on 316L SS by spin coating method. The synthesis conditions were optimized to obtain a nanoporous morphology. The prepared Sr-incorporated Nb2O5 coatings were uniform, smooth and well adherent on to the substrate 316L SS. The coatings were characterized by attenuated total reflectance-infrared spectroscopy (ATR-IR), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), atomic force microscopy (AFM) and transmission electron microscopy (TEM) and the formation of Sr-incorporated Nb2O5 coatings with nanoporous morphology was confirmed. Static water contact angle measurements showed an enhancement in the wettability of the obtained coatings. In vitro bioactivity test of the coated substrates showed that 0.05M Sr-incorporated Nb2O5 coating had better bioactivity compared to 0.1M Sr-incorporated coating. Solution analysis studies confirmed the controlled release of Sr ions from the coating, which aid and enhance hydroxyapatite (HAp) growth. Electrochemical studies confirmed that the coatings provided excellent corrosion protection to the base material as increased charge transfer resistance and decreased double layer capacitance was observed for the coated substrates.