A National Review of Neonatal Jaundice Identification.

Background Physiological neonatal hyperbilirubinemia is a normal transitional phenomenon, however bilirubin encephalopathy can develop due to exposure to very high bilirubin levels. A systematic approach to early detection of high levels can prevent this outcome. Methods We designed a questionnaire to assess local jaundice management practices in Irish maternity units. Results All 19 units responded to our clinical questionnaire. Early discharge (<48 hours) occurs in 12 units (63%). Six units universally screen all babies with a transcutaneous bilirubinometer (TCB) (32%) while 12 units only do so if clinically jaundiced (83%). 12 units follow up <5% of their babies for jaundice monitoring after discharge (67%), which is lower than expected for optimal jaundice management. Conclusion Our survey responses show a high degree of variability in jaundice identification and follow up practices around the country. As maternity units trend towards earlier discharge of mothers due to resource constraints, we need to develop national systems to stratify risk before discharge and monitor jaundice in the out-patient setting. Introduction

Use of a door handle disinfection system to reduce the risks associated with microbial loads on fomites in a healthcare setting.

BACKGROUND: Pathogenic organisms, including those that are multidrug resistant, can survive for extended periods of time on surfaces. Numerous studies show that contaminated hand-touch sites, such as door handles, pose a serious risk for onward transfer to patients. AIM: To compare microbial levels on the handles of ten frequently used door locations, with and without a door handle disinfection system in place, in a busy rehabilitation unit consisting of two wards at the National Orthopaedic Hospital, Dublin. METHODS: A door handle disinfection system (Handle Hygiene®), utilizing an atomizing pump (non-aerosol), automatically delivered a pulse of disinfectant to a door handle each time the door was used. Microbial levels on the handles of frequently used door locations were monitored over a 16-week period, to compare microbial loads with and without a door handle disinfection system in place. Samples of two disinfectant types, Steri-7 (broad-spectrum disinfectant) and Dew (hypochlorous acid), were used in the study. FINDINGS: Levels of ≤2.5 cfu/cm2 were recorded on 93% of samples collected where a door handle disinfection system was in use, with 66% of samples showing no microbes recovered. Where a level of >2.5 cfu/cm2 was recorded, the door handle disinfection system reduced this to a negligible level by the time the next sample was taken, compared with several days where no system was in place. CONCLUSION: Door handle disinfection systems offer an effective solution to reducing microbial levels on frequently touched door handles, as an automated solution with minimal additional costs.

Antibacterial activity and carbapenem re-sensitizing ability of 1,10-phenanthroline-5,6-dione and its metal complexes against KPC-producing Klebsiella pneumoniae clinical strains.

Infections caused by KPC-producing Klebsiella pneumoniae (Kp-KPC) are associated with high mortality rates due to the increased number of resistant isolates and the scarcity of therapeutic options. This scenario reinforces the urgent need for new chemotherapeutics. Herein, we investigated the effects of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Cu(phendione)3 ](ClO4 )2 .4H2 O (Cu-phendione) and [Ag(phendione)2 ]ClO4 (Ag-phendione), both alone and also combined with carbapenems (meropenem (MEM), and imipenem), against 46 clonally distinct clinical strains of Kp-KPC. All isolates were found to be multidrug resistant in accordance with their susceptibility patterns by disk diffusion method. Compounds geometric mean (GM)-MIC and GM-MBC values (µmol l-1 ), respectively, were: phendione, 42·06 and 71·27; Cu-phendione, 9·88 and 13·75; and Ag-phendione, 10·10 and 13·06. Higher synergism rates of MEM-containing combinations were observed by the checkerboard assay, particularly with the two metal complexes. Moreover, drug combinations were able to re-sensitize 87% of the phenotypically non-susceptible strains. Time-kill studies, with MEM plus Cu-phendione or Ag-phendione, indicated that combinations with 0·5× MIC of each agent produce synergistic effects after 9-12 h. The MEM plus Ag-phendione eradicated about 106  CFU per ml of bacteria. These findings support the effectiveness of the re-sensitizing combinatorial approach and provide evidence that phendione-based compounds offer real promise in the fight against Kp-KPC infections.

Deciphering the antimicrobial activity of phenanthroline chelators.

The opportunistic fungal pathogen, Candida albicans, causes a range of diseases in susceptible individuals. The adverse side effects of many of the current anti-fungal prescription drugs and the emergence of C. albicans isolates and other Candida species which are resistant to these compounds have accelerated the search for new drug candidates which have different modes of action. A family of metal chelators, which are based on the 1,10-phenanthroline core, exhibit excellent growth inhibitory effects in vitro against a number of Candida species, including clinical isolates. The compounds sequester transition metal ions, damage mitochondrial function and uncouple cell respiration. Additionally, fungal cell morphology undergoes dramatic changes and there is evidence of apoptotic cell death. Importantly, in vivo studies have confirmed that the compounds have an acceptably low toxicity profile.

Molecular structure and spectroscopic studies on novel complexes of coumarin-3-carboxylic acid with Ni(II), Co(II), Zn(II) and Mn(II) ions based on density functional theory.

Novel Ni(II), Co(II), Zn(II) and Mn(II) complexes of coumarin-3-carboxylic acid (HCCA) were studied at experimental and theoretical levels. The complexes were characterised by elemental analyses, FT-IR, (1)H NMR, (13)C NMR and UV-Vis spectroscopy and by magnetic susceptibility measurements. The binding modes of the ligand and the spin states of the metal complexes were established by means of molecular modelling of the complexes studied and calculation of their IR, NMR and absorption spectra at DFT(TDDFT)/B3LYP level. The experimental and calculated data verified high spin Ni(II), Co(II) and Mn(II) complexes and a bidentate binding through the carboxylic oxygen atoms (CCA2). The model calculations predicted pseudo octahedral trans-[M(CCA2)(2)(H(2)O)(2)] structures for the Zn(II), Ni(II) and Co(II) complexes and a binuclear [Mn(2)(CCA2)(4)(H(2)O)(2)] structure. Experimental and calculated (1)H, (13)C NMR, IR and UV-Vis data were used to distinguish the two possible bidentate binding modes (CCA1 and CCA2) as well as mononuclear and binuclear structures of the metal complexes.

Bubble nucleation in stout beers.

Bubble nucleation in weakly supersaturated solutions of carbon dioxide-such as champagne, sparkling wines, and carbonated beers-is well understood. Bubbles grow and detach from nucleation sites: gas pockets trapped within hollow cellulose fibers. This mechanism appears not to be active in stout beers that are supersaturated solutions of nitrogen and carbon dioxide. In their canned forms these beers require additional technology (widgets) to release the bubbles which will form the head of the beer. We extend the mathematical model of bubble nucleation in carbonated liquids to the case of two gases and show that this nucleation mechanism is active in stout beers, though substantially slower than in carbonated beers and confirm this by observation. A rough calculation suggests that despite the slowness of the process, applying a coating of hollow porous fibers to the inside of a can or bottle could be a potential replacement for widgets.

The effects of hydrogen-bonding environment on the polarization and electronic properties of water molecules.

Adequate representation of the interactions that take place between water molecules has long been a goal of force field design. A full understanding of how the molecular charge distribution of water is altered by adjacent water molecules and by the hydrogen-bonding environment is a vital step toward achieving this task. For this purpose we generated ab initio electron densities of pure water clusters and hydrated serine and tyrosine. Quantum chemical topology enabled the study of a well-defined water molecule inside these clusters, by means of its volume, energy, and multipole moments. Intra- and intermolecular charge transfer was monitored and related to the polarization of water in hydrogen-bonded networks. Our analysis affords a way to define different types of water molecules in clusters.

Rendering of quantum topological atoms and bonds.

In this article, we describe and apply an algorithm that visualizes atoms and bonds in molecules and van der Waals complexes, based on the topology of the electron density. The theory of quantum chemical topology defines both atoms and bonds via a single consistent procedure, and enables the association of an atomic shape with an atomic property (charge, dipole moment, volume, ...). Special attention is paid to the bridging of gaps arising in interatomic surfaces, in the presence of ring critical points or high ellipticity. This algorithm, in conjunction with the graphical user interface of the computer program MORPHY enables robust and efficient rendering of complicated interatomic surfaces, as found in larger systems.

The quantum topological electrostatic potential as a probe for functional group transferability.

The electrostatic potential can be used as an appropriate and convenient indicator of how transferable an atom or functional group is between two molecules. Quantum-chemical topology (QCT) is used to define the electron density of a molecular fragment and the electrostatic potential it generates. The potential generated on a grid by the terminal aldehyde group of the biomolecule retinal is compared with the corresponding aldehyde group in smaller molecules derived from retinal. The terminal amino group in the free amino acid lysine was treated in a similar fashion. Each molecule is geometry-optimized by an ab initio calculation at B3LYP/6-311G+(2d,p)//HF/6-31G(d) level. The amino group in lysine is very little influenced by any part of the molecule further than two C atoms away. However, the aldehyde group in retinal is influenced by molecular fragments six C atoms away. This dramatic disparity is ascribed to the difference in saturation in the carbon chains; retinal contains a conjugated hydrocarbon chain but lysine an aliphatic one.

Synthesis and antimicrobial activity of copper(II) and manganese(II) alpha,omega-dicarboxylate complexes.

Copper(II) alpha,omega-dicarboxylate complexes of general formulae, [Cu(O2C(CH2)nCO2)].xH2O, [Cu(O2C(CH2)nCO2) (phen)2].xH2O and [Cu(O2C(CH2),CO2)(bipy)y].xH2O (n = 1-8; y = 1, 2; phen = 1,10-phenanthroline; bipy = 2,2'-bipyridine) were synthesised. These copper complexes, some related manganese(II) complexes and the metal-free ligands were screened in vitro for their ability to inhibit the growth of Candida albicans. Metal-free 1,10-phenanthroline and all of the copper(II) and manganese(II) phenanthroline complexes were potent growth inhibitors, with only one bipyridine complex, [Cu(O2C(CH2)CO2)(bipy)2].2H2O, having moderate activity. The remaining substances were effectively inactive. Complexes which were active against C. albicans also proved effective against C. glabratta, C. tropicalis and C. kreusi with the manganese complexes retaining superior activity. For the phenanthroline complexes the active drug species is thought to be the dication [M(phen)2(H2O)n]2+ (M = Cu, Mn). Escherichia coli and Staphylococcus aureus were resistant to all of the metal complexes and also to metal-free 1,10-phenanthroline. Only the copper phenanthroline complexes showed intermediate activity against Pseudomonas aeruginosa.

Insights into the mode of action of the anti-Candida activity of 1,10-phenanthroline and its metal chelates.

Metal complexes of malonie acid (metal = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Ag(I)) were prepared and only the Ag(I) complex inhibited the growth of Candida albicans. Malonate complexes incorporating the chelating 1,10-phenanthroline (1,10-phen) ligand showed a range of activities: good (Mn(II), Cu(II), Ag(I)); moderate (Zn(II)); poor (Co(II), Ni(II)). Metal-free 1,10-phen and Ag(CH(3)CO(2)) were also highly active. The metal-free non-chelating ligands 1,7- phenanthroline and 4,7-phenanthroline were inactive and the Cu(II), Mn(II) and Zn(II) complexs of 1,7-phen displayed only marginal activity. Whereas the Cu(II) malonate/1,10-phen complex induces significant cellular oxidative stress the Zn(II) analogue does not.

Synthesis and Biological Activity of Manganese (II) Complexes of Phthalic and Isophthalic Acid: X-Ray Crystal Structures of [Mn(ph)(Phen)(2)(H(2)O)]. 4H(2)O, [Mn(Phen)(2)(H(2)O)(2)](2)(Isoph)(2)(Phen). 12H(2)O and {[Mn(Isoph)(bipy)](4). 2.75biby}(n)(phH(2) = Phthalic Acid; isoph = Isophthalic Acid; phen = 1,10-Phenanthroline; bipy = 2,2-Bipyridine).

Manganese(II) acetate reacts with phthalic acid (phH(2)) to give [Mn(ph)].0.5H(2)O (1). Reaction of 1 with 1,10-phenanthroline produces [Mn(ph)(phen)].2H(2)O (2) and [Mn(ph)(phen)(2)(H(2)O)].4H(2)O (3). Reaction of isophthalic acid (isophH(2)) with manganese(II) acetate results in the formation of [Mn(isoph)].2H(2)O (4). The addition of the N,N-donor ligands 1,10-phenanthroline or 2,2'-bipyridine to 4 leads to the formation of [Mn(2) (isoph)(2)(phen)(3))].4H(2)O (5), [(Mn(phen)(2)(H(2)O)(2)](2)(isoph)(2)(phen).12H(2)O (6) and {[Mn(isoph)(bipy)](4).2.75 biby}(n) (7), respectively. Molecular structures of 3, 6 and 7 were determined crystallographically. In 3 the phthalate ligand is bound to the manganese via just one of its carboxylate groups in a monodentate mode with the remaining coordination sites filled by four phenanthroline nitrogen and one water oxygen atoms. In 6 the isophthalates are uncoordinated with the octahedral manganese center ligated by two phenanthrolines and two waters. In 7 the Isophthalate ligands act as bridges resulting in a polymeric structure. One of the carboxylate groups is chelating a single manganese with the other binding two metal centres in a bridging bidentate mode. The phthalate and isophthalate complexes, the metal free ligands and a number of simple manganes salts were each tested for their ability, to inhibit the growth of Candida albicans. Only the "metal free" 1,10-phenanthroline and its manganese complexes were found to be active.

Synthesis and Anti-Candida Activity of Cobalt(II) Complexes of Benzene-1,2-Dioxyacetic Acid (bdoaH(2)). X-Ray Crystal Structures of [Co(bdoa)(H(2)O)(3)] 3.5H(2)O and {[CO(phen)(3)](bdoa)}(2)24H(2)O (phen = 1,10-Phenanthroline).

Co(CH(3)CO(2))(2)4H(2)O reacts with benzene-1,2-dioxyacetic acid (bdoaH(2)) to give the Co(2+) complexes [Co(bdoa)(H(2)O)(3)]H(2)O (1a) and [Co(bdoa)(H(2)O)(3)] 3.5H(2)O (1b). Subsequent reaction of 1a with 1,10- phenanthroline produces [CO(phen)(3)] bdoa10H(2)O (2a) and {[CO(phen)(3)](bdoa)}(2)24H(2)O (2b). Molecular structures of 1b and 2b were determined crystallographically. In 1b the bdoa(2-)- ligates the metal by two carboxylate oxygens and two ethereal oxygens, whereas in 2b the bdoa(2-) is uncoordinated. The Mn(2+) and Cu(2+) complexes [Mn(bdoa)(phen)(2)]H(2)O (3) and [Cu(pdoa)(imid)(2)] (4) were also synthesised, 1a-4 and other metal complexes of bdoa H(2) (metal = Mn(2+), Co(2+) ,Cu(2+), Cu(+) ) were screened for their ability to inhibit the growth ofhe yeast Candida albicans. Complexes incorporating the 1,10-phenanthroline ligand were the most active.