Identifying strategies to support implementation of interprofessional primary care teams in Nova Scotia: Results of a survey and knowledge sharing event.

BACKGROUND: Interprofessional primary care teams (IPCTs) work together to enhance care. Despite evidence on the benefits of IPCTs, implementation remains challenging. This research aims to 1) identify and prioritize barriers and enablers, and 2) co-develop team-level strategies to support IPCT implementation in Nova Scotia, Canada. METHODS: Healthcare providers and staff of IPCTs were invited to complete an online survey to identify barriers and enablers, and the degree to which each item impacted the functioning of their team. Top ranked items were identified using the sum of frequency x impact for each response. A virtual knowledge sharing event was held to identify strategies to address local barriers and enablers that impact team functioning. RESULTS: IPCT members (n = 117), with a mix of clinic roles and experience, completed the survey. The top three enablers identified were access to technological tools to support their role, standardized processes for using the technological tools, and having a team manager to coordinate collaboration. The top three barriers were limited opportunity for daily team communication, lack of conflict resolution strategies, and lack of capacity building opportunities. IPCT members, administrators, and patients attended the knowledge sharing event (n = 33). Five strategies were identified including: 1) balancing patient needs and provider scope of practice, 2) holding regular and accessible meetings, 3) supporting team development opportunities, 4) supporting professional development, and 5) supporting involvement in non-clinical activities. INTERPRETATION: This research contextualized evidence to further understand local perspectives and experiences of barriers and enablers to the implementation of IPCTs. The knowledge exchange event identified actionable strategies that IPCTs and healthcare administrators can tailor to support teams and care for patients.

Metal Complexes as Antifungals? From a Crowd-Sourced Compound Library to the First In Vivo Experiments.

There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 µM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

Conceptual Developments of Aryldiazonium Salts as Modifiers for Gold Colloids and Surfaces.

Modified colloids and flat surfaces occupy an important place in materials science research due to their widespread applications. Interest in the development of modifiers that adhere strongly to surfaces relates to the need for stability under ambient conditions in many applications. Diazonium salts have evolved as the primary choice for the modification of surfaces. The term "diazonics" has been introduced in the literature to describe "the science and technology of aryldiazonium salt-derived materials". The facile reduction of diazonium salts via chemical or electrochemical processes, irradiation stimuli, or spontaneously results in the efficient modification of gold surfaces. Robust gold-aryl nanoparticles, where gold is connected to the aryl ring through bonding to carbon and films modified by using diazonium salts, are critical in electronics, sensors, medical implants, and materials for power sources. Experimental and theoretical studies suggest that gold-carbon interactions constructed via chemical reactions with diazonium salts are stronger than nondiazonium surface modifiers. This invited feature article summarizes the conceptual development of recent studies of diazonium salts in our laboratories and others with a focus on the surface modification of gold nanostructures, flat surfaces and gratings, and their applications in nanomedicine engineering, sensors, energy, forensic science, and catalysis.

Bronchodilator Dose Responsiveness in Children and Adolescents: Clinical Features and Association with Future Asthma Exacerbations.

BACKGROUND: Bronchodilator reversibility measures are often associated with poor asthma outcomes in children. Whether bronchodilator dose responsiveness is similarly useful in children is unclear. OBJECTIVE: We hypothesized that children and adolescents requiring higher doses of bronchodilator to achieve maximal bronchodilation would have unique risk factors and increased risk of future exacerbation. METHODS: Children (6-11 years, N = 299) and adolescents (12-21 years, N = 331) with confirmed asthma underwent clinical phenotyping procedures and a test of maximal bronchodilation with escalating doses of albuterol sulfate up to 720 mcg. Outcome measures were assessed at 12 months and included exacerbations treated with systemic corticosteroids, emergency department (ED) visits, and hospitalizations for asthma. RESULTS: A total of 6.7% of children and 9.3% of adolescents had poor bronchodilator dose responsiveness, defined as attainment of maximal forced expiratory volume in 1 second with 720 mcg albuterol. Risk factors included type 2 inflammation, prior exacerbations, and greater asthma severity; historical pneumonia and tobacco exposure were also risk factors in children. Children and adolescents with poor bronchodilator dose responsiveness did not have increased current symptoms or impaired quality of life, but had approximately 2-fold increased odds of exacerbation or ED visit and approximately 3-fold increased odds of hospitalization by 12 months, independent of airflow obstruction. CONCLUSIONS: Bronchodilator dose responsiveness may be useful for phenotyping and may be of utility in practice and future studies focused on asthma outcomes or quantification of treatment responses. In children and adolescents, this phenotype of poor bronchodilator responsiveness may be associated with periods of relatively stable disease yet marked airway constriction in response to triggers, including tobacco smoke, respiratory infections/pneumonia, and aeroallergens.

Anxiety Contributes to Poorer Asthma Outcomes in Inner-City Black Adolescents.

BACKGROUND: The factors associated with poor asthma control, exacerbations, and health care utilization in black adolescents are complex and not well understood. Although psychological comorbidities such as anxiety are common in patients with asthma, these have not been studied in this population. OBJECTIVE: This study characterized anxiety and associated asthma features in a cohort of black inner-city adolescents with persistent asthma and determined the association between anxiety symptoms, persistent uncontrolled asthma, and prospective health care utilization over 1 year. METHODS: Eighty-six black adolescents were enrolled, phenotyped, and screened for anxiety symptoms with the Hospital Anxiety and Depression Scale anxiety subscale (HADS-A). Participants were telephoned every 2 months and a second study visit was completed at 1 year. Primary outcomes included persistent uncontrolled asthma, asthma exacerbations requiring systemic corticosteroids, and unscheduled health care utilization during the 1-year study period. RESULTS: A total of 31% (n = 27) of adolescents had probable anxiety (ie, HADS-A score >7) and 27% (n = 23) had possible anxiety (ie, HADS-A score 5-7) at the baseline visit. Anxiety symptoms were associated with poorer asthma control, more impaired quality of life, and more insomnia symptoms. Adolescents with probable anxiety disorders also had increased odds of persistent uncontrolled asthma and emergency department utilization, with no differences in physician visits or systemic corticosteroid receipt. CONCLUSIONS: Inner-city black adolescents with persistent asthma have a high prevalence of anxiety symptoms associated with poorer asthma control, impaired quality of life, insomnia, and increased prospective emergency department utilization for asthma. Routine screening for anxiety disorders may be useful in the clinical management of adolescents with asthma.

Predictors of emergency department use in children with persistent asthma in metropolitan Atlanta, Georgia.

BACKGROUND: Racial disparities are evident among children with asthma in the United States, with non-Hispanic black children at particularly high risk for poor asthma outcomes, including frequent emergency department (ED) use for asthma exacerbations. OBJECTIVE: To compare asthma features in non-Hispanic black vs white children in Atlanta, Georgia, and determine what clinical features predict future ED use for asthma. METHODS: Self-reported black and white children 6 to 17 years of age with persistent asthma treated with controller medications completed medical history questionnaires, lung function testing, aeroallergen sensitization testing, and venipuncture. Medical records were reviewed for asthma-related ED visits for 12 months after the initial study visit. RESULTS: A total of 276 children were enrolled. Black children, compared with white children, resided in more disadvantaged zip code areas and were more likely to have public insurance. Black children also had more features of asthma severity and more ED visits during the study period. Predictors of ED use, aside from a previous ED visit, differed by race. After adjustment for socioeconomic status, predictors of ED use in white children included an ED visit in the previous year and sensitization to pets and dust; in black children, predictors included ED use in the previous year, the number of asthma controller medications, forced expiratory volume in 1 second less than 80% predicted, blood eosinophil count greater than 4%, and mold sensitization. CONCLUSION: Asthma features and ED use differ between black and white children in metropolitan Atlanta. Strategies to eliminate allergen exposure in the home and improve asthma control in these children may require tailoring for different racial groups.

The influence of gold(i) on the mechanism of thiolate, disulfide exchange.

The mechanism of gold(i)-thiolate, disulfide exchange was investigated by using initial-rate kinetic studies, 2D ((1)H-(1)H) ROESY NMR spectroscopy, and electrochemical/chemical techniques. The rate law for exchange is overall second order, first order in gold(i)-thiolate and disulfide. 2D NMR experiments show evidence of association between gold(i)-thiolate and disulfide. Electrochemical/chemical investigations do not show evidence of free thiolate and are consistent with a mechanism involving formation of a [Au-S, S-S], four-centered metallacycle intermediate during gold(i)-thiolate, disulfide exchange.

The influence of zinc(II) on thioredoxin/glutathione disulfide exchange: QM/MM studies to explore how zinc(II) accelerates exchange in higher dielectric environments.

QM/MM studies were performed to explore the energetics of exchange reactions of glutathione disulfide (GSSG) and the active site of thioredoxin [Cys32-Gly33-Pro34-Cys35] with and without zinc(II), in vacuum and solvated models. The activation energy for exchange, in the absence of zinc, is 29.7 kcal mol(-1) for the solvated model. This is 3.3 kcal mol(-1) higher than the activation energy for exchange in the gas phase, due to ground state stabilization of the active site Cys-32 thiolate in a polar environment. In the presence of zinc, the activation energy for exchange is 4.9 kcal mol(-1) lower than in the absence of zinc (solvated models). The decrease in activation energy is attributed to stabilization of the charge-separated transition state, which has a 4-centered, cyclic arrangement of Zn-S-S-S with an estimated dipole moment of 4.2 D. A difference of 4.9 kcal mol(-1) in activation energy would translate to an increase in rate by a factor of about 4000 for zinc-assisted thiol-disulfide exchange. The calculations are consistent with previously reported experimental results, which indicate that metal-thiolate, disulfide exchange rates increase as a function of solvent dielectric. This trend is opposite to that observed for the influence of the dielectric environment on the rate of thiol-disulfide exchange in the absence of metal. The results suggest a dynamic role for zinc in thiol-disulfide exchange reactions, involving accessible cysteine sites on proteins, which may contribute to redox regulation and mechanistic pathways during oxidative stress.

An infrared spectroscopic based method for mercury(II) detection in aqueous solutions.

A new method that uses solid phase extraction (SPE) coupled with FTIR spectroscopy to detect Hg(II) in aqueous samples is described. The technique is envisioned for on-site, field evaluation rather than lab-based techniques. This paper presents the "proof of principle" of this new approach toward measurements of Hg(II) in water and identifies mass transport issues that would need to be overcome in order to migrate from a lab based method to field operation. The SPE material supported on a Si wafer is derivatized with an acylthiosemicarbazide, which undergoes a reaction in the presence of aqueous Hg(II) to form an oxadiazole ring. The progress of the reaction is monitored by IR spectroscopy. Following EPA guidelines, the method of detection limit (MDL) for the SPE/IR was 5 µg of Hg(II)cm(-2). In a 1L sample and a 1cm(2) Si wafer, this translates to a detection limit of 5 ppb. This system shows a high selectivity toward aqueous Hg(II) over other thiophilic heavy metal ions such as Pb(II), Cd(II), Fe(III), and Zn(II) and other metal ions such as Ni(II), Mn(II), Co(II), Cu(II), In(III), Ru(III), Na(I), and Ag(I) in aqueous solutions.

Luminescence, structural, and bonding trends upon varying the halogen in isostructural aurophilic dimers.

The preparation of three isonitrile complexes (p-tosyl)CH(2)NCAu(I)X (X = Cl, Br, and I) along with their structural, spectral, and computational characterization are reported. X-Ray crystallography reveals that these complexes all crystallize in the same space group, C2/c, and have closely related supramolecular structures. The three complexes exhibit crossed-dimer structures with short Au...Au aurophilic distances of 3.0634(4) A, 3.1044(7) A, and 3.1083(5) A, for X = Cl, Br, and I, respectively. These distances are among the shortest ligand-unassisted Au...Au interactions reported. While RNCAuX complexes that we reported earlier associate as anti-parallel, one-dimensional aurophilic polymers with long Au...Au distances (approximately 3.6 A) and exhibit orange-red phosphorescence, the analogous aurophilic dimers herein show seemingly counter-intuitive blue-green emissions despite having much shorter Au...Au distances. DFT computations are used to augment experiment and study the T(1) phosphorescent excited state of [RNCAuX](n) in parallel, anti-parallel, and staggered conformations. Excimeric bonding and large Stokes shifts are predicted for all models, the extent of which is sensitive to both "n" and conformation with trends commensurate with experimental luminescence data. Calculations for the three [MeNCAuX](2) dimeric complexes reveal blue-green phosphorescence with a red shift as a function of increasing halide softness, consistent with experimental data for (p-tosyl)CH(2)NCAu(I)X (Cl > Br > I). The overall experimental and theoretical work signifies the central role of ground-state aurophilic bonding and excited-state excimeric bonding on the electronic structure, hence facilitating development of structure-luminescence relations that may assist in the rational design of novel optoelectronic devices.

Novel metallamacrocyclic gold(I) thiolate cluster complex: structure and luminescence of [Au9(mu-dppm)4(mu-p-tc)6](PF6)3.

The structure of a novel metallamacrocyclic phosphine gold(I) thiolate cluster, [Au9(mu-dppm)4(mu-p-tc)6](PF6)3, where dppm = bis(diphenylphosphine)methane and p-tc = p-thiocresolate, is reported and shows AuAu attractions of approximately 3.0 A and gold(I) atoms linked to thiolate and phosphine ligands in distorted trigonal and nearly linear geometries.

Mu-biphenyl-2,2'-dithiolato-kappa2S:S'-bis[(triphenylphosphine-kappaP)gold(I)].

The reaction of ClAuPPh3 and 1,1'-biphenyl-2,2'-dithiol in the presence of trimethylbenzylammonium chloride and K2CO3 in a tetrahydrofuran/methanol solution gives the title complex, [Au2(C12H8S2)(C18H15P)2]. The molecule contains P-Au-S units which 'cross' with torsion angles of approximately 90 degrees [P-Au-Au-P = 86.23 (5) degrees and S-Au-Au-S = 95.62 (5) degrees]. The intra- and intermolecular Au.Au distances [3.9064 (3) and 6.3797 (5) A, respectively] are outside the range for typical Au...Au interactions. However, the Au atoms appear to be drawn together, leading to a significant bending of the P-Au-S angles [170.24 (5) and 169.52 (5) degrees].

Formation of a cationic gold(I) complex and disulfide by oxidation of the antiarthritic gold drug auranofin.

The mechanism of action of auranofin, an antiarthritic gold(I) drug, is unknown, but several studies suggest that oxidation may be important for its biochemical effect. Bulk electrolysis studies on auranofin [(Et(3)P)Au(TATG); TATG = 2,3,4,6-tetraacetyl-1-thio-d-glucopyranosato] at +1.2 and +1.6 V versus Ag/AgCl in 0.1 M Bu(4)NBF(4)/CH(2)Cl(2) results in n values of 0.5 and >2 electrons, respectively. Oxidation of auranofin with the mild oxidant, Cp(2)Fe(+), results in formation of disulfide and a digold(I) cation with a bridging thiolate ligand, [(Et(3)PAu)(2)(mu-TATG)](+) (1). The X-ray structure of the PMe(3) analogue, [(Me(3)PAu)(2)(mu-TATG)](NO(3)) (2), is reported. Compound 2 forms a tetranuclear cluster containing an almost perfect square of four gold atoms with Au.Au distances averaging 3.14 A. The complex crystallizes in the tetragonal space group P4(2)2(1)2 with cell constants a = 26.1758(6) A, b = 26.1758(6) A, c = 9.7781(3) A, alpha = beta = gamma = 90 degrees, V = 6699.7(3) A(3), Z = 4, R1 = 0.0644, and wR2 = 0.1152. A mechanism for oxidation of auranofin and possible biological implications are discussed.

[Mu-o-phenylenebis(diphenylphosphine)-kappa2P:P']bis[chlorogold(I)], dppbz(AuCl)2.

The Au...Au distance in the title compound, [Au(2)Cl(2)(C(30)H(24)P(2))], is 2.996 (1) A, typical of an Au...Au interaction. The two P-Au-Cl arms 'cross' at the Au centers, with a Cl-Au...Au-Cl torsion angle of -63.92 (7) degrees. Only a small deviation from linearity is observed in the coordination around the Au atoms. Related phosphine-gold(I) chloride structures with intra- and intermolecular Au...Au interactions are surveyed.