Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke.

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18-34.5) and severe periodontitis with an OR of 7.48 (1.24-44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87-23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01-6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72-40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

A novel, integrated curriculum for dental hygiene-therapists and dentists.

Introduction: In certain communities patients may struggle to find access to adequate dental treatment. One proposed strategy to help meet population need is to train more dental hygiene-therapists. However, established attitudes and hierarchies, along with a lack of clear understanding of different roles within some general practice environments has led to underutilised shared-care approaches. Integrating dentists and dental hygiene-therapists in undergraduate education may be an effective approach to promote inter-professional education, dispel inappropriate biases and hierarchies, and nurture team working from an early career stage. As such, we have developed a novel BSc Dental Therapy and Hygiene (BDHT) curriculum, which is integrated with the Bachelor of Dental Surgery (BDS) programme. Aims: The aim of this paper is to describe how two separate BDHT and BDS undergraduate programmes have been uniquely integrated, and to share areas of best practice. Design: The BDHT curriculum was developed based on our established BDS programme introduced in 2013 and is novel in two respects: BDHT students complete their academic and clinical training jointly with BDS students, and are assessed and trained to the same standards; and our patient-centred, primary care clinical training model is designed to prepare BDHT graduates to work under direct access. Results: Key success indicators of the integrated BDHT-BDS programmes are: award of GDC sufficiency; 100% BDHT graduate employment; and 100% BDHT final year pass rate. Conclusion: Inter-professional education is an established pedagogic approach to inhibit the formation of hierarchy and barriers that impede collaborative care. Our BDHT programme is the first of its kind to embed inter-professional education through the entirety of both the BDHT and BDS course structures and be entirely integrated. Further studies are required to provide quantitative and qualitative data to validate the success of our new integrated training programme. This paper presents our curriculum journey, from conception, to design, implementation and review. It describes our vision and its relevance for the future of inter-professional dental education.

Prediction of strong O-H/M hydrogen bonding between water and square-planar Ir and Rh complexes.

Intermolecular O-H/M interactions, between a water molecule and square-planar acac complexes ([M(acac)L2]), with different types of L ligands (en, H2O, CO, CN-, and OH-) and different types of metal atoms (Ir(i), Rh(i), Pt(ii), and Pd(ii)) were studied by high level ab initio calculations. Among the studied neutral complexes, the [Pd(acac)(CN)(CO)] complex forms the weakest interaction, -0.62 kcal mol-1, while the [Ir(acac)(en)] complex forms the strongest interaction, -9.83 kcal mol-1, which is remarkably stronger than the conventional hydrogen bond between two water molecules (-4.84 kcal mol-1).

Aliphatic-aromatic stacking interactions in cyclohexane-benzene are stronger than aromatic-aromatic interaction in the benzene dimer.

Stacking interactions between cyclohexane and benzene were studied in crystal structures from the Cambridge Structural Database and by ab initio calculations. Calculated at the very accurate CCSD(T)/CBS level of theory, the cyclohexane-benzene interaction energy is -3.27 kcal mol-1, which is significantly stronger than the interaction in the benzene dimer (-2.84 kcal mol-1) indicating the importance of aliphatic-aromatic interactions.

Interferon-γ stimulates CD14, TLR2 and TLR4 mRNA expression in gingival fibroblasts increasing responsiveness to bacterial challenge.

OBJECTIVE: To investigate the potential effects of IFN-03A5 on the responsiveness of human gingival fibroblasts to bacterial challenge. DESIGN: mRNA and protein expression of CD14, TLR2 and TLR4 in human gingival fibroblasts was detected by quantitative polymerase chain reaction (Q-PCR) and flow cytometry. The effect of preincubation with IFN-03A5 on subsequent bacterial LPS-induced expression of IL-6 and IL-8 by gingival fibroblasts was determined by ELISA. Bacterial LPS-induced IκBα degradation in human gingival fibroblasts was investigated by western blot. RESULTS: Human gingival fibroblasts express CD14, TLR2 and TLR4 mRNAs. IFN-03A5, but not IL-103B2, induced mRNA expression of all three receptors and the expression of membrane bound CD14 protein. Pre-incubation of fibroblasts with IFN-03A5 and subsequent stimulation with Escherichia coli LPS or Porphyromonas gingivalis LPS led to increased production of IL-6 and IL-8. LPS-induced pro-inflammatory cytokine production was abrogated by a blocking antibody to CD14. Both E. coli LPS and P. gingivalis LPS induced IκBα degradation in human gingival fibroblasts. CONCLUSION: Our data indicate that IFN-03A5 primes human gingival fibroblasts, through the upregulation of CD14 expression, which results in increased responsiveness to bacterial LPS challenge, as determined by pro-inflammatory cytokine production.

Periodontal therapy improves gastric Helicobacter pylori eradication.

The oral cavity has been proposed as a reservoir for H. pylori that could be responsible for the refractoriness of gastric infection to triple therapy (antibiotics, antimicrobials, and proton pump inhibitors). The aim of this study was to evaluate the efficiency of combined periodontal and triple therapy vs. triple therapy alone, in gastric H. pylori eradication in persons with H. pylori in the subgingival biofilm. Individuals positive for H. pylori in their gastric and oral samples, as determined by nested PCR, were treated either with periodontal and triple therapy or with triple therapy alone. Our results indicate that 77.3% of those treated with the combined therapy exhibited successful eradication of gastric H. pylori, compared with 47.6% who underwent only triple therapy. Analysis of these data suggests that periodontal treatment in combination with systemic therapy could be a promising approach to increasing the therapy's efficacy and decreasing the risk of infection recurrence.

Excitons in carbon nanotubes with broken time-reversal symmetry.

Near-infrared magneto-optical spectroscopy of single-walled carbon nanotubes reveals two absorption peaks with an equal strength at high magnetic fields (>55 T). We show that the peak separation is determined by the Aharonov-Bohm phase due to the tube-threading magnetic flux, which breaks the time-reversal symmetry and lifts the valley degeneracy. This field-induced symmetry breaking thus overcomes the Coulomb-induced intervalley mixing which is predicted to make the lowest exciton state optically inactive (or dark).

Stability of high-density one-dimensional excitons in carbon nanotubes under high laser excitation.

Through ultrafast pump-probe spectroscopy with intense pump pulses and a wide continuum probe, we show that interband exciton peaks in single-walled carbon nanotubes (SWNTs) are extremely stable under high laser excitations. Estimates of the initial densities of excitons from the excitation conditions, combined with recent theoretical calculations of exciton Bohr radii for SWNTs, suggest that their positions do not change at all even near the Mott density. In addition, we found that the presence of lowest-subband excitons broadens all absorption peaks, including those in the second-subband range, which provides a consistent explanation for the complex spectral dependence of pump-probe signals reported for SWNTs.

Interband recombination dynamics in resonantly excited single-walled carbon nanotubes.

Wavelength-dependent pump-probe spectroscopy of micelle-suspended single-walled carbon nanotubes reveals two-component dynamics. The slow component (5-20 ps), which has not been observed previously, is resonantly enhanced whenever the pump photon energy coincides with an absorption peak and we attribute it to interband carrier recombination, whereas we interpret the always-present fast component (0.3-1.2 ps) as intraband carrier relaxation in nonresonantly excited nanotubes. The slow component decreases drastically with decreasing pH (or increasing H+ doping), especially in large-diameter tubes. This can be explained as a consequence of the disappearance of absorption peaks at high doping due to the entrance of the Fermi energy into the valence band, i.e., a 1D manifestation of the Burstein-Moss effect.

Artificial cytochrome b: computer modeling and evaluation of redox potentials.

We generated atomic coordinates of an artificial protein that was recently synthesized to model the central part of the native cytochrome b (Cb) subunit consisting of a four-helix bundle with two hemes. Since no X-ray structure is available, the structural elements of the artificial Cb were assembled from scratch using all known chemical and structural information available and avoiding strain as much as possible. Molecular dynamics (MD) simulations applied to this model protein exhibited root-mean-square deviations as small as those obtained from MD simulations starting with the crystal structure of the native Cb subunit. This demonstrates that the modeled structure of the artificial Cb is relatively rigid and strain-free. The model structure of the artificial Cb was used to determine the redox potentials of the two hemes by calculating the electrostatic energies from the solution of the linearized Poisson-Boltzmann equation (LPBE). The calculated redox potentials agree within 20 meV with the experimentally measured values. The dependence of the redox potentials of the hemes on the protein environment was analyzed. Accordingly, the total shift in the redox potentials is mainly due to the low dielectric medium of the protein, the protein backbone charges, and the salt bridges formed between the arginines and the propionic acid groups of the hemes. The difference in the shift of the redox potentials is due to the interactions with the hydrophilic side chains and the salt bridges formed with the propionic acids of the hemes. For comparison and to test the computational procedure, the redox potentials of the two hemes in the native Cb from the cytochrome bc(1) (Cbc(1)) complex were also calculated. Also in this case the computed redox potentials agree well with experiments.

Factors determining the orientation of axially coordinated imidazoles in heme proteins.

Factors determining conformations of imidazole axially coordinated to heme in heme proteins were investigated by analyzing 693 hemes in 432 different crystal structures of heme proteins from the Protein Data Bank (PDB), where at least one histidine is ligated to heme. The results from a search of the PDB for protein structures were interpreted with molecular force field computations. Analysis of data from these crystal structures indicated that there are two main factors that determine the orientations of imidazole ligated to heme. These are the interactions of imidazole with the propionic acid side chains of heme and with the histidine backbone. From the analysis of the crystal structures of heme proteins, it turned out that the hydrogen bonding pattern is often not decisive, though it is probably used by nature to fine-tune the orientation of imidazole axially ligated to heme. We found that in many heme proteins the NdeltaH group of imidazole ligated to heme can assume a number of different hydrogen bonds and that in mutant structures the orientation of the ligated imidazole often does not change significantly, although the mutant altered the hydrogen bonding scheme involving the imidazole. Data from crystal structures of heme proteins show that there are preferred orientations of imidazoles with respect to heme. Generally, the NdeltaH group of imidazole is oriented toward the propionic acid groups of the heme. In some cases, the NdeltaH group of imidazole is close to only one of the propionic acid groups, but it is practically never oriented in the opposite direction. The imidazole also adopts a preferred orientation with respect to its histidine backbone such that the plane of the imidazole ring is practically never parallel to the Calpha-Cbeta bond of its histidine backbone. For a given conformation of histidine backbone with respect to heme, as well as imidazole with respect to histidine backbone, the orientation of the imidazole with respect to heme is uniquely determined, since the three orientations depend on each other. Hence, the interaction of the imidazole with the backbone also influences the orientation of the imidazole with respect to the heme. Force field computations are in agreement with experimental data. With this method, we showed that there is an energy minimum when the NdeltaH group of the imidazole is oriented toward the propionic acid groups and that there are minima of energy for orientations where the imidazole ring is orthogonal to the plane defined by the Calpha-Cbeta and Cbeta-Cgamma bonds of the histidine. The computations also demonstrated that these interactions are mainly of electrostatic origin. By taking into account these two major factors, we were able to understand the orientations of axially coordinated imidazoles for all groups of heme proteins, except for the group of cytochrome c peroxidase. In this group, the orientation of the imidazole is determined by a strong hydrogen bond of the NdeltaH group with Asp235.

Metal ligand aromatic cation-pi interactions in metalloproteins: ligands coordinated to metal interact with aromatic residues.

Cation-pi interactions between aromatic residues and cationic amino groups in side chains and have been recognized as noncovalent bonding interactions relevant for molecular recognition and for stabilization and definition of the native structure of proteins. We propose a novel type of cation-pi interaction in metalloproteins; namely interaction between ligands coordinated to a metal cation--which gain positive charge from the metal--and aromatic groups in amino acid side chains. Investigation of crystal structures of metalloproteins in the Protein Data Bank (PDB) has revealed that there exist quite a number of metalloproteins in which aromatic rings of phenylalanine, tyrosine, and tryptophan are situated close to a metal center interacting with coordinated ligands. Among these ligands are amino acids such as asparagine, aspartate, glutamate, histidine, and threonine, but also water and substrates like ethanol. These interactions play a role in the stability and conformation of metalloproteins, and in some cases may also be directly involved in the mechanism of enzymatic reactions, which occur at the metal center. For the enzyme superoxide dismutase, we used quantum chemical computation to calculate that Trp163 has an interaction energy of 10.09 kcal mol(-1) with the ligands coordinated to iron.

[Personal experience in the treatment of pulmonary tuberculosis in mentally retarded persons]. / Nase iskustvo u lijecenju plucne tuberkuloze u osoba mentalno retardiranih.

The results of the therapy of pulmonary tuberculosis in 90 mentally retarded patients in various forms and degrees of retardation are presented. General and clinical condition of 62 patients was very bad prior to the onset of antituberculotic therapy and most of them were immobile due to the mental retardation and dissemination of pulmonary tuberculosis. In 30 patients advanced form of tuberculosis, in 54 patients mild form and in 6 patients a minimal degree of tuberculosis were found. In hospitalized patients all clinical forms of pulmonary tuberculosis were found. The therapy started with triplicate antituberculotic therapy and the patients were also administered other drugs due to their mental retardation. During the first two months of antituberculotic therapy a high mortality rate was registered (27 or 30%) especially in younger patients. The reason for such high rate cannot be attributed only to pulmonary tuberculosis but also to the primary disease as was the main reason of patients' hospitalization at the institute for mentally retarded persons. Many complications in antituberculotic use could not be registered since many of the basic data could not be obtained from mentally retarded subjects. The complete recovery or improvement of pulmonary tuberculosis was achieved in 63 patients.