Early Steps in C-Type Inactivation of the hERG Potassium Channel

Fast C-type inactivation confers distinctive functional properties to the hERG potassium channel, and its association to inherited and acquired cardiac arrythmias makes the study of the inactivation mechanism of hERG at the atomic detail of paramount importance. At present, two models have been proposed to describe C-type inactivation in K+-channels. Experimental data and computational work on the bacterial KcsA channel support the hypothesis that C-type inactivation results from a closure of the selectivity filter that sterically impedes ion conduction. Alternatively, recent experimental structures of a mutated Shaker channel revealed a widening of the extracellular portion of the selectivity filter, which might diminish conductance by interfering with the mechanism of ion permeation. Here, we performed molecular dynamics simulations of the wild-type hERG, a non-inactivating mutant (hERG-N629D), and a mutant that inactivates faster than the wild-type channel (hERG-F627Y) to find out which and if any of the two reported C-type inactivation mechanisms applies to hERG. Closure events of the selectivity filter were not observed in any of the simulated trajectories but instead, the extracellular section of the selectivity filter deviated from the canonical conductive structure of potassium channels. The degree of widening of the potassium binding sites at the extracellular entrance of the channel was directly related to the degree of inactivation with hERG-F627Y > wild-type hERG > hERG-N629D. These findings support the hypothesis that C-type inactivation in hERG entails a widening of the extracellular entrance of the channel rather than a closure of the selectivity filter

Persistent Homology analysis of Phase Transitions

Persistent homology analysis, a recently developed computational method in algebraic topology, is applied to the study of the phase transitions undergone by the so-called XY-mean field model and by the phi^4 lattice model, respectively. For both models the relationship between phase transitions and the topological properties of certain submanifolds of configuration space are exactly known. It turns out that these a-priori known facts are clearly retrieved by persistent homology analysis of dynamically sampled submanifolds of configuration space.Comment: 10 pages; 10 figure

Clinical Evaluation and Orodental Status in a Group of Elderly Institutionalised Patients

10% of elderly patients are functionally dependents and they therefore need permanent assistance. Orodental alterations may evolve into a pathological state in elderly people, which is increasing in the recent decades. The current study analysed institutionalized patients in the district of Bari (Southern Italy), who have been so far monitored. We assessed 125 elderly institutionalized patients. The assessment has been carried out by an assessment questionnaire aiming at evaluating the patient’s psychophysical health status, objective intraoral test and prosthetic rehabilitations. About 90% of enrolled patients reported a good general health status. The main dental problems are due to the complete lack of specific prevention and treatment programs, together with handicap, presence of systemic diseases and medicines taken. The level of oral hygiene is poor and the conditions of the residual dental elements are precarious because of root caries and periodontal problems. Prostheses are usually old (on average 15) and appear scarcely retentive and unstable. We believe in the need for specific interventions aiming at the various issues emerging from the present study, so as to achieve a smaller prevalence of dental loss, periodontal disease and caries. These relatively simple interventions are now lacking because of the non-demand of treatment from patients and for economical reasons

Assessment of psychopatologic traits in a group of patients with adult chronic periodontitis: Study on 108 cases and analysis of compliance during and after periodontal treatment

Objectives: Although there is nowadays wide agreement on bacteria being the main etiologic agents of periodontal disease, their sole presence cannot damage periodontal tissues in all subjects. This suggests that an individual response and an adaptation to a certain quantity of bacterial biofilm can occur without the disease progressing and vice versa. Depression, stress and anxiety have not been confirmed yet as risk conditions but, in some observational studies, they have been identified as potential risk factors of periodontal disease. The current study aims at investigating the role which these psychological disorder have in the onset and progression of advanced stage periodontitis. Materials and methods: The case selection was carried out by means of clinical and radiological periodontal assessment involving a total of 108 subjects, both male and female, aged between 24 and 67. Patients were then divided in two groups of 54 patients each: the first group included patients with severe periodontal disease, the second group was formed by periodontally healthy subjects. Clinical assessment was performed by a sole examiner who selected and divided periodontopathic patients from non-periodontopathic ones. From the current study were excluded: patients with systemic pathologies; smokers; patients taking antidepressant drugs; pregnant women. Results: For what concerns depression, in the group of periodontopathic patients it was found that the 62.5% of them were depressed, against the 38.86% in the group of periodontally healthy subjects. For the other two psychological conditions taken into consideration, anxiety and stress, it emerged a different percentage of subjects with anxiety in the periodontal group (31.48%) against healthy controls (20.37%). Conclusions: For each of the psychological variables considered (depression, anxiety, stress), a significant correlation could be observed with periodontal disease, it can be therefore be suggested that the importance these disturbs have in the onset and progress of the dental disease which supports the existing available data in literature. The innovative aspect of this research was the focus on the assessment of compliance, monitoring the ability of periodontal patients to follow oral hygiene instructions aiming at the improving and keeping their own periodontal condition, even though this takes more time than the control group

The rise of the C IV mass density at z<2.5

The cosmic evolution of the metal content of the intergalactic medium puts stringent constraints on the properties of galactic outflows and on the nature of UV background. In this paper, we present a new measure of the redshift evolution of the mass density of C IV, Omega_CIV, in the interval 1.5 < z < 4 based on a sample of more than 1500 C IV lines with column densities 10^{12} < N(CIV) < 10^{15} cm^{-2}. This sample more than doubles the absorption redshift path covered in the range z<2.5 by previous samples. The result shows a significant increase of Omega_CIV towards the lower redshifts at variance with the previously pictured constant behaviour.Comment: Accepted for publication in MNRAS (October 2009). Replaced to match published versio

Roughness analysis on composite materials (Microfilled, nanofilled and silorane) after different finishing and polishing procedures

The finishing and polishing of composite materials affect the restoration lifespan. The market shows a variety of finishing and polishing procedures and the choice among them is conditioned by different factors such as the resulting surface roughness. In the present study, 156 samples were realized with three composite materials,-microfilled, nanofilled and silorane-, and treated with different finishing and polishing procedures. Profilometric analyses were carried out on the samples’ surface, the measured roughness values were submitted to statistical analysis. A complete factorial plan was drawn up and two-way analysis of variance (ANOVA) was carried out to investigate whether the following factors affect the values of roughness: (i) material; (ii) polishing/finishing procedure. Tukey post-hoc test was also conducted to evaluate any statistically significant differences between the material/procedure combinations. The results show that the tested materials do not affect the resulting surface quality but roughness values depend on the finishing/polishing procedure adopted. The procedures that involve: (a) the finishing with medium Sof-Lex discs and (b) the finishing with two tungsten carbide multi-blade milling cutters Q series and UF series are those that allow the lowest values of roughness to be obtained

Quality of life in fibromyalgia patients with craniomandibular disorders

Fibromyalgia (FM) is a rheumatic disease which affects fibrous tissues and muscles; it is characterized by chronic pain and it is often associated with craniomandibular disorders (CMD). 31 patients were assessed from March 2012 to October 2012 through the administration of specific questionnaires and following neurologic and gnatologic assessment. A relevant corre-lation between FM and CMD emerges from the present study, as 80.6% of our patients report CMD symptoms with high prevalence of myofascial pain (84%). Multivariate regression analysis revealed that the patients in the present study did not differ in score of quality of life questionnaires from patients with fibromyalgia. The neuropathic pain diagnostic question-naire (DN4) scores were positively affected by belonging to group II of Research Diagnostic Criteria of Temporomandibular Disorders (RDC/ TDM) classification, suggesting the possibility of a neuropathic component in chronic pain in this CMD group, as already speculated in our study on the correlation between burning mouth syndrome and CMD and by other au-thors in studies on chronic low back pain. However, further clinic and instrumental studies are needed in order to test this as-sumption

A Comparison of Manual Nylon Bristle Toothbrushes versus Thermoplastic Elastomer Toothbrushes in Terms of Cleaning Efficacy and the Biological Potential Role on Gingival Health

Featured Application This study was designed to evaluate changes in toothbrush-dependent oral hygiene scores as well as plaque removal efficacy measured as the Oral Hygiene Index (OHI), Gingival Index (GI) and Plaque Index (PI), comparing an entirely rubber-like material called thermoplastic elastomer with a soft toothbrush (nylon bristles, standard control). Background: It is well-known that toothbrushing might be associated with the development of oral soft tissue lesions. There is currently a continuing increase in the demand for new safety and performing materials in daily homecare oral hygiene including soft and extra-soft toothbrush bristles that tend to be safer. The aim of this study was to compare the efficacy of plaque control and the potential effects on gingival health of two different toothbrush bristle models. Methods: In a three-month period, a total of forty subjects were evaluated for Oral Hygiene Index (OHI), Gingival Index (GI) and Plaque Index (PI) scores as well the Gingival Abrasion Assessment (GAA) between a toothbrush entirely made from a rubber-like material called thermoplastic elastomer (TPE) and a soft toothbrush (standard control with nylon bristles) in a clinical, single-blind, controlled, parallel-group trial. Results: The use of the TPE toothbrush allows a reduction in the PI, improves the OHI and modifies the GAA in the TPE group over a period of three months compared with a conventional soft bristle toothbrush applied for the same period, leading in this way evidence for a good influence of the TPE bristles on overall oral hygiene conditions. Conclusions: From the comparison between our data and the literature studies, we can state that the material and shape of the bristles of the toothbrush affect the home practice of oral hygiene. The TPE bristles reduce the presence of plaque formation and gingival bleeding, oral soft tissue injuries acquired during homecare oral hygiene

Effect of Different Irrigating Solutions and Endodontic Sealers on Bond Strength of the Dentin - Post Interface with and without Defects.

Abstract Aims. To investigate how the interfacial shear strength of the dentin – post interface with and without defects changes for different combinations irrigant/sealer. Methods. In forty human decoronated and instrumented teeth, fibreglass posts were in-serted. The obtained root segments were randomly assigned to four different groups ac-cording to the irrigant adopted and the cement used to seal the root canal. The root segments were processed for metyl-methacrylate embedding. Serial sections were obtained and sub-mitted to histomorphometric analyses in order to observe any defect of adhesion at the dentin – post interface and to measure the defects’ dimension. The serial sections were also submitted to micro-push-out test. The measured shear strength values were subjected to statistical analysis by one-way ANOVA. The values of bond strength determined for the defective samples were correlated with the dimension of the defects. Finite element models were built to interpret and corroborate the experimental findings. Results. ANOVA showed that the generic combination irrigant/sealer does not affect the interfacial shear strength values. The bond strength of the samples without defects was av-eragely twice as large as that of the defective samples. The defects occupying more than 12 % of the total transverse section area of the endodontic cement layer led to a reduction of the bond strength of about 70 %. The predictions of the finite element models were in agreement with the experimental results. Conclusion. Defects occupying less than 2 % of the total transverse section area of the cement layer were shown to be acceptable as they have rather negligible effects on the shear strength values. Technologies/protocols should be developed to minimize the number and the size of the defects