Confocal laser scanning, scanning electron, and transmission electron microscopy investigation of Enterococcus faecalis biofilm degradation using passive and active sodium hypochlorite irrigation within a simulated root canal model

Root canal irrigation is an important adjunct to control microbial infection. The aim of this study was to investigate the effect of 2.5% (wt/vol) sodium hypochlorite (NaOCl) agitation on the removal, killing, and degradation of Enterococcus faecalis biofilm. A total of 45 root canal models were manufactured using 3D printing with each model comprising an 18 mm length simulated root canal of apical size 30 and taper 0.06. E. faecalis biofilms were grown on the apical 3 mm of the models for 10 days. A total of 60 s of 9 ml of 2.5% NaOCl irrigation using syringe and needle was performed, the irrigant was either left stagnant in the canal or agitated using manual (Gutta-percha), sonic, and ultrasonic methods for 30 s. Following irrigation, the residual biofilms were observed using confocal laser scanning, scanning electron, and transmission electron microscopy. The data were analyzed using one-way ANOVA with Dunnett post hoc tests at a level of significance p ≤ .05. Consequence of root canal irrigation indicate that the reduction in the amount of biofilm achieved with the active irrigation groups (manual, sonic, and ultrasonic) was significantly greater when compared with the passive and untreated groups (p < .05). Collectively, finding indicate that passive irrigation exhibited more residual biofilm on the model surface than irrigant agitated by manual or automated (sonic, ultrasonic) methods. Total biofilm degradation and nonviable cells were associated with the ultrasonic group

The effect of sodium hypochlorite concentration and irrigation needle extension on biofilm removal from a simulated root canal model

To investigate the effect of sodium hypochlorite concentration and needle extension on removal of Enterococcus faecalis biofilm, sixty root canal models were 3D printed. Biofilms were grown on the apical 3 mm of the canal for 10 days. Irrigation for 60s with 9 mL of either 5.25% or 2.5% NaOCl or water was performed using a needle inserted either 3 or 2 mm from the canal terminus and imaged using fluorescence microscopy and residual biofilm percentages were calculated using imaging software. The data were analysed using analysis of covariance and two-sample t-tests. A significance level of 0.05 was used throughout. Residual biofilm was less using 5.25% than with 2.5% NaOCl. Statistically significant biofilm removal was evident with the needle placed closer to the canal terminus. A greater reduction of available chlorine and pH was noted as the concentration increased. One-minute irrigation was not sufficient for complete biofilm removal

Integration and Comparison of Transcriptomic and Proteomic Data for Meningioma

Meningioma are the most frequent primary intracranial tumour. Management of aggressive meningioma is complex, and development of effective biomarkers or pharmacological interventions is hampered by an incomplete knowledge of molecular landscape. Here, we present an integrated analysis of two complementary omics studies to investigate alterations in the “transcriptome–proteome” profile of high-grade (III) compared to low-grade (I) meningiomas. We identified 3598 common transcripts/proteins and revealed concordant up- and downregulation in grade III vs. grade I meningiomas. Concordantly upregulated genes included FABP7, a fatty acid binding protein and the monoamine oxidase MAOB, the latter of which we validated at the protein level and established an association with Food and Drug Administration (FDA)-approved drugs. Notably, we derived a plasma signature of 21 discordantly expressed genes showing positive changes in protein but negative in transcript levels of high-grade meningiomas, including the validated genes CST3, LAMP2, PACS1 and HTRA1, suggesting the acquisition of these proteins by tumour from plasma. Aggressive meningiomas were enriched in processes such as oxidative phosphorylation and RNA metabolism, whilst concordantly downregulated genes were related to reduced cellular adhesion. Overall, our study provides the first transcriptome–proteome characterisation of meningioma, identifying several novel and previously described transcripts/proteins with potential grade III biomarker and therapeutic significance.</jats:p

Toxic metal enrichment and boating intensity: sediment records of antifoulant copper in shallow lakes of eastern England

Tributyltin (TBT), an aqueous biocide derived from antifouling paint pollution, is known to have impacted coastal marine ecosystems, and has been reported in the sediment of the Norfolk and Suffolk Broads, a network of rivers and shallow lakes in eastern England. In the marine environment, the 1987 TBT ban has resulted in expanded use of alternative biocides, raising the question of whether these products too have impacted the Broads ecosystem and freshwaters in general. Here we examine the lake sediment record in the Norfolk and Suffolk Broads for contamination by copper (Cu) (as an active biocide agent) and zinc (Zn) (as a component of booster biocides), to assess their occurrence and potential for causing environmental harm in freshwater ecosystems. We find that, after the introduction of leisure boating, there is a statistically significant difference in Cu enrichment between heavily and lightly boated sites, while no such difference exists prior to this time. At the heavily boated sites the onset of Cu enrichment coincides with a period of rapid increase in leisure boating. Such enrichment is maintained to the present day, with some evidence of continued increase. We conclude that Cu-based antifouling has measurably contaminated lakes exposed to boating, at concentrations high enough to cause ecological harm. Similar findings can be expected at other boated freshwater ecosystems elsewhere in the world

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Cluster and virial expansions for the multi-species tonks gas

We consider a mixture of non-overlapping rods of different lengths ℓk moving in R or Z. Our main result are necessary and sufficient convergence criteria for the expansion of the pressure in terms of the activities zk and the densities ρk. This provides an explicit example against which to test known cluster expansion criteria, and illustrates that for non-negative interactions, the virial expansion can converge in a domain much larger than the activity expansion. In addition, we give explicit formulas that generalize the well-known relation between non-overlapping rods and labelled rooted trees. We also prove that for certain choices of the activities, the system can undergo a condensation transition akin to that of the zero-range process. The key tool is a fixed point equation for the pressure

No Major Change in vCJD Agent Strain after Secondary Transmission via Blood Transfusion

The identification of transmission of variant Creutzfeldt-Jakob disease (vCJD) by blood transfusion has prompted investigation to establish whether there has been any alteration in the vCJD agent following this route of secondary transmission. Any increase in virulence or host adaptation would require a reassessment of the risk analyses relating to the possibility of a significant secondary outbreak of vCJD. Since there are likely to be carriers of the vCJD agent in the general population, there is a potential for further infection by routes such as blood transfusion or contaminated surgical instruments.We inoculated both wild-type and transgenic mice with material from the first case of transfusion associated vCJD infection.The strain transmission properties of blood transfusion associated vCJD infection show remarkable similarities to the strain of vCJD associated with transmission from bovine spongiform encephalopathy (BSE).Although it has been hypothesized that adaptation of the BSE agent through secondary passage in humans may result in a greater risk of onward transmission due to an increased virulence of the agent for humans, our data presented here in two murine models suggest no significant alterations to transmission efficiency of the agent following human-to-human transmission of vCJD

Newly diagnosed incident dizziness of older patients: a follow-up study in primary care

<p>Abstract</p> <p>Background</p> <p>Dizziness is a common complaint of older patients in primary care, yet not much is known about the course of incident dizziness. The aim of the study was to follow-up symptoms, subjective impairments and needs of older patients (≥65) with incident dizziness and to determine predictors of chronic dizziness. Furthermore, we analysed general practitioners' (GPs') initial diagnoses, referrals and revised diagnoses after six months.</p> <p>Methods</p> <p>An observational study was performed in 21 primary care practices in Germany, including a four-week and six-month follow-up. A questionnaire comprising characteristic matters of dizziness and a series of validated instruments was completed by 66 participants during enrolment and follow-up (after 1 month and 6 months). After six months, chart reviews and face-to-face interviews were also performed with the GPs.</p> <p>Results</p> <p>Mean scores of dizziness handicap, depression and quality of life were not or only slightly affected, and did not deteriorate during follow-up; however, 24 patients (34.8%) showed a moderate or severe dizziness handicap, and 43 (62.3%) showed a certain disability in terms of quality of life at the time of enrolment. In multivariate analysis, n = 44 patients suffering from chronic dizziness (dependent variable, i.e. relapsing or persistent at six months) initially had a greater dizziness handicap (OR 1.42, 95%CI 1.05-1.47) than patients with transient dizziness. GPs referred 47.8% of the patients to specialists who detected two additional cases of benign paroxysmal positional vertigo (BPPV).</p> <p>Conclusions</p> <p>New-onset dizziness relapsed or persisted in a considerable number of patients within six months. This was difficult to predict due to the patients' heterogeneous complaints and characteristics. Symptom persistence does not seem to be associated with deterioration of the psychological status in older primary care patients. Management strategies should routinely consider BPPV as differential diagnosis.</p

Bioassay studies support the potential for latrogenic transmission of variant Creutzfeldt Jakob disease through dental procedures

Background: Evidence is required to quantify the potential risks of transmission of variant Creutzfeldt Jakob (vCJD) through dental procedures. Studies, using animal models relevant to vCJD, were performed to address two questions. Firstly, whether oral tissues could become infectious following dietary exposure to BSE? Secondly, would a vCJD-contaminated dental instrument be able to transmit disease to another patient? Methods: BSE-301V was used as a clinically relevant model for vCJD. VM-mice were challenged by injection of infected brain homogenate into the small intestine (Q1) or by five minute contact between a deliberately-contaminated dental file and the gingival margin (Q2). Ten tissues were collected from groups of challenged mice at three or four weekly intervals, respectively. Each tissue was pooled, homogenised and bioassayed in indicator mice. Findings: Challenge via the small intestine gave a transmission rate of 100% (mean incubation 157±17 days). Infectivity was found in both dental pulp and the gingival margin within 3 weeks of challenge and was observed in all tissues tested within the oral cavity before the appearance of clinical symptoms. Following exposure to deliberately contaminated dental files, 97% of mice developed clinical disease (mean incubation 234±33 days). Interpretation: Infectivity was higher than expected, in a wider range of oral tissues, than was allowed for in previous risk assessments. Disease was transmitted following transient exposure of the gingiva to a contaminated dental file. These observations provide evidence that dental procedures could be a route of cross-infection for vCJD and support the enforcement of single-use for certain dental instruments