Manual versus powered toothbrushes for oral health; an update

Background: Plaque removal is a cornerstone in the prevention and treatment of periodontal diseases. Powered toothbrushes have been devised to assist in plaque removal. An earlier Cochrane systematic review found that only powered toothbrushes with a rotation-oscillation action were more effective at removing plaque and reducing gingivitis. That review requires updating to include recent trials. Objective: To compare the effects of manual and powered toothbrushes on plaque removal and gingival health. Method: We searched the Cochrane Oral Health Group Trials Register, CENTRAL; MEDLINE, EMBASE and CINAHL to 9 March 2011. Manufacturers and authors were contacted for additional data. Trials were selected for random allocation of participants to use a manual or powered toothbrush. Participants were members of the public with uncompromised manual dexterity who brushed unsupervised for at least 4 weeks. There was no language restriction. Primary outcomes were plaque and gingivitis scores at the end of the trial. Assessment of methodological quality and data extraction were conducted in duplicate. Potential sources of heterogeneity were examined, along with sensitivity analyses for quality and publication bias. Results: Fifty trials, involving 4326 participants, provided data. Effect sizes, calculated as standardized mean difference (95% confidence intervals) for brushes with a rotation oscillation action were: 1 to 3 months >3 months Plaque -0.53 (-0.74 to -0.31) -0.66 (-1.28 to -0.03) Gingivitis -0.49 (-0.73 to -0.26) -0.34 (-0.56 to -0.11) This represents approximately 27% fewer sites with bleeding on probing in the long term. No other powered designs were consistently superior to manual toothbrushes. There was considerable heterogeneity between trials. Sensitivity analyses revealed the results to be robust when selecting trials of high quality. Conclusion: Rotation-oscillation powered toothbrushes remove plaque and reduce gingivitis more than manual brushes in the short and long term

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45–60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45–60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke’s Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective

Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort.

INTRODUCTION: This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort. METHODS: The magnitude of association for each genotype was assessed in 1,046 RA subjects from the Yorkshire Early RA cohort and in 5,968 healthy UK controls. Additional exploratory subanalyses were undertaken in subgroups defined by autoantibody status (rheumatoid factor and anti-cyclic citrullinated peptide) or disease severity (baseline articular erosions, Health Assessment Questionnaire (HAQ) score and swollen joint count (SJC)). RESULTS: In the total RA inception cohort, the HLA-DRB1 shared epitope (per-allele odds ratio (OR) = 2.1, trend P < 0.0001), PTPN22 (per-allele OR = 1.5, trend P < 0.0001), OLIG3/TNFAIP3 locus (per-allele OR = 1.2, trend P = 0.009) and TRAF1/C5 locus (per-allele OR = 1.1, trend P = 0.04) were associated with RA. The magnitude of association for these loci was increased in those patients who were autoantibody-positive. PTPN22 was associated with autoantibody-negative RA (per-allele OR = 1.3, trend P = 0.04). There was no evidence of association between these five genetic loci and baseline erosions or SJC in the total RA cohort, after adjustment for symptom duration. TRAF1/C5 was significantly associated with baseline HAQ, however, following adjustment for symptom duration (P trend = 0.03). CONCLUSIONS: These findings support the mounting evidence that different genetic loci are associated with autoantibody-positive and autoantibody-negative RA, possibly suggesting that many of the genes identified to date are associated with autoantibody production. Additional studies with a specific focus on autoantibody-negative RA will be needed to identify the genes predisposing to this RA subgroup. The TRAF1/C5 locus in particular warrants further investigation in RA as a potential disease severity locus

Relação entre eventos vitais e história de ansiedade na infância, história familiar de ansiedade e curso do transtorno do pânico

OBJECTIVES: The authors examined the incidence of significant life events during the year prior to the onset of panic disorder and its relationship to childhood and family history of anxiety difficulties, comorbidity, and the course of illness.MATERIALS AND METHODS: 223 panic patients were followed in a naturalistic study of panic disorder.RESULTS: Similar to previous reports, antecedent negative life events occurred in the majority (80%) of patients. Patients with a childhood history of anxiety and comorbid adulthood major depression were more likely to report an antecedent, stressful life event.CONCLUSIONS: Antecedent events were not linked with comorbid adulthood anxiety disorders or a family history of anxiety difficulties. Despite its associations with childhoodnxiety pathology and adulthood major depression, the presence of an identifiable antecedent at the onset of panic disorder was not associated with the subsequent severity or course of the disorder.OBJETIVO: Os autores examinaram a freqüência de eventos vitais significativos (estressores) durante o ano que antecedeu o transtorno do pânico e sua relação com história de ansiedade na infância, história familiar de ansiedade, comorbidades e curso da doença.MATERIAIS E MÉTODOS: 223 pacientes foram acompanhados em um estudo naturalístico, longitudinal do transtorno do pânico.RESULTADOS: Apesar de 80% dos pacientes com transtorno do pânico referirem a presença de um fator estressor durante o ano anterior ao início da sua doença, sua freqüência é mais elevada em pacientes com história de ansiedade na infância e comorbidade com depressão na vida adulta.CONCLUSÕES: A presença de eventos vitais significativos não está associada com a presença de outros transtornos de ansiedade na vida adulta e nem com história familiar de ansiedade. Apesar de sua associação com história de ansiedade na infância e depressão, a presença de um fator estressor identificável não está associado a severidade ou ao curso do transtorno do pânico

Forgiveness-Reconciliation and Communication-Conflict-Resolution Interventions Versus Retested Controls in Early Married Couples

The first 6 months of marriage are optimal for marriage enrichment interventions. The Hope-Focused Approach to couple enrichment was presented as two 9-hr interventions--(a) Handling Our Problems Effectively (HOPE), which emphasized communication and conflict resolution, and (b) Forgiveness and Reconciliation through Experiencing Empathy (FREE). HOPE and FREE were compared with repeated assessment controls. Couples were randomly assigned and were assessed at pretreatment (t1); 1 month posttreatment (t2) and at 3- (t3), 6- (t4), and 12-month (t5) follow-ups using self-reports. In addition to self-report measures, couples were assessed at t1, t2, and t5 using salivary cortisol, and behavioral coding of decision making. Of 179 couples who began the study, 145 cases were analyzed. Both FREE and HOPE produced lasting positive changes on self-reports. For cortisol reactivity, HOPE and FREE reduced reactivity at t2, but only HOPE at t5. For coded behaviors, control couples deteriorated; FREE and HOPE did not change. Enrichment training was effective regardless of the focus of the training

A substrate mimic allows high-throughput assay of the FabA protein and consequently the identification of a novel inhibitor of <i>Pseudomonas aeruginosa</i> FabA

The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 223461, Senior Investigator Award WT100209MA (JHN), Swedish Science Council (GS), Wellcome Trust Strategic grant 100476/Z/12/Z (DWG) and National Institutes of Health R01GM095970 (MB). JHN & ADS are Royal Society Wolfson Merit Award holders.Eukaryotes and prokaryotes possess fatty acid synthase (FAS) biosynthetic pathway(s) that comprise iterative chain elongation, reduction, and dehydration reactions. The bacterial FASII pathway differs significantly from human FAS pathways and is a long-standing target for antibiotic development against Gram-negative bacteria due to differences from the human FAS, and several existing antibacterial agents are known to inhibit FASII enzymes. N-acetylcysteamine (NAC) fatty acid thioesters have been used as mimics of the natural acyl carrier protein (ACP) pathway intermediates to assay FASII enzymes, and we now report an assay of FabV from Pseudomonas aeruginosa using (E)-2-decenoyl-NAC. In addition, we have converted an existing UV absorbance assay for FabA, the bifunctional dehydration/epimerization enzyme and key target in the FAS II pathway, into a high throughput enzyme coupled fluorescence assay that has been employed to screen a library of diverse small molecules. With this approach, N-(4-chlorobenzyl)-3-(2-furyl)-1H-1,2,4-triazol-5-amine (N42FTA) was found to competitively inhibit (pIC50 = 5.7 ± 0.2) the processing of 3-hydroxydecanoyl-NAC by P. aeruginosa FabA. N42FTA was shown to be potent in blocking crosslinking of E. coli ACP and FabA, a direct mimic of the biological process. The co-complex structure of N42FTA with P. aeruginosa FabA protein rationalizes affinity and suggests future design opportunities. Employing NAC fatty acid mimics to developing further high throughput assays for individual enzymes in the FASII pathway should aid in the discovery of new antimicrobials.Publisher PDFPeer reviewe

Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility

Rheumatoid arthritis (RA) is an archetypal, common, complex autoimmune disease with both genetic and environmental contributions to disease aetiology. Two novel RA susceptibility loci have been reported from recent genome-wide and candidate gene association studies. We, therefore, investigated the evidence for association of the STAT4 and TRAF1/C5 loci with RA using imputed data from the Wellcome Trust Case Control Consortium (WTCCC). No evidence for association of variants mapping to the TRAF1/C5 gene was detected in the 1860 RA cases and 2930 control samples tested in that study. Variants mapping to the STAT4 gene did show evidence for association (rs7574865, P = 0.04). Given the association of the TRAF1/C5 locus in two previous large case–control series from populations of European descent and the evidence for association of the STAT4 locus in the WTCCC study, single nucleotide polymorphisms mapping to these loci were tested for association with RA in an independent UK series comprising DNA from >3000 cases with disease and >3000 controls and a combined analysis including the WTCCC data was undertaken. We confirm association of the STAT4 and the TRAF1/C5 loci with RA bringing to 5 the number of confirmed susceptibility loci. The effect sizes are less than those reported previously but are likely to be a more accurate reflection of the true effect size given the larger size of the cohort investigated in the current study

Spiroindolines Identify the Vesicular Acetylcholine Transporter as a Novel Target for Insecticide Action

The efficacy of all major insecticide classes continues to be eroded by the development of resistance mediated, in part, by selection of alleles encoding insecticide insensitive target proteins. The discovery of new insecticide classes acting at novel protein binding sites is therefore important for the continued protection of the food supply from insect predators, and of human and animal health from insect borne disease. Here we describe a novel class of insecticides (Spiroindolines) encompassing molecules that combine excellent activity against major agricultural pest species with low mammalian toxicity. We confidently assign the vesicular acetylcholine transporter as the molecular target of Spiroindolines through the combination of molecular genetics in model organisms with a pharmacological approach in insect tissues. The vesicular acetylcholine transporter can now be added to the list of validated insecticide targets in the acetylcholine signalling pathway and we anticipate that this will lead to the discovery of novel molecules useful in sustaining agriculture. In addition to their potential as insecticides and nematocides, Spiroindolines represent the only other class of chemical ligands for the vesicular acetylcholine transporter since those based on the discovery of vesamicol over 40 years ago, and as such, have potential to provide more selective tools for PET imaging in the diagnosis of neurodegenerative disease. They also provide novel biochemical tools for studies of the function of this protein family