Adjunctive antimicrobial photodynamic therapy for treating periodontal and peri-implant diseases.

BACKGROUND: Periodontitis and peri-implant diseases are chronic inflammatory conditions occurring in the mouth. Left untreated, periodontitis progressively destroys the tooth-supporting apparatus. Peri-implant diseases occur in tissues around dental implants and are characterised by inflammation in the peri-implant mucosa and subsequent progressive loss of supporting bone. Treatment aims to clean the pockets around teeth or dental implants and prevent damage to surrounding soft tissue and bone, including improvement of oral hygiene, risk factor control (e.g. encouraging cessation of smoking) and surgical interventions. The key aspect of standard non-surgical treatment is the removal of the subgingival biofilm using subgingival instrumentation (SI) (also called scaling and root planing). Antimicrobial photodynamic therapy (aPDT) can be used an adjunctive treatment to SI. It uses light energy to kill micro-organisms that have been treated with a light-absorbing photosensitising agent immediately prior to aPDT. OBJECTIVES: To assess the effects of SI with adjunctive aPDT versus SI alone or with placebo aPDT for periodontitis and peri-implant diseases in adults. SEARCH METHODS: We searched the Cochrane Oral Health Trials Register, CENTRAL, MEDLINE, Embase, two other databases and two trials registers up to 14 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) (both parallel-group and split-mouth design) in participants with a clinical diagnosis of periodontitis, peri-implantitis or peri-implant disease. We compared the adjunctive use of antimicrobial photodynamic therapy (aPDT), in which aPDT was given after subgingival or submucosal instrumentation (SI), versus SI alone or a combination of SI and a placebo aPDT given during the active or supportive phase of therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures, and we used GRADE to assess the certainty of the evidence. We prioritised six outcomes and the measure of change from baseline to six months after treatment: probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment level (CAL), gingival recession (REC), pocket closure and adverse effects related to aPDT. We were also interested in change in bone level (for participants with peri-implantitis), and participant satisfaction and quality of life. MAIN RESULTS: We included 50 RCTs with 1407 participants. Most studies used a split-mouth study design; only 18 studies used a parallel-group design. Studies were small, ranging from 10 participants to 88. Adjunctive aPDT was given in a single session in 39 studies, in multiple sessions (between two and four sessions) in 11 studies, and one study included both single and multiple sessions. SI was given using hand or power-driven instrumentation (or both), and was carried out prior to adjunctive aPDT. Five studies used placebo aPDT in the control group and we combined these in meta-analyses with studies in which SI alone was used. All studies included high or unclear risks of bias, such as selection bias or performance bias of personnel (when SI was carried out by an operator aware of group allocation). We downgraded the certainty of all the evidence owing to these risks of bias, as well as for unexplained statistical inconsistency in the pooled effect estimates or for imprecision when evidence was derived from very few participants and confidence intervals (CI) indicated possible benefit to both intervention and control groups. Adjunctive aPDT versus SI alone during active treatment of periodontitis (44 studies) We are very uncertain whether adjunctive aPDT during active treatment of periodontitis leads to improvement in any clinical outcomes at six months when compared to SI alone: PPD (mean difference (MD) 0.52 mm, 95% CI 0.31 to 0.74; 15 studies, 452 participants), BOP (MD 5.72%, 95% CI 1.62 to 9.81; 5 studies, 171 studies), CAL (MD 0.44 mm, 95% CI 0.24 to 0.64; 13 studies, 414 participants) and REC (MD 0.00, 95% CI -0.16 to 0.16; 4 studies, 95 participants); very low-certainty evidence. Any apparent differences between adjunctive aPDT and SI alone were not judged to be clinically important. Twenty-four studies (639 participants) observed no adverse effects related to aPDT (moderate-certainty evidence). No studies reported pocket closure at six months, participant satisfaction or quality of life. Adjunctive aPDT versus SI alone during supportive treatment of periodontitis (six studies) We were very uncertain whether adjunctive aPDT during supportive treatment of periodontitis leads to improvement in any clinical outcomes at six months when compared to SI alone: PPD (MD -0.04 mm, 95% CI -0.19 to 0.10; 3 studies, 125 participants), BOP (MD 4.98%, 95% CI -2.51 to 12.46; 3 studies, 127 participants), CAL (MD 0.07 mm, 95% CI -0.26 to 0.40; 2 studies, 85 participants) and REC (MD -0.20 mm, 95% CI -0.48 to 0.08; 1 study, 24 participants); very low-certainty evidence. These findings were all imprecise and included no clinically important benefits for aPDT. Three studies (134 participants) reported adverse effects: a single participant developed an abscess, though it is not evident whether this was related to aPDT, and two studies observed no adverse effects related to aPDT (moderate-certainty evidence). No studies reported pocket closure at six months, participant satisfaction or quality of life. AUTHORS' CONCLUSIONS: Because the certainty of the evidence is very low, we cannot be sure if adjunctive aPDT leads to improved clinical outcomes during the active or supportive treatment of periodontitis; moreover, results suggest that any improvements may be too small to be clinically important. The certainty of this evidence can only be increased by the inclusion of large, well-conducted RCTs that are appropriately analysed to account for change in outcome over time or within-participant split-mouth study designs (or both). We found no studies including people with peri-implantitis, and only one study including people with peri-implant mucositis, but this very small study reported no data at six months, warranting more evidence for adjunctive aPDT in this population group.

Motivations for and outcomes of graduate education amongst dental hygienists: A pan-Canadian study.

OBJECTIVES: Motivations and career outcomes of dental hygienists with baccalaureate degrees have been recently reported; however, few studies have explored Canadian dental hygienists pursuing graduate education. There is limited evidence to inform career outcomes and motivating factors for advanced education, limiting knowledge of how professional outcomes have evolved alongside advancements in graduate program offerings. This study focused on understanding motivating factors to pursue graduate education and the professional outcomes of dental hygienists with graduate degrees. METHODS: This nested online anonymous survey was conducted between November and December 2021 with dental hygienists who graduated from one of four Canadian baccalaureate-level dental hygiene degree programs and had further indicated that they were pursuing or had obtained additional graduate-level education (n = 60). Participants were asked to report on any advanced graduate-level education. Open-ended questions on graduate degree education were analysed through thematic analysis. RESULTS: Motivations for pursuing graduate degrees were influenced by personal and professional preferences. Master's degree recipients cited expanded career opportunities, alternate interests, convenience, and dissatisfaction with/desire to leave clinical practice as major motivators. Doctoral degree holding dental hygienists identified expanded/alternate career opportunities as major motivation but also cited program convenience as an influencer. The availability of distance and flexible programming is a novel finding that positively influences the pursuit of advanced education. CONCLUSION: Dental hygienists are pursuing graduate education to expand their scope of knowledge and create new career opportunities. Graduate degree programs that accommodate work-life balance through flexible and online offerings are very attractive to dental hygienists.

Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011-2014 but increased during 2015-2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5-64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

Treatment of periodontitis for glycaemic control in people with diabetes mellitus.

BACKGROUND: Glycaemic control is a key component in diabetes mellitus (diabetes) management. Periodontitis is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontitis.  Treatment for periodontitis involves subgingival instrumentation, which is the professional removal of plaque, calculus, and debris from below the gumline using hand or ultrasonic instruments. This is known variously as scaling and root planing, mechanical debridement, or non-surgical periodontal treatment. Subgingival instrumentation is sometimes accompanied by local or systemic antimicrobials, and occasionally by surgical intervention to cut away gum tissue when periodontitis is severe. This review is part one of an update of a review published in 2010 and first updated in 2015, and evaluates periodontal treatment versus no intervention or usual care.  OBJECTIVES: To investigate the effects of periodontal treatment on glycaemic control in people with diabetes mellitus and periodontitis. SEARCH METHODS: An information specialist searched six bibliographic databases up to 7 September 2021 and additional search methods were used to identify published, unpublished, and ongoing studies.  SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 diabetes mellitus and a diagnosis of periodontitis that compared subgingival instrumentation (sometimes with surgical treatment or adjunctive antimicrobial therapy or both) to no active intervention or 'usual care' (oral hygiene instruction, education or support interventions, and/or supragingival scaling (also known as PMPR, professional mechanical plaque removal)). To be included, the RCTs had to have lasted at least 3 months and have measured HbA1c (glycated haemoglobin). DATA COLLECTION AND ANALYSIS: At least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials, and assessed included trials for risk of bias. Where necessary and possible, we attempted to contact study authors. Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c), which can be reported as a percentage of total haemoglobin or as millimoles per mole (mmol/mol). Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing, clinical attachment level, gingival index, plaque index, and probing pocket depth), quality of life, cost implications, and diabetic complications. MAIN RESULTS: We included 35 studies, which randomised 3249 participants to periodontal treatment or control. All studies used a parallel-RCT design and followed up participants for between 3 and 12 months. The studies focused on people with type 2 diabetes, other than one study that included participants with type 1 or type 2 diabetes. Most studies were mixed in terms of whether metabolic control of participants at baseline was good, fair, or poor. Most studies were carried out in secondary care.  We assessed two studies as being at low risk of bias, 14 studies at high risk of bias, and the risk of bias in 19 studies was unclear. We undertook a sensitivity analysis for our primary outcome based on studies at low risk of bias and this supported the main findings. Moderate-certainty evidence from 30 studies (2443 analysed participants) showed an absolute reduction in HbA1c of 0.43% (4.7 mmol/mol) 3 to 4 months after treatment of periodontitis (95% confidence interval (CI) -0.59% to -0.28%; -6.4 mmol/mol to -3.0 mmol/mol). Similarly, after 6 months, we found an absolute reduction in HbA1c of 0.30% (3.3 mmol/mol) (95% CI -0.52% to -0.08%; -5.7 mmol/mol to -0.9 mmol/mol; 12 studies, 1457 participants), and after 12 months, an absolute reduction of 0.50% (5.4 mmol/mol) (95% CI -0.55% to -0.45%; -6.0 mmol/mol to -4.9 mmol/mol; 1 study, 264 participants). Studies that measured adverse effects generally reported that no or only mild harms occurred, and any serious adverse events were similar in intervention and control arms. However, adverse effects of periodontal treatments were not evaluated in most studies. AUTHORS' CONCLUSIONS: Our 2022 update of this review has doubled the number of included studies and participants, which has led to a change in our conclusions about the primary outcome of glycaemic control and in our level of certainty in this conclusion. We now have moderate-certainty evidence that periodontal treatment using subgingival instrumentation improves glycaemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment versus no treatment/usual care are unlikely to change the overall conclusion reached in this review.

Gender and Regionalization in North America: From NAFTA to CUSMA and Beyond?

The literature on world regions is largely gender-blind. This article suggests ways in which the study of regionalism can incorporate gender analysis, based on the case of North America. It argues that this can be done in three ways: through an examination of the gendered impact of regional integration; through an examination of how gender concerns are, or can be, mainstreamed into regional policies; and through research on new forms of feminist-inspired activism that may shape regional outcomes. After applying these perspectives to the case of North America and the new Canada-United States-Mexico Agreement, it argues that despite the failure of the Canadian government to achieve the inclusion of a gender chapter, the inclusion of language around gender discrimination in the labour chapter makes the new agreement a more effective (if still limited) tool for promotion of some forms of gender equality.

Efficacy and safety of different interventions to accelerate maxillary canine retraction following premolar extraction: A systematic review and network meta-analysis.

Decreasing orthodontic treatment duration is at the forefront of innovation for clinical orthodontics. This network meta-analysis aimed to determine the relative efficacy and safety of treatments for accelerated orthodontic tooth movement (OTM) in patients undergoing extraction of maxillary first premolars followed by canine retraction in any orthodontic setting. MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL and SCOPUS were searched (from inception to 20 April 2020). Study selection and data extraction were performed in duplicate. Eligible randomized controlled trials (RCTs) were meta-analysed to estimate the rate of tooth movement, 95% credible interval and surface under the cumulative ranking curve (SUCRA) in the first 3 months following the application of the adjunctive accelerative method. Eligible RCTs were assessed by Cochrane risk of bias tool, and quality of evidence was assessed by GRADE approach, obtained from CINeMA web application. Interventions were ranked for efficacy and reviewed for safety. Nineteen studies pertaining to eight interventions, with data from 415 patients were included. Quality of evidence was very low to moderate. Very low-to low-quality evidence suggests that corticotomy is an efficacious and safe adjunctive treatment to accelerate OTM in comparison with conventional treatment in the first 2 months of treatment. Low-quality evidence suggests that piezocision and micro-osteoperforations (MOP) are efficacious and safe adjunctive treatments only in the first month of treatment. Frequent MOP in conjunction with low-level laser therapy appeared to be an efficacious and safe adjunctive treatment only in the first month following its initial application but not thereafter.

The relationship between living in urban and rural areas of Scotland and children's physical activity and sedentary levels: a country-wide cross-sectional analysis.

BACKGROUND: Living in urban or rural environments may influence children's levels of physical activity and sedentary behaviours. We know little about variations in device-measured physical activity and sedentary levels of urban and rural children using nationally representative samples, or if these differences are moderated by socioeconomic factors or seasonal variation. Moreover, little is known about the influence of 'walkability' in the UK context. A greater understanding of these can better inform intervention strategies or policy initiatives at the population level. METHODS: Country-wide cross-sectional study in Scotland in which 774 children (427 girls, 357 boys), aged 10/11 years, wore an accelerometer on one occasion for at least four weekdays and one weekend day. Mean total physical activity, time spent in sedentary, light, and moderate-to-vigorous physical activity (MVPA), per day were extracted for weekdays, weekend days, and all days combined. Regression analyses explored associations between physical activity outcomes, urban/rural residence, and a modified walkability index (dwelling density and intersection density); with interactions fitted for household equivalised income and season of data collection. Sensitivity analyses assessed variation in findings by socioeconomic factors and urbanicity. RESULTS: Rural children spent an average of 14 min less sedentary (95% CI of difference: 2.23, 26.32) and 13 min more in light intensity activity (95% CI of difference, 2.81, 24.09) per day than those from urban settlements. No urban-rural differences were found for time spent in MVPA or in total levels of activity. Our walkability index was not associated with any outcome measure. We found no interactions with household equivalised income, but there were urban/rural differences in seasonal variation; urban children engaged in higher levels of MVPA in the spring months (difference: 10 mins, p = 0.06, n.s) and significantly lower levels in winter (difference: 8.7 mins, p = 0.036). CONCLUSIONS: Extrapolated across one-year, rural children would accumulate approximately 79 h (or just over 3 days) less sedentary time than urban children, replacing this for light intensity activity. With both outcomes having known implications for health, this finding is particularly important. Future work should prioritise exploring the patterns and context in which these differences occur to allow for more targeted intervention/policy strategies.

Home use of interdental cleaning devices, in addition to toothbrushing, for preventing and controlling periodontal diseases and dental caries.

BACKGROUND: Dental caries (tooth decay) and periodontal diseases (gingivitis and periodontitis) affect the majority of people worldwide, and treatment costs place a significant burden on health services. Decay and gum disease can cause pain, eating and speaking difficulties, low self-esteem, and even tooth loss and the need for surgery. As dental plaque is the primary cause, self-administered daily mechanical disruption and removal of plaque is important for oral health. Toothbrushing can remove supragingival plaque on the facial and lingual/palatal surfaces, but special devices (such as floss, brushes, sticks, and irrigators) are often recommended to reach into the interdental area. OBJECTIVES: To evaluate the effectiveness of interdental cleaning devices used at home, in addition to toothbrushing, compared with toothbrushing alone, for preventing and controlling periodontal diseases, caries, and plaque. A secondary objective was to compare different interdental cleaning devices with each other. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched: Cochrane Oral Health's Trials Register (to 16 January 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2018, Issue 12), MEDLINE Ovid (1946 to 16 January 2019), Embase Ovid (1980 to 16 January 2019) and CINAHL EBSCO (1937 to 16 January 2019). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared toothbrushing and a home-use interdental cleaning device versus toothbrushing alone or with another device (minimum duration four weeks). DATA COLLECTION AND ANALYSIS: At least two review authors independently screened searches, selected studies, extracted data, assessed studies' risk of bias, and assessed evidence certainty as high, moderate, low or very low, according to GRADE. We extracted indices measured on interproximal surfaces, where possible. We conducted random-effects meta-analyses, using mean differences (MDs) or standardised mean differences (SMDs). MAIN RESULTS: We included 35 RCTs (3929 randomised adult participants). Studies were at high risk of performance bias as blinding of participants was not possible. Only two studies were otherwise at low risk of bias. Many participants had a low level of baseline gingival inflammation.Studies evaluated the following devices plus toothbrushing versus toothbrushing: floss (15 trials), interdental brushes (2 trials), wooden cleaning sticks (2 trials), rubber/elastomeric cleaning sticks (2 trials), oral irrigators (5 trials). Four devices were compared with floss: interdental brushes (9 trials), wooden cleaning sticks (3 trials), rubber/elastomeric cleaning sticks (9 trials) and oral irrigators (2 trials). Another comparison was rubber/elastomeric cleaning sticks versus interdental brushes (3 trials).No trials assessed interproximal caries, and most did not assess periodontitis. Gingivitis was measured by indices (most commonly, Löe-Silness, 0 to 3 scale) and by proportion of bleeding sites. Plaque was measured by indices, most often Quigley-Hein (0 to 5). PRIMARY OBJECTIVE: comparisons against toothbrushing aloneLow-certainty evidence suggested that flossing, in addition to toothbrushing, may reduce gingivitis (measured by gingival index (GI)) at one month (SMD -0.58, 95% confidence interval (CI) -1.12 to -0.04; 8 trials, 585 participants), three months or six months. The results for proportion of bleeding sites and plaque were inconsistent (very low-certainty evidence).Very low-certainty evidence suggested that using an interdental brush, plus toothbrushing, may reduce gingivitis (measured by GI) at one month (MD -0.53, 95% CI -0.83 to -0.23; 1 trial, 62 participants), though there was no clear difference in bleeding sites (MD -0.05, 95% CI -0.13 to 0.03; 1 trial, 31 participants). Low-certainty evidence suggested interdental brushes may reduce plaque more than toothbrushing alone (SMD -1.07, 95% CI -1.51 to -0.63; 2 trials, 93 participants).Very low-certainty evidence suggested that using wooden cleaning sticks, plus toothbrushing, may reduce bleeding sites at three months (MD -0.25, 95% CI -0.37 to -0.13; 1 trial, 24 participants), but not plaque (MD -0.03, 95% CI -0.13 to 0.07).Very low-certainty evidence suggested that using rubber/elastomeric interdental cleaning sticks, plus toothbrushing, may reduce plaque at one month (MD -0.22, 95% CI -0.41 to -0.03), but this was not found for gingivitis (GI MD -0.01, 95% CI -0.19 to 0.21; 1 trial, 12 participants; bleeding MD 0.07, 95% CI -0.15 to 0.01; 1 trial, 30 participants).Very-low certainty evidence suggested oral irrigators may reduce gingivitis measured by GI at one month (SMD -0.48, 95% CI -0.89 to -0.06; 4 trials, 380 participants), but not at three or six months. Low-certainty evidence suggested that oral irrigators did not reduce bleeding sites at one month (MD -0.00, 95% CI -0.07 to 0.06; 2 trials, 126 participants) or three months, or plaque at one month (SMD -0.16, 95% CI -0.41 to 0.10; 3 trials, 235 participants), three months or six months, more than toothbrushing alone. SECONDARY OBJECTIVE: comparisons between devicesLow-certainty evidence suggested interdental brushes may reduce gingivitis more than floss at one and three months, but did not show a difference for periodontitis measured by probing pocket depth. Evidence for plaque was inconsistent.Low- to very low-certainty evidence suggested oral irrigation may reduce gingivitis at one month compared to flossing, but very low-certainty evidence did not suggest a difference between devices for plaque.Very low-certainty evidence for interdental brushes or flossing versus interdental cleaning sticks did not demonstrate superiority of either intervention.Adverse eventsStudies that measured adverse events found no severe events caused by devices, and no evidence of differences between study groups in minor effects such as gingival irritation. AUTHORS' CONCLUSIONS: Using floss or interdental brushes in addition to toothbrushing may reduce gingivitis or plaque, or both, more than toothbrushing alone. Interdental brushes may be more effective than floss. Available evidence for tooth cleaning sticks and oral irrigators is limited and inconsistent. Outcomes were mostly measured in the short term and participants in most studies had a low level of baseline gingival inflammation. Overall, the evidence was low to very low-certainty, and the effect sizes observed may not be clinically important. Future trials should report participant periodontal status according to the new periodontal diseases classification, and last long enough to measure interproximal caries and periodontitis.

Associations between spatial access to physical activity facilities and frequency of physical activity; how do home and workplace neighbourhoods in West Central Scotland compare?

BACKGROUND: Over a third of the Scottish population do not meet physical activity (PA) recommendations, with a greater proportion of those from disadvantaged areas not meeting recommended levels. There is a great need for detailed understanding of why some people are active while others are not. It has been established that features within home neighbourhoods are important for promoting PA, and although around 60% of time spent in exercise daily is undertaken outside the residential environment, relatively little research includes both home and workplace neighbourhood contexts. This study utilised an existing west central Scotland survey and spatial data on PA facilities to examine whether, for working adults, there are links between access to facilities, within home and workplace neighbourhoods, and frequency of PA, and whether such associations differ by socio-economic group. METHODS: Using a Geographic Information System (GIS), home and workplace postcodes of a sub-sample of 'Transport, Health and Well-being' 2010 study respondents (n = 513) were mapped, along with public (i.e. public-sector funded) and private (i.e. private-sector funded) PA facilities (e.g. sports halls, gyms, pools etc.) within 800 m and 1600 m path/street network buffers of home and workplace postcodes. Using Analysis of Variance, associations between spatial access to PA facilities (i.e. facility counts within buffers) and self-reported PA (i.e. days being physically active in past month) were analysed. Models were run separately for access to any, public, private, and home, workplace, and home/workplace facilities. Associations were examined for all respondents, and stratified by age and income deprivation. RESULTS: Respondents' PA frequency was associated with spatial access to specific types of facilities near home and near home or workplace (combined). In general, PA frequency was higher where individuals lived/worked in closer proximity to private facilities and frequency lower where individuals lived/worked nearby to public facilities. Results varied by age and income deprivation sub-groups. CONCLUSION: This research contributes to methods exploring neighbourhood contextual influences on PA behaviour; it goes beyond a focus upon home neighbourhoods and incorporates access to workplace neighbourhood facilities. Results demonstrate the importance of examining both neighbourhood types, and such findings may feed into planning for behaviour-change interventions within both spaces.

Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages.

Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections. Humans are typically infected by aerosol-mediated transmission, and C. burnetii initially targets alveolar macrophages wherein the pathogen replicates in a phagolysosome-like niche known as the parasitophorous vacuole (PV). C. burnetii manipulates host cAMP-dependent protein kinase (PKA) signaling to promote PV formation, cell survival, and bacterial replication. In this study, we identified the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) as a PKA substrate that is increasingly phosphorylated at S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells and primary human alveolar macrophages, and this event required the Cα subunit of PKA. VASP phosphorylation also required bacterial protein synthesis and secretion of effector proteins via a type IV secretion system, indicating the pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation and intracellular bacterial replication required VASP activity, as siRNA-mediated depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic expression of a phospho-mimetic VASP (S239E) mutant protein prevented optimal PV formation, whereas VASP (S157E) mutant expression had no effect. VASP (S239E) expression also prevented trafficking of bead-containing phagosomes to the PV, indicating proper VASP activity is critical for heterotypic fusion events that control PV expansion in macrophages. Finally, expression of dominant negative VASP (S157A) in C. burnetii-infected cells impaired PV formation, confirming importance of the protein for proper infection. This study provides the first evidence of VASP manipulation by an intravacuolar bacterial pathogen via activation of PKA in human macrophages.

Final-impression techniques and materials for making complete and removable partial dentures.

BACKGROUND: Edentulism is relatively common and is often treated with the provision of complete or partial removable dentures. Clinicians make final impressions of complete dentures (CD) and removable partial dentures (RPD) using different techniques and materials. Applying the correct impression technique and material, based on an individual's oral condition, improves the quality of the prosthesis, which may improve quality of life. OBJECTIVES: To assess the effects of different final-impression techniques and materials used to make complete dentures, for retention, stability, comfort, and quality of life in completely edentulous people.To assess the effects of different final-impression techniques and materials used to make removable partial dentures, for stability, comfort, overextension, and quality of life in partially edentulous people. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 22 November 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Register of Studies, to 22 November 2017), MEDLINE Ovid (1946 to 22 November 2017), and Embase Ovid (21 December 2015 to 22 November 2017). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status when searching the electronic databases, however the search of Embase was restricted by date due to the Cochrane Centralised Search Project to identify all clinical trials and add them to CENTRAL. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different final-impression techniques and materials for treating people with complete dentures (CD) and removable partial dentures (RPD). For CD, we included trials that compared different materials or different techniques or both. In RPD for tooth-supported conditions, we included trials comparing the same material and different techniques, or different materials and the same technique. In tooth- and tissue-supported RPD, we included trials comparing the same material and different dual-impression techniques, and different materials with different dual-impression techniques. DATA COLLECTION AND ANALYSIS: Two review authors independently, and in duplicate, screened studies for eligibility, extracted data, and assessed the risk of bias for each included trial. We expressed results as risk ratios (RR) for dichotomous outcomes, and as mean differences (MD) or standardised mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CI), using the random-effects model. We constructed 'Summary of findings' tables for the main comparisons and outcomes (participant-reported oral health-related quality of life, quality of the denture, and denture border adjustments). MAIN RESULTS: We included nine studies in this review. Eight studies involved 485 participants with CD. We assessed six of the studies to be at high risk of bias, and two to be at low risk of bias. We judged one study on RPD with 72 randomised participants to be at high risk of bias.Overall, the quality of the evidence for each comparison and outcome was either low or very low, therefore, results should be interpreted with caution, as future research is likely to change the findings.Complete denturesTwo studies compared the same material and different techniques (one study contributed data to a secondary outcome only); two studies compared the same technique and different materials; and four studies compared different materials and techniques.One study (10 participants) evaluated two stage-two step, Biofunctional Prosthetic system (BPS) using additional silicone elastomer compared to conventional methods, and found no evidence of a clear difference for oral health-related quality of life, or quality of the dentures (denture satisfaction). The study reported that BPS required fewer adjustments. We assessed the quality of the evidence as very low.One study (27 participants) compared selective pressure final-impression technique using wax versus polysulfide elastomeric (rubber) material. The study did not measure quality of life or dentures, and found no evidence of a clear difference between interventions in the need for adjustments (RR 0.81, 95% CI 0.38 to 1.70). We assessed the quality of the evidence as very low.One study compared two stage-two step final impression with alginate versus silicone elastomer. Oral health-related quality of life measured by the OHIP-EDENT seemed to be better with silicone (MD 7.20, 95% CI 2.71 to 11.69; 144 participants). The study found no clear differences in participant-reported quality of the denture (comfort) after a two-week 'confirmation' period, but reported that silicone was better for stability and chewing efficiency. We assessed the quality of the evidence as low.Three studies compared single-stage impressions with alginate versus two stage-two step with elastomer (silicone, polysulfide, or polyether) impressions. There was no evidence of a clear difference in the OHIP-EDENT at one month (MD 0.05, 95% CI -2.37 to 2.47; two studies, 98 participants). There was no evidence of a clear difference in participant-rated general satisfaction with dentures at six months (MD 0.00, 95% CI -8.23 to 8.23; one study, 105 participants). We assessed the quality of the evidence as very low.One study compared single-stage alginate versus two stage-two step using zinc-oxide eugenol, and found no evidence of a clear difference in OHIP-EDENT (MD 0.50, 95% CI -2.67 to 3.67; 39 participants), or general satisfaction (RR 3.15, 95% CI 0.14 to 72.88; 39 participants) at six months. We assessed the quality of the evidence as very low.Removable partial denturesOne study randomised 72 participants and compared altered-cast technique versus one-piece cast technique. The study did not measure quality of life, but reported that most participants were satisfied with the dentures and there was no evidence of any clear difference between groups for general satisfaction at one-year follow-up (low-quality evidence). There was no evidence of a clear difference in number of intaglio adjustments at one year (RR 1.43, 95% CI 0.61 to 3.34) (very low-quality evidence). AUTHORS' CONCLUSIONS: We conclude that there is no clear evidence that one technique or material has a substantial advantage over another for making complete dentures and removable partial dentures. Available evidence for the relative benefits of different denture fabrication techniques and final-impression materials is limited and is of low or very low quality. More high-quality RCTs are required.

Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis.

Autophagy is important for maintaining cellular homeostasis, and thus its deficiency is implicated in a broad spectrum of human diseases. Its role in platelet function has only recently been examined. Our biochemical and imaging studies demonstrate that the core autophagy machinery exists in platelets, and that autophagy is constitutively active in resting platelets. Moreover, autophagy is induced upon platelet activation, as indicated by agonist-induced loss of the autophagy marker LC3II. Additional experiments, using inhibitors of platelet activation, proteases, and lysosomal acidification, as well as platelets from knockout mouse strains, show that agonist-induced LC3II loss is a consequence of platelet signaling cascades and requires proteases, acidic compartments, and membrane fusion. To assess the physiological role of platelet autophagy, we generated a mouse strain with a megakaryocyte- and platelet-specific deletion of Atg7, an enzyme required for LC3II production. Ex vivo analysis of platelets from these mice shows modest defects in aggregation and granule cargo packaging. Although these mice have normal platelet numbers and size distributions, they exhibit a robust bleeding diathesis in the tail-bleeding assay and a prolonged occlusion time in the FeCl3-induced carotid injury model. Our results demonstrate that autophagy occurs in platelets and is important for hemostasis and thrombosis.

Preoperative analgesics for additional pain relief in children and adolescents having dental treatment.

BACKGROUND: Fear of dental pain is a major barrier to treatment for children who need dental care. The use of preoperative analgesics has the potential to reduce postoperative discomfort and intraoperative pain. We reviewed the available evidence to determine whether further research is warranted and to inform the development of prescribing guidelines. This is an update of a Cochrane review published in 2012. OBJECTIVES: To assess the effects of preoperative analgesics for intraoperative or postoperative pain relief (or both) in children and adolescents undergoing dental treatment without general anaesthesia or sedation. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 5 January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 12), MEDLINE via OVID (1946 to 5 January 2016), EMBASE via OVID (1980 to 5 January 2016), LILACS via BIREME (1982 to 5 January 2016) and the ISI Web of Science (1945 to 5 January 2016). We searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials to 5 January 2016. There were no restrictions regarding language or date of publication in the searches of the electronic databases. We handsearched several specialist journals dating from 2000 to 2011.We checked the reference lists of all eligible trials for additional studies. We contacted specialists in the field for any unpublished data. SELECTION CRITERIA: Randomised controlled clinical trials of analgesics given before dental treatment versus placebo or no analgesics in children and adolescents up to 17 years of age. We excluded children and adolescents having dental treatment under sedation (including nitrous oxide/oxygen) or general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors assessed titles and abstracts of the articles obtained from the searches for eligibility, undertook data extraction and assessed the risk of bias in the included studies. We assessed the quality of the evidence using GRADE criteria. MAIN RESULTS: We included five trials in the review, with 190 participants in total. We did not identify any new studies for inclusion from the updated search in January 2016.Three trials were related to dental treatment, i.e. restorative and extraction treatments; two trials related to orthodontic treatment. We did not judge any of the included trials to be at low risk of bias.Three of the included trials compared paracetamol with placebo, only two of which provided data for analysis (presence or absence of parent-reported postoperative pain behaviour). Meta-analysis of the two trials gave arisk ratio (RR) for postoperative pain of 0.81 (95% confidence interval (CI) 0.53 to 1.22; two trials, 100 participants; P = 0.31), which showed no evidence of a benefit in taking paracetamol preoperatively (52% reporting pain in the placebo group versus 42% in the paracetamol group). One of these trials was at unclear risk of bias, and the other was at high risk. The quality of the evidence is low. One study did not have any adverse events; the other two trials did not mention adverse events.Four of the included trials compared ibuprofen with placebo. Three of these trials provided useable data. One trial reported no statistical difference in postoperative pain experienced by the ibuprofen group and the control group for children undergoing dental treatment. We pooled the data from the other two trials, which included participants who were having orthodontic separator replacement without a general anaesthetic, to determine the effect of preoperative ibuprofen on the severity of postoperative pain. There was a statistically significant mean difference in severity of postoperative pain of -13.44 (95% CI -23.01 to -3.88; two trials, 85 participants; P = 0.006) on a visual analogue scale (0 to 100), which indicated a probable benefit for preoperative ibuprofen before this orthodontic procedure. However, both trials were at high risk of bias. The quality of the evidence is low. Only one of the trials reported adverse events (one participant from the ibuprofen group and one from the placebo group reporting a lip or cheek biting injury). AUTHORS' CONCLUSIONS: From the available evidence, we cannot determine whether or not preoperative analgesics are of benefit in paediatric dentistry for procedures under local anaesthetic. There is probably a benefit in using preoperative analgesics prior to orthodontic separator placement. The quality of the evidence is low. Further randomised clinical trials should be completed with appropriate sample sizes and well defined outcome measures.

Interventions for treating bisphosphonate-related osteonecrosis of the jaw (BRONJ).

BACKGROUND: Bisphosphonate drugs can be used to prevent and treat osteoporosis and to reduce symptoms and complications of metastatic bone disease; however, they are associated with a rare but serious adverse event: osteonecrosis of the maxillary and mandibular bones. This condition is called bisphosphonate-related osteonecrosis of the jaw or BRONJ. BRONJ is diagnosed when people who are taking, or have previously taken, bisphosphonates have exposed bone in the jaw area for more than eight weeks in the absence of radiation treatment. There is currently no "gold standard" of treatment for BRONJ. The three broad categories of intervention are conservative approaches (e.g. mouth rinse, antibiotics), surgical interventions and adjuvant non-surgical strategies (e.g. hyperbaric oxygen therapy, platelet-rich plasma), which can be used in combination. OBJECTIVES: To determine the efficacy and safety of any intervention aimed at treating BRONJ. SEARCH METHODS: We searched the following databases to 15 December 2015: the Cochrane Oral Health Group Trials Register, the Cochrane Breast Cancer Group Trials Register (20 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, EMBASE via Ovid, CancerLit via PubMed, CINAHL via EBSCO and AMED via Ovid. We scanned the references cited in retrieved articles and contacted experts in the field, the first authors of included papers, study sponsors, other bisphosphonates investigators and pharmaceutical companies. We searched for ongoing trials through contact with trialists and by searching the US National Institutes of Health Trials Register (clinicaltrials.gov) and the World Health Organization Clinical Trials Registry Platform. We also conducted a grey literature search to September 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of any treatment for BRONJ with another treatment or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed the risk of bias in the included trials and extracted data. When in dispute, we consulted a third review author. MAIN RESULTS: One small trial at high risk of bias met the inclusion criteria. The trial randomised 49 participants, most of whom had cancer. It compared standard care (defined as surgery, antibiotics and oral rinses at the discretion of the oral-maxillofacial surgeon) to standard care plus hyperbaric oxygen therapy (2 atmospheres twice a day for 40 treatments). The trial measured the percentage of participants who improved or healed at three, six, 12 and 18 months and last contact. It also measured mean weekly pain scores.At three months, the study found that the participants in intervention group were more likely to have an improvement in their osteonecrosis than the standard care group participants (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.01 to 3.74). There was no clear difference between the groups for the outcome 'healed' at three months (RR 3.60, 95% CI 0.87 to 14.82). There was no clear difference between the groups for improvement or healing when they were evaluated at six, 12 and 18 months and last contact.The study did not give any information on adverse events.Although the findings suggest adjunctive hyperbaric oxygen improved BRONJ, the quality of the evidence is very low since the only study was underpowered and was at high risk of bias due to lack of blinding, cross-over of participants between groups and very high attrition (50% at 12 months and 80% at 18 months in this study, which was designed for an intended follow-up of 24 months). AUTHORS' CONCLUSIONS: There is a lack of evidence from randomised controlled trials to guide treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). One small trial at high risk of bias evaluated hyperbaric oxygen therapy (HBO) as an adjunct to "standard" care and could not confirm or refute the effectiveness of HBO. There are two ongoing trials of teriparatide treatment for BRONJ. We found no randomised controlled trials of any other BRONJ treatments. High quality randomised controlled trials are needed. We provide recommendations for their focus and design.

Walkability around primary schools and area deprivation across Scotland.

BACKGROUND: A number of studies based in the US, Canada, and Australia, have found evidence of associations between the built environment (BE) and mode of transport to school, and links between active travel and deprivation. Limited research in the UK compares potential BE supports for walking to school by area deprivation. Within this study, we gathered data on BE attributes previously linked to active travel, i.e., street/path connectivity, and dwelling density, created a composite 'walkability score' (WS) for areas around primary schools across urban Scotland, and explored whether poorer areas exhibit lower scores than more affluent areas, or vice versa. We consider this to be a novel approach as few studies have compared BE features by deprivation across a whole country. METHODS: Address and road/path maps were obtained and primary schools (N = 937) across mainland Scotland were mapped. Schools were attributed income deprivation scores (scores divided into quintiles (Q1: least deprived, Q5: most deprived)). Catchment area (CA) boundaries, i.e., the geographic area representing eligibility for local school attendance, were drawn around schools, and WS calculated for each CA. We compared mean WS by income quintile (ANOVA), for all local authorities (LAs) combined (N = 29), and separately for the four LAs with the greatest number of schools included in the analysis. RESULTS: For all LAs combined, the least deprived quintile (Q1) showed a significantly lower WS (-0.61), than quintiles 3, 4 and 5 (Q2: -0.04 (non-sig), Q3: 0.38, Q4: 0.09, Q5: 0.18); while for Glasgow the second least deprived quintile (Q2) showed significantly higher WS (Q1: 1.35, Q2: 1.73), than middling (Q3: 0.18) and most deprived quintiles (Q4: 0.06, Q5: -0.10). CONCLUSION: WS differ by deprivation with patterns varying depending on the spatial scale of the analysis. It is essential that less walkable areas are provided with the resources to improve opportunities to engage in active travel.

Coxiella burnetii exploits host cAMP-dependent protein kinase signalling to promote macrophage survival.

Intracellular bacterial pathogens often subvert apoptosis signalling to regulate survival of their host cell, allowing propagation of the bacterial population. Coxiella burnetii, the intracellular agent of human Q fever, inhibits host cell apoptosis through several mechanisms, including prevention of mitochondrial cytochrome c release, triggering of an anti-apoptotic transcriptional programme, and activation of pro-survival kinases. To control host cell survival, C. burnetii delivers effector proteins to the eukaryotic cytosol using a specialized Dot/Icm type IV secretion system (T4SS). Effectors are predicted to regulate activity of pro-survival host signalling proteins, such as Akt and cAMP-dependent protein kinase (PKA), to control infection. Here, we show that host PKA activity is required for C. burnetii inhibition of macrophage apoptosis. PKA is activated during infection and inhibits activity of the pro-apoptotic protein Bad via phosphorylation. Bad is also phosphorylated at an Akt-specific residue, indicating C. burnetii uses two kinases to fully inactivate Bad. Additionally, Bad and the tethering protein 14-3-3ß colocalize at the C. burnetii parasitophorous vacuole (PV) membrane during infection, an event predicted to alter Bad promotion of apoptosis. Inhibiting PKA activity prevents Bad recruitment to the PV, but the protein is retained at the membrane during induction of apoptosis. Finally, PKA regulatory subunit I (RI) traffics to the PV membrane in a T4SS-dependent manner, suggesting a C. burnetii effector(s) regulates PKA-dependent activities. This study is the first to demonstrate subversion of host PKA activity by an intracellular bacterial pathogen to prevent apoptosis and survive within macrophages.

Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages.

The intracellular bacterial pathogen Coxiella burnetii is a category B select agent that causes human Q fever. In vivo, C. burnetii targets alveolar macrophages wherein the pathogen replicates in a lysosome-like parasitophorous vacuole (PV). In vitro, C. burnetii infects a variety of cultured cell lines that have collectively been used to model the pathogen's infectious cycle. However, differences in the cellular response to infection have been observed, and virulent C. burnetii isolate infection of host cells has not been well defined. Because alveolar macrophages are routinely implicated in disease, we established primary human alveolar macrophages (hAMs) as an in vitro model of C. burnetii-host cell interactions. C. burnetii pathotypes, including acute disease and endocarditis isolates, replicated in hAMs, albeit with unique PV properties. Each isolate replicated in large, typical PV and small, non-fused vacuoles, and lipid droplets were present in avirulent C. burnetii PV. Interestingly, a subset of small vacuoles harboured single organisms undergoing degradation. Prototypical PV formation and bacterial growth in hAMs required a functional type IV secretion system, indicating C. burnetii secretes effector proteins that control macrophage functions. Avirulent C. burnetii promoted sustained activation of Akt and Erk1/2 pro-survival kinases and short-termphosphorylation of stress-related p38. Avirulent organisms also triggered a robust, early pro-inflammatory response characterized by increased secretion of TNF-α and IL-6, while virulent isolates elicited substantially reduced secretion of these cytokines. A corresponding increase in pro- and mature IL-1ß occurred in hAMs infected with avirulent C. burnetii, while little accumulation was observed following infection with virulent isolates. Finally, treatment of hAMs with IFN-γ controlled intracellular replication, supporting a role for this antibacterial insult in the host response to C. burnetii. Collectively, the current results demonstrate the hAM model is a human disease-relevant platform for defining novel innate immune responses to C. burnetii.

Looking into the glass: glassware as an alcohol marketing tool, and the implications for policy.

AIMS: To examine how glassware functions as a marketing tool. METHODS: Content analysis of trade journals. RESULTS: Glassware is used as an integral part of marketing activity to recruit customers, revive brands, build profits and increase consumption. CONCLUSION: Glassware should be subject to the same control as other forms of marketing. Glasses could be re-engineered to promote safer drinking.

Determining the impact of smoking point of sale legislation among youth (Display) study: a protocol for an evaluation of public health policy.

BACKGROUND: Tobacco advertising and product promotions have been largely banned in the UK but point of sale (POS) tobacco advertising is one of the few places where tobacco products may be legitimately advertised. POS displays have been shown to increase susceptibility to smoking, experimentation and initiation into smoking. These displays may also influence perceived prevalence of smoking and the perception that tobacco products are easily obtained and are a 'normal' product. A ban of POS tobacco advertising was introduced in Scotland in large tobacco retail outlets of over 280 m2 internal sales floor areas (mainly supermarkets) in April 2013 and will be extended to include smaller tobacco retail outlets in April 2015. However, the impact of POS bans on smoking attitudes, behaviours and prevalence has yet to be determined. METHODS/DESIGN: This study has a multi-modal before and after design and uses mixed methods to collect data, at baseline and then with longitudinal follow-up for 4 years, in four purposively selected communities. For the purposes of the study, community is defined as the catchment areas of the secondary schools selected for study. There are four main components to the on-going study. In each of the four communities, at baseline and in follow-up years, there will be: mapping and spatial analyses of tobacco retail outlets; tobacco advertising and marketing audits of tobacco retail outlets most used by young people; cross-sectional school surveys of secondary school pupils; and focus group interviews with purposive samples of secondary school pupils. The tobacco audit is supplemented by interviews and observations conducted with a panel of tobacco retailers recruited from four matched communities. DISCUSSION: This study examines the impact of the implementation of both a partial and comprehensive ban on point of sale (POS) tobacco advertising on attitudes to smoking, brand awareness, perceived ease of access to tobacco products and youth smoking prevalence. The results will be of considerable interest to policy makers both from the UK and other jurisdictions where they are considering the development and implementation of similar legislation.

Decarbonizing Water: The Potential to Apply the Voluntary Carbon Market toward Global Water Security.

The increase in global water insecurity is one of the first perceivable effects of climate change. Two billion people are now without access to safe drinking water, and four billion experience water stress at least once a year, primarily in low per-capita emission countries. This nexus between climate change and water insecurity has significant implications for the global economy, with the water sector contributing 10% of global emissions. Though traditionally a local issue, climate finance mechanisms like the voluntary carbon market (VCM) present opportunities for a global, sustainable, performance-based funding stream to address water insecurity. Since 2010, water-related carbon projects have yielded over 45 million emission reduction credits. Our analysis estimates a global potential of over 1.6 billion tCO2e per year across various water project subsectors. At a $10 per credit average, this could attract over $160 billion in investments over the next decade, enhancing global water security. However, barriers like high intervention costs and limited technologies hinder widespread implementation, creating a tension between standardized and bespoke credits. We present case studies, spanning drinking water initiatives to the wastewater treatment sector that illustrate VCM's role in channeling private sector capital for water security in climate-vulnerable regions.